Comprehensive analysis of the gut microbiome and posttranslational modifications elucidates the route involved in microbiota-host interactions

The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

Clinical Effect of Yinhuang Qingfei Capsules in Treatment of Asymptomatic and Mild/Common Severe Acute Respiratory Syndrome Coronavirus 2 Infection:An Analysis of 242 Cases

[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.

Analysis of the genetic interactions between Cyclin A1, Atm and p53 during spermatogenesis

Aim： To analyze the functional interactions of Cyclin with p53 and Atm in spermatogenesis and DNA double- strand break repair. Methods： Two lines of double knockout mice were generated. Spermatogenesis and double strand break repair mechanisms were analyzed in Cyclin A1 （Ccnal）; p53- and Ccnal; Atm-double knockout mice. Results： The block in spermatogenesis observed in Cyclin A1-/- （Ccnal-/-） testes at the mid-diplotene stage is associated with polynucleated giant cells. We found that Ccnal-deficient testes and especially the giant cells accumulate unrepaired DNA double-strand breaks, as detected by immunohistochemistry for phosphorylated H2AX. In addition, the giant cells escape from apoptosis. The development of giant cells occurred in meiotic prophase I, because testes lacking ATM, which are known to develop spermatogenic arrest earlier than prophase I, do not develop giant cells in the absence of cyclin A1. Cyclin A1 interacted with p53 and phosphorylated p53 in complex with CDK2. Interestingly, p53-deficiency significantly increased the number of giant cells in Ccnal-deficient testes. Gene expression analyses of a panel of DNA repair genes in the mutant testes revealed that none of the genes examined were consistently misregulated in the absence of cyclin A1. Conclusion： Ccnal-deficiency in spermatogenesis is associated with defects in DNA double-strand break repair, which is enhanced by loss of p53.

The RNA-binding protein Musashi2 governs osteoblast-adipocyte lineage commitment by suppressing PPARγsignaling

Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells(BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2(Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling.RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.

Expression of NOS and HIF-1αin human colorectal carcinoma and implication in tumor angiogenesis

AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1)αexpression in human colorectal carcinomas. METHODS: The tissue microarrays (TMAs) were made up of 80 cases of colorectal carcinoma and 80 cases of non-neoplasm colorectal mucosa. The expression of CD34, CD105, NOS and HIF-1αwas detected by immunohistochemistry (S-P). RESULTS: iNOS and HIF-1αexpression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa (X2 = 43.166, P < 0.01; X2 = 10.4278, P < 0.01); eNOS expression in colorectal carcinoma was significantly lower than in non-neoplasm colorectal mucosa (X2 = 11.354, P < 0.01). The expression of iNOS correlated with differentiation (X2 = 18.141, P < 0.01), invasive depth (X2 = 4.748, P < 0.01), and Micro vessel density (MVD) (t = 2.327, P < 0.05). The expression of HIF-1αwas correlated with infiltrating depth (X2 = 4.397, P < 0.05), Duke's staging (X2= 4.255, P < 0.05), and MVD (t = 2.272, P < 0.05). No correlation was found in eNOS expression. CONCLUSION: Over-expression of iNOS and HIF-1αin colorectal carcinoma is correlated with the biological character MVD.

DynamicMechanical and Chemorheology Analysis for the Blended Epoxy System with Polyurethane Modified Resin

As the important matrix material,epoxy resin has been widely used in the composites for various fields.On account of the poor toughness of epoxy resin limiting their suitability for advanced applications,considerable interests have been conducted to modify the epoxy resin to meet the engineering requirements.In this study,the bio-based polyurethane(PU)modified resin was adopted to modify the pure bisphenol-A epoxy by blending method with various proportions.Aiming to illuminate the curing behavior,mechanical and thermal properties,the blended epoxy systems were characterized by viscosity-time analysis,dynamic mechanical analysis(DMA)at different frequencies and temperatures,mechanical tensile test,thermogravimetric analysis(TGA)and Fourier transform infrared(FT-IR)spectroscopy.The results indicated that the introduction of PU modified epoxy was found to significantly inhibit the viscosity growth rates especially when the content of PU modified epoxy resin is higher than 60%.Notwithstanding the dynamic modulus and T_(g)reduced with the increment of PU modified epoxy,remarkable increment on the elongation at break was found and the flexibility was greatly promoted with the introduction of PU modified epoxy.The proportion of PU modified epoxy in the blends should be put balance considerations to obtain optimal mechanical properties.TGA results and FTIR spectrum demonstrated that the addition of PU modified epoxy did not change the thermal decomposition mechanism and chemical reaction mechanism,but the addition of PU modified epoxy inhibits the curing reaction of epoxy resin by measured and calculated the damping temperature domain
T from 35.7℃ to 48.9℃.

Stress Field Changes before the <i>M</i>_S8.0 Wenchuan Earthquake

The apparent lack of pre-seismic crustal deformation preceding the 2008 Ms8.0 Wenchuan earthquake has been the subject of debate. In this study, tiltmeter data recorded close to the earthquake epicenter were analysed using spectrum and wavelet analysis. Changes in the stress field before the earthquake were analyzed based on the Benioff creep release and changes in regional Global Navigation Satellite System (GNSS) baselines. The characteris-tics of far- and near-field seismicity and deformation processes were investigated using rock fracture experiments. The results show that during pre-seismic strain energy accumu-lation, there was a synergy between stress field changes both proximal and distal to the ep-icenter;moreover, we identified a strong correlation between Benioff creep release and shortening of the LUZH-GUAN GNSS baseline. During the sub-instability stage, the de-formation characteristics of different structural sectors differed;faults near the epicenter were in a highly locked state, and the deformation rate and wave spectra of main period waves obviously decreased. This reflects fixed point deformation driven by deep stress. These results are of great significance for understanding geophysical field observations, for clarifying pre-seismic deformation and for earthquake prediction.

延长腺相关病毒递送药物的半衰期提高治疗效果

延长基于蛋白质治疗药物的半衰期可以提高药物疗效。然而,基因治疗本质上是长期表达所需的治疗性药物,药物半衰期对基因治疗疗效的影响尚不清楚。在这项腺相关病毒(adeno-associated virus,AAV)基因治疗研究中,通过与免疫球蛋白G1(immunoglobulin G 1,IgG1)可溶性单体Fc区(soluble monomeric IgG1 fragment crystallizable,sFc)或Fc区融合,设计了几种能够延长半衰期的蛋白质。研究表明,延长AAV递送的小分子双功能蛋白和成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)的半衰期显著增加了它们在血液循环中的浓度。此外,AAV递送FGF21延长其半衰期使2型糖尿病动物模型中肝损伤和血糖显著降低,并改善了葡萄糖耐量和胰岛素敏感性。这些结果证明了延长药物半衰期的基因治疗在应对人类疾病中的治疗潜力。

Identification of ferroptosis-associated tumor antigens as the potential targets to prevent head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma(HNSC)represents nearly 90%of all head and neck tumors.The current treatment modality for HNSC patients primarily involves surgical intervention and radiotherapy,but its therapeutic efficacy remains limited.The mRNA vaccine based on tumor antigens seems promising for cancer treatment.Ferroptosis,a novel form of cell death,is linked to tumor progression and cancer immunotherapy.Nevertheless,the effectiveness of ferroptosis-associated tumor antigens in treating HNSC remains uncertain.In this study,we identified three ferroptosis-associated tumor antigens,namely caveolin1(CAV1),ferritin heavy chain(FTH1),and solute carrier 3A2(SLC3A2),as being overexpressed and mutated based on data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases.These antigens were strongly associated with poor prognosis and infiltration of antigen-presenting cells in HNSC.We further identified two ferroptosis subtypes(FS1 and FS2)with distinct molecular,cellular,and clinical properties to identify antigen-sensitive individuals.Our findings indicate that FS1 exhibits an immune“hot”phenotype,whereas FS2 displays an immune“cold”phenotype.Additionally,differential expression of immunogenic cell death modulators and immune checkpoints was observed between these two immune subtypes.Further exploration of the HNSC's immune landscape revealed significant heterogeneity among individual patients.Our findings suggest that CAV1,FTH1,and SLC3A2 are potential targets to prevent HNSC in FS2 patients.Overall,our research reveals the potential of ferroptosis-associated mRNA vaccines for HNSC and identifies an effective patient population for vaccine treatment.

脱落酸对水稻抽穗开花期高温胁迫的诱抗效应

为探究脱落酸(ABA)对水稻(Oryza sativa)抽穗开花期高温胁迫的诱抗效应,以江西省主推水稻品种黄华占为材料,于孕穗期用蒸馏水、ABA溶液(10、50和100µmol·L^(-1))、氟啶酮(FLU)和原花青素(PC)6种溶液进行叶面喷施,然后移入对照(CK)和高温胁迫(HS)环境处理8天,考查籽粒活性氧(ROS)积累、抗氧化防御能力、产量构成及相关基因的表达。结果表明,高温胁迫下,水稻的穗长、穗重、结实率、千粒重和产量与超氧阴离子和过氧化氢含量呈显著负相关。高温胁迫下,喷施ABA显著上调了ABA应答和抗氧化防御基因的表达,籽粒中活性氧含量下降了8.24%-31.35%;喷施ABA显著增加了水稻的穗长、穗重、结实率和千粒重,显著上调了产量形成基因的表达,增产12.73%-20.77%。高温胁迫下,喷施FLU可抑制ABA的生物合成,导致ROS过量积累和水稻减产;喷施抗氧化剂PC则抑制ROS过量积累,使产量增加。以上结果表明,高温胁迫下,孕穗期喷施ABA不仅能够激发ABA信号通路,而且上调抗氧化防御能力和产量形成基因的表达,进而提高水稻在抽穗开花期的耐热性,达到增产目的。

Wnt and BMP signaling crosstalk in regulating dental stem cells:Implications in dental tissue engineering

Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

OUTSOURCE TO AN OEM OR AN ODM？ PROFITABILITY AND SUSTAINABILITY ANALYSIS OF A FASHION SUPPLY CHAIN

Consider a fashion supply chain comprising a supplier, a contract manufacturer and a fashion brand, we examine the fashion brand＇s profit performances when the contract manufacturer is either an OEM （having no design capability） or an ODM （having design capability）. Regarding OEM, the fashion brand designs the products, outsources the manufacturing function, and has the option of outsourcing procurement function. Regarding ODM, the fashion brand buys unlabeled products from the ODM, which is charge of designing and manufacturing. In this case, buy-back contract is widely adopted so as to share the risk of demand uncertainty between the ODM and the fashion brand. We solve the wholesale pricing problems via sequential/simultaneous optimization, and derive the buy-back price via generalize Nash bargaining. We find that, fashion brand prefers contracting with an ODM when its bargaining power in buy-back negotiation is larger than a threshold, although the fashion brand＇s order size under ODM is always larger than that under OEM. Interestingly, we find that the buy-back price is decreasing in the fashion brand＇s bargaining power. We further analyze the supply chain sustainability in both ODM and OEM scenarios, fmding that the supply chain might achieve both environmental sustainability and economic sustainability in OEM scenario when the fashion brand＇s bargaining power in buy-back negotiation is small.

Activity Recognition with Smartphone Sensors

The ubiquity of smartphones together with their ever-growing computing,networking,and sensing powers have been changing the landscape of people＇s daily life.Among others,activity recoginition,which takes the raw sensor reading as inputs and predicts a user＇s motion activity,has become an active research area in recent years.It is the core building block in many high-impact applications,ranging from health and fitness monitoring,personal biometric signature,urban computing,assistive technology,and elder-care,to indoor localization and navigation,etc.This paper presents a comprehensive survey of the recent advances in activity recognition with smartphones＇ sensors.We start with the basic concepts such as sensors,activity types,etc.We review the core data mining techniques behind the main stream activity recognition algorithms,analyze their major challenges,and introduce a variety of real applications enabled by activity recognition.

Cooperative Sensor Anomaly Detection Using Global Information

Sensor networks are deployed in many application areas nowadays ranging from environment monitoring, industrial monitoring, and agriculture monitoring to military battlefield sensing. The accuracy of sensor readings is without a doubt one of the most important measures to evaluate the quality of a sensor and its network. Therefore, this work is motivated to propose approaches that can detect and repair erroneous （i.e., dirty） data caused by inevitable system problems involving various hardware and software components of sensor networks. As information about a single event of interest in a sensor network is usually reflected in multiple measurement points, the inconsistency among multiple sensor measurements serves as an indicator for data quality problem. The focus of this paper is thus to study methods that can effectively detect and identify erroneous data among inconsistent observations based on the inherent structure of various sensor measurement series from a group of sensors. Particularly, we present three models to characterize the inherent data structures among sensor measurement traces and then apply these models individually to guide the error detection of a sensor network. First, we propose a multivariate Gaussian model which explores the correlated data changes of a group of sensors. Second, we present a Principal Component Analysis （PCA） model which captures the sparse geometric relationship among sensors in a network. The PCA model is motivated by the fact that not all sensor networks have clustered sensor deployment and clear data correlation structure. Further, if the sensor data show non-linear characteristic, a traditional PCA model can not capture the data attributes properly. Therefore, we propose a third model which utilizes kernel functions to map the original data into a high dimensional feature space and then apply PCA model on the mapped linearized data. All these three models serve the purpose of capturing the underlying phenomenon of a sensor network from its global view, and then guide the error detection to discover any anomaly observations. We conducted simulations for each of the proposed models, and evaluated the performance by deriving the Receiver Operating Characteristic （ROC） curves.

Vascular disrupting agent-induced amplification of tumor targeting and prodrug activation boosts anti-tumor efficacy

Vadimezan,one of the typical vascular disrupting agents(VDAs) currently in clinical trials,has been extensively implemented for cancer research,whereas its clinical efficacy is adversely affected by the inevitable side effects.Inspired by Vadimezaninduced intratumoral coagulation activation and hypoxia aggravation,we report a strategy by utilizing these biological effects to achieve targeted delivery and activation of hypoxia-activated prodrug(HAP) thus to maximize the therapeutic effect of Vadimezan.By encapsulating HAP tirapazamine into poly(lactic-co-glycolic acid)(PLGA) nanocarriers along with the modification of clot-binding peptide,the obtained nanoplatform could target tumors under the coagulation activation effect of Vadimezan.Meanwhile,the aggravated hypoxia tumor microenvironment induced by Vadimezan can also boost hypoxia-activated chemotherapy.In the murine tumor model,this strategy showed 80.0% suppression of tumor growth,indicating its great potential in tumor treatment.This study offers an ingenious tactic for the combination of vascular disrupting therapy and hypoxia-activated chemotherapy,which may open up a window of the VDAs-based combination therapy.

Transport of a volatile contaminant in a free-surface wetland flow

Presented in this paper is an analytical study of a pulsed volatile contaminant emission into a free-surface wetland flow. A simplified model is given for contaminant transport under the combined action of advection, mass dispersion, apparent reaction, and volatilization at the free water surface. The effect of periodic apparent reaction on contaminant transport is separated from the hydraulic effect via an extended transformation, with a limiting case covering the known transformation for constant apparent reaction rate. The analytical solutions of zeroth and first order concentration moments are rigorously derived and illustrated. It was found that the amount of contaminant decreases from the bottom bed to the free-surface under volatilization, and the total amount of contaminant decays with time. It was also found that the moving speed of the mass center of the whole contaminant cloud increases, as the ratio of volatilization coefficient to vertical effective mass dispersivity increases.

A Primal-dual Large-update Interior-point Algorithm for P_*(κ)-LCP Based on a New Class of Kernel Functions

In this paper, we propose a large-update primal-dual interior point algorithm for P_＊（κ）-linear complementarity problem. The method is based on a new class of kernel functions which is neither classical logarithmic function nor self-regular functions. It is determines both search directions and the proximity measure between the iterate and the center path. We show that if a strictly feasible starting point is available, then the new algorithm has O（1 ＋ 2κ）p√n（1/plog n ＋ 1）^2 lognε iteration complexity which becomes O（（1 ＋ 2κ）√nlog n logn/ε）with special choice of the parameter p. It is matches the currently best known iteration bound for P＊（κ）-linear complementarity problem. Some computational results have been provided.

Efficient scarless skin regeneration enabled by loading micronized amnion in a bioinspired adhesive wound dressing

Complete skin reconstruction is a hierarchical,physiological assembly process involving healing of the epidermis,dermis,vasculature,nerves,and cutaneous appendages.To date,few works have reported complete skin regeneration,particularly lacking vascular structures and hair follicles after full skin defects.In this study,a hydrogel derived from the skin secretion of Andrias davidianus(SSAD)that features adhesiveness was used as a bioactive scaffold to load micronized amnion(MA).The SSAD hydrogel was found to promote the migration and proliferation of amnion stem cells and human keratinocytes,as well as inhibit their apoptosis in vitro.In a rat full-skin defect model,the regeneration of skin appendages was observed at the wound area,achieving scarless healing.Transcriptome analyses further validated that SSAD could positively regulate cell migration,proliferation,and differentiation.These functions might be attributed to the abundant growth factors present in the SSAD.Synergized by the delivery of MA,SSAD loaded with the MA could achieve a significantly better skin regeneration effect than SSAD or MA used alone,providing a simple yet highly effective means to obtain complete,scarless skin regeneration,suggesting favorable potential for clinical translation.