Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Geometric regulation of collective cell tangential ordering migration

Collective cell migration is a coordinated movement of multi-cell systems essential for various processes throughout life.The collective motions often occur under spatial restrictions,hallmarked by the collective rotation of epithelial cells confined in circular substrates.Here,we aim to explore how geometric shapes of confinement regulate this collective cell movement.We develop quantitative methods for cell velocity orientation analysis,and find that boundary cells exhibit stronger tangential ordering migration than inner cells in circular pattern.Furthermore,decreased tangential ordering movement capability of collective cells in triangular and square patterns are observed,due to the disturbance of cell motion at unsmooth corners of these patterns.On the other hand,the collective cell rotation is slightly affected by a convex defect of the circular pattern,while almost hindered with a concave defect,also resulting from different smoothness features of their boundaries.Numerical simulations employing cell Potts model well reproduce and extend experimental observations.Together,our results highlight the importance of boundary smoothness in the regulation of collective cell tangential ordering migration.

Cooperative UAV search strategy based on DMPC-AACO algorithm in restricted communication scenarios

Improvement of integrated battlefield situational awareness in complex environments involving dynamic factors such as restricted communications and electromagnetic interference(EMI)has become a contentious research problem.In certain mission environments,due to the impact of many interference sources on real-time communication or mission requirements such as the need to implement communication regulations,the mission stages are represented as a dynamic combination of several communication-available and communication-unavailable stages.Furthermore,the data interaction between unmanned aerial vehicles(UAVs)can only be performed in specific communication-available stages.Traditional cooperative search algorithms cannot handle such situations well.To solve this problem,this study constructed a distributed model predictive control(DMPC)architecture for a collaborative control of UAVs and used the Voronoi diagram generation method to re-plan the search areas of all UAVs in real time to avoid repetition of search areas and UAV collisions while improving the search efficiency and safety factor.An attention mechanism ant-colony optimization(AACO)algorithm is proposed for UAV search-control decision planning.The search strategy is adaptively updated by introducing an attention mechanism for regular instruction information,a priori information,and emergent information of the mission to satisfy different search expectations to the maximum extent.Simulation results show that the proposed algorithm achieves better search performance than traditional algorithms in restricted communication constraint scenarios.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Genome-wide association with transcriptomics reveals a shade-tolerance gene network in soybean

Shade tolerance is essential for soybeans in inter/relay cropping systems.A genome-wide association study(GWAS)integrated with transcriptome sequencing was performed to identify genes and construct a genetic network governing the trait in a set of recombinant inbred lines derived from two soybean parents with contrasting shade tolerance.An improved GWAS procedure,restricted two-stage multi-locus genome-wide association study based on gene/allele sequence markers(GASM-RTM-GWAS),identified 140 genes and their alleles associated with shade-tolerance index(STI),146 with relative pith cell length(RCL),and nine with both.Annotation of these genes by biological categories allowed the construction of a protein–protein interaction network by 187 genes,of which half were differentially expressed under shading and non-shading conditions as well as at different growth stages.From the identified genes,three ones jointly identified for both traits by both GWAS and transcriptome and two genes with maximum links were chosen as beginners for entrance into the network.Altogether,both STI and RCL gene systems worked for shade-tolerance with genes interacted each other,this confirmed that shadetolerance is regulated by more than single group of interacted genes,involving multiple biological functions as a gene network.

Paradigm shift in transfusion practices during early COVID-19 pandemic:A single center retrospective study

BACKGROUND The advent of coronavirus disease 2019(COVID-19)unveiled the worst national blood crisis that the United States had witnessed in over a decade.With the pandemic influencing the different stages of the acquisition of blood products outside the hospital setting,we aimed to explore the possible barriers contributing to the shortage of blood products within the medical community.the COVID era and pre-COVID era.METHODS We conducted a retrospective cross-sectional study on hospitalized patients distinguishing the pattern of blood transfusion during the COVID and pre-COVID era in a community hospital.Data was tabulated to include the number of red blood cell(RBC)transfusions and if transfusions met restrictive blood transfusion criteria as per institutional guidelines.Chi-square was applied to test the statistical association between qualitative variables.Unpaired t test and Mann Whitney U test were applied respectively to test the mean difference of quantitative variables.RESULTS A total of 208 patients were included in the study,of which 108 were during COVID era and 100 were during pre-COVID era.The leading reason for admission in both the COVID era and pre-COVID era transfused patients was shortness of breath(53.7%and 36%P=0.001),followed by gastrointestinal bleeding(25.9%and 21%P=0.001).There was a higher percentage of RBC transfusions in the intensive care unit in the COVID-era group than in the pre-COVID era group(38.9%vs 22%,P=0.008).The restrictive transfusion criteria were met in 62%vs 79%in the COVID and pre-COVID eras,respectively(P=0.008).CONCLUSION The COVID-era group received RBC transfusions with less stringent adherence to restrictive blood transfusion practices in comparison to pre-COVID era group.

The Effect of Macronutrient Restrictions on Gut Microbiome and Biochemical Parameters of Wistar Albino Rats

Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.

A Study of Evaluation System of Restricting Factors in Training Students' Qualities

This paper studies evaluation system of restricting factors in training students’ qualities by modern mathematical method of analysis hierarchy process and principal factor analysis, and to build up a mathematical model of evaluation system.

Velocity Form Calculations of Generalized Oscillator Strengths for 3s→ (3p, 4p, 5p, 6p) Dipole Transitions of Atomic Sodium in Debye Plasma

In this paper, the generalized oscillator strengths (GOSs) of excitations of atomic sodium from ground state to 2p63s0 (3p, 4p, 5p, 6p) states, immersed in Debye plasma, were calculated by using wavefunctions which were obtained numerically from the restricted Hartree-Fock (RHF) equation. This RHF equation employs the local density approach for exchange interactions including plasma Debye screening. Theoretical RHF and random phase approximation with exchange (RPAE) velocity calculations have shown that the GOSs for excitations to 3 s0(3 p,4 p,5 p,6 p)depend on the plasma Debye screening effects, as shown by the reduction in the GOS amplitude with decreasing Debye length λD. The agreement between the present RPAE V results for the transitions 3 s→3 s0(3 p,4 p,5 p)and the length calculations of Martínez-Flores was satisfactory. Correlation effects were found quite to be significant in the vicinity of the maxima of the GOS of the 3 s→3 s0(4 p,5 p,6 p)excitations by using the RPAE V approach. We note the poor influence of many electron correlations on the GOS of (3 s→3 p)transition with the same principal quantum number. Finally, we comment that the RPAE V calculations are useful in investigating electron correlation effects on the transition GOS of atomic sodium planted in Debye plasma. The present velocity results also reveal that the 3 s→3 s0(5p, 6p)transition GOSs tend to be delocalized due to more significant screening effects at Debye lengths λD=20and 30 a.u. for excited subshells 5p and 6p, respectively. We report here novel results of GOS for 3 s→3 s06ptransition obtained from different Debye lengths.

A Perturbation Analysis of Low-Rank Matrix Recovery by Schatten p-Minimization

A number of previous papers have studied the problem of recovering low-rank matrices with noise, further combining the noisy and perturbed cases, we propose a nonconvex Schatten p-norm minimization method to deal with the recovery of fully perturbed low-rank matrices. By utilizing the p-null space property (p-NSP) and the p-restricted isometry property (p-RIP) of the matrix, sufficient conditions to ensure that the stable and accurate reconstruction for low-rank matrix in the case of full perturbation are derived, and two upper bound recovery error estimation ns are given. These estimations are characterized by two vital aspects, one involving the best r-approximation error and the other concerning the overall noise. Specifically, this paper obtains two new error upper bounds based on the fact that p-RIP and p-NSP are able to recover accurately and stably low-rank matrix, and to some extent improve the conditions corresponding to RIP.

气象观测场在汽车试验场中的应用研究

汽车试验场作为汽车开展道路测试的重要场所,用于验证汽车产品的品质以及可靠性。除了场地道路外,气象条件作为汽车道路测试的重要一环,在《GB/T12534-1990汽车道路试验方法通则》中也有明确要求,如:试验时应是无雨无雾天气,相对湿度小于95%,气温0-40℃,风速不大于3m/s。同时气象条件也作为试验场道路管控的重要依据,实时风速、雨量、能见度等信息为场地管理者发布限速、限行、封场等通知提供必要参考依据,直接影响道路测试安全管控的及时性。因此,文章从气象观测场的建设、气象服务、异常天气道路管控等方面开展气象观测场在汽车试验场中的应用研究。

Leucocyte telomere length,brain volume and risk of dementia:a prospective cohort study

Background The evidence regarding the association between leucocyte telomere length(LTL)and brain health is sparse and inconclusive.Aims To investigate the associations of LTL with brain structure and the risk of dementia based on a large-scale prospective study.Methods LTL in the peripheral blood was measured by the quantitative polymerase chain reaction(qPCR)assay from 439961 individuals in the UK Biobank recruited between 2006 and 2010 and followed up until 2020.Electronic health records were used to record the incidence of dementia,including Alzheimer’s disease(AD)and vascular dementia(VD).The brain structure,including total and regional brain volume,of 38740 participants was then assessed by magnetic resonance imaging(MRI).Results During a median follow-up of 11.6 years,a total of 5820(1.3%)dementia cases were documented.The restricted cubic spline model showed significant overall associations between LTL and the risk of dementia and AD(p for overall<0.05).The multivariable adjusted hazard ratios(HRs)for the lowest LTL tertile compared with the highest LTL tertile were 1.14(95%confidence interval(CI):1.06 to 1.21)for dementia,1.28(95%CI:1.12 to 1.46)for AD and 1.18(95%CI:0.98 to 1.42)for VD.Furthermore,we found that shorter LTL was associated with smaller total brain volume(β=−0.0128,p=0.003),white matter volume(β=−0.0224,p<0.001),hippocampus volume(β=−0.0172,p<0.001),thalamus volume(β=−0.0239,p<0.001)and accumbens(β=−0.0155,p=0.001).Conclusions Shorter LTL is associated with total and regional brain structure and a higher risk of incident dementia and AD,implying the potential of telomere length as a predictive biomarker of brain health.

Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets

Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,has been reported to effectively attenuate lipid metabolism dysfunctions.Therefore,the objective of this study was to investigate the effects of C.butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.Methods Sixteen IUGR and eight normal birth weight(NBW)neonatal male piglets were used in this study.From d 3to d 24,in addition to drinking milk,the eight NBW piglets(NBW-CON group,n=8)and eight IUGR piglets(IUGR-CON group,n=8)were given 10 mL sterile saline once a day,while the remaining IUGR piglets(IUGR-CB group,n=8)were orally administered C.butyricum at a dose of 2×108colony-forming units(CFU)/kg body weight(suspended in 10 mL sterile saline)at the same frequency.Results The IUGR-CON piglets exhibited restricted growth,impaired hepatic morphology,disordered lipid metabolism,increased abundance of opportunistic pathogens and altered ileum and liver bile acid(BA)profiles.However,C.butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets,characterized by a decreased abundance of opportunistic pathogens in the ileum,including Streptococcus and Enterococcus.The decrease in these bile salt hydrolase(BSH)-producing microbes increased the content of conjugated BAs,which could be transported to the liver and function as signaling molecules to activate liver X receptorα(LXRα)and farnesoid X receptor(FXR).This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol.As a result,the growth performance and morphological structure of the liver improved in the IUGR piglets.Conclusion These results indicate that C.butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes(Streptococcus and Enterococcus).This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRαand FXR.The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.

A Restricted SIR Model with Vaccination Effect for the Epidemic Outbreaks Concerning COVID-19

This paper presents a restricted SIRmathematicalmodel to analyze the evolution of a contagious infectious disease outbreak(COVID-19)using available data.The new model focuses on two main concepts:first,it can present multiple waves of the disease,and second,it analyzes how far an infection can be eradicated with the help of vaccination.The stability analysis of the equilibrium points for the suggested model is initially investigated by identifying the matching equilibrium points and examining their stability.The basic reproduction number is calculated,and the positivity of the solutions is established.Numerical simulations are performed to determine if it is multipeak and evaluate vaccination’s effects.In addition,the proposed model is compared to the literature already published and the effectiveness of vaccination has been recorded.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.