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For many years, oil and natural gas geochemistry has been key to hydrocarbon exploration and exploitation in offshore China. Onshore oil fields have been thoroughly explored and exploited and have now entered the later stages of development. However, the oil and gas resources in the offshore basin of China are still abundant, and they have been relatively little explored, so they will be the main growth target for oil and gas production in the future. China has made many breakthroughs in offshore oil exploration in recent years. A large condensate field—Bozhong 19-6—has been discovered in the Bozhong Depression. Its main source rock is associated with algal blooming in the third member of the Shahejie Formation. The Baodao 21-1 gas field in the Qiongdongnan Basin shows clear signs of receiving terrestrial organic matter from the Yacheng and Lingshui formations. The first ultra-deep water and ultra-shallow gas, found in the Lingshui 36-1 gas field in the Qiongdongnan Basin, has thermogenetic and biogenetic origins. Well WY-1 in the Weixinan Depression marked the initiation of offshore shale oil exploration. Its sweet interval consists of two stable oil shale beds developed at the base and the top of the second member of the Liushagang Formation. However, samples from offshore exploration are often severely contaminated, and the corresponding data can be seriously distorted, which yields fewer core and more cutting samples. Therefore, it is necessary to thoroughly screen test data and to apply decontamination treatment and data correction to contaminated samples. The success rate of offshore exploration usually relies on the accurate prediction of source kitchens. Reservoir geochemistry thus has great significance for the future, as source input geochemical information can be used to trace materials backwards, and source kitchens can be predicted, when geochemistry is combined with enrichment and development models of source rocks and geophysical data.

Abstract Background Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. Methods In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. Results We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-β1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. Conclusions This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

With advances in liquid cell transmission electron microscopy (LCTEM), it is possible to real-time characterize nanomaterials at atomic resolution in a liquid environment. This provides a key tool for understanding the underlying mechanisms of various of (bio)chemical processes. In this review, various of strategies employed in high performance LCTEM characterization are introduced. It presents the structure and manufacturing processes of different liquid cells, and summarizes the methods to improve the spatial resolution and reduce the irradiation damage of LCTEM. It also describes the liquid cells integration with external energy field for observing the dynamic response of nanomaterials under electrical, thermal or irradiating stimuli. Then recent advances in LCTEM images and data automated analysis by machine learning are highlighted. Finally, we present a perspective on the challenges and future directions for the development of in situ LCTEM.

Objectives Different intrathoracic perfusion therapeutic regimens are available for non-small cell lung cancer with malignant pleural effusion (MPE). Antiangiogenic agents are often used to control MPE, and the results are satisfactory. Here, we performed a network meta-analysis to reveal optimal combinations of antiangiogenic agents and chemical agents and assess their effectiveness and safety.Design Systematic review and network meta-analysis.Data sources PubMed/Medline, Embase, Cochrane, Web of Science, Wanfang, VIP Database and Chinese National Knowledge Infrastructure were searched from inception to May 2023. Eligible studies were randomised controlled trials that reported on curative effect of MPE.Data extraction and synthesis The Cochrane Collaboration tool was used to assess risk of bias. The consistency was evaluated by examining the agreement between direct and indirect effects. Network meta-analysis was performed and the ranking probabilities of being at each possible rank for each intervention were estimated. Comparison-adjusted funnel plots were obtained to assess publication bias.Results A total of 46 studies were included in the analysis. Among them, we included a total of seven interventions. A total of 3026 patients participated in this analysis. According to the results of the network meta-analysis, some antiangiogenic agents combined with chemotherapy regimens improved objective response rate (ORR) and disease control rate (DCR) and quality of life (QOL). The rank probabilities suggested that in terms of ORR, DCR and QOL, Endostar plus lobaplatin was the first-ranked intervention.Conclusion Administration of antiangiogenic agents plus chemical agents significantly improved the clinical response and QOL. In addition, Endostar plus lobaplatin was the most effective combination.PROSPERO registration number CRD42021284786.

Summary: The lack of an etiologic Parkinson’s disease (PD) model in non-human primates has inhibited our understanding of the disease and the development of therapies. Here, we present a protocol for generating a PD model in Macaca fascicularis. We describe steps for localizing the substantia nigra and striatum using magnetic resonance imaging (MRI). We then detail a technique for the intracerebral administration of adeno-associated virus (AAV)-mediated overexpression of α-synuclein into the substantia nigra plus the injection of poly(ADP-ribose) (PAR) into the striatum.For complete details on the use and execution of this protocol, please refer to Liu et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundThe Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a threat to human health. Although the COVID-19 pandemic is finished, some peoples are still suffering from this disease. Herein, we report the first case of SARS-CoV-2-associated Guillain-Barré syndrome (GBS) presenting as polyneuritis cranialis (PNC) and acute panautonomic neuropathy (APN) variants, accompanied by mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and hyponatremia.Case presentationA 32-year-old female patient with symptoms indicating multiple cranial nerve involvement, as well as sympathetic and parasympathetic nervous system dysfunction, was diagnosed as SARS-CoV-2-associated GBS presenting as PNC and APN variants, accompanied by MERS and hyponatremia. Following treatment with immunoglobulin, methylprednisolone, and symptomatic care, the patient’s inflammatory cytokines and serum sodium became normal. However, some residual symptoms such as postural hypotension, fatigue, and mild dysarthria persisted at the 9-month follow-up.ConclusionThis case highlights the unique presentation of SARS-CoV-2 infection. The involvement of both the central nervous system (CNS) and the peripheral nervous system (PNS) in this case underscores the complex neurological manifestations of COVID-19. Although the exact underlying pathogenesis of this case is unclear, inflammatory cytokines, particularly IL-6, may be implicated. Further research is needed to better understand the mechanisms underlying these complications and to optimize treatment strategies for affected patients.

Abstract Objectives This study aimed to identify the risk factors for postoperative atrial fibrillation in patients with valvular atrial fibrillation, and establish predictive models of atrial fibrillation recurrence. Methods Overall, 224 patients who underwent radiofrequency ablation of atrial fibrillation from November 2014 to November 2020 were included. The statistical package for social sciences, X-tile, and R-studio were used for statistical analysis. Results Patients were divided into training and validation sets according to a ratio of 3:1. The training set was analysed using univariate and multivariate Cox regression analysis and showed that preoperative uric acid > 401 μmol/L (P = 0.006), B-type natriuretic peptide > 202 ng/L (P = 0.042), hypersensitivity C-reactive protein > 6.1 mg/L (P = 0.026), erythrocyte sedimentation rate > 7.0 mm/h (P = 0.016), preoperative left atrial diameter > 48 mm (P = 0.031) were significantly correlated with the recurrence of atrial fibrillation after radiofrequency ablation in patients with valvular atrial fibrillation. In the training set, a Cox regression model of the five related factors was established using the R language. The C-index of the model was 0.82, and the area under the receiver operating characteristic curve was 0.831 (P

C50 manufactured sand concrete requires good workability and strength, and economic efficiency and carbon emissions also need to be considered. This study incorporates sensitivity and significance analyses to recommend the optimal economic mix composition for C50 manufactured sand concrete. The relationship between cost, workability, and mechanical properties was analyzed by considering the water/binder ratio, sand ratio, fly ash content, and superplasticizer dosage. An optimal composition of C50 manufactured sand concrete was recommended. The cost and carbon emissions were quantified at the optimal composition. The results showed that the water/binder ratio had the most significant impact on the cost and carbon emission, while the sand ratio and superplasticizer dosage had the least. All factors significantly affected its cost and carbon emission. Compared to natural sand concrete, manufactured sand concrete achieved a lower cost but higher carbon emissions. Considering the workability, strength, and cost per cubic meter of concrete, the most economical mix proportion for C50 concrete was recommended with a water/binder ratio of 0.36, a fly ash content of 25%, a sand ratio of 0.42, and a superplasticizer dosage of 1.2%. This composition cost 356 yuan, and carbon emission was 352.6 kg CO2 per cubic meter of concrete. Compared to a composition with a water/binder ratio of 0.34 and fly ash content of 15%, the unit cost can be reduced by 18.4 yuan, and carbon emission can be minimized by 56.6 kg CO2 e/m3. The appropriate water/binder ratio and fly ash content can reduce cost and carbon emissions without compromising the workability, compressive strength, or elastic modulus of C50 concrete. This achieves triple benefits in terms of performance, economy, and the environment when applying C50 manufactured sand concrete.

Soil salinization is a serious threat to the ecological environment and sustainable agricultural development in the arid regions of northwest China. Optimal soil salinization amelioration methods were eagerly explored under different soil salinity levels. Sesbania and hairy vetch are salt-tolerant plants, and green manure improved the saline environment. In this study, two leguminous halophytic crops, sesbania (Sesbania cannabina) and hairy vetch (Vicia villosa), were planted under different salinity levels, combined with three saline soil improvement measures, namely gravel mulching, manure application, and straw returning. No improvement measures and no salinity treatment was set as the control (CK). This study was conducted to analyze the effects of soil salinization improvement measures on the growth and ion uptake of sesbania and hairy vetch as biological measures under different soil salinity levels. Sesbania under manure application absorbed the highest soil Na+ (2.71 g kg−1) and Cl− (2.66 g kg−1) amounts at a soil salinity of 3.2 g kg−1, which was 14.7% and 10.95% higher than under gravel mulching and straw returning, respectively. Na+ and Cl− absorption of hairy vetch under manure application reached the highest value of 1.39 g kg−1 and 1.38 g kg−1 at a soil salinity of 1.6 g kg−1, which was 24.46% and 22.31% higher than under gravel mulching and straw returning, respectively. Plant height and stem diameter as well as root growth and development of sesbania and hairy vetch were limited at soil salinities greater than 1.6 g kg−1 and 0.8 g kg−1. Overall, sesbania and hairy vetch effectively absorbed both soil Na+ and Cl− under manure application, thus regulating soil salinity and reducing soil salinization. However, soil salinity levels greater than 3.2 g kg−1 and 1.6 g kg−1 not only weakened the ionic absorption capacity but also inhibited the growth and development of sesbania and hairy vetch. This study provides evidence that soil salt ion absorption by sesbania and hairy vetch is promoted effectively, ameliorating soil salinity, under manure application as compared to under gravel mulching and straw returning.

This paper delivers an in-depth risk analysis of asphalt pavement structural strength in the cold Qinghai-Tibet Plateau region. It encompasses a wide range of risk factors, including environmental conditions, traffic dynamics, pavement structures and materials, and various human-related factors. These risk factors are quantified using probability distributions, with emphasis on the changes in their mean and variance to simulate the effects of risk. A novel risk metric, termed “CVall”, is introduced to encapsulate the cumulative risk associated with each random variable. The paper describes the risk in the load and resistance equations, which govern the asphalt pavement strength, using the probability density function distribution. This approach takes into account the variation coefficient of each parameter. The study highlights that the risk related to the pavement structure number following freeze-thaw cycles significantly influences the reliability of pavement structural strength. These insights are particularly crucial for highway design, construction, and maintenance in cold regions, where the durability and longevity of pavement are paramount.

Over the past few decades, the Internet has rapidly diffused across China. The spread of the Internet has had a profound economic and social impact on Chinese rural areas. Existing research shows that Internet access significantly impacts agricultural production and improves smallholder farmers’ income. Beyond these, the Internet can affect other dimensions of social welfare. However, research about the impact of Internet access on dietary quality in rural China remains scarce. This study utilizes multi-period panel data from Fixed Observation Point in rural China from 2009 to 2015 to estimate the impact of Internet access on dietary quality and food consumption of rural households and conducts a causal analysis. Regression models with time and household fixed effects allow robust estimation while reducing potential issues of unobserved heterogeneity. The estimates show that Internet access has significantly increased rural household dietary quality (measured by the Chinese Diet Balance Index). Further research finds that Internet access has increased the consumption of animal products, such as aquatic and dairy products. We also examine the underlying mechanisms. Internet access improves dietary quality and food consumption mainly through increasing household income and food expenditure. These results encourage the promotion of Internet access as a valuable tool for nutritional improvements, especially in rural areas.

Summary: The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing. However, natural nucleases of this system often exhibit low efficiency, limiting their application. Here, we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease, Cas12i3. As a result, we developed Cas-SF01, a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells. Cas-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 nucleases. Compared to natural Cas12i3, Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN PAMs. In addition, we identified an amino acid substitution, D876R, that markedly reduced the off-target effect while maintaining high on-target activity, leading to the development of Cas-SF01HiFi (high-fidelity Cas-SF01). Finally, we show that Cas-SF01 has high gene editing activities in mice and plants. Our results suggest that Cas-SF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.

Abstract Fetal stages are critical periods for brain development. However, the protein molecular signature and dynamics of the human brain remain unclear due to sampling difficulty and ethical limitations. Non-human primates present similar developmental and neuropathological features to humans. This study constructed a spatiotemporal proteomic atlas of cynomolgus macaque brain development from early fetal to neonatal stages. Here we showed that (1) the variability across stages was greater than that among brain regions, and comparisons of cerebellum vs. cerebrum and cortical vs. subcortical regions revealed region-specific dynamics across early fetal to neonatal stages; (2) fluctuations in abundance of proteins associated with neural disease suggest the risk of nervous disorder at early fetal stages; (3) cross-species analysis (human, monkey, and mouse) and comparison between proteomic and transcriptomic data reveal the proteomic specificity and genes with mRNA/protein discrepancy. This study provides insight into fetal brain development in primates.

Asphalt pavement performance remains pivotal in ensuring the longevity and safety of our transport networks, especially in regions that face unique environmental challenges such as the Qinghai-Tibet plateau. This study presents a groundbreaking reliability model for the evaluation of asphalt pavement performance, based on the esteemed AASHTO design equation. Four cardinal uncertainty factors, encompassing the environment, traffic loads, pavement structures and materials, and anthropogenic activities, were meticulously integrated into the performance analysis. Delving deep into the intricate dynamics of the pavement structure strength, five random variables - SN, ΔPSI, Mr, ESAL0 and r - were identified and analyzed, reflecting the inherent uncertainties during its lifecycle. A notable observation was the linear decline of SNF-T with increasing freeze-thaw actions. Additionally, a comprehensive sensitivity analysis highlighted the profound influence of ESAL0 on the sensitivity of the load equation and emphasized the dominant role of SNF-T in pavement structural performance evaluation. This investigation not only unravels the complex interactions governing asphalt pavement behavior but also provides an invaluable framework for future research, design optimization, and infrastructure maintenance strategies in challenging terrains.

Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) is a group of autoimmune-mediated disorders of the central nervous system primarily involving the optic nerve and spinal cord. There are limited reports of NMOSD associated with peripheral nerve damage. Case presentation We report a 57-year-old female patient who met the diagnostic criteria for aquaporin 4 (AQP4)-IgG positive NMOSD with undifferentiated connective tissue disease and multiple peripheral neuropathy. In addition, the patient was positive for multiple anti-ganglioside antibodies (anti-GD1a IgG antibodies and anti-GD3 IgM antibodies) and anti-sulfatide IgG antibodies in serum and cerebrospinal fluid. After treatment with methylprednisolone, gamma globulin, plasma exchange, and rituximab, the patient’s status improved and was subsequently discharged from our hospital. Conclusions The neurologist should be aware of the unusual association between NMOSD and immune-mediated peripheral neuropathy undifferentiated connective tissue disease and nerve damage mediated by multiple antibodies may have combined to cause peripheral nerve damage in this patient.

Phase change materials (PCMs) can regulate the temperature in asphalt pavement and minimize temperature-related problems, such as rutting and thermal cracking, because of their ability to store and release latent heat. Suitable PCMs can also enable additional road surface functions, such as snow melting ability, freeze-thaw cycle resistance, and heat island reduction. These functions are helpful in achieving intelligent, green, and sustainable transportation systems. Although the research on PCMs for asphalt pavement has been carried out for more than 10 years, a systematic material system and mature application technology have not yet been formed. The main reasons for restricting the development of this technology include the lack of suitability between the PCMs and asphalt pavement, the quantitative characterization of phase change temperature regulation property, and the evaluation of the effect of phase change energy storage on improving pavement performance. Although the published review has made a comprehensive summary of the existing research, it has yet to identify the key restricting the development of this technology and carry out a review and discussion based on it. To grasp the development status of the application of PCMs in asphalt pavement, sort out the development needs and break through the technical barriers, this study systematically summarizes the preparation and performance of PCMs for asphalt pavement, compares the performance and evaluation methods of asphalt mixtures with different PCMs, and summarizes the numerical simulation methods of phase change asphalt mixtures. Finally, this study presents potential approaches to address critical technical issues and discusses possible future research.

Changes in precipitation storm characteristics especially extreme precipitation events have been frequently reported during recent years, which poses great challenges for flood controls of reservoir basins. In this study, we present a comprehensive examination on the evolution of storm properties during two distinct rainy seasons in Changtan Reservoir Basin located on the southeastern coast of China. We compare the differences in storm duration, inter-storm period, the average storm intensity, and with-in storm pattern between the Meiyu flood season (MFS) and typhoon flood season (TFS). We also explore the future projections of these storm properties based on Coupled Model Inter-comparison Project 6 (CMIP6) precipitation outputs. Our results indicate that precipitation storms in TFS exhibit shorter duration and higher average storm intensity than those of MFS, the flood risk in June is mainly due to accumulative precipitation (longer duration), while in July to September, is mainly due to the storms with high intensity. The projected precipitation shows uncertainties for different emission scenarios, especially during TFS. However, the increasing trend of the average storm intensity is relatively consistent, which is supposed to bring more pressure on flood control in the study area. The results can provide a beneficial reference to water resources management. HIGHLIGHTS The evolution of storm properties was investigated.; Precipitation in typhoon flood season exhibits shorter duration and higher intensity than those of the Meiyu flood season.; Flood risk in June is mainly due to accumulative precipitation in the study area.; Flood risk from July to September is due to storms with high intensity.; Projected precipitation shows uncertainties but a consistent increasing trend in storm intensity.;

Abstract Background The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder the therapeutic application. Exosomes derived from MSCs have shown promising therapeutic potential in many diseases. However, the heterogeneity of MSCs may lead to differences in the function of secreting exosomes. In this study, the therapeutic effects of hUC-Exos and hFP-Exos on the DSS-induced colitis mouse model were investigated. Methods The colitis mouse models were randomly divided into four groups: (1) DSS administered for 7 days and euthanasia (DSS7D), (2) DSS administered for 7 days and kept for another 7 days without any treatment (DSS14D), (3) DSS administered for 7 days and followed with hUC-EVs infusion for 7 days (hUC-EVs) and (4) DSS administered for 7 days and followed with hFP-EVs infusion for 7 days (hFP-EVs). We analyzed colon length, histopathology, Treg cells, cytokines and gut microbiota composition in each group. Results A large amount of IL-6, IL-17 and IFN-γ were produced along with the decrease in the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells in DSS7D group, which indicated that Th17 cells were activated and Treg cells were suppressed. We found that the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells increased in order to suppress inflammation, but the length of colon did not recover and the symotoms were worsened of the colonic tissue in DSS14D group. The subsequent infusion of either hUC-Exos or hFP-Exos mediated the transformation of Treg and Th17 cells in colitis mice to maintain immune balance. The infusion of hUC-Exos and hFP-Exos also both reduced the abundance of pro-inflammatory intestinal bacterial such as Verrucomicrobia and Akkermansia muciniphila to improve colitis. Conclusions We found that Foxp3 + Treg cells can inhibit the inflammatory response, and the over-activated Treg cells can still further damage the intestinal mucosa. hUC-Exos and hFP-Exos can control inflammation by regulating the balance between Th17 cells and Treg cells. Decreased inflammatory response improved the structure of colon wall in mice and reduced the abundance of pro-inflammatory bacteria in the intestine. The improvement of intestinal wall structure provides conditions for the reproduction of beneficial bacteria, which further contributes to the reduction of colitis.

With the development of urbanization and industrialization, more and more chemicals were produced in large quantities and widely used. As a result, they entered the water environment through sewage discharge and agricultural drainage. Currently, the analytical methods of contaminants in water include three main strategies, including target screening, suspect analysis and nontarget screening. The number of compounds identified using target screening methods has increased to hundreds, which is far from meeting the current demand for emerging contaminants (ECs) detection in water environment. To comprehensively screen potential emerging contaminants in the Yangtze River in Jiangsu Province, a nontarget screening strategy combined spectral library search with a molecular network was proposed in Jiangsu-Anhui provincial boundary cross section and 22 drinking water sources in Jiangsu section of Yangtze River. Under this strategy, through spectral library screening using a in-house library, a total of 118 emerging contaminants were identified by accurate mass, isotope distribution and MS/MS fragment ions. These contaminants involved pesticides, herbicides, fungicides, drugs, antibiotics, persistent organic pollutants, flame retardants, plasticizers, indicated active agents, chemical intermediates, and other categories. Since traditional targeted screening relies on commercial standards and screening lists, nontarget screening is a more favorable approach to study ECs and their transformation products in water. Therefore, unannotated chemical substances with similar structures to known contaminants were identified through molecular network technology based on the premise that structurally similar compounds have similar fragment ions. Through using the Global Natural Products Society molecular network (GNPS) to extract molecular families, another contaminant with similar toxicity to amantadine, N-methyl-1-adamantaneamine was found. Furthermore, twenty-three contaminants were confirmed through commercial standard, and 14 of them were detected at a rate of 100%. The quantitative analysis revealed the prevalence of perfluorinated compounds, pharmaceuticals, and personal care products in water bodies, and the total concentrations of the 23 contaminants in each sample ranged from 6.46×102 ng/L to 1.72×103 ng/L. Seven drugs and personal care products were detected. Amantadine was detected at the highest concentration among all locations, and perfluorooctanoic acid (PFOA), amantadine and 2,4-dinitrophenol were detected with the highest mean concentration levels in each location. The nontarget screening strategy using spectral library search and molecular network enabled high-throughput identification of contaminants in water without prior information and standards, in which the structures of unannotated characteristic peaks were inferred from annotated substances with spectral libraries. This strategy will accelerate the systematic discovery of emerging and unknown contaminants in the aqueous environment.

Abstract Background Growth-promoting antibiotics have been banned by law in the livestock and poultry breeding industry in many countries. Various alternatives to antibiotics have been investigated for using in livestock. Epimedium (EM) is an herb rich in flavonoids that has many beneficial effects on animals. Therefore, this study was planned to explore the potential of EM as a new alternative antibiotic product in animal feed. Methods A total of 720 1-day-old male broilers (Arbor Acres Plus) were randomly divided into six groups and fed basal diet (normal control; NC), basal diet supplemented with antibiotic (75 mg/kg chlortetracycline; CTC), and basal diet supplemented with 100, 200, 400 or 800 mg/kg EM extract for 6 weeks (EM100, EM200, EM400 and EM800 groups). The growth performance at weeks 3 and 6 was measured. Serum, intestinal tissue and feces were collected to assay for antioxidant indexes, intestinal permeability, lactic acid and short-chain fatty acids (SCFAs) profiles, microbial composition, and expression of intestinal barrier genes. Results The average daily feed intake in CTC group at 1–21 d was significantly higher than that in the NC group, and had no statistical difference with EM groups. Compared with NC group, average daily gain in CTC and EM200 groups increased significantly at 1–21 and 1–42 d. Compared with NC group, EM200 and EM400 groups had significantly decreased levels of lipopolysaccharide and D-lactic acid in serum throughout the study. The concentrations of lactic acid, acetic acid, propionic acid, butyric acid and SCFAs in feces of birds fed 200 mg/kg EM diet were significantly higher than those fed chlortetracycline. The dietary supplementation of chlortetracycline and 200 mg/kg EM significantly increased ileal expression of SOD1, Claudin-1 and ZO-1 genes. Dietary supplemented with 200 mg/kg EM increased the relative abundances of g_NK4A214_group and Lactobacillus in the jejunal, while the relative abundances of Microbacterium, Kitasatospora, Bacteroides in the jejunal and Gallibacterium in the ileum decreased. Conclusion Supplementation with 200 mg/kg EM extract improved the composition of intestinal microbiota by regulating the core bacterial genus Lactobacillus, and increased the concentration of beneficial metabolites lactic acid and SCFAs in the flora, thereby improving the antioxidant capacity and intestinal permeability, enhancing the function of tight junction proteins. These beneficial effects improved the growth performance of broilers. Graphical Abstract

Oxidative stress causes gut dysfunction and is a contributing factor in several intestinal disorders. Intestinal epithelial cell survival is essential for maintaining human and animal health under oxidative stress. 18beta-Glycyrrhetinic acid (GA) is known to have multiple beneficial effects, including antioxidant activity; however, the underlying molecular mechanisms have not been well established. Thus, the present study evaluated the therapeutic effects of GA on H2O2-induced oxidative stress in intestinal porcine epithelial cells. The results showed that pretreatment with GA (100 nM for 16 h) significantly increased the levels of several antioxidant enzymes and reduced corresponding intracellular levels of reactive oxidative species and malondialdehyde. GA inhibited cell apoptosis via activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as confirmed by RNA sequencing. Further analyses demonstrated that GA upregulated the phosphorylation levels of PI3K and Akt and the protein level of B cell lymphoma 2, whereas it downregulated Cytochrome c and tumor suppressor protein p53 levels. Moreover, molecular docking analysis predicted the binding of GA to Vasoactive intestinal peptide receptor 1, a primary membrane receptor, to activate the PI3K/Akt signaling pathway. Collectively, these results revealed that GA protected against H2O2-induced oxidative damage and cell apoptosis via activating the PI3K/Akt signaling pathway, suggesting the potential therapeutic use of GA to alleviate oxidative stress in humans/animals.

The growing need for the multiband photodetection of a single scene has promoted the development of both multispectral coupling and broadband detection technologies. Photodetectors operating across the infrared (IR) to terahertz (THz) regions have many applications such as in optical communications, sensing imaging, material identification, and biomedical detection. In this review, we present a comprehensive overview of the latest advances in broadband photodetectors operating in the infrared to terahertz range, highlighting their classification, operating principles, and performance characteristics. We discuss the challenges faced in achieving broadband detection and summarize various strategies employed to extend the spectral response of photodetectors. Lastly, we conclude by outlining future research directions in the field of broadband photodetection, including the utilization of novel materials, artificial microstructure, and integration schemes to overcome current limitations. These innovative methodologies have the potential to achieve high-performance, ultra-broadband photodetectors.

Poly(PR) is a dipeptide repeat protein comprising proline and arginine residues. It is one of the translational product of expanded G4C2 repeats in the C9orf72 gene, and its accumulation is contributing to the neuropathogenesis of C9orf72-associated amyotrophic lateral sclerosis and/or frontotemporal dementia (C9-ALS/FTD). In this study, we demonstrate that poly(PR) protein alone is sufficient to induce neurodegeneration related to ALS/FTD in cynomolgus monkeys. By delivering poly(PR) via AAV, we observed that the PR proteins were located within the nucleus of infected cells. The expression of (PR)50 protein, consisting of 50 PR repeats, led to increased loss of cortical neurons, cytoplasmic lipofuscin, and gliosis in the brain, as well as demyelination and loss of ChAT positive neurons in the spinal cord of monkeys. While, these pathologies were not observed in monkeys expressing (PR)5, a protein comprising only 5 PR repeats. Furthermore, the (PR)50-expressing monkeys exhibited progressive motor deficits, cognitive impairment, muscle atrophy, and abnormal electromyography (EMG) potentials, which closely resemble clinical symptoms seen in C9-ALS/FTD patients. By longitudinally tracking these monkeys, we found that changes in cystatin C and chitinase-1 (CHIT1) levels in the cerebrospinal fluid (CSF) corresponded to the phenotypic progression of (PR)50-induced disease. Proteomic analysis revealed that the major clusters of dysregulated proteins were nuclear-localized, and downregulation of the MECP2 protein was implicated in the toxic process of poly(PR). This research indicates that poly(PR) expression alone induces neurodegeneration and core phenotypes associated with C9-ALS/FTD in monkeys, which may provide insights into the mechanisms of disease pathogenesis.

BackgroundPD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC.AimTo systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC.MethodsAs of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4.ResultsA total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I2 = 0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P

Abstract Background Mesenchymal stem cells (MSCs) derived from different tissues have variant biological characteristics, which may induce different performances in the treatment of diseases. At present, it is difficult to know which type of MSC is most suitable for acute liver failure (ALF), and there is no parallel study to compare MSCs from different tissues of the same donor. Methods In this study, we derived MSCs from three different perinatal tissues of the same donor: cord lining (CL), cord–placenta junction (CPJ) and fetal placenta (FP), respectively, for compared gene expression profiles by transcriptome sequencing, and ability of proliferation and immune regulation in vitro. In addition, the therapeutic effects (e.g., survival rate, histological evaluation, biochemical analysis) of CL-MSCs, FP-MSCs and CPJ-MSCs on ALF mouse model were compared. Results The transcriptome analysis showed that FP-MSCs have significantly high expression of chemokines compared to CPJ-MSCs and CL-MSCs, similar to the q-PCR result. Of note, we found that CPJ-MSCs and FP-MSCs could improve the survival rate of mice with ALF induced by carbon tetrachloride, but CL-MSCs had no difference with Sham group. Moreover, we also found that biomarkers of ALF (e.g., MDA, SOD and GSH-px) significantly improved post-CPJ-MSCs and FP-MSCs treatment, but not CL-MSCs and Sham group. However, CL-MSCs treatment leads to inflammatory reaction in the early stage (day 3) of ALF treatment but not found with other groups. Conclusions It is important to select the MSCs derived from different tissues with variant performance for therapeutic purpose, and the CPJ-MSCs and FP-MSCs cells can significantly improve the syndrome of ALF which is highly recommended for a potential therapeutic options for ALF.

Summary: Highway constructions on the Qinghai-Tibet Plateau (QTP) face great challenges induced by the unique local environmental, geological, and engineering conditions. The large area of permafrost, great temperature variability, strong UV rays, and complex geological conditions are the major factors that adversely influence the long-term performance of pavement systems. Since 1960s, Chinese engineers and researchers have started conducting research on the QTP to enhance the performance and durability of pavement systems. The present paper provide a comprehensive review of challenge, research and practice of highway constructions on the QTP including the special environmental and geological conditions, history of highway constructions on the QTP, major challenges and the state-of-the-art technology of subgrade constructions on permafrost, developments of the pavement structures and materials, performance prediction and maintenance methods of pavement surfaces, and applications of the research achievements on the first expressway on the QTP (i.e., Gongyu Expressway). Based on the comprehensive literature review, it can be found that (1) frost heave and thaw weakening induced subgrade disease and longitudinal cracks on the pavement surface are complex coupled water-thermal-load problems. Engineering solutions are focusing on active cooling and thermal insulation methods, which can help to reduce temperature variations in the subgrade and thus improving its stability, (2) the harsh environmental and construction conditions may reduce the early strength and induce premature damage of cement-treated base materials. Some field validations showed that geocell-reinforced or asphalt-treated flexible base materials can provide better long-term performance, (3) the large temperature variability and strong UV rays can significantly accelerate aging of asphalt binders and greatly reduce the service life of asphalt mixtures. Various binder modification methods were developed for improving their viscoelasticity and enhance the low-temperature cracking resistance of pavement surface materials but are still lack of field validation data and comparisons of their life cycle costs. Therefore, it is recommended that a demonstration research project build test sections to examine a range of pavement structures and materials, and compare their long-term performance and life cycle costs, which can serve as important reference for future highway constructions on the QTP.

This paper presents nano-SiO2 modified microcapsules prepared by in-situ polymerization to improve their performance. Low-quality vegetable oil was selected as the main material and Melamine Urea Formaldehyde (MUF) modified by nano-SiO2 was selected as the shell material. Firstly, the optimal preparation parameters of the nano-SiO2 modified microcapsules were determined, including the emulsifier type, emulsifier concentration, emulsifier shearing speed, the core-shell ratio, reaction pH, reaction temperature, and nano-SiO2 content, respectively, by using the Scanning Electronic Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Thermo-Gravimetric analysis (TGA) and nanoindentation test, etc. Secondly, the properties of the prepared microcapsules were evaluated. The particle size of the prepared nano-SiO2 modified microcapsules was ∼ 78–96 μm, and the average size was 88.16 μm. The average core content was 85.39 %, which exceeds the upper limit of 80 % of existing microcapsules. The nano-hardness and Young’s modulus were 0.33 and 2.63 GPa, respectively, improved by at least 1.4 times compared to existing microcapsules. The mass loss of microcapsules was 0.95 % at 182.73 °C, which is at least 2.9 times higher than the thermal stability of existing microcapsules. The results showed that the addition of nano-SiO2 can obviously improve the performance of microcapsules.

Abstract Background Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Although great advances in HCC diagnosis and treatment have been achieved, due to the complicated mechanisms in tumor development and progression, the prognosis of HCC is still dismal. Recent studies have revealed that the Warburg effect is related to the development, progression and treatment of various cancers; however, there have been a few explorations of the relationship between glycolysis and HCC prognosis. Methods mRNA expression profiling was downloaded from public databases. Gene set enrichment analysis (GSEA) was used to explore glycolysis-related genes (GRGs), and the LASSO method and Cox regression analysis were used to identify GRGs related to HCC prognosis and to construct predictive models associated with overall survival (OS) and disease-free survival (DFS). The relationship between the predictive model and the tumor mutation burden (TMB) and tumor immune microenvironment (TIME) was explored. Finally, real-time PCR was used to validate the expression levels of the GRGs in clinical samples and different cell lines. Results Five GRGs (ABCB6, ANKZF1, B3GAT3, KIF20A and STC2) were identified and used to construct gene signatures to predict HCC OS and DFS. Using the median value, HCC patients were divided into low- and high-risk groups. Patients in the high-risk group had worse OS/DFS than those in the low-risk group, were related to higher TMB and were associated with a higher rate of CD4+ memory T cells resting and CD4+ memory T cells activated. Finally, real-time PCR suggested that the five GRGs were all dysregulated in HCC samples compared to adjacent normal samples. Conclusions We identified five GRGs associated with HCC prognosis and constructed two GRGs-related gene signatures to predict HCC OS and DFS. The findings in this study may contribute to the prediction of prognosis and promote HCC treatment.

The study takes 10 urban agglomerations in China as the research object, focusing on the Chengdu-Chongqing urban agglomeration, and applies Data Envelopment Analysis (DEA) to measure and compare their scientific input and output efficiency of universities. First, this paper analyzes the input and output of scientific research in universities in major provinces in China in detail. Second, according to the construction principles of the indicator system, using qualitative interview to construct evaluation indicators of university research efficiency. Third, using DEA method, first analyze the input and output profile of some urban agglomeration universities such as Chengdu-Chongqing economic circle, measure and compare their research input and output efficiency, then compare and analyze the research efficiency of research-type sample universities within Chengdu-Chongqing economic circle, and conduct a projection study of non-DEA effective sample universities. The main conclusions are as follows: first, the average efficiency of scientific research in universities in Chengdu-Chongqing and other urban agglomerations in 2020 has slightly increased compared with that in 2016, but the gap between urban agglomerations is prominent, and the innovation level of scientific research in higher education institutions in urban agglomerations needs to be improved. Second, there is a mismatch between the themes of research, funding and human resources in research-oriented universities in the Chengdu-Chongqing economic circle. Third, there is considerable room for improvement in research efficiency, and the influence of scale on overall efficiency is weak. We found that excessive investment in scientific research in universities is the main reason for the non-effect.

Lithium-ion batteries experience rapid temperature increases with a high risk of combustion and explosion during thermal runaway, and water mist has been considered as one of the most effective cooling strategies. The water mist field can be impacted by the safety valve airflow, subsequently affecting the cooling characteristics. In this paper, the water mist nozzle with a fixed working pressure is located 1 m above the 100 Ah LiFePO4 battery to suppress the thermal runaway, and the cooling characteristics under various stages have been compared and analyzed. The results show that the development of thermal runaway can be inhibited before thermal runaway is initiated, and the water mist presents a better cooling effect after the battery safety valve is opened. The critical accumulation heat density of 155 kJ/kg has been identified, which is the threshold for thermal runaway suppression. The confrontation between water mist and the flame has been analyzed, and the water mist droplets cannot fall on the battery surface, resulting in a poor cooling rate of 0.57 kW. This means the suppression effect of water mist will be affected by the airflow impact of the safety valve.

Abstract Background The spontaneous osteoarthritis (OA) in rhesus macaque is similar to OA in human, which maintains an upright body posture and shows very similar biomechanical properties of bones to humans. At present, there is no good treatment for OA. This study aims to explore relationship between OA and intestinal microbiota, and provide a reference for the treatment of clinical OA. Results We collected colonic contents of the 20 rhesus macaque (6–15 years old, female) for intestinal microbiota analysis by metagenomics sequencing, of which 10 were spontaneous OA monkeys and 10 were normal monkeys. Our results showed the diversity of gut microbiota in monkeys with OA was decreased compared to the normal monkeys (p = 0.16). Mollicutes, Tenericutes, Coprobacillus and Faecalitalea may be biomarkers for the monkeys of OA. Lactobacillus found significantly increased in OA monkeys. Prevotella and Ruminococcus were higher in the normal group than OA group. Zinc/manganese transport system permease protein (p = 0.0011) and Cyclopropane-fatty-acyl-phospholipid synthase (p = 0.0012) are a microbiota metabolic pathway related to cartilage production. Conclusions Our results indicate that the diversity and composition of intestinal microbiota in monkeys with OA are different compared to the normal monkeys. we have found microbes that may be a biomarker for the diagnosis of osteoarthritis. Functional analysis of the microbiota also predicts cartilage damage in the monkeys with osteoarthritis. Non-human primates are closely related to humans, so this study can provide a reference for the development of drugs for the treatment of OA.

Abstract Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. However, it is unclear whether microbiota and metabolites have demonstrated changes at early PD due to the difficulties in diagnosis and identification of early PD in clinical practice. In a previous study, we generated A53T transgenic monkeys with early Parkinson’s symptoms, including anxiety and cognitive impairment. Here we analyzed the gut microbiota by metagenomic sequencing and metabolites by targeted gas chromatography. The gut microbiota analysis showed that the A53T monkeys have higher degree of diversity in gut microbiota with significantly elevated Sybergistetes, Akkermansia, and Eggerthella lenta compared with control monkeys. Prevotella significantly decreased in A53T transgenic monkeys. Glyceric acid, L-Aspartic acid, and p-Hydroxyphenylacetic acid were significantly elevated, whereas Myristic acid and 3-Methylindole were significantly decreased in A53T monkeys. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (KO0131) and the oxidative phosphorylation reaction (KO2147) were significantly increased in metabolic pathways of A53T monkeys. Our study suggested that the transgenic A53T and α-syn aggregation may affect the intestine microbiota and metabolites of rhesus monkeys, and the identified five compositional different metabolites that are mainly associated with mitochondrial dysfunction may be related to the pathogenesis of PD.

Daily streamflow modeling is an important tool for water resources management and flood mitigation. This study compared the performance of the Xinanjiang (XAJ) model and random forests (RF) method in a daily streamflow simulation, and proposed several hybrid models based on the XAJ model, wavelet analysis, and RF method (including XAJ-RF model, WRF model, and XAJ-WRF model). The proposed methods were applied to Shiquan station, located in the Upper Han River basin in China. Five performance measures (NSE, RMSE, PBIAS, MAE, and R) were adopted to evaluate the modeling accuracy. Results showed that XAJ-RF model had a relatively higher level of accuracy than that of the XAJ model and the RF model. Compared to the RF and XAJ-RF models, the performance statistics of WRF and XAJ-WRF were better. The results indicated that the coupled XAJ-RF model can be effectively applied and provide a useful alternative for daily streamflow modeling and the application of wavelet analysis contributed to the increasing accuracy of streamflow modeling. Moreover, 14 wavelet functions from various families were tested to analyze the impact of various mother wavelets on the XAJ-WRF model. HIGHLIGHTS This study proposed several hybrid models based on the Xinanjiang (XAJ) model, wavelet analysis and the random forests (RF) method (XAJ-RF, WRF and XAJ-WRF model).; The results indicated that the XAJ-RF model can provide a useful alternative and the application of wavelet analysis contributed to the increasing accuracy in streamflow modeling.;

ABSTRACT The strategy of adjusting the composition of gastrointestinal microbiota has shown great promise for the treatment of diseases. Currently, the relationship between gut microbes and human diseases is mainly presented by the fecal microbiota from the colon. Due to the limits of sampling, the healthy baseline of biogeographic microbiota in the human gastrointestinal tract remains blurry. Captive nonhuman primates (NHPs) present a “humanized” intestinal microbiome and may make up for the lack of atlas data for better understanding of the gut microbial composition and diseases. Therefore, the intestinal microbiota of 6 GIT regions of healthy rhesus monkeys were analyzed in this study; our results showed that Proteobacteria gradually decreased from the small intestine to the large intestine but Bacteroidetes gradually increased from the small intestine to the large intestine. Streptococcus and Lactobacillus can be used as markers to distinguish the small intestine from the large intestine. Sarcina is the most enriched in the middle site of the connection between the large intestine and the small intestine. Cyanobacteria are enriched in the small intestine, especially the duodenum and jejunum, and are absent in the large intestine. The lumenal microbiota of the small intestine is more susceptible to individual differences than is that of the large intestine. Metabolism and oxygen affect the distribution of the microbes, and the diversity of microbiota is the highest in the colon. Our results provide accurate comprehensive GIT microbiota data on nonhuman primates and will be beneficial for the better understanding of the composition of microbiota in the human gastrointestinal tract. IMPORTANCE For the study of upper gastrointestinal microbiota in humans, endoscopic sampling is the main source of information, which limits the understanding of healthy upper gastrointestinal microbiota. Rhesus monkeys show very close similarity to humans in physiology, genetics, and behavior and act as the most suitable animal models for human diseases. The present research made up for the lack of atlas data due to the ethical limitations of sampling in humans and provided baseline data on microbiota in 6 GIT regions of healthy NHPs. These important references will be beneficial for the better understanding of the regional organization and functions of gut microbial communities along the GIT and their relevance to conditions of health and disease.

Fog-to-cloud computing has now become a new cutting-edge technique along with the rapid popularity of Internet of Things (IoT). Unlike traditional cloud computing, fog-to-cloud computing needs more entities to participate in, including mobile sinks and fog nodes except for cloud service provider (CSP). Hence, the integrity auditing in fog-to-cloud storage will also be different from that of traditional cloud storage. In the recent work of Tian et al., they took the first step to design public auditing system for fog-to-cloud computing. However, their scheme becomes very inefficient since they uses intricate public key cryptographic techniques, including bilinear mapping, proof of knowledge etc. In this paper, we design a general and more efficient auditing system based on MAC and HMAC, both of which are popular private key cryptographic techniques. By implementing MAC and HMAC, we give a concrete instantiation of our auditing system. Finally, the theoretical analysis and experiment results show that our proposed system has more efficiency in terms of communication and computational costs.

Objective To investigate the effect of Helicobacter pylori-400 that was isolated from high incidence area of gastric cancer on the proteome of gastric epithelial cell line GES1. Methods The gastric mucosa of patients with positive C-13 breath test was sampled with gastroscope, and H.pylori was isolated. GES1 was co-cultured with H.pylori-400 in the ratio of 1∶50, cellular RNA was extracted,and the mRNA expressions of IL-8, IL-1β and TNF-α were detected by RT-qPCR. Cellular proteins were extracted and analyzed by HPLC-MS, lable-free was used for quantitative analysis. The differentially expressed proteins were selected for enrichment analysis of GO and KEGG, and the hub genes were screened out for further analysis. Results H.pylori-400 promoted mRNA expres- sion of IL-8, IL-1β and TNF-α of gastric epithelial cells. HPLC-MS showed that 373 proteins molecules changed(|Fold change|≥2) after GES1 co-cultured with H.pylori-400, among them, 143 proteins molecules decreased and 230 protein molecules increased. GO and KEGG enrichment analysis showed that H.pylori-400 regulated the secretion of inflammatory factors by regulating cell cycle, T cell immune activity and p53 pathway, which may lead to tumor genesis. Conclusions H.pylori-400 isolated from the high incidence area of gastric cancer can promote the expression of inflammatory factors and promote the tumor genesis by affecting the proteome of GES1 cells.

BackgroundTricuspid regurgitation after left-sided valve surgery was associated with terrible outcomes and high perioperative mortality for surgical treatment. In current years, minimally invasive isolated tricuspid valve repair is increasingly performed in our institution to address tricuspid regurgitation.MethodsThirty-seven consecutive patients with previous left-sided valve surgery underwent minimally invasive isolated tricuspid valve repair in our institution between November 2017 and December 2020. Twenty-nine patients(78.4%) were women and the mean age of patients was 58.4 ± 8.5 years. Follow-up was 100% complete with a mean follow-up time of 17.2 ± 9.5 months.ResultsBoth the in-hospital and 30-day mortalities were 2.7%. The overall NYHA class had improved significantly during the follow-up (p < 0.001). The grade of TR had decreased before discharge (p < 0.001) and during the follow-up (p < 0.001) compared with the preoperative level although severe TR was recurrent in one patient.ConclusionsMinimally invasive isolated tricuspid valve repair has acceptable early and midterm outcomes, may be the preferred surgical option to address tricuspid regurgitation after previous left-sided valve surgery when it is feasible.

Neural stem cells (NSCs) and derivatives are potential cellular sources to treat neurological diseases. In the current study, we reprogrammed human peripheral blood mononuclear cells into induced NSCs (iNSCs) and inserted GFP gene into the AAVS1 site for graft tracing. Targeted integration of GFP does not affect the proliferation and differentiation capacity of iNSCs. iNSC-GFP can be further differentiated into dopaminergic precursors (DAPs) and motor neuron precursors (MNPs), respectively. iNSCs were engrafted into the motor cortex and iNSC-DAPs into the striatum and substantia nigra (SN) of a nonhuman primate, respectively. The surviving iNSCs could respond to the microenvironment of the cortex and spontaneously differentiate into mature neurons that extended neurites. iNSC-DAPs survived well and matured into DA neurons following transplantation into the striatum and SN. iNSC-MNPs could also survive and turn into motor neurons after being engrafted into the spinal cord of rats. The results suggest that iNSCs and derivatives have a potential to be used for the treatment of neurological diseases.

Peganum harmala L. is a perennial herbaceous plant belonging to the family of Zygophyllaceae, and is grows in semi-arid climates, such as Xinjiang, Gansu, Ningxia, Qinghai, and Inner Mongolia in China, and also Middle East and North Africa. This species is of high medicinal value. The complete chloroplast genome was reported in this study. The chloroplast genome with a total size of 159,957 bp consists of two inverted repeats (IR, 26,550 bp) separated by a large single-copy region (LSC, 88,098 bp) and a small single-copy region (SSC, 18,759 bp). Further annotation revealed the chloroplast genome contains 113 genes, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. A total of 90 simple sequence repeats (SSRs) were identified in the chloroplast genome. This information will be useful for study on the evolution and genetic diversity of Peganum harmala in the future.

Nonhuman primates (NHPs) have been considered as the best models for biomedical research due to their high similarities in genomic, metabolomic, physiological and pathological features to humans. However, generation of genetically modified NHPs through traditional methods, such as microinjection into the pronuclei of one-cell embryos, is prohibitive due to the targeting efficiency and the number of NHPs needed as oocyte/zygote donors. Using spermatogonial stem cells (SSCs) as the target of gene editing, producing gene-edited sperm for fertilization, is proven to be an effective way to establish gene editing animal disease models. In this experiment, we used ultrasound to guide the echo dense injection needle into the rete testis space, allowing the EGFP lentivirus to be slowly injected at positive pressure from the rete testis into seminiferous tubules. We found Thy1 can be used as a surface marker of cynomolgus monkey SSCs, confirming that SSCs carry the GFP gene. Finally, we successfully obtained transgenic sperm, with a similar freezing and recovery rate to that of WT animals.

Antifreeze protein III (AFP III) is used for the cryopreservation of germ cells in various animal species. However, the exact mechanism of its cryoprotection is largely unknown at the molecular level. In this study, we investigated the motility, acrosomal integrity, and mitochondrial membrane potential (MMP), as well as proteomic change, of cynomolgus macaque sperm after cryopreservation. Sperm motility, acrosomal integrity, and MMP were lower after cryopreservation (p < 0.001), but significant differences in sperm motility and MMP were observed between the AFP-treated sperm sample (Cryo+AFP) and the non-treated sample (Cryo–AFP) (p < 0.01). A total of 141 and 32 differentially expressed proteins were, respectively, identified in cynomolgus macaque sperm cryopreserved without and with 0.1 μg/ml AFP III compared with fresh sperm. These proteins were mainly involved in the mitochondrial production of reactive oxygen species (ROS), glutathione (GSH) synthesis, and cell apoptosis. The addition of AFP III in the sperm freezing medium resulted in significant stabilization of cellular molecular functions and/or biological processes in sperm, as illustrated by the extent of proteomic changes after freezing and thawing. According to the proteomic change of differentially expressed proteins, we hypothesized a novel molecular mechanism for cryoprotection that AFP III may reduce the release of cytochrome c and thereby reduce sperm apoptosis by modulating the production of ROS in mitochondria. The molecular mechanism that AFP III acts with sperm proteins for cellular protection against cryoinjuries needs further study.

Abstract Background and aim of the study Atrial fibrillation (AF) is the most common atrial arrhythmia. Our aim was to compare the outcomes of atrial fibrillation treatment with original modified minimally invasive MAZE using monopolar radiofrequency ablation (mi-MAZE) and open surgery MAZE using bipolar radiofrequency ablation (os-MAZE). Methods We searched the associated patients’ information on the medical record system of the First Affiliated Hospital, School of Medicine, Zhejiang University. Statistical Package for Social Sciences (SPSS) was used to analyse the data. The primary outcome is the atrial fibrillation ablation rate 3 months, 6 months, 12 months after operation. And secondary outcome is the postoperative quality of life. Results The mi-MAZE group included 42 patients and the os-MAZE group had 65 patients. Three months after surgery, we found that 31 patients (77.5%) in the mi-MAZE group were sinus rhythm and 44 (71.0%) recovered sinus rhythm in the os-MAZE group. We followed up these patients on the phone or in person and scored them on the SF-36 scale. The results were found to be 120.2 ± 8.10 vs 110.6 ± 6.58 (mi-MAZE vs os-MAZE, P

Production animals are often exposed to several oxidative stress conditions, including, but not limited to, heavy metals, alternative protein sources, environmental stress, disease, high densities, as well as handling, which may suppress growth performance, animal health and production, subsequently impacting economic feasibility [...]

BackgroundSecond primary malignancy (SPM) is becoming a threat for the health of cancer survivors. However, data on the features and results of patients with hepatocellular carcinoma (HCC) with SPMs are scarce. This study aimed to explore the characteristics of HCC patients with SPMs and to screen HCC patients who are at a high risk of developing SPMs.MethodHCC patients diagnosed between 2000 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Eligible patients were divided into the only one primary malignancy and SPM groups. The Fine-Gray proportional subdistribution hazards model was used to explore the risk factors of developing SPMs, and a competing-risk model was established to predict the probability of developing SPMs for HCC patients after initial diagnosis. The calibration curves, concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.ResultsA total of 40,314 HCC patients were identified, 1,593 (3.95%) of whom developed SPMs 2 months after the initial diagnosis with a maximum follow-up time of approximately 18 years. The 3-, 5-, and 10-year cumulative incidence of SPMs were 2.35%, 3.12%, and 4.51%, respectively. Age at initial diagnosis, extent of disease, tumor size, and treatment were identified as the independent risk factors of developing SPMs and integrated into the competing-risk nomogram. The C-index of the nomogram was 0.677 (95% confidence interval 0.676–0.678), and the calibration curves showed an excellent agreement between the nomogram prediction and the actual observations. Furthermore, DCA indicated that the nomogram had good net benefits in clinical scenarios.ConclusionsHCC survivors remain at a high risk of developing SPMs. The development of SPMs was associated with the clinical features and treatment strategies. A competing-risk nomogram was constructed to help surgeons identify the patients who are at a high risk of developing SPMs and contribute to the further management of SPMs.