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Abstract Various pathogens from oomycete, fungi, and bacteria kingdoms can infect potato and significantly reduce potato yield. The early diagnosis of potato pathogens is important for tracing disease epidemics and the subsequent disease management. Loop-mediated isothermal amplification (LAMP) is a critical technique for pathogen detection, but available LAMP assays do not effectively meet the requirement of field diagnoses due to complexities including co-infection of different pathogens. Hence, this study aims to develop integrated-LAMP assays (iLAMPs) for simultaneous detection of eight common potato pathogens and apply iLAMPs to pathogen detection in field samples from the four main potato-growing regions of China in 2023. Therefore, eight sets of primers showing gene- and genus-specificity were designed and used for iLAMPs to determine their specificity, sensitivity, and visualization. Subsequently, iLAMPs-mediated pathogen detection revealed that 72.82% of 206 diseased leaves and 84.94% of 239 diseased tubers carry more than one pathogen. The detection rate for each pathogen significantly varies from 1.94 to 65.53% in diseased leaves, and ranges from 26.78 to 52.72% in diseased tubers, respectively. In addition, the detection rate of Phytophthora infestans and Alternaria solani positively correlates in both leaves and tubers, especially for those samples from the southwestern and southern regions. Taken together, iLAMPs developed in this study enables simultaneous detection of eight common potato pathogens from field samples and may have broad applications in early management of potato diseases.

Objective: The ultra-high pressure (UHP) pretreatment combined with hot air drying (HAD) process of Chinese yam (CY) was established and optimized in this study, in order to shorten the drying time of CY and improve its quality. Methods: The drying time, rehydration ratio (RR), color difference value, polysaccharide and total phenol content (TPC) were used as indicators to investigate the effects of different UHP pressure, holding time and drying temperature conditions on CY processing by single factor experiment, the weight coefficient of five indicators and the comprehensive score under different conditions were calculated by the CRITIC method, using the comprehensive score as the response value to optimize the processing technology of UHP pretreatment combined with HAD by response surface methodology. Results: UHP pretreatment could significantly shorten the drying time (P

Abstract Objective To explore the clinical efficacy of modified limbal stem cell transplantation(Modified LSC transplantation) and bandage contact lens(BCL) implantation in pterygium surgery. Methods A total of 479 patients with primary pterygium who were admitted to our hospital from March 2019 to March 2023 were randomly divided into three groups: the normal group (Group A: 89 patients), the control group (Group B: 195 patients), and the modified group (Group C: 195 patients). Each group received different intervention measures. Group A did not undergo surgical treatment and were required to follow up as outpatients. Group B received LSC transplantation combined with interrupted suturing plus BCL, whereas Group C received modified LSC transplantation combined with BCL. The degree of corneal irritation symptoms, wound healing and graft status under slit lamp, incidence and recurrence rate of complications, tear film rupture time, tear secretion test, intraocular pressure, ocular surface inflammation response(IL-1β, PGE2, TNF-α, VEGF), and visual quality were compared and analyzed at various time points after surgery. Results Compared with those in the Group B, patients in the Group C experienced faster normalization of corneal epithelium recovery, fewer corneal irritation symptoms, and better wound healing. The break-up time (BUT) of the tear film at 1 week to 1 year postoperatively was significantly greater in the Group C than Group B, with values approaching those of Group A by 3 months (P 0.05). The ELISA results indicated that the expression levels of the ocular surface inflammatory factors IL-1β, TNF-α, PEG2, and VEGF in the Group C were lower than those in Group B from 1 week to 1 year post surgery. Under both natural light and low-light conditions (spatial frequency/6 cd), Group C had better best-corrected visual acuity and contrast sensitivity than Group B at 1 week to 1 year postoperatively. Additionally, Group C had lower corneal higher-order aberrations (including astigmatism, spherical aberrations, and total higher-order aberrations) and superior vision-related quality of life scores at 1 year postoperatively than Group B, with statistically significant differences (P

Energy is transferred to the airflow during the rotation of impeller. In engineering, the efficient energy conversion is a key issue. Mastering the energy transfer process in impeller is the premise and basis for realizing efficient energy conversion. In order to clarify the energy transfer mechanism in impeller of contra-rotating axial fan, the internal flow field in impeller was obtained by numerical simulation and experiment. Based on the turbomachine energy conversion theory, the evolution characteristics of parameters such as flow angle, axial velocity and local theory total pressure rise were analyzed, and the laws of energy distribution and flow loss process in impeller were clarified. The results show that the efficiency of front impeller is significantly higher than that of the rear impeller when the flow rate is greater than 0.7 QBEP (QBEP is flow rate at the best efficiency point). When Q=1.0 QBEP, the efficiency difference between the two-stage impellers is about 26.5%, and the efficiency difference is as high as 66.6% when the flowrate increases to 1.22 QBEP, which indicate that the low efficiency of the rear impeller is the main reason for the efficiency reduction of the fan. In the streamwise location, the flow loss of the rear impeller is concentrated within STL=0−0.3 (STL represents the dimensionless distance from the inlet to outlet of the impeller in the flow direction), and reducing the flow loss in this region is the key to improve the efficiency of rear impeller. The hump characteristic of actual total pressure rise curve is the result of the combined effect of theory total pressure rise and flow loss, but mainly related to the theory total pressure rise at the outlet of front impeller and inlet of rear impeller. The sharp decrease or increase in flow angle at the spanwise direction is the main cause of a significant decrease in axial velocity, which in turn leads to backflow in the inlet and outlet of the front impeller and inlet of the rear impeller within SPN=0.8−1.0 (SPN represents the dimensionless distance from the hub to shroud of the impeller in the spanwise direction), and ultimately affects the theory total pressure rise in impeller. Therefore, the flow angle and axial velocity jointly affect the energy evolution law in impeller. The local theory total pressure rise is greatly improved in the middle region of the impeller, while the change in the inlet and outlet region is negligible. The significant increase growth rate of local theory total pressure rise is the key factor determining the theory total pressure rise of the impeller.

Constructing van der Waals materials with spontaneous out-of-plane polarization through interlayer engineering expands the family of two-dimensional ferroelectrics and provides an excellent platform for enhancing the photoelectric conversion efficiency. Here, we reveal the effect of spontaneous polarization on ultrafast carrier dynamics in rhombohedral stacked bilayer WSe2. Using precise stacking techniques, a 3R WSe2-based vertical heterojunction was successfully constructed and confirmed by polarization-resolved second harmonic generation measurements. Through output characteristics and the scanning photocurrent map under zero bias, we reveal a non-zero short-circuit current in the graphene/3R WSe2/graphene heterojunction region, demonstrating the bulk photovoltaic effect. Furthermore, the out-of-plane polarization enables the 3R WSe2 heterojunction region to achieve an ultrafast intrinsic photoresponse time of approximately 3 ps. The ultrafast response time remains consistent across varying detection powers, demonstrating environmental stability and highlighting the potential in optoelectronic applications. Our study presents an effective strategy for enhancing the response time of photodetectors.

Abstract Objective This study explored how the weight-adjusted waist index (WWI) and a body shape index (ABSI) are related to serum neurofilament light chain (sNfL) levels among U.S. adults. We aimed to evaluate sNfL, which plays key roles in neuronal injury in neurological diseases, given its understudied connection to obesity. Methods We used cross-sectional data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) of people with complete information on the weight-adjusted waist index (WWI), a body shape index (ABSI), and serum neurofilament light chain (sNfL). Multiple linear regression analysis allowed us to investigate the separate connections among the WWI, ABSI, and sNfL. Moreover, interaction testing and subgroup analysis were performed to improve the general validity of our results. To assess any nonlinear correlations, we also performed threshold effect analysis and smoothed curve fitting. Results WWI and ABSI were positively linked with sNfL (WWI: β = 0.05, 95% CI 0.01–0.09; ABSI: β = 1.65, 95% CI 3.53–13.72). There was no clear reliance on this association according to subgroup analysis and interaction tests. Smoothed curve fitting and saturation effects also demonstrated nonlinear associations between WWI and ABSI and sNfL, with inflection points of 10.38 and 0.38, respectively. Conclusion In the adult American population, while the WWI and ABSI are linearly positively correlated with serum neurofilament light protein (sNfL), the effect size is greater for the ABSI. This correlation provides fresh evidence connecting obesity to neurological conditions, deepening our comprehension of the extensive health impacts associated with obesity. Level of Evidence Level I, experimental studies.

Abstract Background Hospitalized patients often present with complex clinical conditions, but there is a lack of effective tools to assess their risk of pulmonary embolism (PE). Therefore, our study aimed to develop a nomogram model for better predicting PE in hospitalized populations. Methods Data from hospitalized patients (aged ≥ 15 years) who underwent computed tomography pulmonary angiography (CTPA) to confirm PE and non-PE were collected from December 2013 to April 2023. Univariate and multivariate stepwise logistic regression analyses were conducted to identify independent predictors of PE, followed by the construction of a predictive nomogram and internal validation. The efficiency and clinical utility of the nomogram model were assessed using receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve (CIC). Results The study included 313 PE and 339 non-PE hospitalized patients. Male gender, dyspnea or shortness of breath, interstitial lung disease, lower limb deep vein thrombosis, elevated fibrin degradation product (FDP), pulmonary arterial hypertension, and tricuspid regurgitation were identified as independent risk factors. The AUC of the predictive nomogram model was 0.956 (95% CI: 0.939–0.974), demonstrating superior performance compared with the simplified Wells score of 0.698 (95% CI: 0.654–0.741) and the modified Geneva score of 0.758 (95% CI: 0.717–0.799). Conclusion Our study demonstrated that challenges remain in the accuracy of the Wells score and revised Geneva score in assessing PE in hospitalized patients. Fortunately, the nomogram we developed has shown a favorable ability to discriminate PE cases, providing high reference value for clinical practice. However, given that this was a single-center study, we plan to expand efforts to collect data from additional centers to further validate our model.

Abstract Background This randomized, open-label study examined the therapeutic effects of Neurocognitive Adaptive Training for Depression (NCAT-D) combined with selective serotonin reuptake inhibitors (SSRIs) on cognitive impairment among patients with late-life depression (LLD). Method Study data were collected from May 5, 2021, to April 21, 2023. Outpatients who met the diagnostic criteria for major depressive disorder according to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (i.e., a total score on the 17-item Hamilton Depression Rating Scale (HAMD-17) ≥ 18 and a total score on the Montreal Cognitive Assessment scale (MOCA)

Highlights Recent advances in the combined delivery platform that integrate nano-/microscale carriers and with 3D hydrogel network for bone regeneration are summarized. The strategies for bioactive molecules delivery involving nanoparticles, nanosheets, and microspheres, along with extra stimuli such as near-infrared light, temperature changes, ultrasonication, and inflammatory conditions, are introduced. The prospects and challenges for the clinical translation and the development of nano-/microscale incorporated hydrogel-based delivery platform are discussed.

Abstract The present study aims to explore group types of job stress in university teachers in China. Utilizing an indigenously developed university teachers’ job stress scale in China alongside other tools, a survey was conducted on 1988 teachers from 22 Chinese higher education institutions from a person-oriented perspective. Stratified cluster random sampling and K-means clustering techniques were employed to derive a classification model for job stress among university educators. According to job stress characteristics, Chinese university teachers were classified into six significantly heterogeneous groups: relatively high stress, task-related stress, relatively low stress, interpersonal-related stress, extremely low stress, and extremely high stress. The average job burnout and job satisfaction scores of the different groups exhibited varying features. In general, the extremely high stress group should be the most concerned, whereas university teachers with mid-level stress merit less attention. But the medium-stress group was further subdivided. University teachers under task-related stress have more stress-related consequences than those of university teachers under interpersonal-related stress. There are significant differences in the distribution of university teachers’ job stress group types across demographic groups defined by gender and university types. University administrators should focus on university teachers under task-related stress. This classification model offers direct references for the stress management and psychological aid of university teachers.

Abstract Objectives Anteroposterior pelvic radiographs remains the most widely employed method for diagnosing developmental dysplasia of the hip. This study aims to evaluate the accuracy of an artificial intelligence model in measuring angles in pelvic radiographs of the hip. The assessment seeks to demonstrate the efficacy of the artificial intelligence model in diagnosing both developmental dysplasia of the hip and borderline developmental dysplasia of the hip through the analysis of pelvic radiographs. Methods A total of 1,029 patients, including 273 men and 757 women, were retrospectively included in this study. The anteroposterior pelvic radiographs were randomly divided into three sets: the training set (720 cases), the validation set (103 cases), and the test set (206 cases). Key anatomical points on the anteroposterior pelvic radiographs were identified. The Sharp, Tönnis, and Center Edge angles were calculated automatically based on the corresponding criteria. The hip development status was compared between measurements obtained from the artificial intelligence model and those defined manually by two radiologists. The area under the receiver operating characteristic curve was utilized to assess the diagnostic performance of the artificial intelligence model. Results The results obtained from both manual measurements and the artificial intelligence model demonstrated no significant differences in the Sharp, Tönnis, and Center edge angles (all p > 0.05). The intra-class correlation coefficients and correlation coefficient r values exceeded 0.75, indicating that both the artificial intelligence model and manual measurements exhibited good repeatability and a positive correlation. Notably, the artificial intelligence model provided measurements more faster than those conducted by radiologists (p = 0.001). The artificial intelligence model also demonstrated high diagnostic accuracy, sensitivity, and specificity for developmental dysplasia of the hip. The performance of the artificial intelligence model in diagnosing developmental dysplasia of the hip was robust. Additionally, the results from the artificial intelligence model and manual measurements were largely consistent with clinical diagnosis results (p = 0.01). The artificial intelligence model can effectively evaluate hip conditions by measuring the Sharp, Tönnis, and Center edge angles, which are consistent closely with clinical diagnosis results. Conclusions The results of the artificial intelligence model measurements demonstrate a high degree of consistency with those obtained through manual measurements. The angles of Sharp, Tönnis, and Center edge, as evaluated by the deep learning-based convolutional neural network model, exhibit robust diagnostic performance in identifying both developmental dysplasia of the hip and borderline developmental dysplasia of the hip. Consequently, the artificial intelligence model has the potential to fully replace manual measurements of these critical hip angles, providing a more efficient and precise alternative for diagnosing both conditions of the hip.

Abstract Subduction zones metamorphic fluids are pivotal in geological events such as volcanic eruptions, seismic activity, mineralization, and the deep carbon cycle. However, the mechanisms governing carbon mobility in subduction zones remain largely unresolved. Here we present the first observations of immiscible H2O-CH4 fluids coexisting in retrograde carbonated eclogite from the Western Tianshan subduction zone, China. We identified two types of fluid inclusions in host ankerite and amphibole, as well as in garnet and omphacite. Type-1 inclusions are water-rich with CH4 vapor, whereas Type-2 are CH4-rich, with minimal or no H2O. The coexistence of these fluid types indicates the presence of immiscible fluid phases under high-pressure conditions (P = 1.3-2.1 GPa). Carbonates in subduction zones can effectively decompose through reactions with silicates, leading to the generation of abiotic CH4. Our findings suggest that substantial amounts of carbon could be transferred from the slab to mantle wedge as immiscible CH4 fluids. This process significantly enhances decarbonation efficiency and may contribute to the formation of natural gas deposits.

Abstract To investigate the difference in preoperative retinal function in patients with type 2 diabetes cataract (DC) without obvious retinopathy and to explore the clinical application of full blood glucose management for improving the postoperative vision in DC patients. This was a retrospective analysis in which we estimated the changes in visual electrophysiology (N75, P100, photopic flash electroretinogram(FERG), and scotopic FERG, paraoptic retinal nerve fibre layer thickness (pRNFL) and paraoptic radial capillary network blood flow density (ppVD) of type 2 diabetes (T2DM) patients at different phases of disease progression along with fasting blood glucose (FBG) and glycosylated haemoglobin (HbAlC) levels before and after DC surgery at Ziyang Central Hospital from January 2020 to December 2022. Additionally, trends in the above data throughout the entire process of glucose management intervention were examined. As the course of T2DM progressed, FBG and HbA1c increased, the N75 and P100 latency periods of patients gradually increased, and the values of photopic FERG, scotopic FERG, pRNFL, and ppVD gradually decreased at each postoperative time point. Moreover, the best corrected visual acuity(BCVA) of patients after surgery gradually decreased (P

Abstract In order to improve the crushing efficiency of high-pressure roller mill and reduce energy consumption, the optimal parameter combination of high-pressure roller mill is sought, GM160-140 high-pressure roller mill is taken as the research object, and the discrete element simulation calculation model of high-pressure roller mill is established to simulate the crushing process. Taking the roll surface pressure, productivity, and the proportion of discharge particle diameter as the performance evaluation indexes, the simulation data are used to analyze the influence of each working condition parameter of the high-pressure roller mill on its performance law. Through the entropy weighting method to determine the weights of high-pressure roller mill productivity, roll surface pressure, the proportion of discharge particle diameter, and through the extreme difference analysis to get the optimal parameter combination. Minitab software is used to carry out the response surface method (RSM) experimental design, the optimal parameter combinations are derived from the optimization using the response surface apparatus, the optimal parameter combinations derived from the two optimization methods are compared and analyzed, and ultimately it is concluded that the optimization of the response surface is the global optimal, and the optimal parameter combinations are as follows: the roller speed is 2.50 rad/s, the roller gap is 28.87 mm, and the feed size is 31.97 mm, Under the above optimal parameters, the roll surface pressure is 150450.00 N, the productivity is 1268.00t/h, the percentage of the material less than 6 mm is 58.14%, so as to achieve the purpose of optimizing the parameters of the high-pressure roller mill, It is of significance to save resources and respond to the national green development and intelligent development.

Because basalt formation is rich in calcium, magnesium, iron and other bivalent metal elements, it can transform injected CO2 into carbonate rock through efficient mineralization reaction, so as to achieve a safe and effective permanent storage of CO2. However, the research on the mechanism of CO2 mineralization and storage is incomplete, and most studies ignore the effect of diffusion on the mechanism of CO2 mineralization. By conducting experiments with the sand grains being filled in the tube or scatted in a beaker, the CO2-water-rock reactions with different minerals, different particle sizes and different reaction time are investigated. The rock samples after the reaction are analyzed by multi-dimensional analysis, including Raman spectra, inorganic carbon content and SEM-EDS, thus clarifying the importance of diffusion in the CO2 mineralization and the spatio-temporal evolution of CO2 mineralization products under diffusion control. At the same time, the numerical simulation model of the tube filling experiment is established by TOUGHREACT, and the accuracy of the numerical simulation model is ensured by fitting the physical experiment results. On this basis, more studies on the law of the influencing factors are carried out, and the mechanistic explanation for the physical experimental phenomena is provided. The results of physical experiment and numerical simulation show that: ① For the experiment carried out with olivine grains scattered at the bottom of beaker, no diffusion occurred. At this situation, after 14 days’ reaction, no mineral carbonation was observed. Meanwhile, after 28 days marginal amount of magnesite was observed. ② In contrast, in the filled tubes, under the control of diffusion, the main precipitates in the olivine filled tube are magnesite, and the precipitates in the natural basalt filled tube are mainly calcite and siderite, with magnesite as auxiliary. At the same mineral particle size and the same reaction time, the CO2 mineralization rate in natural basalt is much smaller than that of olivine, because olivine has the fastest dissolution rate compared with other constituent minerals of basalt. ③ In olivine or basalt filled tubes, the carbonate precipitates are distributed ununiformly along the filled tubes. The root cause of this phenomenon is explained by numerical simulation, i.e., under the control of diffusion, there are concentration gradients of pH, DIC and bivalent metal cations in the packed bed, and the concentration gradients are different in different directions. ④ The specific mineral surface has a significant influence on the CO2-water-rock reaction, which not only affects the mineralization efficiency but also affects the spatial distribution of the mineralized products, and finally affects the porosity distribution of the porous media after the reaction. ⑤ Compared with pressure, temperature has more influence on CO2 mineralization. The precipitation of calcite, siderite and carbonate increases significantly when the temperature increases from 65 ℃ to 85 ℃, but only the precipitation of magnesite increases significantly when the temperature increases from 85 ℃ to 100 ℃. The pressure has little effect on the formation of calcite precipitate, but has no effect on the formation of magnesite and siderite.

Abstract Previous environmental research used a general conceptualization of moral norms (e.g., it is my moral obligation to recycle) without specifying the exact moral underpinning of such a conceptualization. This analysis examined how five basic moral foundations (i.e., harm, fairness, ingroup loyalty, authority, and purity) were associated with Chinese residents’ waste-sorting attitudes and intentions. This analysis used data from a cross-sectional online survey of 459 Chinese residents conducted in 2021. The results revealed that value-expressive attitudes were a fairly strong predictor of waste-sorting intentions, whereas attitudes about inconvenience and time were a weak predictor. Further analysis of direct and total relationships revealed that the moral foundations of ingroup loyalty and authority were the primary moral foundations for the Chinese participants; the effects were both direct and mediated by the value-expressive attitudes. Using detailed attitudinal and moral foundations can provide explanatory adequacy and specificity for environmental research and education efforts.

The capacity and cycling performance of cathodes are key factors in aqueous zinc batteries (AZBs). The search for cathode materials with long cycle lives and high specific capacities is of paramount importance. In this study, a bimetallic telluride with a hollow polyhedral structure was synthesized using a hydrothermal method followed by vapor deposition. This composite exhibits high conductivity, facilitates rapid diffusion of electrolyte ions into the interior, and accelerates redox reactions, thereby enhancing electrochemical performance. The CoTe2-NiTe2 electrode demonstrates an impressive specific capacity of 188.8 mAh/g at 1 A/g, highlighting its efficiency in storing a significant amount of charge per unit mass during electrochemical reactions. The assembled CoTe2-NiTe2//Zn battery shows favorable capacity retention (76.4%) after 10000 cycles. The energy density is remarkably high, reaching 290.3 Wh/kg, while maintaining a power density of 1.75 kW/kg. This bimetallic telluride strategy holds great promise as an alternative cathode for AZBs.

Abstract. Chimeric antigen receptor T (CAR-T) cell therapy, renowned for its successes in cancer treatment, is now entering the field of human immunodeficiency virus (HIV) therapy, presenting both opportunities and challenges. With the emergence of broadly neutralizing antibodies, multi-target CARs, and T cell receptor–like antibodies aimed at increasing specificity in targeting HIV reservoirs, CAR-T therapy is synergizing with other cutting-edge treatments, including gene-editing technologies, therapeutic vaccines, and latency-reversing agents, in pursuit of a potential functional cure. In this review, we delve into the role of CAR-T therapy in HIV treatment, highlighting its potential to overcome clinical obstacles. We discuss advancements in targeting strategies within CAR constructs and the intricate regulation of T cell proliferation and chemotaxis. Moreover, we explore the use of diverse immune cells, such as gamma-delta T cells and natural killer cells. We review advanced biotechnologies, manufacturing innovations, viral mechanisms, and immune microenvironments. We also discuss the current research landscape and potential future applications of CAR-T therapy against HIV, which remains a critical global health challenge.

Abstract Background The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients. Methods In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA. Results A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20–3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84–1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar. Conclusion OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population. Trial registration Clinicaltrials.gov; No: NCT03362385.

Abstract Red clay as a special soil has a high liquid-plastic limit, water swelling and water loss shrinkage. To solve the problems red clay was modified by calcium carbonate produced in Hezhou, Guangxi. The Liquid-plastic limit, water loss shrinkage, nuclear magnetic resonance (NMR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and consolidated drained (CD) triaxial shear test were carried out on the modified soils. The results show that when the calcium carbonate content is 20%, the plastic limit is 24.38 and the liquid limit is 38.67, which are reduced by 35.04% and 22.16%, respectively. The Montmorillonite content in the modified soil is reduced by 27.7%. The shrinkage coefficient decreased from 0.325 to 0.102. The NMR test shows that the content is 5% and 10% would lead to a decrease in the macropores and an increase in the micropores pores. The phenomenon is the opposite (15% and 20%). All contents led to the porosity increase. The calcium carbonate content of 5% was selected for triaxial shear tests to obtain the stress-strain curves. The Duncan-Zhang was used to predict the modified soil. The model has a large error in the prediction of the peak of the principal stress difference, but the overall trend is relatively consistent. Therefore, the correction coefficient related to the confining pressure was introduced. The corrected model fits the triaxial shear test well. The research provides a method for the liquid-plastic limits and shrinkage properties of modified red clay, explores the influence of calcium carbonate content on microscopic pores, and the correction of the model provides a theoretical basis for practical application.

Abstract Owing to high pixel density and brightness, gallium nitride (GaN) based micro-light-emitting diodes (Micro-LEDs) are considered revolutionary display technology and have important application prospects in the fields of micro-display and virtual display. However, Micro-LEDs with pixel sizes smaller than 10 μm still encounter technical challenges such as sidewall damage and limited light extraction efficiency, resulting in reduced luminous efficiency and severe brightness non-uniformity. Here, we reported high-brightness green Micro-displays with a 5 μm pixel utilizing high-quality GaN-on-Si epilayers. Four-inch wafer-scale uniform green GaN epilayer is first grown on silicon substrate, which possesses a low dislocation density of 5.25 × 108 cm− 2, small wafer bowing of 16.7 μm, and high wavelength uniformity (standard deviation STDEV

Abstract Elevated circulating branched-chain amino acids (BCAAs) are tightly linked to an increased risk in the development of type 2 diabetes mellitus. The rate limiting enzyme of BCAA catabolism branched-chain α-ketoacid dehydrogenase (BCKDH) is phosphorylated at E1α subunit (BCKDHA) by its kinase (BCKDK) and inactivated. Here, the liver-specific BCKDK or BCKDHA knockout mice displayed normal glucose tolerance and insulin sensitivity. However, knockout of BCKDK in the liver inhibited hepatic glucose production as well as the expression of key gluconeogenic enzymes. No abnormal gluconeogenesis was found in mice lacking hepatic BCKDHA. Consistent with the vivo results, BT2-mediated inhibition or genetic knockdown of BCKDK decreased hepatic glucose production and gluconeogenic gene expressions in primary mouse hepatocytes while BCKDK overexpression exhibited an opposite effect. Whereas, gluconeogenic gene expressions were not altered in BCKDHA-silenced hepatocytes. Mechanistically, BT2 treatment attenuated the interaction of cAMP response element binding protein (CREB) with CREB-binding protein and promoted FOXO1 protein degradation by increasing its ubiquitination. Our findings suggest that BCKDK regulates hepatic gluconeogenesis through CREB and FOXO1 signalings, independent of BCKDHA-mediated BCAA catabolism.

Abstract Copper (Cu) is used as a cofactor in all organisms, and yet it can be toxic at high intracellular concentrations, causing cell death. Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients’ disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa.

Background/purpose: South Asia and Southeast Asia are the regions with relatively high and increased disease burden of oral cancer. The purpose of this study was to analyze the scientometric characteristics of oral cancer research in these regions. Materials and methods: There are 8 countries from South Asia and 11 countries from Southeast Asia. All the articles on oral cancer from these countries were retrieved in the Scopus database. Results: A total of 5660 articles originated from South Asia (n = 4718) and Southeast Asia (n = 942). India (n = 4302; 91.2%) was the country publishing most articles on oral cancer in South Asia, and Malaysia (n = 355; 37.7%) was first in Southeast Asia. Tobacco smoking, alcohol consumption, and areca nut as risk factors were common keywords, attention should be paid to them while developing polices for oral cancer control. In India, the most topic including distinctive keywords was diagnostics (sensitivity/specificity, saliva, and predictive value), followed by molecular biology (antioxidants, lipid peroxidation, and glutathione), experimental in vivo (hamster and cheek pouch), and risk factor (smokeless tobacco). In Malaysia, the most topic containing keywords was molecular biology followed by epidemiology and drug research. Conclusion: This study for the first time reported the scientometric characteristics of oral cancer research in South Asia (India) and Southeast Asia (Malaysia). It is essential to improve the public awareness of risk factors control to reduce the oral cancer burden, especially in low-and middle-income countries.

The treatment of refractory bone defects is a major clinical challenge, especially in steroid-associated osteonecrosis (SAON), which is characterized by insufficient osteogenesis and angiogenesis. Herin, a microenvironment responsiveness scaffold composed of poly-L-lactide (PLLA), and manganese dioxide (MnO2) nanoparticles is designed to enhance bone regeneration by scavenging endogenous reactive oxygen species (ROS) and modulating immune microenvironment in situ. A catalase-like catalytic reaction between MnO2 and endogenous hydrogen peroxide (H2O2) generated at the bone defect area, which typically becomes acidic and ROS-rich, triggers on-demand release of oxygen and Mn2+, significantly ameliorating inflammatory response by promoting M2-type polarization of macrophages, reprograming osteoimmune microenvironment conducive to angiogenesis and osteogenesis. Furthermore, the fundamental mechanisms were explored through transcriptome sequencing analysis, revealing that PLLA/MnO2 scaffolds (PMns) promote osteogenic differentiation by upregulating the TGF-β/Smad signaling pathway in human bone marrow mesenchymal stem cells (hBMSCs). Overall, the PMns exhibit superior immunomodulatory, excellent osteogenic-angiogenic properties and promising candidates as bone graft substitutes for therapy clinical refractory bone defects.

Abstract Background Many studies have explored the clinicopathological features and prognosis between colorectal mucinous adenocarcinoma (MAC) and adenocarcinoma (AC) and have given different results. This meta-analysis summarizes previous evidence and evaluates the clinicopathological and prognostic features of MAC relative to AC in colorectal cancers (CRCs). Methods The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the clinicopathological and prognostic differences between MAC and AC. Results Fifty-six studies involving 803157 patients met the inclusion criteria and were included in this meta-analysis. The clinicopathological features of MAC were greatly different from AC, except for lymphatic invasion (OR = 1.07, 95% CI: 0.99–1.15, P = 0.09) and perineural invasion (OR = 0.92, 95% CI: 0.79–1.06, P = 0.09). Further investigation found that MAC predicted poor OS (HR = 1.04, 95% CI: 1.03–1.04, P

Abstract Prostate cancer (PCa) is a commonly occurring malignancy in elderly men. Olaparib, a poly ADP-ribose polymerase inhibitor, is utilized in PCa treatment. However, patients often develop resistance to olaparib after a period of treatment. Genetic alterations may play a significant role in this resistance, but the specific genes involved remain unclear. This study collected RNA-sequence data from the Gene Expression Omnibus database on both olaparib-sensitive and -resistant PCa cells to identify genes crucial for resistance. Subsequently, the enriched pathways of these genes were analyzed, and a protein–protein interaction (PPI) network was constructed to identify hub genes. The effect of these hub genes on PCa occurrence, progression, and prognosis was assessed using data from The Cancer Genome Atlas and Chinese Prostate Cancer Genome and Epigenome Atlas databases. Finally, this study validated our findings in clinical PCa samples and cells. From the GSE189186 dataset, 50 upregulated genes and 2 downregulated genes were identified in olaparib-resistant C4-2B and LNCaP cells. Utilizing the PPI network, eight upregulated genes (BBC3, TP53I3, FDXR, DDB2, CDKN1A, GADD45A, ZMAT3, and SESN1) were identified as hub genes for olaparib-resistant PCa cells. Furthermore, some of these genes were central to PCa occurrence, with BBC3 also influencing progression and prognosis. Importantly, BBC3 expression was upregulated in clinical PCa samples and affected PCa cells sensitive to olaparib, suggesting its potential as a predictive marker for PCa development and olaparib resistance.

Abstract To investgate the effects of potassium (K) application on the agronomic traits and fruit quality of Lycium barbarum L. (Goji), three levels of K fertilizer, namely LK (25 g/plant), CK (50 g/plant), and HK (75 g/plant), were applied to plants in phytotron for observing and measuring relevant indicators. The investigation involved seven agronomic traits: plant height, plant stem diameter, new branch increment, yield of fresh fruits per plant, dry fruit quantity within 50 g, ratio of different grade fruits, and ratio of longitudinal diameter to transverse diameter of Goji fruits. The results showed that K application level had significant effect on ratio of the longitudinal diameter to the transverse diameter of fresh Goji fruits, and that the influence on other agronomic traits was slight. In the meanwhile, the concentrations of amino acids, betaine, polysaccharides and flavonoids of Goji fruits in different levels of K fertilizer were tested. The K treatment increased the content of glutamic acid, and decreased that of flavonoids (P

Abstract Classical swine fever virus (CSFV) p7 viroporin plays crucial roles in cellular ion balance and permeabilization. The antiviral drug amantadine effectively inhibits viral replication by blocking the activity of CSFV p7 viroporin. However, little information is available for the binding mode of amantadine with CSFV p7 viroporin, due to the lack of a known polymer structure for CSFV p7. In this study, we employed AlphaFold2 to predict CSFV p7 structures. Subsequently, we conducted a docking study to investigate the binding sites of amantadine to CSFV p7. Computational analysis showed that CSFV p7 forms a pore channel in a hexameric structure. Furthermore, molecular dynamics (MD) simulations and mutant analyses further suggest that CSFV p7 likely exists as a hexamer. Docking studies and MD simulations showed that amantadine interacts with the hydrophibic regions of tetramer and pentamer, as well as with the hydrophobic pore channel of the hexamer. Considering the potential hexameric assembly of CSFV p7, along with docking results, MD simulations, and the characteristics of the gated ion channels, we propose a model of CSFV p7 ion channel based on its hexameric configuration. In this model, residues E21, Y25, and R34 are suggested to selectively recruit and dehydrate ions, while residues L28 and L31 likely act as hydrophobic constrictors, thereby restricting the free movement of water. The binding of amantadine to residues I20, E21, V24 and Y25 effectively blocks ion transport. However, this proposed molecular model requires experimental validation. Our findings give a structural insight into the models of CSFV p7 as an ion channel and provide a molecular explanation for the inhibition effects of amantadine on CSFV p7-mediated ion channel conductance.

Objective: The mechanism of action of Nelumbo nucifera leaf alkaloids in the treatment of hyperuricemia was analyzed based on network pharmacology and molecular docking. Methods: The target of Nelumbo nucifera leaf alkaloids and disease targets related to hyperuricemia were obtained through database search. The "component-disease-target" network of Nelumbo nucifera leaf alkaloids was established through Cytoscape 3.8.0, and the gene ontology (GO) analysis and Kyoto encyclopedia of genes and genome (KEGG) pathway analysis were carried out using the bioinformatics-based platform. The core target and key components were verified by molecular docking. Results: The information of 27 kinds of Nelumbo nucifera leaf alkaloids, including nuciferine, coclaurine, liensinine, was obtained by literature search, and 337 corresponding targets, 926 hyperuricemia-related targets and 57 key targets were piedicted. The mechanism of action of Nelumbo nucifera leaf alkaloids in the treatment of hyperuricemia mainly involved GAPDH, STAT3, JUN, CASP3, PTGS2, XDH, MAPK1 and other target genes. These genes mainly played a role in regulating protein expression through AGE-RAGE signaling pathway, PD-L1 expression and PD-1 checkpoint pathway, TNF signaling pathway, IL-17 signaling pathway and p53 signaling pathway. The results of molecular docking showed that the compound had good docking results with the molecular target. Nuciferine, coclaurine and liensinine bound to the key targets spontaneously, among which liensinine formed the most stable structure with PTGS2 and JUN, and the binding energy could reach −9.3 kcal/mol. Conclusion: This study predicted that Nelumbo nucifera leaf alkaloids could ameliorate hyperuricemia by regulating multiple targets and action multiple pathways, which could provide scientific basis for molecular research of Nelumbo nucifera leaf alkaloids in the treatment of hyperuricemia.

Macroporous cryogel has the advantages of nutrient exchange and cell growth, and is an ideal material for tissue regeneration. In order to strengthen the machenical properties of cryogel for the widely use, a high strength gelatin/sodium alginate/nano hydroxyapatite (nHA) porous cryogel (GA-HA cryogel) was prepared by a simple freeze-thaw process. The mechanical strength of GA-HA cryogel increased significantly with the increase of nHA content. In vitro studies showed that GA-HA cryogel had good biocompatibility and no obvious cytotoxicity to MC3T3-E1 cells. The results of alkaline phosphatase activity assay and osteocalcin immunofluorescence staining showed that GA-HA1 porous hydrogel system could significantly increase the expression of MC3T3-E1 alkaline phosphatase and osteocalcin when the content of nHA was 1 ​%. In addition, porous GA-HA cryogel showed good performance in promoting bone regeneration in rat skull defect model. Therefore, the high-strength double network cryogel prepared in this study can provide new applications in bone repair and tissue regeneration.

Abstract Innate immune activation is critical for initiating hepatic inflammation during nonalcoholic steatohepatitis (NASH) progression. However, the mechanisms by which immunoregulatory molecules recognize lipogenic, fibrotic, and inflammatory signals remain unclear. Here, we show that high-fat diet (HFD)-induced oxidative stress activates Foxo1, YAP, and Notch1 signaling in hepatic macrophages. Macrophage Foxo1 deficiency (Foxo1M-KO) ameliorated hepatic inflammation, steatosis, and fibrosis, with reduced STING, TBK1, and NF-κB activation in HFD-challenged livers. However, Foxo1 and YAP double knockout (Foxo1/YAPM-DKO) or Foxo1 and Notch1 double knockout (Foxo1/Notch1M-DKO) promoted STING function and exacerbated HFD-induced liver injury. Interestingly, Foxo1M-KO strongly reduced TGF-β1 release from palmitic acid (PA)- and oleic acid (OA)-stimulated Kupffer cells and decreased Col1α1, CCL2, and Timp1 expression but increased MMP1 expression in primary hepatic stellate cells (HSCs) after coculture with Kupffer cells. Notably, PA and OA challenge in Kupffer cells augmented LIMD1 and LATS1 colocalization and interaction, which induced YAP nuclear translocation. Foxo1M-KO activated PGC-1α and increased nuclear YAP activity, modulating mitochondrial biogenesis. Using chromatin immunoprecipitation (ChIP) coupled with massively parallel sequencing (ChIP-Seq) and in situ RNA hybridization, we found that NICD colocalizes with YAP and targets Mb21d1 (cGAS), while YAP functions as a novel coactivator of the NICD, which is crucial for reprogramming STING function in NASH progression. These findings highlight the importance of the macrophage Foxo1–YAP–Notch1 axis as a key molecular regulator that controls lipid metabolism, inflammation, and innate immunity in NASH.

Abstract Background There is increasing evidence implicating hemoglobin/heme and their scavengers in oxidative stress-mediated pathologies, but information is limited in abdominal aortic aneurysm (AAA). Methods and results In this case-control study, we assessed heme/heme-related markers in 142 men with AAA and 279 men with a normal aortic diameter consecutively recruited from an ultrasound screening program in Sweden. Enzyme-linked immunosorbent assays (ELISAs) were used to measure heme oxygenase-1 (HO-1) and hemopexin (Hpx) plasma levels, colorimetric assays for cell-free heme and whole blood hemoglobin (Hb) levels, and droplet digital PCR (ddPCR) and real-time PCR to determine haptoglobin (Hp) (pheno)type and genotype, respectively. Hpx and heme plasma levels at baseline were elevated, while HO-1 levels were lower in men with AAA (p

Abstract Background Previous studies into the interactions between native and invasive species under nitrogen (N) deposition have often overlooked the presence of co-occurring native species, a factor that could influence the outcomes of interspecific competition. Furthermore, publication bias may lead researchers to focus on rare native species with limited adaptability. In this study, we examined how two levels of N deposition affected the physiological and ecological traits and the interspecies interactions between three invasive and three common native species. Results N deposition promoted the growth of both invasive and native species. The relative dominance index (RDI) of invasive species was consistently higher than that of native species. Invasive species had an advantage over common native species in using the increased N effectively. The biomass distribution of invasive species was biased toward the aboveground parts, indicating competition for light resources. Conclusions N deposition conferred a stronger competitive advantage to invasive species than to native species, suggesting that the distribution range of invasive species may expand further under increased N deposition.

Abstract Purpose The assessment of sarcoma during clinical practice is primarily based on imaging examination, with no effective biomarkers available. Although it has been established that 1,25(OH)2D3 is abnormally expressed in patients with sarcoma, it remains unclear whether 1,25(OH)2D3 level could be used as an evaluation marker in these patient population. Methods This real-world study investigated 1,25(OH)2D3 level and its association with clinical features in sarcoma patients. Data on 1,25(OH)2D3, parathyroid hormone, calcium, and calcitonin were collected from 331 patients with sarcoma, while the imaging results and the variation in 1,25(OH)2D3 among 213 patients with sarcoma before and after treatment was further analyzed. Results We found that the serum 1,25(OH)2D3 level was predominantly decreased in patients with sarcoma, with a mean of 45.68 nmol/L. 1,25(OH)2D3 was significantly correlated with the gender and age of sarcoma patients, with more substantial reductions in women and younger patients. Among sarcoma patients, those with progressive disease exhibited a 7.08 nmol/L (−13.73%) decrease in serum 1,25(OH)2D3 levels compared to baseline, while patients with non-progressive disease showed a 1.11 nmol/L (+ 7.0%) increase. Conclusion The variation of serum 1,25(OH)2D3 can predict the disease status of patients with sarcoma. Decreased serum 1,25(OH)2D3 levels are indicative of disease progression in sarcoma patients, suggesting its potential for application as a prognostic marker for disease assessment in this patient population.

Abstract Currently, there is still debate over the effectiveness of transcranial direct current stimulation (tDCS) in treating obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and anxiety disorders (ADs). To investigate the immediate and long-term effectiveness of tDCS in these diseases, we conducted a systematic review and quantitative analysis of existing literature on the treatment of OCD, PTSD, and ADs with tDCS. Following the PRISMA guidelines, we searched seven electronic databases and systematically retrieved articles published from May 2012 to June 2024 that compared the effects of active tDCS with sham stimulation in the treatment of these disorders. We included primary outcome measures such as the change scores in disorder-specific and general anxiety symptoms before and after treatment, as well as secondary outcomes such as changes in disorder-specific and general anxiety symptoms at follow-up. We also assessed the impact of tDCS on depressive symptoms. Fifteen papers met the eligibility criteria. Overall, the results of meta-analysis indicated that tDCS had a high effect in improving specific symptoms (SMD = −0.73, 95% CI: −1.09 to −0.37) and general anxiety symptoms (SMD = −0.75; 95% CI: −1.23 to −0.26) in OCD, PTSD and ADs, with effects lasting up to 1 month and showing a moderate effect size. Furthermore, tDCS demonstrated immediate and significant alleviation of depressive symptoms in these diseases. This study concludes that tDCS can serve as a non-invasive brain stimulation technology for treating these disorders, and the therapeutic effects can be maintained for a period of time.

Abstract Background Camptothecin (CPT) is one of the frequently used small chemotherapy drugs for treating hepatocellular carcinoma (HCC), but its clinical application is limited due to severe toxicities and acquired resistance. Combined chemo-gene therapy has been reported to be an effective strategy for counteracting drug resistance while sensitizing cancer cells to cytotoxic agents. Thus, we hypothesized that combining CPT with miR-145 could synergistically suppress tumor proliferation and enhance anti-tumor activity. Methods Lactobionic acid (LA) modified lipid nanoparticles (LNPs) were developed to co-deliver CPT and miR-145 into asialoglycoprotein receptors-expressing HCC in vitro and in vivo. We evaluated the synergetic antitumor effect of miR-145 and CPT using CCK8, Western blotting, apoptosis and wound scratch assay in vitro, and the mechanisms underlying the synergetic antitumor effects were further investigated. Tumor inhibitory efficacy, safety evaluation and MRI-visible ability were assessed using diethylnitrosamine (DEN) + CCl4-induced HCC mouse model. Results The LA modification improved the targeting delivery of cargos to HCC cells and tissues. The LA-CMGL-mediated co-delivery of miR-145 and CPT is more effective on tumor inhibitory than LA-CPT-L or LA-miR-145-L treatment alone, both in vitro and in vivo, with almost no side effects during the treatment period. Mechanistically, miR-145 likely induces apoptosis by targeting SUMO-specific peptidase 1 (SENP1)-mediated hexokinase (HK2) SUMOylation and glycolysis pathways and, in turn, sensitizing the cancer cells to CPT. In vitro and in vivo tests confirmed that the loaded Gd-DOTA served as an effective T1-weighted contrast agent for noninvasive tumor detection as well as real-time monitoring of drug delivery and biodistribution. Conclusions The LA-CMGL-mediated co-delivery of miR-145 and CPT displays a synergistic therapy against HCC. The novel MRI-visible, actively targeted chemo-gene co-delivery system for HCC therapy provides a scientific basis and a useful idea for the development of HCC treatment strategies in the future.

Abstract Human society is facing increasingly serious problems of environmental pollution and energy shortage, and up to now, achieving high NH3-SCR activity at ultra-low temperatures (

Abstract Background Esophageal cancer is a significant global health concern, ranking seventh in incidence and sixth in mortality. It encompasses two pathological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, with ESCC being more prevalent globally and associated with higher mortality rates. The POU (Pit-Oct-Unc) domain family transcription factors, comprising 15 members, play important roles in embryonic development and organ formation. Aberrant expression of POUs has been observed in several human cancers, influencing cell proliferation, tumor invasion, and drug resistance. However, their specific role in ESCC remains unknown. Methods We analyzed TCGA and GEO databases to assess POUs expression in ESCC tissues. Kaplan-Meier and ROC analyses were used to evaluate the prognostic value of POUs. Gene Set Enrichment Analysis and Protein-Protein interaction network were used to explore the potential pathway. Functional assays (Cell Counting Kit-8, EdU Staining assay, and cloning formation assay) and mechanism analyses (RNA-seq, flow cytometry, and Western blot) were conducted to determine the effects of POU4F1 knockdown on ESCC cell phenotypes and signaling pathways. Results POU4F1 and POU6F2 were upregulated in various cancer tissues, including ESCC, compared to normal tissues. POU4F1 expression was significantly correlated with patient survival and superior to previous models (AUC = 0.776). Knockdown of POU4F1 inhibited ESCC cell proliferation and affected cell cycle, autophagy, and DNA damage pathways in ESCC cells. Conclusion POU4F1 is a novel and promising prognostic and therapeutic target for ESCC patients, providing insights into potential treatment strategies.

Abstract Autophagy is closely related to the occurrence and development of human malignancies; however, the detailed mechanisms underlying autophagy in cervical cancer require further investigation. Previously, we found that the ectopic expression of NCAPH, a regulatory subunit of condensed protein complexes, significantly enhanced the proliferation of tumor cells; however, the underlying mechanisms were unclear. Here, we revealed that NCAPH is a novel autophagy-associated protein in cervical cancer that promotes cell proliferation by inhibiting autophagosome formation and reducing autophagy, with no effect on the cell cycle, apoptosis, or aging. Tripartite motif-containing protein 21 (TRIM21) is well known to be involved in inflammation, autoimmunity and cancer, mainly via its E3 ubiquitin ligase activity. Mass spectrometry and immunoprecipitation assays showed that TRIM21 interacted with NCAPH and decreased the protein stability of NCAPH via ubiquitination at the K11 lysine residue. Structural domain mutation analysis revealed that TRIM21 combined with NCAPH through its PRY/SPRY and CC domains and accelerated the degradation of NCAPH through the RING domain. Furthermore, TRIM21 promoted autophagosome formation and reduced cell proliferation by inhibiting NCAPH expression and the downstream AKT/mTOR pathway in cervical cancer cells. Immunohistochemical staining revealed that the protein expression of TRIM21 was negatively correlated with that of NCAPH and positively correlated with that of beclin-1 in cervical cancer tissues. Therefore, we provide evidence for the role of the TRIM21-NCAPH axis in cervical cancer autophagy and proliferation and the involvement of the AKT/mTOR signaling pathway in this process. These results deepen our understanding of the carcinogenesis of cervical cancer, broaden the understanding of the molecular mechanisms of TRIM21 and NCAPH, and provide guidance for individualized treatment of cervical cancer in the future.

Land use influences soil biota community composition and diversity, and then belowground ecosystem processes and functions. To characterize the effect of land use on soil biota, soil nematode communities in crop land, forest land and fallow land were investigated in six regions of northern China. Generic richness, diversity, abundance and biomass of soil nematodes was the lowest in crop land. The richness and diversity of soil nematodes were 28.8 and 15.1% higher in fallow land than in crop land, respectively. No significant differences in soil nematode indices were found between forest land and fallow land, but their network keystone genera composition was different. Among the keystone genera, 50% of forest land genera were omnivores-predators and 36% of fallow land genera were bacterivores. The proportion of fungivores in forest land was 20.8% lower than in fallow land. The network complexity and the stability were lower in crop land than forest land and fallow land. Soil pH, NH4+-N and NO3−-N were the major factors influencing the soil nematode community in crop land while soil organic carbon and moisture were the major factors in forest land. Soil nematode communities in crop land influenced by artificial management practices were more dependent on the soil environment than communities in forest land and fallow land. Land use induced soil environment variation and altered network relationships by influencing trophic group proportions among keystone nematode genera.

Abstract Background Cardiometabolic multimorbidity (CMM) is a growing global health problem, and obstructive sleep apnea (OSA) is recognized as an important risk factor for cardiovascular disease. However, the impact of OSA on the prognosis of CMM patients remains unclear. Methods This study was a sub-study of OSA-acute coronary syndrome (ACS) and included 1, 927 hospitalized ACS patients. Patients were divided into the CMM group and the non-CMM group. OSA was diagnosed using the apnea-hypopnea index (AHI). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The secondary endpoint included cardiac events, all-cause death and all repeat revascularizations. Results This study enrolled 1, 927 patients hospitalized for ACS, with a median follow-up of 3 years. Among them, 723 patients (37.5%) had CMM, while 1, 204 patients (62.5%) did not have CMM. Over half of the patients in each group had OSA. OSA patients exhibited worse cardiometabolic profiles than their non-OSA counterparts, including higher body mass index (BMI), glycemic indices, lipids and inflammation. In the CMM group, OSA patients had a significantly higher incidence of MACCE than non-OSA patients (34.7% vs. 23.7%, p = 0.004). These results remained significant after adjustment, indicating that OSA substantially increased the risk of MACCE in the CMM group (adjusted hazard ratio [HR]: 1.432; 95% confidence interval [CI]: 1.017–2.016; p = 0.040). Conversely, the incidence of MACCE was similar between OSA and non-OSA subgroups within the non-CMM cohort. Subgroup analyses showed that OSA increased the risk of MACCE in CMM patients aged ≥ 60 years (adjusted HR: 1.642; 95% CI: 1.031–2.615; p = 0.037) and in those with specific clinical characteristics. Conclusion OSA significantly impacts the prognosis of CMM patients, highlighting the need for targeted OSA screening and management strategies to improve outcomes in this population potentially.

Clostridium perfringens (C. perfringens) is an important veterinary pathogen and a noteworthy threat to human and animal health. Recently, there has been a significant rise in the number of moose fatalities caused by this rare, endemic species in China. Currently, there is an increasing trend in conducting whole-genome analysis of C. perfringens strains originating from pigs and chickens, whereas fewer studies have been undertaken on Elaphurus davidianus-originating strains at the whole-genome level. Our laboratory has identified and isolated five C. perfringens type A from affected Elaphurus davidianus. The current study identified the most potent strain of C. perfringens, which originated from Elaphurus davidianus, and sequenced its genome to reveal virulence genes and pathogenicity. Our findings show that strain CX1-4 exhibits the highest levels of phospholipase activity, hemolytic activity, and mouse toxicity compared to the other four isolated C. perfringens type A strains. The chromosome sequence length of the CX1-4 strain was found to be 3,355,389 bp by complete genome sequencing. The current study unveils the genomic characteristics of C. perfringens type A originating from Elaphurus davidianus. It provides a core foundation for further investigation regarding the prevention and treatment of such infectious diseases in Elaphurus davidianus.

Abstract Objectives To explore the value of preoperative magnetic resonance imaging (MRI) characterization of intracranial solitary fibrous tumors (ISFT) and to evaluate the effectiveness of preoperative MRI features in predicting pathological grading. Materials and methods This retrospective analysis comprised the clinical and preoperative MRI characterization of 55 patients with ISFT in our hospital, including 27 grade II cases and 28 grade III cases confirmed by postoperative pathology. Variables included age, sex, tumor location, cross-midline status, signal characteristics of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), T2-fluid-attenuated inversion recovery (T2-FLAIR), and diffusion‑weighted imaging (DWI), peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel, maximum tumor diameter, maximum, minimum, and average values of apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumors enhancement mode, meningeal tail sign, skull invasion, cerebral parenchymal invasion, and venous sinus involvement. The independent samples t test or Mann–Whitney U test was performed to compare continuous data between the two groups, and the Pearson chi-squared test or Fisher’s exact test was used to compare categorical data. In addition, bivariate logistic regression was performed to construct a comprehensive model, and receiver operating characteristic (ROC) curves were generated to calculate the areas under the curve (AUCs), thereby determining the value of each parameter in the differential diagnosis of grades II and III ISFT. Results The mean age at onset was similar between patients with grades II and III ISFT (46.77 ± 14.66 years and 45.82 ± 12.07 years, respectively). The proportions of men among patients with grades II and III ISFT were slightly higher than those of female patients (male/female: 1.25 [15/12] and 1.33 [16/12], respectively). There were significant differences between grades II and III ISFT in the T2-FLAIR and DWI signal characteristics, maximum, minimum, and average values of the apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumor location, and skull invasion (P = 0.001, P = 0.018, P = 0.000, P = 0.000, P = 0.000, P = 0.010, and P = 0.032, respectively). However, no significant differences were noted between grades II and III ISFT in age, sex, cross-midline status, T1WI and T2WI signal characteristics, peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel shadow, enhancement mode, meningeal tail sign, maximum tumor diameter, brain parenchyma invasion, or venous sinus involvement (all P > 0.05). Moreover, binary logistic regression analysis showed that the model accuracy was 89.1% when ADCmin was included in the regression equation. Moreover, ROC curve analysis showed that the AUC of ADCmin was 0.805 (0.688, 0.922), sensitivity was 74.1%, specificity was 75.0%, and the cutoff value was 672 mm2/s. Conclusions Grade III ISFT patients displayed more mixed T2-FLAIR signal characteristics and DWI signal characteristics than grade II patients, as shown by higher skull invasion and tumor mass collapse midline distribution and lower ADCmax, ADCmean, and ADCmin values. The ADCmin value was significant in the preoperative assignment of grades II and III ISFT, thereby contributing to enhanced accuracy in the imaging grading diagnosis of the disease.

Abstract Integration of functional fillers into liquid metals (LM) induces rheology modification, enabling the free-form shaping of LM at the micrometer scale. However, integrating non-chemically modified low-dimensional materials with LM to form stable and uniform dispersions remain a great challenge. Herein, we propose a solvent-assisted dispersion (SAD) method that utilizes the fragmentation and reintegration of LM in volatile solvents to engulf and disperse fillers. This method successfully integrates MXene uniformly into LM, achieving better internal connectivity than the conventional dry powder mixing (DPM) method. Consequently, the MXene/LM (MLM) coating exhibits high electromagnetic interference (EMI) shielding performance (105 dB at 20 μm, which is 1.6 times that of coatings prepared by DPM). Moreover, the rheological characteristic of MLM render it malleable and facilitates direct printing and adaptation to diverse structures. This study offers a convenient method for assembling LM with low-dimensional materials, paving the way for the development of multifunctional soft devices.

Abstract Background Toxoplasma gondii infection causes adverse pregnancy outcomes by affecting the expression of immunotolerant molecules in decidual immune cells. Galectin-9 (Gal-9) is widely expressed in decidual macrophages (dMφ) and is crucial for maintaining normal pregnancy by interacting with the immunomodulatory protein T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3). However, the effects of T. gondii infection on Gal-9 expression in dMφ, and the impact of altered Gal-9 expression levels on the maternal–fetal tolerance function of decidual natural killer (dNK) cells, are still unknown. Methods Pregnancy outcomes of T. gondii-infected C57BL/6 and Lgals9 −/− pregnant mice models were recorded. Expression of Gal-9, c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), and Forkhead box protein O1 (FOXO1) was detected by western blotting, flow cytometry or immunofluorescence. The binding of FOXO1 to the promoter of Lgals9 was determined by chromatin immunoprecipitation–polymerase chain reaction (ChIP-PCR). The expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP-response element binding protein (CREB), phosphorylated CREB (p-CREB), T-box expressed in T cells (T-bet), interleukin 10 (IL-10), and interferon gamma (IFN-γ) in dNK cells was assayed by western blotting. Results Toxoplasma gondii infection increased the expression of p-JNK and FOXO1 in dMφ, resulting in a reduction in Gal-9 due to the elevated binding of FOXO1 with Lgals9 promoter. Downregulation of Gal-9 enhanced the phosphorylation of ERK, inhibited the expression of p-CREB and IL-10, and promoted the expression of T-bet and IFN-γ in dNK cells. In the mice model, knockout of Lgals9 aggravated adverse pregnancy outcomes caused by T. gondii infection during pregnancy. Conclusions Toxoplasma gondii infection suppressed Gal-9 expression in dMφ by activating the JNK/FOXO1 signaling pathway, and reduction of Gal-9 contributed to dysfunction of dNK via Gal-9/Tim-3 interaction. This study provides new insights for the molecular mechanisms of the adverse pregnancy outcomes caused by T. gondii. Graphical Abstract

Abstract Purpose To evaluate the availability, cost, affordability of anti-cancer medicines in Nanjing, Jiangsu. Methods A longitudinal tracking investigation study was performed to collect information about 24 essential anti-cancer medicines (EAMs) and 17 innovative anti-cancer medicines (IAMs) in 26 healthcare institutions in Nanjing from 2016 to 2020. The availability, cost, drug utilization and affordability of EAMs and IAMs were investigated. Results The availability of EAMs showed no significant changes in Nanjing, but the availability of IAMs showed a significant increase in 2018 and 2019 and tended to stabilize in 2020. For EAMs, the DDDc(Defined Daily Dose cost) of LPGs (Lowest-Priced Generics) showed no significant changes, and the DDDc of OBs (Originator Brands) and IAMs significantly decreased. The DDDs(Defined Daily Doses) of EAMs (LPGs) showed a decreasing trend since 2016 and rose again in 2019. Overall, the DDDs of EAMs (LPGs) decreased by 25.18% between 2016 and 2020, but the proportion selected for clinical treatment remained at 67.35% in 2020. The DDDs of EAMs (OBs) and IAMs both showed an increasing trend year by year, with a proportional increase of 207.72% and 652.68%, respectively; but the proportion selected for clinical treatment was only 16.09% and 16.56% respectively in 2020. EAMs (LPGs) had good affordability for urban residents but poor affordability for rural residents; the affordability of EAMs (OBs) and IAMs was poor for both urban and rural residents. Conclusions There were no significant changes in the availability and cost of EAMs (LPGs), whose lower prices showed better affordability. Although their relative change in drug utilization showed a decreasing trend, they still dominated clinical treatment. Driven by the national drug price negotiation (NDPN) policy, the availability of IAMs was on the rise. It is necessary to further develop and strengthen policies for essential medicines procurement assessment to improve the accessibility of EAMs.

Abstract Babesia spp. and Theileria spp. are tick-borne protozoan parasites with veterinary importance. In China, epidemiological and genetic investigations on many Babesia and Theileria species were still absent in many areas and many tick species. From Aug 2021 to May 2023, 645 ticks were collected from the body surface of domestic animals (camels, goats, sheep, and cattle) using tweezers in seven counties in three provinces including Xinjiang (Qitai, Mulei, Hutubi, and Shihezi counties), Chongqing (Youyang and Yunyang counties), and Qinghai (Huangzhong county). Three tick species were morphologically and molecularly identified (334 Hyalomma asiaticum from Xinjiang, 245 Rhipicephalus microplus from Chongqing, and 66 Haemaphysalis qinghaiensis from Qinghai). A total of three Babesia species and two Theileria species were detected targeting the 18S gene. The COI and cytb sequences were also recovered from Babesia strains for further identification. In R. microplus from Chongqing, Babesia bigemina, the agent of bovine babesiosis, was detected. Notably, in H. asiaticum ticks from Xinjiang, a putative novel genotype of Babesia caballi was identified (0.90%, 3/334), whose COI and cytb genes have as low as 85.82% and 90.64–90.91% nucleotide identities to currently available sequences. It is noteworthy whether the sequence differences of its cytb contribute to the drug resistance of this variant due to the involvement of cytb in the drug resistance of Babesia. In addition, Theileria orientalis and Theileria annulata were detected in R. microplus from Chongqing (12.20%, 31/245) and H. asiaticum from Xinjiang (1.50%, 5/334), respectively. These results suggest that these protozoan parasites may be circulating in domestic animals in these areas. The pathogenicity of the novel genotype of B. caballi also warrants further investigation.

Abstract Background Previous evidence suggests that low-quality embryos may send negative signals to the endometrium and affect the receptivity of the endometrium. This study aimed to evaluate the influence of transferring an additional low-quality embryo with a high-quality embryo on the pregnancy outcome. Methods A total of 1506 fresh embryo transfer cycles between January 2018 and June 2020 were included. The patients were separated into two groups: a single embryo transfer group (SET, patients receiving a single high-quality embryo) and a double embryo transfer group (DET, patients receiving a high-quality embryo and a low-quality embryo). Main outcome measures including multiple pregnancy rate and live birth rate were discussed. Overall, in the primary analysis, patients who receive an additional low-quality embryo improved the live birth by 8.7% and multiple pregnancy rate by 10.0%. In women aged less than 35 years, compared with SET, DET increased the birth rate by 6.0% but resulted in a 13.5% increase in multiples. Women of 35 years above, adding a low-quality embryo increased the live birth rate by only 2.2% but increased multiples by 14.7%. In patients with one cycle of ET, the same results were obtained. In patients with multiple cycles of ET and adding a low-quality embryo, the live birth rate was similar to SET but with a 14.7% increase in multiples. Conclusions Compared to DET, we prefer to transfer a high-quality embryo. Nevertheless, in women 35 years or older or in patients with multiple cycles of embryo transfer, adding a low-quality embryo did not significantly improve live birth but increased the multiple rate.