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Abstract Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients’ quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980–September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

Abstract Background Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China. Results A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus’s adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus. Conclusions This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks.

Abstract Background The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and triglyceride-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute indicators for insulin resistance (IR). This study aimed to compare the predictive value of these indicators for 5-year mortality in critically ill patients with chronic heart failure (CHF). Methods Critically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases. The primary outcome was 5-year mortality. The relationship between the three indices and mortality risk was determined using multivariate Cox proportional hazards models, Kaplan–Meier (K‒M) analysis and restricted cubic splines analysis. A receiver operating characteristic (ROC) curve was generated to compare the ability of the three indices to predict mortality. Finally, whether the IR indices would further increase the predictive ability of the basic model including baseline variables with a significance level between survivors and non-survivors was evaluated by ROC curve. Results Altogether, 1329 patients with CHF were identified from the databases. Cox proportional hazards models indicated that the TyG index was independently associated with an elevated risk of 5-year mortality (hazard ratio [HR], 1.56; 95% confidence interval [CI] 1.29–1.9), while the TyG-BMI index and TG/HDL-C level were significantly associated with 5-year mortality, with an HR (95% CI) of 1.002 (1.000–1.003) and 1.01 (1.00–1.03), respectively. The K–M analysis revealed that the cumulative incidence of all-cause 5-year death increased with increasing quartiles of the TyG index, TyG-BMI index, or TG/HDL-C ratio. According to the ROC curve, the TyG index outperformed the TyG-BMI and TG/HDL-C ratio at predicting all-cause 5-year mortality (0.608 [0.571–0.645] vs. 0.558 [0.522–0.594] vs. 0.561 [0.524–0.598]). The effect of the TyG index on all-cause mortality was consistent across subgroups, with no significant interaction with randomized factors. Furthermore, adding the TyG index to the basic model for 5-year mortality improved its predictive ability (area under the curve, 0.762 for the basic model vs. 0.769 for the basic model + TyG index); however, the difference was not statistically significant. Conclusion As continuous variables, all three indices were significantly associated with 5-year mortality risk in critically ill patients with CHF. Although these IR indices did not improve the predictive power of the basic model in patients with CHF, the TyG index appears to be the most promising index (vs. TyG-BMI and TG/HDL-C ratio) for prevention and risk stratification in critically ill patients with CHF.

Abstract Aims The study aims to provide comprehensive evidence for the selection of agents in type 2 diabetes mellitus (T2DM) patients with cardiovascular risk and summarize the lasted evidence for the cardiovascular effects of sodium glucose cotransporter‐2 inhibitor (SGLT2i) in patients with heart failure (HF). Methods and results Several online databases were searched. All studies that explored the cardiovascular effects of SGLT2i or glucagon‐like peptide 1 receptor agonist (GLP1‐RA) were screened and reviewed. A total of 38 studies were included. Compared with GLP1‐RA, the use of SGLT2i significantly reduced the risk of cardiovascular death [risk ratio (RR) = 0.59; 95% confidence interval (CI), 0.44–0.58], hospitalization of heart failure (HHF) (RR = 0.77; 95% CI, 0.74–0.80), death from any cause (RR = 0.64; 95% CI, 0.60–0.68), and myocardial infarction (MI) (RR = 0.81; 95% CI, 0.76–0.87). However, SGLT2i significantly increased the risk of stroke (RR = 1.10; 95% CI, 1.04–1.17). Compared with the control group, SGLT2i treatment reduced the risk of cardiovascular death by 14% (RR = 0.86; 95% CI, 0.79–0.94), HHF by 25%, and death from any cause by 9% in patients with HF, regardless of diabetes status. Conclusions SGLT2i is associated with a lower risk of cardiovascular death, HHF, death from any cause, and MI in patients with T2DM compared with GLP1‐RA. In addition, SGLT2i brought more benefits with respect to the effects of cardiovascular death, HHF, and death from any cause in patients with HF, regardless of diabetes status.

A novel type of tailless FBG smart bolt with good performance is developed. Owe to the innovative design of an integrated FBG sensor comprising a strain measured FBG and a temperature-compensated FBG, the tailless FBG smart bolt serves the purpose of torque monitoring or bolt looseness monitoring. We use a theoretical approach to establish the linear correlation between the applied torque and the central wavelength of the tailless FBG smart bolt. Additionally, a newly designed M24 bolt with a nominal strength has been integrated as a crucial component of the tailless FBG smart bolt. To enable the experimental study, the tailless FBG smart bolt is newly designed, fabricated and tested. The experimental results show a strong linear correlation between the applied torque and the central wavelength of the tailless FBG smart bolt, showing good agreement with the theory.

Wastewater treatment plants produce large amounts of sludge requiring stabilization before safe disposal. Traditional biological stabilization approaches are cost-effective but generally require either an extended retention time (10–40 days), or elevated temperatures (40–80 °C) for effective pathogens inactivation. This study overcomes these limitations via a novel acidic aerobic digestion process, leveraging an acid-tolerant ammonia-oxidizing bacterium (AOB) Candidatus Nitrosoglobus. To retain this novel but slowly growing AOB, we proposed the first-ever application of a classical wastewater configuration—moving bed biofilm reactor (MBBR)—for sludge treatment. The AOB in biofilm maintains acidic pH and high nitrite levels in sludge, generating free nitrous acid in situ to expedite sludge stabilization. This process was tested in two laboratory-scale aerobic digesters processing full-scale anaerobically digested sludge. At an ambient temperature of 20 °C, pathogens were reduced to levels well below the threshold specified for the highest stabilization level (Class A), within a retention time of 3.5 days. A high volatile solids reduction of 27.4 ± 5.2% was achieved. Through drastically accelerating stabilization and enhancing reduction, this process substantially saves capital and operational costs for sludge disposal.

Chemicals are commonly dosed in sewer systems to reduce the emission of hydrogen sulfide (H2S) and methane (CH4), incurring high costs and environmental concerns. Nitrite dosing is a promising approach as nitrite can be produced from urine wastewater, which is a feasible integrated water management strategy. However, nitrite dosing usually requires strict conditions, e.g., relatively high nitrite concentration (e.g., ∼200 mg N/L) and acidic environment, to inhibit microorganisms. In contrast to “microbial inhibition”, this study proposes “microbial utilization” concept, i.e., utilizing nitrite as a substrate for H2S and CH4 consumption in sewer. In a laboratory-scale sewer reactor, nitrite at a relatively low concentrations of 25–48 mg N/L was continuously dosed. Two nitrite-dependent microbial utilization processes, i.e., nitrite-dependent anaerobic methane oxidation (n-DAMO) and microbial sulfide oxidation, successfully occurred in conjunction with nitrite reduction. The occurrence of both processes achieved a 58 % reduction in dissolved methane and over 90 % sulfide removal in the sewer reactor, with microbial activities measured as 15.6 mg CH4/(L·h) and 29.4 mg S/(L·h), respectively. High copy numbers of n-DAMO bacteria and sulfide-oxidizing bacteria (SOB) were detected in both sewer biofilms and sediments. Mechanism analysis confirmed that the dosed nitrite at a relatively low level did not cause the inhibition of sulfidogenic process due to the downward migration of activity zones in sewer sediments. Therefore, the proposed “microbial utilization” concept offers a new alternative for simultaneous removal of sulfide and methane in sewers.

ObjectiveThis paper aims to examine the gendered differences in the subjective wellbeing of older adults and underlying determinant factors which contribute to these differences in China where the unique social and cultural systems, the consequent concept of filial piety and the perceptions towards different living arrangements in later life provide an excellent laboratory for studying the topic.MethodsHierarchical linear models are employed to analyze the impacts of household structure and built environment on the subjective wellbeing of older adults based on a survey conducted in Nanjing in 2021.ResultsThere are significant gender differences in the subjective wellbeing of older adults, with older women reporting higher levels of subjective wellbeing (4.95 vs.4.69). Gender differences also exist in how the built environment affects the subjective wellbeing of older adults, with a greater impact on older adult women (33.68% vs. 28.50%). Household structure impacts the subjective wellbeing of older adults through the division of housework and the company of family members.ConclusionThere are three major mechanisms through which gender affects the subjective wellbeing of older adults, including structural mechanisms, socio-cultural mechanisms, and physiological mechanisms. Targeted environmental interventions and urban planning policies are recommended to promote the subjective wellbeing of older adults.

Circular RNA (circRNA) has been widely studied as a competitive endogenous RNA targeting microRNA (miRNA)/messenger RNA to regulate cancer progression. However, the regulatory mechanism of circ_0023179 in non-small cell lung cancer (NSCLC) remains unclear. The expression levels of circ_0023179, miR-615-5p and Cadherin 3 (CDH3) in NSCLC were detected using quantitative real-time polymerase chain reaction. The stability of circ_0023179 was verified using ribonuclease R enzyme, Actinomycin D and agarose gel electrophoresis. Colony formation and thymidine analog 5-ethynyl-2’-deoxyuridine assays were performed to examine proliferation changes in NSCLC cells. Western blot was used to assess the levels of CDH3 and epithelial-mesenchymal transition (EMT)–related marker proteins to evaluate EMT. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to explore the potential mechanisms of circ_0023179 in regulating NSCLC progression. Finally, the effects of circ_0023179 on NSCLC tumour growth in vivo were explored using a nude mouse subcutaneous tumour model. The results showed that the expression of circ_0023179 was remarkably higher in NSCLC tissues and cells, and it had a significant effect on NSCLC cell proliferation. Additionally, the knockdown of circ_0023179 significantly inhibited tumour growth in NSCLC mice. Mechanistically, circ_0023179 alleviated its inhibition of downstream CDH3 through the sponge-like adsorption of miR-615-5p. The downregulation of miR-615-5p and the upregulation of CDH3 mitigated the inhibitory effect of silencing circ_0023179 on NSCLC cell proliferation. In conclusion, silencing circ_0023179 inhibited NSCLC cell proliferation by targeting the miR-615-5p/CDH3 axis involved in NSCLC progression.

Abstract Exposure of the eyes to blue light can induce the overproduction of reactive oxygen species (ROS) in the retina and retinal pigment epithelium (RPE) cells, potentially leading to pathological damage of age‐related macular degeneration (AMD). While the melanin in RPE cells absorbs blue light and prevents ROS accumulation, the loss and dysfunction of RPE melanin due to age‐related changes may contribute to photooxidation toxicity. Herein, a novel approach utilizing a polydopamine‐replenishing strategy via a single‐dose intravitreal (IVT) injection is presented to protect retinal cells against blue light‐induced phototoxicity. To investigate the effects of overexposure to blue light on retinal cells, a blue light exposure Nrf2‐deficient mouse model is created, which is susceptible to light‐induced retinal lesions. After blue light irradiation, retina degeneration and an overproduction of ROS are observed. The polydopamine‐replenishing strategy demonstrated effectiveness in maintaining retinal structural integrity and preventing retina degeneration by reducing ROS production in retinal cells and limiting the phototoxicity of blue light exposure. These findings highlight the potential of polydopamine as a simple and effective replenishment for providing photoprotection against high‐energy blue light exposure.

Picrasma quassioides (D.Don) Benn is a member of the Simaroubaceae family, which has a long history of medicinal use in China, the composition of compounds is complex, mainly including alkaloids, lignin, triterpenoids, and other compounds. As a traditional Chinese medicine, P. quassioides has pharmacological effects such as anti-inflammatory, antipyretic, antiviral, blood pressure lowering and anticancer. Scholars at home and abroad have been studying P. quassioides for about 50 years. In the present review, the research status of the chemical composition, pharmacological activity and pharmacokinetics of P. quassioides was provided, as a reference for further developing the value of P. quassioides.

Abstract Bach2 was initially discovered in B cells, where it was revealed to control the transcription involved in cell differentiation. Bach2 is intimately connected to CD8 + T lymphocytes in various differentiation states and subsets according to recent findings. Bach2 can regulate primitive T cells, stimulate the development and differentiation of memory CD8 + T cells, inhibit the differentiation of effector CD8 + T cells, and play a significant role in the exhaustion of CD8 + T cells. The appearance and development of diseases are tightly linked to irregular CD8 + T cell differentiation and function. Accordingly, Bach2 offers novel approaches and possible targets for the clinical treatment of associated disorders based on research on these pathways. Here, we summarize the role of Bach2 in the function and differentiation of CD8 + T cells and its potential clinical applications.

Technological innovation represents the core driving force for the green development of resource-based enterprises. How to effectively promote enterprises’ technological innovation has received considerable attention in academia and practice. However, most of existing studies have been focused on the influence of industrial level or organizational level, the impact of leadership has received little attention. Therefore, this study explores the impact of environmental leadership, which focuses on environmental protection and sustainable development, on technological innovation. Using Stata 18 software, this study analyzes 170 resource-based enterprises listed on the Shenzhen and Shanghai A-share stock markets, for the time periods spanning from 2013 to 2022. The results indicate a positive impact of environmental leadership on technological innovation, with green investment mediating the relationship between environmental leadership and technological innovation. However, the moderating effect of government subsidies between environmental leadership and green investment is not significant. Our findings offer a better understanding of technological innovation in resource-based enterprises by considering the influence factors from both internal and external pespectives, especially the critical role of leader. Therefore, this study contributes to the literature on leadership theory and technological innovation theory.

Aim: In the global phase 3 POETYK PSO-1 and PSO-2 trials, significantly greater proportions of deucravacitinib-treated patients met the coprimary endpoints (PASI 75, sPGA 0/1) at Week 16 versus placebo or apremilast-treated patients. This analysis evaluated onset of action and maintenance of response in patients randomized to deucravacitinib and placebo only. Methods: Adults with moderate to severe plaque psoriasis at baseline were randomized 1:2:1 to oral placebo, deucravacitinib, or apremilast. Onset of action was determined through changes from baseline in mean PASI, BSA, BSA × sPGA, and DLQI. Maintenance of response was assessed using PASI 75, PASI 90, PASI 100, sPGA 0/1, and sPGA 0 response rates through Week 52 in patients who were treated continuously with deucravacitinib, crossed over from placebo to deucravacitinib at Week 16, or received deucravacitinib and achieved PASI 75 by Week 24. Results: Deucravacitinib showed significantly higher increases in mean percent change from baseline in PASI versus placebo by Week 1. Significant improvement versus placebo was observed in all other efficacy measures by Week 8. Efficacy with deucravacitinib was maintained through Week 52. Conclusion: Deucravacitinib displayed efficacy as early as 1 week and clinical responses were maintained over 52 weeks in patients with moderate to severe plaque psoriasis.

AbstractBackground: Clinical studies have shown that the onset and exacerbation of chronic obstructive pulmonary disease (COPD) are related to obesity and dietary behaviours, but the genetic relationship between them is not clear.Aims: To investigate the relationship between the genetic determinants of obesity, dietary habits (alcohol consumption, intake of sweets, salt intake) and COPD.Methods: Exposure and outcome datasets were obtained from the IEU Open GWAS project. The exposure dataset includes dietary habits (Salt added to food, Sweets intake, Alcohol consumption), obesity level (represented by body mass index (BMI) and body fat percentage (BFP) data sets.). The outcome dataset includes COPD and acute COPD admissions. The collected data were imported into the RStudio software and conducted Mendelian randomisation analysis. Additionally, heterogeneity and horizontal pleiotropy tests were conducted on the data to ensure the veracity of the results.Results: The results showed that BMI was positively correlated with the risk of acute COPD admission (OR = 1.74, 95% CI 1.39–2.18) and COPD (OR = 1.81, 95%CI 1.41–2.33). In addition, BFP was also a risk factor for COPD (OR = 1.98, 95% CI 1.42–2.77) and acute exacerbation of COPD admission (OR = 1.99, 95%CI 1.43–2.77). The increase of salt, sugar and alcohol consumption will not increase the risk of COPD and the risk of hospitalisation due to COPD.Conclusion: Therefore, we should strengthen the guidance of diet and living habits of obese patients. For patients with heavier weight and higher body fat rate, they should be instructed to lose weight and fat to prevent the occurrence of COPD. For obese patients with COPD, more attention should be paid to prevent the occurrence of acute exacerbation of COPD in advance.

Equine influenza (EI) is a severe infectious disease that causes huge economic losses to the horse industry. Spatial epidemiology technology can explore the spatiotemporal distribution characteristics and occurrence risks of infectious diseases, it has played an important role in the prevention and control of major infectious diseases in humans and animals. For the first time, this study conducted a systematic analysis of the spatiotemporal distribution of EI using SaTScan software and investigated the important environmental variables and suitable areas for EI occurrence using the Maxent model. A total of 517 occurrences of EI from 2005 to 2022 were evaluated, and 14 significant spatiotemporal clusters were identified. Furthermore, a Maxent model was successfully established with high prediction accuracy (AUC = 0.920 ± 0.008). The results indicated that annual average ultraviolet radiation, horse density, and precipitation of the coldest quarter were the three most important environmental variables affecting EI occurrence. The suitable areas for EI occurrence are widely distributed across all continents, especially in Asia (India, Mongolia, and China) and the Americas (Brazil, Uruguay, USA, and Mexico). In the future, these suitable areas will expand and move eastward. The largest expansion is predicted under SSP126 scenarios, while the opposite trend will be observed under SSP585 scenarios. This study presents the spatial epidemiological characteristics of EI for the first time. The results could provide valuable scientific insights that can effectively inform prevention and control strategies in regions at risk of EI worldwide.

Abstract Objective The purpose of this study was to investigate the predictive value of mean platelet volume (MPV) and platelet count (PC) in branch atheromatous disease (BAD). Methods This retrospective study included 216 patients with BAD‐stroke within 48 h of symptom onset. These patients were divided into good and poor prognosis groups according to their 3‐month modified Rankin scale scores after discharge. Multiple logistic regression analysis was used to evaluate independent predictors of poor prognosis in BAD‐stroke patients. Receiver‐operating characteristic (ROC) analysis was used to estimate the predictive value of MPV and PC on BAD‐stroke. Results Our research showed that a higher MPV (aOR, 2.926; 95% CI, 2.040–4.196; p

Canine circovirus (CanineCV), which is a new mammalian circovirus first reported in the United States in 2012, mainly causes diarrhea and vomiting in dogs. As CanineCV evolves and new subtypes emerge, there is an urgent need for new detection technologies to improve the sensitivity and detection rates of viruses in complex scenarios. A chip digital PCR(cdPCR) assay was established for the detection of CanineCV in this study. The results showed good reproducibility, specificity and a linear relationship; the minimum detection limit of CanineCV by cdPCR was 6.62 copies/μL, which is 10 times more sensitive than quantitative real-time PCR (qPCR). The qPCR-positive detection rate was 1 %, while CanineCV cdPCR (2.1 %) exhibited a greater positive detection rate. Fifteen complete genomes were sequenced and subdivided into CanineCV-1 and CanineCV-3. In conclusion, we developed a rapid, reliable, and specific cdPCR method for screening and monitoring canine CV.

The aim of this study was to investigate whether the therapeutic effect of theabrownin extracted from Qingzhuan tea (QTB) on metabolic dysfunction-associated steatosis liver disease (MASLD) is related to the regulation of intestinal microbiota and its metabolite short-chain fatty acids (SCFAs). Mice were divided into four groups and received normal diet (ND), high-fat diet (HFD) and HFD+QTB (180, 360 mg/kg) for 8 weeks. The results showed that QTB significantly reduced the body weight of HFD mice, ameliorated liver lipid and dyslipidemia, and increased the level of intestinal SCFAs in HFD mice. The results of 16 S rRNA showed that the relative abundance of Bacteroides, Blautia and Lachnoclostridium and their main metabolites acetate and propionate were significantly increased after QTB intervention. The relative abundance of Colidextribacter, Faecalibaculum and Lactobacillus was significantly reduced. QTB can also significantly up-regulate the expression of ATGL, PPARα, FFAR2 and FFAR3, and inhibit the expression of LXRα, SREBP-1c, FAS and HMGCR genes. This makes it possible to act as a prebiotic to prevent MASLD.

Abstract Industrial CO2 electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis, but its performance is greatly limited by mass transport at high current density. In this work, an ion‐polymer‐modified gas‐diffusion electrode is used to tackle this proton limit. It is found that gas diffusion electrode‐Nafion shows an impressive performance of 75.2% Faradaic efficiency in multicarbon products at an industrial current density of 1.16 A/cm2. Significantly, in‐depth electrochemical characterizations combined with in situ Raman have been used to determine the full workflow of protons, and it is found that HCO3− acts as a proton pool near the reaction environment, and HCO3− and H3O+ are local proton donors that interact with the proton shuttle −SO3− from Nafion. With rich proton hopping sites that decrease the activation energy, a “Grotthuss” mechanism for proton transport in the above system has been identified rather than the “Vehicle” mechanism with a higher energy barrier. Therefore, this work could be very useful in terms of the achievement of industrial CO2 reduction fundamentally and practically.

Abstract Platinum resistance represents a major barrier to the survival of patients with ovarian cancer (OC). Cdc2‐like kinase 2 (CLK2) is a major protein kinase associated with oncogenic phenotype and development in some solid tumors. However, the exact role and underlying mechanism of CLK2 in the progression of OC is currently unknown. Using microarray gene expression profiling and immunostaining on OC tissues, we found that CLK2 was upregulated in OC tissues and was associated with a short platinum‐free interval in patients. Functional assays showed that CLK2 protected OC cells from platinum‐induced apoptosis and allowed tumor xenografts to be more resistant to platinum. Mechanistically, CLK2 phosphorylated breast cancer gene 1 (BRCA1) at serine 1423 (Ser1423) to enhance DNA damage repair, resulting in platinum resistance in OC cells. Meanwhile, in OC cells treated with platinum, p38 stabilized CLK2 protein through phosphorylating at threonine 343 of CLK2. Consequently, the combination of CLK2 and poly ADP‐ribose polymerase inhibitors achieved synergistic lethal effect to overcome platinum resistance in patient‐derived xenografts, especially those with wild‐type BRCA1. These findings provide evidence for a potential strategy to overcome platinum resistance in OC patients by targeting CLK2.

Several vascular embolization materials are commonly used in clinical practice, however, having application defects of varying degrees, such as poor intraoperative imaging and easy recanalization of embolized blood vessels, they are challenging for application during Transcatheter arterial embolization (TAE). Thus, an intraoperative visible vascular embolization material with good embolization effect and biocompatibility can improve transcatheter arterial embolization clinical efficacy to some extent. Our study aimed to synthesize a novel vascular embolization material that can achieve complete embolization of arterial trunks and peripheral vessels, namely poly (N-isopropyl acrylamide)-co-acrylic acid nanogel (NIPAM-co-AA). Iohexol 200 mg/mL was co-assembled with 7 wt% NIPAM-co-AA nanogel to create an intelligent thermosensitive radiopaque nanogel (INCA), which achieves a good intraoperative imaging effect and is convenient for transcatheter arterial bolus injection due to its good fluidity and temperature-sensitive sol-gel phase transition. The normal rabbit kidney embolism model further confirmed that INCA could effectively use Digital subtraction angiography (DSA) to achieve intraoperative imaging, and real-time monitoring of the embolization process could avoid mis-embolization and leakage. Meanwhile, in a 42-day study, INCA demonstrated an excellent embolization effect on the right renal artery of New Zealand white rabbits, with no vascular recanalization and ischemic necrosis and calcification remaining. As a result, this radiopaque thermosensitive nanogel has the potential to be an intelligent thermosensitive medical vascular embolization material, providing dual benefits in TAE intraoperative imaging and long-term postoperative embolization while effectively addressing the shortcomings and challenges of commonly used clinical vascular embolization agents.

Abstract Various X-ray imaging technologies like computed tomography (CT) and digital subtraction angiography (DSA) are widely used in transcatheter arterial embolization (TAE) therapy for treating hepatocellular cancer (HCC) patients. Although they display high-contrast imaging, they have a few disadvantages, such as complex operation and exposure to ionizing radiation. Thus, ultrasound (US) imaging plays an important role in medical diagnosis because of its advantages, like simple and fast operation, no ionizing radiation exposure, and accurate real-time imaging. Subsequently, Poly N-isopropylacrylamide-co-2,2,3,4,4,4-Hexafluorobutyl methacrylate (PNF) nanogels were synthesized for stabilizing TGFPE, the Pickering emulsions of 2H, 3H-decafluoropentane (HDFP). These emulsions displayed dual abilities of thermosensitive sol–gel transition and long-term US imaging in vitro. Thus, it was concluded that these emulsions could achieve vascular embolization and long-term US imaging in vivo as per the TAE animal model results. The emulsion droplets’ flow and accumulation were visualized under the US imaging guidance. In summary, the Pickering emulsions have the potential to be used as US-guided embolization material for mediating TAE surgeries.

304 stainless steel (304SS) and polyethylene terephthalate (PET) were lapped joined by laser conduction welding using a semiconductor laser with a flat-top thermal distribution. Experimental investigation and numerical simulation were conducted to analyze the weld morphology, pores distribution, interfacial microstructure, temperature field, joint strength and fracture behavior of the laser dissimilar joints. Because of the uniform thermal distribution of the laser, the decomposition of the PET base material was well controlled with pore-free joints obtaining at the welding speed over 25 mm/s. Besides, a compound layer was generated at the interface between 304SS and PET with its thickness decreased when the welding speed increased. Chemical reactions and mechanical anchoring were both observed at the interface suggesting a dual joining mechanism. The joint fracture load first increased then decreased with the increased welding speed. Besides, a ductile to brittle failure transition was clearly seen. The underlying mechanism was also discussed.

Abstract Introduction Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening skin disease. The global Effisayil 1 study investigated the efficacy and safety of spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, in patients experiencing GPP flare. This analysis aimed to explore the efficacy and safety of spesolimab in the Chinese subgroup of Effisayil 1. Methods Effisayil 1 was a multicenter, randomized, double-blind, placebo-controlled phase II study. Eligible patients with a GPP flare were randomly assigned (2:1) to receive a single intravenous dose of spesolimab (900 mg) or placebo on day 1. On day 8, patients who had persistent symptoms that met a predefined criterion could receive open-label spesolimab. After day 8, patients with recurrent flares following clinical response could receive rescue treatment with open-label spesolimab. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation sub-score of 0 at week 1. The key secondary end point was a GPPGA total score of 0 or 1 at week 1. Results Eleven Chinese patients were randomized, with five patients receiving spesolimab and six receiving placebo. At week 1, 60.0% (3/5) of patients in the spesolimab group and 16.7% (1/6) of patients in the placebo group achieved a GPPGA pustulation sub-score of 0 (risk difference 43.3%; 95% CI –22.6, 86.2); 60.0% and 16.7% of patients in the spesolimab and placebo group, respectively, achieved a GPPGA total score 0 or 1 (risk difference 43.3%; 95% CI –22.6, 86.2). Overall, four patients in each group of the spesolimab and the placebo groups reported at least one adverse event (AE) by week 1, with two and three reporting drug-related AEs, respectively. One patient reported a serious AE that was not considered to be drug related. No death occurred during the study period. Conclusion In the Chinese subgroup of the Effisayil 1 study, more patients receiving spesolimab experienced lesion clearance than those on placebo at week 1, with an acceptable safety profile that was consistent with the global study population. Trial Registration NCT03782792.

Abstract Background An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored. Methods A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies—namely RNA-sequencing, western blotting, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay—were used to reveal the mechanisms of MYBL2 in the OVC microenvironment. Results We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance. Conclusions The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy.

Abstract Integrated urban water management is a well-accepted concept for managing urban water. It requires efficient and integrated technological solutions that enable system-wide gains via a whole-of-system approach. Here, we create a solid link between the manufacturing of an iron salt, its application in an urban water system, and high-quality bioenergy recovery from wastewater. An iron-oxidising electrochemical cell is used to remove CO2 (also H2S and NH3) from biogas, thus achieving biogas upgrading, and simultaneously producing FeCO3. The subsequent dose of the electrochemically produced FeCO3 to wastewater and sludge removes sulfide and phosphate, and enhances sludge settleability and dewaterability, with comparable or superior performance compared to the imported and hazardous iron salts it substitutes (FeCl2, and FeCl3). The process enables water utilities to establish a self-reliant and more secure supply chain to meet its demand for iron salts, at lower economic and environmental costs, and simultaneously achieve recovery of high-quality bioenergy.

The third-generation aromatase inhibitors (AIs), represented by letrozole, anastrozole, and exemestane, have been used as a standard first-line adjuvant therapy for postmenopausal breast cancer patients with positive hormone receptor. However, their safety in the real world has not been systematically analyzed. We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate adverse event (AE) profiles of the three AIs, covering the period from Q1 2004 to Q3 2023. The time-to-event onset profiles and cumulative incidence were analyzed by Weibull shape parameter test and Kaplan–Meier method, respectively. The disproportionality analysis was utilized to assess drug toxicity risk. Based on the FAERS database, 18,035, 8242, and 7011 reports listing letrozole, anastrozole, and exemestane as primary suspected drugs were extracted, respectively. AEs associated with anastrozole displayed the latest onset (p < 0.0001); meanwhile, WSP test showed that all three AIs had early failure-type profiles. At the preferred term level, we acquired 95, 59, and 42 significant signals associated with letrozole, anastrozole, and exemestane, which involved 18, 13, and 15 system organ classes, respectively. The three AIs all reported that their strongest AE signal was trigger finger. Neutropenia was the most frequent AE for letrozole, while the highest occurrences of anastrozole and exemestane were arthralgia. We also found that interstitial lung disease, a rare but serious AE, showed strong signal intensity in all three AIs. Additionally, letrozole was also associated with lots of other rare but serious AEs in hematologic, respiratory, and hepatic systems, which were not recorded in the instructions. Our analysis of safety warning signals of the third-generation AIs from the FAERS database provided reference for clinical safe and rational drug use.

PROTACs, proteolysis targeting chimeras, are bifunctional molecules inducing protein degradation through a unique proximity-based mode of action. While offering several advantages unachievable by classical drugs, PROTACs have unfavorable physicochemical properties that pose challenges in application and formulation. In this study, we show the solubility enhancement of two PROTACs, ARV-110 and SelDeg51, using Poly(vinyl alcohol). Hereby, we apply a three-fluid nozzle spray drying set-up to generate an amorphous solid dispersion with a 30% w/w drug loading with the respective PROTACs and the hydrophilic polymer. Dissolution enhancement was achieved and demonstrated for t = 0 and t = 4 weeks at 5 °C using a phosphate buffer with a pH of 6.8. A pH shift study on ARV-110-PVA is shown, covering transfer from simulated gastric fluid (SGF) at pH 2.0 to fasted-state simulated intestinal fluid (FaSSIF) at pH 6.5. Additionally, activity studies and binding assays of the pure SelDeg51 versus the spray-dried SelDeg51-PVA indicate no difference between both samples. Our results show how modern enabling formulation technologies can partially alleviate challenging physicochemical properties, such as the poor solubility of increasingly large ‘small’ molecules.

The accurate identification of different restoration stages of degraded alpine meadow patches is essential to effectively curb the deterioration trend of ‘Heitutan’ (areas of severely degraded alpine meadows in western China). In this study, hyperspectral imaging (HSI) and machine learning techniques were used to develop a method for accurately distinguishing the different restoration stages of alpine meadow patches. First, hyperspectral images representing the four restoration stages of degraded alpine meadow patches were collected, and spectral reflectance, vegetation indexes (VIs), color features (CFs), and texture features (TFs) were extracted. Secondly, valid features were selected by competitive adaptive reweighted sampling (CARS), ReliefF, recursive feature elimination (RFE), and F-test algorithms. Finally, four machine learning models, including the support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and extreme gradient boosting (XGBoost), were constructed. The results demonstrated that the SVM model based on the optimal wavelengths (OWs) and prominent VIs achieved the best value of accuracy (0.9320), precision (0.9369), recall (0.9308), and F1 score (0.9299). In addition, the models that combine multiple sets of preferred features showed a significant performance improvement over the models that relied only on a single set of preferred features. Overall, the method combined with HSI and machine learning technology showed excellent reliability and effectiveness in identifying the restoration stages of meadow patches, and provided an effective reference for the formulation of grassland degradation management measures.

Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wide-ranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment methods. Acquiring an in-depth understanding of genetic alterations implicated in the development of NB is essential for creating safer and more efficient therapies for this severe condition. Several molecular signatures are being studied as potential targets for developing new treatments for NB patients. In this article, we have examined the molecular factors and genetic irregularities, including those within insulin gene enhancer binding protein 1 (ISL1), dihydropyrimidinase-like 3 (DPYSL3), receptor tyrosine kinase-like orphan receptor 1 (ROR1) and murine double minute 2-tumor protein 53 (MDM2-P53) that play an essential role in the development of NB. A thorough summary of the molecular targeted treatments currently being studied in pre-clinical and clinical trials has been described. Recent studies of immunotherapeutic agents used in NB are also studied in this article. Moreover, we explore potential future directions to discover new targets and treatments to enhance existing therapies and ultimately improve treatment outcomes and survival rates for NB patients.

Quality of life impairment in dermatology patients and severity of psoriasis are quantified by the Dermatology Life Quality Index (DLQI) and the Psoriasis Area and Severity Index (PASI), respectively. The aim of this study is to compare the correlation between PASI and DLQI in patients from different geographical areas and to identify predictors of high DLQI across geographical regions. Correlations between PASI and DLQI were evaluated using Spearman’s rank correlation tests and quantile regression. The study included 1,158 patients with psoriasis, with a median (interquartile range) PASI and DLQI of 6.0 (3.0–12.0) and 8.0 (4.0–15.0), respectively. Correlations were demonstrated between PASI and DLQI, both overall and stratified by geographical region. Quantile (median) regression yielded coefficients of 0.75 (95% confidence interval (95% CI) 0.62, 0.88) for Switzerland, 0.50 (95% CI 0.42, 0.58) for Latin America, 0.34 (95% CI 0.16, 0.51) for Asia, and 0.31 (95% CI 0.08, 0.53) for the USA. Current age, age at diagnosis, sex, body mass index, and psoriasis arthritis affected DLQI in Latin America, while education had an impact among patients treated in Switzerland. Few countries were included within each continent; hence, more data from different countries are necessary for generalizability. The study showed correlations between PASI and DLQI among patients in all included geographical regions. The patients’ characteristics affecting DLQI vary worldwide.

Background: Feeding on a high-fat diet (HFD) results in obesity and chronic inflammation, which may have long-term effects on neuroinflammation and hippocampal injury. Theabrownin, a biologically active compound derived from the microbial fermentation of Qingzhuan dark tea, exhibits anti-inflammatory properties and lipid-lowering effects. Nevertheless, its potential in neuroprotection has yet to be investigated. Consequently, this study aims to investigate the neuroprotective effects of Theabrownin extracted from Qingzhuan dark tea, as well as its potential therapeutic mechanisms. Methods: Male C57 mice were subjected to an 8-week HFD to induce obesity, followed by oral administration of Theabrownin from Qingzhuan dark tea. Lipid levels were detected by Elisa kit, hippocampal morphological damage was evaluated by HE and Nissl staining, and the expression levels of GFAP, IBA1, NLRP3, MARK4, and BAX in the hippocampus were detected by immunofluorescence (IF), and protein expression levels of NLRP3, MARK4, PSD95, SYN1, SYP, and Bcl-2 were detected by Western Blot (WB). Results: Theabrownin treatment from Qingzhuan dark tea prevents alterations in body weight and lipid levels in HFD-fed mice. Furthermore, Theabrownin decreased hippocampal morphological damage and reduced the activation of astrocytes and microglia in HFD-fed mice. Moreover, Theabrownin decreased the expression of MARK4 and NLRP3 in HFD-fed mice. Besides, Theabrownin elevated the expression of PSD95, SYN1, and SYP in HFD-fed obese mice. Finally, Theabrownin prevented neuronal apoptosis, reduced the expression of BAX, and increased the expression of Bcl-2 in HFD-fed obese mice. Conclusions: In summary, our current study presents the first demonstration of the effective protective effect of Theabrownin from Qingzhuan dark tea against HFD-induced hippocampal damage in obese mice. This protection may result from the regulation of the MARK4/NLRP3 signaling pathway, subsequently inhibiting neuroinflammation, synaptic plasticity, and neuronal apoptosis.

Abstracts: Background: Patients with psoriasis may experience an exacerbation in symptoms following COVID-19 infection. After abandoning 'zero COVID' strategies, China experienced a surge of Omicron infections. Objectives: We aimed to investigate psoriasis exacerbation in psoriatic patients with COVID-19, following treatment with three different biologics, adalimumab, secukinumab, and ixekizumab. Methods: We performed a prospective study (n = 209) at our hospital between November 01, 2022, and February 15, 2023. We defined △ PASI as post-COVID-19 PASI minus pre-COVID-19 PASI. Two endpoints were set in this study. △ PASI >0 was defined as exacerbation of psoriasis after infection. △ PASI >3 was defined as a severe exacerbation of psoriasis symptoms after infection. In addition, serum OAS1, OAS2, and OAS3 were also assessed. Results: Results showed that the severity of psoriasis can worsen after COVID-19 infection, and a smaller proportion of patients taking biologics developed worsening psoriasis compared to those not using biologics; however, only the patients taking ixekizumab demonstrated a statistically significant difference (p

Abstract Mesenchymal stem cells (MSCs) have emerged as a promising alternative treatment for liver disease due to their roles in regeneration, fibrosis inhibition, and immunoregulation. Mitochondria are crucial in maintaining hepatocyte integrity and function. Mitochondrial dysfunction, such as impaired synthesis of adenosine triphosphate (ATP), decreased activity of respiratory chain complexes, and altered mitochondrial dynamics, is observed in most liver diseases. Accumulating evidence has substantiated that the therapeutic potential of MSCs is mediated not only through their cell replacement and paracrine effects but also through their regulation of mitochondrial dysfunction in liver disease. Here, we comprehensively review the involvement of mitochondrial dysfunction in the development of liver disease and how MSCs can target mitochondrial dysfunction. We also discuss recent advances in a novel method that modifies MSCs to enhance their functions in liver disease. A full understanding of MSC restoration of mitochondrial function and the underlying mechanisms will provide innovative strategies for clinical applications. Video Abstract

Abstract Background The teaching of critical care medicine is a very important task, especially during the COVID-19 pandemic. The understanding of critical care parameters is the foundation and core, which is conducive to the formation of clinical thinking. This study is to evaluate the training effect of teaching of critical care parameters based on an online platform, and explore the teaching methods of critical care medicine that can help to cultivate trainees’ clinical thinking and practical ability. Methods Questionnaires were released before and after the training through the official new media platform “Yisheng” application (APP) of China Medical Tribune involving 1109 participants. The trainees who filled in the questionnaire in APP and received training were randomly selected as the investigated population. Statistical description and analysis were carried out using SPSS 20.0 and Excel 2020. Results The trainees were mainly attending physicians in tertiary hospitals and above. Among all critical care parameters, trainees paid more attention to critical hemodynamics, respiratory mechanics, severity of illness scoring systems, critical ultrasound, and critical hemofiltration. The degree of satisfaction with the courses was high, especially the course of critical hemodynamics was scored the highest. The trainees believed that the course contents were of great help to clinical work. However, no significant difference was found in the trainees’ understanding or cognition of the connotation of the parameters before and after the training. Conclusion Teaching of critical care parameters based on an online platform is conducive to improving and consolidating the clinical care ability of trainees. However, it is still necessary to strengthen the cultivation of clinical thinking in critical care. In the future, the integration of theory with practice must be strengthened in clinical practice, ultimately achieving the homogeneous diagnosis and treatment of patients with critical illness.

Abstract How climate change in the middle to late Holocene has influenced the early human migrations in Central Asian Steppe remains poorly understood. To address this issue, we reconstructed a multiproxy-based Holocene climate history from the sediments of Kanas Lake and neighboring Tiewaike Lake in the southern Altai Mountains. The results show an exceptionally warm climate during ~6.5–3.6 kyr is indicated by the silicon isotope composition of diatom silica (δ30Sidiatom) and the biogenic silica (BSi) content. During 4.7-4.3 kyr, a peak in δ30Sidiatom reflects enhanced lake thermal stratification and periodic nutrient limitation as indicated by concomitant decreasing BSi content. Our geochemical results indicate a significantly warm and wet climate in the Altai Mountain region during 6.5–3.6 kyr, corresponding to the Altai Holocene Climatic Optimum (AHCO), which is critical for promoting prehistoric human population expansion and intensified cultural exchanges across the Central Asian steppe during the Bronze Age.

Casting technology plays a crucial role in the advanced production of vehicle parts due to its relatively low manufacturing cost and flexibility. However, a major challenge is to improve surface strength, surface finish, and production efficiency in order to produce the next generation of lightweight, long-lasting, energy-efficient vehicles. In this study, we propose an efficient AlSi7Mg casting-forging technology that significantly enhances the mechanical properties of the samples compared to those produced by casting alone. The ultimate tensile strength (UTS) and elongation were increased from 290 MPa to 11% to 311 MPa and 13%, respectively, which represents an improvement of 7.2% and 18%. Our research results demonstrate that the casting-forging technique introduces favorable and stable microstructural features, including optimized surface quality and refined grains, which improve mechanical properties.

Abstract Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

Abstract Background Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.

ABSTRACTThis anonymous cross-sectional study aimed to investigate the relationships between HIV infection and mpox-related focus issues among Chinese men who have sex with men (MSM). This study involved in 27 MSM social organizations and was conducted from July 31 to August 4, 2023. Mpox vaccination hesitancy was defined as the proportion of participants who expressed unwillingness to receive self-funded and free vaccines. Logistic regression models were employed to estimate odds ratios (OR) and 95% confidence interval (95%CI). Of 7196 MSMs, the prevalence of mpox differed between people living with HIV (PLWH) (1.04%, 20/1920) and people living without HIV (PLWoH) (0.55%, 29/5276) (P = .037). However, after adjusting for all covariates, there was no significant association between HIV status and mpox (aOR = 1.17; 95%CI = 0.58, 2.39; P = .658). Furthermore, the crude rates of vaccination hesitation (PLWoH: 5.91%, PLWH: 4.11%; P = .004) and consultation hesitation (PLWoH: 16.22%, PLWH: 10.78%; P

Background This study was designed to investigate the relationship between the renal resistive index (RRI), renal microvessel density (RMD), and fibrosis in patients with chronic kidney disease (CKD).Methods A total of 73 CKD patients were included in the study. Prior to kidney biopsy, we recorded the RRI of the interlobar artery and the estimated glomerular filtration rate (eGFR). Immunohistochemical analysis was performed to assess CD34 expression, and Masson staining was used to evaluate histopathological specimens for RMD and the degree of fibrosis. The percentage of the positive area (PPA) was recorded. Subsequently, we investigated the correlation between RRI, RMD, and kidney fibrosis.Results RMD (CD34 PPA-total and CD34 PPA-peritubular capillary) showed a slight increase in early CKD stages (1-2) and gradually declined from CKD stages 2 to 5. No correlation was observed between the RRI and RMD or between the RRI and fibrosis across CKD stages 1 to 5. However, across CKD stages 2 to 5, RRI negatively correlated with CD34 PPA-glomerulus (r = −0.353, p = 0.022), but no correlation was found with CD34 PPA-total, CD34 PPA-peritubular capillary, or kidney fibrosis. eGFR showed a positive correlation with RMD (CD34 PPA-total, CD34 PPA-peritubular capillary, and CD34 PPA-glomerulus) across CKD stages 2 to 5, while no correlation was found from CKD stages 1 to 5.Conclusion There was no correlation between RRI and RMD or between RRI and fibrosis across CKD stages 1 to 5 (RRI ≤ 0.7).

Background Although decreased influenza activity has been reported in many countries during the COVID-19 pandemic, it remains unknown how global influenza activity has changed. We described the global variability of influenza activity and virus subtype circulation from 2011 to 2023 to prepare for the potential influenza outbreak with the control of the COVID-19 pandemic.Methods Influenza virological surveillance data between 2011 and 2023 were obtained from the WHO-FluNet database. We first calculated and compared the influenza activity before and during the COVID-19 pandemic. For countries whose influenza activity has recovered, we also described changes in the duration of influenza epidemics. We then determined the proportion of influenza cases caused by the different influenza virus types.Results In total, 73 countries with 2.17 million influenza cases were included. In the early stage of the COVID-19 pandemic, decreased influenza activity was observed in all WHO regions. In 2022 and 2023, rebound in influenza activity was observed in all WHO regions, especially in Western Pacific Region. At the same time, a change in the duration of the influenza epidemic was observed in several Southern Hemisphere countries. Moreover, in all WHO regions, few B/Yamagata viruses were detected during the COVID-19 pandemic.Conclusions Lack of exposure to influenza will diminish population immunity and increase the severity of large epidemics on a future global resurgence. Ongoing monitoring of the changes in the duration of the influenza epidemic and circulation subtypes should be the focus of future work.

Objective: Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease. We have developed a Korean Red Ginseng Formula (KRGF) containing extracts of Korean Red Ginseng (KRG), Crataegus Fructus, and Cassiae Semen. In this study, our aims were to investigate the therapeutic potential and underpinning mechanisms of KRGF in NAFLD complicated by hyperlipidemia. Methods: In the in vitro assays, HepG2 cells were treated with KRGF for 24 h in the presence or absence of oleic acid (OA). To assess the in vivo protective effect of KRGF against NAFLD, rats fed a high-fat diet (HFD) were given intragastric administration for 30 days. Results: KRGF exerted protective effects against NAFLD by reducing lipid accumulation and steatosis in OA-stimulated HepG2 cells and HFD-fed rats. In HFD-fed rats, KRGF effectively decreased triglyceride levels in both blood and liver tissue and modulated the expression of key regulators of lipogenesis and fatty acid oxidation. KRGF downregulated the expression of lipogenesis factors, namely C/EBPα, FAS, SREBP-1c, and PPARγ, while upregulating the expression of PPARα and CPT-1, thus promoting fatty acid oxidation. Additionally, KRGF intensified the phosphorylation of AMPK and ACC, which are two enzymes that suppress fatty acid synthesis and promote fatty acid oxidation. KRGF effectively decreased total cholesterol (TC) levels in both blood and liver tissue, and it modulated the expression of major enzymes related to TC metabolism, namely apoB, ACAT2, CYP7A1, and HMGCR. Conclusion: In conclusion, KRGF mitigated NAFLD complicated by hyperlipidemia by modulating triglyceride and cholesterol metabolism, suggesting its potential for future development in the treatment of NAFLD.

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome abnormalities and type-2-skewed immune dysregulation. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays critical roles in various biological processes. However, the role of STAT3 in epidermal keratinocytes in AD remains unclear. In this study, we generated an epidermal keratinocyte-specific Stat3-deficient mouse strain (termed Stat3 cKO mice). After topical 2,4-dinitrochlorobenzene (DNCB) treatment, Stat3 cKO mice developed worsened AD-like skin inflammation with increased Ki67+ cells, decreased filaggrin and loricrin expression, and downregulated S100A9 and LL37. The dominant microbial population in Stat3 cKO mice changed from Ralstonia to Staphylococcus. DNCB-treated Stat3 cKO mice displayed more infiltrating type-2 inflammatory cells, including mast cells, eosinophils, and CD4+T cells, accompanied by increased skin IL-4 and serum IgE levels. Moreover, thymic stromal lymphopoietin (TSLP), mainly produced by keratinocytes, was highly expressed in the ear skin of Stat3 cKO mice and chemoattracted more TSLPR+ cells. TSLP blockade significantly alleviated DNCB-induced AD-like skin inflammation in Stat3 cKO mice. Thus, epidermal keratinocyte-specific STAT3 deficiency can aggravate AD-like skin inflammation in mice, possibly through TSLP dysregulation.

BackgroundThe primary objective of this study was to investigate the effects of oral omega-3 fatty acids in lowering the risk of malnutrition and improving the inflammatory response in patients with stage II-III lung cancer receiving postoperative chemotherapy.MethodsOne hundred and three lung cancer patients identified as being at risk for malnutrition according to the 2002 nutritional risk screening criteria were randomized into either the omega-3 fatty acid supplementation group or the placebo group during postoperative chemotherapy. Data on anthropometric parameters, laboratory nutritional indicators, and inflammatory markers were collected, and changes and differences between the two groups were compared and analyzed.ResultsSixty three patients were included in the final analysis. The baseline information of the two groups of patients was comparable (p > 0.05). After 12 weeks, patients in the treatment group exhibited significantly higher levels of hemoglobin (11.26 ± 1.25 vs.10.60 ± 0.94, p = 0.021) and serum albumin (45.38 ± 5.06 vs.42.66 ± 5.06, p = 0.036) compared with those in the placebo group. Meanwhile, the levels of inflammatory factors C-reactive protein (2.16 ± 1.06 vs. 4.11 ± 1.72, p 0.05). Finally, in the treatment group, the levels of hemoglobin (10.89 ± 1.15 vs. 11.82 ± 1.21, p = 0.042), triglyceride (0.92 ± 0.29 vs. 1.03 ± 0.22, p = 0.043), and cholesterol (3.56 ± 0.82 vs. 4.23 ± 0.88, p = 0.045) were higher in stage II patients after the intervention compared with stage III patients.ConclusionSupplementation with omega-3 fatty acids improved nutritional status and reduced chronic inflammatory responses in patients with stage II-III non-small cell lung cancer undergoing postoperative chemotherapy.Clinical Trial RegistrationAEA RCT Registry, identifier AEARCTR-0007165.

Abstract Calcipotriol (CAL) has been widely studied as a fibrosis inhibitor and used to treat plaque psoriasis via transdermal administration. The clinical application of CAL to treat liver fibrosis is bottlenecked by its unsatisfactory pharmacokinetics, biodistribution, and side effects, such as hypercalcemia in patients. The exploration of CAL as a safe and effective antifibrotic agent remains a major challenge. Therefore, we rationally designed and synthesized a self‐assembled drug nanoparticle encapsulating CAL in its internal hydrophobic core for systematic injection (termed NPs/CAL) and further investigated the beneficial effect of the nanomaterial on liver fibrosis. C57BL/6 mice were used as the animal model, and human hepatic stellate cell line LX‐2 was used as the cellular model of hepatic fibrogenesis. Immunofluorescence staining, flow cytometry, western blotting, immunohistochemical staining, and in vitro imaging were used for evaluating the efficacy of NPs/CAL treatment. We found NPs/CAL can be quickly internalized in vitro, thus potently deactivating LX‐2 cells. In addition, NPs/CAL improved blood circulation and the accumulation of CAL in liver tissue. Importantly, NPs/CAL strongly contributed to the remission of liver fibrosis without inducing hypercalcemia. Overall, our work identifies a promising paradigm for the development of nanomaterial‐based agents for liver fibrosis therapy.

Abstract Background With the rapid spread of the mpox epidemic, cases have emerged in multiple countries, mainly among men who have sex with men. Because of the connectedness of today’s world, countries have to be prepared to face risks in advance. Therefore, this study aimed to investigate awareness of mpox-related knowledge among men who have sex with men in China. Methods With the assistance of the social organizations of men who have sex with men, a cross-sectional survey of men who have sex with men in China was conducted through an online questionnaire between July 1 and July 18, 2022. A nationwide sample of Chinese men who have sex with men (N = 3,257) was recruited. Results Only 36.9% of participants had mpox-related knowledge. Awareness of mpox-related knowledge among respondents was positively associated with those in older age groups (33 to 42 years and 51 years or older) (adjusted odds ratio [AOR] = 1.31; 95% confidence interval [CI]: 1.03–1.67, AOR = 1.61; 95% CI: 1.16–2.24; respectively), married (AOR = 1.55; 95% CI: 1.09–2.19), and those with a graduate degree or above (AOR = 2.14; 95% CI: 1.11–4.13), while negatively associated with those living in the western parts of China (AOR = 0.74; 95% CI: 0.60–0.92), and those who were unsure of their history of Human Immunodeficiency Virus (HIV) status (AOR = 0.44; 95% CI: 0.30–0.63). Conclusion Mpox-related knowledge is fairly low among men who have sex with men in China. China needs to spread knowledge to the public through multiple channels, especially in key populations (men who have sex with men, HIV-infected, etc.), and take preventive measures to effectively avoid outbreaks of mpox.

Objective: To develop a nomogram for predicting lymph node metastasis (LNM) in patients with epithelial ovarian cancer (EOC). Methods: Between December 2012 and August 2022, patients with EOC who received computed tomography (CT) and serological examinations and were treated with upfront staging or debulking surgery were included. Systematic pelvic and para-aortic lymphadenectomy was performed in all patients. Univariate and multivariate analysis was used to identify significant risk factors associated with LNM. A nomogram was then constructed to assess the risk of LNM, which was evaluated with respect to its area under the receiver operating characteristic curve (AUC), calibration, and clinical usefulness. Results: Of 212 patients enrolled in this study, 78 (36.8%) had positive LNs. The nomogram integrating CT-reported LN status, child-bearing status, tumour laterality, and stage showed good calibration and discrimination with an AUC of 0.775, significantly improving performance over the CT results (0.699, p = 0.0002) with a net reclassification improvement of 0.593 (p < 0.001) and integrated discrimination improvement of 0.054 (p < 0.001). The decision curve analysis showed the nomogram was of clinical use. Conclusions: A nomogram was constructed and internally validated, which may act as a decision aid in patients with EOC being considered for systemic lymphadenectomy.