CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing.However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Copy number alteration profiling facilitates differential diagnosis between ossifying fibroma and fibrous dysplasia of the jaws

Ossifying fibroma(OF)and fibrous dysplasia(FD)are two fibro-osseous lesions with overlapping clinicopathological features,making diagnosis challenging.In this study,we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations(CNAs)using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples.Freshly frozen tissue specimens from OF(n=29)and FD(n=28)patients were obtained for analysis.Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection(LCM),with~30–50 cells(5000–10000µm2)per sample.We found that the rate of recurrent CNAs in OF cases was much higher(44.8%,13 of 29)than that in FD cases(3.6%,1 of 28).Sixty-nine percent(9 of 13)of the CNA-containing OF cases involved segmental amplifications and deletions on Chrs 7 and 12.We also identified eight CNA-associated genes(HILPDA,CALD1,C1GALT1,MICALL2,PHF14,AIMP2,MDM2,and CDK4)with amplified expression,which was consistent with the copy number changes.We further confirmed a jaw lesion with a previous uncertain diagnosis due to its ambiguous morphological features and the absence of GNAS mutation as OF based on the typical Chr 12 amplification pattern in its CNA profile.Moreover,analysis of a set of longitudinal samples collected from an individual with a cellular lesion in suspicion of OF at the first surgery,recurrence and the latest malignant transformation revealed identical CNA patterns at the three time points,suggesting that copy number profiling can be used as an important tool to identify borderline lesions or lesions with malignant potential.Overall,CNA profiling of fibro-osseous lesions can greatly improve differential diagnosis between OF and FD and help predict disease progression.

Robotic Walker for Slope Mobility Assistance with Active-Passive Hybrid Actuator

Walking assistance can be realized by active and passive robotic walkers when their users walk on even roads.However,fast signal processing and real-time control are necessary for active robotic walkers when the users walk on slopes,while assistive forces cannot be provided by passive robotic walkers when the users walk uphill.A robotic walker with an active-passive hybrid actuator(APHA)was developed in this study.The APHA,which consists of a rotary magnetorheological(MR)brake and a DC motor,can provide mobility assistance to users walking both uphill and downhill via the cooperative operation of the MR brake and DC motor.The rotary MR brake was designed with a T-shaped configuration,and the system was optimized to minimize the brake volume.Prototypes of the APHA and robotic walker were constructed.A control algorithm for the robotic walker was developed based on the characteristics of the APHA and the structure of the robotic walker.The mechanical properties of the APHA were characterized,and experiments were conducted to evaluate the mobility assistance supplied by the robotic walker on different roads.The results show that the APHA can meet the requirements of the robotic walker,and suitable assistive forces can be provided by the robotic walker,which has a simple mechanical structure and control method.

Cyclo (MQCNS) has the potential to treat ischemic stroke

We previously found that monocyte locomotion inhibitory factor has a neuroprotective effect on ischemic brain injury during the acute phase of stro ke.Therefore,we modified the structure of an anti-inflammato ry monocyte locomotion inhibitory factor peptide to construct an active cyclic peptide—Cyclo(MQCNS)(LZ-3)—and investigated its effects on ischemic stroke.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery and then administered LZ-3(2 or 4 mg/kg) via the tail vein for 7 consecutive days.Our res ults showed that LZ-3(2 or 4 mg/kg) substantially decreased infarct volu m e,reduced co rtical ne rve cell death,improved neurological function,reduced cortical and hippocampal injury,and decreased the levels of inflammatory factors in the blood and brain tissues.In a well-diffe rentiated,oxygen-glucose deprivation/reoxygenation-induced BV2 cell model of poststroke,LZ-3(100 μM) inhibited the JAK1-STAT6 signaling pathway.LZ-3 regulated microglia/macrophage polarization from the M1 to the M2 type and inhibited microglia/macrophage phagocytosis and migration via the JAK1/STAT6 signaling pathway.To conclude,LZ-3 regulates microglial activation by inhibiting the JAK1/STAT6 sign aling pathway and improves functional recovery post-stroke.

基于漆酶催化的没食子酸酯接枝真丝疏水改性

采用漆酶作为生物催化剂,以没食子酸月桂酯(DG)为单体对真丝进行了疏水改性研究。实验结果表明,在浴比1∶50,温度50℃,pH 4,漆酶用量2 U/mL,单体用量12 mmol/L,Cu^(2+)浓度15 mmol/L,2,6-二甲氧基苯酚(DMP)0.15 mol/L,处理时间5 h条件下,真丝织物可获得较佳接枝率。通过红外光谱(FTIR)、扫描电镜(SEM)、拒水度、接触角、断裂强力等测试,对接枝前后的真丝结构及性能进行分析。结果显示,漆酶催化真丝接枝改性处理对纤维损伤较小,且改性后的真丝织物可获得优异疏水效果。本文将酶催化氧化酪氨酸的酚羟基引发接枝聚合反应的特点与真丝纤维功能改性有机结合,提出了一种天然蛋白纤维改性的新方法。此外,真丝纤维的酶法催化改性整理高效温和、节能环保,可在提高真丝产品品质的同时,降低企业能耗,缓解社会的环保压力,具有重要的应用价值。

发酵饲料对猪肉品质的影响及应用研究进展

发酵饲料作为一种新型绿色环保的功能性饲料,具有提高饲料营养价值、降低抗营养因子含量、改善饲料适口性、有益动物肠道健康、促进动物生长发育、改善动物产品质量和减排环保等特点。文章对发酵饲料的定义和益处进行了简要的概述,重点讨论了其对猪肉品质的影响、机理和其在猪肉生产上的应用,以期为发酵饲料的合理开发与高效应用提供参考。

Effects of dietary protein restriction on muscle fiber characteristics and m TORC1 pathway in the skeletal muscle of growing-finishing pigs

Background： To investigate the effects of dietary crude protein（CP） restriction on muscle fiber characteristics and key regulators related to protein deposition in skeletal muscle, a total of 18 growing-finishing pigs（62.30 ± 0.88 kg）were allotted to 3 groups and fed with the recommended adequate protein（AP, 16 % CP） diet, moderately restricted protein（MP, 13 % CP） diet and low protein（LP, 10 % CP） diet, respectively. The skeletal muscle of different locations in pigs, including longissimus dorsi muscle（LDM）, psoas major muscle（PMM） and biceps femoris muscle（BFM） were collected and analyzed.Results： Results showed that growing-finishing pigs fed the MP or AP diet improved（P 〈 0.01） the average daily gain and feed： gain ratio compared with those fed the LP diet, and the MP diet tended to increase（P = 0.09） the weight of LDM. Moreover, the ATP content and energy charge value were varied among muscle samples from different locations of pigs fed the reduced protein diets. We also observed that pigs fed the MP diet up-regulated（P 〈 0.05） muscular m RNA expression of all the selected key genes, except that myosin heavy chain（My HC） IIb,My HC IIx, while m RNA expression of ubiquitin ligases genes was not affected by dietary CP level. Additionally, the activation of mammalian target of rapamycin complex 1（m TORC1） pathway was stimulated（P 〈 0.05） in skeletal muscle of the pigs fed the MP or AP diet compared with those fed the LP diet.Conclusion： The results suggest that the pigs fed the MP diet could catch up to the growth performance and the LDM weight of the pigs fed the AP diet, and the underlying mechanism may be partly due to the alteration in energy status, modulation of muscle fiber characteristics and m TORC1 activation as well as its downstream effectors in skeletal muscle of different locations in growing-finishing pigs.

Aflatoxin B1, zearalenone and deoxynivalenol in feed ingredients and complete feed from different Province in China

Background： The current study was carried out to provide a reference for monitory of aflatoxin B_1（AFB_1）,zearalenone（ZEN） and deoxynivalenol（DON） contamination in feed ingredients and complete feeds were collected from different Province in China from 2013 to 2015.Methods： A total of 443 feed ingredients, including 220 corn, 24 wheat, 24 domestic distillers dried grains with soluble（DDGS）, 55 bran, 20 wheat shorts and red dog, 37 imported DDGS, 34 corn germ meal and 29 soybean meal as well as 127 complete feeds including 25 pig complete feed（powder）, 90 pig complete feed（pellet）, six duck complete feed and six cattle complete feed were randomly collected from different Province in China,respectively, by high-performance chromatography in combined with UV or fluorescence analysis.Results： The incidence rates of AFB_1, ZEN and DON contamination of feed ingredients and complete feeds were80.8, 92.3 and 93.9 %, respectively. The percentage of positive samples for DON ranged from 66.7 to 100 %.Domestic DDGS and imported DDGS presented the most serious contamination AFB_1, ZEN and DON contamination levels of feeds ranged from 61.5 to 100 %, indicated that serious contamination over the studied 3-year period.Conclusion： The current data provide clear evidence that AFB_1, ZEN and DON contamination of feed ingredients and complete feeds in different Province in China is serious and differs over past 3-year. The use of corn, domestic DDGS, imported DDGS and corn germ meal, which may be contaminated with these three mycotoxins, as animal feed may triggered a health risk for animal. Feeds are most contaminated with DON followed by ZEN and AFB_1.Mycotoxins contamination in feed ingredients and complete feeds should be monitored routinely in China.

Effect of the sonic hedgehog inhibitor GDC-0449 on an in vitro isogenic cellular model simulating odontogenic keratocysts

Odontogenic keratocysts(OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome(NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations(at ～80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog(SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1^(R135 X/+) cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403 C>T(p.R135 X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated 9(Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 R135 X/+heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.

Effects of Dietary Starch Source on Nutrient and Energy Absorption via the Portal Vein of Growing Pigs

Four crossbred （Duroc x Landrace x Yorkshire） boars, weighing an average of 22.40 ± 1.08 kg and fitted with permanent catheters in their portal and mesenteric veins as well as their carotid artery,were utilized in a 4 × 4 latin square design experiment in order to investigate the effects of different starch sources （maize ,brown rice, sticky rice, and resistant starch） on the absorption of energy sources through the portal vein. Portal blood flow averaged 30.68, 28.40, 29.99, and 30. 12 mL/min per kg BW for pigs fed the maize, brown rice, sticky rice, and resistant starch diets, respectively, and did not dif- fer （P 〉 0.05） between treatments. The absorptions of glucose, plasma ammonia, and total amino acids were significantly lower （P 〈 0.05 ） in pigs fed the resistant starch diet than pigs fed the other starch sources. In contrast, significantly （ P 〈 0.05 ） higher amounts of propionate and total volatile fatty acids were absorbed from the portal vein of pigs fed resistant starch than pigs fed diets based on maize, brown rice, or sticky rice. In addition, significantly （P 〈 0.05） more lactic acid was absorbed from the portal vein by pigs fed the sticky rice diet than pigs fed the other three diets. The energy absorbed from the portal vein in the form of glucose and amino-N as well as the total energy absorbed was significantly （P 〈 0.05） lower in pigs fed the resistant starch diet than pigs fed the other three starch sources. In contrast, the amount of energy absorbed in the form of volatile fatty acids was significantly （P 〈 0.05 ） higher in pigs fed resistance starch than pigs fed the other three starch sources. The total energy absorbed through the portal vein as a percentage of the gross energy and digestible energy consumed in pigs fed maize were 50.8% and 54.6%, respectively, which were significantly （P 〈 0.05 ） higher than the values in pigs fed resistant starch （41.5% and 46.6% respectively）. The results indicate that energy is absorbed in different forms and with different utilization efficiencies in the digestive tract of pigs as a result of feeding different starch sources. Starch sources supplying most of their energy in the form of glucose had higher energy utilization efficiencies, while starch sources supplying most of their energy in the form of volatile fatty acids or lactic acid had lower energy utilization efficiencies.

Crosstalk between trace elements and T-cell immunity during early-life health in pigs

With gradual ban on the use of antibiotics, the deficiency and excessive use of trace elements in intestinal health is gaining attention. In mammals, trace elements are essential for the development of the immune system, specifically T-cell proliferation,and differentiation. However, there remain significant gaps in our understanding of the effects of certain trace elements on T-cell immune phenotypes and functions in pigs. In this review, we summarize the specificity, development, subpopulations, and responses to pathogens of porcine T cells and the effects of functional trace elements(e.g., iron, copper, zinc, and selenium) on intestinal T-cell immunity during early-life health in pigs. Furthermore, we discuss the current trends of research on the crosstalk mechanisms between trace elements and T-cell immunity. The present review expands our knowledge of the association between trace elements and T-cell immunity and provides an opportunity to utilize the metabolism of trace elements as a target to treat various diseases.

Biomarkers of malignant transformation in oral leukoplakia:from bench to bedside

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.

Effect of dietary supplementation with protease on growth performance,nutrient digestibility, intestinal morphology, digestive enzymes and gene expression of weaned piglets

This study was conducted to investigate the effect of dietary protease supplementation on the growth performance, nutrient digestibility, intestinal morphology, digestive enzymes and gene expression in weaned piglets. A total of 300 weaned piglets(21 days of age Duroc x Large White x Landrace; initial BW = 6.27 ± 0.45 kg) were randomly divided into 5 groups. The 5 diets were: 1) positive control diet(PC), 2) negative control diet(NC), and 3) protease supplementations, which were 100, 200, and 300 mg per kg NC diet. Results indicated that final BW, ADG, ADFI, crude protein digestibility, enzyme activities of stomach pepsin, pancreatic amylase and trypsin, plasma total protein, and intestinal villus height were higher for the PC diet and the supplementations of 200 and 300 mg protease per kg NC diet than for the NC diet(P < 0.05). Supplementations of 200 and 300 mg protease per kg NC diet significantly increased the ratio of villus height to crypt depth(VH:CD) of duodenum, jejunum and ileum compared with NC diet(P < 0.05). Feed to gain ratio, diarrhea index, blood urea nitrogen, and diamine oxidase were lower for the PC diet and supplementations of 200 and 300 mg protease per kg NC diet than for the NC diet(P < 0.05). Piglets fed the PC diet had a higher peptide transporter 1(PepTl) mRNA abundance in duodenum than piglets fed the NC diet(P < 0.05), and supplementations of 100, 200 and 300 mg protease per kg NC diet increased the PepTl mRNA abundance in duodenum(P < 0.05) comparing with the NC diet. Piglets fed the PC diet had a higher b0,+AT mRNA abundance in jejunum than piglets fed the NC diet(P < 0.05), and supplementations of 200 and 300 mg protease per kg NC diet increased the b0,+AT mRNA abundance in jejunum and ileum comparing with the NC diet(P < 0.05). In summary, dietary protease supplementation increases growth performance in weaned piglets, which may contribute to the improvement of intestinal development, protein digestibility, nutrient transport efficiency, and health status of piglets when fed low digestible protein sources.

Gut microbial profiles and the role in lipid metabolism in Shaziling pigs

Shaziling pig,a Chinese indigenous breed,has been classified as a fatty pig model.However,the gut microbial development and role in lipid metabolism in Shaziling pigs has been rarely reported.Here,we compared the lipid metabolic and microbial profiles at 30,60,90,150,210,and 300 d of age between Shaziling and Yorkshire pigs.Predictably,there were marked differences in the liver lipids(i.e.,cholesterol,glucose,and low-density lipoprotein)and the lipid related expressions(i.e.,SREBP1/2,LXRa/b,DGAT1/2,and FABP1-3)between Shaziling and Yorkshire pigs.Bacteria sequencing in the ileal digesta and mucosa showed that Shaziling pigs had a higher a-diversity and higher abundances of probiotics,such as Lactobacillus johnsonii,Lactobacillus amylovorus,and Clostridium butyricum.Thirty-five differentiated metabolites were further identified in the mucosa between Shaziling and Yorkshire pigs,which were enriched in the carbohydrate,protein,glucose and amino acid metabolism and bile acid biosynthesis.Furthermore,7 differentiated microbial species were markedly correlated with metabolites,indicating the role of gut microbiota in the host metabolism.Next,the role of differentiated L.johnsonii in lipid metabolism was validated in Duroc×Landrace×Yorkshire(DLY)pigs and the results showed that L.johnsonii mono-colonization promoted lipid deposition and metabolism by altering gut microbiota(i.e.,Megasphaera elsdenii and L.johnsonii)and DGAT1/DGAT2/CD36-PPARg gene expressions.In conclusion,Shaziling pigs exhibited different metabolic and microbial profiles compared with Yorkshire pigs,which might have contributed to the diverse metabolic phenotypes,and the significant enrichment of L.johnsonii in Shaziling pigs promoted lipid metabolism and obesity of DLY pigs,which provided a novel idea to improve the fat content of lean pigs.

Low-protein diets supplemented with glutamic acid or aspartic acid ameliorate intestinal damage in weaned piglets challenged with hydrogen peroxide

Glutamic acid(Glu)and aspartic acid(Asp)are acidic amino acids with regulatory roles in nutrition,energy metabolism,and oxidative stress.This study aimed to evaluate the effects of low-protein diets supplemented with Glu and Asp on the intestinal barrier function and energy metabolism in weaned piglets challenged with hydrogen peroxide(H2O2).Forty piglets were randomly divided into 5 groups:NC,PC,PGA,PG,and PA(n=8 for each group).Pigs in the NC and PC groups were fed a low-protein diet,while pigs in the PGA,PG,or PA groups were fed the low-protein diet supplemented with 2.0%Glu+1.0%Asp,2.0%Glu,or 1.0%Asp,respectively.On day 8 and 11,pigs in the NC group were intraperitoneally injected with saline(1 mL/kg BW),while pigs in the other groups were intraperitoneally administered 10%H2O2(1 mL/kg BW).On day 14,all pigs were sacrificed to collect jejunum and ileum following the blood sample collection in the morning.Notably,low-protein diets supplemented with Glu or Asp ameliorated the intestinal oxidative stress response in H2O2-challenged piglets by decreasing intestinal expression of genes(P<0.05)(e.g.,manganese superoxide dismutase[MnSOD],glutathione peroxidase[Gpx]-1,and Gpx-4)encoding oxidative stress-associated proteins,reducing the serum concentration of diamine oxidase(P<0.05),and inhibiting apoptosis of the intestinal epithelium.Glu and Asp supple-mentation attenuated the upregulated expression of energy metabolism-associated genes(such as hexokinase and carnitine palmitoyltransferase-1)and the H2O2-induced activation of acetyl-coenzyme A carboxylase(ACC)in the jejunum and adenosine monophosphate-activated protein kinase-acetyl-ACC signaling in the ileum.Dietary Glu and Asp also ameliorated intestinal barrier damage as indicated by restored intestinal histology and morphology.In conclusion,low-protein diets supplemented with Glu and Asp protected against oxidative stress-induced intestinal dysfunction in piglets,suggesting that this approach could be used as a nutritional regulatory protectant against oxidative stress.

Glutamine in suppression of lipopolysaccharide-induced piglet intestinal inflammation:The crosstalk between AMPK activation and mitochondrial function

The study was conducted to investigate the regulatory mechanism of glutamine(Gln)on intestinal inflammation in an Escherichia coli lipopolysaccharide(E.coli LPS)-induced in vivo and in vitro models.Piglets(n=8)weaned at 21 d of age were fed a basal diet(control and LPS groups)or 1%Gln diet(Gln t LPS group)ad libitum for 4 weeks.On d 22,24,26 and 28,piglets in the LPS and Gln t LPS groups were intraperitoneally injected with E.coli LPS.Intestinal porcine epithelial cells(IPEC-J2)(n=6)induced by LPS were used to assess related mechanisms and compound C was used to inhibit adenosine 50-monophosphate-activated protein kinase(AMPK)activity.Our current results showed that compared with the LPS treatment,the Gln t LPS treatment had better growth performance and greater villus height(P<0.05),and the Gln t LPS treatment reduced the rate of diarrhea by 6.4%(P<0.05);the Gln t LPS treatment decreased serum tumor necrosis factor(TNF-ɑ),interleukin-6(IL-6),Kt,cortisol and insulin levels,whereas increased(P<0.05)serum immunoglobulin M and epidermal growth factor levels;the Gln t LPS treatment increased(P<0.05)the expression of aquaporins and AMPK pathwayassociated targets in the jejunum and ileum of piglets,whereas decreased the expression of ion transporters(P<0.05).The in vitro results showed that 4 mmol/L Gln administration could inhibit(P<0.05)cell apoptosis and interleukin-1b(IL-1b),IL-6 and TNF-ɑsecretion in LPS-induced IPEC-J2 cells,promote(P<0.05)mitochondrial respiratory metabolism and increase(P<0.05)the number of mitochondria and mitochondrial membrane potential.The activity of AMPK was elevated by 70%to 300%in Gln-treated IPEC-J2 cells under LPS challenge or normal conditions.Our results indicate that pre-administration of Gln to piglets suppresses intestinal inflammation by modulating the crosstalk between AMPK activation and mitochondrial function.

The graph limit of the minimizer of the Onsager-Machlup functional and its computation

The Onsager-Machlup(OM)functional is well known for characterizing the most probable transition path of a diffusion process with non-vanishing noise.However,it suffers from a notorious issue that the functional is unbounded below when the specified transition time T goes to infinity.This hinders the interpretation of the results obtained by minimizing the OM functional.We provide a new perspective on this issue.Under mild conditions,we show that although the infimum of the OM functional becomes unbounded when T goes to infinity,the sequence of minimizers does contain convergent subsequences on the space of curves.The graph limit of this minimizing subsequence is an extremal of the abbreviated action functional,which is related to the OM functional via the Maupertuis principle with an optimal energy.We further propose an energy-climbing geometric minimization algorithm(EGMA)which identifies the optimal energy and the graph limit of the transition path simultaneously.This algorithm is successfully applied to several typical examples in rare event studies.Some interesting comparisons with the Freidlin-Wentzell action functional are also made.

NAD^(+) and its possible role in gut microbiota:Insights on the mechanisms by which gut microbes influence host metabolism

Nicotinamide adenine dinucleotide(NAD^(+))is an enzyme cofactor,co-substrate,and redox factor in all living cells and is necessary for maintaining cell metabolism.It has been shown that appropriate supplementation of NAD^(+)precursors or inhibition of NAD^(+)-depleting enzymes can promote mitochondrial oxidative phosphorylation and improve host energy utilization efficiency.In addition,increasing evidence indicates that the gut microbiota plays a pivotal role in host metabolism.Theoretically,there should be a close correlation among NAD^(+),gut microbiota,and host metabolism;however,the information is limited.In this review,we summarize the metabolic process of NAD^(+)and its impact on host metabolism,the link between gut microbiota and host metabolism,as well as the potential effects of NAD^(+)on microbial metabolism,providing a new perspective on the interaction between gut microbiota and host metabolism.

Effectiveness of Implicit Methods for Stiff Stochastic Differential Equations

In this paper we study the behavior of a family of implicit numerical methods applied to stochastic differential equations with multiple time scales.We show by a combination of analytical arguments and numerical examples that implicit methods in general fail to capture the effective dynamics at the slow time scale.This is due to the fact that such implicit methods cannot correctly capture non-Dirac invariant distributions when the time step size is much larger than the relaxation time of the system.

氨基酸转运载体SLC1A3的功能及对神经系统和线粒体功能的调节作用机制研究进展

溶质载体家族1成员3(the solute carrier family 1 member 3 gene,SLC1A3)是一种重要的兴奋性氨基酸转运载体,在动物各组织器官中均有表达,主要负责细胞的酸性氨基酸转运,对动物健康与生长发育具有重要作用.目前关于SLC1A3的研究主要集中于对神经系统的调控以及表达异常造成的相关疾病,而对SLC1A3在其他组织器官中的研究较少.近期研究表明,SLC1A3可负责细胞内胞浆与线粒体之间的谷氨酸和天冬氨酸的转运,以维持线粒体内三羧酸循环和电子传递链的正常运转,促进细胞增殖,恢复细胞功能.本文主要综述了SLC1A3在动物各组织器官中的表达情况及其发挥的生物学功能,并解析了其对神经系统和线粒体功能的调控机制,以期SLC1A3作为关键靶点为调控动物机体健康和疾病治疗提供理论依据.