In this study,the in vitro digestion and fermentation of two intra-polysaccharide fractions(IPS1 and IPS2)from Paecilomyces cicadae TJJ1213 were investigated.The constituent monosaccharides of IPS1 and IPS2 were not c...In this study,the in vitro digestion and fermentation of two intra-polysaccharide fractions(IPS1 and IPS2)from Paecilomyces cicadae TJJ1213 were investigated.The constituent monosaccharides of IPS1 and IPS2 were not changed after simulated saliva,gastric and small intestinal digestion.However,they can be hydrolyzed and utilized by gut microbiota,and short-chain fatty acids(SCFAs)level were increased after IPS1 and IPS2 treatments.Furthermore,16 S r RNA sequencing analysis of fermentation samples were performed.Alpha-diversity,beta-diversity and taxonomic composition differences analysis revealed that IPS1 and IPS2 promoted the proliferation of beneficial bacteria and modulated the overall structure of gut microbiota.Taxonomic comparison analysis found that IPS1 increased the relative abundances of beneficial bacteria including Megamonas,Bifidobacterium and Lactobacillus,while IPS2 could increase the abundance of Bacteroides,Parabacteroides and Phascolarctobacterium.In addition,they can also decrease the levels of pathogenic bacteria containing Escherichia-Shigella,Klebsiella and Fusobacterium.These results indicated that IPS from Paecilomyces cicadae TJJ1213 could be used as potential candidates for new functional foods.展开更多
BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CR...BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.展开更多
The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multi...The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.展开更多
Pressure is an effective and clean way to modify the electronic structures of materials,cause structural phase transitions and even induce the emergence of superconductivity.Here,we predicted several new phases of the...Pressure is an effective and clean way to modify the electronic structures of materials,cause structural phase transitions and even induce the emergence of superconductivity.Here,we predicted several new phases of the Zr XY family at high pressures using the crystal structures search method together with first-principle calculations.In particular,the Zr Ge S compound undergoes an isosymmetric phase transition from P4/nmm-I to P4/nmm-II at approximately 82 GPa.Electronic band structures show that all the high-pressure phases are metallic.Among these new structures,P4/nmm-II Zr Ge S and P4/mmm Zr Ge Se can be quenched to ambient pressure with superconducting critical temperatures of approximately 8.1 K and 8.0 K,respectively.Our study provides a way to tune the structure,electronic properties,and superconducting behavior of topological materials through pressure.展开更多
Polymeric nitrogen has attracted much attention owing to its possible application as an environmentally safe high-energy-density material.Based on a crystal structure search method accelerated by the use of machine le...Polymeric nitrogen has attracted much attention owing to its possible application as an environmentally safe high-energy-density material.Based on a crystal structure search method accelerated by the use of machine learning and graph theory and on first-principles calculations,we predict a series of metal nitrides with chain-like polynitrogen(P_(21)-AlN_(6),P2_(1)-GaN_(6),P-1-YN_(6),and P_(4)/mnc-TiN_(8)),all of which are estimated to be energetically stable below 40.8 GPa.Phonon calculations and ab initio molecular dynamics simulations at finite temperature suggest that these nitrides are dynamically stable.We find that the nitrogen in these metal nitrides can polymerize into two types of poly-N^(2-)_(4)chains,in which theπelectrons are either extended or localized.Owing to the presence of the polymerized N4 chains,these metal nitrides can store a large amount of chemical energy,which is estimated to range from 4.50 to 2.71 kJ/g.Moreover,these compounds have high detonation pressures and detonation velocities,exceeding those of conventional explosives such as TNT and HMX.展开更多
Helium is the second most abundant element in the universe, and together with silica, they are important components of giant planets. Exploring the reactivity and state of helium and silica under high pressure is cruc...Helium is the second most abundant element in the universe, and together with silica, they are important components of giant planets. Exploring the reactivity and state of helium and silica under high pressure is crucial for understanding of the evolution and internal structure of giant planets. Here, using first-principles calculations and crystal structure predictions, we identify four stable phases of a helium-silica compound with seven/eight-coordinated silicon atoms at pressure of 600–4000 GPa, corresponding to the interior condition of the outer planets in the solar system. The density of He Si O2 agrees with current structure models of the planets.This helium-silica compound exhibits a superionic-like helium diffusive state under the high-pressure and hightemperature conditions along the isentropes of Saturn, a metallic fluid state in Jupiter, and a solid state in the deep interiors of Uranus and Neptune. These results show that helium may affect the erosion of the rocky core in giant planets and may help to form a diluted core region, which not only highlight the reactivity of helium under high pressure but also provide evidence helpful for building more sophisticated interior models of giant planets.展开更多
Inactivation of cyanobacterial cells and simultaneous control of secondary metabolites is of significant necessity for the treatment of cyanobacteria-laden water.Acetylacetone(AcAc)has been reported a specific algicid...Inactivation of cyanobacterial cells and simultaneous control of secondary metabolites is of significant necessity for the treatment of cyanobacteria-laden water.Acetylacetone(AcAc)has been reported a specific algicide to inactivate Microcystis aeruginosa(M.aeruginosa)and an effective light activator to degrade pollutants.This study systematically investigated the photodegradation ability of AcAc under xenon(Xe)irradiation on the secondary metabolites of M.aeruginosa,mainly algal organic matter(AOM),especially toxic microcystin-LR(MC-LR).Results showed that AcAc outperformed H_(2)O_(2)in destructing the protein-like substances,humic acid-like matters,aromatic proteins and fulvic-like substances of AOM.For MC-LR(250μg/L),0.05 mmol/L AcAc attained the same degradation efficiency(87.0%)as 0.1mmol/L H_(2)O_(2).The degradation mechanism of Xe/AcAc might involve photo-induced energy/electron transfer and formation of carbon center radicals.Alkaline conditions(pH>9.0)were detrimental to the photoactivity of AcAc,corresponding to the observed degradation rate constant(k_(1)value)of MC-LR drastically decreasing to 0.0013 min^(-1)as solution pH exceeded 9.0.The PO_(4)^(3-)and HCO_(3)^(-)ions had obvious inhibition effects,whereas NO_(3)^(-)slightly improved k_(1)value from 0.0277 min^(-1)to 0.0321 min^(-1).The presence of AOM did not significantly inhibit MC-LR degradation in Xe/AcAc system.In addition,the biological toxicity of MC-LR was greatly reduced after photoreaction.These results demonstrated that AcAc was an alternative algicidal agent to effectively inactivate algal cells and simultaneously control the secondary metabolites after cell lysis.Nevertheless,the concentration and irradiation conditions should be further optimized in practical application.展开更多
Smart manufacturing still remains critical challenges for pharmaceutical manufacturing.Here,an original data-driven engineering framework was proposed to tackle the challenges.Firstly,from sporadic indicators to five ...Smart manufacturing still remains critical challenges for pharmaceutical manufacturing.Here,an original data-driven engineering framework was proposed to tackle the challenges.Firstly,from sporadic indicators to five kinds of systematic quality characteristics,nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing.Then,from simplex to the multivariate system,the digital process capability diagnosis strategy was proposed by multivariate C_(pk)integrated Bootstrap-t.The C_(pk)of Ginkgo Folium extracts,granules,and tablets were discovered,which was 0.59,0.42,and 0.78,respectively,indicating a relatively weak process capability,especially in granulating.Furthermore,the quality traceability was discovered from unit to end-to-end analysis,which decreased from 2.17 to 1.73.This further proved that attention should be paid to granulating to improve the quality characteristic.In conclusion,this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.展开更多
Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects.Hence,an increasing number of computational methods are developed to pred...Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects.Hence,an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences.However,it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods.To solve this issue,we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets:(1)rare germline variants from clinical relevant sequence variants(ClinVar),(2)rare somatic variants from Catalogue Of Somatic Mutations In Cancer(COSMIC),(3)common regulatory variants from curated expression quantitative trait locus(eQTL)data,and(4)disease-associated common variants from curated genomewide association studies(GWAS).All 24 tested methods performed differently under various conditions,indicating varying strengths and weaknesses under different scenarios.Importantly,the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve(AUROC)of 0.4481–0.8033 and poor for rare somatic variants from COSMIC(AUROC=0.4984–0.7131),common regulatory variants from curated eQTL data(AUROC=0.4837–0.6472),and disease-associated common variants from curated GWAS(AUROC=0.4766–0.5188).We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder,and found that the combined annotation-dependent depletion(CADD)and context-dependent tolerance score(CDTS)methods showed better performance.Summarily,we assessed the performance of 24 computational methods under diverse scenarios,providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants.展开更多
Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limite...Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limited outcomes in the repair and regeneration of bone defects that might be attributed to the reciprocal interventions of these pathways. In order to satisfy the combinational and sequential activation of BMP and WNT pathways, inspired by the heterogeneous hydrogel-liked structures of Brasenia, heterogeneous alginate/chitosan hydrogels were fabricated and spatially loaded with FK506 and BIO to achieve sustained and sequential release of the activators. Alkaline phosphatase staining, alizarin red staining and q RT-PCR results suggested that FK506 and BIO enhanced osteoblastic differentiation in vitro when used separately. Besides, by mixing and matching the activators and the hydrogel layers, a superior releasing mode that a combination of early FK506 release and following BIO release was identified via both in vitro and in vivo explorations for most efficient bone regeneration. These results suggested that drug-loaded heterogeneous hydrogels possess great potentials in treating bone loss defects for future clinical practice.展开更多
In this paper,based on the statistical data,we investigate the effects of long-term exposure to ambient particulate air pollution on the transmission dynamics of tuberculosis(TB)in Jiangsu,China by studying the thresh...In this paper,based on the statistical data,we investigate the effects of long-term exposure to ambient particulate air pollution on the transmission dynamics of tuberculosis(TB)in Jiangsu,China by studying the threshold dynamics of the TB epidemic model via the statistical data analytically and numerically.The basic reproduction number R_(0)>1 reveals that TB in Jiangsu,China is an endemic disease and will persist for a long time.And the numerical results show that,in order to control the TB in Jiangsu effectively,we must decrease the depuration coefficient of PM10 in the body,the proportion of TB symptomatic infectious by direct transmission,the reactivation rate of the pre-symptomatic infectious and the effect coefficient of PM10 and MTB inhaled of TB transmission,and increase the uptake coefficient,the recovery rate of the symptomatic/pre-symptomatic infectious and the influence coefficient of PM10 on the body of mortality.Our study shows that PM10 is closely related to the incidence of TB,and the effective control efforts are suggested to focus on increasing close-contact distance and wearing protective mask to decrease the influence of PM10 on the TB transmission,which may shed a new light on understanding the environmental drivers to TB.展开更多
Fluorinated alcohols exhibit promising prospects in chemical industry because of their special structure and many exciting properties,in which tetrafluoropropanol(TFP)is extensive applied in synthesis of pesticides,dy...Fluorinated alcohols exhibit promising prospects in chemical industry because of their special structure and many exciting properties,in which tetrafluoropropanol(TFP)is extensive applied in synthesis of pesticides,dyestuffs,variety of solvents and detergents.However,the presence of TFP in water garners increasing attention globally because of their intrinsic potential to threat ecosystems and human health.Carbon nanotubes(CNTs)membranes are burgeoning candidates for TFP-water separation owing to well-endowed extraordinary structural and transport properties.However,a grand challenge lies in the rational design of CNTs for improving separation performance.Herein,molecular dynamics(MD)simulations were performed to investigate the effects of various parameters on the separation of TFP-water mixtures including feed temperature,CNTs pore diameters,and fluorine functionalization position.It was found that TFP was pre-selected in CNTs ranging from 9.48 to 18.98Ådue to preferential adsorption and diffusion mechanism.Excellent separation factor of 16 was achieved by(7,7)CNTs and the mass fraction of TFP was purified from 75%to 97.51%.Fluorine modified CNTs separated TFP and water by preferentially permeating water due to hydrogen bonding interaction.Simulation results showed that CNTs modified at both the entrance and interior had better separation performance than CNT modified only at one of these positions.The 100wt%water content in permeate was achieved by(11,11)CNTs modified with fluorine at the entrance and interior.These findings provide valuable insights for designing potential candidates for fluorinated alcohol-water azeotropic mixtures membrane separation,and promise extensive application aspects for the reclamation of fluorinated alcohol.展开更多
In this work,we focus on the structural and electronic properties of lanthanum mono-nitride s under high pressure.Based on firstprinciples calculations and crystal structure predictions,we identified an anti-ferroelec...In this work,we focus on the structural and electronic properties of lanthanum mono-nitride s under high pressure.Based on firstprinciples calculations and crystal structure predictions,we identified an anti-ferroelectric orthogonal phase with space group Pbcm.It is predicted to be thermodynamically stable from 20 to 60 GPa,above which the tetragonal phase without the antiferroelectric distortion will substitute it.However,the anti-ferroelectric distortion can be enhancedby reducing the pressure,and a phase transition to a NiAs-type(B8,P63/mmc) structure occurs at about 20 GPa.The calculated double-well potential for La atoms along the c direction in the B8 phase reveals that it should exhibit ferroelectric properties at low temperatures.Enthalpy calculations well confirm their phase transition sequences under high pressure.Electtonic properties calculations suggest that all the newly identified phases are semiconductors and the corresponding structural distortions can increase their bandgaps.When increasing the pressure to 50 GPa,the tetragonal phase undergoes a semiconductor-to-semimetal transition.Taking the spin-orbit coupling into account,the semimetal phase becomes a topological insulator with a small bandgap.Finally,given the similarities between the ionic compounds LaN and BaO,we predict that the most stable phase for BaO at about 25 GPa should also be the anti-ferroelectric orthogonal phase instead of the tetragonal phase.展开更多
Background:Tuberculosis(TB)is an infectious disease of major public health concern.The disease has demonstrated large space-time variations.This study aims to explore the space-time dynamics of TB cases in an economic...Background:Tuberculosis(TB)is an infectious disease of major public health concern.The disease has demonstrated large space-time variations.This study aims to explore the space-time dynamics of TB cases in an economically and geographically dynamic province in China with specific references of TB control for policy makers.Methods:Data on all reported TB cases from 2009 to 2012 were collected from the TB program at the Zhejiang Provincial Center for Disease Control and Prevention.We employed time series and exploratory spatial data analyses,including Moran’s I,Local Getis’s G_(i)^(*),and Kulldorff’s space-time scan statistics,to identify the temporal trends and spatial patterns of TB at a county level.Results:A total of 147,941 TB cases were reported during 2009–2012 in Zhejiang.A higher proportion of TB cases were younger,male,and registered permanent residents among all TB cases notified in the province.TB cases were reported most frequently in April with small peaks in June,July,and October.This disease was spatially clustering with Moran’s I values ranged from 0.29 to 0.32(p<0.001).A most likely cluster and ten secondary clusters were identified,mainly concentrated in the southeast and west counties of the province.Conclusions:This study identified seasonal patterns and significant space-time clusters of TB cases in Zhejiang,China.Poverty,migration,and seasonal effects may play important roles in potential clusters.展开更多
The laterodorsal tegmentum(LDT) is a brain structure involved in distinct behaviors including arousal,reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical...The laterodorsal tegmentum(LDT) is a brain structure involved in distinct behaviors including arousal,reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear.Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex(VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive(PV?) GABAergic cells received preferential projections from local LDT neurons.With regard to the different subtypes of GABAergic cells, aconsiderable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatinpositive cells than to PV?cells. Diverse inputs to the LDT on a system-wide level were revealed.展开更多
Brønsted acidic ionic liquids(ILs),N-methylimidazole hydrogen sulfate([HMIm]HSO_(4))and N-methylpyrrolidone hydrogen sulfate([HNMP]HSO_(4)),are synthesized and employed as extractants to extract thiophene from mo...Brønsted acidic ionic liquids(ILs),N-methylimidazole hydrogen sulfate([HMIm]HSO_(4))and N-methylpyrrolidone hydrogen sulfate([HNMP]HSO_(4)),are synthesized and employed as extractants to extract thiophene from model gasoline(thiophene dissolved in noctane).The effect of extraction temperature,extraction time and volume ratio of ILs to model gasoline on desulfurization rates is investigated.Then,the optimal desulfurization conditions are obtained:the ratio of ILs to model gasoline is 1∶1,extraction temperature is 50℃ for[HMIm]HSO_(4)and 60℃ for[HNMP]HSO_(4),extraction time is 60 min.Meanwhile,the desulfurization rate of[HNMP]HSO_(4)for model gasoline is 62.8%,which is higher than that of[HMIm]HSO_(4)(55.5%)under optimal conditions.The reason is discussed on the basis of the interaction energy between thiophene and ILs at the B3LYP/6-311++G(d,p)level.Furthermore,the total desulfurization rate of[HNMP]HSO_(4)and[HMIm]HSO_(4)reaches 96.4%and 94.4%,respectively,by multistage extraction.Finally,the used ILs can be reused by vacuum drying,and their desulfurization rates are not significantly decreased after recycling 7 times in single-stage desulfurization.展开更多
基金co-financed by National Natural Science Foundation of China(U1903108,31871771 and 31571818)Natural Science Foundation of Jiangsu Province(BK20201320)+2 种基金Jiangsu Agriculture Science and Technology Innovation Fund(CX(20)3043)Postgraduate Research&Practice innovation Program of Jiangsu Province(KYCX19_0589)Qing Lan Project of Jiangsu Province and Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘In this study,the in vitro digestion and fermentation of two intra-polysaccharide fractions(IPS1 and IPS2)from Paecilomyces cicadae TJJ1213 were investigated.The constituent monosaccharides of IPS1 and IPS2 were not changed after simulated saliva,gastric and small intestinal digestion.However,they can be hydrolyzed and utilized by gut microbiota,and short-chain fatty acids(SCFAs)level were increased after IPS1 and IPS2 treatments.Furthermore,16 S r RNA sequencing analysis of fermentation samples were performed.Alpha-diversity,beta-diversity and taxonomic composition differences analysis revealed that IPS1 and IPS2 promoted the proliferation of beneficial bacteria and modulated the overall structure of gut microbiota.Taxonomic comparison analysis found that IPS1 increased the relative abundances of beneficial bacteria including Megamonas,Bifidobacterium and Lactobacillus,while IPS2 could increase the abundance of Bacteroides,Parabacteroides and Phascolarctobacterium.In addition,they can also decrease the levels of pathogenic bacteria containing Escherichia-Shigella,Klebsiella and Fusobacterium.These results indicated that IPS from Paecilomyces cicadae TJJ1213 could be used as potential candidates for new functional foods.
基金Supported by the Ministry of Higher Education Malaysia for the Fundamental Research Grant Scheme,No. FRGS/1/2021/SKK06/USM/02/7
文摘BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.
文摘The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.
基金the financial support from the National Natural Science Foundation of China(Grant Nos.12125404,11974162,and 11834006)the Fundamental Research Funds for the Central Universities,China。
文摘Pressure is an effective and clean way to modify the electronic structures of materials,cause structural phase transitions and even induce the emergence of superconductivity.Here,we predicted several new phases of the Zr XY family at high pressures using the crystal structures search method together with first-principle calculations.In particular,the Zr Ge S compound undergoes an isosymmetric phase transition from P4/nmm-I to P4/nmm-II at approximately 82 GPa.Electronic band structures show that all the high-pressure phases are metallic.Among these new structures,P4/nmm-II Zr Ge S and P4/mmm Zr Ge Se can be quenched to ambient pressure with superconducting critical temperatures of approximately 8.1 K and 8.0 K,respectively.Our study provides a way to tune the structure,electronic properties,and superconducting behavior of topological materials through pressure.
基金J.S.gratefully acknowledges financial support from the National Natural Science Foundation of China(Grant Nos.12125404,11974162,and 11834006)the Fundamental Research Funds for the Central Universities.K.X.acknowledges support from the National Natural Science Foundation of China under Grant No.12004185+2 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China under Grant No.20KJB140016the Scientific Research Start-up Funds of Nanjing Forestry University(No.163101110)the China Postdoctoral Science Foundation(Grant No.2019M651767).
文摘Polymeric nitrogen has attracted much attention owing to its possible application as an environmentally safe high-energy-density material.Based on a crystal structure search method accelerated by the use of machine learning and graph theory and on first-principles calculations,we predict a series of metal nitrides with chain-like polynitrogen(P_(21)-AlN_(6),P2_(1)-GaN_(6),P-1-YN_(6),and P_(4)/mnc-TiN_(8)),all of which are estimated to be energetically stable below 40.8 GPa.Phonon calculations and ab initio molecular dynamics simulations at finite temperature suggest that these nitrides are dynamically stable.We find that the nitrogen in these metal nitrides can polymerize into two types of poly-N^(2-)_(4)chains,in which theπelectrons are either extended or localized.Owing to the presence of the polymerized N4 chains,these metal nitrides can store a large amount of chemical energy,which is estimated to range from 4.50 to 2.71 kJ/g.Moreover,these compounds have high detonation pressures and detonation velocities,exceeding those of conventional explosives such as TNT and HMX.
基金the financial support from the National Natural Science Foundation of China (Grant Nos. 12125404, 11974162, and 11834006)the Fundamental Research Funds for the Central Universities。
文摘Helium is the second most abundant element in the universe, and together with silica, they are important components of giant planets. Exploring the reactivity and state of helium and silica under high pressure is crucial for understanding of the evolution and internal structure of giant planets. Here, using first-principles calculations and crystal structure predictions, we identify four stable phases of a helium-silica compound with seven/eight-coordinated silicon atoms at pressure of 600–4000 GPa, corresponding to the interior condition of the outer planets in the solar system. The density of He Si O2 agrees with current structure models of the planets.This helium-silica compound exhibits a superionic-like helium diffusive state under the high-pressure and hightemperature conditions along the isentropes of Saturn, a metallic fluid state in Jupiter, and a solid state in the deep interiors of Uranus and Neptune. These results show that helium may affect the erosion of the rocky core in giant planets and may help to form a diluted core region, which not only highlight the reactivity of helium under high pressure but also provide evidence helpful for building more sophisticated interior models of giant planets.
基金supported by the National Natural Science Foundation of China (No.21906085)the Natural Science Foundation of Jiangsu Province of China (No.BK20190547)the State Key Laboratory of Pollution Control and Resource Reuse Foundation (No.PCRRF21046)。
文摘Inactivation of cyanobacterial cells and simultaneous control of secondary metabolites is of significant necessity for the treatment of cyanobacteria-laden water.Acetylacetone(AcAc)has been reported a specific algicide to inactivate Microcystis aeruginosa(M.aeruginosa)and an effective light activator to degrade pollutants.This study systematically investigated the photodegradation ability of AcAc under xenon(Xe)irradiation on the secondary metabolites of M.aeruginosa,mainly algal organic matter(AOM),especially toxic microcystin-LR(MC-LR).Results showed that AcAc outperformed H_(2)O_(2)in destructing the protein-like substances,humic acid-like matters,aromatic proteins and fulvic-like substances of AOM.For MC-LR(250μg/L),0.05 mmol/L AcAc attained the same degradation efficiency(87.0%)as 0.1mmol/L H_(2)O_(2).The degradation mechanism of Xe/AcAc might involve photo-induced energy/electron transfer and formation of carbon center radicals.Alkaline conditions(pH>9.0)were detrimental to the photoactivity of AcAc,corresponding to the observed degradation rate constant(k_(1)value)of MC-LR drastically decreasing to 0.0013 min^(-1)as solution pH exceeded 9.0.The PO_(4)^(3-)and HCO_(3)^(-)ions had obvious inhibition effects,whereas NO_(3)^(-)slightly improved k_(1)value from 0.0277 min^(-1)to 0.0321 min^(-1).The presence of AOM did not significantly inhibit MC-LR degradation in Xe/AcAc system.In addition,the biological toxicity of MC-LR was greatly reduced after photoreaction.These results demonstrated that AcAc was an alternative algicidal agent to effectively inactivate algal cells and simultaneously control the secondary metabolites after cell lysis.Nevertheless,the concentration and irradiation conditions should be further optimized in practical application.
基金co-National Outstanding Youth Science Fund Project of National Natural Science Foundation of China(Grant No.82022073,China)Major scientific and technological R&D projects in Jiangxi Province(Grant No.20203ABC28W018,China)National Key Research and Development Program of China(Grant No.2018YFC1706900,China)。
文摘Smart manufacturing still remains critical challenges for pharmaceutical manufacturing.Here,an original data-driven engineering framework was proposed to tackle the challenges.Firstly,from sporadic indicators to five kinds of systematic quality characteristics,nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing.Then,from simplex to the multivariate system,the digital process capability diagnosis strategy was proposed by multivariate C_(pk)integrated Bootstrap-t.The C_(pk)of Ginkgo Folium extracts,granules,and tablets were discovered,which was 0.59,0.42,and 0.78,respectively,indicating a relatively weak process capability,especially in granulating.Furthermore,the quality traceability was discovered from unit to end-to-end analysis,which decreased from 2.17 to 1.73.This further proved that attention should be paid to granulating to improve the quality characteristic.In conclusion,this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.
基金supported by the National Natural Science Foundation of China(Grant No.81801133 to JL)the Young Elite Scientist Sponsorship Program by China Association for Science and Technology(Grant No.2018QNRC001 to JL)+2 种基金the Innovation-Driven Project of Central South University,China(Grant No.20180033040004 to JL)the Natural Science Foundation for Young Scientists of Hunan Province,China(Grant No.2019JJ50974 to GZ)the Natural Science Foundation of Hunan Province for outstanding Young Scholars,China(Grant No.2020JJ3059 to JL).
文摘Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects.Hence,an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences.However,it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods.To solve this issue,we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets:(1)rare germline variants from clinical relevant sequence variants(ClinVar),(2)rare somatic variants from Catalogue Of Somatic Mutations In Cancer(COSMIC),(3)common regulatory variants from curated expression quantitative trait locus(eQTL)data,and(4)disease-associated common variants from curated genomewide association studies(GWAS).All 24 tested methods performed differently under various conditions,indicating varying strengths and weaknesses under different scenarios.Importantly,the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve(AUROC)of 0.4481–0.8033 and poor for rare somatic variants from COSMIC(AUROC=0.4984–0.7131),common regulatory variants from curated eQTL data(AUROC=0.4837–0.6472),and disease-associated common variants from curated GWAS(AUROC=0.4766–0.5188).We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder,and found that the combined annotation-dependent depletion(CADD)and context-dependent tolerance score(CDTS)methods showed better performance.Summarily,we assessed the performance of 24 computational methods under diverse scenarios,providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants.
基金supported by the National Natural Science Foundation of China (Nos. 81970903 and 81920108012)Fundamental Research Funds for the Central Universities,Jilin Provincial Science & Technology Department (No. 20200201527JC)+1 种基金Jilin Department of Health (No. 2019Q013)Department of Finance of Jilin Province (No. JCSZ2019378-6)。
文摘Although bone morphogenetic protein(BMP) and WNT signaling play pivotal roles in bone development,homeostasis, and regeneration, the applications of proteins to stimulate corresponding signaling pathways showed limited outcomes in the repair and regeneration of bone defects that might be attributed to the reciprocal interventions of these pathways. In order to satisfy the combinational and sequential activation of BMP and WNT pathways, inspired by the heterogeneous hydrogel-liked structures of Brasenia, heterogeneous alginate/chitosan hydrogels were fabricated and spatially loaded with FK506 and BIO to achieve sustained and sequential release of the activators. Alkaline phosphatase staining, alizarin red staining and q RT-PCR results suggested that FK506 and BIO enhanced osteoblastic differentiation in vitro when used separately. Besides, by mixing and matching the activators and the hydrogel layers, a superior releasing mode that a combination of early FK506 release and following BIO release was identified via both in vitro and in vivo explorations for most efficient bone regeneration. These results suggested that drug-loaded heterogeneous hydrogels possess great potentials in treating bone loss defects for future clinical practice.
基金supported by the National Natural Science Foundation of China(Grant numbers 12071173 and 12171192)Huaian Key Laboratory for Infectious Diseases Control and Prevention,China(HAP201704).
文摘In this paper,based on the statistical data,we investigate the effects of long-term exposure to ambient particulate air pollution on the transmission dynamics of tuberculosis(TB)in Jiangsu,China by studying the threshold dynamics of the TB epidemic model via the statistical data analytically and numerically.The basic reproduction number R_(0)>1 reveals that TB in Jiangsu,China is an endemic disease and will persist for a long time.And the numerical results show that,in order to control the TB in Jiangsu effectively,we must decrease the depuration coefficient of PM10 in the body,the proportion of TB symptomatic infectious by direct transmission,the reactivation rate of the pre-symptomatic infectious and the effect coefficient of PM10 and MTB inhaled of TB transmission,and increase the uptake coefficient,the recovery rate of the symptomatic/pre-symptomatic infectious and the influence coefficient of PM10 on the body of mortality.Our study shows that PM10 is closely related to the incidence of TB,and the effective control efforts are suggested to focus on increasing close-contact distance and wearing protective mask to decrease the influence of PM10 on the TB transmission,which may shed a new light on understanding the environmental drivers to TB.
基金supported by the Shandong Provincial Natural Science Foundation(Nos.ZR2020MB118,ZR2020QB175)the National Natural Science Foundation of China(Nos.2197080534,22008143,52070123)+3 种基金the State Key Laboratory of High-efficiency Utilization of Coal and Green Chemical Engineering(No.2022-K10)the Project funded by China Postdoctoral Science Foundation(No.2022M711958)the Applied Research Project of Qingdao Postdoctoral(No.01020240119)the China Postdoctoral Science Foundation(No.2022M720083).
文摘Fluorinated alcohols exhibit promising prospects in chemical industry because of their special structure and many exciting properties,in which tetrafluoropropanol(TFP)is extensive applied in synthesis of pesticides,dyestuffs,variety of solvents and detergents.However,the presence of TFP in water garners increasing attention globally because of their intrinsic potential to threat ecosystems and human health.Carbon nanotubes(CNTs)membranes are burgeoning candidates for TFP-water separation owing to well-endowed extraordinary structural and transport properties.However,a grand challenge lies in the rational design of CNTs for improving separation performance.Herein,molecular dynamics(MD)simulations were performed to investigate the effects of various parameters on the separation of TFP-water mixtures including feed temperature,CNTs pore diameters,and fluorine functionalization position.It was found that TFP was pre-selected in CNTs ranging from 9.48 to 18.98Ådue to preferential adsorption and diffusion mechanism.Excellent separation factor of 16 was achieved by(7,7)CNTs and the mass fraction of TFP was purified from 75%to 97.51%.Fluorine modified CNTs separated TFP and water by preferentially permeating water due to hydrogen bonding interaction.Simulation results showed that CNTs modified at both the entrance and interior had better separation performance than CNT modified only at one of these positions.The 100wt%water content in permeate was achieved by(11,11)CNTs modified with fluorine at the entrance and interior.These findings provide valuable insights for designing potential candidates for fluorinated alcohol-water azeotropic mixtures membrane separation,and promise extensive application aspects for the reclamation of fluorinated alcohol.
基金supported by the National Natural Science Foundation of China (Grant Nos. 12125404, 11974162, and 11834006)the Fundamental Research Funds for the Central Universities。
文摘In this work,we focus on the structural and electronic properties of lanthanum mono-nitride s under high pressure.Based on firstprinciples calculations and crystal structure predictions,we identified an anti-ferroelectric orthogonal phase with space group Pbcm.It is predicted to be thermodynamically stable from 20 to 60 GPa,above which the tetragonal phase without the antiferroelectric distortion will substitute it.However,the anti-ferroelectric distortion can be enhancedby reducing the pressure,and a phase transition to a NiAs-type(B8,P63/mmc) structure occurs at about 20 GPa.The calculated double-well potential for La atoms along the c direction in the B8 phase reveals that it should exhibit ferroelectric properties at low temperatures.Enthalpy calculations well confirm their phase transition sequences under high pressure.Electtonic properties calculations suggest that all the newly identified phases are semiconductors and the corresponding structural distortions can increase their bandgaps.When increasing the pressure to 50 GPa,the tetragonal phase undergoes a semiconductor-to-semimetal transition.Taking the spin-orbit coupling into account,the semimetal phase becomes a topological insulator with a small bandgap.Finally,given the similarities between the ionic compounds LaN and BaO,we predict that the most stable phase for BaO at about 25 GPa should also be the anti-ferroelectric orthogonal phase instead of the tetragonal phase.
基金supported by the General Research Fund grant through the Hong Kong Research Grants Council(ref CUHK 14411614).
文摘Background:Tuberculosis(TB)is an infectious disease of major public health concern.The disease has demonstrated large space-time variations.This study aims to explore the space-time dynamics of TB cases in an economically and geographically dynamic province in China with specific references of TB control for policy makers.Methods:Data on all reported TB cases from 2009 to 2012 were collected from the TB program at the Zhejiang Provincial Center for Disease Control and Prevention.We employed time series and exploratory spatial data analyses,including Moran’s I,Local Getis’s G_(i)^(*),and Kulldorff’s space-time scan statistics,to identify the temporal trends and spatial patterns of TB at a county level.Results:A total of 147,941 TB cases were reported during 2009–2012 in Zhejiang.A higher proportion of TB cases were younger,male,and registered permanent residents among all TB cases notified in the province.TB cases were reported most frequently in April with small peaks in June,July,and October.This disease was spatially clustering with Moran’s I values ranged from 0.29 to 0.32(p<0.001).A most likely cluster and ten secondary clusters were identified,mainly concentrated in the southeast and west counties of the province.Conclusions:This study identified seasonal patterns and significant space-time clusters of TB cases in Zhejiang,China.Poverty,migration,and seasonal effects may play important roles in potential clusters.
基金supported by grants from the National Natural Science Foundation of China (31671100, 31471022, 31622027, 31490592, 81527901, and 81521062)Zhejiang Provincial Natural Science Foundation, China (LR18H090001)+1 种基金the Program for Introducing Talents in Disciplines to Universitiesthe Fundamental Research Funds for the Central Universities, China (2017YFA7002, and 2019QNA5001)
文摘The laterodorsal tegmentum(LDT) is a brain structure involved in distinct behaviors including arousal,reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear.Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex(VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive(PV?) GABAergic cells received preferential projections from local LDT neurons.With regard to the different subtypes of GABAergic cells, aconsiderable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatinpositive cells than to PV?cells. Diverse inputs to the LDT on a system-wide level were revealed.
基金This research was financially supported by the Natural Science Fund for Colleges and Universities of Jiangsu Province(09KJB530002).
文摘Brønsted acidic ionic liquids(ILs),N-methylimidazole hydrogen sulfate([HMIm]HSO_(4))and N-methylpyrrolidone hydrogen sulfate([HNMP]HSO_(4)),are synthesized and employed as extractants to extract thiophene from model gasoline(thiophene dissolved in noctane).The effect of extraction temperature,extraction time and volume ratio of ILs to model gasoline on desulfurization rates is investigated.Then,the optimal desulfurization conditions are obtained:the ratio of ILs to model gasoline is 1∶1,extraction temperature is 50℃ for[HMIm]HSO_(4)and 60℃ for[HNMP]HSO_(4),extraction time is 60 min.Meanwhile,the desulfurization rate of[HNMP]HSO_(4)for model gasoline is 62.8%,which is higher than that of[HMIm]HSO_(4)(55.5%)under optimal conditions.The reason is discussed on the basis of the interaction energy between thiophene and ILs at the B3LYP/6-311++G(d,p)level.Furthermore,the total desulfurization rate of[HNMP]HSO_(4)and[HMIm]HSO_(4)reaches 96.4%and 94.4%,respectively,by multistage extraction.Finally,the used ILs can be reused by vacuum drying,and their desulfurization rates are not significantly decreased after recycling 7 times in single-stage desulfurization.
