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Introduction: Hair loss is one of the common clinical conditions in modern society. Although it is not a serious disease that threatens human life, it brings great mental stress and psychological burden to patients. This study investigated the role of dendrobium officinale polysaccharide (DOP) in hair follicle regeneration and hair growth and its related mechanisms. Methods: After in vitro culture of mouse antennal hair follicles and mouse dermal papilla cells (DPCs), and mouse vascular endothelial cells (MVECs), the effects of DOP upon hair follicles and cells were evaluated using multiple methods. DOP effects were evaluated by measuring tentacle growth, HE staining, immunofluorescence, Western blot, CCK-8, ALP staining, tube formation, scratch test, and Transwell. LDH levels, WNT signaling proteins, and therapeutic mechanisms were also analyzed. Results: DOP promoted tentacle hair follicle and DPCs growth in mice and the angiogenic, migratory and invasive capacities of MVECs. Meanwhile, DOP was also capable of enhancing angiogenesis and proliferation-related protein expression. Mechanistically, DOP activated the WNT signaling and promoted the expression level of β-catenin, a pivotal protein of the pathway, and the pathway target proteins Cyclin D1, C-Myc, and LDH activity. The promotional effects of DOP on the biological functions of DPCs and MVECs could be effectively reversed by the WNT signaling pathway inhibitor IWR-1. Conclusion: DOP advances hair follicle and hair growth via the activation of the WNT signaling. This finding provides a mechanistic reference and theoretical basis for the clinical use of DOP in treating hair loss.

Improving the number of amino acids and unsaturated fatty acids in the diet is a good way to raise the quality of the meat. Currently, most research on the quality of broiler meat focuses on genetic traits; nevertheless, it is unclear how meat quality is regulated. This experiment was conducted to investigate the effects of different supplemental levels of walnut meal (WM) on growth performance, amino acid and fatty acid composition, microbial composition, and meat quality of white feather broilers. 1 week old white feather broilers (n = 120; Body weight 83.76 ± 2.32 g), were randomly divided into 3 treatments and 4 replicates. Walnut meal of basic diet (CK), 5 %(WM-L) and 10 %(WM-H) were added to the diets of white feather broilers, respectively. The results showed that walnut meal could increase L* 24 h (24 h brightness) of breast muscle of white feathered broilers (p

In the present study, in-situ TiN ceramic particles were introduced into Ti–V–Al based shape memory alloys to optimize mechanical properties and friction resistance. The results revealed that increasing the TiN content resulted in the transition from α'' to β phase, and led to a reduction in the martensitic transformation temperature. Additionally, the TiN ceramic particles were found to significantly reduced the grain size of the Ti–V–Al based shape memory alloys. Compared to other Ti–V–Al-X shape memory alloys, the introduction of TiN ceramic particles enhanced the mechanical and wear properties of the Ti–V–Al shape memory alloy. These improvements can be attributed to a combination of solid solution strengthening, grain refinement and precipitation strengthening. Notably, the (Ti–V–Al)100-xNx shape memory alloy exhibited a maximum yield strength of 568 MPa and a fracture strength of 788 MPa. Furthermore, the micro-hardness of the Ti–V–Al based shape memory alloy increased monotonously from 355HV to 393HV, while the wear coefficient steadily decreased from 0.53 to 0.48. In conclusion, by adjusting content of TiN ceramic particles, it is possible to obtain a lightweight Ti–V–Al shape memory alloy with tailored martensitic transformation temperatures, enhanced strength and hardness, as well as excellent friction properties.

Hematopoietic stem progenitor cells (HSPCs) are derived from a specialized subset of endothelial cells named hemogenic endothelial cells (HECs) via a process of endothelial-to-hematopoietic transition during embryogenesis. Recently, with the usage of multiple single-cell technologies and advanced genetic lineage tracing techniques, namely, “TIF” approaches that combining transcriptome, immunophenotype and function/fate analyses, massive new insights have been achieved regarding the cellular and molecular evolution underlying the emergence of HSPCs from embryonic vascular beds. In this review, we focus on the most recent advances in the enrichment markers, functional characteristics, developmental paths, molecular controls, and the embryonic site-relevance of the key intermediate cell populations bridging embryonic vascular and hematopoietic systems, namely HECs and pre-hematopoietic stem cells, the immediate progenies of some HECs, in mouse and human embryos. Specifically, using expression analyses at both transcriptional and protein levels and especially efficient functional assays, we propose that the onset of Kit expression is at the HEC stage, which has previously been controversial.

The presence of antioxidant peptides in cooked foxtail millet prolamin (CFMP) is pivotal for its ability to mitigate oxidative stress and subsequently exert an anti-diabetic effect. However, the alterations in structural characteristics and antioxidant activities of foxtail millet prolamin following cooking remain unclear. Furthermore, the identification of antioxidant peptides in CFMP targeting myeloperoxidase (MPO), a key enzyme implicated in oxidative stress, has yet to be achieved. This study aims to examine the changes in physicochemical, digestibility, and antioxidant properties of foxtail millet prolamin post-cooking, and to identify potential antioxidant peptides from CFMP targeting MPO. The findings revealed significant reductions in water and oil holding capacities, foaming and emulsifying capacities, surface hydrophobicity, and zeta potential of foxtail millet prolamin after cooking, along with a notable increase in average particle size, indicative of protein molecule aggregation and increased resistance to digestion. Three potential antioxidant peptides (IFVFPSGAG, MMFPM, and VLIPMP) were identified in CFMP hydrolysate. Molecular dynamic simulation demonstrated favorable binding interactions between all three peptides and MPO, primarily mediated by hydrogen bonds. In vitro antioxidant activity assays confirmed IFVFPSGAG as the most potent antioxidant peptide. This study sheds light on the properties of CFMP and the antioxidant potential of its derived peptides.

Age-related functional deterioration in skeletal muscle raises the risk for falls, disability, and mortality in the elderly, particularly in obese people or those with type 2 diabetes mellitus (T2D). However, the response of the skeletal muscle to transitioning from obesity to diabetes remains poorly defined, despite that obesity is classified as a stage of pre-diabetes. We screened and selected spontaneously obese and diabetic rhesus monkeys and examined altered protein expression in skeletal muscle of healthy aging (CON), obesity aging (OB), and type 2 diabetes mellitus aging (T2D) rhesus monkeys using Tandem Mass Tags (TMT)-based quantitative proteomic analysis. In total, we identified 142 differentially expressed proteins. Muscle-nerve communication proteins were firstly suppressed at obese-stage. With the disintegration of skeletal muscle, mitochondrial complex I and other energy homeostasis relate proteins were significantly disordered at T2D stage. Indicating that aging related obesity suppressed muscle-nerve communication and contribute to T2D related functional deterioration of skeletal muscles in elderly rhesus monkeys. Some alterations of muscular functional regulator are detected in both obesity and T2D samples, suggesting some T2D related skeletal muscular hypofunctions are occurring at obesity or pre-obesity stage. Muscle-nerve communication proteins and muscular function related proteins could be potential therapy target or early diagnose marker of for skeletal muscular hypofunctions in aging obesity populations.

Abstract The investigation of image deblurring techniques in dynamic scenes represents a prominent area of research. Recently, deep learning technology has gained extensive traction within the field of image deblurring methodologies. However, such methods often suffer from limited inherent interconnections across various hierarchical levels, resulting in inadequate receptive fields and suboptimal deblurring outcomes. In U-Net, a more adaptable approach is employed, integrating diverse levels of features effectively. Such design not only significantly reduces the number of parameters but also maintains an acceptable accuracy range. Based on such advantages, an improved U-Net model for enhancing the image deblurring effect was proposed in the present study. Firstly, the model structure was designed, incorporating two key components: the MLFF (multilayer feature fusion) module and the DMRFAB (dense multi-receptive field attention block). The aim of these modules is to improve the feature extraction ability. The MLFF module facilitates the integration of feature information across various layers, while the DMRFAB module, enriched with an attention mechanism, extracts crucial and intricate image details, thereby enhancing the overall information extraction process. Finally, in combination with fast Fourier transform, the FRLF (Frequency Reconstruction Loss Function) was proposed. The FRLF obtains the frequency value of the image by reducing the frequency difference. The present experiment results reveal that the proposed method exhibited higher-quality visual effects. Specifically, for the GoPro dataset, the PSNR (peak signal-to-noise ratio) reached 31.53, while the SSIM (structural similarity index) attained a value of 0.948. Additionally, for the Real Blur dataset, the PSNR achieved 31.32, accompanied by an SSIM score of 0.934.

Introduction The widespread application of extracorporeal membrane oxygenation (ECMO) has enhanced clinical outcomes for patients experiencing cardiac arrest. However, its effectiveness is still limited and falls short of the desired level. Therapeutic hypothermia, which maintains body temperatures between 32°C and 36°C in cardiac arrest patients treated with ECMO, has been proposed as a potential means of neuroprotection and increased survival rates. Nevertheless, it remains controversial, and its impact on patient complications has yet to be fully understood. Thus, this paper aims to update the protocol for a systematic review of patients treated with ECMO and therapeutic hypothermia, in order to explore its effects on survival and neurological function.Method and analysis This protocol has been developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015. The following databases will be systematically searched: PubMed, Web of Science, Cochrane Library, Embase, Ovid, CNKI, Wanfang and China Biology Medicine Disc. The database search strategy will use a combination of subject terms and free-text keywords. The search will encompass articles from the inception of each database up to 15 June 2023. Inclusion criteria encompass randomised controlled trials, cohort studies, case–control studies and quasi-experimental studies. Two researchers will independently review articles and extract relevant data based on these criteria. Any disagreements will be resolved through discussion. Data analysis will be performed using Review Manager software.Ethics and dissemination Since no patient data were collected in this study, ethical approval was not required. Research findings will be released in a peer-reviewed journal.PROSPERO registration number CRD42023435353.

Daylily is a functional food with high nutritional value in China. Datong (DT) in Shanxi Province is one of the four main production areas of daylily. Therefore, Linfen (LF), Lvliang (LL), and Yangquan (YQ) in Shanxi Province have also introduced daylily from DT. However, geographical and climatic conditions and producing patterns cause variations in the daylily quality. In the present study, we found that the nutrient composition of daylilies from different producing areas of Shanxi Province varied. The key environmental factors affecting the nutrition of daylily in different regions were altitude and temperature. The widely targeted metabolomics results showed that 1642 metabolites were found in daylily. The differential metabolites between DT and YQ, LL and LF were 557, 667, and 359, respectively. Notably, 9 metabolic pathways and 59 metabolite markers were associated with daylily from different areas. This study provides a theoretical basis for the quality maintenance and health efficacy research of daylily.

BackgroundSerious games have emerged as an innovative educational strategy with the potential to significantly enhance the quality and effectiveness of cardiopulmonary resuscitation (CPR) training. Despite their promise, there remains a degree of controversy when comparing the advantages of serious games with traditional CPR training methods. This study seeks to provide a comprehensive assessment of the impact of serious games on CPR training and education by systematically analyzing the results of previous research. ObjectiveThis study aimed to assess the effect of serious games on CPR training and education by summarizing and pooling the results of previous studies. MethodsWe conducted a thorough and systematic search across 9 prominent web-based databases, encompassing the period from the inception of these databases until April 1, 2023. The databases included in our search were PubMed, Cochrane Library, Wiley Online Library, EBSCO (PsycInfo), SpringerLink, Chinese Biology Medicine Disc, Vip Journal Integration Platform, Wanfang Database, and Chinese National Knowledge Infrastructure. The studies selected adhered to the following criteria: (1) being a randomized controlled trial comparing serious games and traditional methods for CPR training; (2) having participants aged 12 years or older in CPR; (3) having an experimental group using serious games and a control group using nongame methods for CPR instruction; and (4) having outcomes including theoretical and skill assessments, compression depth, and rate. The Cochrane risk of bias assessment tool was used to evaluate the risk of bias. Data analysis was performed using RevMan (version 5.3; Cochrane Training), and mean differences (MDs) and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables. ResultsA total of 9 articles were included, involving 791 study participants, of whom 395 in the experimental group taught CPR training using serious games and 396 in the control group taught CPR training using traditional methods. The results of our meta-analysis indicate that the use of serious games in CPR training yields outcomes that are comparable in effectiveness to traditional training methods across several key areas. Specifically, serious games demonstrated equivalence to traditional formats in theory assessment (SMD –0.22, 95% CI – 0.96 to 0.51; P=.55), skill assessment (SMD –0.49, 95% CI –1.52 to 0.55; P=.36), compression depth (MD –3.17, 95% CI –0.18 to 6.53; P=.06), and compression rate (MD –0.20, 95% CI –7.29 to 6.89; P=.96). ConclusionsIn summary, serious games offer a viable and effective CPR education approach, yielding results comparable to traditional formats. This modality is a valuable addition to CPR training methodologies. However, caution is warranted in interpreting these findings due to limited controlled trials, small sample sizes, and low-quality meta-analyzed evidence.

In the present work, minor Sc addition was employed to control the microstructural features, further optimizing the mechanical/functional performances of Ti–V–Al based shape memory alloy. The results revealed that phase constituents of Ti–V–Al based shape memory alloys were dominated by single αˊˊ martensite phase, regardless of Sc content. Nevertheless, Sc addition caused the significant lattice distortion of Ti–V–Al based shape memory alloy. Meanwhile, the grain size of Ti–V–Al based shape memory alloys were reduced due to Sc addition. Besides, the martensite morphologies evolved from self-accommodation configuration to optimal orientation configuration, but the types of twins kept unchanged. All Ti–V–Al based shape memory alloys showed the reversible αˊˊ→β martensitic transformation in heating curves, irrespective of Sc content. With Sc content increasing, the martensitic transformation temperatures increased linearly due to the chemical composition effect and mechanical effect. Moderate Sc addition was favor to the improvement of thermal cycling stability of Ti–V–Al based shape memory alloys, which can enhance its functional stability. In proportion, the mechanical and functional properties of Ti–V–Al based shape memory alloys firstly increased and then decreased. Ti–V–Al based shape memory alloy with moderate Sc content of 0.025 at.% possess the higher fracture strength of 748.4 MPa, superior ductility of 18.7% and the larger shape memory effect strain of 4.31% under the 8% pre-strain condition. The higher performances in Ti–V–Al shape memory alloy with 0.025 at.% Sc can be attributed to the compressive effect of solution strengthening and grain refinement.

Moringa oleifera addition to animal diets can improve the growth performance, intestinal health, and immunity of animals, without adverse effects. We investigated the effects of Moringa oleifera on the growth performance, meat quality, and intestinal health of broilers. Moringa oleifera and fermented Moringa oleifera could improve the flesh color and breast muscle tenderness of broilers (p

Hemp is an environmentally friendly porous fiber, and has good sound absorption properties, which can be used to reduce noise. In recent years, hemp-based composites have been widely studied, but most of them study the preparation methods of materials, Therefore, this paper studies the topic. Firstly, the material and specimens with different thickness and diameter were prepared, then, the standing wave tube method experiment was carried out, and the values of sound absorption coefficient of the specimens were measured and analyzed, while a novel model using genetic algorithm and artificial neural network is proposed. Secondly, the artificial neural network structure was designed, and the training data, verification data, test data are divided and the data is preprocessed. Thirdly, improved genetic algorithm is proposed to design to determine an optimal solution. Fourthly, the optimal solution was as the initial weight and threshold, and were input into the artificial neural network together with training data and verification data. Levenberg Marquardt algorithm were used to train the network. Finally, input the test data into the trained network to test the model. The results showed that there is only a minor deviation between the model output values and the measured values, the values of sound absorption coefficient of specimens with 10 mm thickness are between 0.9 and 1. It was also found that compared with artificial neural network model without genetic algorithm, the proposed model has the lower root mean squared error (RMSE) value, the larger coefficient of determination (R2) value.

The effect of V addition on the microstructural evolution, martensitic transformation behaviors and mechanical performances of Ti–Ni–Nb shape memory alloys was systematically investigated. The results reveal that the phase remains almost equal in Ti–Ni–Nb–V shape memory alloys, irrespective of the V content. With increasing V content, the amount of β-Nb phase is increased, which further leads to a reduction in the interspace and width of the β-Nb phase. When the V content changes, Ti–Ni–Nb–V shape memory alloys possess a single stage B2⇌B19´ martensitic transformation. In addition, the martensitic transformation temperatures first increase and then decrease owing to the variation in the chemical composition of the TiNi matrix and microstructural features as the V content increases. The higher yield strength of Ti–Ni–Nb shape memory alloys can be obtained by adding a moderate V content. In conclusion, the lower martensitic transformation temperature and the higher yield strength can be tailored by optimizing the V content in Ti–Ni–Nb shape memory alloys, which would further widen their application fields.

Summary: The mammalian target of rapamycin complex1 (mTORC1) is a central regulator of metabolism and cell growth by sensing diverse environmental signals, including amino acids. The GATOR2 complex is a key component linking amino acid signals to mTORC1. Here, we identify protein arginine methyltransferase 1 (PRMT1) as a critical regulator of GATOR2. In response to amino acids, cyclin-dependent kinase 5 (CDK5) phosphorylates PRMT1 at S307 to promote PRMT1 translocation from nucleus to cytoplasm and lysosome, which in turn methylates WDR24, an essential component of GATOR2, to activate the mTORC1 pathway. Disruption of the CDK5-PRMT1-WDR24 axis suppresses hepatocellular carcinoma (HCC) cell proliferation and xenograft tumor growth. High PRMT1 protein expression is associated with elevated mTORC1 signaling in patients with HCC. Thus, our study dissects a phosphorylation- and arginine methylation-dependent regulatory mechanism of mTORC1 activation and tumor growth and provides a molecular basis to target this pathway for cancer therapy.

Summary: Elucidating the mechanisms of resistance to immunotherapy and developing strategies to improve its efficacy are challenging goals. Bioinformatics analysis demonstrates that high CDK6 expression in melanoma is associated with poor progression-free survival of patients receiving single-agent immunotherapy. Depletion of CDK6 or cyclin D3 (but not of CDK4, cyclin D1, or D2) in cells of the tumor microenvironment inhibits tumor growth. CDK6 depletion reshapes the tumor immune microenvironment, and the host anti-tumor effect depends on cyclin D3/CDK6-expressing CD8+ and CD4+ T cells. This occurs by CDK6 phosphorylating and increasing the activities of PTP1B and T cell protein tyrosine phosphatase (TCPTP), which, in turn, decreases tyrosine phosphorylation of CD3ζ, reducing the signal transduction for T cell activation. Administration of a PTP1B and TCPTP inhibitor prove more efficacious than using a CDK6 degrader in enhancing T cell-mediated immunotherapy. Targeting protein tyrosine phosphatases (PTPs) might be an effective strategy for cancer patients who resist immunotherapy treatment.

Abstract In the aorta of mid‐gestational mouse embryos, a specialized endothelial subpopulation termed hemogenic endothelial cells (HECs) develops into hematopoietic stem and progenitor cells (HSPCs), through a conserved process of endothelial‐to‐hematopoietic transition (EHT). EHT is tightly controlled by multiple intrinsic and extrinsic mechanisms. Nevertheless, the molecular regulators restraining this process remain poorly understood. Here, it is uncovered that, one of the previously identified HEC signature genes, Nupr1, negatively regulates the EHT process. Nupr1 deletion in endothelial cells results in increased HSPC generation in the aorta‐gonad‐mesonephros region. Furthermore, single‐cell transcriptomics combined with serial functional assays reveals that loss of Nupr1 promotes the EHT process by promoting the specification of hematopoiesis‐primed functional HECs and strengthening their subsequent hematopoietic differentiation potential toward HSPCs. This study further finds that the proinflammatory cytokine, tumor necrosis factor α (TNF‐α), is significantly upregulated in Nupr1‐deficient HECs, and the use of a specific TNF‐α neutralizing antibody partially reduces excessive HSPC generation in the explant cultures from Nupr1‐deficient embryos. This study identifies a novel negative regulator of EHT and the findings indicate that Nupr1 is a new potential target for future hematopoietic stem cell regeneration research.

Objectives. Prediction models for the return of spontaneous circulation (ROSC) in patients with cardiac arrest play an important role in helping physicians evaluate the survival probability and providing medical decision-making reference. Although relevant models have been developed, their methodological rigor and model applicability are still unclear. Therefore, this study aims to summarize the evidence for ROSC prediction models and provide a reference for the development, validation, and application of ROSC prediction models. Methods. PubMed, Cochrane Library, Embase, Elsevier, Web of Science, SpringerLink, Ovid, CNKI, Wanfang, and SinoMed were systematically searched for studies on ROSC prediction models. The search time limit was from the establishment of the database to August 30, 2022. Two reviewers independently screened the literature and extracted the data. The PROBAST was used to evaluate the quality of the included literature. Results. A total of 8 relevant prediction models were included, and 6 models reported the AUC of 0.662–0.830 in the modeling population, which showed good overall applicability but high risk of bias. The main reasons were improper handling of missing values and variable screening, lack of external validation of the model, and insufficient information of overfitting. Age, gender, etiology, initial heart rhythm, EMS arrival time/BLS intervention time, location, bystander CPR, witnessed during sudden arrest, and ACLS duration/compression duration were the most commonly included predictors. Obvious chest injury, body temperature below 33°C, and possible etiologies were predictive factors for ROSC failure in patients with TOHCA. Age, gender, initial heart rhythm, reason for the hospital visit, length of hospital stay, and the location of occurrence in hospital were the predictors of ROSC in IHCA patients. Conclusion. The performance of current ROSC prediction models varies greatly and has a high risk of bias, which should be selected with caution. Future studies can further optimize and externally validate the existing models.

In the present study, the effects of annealing temperature on the microstructure, martensitic transformation and mechanical properties of Ti–V–Al-Gd shape memory alloys were investigated. The results revealed that the phase constituents were dependent on annealing temperatures. The coexistence of the α'´ martensite phase, β phase, hard α second phase and ω phase was found in Ti–V–Al-Gd shape memory alloy annealed at 650 °C. With increasing annealing temperature, the amount of β phase and α second phase gradually decreased. Meanwhile, the grain size of the Ti–V–Al-Gd shape memory alloy increased continuously with increasing annealing temperature. Merely α'´→β reverse martensitic transformation was found in all annealed Ti–V–Al-Gd shape memory alloys, regardless of the annealing temperature. The evolution of the martensitic transformation temperatures can be attributed to the compressive effect of the chemical composition, grain size and type and number of second phases. In addition, the yield strength gradually decreased owing to the coarsening of the grain size and reduction in the amount of the α phase, whereas the elongation became superior in Ti–V–Al-Gd shape memory alloy annealed at higher annealing temperatures due to the elimination of dislocations and defects. In proportion, the strain recovery characteristics gradually decreased as the annealing temperature increased from 700 °C to 800 °C.

The regulatory mechanisms of PD-L1 posttranslational modifications are not completely understood. Here the authors show that USP8 negatively regulates PD-L1 protein abundance by removing the K63-linked ubiquitination of PD-L1; while USP8 inhibition increases MHC-I expression and triggers anti-tumour immune responses through activating NF-κB signalling.

High-entropy shape-memory alloys (HESMAs) exhibit unique properties, including high yield strength, a wide temperature range of phase transformation, and excellent thermal cycling stability, among others. Hence, they have broad prospects for research and application. Currently, various new high-entropy shape-memory alloys have been developed based on TiNi, Fe-based, Ti-based, and NiMn-based alloys. This article focuses on summarizing and analyzing the research status of various types of high-entropy shape-memory alloys, including their microstructure characteristics, martensitic phase transformation, and functional properties. The advantages and disadvantages of high-entropy shape-memory alloys compared to traditional shape-memory alloys are briefly discussed. Finally, based on the analysis of existing problems, future research prospects are proposed, hoping to provide assistance for the development and application of high-entropy shape-memory alloys in the future.

Abstract Since the clinical approval of imatinib, the discovery of protein kinase downregulators entered a prosperous age. However, challenges still exist in the discovery of kinase downregulator drugs, such as the high failure rate during development, side effects, and drug-resistance problems. With the progress made through multidisciplinary efforts, an increasing number of new approaches have been applied to solve the above problems during the discovery process of kinase downregulators. In terms of in vitro and in vivo drug evaluation, progress was also made in cellular and animal model platforms for better and more clinically relevant drug assessment. Here, we review the advances in drug design strategies, drug property evaluation technologies, and efficacy evaluation models and technologies. Finally, we discuss the challenges and perspectives in the development of kinase downregulator drugs.

Current therapies for T-cell acute leukemia are based on risk stratification and have greatly improved the survival rate for patients, but mortality rates remain high owing to relapsed disease, therapy resistance, or treatment-related toxicities/infection. Patients with relapsed disease continue to have poor outcomes. In the past few years, newer agents have been investigated to optimize upfront therapies for higher-risk patients in the hopes of decreasing relapse rates. This review summarizes the progress of chemo/targeted therapies using Nelarabine/Bortezomib/CDK4/6 inhibitors for T-ALL in clinical trials and novel strategies to target NOTCH-induced T-ALL. We also outline immunotherapy clinical trials using monoclonal/bispecific T-cell engaging antibodies, anti-PD1/anti-PDL1 checkpoint inhibitors, and CAR-T for T-ALL therapy. Overall, pre-clinical studies and clinical trials showed that applying monoclonal antibodies or CAR-T for relapsed/refractory T-ALL therapy is promising. The combination of target therapy and immunotherapy may be a novel strategy for T-ALL treatment.

Enrofloxacin (ENR) is one of the most common drugs used in poultry production to treat bacterial diseases, and there is a high risk of drug interactions (DDIs) between polyether anticoccidial drugs added to poultry feed over time. This may affect the efficacy of antibiotics or lead to toxicity, posing a potential risk to the environment and food safety. This study aimed to investigate the DDI of ENR and salinomycin (SAL) in broilers and the mechanism of their DDI. We found that SAL increased the area under the curve and elimination half-life of ENR and ciprofloxacin (CIP) by 1.3 and 2.4 times, 1.2 and 2.5 times, respectively. Cytochrome 3A4 (CYP3A4), p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) were important factors for the DDI between ENR and SAL in broilers. ENR and SAL are substrates of CYP3A4, P-gp and BCRP in broilers; ENR and SAL inhibited the expression of CYP3A4 activity in a time- and concentration-dependent. Meanwhile, ENR downregulated the expression of P-gp and BCRP in a time- and concentration-dependent manner. A single oral administration of SAL inhibited CYP3A4, P-gp, and BCRP, but long-term mixed feeding upregulated the expression of CYP3A4, P-gp, and BCRP. Molecular docking revealed that ENR and SAL compete with each other for CYP3A4 to affect hepatic metabolism, and compete with ATP for P-gp and BCRP binding sites to inhibit efflux. ENR and SAL in broilers can lead to severe DDI. Drug residues and resistance following co-administration of ENR and SAL and other SAL-based drug-feed interactions warrant further study.

Two-dimensional (2D)/quasi-2D organic-inorganic halide perovskites are regarded as naturally formed multiple quantum wells with inorganic layers isolated by long organic chains, which exhibit layered structure, large exciton binding energy, strong nonlinear optical effect, tunable bandgap via changing the layer number or chemical composition, improved environmental stability, and excellent optoelectronic properties. The extensive choice of long organic chains endows 2D/quasi-2D perovskites with tunable electron-phonon coupling strength, chirality, or ferroelectricity properties. In particular, the layered nature of 2D/quasi-2D perovskites allows us to exfoliate them to thin plates to integrate with other materials to form heterostructures, the fundamental structural units for optoelectronic devices, which would greatly extend the functionalities in view of the diversity of 2D/quasi-2D perovskites. In this paper, the recent achievements of 2D/quasi-2D perovskite-based heterostructures are reviewed. First, the structure and physical properties of 2D/quasi-2D perovskites are introduced. We then discuss the construction and characterizations of 2D/quasi-2D perovskite-based heterostructures and highlight the prominent optical properties of the constructed heterostructures. Further, the potential applications of 2D/quasi-2D perovskite-based heterostructures in photovoltaic devices, light emitting devices, photodetectors/phototransistors, and valleytronic devices are demonstrated. Finally, we summarize the current challenges and propose further research directions in the field of 2D/quasi-2D perovskite-based heterostructures.

The diversity and composition of T-cell receptor (TCR) repertoire, which is the result of V, (D), and J gene recombination in TCR gene locus, has been found to be implicated in T-cell responses in autoimmunity, cancer, and organ transplantation. The correlation of T-cell repertoire with the pathogenesis of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation remains largely undefined. Here, by utilizing high-throughput sequencing of the genes encoding TCRβ-chain, we comprehensively analyzed the profile of T-cell repertoire in recipient lymphoid and GVHD target organs after bone marrow transplantation (BMT) in mice. In lymphoid organs, TCR diversity was narrowed, accompanied with reduced numbers of unique clones while increased accumulation of dominant clones in allogeneic T cells compared to syngeneic T cells. In an individual allogeneic recipient, donor-derived TCR clones were highly overlapped among tissue sites, and the degree of overlapping was increasing from day 7 to 14 after allogeneic BMT. The top clones in peripheral blood, gut, liver, and lungs were highly mutually shared in an allogenic recipient, indicating that blood has the potential to predict dominant clones in these GVHD target organs. T cells in GVHD target organs from allogeneic recipients had fewer overlapped clones with pre-transplant donor T cells compared to those from syngeneic recipients. Importantly, the top 10 clones in allogeneic recipients were not detectable in pre-transplant donor T cells, indicating clonal expansion of rare rearrangements. Interestingly, even starting from the same pool of donor repertoires, T cells had very few overlapped clones between each allogeneic recipient who developed completely different dominant clones. We were only able to trace a single clone shared by three replicate allogeneic recipients within the top 500 clones. Although dominant clones were different among allogeneic recipients, V26 genes were consistently used more frequently by TCR clones in allogeneic than syngeneic recipients. This is the first study to extensively examine the feature of T-cell repertoire in multiple lymphoid and parenchyma organs, which establishes the association between T-cell activation and GVHD pathogenesis at the level of TCR clones. Immune repertoire sequencing-based methods may represent a novel personalized strategy to guide diagnosis and therapy in GVHD.

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.

Hematopoietic stem cells (HSCs) are derived from hemogenic endothelial cells (HECs) during embryogenesis. The HSC-primed HECs increased to the peak at embryonic day (E) 10 and have been efficiently captured by the marker combination CD41–CD43–CD45–CD31+CD201+Kit+CD44+ (PK44) in the aorta-gonad-mesonephros (AGM) region of mouse embryos most recently. In the present study, we investigated the spatiotemporal and functional heterogeneity of PK44 cells around the time of emergence of HSCs. First, PK44 cells in the E10.0 AGM region could be further divided into three molecularly different populations showing endothelial- or hematopoietic-biased characteristics. Specifically, with the combination of Kit, the expression of CD93 or CD146 could divide PK44 cells into endothelial- and hematopoietic-feature biased populations, which was further functionally validated at the single-cell level. Next, the PK44 population could also be detected in the yolk sac, showing similar developmental dynamics and functional diversification with those in the AGM region. Importantly, PK44 cells in the yolk sac demonstrated an unambiguous multilineage reconstitution capacity after in vitro incubation. Regardless of the functional similarity, PK44 cells in the yolk sac displayed transcriptional features different from those in the AGM region. Taken together, our work delineates the spatiotemporal characteristics of HECs represented by PK44 and reveals a previously unknown HSC competence of HECs in the yolk sac. These findings provide a fundamental basis for in-depth study of the different origins and molecular programs of HSC generation in the future.

Gastrointestinal (GI) microbiota play an important role in promoting growth in piglets. However, studies on microbiota composition at various growth stages are lacking. We measured body weights of Jinfen White and Mashen piglets every 7 days and collected their fecal samples by rectal swabbing at nine time points during suckling (1–28 days) and nursery (35–70 days) stages to gain insight into microbiota variability during piglet growth. The fecal microbiota were characterized via 16S rRNA gene sequencing to analyze the effects of microbial diversity on piglet growth and development preliminarily. The results showed that although the two breeds of piglets have similar body weights at birth, weaned Jinfen White piglets demonstrated a significantly greater body weight and daily weight gain than weaned Mashen piglets (P < 0.01). A total of 1,976 operational taxonomic units (OTUs) belonging to 27 phyla and 489 genera were uncovered, in which the highest numbers of OTUs belong to the phyla Firmicutes and Bacteroidetes. Lactobacillus, Bacteroides, and Prevotellaceae NK3B31 groups accounting for 12.4, 8.8, and 5.8% of OTUs, respectively, showed relatively high abundance at the genus level. Nine sampling time points were divided into three growth stages, namely, immediate postfarrowing (1 day old), suckling (7, 14, and 21 days old), and nursery (28, 35, 49, 63, and 70 days old), on the basis of the results of microbial diversity, principal coordinate, and co-occurrence network analyses. In addition, it identified 54 discriminative features in the microbiota between two breeds of piglets by LEfSe analysis, in which 17 genera enriched the microbiota community of Jinfen White piglets. Finally, abundances of 29 genera showed significant positive correlations with body weights and daily weight gain of piglets. Conversely, abundances of 12 genera demonstrated significant negative correlations with body weights of piglets. The results of our study will provide a theoretical basis for succession patterns in fecal microbiota of piglets and suggest the need for meticulous management of piglets in pig production.

The aim of this research was to screen candidate genes affecting growth traits in pigs by studying the difference expression genes (DEGs) between the longissimus dorsi of Large White (LW) and Mashen (MS) pigs. RNA-sequencing (RNA-seq) technology was applied to analyse the transcriptomes from six longissimus dorsi in two pig breeds (LW and MS). Based on sequencing, the DEGs were screened, and functional annotation and enrichment analysis were performed. The results showed that 697 different significant genes were obtained (p

Current acoustic modeling methods face problems such as complex processes or inaccurate sound absorption coefficients, etc. Therefore, this paper studies the topic. Firstly, the material samples were prepared, and standing wave tube method experiments were conducted. Material acoustic data were obtained, while a model using improved genetic algorithm and neural network was subsequently proposed. Secondly, the acoustic data obtained from the experiment were analyzed; a neural network structure was designed; and the training, verification, and test data were all divided. In order to facilitate data processing, a symmetrical method was used to inversely normalize all the data. Thirdly, by the design of real coding scheme, fitness function, crossover, and mutation operators, an improved genetic algorithm was proposed to obtain the optimal solution, as the initial weight and threshold, which were then input into the neural network along with the training and verification data. Finally, the test data were input into the trained neural network in order to test the model. The test results and statistical analysis showed that compared with other algorithms, the proposed model has the lower root mean squared error (RMSE) value, the maximum coefficient of determination (R2) value, and shorter convergence time.

Microbial ecological studies have been remarkably promoted by the high-throughput sequencing approach with explosive information of taxonomy and relative abundance. However, relative abundance does not reflect the quantity of the microbial community and the inter-sample differences among taxa. In this study, we refined and applied an integrated high-throughput absolute abundance quantification (iHAAQ) method to better characterize soil quantitative bacterial community through combining the relative abundance (by high-throughput sequencing) and total bacterial quantities (by quantitative PCR). The proposed iHAAQ method was validated by an internal reference strain EDL933 and a laboratory strain WG5. Application of the iHAAQ method to a soil phenanthrene biodegradation study showed that for some bacterial taxa, the changes of relative and absolute abundances were coincident, while for others the changes were opposite. With the addition of a microbial activity inhibitor (NaN3), the absolute abundances of soil bacterial taxa, including several dominant genera of Bacillus, Flavobacterium, and Paenibacillus, decreased significantly, but their relative abundances increased after 28 days of incubation. We conclude that the iHAAQ method can offer more comprehensive information to reflect the dynamics of soil bacterial community with both relative and absolute abundances than the relative abundance from high-throughput sequencing alone.

ABSTRACT The natural forest ecosystem in Eastern China, from tropical forest to boreal forest, has declined due to cropland development during the last 300 years, yet little is known about the historical biogeographic patterns and driving processes for the major domains of microorganisms along this continental-scale natural vegetation gradient. We predicted the biogeographic patterns of soil archaeal, bacterial, and fungal communities across 110 natural forest sites along a transect across four vegetation zones in Eastern China. The distance decay relationships demonstrated the distinct biogeographic patterns of archaeal, bacterial, and fungal communities. While historical processes mainly influenced bacterial community variations, spatially autocorrelated environmental variables mainly influenced the fungal community. Archaea did not display a distance decay pattern along the vegetation gradient. Bacterial community diversity and structure were correlated with the ratio of acid oxalate-soluble Fe to free Fe oxides (Feo/Fed ratio). Fungal community diversity and structure were influenced by dissolved organic carbon (DOC) and free aluminum (Ald), respectively. The role of these environmental variables was confirmed by the correlations between dominant operational taxonomic units (OTUs) and edaphic variables. However, most of the dominant OTUs were not correlated with the major driving variables for the entire communities. These results demonstrate that soil archaea, bacteria, and fungi have different biogeographic patterns and driving processes along this continental-scale natural vegetation gradient, implying different community assembly mechanisms and ecological functions for archaea, bacteria, and fungi in soil ecosystems. IMPORTANCE Understanding biogeographic patterns is a precursor to improving our knowledge of the function of microbiomes and to predicting ecosystem responses to environmental change. Using natural forest soil samples from 110 locations, this study is one of the largest attempts to comprehensively understand the different patterns of soil archaeal, bacterial, and fungal biogeography at the continental scale in eastern China. These patterns in natural forest sites could ascertain reliable soil microbial biogeographic patterns by eliminating anthropogenic influences. This information provides guidelines for monitoring the belowground ecosystem’s decline and restoration. Meanwhile, the deviations in the soil microbial communities from corresponding natural forest states indicate the extent of degradation of the soil ecosystem. Moreover, given the association between vegetation type and the microbial community, this information could be used to predict the long-term response of the underground ecosystem to the vegetation distribution caused by global climate change. Author Video: An author video summary of this article is available.

Escherichia coli O157:H7 (E. coli O157:H7) is recognized as a hazardous microorganism in the environment and for public health. The E. coli O157:H7 survival dynamics were investigated in 12 representative soils from Jiangsu Province, where the largest E. coli O157:H7 infection in China occurred. It was observed that E. coli O157:H7 declined rapidly in acidic soils (pH, 4.57 - 5.14) but slowly in neutral soils (pH, 6.51 - 7.39). The survival dynamics were well described by the Weibull model, with the calculated td value (survival time of the culturable E. coli O157:H7 needed to reach the detection limit of 100 CFU g(-1)) from 4.57 days in an acidic soil (pH, 4.57) to 34.34 days in a neutral soil (pH, 6.77). Stepwise multiple regression analysis indicated that soil pH and soil organic carbon favored E. coli O157:H7 survival, while a high initial ratio of Gram-negative bacteria phospholipid fatty acids (PLFAs) to Gram-positive bacteria PLFAs, and high content of exchangeable potassium inhibited E. coli O157:H7 survival. Principal component analysis clearly showed that the survival profiles in soils with high pH were different from those with low pH.

The effects of a high-velocity impact on the microstructure, phase transformation and mechanical property of aged Ti49Ni51 alloy are investigated. The transformation behavior and microstructure along the impact direction after impact emerge with regionalization characteristics, including a deformed region near the crater (0–4 mm) and an un-deformed region of the distal crater (5–6 mm). Stress-induced martensite is the main deformation mechanism in the deforming region of aged Ti49Ni51 alloy under high-velocity impact.

Assimilable organic carbon (AOC) is commonly used to measure the growth potential of microorganisms in water, but has not yet been investigated for measuring microbial growth potential in soils. In this study, a simple, rapid, and non-growth based assay to determine AOC in soil was developed using a naturally occurring luminous strain Vibrio harveyi BB721 to determine the fraction of low molecular weight organic carbon in soil water extract. Calibration of the assay was achieved by measuring the luminescence intensity of starved V. harveyi BB721 cells in the late exponential phase with a concentration range from 0 to 800 µg l(-1) glucose (equivalent to 0-16.0 mg glucose C kg(-1) soil) with the detection limit of 10 µg l(-1) equivalent to 0.20 mg glucose C kg(-1) soil. Results showed that bioluminescence was proportional to the concentration of glucose added to soil. The luminescence intensity of the cells was highly pH dependent and the optimal pH was about 7.0. The average AOC concentration in 32 soils tested was 2.9±2.2 mg glucose C kg(-1). Our data showed that AOC levels in soil water extracts were significantly correlated (P

The persistence of Shiga toxin-producing E. coli O157:H7 in the environment poses a serious threat to public health. However, the role of Shiga toxins and other virulence factors in the survival of E. coli O157:H7 is poorly defined. The aim of this study was to determine if the virulence factors, stx₁, stx₂, stx₁₋₂, and eae in E. coli O157:H7 EDL933 play any significant role in the growth of this pathogen in rich media and in soils. Isogenic deletion mutants that were missing one of four virulence factors, stx₁, stx₂, stx₁₋₂, and eae in E. coli O157:H7 EDL933 were constructed, and their growth in rich media and survival in soils with distinct texture and chemistry were characterized. The survival data were successfully analyzed using Double Weibull model, and the modeling parameters of the mutant strains were not significantly different from those of the wild type. The calculated T(d) (time needed to reach the detection limit, 100 CFU/g soil) for loamy sand, sandy loam, and silty clay was 32, 80, and 110 days, respectively. It was also found that T(d) was positively correlated with soil structure (e.g. clay content), and soil chemistry (e.g. total nitrogen, total carbon, and water extractable organic carbon). The results of this study showed that the possession of Shiga toxins and intimin in E. coli O157:H7 might not play any important role in its survival in soils. The double deletion mutant of E. coli O157:H7 (stx₁⁻stx₂⁻) may be a good substitute to use for the investigation of transport, fate, and survival of E. coli O157:H7 in the environment where the use of pathogenic strains are prohibited by law since the mutants showed the same characteristics in both culture media and environmental samples.

The relationship between users and items, which cannot be recovered by traditional techniques, can be extracted by the recommendation algorithm based on the graph convolution network. The current simple linear combination of these algorithms may not be sufficient to extract the complex structure of user interaction data. This paper presents a new approach to address such issues, utilizing the graph convolution network to extract association relations. The proposed approach mainly includes three modules: Embedding layer, forward propagation layer, and score prediction layer. The embedding layer models users and items according to their interaction information and generates initial feature vectors as input for the forward propagation layer. The forward propagation layer designs two parallel graph convolution networks with self-connections, which extract higher-order association relevance from users and items separately by multi-layer graph convolution. Furthermore, the forward propagation layer integrates the attention factor to assign different weights among the hop neighbors of the graph convolution network fusion, capturing more comprehensive association relevance between users and items as input for the score prediction layer. The score prediction layer introduces MLP (multi-layer perceptron) to conduct nonlinear feature interaction between users and items, respectively. Finally, the prediction score of users to items is obtained. The recall rate and normalized discounted cumulative gain were used as evaluation indexes. The proposed approach effectively integrates higher-order information in user entries, and experimental analysis demonstrates its superiority over the existing algorithms. [ABSTRACT FROM AUTHOR]