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Abstract Type 2 diabetes mellitus (T2DM) patients have compromised mandibular bone architecture/quality, which markedly increase the risks of tooth loosening, tooth loss, and failure of dental implantation. However, it remains lacks effective and safe countermeasures against T2DM-related mandibular bone deterioration. Herein, we studied the effects of pulsed electromagnetic fields (PEMF) on mandibular bone microstructure/quality and relevant regulatory mechanisms in T2DM db/db mice. PEMF exposure (20 Gs, 15 Hz) for 12 weeks preserved trabecular bone architecture, increased cortical bone thickness, improved material properties and stimulated bone anabolism in mandibles of db/db mice. PEMF also upregulated the expression of canonical Wnt3a ligand (but not Wnt1 or Wnt5a) and its downstream β-catenin. PEMF improved the viability and differentiation of primary osteoblasts isolated from the db/db mouse mandible, and stimulated the specific activation of Wnt3a/β-catenin signaling. These positive effects of PEMF on mandibular osteoblasts of db/db mice were almost totally abolished after Wnt3a silencing in vitro, which were equivalent to the effects following blockade of canonical Wnt signaling using the broad-spectrum antagonist DKK1. Injection with Wnt3a siRNA abrogated the therapeutic effects of PEMF on mandibular bone quantity/quality and bone anabolism in db/db mice. Our study indicates that PEMF might become a non-invasive and safe treatment alternative resisting mandibular bone deterioration in T2DM patients, which is helpful for protecting teeth from loosening/loss and securing the dental implant stability.

Abstract Background Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort. Methods We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China’s national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7–50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50–200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels. Results Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50–999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts

The filling rate of adhesive is defined based on the geometric dimensions of the hemming model, and the numerical simulation model of the hemming process with adhesive is established by using the finite element method-smoothed particle hydrodynamics (FEM-SPH) method. By comparing and verifying with the hemming experiment with adhesive, the quantitative study of the influences of the hemming adhesive diameter, the edge distance, and the hemming thickness on the filling rate is realized. The research results show that the flow state and the final filling state of the adhesive layer obtained in the experiment are similar to the numerical simulation results, and the filling rate of the adhesive layer obtained in the experiment is highly consistent with the numerical simulation result, which verifies the feasibility and accuracy of the numerical simulation model. Further analysis shows that the influences of the hemming adhesive diameter, the edge distance, and the hemming thickness on the filling rate decrease in order, and the relationship formulas between the filling rate and process parameters, such as the hemming adhesive diameter, the edge distance, and the hemming thickness, are obtained by fitting, which provides a basis for the optimization design of the hemming process with adhesive of the automobile body sheet.

Abstract HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count

Abstract Accurate quantification of external force is the key to improve the high-precision hemming of autobody closure panels. However, the mechanism of external force on forming quality of complex contour sheet metal with adhesive is not clear subjected to geometric curvature and materials. In the present study, taking the curved edge aluminum sheet as the research object, SPH (smooth particle hydrodynamics) is introduced to simulate the viscous adhesive, and the SPH-FEM (Finite element method) coupling model of adhesive and panels considering the viscosity-pressure effect is established. The numerical simulation of the roller hemming process is carried out, then the validity and reliability of the proposed method are verified by measuring the external force in real time using triaxial force sensor. The multi-step forming process and the effect of external force on the roll in/out, surface wave and plastic strain of aluminum alloy sheet under the viscosity-pressure effect are studied, and the relationship between process parameters and external force is discussed. Results show that the coupling SPH-FEM model can well reflect the hemming process of curved edge structure. The normal force is about 2–3 times of the tangential force in the pre and final hemming process. Compared with the case without adhesive, the surface wave of flange part of the hemming with adhesive is slightly larger. The normal force and the tangential force increase about 90 N and 30 N respectively, when the height increases by 1 mm. It provides an important basis for the accurate control of hemming trajectory and the improvement of manufacturing quality of autobody closure panels.

Abstract Background Monocyte to lymphocyte ratio (MLR) represents a pro-inflammatory immune microenvironment. The aim of this study was to elucidate the effect of MLR and subsequent MLR when relapse occurred (R-MLR) on prognosis for hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) combined with ablation. Methods A prospective analysis was conducted on 606 patients with HCC who were treated with TACE combined with local ablation in Beijing You’an Hospital affiliated to Capital Medical University from January 1, 2012 to December 31, 2016. MLR or R-MLR were stratified according to the optimal cut-off values. The cumulative recurrence-free survival (RFS), overall survival (OS) , and recurrence-death survival (RDS) rates were calculated by Kaplan–Meier method. The Cox proportion hazard model and logistic regression analysis was conducted to screen for independent predictive factors for indicating early relapse and long-term prognosis. Results High MLR was significantly associated with relapse, early recurrence, and overall survival. After a median follow-up of 59.4 months, The cumulative 1-, 3-, 5-year RFS rates of low MLR were 74.6%, 43.8%, and 34.0%; while 66.1%, 32.2%, and 22.6% for high group (P

Weaning stress may cause reduced energy intake for maintenance of mucosal structure. Gln, Glu, and Asp are major energy sources for the small intestine. This study investigated whether Gln, Glu, and Asp improve the intestinal morphology via regulating the energy metabolism in weaning piglets. A total of 198 weaned piglets were assigned to 3 treatments: Control (Basal diet + 1.59% L-Ala); T1 (Basal diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp); T2 (Low energy diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp). Jejunum and ileum were obtained on d 5 or 21 post-weaning. T1 enhanced growth performance. T1 and T2 treatments improved small intestinal morphology by increasing villus height, goblet cell number and decreasing crypt depth. Days post-weaning affected the efficacy of T2, but not T1, on energy metabolism. At normal energy supplementation, Gln, Glu, and Asp restored small intestinal energy homeostasis via replenishing the Krebs' cycle and down-regulating the AMPK (adenosine monophosphate activated protein kinase) pathway. As these are not sufficient to maintain the intestinal energy-balance of piglets fed with a low energy diet on d 5 post-weaning, the AMPK, glycolysis, beta-oxidation, and mitochondrial biogenesis are activated to meet the high energy demand of enterocytes. These data indicated that Gln, Glu, and Asp could restore the energy homeostasis of intestinal mucosa of weaning piglets under normal energy fed. Low energy feeding may increase the susceptibility of piglets to stress, which may decrease the efficacy of Gln, Glu, and Asp on the restoration of energy balance. These findings provide new information on nutritional intervention for insufficient energy intake in weaning piglets.

Abstract Aerobic glycolysis (the Warburg effect) has been demonstrated to facilitate tumor progression by producing lactate, which has important roles as a proinflammatory and immunosuppressive mediator. However, how aerobic glycolysis is directly regulated is largely unknown. Here, we show that ectopic Zeb1 directly increases the transcriptional expression of HK2, PFKP, and PKM2, which are glycolytic rate-determining enzymes, thus promoting the Warburg effect and breast cancer proliferation, migration, and chemoresistance in vitro and in vivo. In addition, Zeb1 exerts its biological effects to induce glycolytic activity in response to hypoxia via the PI3K/Akt/HIF-1α signaling axis, which contributes to fostering an immunosuppressive tumor microenvironment (TME). Mechanistically, breast cancer cells with ectopic Zeb1 expression produce lactate in the acidic tumor milieu to induce the alternatively activated (M2) macrophage phenotype through stimulation of the PKA/CREB signaling pathway. Clinically, the expression of Zeb1 is positively correlated with dysregulation of aerobic glycolysis, accumulation of M2-like tumor-associated macrophages (TAMs) and a poor prognosis in breast cancer patients. In conclusion, these findings identify a Zeb1-dependent mechanism as a driver of breast cancer progression that acts by stimulating tumor–macrophage interplay, which could be a viable therapeutic target for the treatment of advanced human cancers.

The term "micro-entrapment syndrome of nerves innervating the face (MESNIF)" is a relatively new concept. It refers to the micro-entrapment of facial nerve (trigeminal nerve and facial nerve) terminals for various reasons, resulting in one-side facial discomfort, subjective sensory abnormalities, or stiffness, and in certain cases, localized micro muscle movement abnormalities and motor disharmony. It is frequently caused by facial paralysis or chronic trigeminal neuritis or injury, and is prevalent in clinical practice. Peripheral facial paralysis affects 60%-70% of people. Both men and women are susceptible to it. It is most common in young and middle-aged women. At the moment, there are two types of therapy options for this disease: nonsurgical treatments and surgical treatments. Among surgical treatments, pulsed radiofrequency has good curative results. This paper describes two typical situations that had good curative effects.

PurposeTo explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis.Patients and methodsThree independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC).ResultsIn the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue.ConclusionA novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

Abstract Background During the tumourigenesis and development of colorectal cancer (CRC), the inactivation of tumour suppressor genes is closely involved, although detailed molecular mechanisms remain elusive. Accumulating studies, including ours, have demonstrated that basic leucine zipper transcription factor ATF (activating transcription factor)‐like 2 (BATF2) is a capable tumour suppressor that localises in the nucleus. However, its different subcellular localisation, potential functions and underlying mechanisms are unclear. Methods The translocation of BATF2 and its clinical relevance were detected using CRC samples, cell lines and xenograft nude mice. Candidate BATF2‐binding proteins were screened using co‐immunoprecipitation, quantitative label‐free liquid chromatography–tandem mass spectrometry proteomic analysis, Western blotting and immunofluorescence. Recombinant plasmids, point mutations and siRNAs were applied to clarify the binding sites between BATF2 and chromosome region maintenance 1 (CRM1). Results The present study found that BATF2 was mainly localised in the cytoplasm, rather than nucleus, of CRC cells in vitro and in vivo, while cytoplasmic BATF2 expression was inversely correlated with the prognosis of CRC patients. Furthermore, we identified the nuclear export and subsequent ubiquitin‐mediated degradation of BATF2 in CRC cells. Mechanistically, a functional nuclear export sequence (any amino acid) was characterised in BATF2 protein, through which BATF2 bound to CRM1 and translocated out of nucleus, ultimately enhancing CRC growth via inducing activator protein 1 (AP‐1)/cyclin D1/phosphorylated retinoblastoma protein (pRb) signalling pathway. Additionally, nuclear export of BATF2 can be retarded by the mutation of NES in BATF2 or the knockdown of CRM1, whereas CRM1 expression was negatively associated with nuclear BATF2 expression and the prognosis of CRC patients. Conclusion These findings revealed the biological effects and underlying mechanisms of cytoplasmic localisation of BATF2. Furthermore, suppressing nuclear export of BATF2 via mutating its NES region or inhibiting CRM1 expression may serve as a promising therapeutic strategy against CRC.

Sponge City Construction (SCC) has been extensively explored for controlling frequent urban waterlogging and non-point source pollution. Assessing the “supply” and “demand” of SCC as a city-wide approach may aid in appropriate areal coverage to achieve optimal performance on flood control based on local priorities and sustainable urban development plans. However, to date, very few studies have examined the potential spatial mismatches in the “supply” and “demand” of SCC. This study presented the development of a framework to explore the supply–demand relationship based on a spatial multi-criteria evaluation of the existing SCC facilities, risk exposure, and socio-economic vulnerability. The feasibility and application of such a framework were successfully demonstrated in a field application in Guangzhou, China. The results indicated that most of the high-density areas in the city centres of Guangzhou were exposed to high risk with strong SCC demands. Furthermore, Liwan and Yuexiu districts exhibited SCC supply deficits, while SCC supply surpluses were observed in other central districts in Guangzhou. The findings of this study provided insight into the development of a generalised and replicable method that could be used to achieve a balance between the “supply” and “demand” of SCC for more participatory, strategic and multifunctional planning of SCC in various urban contexts.

Malignant melanoma (MM) is the most metastatic and aggressive form of skin cancer, and carries a high risk of death. Immune-checkpoint inhibitor therapy and molecular-targeted therapy can prolong the survival of patients with advanced MM significantly. However, the low response rate and inevitable drug resistance prevent further improvements in efficacy, which is closely related to the tumor microenvironment (TME). The TME refers to the tumor stroma, including fibroblasts, keratinocytes, immune cells, soluble molecules, and extracellular matrix (ECM). The dynamic interaction between the TME and tumor cells is very important for the growth, local invasion, and metastatic spread of tumor cells. A patient-derived organoid (PDO) model involves isolation of tumor tissue from patients with MM and culturing it in vitro in a three-dimensional pattern. Compared with traditional cultivation methods, the PDO model preserves the heterogeneity of the tissue structure of MM and demonstrates the interaction between MM cells and the TME. It can reproduce the characteristics of proliferation, migration, and invasion of MM cells, and better simulate the structural function of MM in vivo. This review explores the role of each TME component in development of the PDO model. This review will provide a reference for research on the drug screening and targeted treatment using PDOs, particularly for the immunotherapy of MM.

ABSTRACT: Earthworm has a variety of molecular biological characteristic, for example, growth promotion, antioxidant, and anti-bacteria. Thus, we decomposed earthworm by earthworm's own protease for preparing of earthworm hydrolysate. Muscovy ducks were fed with basal diet that formulated to contain 1.5% and 2.5% earthworm hydrolysate. Then, we investigated the influences of earthworm hydrolysate on growth performance in Muscovy ducks by performance terminology and measurement for poultry (NY/T 823-2020). The morphology of duodenum and number of intraepithelial lymphocytes were tested by HE staining and immunohistochemical method. Serum biochemical parameters and antioxidant capacity were also determined. High-throughput sequencing technology can sequence 16S rDNA of cecal contents from experimental Muscovy ducks. Results showed that 1.5% earthworm hydrolysate increased ADG (16–70 days old), ALB, HDL-C, T-AOC, CAT, SOD, GSH-PX, villi length, intestine thickness and surface area of villi (P < 0.05 or P < 0.01), and reduced FCR (16–70 days old), UREA, CRE, LDL-C, MDA (P < 0.05 or P < 0.01). Meanwhile, 2.5% improved ADG (16–70 days old), abdominal fat yield, breast muscle yield, heart index, spleen index, ALP, UA, T-AOC, CAT, SOD, GSH-PX, villi length, crypt depth, intestine thickness, surface area of villi, the percentage of intraepithelial lymphocytes (P < 0.05 or P < 0.01), and decreased FCR (42–70 days old and 16–70 days old), UREA, UA, MDA (P < 0.05 or P < 0.01). The sequencing results of gut flora demonstrated that earthworm hydrolysate improved variety of the gut flora in the V4 area of ducks immensely. In a word, our results provide the foundation for preliminary researching the potential principles of earthworm hydrolysate in promoting production performance, adjusting antioxidant function and intestinal functions in the Muscovy duck industry.

ABSTRACT: The study aimed to examine the effects of unfermented and fermented Andrographis paniculata on growth performance, carcass traits, immune function, and intestinal health in Muscovy ducks. A total of 450 (16-day-old) Muscovy ducks weighing 271.44 ± 8.25 g were randomly assigned to 5 dietary treatments (6 replicate pens of 15 ducks per treatment), consisting of one control treatment (basal diet without A. paniculata), one unfermented A. paniculata treatment (basal diet plus 30 g/kg unfermented A. paniculata) and 3 fermented A. paniculata treatments (basal diet plus 10, 30, and 50 g/kg). 30 g/kg unfermented A. paniculata increased the ADG, thymus index, peripheral blood lymphocyte conversion rate, villi height, intestinal thickness, villi surface area, intraepithelial lymphocytes rate, while decreased the FCR. 10 g/kg fermented A. paniculata markedly boosted ADG, bursa of fabricius index, thymus index, serum lysozyme, lymphocyte conversion rate, villi height, vilii width, intestinal thickness, villi surface area, while decreased the FCR. 30 g/kg fermented A. paniculata clearly improved ADG, bursa of fabricius index, thymus index, serum lysozyme, lymphocyte conversion rate, villi height, vilii width, intestinal thickness, villi surface area, intraepithelial lymphocytes, while decreased FCR. 50 g/kg fermented A. paniculata significantly increased villi height, vilii width, and villi surface area, while clearly reduced BW. Additionally, compared to 30 g/kg unfermented A. paniculata, 30 g/kg fermented A. paniculata obviously increased bursa of fabricius indices, lymphocyte conversion rate, vilii width, villi surface area. On top of that, supplementation with unfermented and fermented A. paniculata (30 g/kg each) decreased the relative abundance of harmful bacteria (Succinivibrio, Succinatimonas, Sphaerochaeta, and Mucispirillum) and increase the abundance of beneficial bacteria (Rikenellaceae, Methanocorpusculum, Fournierella, Ruminococcaceae) in the ceca of the ducks. However, fermented A. paniculata had considerable better effects than unfermented A. paniculate on all above measured indices. Overall, these results revealed that supplementation with unfermented and fermented A. paniculata across different treatments improved growth, immune status, intestinal morphology, and intestinal microbiota composition and structure in Muscovy ducks, making it a potential alternative to antibiotics in poultry production.

IntroductionThe flower buds of Lonicera japonica Thunb. are widely used in Chinese medicine for their anti-inflammatory properties, and they have played an important role in the fight against SARS COVID-19 and other major epidemics. However, due to the lack of scientific and accurate variety identification methods and national unified standards, scattered and non-standardized management in flower bud production has led to mixed varieties that have caused significant difficulties in the cataloging and preservation of germplasm resources and the identification, promotion, and application of new L. japonica varieties.MethodsIn this study, we evaluated the population structure, genetic relationships, and genetic fingerprints of 39 germplasm resources of Lonicera in China using simplified genome sequencing technology.ResultsA total of 13,143,268 single nucleotide polymorphisms (SNPs) were identified. Thirty-nine samples of Lonicera were divided into four subgroups, and the population structure and genetic relationships among existing Lonicera germplasm resources were determined using principal component analysis, population structure analysis, and phylogenetic tree analysis. Through several stringent selection criteria, 15 additional streamlined, high-quality DNA fingerprints were filtered out of the validated 50 SNP loci and verified as being able to effectively identify the 39 Lonicera varieties.DiscussionTo our knowledge, this is the first comprehensive study measuring the diversity and population structure of a large collection of Lonicera varieties in China. These results have greatly broadened our understanding of the diversity, phylogeny, and population structure of Lonicera. The results may enhance the future analysis of genetic diversity, species identification, property rights disputes, and molecular breeding by providing a scientific basis and reference data for these efforts.

Background: This study aims to build a focal adhesion-related genes-based prognostic signature (FAS) to accurately predict gastric cancer (GC) prognosis and identify key prognostic genes related to gastric cancer.Results: Gene expression and clinical data of gastric cancer patients were sourced from Gene Expression Omnibus and The Cancer Genome Atlas. Subsequently, the GEO dataset was randomly distributed into training and test cohorts. The TCGA dataset was used to validate the external cohort. Lasso Cox regression was used to detect OS-related genes in the GEO cohort. A risk score model was established according to the screened genes. A nomogram, based on the clinical characteristics and risk score, was generated to predict the prognosis of gastric cancer patients. Using time-dependent receiver operating characteristic (ROC) and calibration performances, we evaluated the models’ validity. The patients were grouped into a high- or low-risk group depending on the risk score. Low-risk patients exhibited higher OS than high-risk patients (entire cohort: p < 0.001; training cohort: p < 0.001, test cohort: p < 0.001). Furthermore, we found a correlation between high-risk gastric cancer and extracellular matrix (ECM) receptor interaction, high infiltration of macrophages, CD44, and HLA-DOA.Conclusion: The generated model based on the genetic characteristics of the focal adhesion prognostic gene can aid in the prognosis of gastric cancer patients in the future.

We prepare carbon nanotubes based on the cross-linking reaction between small organic molecules citric acid and amino urea or ethylenediamine. Factors affecting the yield of carbon nanotube are optimized and catalytic effect of hydrated metal nitrate on carbon nanotube growth is investigated. The results demonstrate that carbon nanotube can grow in a wide range of urea content. Even two-dimensional sheet assembled by the prepared carbon nanotubes is observed when ethylenediamine is used. It is believed that such competitive strategy can expand the techniques for efficient, large-scale and low-cost synthesis of carbon nanotubes.

Extracellular vesicles (EVs) are increasingly recognized as important intermediaries of intercellular communication. They have significant roles in many physiological and pathological processes and show great promise as novel biomarkers of disease, therapeutic agents, and drug delivery tools. Existing studies have shown that natural killer cell-derived EVs (NEVs) can directly kill tumor cells and participate in the crosstalk of immune cells in the tumor microenvironment. NEVs own identical cytotoxic proteins, cytotoxic receptors, and cytokines as NK cells, which is the biological basis for their application in antitumor therapy. The nanoscale size and natural targeting property of NEVs enable precisely killing tumor cells. Moreover, endowing NEVs with a variety of fascinating capabilities via common engineering strategies has become a crucial direction for future research. Thus, here we provide a brief overview of the characteristics and physiological functions of the various types of NEVs, focusing on their production, isolation, functional characterization, and engineering strategies for their promising application as a cell-free modality for tumor immunotherapy.

Abstract Background Antiretroviral therapy (ART) has reduced mortality among people living with HIV (PLWH) in China, but co-infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) may individually or jointly reduce the effect of ART. This study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ART. Methods A retrospective cohort study analysis of 58 239 people living with HIV (PLWH) who initiated antiretroviral therapy (ART) during 2010–2018 was conducted in Guangxi Province, China. Data were from the observational database of the National Free Antiretroviral Treatment Program. Cox proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among PLWH. Results Our study showed high prevalence of HBV (11.5%), HCV (6.6%) and HBV-HCV (1.5%) co-infections. The overall mortality rate and treatment attrition rate was 2.95 [95% confidence interval (CI) 2.88–3.02] and 5.92 (95% CI 5.82–6.01) per 100 person-years, respectively. Compared with HIV-only patients, HBV-co-infected patients had 42% higher mortality [adjusted hazard ratio (aHR) = 1.42; 95% CI 1.32–1.54], HCV-co-infected patients had 65% higher mortality (aHR = 1.65; 95% CI 1.47–1.86), and patients with both HCV and HBV co-infections had 123% higher mortality (aHR = 2.23; 95% CI 1.87–2.66). Conclusions HBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on ART. It is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH. Graphical Abstract

Abstract Background Late presentation to HIV/AIDS care presents serious health concerns, like increased transmission and high healthcare costs, increased mortality, early development of opportunistic infection, increased risk of antiretroviral therapy drug resistance. Despite the effort to contain the HIV/AIDS epidemic, LP has remained an impediment to individual immune reconstitution and public health. Objective This review aimed to estimate the prevalence and determine the factors associated with late presentation to HIV/AIDS care. Methods We searched PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Wanfang, and Weipu database for articles published from 2010 to 2020. We utilized I 2 statistics and Q-test to estimate heterogeneity between studies. Random-effects meta-analysis models were used to calculate the aggregate odds ratio of late presentation to HIV/AIDS care. Results Of 9563 titles and abstracts retrieved, 189 were identified as potentially eligible and 39 fulfilled the inclusion criteria. The pooled prevalence of late presentation to HIV/AIDS care was 43.26%. The major risk factors were patients ≥ 50 years old (OR = 2.19, 95% CI: 1.85–2.58; I 2 = 97.44%), married (OR = 1.50, 95% CI: 1.35–1.68; I 2 = 96.58%), with heterosexual contact as risk factor for infection (OR = 1.91, 95% CI: 1.73–2.11; I 2 = 90.74%) and diagnosed in medical institutions (OR = 2.35,95% CI: 2.11–2.62; I 2 = 96.05%). In middle or low HIV prevalence areas, patients ≥ 50 years old (P = 0.01), married (P

Abstract. Objective:. Regarding the secondary prevention of cardiovascular disease (CVD), there is great interest in preventing recurrent cardiovascular events (RCVEs). The prognostic importance of liver fibrosis scores (LFSs) has previously been reported in various CVDs. We hypothesized that LFSs might also be useful predictors for RCVEs in patients with prior cardiovascular events (CVEs). Herein, we aimed to evaluate the associations of LFSs with RCVEs in a large, real-world cohort of coronary artery disease (CAD) patients with a prior CVE. Methods:. In this multicenter prospective study, 6527 consecutive patients with angiography-diagnosed CAD who had experienced a prior CVE (acute coronary syndrome, stroke, percutaneous coronary intervention, or coronary artery bypass grafting) were enrolled. LFSs were computed according to the published formulas: non-alcoholic fatty liver disease fibrosis score (NFS) includes age, body mass index (BMI), impaired fasting glycemia or diabetes mellitus (DM), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, platelets, and albumin; fibrosis-4 (FIB-4) includes age, AST, ALT, and platelets; Forns score includes age, gamma-glutamyltransferase (GGT), and platelets; BARD includes BMI, AST/ALT ratio, and DM; GGT/platelet ratio includes GGT and platelets; AST/ALT ratio includes AST and ALT; and AST/platelet ratio index includes AST and platelets. The originally reported cutoffs were used for the categorization of low-, intermediate-, and high-score subgroups. All patients were followed up for the occurrence of RCVEs (comprising cardiovascular death, non-fatal myocardial infarction, and stroke). Cox and Poisson regression analyses were used to assess the relationship of baseline LFSs with the risk of RCVE. Results:. During a mean follow-up of (54.67 ± 18.80) months, 532 (8.2%) RCVEs were recorded. Intermediate and high NFS, FIB-4, Forns, and BARD scores were independently associated with an increased risk of RCVE (hazard ratios ranging from 1.42 to 1.75 for intermediate scores and 1.35 to 2.52 for high scores). In the subgroup analyses of sex, age, BMI, DM, and hypertension status, the increased risk of RCVEs with high LFSs (NFS, FIB-4, Forns, and BARD) was maintained across the different subgroups (all P

Study region: The Shejiagou catchment on the Loess Plateau, China Study focus: This study used CAESAR-lisflood to simulate the impacts on flood processes of fully-filled check dams with different numbers, silt land areas and connection modes. According to the model results, the protective measures of fully-filled check dams and recommendations for promoting the construction of check dams were proposed in the study. New hydrological insights for the region: CAESAR-lisflood model in the study obtained higher accuracy with both the Nash-Sutcliff coefficient of efficiency and the coefficient of determination greater than 0.8. Our results showed the presence of fully-filled check dams made the flood process tend to balance, and reduced the flood volume by 9.56–75.52%, peak discharge by 14.25–89.74%, runoff kinetic energy by 30.21–99.75% and runoff power by 20.17–95.23% under different layout scenarios. Meanwhile, the results indicated that the impacts of fully-filled check dams in main channel mainly manifested in the energy dissipation of silt land and energy increase at the outside slope of dam body, which was aggravated by downstream channel with steep slope. The combination of fully-filled check dams could amplify the flood control efficiency of individual dam. These results provide a scientific basis for reinforcement of fully-filled check dams and optimization of check dams layout in the future on the Chinese Loess Plateau.

Azoxystrobin, a quinone outside inhibitor fungicide, reduced tobacco target spot caused by Rhizoctonia solani by 62%, but also affected the composition and diversity of other microbes on the surface and interior of treated tobacco leaves. High-throughput sequencing showed that the dominant bacteria prior to azoxystrobin treatment were Methylobacterium on healthy leaves and Pseudomonas on diseased leaves, and the dominant fungi were Thanatephorous (teleomorph of Rhizoctonia) and Symmetrospora on healthy leaves and Thanatephorous on diseased leaves. Both bacterial and fungal diversity significantly increased 1 to 18 days post treatment (dpt) with azoxystrobin for healthy and diseased leaves. For bacteria on healthy leaves, the relative abundance of Pseudomonas, Sphingomonas, Unidentified-Rhizobiaceae and Massilia declined, while Methylobacterium and Aureimonas increased. On diseased leaves, the relative abundance of Sphingomonas and Unidentified-Rhizobiaceae declined, while Methylobacterium, Pseudomonas and Pantoea increased. For fungi on healthy leaves, the relative abundance of Thanatephorous declined, while Symmetrospora, Sampaiozyma, Plectosphaerella, Cladosporium and Cercospora increased. On diseased leaves, the relative abundance of Thanatephorous declined, while Symmetrospora, Sampaiozyma, Plectosphaerella, Cladosporium, Phoma, Pantospora and Fusarium, increased. Compared to healthy leaves, azoxystrobin treatment of diseased leaves resulted in greater reductions in Thanatephorous, Sphingomonas and Unidentified-Rhizobiaceae, a greater increase in Methylobacterium, and similar changes in Phoma, Fusarium, Plectosphaerella and Cladosporium. Azoxystrobin had a semi-selective effect altering the microbial diversity of the tobacco leaf microbiome, which could be due to factors, such as differences among bacterial and fungal species in sensitivity to quinone outside inhibitors, ability to use nutrients and niches as certain microbes are affected, and metabolic responses to azoxystrobin.

Spinal cord injury (SCI) is a global medical problem with high disability and mortality rates. At present, the diagnosis and treatment of SCI are still lacking. Spinal cord injury has a complex etiology, lack of diagnostic methods, poor treatment effect and other problems, which lead to the difficulty of spinal cord regeneration and repair, and poor functional recovery. Recent studies have shown that gene expression plays an important role in the regulation of SCI repair. MicroRNAs (miRNAs) are non-coding RNA molecules that target mRNA expression in order to silence, translate, or interfere with protein synthesis. Secondary damage, such as oxidative stress, apoptosis, autophagy, and inflammation, occurs after SCI, and differentially expressed miRNAs contribute to these events. This article reviews the pathophysiological mechanism of miRNAs in secondary injury after SCI, focusing on the mechanism of miRNAs in secondary neuroinflammation after SCI, so as to provide new ideas and basis for the clinical diagnosis and treatment of miRNAs in SCI. The mechanisms of miRNAs in neurological diseases may also make them potential biomarkers and therapeutic targets for spinal cord injuries.

Tobacco target spot is a serious fungal disease and it is important to study the similarities and differences between fungal and bacterial community under different disease severities to provide guidance for the biological control of tobacco target spot. In this study, tobacco leaves at disease severity level of 1, 5, 7 and 9 (S1, S5, S7, and S9) were collected, both healthy and diseased leaf tissues for each level were sampled. The community structure and diversity of fungi and bacteria in tobacco leaves with different disease severities were compared using high-throughput sequencing technology. The results indicated that there was a significant differences in the community structure of fungi and bacteria for both healthy and diseased samples depending on the disease severity. In both healthy and diseased tobacco leaves for all four different disease severities, the most dominant fungal phylum was Basidiomycota with a high prevalence of genus Thanatephorus. The relative abundance of Thanatephorus was most found at S9 diseased samples. Proteobacteria represent the most prominent bacterial phylum, with Pseudomonas as predominant genus, followed by Pantoea. The relative abundance of Pseudomonas was most found at S7 healthy samples. In fungal community, the Alpha-diversity of healthy samples was higher than that of diseased samples. In contrast, in bacterial community, the Alpha-diversity of healthy samples was lower than that of diseased samples. LEfSe analysis showed that the most enrich fungal biomarker was Thanatephorus cucumeris in diseased samples. Clostridium disporicum and Ralstonia pickettii were the most enrich bacterial biomarker in healthy samples. FUNGuild analysis showed that the pathotroph mode was the most abundant trophic modes. The relative abundance of pathotroph mode in diseased samples changes insignificantly, but a peak at S5 was observed for healthy samples. PICRUSt analysis showed that most bacterial gene sequences seem to be independent of the disease severity. The results of this study provide scientific references for future studies on tobacco phyllosphere microecology aiming at prevention and control of tobacco target spot.

Ethnopharmacological relevanceDanshen preparations are widely used in the treatment of ischaemic cerebrovascular disease. However, the clinical efficacy of such preparations remains unclear. Consequently, Danshen preparations are used to a lesser extent in vascular cognitive impairment (VCI).Aim of the studyIn this study, we aimed to systematically assess the clinical efficacy and safety of Danshen preparations in VCI. To this end, we examined and performed a meta-analysis (MA) of the evidence available from randomised controlled trials (RCTs) of Danshen preparations conducted in patients with VCI.MethodsWe queried the following sources and collected all articles reporting on RCTs of Danshen preparations published prior to December 2021: PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chongqing VIP Database (CQVIP), and China Biology Medicine (CBM) disc databases. The assessment of treatments that were included in references were performed by RevMan 5.2 software based on guidelines from Cochrane Handbook for Systematic Reviews of Interventions.ResultsWe included a total of 12 RCTs that included data on clinical therapeutic effects. The evaluation criteria included the following: National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI), Mini-Mental State Assessment (MMSE), Montreal Cognitive Assessment (MOCA), Activities of Daily Living Scale (ADL), treatment effect index, and incidence of adverse reaction index. In the included studies, the observation groups included 656 cases and the control groups included 660 cases. The results of the MA were as follows: the mean difference (MD) value after combining the effect size for NIHSS was −2.91, with a 95% confidence interval (CI) of −4.22 to −1.59; the combined effect quantity hypothesis test revealed that Z = 4.33 (p

The health of the trees in the forest affects the ecological environment, so timely detection of Standing Dead Trees (SDTs) plays an important role in forest management. However, due to the large spatial scope of forests, it is difficult to find SDTs through conventional approaches such as field inventories. In recent years, the development of deep learning and Unmanned Aerial Vehicle (UAV) has provided technical support for low-cost real-time monitoring of SDTs, but the inability to fully utilize global features and the difficulty of small-scale SDTs detection have brought challenges to the detection of SDTs in visible light images. Therefore, this paper proposes a multi-scale attention mechanism detection method for identifying SDTs in UAV RGB images. This method takes Faster-RCNN as the basic framework and uses Swin-Transformer as the backbone network for feature extraction, which can effectively obtain global information. Then, features of different scales are extracted through the feature pyramid structure and feature balance enhancement module. Finally, dynamic training is used to improve the quality of the model. The experimental results show that the algorithm proposed in this paper can effectively identify the SDTs in the visible light image of the UAV with an accuracy of 95.9%. This method of SDTs identification can not only improve the efficiency of SDTs exploration, but also help relevant departments to explore other forest species in the future.

Background. Necroptosis is progressively becoming an important focus of research because of its role in the pathogenesis of cancer and other inflammatory diseases. Our study is designed to anticipate the survival time of kidney renal clear cell carcinoma (KIRC) by constructing a prognostic signature of necroptosis-related genes. Materials. Clinical information and RNA-seq data were acquired from Renal Cell Cancer-European Union (RECA-EU) and The Cancer Genome Atlas- (TCGA-) KIRC, respectively. ConsensusClusterPlus was used to identify molecular subtypes, and the distribution of immune cell infiltration, anticancer drug sensitivity, and somatic gene mutations was studied in these subtypes. Subsequently, LASSO-Cox regression and univariate Cox regression were also carried out to construct a necroptosis-related signature. Cox regression, survival analysis, clinicopathological characteristic correlation analysis, nomogram, cancer stem cell analysis, and receiver operating characteristic (ROC) curve were some tools employed to study the prognostic power of the signature. Results. Based on the expression patterns of 66 survival-related necroptosis genes, we classified the KIRC into three subtypes (C1, C2, and C3) that are associated with necroptosis, which had significantly different tumor stem cell components. Among these, C2 patients had a longer survival time and enhanced immune status and were more sensitive to conventional chemotherapeutic drugs. Moreover, in order to predict the prognosis of KIRC patients, five genes (BMP8A, TLCD1, CLGN, GDF7, and RARB) were used to develop a necroptosis-related prognostic signature, which had an acceptable predictive potency. The results from Cox regression and stratified survival analysis revealed that the signature was an independent prognostic factor, whereas the nomogram and calibration curve demonstrated satisfactory survival time prediction based on the risk score. Conclusions. Three molecular subtypes and five necroptosis-related genes were discovered in KIRC using data from TCGA-KIRC and RECA-EU. Thus, a new biomarker and a potentially effective therapeutic approach for KIRC patients were provided in the current study.

The development of radiotherapy technology improved outcomes in rectal cancer. Nevertheless, radiotherapy resistance has become a significant problem. This resistance is associated with tumor microenvironment (TME) hypoxia, cell cycle block, and related genetic alterations. We designed a novel miRNA-delivered and improved hypoxic microenvironment sensitization therapy for rectal cancer. With the protection of Zeolitic Imidazolate Framework-8 (ZIF-8) and the delivery of nano-manganese dioxide particles, the nanocomplex exhibited outstanding catalytic mimetic activity in decomposing hydrogen peroxide into oxygen, thus significantly reversing the TME hypoxia. The radiosensitizer miRNA-181a induces DNA damage directly after radiotherapy. We loaded miR181a into the MnO2@ZIF-8-polyethylene glycol nanocomplex to prevent its degradation in the circulatory system and successfully carry miR181a into the tumor. MiR181a-MnO2@ZIF-8 overcame radioresistance and enhanced therapeutic efficacy in a subcutaneous tumor model. This multiple sensitization strategy of the combined delivery of miR181a with MnO2@ZIF-8 nanoenzymes provides a promising therapeutic approach for rectal cancer.

The balance of ion concentrations inside and outside the cell is an essential homeostatic mechanism in neurons and serves as the basis for a variety of physiological activities. In the central nervous system, NKCC1 and KCC2, members of the SLC12 cation-chloride co-transporter (CCC) family, participate in physiological and pathophysiological processes by regulating intracellular and extracellular chloride ion concentrations, which can further regulate the GABAergic system. Over recent years, studies have shown that NKCC1 and KCC2 are essential for the maintenance of Cl− homeostasis in neural cells. NKCC1 transports Cl− into cells while KCC2 transports Cl− out of cells, thereby regulating chloride balance and neuronal excitability. An imbalance of NKCC1 and KCC2 after spinal cord injury will disrupt CI− homeostasis, resulting in the transformation of GABA neurons from an inhibitory state into an excitatory state, which subsequently alters the spinal cord neural network and leads to conditions such as spasticity and neuropathic pain, among others. Meanwhile, studies have shown that KCC2 is also an essential target for motor function reconstruction after spinal cord injury. This review mainly introduces the physiological structure and function of NKCC1 and KCC2 and discusses their pathophysiological roles after spinal cord injury.

Net primary production (NPP) serves as a crucial indicator of the ecosystem’s capacity to capture atmospheric CO2. Gaining insights into the dynamics of NPP and its driving mechanisms is pivotal for optimizing ecosystem carbon sink resource management. Since the implementation of the Grain-for-Green Program (GFGP) in 1999, the Yellow River Basin (YRB) has been one of the most significant areas for ecological restoration in China. However, our knowledge regarding the interannual variability (IAV) of NPP and the underlying driving forces in this region remains incomplete. In this study, we utilized a light use efficiency model to assess the spatiotemporal dynamics, IAV, and driving factors of NPP in the YRB during the period from 1999 to 2018. Our findings revealed that the average annual NPP in the YRB approximated 189.81 Tg C. Over the study duration, NPP significantly increased in 79.63% of the basin with an overall increasing rate of 6.76 g C m−2 yr−1. The most prominent increase was observed in the key GFGP implementation area, predominantly in the semi-humid region. Notably, the middle altitude region (1–1.5 km), semi-humid region, and grassland emerged as the primary contributors to the basin’s total vegetation carbon sequestration. However, it is worth emphasizing that there was substantial IAV in the temporal trends of NPP, with the semi-humid region being the most influential contributor (62.66%) to the overall NPP IAV in the YRB. Further analysis of the driving mechanisms unveiled precipitation as the primary driver of NPP IAV in the YRB with a contribution of 62.9%, followed by temperature (23.07%) and radiation (14.03%). Overall, this study deepened our understanding of the IAV and driving mechanisms of NPP in the YRB under ecological restoration, and provided scientific support for optimizing the management of regional carbon sequestration resources.

The technology of submerged carbon powder injection with CO2 and O2 mixed gas (SCPI-COMG) is a new type of powder injection technology. It can increase the molten bath carbon content and improve the molten steel quality by injecting carbon powder directly into the molten steel with CO2 and O2 mixed gas. To optimize the process parameters of this novel technology, the mechanism of this technology and the effect of SCPI-COMG on EAF steelmaking were investigated in this study. Based on an induction furnace experiment, the effects of molten bath carburization and fluid flow on the scrap melting were analyzed. A mathematical model of the axis of gas jets in liquid steel was built to analyze the impact behaviors of gas jets in liquid steel. Based on the results of this theoretical model, for a gas jet in liquid steel, with α ≥ 20°, the horizontal inject distance decreases with α increasing and with 0° ≤ α ≤ 20°, the horizontal inject distance increases with α increasing. Finally, based on the newly built materials and energy balance model of EAF steelmaking with SCPI-COMG, the influences of the gas-solid parameters on the EAF steelmaking technical indexes were also analyzed.is very useful for optimizing the process parameters of EAF steelmaking with SCPI-COMG. The results of this study are very useful to optimize the process parameters of EAF steelmaking with SCPI-COMG of Gas Jet in Liquid Steel.

Assessing the impact of land use and land cover change (LUCC) on soil erosion by wind and water is crucial for improving regional ecosystem services and sustainable development. In this study, the Revised Wind Erosion Equation (RWEQ) and Revised Universal Soil Loss Equation (RUSLE) were used to reveal changes in the extent of soil erosion by wind and water in the Qaidam Basin from 2000 to 2018 and the impact of LUCC on them. From 2000 to 2018, with global climate change, the areas and intensities of soil erosion by wind decreased, whereas those of soil erosion by water increased. With increased human activities, approximately 12.96% of the total area underwent conversion of the type of use: the areas of cropland, woodland, grassland, and construction land increased, whereas the areas of shrubbery, desert, and other unused land decreased. Land use/cover changes are positive to the soil erosion of water but negative to the soil erosion of wind. Among them, the changes in vegetation coverage of other unused land and grassland contributed to 83.19% of the total reduction in soil erosion by water. Converting other unused land to grassland reduced the total reductions in soil erosion by wind by 94.69%. These results indicate that the increase in vegetative cover and area of grasslands in the Qaidam Basin had a positive impact on the reduction in soil erosion. It is recommended that the arrangement of grasses, shrubs, and trees be optimized to prevent compound erosion by wind and water for protecting regional ecological environments.

Abstract Background Pretreatment drug resistance (PDR) can limit the effectiveness of HIV antiretroviral therapy (ART). The aim of this study was to assess the prevalence of PDR among HIV-positive individuals that initiated antiretroviral therapy in 2014–2020 in southwestern China. Methods Consecutive cross-sectional surveys were conducted in Qinzhou, Guangxi. We obtained blood samples from individuals who were newly diagnosed with HIV in 2014–2020. PDR and genetic networks analyses were performed by HIV-1 pol sequences using the Stanford HIV-database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression models were used to explore the potential factors associated with PDR. Results In total, 3236 eligible HIV-positive individuals were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that of NRTI (1.7%, p

Abstract Objective We aimed to determine the association between serum receptor activator of nuclear factor-kappa B ligand (sRANKL) levels and ankylosing spondylitis (AS) in Chinese patients. Methods The PubMed, Cochrane Library, Embase, Chinese Biomedical Database, Web of Science, China National Knowledge Infrastructure, VIP, and Wan Fang databases were searched for studies conducted before October 1, 2020, without language restrictions. STATA version 12.0 and Revman version 5.3 were used to analyze the data. The standard mean differences (SMDs) and corresponding 95% confidence intervals (95% CIs) were calculated. Results Twelve clinical case–control studies, including 585 patients with AS and 423 healthy controls, were included. The combined SMD for sRANKL suggested that the sRANKL level was significantly higher in Chinese patients with AS than in healthy controls (SMD: 3.27, 95% CI 2.11–4.43, P 4 than those of patients in other subgroups. In terms of duration, patients with AS for > 8 years had higher sRANKL levels than health controls. Other subgroup analyses were conducted by region, language, source of control, age, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In these subgroups, the sRANKL levels were significantly higher in the patients with AS than in healthy controls. The BASFI and BASDAI were sources of heterogeneity. Conclusions The sRANKL levels are higher in Chinese patients with AS, especially among those from South China. sRANKL levels may be positively correlated with the pathogenesis of AS among Chinese patients.