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Loess slopes are often prone to creeping after being subjected to rainfall, artificial irrigation, river water infiltration, etc. Eventually a landslide occurred, even causing a catastrophic accident. There are few studies on the creep properties of loess landslide soil under different water content in the existing literature, and there is a lack of quantitative analysis of the law. A series of triaxial creep tests of sliding zone soil of loess landslide in the Secaowan Village, Yulin City have been carried. The stress-strain-time curves and isochronous stress-strain curves with different water contents (w=10%，12%，14%，16%，18%, w represents the water content) are obtained and the influence of water content on the creep characteristics of loess is analyzed as well. The long-term strength of loess is obtained by using the isochronous curve method. The research results show that (1) When the water content of the sample is larger, the deviator stress required for the creep failure of the sample is smaller, and the axial strain is larger. This phenomenon can be explained by the electric double layer theory as follows: The thickness of free water increases, the degree of cementation among soil particles decreases, and the water film will lubricate the soil particles and make them easy to slip. (2) When the water content of the sample is larger, the time required for the creep strain to reach a stable state after each level of load is applied is longer. This phenomenon can be explained as follows: The increase of loess moisture reduces the structural integrity of the soil, and the adjustment of the internal structure of the soil is relatively slow under the action of stress. Therefore, it takes a longer time for the pore water pressure to dissipate during consolidation and creep. (3) By analyzing the surface morphology of the creep failure of the loess sample, it is found that when the water content is small, the sample after the creep failure has an obvious shear failure surface. When the water content of the sample is larger, the lateral swelling is more likely to occur, showing the characteristics of plastic failure, and indicating that when the moisture content is larger, the softening effect of water is greater than the effect of water on the crack expansion of the soil. (4) The long-term strength loss rate of loess is introduced. It reveals the law of long-term strength and long-term strength loss rate of loess landslide soil under different water content. The research results can provide a reference for the long-term stability analysis of loess landslides.

Objective: This study elaborated the natural history parameters of Delta variant, explored the differences in detection cycle thresholds (Ct) among cases. Methods: Natural history parameters were calculated based on the different onset time and exposure time of the cases. Intergenerational relationships between generations of cases were calculated. Differences in Ct values of cases by gender, age, and mode of detection were analyzed statistically to assess the detoxification capacity of cases. Results: The median incubation period was 4 days; the detection time for cases decreased from 25 to 7 h as the outbreak continued. The average generation time (GT), time interval between transmission generations (TG) and serial interval (SI) were 3.6 ± 2.6 days, 1.67 ± 2.11 days and 1.7 ± 3.0 days. Among the Ct values, we found little differences in testing across companies, but there were some differences in the gender of detected genes. The Ct values continuous to decreased with age, but increased when the age was greater than 60. Conclusion: This epidemic was started from aggregation of factories. It is more reasonable to use SI to calculate the effective reproduction number and the time-varying reproduction number. And the analysis of Ct values can improve the positive detection rate and improve prevention and control measures.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), one kind of tick-borne acute infectious disease, is caused by a novel bunyavirus. The relationship between meteorological factors and infectious diseases is a hot topic of current research. Liaoning Province has reported a high incidence of SFTS in recent years. However, the epidemiological characteristics of SFTS and its relationship with meteorological factors in the province remain largely unexplored. Methods Data on reported SFTS cases were collected from 2011 to 2019. Epidemiological characteristics of SFTS were analyzed. Spearman’s correlation test and generalized linear models (GLM) were used to identify the relationship between meteorological factors and the number of SFTS cases. Results From 2011 to 2019, the incidence showed an overall upward trend in Liaoning Province, with the highest incidence in 2019 (0.35/100,000). The incidence was slightly higher in males (55.9%, 438/783), and there were more SFTS patients in the 60–69 age group (31.29%, 245/783). Dalian City and Dandong City had the largest number of cases of SFTS (87.99%, 689/783). The median duration from the date of illness onset to the date of diagnosis was 8 days [interquartile range (IQR): 4–13 days]. Spearman correlation analysis and GLM showed that the number of SFTS cases was positively correlated with monthly average rainfall (r s = 0.750, P

BackgroundMost patients with Alzheimer's disease (AD) have an insidious onset and frequently atypical clinical symptoms, which are considered a normal consequence of aging, making it difficult to diagnose AD medically. But then again, accurate diagnosis is critical to prevent degeneration and provide early treatment for AD patients.ObjectiveThis study aims to establish a novel EEG-based classification framework with deep learning methods for AD recognition.MethodsFirst, considering the network interactions in different frequency bands (δ, θ, α, β, and γ), multiplex networks are reconstructed by the phase synchronization index (PSI) method, and fourteen topology features are extracted subsequently, forming a high-dimensional feature vector. However, in feature combination, not all features can provide effective information for recognition. Moreover, combining features by manual selection is time-consuming and laborious. Thus, a feature selection optimization algorithm called MOPSO-GDM was proposed by combining multi-objective particle swarm optimization (MOPSO) algorithm with Gaussian differential mutation (GDM) algorithm. In addition to considering the classification error rates of support vector machine, naive bayes, and discriminant analysis classifiers, our algorithm also considers distance measure as an optimization objective.ResultsFinally, this method proposed achieves an excellent classification error rate of 0.0531 (5.31%) with the feature vector size of 8, by a ten-fold cross-validation strategy.ConclusionThese findings show that our framework can adaptively combine the best brain network features to explore network synchronization, functional interactions, and characterize brain functional abnormalities, which can improve the recognition efficiency of diseases. While improving the classification accuracy of application algorithms, we aim to expand our understanding of the brain function of patients with neurological disorders through the analysis of brain networks.

Background and objectives: In recent years, there has been a significant increase in the prevalence of pulmonary mycosis disease, and its mortality has increased. There are very few studies on treating pulmonary mycosiss with bronchoscopic instillation of amphotericin B. This study investigated the clinical efficacy and safety of bronchoscopic instillation of amphotericin B for treating pulmonary mycosiss.Methods: This was a multi-centre, retrospective clinical study of 80 patients with pulmonary mycosiss who were treated with bronchoscopic instillation of amphotericin B. The efficacy and safety of this treatment were evaluated.Results: Eighty patients were included {51 males; mean [standard deviation (SD)] age, 46 (15.9) years}. The most common underlying cause was haematological malignancy (73.75%). The mean number of bronchoscopic instillations of amphotericin B was 2.4 (SD 1.5). In terms of treatment success, 58 (72.5%) patients achieved complete or partial changes on imaging after treatment. A total of 62 (77.5%) patients achieved complete or partial changes on imaging and/or local limitation of the mycosis infection. Seventy-six (95%) patients achieved complete or partial changes on imaging and/or local limitation of mycosis infection and/or an immunotherapy time window. The efficacy rates for treatment of Aspergillus and Mucor infections in terms of the three treatment success criteria described above were 73.81% vs. 63.64%, 80.95% vs. 72.73%, and 92.86% vs. 90.91%, respectively.Conclusion: Bronchoscopic instillation of amphotericin B is safe and effective for treatment of pulmonary mycosiss.

IntroductionPerilla oil is a natural vegetable oil rich in alpha-linolenic acid extracted from Perilla seeds. Fish oil is a commonly used animal fat containing a large amount of n-3 polyunsaturated fatty acids. Soybean oil is a commonly used vegetable oil rich in linoleic acid. This study aimed to determine whether perilla, fish, or soybean oil can be used as a lipid source in the diet of the Chinese giant salamander (Andrias davidianus).MethodsThree isonitrogenous and isolipidic diets were created by adding 3.0% each of soybean oil (SO), fish oil (FO), and perilla seed oil (PSO). Eight adolescent giant salamanders were fed in rectangular tanks for 98 days with a total of 96 giant salamanders (mean body weight = 75.20g) and were fed an experimental diet until satiation.Results and DiscussionThe viscerosomatic index and crude lipid content of muscle were found to be considerably lower and the muscle crude protein was substantially higher in the PSO group than in the other groups (P

Background E-health has the potential to promote health accessibility, performance and cost-saving. However, the adoption and penetration of e-health in underprivileged areas remains insufficient. We aim to investigate patients’ and doctors’ perception, acceptance, and utilization of e-health in a rural, spatially isolated and poverty-stricken county in southwestern China. Methods A retrospective analysis based on a cross-sectional survey of patients and doctors in 2016 was conducted. Participants were recruited through convenience and purposive sampling, and questionnaires were self-designed and validated by investigators. The utilization, intention to use and preference of four e-health services were evaluated, including e-appointment, e-consultation, online drug purchase, and telemedicine. Predictors of utilization and intention to use e-health services were investigated by multivariable logistic regression. Results A total of 485 patients were included. The utilization rate of any type of e-health services was 29.9%, ranging from 6% in telemedicine to 18% in e-consultation. Additionally, 13.9%-30.3% of respondents as non-users revealed their willingness to use such services. Users and potential users of e-health services were inclined to specialized care from county, city or province hospitals, and they were most concerned with the quality, ease of use and price of e-health service. Patients’ utilization and intention to use e-health could be associated with education and income level, cohabitants, working location, previous medical utilization, and access to digital device and internet. There remained 53.9%-78.3% of respondents reluctant to use e-health services, mainly due to perceived inability to use them. Of 212 doctors, 58% and 28% had provided online consultation and telemedicine before, and over 80% of county-hospital doctors (including actual providers) indicated their willingness to provide such services. Reliability, quality and ease of use were doctors’ major concerns regarding e-health. Doctors’ actual provision of e-health was predicted by their professional title, number of years in work, satisfaction with the wage incentive system, and self-rated health. Nevertheless, their willingness to adopt was only associated with the possession of smartphone. Conclusions E-health is still in its infancy in western and rural China, where health resources are most scarce, and where e-health could prove most beneficial. Our study reveals the wide gaps between patients’ low usage and their certain willingness to use e-health, as well as gaps between patients’ moderate attention to use and physician’s high preparedness to adopt e-health. Patients’ and doctors’ perceptions, needs, expectations, and concerns should be recognized and considered to promote the development of e-health in these underprivileged regions.

To solve grid-scale problems and evaluation indicator selection in landscape ecological risk index (LERI) evaluation, this paper takes the Bailong River Basin in Gansu Province (BLRB) as an example. The LERI evaluation formulae and optimal grid scales were determined by screening landscape indices and area changes in the LERI at different grid scales. The evaluation indices were finally obtained according to the landscape characteristics and the correlation analysis of the landscape index value. Through the statistical analysis of the area of the LERI at the grid scale of 1–6 km, the optimal grid scale was determined to be 5 km. There was little change in land use patterns, with the most significant increases in artificial surfaces at 3.29% and 3.58%, respectively. Cultivated land was the only land use type to decrease by 184.3 km2. The LERI drops with the reduced cultivated land area; the landscape ecological medium risk area and cultivated land keep the same spatial distribution. Due to the limitation of the topography, cultivated land is generally distributed below 2500 m altitude, so 2500 m becomes the turning point in the spatial distribution of the LERI. The medium risk below 2500 m dominates the LERI type. Reduced cultivated land was the leading cause of reduced ecological risk according to an overlay analysis. The study of LERI evaluations provides a theoretical basis for sustainable and ecological environmental protection in the BLRB.

Objective: Mumps is a seasonal infectious disease, always occurring in winter and spring. In this study, we aim to analyze its epidemiological characteristics, transmissibility, and its correlation with meteorological variables. Method: A seasonal Susceptible–Exposed–Infectious/Asymptomatic–Recovered model and a next-generation matrix method were applied to estimate the time-dependent reproduction number (Rt). Results: The seasonal double peak of annual incidence was mainly in May to July and November to December. There was high transmission at the median of Rt = 1.091 (ranged: 0 to 4.393). Rt was seasonally distributed mainly from February to April and from September to November. Correlations were found between temperature (Pearson correlation coefficient [r] ranged: from 0.101 to 0.115), average relative humidity (r = 0.070), average local pressure (r = -0.066), and the number of new cases. In addition, average local pressure (r = 0.188), average wind speed (r = 0.111), air temperature (r ranged: -0.128 to -0.150), average relative humidity (r = -0.203) and sunshine duration (r = -0.075) were all correlated with Rt. Conclusion: A relatively high level of transmissibility has been found in Xiamen City, leading to a continuous epidemic of mumps. Meteorological factors, especially air temperature and relative humidity, may be more closely associated with mumps than other factors.

Abstract Purpose Cholecystectomy (XGB) is widely recognized as a risk factor for colon cancer (CC). Continuous exposure of the colonic epithelium to deoxycholic acid (DCA) post-XGB may exert cytotoxic effects and be involved in the progression of CC. However, the functions of the XGB-induced DCA increase and the underlying mechanism remain unclear. Methods Colitis-associated CC (CAC) mouse models constructed by AOM-DSS inducement were used to confirm the effect of XGB on the CC progression. Hematoxylin & eosin staining was performed to assess the tumor morphology of CAC mouse models tissues. Various cell biological assays including EdU, live-cell imaging, wound-healing assays, and flow cytometry for cell cycle and apoptosis were used to evaluate the effect of DCA on CC progression. The correlation among XGB, DCA, and CC and their underlying mechanisms were detected with immunohistochemistry, mass spectrometry, transcriptome sequencing, qRT-PCR, and western blotting. Results Here we proved that XGB increased the plasma DCA level and promoted colon carcinogenesis in a colitis-associated CC mouse model. Additionally, we revealed that DCA promoted the proliferation and migration of CC cells. Further RNA sequencing showed that 120 mRNAs were upregulated, and 118 downregulated in DCA-treated CC cells versus control cells. The upregulated mRNAs were positively correlated with Wnt signaling and cell cycle-associated pathways. Moreover, DCA treatment could reduced the expression of the farnesoid X receptor (FXR) and subsequently increased the levels of β-Catenin and c-Myc in vitro and in vivo. Moreover, the FXR agonist GW4064 decreased the proliferation of CC cells by repressing the expression of β-catenin. Conclusion We concluded that XGB-induced DCA exposure could promote the progression of CC by inhibiting FXR expression and enhancing the Wnt-β-catenin pathway. Video Abstract

Abstract Background Social wasps Polistes, Ropalidia, and Parapolybia, belonging to the subfamily Polistinae, have obviously different distribution patterns, yet the factors leading to this difference remain unknown. Results The 17 newly sequenced mitogenomes of Polistes, Ropalidia, and Parapolybia contain 37 genes, and there are obvious differences among the compositions of the three genera. The monophyly of the genus Polistes and a monophyletic Ropalidiini: (Ropalidia + Parapolybia) are concordant with previous morphological analysis of the subfamily Polistinae. Our inferred divergence time demonstrates Polistes (at around 69 Ma) was diverged earlier than Ropalidia and Parapolybia (at around 61 Ma). The rearrangement of both trnY and trnL1 are shared by all the Polistinae. In addition, the unique rearrangement of TDRL derived at 69 Ma is detected in Polistes, and Ropalidia contains a Reversal which may derive at 61 Ma. Hereafter, the possibility is elaborated that Polistes originated in Aisa and then dispersed from Africa to South America, and Polistes and Ropalidia spread from Southeast Asia to Australia. At last, continental drift and Quaternary Ice Ages are inferred to be two main limiting factors in the current distributions of the three genera. Conclusions Obvious differences occur in the mitochondrial composition of Polistes, Ropalidia, and Parapolybia. According to the reconstructed time-calibrated framework, it is inquired that the continental drifts and the climate are mainly diffusion limiting factors of the three genera.

Baylisascaris schroederi, a roundworm (ascaridoid) parasite specific to the bamboo-feeding giant panda (Ailuropoda melanoleuca), represents a leading cause of mortality in wild giant panda populations. Here, we present a 293-megabase chromosome-level genome assembly of B. schroederi to infer its biology, including host adaptations. Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations, suggesting their potential for transmission and rapid adaptation to new hosts. Genomic and anatomical lines of evidence, including expansion and positive selection of genes related to the cuticle and basal metabolisms, indicate that B. schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism. Additionally, we characterized the secretome of B. schroederi and predicted potential drug and vaccine targets for new control strategies. Overall, this genome resource provides new insights into the host adaptation of B. schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages. Our findings on the unique biology of B. schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

Abstract Background Muscle mass and muscle quality assessed by computed tomography (CT) have been associated with poor prognosis in oncology and surgery patients, but the relevant evidence was limited in older patients. We hypothesized that muscle mass and muscle quality indicators derived from opportunistic chest CT images at the 12th thorax vertebra level (T12) could predict in‐hospital death, length of hospital stay (hospital LOS), and hospital costs among older patients in acute care wards. Methods We conducted a prospective cohort study. Older patients admitted to the acute geriatric wards of a teaching hospital were continuously recruited. Chest CT images were analysed using SliceOmatic software. The skeletal muscle area, skeletal muscle radiodensity, and intermuscular adipose tissue (IMAT) at the T12 level were measured. Skeletal muscle index (SMI) was calculated using skeletal muscle area divided by body height squared. Results We included 1135 older patients with a median age of 80 years (interquartile range, 73 to 85 years), 498 (44%) were women, 148 (13%) patients died during hospitalization. The SMI and SMD were negatively correlated to age (ρ = −0.11, P

Abstract A patient presented to our hospital with myocarditis caused by mushroom poisoning. The early ECG changes in this patient were very similar to the ECG of hyperacute ST‐segment elevation myocardial infarction or hyperkalemia, but further tests eliminated these options. The patient was fully treated by timely hemodialysis treatment, confirming the diagnosis of mushroom poisoning‐induced myocarditis. Although not specific to mushroom poisoning myocarditis, our experience shows that the observed ECG changes. Our findings have the potential to help diagnose and manage this potentially fatal disease in the future.

Objective: Diabetes is an important risk factor for sarcopenia and contributes to poor prognosis; it is important for clinicians to identify sarcopenia early in the population with type 2 diabetes mellitus. Our aim was to establish a clinical screening model of sarcopenia in Chinese patients with type 2 diabetes mellitus. Methods: A cross-sectional study was conducted involving 1131 hospitalized patients (62.67 ± 11.25 years) with type 2 diabetes mellitus, including 560 men and 571 women. All muscle/fat parameters were measured by dual energy X-ray absorptiometry and the clinical correlation with sarcopenia was evaluated. The least absolute shrinkage and selection operator was used to select optimal variables and build a nomogram chart of the sarcopenic screening model for patients with type 2 diabetes mellitus, respectively. The area under the receiver operating characteristic curve (AUC), the calibration curve, the analysis of the decision curve, the clinical impact curve, and external validations were used to evaluate discriminative ability and clinical applicability. Results: The prevalence of sarcopenia in patients with type 2 diabetes mellitus was 30.06 % (340/1131). Compared to the non-sarcopenic group, the sarcopenic group was older, more likely to be men, and had a higher heart rate and lower body mass index (BMI), waist-hip ratio (WHR), upper limb muscle mass, lower limb muscle mass and fat paraments (all P

Canine parvovirus (CPV) and Canine distemper virus (CDV) can cause fatal diseases in giant panda (Ailuropoda melanoleuca). The main capsid protein of CPV VP2 can be self-assembled to form virus-like particles (VLPs) in vitro, which is of great significance for potential vaccine development. In the present study, we remodeled the VP2 protein of a giant panda-derived CPV, where the major CDV F and N epitopes were incorporated in the N-terminal and loop2 region in two combinations to form chimeric VLPs. The reactivity ability and morphology of the recombinant proteins were confirmed by Western blot, hemagglutination (HA) test and electron microscopy. Subsequently, the immunogenicity of the VLPs was examined in vivo. Antigen-specific antibodies and neutralizing activity were measured by ELISA, hemagglutination inhibition (HI) test and serum neutralization test (SNT), respectively. In addition, antigen specific T cell activation were determined in splenic lymphocytes. The results indicated that the VLPs displayed good reaction with CDV/CPV antibodies, and the heterologous epitopes do not hamper solubility or activity. The VLPs showed decent HA activity, and resembled round-shaped particles with a diameter of 22–26 nm, which is identical to natural virions. VLPs could induce high levels of specific antibodies to CPV and CDV, shown by the indication of neutralizing antibodies in both VP2N and VP2L VLPs group. In addition, splenic lymphocytes of mice immunized with VLPs could proliferate rapidly after stimulation by specific antigen. Taken together, the CPV VP2 VLPs or chimeric VLPs are highly immunogenic, and henceforth could function as CPV/CDV vaccine candidates for giant pandas.

BackgroundQuantitative assessment of the risk of local transmission from imported dengue cases makes a great challenge to the development of public health in China. The purpose of this study is to observe the risk of mosquito-borne transmission in Xiamen City through ecological and insecticide resistance monitoring. Quantitative evaluation of mosquito insecticide resistance, community population and the number of imported cases affecting the transmission of dengue fever (DF) in Xiamen was carried out based on transmission dynamics model, so as to reveal the correlation between key risk factors and DF transmission.MethodsBased on the dynamics model and combined with the epidemiological characteristics of DF in Xiamen City, a transmission dynamics model was built to simulate the secondary cases caused by imported cases to evaluate the transmission risk of DF, and to explore the influence of mosquito insecticide resistance, community population and imported cases on the epidemic situation of DF in Xiamen City.ResultsFor the transmission model of DF, when the community population is between 10,000 and 25,000, changing the number of imported DF cases and the mortality rate of mosquitoes will have an impact on the spread of indigenous DF cases, however, changing the birth rate of mosquitoes did not gain more effect on the spread of local DF transmission.ConclusionsThrough the quantitative evaluation of the model, this study determined that the mosquito resistance index has an important influence on the local transmission of dengue fever caused by imported cases in Xiamen, and the Brayton index can also affect the local transmission of the disease.

The impact of biomass burning (BB) emissions on concentrations and depositions of major aerosol components in the northern South China Sea (NSCS) region (105∼115°E and 15∼21°N) from December 2020 to April 2021 has been investigated using the WRF-chem model (weather research and forecasting model coupled with chemistry) in combination with aerosol composition measurement at a mountain site in the Hainan Island of China. Model comparisons with observations in Hainan demonstrated the effectiveness of WRF-chem in simulating aerosol components (PM2.5, black carbon (BC), organic matter (OM), sulfate, nitrate, and ammonium) in the NSCS region. The influences of BB emissions were significant on near-surface PM2.5, BC, and OM but nearly negligible on secondary inorganic components (i.e., sulfate, nitrate, and ammonium). The NSCS regional and period mean PM2.5, BC, and OM concentrations were 17.2 μg/m3, 0.65 μg/m3, and 6.7 μg/m3, in which 20%, 13%, and 35%, respectively, were from BB emissions. The mean PM2.5, BC, and OM deposition fluxes were 73.8 mg/m2/month, 2.9 mg/m2/month, and 29.3 mg/m2/month, respectively, and 22%, 15%, and 38% of these depositions were from BB emissions. Dry deposition dominated the removal of aerosols. For both aerosol concentrations and depositions, the influences of BB emissions exhibited evidently larger contributions in spring (March and April) than those in winter (December to February). Most of the BB emissions were from mainland Southeast Asia (MSEA), in terms of period mean, 79%, 72%, and 81% of the BB PM2.5, BB BC, and BB OM concentrations and 82%, 77%, and 83% of their depositions in the NSCS region were attributed to the MSEA region. The results of this study suggested that BB emissions have strong implications for air quality and biogeochemical cycle of the NSCS region.

China's green development in the context of carbon neutrality is facing both new constraints and new practices. In the new situation, it is crucial to further refine the indicator system and re-measure green development. Based on previous studies and carbon neutral background, the theoretical framework of green development is improved and an indicator system is constructed, and the panel entropy method, Thiel index and Moran index are used to measure and analyze green development level and its spatial evolution pattern in China from 2010 to 2019. The study shows that: (1) China's green development level is on the rise and its growth rate is high, and it generally shows a spatial distribution pattern of northeast >east > west > central, and the fastest growth rate in the east; (2) There are some spatial differences in green development level in China and the spatial differences are gradually narrowing, while only the spatial differences in the green wealth index and the inter-regional differences in the green growth index are slightly expanding; (3) There is no obvious spatial clustering phenomenon in China's green development level as a whole, and there is a positive spatial matching relationship between green development level and green wealth index and green growth index locally, which does not form a close correlation with green welfare index. The study proposes countermeasures based on stimulating the endogenous power of green development and narrowing the regional differences of green growth index, which are of reference value for China to promote green development in the context of carbon neutrality.

IntroductionWe are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.MethodsFollowing a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay).ResultsSufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (pConclusionOur experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.

Introduction: The Southwestern United States (SWUS) has an extensive history of coal and metal mining, including uranium (U) mining. Lung diseases, including but not limited to, lung cancer and pulmonary fibrosis, have been studied extensively in miners due to occupational, dust-related exposures. However, high-throughput autoimmune biomarkers are largely understudied in miners, despite the fact that ore miners, such as U-miners, are at an increased risk for the development of autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus (SLE). Additionally, there are current gaps in knowledge regarding which signaling pathways may play a role in occupational exposure-associated autoimmunity. Methods: Most current and former miners in the SWUS live close to their previous workplaces, in remote areas, with limited access to healthcare. In this pilot study, by leveraging a mobile clinical platform for patient care and clinical outreach, we recruited 44 miners who self-identified as either U (n = 10) or non-U miners (n = 34) and received health screenings. Serum IgG and IgM autoantibodies against 128 antigens were assessed using a high-throughput molecular technique, as a preliminary health screening opportunity. Results: Even when adjusting for age as a covariate, there was a significant (p

Background: Tumorous bone defect reconstructions of the proximal humerus with joint sparing is a challenge. Numerous reconstruction methods have been proposed but the proximal residual humerus is commonly sacrificed because of its extremely short length. To preserve the proximal humerus and improve clinical outcomes, we designed a three-dimensional (3D) printed uncemented prosthesis with a porous structure to treat tumorous bone defects of the proximal humerus.Methods: Our analysis included seven patients treated between March 2018 and July 2019. A 3D model was established, and related data were obtained, including the diameter of the humeral head, the resection length, and the residual length. A prosthesis was designed and fabricated based on these data. Functional and oncologic outcomes were recorded, and complications and osseointegration were evaluated.Results: The mean age of the patients was 20.3 years, and the median follow-up period was 26 months. The lengths of the residual proximal humerus were 17.9 mm on average. All the patients had preserved humeral heads and most of the rotator cuff was intact. The average postoperative range of motion (ROM) of the affected shoulder was 83.8°; flexion was 82.5°, extension was 43.8°, and adduction was 16.3°. The average Musculoskeletal Tumor Society score (MSTS) was 94.3%. Good osseointegration was observed on the interface between the bone and prosthesis.Conclusion: A 3D printed porous prosthesis with cone-like structures successfully achieved joint-sparing reconstruction of proximal humeral tumorous defects with satisfying functional outcomes. The preservation of the rotator cuff and humeral head plays an essential role in the function of the shoulder joint.

ObjectivesTo explore the effect of glucose-insulin-potassium (GIK) therapy on uterine cramping pain (UCP) following cesarean delivery (CD).DesignSingle-center, randomized controlled study.SettingSecond Affiliated Hospital of Army Medical University, Chongqing, China.ParticipantsA total of 140 women, aged 20–40 years, who underwent CD with a transverse incision were randomly assigned to the GIK (P) or control (C) groups in a 1:1 ratio.InterventionsGIK was intravenously administered to patients in Group P. Patients in Group C received normal saline (NS). After umbilical cord clamping, oxytocin was administered intravenously. The same GIK and NS regimens were administered on postoperative days 1 and 2, followed by oxytocin 10 min later.Primary and secondary outcome measuresFollowing oxytocin administration, UCP was assessed using the visual analog scale (VAS), and the maximum VAS score (primary outcome) was recorded.ResultsPatients in Group P had significantly lower maximum VAS scores than those in Group C on postoperative days 1 (38.4 ± 21.1 vs. 52.3 ± 20.8, p

Hepatocellular carcinoma (HCC) remains a global health burden, and is mostly diagnosed at late and advanced stages. Currently, limited and insensitive diagnostic modalities continue to be the bottleneck of effective and tailored therapy for HCC patients. Moreover, the complex reprogramming of metabolic patterns during HCC initiation and progression has been obstructing the precision medicine in clinical practice. As a noninvasive and global screening approach, metabolomics serves as a powerful tool to dynamically monitor metabolic patterns and identify promising metabolite biomarkers, therefore holds a great potential for the development of tailored therapy for HCC patients. In this review, we summarize the recent advances in HCC metabolomics studies, including metabolic alterations associated with HCC progression, as well as novel metabolite biomarkers for HCC diagnosis, monitor, and prognostic evaluation. Moreover, we highlight the application of multi-omics strategies containing metabolomics in biomarker discovery for HCC. Notably, we also discuss the opportunities and challenges of metabolomics in nowadays HCC precision medicine. As technologies improving and metabolite biomarkers discovering, metabolomics has made a major step toward more timely and effective precision medicine for HCC patients.

Extracellular vesicles (EVs) are increasingly used as delivery vehicles for drugs and bioactive molecules, which usually require intravascular administration. The endothelial cells covering the inner surface of blood vessels are susceptible to the shear stress of blood flow. Few studies demonstrate the interplay of red blood cell-derived EVs (RBCEVs) and endothelial cells. Thus, the phagocytosis of EVs by vascular endothelial cells during blood flow needs to be elucidated. In this study, red blood cell-derived extracellular vesicles (RBCEVs) were constructed to investigate endothelial cell phagocytosis in vitro and animal models. Results showed that low magnitude shear stress including low shear stress (LSS) and oscillatory shear stress (OSS) could promote the uptake of RBCEVs by endothelial cells in vitro. In addition, in zebrafish and mouse models, RBCEVs tend to be internalized by endothelial cells under LSS or OSS. Moreover, RBCEVs are easily engulfed by endothelial cells in atherosclerotic plaques exposed to LSS or OSS. In terms of mechanism, oxidative stress induced by LSS is part of the reason for the increased uptake of endothelial cells. Overall, this study shows that vascular endothelial cells can easily engulf EVs in areas of low magnitude shear stress, which will provide a theoretical basis for the development and utilization of EVs-based nano-drug delivery systems in vivo.

Abstract. Background:. Since the diagnostic value of aldosterone to renin ratio (ARR) calculated by plasma renin concentration (PRC) or plasma renin activity (PRA) is still inconclusive, we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA, so as to provide guidance for clinical diagnosis. Methods:. We searched PubMed, Embase, and Cochrane Library from the establishment of the database to March 2021. We included studies that report the true positive, false positive, true negative, and false negative values for the diagnosis of primary aldosteronism, and we excluded duplicate publications, research without full text, incomplete information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. Results:. The pooled results showed that ARR (plasma aldosterone concentration [PAC]/PRC) had a sensitivity of 0.82 (95% confidence interval [CI]: 0.78–0.86), a specificity of 0.94 (95% CI: 0.92–0.95), a positive-likelihood ratio (LR) of 12.77 (95% CI: 7.04–23.73), a negative LR of 0.11 (95% CI: 0.07–0.17), and symmetric area under the curve (SAUC) of 0.982, respectively. Furthermore, the diagnostic odds ratio (DOR) of ARR (PAC/PRC) was 180.21. Additionally, the pooled results showed that ARR (PAC/PRA) had a sensitivity of 0.91 (95% CI: 0.86–0.95), a specificity of 0.91 (95% CI: 0.90–0.93), a positive LR of 7.30 (95% CI: 2.99–17.99), a negative LR of 0.10 (95% CI: 0.04–0.26), and SAUC of 0.976, respectively. The DOR of ARR (PAC/PRA) was 155.52. Additionally, we conducted a subgroup analysis for the different thresholds (

In this paper, a new 3D visualization technical method was developed for hydraulic fractures using micro-seismic monitoring. This technical method consists of four steps: i. interpret the geologic hydraulic fracture model based on seismic source location data from micro-seismic monitoring; ii. develop a hydraulic fracture indication model, relying on the 3D spatial freeze-frame of micro-seismic monitoring sources from hydraulic fracturing; iii. construct a hydraulic fracture density model using the intensity from the micro-seismic monitoring; and iv. implement a 3D visualization of the hydraulic fractures, relying on the spatial constraints of the density model, the hydraulic fracture indication model, and the properties of the hydraulic fractures. This proposed technical method was used to produce 3D visualizations of the hydraulic fractures in well X in the Jiao reservoir, China, and the 3D visualizations of the distribution, development, extent and cutting relationships of hydraulic fractures were successfully realized. The results show that this technical method can be used as a practical and reliable approach to characterize hydraulic fractures.

Abstract Background The zinc transporter ZIP12 is a membrane-spanning protein that transports zinc ions into the cytoplasm from the extracellular space. Recent studies demonstrated that upregulation of ZIP12 is involved in elevation of cytosolic free zinc and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia. However, the expression of ZIP12 and its role in pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats have not been evaluated previously. The aim of this study was to investigate the effect of ZIP12 on the proliferation and migration of PASMCs and its underlying mechanisms in MCT-induced PAH. Methods A PAH rat model was generated by intraperitoneal injection of 20 mg/kg MCT twice at one-week intervals. PASMCs were isolated from the pulmonary arteries of rats with MCT-induced PAH or control rats. The expression of ZIP12 and related molecules was detected in the lung tissues and cells. A ZIP12 knockdown lentivirus and an overexpressing lentivirus were constructed and transfected into PASMCs derived from PAH and control rats, respectively. EdU assays, wound healing assays and Western blotting were carried out to explore the function of ZIP12 in PASMCs. Results Increased ZIP12 expression was observed in PASMCs derived from MCT-induced PAH rats. The proliferation and migration of PASMCs from PAH rats were significantly increased compared with those from control rats. These results were corroborated by Western blot analysis of PCNA and cyclin D1. All these effects were significantly reversed by silencing ZIP12. Comparatively, ZIP12 overexpression resulted in the opposite effects as shown in PASMCs from control rats. Furthermore, selective inhibition of AKT phosphorylation by LY294002 abolished the effect of ZIP12 overexpression on enhancing cell proliferation and migration and partially suppressed the increase in ERK1/2 phosphorylation induced by ZIP12 overexpression. However, inhibition of ERK activity by U0126 resulted in partial reversal of this effect and did not influence an increase in AKT phosphorylation induced by ZIP12 overexpression. Conclusions ZIP12 is involved in MCT-induced pulmonary vascular remodeling and enhances the proliferation and migration of PASMCs. The mechanism of these effects was partially mediated by enhancing the AKT/ERK signaling pathways.

Abstract Background Acquired resistance of 5-fluorouracil (5-FU) remains a clinical challenge in colorectal cancer (CRC), and efforts to develop targeted agents to reduce resistance have not yielded success. Metabolic reprogramming is a key cancer hallmark and confers several tumor phenotypes including chemoresistance. Glucose metabolic reprogramming events of 5-FU resistance in CRC has not been evaluated, and whether abnormal glucose metabolism could impart 5-FU resistance in CRC is also poorly defined. Methods Three separate acquired 5-FU resistance CRC cell line models were generated, and glucose metabolism was assessed by measuring glucose and lactate utilization, RNA and protein expressions of glucose metabolism-related enzymes and changes of intermediate metabolites of glucose metabolite pool. The protein levels of hypoxia inducible factor 1α (HIF-1α) in primary tumors and circulating tumor cells of CRC patients were detected by immunohistochemistry and immunofluorescence. Stable HIF1A knockdown in cell models was established with a lentiviral system. The influence of both HIF1A gene knockdown and pharmacological inhibition on 5-FU resistance in CRC was evaluated in cell models in vivo and in vitro. Results The abnormality of glucose metabolism in 5-FU-resistant CRC were described in detail. The enhanced glycolysis and pentose phosphate pathway in CRC were associated with increased HIF-1α expression. HIF-1α-induced glucose metabolic reprogramming imparted 5-FU resistance in CRC. HIF-1α showed enhanced expression in 5-FU-resistant CRC cell lines and clinical specimens, and increased HIF-1α levels were associated with failure of fluorouracil analog-based chemotherapy in CRC patients and poor survival. Upregulation of HIF-1α in 5-FU-resistant CRC occurred through non-oxygen-dependent mechanisms of reactive oxygen species-mediated activation of PI3K/Akt signaling and aberrant activation of β-catenin in the nucleus. Both HIF-1α gene knock-down and pharmacological inhibition restored the sensitivity of CRC to 5-FU. Conclusions HIF-1α is a potential biomarker for 5-FU-resistant CRC, and targeting HIF-1a in combination with 5-FU may represent an effective therapeutic strategy in 5-FU-resistant CRC.

Abstract Fibrotic hypersensitivity pneumonitis (FHP) remains one of fatal interstitial pulmonary disease. Comprehensively dissecting the cellular heterogeneity of FHP paves the way for developing general gene therapeutic solutions for FHP. Here, utilizing an integrated strategy based on scRNA-seq, scTCR-seq, and bulk RNA-seq analysis of FHP profiles, we identified ten major cell types and 19 unique subtypes. FHP exhibited higher features of EMT and inflammation-promoting than normal control. In distinct subsets of lung macrophages in FHP, FN1high, PLA2G7high, and MS4A6Ahigh macrophages with predominant M2 phenotype exhibited higher activity of inflammatory responses and para-inflammation than other macrophages. KRT17high basal-like epithelial cells were significantly increased in FHP, and showed higher ability to induce EMT. We identified roles for ACTA2high, COL1A1high, and PLA2G2Ahigh fibroblasts in FHP, which were significantly related to interstitial fibrosis. NK cells and KLRG1+ effector CD8+ T cells had greater activity in inflammation-promoting. Our results provide a comprehensive portrait of cellular heterogeneity in FHP, and highlight the indispensable role of cell subpopulations in shaping the complexity and heterogeneity of FHP. These subpopulations are potentially key players for FHP pathogenesis.

Lanzhou is the only provincial capital city in Northwest China where the main stream of the Yellow River and its tributaries flow through the city. Due to its geographical location and the influence of various factors, it is difficult to evaluate and simulate the climatic, hydrological, and ecological processes of the main stream of the Yellow River and its tributaries in the region. In this study, the Wanchuan River basin, currently undergoing ecological restoration, was selected as the study area. Seasonal backscatter differences generated using Sentinel-1/2 (S1/S2) data and the CD algorithm were used to reduce the effects of surface roughness; vegetation indices, soils, and field measurements were used to jointly characterize the vegetation contribution and soil contribution. Then, SM maps with a grid spacing of 10 m × 10 m were generated in the Wanchuan River basin, covering an area of 1767.78 km2. To validate the results, optimal factors were selected, and a training set and validation set were constructed. The results indicated a high level of the coefficient of determination (R2) of 0.78 and the root mean square error (RMSE) of 0.08 for the comparison of measured and inverted water contents, indicating that the algorithm retrieved the SM values of the study area well. Furthermore, Box line plots with ERA5-Land and GLDAS confirmed that the algorithm is in good agreement with current SM products and feasibility for soil water content inversion work in the Wanchuan River basin.

Bisphenol S (BPS) is an environmental pollutant that can accumulate in the human body and cause harm. Puerarin (PUE) is a flavonoid with anti-inflammatory and antioxidant effects. In this study, we used 50 mg/kg/d BPS as a poison and PUE as an intervention for model mice for 42 d. BPS exposure significantly increased the levels of the impairment of the mice’s liver function, T-CHO, TG, LDL-C, ALT, and AST in the BPS group were significantly increased (p < 0.05). Additionally, BPS exposure caused inflammatory cell infiltration in the mice liver tissue and enhanced oxidative stress response, the level of MDA was significantly increased (p < 0.05). The expression of CD36 and pparγ was stimulated after BPS exposure. Moreover, the expression of cpt1a and cpt1b, which promote fatty acid oxidation, was downregulated. After PUE intervention, the levels of genes and proteins involved in lipid synthesis (PPARγ, SREBP1C, and FASN) and metabolism (Cpt1a, Cpt1b, and PPARα) in mice returned to those of the control group, or much higher than those in the BPS group. Therefore, we hypothesized that BPS causes lipid accumulation in the liver by promoting lipid synthesis and reducing lipid metabolism, whereas PUE reduces lipid synthesis and promotes lipid metabolism. Conclusively, our results imply that long-term exposure to BPS in mice affects liver lipid metabolism and that PUE intervention could maintain the liver function of mice at normal metabolic levels.

Hand hygiene is a crucial measure in the prevention and control of infections, and there is a growing awareness among individuals who are making a conscious effort to maintain hand cleanliness. With the advent of the SARS-CoV-2 outbreak, the demand for hand hygiene products has also gradually shifted towards those with antimicrobial properties. Among these products, hand sanitizer gels (HSGs) have gained considerable popularity as an efficient method of hand cleaning, due to their rapid drying and sustained antimicrobial efficacy. Concurrently, there has been a growing interest in novel HSGs that offer additional functions such as skin whitening, moisturizing, and anti-inflammatory effects. These novel HSGs effectively address concerns associated with the ingestion of antimicrobial ingredients and demonstrate reduced skin irritation, thereby alleviating hand dermatological issues. This review provides an extensive overview of the application scenarios, classification, and challenges associated with HSGs while emphasizing the emergence of novel components with biological functions, aiming to contribute to the advancement of hand hygiene practices and offer novel insights for the development of novel HSGs with outstanding antimicrobial properties with other multiple biological functions and desirable biosafety profiles.

The magnetic domains of non-oriented electrical steel bearing cumulative thermal compressions made by a Gleeble 3500 Thermal System were observed using an atomic force microscope (AFM). The component forces, comprising the magnetic forces between the AFM probe and magnetic domains of the samples, along the freedom direction of the probe, were measured, and they formed the value fluctuation of the magnetic domains. The fluctuations of the magnetic domains were analyzed by examining the power spectral density (PSD) curves. The hysteresis curves of the samples were measured using a highly sensitive magnetic measurement system. An analysis of the magnetic force microscope (MFM) maps suggested that some magnetic domains were compressed into crushed and fragmented shapes, similar to the microstructure of deformed grains. Meanwhile, some were reconstructed within the thermal compressions, like dynamic recrystallization microstructures. Meaningfully, the MFM probe moved and deformed the proximal magnetic domains of tested samples within the region of its weak magnetic field. The peak positions of the magnetic domains with a high deformation rate were shifted and moved during the measuring processes by the weakly polarized probe. Both windward and leeward sides simultaneously expressed a slope towards each co-adjacent valley in the MFM maps and induced a statistical throbbing within a narrow band in the PSD curves. Thus, the MFM scanning mode was also analyzed and improved to obtain accurate MFM maps with low disturbances from the weak magnetic field of the probe. Swapping the order positions of the middle processes in the MFM scanning and adding a gliding step between them could offset the peak skewing of magnetic domains caused by the weakly polarized probe during MFM measurement process without incurring excessive replacement costs. Accumulative compression at a high rate (10 s−1) would crush magnetic domains into irregularly decreasing sizes with messy boundaries. This investigation provides an example of the complete relationships among deformations, magnetic domains, and magnetic properties.

Feline panleukopenia (FPL) is a highly contagious acute infectious disease caused by feline parvovirus (FPV). FPV has also been found in giant pandas with clinical signs of vomiting and mild diarrhea, posing a threat to this vulnerable species. Cleaning and disinfection may be one of the most efficacious ways to prevent FPV spread in the habitat of giant pandas. This study evaluated the inactivation effect of peracetic acid (PAA), povidone-iodine (PVP-I), glutaral and deciquam solution (JM) and Virkon S. The tissue culture infective dose (TCID50) assay indicated that the virus may be totally inactivated by JM, PAA and Virkon S. Meanwhile, the hemagglutination (HA) assay showed a high inactivation efficiency of PAA and Virkon S. The analysis of Western blot revealed that PAA, Virkon S and JM can inhibit the structural protein synthesis. Taken together, our findings demonstrated that PAA could rapidly and efficiently inactivate FPV, representing an efficacious disinfectant for FPV control.

As non-noble metal co-catalysts, Nitrides have received extensive attention for their high efficiency and low cost in photocatalytic hydrogen production. In this study, we develop a novel composite co-catalyst of Au/Ta3N5 that significantly enhanced the photocatalytic hydrogen production activity of CdS. The activity of photocatalyst (Au/Ta3N5)/CdS is 7.3 times of bare CdS and 2.2 times of Ta3N5/CdS. The proper capacitance and enhanced activity of Ta3N5 demonstrates the capacitance catalysis effect of Ta3N5, which improves the charges separation and storing of the photoexcited electrons from CdS. Au acts as an active site for proton reduction to further improve the activity.

In order to practice the concept of‘lucid waters and lush mountains are invaluable assets’ and promote the green development of agriculture, it is necessary to improve the efficiency of agricultural energy utilization. Based on the panel data of 28 provinces from 1995 to 2018, this paper calculated China’s agricultural energy input from two categories of direct energy and indirect energy, and used EBM (Epsilon-based Measure) mixed distance function model to measure the energy efficiency of agriculture in China. The nuclear density function and spatial autocorrelation were used to analyze the dynamic evolution of agricultural energy efficiency, and the dynamic panel model was used to analyze the influencing factors of agricultural energy efficiency. The results showed that: ① From 1995 to 2018, the total agricultural energy input had increased year by year in China, with an average annual growth rate of 2% . Energy input structure changed from indirect energy-based to direct energy-based. Agricultural energy efficiency showed an evolutionary trend of ‘rising-stagnating-rising rapidly’in China. The agricultural energy efficiency was generally low in China, and there was a large space for improvement in agricultural energy efficiency. ② From 1995 to 2018, the average annual growth rate of agricultural energy efficiency in the eastern, central and western regions was 2. 7%, 1. 9% and 1. 4% respectively. In 2018, the agricultural energy efficiency in the eastern, central and western regions was 0. 81, 0. 71 and 0. 59 respectively. The gap between regions was expanding rapidly, and the agricultural energy efficiency in the central and western regions needed to be improved. ③ From 1995 to 2018, the agricultural energy efficiency of each province was polarized and the absolute gap was widened. There was obvious improvement in agricultural energy efficiency in Guangdong, Shandong, Jiangxi, Jiangsu, Liaoning and Tianjin, while the agricultural energy efficiency of Xinjiang, Guizhou, Zhejiang, Shanghai, and Inner Mongolia deteriorated. ④ From 1995 to 2018, there was no global spatial correlation of China’s agricultural energy efficiency. However, local ‘high-high’concentration gradually appeared in the eastern region since 2010. ⑤ The first lag of energy efficiency had a significant positive impact on agricultural energy efficiency, and agricultural energy efficiency improvement had a time lag. The level of human capital, per capita net income of farmers and the level of urbanizaton had a significant positive impact on agricultural energy efficiency. The disaster rate, the level of development of secondary and tertiary industries, and the level of opening up had a significant negative impact on agricultural energy efficiency. In the implementation of the strategy of rural revitalization, we should focus on the central and western regions, take the cultivation of professional farmers as the key, focus on improving agricultural production conditions, enhance the level of cooperation between regions, exert the leading role of the secondary and tertiary industries, and enhance the ability of agricultural disaster prevention and mitigation.

Abstract Background For liver cancer patients, the occurrence of postoperative complications increases the difficulty of perioperative nursing, prolongs the hospitalization time of patients, and leads to large increases in hospitalization costs. The ability to identify influencing factors and to predict the risk of complications in patients with liver cancer after surgery could assist doctors to make better clinical decisions. Objective The aim of the study was to develop a postoperative complication risk prediction model based on machine learning algorithms, which utilizes variables obtained before or during the liver cancer surgery, to predict when complications present with clinical symptoms and the ways of reducing the risk of complications. Methods The study subjects were liver cancer patients who had undergone liver resection. There were 175 individuals, and 13 variables were recorded. 70% of the data were used for the training set, and 30% for the test set. The performance of five machine learning models, logistic regression, decision trees-C5.0, decision trees-CART, support vector machines, and random forests, for predicting postoperative complication risk in liver resection patients were compared. The significant influencing factors were selected by combining results of multiple methods, based on which the prediction model of postoperative complications risk was created. The results were analyzed to give suggestions of how to reduce the risk of complications. Results Random Forest gave the best performance from the decision curves analysis. The decision tree-C5.0 algorithm had the best performance of the five machine learning algorithms if ACC and AUC were used as evaluation indicators, producing an area under the receiver operating characteristic curve value of 0.91 (95% CI 0.77–1), with an accuracy of 92.45% (95% CI 85–100%), the sensitivity of 87.5%, and specificity of 94.59%. The duration of operation, patient’s BMI, and length of incision were significant influencing factors of postoperative complication risk in liver resection patients. Conclusions To reduce the risk of complications, it appears to be important that the patient's BMI should be above 22.96 before the operation, and the duration of the operation should be minimized.

Abstract Background Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. Methods We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (R eff) was used to estimate the transmission interaction in different age groups. Results A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (R eff = 4.28), followed by group 2 to 3 (R eff = 2.61), and group 2 to 4 (R eff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45–64 years old. Conclusions Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15–64 years should first be vaccinated to prevent transmission in China. Graphical Abstract

Abstract Arsenic exposure poses numerous threats to human health. Our previous work in mice has shown that arsenic causes anemia by inhibiting erythropoiesis. However, the impacts of arsenic exposure on human erythropoiesis remain largely unclear. We report here that low-dose arsenic exposure inhibits the erythroid differentiation of human hematopoietic progenitor cells (HPCs). The impacts of arsenic (in the form of arsenite; As3+) on red blood cell (RBC) development was evaluated using a long-term culture of normal human bone marrow CD34+-HPCs stimulated in vitro to undergo erythropoiesis. Over the time course studied, we analyzed the expression of the cell surface antigens CD34, CD71 and CD235a, which are markers commonly used to monitor the progression of HPCs through the stages of erythropoiesis. Simultaneously, we measured hemoglobin content, which is an important criterion used clinically for diagnosing anemia. As compared to control, low-dose As3+ exposure (100 nM and 500 nM) inhibited the expansion of CD34+-HPCs over the time course investigated; decreased the number of committed erythroid progenitors (BFU-E and CFU-E) and erythroblast differentiation in the subsequent stages; and caused a reduction of hemoglobin content. These findings demonstrate that low-dose arsenic exposure impairs human erythropoiesis, likely by combined effects on various stages of RBC formation.

Abstract Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.

Genome-wide association studies (GWAS) and candidate pathway studies have identified low-penetrant genetic variants associated with cutaneous melanoma. We investigated the association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival. The Genes, Environment, and Melanoma Study enrolled 3285 European origin participants with incident invasive primary melanoma. For each of 47 melanoma-risk single nucleotide polymorphisms (SNPs), we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and odds ratios for presence of ulceration, mitoses, and tumor-infiltrating lymphocytes (TILs). We also used Cox proportional hazards regression modeling to estimate the per allele hazard ratios for melanoma-specific survival. Passing the false discovery threshold (p = 0.0026) were associations of IRF4 rs12203592 and CCND1 rs1485993 with log of Breslow thickness, and association of TERT rs2242652 with presence of mitoses. IRF4 rs12203592 also had nominal associations (p < 0.05) with presence of mitoses and melanoma-specific survival, as well as a borderline association (p = 0.07) with ulceration. CCND1 rs1485993 also had a borderline association with presence of mitoses (p = 0.06). MX2 rs45430 had nominal associations with log of Breslow thickness, presence of mitoses, and melanoma-specific survival. Our study indicates that further research investigating the associations of these genetic variants with underlying biologic pathways related to tumor progression is warranted.

Abstract Background Intimal hyperplasia caused by vascular injury is an important pathological process of many vascular diseases, especially occlusive vascular disease. In recent years, Nano-drug delivery system has attracted a wide attention as a novel treatment strategy, but there are still some challenges such as high clearance rate and insufficient targeting. Results In this study, we report a biomimetic ROS-responsive MM@PCM/RAP nanoparticle coated with macrophage membrane. The macrophage membrane with the innate “homing” capacity can superiorly regulate the recruitment of MM@PCM/RAP to inflammatory lesion to enhance target efficacy, and can also disguise MM@PCM/RAP nanoparticle as the autologous cell to avoid clearance by the immune system. In addition, MM@PCM/RAP can effectively improve the solubility of rapamycin and respond to the high concentration level of ROS accumulated in pathological lesion for controlling local cargo release, thereby increasing drug availability and reducing toxic side effects. Conclusions Our findings validate that the rational design, biomimetic nanoparticles MM@PCM/RAP, can effectively inhibit the pathological process of intimal injury with excellent biocompatibility. Graphical Abstract

Plain English summary Transcription factor CREB plays an important role in the development of pulmonary hypertension (PH). However, paradoxical roles have been reported in the pathogenesis of PH, and the regulatory mechanisms of CREB activation in pulmonary artery smooth muscle cells (PASMCs) proliferation remained unknown. In this study, we showed that CRE-containing genes were overrepresented among the differentially expressed genes in experimental PH, which resulted from the sustained activation of CREB pathway. The sustained activation of CREB pathway may be associated with the activation of multiple protein kinases that positively regulate CREB and down-regulation of numerous phosphatases involved in CREB dephosphorylation. Additionally, we found that the proliferation of PAMSCs was dependent on the CREB-mediated transcriptional activity in experimental PH. Moreover, the raised intracellular labile zinc possibly from ZIP12 may be associated with reduced protein phosphatases, increased CREB-mediated transcriptional activity and PASMCs proliferation. Collectively, we found CREB-mediated transcriptional activity in the proliferation of PASMCs in PH, which may be associated with multiple protein kinases and/or reduced phosphatases and elevated intracellular zinc. This study may reveal a critical role of zinc-mediated activation of CREB pathway in the proliferation of PASMCs, thus providing a more comprehensive understanding of CREB pathway in the pathogenesis of PH.

Phytosulfokines (PSKs) are a class of tyrosine-sulfated pentapeptides. PSK-α, PSK-γ, and PSK-δ are three reported PSK members involved in regulating plant growth, development, and resistance to biotic and abiotic stresses. Here, we reported a novel type of PSK, PSK-ε with the sequence YSO3VYSO3TN, and its precursor proteins (MtPSKε, LjPSKε, and GmPSKε), specifically from legume species. PSK-ε peptide differs from PSK-δ by one amino acid and is close to PSK-δ in the phylogenetic relationship. Expression profile analysis showed that MtPSKε was highly expressed in Medicago truncatula roots, especially in root tips and emerged lateral roots. Application of the synthetic sulfated PSK-ε peptide and overexpression of MtPSKε significantly promoted M. truncatula root elongation and increased lateral root number, probably by inducing cell division and expansion in roots. Furthermore, MtPSKε expression was induced by rhizobia infection and was detected in root nodules including nodule primordia. Both PSK-ε peptide treatment and MtPSKε overexpression significantly increased nodule number in M. truncatula. Taken together, these results demonstrate that PSK-ε, a novel type of phytosulfokine, positively regulates root elongation and formation of lateral root and root nodule in M. truncatula.

Stigma toward people with HIV or AIDS produces significant harms to their life and also hinders the prevention of AIDS. In the present study, we tested whether awe can weaken AIDS-related stigma and the mediating role of connectedness and empathy between them through a cross-sectional study (Study 1, N = 372) and two experimental studies (Study 2a and 2b, N = 110 and N = 180, respectively). Results showed that awe reduced AIDS-related stigma (Study 2a and 2b), via the serial mediation of connectedness and empathy (Study 1 and 2b). These findings suggest that the experience of awe increases one’s connectedness to the world, which then enhances empathy and decreases AIDS-related stigma. This study expands our understanding of the relationship between awe and stigma, providing empirical basis for decreasing social prejudice to others.

Background: Given the increasing burden of chronic conditions, multimorbidity is now a priority for public health systems worldwide. However, the relationship between household air pollution (HAP) exposure with multimorbidity remains unclear. Methods: We used three waves data (2011, 2013, and 2015) including 19,295 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, to investigate the association between HAP exposure from solid fuel use for heating and cooking with the risk of chronic multimorbidity. Multimorbidity was defined as the coexistence of two or more of 15 chronic diseases (hypertension, diabetes, dyslipidemia, heart disease, stroke, cardiovascular disease, chronic lung disease, asthma, kidney disease, liver disease, digestive disease, cancer, psychiatric disease, memory-related disease, and arthritis). Multiple logistic regression investigated the association between solid fuel use for heating and cooking, separately or simultaneously, with the risk of multimorbidity. Poisson regression with quasi-likelihood estimation explored whether solid fuel exposure could increase the number of morbidities. Stratified analyses and sensitivity analyses examined the effect modification and robustness of the association. Results: Of the 19,295 participants (mean age: 58.9 years), 40.9 % have multimorbidity. Compared with participants who used clean fuels for heating and cooking, the risk was higher in mixed fuel (adjusted odds ratio, aOR = 1.26, 95 %CI:1.16–1.36) and solid fuel users (aOR = 1.81, 1.67–1.98) separately. HAP from solid fuel use was positively associated with an increased number of morbidities (adjusted β = 0.329, 0.290 to 0.368), after controlling for confounders. Those living in a one-story building, with poor household cleanliness have a higher risk of multimorbidity. No significant modifications of those associations by the socio-demographic and behaviour characteristics was observed. Conclusions: HAP from solid fuel use is associated with a high risk of chronic multimorbidity in Chinese adults. Our findings provide important implications for reducing chronic disease burden by restricting solid fuel use.

In recent years, student development and learning outcomes have become a central focus of quality higher education research. Identifying factors associated with student learning outcomes is the key to continuous quality improvement. The purpose of this study was to explore the impact of college experiences on student learning outcomes. A sample of 17,609 undergraduates from 23 Chinese colleges/universities were selected for the study and asked to complete the Chinese version of the College Student Experiences Questionnaire. Structural equation modeling analyses suggested academic and social activity involvement was an important factor influencing student learning outcomes. Campus facilities and the college environment also predicted student learning outcomes. Family background, on the other hand, exerted minimal influence on student learning outcomes. Students’ involvement in academic and social activities served as strong mediators between campus facilities/environment and student learning outcomes. The results highlighted the significance of providing high-quality college experiences. They also informed policymakers and practitioners of possible pathways to support student learning outcomes by enhancing students’ involvement in social and academic activities.

Soil water–salt variations at different spatiotemporal scales and their influencing factors are essential for regional vegetation restoration and management. However, the study of soil water–salt of the alpine area has not taken into account the effect of topography, especially in the long time series. This work investigated the spatiotemporal characteristics of water and salt in topsoil from 2000 to 2021, using regression analysis of on-site data and MODIS products. The heterogeneity and trends of soil water–salt in various topographic factors (elevation, slope, and aspect) were also explored by selecting the maximum area of each gradient factor as the constrained condition with the help of ArcGIS software. The results revealed that 1) the models applied to SWC (soil water content), EC (electrical conductivity), and pH utilizing vegetation indices were suitable for estimating the spatiotemporal variations of soil water–salt. 2) Soil water–salt exhibited local aggregation characteristics with an upward trend in SWC and a downward trend in EC and pH as a whole. 3) Mean annual SWC peaked at 3,400–3,800 m with increasing elevation and trended downward with increasing slope. The aspect of mean annual SWC was characterized by lower values in the southwest and south and higher values in the north, while the results for pH were reversed. The slope had a greater influence on EC than on SWC and pH. 4) The trend change of SWC, EC, and pH fluctuated at 2000–2,400 m and >4,600 m with a clear inflection point at 4°–8° and 20°–24°, respectively. In summary, the effects of topography responded to the distribution and trends of soil water–salt. The results have significant implications for implementing ecological improvements in regions with complicated topography and can serve as a reference for formulating future ecological policies.