Search

The Central Asian region is subject to frequent seasonal floods, resulting in substantial losses. These recurrent floods have induced certain changes in human flood adaptation characteristics in Central Asia, an area that is currently under-researched. This study, grounded in meticulously simulated flood inundation outcomes, multisource population distribution data, and flood protection infrastructure data, introduces an improved approach to calculating the distance between human and flood (HFD) and investigates human flood adaptation characteristics in Central Asia. Our findings indicate that residents in Central Asia get close to flood-prone areas from 1970 to 2007, with the exceptions of Turkmenistan (TKM) and Kyrgyzstan (KGZ). Notably, this trend is particularly pronounced in regions such as Xinjiang, China, and Tajikistan (TJK). An intricate exponential increase is observed in the population exposed to floods as the HFD decreases. Under future scenarios, KGZ exhibits the most significant trend of staying away from flood-prone areas, while TJK presents the opposite trend, and TKM experiences minimal changes. Additionally, compared with urban areas, rural areas of Central Asia exhibit a trend towards approaching floods. This study underscores the optimum nature of human flood adaptation when the HFD reaches 4.23 km, showing the potential for substantial benefits by implementing population evacuation within this threshold buffer zone. These insights highlight the complex interplay between human behaviours and floods and can inform the formulation of effective flood risk mitigation strategies.

Cannabinoid metabolites have been reported to be more potent than their parent compounds. Among them, ajulemic acid (AJA) is a side-chain analog of Δ9-THC-11-oic acid, which would be a good template structure for the discovery of more potent analogues. Herein, we optimized the key allylic oxidation step to introduce the C-11 hydroxy group with a high yield. A series of compounds was prepared with this condition applied including HU-210, 11-nor-Δ8-tetrahydrocannabinol (THC)-carboxylic acid and Δ9-THC-carboxylic acid.

Hexabromocyclododecane (HBCD) is the most important flame retardant that has been used in Expanded Polystyrene foam and Extruded Polystyrene foam in the past forty years across the world. China was the major producer and user of HBCD, and the total HBCD production was about 0.3 million tons. Although HBCD was completely banned in China in 2021 because of its long-range transport, bioaccumulation and toxicity, there is still a lot of residue in the environment. Therefore, we reviewed multiple studies concerning the distribution of HBCD in diverse environmental matrices, such as in the air, dust, soil, water, sediment, and biota. Results revealed that HBCD levels in different environments in China present geographical variation and were at a high level compared with other countries. In all environmental media, relatively high HBCD concentrations have been found in industrial and urban areas. Industrialization and urbanization are two important factors that influence the concentration and distribution of HBCD in the environment. In terms of isomer, γ-HBCD was the dominant isomer in soil, water, and sediment, while in the biota α-HBCD was the predominant isomer.

Introduction: Rapid development in synthetic technologies has boosted DNA as a potential medium for large-scale data storage. Meanwhile, how to implement data security in the DNA storage system is still an unsolved problem.Methods: In this article, we propose an image encryption method based on the modulation-based storage architecture. The key idea is to take advantage of the unpredictable modulation signals to encrypt images in highly error-prone DNA storage channels.Results and Discussion: Numerical results have demonstrated that our image encryption method is feasible and effective with excellent security against various attacks (statistical, differential, noise, and data loss). When compared with other methods such as the hybridization reactions of DNA molecules, the proposed method is more reliable and feasible for large-scale applications.

Objective: To observe the clinical efficacy and safety of Yiqi Yangxue formula (YQYXF) on knee osteoarthritis (KOA), and to explore the underlying therapeutic mechanism of YQYXF through endogenous differential metabolites and their related metabolic pathways.Methods: A total of 61 KOA patients were recruited and divided into the treatment group (YQYXF, 30 cases) and the control group (celecoxib, Cxb, 31 cases). Effects of these two drugs on joint pain, swelling, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) were observed, and their safety and adverse reactions were investigated. In animal experiments, 63 SD rats were randomly divided into normal control (NC) group, sham operation (sham) group, model (KOA) group, Cxb group, as well as low-dose (YL), medium-dose (YM), and high-dose groups of YQYXF (YH). The KOA rat model was established using a modified Hulth method. Ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS)-based metabolomics technology was used to analyze the changes of metabolites in plasma samples of rats. Comprehensive (VIP) >1 and t-test p < 0.05 conditions were used to screen the disease biomarkers of KOA, and the underlying mechanisms of YQYXF were explored through metabolic pathway enrichment analysis. The related markers of YQYXF were further verified by ELISA (enzyme-linked immunosorbent assay).Results: YQYXF can improve joint pain, swelling, range of motion, joint function, Michel Lequesen index of severity for osteoarthritis (ISOA) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, ESR, and CRP. No apparent adverse reactions were reported. In addition, YQYXF can improve cartilage damage in KOA rats, reverse the abnormal changes of 16 different metabolites, and exert an anti-KOA effect mainly through five metabolic pathways. The levels of reactive oxygen species (ROS) and glutathione (GSH) were significantly decreased after the treatment of YQYXF.Conclusion: YQYXF can significantly improve the clinical symptoms of KOA patients without obvious adverse reactions. It mainly improved KOA through modulating lipid metabolism-related biomarkers, reducing lipid peroxidation and oxidative stress.

The key to critical bone regeneration in tissue engineering relies on an ideal bio-scaffold coated with a controlled release of growth factors. Gelatin methacrylate (GelMA) and Hyaluronic acid methacrylate (HAMA) have been a novel topic of interest in bone regeneration while introducing appropriate nano-hydroxyapatite (nHAP) to improve its mechanical properties. And the exosomes derived from human urine-derived stem cells (human USCEXOs) have also been reported to promote osteogenesis in tissue engineering. The present study aimed to design a new GelMA-HAMA/nHAP composite hydrogel as a drug delivery system. The USCEXOs were encapsulated and slow-released in the hydrogel for better osteogenesis. The characterization of the GelMA-based hydrogel showed excellent controlled release performance and appropriate mechanical properties. The in vitro studies showed that the USCEXOs/GelMA-HAMA/nHAP composite hydrogel could promote the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and the angiogenesis of endothelial progenitor cells (EPCs), respectively. Meanwhile, the in vivo results confirmed that this composite hydrogel could significantly promote the defect repair of cranial bone in the rat model. In addition, we also found that USCEXOs/GelMA-HAMA/nHAP composite hydrogel can promote the formation of H-type vessels in the bone regeneration area, enhancing the therapeutic effect. In conclusion, our findings suggested that this controllable and biocompatible USCEXOs/GelMA-HAMA/nHAP composite hydrogel may effectively promote bone regeneration by coupling osteogenesis and angiogenesis.

BackgroundTransition into menopause is associated with an increased risk of cardiovascular disease (CVD). However, it is unclear whether the association exists between premature menopause (defined as age at menopause 40 years) or early menopause (defined as age at menopause 40–45 years) and CVD or cardiovascular risk factors. The aim of this review was to comprehensively evaluate and meta-analyze the most reliable evidence about the relationship between menopausal age and the risk of long-term cardiometabolic disease.MethodsA comprehensive literature search of the PubMed, Web of Science, and Embase databases from inception to October 1, 2022, for titles and abstracts with a restriction to English language papers led to the discovery of the studies. Data are expressed as the Hazard Ratio (HR) with 95% confidence intervals (CI). The degree of heterogeneity was measured using the I-square (I2) index.Results921,517 participants from 20 cohort studies published between 1998 and 2022 were considered. Compared to women with menopause at age >45 years, women with premature menopause (PM) or early menopause (EM) had a higher risks of type 2 diabetes (RR: 1.32, 95% CI: 1.08–1.62; RR: 1.11, 95% CI: 0.91–1.36, respectively), hyperlipidemia (RR: 1.21, 95% CI: 1.05–1.39; RR: 1.17, 95% CI: 1.02–1.33, respectively), coronary heart disease (RR: 1.52, 95% CI: 1.22–1.91; RR: 1.19, 95% CI: 1.07–1.32, respectively), stroke (RR: 1.27, 95% CI: 1.02–1.58; RR: 1.13, 95% CI: 0.97–1.32, respectively) and total cardiovascular event (RR: 1.36, 95% CI: 1.16–1.60; RR: 1.14, 95% CI: 0.97–1.35, respectively). No difference was found for hypertension in PM or EM women (RR: 0.98, 95% CI: 0.89–1.07; RR: 0.97, 95% CI: 0.91–1.04, respectively). Additionally, we also found that PM women, but not EM women, were linked with an increased risk of ischemic and hemorrhagic stroke. However, this is not in line with the conclusion that both PM and EM had a higher risk of total stroke.ConclusionWomen with PM or EM have a higher risk of developing long-term CVD, compared to women with menopause at age >45 years. Therefore, we recommend early lifestyle interventions (e.g., maintaining a healthy lifestyle) and medical treatments (e.g., timely initiation of menopausal hormone therapy) to decrease the risk of cardiometabolic disease in early or premature menopausal women.Systematic Review RegistrationPROSPERO, identifier CRD42022378750

Abstract Neural progenitor cell (NPC) transplantation is a promising approach for repairing spinal cord injury (SCI). However, cell survival, maturation and integration after transplantation are still major challenges. Here, we produced a novel centimeter‐scale human spinal cord neural tissue (hscNT) construct with human spinal cord neural progenitor cells (hscNPCs) and human spinal cord astrocytes (hscAS) on a linearly ordered collagen scaffold (LOCS). The hscAS promoted hscNPC adhesion, survival and neurite outgrowth on the LOCS, to form a linearly ordered spinal cord‐like structure consisting of mature neurons and glia cells. When transplanted into rats with SCI, the hscNT created a favorable microenvironment by inhibiting inflammation and glial scar formation, and promoted neural and vascular regeneration. Notably, the hscNT promoted neural circuit reconstruction and motor functional recovery. Engineered human spinal cord implants containing astrocytes and neurons assembled on axon guidance scaffolds may therefore have potential in the treatment of SCI.

Knowledge on the distribution of rapeseed enables accurate yield forecasting and supports agricultural planning to assist global security in edible oil supply. Large-scale remotely sensed maps of rapeseed nevertheless are non-existent in China because of landscape fragmentation, cloudy weather conditions, and phenological variations. Existing rapeseed mapping methods based on spectral, phenological, and machine learning algorithms are challenging to accurately and seamlessly extract the planting distribution of rapeseed over a large spatial region. In view of this, the annual extent of rapeseed in the Yangtze River Economic Belt (YREB) of China from 2017 to 2021 was mapped. Multisource data including Sentinel-1/2, Google Earth very-high-resolution (GE-VHR) images, and Global Land Data Assimilation System (GLDAS) data were used to develop a systematic methodology. First, the ground reference dataset was collected from fieldwork and all available GE-VHR images to construct a rapeseed point collection (RPC). Second, RPC, Sentinel-1, and GLDAS data were used to estimate the annual rapeseed peak-flowering date maps (RPDMs) based on a random forest regression model. Third, a hybrid mapping strategy was implemented on Google Earth Engine leveraging the dense Sentinel-1/2 data to generate the annual seamless 10 m rapeseed extent maps (REMs). Accuracy assessment illustrates the reliability of the RPDM with an R2 of 0.86 (RMSE = 5.32 days). Comparisons with other rapeseed mapping methods and comprehensive validation attest to the high precision of the REMs, with an average F1 score of 0.93. Moreover, the rapeseed cultivation area decreased over the five study years. Rapeseed fields in the YREB are highly fragmented, averaging 18 per ha, but trend analysis suggests a potential for crop intensification. This study provides an essential reference and information service for rapeseed production and agricultural resource survey in China.

Objective: To investigate the protective effect and potential mechanism of Rabdosia serra on alcoholic liver injury. Method: Forty female Kunming mice were randomly divided into blank group, model group, Rabdosia serra group and positive control group. All mice received 0.1 mL/10 g white spirit to established alcoholic liver injury model, and continuous administration for 10 days. After the last administration, HE staining was used to observe the pathological changes of liver tissue. Serum indexes were determined by kit method. Network pharmacology method was used to analyze the potential effective components, signal pathways and molecular targets of Rabdosia serra in the treatment of alcoholic liver injury, and Western blot was used to verify the related molecular targets. Results: The protein expression levels of AST, m-AST and GDH in Rabdosia serra group were significantly higher than those in model group (P

Abstract Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of Skp2 confers sensitivity to irradiation of CRC cells. Skp2 deficiency enhances irradiation-induced intrinsic apoptosis by facilitating E3 ligase FBW7-mediated Mcl-1 ubiquitination and degradation. Knockout of Skp2 sensitizes CRC cells to irradiation treatments in vivo. Our findings indicate that Skp2 stabilizes Mcl-1, and targeting Skp2 in combination with traditional radiotherapy might be efficacious in treating CRC.

Plant protein hydrolysates could enhance the growth performance and diet utilization of aquaculture species. The mechanisms underlying their beneficial effects, however, remain unclear. The purpose of this study was to appraise the effects of cottonseed meal protein hydrolysate (CPH) supplementation on the growth performance, amino acid profiles, and protein turnover and metabolism of Eriocheir sinensis. A total of 240 crabs (initial weight: 37.32 ± 0.38 g) were randomly assigned to six groups, and fed six iso-protein feeds supplemented with varying levels of 0% (the control group), 0.2%, 0.4%, 0.8%, 1.6% and 3.2% of CPH. These diets were continuously fed to the crabs for 12 weeks. The findings demonstrated that, compared with the control group, adding 0.4–0.8% CPH to the diet significantly increased the specific growth rate, nitrogen retention efficiency, hepatopancreas index, body crude protein content, hepatopancreas alanine aminotransferase and glutamine synthetase activities, hemolymph total protein content, the hepatopancreas transcription of S6 kinase-poly-peptide 1, and the hepatopancreas protein levels of insulin-like growth factor-1 (IGF-1), protein kinase B (Akt), and target of rapamycin (TOR) of crabs. In contrast, when the dose of dietary CPH reached 3.2%, the forkhead box O1 (FoxO1) protein expression showed a significant decrease compared with the control group. In addition, CPH supplementation also increased the amount of amino acids and free amino acids in hepatopancreas and hemolymph, respectively. Together, these findings demonstrated that dietary supplementation of 0.4–0.8% CPH could activate the IGF-1/Akt/TOR pathway of E. sinensis, thereby improving growth performance, protein synthesis, and utilization. For cost considerations, the recommended dietary dose of CPH for E. sinensis is 0.8%. Due to the above benefits, CPH has the potential to be used as a growth promoter for other aquatic animals, especially crustaceans.

Landing impact load design is essential, but the process has rarely been fully described, and some designers have even neglected the differences between wheel-axle and ground-contact loads, as well as loads in the longitudinal direction, especially in experimental validations. In this paper, the entire design process of a nose landing gear is addressed, including a theoretical analysis of the unit and its experimental validation. In the theoretical analysis, a mathematical model of a two-mass system with four degrees of freedom was adopted, a computer simulation model was built accordingly, and a preliminary analysis was subsequently conducted to analyze the landing impact loads, verify the landing gear performance, and gauge the difference between the wheel-axle and ground-contact loads. For the experimental validation of the gear, a landing gear drop test was conducted in an optimized manner that emphasized pre-test preparation and during-test wheel-axle load measurement. The test results showed that both the vertical and less studied longitudinal loads, as well as the wheel-axle and ground-contact loads, had good agreement with the analysis; thus, the model, the tool, and the preliminary design were considered to be experimentally validated.

Carfentanil is an ultra-potent synthetic opioid. The Russian police force used both carfentanil and remifentanil to resolve a hostage incident in Moscow. This reported use sparked an interest in the pharmacology and toxicology of carfentanil in the human body, and data on its metabolites were later published. However, there have been few studies on the synthesis of carfentanil metabolites, and biological extraction has also put forward large uncertainty in subsequent studies. The aim of the present study is to investigate the synthesis of biphasic metabolites that are unique to carfentanil. The purpose was to produce corresponding metabolites conveniently, quickly, and at low cost that can be used for comparison with published structures and to confirm the administration of carfentanil.

The abundant neurovascular network in the periosteal fibrous layer is essential for regulating bone homeostasis and repairing bone defects. However, the majority of the current studies only focus on the structure or function, and most of them merely involve osteogenesis and angiogenesis, lacking an in-depth study of periosteal neurogenesis. In this study, a photothermal double-layer biomimetic periosteum with neurovascular coupling was proposed. The outer layer of biomimetic periosteum is a conventional electrospinning membrane to prevent soft tissue invasion, and the inner layer is an oriented nanofiber membrane to promote cell recruitment and angiogenesis. From the perspective of functional bionics, based on the whitlockite (WH) similar to bone composition, we doped Nd (the trivalent form of neodymium element) in it as the inducing element of photothermal response to prepare photothermal whitlockite (Nd@WH). The sustained release of Mg2+ in Nd@WH can effectively promote the up-regulation of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). The release of Ca2+ and PO43− ions and photothermal osteogenesis jointly promote bone regeneration. Under the combined effect of structure and function, the formation of nerves, blood vessels, and related collagens greatly simulates the microenvironment of extracellular matrix and periosteum regeneration and ultimately promotes bone regeneration. In this study, physical and chemical characterization proved that the bionic periosteum has good flexibility and operability. The in vitro cell experiment and in vivo calvarial defect model verified that PPCL/Nd@WH biomimetic periosteum had excellent bone tissue regeneration function compared with other groups. Finally, PPCL/Nd@WH provides a new idea for the design of bionic periosteum.

ObjectiveThe aim of this study was to assess the diagnostic performance of radiomics-based MRI in predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC).MethodThe databases of PubMed, Cochrane library, Embase, Web of Science, Ovid MEDLINE, Springer, and Science Direct were searched for original studies from their inception to 20 August 2022. The quality of each study included was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2 and the radiomics quality score. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic accuracy. Sensitivity analysis and subgroup analysis were performed to explore the source of the heterogeneity. Deeks’ test was used to assess publication bias. ResultsA total of 15 studies involving 981 patients were included. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.79 (95%CI: 0.72–0.85), 0.81 (95%CI: 0.73–0.87), 4.1 (95%CI:2.9–5.9), 0.26 (95%CI: 0.19–0.35), 16 (95%CI: 9–28), and 0.87 (95%CI: 0.84–0.89), respectively. The results showed great heterogeneity among the included studies. Sensitivity analysis indicated that the results of this study were statistically reliable. The results of subgroup analysis showed that hepatocyte-specific contrast media (HSCM) had equivalent sensitivity and equivalent specificity compared to the other set. The least absolute shrinkage and selection operator method had high sensitivity and specificity than other methods, respectively. The investigated area of the region of interest had high specificity compared to the volume of interest. The imaging-to-surgery interval of 15 days had higher sensitivity and slightly low specificity than the others. Deeks’ test indicates that there was no publication bias (P=0.71).ConclusionRadiomics-based MRI has high accuracy in predicting MVI in HCC, and it can be considered as a non-invasive method for assessing MVI in HCC.

PurposeTo evaluate the diagnostic performance of radiomics model based on fully automatic segmentation of pancreatic tumors from non-enhanced magnetic resonance imaging (MRI) for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC).Materials and methodsIn this retrospective study, patients with surgically resected histopathologically confirmed PASC and PDAC who underwent MRI scans between January 2011 and December 2020 were included in the study. Multivariable logistic regression analysis was conducted to develop a clinical and radiomics model based on non-enhanced T1-weighted and T2-weighted images. The model performances were determined based on their discrimination and clinical utility. Kaplan-Meier and log-rank tests were used for survival analysis.ResultsA total of 510 consecutive patients including 387 patients (age: 61 ± 9 years; range: 28–86 years; 250 males) with PDAC and 123 patients (age: 62 ± 10 years; range: 36–84 years; 78 males) with PASC were included in the study. All patients were split into training (n=382) and validation (n=128) sets according to time. The radiomics model showed good discrimination in the validation (AUC, 0.87) set and outperformed the MRI model (validation set AUC, 0.80) and the ring-enhancement (validation set AUC, 0.74).ConclusionsThe radiomics model based on non-enhanced MRI outperformed the MRI model and ring-enhancement to differentiate PASC from PDAC; it can, thus, provide important information for decision-making towards precise management and treatment of PASC.

BackgroundHand grip strength (HGS) is a fast, useful, and inexpensive outcome predictor of nutritional status and muscular function assessment. Numerous demographic and anthropometric factors were reported to be associated with HGS, while which one or several factors produce greater variations in HGS has not been discussed in detail. This is important for answering how should HGS be normalized for eliminating the influence of individual differences in clinical practice.AimsTo compare the contribution of age, sex, height, weight, and forearm circumference (FCF) to variations in HGS based on a large-scale sample.MethodsWe enrolled 1,511 healthy undergraduate students aged 18–23 years. Age, weight, height, and sex were obtained. HGS was measured using a digital hand dynamometer, and FCF was measured at the point of greatest circumference using a soft ruler in both hands. Pearson’s or Spearman’s correlation coefficients were calculated with data of women and men separated and mixed for comparison. Partial correlation analysis and multivariate linear regression were used to compare the effect of variables on HGS.ResultsAnalysis results confirmed the correlates of higher HGS include higher height, heavier weight, being men and dominant hand, and larger FCF. The correlation between HGS and FCF was the highest, and the bivariate correlation coefficient between weight and HGS was largerata of women and men were mixed, than that between height and HGS. When data of women and men were mixed, there were moderate correlations between HGS and height and weight (r = 0.633∼0.682). However, when data were separated, there were weak correlations (r = 0.246∼0.391). Notably, partial correlation analysis revealed no significant correlation between height and HGS after eliminating the weight effect, while the correlation between weight and HGS was still significant after eliminating the height effect. Multivariate linear regression analyses revealed sex was the most significant contributor to the variation in HGS (Beta = –0.541 and –0.527), followed by weight (Beta = 0.243 and 0.261) and height (Beta = 0.102 and 0.103).ConclusionHGS and FCF reference values of healthy college students were provided. Weight was more correlate with hand grip strength, at least among the healthy undergraduates.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=165914, identifier ChiCTR2200058586.

Long-term feed route exposure to T-2 toxin was proved to elicit growth retarding effects and induction of oxidative stress and apoptosis in Chinese mitten crab (Eriocheir sinensis). However, no study with a holistic perspective has been conducted to date to further describe the in-depth toxicological mechanism of T-2 toxin in E.sinensis. In this study, an RNA-Sequencing (RNA-seq) was used in this study to investigate the effects of feed supplementation with 0 mg/kg and 4 mg/kg T-2 toxin on the hepatopancreas transcriptome of E.sinensis and establish a hepatopancreas transcriptome library of T-2 toxin chronically exposed crabs after five weeks, where 14 differentially expressed genes (DEGs) were screened out across antioxidant, apoptosis, autophagy, glucolipid metabolism and protein synthesis. The actual expression of all the DEGs (Caspase, ATG4, PERK, ACSL, CAT, BIRC2, HADHA, HADHB, ACOX, PFK, eEFe1, eIF4ɑ, RPL13Ae) was also analyzed by real-time quantitative PCR (RT-qPCR). It was demonstrated that long-term intake of large amounts of T-2 toxin could impair antioxidant enzyme activity, promote apoptosis and protective autophagy, disrupt lipid metabolism and inhibit protein synthesis in the hepatopancreas of E.sinensis. In conclusion, this study explored the toxicity mechanism of T-2 toxin on the hepatopancreas of E.sinensis at the mRNA level, which lays the foundation for further investigation of the molecular toxicity mechanism of T-2 toxin in aquatic crustaceans.

This study was conducted to evaluate the effect of cholesterol (CHO) on ovarian development of Eriocheir sinensis through a feeding trial. Crabs (average weight 43.35 ± 0.05 g) were randomly fed with one of three diets: 0% CHO, 0.4% CHO and 1.6% CHO for 16 weeks. Results indicated that the hepatosomatic index (HSI) and gonad index (GSI) of crabs fed with 0.4% CHO diet were significantly higher than those in the control group. (P < 0.05). Meanwhile, 0.4% CHO can significantly increase the gene expression of vtg and vgr in ovary (P < 0.05), thus promoting the accumulation of Vtg. The protein expression of MEK1/2, ERK, p-ERK1/2, Cyclin B and CDC2 were significantly increased in the 0.4% CHO group, therefore dietary CHO might promote oocyte maturation by activating MAPK signal pathway and cooperating with maturation promoting factor (MPF). Further exploration results showed that 0.4% CHO was able to significantly up-regulate the protein expression of STAR and SR-B1 to promote the transport of CHO to ovary, thereby providing sufficient substrates for estradiol (E2) synthesis. In addition, the results in vivo and in vitro shown that CHO could regulate the activities of enzymes such as CYP11A1 and CYP19A1 through the cAMP-PKA-CREB/SF-1 signal pathway and then affects the level of E2 in the organism. In summary, supplementing the appropriate amount of CHO in the diet can improve the E2 level of the organism, thus increasing the accumulation of nutrients in the ovary, promoting the completion of meiosis, and finally achieving the purpose of promoting ovarian maturation.

Understanding how bushfire affects basin-wide ecohydrological processes is critical for ecological restoration and water supply. However, the mechanisms responsible for post-fire streamflow remain poorly explored in forested basins of China due to complex scale-dependent relationships between fire-induced forest changes and ecohydrological processes, lack of reasonable design of paired watershed experiments, and especially data scarcity. Here, we re-examine ecohydrological responses of the Black Dragon fire (one of the largest and most damaging forest fires on record globally) on an annual scale in three forest basins (two fire-impacted basins, namely Emuer and Pangu, and a nearly unimpacted basin, Huma) in the Daxing’an Mountains using multiple most recent datasets and methods. We found that the Black Dragon fire decreased annual- and basin-averaged vegetation leaf area, evapotranspiration, interception loss, transpiration, soil moisture, runoff, and discharge capacity in 1987 in the two fire-impacted basins compared with the unimpacted basin. The annual- and basin-averaged evapotranspiration (runoff) did not reduce (increase) as much as that expected with decreased LAI given the precipitation amount in 1987 in the two fire-impacted basins, which properly linked to the quick postfire regrowth of vegetation in the growing season. Vegetation leaf area and productivity can quickly recover in the following two to three years postfire, but the hydrological systems need more than 10 years to adapt this disturbance. These findings improve the understanding of ecohydrological responses to bushfire disturbance and provide scientific evidence for ecological protection and water resources management under intensified natural and anthropogenic disturbances.

The inflammatory microenvironment created by macrophages has been proven critical for bone regeneration. Both tantalum nanoparticles and micron particles have been applied to bone tissue engineering and have achieved good efficacy, but their effects on immune microenvironment remain unclear. Herein, we explored the different effects between nano- and micro-tantalum particles on the innate immunity of macrophages in vitro and in vivo. RAW 264.7 ​cells were co-cultured with nano- and micro-tantalum particles under inflammatory conditions to evaluate the effects on the morphology and behavior of macrophages. Air pouch model was used to evaluate the material-induced macrophage polarization in vivo. Compared to the tantalum micron particles (TaMPs), the morphology of macrophages was more similar to the M2 phenotype in co-culture with tantalum nanoparticles (TaNPs). At the same time, the TaNPs could also decrease the gene expression of interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α), inducible nitric oxide synthase (iNOS), and increase the expression of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10). Furthermore, the air pouch model showed more M2 macrophage infiltration under the intervention of TaNPs. Our findings demonstrated that TaNPs could significantly increase the polarization of M2 macrophages and decrease the macrophage polarization to the M1 phenotype under the inflammatory microenvironment, showing better immunomodulatory properties.

Bone nonunion or delayed union, caused by stripping or injuring of periosteum, is the most common sequelae of segmental bone defects. The preservation of periosteum, or the use of periosteal grafts, can significantly improve the integration of bone graft, speeding up the process of bone reconstruction. However, in most cases, periosteum cannot be preserved with bioactivity. Thus, it is pivotal to develop artificial periosteum. In this study, artificial periosteum of PLGA/MgO/Quercetin was prepared by electrospinning. PLGA/MgO/Quercetin membranes were shown to have a highly porous surface and microstructure, as observed by scanning electron microscopy. Along with excellent biocompatibility, PLGA/MgO/Quercetin membranes promoted cell proliferation and migration, as well as osteogenic differentiation of BMSCs (Bone marrow mesenchymal stem cells) in a dose-dependent manner through the activation of Wnt/β-Catenin pathway. The PLGA/MgO/Quercetin membranes, with an appropriate concentration of quercetin (

Protein tyrosine phosphatase non-receptor type 18 (PTPN18) is often highly expressed in colorectal cancer (CRC), but its role in this disease remains unclear. We demonstrated that PTPN18 overexpression promotes growth and tumorigenesis in CRC cells and that PTPN18 deficiency yields the opposite results in vitro. Moreover, a xenograft assay showed that PTPN18 deficiency significantly inhibited tumorigenesis in vivo. PTPN18 activated the MYC signaling pathway and enhanced CDK4 expression, which is tightly associated with the cell cycle and proliferation in cancer cells. Finally, we found that MYC interacted with PTPN18 and increased the protein level of MYC. In conclusion, our results suggest that PTPN18 promotes CRC development by stabilizing the MYC protein level, which in turn activates the MYC-CDK4 axis. Thus, PTPN18 could be a novel therapeutic target in the future.

Abstract Background The long‐term trend in cancer death in a rapidly developing country provides information for cancer prophylaxis. Here, we aimed to identify the trends in cancer mortality in China during the 2004‐2018 period. Methods Using raw data from the national mortality surveillance system of China, we assessed the mortalities of all cancer and site‐specific cancers during the 2004‐2018 period. The participants were divided into three age groups: ≥65 years, 40‐64 years, and ≤39 years. Changing trends in cancer death by gender, residency, and tumor location were estimated using fitting joinpoint models to log‐transformed crude mortality rates (CMRs) and age‐standardized mortality rates (ASMRs). Results Cancer death accounted for 24% of all‐cause of death in China during 2014‐2018. The CMR of all cancer was 150.0 per 100,000 persons. Cancer was the leading cause of death in the population

Elopichthys bambusa is an economically important freshwater fish with high nutritional value. In this study, we compared domesticated and wild fish at the physiological, biochemical, histological, and molecular levels to better understand the changes that occur in farmed fish in order to provide ideas about how to optimize the artificial feed formulation used in aquaculture of this species. Water, ash, and crude protein contents did not differ significantly between the two groups. The methionine and glutamic acid contents were 20% and 13.4% higher in the domesticated group than that in the wild group, respectively. Twenty-three types of fatty acids were detected in the wild group compared to 11 in the domesticated group. The iron content in the domesticated group was higher than that in the wild group. The blood index values did not differ significantly between the two groups, except for alanine aminotransferase (ALT), total protein (TP), and globulin (GLO) contents. The ALT content in the wild group was significantly higher and the TP and GLO contents were significantly lower than those in the domesticated group. Histologically, significant differences in the numbers of folds, villi, and goblet cells were detected between the two groups. The expression of t1r1 and t1r3 in the intestines and gills of the domesticated group was significantly lower than that of the wild group. This study provides an important theoretical basis for the reproduction and breeding studies and the quality identification of domesticated Elopichthys bambusa. It will promote the development of large-scale farming of Elopichthys bambusa.

BackgroundMultimorbidity has become an essential public health issue that threatens human health and leads to an increased disease burden. Primary care is the prevention and management of multimorbidity by providing continuous, comprehensive patient-centered services. Therefore, the study aimed to investigate the determinants of primary care utilization and out-of-pocket expenses (OOPE) among multimorbid elderly to promote rational utilization of primary care and reduce avoidable economic burdens.MethodsThe study used data from CHARLS 2015 and 2018, which included a total of 4,384 multimorbid elderly aged 60 and above. Guided by Grossman theory, determinants such as education, gender, marriage, household economy, and so on were included in this study. A two-part model was applied to evaluate primary care utilization and OOPE intensity in multimorbid populations. And the robustness testing was performed to verify research results.ResultsPrimary care visits rate and OOPE indicated a decline from 2015 to 2018. Concerning primary outpatient care, the elderly who were female (OR = 1.51, P < 0.001), married (OR = 1.24, P < 0.05), living in rural areas (OR = 1.77, P < 0.001) and with poor self-rated health (OR = 2.23, P < 0.001) had a significantly higher probability of outpatient utilization, whereas those with middle school education (OR = 0.61, P < 0.001) and better household economy (OR = 0.96, P < 0.001) had a significantly less likelihood of using outpatient care. Rural patients (β = −0.72, P < 0.05) may have lower OOPE, while those with better household economy (β = 0.29, P < 0.05; β = 0.58, P < 0.05) and poor self-rated health (β = 0.62, P < 0.001) occurred higher OOPE. Regarding primary inpatient care, adults who were living in rural areas (OR = 1.48, P < 0.001), covered by Urban Employee Basic Medical Insurance (UEBMI) or Urban Rural Basic Medical Insurance (URBMI) (OR = 2.46, P < 0.001; OR = 1.81, P < 0.001) and with poor self-rated health (OR = 2.30, P < 0.001) had a significantly higher probability of using inpatient care, whereas individuals who were female (OR = 0.74, P < 0.001), with middle school education (OR = 0.40, P < 0.001) and better household economy (OR = 0.04, P < 0.001) had a significantly lower tendency to use inpatient care. Significantly, more OOPE occurred by individuals who were women (β = 0.18, P < 0.05) and with better household economy (β = 0.40, P < 0.001; β = 0.62, P < 0.001), whereas those who were covered by URBMI (β = −0.25, P < 0.05) and satisfied with their health (β = −0.21, P < 0.05) had less OOPE.ConclusionTo prompt primary care visits and reduce economic burden among subgroups, more policy support is in need, such as tilting professional medical staff and funding to rural areas, enhancing awareness of disease prevention among vulnerable groups and so on.

Segmental bone defects, accompanied by periosteum stripping or injury, usually lead to delayed bone union or nonunion, which have challenged orthopedic surgeons. The periosteum, which provides essential blood supply and initial stem cells for bone tissue, plays an important role in the repair of bone defects. The reconstruction of the destroyed periosteum has attracted the attention of researchers exploring more satisfactory therapies to repair bone defects. However, periosteum-like biomaterials have yet to meet the clinical requirements and resolve this challenging problem. In this study, we manufactured a nanofiber periosteum replacement based on poly-ε-caprolactone (PCL), in which tantalum nanoparticles (TaNPs) and nanoscale magnesium oxide (MgO) were introduced to enhance its osteogenic and angiogenic ability. The results of in vitro experiments indicated that the PCL/Ta/MgO periosteum replacement, with excellent cytocompatibility, promoted the proliferation of both bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs). Furthermore, the incorporation of TaNPs and nano-MgO synergistically enhanced the osteogenic differentiation of BMSCs and the angiogenic properties of EPCs. Similarly, the results of in vivo experiments from subcutaneous implantation and critical-sized calvarial defect models showed that the PCL/Ta/MgO periosteum replacement combined the osteogenesis and angiogenesis abilities, promoting vascularized bone formation to repair critical-sized calvarial defects. The results of our study suggest that the strategy of stimulating repairing bone defects can be achieved with the periosteum repaired in situ and that the proposed periosteum replacement can act as a bioactive medium to accelerate bone healing.

Primary membranous nephropathy (PMN), is an autoimmune glomerular disease and the main reason of nephrotic syndrome in adults. Studies have confirmed that the incidence of PMN increases yearly and is related to fine air pollutants particulate matter 2.5 (PM2.5) exposure. These imply that PM2.5 may be associated with exposure to PMN-specific autoantigens, such as the M-type receptor for secretory phospholipase A2 (PLA2R1). Emerging evidence indicates that Th17/Treg turns to imbalance under PM2.5 exposure, but the molecular mechanism of this process in PMN has not been elucidated. As an important indicator of immune activity in multiple diseases, Th17/Treg immune balance is sensitive to antigens and cellular microenvironment changes. These immune pathways play an essential role in the disease progression of PMN. Also, microRNAs (miRNAs) are susceptible to external environmental stimulation and play link role between the environment and immunity. The contribution of PM2.5 to PMN may induce Th17/Treg imbalance through miRNAs and then produce epigenetic affection. We summarize the pathways by which PM2.5 interferes with Th17/Treg immune balance and attempt to explore the intermediary roles of miRNAs, with a particular focus on the changes in PMN. Meanwhile, the mechanism of PM2.5 promoting PLA2R1 exposure is discussed. This review aims to clarify the potential mechanism of PM2.5 on the pathogenesis and progression of PMN and provide new insights for the prevention and treatment of the disease.

IntroductionIn December 2021, a large-scale epidemic broke out in Xi’an, China, due to SARS-CoV-2 infection. This study reports the effect of vaccination on COVID-19 and evaluates the impact of different vaccine doses on routine laboratory markers.MethodsThe laboratory data upon admission, of 231 cases with COVID-19 hospitalized from December 8, 2021 to January 20, 2022 in Xi’an, including blood routine, lymphocyte subtypes, coagulative function tests, virus specific antibodies and blood biochemical tests were collected and analyzed.ResultsOf the 231 patients, 21 were not vaccinated, 158 were vaccinated with two doses and 52 with three doses. Unvaccinated patients had a higher proportion of moderate and severe symptoms than vaccinated patients, while two-dose vaccinated patients had a higher proportion than three-dose vaccinated patients. SARS-CoV-2 specific IgG levels were significantly elevated in vaccinated patients compared with unvaccinated patients. Particularly, unvaccinated patients had lower counts and percentages of lymphocytes, eosinophils and CD8+ T-lymphocytes, and elevated coagulation-related markers. In addition, vaccination had no effect on liver and kidney function.ConclusionsVaccination against SARS-CoV-2, inducing high IgG level and increased CD8+ T cells and eosinophils, and regulating coagulation function, can significantly attenuate symptoms of COVID-19, suggesting that the vaccine remains protective against SARS-CoV-2.

Promoting clinicians’ knowledge sharing of appropriate health technology within the integrated care system (ICS) is of great vitality in bridging the technological gap between member institutions. However, the role of social networks in knowledge sharing of health technology is still largely unknown. To address this issue, the study aims to clarify the influence of clinicians’ social networks on knowledge sharing of health technology within the ICS. A questionnaire survey was conducted among the clinicians in the Alliance of Liver Disease Specialists in Fujian Province, China. Social network analysis was conducted using NetDraw and UCINET, and the quadratic assignment procedure (QAP) multiple regression was used to analyze the influencing factors of knowledge sharing of health technology. The results showed that the ICS played an insufficient role in promoting overall knowledge sharing, especially inter-institutional knowledge sharing. Trust, emotional support, material support, and cognitive proximity positively influenced knowledge sharing of health technology, while the frequency of interaction and relationship importance had a negative impact on it. The finding extended the research scope of social network theory to the field of healthcare and will bridge the evidence gap in the influence of the clinicians’ social networks on their knowledge sharing within the ICS, providing new ideas to boost knowledge sharing and diffusion of appropriate health technology.

Elucidating the impact of reservoir operation on hydrological signatures is crucial for the effective management of large rivers under the changing climate. This study first revised the reservoir operation scheme in the Soil and Water Assessment Tool (SWAT) model to improve its description of actual operation laws of reservoirs in the upper Yangtze River basin (UYRB). Then, we identified the reservoir-induced hydrological alteration through a hydrological index method driven by observed and simulated daily streamflow from 1960 to 2017. The results revealed the superiority of the revised reservoir algorithm in the SWAT model in simulating streamflow and floods at Cuntan and Yichang stations with the Nash-Sutcliffe efficiency (NSE) coefficient and the Kling-Gupta efficiency (KGE) coefficient improved from 0.01 to 0.08 and 0.01 to 0.05, respectively. Relative to the baseline period (1960–2002), the hydrological signatures in the impact period (2003–2017) changed substantially after 2003. Reservoirs induced a remarkable increase of 27.76% and 55.97% in streamflow from January to March, accompanied by a notable decrease of 6.95% and 20.92% in streamflow from September to October after 2003 at Cuntan and Yichang stations, respectively. Meanwhile, the annual streamflow range contracted, and the flow became more stable with a reduced variation in daily streamflow, extremely low flow spell duration, and extremely high flow spell duration. Consequently, our results improved the quantitative understanding of reservoir-induced alteration and informed the management and planning of reservoir construction in the UYRB under climate change.

This study evaluated the effects of dietary magnesium oxide nanoparticles (MgO NPs) on the growth, redox defense, glucose metabolism, and magnesium homeostasis in blunt snout bream. Fish (12.42 ± 0.33 g) were fed seven diets containing graded levels of MgO NPs (0, 60, 120, 240, 480, 960, and 1920 mg/kg) for 12 weeks. Whole-body Mg retention decreased significantly as the dietary Mg increased. As dietary MgO NPs levels reached 120 mg/kg, the growth performance and feed utilization remarkably improved. When added at 240 mg/kg, oxidative stress was significantly reduced evidenced by the increased Mn-sod transcription and the decreased CAT and GSH-Px activities and the MDA content. Meanwhile, it enhanced glucose transport, glycolysis, and glycogen synthesis, while inhibiting gluconeogenesis, as was characterized by the increased transcriptions of glut2, gk, and pk, and the decreased transcriptions of fbpase and g6pase. In addition, the supplementation of 120 mg/kg MgO NPs promoted Mg transport marked by a significant increase in the protein expressions of TRMP7, S41A3, and CNNM1. In conclusion, the moderate supplementation of MgO NPs improved the growth performance, reduced hepatic oxidative stress, and promoted glucose transport, glycolysis, glycogen synthesis, and magnesium homeostasis in fish while inhibiting glu.

Under the current trend of power electronics in energy systems, a high percentage of renewable energy transports clean energy to the grid through grid-connected inverters. The pulse-width modulation (PWM) technique brings high-order harmonics near to the switching frequency, and LCL filters with low-pass characteristics become the common choice for grid-connected inverters. However, the low-order harmonics caused by nonideal switching characteristics are difficult to filter out, and the new resonance point introduced by the LCL filter causes a security problem for the energy systems. Firstly, the generation mechanism of the 6 k ± 1 order harmonic and high-frequency resonance from a PV grid-connected inverter is analyzed. Then, a virtual resistor is constructed by the active damping method to absorb the resonant component. Meanwhile, this paper also presents an adaptive modulation voltage compensation method to decrease the low-order harmonics. Finally, the actual measured data of user photovoltaic (PV) and multiple comparative simulations verify these theories. Simulation results show that the proposed coordinated control algorithm reduces the peak of the resonance point, and the rate of low-order harmonics mitigation is more than 50%. The proposed method is suitable for various operating conditions.

Abstract Gordonia sp. are members of the actinomycete family, their contribution to the environment improvement and environmental protection by their biological degradation ability, but there are few studies on the antimicrobial activity of their secondary metabolites. Our team isolated and purified an actinomycete WA 4-31 from the intestinal tract of Periplaneta americana, firstly identified the strain WA 4-31 by the morphological characteristics and the phylogenetic analyses, and found it was completely homologous to the strain of Gordonia terrae from the Indian desert. Meanwhile, actinomycin D (1), actinomycin X2 (2), mojavensin A (3) and cyclic (leucine-leucne) dipeptide (4) were obtained from the EtOAc extract from the broth of WA 4-31. Compounds 1–4 showed anti-fungus activities against Candida albicans, Aspergillus niger, A. fumigatus and Trichophyton rubrum, also anti-MRSA and inhibited Escherichia coli in different degree. Interestingly, we found when 3 was mixed with 4 with ratio of 1:1, the activity of the mixture on anti-Candida albicans was better than the single. Besides, compounds 1–3 had varying degrees of antiproliferative activities on CNE-2 and HepG-2 cell lines. These indicated that Gordonia rare actinomycete from the intestinal tract of Periplaneta americana possessed a potential as a source of active secondary metabolites.

Sterol lipids are crucial for maintaining proper brain function. Here, the authors combine ion mobility-mass spectrometry and machine learning to assemble a sterol lipid library and characterize differences in sterol lipids across ten brain regions and two age groups in mice.

In distant hybridization of fishes, there is a low hatching rate of hybrid progenies. To further understand the causes of low hatchability, in this article, cross-breeding between zebrafish (ZF) and crucian carp (CC) are generated, in which the hatching rate of cross progenies (ZF♀ × CC♂, ZC) is 35.67%, while that of reciprocal cross progenies (CC♀ × ZF♂, CZ) is about zero. The structures and SDS-PAGE protein pattern of egg envelopes in hybrid early embryos are like their maternal fish, however, during the process of embryo development, some differences are detected between the CZ and CC. The hatching enzyme gene 1 (he1) nucleotide sequences from ZF and CC were 85.1% identity, while that of 99.6% identity was between the ZF and ZC, and 98.4% from CC and hybrid of CZ. There are differences in predictive protein physicochemical properties of he1 between CZ and CC, but no significant change in he1 mRNA levels during embryonic development. Our data furtherly verify that the characteristics of egg envelope and hatching enzyme in hybrid progenies are inherited from maternal fish. Moreover, there are obvious differences between CZ and maternal parent in both egg envelope and hatching enzyme during embryonic development, which are considered to be related to its low hatching rate.

Sediment samples collected from the river Shitalakhya, Bangladesh, were analyzed using atomic absorption spectroscopy (AAS) to investigate site-to-site (spatial) and seasonal (i.e., dry, pre-monsoon, post-monsoon) variation of Cr, Mn, Ni, Cu and Zn. The mean concentrations of Cr, Mn, Ni, Cu and Zn were 22.37 ± 6.09, 612.59 ± 160.08, 54.11 ± 11.21, 50.36 ± 9.40 and 103.62 ± 62.74 mg/kg in the dry, 31.58 ± 5.22, 569.71 ± 112.16, 58.35 ± 7.82, 49.93 ± 17.36 and 110.88 ± 95.83 mg/kg in the pre-monsoon and 18.09± 6.32, 567.02 ± 115.55, 50.89 ± 6.58, 39.75 ± 4.56 and 55.22 ± 11.33 mg/kg in the post-monsoon, respectively. Based on the metals’ concentrations, no considerable difference was observed among the three seasons, but the concentrations were slightly elevated in the dry and pre-monsoon compared to that in the post-monsoon with respect to site-to-site variation. Among the metals examined, concentrations of Ni and Cu were elevated because of the use of oxides of these heavy metals as catalysts in the ammonia plant. The following statistical indices i.e., Pearson correlation matrix, geo-accumulation index (Igeo), contamination factor (Cf), degree of contamination (Cd), pollution load index (PLI) and ecological risk potential (RI) factors were taken into account to assess the heavy metals contamination of the sediments. According to the values of the statistical indices for Cr, Mn, Ni, Cu and Zn, it is concluded that the study area was with low contamination while concentrations of Ni and Cu were higher than the Threshold Effect Level (TEL) and Toxicity Reference Value (TRV) values suggesting unsafe to use the sediments for vegetation and other uses.

Abstract Background With inappropriate use of antimicrobials becoming a great public health concern globally, the issue of applying clinical practice guidelines (CPGs) to regulate the rational use of antimicrobials has attracted increasing attention. Taking tertiary general hospitals in China for example, this study aimed to identify factors to investigate the comprehensive influencing mechanism for physicians’ intention to use CPGs on antimicrobials. Methods Based on the integration of Theory of Planned Behavior (TPB), Technology Acceptance Model (TAM), and Technology-Organization-Environment framework (TOE), a questionnaire survey was conducted covering potential determinants of affecting physicians’ intentions to use CPGs on antimicrobials at the individual level (attitude, subjective norms and perceived risk), technical level (relative advantage and ease of use), and organizational level (top management support and organizational implementation). Data were collected from 644 physicians in tertiary general hospitals in eastern, central and western China, which were obtained by multi-stage random sampling. The structural equation modeling (SEM) was used to link three-level factors with physicians’ behavioral intentions. Results The majority of the participants (94.57%) showed a positive tendency toward intention to use CPGs on antimicrobials. The reliability and validity analysis showed the questionnaire developed from the theoretical model was acceptable. SEM results revealed physicians’ intentions to use CPGs on antimicrobials was associated with attitude (β = 0.166, p

Bioconversion (e.g. anaerobic fermentation and compost) is the common recycling method of waste activated sludge (WAS) and its hydrolysis, as the rate-limiting step of fermentation, could be accelerated by protease. However, the commercial protease was unstable in a sludge environment, which increased the cost. An endogenous alkaline protease stable in sludge environment was screened in this study and its suitability for treating the sludge was analyzed. The optimal production medium was determined by Response Surface Methodology as starch 20 g/L, KH2PO4 4 g/L, MgSO4·7H2O 1 g/L, sodium carboxy-methyl-cellulose 4 g/L, casein 4 g/L and initial pH 11.3, which elevated the yield of protease by up to 15 times (713.46 U/mL) compared with the basal medium. The obtained protease was active and stable at 35 °C–50 °C and pH 7.0–11.0. Furthermore, it was highly tolerant to sludge environment and maintained high efficiency of sludge hydrolysis for a long time. Thus, the obtained protease significantly hydrolyzed WAS and improved its bioavailability. Overall, this work provided a new insight for enzymatic treatment of WAS by isolating the endogenous and stable protease in a sludge environment, which would promote the resource utilization of WAS by further bioconversion. HIGHLIGHTS A novel protease-producing bacterium was isolated from the sludge.; The screened protease was highly tolerant to the sludge environment.; Treatment of the sludge by the screened protease elevated its bioavailability.; The screened protease was a promising biocatalyst for sludge treatment.;

ObjectiveAs a member of interleukin-12 family, interleukin-35 (IL-35) plays an important regulatory role in immune response. The relationship between IL-35 and idiopathic membranous nephropathy (IMN) is still unclear, and the purpose of this study is to clarify the relationship between IL-35 and disease activity and remission of IMN.MethodsThis study was a single-center, retrospective study in which all patients were diagnosed with IMN by renal biopsy or aPLA2R titer and treated with Mahuang Fuzi and Shenzhuo Decoction (MFSD). A follow-up was conducted with the endpoint of clinical complete or partial remission (CR+PR). Levels of serum IL-35 were measured and its relationship with IMN remission were analyzed. The regulatory T cell (Treg) and inducible IL-35 producing Tregs (iTR35) in peripheral blood of IMN patients were detected by flow cytometry.ResultsA total of 76 IMN patients (age 51.95 ± 13.29) were followed-up for 18 (12, 24) months. The level of serum IL-35 in all patients increased after treatment, but the degree of increase in remission group was significantly higher than that in no remission (NR) group (117.6% vs 83.7%, P 203.05 pg/ml) (12mon vs. 24mon, P

BackgroundNumerous studies showed that preoperative platelet-albumin-bilirubin (PALBI) grade was closely related to the prognostic outcome of patients with hepatocellular carcinoma (HCC). However, the conclusions were inconsistent. Therefore, we implemented the study to comprehensively evaluate the association between PALBI grade and prognosis in patients with HCC.MethodsRelevant articles were collected from the specified databases until February 10, 2022. We included all studies exploring the relationship between PALBI grade and prognosis in HCC patients. We used the hazard ratio (HR) and 95% confidence interval (CI) to calculate the comprehensive analysis. All data analyses were performed using STATA 12.0.ResultsThirteen retrospective articles containing 15534 patients were included in the meta-analysis. The pooled results displayed that the high PALBI grade was obviously correlated with poor overall survival (OS) (HR: 1.71, 95% CI: 1.46-2.02) and disease-free survival/relapse-free survival (DFS/RFS) (HR:1.31; 95% CI: 1.11–1.54). Subgroup analyses further confirmed the reliability of the comprehensive results.ConclusionsPALBI may be a valid prognostic indicator in HCC patients. More investigations were needed to test our findings.

CD4+ T cells, also known as T helper (Th) cells, contribute to the adaptive immunity both in the periphery and in the central nervous system (CNS). At least seven subsets of Th cells along with their signature cytokines have been identified nowadays. Neuroinflammation denotes the brain’s immune response to inflammatory conditions. In recent years, various CNS disorders have been related to the dysregulation of adaptive immunity, especially the process concerning Th cells and their cytokines. However, as the functions of Th cells are being discovered, it’s also found that their roles in different neuroinflammatory conditions, or even the participation of a specific Th subset in one CNS disorder may differ, and sometimes contrast. Based on those recent and contradictory evidence, the conflicting roles of Th cells in multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, epilepsy, traumatic brain injury as well as some typical mental disorders will be reviewed herein. Research progress, limitations and novel approaches concerning different neuroinflammatory conditions will also be mentioned and compared.

BackgroundThe contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) and their association with cancer aggressiveness remains uncertain in China, a country with half of global PLC. We aimed to characterize this using data from four representative medical centers.MethodsIn total, 15,801 PLC patients were enrolled from the centers distributed in Easter5n, Southern, Northern, and Western China from 2003 to 2020. Of those, 7585 with curative surgery were involved in survival analysis. A nomogram was constructed using preoperative parameters to predict postoperative survival.ResultsHepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma accounted for 93.0%, 4.3%, and 1.6% in PLC, respectively. The seropositivities of HBV and HCV were 84.4% and 3.2% in HCC, respectively. The seropositivity of anti-HCV antibody was significantly higher in HBV-negative than in HBV-positive HCC patients (13.2% vs. 1.1%). Compared to HCV-positive HCC (HCV-HCC), HBV-positive HCC (HBV-HCC) was associated with 12-year earlier onset, higher proportions of males, high α-fetoprotein, large tumor size, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and vascular tumor thrombus. The proportions of HCC and HBV seropositivity increased, whereas that of anti-HCV decreased, from 2003 to 2020. Postoperative five-year survival rate was 73.5%, 64.1%, 34.9%, and 19.7% in HCC at BCLC stage 0, A, B, and C, respectively. The multivariate Cox regression analysis showed that HBV seropositivity, incomplete tumor capsule, vascular tumor thrombus, tumor diameter (≥3 cm), advanced BCLC stage (B+C), α-fetoprotein (≥20ng/ml), and direct bilirubin (>8µmol/L) contributed independently to shorter overall survival (OS); whereas post-operative radiofrequency ablation and second resection independently improved OS in HCC. HCV-HCC had a more favorable prognosis than did HBV-HCC (Log-rank test, P

Abstract Background The promotion of early diagnosis is undoubtedly effective in reducing the burden of disease. Contrast-enhanced ultrasound (CEUS) is a diagnostic technology for liver cancer, but its implementation faces some challenges. Understanding the influencing factors of CEUS utilization is crucial for its successful implementation. However, such research is rare. The aims of this study were to investigate the status of CEUS utilization and its predictors in China. Methods Through multistage random sampling, a cross-sectional study design was conducted among physicians in charge of direct use of CEUS working at liver disease-related departments of sampled health institutions. To access the potential influencing factors of physicians' CEUS utilization, a structured questionnaire was developed based on the theoretical model, which was developed by integration of the Theory of Planned Behavior (TPB) and Technology Acceptance Model (TAM). Structural equation modeling was used to verify the proposed hypotheses, and analyze the relationship and mechanism between the factors. Results A total of 309 physicians were enrolled. The mean score of utilization behavior was 2.04 (SD = 1.07), and 37.22% above the mean. The favorable fitting results demonstrated that the integration of TAM and TPB was an acceptable model. SEM results also identified physicians’ intentions to use CEUS was directly associated with utilization behavior (β = 0.287, P

Abstract Background The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future. Methods In this research, bone marrow mesenchymal stem cells (BMSCs) seeded on 3D-printed scaffolds were treated with sinusoidal EMFs in vitro. Then, 5.5 mm critical-sized calvarial defects were created in rats, and the cell scaffolds were implanted into the defects. In addition, the molecular and cellular mechanisms by which EMFs regulate BMSCs were explored with various approaches to gain deeper insight into the effects of EMFs. Results The cell scaffolds treated with EMF successfully accelerated the repair of critical-sized calvarial defects. Further studies revealed that EMF could not directly induce the differentiation of BMSCs but improved the sensitivity of BMSCs to BMP signals by upregulating the quantity of specific BMP (bone morphogenetic protein) receptors. Once these receptors receive BMP signals from the surrounding milieu, a cascade of reactions is initiated to promote osteogenic differentiation via the BMP/Smad signalling pathway. Moreover, the cytokines secreted by BMSCs treated with EMF can better facilitate angiogenesis and osteoimmunomodulation which play fundamental roles in bone regeneration. Conclusion In summary, EMF can promote the osteogenic potential of BMSCs and enhance the paracrine function of BMSCs to facilitate bone regeneration. These findings highlight the profound impact of EMF on tissue engineering and provide a new strategy for the clinical treatment of bone defects.

Abstract Background Despite there is growing evidence focusing on health inequalities in China, socioeconomic inequalities in cognitive impairment among older adults have received little attention. This study aims to measure socioeconomic inequalities in cognitive impairment among Chinese older adults, and determine the contributing social factors to the inequalities. Methods A cross-sectional analysis was performed using data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 10,556 older adults aged 65 and over were included in the study. The prevalence of cognitive impairment was measured by using the Chinese version of the Mini-Mental State Examination. The socioeconomic inequalities in cognitive impairment were illustrated and quantified by the concentration curve and normalized concentration index. Multivariate logistic regression was conducted to identify the associated factors of cognitive impairment. And decomposition analysis was further applied to decompose the contribution of each determinant to the observed inequalities in cognitive impairment. Results The study indicated that the prevalence of cognitive impairment among Chinese older adults was 18.95%. The overall concentration index for cognitive impairment was − 0.046, which suggested a higher concentration of cognitive impairment among socioeconomically disadvantaged older adults. The results showed the prevalence of cognitive impairment was associated with sex, age, marital status, education level, occupation, economic status, emotional support, financial support, living arrangement, and participation in informal activities. Decomposition results further revealed the contributions of the determinants to the inequalities in cognitive impairment. Specifically, age (131.61%), marital status (85.68%), emotional support (84.85%), education level (39.73%), occupation (21.24%), sex (17.25%), financial support (− 4.19%), economic status (1.02%), living arrangement (0.88%), and informal activities (0.30%) have varying degrees of contributions to the inequality in cognitive impairment. Conclusion This study sheds light on the pro-rich inequality in cognitive impairment among older adults in China. It suggests that policymakers should pay more attention to older adults who are female, old-old, widowed, illiterate, economically disadvantaged, with no social support, and less socially involved. Also, more targeted interventions should be undertaken to improve the socioeconomic conditions of these vulnerable individuals and strengthen their ability to cope with the risk of cognitive impairment.

Soil acidification in tea plantations leads to an excessive heavy metal content in tea, decreasing its yield and quality. How to apply shellfish and organic fertilizers to improve soil and ensure the safe production of tea is still not clear. A two-year field experiment was conducted in tea plantations in which the soil was characterized by a pH of 4.16 and concentrations of lead (Pb) (85.28 mg/kg) and cadmium (Cd) (0.43 mg/kg) exceeding the standard. We used shellfish amendments (750, 1500, 2250 kg/ha) and organic fertilizers (3750, 7500 kg/ha) to amend the soils. The experimental results showed that compared with the treatment without any amendment (CK), the soil pH increased by 0.46 on average; the soil available nitrogen, phosphorus, and potassium contents increased by 21.68%, 19.01%, and 17.51% respectively; and the soil available Pb, Cd, Cr, and As contents decreased by 24.64%, 24.36%, 20.83%, and 26.39%, respectively. In comparison to CK, the average yield of tea also increased by 90.94 kg/ha; tea polyphenols, free amino acids, caffeine, and water extract increased by 9.17%, 15.71%, 7.54%, and 5.27%, respectively; and the contents of Pb, Cd, As, and Cr in the tea decreased significantly (p < 0.05) by 29.44–61.38%, 21.43–61.38%, 10.43–25.22%, and 10.00–33.33%, respectively. The greatest effects on all parameters occurred with the largest amendment of both shellfish (2250 kg/ha) and organic fertilizer (7500 kg/ha) combined. This finding suggests that the optimized amendment of shellfish could be used as a technical measure to improve the health quality of both soil and tea in acidified tea plantations in the future.