Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretio...Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.展开更多
CO_(2) utilizations are essential to curbing the greenhouse gas effect and managing the environmental pollutant in an energy-efficient and economically-sound manner.This paper seeks to critically analyze these technol...CO_(2) utilizations are essential to curbing the greenhouse gas effect and managing the environmental pollutant in an energy-efficient and economically-sound manner.This paper seeks to critically analyze these technologies in the context of each other and highlight the most important utilization avenues available thus far.This review will introduce and analyze each major pathway,and discuss the overall applicability,potential extent,and major limitations of each of these pathways to utilizing CO_(2).This will include the analysis of some previously underreported utilization avenues,including CO_(2) utilization in industrial filtration and the processing of raw industrial materials such as iron and alumina.The core theme of this paper is to seek to treat CO_(2) as a commodity instead of a liability.展开更多
Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon c...Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.展开更多
Incorporating aluminum metal-organic frameworks(Al-MOFs)as energetic additives for solid fuels presents a promising avenue for enhancing combustion performance.This study explores the potential benefits of Al-MOF(MIL-...Incorporating aluminum metal-organic frameworks(Al-MOFs)as energetic additives for solid fuels presents a promising avenue for enhancing combustion performance.This study explores the potential benefits of Al-MOF(MIL-53(Al))energetic additive on the combustion performance of hydroxyl-terminated polybutadiene(HTPB)fuel.The HTPB-MOF fuel samples were manufactured using the vacuum-casting technique,followed by a comprehensive evaluation of their ignition and combustion properties using an opposed flow burner(OFB)setup utilizing gaseous oxygen as an oxidizer.To gauge the effectiveness of Al-MOFs as fuel additives,their impact is compared with that of nano-aluminum(nAl),another traditional additive in HTPB fuel.The results indicate that the addition of 15%(mass fraction)nAl into HTPB resulted in the shortest ignition delay time(136 ms),demonstrating improved ignition performance compared to pure HTPB(273 ms).The incorporation of Al-MOF in HTPB also reduced ignition delay times to 227 ms and 189 ms,respectively.Moreover,under high oxidizer mass flux conditions(79—81 kg/(m^(2)s)),HTPB fuel with 15%nAl exhibited a substantial 83.2%increase in regression rate compared to the baseline HTPB fuel,highlighting the positive influence of nAl on combustion behavior.In contrast,HTPB-MOF with a 15%Al-MOF additive showed a 32.7%increase in regression rate compared to pure HTPB.These results suggest that HTPB-nAl outperforms HTPB-MOF in terms of regression rates,indicating a more vigorous and rapid burning behavior.展开更多
A key topic for aneurysmal subarachnoid hemorrhage is neuroinflammation.Neuroinflammation can predispose to aneurysm formation and rupture.Neuroinflammation can also result from the blood breakdown products after aneu...A key topic for aneurysmal subarachnoid hemorrhage is neuroinflammation.Neuroinflammation can predispose to aneurysm formation and rupture.Neuroinflammation can also result from the blood breakdown products after aneurysm rupture.Recent evidence has shown that perpetual neuroinflammation can contribute to vasospasm and hydrocephalus.Targeting neuroinflammation is a novel mechanism for preventing subsequent neurologic sequalae.In this review,we highlight the pathophysiology of aneurysm formation,the neuroinflammatory surge after rupture including the involved cytokines,and ultimately tie in the contributory clinical relevance.In the last sections,we look at the pre-clinical data and novel avenues for further discovery.This paper will be a useful resource to both the clinician and scientific investigator.展开更多
Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),natur...Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins,lipids,and nucleic acids,have drawn wide attention due to their ability to promote wound healing and tissue regeneration.However,current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes.To circumvent these challenges,bioinspired cell-derived nanovesicles(CDNs)that mimic EVs were obtained by shearing mesenchymal stem cells(MSCs)through membranes with different pore sizes.Physical characterisations and highthroughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs.Moreover,these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway,resulting in enhancement of cell proliferation,cell migration,secretion of growth factors and extracellular matrix proteins,which all promoted tissue regeneration.Of note,MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEGfibrin scaffold and animal model,accelerating wound healing in vitro and in vivo.These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.展开更多
Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl...Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose, carbopol 934 P and cellulose acetate phthalate as coat materials. Ionotropic gelation is a method to prepare microspheres using combination of Ca<sup>2+</sup> as cationic components and alginate as anion. The practical yield of prepared microspheres using the ionotropic gelation technique was between 172 mg and 604 mg. The result of the Chi-squared test carried out between the actual (practical) and expected (theoretical) yields showed no significant difference (P < 0.05) which indicated that the ionotropic gelation technique could be successfully employed to prepare pioglitazone microspheres using sodium alginate, sodium carboxy methyl cellulose, carbopol 934 P, HPMC, cellulose acetate butyrate polymers. The drug entrapment efficiency of prepared microspheres showed between 56.12% ± 3.86% to 84.68% ± 2.93% which was significantly higher for ionotropic gelation technique. The highest drug entrapment was found in formulation PMI 8. Swelling index is the capability of a polymer to swell before the drug is released which influences the rate and mechanism of drug release from the polymer matrix. The swelling index of prepared microspheres was in the range of 68% ± 4.52% to 87% ± 0.98%. Pioglitazone HCl microspheres showed controlled release of drug without initial peak level achieving. This type of properties in Pioglitazone HCl microspheres used to decrease side effects, reduce dosing frequency and improve patient compliances. From the all batches PMI 8 is considered the best formulation, because among all other formulations, it shows better extent of drug release up to 82.12% (18 h), good entrapment efficiency (84.68%) and the ex-vivo wash-off test shows the best mucoadhesive property. The in vitro drug release studies do up to 18 h. As observed from the various plots, most of th展开更多
Bacteriophages represent a rich and unique resource of anti-infectives to counter the global problem of antibiotic resis- tance. In this work, we assessed the bactericidal activity of two virulent staphylococcal phage...Bacteriophages represent a rich and unique resource of anti-infectives to counter the global problem of antibiotic resis- tance. In this work, we assessed the bactericidal activity of two virulent staphylococcal phages, K and 44AHJD, against S. aureus isolates of clinical significance, and tested their efficacy in vivo. The phage cocktail lysed >85% of the clinical isolates tested. Both the phages were purified by ion-exchange column chromatography following propagation in bioreactors. The purity profiles of the ion-exchange purified phages were compared with those of phages purified using cesium chloride density gradient ultracentrifugation, and infectiousness of the purified phages was confirmed by plaque forming assay. The in vivo efficacy of a phage cocktail was evaluated in an experimental murine nasal colonization model, which showed that the phage cocktail was efficacious. To our knowledge, this is the first report of phage use in an in vivo model of nasal carriage.展开更多
Objectives: This study aimed to identify the contaminating bacteria in the extract of Garcinia cambogia, which is regularly used as a dietary supplement for addressing obesity in humans. Methods: The Garcinia cambogia...Objectives: This study aimed to identify the contaminating bacteria in the extract of Garcinia cambogia, which is regularly used as a dietary supplement for addressing obesity in humans. Methods: The Garcinia cambogia extract was used and experiments were conducted to isolate the contaminating bacteria and antibiotic susceptibility was tested. The organism was identified using BIOLOG system. Such an extract was used in a placebo-controlled animal study when 6 eight adult male rats weighing between 200 and 220 g were randomly distributed into three groups (n = 3) and in test group 1, a single dose of 100 mg/kg bw of Garcinia cambogia extract was given while in the test group 2, 100 mg Garcinia cambogia extract + 116 mg Picrorhiza kurroa extract were administered through oral gavage. The normal control rats were given distilled water, and the treatment lasted for 30 days. Blood plasma and liver tissues were prepared for biochemical analysis and histology studies. Results: Nearly ~10<sup>3</sup> cfu/g of Bacillus atrophaeus was present in the Garcinia cambogia extract and we demonstrate >99% reduction in the microbial load with tetracycline. Such an extract at a dose of 100 mg/kg, showed weight loss in Wistar rats when administered orally for 1 month with no significant changes in liver histopathology. Picrorhiza kurroa, also known for its hepatoprotective properties, has been administered at a dose of 116 mg/kg along with Garcinia extract at 100 mg/kg orally and found to improve levels of hepatic enzymes as similar to control animals, although not statistically significant. Conclusions: The study revealed that Garcinia cambogia could prevent weight gain in Wistar rats when given orally and the weight gain in Garcinia-treated animals was almost 4 times less (7.31%), as against weight gain of 25.36% seen in vehicle control animals. The antibiotic susceptibility data indicated that the isolated bacterium is resistant to many antibiotics with a strong susceptibility to tetracycline.展开更多
The minimum inhibitory concentration (MIC) is the concentration at which an antibacterial agent experiences the complete inhibition of organism growth. Bacteriophages represent a rich and unique resource of anti-infec...The minimum inhibitory concentration (MIC) is the concentration at which an antibacterial agent experiences the complete inhibition of organism growth. Bacteriophages represent a rich and unique resource of anti-infectives to counter the growing world-wide problem of antibiotic resistance. In this study, we compared the host range of lytic bacteriophages and temperate phagesbelonging to various genera, namely Staphylococcus, E. coli and Salmonella, with a range of clinical isolates using two methods: the classical agar overlay method and a newly developed MIC method. MIC was only observed with isolates that were susceptible to phage infection, which correlated with the agar overlay assay, whereas no MIC was detected with isolates that were resistant to phage infection. The simple MIC method was useful in determining phage adsorption and host range, and detecting possible prophage contamination in phage preparations. Interestingly, this method was also applicable to strain differentiation through phage susceptibility testing using a 96-well, high throughput format that proved to be easy, cost-effective, fast and reliable.展开更多
The Paleocene-recent post-rift subsidence history recorded in the Mumbai Offshore Basin off western continental margin of India is examined. Results obtained through 2-D flexural backstripping modelling of new seismic...The Paleocene-recent post-rift subsidence history recorded in the Mumbai Offshore Basin off western continental margin of India is examined. Results obtained through 2-D flexural backstripping modelling of new seismic data reveal considerable thermo-tectonic subsidence over last ca. 56 Myr. Reverse postrift subsidence modelling with variable β stretching factor predicts residual topography of ca. 2000 m to the west of Shelf Margin Basin and fails to restore late Paleocene horizon and the underlying igneous basement to the sea level. This potentially implies that:(1) either the igneous basement formed during the late Cretaceous was emplaced under open marine environs; or(2) a laterally varying cumulative subsidence occurred within Mumbai Offshore Basin(MOB) during ca. 68 to ca. 56 Ma. Pre-depositional topographic variations at ca. 56 Ma across the basin could be attributed to the extensional processes such as varied lower crustal underplating along Western Continental Margin of India(WCMI). Investigations about basement tectonics after unroofing of sediments since late Paleocene from this region support a transitional and heavily stretched nature of crust with high to very high β factors. Computations of past sediment accumulation rates show that the basin sedimentation peaked during late Miocene concurrently with uplift of Himalayan-Tibetan Plateau and intensification of Indian monsoon system. Results from basin subsidence modelling presented here may have significant implications for further studies attempting to explore tectono-climatic interactions in Asia.展开更多
This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide der...This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide derivatives（8a–x）. The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv（MTB） revealed that 2-chloro-N-（4-（5-（4-chlorophenyl）-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）benzamide（8n） is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative（8o） is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity（MIC = 3.13 mg/m L）. Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.展开更多
Capturing flue gases often require multiple stages of scrubbing, increasing the capital and operating costs. So far, no attempt has been made to study the absorption characteristics of all the three gases(NO, SO_(2) a...Capturing flue gases often require multiple stages of scrubbing, increasing the capital and operating costs. So far, no attempt has been made to study the absorption characteristics of all the three gases(NO, SO_(2) and CO_(2)) in a single stage absorption unit at alkaline p H conditions. We have attempted to capture all the three gases with a single wet scrubbing column. The absorption of all three gases with sodium carbonate solution promoted with oxidizers was investigated in a tall absorption column. The absorbance was found to be 100% for CO_(2), 30% for NO and 95% for SO_(2) respectively. The capture efficiency of sodium carbonate solution was increased by 40% for CO_(2) loading, with the addition of oxidizer. Absorption kinetics and reaction pathways of all the three gases were discussed individually in detail.展开更多
One of the standout problems in rural regions of India is the lack of a comprehensive medical record system.Medical records are a vital part of any diagnosis as they provide a glimpse into the patient’s past,which is...One of the standout problems in rural regions of India is the lack of a comprehensive medical record system.Medical records are a vital part of any diagnosis as they provide a glimpse into the patient’s past,which is influential to the current diagnosis.Medical records help practitioners spot anomalies and patterns in a variety of medical cases.It is also utilized to gain a better understanding of the health situation in certain demographics.In this paper,the authors have proposed a comprehensive distributed system which can be used to preserve the medical history of individuals,and also provide a valuable insight into the health situation of the rural populous.The distributed data are aggregated into a single entity from which observations are gathered.The data acquired could be of extreme importance to the government,as it can be utilized to determine the health issues which require immediate attention,and to evaluate possible mitigation plans.The data collected would be portable and easily accessible with the help of mobile devices.展开更多
The choroid plexus is a complex structure which hangs inside the ventricles of the brain and consists mainly of choroid plexus epithelial（CPE） cells surrounding fenestrated capillaries.These CPE cells not only form ...The choroid plexus is a complex structure which hangs inside the ventricles of the brain and consists mainly of choroid plexus epithelial（CPE） cells surrounding fenestrated capillaries.These CPE cells not only form an anatomical barrier,called the blood-cerebrospinal fluid barrier（BCSFB）,but also present an active interface between blood and cerebrospinal fluid（CSF）.CPE cells perform indispensable functions for the development,maintenance and functioning of the brain.Indeed,the primary role of the choroid plexus in the brain is to maintain homeostasis by secreting CSF which contains different molecules,such as nutrients,neurotrophins,and growth factors,as well as by clearing toxic and undesirable molecules from CSF.The choroid plexus also acts as a selective entry gate for leukocytes into the brain.Recent findings have revealed distinct changes in CPE cells that are associated with aging and Alzheimer＇s disease.In this review,we review some recent findings that highlight the importance of the CPE-CSF system in Alzheimer＇s disease and we summarize the recent advances in the regeneration of brain tissue through use of CPE cells as a new therapeutic strategy.展开更多
Background: Pre-cutting techniques have been used to gain biliary access at the expense of an increased complication rate. This may be because of the multiple attempts to achieve cannulation by using standard methods ...Background: Pre-cutting techniques have been used to gain biliary access at the expense of an increased complication rate. This may be because of the multiple attempts to achieve cannulation by using standard methods before pre-cutting and causing excess edema and papillary trauma. There are limited data on the early use of pre-cutting techniques. Methods: We performed a prospective study of the early introduction of needle-knife techniques in patients with difficult biliary cannulation. Standard biliary cannulation was attempted with a sphincterotome and a guidewire. If this failed within 10 minutes or if there were more than 5 pancreatic cannulations, the needle-knife technique was used. Either a standard method of pre-cutting (below-up-ward) from the papillary orifice or the modified technique of pre-cutting (above-downward), stopping short of the papillary orifice, was adopted, as per the discretion of the endoscopist. If pre-cutting failed, the cannulation was reattempted 24 to 48 hours later. Results: A total of 346 therapeutic biliary ERCP procedures were performed between April and August 2003. Of these, 70 patients (20%) (mean age, 54 years; 38 men) underwent needle-knife pre-cut sphincterotomy (16 with the standard technique). In 58 patients (83%), the procedure was successful with the initial pre-cutting, making the total success at initial ERCP 334/346 (96.5%). Nine patients in whom pre-cut failed, returned for a second-attempt ERCP, with 7 completed successfully. The total success rate of pre-cutting was 65/70 (93%). The overall success rate of biliary cannulation, after two ERCP attempts, was 341/346 (98.5%). Six patients had mild bleeding, and one had mild pancreatitis. There was no difference in these complications between the two types of precut techniques. Conclusions: The early use of needle knife for difficult biliary cannulation is safe and effective, irrespective of the technique used.展开更多
Chaotic behavior can be observed in continuous and discrete-time systems.This behavior can appear in one-dimensional nonlinear maps;however,having at least three state variables in flows is necessary.Due to the lower ...Chaotic behavior can be observed in continuous and discrete-time systems.This behavior can appear in one-dimensional nonlinear maps;however,having at least three state variables in flows is necessary.Due to the lower mathematical complexity and computational cost of maps,lots of research has been conducted based on them.This paper aims to present a novel one-dimensional trigonometric chaotic map that is multi-stable and can act attractively.The proposed chaotic map is first analyzed using a single sinusoidal function;then,its abilities are expanded to a map with a combination of two sinusoidal functions.The stability conditions of both maps are investigated,and their different behaviors are validated through time series,state space,and cobweb diagrams.Eventually,the influence of parameter variations on the maps’outputs is examined by one-dimensional and two-dimensional bifurcation diagrams and Lyapunov exponent spectra.Besides,the diversity of outputs with varying initial conditions reveals this map’s multi-stability.The newly designed chaotic map can be employed in encryption applications.展开更多
It is now recognized that nanoscale particulate matter(PM)represents a substantial health hazard for our society,including PM from restaurant smoke.In this study,we explored the use of a transient pulsed plasma in con...It is now recognized that nanoscale particulate matter(PM)represents a substantial health hazard for our society,including PM from restaurant smoke.In this study,we explored the use of a transient pulsed plasma in conjunction with an applied DC bias to treat oil aerosols that closely resemble restaurant(i.e.,charbroiler)smoke emissions.For polyaromatic olefin PAO-4 and soybean oil,we found that a three-order-of-magnitude reduction in particulates(i.e.,99.9%remediation)could be achieved with this system.Here,the plasma discharge was produced in a 4-in.-diameter cylindrical reactor with a 5-10 ns high voltage(30 kV)pulse generator together with applied DC bias voltages up to 10 kV.The distribution of nanoparticle sizes was measured using a scanning mobility particle sizer(SMPS)with diameter centered around 225 nm.Here,the main mechanism of remediation occurs in a two-step process in which the oil nanoparticles are first ionized by the free electrons and free radicals in the plasma and then the charged particles are swept out to the sidewalls of the reactor by the applied DC potential.We believe this general approach opens up new degrees of freedom in the design of electrostatic oil aerosol pollution control devices.展开更多
Harnessing the enhanced light-matter coupling and quantum vacuum fluctuations resulting from mode volume compression in optical cavities is a promising route towards functionalizing quantum materials and realizing exo...Harnessing the enhanced light-matter coupling and quantum vacuum fluctuations resulting from mode volume compression in optical cavities is a promising route towards functionalizing quantum materials and realizing exotic states of matter.Here,we extend cavity quantum electrodynamical materials engineering to correlated magnetic systems,by demonstrating that a Fabry-Pérot cavity can be used to control the magnetic state of the proximate quantum spin liquidα-RuCl_(3).Depending on specific cavity properties such as the mode frequency,photon occupation,and strength of the light-matter coupling,any of the magnetic phases supported by the extended Kitaev model can be stabilized.In particular,in the THz regime,we show that the cavity vacuum fluctuations alone are sufficient to bringα-RuCl_(3) from a zigzag antiferromagnetic to a ferromagnetic state.By external pumping of the cavity in the few photon limit,it is further possible to push the system into the antiferromagnetic Kitaev quantum spin liquid state.展开更多
基金Supported by NIH,No.UG3TR003289 to Soto-Gutierrez A.
文摘Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.
文摘CO_(2) utilizations are essential to curbing the greenhouse gas effect and managing the environmental pollutant in an energy-efficient and economically-sound manner.This paper seeks to critically analyze these technologies in the context of each other and highlight the most important utilization avenues available thus far.This review will introduce and analyze each major pathway,and discuss the overall applicability,potential extent,and major limitations of each of these pathways to utilizing CO_(2).This will include the analysis of some previously underreported utilization avenues,including CO_(2) utilization in industrial filtration and the processing of raw industrial materials such as iron and alumina.The core theme of this paper is to seek to treat CO_(2) as a commodity instead of a liability.
文摘Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.
文摘Incorporating aluminum metal-organic frameworks(Al-MOFs)as energetic additives for solid fuels presents a promising avenue for enhancing combustion performance.This study explores the potential benefits of Al-MOF(MIL-53(Al))energetic additive on the combustion performance of hydroxyl-terminated polybutadiene(HTPB)fuel.The HTPB-MOF fuel samples were manufactured using the vacuum-casting technique,followed by a comprehensive evaluation of their ignition and combustion properties using an opposed flow burner(OFB)setup utilizing gaseous oxygen as an oxidizer.To gauge the effectiveness of Al-MOFs as fuel additives,their impact is compared with that of nano-aluminum(nAl),another traditional additive in HTPB fuel.The results indicate that the addition of 15%(mass fraction)nAl into HTPB resulted in the shortest ignition delay time(136 ms),demonstrating improved ignition performance compared to pure HTPB(273 ms).The incorporation of Al-MOF in HTPB also reduced ignition delay times to 227 ms and 189 ms,respectively.Moreover,under high oxidizer mass flux conditions(79—81 kg/(m^(2)s)),HTPB fuel with 15%nAl exhibited a substantial 83.2%increase in regression rate compared to the baseline HTPB fuel,highlighting the positive influence of nAl on combustion behavior.In contrast,HTPB-MOF with a 15%Al-MOF additive showed a 32.7%increase in regression rate compared to pure HTPB.These results suggest that HTPB-nAl outperforms HTPB-MOF in terms of regression rates,indicating a more vigorous and rapid burning behavior.
文摘A key topic for aneurysmal subarachnoid hemorrhage is neuroinflammation.Neuroinflammation can predispose to aneurysm formation and rupture.Neuroinflammation can also result from the blood breakdown products after aneurysm rupture.Recent evidence has shown that perpetual neuroinflammation can contribute to vasospasm and hydrocephalus.Targeting neuroinflammation is a novel mechanism for preventing subsequent neurologic sequalae.In this review,we highlight the pathophysiology of aneurysm formation,the neuroinflammatory surge after rupture including the involved cytokines,and ultimately tie in the contributory clinical relevance.In the last sections,we look at the pre-clinical data and novel avenues for further discovery.This paper will be a useful resource to both the clinician and scientific investigator.
基金the National University of Singapore(Nano Nash Program A-0004336-00-00&A-000850400-00,Singapore)Nanyang Technological University,Singapore(grant number 001487-00001)+4 种基金the Industry Alignment Fund—Pre-Positioning(IAF-PP)grant(A20G1a0046 and R-148-000-307-305/A0004345-00-00)the Singapore Ministry of Education,under its Singapore Ministry of Education Academic Research Fund Tier 1(10051-MOE AcRF Tier 1:Thematic Call 2020)from Bertrand Czarnythe National University of Singapore Nano-NASH Program(NUHSRO/2020/002/Nano Nash/LOA)the National University of Singapore Yong Loo Lin School of Medicine Nanomedicine Translational Research Program(NUHSRO/2021/034/TRP/09/Nanomedicine)the financial supports from Agency for Science,Technology,and Research(A~*STAR,Singapore)Advanced Manufacturing and Engineering Individual Research Grant(AME IRG)(Project ID:A1883c0013,Singapore)。
文摘Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers.Recently,extracellular vesicles(EVs),naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins,lipids,and nucleic acids,have drawn wide attention due to their ability to promote wound healing and tissue regeneration.However,current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes.To circumvent these challenges,bioinspired cell-derived nanovesicles(CDNs)that mimic EVs were obtained by shearing mesenchymal stem cells(MSCs)through membranes with different pore sizes.Physical characterisations and highthroughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs.Moreover,these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway,resulting in enhancement of cell proliferation,cell migration,secretion of growth factors and extracellular matrix proteins,which all promoted tissue regeneration.Of note,MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEGfibrin scaffold and animal model,accelerating wound healing in vitro and in vivo.These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.
文摘Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose, carbopol 934 P and cellulose acetate phthalate as coat materials. Ionotropic gelation is a method to prepare microspheres using combination of Ca<sup>2+</sup> as cationic components and alginate as anion. The practical yield of prepared microspheres using the ionotropic gelation technique was between 172 mg and 604 mg. The result of the Chi-squared test carried out between the actual (practical) and expected (theoretical) yields showed no significant difference (P < 0.05) which indicated that the ionotropic gelation technique could be successfully employed to prepare pioglitazone microspheres using sodium alginate, sodium carboxy methyl cellulose, carbopol 934 P, HPMC, cellulose acetate butyrate polymers. The drug entrapment efficiency of prepared microspheres showed between 56.12% ± 3.86% to 84.68% ± 2.93% which was significantly higher for ionotropic gelation technique. The highest drug entrapment was found in formulation PMI 8. Swelling index is the capability of a polymer to swell before the drug is released which influences the rate and mechanism of drug release from the polymer matrix. The swelling index of prepared microspheres was in the range of 68% ± 4.52% to 87% ± 0.98%. Pioglitazone HCl microspheres showed controlled release of drug without initial peak level achieving. This type of properties in Pioglitazone HCl microspheres used to decrease side effects, reduce dosing frequency and improve patient compliances. From the all batches PMI 8 is considered the best formulation, because among all other formulations, it shows better extent of drug release up to 82.12% (18 h), good entrapment efficiency (84.68%) and the ex-vivo wash-off test shows the best mucoadhesive property. The in vitro drug release studies do up to 18 h. As observed from the various plots, most of th
文摘Bacteriophages represent a rich and unique resource of anti-infectives to counter the global problem of antibiotic resis- tance. In this work, we assessed the bactericidal activity of two virulent staphylococcal phages, K and 44AHJD, against S. aureus isolates of clinical significance, and tested their efficacy in vivo. The phage cocktail lysed >85% of the clinical isolates tested. Both the phages were purified by ion-exchange column chromatography following propagation in bioreactors. The purity profiles of the ion-exchange purified phages were compared with those of phages purified using cesium chloride density gradient ultracentrifugation, and infectiousness of the purified phages was confirmed by plaque forming assay. The in vivo efficacy of a phage cocktail was evaluated in an experimental murine nasal colonization model, which showed that the phage cocktail was efficacious. To our knowledge, this is the first report of phage use in an in vivo model of nasal carriage.
文摘Objectives: This study aimed to identify the contaminating bacteria in the extract of Garcinia cambogia, which is regularly used as a dietary supplement for addressing obesity in humans. Methods: The Garcinia cambogia extract was used and experiments were conducted to isolate the contaminating bacteria and antibiotic susceptibility was tested. The organism was identified using BIOLOG system. Such an extract was used in a placebo-controlled animal study when 6 eight adult male rats weighing between 200 and 220 g were randomly distributed into three groups (n = 3) and in test group 1, a single dose of 100 mg/kg bw of Garcinia cambogia extract was given while in the test group 2, 100 mg Garcinia cambogia extract + 116 mg Picrorhiza kurroa extract were administered through oral gavage. The normal control rats were given distilled water, and the treatment lasted for 30 days. Blood plasma and liver tissues were prepared for biochemical analysis and histology studies. Results: Nearly ~10<sup>3</sup> cfu/g of Bacillus atrophaeus was present in the Garcinia cambogia extract and we demonstrate >99% reduction in the microbial load with tetracycline. Such an extract at a dose of 100 mg/kg, showed weight loss in Wistar rats when administered orally for 1 month with no significant changes in liver histopathology. Picrorhiza kurroa, also known for its hepatoprotective properties, has been administered at a dose of 116 mg/kg along with Garcinia extract at 100 mg/kg orally and found to improve levels of hepatic enzymes as similar to control animals, although not statistically significant. Conclusions: The study revealed that Garcinia cambogia could prevent weight gain in Wistar rats when given orally and the weight gain in Garcinia-treated animals was almost 4 times less (7.31%), as against weight gain of 25.36% seen in vehicle control animals. The antibiotic susceptibility data indicated that the isolated bacterium is resistant to many antibiotics with a strong susceptibility to tetracycline.
文摘The minimum inhibitory concentration (MIC) is the concentration at which an antibacterial agent experiences the complete inhibition of organism growth. Bacteriophages represent a rich and unique resource of anti-infectives to counter the growing world-wide problem of antibiotic resistance. In this study, we compared the host range of lytic bacteriophages and temperate phagesbelonging to various genera, namely Staphylococcus, E. coli and Salmonella, with a range of clinical isolates using two methods: the classical agar overlay method and a newly developed MIC method. MIC was only observed with isolates that were susceptible to phage infection, which correlated with the agar overlay assay, whereas no MIC was detected with isolates that were resistant to phage infection. The simple MIC method was useful in determining phage adsorption and host range, and detecting possible prophage contamination in phage preparations. Interestingly, this method was also applicable to strain differentiation through phage susceptibility testing using a 96-well, high throughput format that proved to be easy, cost-effective, fast and reliable.
文摘The Paleocene-recent post-rift subsidence history recorded in the Mumbai Offshore Basin off western continental margin of India is examined. Results obtained through 2-D flexural backstripping modelling of new seismic data reveal considerable thermo-tectonic subsidence over last ca. 56 Myr. Reverse postrift subsidence modelling with variable β stretching factor predicts residual topography of ca. 2000 m to the west of Shelf Margin Basin and fails to restore late Paleocene horizon and the underlying igneous basement to the sea level. This potentially implies that:(1) either the igneous basement formed during the late Cretaceous was emplaced under open marine environs; or(2) a laterally varying cumulative subsidence occurred within Mumbai Offshore Basin(MOB) during ca. 68 to ca. 56 Ma. Pre-depositional topographic variations at ca. 56 Ma across the basin could be attributed to the extensional processes such as varied lower crustal underplating along Western Continental Margin of India(WCMI). Investigations about basement tectonics after unroofing of sediments since late Paleocene from this region support a transitional and heavily stretched nature of crust with high to very high β factors. Computations of past sediment accumulation rates show that the basin sedimentation peaked during late Miocene concurrently with uplift of Himalayan-Tibetan Plateau and intensification of Indian monsoon system. Results from basin subsidence modelling presented here may have significant implications for further studies attempting to explore tectono-climatic interactions in Asia.
基金National Institute of Technology Karnataka,India for the financial support and laboratory facility
文摘This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide derivatives（8a–x）. The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv（MTB） revealed that 2-chloro-N-（4-（5-（4-chlorophenyl）-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）benzamide（8n） is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative（8o） is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity（MIC = 3.13 mg/m L）. Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.
基金Michigan Technological University for their continued support for our research。
文摘Capturing flue gases often require multiple stages of scrubbing, increasing the capital and operating costs. So far, no attempt has been made to study the absorption characteristics of all the three gases(NO, SO_(2) and CO_(2)) in a single stage absorption unit at alkaline p H conditions. We have attempted to capture all the three gases with a single wet scrubbing column. The absorption of all three gases with sodium carbonate solution promoted with oxidizers was investigated in a tall absorption column. The absorbance was found to be 100% for CO_(2), 30% for NO and 95% for SO_(2) respectively. The capture efficiency of sodium carbonate solution was increased by 40% for CO_(2) loading, with the addition of oxidizer. Absorption kinetics and reaction pathways of all the three gases were discussed individually in detail.
基金This work was supported by the Department Science and Technology, India.
文摘One of the standout problems in rural regions of India is the lack of a comprehensive medical record system.Medical records are a vital part of any diagnosis as they provide a glimpse into the patient’s past,which is influential to the current diagnosis.Medical records help practitioners spot anomalies and patterns in a variety of medical cases.It is also utilized to gain a better understanding of the health situation in certain demographics.In this paper,the authors have proposed a comprehensive distributed system which can be used to preserve the medical history of individuals,and also provide a valuable insight into the health situation of the rural populous.The distributed data are aggregated into a single entity from which observations are gathered.The data acquired could be of extreme importance to the government,as it can be utilized to determine the health issues which require immediate attention,and to evaluate possible mitigation plans.The data collected would be portable and easily accessible with the help of mobile devices.
基金supported by the Research Foundation-Flanders (FWO)the Concerted Research Actions (GOA) of Ghent University+2 种基金the Belgian Science Policy (Interuniversity Attraction Pools-IAP7/07)the Belgain Foundation of Alzheimer's Researoh (SAO)the Ministry of Education,Science and Technological Development of the Republic of Serbia (Grant ON173056) and COST Action BM1402
文摘The choroid plexus is a complex structure which hangs inside the ventricles of the brain and consists mainly of choroid plexus epithelial（CPE） cells surrounding fenestrated capillaries.These CPE cells not only form an anatomical barrier,called the blood-cerebrospinal fluid barrier（BCSFB）,but also present an active interface between blood and cerebrospinal fluid（CSF）.CPE cells perform indispensable functions for the development,maintenance and functioning of the brain.Indeed,the primary role of the choroid plexus in the brain is to maintain homeostasis by secreting CSF which contains different molecules,such as nutrients,neurotrophins,and growth factors,as well as by clearing toxic and undesirable molecules from CSF.The choroid plexus also acts as a selective entry gate for leukocytes into the brain.Recent findings have revealed distinct changes in CPE cells that are associated with aging and Alzheimer＇s disease.In this review,we review some recent findings that highlight the importance of the CPE-CSF system in Alzheimer＇s disease and we summarize the recent advances in the regeneration of brain tissue through use of CPE cells as a new therapeutic strategy.
文摘Background: Pre-cutting techniques have been used to gain biliary access at the expense of an increased complication rate. This may be because of the multiple attempts to achieve cannulation by using standard methods before pre-cutting and causing excess edema and papillary trauma. There are limited data on the early use of pre-cutting techniques. Methods: We performed a prospective study of the early introduction of needle-knife techniques in patients with difficult biliary cannulation. Standard biliary cannulation was attempted with a sphincterotome and a guidewire. If this failed within 10 minutes or if there were more than 5 pancreatic cannulations, the needle-knife technique was used. Either a standard method of pre-cutting (below-up-ward) from the papillary orifice or the modified technique of pre-cutting (above-downward), stopping short of the papillary orifice, was adopted, as per the discretion of the endoscopist. If pre-cutting failed, the cannulation was reattempted 24 to 48 hours later. Results: A total of 346 therapeutic biliary ERCP procedures were performed between April and August 2003. Of these, 70 patients (20%) (mean age, 54 years; 38 men) underwent needle-knife pre-cut sphincterotomy (16 with the standard technique). In 58 patients (83%), the procedure was successful with the initial pre-cutting, making the total success at initial ERCP 334/346 (96.5%). Nine patients in whom pre-cut failed, returned for a second-attempt ERCP, with 7 completed successfully. The total success rate of pre-cutting was 65/70 (93%). The overall success rate of biliary cannulation, after two ERCP attempts, was 341/346 (98.5%). Six patients had mild bleeding, and one had mild pancreatitis. There was no difference in these complications between the two types of precut techniques. Conclusions: The early use of needle knife for difficult biliary cannulation is safe and effective, irrespective of the technique used.
基金funded by the Centre for Nonlinear Systems,Chennai Institute of Technology,India[grant number CIT/CNS/2023/RP/008].
文摘Chaotic behavior can be observed in continuous and discrete-time systems.This behavior can appear in one-dimensional nonlinear maps;however,having at least three state variables in flows is necessary.Due to the lower mathematical complexity and computational cost of maps,lots of research has been conducted based on them.This paper aims to present a novel one-dimensional trigonometric chaotic map that is multi-stable and can act attractively.The proposed chaotic map is first analyzed using a single sinusoidal function;then,its abilities are expanded to a map with a combination of two sinusoidal functions.The stability conditions of both maps are investigated,and their different behaviors are validated through time series,state space,and cobweb diagrams.Eventually,the influence of parameter variations on the maps’outputs is examined by one-dimensional and two-dimensional bifurcation diagrams and Lyapunov exponent spectra.Besides,the diversity of outputs with varying initial conditions reveals this map’s multi-stability.The newly designed chaotic map can be employed in encryption applications.
文摘It is now recognized that nanoscale particulate matter(PM)represents a substantial health hazard for our society,including PM from restaurant smoke.In this study,we explored the use of a transient pulsed plasma in conjunction with an applied DC bias to treat oil aerosols that closely resemble restaurant(i.e.,charbroiler)smoke emissions.For polyaromatic olefin PAO-4 and soybean oil,we found that a three-order-of-magnitude reduction in particulates(i.e.,99.9%remediation)could be achieved with this system.Here,the plasma discharge was produced in a 4-in.-diameter cylindrical reactor with a 5-10 ns high voltage(30 kV)pulse generator together with applied DC bias voltages up to 10 kV.The distribution of nanoparticle sizes was measured using a scanning mobility particle sizer(SMPS)with diameter centered around 225 nm.Here,the main mechanism of remediation occurs in a two-step process in which the oil nanoparticles are first ionized by the free electrons and free radicals in the plasma and then the charged particles are swept out to the sidewalls of the reactor by the applied DC potential.We believe this general approach opens up new degrees of freedom in the design of electrostatic oil aerosol pollution control devices.
基金We acknowledge support by the Max Planck Institute New York City Center for Non-Equilibrium Quantum Phenomena,the Cluster of Excellence‘CUI:Advanced Imaging of Matter’-EXC 2056-project ID 390715994 and SFB-925“Light induced dynamics and control of correlated quantum systems”-project 170620586 of the Deutsche Forschungsgemeinschaft(DFG),and Grupos Consolidados(IT1453-22).E.V.B.acknowledges funding from the European Union’s Horizon Europe research and innovation program under the Marie Skłodowska-Curie grant agreement No.101106809.The Flatiron Institute is a Division of the Simons Foundation.
文摘Harnessing the enhanced light-matter coupling and quantum vacuum fluctuations resulting from mode volume compression in optical cavities is a promising route towards functionalizing quantum materials and realizing exotic states of matter.Here,we extend cavity quantum electrodynamical materials engineering to correlated magnetic systems,by demonstrating that a Fabry-Pérot cavity can be used to control the magnetic state of the proximate quantum spin liquidα-RuCl_(3).Depending on specific cavity properties such as the mode frequency,photon occupation,and strength of the light-matter coupling,any of the magnetic phases supported by the extended Kitaev model can be stabilized.In particular,in the THz regime,we show that the cavity vacuum fluctuations alone are sufficient to bringα-RuCl_(3) from a zigzag antiferromagnetic to a ferromagnetic state.By external pumping of the cavity in the few photon limit,it is further possible to push the system into the antiferromagnetic Kitaev quantum spin liquid state.
