Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a com...Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors, including water status, light, CO2 levels and pathogen attack, as well as endogenous signals, such as abscisic acid and apoplastic reactive oxygen species （ROS）. Under abiotic and biotic stress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network, primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO2 signaling, and immunity responses. Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli.展开更多
This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these...This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.展开更多
The red blood cell distribution width(RDW) is a simple, rapid, inexpensive and straightforward hematological parameter, reflecting the degree of anisocytosis in vivo. The currently available scientific evidence sugges...The red blood cell distribution width(RDW) is a simple, rapid, inexpensive and straightforward hematological parameter, reflecting the degree of anisocytosis in vivo. The currently available scientific evidence suggests that RDW assessment not only predicts the risk of adverse outcomes(cardiovascular and all-cause mortality, hospitalization for acute decompensation or worsened left ventricular function) in patients with acute and chronic heart failure(HF), but is also a significant and independent predictor of developing HF in patients free of this condition. Regarding the biological interplay between impaired hematopoiesis and cardiac dysfunction, many of the different conditions associated with increased heterogeneity of erythrocyte volume(i.e., ageing, inflammation, oxidative stress, nutritional deficiencies and impaired renal function), may be concomitantly present in patients with HF, whilst anisocytosis may also directly contribute to the development and worsening of HF. In conclusion, the longitudinal assessment of RDW changes over time may be considered an efficient measure to help predicting the risk of both development and progression of HF.展开更多
Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features ...Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.展开更多
Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added t...Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen （HLA） associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1＊11/＊12 alleles and DQB1＊0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1＊03 and ＊07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors （KIR） of natural killer （NK） cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic stra展开更多
The measurement of procalcitonin has recently become a mainstay for the diagnosis and therapeutic management of severe bacterial infections, especially those sustained by Gram-negative bacteria. Therefore, the aim of ...The measurement of procalcitonin has recently become a mainstay for the diagnosis and therapeutic management of severe bacterial infections, especially those sustained by Gram-negative bacteria. Therefore, the aim of this article is to provide a narrative overview on the potential role of procalcitonin measurement in patients with inflammatory bowel disease(IBD). According to the available scientific literature, the clinical significance of procalcitonin for diagnosing IBD or monitoring disease activity remains elusive, and its association with disease severity is confined to a limited number of case-control studies, with low sample size. Nevertheless, literature data also suggests that a supranormal procalcitonin serum concentration(i.e., > 0.5 ng/m L) may reflect the presence of a number of infective complications in IBD, especially bacterial enterocolitis, bacterial gastroenteritis, intraabdominal abscess, postsurgical infection and sepsis. Rather than for diagnosing or assessing disease activity, the measurement of this biomarker may hence retain practical clinical significance for early prediction, timely diagnosis and therapeutic monitoring of many IBDassociated infections and complications.展开更多
Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy(DN), which classically presents with proteinuria followed by a progressive decrease in re...Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy(DN), which classically presents with proteinuria followed by a progressive decrease in renal function.However, an increasing proportion of DN patients have a decline in kidney function and vascular complications without proteinuria, known as nonproteinuric DN(NP-DN). Despite the increased incidence of NP-DN, few clinical or experimental studies have thoroughly investigated the pathophysiological mechanisms and targeted treatment for this form of DN. In this review, we will examine the differences between conventional DN and NP-DN and consider potential pathophysiological mechanisms, diagnostic markers, and treatment for both DN and NP-DN. The investigation of the pathophysiology of NP-DN should provide additional insight into the cardiovascular factors influencing renal function and disease and provide novel treatments for the vascular complications seen in diabetic patients.展开更多
Cells are compartmentalized by numerous membrane-enclosed organelles and membraneless compartments to ensure that a wide variety of cellular activities occur in a spatially and temporally controlled manner. The molecu...Cells are compartmentalized by numerous membrane-enclosed organelles and membraneless compartments to ensure that a wide variety of cellular activities occur in a spatially and temporally controlled manner. The molecular mechanisms underlying the dynamics of membrane-bound organelles, such as their fusion and fission, vesicle-mediated trafficking and membrane contactmediated inter-organelle interactions, have been extensively characterized. However, the molecular details of the assembly and functions of membraneless compartments remain elusive. Mounting evidence has emerged recently that a large number of membraneless compartments, collectively called biomacromolecular condensates, are assembled via liquid-liquid phase separation(LLPS). Phase-separated condensates participate in various biological activities, including higher-order chromatin organization,gene expression, triage of misfolded or unwanted proteins for autophagic degradation, assembly of signaling clusters and actin-and microtubule-based cytoskeletal networks, asymmetric segregations of cell fate determinants and formation of pre-and post-synaptic density signaling assemblies. Biomacromolecular condensates can transition into different material states such as gel-like structures and solid aggregates. The material properties of condensates are crucial for fulfilment of their distinct functions, such as biochemical reaction centers, signaling hubs and supporting architectures. Cells have evolved multiple mechanisms to ensure that biomacromolecular condensates are assembled and disassembled in a tightly controlled manner. Aberrant phase separation and transition are causatively associated with a variety of human diseases such as neurodegenerative diseases and cancers. This review summarizes recent major progress in elucidating the roles of LLPS in various biological pathways and diseases.展开更多
AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two ...AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two patients (15 men and 7 women; median age 68 years,range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC. Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition,the degree of staining within tumor tissue was compared according to a number of clinicopathological variables. RESULTS:The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues,even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.展开更多
Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human dise...Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.展开更多
AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infe...AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.展开更多
BACKGROUND： Pancreatic ductal adenocarcinoma（PDAC）is a devastating malignancy with a poor prognosis and little treatment options. The development and progression of the disease is fostered by inflammatory cells and...BACKGROUND： Pancreatic ductal adenocarcinoma（PDAC）is a devastating malignancy with a poor prognosis and little treatment options. The development and progression of the disease is fostered by inflammatory cells and cytokines. One of these cytokines is interleukin-6（IL-6）, which plays an important role in a wide range of biologic activities.DATA SOURCES： A systematic search of PubMed was performed to identify relevant studies using key words such as interleukin-6,inflammatory cytokines, inflammation and pancreatic cancer or PDAC. Articles related to IL-6 and pancreatic cancer were systematically reviewed.RESULTS： IL-6 is elevated in the serum of pancreatic cancer patients and correlates with cachexia, advanced tumor stage and poor survival. Its expression is enhanced by hypoxia and proteins involved in pancreatic cancer development like Kras,mesothelin or ZIP4. IL-6 in turn contributes to the generation of a pro-tumorigenic microenvironment and is probably involved in angiogenesis and metastasis. In experimental mouse models of PDAC, IL-6 was important for the development and progression of precursor lesions.CONCLUSION： IL-6 emerges as a key player in pancreatic cancer development and progression, and hence should be considered as a new therapeutic target.展开更多
Indole-3-acetic acid （IAA）, a major plant auxin, is produced in both tryptophan-dependent and tryptophan-independent pathways. A major pathway in Arabidopsis thaliana generates IAA in two reactions from tryptophan. ...Indole-3-acetic acid （IAA）, a major plant auxin, is produced in both tryptophan-dependent and tryptophan-independent pathways. A major pathway in Arabidopsis thaliana generates IAA in two reactions from tryptophan. Step one converts tryptophan to indole-3-pyruvic acid （IPA） by tryptophan aminotransferases followed by a rate-limiting step converting IPA to IAA catalyzed by YUCCA proteins. We identified eight putative StYUC （Solanum tuberosum YUCCA） genes whose deduced amino acid sequences share 50%-70% identity with those of Arabidopsis YUCCA proteins. All include canonical, conserved YUCCA sequences： FATGY motif, FMO signature sequence, and FAD-binding and NADP-binding sequences. In addition, five genes were found with -50% amino acid sequence identity to Arabidopsis trypto-phan aminotransferases. Transgenic potato （Solanum tuberosum cv. Jowon） constitutively overexpressing Arabidopsis AtYUC6 displayed high-auxin phenotypes such as narrow downward-curled leaves, increased height, erect stature, and longevity. Transgenic potato plants overexpressing AtYUC6 showed enhanced drought tolerance based on reduced water loss. The phenotype was correlated with reduced levels of reactive oxygen species in leaves. The results suggest a func-tional YUCCA pathway of auxin biosynthesis in potato that may be exploited to alter plant responses to the environment.展开更多
During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation,as a result of large international research projects(Human Genome Project,...During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation,as a result of large international research projects(Human Genome Project,the 1000 Genomes Project International HapMap Project,and Programs for Genomic Applications NHLBI-PGA).This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of cancer.For clinical use in the treatment of patients with colorectal cancer(CRC),in addition to fluoropyrimidines,another two new cytostatic drugs were allowed:irinotecan and oxaliplatin.Intensive research into new treatment regimens and a new generation of drugs used in targeted therapy has also been conducted.The last 20years was a time of numerous in vitro and in vivo studies on the molecular basis of drug resistance.One of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer cells.Understanding the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized medicine.Scientists hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/pharmacogenomics.Over the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application potential.This review is a synthetic presentation of drug resistance in the context of CRC patient chemotherapy.The multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review.展开更多
For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients...For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients and clinicians in need of additional diagnostic biomarkers. Seminal fluid contains the highest concentration of molecules from the male reproductive glands, therefore, this review focuses on current and novel seminal biomarkers in certain male infertility scenarios, including natural fertility, differentiating azoospermia etiologies, and predicting assisted reproductive technique success. Currently available tests include antisperm antibody assays, DNA fragmentation index, sperm fluorescence in situ hybridization, and other historical sperm functional tests. The poor diagnostic ability of current assays has led to continued efforts to find more predictive biomarkers. Emerging research in the fields of genomics, epigenetics, proteomics, transcriptomics, and metabolomics holds promise for the development of novel male infertility biomarkers. Seminal protein-based assays of TEXI01, ECM 1, and ACRV1 are already available or under final development for clinical use. Additional panels of DNA, RNA, proteins, or metabolites are being explored as we attempt to understand the pathophysiologic processes of male infertility. Future ventures will need to continue data integration and validation for the development of clinically useful infertility biomarkers to aid in male infertility diagnosis, treatment, and counseling.展开更多
AIM To investigate the effects of hydrogen-rich water(HRW) treatment on prevention of ethanol(Et OH)-induced early fatty liver in mice.METHODS In vitro reduction of hydrogen peroxide by HRW was determined with a chemi...AIM To investigate the effects of hydrogen-rich water(HRW) treatment on prevention of ethanol(Et OH)-induced early fatty liver in mice.METHODS In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control,Et OH,Et OH + silymarin,Et OH + HRW and Et OH + silymarin + HRW. Each group was fed a Lieber-De Carli liquid diet containing Et OH or isocaloric maltose dextrin(control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic Et OH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 m L/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk.RESULTS The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin,which was correlated with food intake. HRW treatment significantly reduced Et OH-induced increases in serum alanine aminotransferase,aspartate aminotransferase,triglycerol and total cholesterol levels,hepatic lipid accumulation and inflammatory cytokines,including tumor necrosis factor-alpha(TNF-α) and interleukin(IL)-6. HRW attenuated malondialdehyde level,restored glutathione depletion and increased superoxide dismutase,glutathione peroxidase and catalase activities in the liver. Moreover,HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels.CONCLUSION HRW protects against chronic Et OH-induced liver injury,possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22,thus activating antioxidant enzymes against oxidative stress.展开更多
The Joint Automated Repository for Various Integrated Simulations(JARVIS)is an integrated infrastructure to accelerate materials discovery and design using density functional theory(DFT),classical force-fields(FF),and...The Joint Automated Repository for Various Integrated Simulations(JARVIS)is an integrated infrastructure to accelerate materials discovery and design using density functional theory(DFT),classical force-fields(FF),and machine learning(ML)techniques.JARVIS is motivated by the Materials Genome Initiative(MGI)principles of developing open-access databases and tools to reduce the cost and development time of materials discovery,optimization,and deployment.展开更多
The realization of an efficient optical sensor based on a photonic crystal metasurface supporting bound states in the continuum is reported. Liquids with different refractive indices, ranging from 1.4000 to 1.4480, ar...The realization of an efficient optical sensor based on a photonic crystal metasurface supporting bound states in the continuum is reported. Liquids with different refractive indices, ranging from 1.4000 to 1.4480, are infiltrated in a microfluidic chamber bonded to the sensing dielectric metasurface. A bulk liquid sensitivity of 178 nm/RIU is achieved, while a Q-factor of about 2000 gives a sensor figure of merit up to 445 in air at both visible and infrared excitations. Furthermore, the detection of ultralow-molecular-weight(186 Da) molecules is demonstrated with a record resonance shift of 6 nm per less than a 1 nm thick single molecular layer. The system exploits a normal-to-the-surface optical launching scheme, with excellent interrogation stability and demonstrates alignment-free performances, overcoming the limits of standard photonic crystals and plasmonic resonant configurations.展开更多
The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live.Metabolic reprogramming supports tumor cells’high demand of biogenesis for their rapid proliferat...The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live.Metabolic reprogramming supports tumor cells’high demand of biogenesis for their rapid proliferation,and helps tumor cells to survive under certain genetic or environmental stresses.Emerging evidence suggests that metabolic alteration is ultimately and tightly associated with genetic changes,in particular the dysregulation of key oncogenic and tumor suppressive signaling pathways.Cancer cells activate HIF signaling even in the presence of oxygen and in the absence of growth factor stimulation.This cancer metabolic phenotype,described firstly by German physiologist Otto Warburg,ensures enhanced glycolytic metabolism for the biosynthesis of macromolecules.The conception of metabolite signaling,i.e.,metabolites are regulators of cell signaling,provides novel insights into how reactive oxygen species(ROS)and other metabolites deregulation may regulate redox homeostasis,epigenetics,and proliferation of cancer cells.Moreover,the unveiling of noncanonical functions of metabolic enzymes,such as the moonlighting functions of phosphoglycerate kinase 1(PGK1),reassures the importance of metabolism in cancer development.The metabolic,microRNAs,and ncRNAs alterations in cancer cells can be sorted and delivered either to intercellular matrix or to cancer adjacent cells to shape cancer microenvironment via media such as exosome.Among them,cancer microenvironmental cells are immune cells which exert profound effects on cancer cells.Understanding of all these processes is a prerequisite for the development of a more effective strategy to contain cancers.展开更多
基金supported by the National Key Scientific Research Project(2011CB915400)supported by the National Natural Science Foundation of China(31730007)
文摘Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors, including water status, light, CO2 levels and pathogen attack, as well as endogenous signals, such as abscisic acid and apoplastic reactive oxygen species （ROS）. Under abiotic and biotic stress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network, primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO2 signaling, and immunity responses. Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli.
文摘This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.
文摘The red blood cell distribution width(RDW) is a simple, rapid, inexpensive and straightforward hematological parameter, reflecting the degree of anisocytosis in vivo. The currently available scientific evidence suggests that RDW assessment not only predicts the risk of adverse outcomes(cardiovascular and all-cause mortality, hospitalization for acute decompensation or worsened left ventricular function) in patients with acute and chronic heart failure(HF), but is also a significant and independent predictor of developing HF in patients free of this condition. Regarding the biological interplay between impaired hematopoiesis and cardiac dysfunction, many of the different conditions associated with increased heterogeneity of erythrocyte volume(i.e., ageing, inflammation, oxidative stress, nutritional deficiencies and impaired renal function), may be concomitantly present in patients with HF, whilst anisocytosis may also directly contribute to the development and worsening of HF. In conclusion, the longitudinal assessment of RDW changes over time may be considered an efficient measure to help predicting the risk of both development and progression of HF.
基金Supported by Department of Science and Technology,Government of India to Iqra Hameed,No.Wos-A LS 509/2012
文摘Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.
文摘Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen （HLA） associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1＊11/＊12 alleles and DQB1＊0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1＊03 and ＊07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors （KIR） of natural killer （NK） cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic stra
文摘The measurement of procalcitonin has recently become a mainstay for the diagnosis and therapeutic management of severe bacterial infections, especially those sustained by Gram-negative bacteria. Therefore, the aim of this article is to provide a narrative overview on the potential role of procalcitonin measurement in patients with inflammatory bowel disease(IBD). According to the available scientific literature, the clinical significance of procalcitonin for diagnosing IBD or monitoring disease activity remains elusive, and its association with disease severity is confined to a limited number of case-control studies, with low sample size. Nevertheless, literature data also suggests that a supranormal procalcitonin serum concentration(i.e., > 0.5 ng/m L) may reflect the presence of a number of infective complications in IBD, especially bacterial enterocolitis, bacterial gastroenteritis, intraabdominal abscess, postsurgical infection and sepsis. Rather than for diagnosing or assessing disease activity, the measurement of this biomarker may hence retain practical clinical significance for early prediction, timely diagnosis and therapeutic monitoring of many IBDassociated infections and complications.
文摘Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy(DN), which classically presents with proteinuria followed by a progressive decrease in renal function.However, an increasing proportion of DN patients have a decline in kidney function and vascular complications without proteinuria, known as nonproteinuric DN(NP-DN). Despite the increased incidence of NP-DN, few clinical or experimental studies have thoroughly investigated the pathophysiological mechanisms and targeted treatment for this form of DN. In this review, we will examine the differences between conventional DN and NP-DN and consider potential pathophysiological mechanisms, diagnostic markers, and treatment for both DN and NP-DN. The investigation of the pathophysiology of NP-DN should provide additional insight into the cardiovascular factors influencing renal function and disease and provide novel treatments for the vascular complications seen in diabetic patients.
基金supported by grants from the Beijing Municipal Science and Technology Committee (Z181100001318003)the National Natural Science Foundation of China (31421002, 31561143001,31630048, and 31790403)+17 种基金the National Natural Science Foundation of China (91853113 and 31872716)the National Natural Science Foundation of China (11672317)the National Natural Science Foundation of China (31871394 and 31670730)supported by grants from the National Natural Science Foundation of China (31420103916 and 31991192)the Ministry of Science and Technology of China (2017YFA0503401)supported by grants from the Ministry of Science and Technology of China (2019YFA0707000)supported by grants from the Ministry of Science and Technology of China (2019YFA0508401)the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB19000000)the Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SMC006)supported by funds from the Ministry of Science and Technology of China and the National Natural Science Foundation of China (2017YFA0506600 and 31871309)supported by funds from the Ministry of Science and Technology of China and the National Natural Science Foundation of China (2019YFA0508403 and 31871443)supported by grants from the Ministry of Science and Technology of China (2016YFA0501902)the Science and Technology Commission of Shanghai Municipality (18JC1420500)the Shanghai Municipal Science and Technology Major Project (2019SHZDZX02)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)CAS (XDB19020102)supported by grants from RGC of Hong Kong (AoE-M09-12 and C6004-17G)National Key R&D Program of China (2016YFA0501903 and 2019YFA0508402)。
文摘Cells are compartmentalized by numerous membrane-enclosed organelles and membraneless compartments to ensure that a wide variety of cellular activities occur in a spatially and temporally controlled manner. The molecular mechanisms underlying the dynamics of membrane-bound organelles, such as their fusion and fission, vesicle-mediated trafficking and membrane contactmediated inter-organelle interactions, have been extensively characterized. However, the molecular details of the assembly and functions of membraneless compartments remain elusive. Mounting evidence has emerged recently that a large number of membraneless compartments, collectively called biomacromolecular condensates, are assembled via liquid-liquid phase separation(LLPS). Phase-separated condensates participate in various biological activities, including higher-order chromatin organization,gene expression, triage of misfolded or unwanted proteins for autophagic degradation, assembly of signaling clusters and actin-and microtubule-based cytoskeletal networks, asymmetric segregations of cell fate determinants and formation of pre-and post-synaptic density signaling assemblies. Biomacromolecular condensates can transition into different material states such as gel-like structures and solid aggregates. The material properties of condensates are crucial for fulfilment of their distinct functions, such as biochemical reaction centers, signaling hubs and supporting architectures. Cells have evolved multiple mechanisms to ensure that biomacromolecular condensates are assembled and disassembled in a tightly controlled manner. Aberrant phase separation and transition are causatively associated with a variety of human diseases such as neurodegenerative diseases and cancers. This review summarizes recent major progress in elucidating the roles of LLPS in various biological pathways and diseases.
文摘AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two patients (15 men and 7 women; median age 68 years,range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC. Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition,the degree of staining within tumor tissue was compared according to a number of clinicopathological variables. RESULTS:The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues,even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.
基金supported by the National Natural Science Foundation of China(31871380,32000500,32070730,32170756,32170804,81330008,81671377,81725010,81725010,81872874,81921006,81922027,81971312,81991512,82030041,82103167,82122024,82125009,82125011,82130044,91749126,91949101,91949207,92049302)the National Key Research and Development Program of China(2017YFA0506400,2018YFA0800200,2018YFA0800700,2018YFA0900200,2018YFC2000100,2018YFC2000400,2018YFE-0203700,20192ACB70002,2019YFA0802202,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002800,2020YFC-2002900,2021ZD0202401)+11 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100,XDA16010603,XDA16020400,XDB29020000,XDB39000000,XDB39000000,XDB39030300)the China Association for Science and Technology(2021QNRC001)the Beijing Municipal Science and Technology Commission(Z200022)the Natural Science Foundation of Shanghai(21JC1406400)the Key Programs of the Jiangxi ProvinceChina(20192ACB70002)the“Shu Guang”Project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation(19SG18)the Shanghai Sailing Program(22YF1434300)the Research Project of Joint Laboratory of University of Science and Technology of China and Anhui Mental Health Center(2019LH03)the Fundamental Research Funds for the Central Universities(WK2070210004)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(YESS20210002)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022083)。
文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.
文摘AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.
基金supported by grants from the Cluster of Excellence"Inflammation at Interfaces"(HR+KH+R-JS)by intramural funding from the Medical Faculty of CAU Kiel(GFA)+1 种基金the DFG(SFB841,project C1SFB877,project A1,R-JS)
文摘BACKGROUND： Pancreatic ductal adenocarcinoma（PDAC）is a devastating malignancy with a poor prognosis and little treatment options. The development and progression of the disease is fostered by inflammatory cells and cytokines. One of these cytokines is interleukin-6（IL-6）, which plays an important role in a wide range of biologic activities.DATA SOURCES： A systematic search of PubMed was performed to identify relevant studies using key words such as interleukin-6,inflammatory cytokines, inflammation and pancreatic cancer or PDAC. Articles related to IL-6 and pancreatic cancer were systematically reviewed.RESULTS： IL-6 is elevated in the serum of pancreatic cancer patients and correlates with cachexia, advanced tumor stage and poor survival. Its expression is enhanced by hypoxia and proteins involved in pancreatic cancer development like Kras,mesothelin or ZIP4. IL-6 in turn contributes to the generation of a pro-tumorigenic microenvironment and is probably involved in angiogenesis and metastasis. In experimental mouse models of PDAC, IL-6 was important for the development and progression of precursor lesions.CONCLUSION： IL-6 emerges as a key player in pancreatic cancer development and progression, and hence should be considered as a new therapeutic target.
文摘Indole-3-acetic acid （IAA）, a major plant auxin, is produced in both tryptophan-dependent and tryptophan-independent pathways. A major pathway in Arabidopsis thaliana generates IAA in two reactions from tryptophan. Step one converts tryptophan to indole-3-pyruvic acid （IPA） by tryptophan aminotransferases followed by a rate-limiting step converting IPA to IAA catalyzed by YUCCA proteins. We identified eight putative StYUC （Solanum tuberosum YUCCA） genes whose deduced amino acid sequences share 50%-70% identity with those of Arabidopsis YUCCA proteins. All include canonical, conserved YUCCA sequences： FATGY motif, FMO signature sequence, and FAD-binding and NADP-binding sequences. In addition, five genes were found with -50% amino acid sequence identity to Arabidopsis trypto-phan aminotransferases. Transgenic potato （Solanum tuberosum cv. Jowon） constitutively overexpressing Arabidopsis AtYUC6 displayed high-auxin phenotypes such as narrow downward-curled leaves, increased height, erect stature, and longevity. Transgenic potato plants overexpressing AtYUC6 showed enhanced drought tolerance based on reduced water loss. The phenotype was correlated with reduced levels of reactive oxygen species in leaves. The results suggest a func-tional YUCCA pathway of auxin biosynthesis in potato that may be exploited to alter plant responses to the environment.
文摘During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation,as a result of large international research projects(Human Genome Project,the 1000 Genomes Project International HapMap Project,and Programs for Genomic Applications NHLBI-PGA).This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of cancer.For clinical use in the treatment of patients with colorectal cancer(CRC),in addition to fluoropyrimidines,another two new cytostatic drugs were allowed:irinotecan and oxaliplatin.Intensive research into new treatment regimens and a new generation of drugs used in targeted therapy has also been conducted.The last 20years was a time of numerous in vitro and in vivo studies on the molecular basis of drug resistance.One of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer cells.Understanding the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized medicine.Scientists hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/pharmacogenomics.Over the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application potential.This review is a synthetic presentation of drug resistance in the context of CRC patient chemotherapy.The multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review.
文摘For men struggling to conceive with their partners, diagnostic tools are limited and often consist of only a standard semen analysis. This baseline test serves as a crude estimation of male fertility, leaving patients and clinicians in need of additional diagnostic biomarkers. Seminal fluid contains the highest concentration of molecules from the male reproductive glands, therefore, this review focuses on current and novel seminal biomarkers in certain male infertility scenarios, including natural fertility, differentiating azoospermia etiologies, and predicting assisted reproductive technique success. Currently available tests include antisperm antibody assays, DNA fragmentation index, sperm fluorescence in situ hybridization, and other historical sperm functional tests. The poor diagnostic ability of current assays has led to continued efforts to find more predictive biomarkers. Emerging research in the fields of genomics, epigenetics, proteomics, transcriptomics, and metabolomics holds promise for the development of novel male infertility biomarkers. Seminal protein-based assays of TEXI01, ECM 1, and ACRV1 are already available or under final development for clinical use. Additional panels of DNA, RNA, proteins, or metabolites are being explored as we attempt to understand the pathophysiologic processes of male infertility. Future ventures will need to continue data integration and validation for the development of clinically useful infertility biomarkers to aid in male infertility diagnosis, treatment, and counseling.
基金Supported by a grant from the Chung Shan Medical University,No.CSMU0150011
文摘AIM To investigate the effects of hydrogen-rich water(HRW) treatment on prevention of ethanol(Et OH)-induced early fatty liver in mice.METHODS In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control,Et OH,Et OH + silymarin,Et OH + HRW and Et OH + silymarin + HRW. Each group was fed a Lieber-De Carli liquid diet containing Et OH or isocaloric maltose dextrin(control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic Et OH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 m L/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk.RESULTS The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin,which was correlated with food intake. HRW treatment significantly reduced Et OH-induced increases in serum alanine aminotransferase,aspartate aminotransferase,triglycerol and total cholesterol levels,hepatic lipid accumulation and inflammatory cytokines,including tumor necrosis factor-alpha(TNF-α) and interleukin(IL)-6. HRW attenuated malondialdehyde level,restored glutathione depletion and increased superoxide dismutase,glutathione peroxidase and catalase activities in the liver. Moreover,HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels.CONCLUSION HRW protects against chronic Et OH-induced liver injury,possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22,thus activating antioxidant enzymes against oxidative stress.
基金K.C.thanks the computational support from XSEDE computational resources under allocation number TGDMR 190095Contributions from K.C.were supported by the financial assistance award 70NANB19H117 from the U.S.Department of Commerce,National Institute of Standards and Technology+3 种基金Contributions by S.M.,K.H.,K.R.,and D.V.were supported by NSF DMREF Grant No.DMR-1629059 and No.DMR-1629346X.Q.was supported by NSF Grant No.OAC-1835690A.A.acknowledges partial support by CHiMaD(NIST award#70NANB19H005)G.P.was supported by the Los Alamos National Laboratory’s Laboratory Directed Research and Development(LDRD)program’s Directed Research(DR)project#20200104DR。
文摘The Joint Automated Repository for Various Integrated Simulations(JARVIS)is an integrated infrastructure to accelerate materials discovery and design using density functional theory(DFT),classical force-fields(FF),and machine learning(ML)techniques.JARVIS is motivated by the Materials Genome Initiative(MGI)principles of developing open-access databases and tools to reduce the cost and development time of materials discovery,optimization,and deployment.
文摘The realization of an efficient optical sensor based on a photonic crystal metasurface supporting bound states in the continuum is reported. Liquids with different refractive indices, ranging from 1.4000 to 1.4480, are infiltrated in a microfluidic chamber bonded to the sensing dielectric metasurface. A bulk liquid sensitivity of 178 nm/RIU is achieved, while a Q-factor of about 2000 gives a sensor figure of merit up to 445 in air at both visible and infrared excitations. Furthermore, the detection of ultralow-molecular-weight(186 Da) molecules is demonstrated with a record resonance shift of 6 nm per less than a 1 nm thick single molecular layer. The system exploits a normal-to-the-surface optical launching scheme, with excellent interrogation stability and demonstrates alignment-free performances, overcoming the limits of standard photonic crystals and plasmonic resonant configurations.
文摘The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live.Metabolic reprogramming supports tumor cells’high demand of biogenesis for their rapid proliferation,and helps tumor cells to survive under certain genetic or environmental stresses.Emerging evidence suggests that metabolic alteration is ultimately and tightly associated with genetic changes,in particular the dysregulation of key oncogenic and tumor suppressive signaling pathways.Cancer cells activate HIF signaling even in the presence of oxygen and in the absence of growth factor stimulation.This cancer metabolic phenotype,described firstly by German physiologist Otto Warburg,ensures enhanced glycolytic metabolism for the biosynthesis of macromolecules.The conception of metabolite signaling,i.e.,metabolites are regulators of cell signaling,provides novel insights into how reactive oxygen species(ROS)and other metabolites deregulation may regulate redox homeostasis,epigenetics,and proliferation of cancer cells.Moreover,the unveiling of noncanonical functions of metabolic enzymes,such as the moonlighting functions of phosphoglycerate kinase 1(PGK1),reassures the importance of metabolism in cancer development.The metabolic,microRNAs,and ncRNAs alterations in cancer cells can be sorted and delivered either to intercellular matrix or to cancer adjacent cells to shape cancer microenvironment via media such as exosome.Among them,cancer microenvironmental cells are immune cells which exert profound effects on cancer cells.Understanding of all these processes is a prerequisite for the development of a more effective strategy to contain cancers.
