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This article proposes a voltage compensation control strategy for the distribution network based on the unified power quality conditioner (UPQC) with battery energy storage systems (BESS) to achieve comprehensive management of the power quality and improve the system dynamic responses. Specifically, aiming at that amplitude and phase jump of the terminal voltage, a capacity configuration compensation scheme is proposed to achieve voltage vector compensation. The series converter is designed to compensate for the amplitude and phase of the load voltage. The parallel converter is designed to realize power compensation and ensure that the grid voltage and current are sinusoidal and in phase. A voltage control approach based on the nonlinear disturbance observer (NDO) is developed for BESS to stabilize the DC bus voltage and improve the anti-interference performance of the current. An NDO is designed to accomplish current disturbance tracking and provide disturbance feedforward compensation. Simulations validate that the proposed approach is effective and feasible.

Abstract Background The Enhanced Recovery After Surgery (ERAS) Society recommends that after total knee arthroplasty (TKA), patients should be mobilized early. However, there is no consensus on how early physical therapy should be commenced. We aim to investigate whether ultra-early physical therapy (

Objective Non-malignant pleural effusions (NMPE) are common in hospitalised patients. Data on NMPE inpatients are scarce and the factors influencing the prognosis are unknown.Design This was a retrospective cohort study.Setting and participants We conducted a retrospective cohort of inpatients (n=86 645) admitted to the Chinese PLA General Hospital from 2018 to 2021, based on electronic medical records. The observations of 4934 subjects with effusions confirmed by chest radiological tests (CT or X-ray) without a diagnosis of malignancy were followed during admission. Logistic regression was used to analyse organ damage and other factors associated with in-hospital death. Patients were clustered according to their laboratory indicators, and the association between the clustering results and outcomes was studied.Outcome The outcome of this study was in-hospital mortality.Results Among 4934 patients, heart failure + pneumonia + renal dysfunction was the most common (15.12%) among 100 different diagnostic groups. 318 (6.4%) patients died during hospitalisation. Lung (OR 3.70, 95% CI 2.42 to 5.89), kidney (OR 2.88, 95% CI 2.14 to 3.90) and heart (1.80, 95% CI 1.29 to 2.55) damage were associated with in-hospital mortality. Hierarchical clustering of laboratory indicators (estimated glomerular filtration rate, white blood cell count, platelet count, haemoglobin, N-terminal pro-B-type natriuretic peptide, serum albumin) demonstrated the ability to discriminate patients at high risk of in-hospital death.Conclusion Comorbidities and multiorgan failure are the prominent characteristics of NMPE patients, which increase the risk of in-hospital mortality, and comprehensive intervention for specific comorbidity patterns is suggested.

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancer types, with a low 5-year survival rate of ~20%. Our prior research has suggested that DNA Polymerase iota (Pol ι), a member of Y-family DNA polymerase, plays a crucial role in the invasion and metastasis of ESCC. However, the underlying mechanism is not well understood. In this study, we utilized ChIP-PCR and luciferase reporter assays to investigate the binding of HIF-1α to the promoter of the Pol ι gene. Transwell, wound healing, and mouse models were employed to assess the impact of Pol ι and HIF-1α on the motility of ESCC cells. Co-immunoprecipitation and Western blot were carried out to explore the interaction between Pol ι and HIF-1α, while qRT-PCR and Western blot were conducted to confirm the regulation of Pol ι and HIF-1α on their downstream targets. Our results demonstrate that HIF-1α activates the transcription of the Pol ι gene in ESCC cells under hypoxic conditions. Furthermore, the knockdown of Pol ι impeded HIF-1α-induced invasion and metastasis. Additionally, we found that Pol ι regulates the expression of genes involved in epithelial-mesenchymal transition (EMT) and initiates EMT through the stabilization of HIF-1α. Mechanistically, Pol ι maintains the protein stability of HIF-1α by recruiting USP7 to mediate the deubiquitination of HIF-1α, with the residues 446–578 of Pol being crucial for the interaction between Pol ι and USP7. Collectively, our findings unveil a novel feedforward molecular axis of HIF-1α- Pol ι -USP7 in ESCC that contributes to ESCC metastasis. Hence, our results present an attractive target for intervention in ESCC.

Abstract Background Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable‐risk by European Leukemia Net (ELN), CBF‐AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF‐AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors. Methods Retrospective analysis of 149 AML patients (75 CBF‐AML, 74 non‐CBF) at Peking University First Hospital (March 2012–March 2022). Results CBF‐AML patients have significantly lower disease‐free survival (DFS) (p = 0.005) and higher non‐relapse mortality (NRM) (p = 0.028) compared to non‐CBF AML. inv (16) and t(8;21) show distinct co‐occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) improves prognosis in low‐risk t(8;21). Conclusion Prognosis of CBF‐AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo‐HSCT may benefit low‐risk t(8;21), but further research is needed for conclusive evidence.

BackgroundAccelerated modern industrial processes, extensive use of pesticides and fertilizers and remaining issues of wastewater irrigation have led to an increasingly severe composite pollution of heavy metals in arable land. Soil contamination can cause significant damage to ecological environments and human health. Mineral resource mining can result in varying degrees of heavy metal pollution in surrounding water systems and soil. As a plateau lake, Hongfeng Lake has a fragile watershed ecosystem. Coupled with the rapid development of the current socio-economy and the ongoing activities of mining, urbanization and agricultural development, the water and soil environment of the lake and arable land are facing serious heavy metal pollution. Therefore, the situation warrants attention.MethodsThis study focused on characterizing soil types and conducted sampling and laboratory testing on the farmland soil in Hongfeng Lake. The integrated Nemero comprehensive pollution assessment and potential ecological pollution assessment methods were used to evaluate the heavy metal pollution status. The APCS-MLR model was employed to explore the sources of heavy metal pollution. In addition, the human health risk model was used to analyze the association between heavy metal content in cultivated land and human health risks.ResultsThe single-factor pollution of each element was ranked in descending order: Hg > As > Pb > Cr > Cd, with Hg being the main pollutant factor. The entire area was subjected to mild pollution according to the pollution index. Pollution source analysis indicated two main pollution sources. Hg, As, Pb and Cr pollution mainly resulted from Source 1 (industrial and natural activities), accounting for 71.99%, 51.57%, 67.39% and 68.36%, respectively. Cd pollution was mainly attributed to Source 2 (agricultural pollution source), contributing 84.12%. The health risk assessment model shows that heavy metals posed acceptable carcinogenic risks to humans rather than non-carcinogenic risks. As was the main non-carcinogenic risk factor, while Cr was the main carcinogenic risk factor, with higher risks in children than adults.ConclusionOur study identified the heavy metal pollution in farmland soil in Hongfeng Lake, evaluated and analyzed the pollution sources and identified the heavy metal elements in cultivated lands that have the greatest impact on human health risks. The aim of this study is to provide a scientific basis for soil heavy metal pollution control.

Sphingolipids, as members of the large lipid family, are important components of plasma membrane. Sphingolipids participate in biological signal transduction to regulate various important physiological processes such as cell growth, apoptosis, senescence, and differentiation. Numerous studies have demonstrated that sphingolipids are strongly associated with glucose metabolism and insulin resistance. Insulin resistance, including peripheral insulin resistance and brain insulin resistance, is closely related to the occurrence and development of many metabolic diseases. In addition to metabolic diseases, like type 2 diabetes, brain insulin resistance is also involved in the progression of neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. However, the specific mechanism of sphingolipids in brain insulin resistance has not been systematically summarized. This article reviews the involvement of sphingolipids in brain insulin resistance, highlighting the role and molecular biological mechanism of sphingolipid metabolism in cognitive dysfunctions and neuropathological abnormalities of the brain.

Anemia is a common and important complication in patients with chronic kidney disease (CKD). Accordingly, the current treatment is based on erythropoiesis stimulating agents (ESAs) and iron. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors (HIF-PHIs) have been developed to treat renal anemia through a novel mechanism. HIF-PHIs increase EPO at physiologic blood concentrations and also improve the supply of hematopoietic iron. Iron is the main component of hemoglobin, and ensuring efficient iron metabolism is essential in the treatment of anemia. HIF-PHIs may have advantages in improving iron utilization and mobilization compared to ESAs. Most HIF-PHIs trials revealed a significant decline of hepcidin, increase transferrin level and total iron binding capacity in patients. From a clinical point of view, improvements in iron metabolism should translate into a reduction in the need for iron supplementation, although timely and comparative assessment of iron supplementation across studies are complicated due to the large variability in the iron regimen employed. This review summarizes the mechanism of HIF-PHIs on improved iron metabolism and the route of iron usage in the trials for dialysis-dependent CKD and non-dialysis CKD. And this review also makes an interpretation of the clinical practice guidelines in China and recommendation by Asia Pacific Society of Nephrology.

ABSTRACT Ectomycorrhizal fungi play an irreplaceable role in phosphorus cycling. However, ectomycorrhizal fungi have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. Endofungal bacteria in ectomycorrhizal fruiting bodies are always closely related to the ecological function of ectomycorrhizal fungi. In this study, we explore endofungal bacteria in the fruiting body of Tylopilus neofelleus and their function during the absorption of chelated inorganic phosphorus by host pine through the ectomycorrhizal system. The results showed that the endofungal bacterial microbiota in the fruiting body of T. neofelleus might be related to the dissolution of chelated inorganic phosphorus in soil. The soluble phosphorus content in the combined system of T. neofelleus and endofungal bacteria Bacillus sp. strain B5 was five times higher than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment in the dissolution experiment of chelated inorganic phosphorus. The results showed that T. neofelleus not only promoted the proliferation of Bacillus sp. strain B5 in the combined system but also improved the expression of genes related to organic acid metabolism, as assesed by transcriptomic analysis. Lactic acid content was five times higher in the combined system than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment. Two essential genes related to lactate metabolism of Bacillus sp. strain B5, gapA and pckA, were significantly upregulated. Finally, in a pot experiment, we verified that T. neofelleus and Bacillus sp. strain B5 could synergistically promote the absorption of chelated inorganic phosphorus by Pinus sylvestris in a ternary symbiotic system. IMPORTANCE Ectomycorrhizal fungi (ECMF) have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. In the natural environment, the extraradical hyphae of ECMF alone may not satisfy the phosphorus demand of the plant ectomycorrhizal system. In this study, our results innovatively show that the ectomycorrhizal system might be a ternary symbiont in which ectomycorrhizal fungi might recruit endofungal bacteria that could synergistically promote the mineralization of chelated inorganic phosphorus, which ultimately promotes plant phosphorus absorption by the ectomycorrhizal system.

Ferroptosis is iron-dependent regulatory cell death (RCD). Morphologically, ferroptosis is manifested as mitochondrial atrophy and increased mitochondrial membrane density. Biochemically, ferroptosis is characterized by the depletion of glutathione (GSH), the inactivation of glutathione peroxidase 4 (GPX4), and an increase in lipid peroxides (LPO)and divalent iron ions. Ferroptosis is associated with various diseases, but the relationship with diabetic retinopathy(DR) is less studied. DR is one of the complications of diabetes mellitus and has a severe impact on visual function. The pathology of DR is complex, and the current treatment is unsatisfactory. Therefore, exploring pathogenesis is helpful for the clinical treatment of DR. This paper reviews the pathological mechanism of ferroptosis and DR in recent years and the involvement of ferroptosis in the pathology of DR. In addition, we propose problems that need to be addressed in this research field. It is expected to provide new ideas for treating DR by analyzing the role of ferroptosis in DR.

Abstract Background The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. Methods We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. Results We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. Conclusion This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

Intrinsic self-healing polymers attract increasing attention but often suffer from a narrow self-healing temperature range and unsatisfactory mechanical performance. Here, the authors use click chemistry to develop a library of catalyst-free reversible polythioureas and demonstrate that the self-healing temperature and mechanical properties can be adjusted by controlling the flexibility and the steric environment.

The low-temperature environment of the Tibetan Plateau presents a technical challenge to composting. This study screened cold-adapted microbes with strong degradation ability and selected five strains to experimentally test and evaluate composting cattle manure in a natural environment in the plateau region. The results showed that both the control and the treatment groups had a slow temperature rise at the beginning of the composting. However, after the first turning, the temperature rise in the inoculated group accelerated. The inoculation of cold-adapted bacteria increased the OM loss in the compost by 8.6%, decreased the retention of nitrogen of the compost by 3%, and increased the seed germination index (GI) value from 44.4% to 73.9%. Microbial community structure analysis showed that the relative abundance of Psychrobacter was more than 50% at the beginning of the composting in the two experimental groups. The cold-adapted microbial inoculation increased the diversity of the microbial community, i.e., Truepera and Luteimona, and the abundance of specific microorganisms during the thermophilic and maturation stages. This study demonstrates that inoculation of cold-adapted bacteria improves the maturity and efficiency of cattle manure composting in a natural plateau environment.

Abstract Background Colorectal cancer is a malignant gastrointestinal cancer, in which some advanced patients would develop cancer cachexia (CAC). CAC is defined as a multi-factorial syndrome characterized by weight loss and muscle loss (with or without fat mass), leading to progressive dysfunction, thereby increasing morbidity and mortality. ApcMin/+ mice develop spontaneous intestinal adenoma, which provides an established model of colorectal cancer for CAC study. Upon studying the ApcMin/+ mouse model, we observed a marked decrease in weight gain beginning around week 15. Such a reduction in weight gain was rescued when ApcMin/+ mice were crossed with MMP12−/− mice, indicating that MMP12 has a role in age-related ApcMin/+-associated weight loss. As a control, the weight of MMP12−/− mice on a weekly basis, their weight were not significantly different from those of WT mice. Methods ApcMin/+; MMP12−/− mice were obtained by crossing ApcMin/+ mice with MMP12 knockout (MMP12 −/−) mice. Histological scores were assessed using hematoxylin-eosin (H&E) staining. MMP12 expression was confirmed by immunohistochemistry and immunofluorescence staining. ELISA, protein microarrays and quantitative Polymerase Chain Reaction (qPCR) were used to investigate whether tumor could up-regulate IL-6. Cell-based assays and western blot were used to verify the regulatory relationship between IL-6 and MMP12. Fluorescence intensity was measured to determine whether MMP12 is associated with insulin and insulin-like growth factor 1 (IGF-1) in vitro. MMP12 inhibitors were used to explore whether MMP12 could affect the body weight of ApcMin/+ mice. Results MMP12 knockout led to weight gain and expansion of muscle fiber cross-sectional area (all mice had C57BL/6 background) in ApcMin/+ mice, while inhibiting MMP12 could suppress weight loss in ApcMin/+ mice. MMP12 was up-regulated in muscle tissues and peritoneal macrophages of ApcMin/+ mice. IL-6 in tumor cells and colorectal cancer patients is up-regulation. IL-6 stimulated MMP12 secretion of macrophage. Conclusions MMP12 is essential for controlling body weight of Apc Min/+ mice. Our study shows that it exists the crosstalk between cancer cells and macrophages in muscle tissues that tumor cells secrete IL-6 inducing macrophages to up-regulate MMP12. This study may provide a new perspective of MMP12 in the treatment for weight loss induced by CAC.

Objective: This study aims to develop a combined population pharmacokinetic (PPK) model for aripiprazole (ARI) and its main active metabolite dehydroaripiprazole (DARI) in pediatric patients with tic disorders (TD), to investigate the inter-individual variability caused by physiological and genetic factors in pharmacokinetics of ARI and optimize the dosing regimens for pediatric patients.Methods: A prospective PPK research was performed in Chinese children with TD. Totally 84 patients aged 4.83–17.33 years were obtained for the pharmacokinetic analysis. 27 CYP2D6 and ABCB1 gene alleles were detected. Moreover, the clinical efficacy was evaluated according to reduction rate of Yale Global Tic Severity Scale (YGTSS) score at the 12th week comparing with the baseline. Monte Carlo simulations were used to evaluate and optimize dosing regimens.Results: The PPK model was established to predict the concentrations of ARI and DARI. Body weight and CYP2D6 genotype were the significant covariates affecting the clearance of ARI. The DARI/ARI metabolic ratios (MRs) of AUC24h, Cmin and Cmax at the steady state of results were ultra-rapid metabolizers (UMs) > normal metabolizers (NMs) > intermediated metabolizers (IMs). MRs could be used to distinguish UMs or IMs from other patients. The best predictor of clinical efficacy for TD was the trough concentration of ARI and the cut-off point was 101.636 ng/ml.Conclusion: The pharmacokinetics of ARI and DARI in pediatric TD were significantly influenced by body weight and CYP2D6 genotype. Individualized dosing regimens were recommended for pediatric patients with TD to ensure clinical efficacy.

Objective To explore the technical research and application characteristics of deep learning in tongue-facial diagnosis. Methods Through summarizing the merits and demerits of current image processing techniques used in the traditional medical tongue and face diagnosis, the research status of deep learning in tongue image preprocessing, segmentation, and classification was analyzed and reviewed, and the algorithm was compared and verified with the real tongue and face image. Images of the face and tongue used for diagnosis in conventional medicine were systematically reviewed, from acquisition and pre-processing to segmentation, classification, algorithm comparison, result from analysis, and application. Results Deep learning improved the speed and accuracy of tongue and face diagnostic image data processing. Among them, the average intersection ratio of U-net and Seg-net models exceeded 0.98, and the segmentation speed ranged from 54 to 58 ms. Conclusion There is no unified standard for lingual-facial diagnosis objectification in terms of image acquisition conditions and image processing methods, thus further research is indispensable. It is feasible to use the images acquired by mobile in the field of medical image analysis by reducing the influence of environmental and other factors on the quality of lingual-facial diagnosis images and improving the efficiency of image processing.

Volatile aldehydes can be enriched in esophageal adenocarcinoma patients’ breath. Here, the authors reveal corresponding metabolic changes in EAC tumours, which may be caused by impaired detoxification of endogenous metabolites.

Composting is an effective way to dispose of agricultural waste; however, its application is limited in the winter and in areas with low average annual temperatures. This study screened out a composite microbial agent (CMA) including Bacillus (B.) cereus QS7 and B. pumilus QM6 that could grow at 10–15 °C and investigated the effects of the CMA as an inoculant on the physicochemical parameters and microbial communities of compost made from mushroom residue mixed with sheep manure. The results showed that CMA inoculation prolonged the days of high temperature above 60 °C. When the ratio of mushroom residue to sheep manure was at 9:1, compost increased the accumulation of nitrogen, and reduced the electrical conductivity (EC). Under this ratio, the inoculation of CMA accelerated the degradation of organic matter (OM) (decreased by 12.22%) and total organic carbon (TOC) (decreased by 8.13%) and increased the germination rate and seed germination index (GI) to 100% and 106.86, respectively. Microbial community structure analysis showed that the relative abundance of Flavobacterium was 30.62% on day 15 and was higher after CMA inoculation in the high mushroom residue condition, which was higher than that of other groups, and the relative abundance of thermophilic fungi increased. This study demonstrated that CMA improves the quality and efficiency of mushroom residue and sheep manure composting, and it provides evidence to improve the efficiency of low-temperature composting.

Abstract Background It has been known for years that the same genetic defects drive breast cancer formation, yet, the onset of breast cancer in different individuals among the same population differs greatly in their life spans with unknown mechanisms. Methods We used a MMTV-PyMT mouse model with different genetic backgrounds (FVB/NJ vs. C57BL/6J) to generate different cancer onset phenotypes, then profiled and analyzed the gene expression of three tumor stages in both Fvb.B6 and Fvb mice to explore the underlying mechanisms. Results We found that in contrast with the FVB/N-Tg (MMTV-PyMT) 634Mul mice (Fvb mice), mammary tumor initiation was significantly delayed and tumor progression was significantly suppressed in the Fvb.B6 mice (generated by crossing FVB/NJ with C57BL/6J mice). Transcriptome sequencing and analysis revealed that the differentially expressed genes were enriched in immune-related pathways. Flow cytometry analysis showed a higher proportion of matured dendritic cells in the Fvb.B6 mice. The plasma levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were significantly reduced in the Fvb.B6 mice. IL-6 also impaired the maturation of bone marrow dendritic cells (BMDCs) of the Fvb mice in vitro. Conclusion All these findings suggest that immunity levels (characterized by a reduced IL-6 level and intact DC maturation in Fvb.B6 mice) are the key factors affecting tumor onset in a murine mammary cancer model.

Dignity therapy is a personalized psychological intervention method for advanced cancer patients based on the dignity model. Dignity therapy reviews the patient's life through in-depth conversations with patients about dignity issues through interviews. The purpose is to reduce the psychological burden of patients, so that patients can open their hearts to express their true thoughts, thereby enhancing their sense of existence and dignity. And organize the content of the interview into a text and give it to the family, so as to alleviate the family's grief caused by the loss of a loved one. This article mainly reviewed the application status of dignity therapy in end-stage cancer patients at home and abroad. (尊严疗法是在尊严模型的基础上针对晚期癌症患者个性化的一种心理干预方法。尊严疗法通过访谈的形式来与患者深入的交谈相关的尊严性问题来回顾患者一生。其目的是希望减轻患者心理负担, 让患者能够敞开心扉表达自我真实想法, 从而来提升自我的存在感和尊严感。并且将访谈的内容整理成文本交给其家属, 以减缓家属因失去亲人是所产生的悲痛心理。本文主要对尊严疗法在国内外终末期癌症患者中的应用现状进行综述。)

Abstract Background Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. Methods Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. Results Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. Conclusions Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.

Background: Elective surgery is the treatment of choice for symptomatic giant hiatus hernia (GHH), and quality of life (QoL) has become an important outcome measure following surgery. The aim of this study is to review the literature assessing QoL following repair of GHH. Methodology: A systematic literature search was performed by two reviewers independently to identify original studies evaluating QoL outcomes after GHH surgery. MeSH terms such as paraoesophageal; hiatus hernia; giant hiatus hernia and quality of life were used in the initial search. Original studies in English language using validated questionnaires on humans were included. Review articles, conference abstracts and case reports and studies with duplicate data were excluded. Results: Two hundred and eight articles were identified on initial search, of which 38 studies (4404 patients) were included. Studies showed a significant heterogeneity in QoL assessment tools, surgical techniques and follow-up methods. All studies assessing both pre-operative and post-operative QoL (n = 31) reported improved QoL on follow-up after surgical repair of GHH. Improvement in QoL following GHH repair was not affected by patient age, surgical technique or the use of mesh. Recurrence of GHH after surgery may, however, adversely impact QoL. Conclusion: Surgical repair of GHH improved QoL scores in all the 38 studies. The impact of recurrence on QoL needs further assessment. The authors also recommend uniform reporting of surgical outcomes in future studies.

Temperature changes have a great impact on fish feeding, intestinal microorganisms, metabolism, and immune function. Therefore, it is necessary to develop effective methods to enhance the survival rates and growth of fish under water temperature changes. Lactic acid bacteria (LAB) are promising immunostimulatory feed additive, as demonstrated by their beneficial effects in several fish species. This study investigated the short-term effects of dietary LAB on intestinal microbiota composition and immune responses of crucian carp (Carassius auratus) when water temperature decreased from 30 ± 1°C to 18 ± 1°C. Lactococcus (L.) lactis 1,209 and L. lactis 1,242 with potential probiotics isolated from the intestine of Qinghai naked carp (Gymnocypris przewalskii) were selected as feed additives for the crucian carp feeding experiment. A total of 225 commercially available healthy crucian carp (250 ± 10 g) of similar age were kept in 30°C water for a week and then immediately transferred to 18 ± 1°C water, assigned to three dietary treatments for a 16-day feeding trial randomly: (1) HC, diets without additives (the control group); (2) HT, diets with 106 CFU/ml L. lactis 1,209; and (3) HL, with 106 CFU/ml L. lactis 1,242. Each group was set up with 3 replicates and each with 25 fish. The results showed that the mortality rate of crucian carp in HC, HT, and HL group was 50, 27, and 33%, respectively. High-throughput sequencing results displayed that the composition of the intestinal microorganism varied dynamically in response to different treatments and water temperature decrease. Among them, compared with the HC group, a higher abundance of Firmicutes and Proteobacteria, and a lower of Actinobacteria appeared in HT and HL. The cytokines heat shock protein 70 (HSP-70) in crucian carp intestinal tract significantly decreased when water temperature decreased (p < 0.05).

Head and neck squamous cell carcinoma (HNSCC) constitute approximately 4% of all cancers worldwide. In this study, we analyzed the expression profile of the long noncoding RNA (lncRNA) of 502 HNSCC patients from The Cancer Genome Atlas database. Among the differentially expressed lncRNAs between HNSCC and normal samples, LNCAROD is overexpressed in HNSCC and associated with advanced T stage and shortened overall survival. The N6‐methyladenosine (m6A) modification mediated by METTL3 and METTL14 enhanced the stability of LNCAROD in HNSCC cells. Depletion of LNCAROD attenuated cell proliferation, mobility in vitro, and tumorigenicity in vivo, whereas overexpression of LNCAROD exerted opposite effects. LNCAROD is mainly distributed in nucleus and binds with YBX1 and HSPA1A proteins. Silencing either YBX1 or HSPA1A did not affect the level of LNCAROD. However, loss of LNCAROD led to shortened half‐life of YBX1 protein. Mechanistically, LNCAROD protected YBX1 from proteasomal degradation by facilitating YBX1‐HSPA1A protein–protein interaction. Depletion of HSPA1A in LNCAROD‐overexpressing cells resulted in accelerated proteasomal degradation of YBX1 protein. Moreover, re‐expression of Flag‐YBX1 in LNCAROD‐silenced cells rescued malignant behavior of HNSCC cells. Our study indicates that LNCAROD is an oncogenic lncRNA and dysregulation of m6A modification might account for aberrant expression of LNCAROD in HNSCC. LNCAROD acts as a scaffold for the interaction between YBX1 and HSPA1A, preventing proteasomal degradation of YBX1 in HNSCC cells.

A binary copolymer water treatment agent was synthesized by using maleic anhydride and sodium allyl sulfonate as raw materials and ammonium persulfate as initiator. The scale inhibition and dispersion properties of the copolymer were studied through static experiments. The results show that the binary water treatment agent has excellent scale inhibition and dispersion performance. Moreover, the polymer is an environment-friendly agent with good application prospects.

The research results of maleic anhydride water treatment agents in the past years were summarized and analyzed, which provided reference for further research and preparation of environmental protection water treatment agents. A binary copolymer product with excellent scale inhibition and dispersion properties was synthesised using maleic anhydride and sodium allyl sulfonate as monomers. The product was characterized and its properties were investigated. It was concluded that the product has excellent scale inhibition and dispersion performance and good biodegradability. The product is an environmentally friendly water treatment agent.

The complete mitochondrial genome of Brachionus rubens was sequenced using primers design, clone culture, DNA extraction, LONG-PCR amplification, purification and clone sequencing. We found that it is composed of two circular chromosomes, designated mtDNA I (11,398 bp) and mtDNA II (12,820 bp). The gene content of the B. rubens mitochondrial genome was similar to that of the previously reported mitochondrial genome of B. plicatilis. It contained 22 tRNA genes, 2 rRNA genes and 12 protein-coding genes (PCGs). Four of the 12 PCGs had an incomplete stop codons, TA（cob, atp6, nd3）or T(cox3). The A + T content of B. rubens mitochondrial genome was apparently higher (mtDNA-I 70.2% and mtDNA II 70.4%) than that of the mitochondrial genome of B. plicatilis (mtDNA-I 63.9% and mtDNA-II 62.9%).

Abstract Profiling heterologous cell types within tumors is essential to decipher tumor microenvironment that shapes tumor progress and determines the outcome of therapeutic response. Here, we comprehensively characterized transcriptomes of 34,037 single cells obtained from 12 treatment‐naïve patients with colorectal cancer. Our comprehensive evaluation revealed attenuated B‐cell antigen presentation, distinct regulatory T‐cell clusters with different origin and novel polyfunctional tumor associated macrophages associated with CRC. Moreover, we identified expanded XCL1+ T‐cell clusters associated with tumor mutational burden high status. We further explored the underlying molecular mechanisms by profiling epigenetic landscape and inferring transcription factor motifs using single‐cell ATAC‐seq. Our dataset and analysis approaches herein provide a rich resource for further study of the impact of immune cells and translational research for human colorectal cancer.

IgA nephropathy is the most prevalent primary glomerulonephritis worldwide, with identical immunopathological characteristics caused by multiple etiologies as well as influenced by geographical and ethnical factors. To elucidate the role of immunologic and inflammatory mechanisms in the susceptibility to IgA nephropathy, we explored single nucleotide polymorphisms of related molecules in the immune pathways. We searched the PubMed database for studies that involved all gene variants of molecules in the 20 immunologic and inflammatory pathways selected from the Kyoto Encyclopedia of Genes and Genomes database. The odds ratios with their corresponding 95% confidence intervals in six genetic models (allele model, dominant model, homozygote model, heterozygote model, overdominant model, and recessive model) were summarized using fixed or random effect models. Subgroup analysis was conducted based on different ethnicities with generalized odds ratios. Heterogeneity was evaluated using the Q and I2 tests. Begg’s funnel plot and Egger’s linear regression test were used to evaluating possible publication bias among the included studies, and sensitivity analysis was used to test the stability of the overall results. A total of 45 studies met our selection criteria and eight related genetic association studies were retrieved, including 320 single-nucleotide polymorphisms from 20 candidate pathways, ranging from 2000 to 2021. A total of 28,994 healthy people versus 20,600 IgA nephropathy patients were enrolled. Upon meta-analyzed results that TGFB1 (rs1800469, rs1982073, rs1800471), IL-1B (rs1143627), IL-18 (rs1946518), and TLR1 (rs5743557) showed effect with or without ethnicity difference. And 10 variants presented stable and robust related to IgA nephropathy. This research showed that genetic variants are related to the immunologic and inflammatory effects of IgA nephropathy pathogenesis. The meta-analysis results supported the previous researches, and may help deepen the understanding of pathogenesis and explore new targets for IgA nephropathy-specific immunotherapy.

Predicting the suitable growth areas (SGAs) of WH under different environmental scenarios are important for sustainable management of water hyacinth (WH) which is more severe than ever due to increased water pollution caused by human activities. Based on an integrated method of Weight-of-Evidence (WOE) and Analytical Hierarchy Process (AHP), this study developed habitat adaptability index (HAI) to predict the SGA under four environmental scenarios using 412 WH events and 15 environmental variables in Guangdong of South China, which has significantly meteorological and hydrological characteristics of annual average (AAS), April to September (high flow season, HFS), October to March (low flow season, LFS), and December or next January (the coldest month, CMS). In each scenario, multi-classified environmental variables (i.e., topography, meteorology, socioeconomics, land cover, and urban sewage treatment) of WH events were firstly weighted by the WOE model. Then, the WOE weights were further input to AHP as data matrix for calculating the final weights which were used to analyze the impact of environmental variables on WH growth. The integrated WOE-AHP method under four scenarios performs well with the area under the curve (AUC > 0.85) of Receiver Operating Characteristic (ROC). Under different scenarios, the risk simulation of WH disaster shows the following distribution law: HFS > LFS > AAS > CMS. More than 54% of water areas in the study area is suitable for the growth of WH. WH density increased from north to south (or upstream to downstream) along rivers while the density decreased from central to both east and west wings of Guangdong province. The most WH-prone occurrence regions are located at elevation RMB 10, 000 million yuan, people > 5 million persons, air temperature between 25.4 °C and 27.7 °C, precipitation between 1575 mm and 1864 mm, and annual average evapotranspiration between 904 mm and 1,065 mm. The Pearl River Delta, Zhanjiang-Maoming regions of western Guangdong, and Teochew area of Eastern Guangdong are three major risk areas. Under the background of global warming and serious deterioration of the aquatic environment, the SGA of WH is expanding northward. Based on the location of the water system in Guangdong province, we proposed two WH management strategies for rural and urban water systems. Given macroscopic and rapid advantages of WOE-AHP in simulating WH’s SGA, this method can be applied to other areas invaded by WH, and the scenario setting and selection criteria of environmental factors can provide important reference for adopting targeted WH management measures.

Objective Sixty Pengbo semi-wool sheep ewes (approximately 1.5-years-old; 31.33±0.43 kg) were randomly assigned to two groups, either grazing (G) or dry lot feeding (D), to examine the effects of traditional daily grazing and dry lot feeding on performance and blood metabolites during the cold season in Tibetan Plateau. Methods The ewes in the G group were grazed continuously each day and housed in one shed each evening, while the ewes in the D group were housed in another shed all day. All animals were fed 400 g/d of commercial concentrate, and grass hay was available freely throughout the experimental period. Results Compared with the G group, the ewes in the D group had higher (p

Background/Aims: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. Methods: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). Results: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21–0.74; Oxford classification 0.48, 95% CI 0.28–0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23–0.92; Oxford classification 0.59, 95% CI 0.10–0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. Conclusions: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

The chemical vapor deposition technique was used to prepare the Ag doped ZnO microrods, which were located on Si substrates at two different positions. The scanning electron microscopy revealed that the samples have a clear hexagonal shape. X-ray diffraction provided information about the preferential orientation along the c-axis. The Raman analysis revealed that a new Raman mode appears at 492 cm-1 due to Ag doping. As this mode has not been reported early, it could be used as a characteristic mode of Ag doping in Raman spectrum. The red shift of the E2 (high) mode proves the existence of tensile stress in the samples. DOI: http://dx.doi.org/10.5755/j01.ms.25.3.19130

Abstract Background With the rapid development of the high throughput detection techniques, tumor-related Omics data has become an important source for studying the mechanism of tumor progression including breast cancer, one of the major malignancies worldwide. A previous study has shown that the G2 and S phase-expressed-1 (GTSE1) can act as an oncogene in several human cancers. However, its functional roles in breast cancer remain elusive. Method In this study, we analyzed breast cancer data downloaded from The Cancer Genome Atlas (TCGA) databases and other online database including the Oncomine, bc-GenExMiner and PROGgeneV2 database to identify the molecules contributing to the progression of breast cancer. The GTSE1 expression levels were investigated using qRT-PCR, immunoblotting and IHC. The biological function of GTSE1 in the growth, migration and invasion of breast cancer was examined in MDA-MB-231, MDA-MB-468 and MCF7 cell lines. The in vitro cell proliferative, migratory and invasive abilities were evaluated by MTS, colony formation and transwell assay, respectively. The role of GTSE1 in the growth and metastasis of breast cancer were revealed by in vivo investigation using BALB/c nude mice. Results We showed that the expression level of GTSE1 was upregulated in breast cancer specimens and cell lines, especially in triple negative breast cancer (TNBC) and p53 mutated breast cancer cell lines. Importantly, high GTSE1 expression was positively correlated with histological grade and poor survival. We demonstrated that GTSE1 could promote breast cancer cell growth by activating the AKT pathway and enhance metastasis by regulating the Epithelial-Mesenchymal transition (EMT) pathway. Furthermore, it could cause multidrug resistance in breast cancer cells. Interestingly, we found that GTSE1 could regulate the p53 function to alter the cell cycle distribution dependent on the mutation state of p53. Conclusion Our results reveal that GTSE1 played a key role in the progression of breast cancer, indicating that GTSE1 could serve as a novel biomarker to aid in the assessment of the prognosis of breast cancer.

Background Extracellular matrix (ECM) is remodeled during carcinogenesis. An abundant constituent of ECM is collagen. Type I collagen is secreted by fibroblasts, is important for tumor growth and epithelial‐mesenchymal transition, and may also be secreted by cancer cells. However, the role and function of cancer‐derived Type I collagen in the tumor microenvironment remains unclear. Methods We used immunohistochemistry and Western blot to detect Type I collagen expression in non‐small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma (ESCC) cell lines, respectively. We assessed the migration and adhesion capability of these cells in vivo by inhibiting Type I collagen in tumors. Relevant data were extracted from a large cohort study of The Cancer Genome Atlas to analyze messenger RNA levels. Protein expression of Type I collagen was further determined in tumor tissues of patients using tissue microarray. Results Cancer cell lines secreted Type I collagen. The molecular weight of cancer‐derived Type I collagen was different from that secreted by cancer‐associated fibroblasts and normal fibroblasts. Expression levels of COL1A1 and COL1A2 (subtypes of Type I collagen) messenger RNA in NSCLC and ESCC tumors were higher than in normal tissues, but were not associated with tumor node metastasis stages. Low expression of Type I collagen was significantly associated with poor overall survival and cancer cell differentiation. Conclusion NSCLC and ESCC cells could produce Type I collagen endogenously, revealing the potential functions of Type I collagen in cancer development. Cancer‐derived Type I collagen was associated with overall survival and cancer cell differentiation.

Purpose. Corneal endothelial cells are usually exposed to shear stress caused by the aqueous humour, which is similar to the exposure of vascular endothelial cells to shear stress caused by blood flow. However, the effect of fluid shear stress on corneal endothelial cells is still poorly understood. The purpose of this study was to explore whether the shear stress that results from the aqueous humour influences corneal endothelial cells. Methods. An in vitro model was established to generate fluid flow on cells, and the effect of fluid flow on corneal endothelial cells after exposure to two levels of shear stress for different durations was investigated. The mRNA and protein expression of corneal endothelium-related markers in rabbit corneal endothelial cells was evaluated by real-time PCR and western blotting. Results. The expression of the corneal endothelium-related markers ZO-1, N-cadherin, and Na+-K+-ATPase in rabbit corneal endothelial cells (RCECs) was upregulated at both the mRNA and protein levels after exposure to shear stress. Conclusion. This study demonstrates that RCECs respond favourably to fluid shear stress, which may contribute to the maintenance of corneal endothelial cell function. Furthermore, this study also provides a theoretical foundation for further investigating the response of human corneal endothelial cells to the shear stress caused by the aqueous humour.

The present study aimed to establish population pharmacokinetic models of latamoxef, as well as its R- and S-epimers, and generate findings to guide the individualized administration of latamoxef in pediatric patients. A total of 145 in-hospital children aged 0.08–10.58 years old were included in this study. Three population pharmacokinetic models of latamoxef and its R- and S-epimers were established. The stability and predictive ability of the final models were evaluated by utilizing goodness-of-fit plots, nonparametric bootstrapping, and normalized prediction distribution errors. The final model of total latamoxef was considered as a basis for the dosing regimen. A two-compartment model with first-order elimination best described the pharmacokinetics of total latamoxef. The population typical values of total latamoxef were as follows: central compartment distribution volume (V1) of 4.84 L, peripheral compartment distribution volume (V2) of 16.18 L, clearance (CL) of 1.00 L/h, and inter-compartmental clearance (Q) of 0.97 L/h. Moreover, R-epimer has a higher apparent volume of distribution and lower clearance than S-epimer. Body surface area (BSA) was identified as the most significant covariate to V, CL, and Q. Specific recommendations are given for dosage adjustment in pediatric patients based on BSA. This study highlights that a BSA-normalized dose of latamoxef was required when treating different bacteria to reach the therapeutic target more effectively.

Objectives Geographical disparities have been identified as a specific barrier to cancer screening and a cause of worse outcomes for patients with cancer. In the present study, our aim was to assess the influence of geographical disparities on the survival outcomes of patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT).Design Cohort study.Setting Guangzhou, China.Participants A total of 1002 adult patients with NPC (724 males and 278 females) who were classified by area of residence (rural or urban) received IMRT from 1 January 2010 to 31 December 2014, at Sun Yat-sen University Cancer Center. Following propensity score matching (PSM), 812 patients remained in the analysis.Main outcome measures We used PSM to reduce the bias of variables associated with treatment effects and outcome prediction. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariate Cox regression was used to identify independent prognostic factors.Results In the matched cohort, 812 patients remained in the analysis. Kaplan-Meier survival analysis revealed that the rural group was significantly associated with worse overall survival (OS, p

Few cases of portal vein thrombosis secondary to gastric cancer surgery have been reported. Here we report the diagnosis and management of two such cases. Case 1: Gastric carcinoma with acute hematemesis was detected by endoscopy in the gastric body of a 48-year-old woman. Histologic examination revealed signet-ring cell carcinoma with marked invasion of the vessels and nerves. Laparoscopic partial gastrectomy and Roux-en-Y gastrogastrostomy were performed. One month after surgery, imaging examination showed the formation of thrombi in the main portal vein and the right hepatic vein. Case 2: Gastric carcinoma with pyloric obstruction was clinically diagnosed in a 66-year-old woman. Laparoscopic partial gastrectomy and Billroth Roux-en-Y gastrogastrostomy were again performed. Two months after surgery, an abdominal imaging examination detected a thrombus in the right hepatic vein. Clinicians should consider portal vein thrombosis in patients with hyperthermia combined with an abnormal increase in procalcitonin.