Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most c...Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstaysof current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.展开更多
In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell.The functions of ion channels in the gastrointestinal(GI)tract influence a variet...In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell.The functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of cancer.In this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and migration.Various members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer.Voltage-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells.The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples.Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression.Zn2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract.Several distinct types of K+channels are found dysregulated in the GI tract.Notable are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CRC,where KCNQ1 expression is associated with enha展开更多
The recent review for the Restriction of Hazardous Substances Directive(RoHS)by the expert committee,appointed by the European Union,stated that the replacement of PZT“…may be scientifically and technologically prac...The recent review for the Restriction of Hazardous Substances Directive(RoHS)by the expert committee,appointed by the European Union,stated that the replacement of PZT“…may be scientifically and technologically practical to a certain degree…”,although replacement“…is scientifically and technically still impractical in the majority of applications.”Thus,two decades of sustained research and development may be approaching fruition,at first limited to a minority of applications.Therefore,it is of paramount importance to assess the viability of lead-free piezoceramics over a broad range of application-relevant properties.These are identified and discussed in turn:1.Cost,2.Reproducibility,3.Mechanical and Thermal Properties,4.Electrical Conductivity,and 5.Lifetime.It is suggested that the worldwide efforts into the development of lead-free piezoceramics now require a broader perspective to bring the work to the next stage of development by supporting implementation into real devices.Guidelines about pertinent research requirements into a wide range of secondary properties,measurement techniques,and salient literature are provided.展开更多
Non-alcohol-associated fatty liver/steatohepatitis(NAFL/NASH)has become the leading cause of liver disease worldwide.NASH,an advanced form of NAFL,can be progressive and more susceptible to developing cirrhosis and he...Non-alcohol-associated fatty liver/steatohepatitis(NAFL/NASH)has become the leading cause of liver disease worldwide.NASH,an advanced form of NAFL,can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma.Currently,lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis.While there are stll limited appropriate drugs specifically to treat NAFL/NASH,growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets.In this review,we discussed recent developments in etiology and prospective therapeutic targets,as well as pharmacological candidates in pre/clinical trials and patents,with a focus on diabetes,hepatic lipid metabolism,inflammation,and fibrosis.Importantly,growing evidence elucidates that the disruption of the gut-liver axis and microbederived metabolites drive the pathogenesis of NAFL/NASH.Extracellular vesicles(EVs)act as a signaling mediator,resulting in lipid accumulation,macrophage and hepatic stellate cell activation,further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH.Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH.Finally,other mechanisms,such as cell therapy and genetic approaches,also have enormous therapeutic potential.Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.展开更多
In this work we propose a centrality measure for networks, which we refer to as Laplacian centrality, that provides a general framework for the centrality of a vertex based on the idea that the importance (or centrali...In this work we propose a centrality measure for networks, which we refer to as Laplacian centrality, that provides a general framework for the centrality of a vertex based on the idea that the importance (or centrality) of a vertex is related to the ability of the network to respond to the deactivation or removal of that vertex from the network. In particular, the Laplacian centrality of a vertex is defined as the relative drop of Laplacian energy caused by the deactivation of this vertex. The Laplacian energy of network G with?n?vertices is defined as , where ?is the eigenvalue of the Laplacian matrix of G. Other dynamics based measures such as that of Masuda and Kori and PageRank compute the importance of a node by analyzing the way paths pass through a node while our measure captures this information as well as the way these paths are “redistributed” when the node is deleted. The validity and robustness of this new measure are illustrated on two different terrorist social network data sets and 84 networks in James Moody’s Add Health in school friendship nomination data, and is compared with other standard centrality measures.展开更多
Mutations in the KRAS oncogene represent one of the most prevalent genetic alterations in colorectal cancer(CRC),the third leading cause of cancer-related death in the US.In addition to their well-characterized functi...Mutations in the KRAS oncogene represent one of the most prevalent genetic alterations in colorectal cancer(CRC),the third leading cause of cancer-related death in the US.In addition to their well-characterized function in driving tumor progression,KRAS mutations have been recognized as a critical determinant of the therapeutic response of CRC.Recent studies demonstrate that KRAS-mutant tumors are intrinsically insensitive to clinically-used epidermal growth factor receptor(EGFR)targeting antibodies,including cetuximab and panitumumab.Acquired resistance to the anti-EGFR therapy was found to be associated with enrichment of KRAS-mutant tumor cells.However,the underlying molecular mechanism of mutant-KRAS-mediated therapeutic resistance has remained unclear.Despite intensive efforts,directly targeting mutant KRAS has been largely unsuccessful.This review summarizes the recent advances in understanding the biological function of KRAS mutations in determining the therapeutic response of CRC,highlighting several recently developed agents and strategies for targeting mutant KRAS,such as synthetic lethal interactions.展开更多
Throughout their life, plants are challenged by various abiotic and biotic stress factors. Among those are attacks from herbivorous insects. The molecular mechanisms underlying the detection of herbivores and the subs...Throughout their life, plants are challenged by various abiotic and biotic stress factors. Among those are attacks from herbivorous insects. The molecular mechanisms underlying the detection of herbivores and the subsequent signal transduction are not well understood. As a second messenger, fluxes in intracellular Ca2+ levels play a key role in mediating stress response pathways. Ca2+ signals are decoded by Ca2+ sensor proteins such as calmodulin-like proteins (CMLs). Here, we demonstrate that recombinant CML37 behaves like a Ca2+ sensor in vitro and, in Arabidopsis, AtCML37 is induced by mechanical wounding as well as by infestation with larvae of the generalist lepidopteran herbivore Spodoptera littoralis. Loss of function of CML37 led to a better feeding performance of larvae suggesting that CML37 is a positive defense regulator. No herbivory-induced changes in secondary metabolites such as glucosinolates or flavonoids were detected in cml37 plants, although a significant reduction in the accumulation of jasmonates was observed, due to reduced expression of JAR1 mRNA and cellular enzyme activity. Consequently, the expression of jasmonate-responsive genes was reduced as well. Summarizing, our results suggest that the Ca2+ sensor protein, CML37, functions as a positive regulator in Ca2+ signaling during herbivory, connecting Ca2+ and jasmonate signaling.展开更多
In this review,we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes.On a global scale,diabetes causes a s...In this review,we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes.On a global scale,diabetes causes a significant negative impact to the health status of human populations.This review covers type 1 diabetes and type 2 diabetes.We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases.It appears that the human oral and gut microbiota are deeply interdigitated with diabetes.It is that simple.Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes.These studies focus on the role and the potential impact of intestinal microflora in diabetes.We paint a clear picture of how strongly microbes are linked and associated,both positively and negatively,with the fundamental and essential parts of diabetes in humans.The microflora seems to have an endless capacity to impact and transform diabetes.We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.展开更多
The prevalence of kidney stone disease is increasing,afflicting 7%-11% of the United States population.Multiple systemic conditions,including obesity and diabetes,are also on the rise.Further,the literature has demons...The prevalence of kidney stone disease is increasing,afflicting 7%-11% of the United States population.Multiple systemic conditions,including obesity and diabetes,are also on the rise.Further,the literature has demonstrated a strong association between metabolic syndrome,its components,and kidney stone disease.In this article,we aim to review the associations of metabolic syndrome and nephrolithiasis,discussing the pathophysiology,urinary parameters,and clinical presentations.With this knowledge,urologists will have a more comprehensive understanding of this complex population of metabolic stone formers enabling improved patient management and treatment of stone disease.展开更多
AIM: To determine effect of irritable bowel syndrome(IBS) subtype on IBS-specific quality of life(QOL) questionnaire and its subscales.METHODS: We studied IBS patients visiting our functional gastroenterology disorder...AIM: To determine effect of irritable bowel syndrome(IBS) subtype on IBS-specific quality of life(QOL) questionnaire and its subscales.METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States.IBS and IBS subtype were diagnosed using Rome-Ⅲ questionnaire.QOL was assessed using IBS-QOL questionnaire.IBSQOL assesses quality of life along eight subscales: dysphoria,interference with activities,body image,health worry,food avoidance,social reactions,sexual health,and effect on relationships.IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL.Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI.We compared mean IBS-QOL score and its subscales among various IBSsubtypes.Analysis of variance(ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender.A posthoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05.RESULTS: Of 542 patients screened,243 had IBS as per Rome-Ⅲ criteria.IBS-mixed(IBS-M) was the most common IBS subtype(121 patients,49.8%) followed by IBS- diarrhea(IBS-D)(56 patients,23.1%),IBSconstipation(IBS-C)(54 patients,22.2%) and IBSunspecified(IBS-U)(12 patients,4.9%).Overall IBSQOL scores were significantly different among various IBS-subtypes(P = 0.01).IBS-QOL of patients with IBS-D(61.6,95%CI: 54.0-69.1) and IBS-M(63.0,95%CI: 58.1-68.0) was significantly lower than patients with IBS-C(74.5,95%CI: 66.9-82.1)(P = 0.03 and 0.02 respectively).IBS-D patients scored significantly lower than IBS-C on food avoidance(45.0,95%CI: 34.8-55.2 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and interference with activity(59.6,95%CI: 51.4-67.7 vs 82.3,95%CI: 74.1-90.6,P < 0.001).IBS-M patients had more interference in their activities(61.6,95%CI: 56.3-66.9 vs 82.3,95%CI: 74.1-90.6,P = 0.001) and greater impact on their relationships(73.3,95%CI: 68.4-78.2 vs 84.7,95%CI: 77.2展开更多
Neuroinflammation plays a critical role in the pathological process of multiple neurological disorders and pathological pain conditions.GPR109A,a Gi protein-coupled receptor,has emerged as an important therapeutic tar...Neuroinflammation plays a critical role in the pathological process of multiple neurological disorders and pathological pain conditions.GPR109A,a Gi protein-coupled receptor,has emerged as an important therapeutic target for controlling inflammation in various tissues and organs.In this review,we summarized current data about the role of GPR109A in neuroinflammation.Specifically,we focused on the pharmacological features of GPR109A and signaling pathways used by GPR109A to ameliorate neuroinflammation and symptoms in Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,stroke,and pathological pain conditions.展开更多
We present a narrative of the eruptive events culminating in the cataclysmic January 15, 2022 eruption of Hunga Tonga-Hunga Ha’apai Volcano by synthesizing diverse preliminary seismic, volcanological, sound wave, and...We present a narrative of the eruptive events culminating in the cataclysmic January 15, 2022 eruption of Hunga Tonga-Hunga Ha’apai Volcano by synthesizing diverse preliminary seismic, volcanological, sound wave, and lightning data available within the first few weeks after the eruption occurred. The first hour of eruptive activity produced fast-propagating tsunami waves, long-period seismic waves, loud audible sound waves, infrasonic waves, exceptionally intense volcanic lightning and an unsteady volcanic plume that transiently reached-at 58km-the Earth’s mesosphere. Energetic seismic signals were recorded worldwide and the globally stacked seismogram showed episodic seismic events within the most intense periods of phreatoplinian activity, and they correlated well with the infrasound pressure waveform recorded in Fiji. Gravity wave signals were strong enough to be observed over the entire planet in just the first few hours, with some circling the Earth multiple times subsequently. These large-amplitude, long-wavelength atmospheric disturbances come from the Earth’s atmosphere being forced by the magmatic mixture of tephra, melt and gasses emitted by the unsteady but quasicontinuous eruption from 0402±1–1800 UTC on January 15, 2022. Atmospheric forcing lasted much longer than rupturing from large earthquakes recorded on modern instruments, producing a type of shock wave that originated from the interaction between compressed air and ambient(wavy) sea surface. This scenario differs from conventional ideas of earthquake slip, landslides, or caldera collapse-generated tsunami waves because of the enormous(~1000x) volumetric change due to the supercritical nature of volatiles associated with the hot,volatile-rich phreatoplinian plume. The time series of plume altitude can be translated to volumetric discharge and mass flow rate. For an eruption duration of ~12 h, the eruptive volume and mass are estimated at 1.9 km^(3) and~2 900 Tg, respectively, corresponding to a VEI of 5–6 for this event. The high freq展开更多
As climate has warmed in recent decades, Alaska has experienced a variety of high-impact extreme events that include heat waves, wildfires, coastal storms and freezing rain. Because the warming is projected to continu...As climate has warmed in recent decades, Alaska has experienced a variety of high-impact extreme events that include heat waves, wildfires, coastal storms and freezing rain. Because the warming is projected to continue, it is essential to consider future changes when planning adaptation actions and building resilience. In this study, we synthesize information on future changes in extreme events in Alaska from an ensemble of regional climate model simulations performed as part of Arctic-CORDEX (Coordinated Regional Climate Downscaling Experiment). A set of 13 extreme event indices, based on those developed by the World Climate Research Programme’s Expert Team on Climate Change Detection and Indices (ETCCDI), are evaluated from the Arctic-CORDEX output for Alaska. Of the 13 indices, six pertain to temperature, five to total precipitation, one to wind and one to snow. The results for locations in seven different climate zones of Alaska include large increases (5˚C - 10˚C) in the temperature thresholds for the five hottest and coldest days of the year, and large increases in warm spell duration and decreases in cold spell duration. Changes in the cold day temperature threshold are generally larger than the changes in the hot day temperature threshold, consistent with the projections of a stronger warming in winter than in summer in Alaska yearly maximum 1-day and 5-day precipitation amounts as well as the yearly number of consecutive wet days are projected to increase at all locations. The indices for heavy snow days and high-wind days show mixed changes, although the results indicate increases in heavy snow days at the more northern locations and increases in windy days at coastal locations. The changes in the extreme event indices continue through 2100 under the higher-emission (RCP 8.5) emission scenario, while the changes generally stabilize under the lower-emission (RCP 4.5) scenario. .展开更多
Previously, we showed that prophylactic addition of glucose to Harsha Lake water samples could inhibit cyanobacteria growth, at least for a short period of time. The current study tested cyanobacterial control with gl...Previously, we showed that prophylactic addition of glucose to Harsha Lake water samples could inhibit cyanobacteria growth, at least for a short period of time. The current study tested cyanobacterial control with glucose for the entire Harsha Lake bloom season. Water samples (1000 ml) were collected weekly from Harsha Lake during the algal-bloom season starting June 9 and lasting until August 24, 2022. To each of two 7-liter polypropylene containers, 500 ml of Harsha Lake water was added, and the containers were placed in a controlled environment chamber. To one container labeled “Treated,” 0.15 g of glucose was added, and nothing was added to the container labeled “Control.” After that, three 25 ml samples from each container were collected and used for 16S rRNA gene sequencing each week. Then 1000 ml of Harsha Lake water was newly collected each week, with 500 ml added to each container, along with the addition of 0.15 g glucose to the “Treated” container. Sequencing data were used to examine differences in the composition of bacterial communities between Treated and Control containers. Treatment with glucose altered the microbial communities by 1) reducing taxonomic diversity, 2) largely eliminating cyanobacterial taxa, and 3) increasing the relative abundance of subsets of non-cyanobacterial taxa (such as Proteobacteria and Actinobacteriota). These effects were observed across time despite weekly inputs derived directly from Lake water. The addition of glucose to a container receiving weekly additions of Lake water suppressed the cyanobacterial populations during the entire summer bloom season. The glucose appears to stimulate the diversity of certain bacterial taxa at the expense of the cyanobacteria.展开更多
Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via trans...Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompt-ing increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.展开更多
Muscle wasting is common in mammals during extended periods of immobility. However, many small hibernating mammals manage to avoid muscle atrophy despite remaining stationary for long periods during hibernation. Recen...Muscle wasting is common in mammals during extended periods of immobility. However, many small hibernating mammals manage to avoid muscle atrophy despite remaining stationary for long periods during hibernation. Recent research has highlighted roles for short non-coding microRNAs (miRNAs) in the regulation of stress tolerance. We proposed that they could also play an important role in muscle maintenance during hibernation. To explore this possibility, a group of 10 miRNAs known to be normally expressed in skeletal muscle of non-hibernating mammals were analyzed by RT-PCR in hibernating little brown bats, Myotis lucifugus. We then compared the expression of these miRNAs in euthermic control bats and bats in torpor. Our results showed that compared to euthermic controls, sig- nificant, albeit modest (1.2-1.6 fold), increases in transcript expression were observed for eight mature miRNAs, including miR-la-1, miR-29b, miR-181b, miR-15a, miR-20a, miR-206 and miR-128-1, in the pectoral muscle of torpid bats. Conversely, expression of miR-21 decreased by 80% during torpor, while expression of miR-107 remained unaffected. Interestingly, these miRNAs have been either validated or predicted to affect multiple muscle-specific factors, including myostatin, FoxO3a, HDAC4 and SMADT, and are likely involved in the preservation of pectoral muscle mass and functionality during bat hibernation.展开更多
文摘Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstaysof current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.
基金grants from the National Cancer Institute(NIH R15CA195061A-01)Whiteside Institute for Clinical Research+3 种基金Essentia Health SystemsMezin-Koats Colorectal Cancer FoundationRandy Shaver Cancer Research and Community Fundthe University of Minnesota Masonic Cancer Center
文摘In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell.The functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of cancer.In this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and migration.Various members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer.Voltage-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells.The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples.Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression.Zn2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract.Several distinct types of K+channels are found dysregulated in the GI tract.Notable are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CRC,where KCNQ1 expression is associated with enha
文摘The recent review for the Restriction of Hazardous Substances Directive(RoHS)by the expert committee,appointed by the European Union,stated that the replacement of PZT“…may be scientifically and technologically practical to a certain degree…”,although replacement“…is scientifically and technically still impractical in the majority of applications.”Thus,two decades of sustained research and development may be approaching fruition,at first limited to a minority of applications.Therefore,it is of paramount importance to assess the viability of lead-free piezoceramics over a broad range of application-relevant properties.These are identified and discussed in turn:1.Cost,2.Reproducibility,3.Mechanical and Thermal Properties,4.Electrical Conductivity,and 5.Lifetime.It is suggested that the worldwide efforts into the development of lead-free piezoceramics now require a broader perspective to bring the work to the next stage of development by supporting implementation into real devices.Guidelines about pertinent research requirements into a wide range of secondary properties,measurement techniques,and salient literature are provided.
基金This work was supported by the Major Program of National Natural Science Foundation of China(81991525)Key R&D Program of Shandong Province(2020CXGC010503)This work was also supported by grants from the National Institutes of Health(R00AA026648 to K.L.P.).
文摘Non-alcohol-associated fatty liver/steatohepatitis(NAFL/NASH)has become the leading cause of liver disease worldwide.NASH,an advanced form of NAFL,can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma.Currently,lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis.While there are stll limited appropriate drugs specifically to treat NAFL/NASH,growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets.In this review,we discussed recent developments in etiology and prospective therapeutic targets,as well as pharmacological candidates in pre/clinical trials and patents,with a focus on diabetes,hepatic lipid metabolism,inflammation,and fibrosis.Importantly,growing evidence elucidates that the disruption of the gut-liver axis and microbederived metabolites drive the pathogenesis of NAFL/NASH.Extracellular vesicles(EVs)act as a signaling mediator,resulting in lipid accumulation,macrophage and hepatic stellate cell activation,further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH.Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH.Finally,other mechanisms,such as cell therapy and genetic approaches,also have enormous therapeutic potential.Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.
文摘In this work we propose a centrality measure for networks, which we refer to as Laplacian centrality, that provides a general framework for the centrality of a vertex based on the idea that the importance (or centrality) of a vertex is related to the ability of the network to respond to the deactivation or removal of that vertex from the network. In particular, the Laplacian centrality of a vertex is defined as the relative drop of Laplacian energy caused by the deactivation of this vertex. The Laplacian energy of network G with?n?vertices is defined as , where ?is the eigenvalue of the Laplacian matrix of G. Other dynamics based measures such as that of Masuda and Kori and PageRank compute the importance of a node by analyzing the way paths pass through a node while our measure captures this information as well as the way these paths are “redistributed” when the node is deleted. The validity and robustness of this new measure are illustrated on two different terrorist social network data sets and 84 networks in James Moody’s Add Health in school friendship nomination data, and is compared with other standard centrality measures.
基金supported in part by the graduate student fellowship from the Department of Pharmacology&Chemical BiologyResearch in L.Z.’s lab is supported by the National Institute of Health grants R01CA106348 and R01CA172136.
文摘Mutations in the KRAS oncogene represent one of the most prevalent genetic alterations in colorectal cancer(CRC),the third leading cause of cancer-related death in the US.In addition to their well-characterized function in driving tumor progression,KRAS mutations have been recognized as a critical determinant of the therapeutic response of CRC.Recent studies demonstrate that KRAS-mutant tumors are intrinsically insensitive to clinically-used epidermal growth factor receptor(EGFR)targeting antibodies,including cetuximab and panitumumab.Acquired resistance to the anti-EGFR therapy was found to be associated with enrichment of KRAS-mutant tumor cells.However,the underlying molecular mechanism of mutant-KRAS-mediated therapeutic resistance has remained unclear.Despite intensive efforts,directly targeting mutant KRAS has been largely unsuccessful.This review summarizes the recent advances in understanding the biological function of KRAS mutations in determining the therapeutic response of CRC,highlighting several recently developed agents and strategies for targeting mutant KRAS,such as synthetic lethal interactions.
文摘Throughout their life, plants are challenged by various abiotic and biotic stress factors. Among those are attacks from herbivorous insects. The molecular mechanisms underlying the detection of herbivores and the subsequent signal transduction are not well understood. As a second messenger, fluxes in intracellular Ca2+ levels play a key role in mediating stress response pathways. Ca2+ signals are decoded by Ca2+ sensor proteins such as calmodulin-like proteins (CMLs). Here, we demonstrate that recombinant CML37 behaves like a Ca2+ sensor in vitro and, in Arabidopsis, AtCML37 is induced by mechanical wounding as well as by infestation with larvae of the generalist lepidopteran herbivore Spodoptera littoralis. Loss of function of CML37 led to a better feeding performance of larvae suggesting that CML37 is a positive defense regulator. No herbivory-induced changes in secondary metabolites such as glucosinolates or flavonoids were detected in cml37 plants, although a significant reduction in the accumulation of jasmonates was observed, due to reduced expression of JAR1 mRNA and cellular enzyme activity. Consequently, the expression of jasmonate-responsive genes was reduced as well. Summarizing, our results suggest that the Ca2+ sensor protein, CML37, functions as a positive regulator in Ca2+ signaling during herbivory, connecting Ca2+ and jasmonate signaling.
基金Supported by Shandong Provincial Key Research and Development Program,No.2018CXGC1219City of Weihai Technique Extension Project,No.2016GNS023+1 种基金TaiShan Scholars Program of Shandong Province,No.tshw20120206TaiShan Industrial Experts Program,No.tscy20190612.
文摘In this review,we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes.On a global scale,diabetes causes a significant negative impact to the health status of human populations.This review covers type 1 diabetes and type 2 diabetes.We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases.It appears that the human oral and gut microbiota are deeply interdigitated with diabetes.It is that simple.Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes.These studies focus on the role and the potential impact of intestinal microflora in diabetes.We paint a clear picture of how strongly microbes are linked and associated,both positively and negatively,with the fundamental and essential parts of diabetes in humans.The microflora seems to have an endless capacity to impact and transform diabetes.We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.
文摘The prevalence of kidney stone disease is increasing,afflicting 7%-11% of the United States population.Multiple systemic conditions,including obesity and diabetes,are also on the rise.Further,the literature has demonstrated a strong association between metabolic syndrome,its components,and kidney stone disease.In this article,we aim to review the associations of metabolic syndrome and nephrolithiasis,discussing the pathophysiology,urinary parameters,and clinical presentations.With this knowledge,urologists will have a more comprehensive understanding of this complex population of metabolic stone formers enabling improved patient management and treatment of stone disease.
文摘AIM: To determine effect of irritable bowel syndrome(IBS) subtype on IBS-specific quality of life(QOL) questionnaire and its subscales.METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States.IBS and IBS subtype were diagnosed using Rome-Ⅲ questionnaire.QOL was assessed using IBS-QOL questionnaire.IBSQOL assesses quality of life along eight subscales: dysphoria,interference with activities,body image,health worry,food avoidance,social reactions,sexual health,and effect on relationships.IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL.Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI.We compared mean IBS-QOL score and its subscales among various IBSsubtypes.Analysis of variance(ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender.A posthoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05.RESULTS: Of 542 patients screened,243 had IBS as per Rome-Ⅲ criteria.IBS-mixed(IBS-M) was the most common IBS subtype(121 patients,49.8%) followed by IBS- diarrhea(IBS-D)(56 patients,23.1%),IBSconstipation(IBS-C)(54 patients,22.2%) and IBSunspecified(IBS-U)(12 patients,4.9%).Overall IBSQOL scores were significantly different among various IBS-subtypes(P = 0.01).IBS-QOL of patients with IBS-D(61.6,95%CI: 54.0-69.1) and IBS-M(63.0,95%CI: 58.1-68.0) was significantly lower than patients with IBS-C(74.5,95%CI: 66.9-82.1)(P = 0.03 and 0.02 respectively).IBS-D patients scored significantly lower than IBS-C on food avoidance(45.0,95%CI: 34.8-55.2 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and interference with activity(59.6,95%CI: 51.4-67.7 vs 82.3,95%CI: 74.1-90.6,P < 0.001).IBS-M patients had more interference in their activities(61.6,95%CI: 56.3-66.9 vs 82.3,95%CI: 74.1-90.6,P = 0.001) and greater impact on their relationships(73.3,95%CI: 68.4-78.2 vs 84.7,95%CI: 77.2
文摘Neuroinflammation plays a critical role in the pathological process of multiple neurological disorders and pathological pain conditions.GPR109A,a Gi protein-coupled receptor,has emerged as an important therapeutic target for controlling inflammation in various tissues and organs.In this review,we summarized current data about the role of GPR109A in neuroinflammation.Specifically,we focused on the pharmacological features of GPR109A and signaling pathways used by GPR109A to ameliorate neuroinflammation and symptoms in Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,stroke,and pathological pain conditions.
基金partially supported by US Department of Energy Grant DE-SC0019759National Science Foundation (NSF) Grants EAR-1918126, EAR-2027150, EAR-1925965, and OCE-1842989。
文摘We present a narrative of the eruptive events culminating in the cataclysmic January 15, 2022 eruption of Hunga Tonga-Hunga Ha’apai Volcano by synthesizing diverse preliminary seismic, volcanological, sound wave, and lightning data available within the first few weeks after the eruption occurred. The first hour of eruptive activity produced fast-propagating tsunami waves, long-period seismic waves, loud audible sound waves, infrasonic waves, exceptionally intense volcanic lightning and an unsteady volcanic plume that transiently reached-at 58km-the Earth’s mesosphere. Energetic seismic signals were recorded worldwide and the globally stacked seismogram showed episodic seismic events within the most intense periods of phreatoplinian activity, and they correlated well with the infrasound pressure waveform recorded in Fiji. Gravity wave signals were strong enough to be observed over the entire planet in just the first few hours, with some circling the Earth multiple times subsequently. These large-amplitude, long-wavelength atmospheric disturbances come from the Earth’s atmosphere being forced by the magmatic mixture of tephra, melt and gasses emitted by the unsteady but quasicontinuous eruption from 0402±1–1800 UTC on January 15, 2022. Atmospheric forcing lasted much longer than rupturing from large earthquakes recorded on modern instruments, producing a type of shock wave that originated from the interaction between compressed air and ambient(wavy) sea surface. This scenario differs from conventional ideas of earthquake slip, landslides, or caldera collapse-generated tsunami waves because of the enormous(~1000x) volumetric change due to the supercritical nature of volatiles associated with the hot,volatile-rich phreatoplinian plume. The time series of plume altitude can be translated to volumetric discharge and mass flow rate. For an eruption duration of ~12 h, the eruptive volume and mass are estimated at 1.9 km^(3) and~2 900 Tg, respectively, corresponding to a VEI of 5–6 for this event. The high freq
基金supported by the National Natural Science Foundation of China(Grant Nos.12222202 and 11972075)the Innovative Program from Beijing Institute of Technology(Grant No.2021CX01029).
文摘As climate has warmed in recent decades, Alaska has experienced a variety of high-impact extreme events that include heat waves, wildfires, coastal storms and freezing rain. Because the warming is projected to continue, it is essential to consider future changes when planning adaptation actions and building resilience. In this study, we synthesize information on future changes in extreme events in Alaska from an ensemble of regional climate model simulations performed as part of Arctic-CORDEX (Coordinated Regional Climate Downscaling Experiment). A set of 13 extreme event indices, based on those developed by the World Climate Research Programme’s Expert Team on Climate Change Detection and Indices (ETCCDI), are evaluated from the Arctic-CORDEX output for Alaska. Of the 13 indices, six pertain to temperature, five to total precipitation, one to wind and one to snow. The results for locations in seven different climate zones of Alaska include large increases (5˚C - 10˚C) in the temperature thresholds for the five hottest and coldest days of the year, and large increases in warm spell duration and decreases in cold spell duration. Changes in the cold day temperature threshold are generally larger than the changes in the hot day temperature threshold, consistent with the projections of a stronger warming in winter than in summer in Alaska yearly maximum 1-day and 5-day precipitation amounts as well as the yearly number of consecutive wet days are projected to increase at all locations. The indices for heavy snow days and high-wind days show mixed changes, although the results indicate increases in heavy snow days at the more northern locations and increases in windy days at coastal locations. The changes in the extreme event indices continue through 2100 under the higher-emission (RCP 8.5) emission scenario, while the changes generally stabilize under the lower-emission (RCP 4.5) scenario. .
文摘Previously, we showed that prophylactic addition of glucose to Harsha Lake water samples could inhibit cyanobacteria growth, at least for a short period of time. The current study tested cyanobacterial control with glucose for the entire Harsha Lake bloom season. Water samples (1000 ml) were collected weekly from Harsha Lake during the algal-bloom season starting June 9 and lasting until August 24, 2022. To each of two 7-liter polypropylene containers, 500 ml of Harsha Lake water was added, and the containers were placed in a controlled environment chamber. To one container labeled “Treated,” 0.15 g of glucose was added, and nothing was added to the container labeled “Control.” After that, three 25 ml samples from each container were collected and used for 16S rRNA gene sequencing each week. Then 1000 ml of Harsha Lake water was newly collected each week, with 500 ml added to each container, along with the addition of 0.15 g glucose to the “Treated” container. Sequencing data were used to examine differences in the composition of bacterial communities between Treated and Control containers. Treatment with glucose altered the microbial communities by 1) reducing taxonomic diversity, 2) largely eliminating cyanobacterial taxa, and 3) increasing the relative abundance of subsets of non-cyanobacterial taxa (such as Proteobacteria and Actinobacteriota). These effects were observed across time despite weekly inputs derived directly from Lake water. The addition of glucose to a container receiving weekly additions of Lake water suppressed the cyanobacterial populations during the entire summer bloom season. The glucose appears to stimulate the diversity of certain bacterial taxa at the expense of the cyanobacteria.
文摘Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompt-ing increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.
基金supported by a Discovery grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada (Grant No. 6793)
文摘Muscle wasting is common in mammals during extended periods of immobility. However, many small hibernating mammals manage to avoid muscle atrophy despite remaining stationary for long periods during hibernation. Recent research has highlighted roles for short non-coding microRNAs (miRNAs) in the regulation of stress tolerance. We proposed that they could also play an important role in muscle maintenance during hibernation. To explore this possibility, a group of 10 miRNAs known to be normally expressed in skeletal muscle of non-hibernating mammals were analyzed by RT-PCR in hibernating little brown bats, Myotis lucifugus. We then compared the expression of these miRNAs in euthermic control bats and bats in torpor. Our results showed that compared to euthermic controls, sig- nificant, albeit modest (1.2-1.6 fold), increases in transcript expression were observed for eight mature miRNAs, including miR-la-1, miR-29b, miR-181b, miR-15a, miR-20a, miR-206 and miR-128-1, in the pectoral muscle of torpid bats. Conversely, expression of miR-21 decreased by 80% during torpor, while expression of miR-107 remained unaffected. Interestingly, these miRNAs have been either validated or predicted to affect multiple muscle-specific factors, including myostatin, FoxO3a, HDAC4 and SMADT, and are likely involved in the preservation of pectoral muscle mass and functionality during bat hibernation.