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Abstract Objective The cross-sectional study was designed to evaluate the association of ocular surface inflammation with systemic conditions in patients with systemic lupus erythematosus (SLE). Methods The study enrolled 30 SLE patients and 30 controls. Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Tear samples from all participants were collected for tear multi-cytokine and chemokine concentration analysis. All participants were assessed for dry eye disease (DED), including Schirmer I test, tear break-up time (TBUT), corneal fluorescein staining (CFS), meibomian gland secretion (MGS), lid-parallel conjunctival folds (LIPCOF), corneal clarity, and symblepharon. Besides, all participants were also examined for conjunctival impression cytology to measure the density of conjunctival goblet cells (CGCs). The peripheral blood indicators from SLE patients were also collected to measure the SLE-associated autoantibody specificities and systemic inflammatory indicators. Pearson and Spearman’s analysis were uesd to examine the correlation between tear cytokines, CGCs, DED-related indicators, and systemic conditions. Results The two groups were matched for age and gender in this study. 36.67% of eyes (11 in 30) of SLE patients and 13.33% of eyes (4 in 30) of controls were diagnosed with DED. OSDI scores, abnormal TBUT percentages, CFS percentages, and DED grading were all higher in SLE patients than in control group, while density of CGCs was lower. There were no significant differences in Schirmer I test, MGS, LIPCOF, corneal clarity, and symblepharon between SLE patients and controls. The levels of tear chemokine (C-X-C motif) ligand 11 (CXCL11) and cytokine interleukin-7 (IL-7) in patients with SLE were significantly higher than those in control group. Moreover, among SLE patients, the severity of DED and the level of tear chemokine CXCL11 were significantly positively correlated with SLE-associated autoantibody specificities. Conclusion Dry eye and tear cytokines and chemokines-mediated ocular surface inflammation persist in SLE patients and are associated with systemic conditions. Therefore, it is necessary for patients with SLE to combine systemic and ocular assessments.

Abstract Intermetallic phases with atomic ordering are highly active and stable in catalysts. However, understanding the atomistic mechanisms of disorder-to-order phase transition, particularly in multi-component systems, remains challenging. Here, we investigate the atom diffusion and phase transition within Pd@Pt-Co cubic nanoparticles during annealing, using in-situ electron microscopy and ex-situ atomic resolution element analysis. We reveal that initial outward diffusing Pd partially substitutes Pt, forming a (Pt, Pd)-Co ternary system in the surface region, enabling the phase transition at a low temperature of 400 °C, followed by shape-preserved inward propagation of the ordered phase. At higher temperatures, excessive interdiffusion across the interface changes the stoichiometric ratio, diminishing the atomic ordering, leading to obvious change in morphology. Calculations indicate that the Pd-substitute in (Pt, Pd)-Co system leads to a significantly lower phase transition temperature compared to that of Pt-Co alloy and thus a lower activation energy for atomic diffusion. These insights into atomistic behavior are crucial for future design of multi-component systems.

Abstract Accurate climate projections are critical for various applications and impact assessments in environmental science and management. This study presents HiCPC (High-resolution CMIP6 downscaled daily Climate Projections over China), a novel dataset tailored to China’s specific needs. HiCPC leverages outputs from 22 global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6). To address inherent biases in daily GCM simulations, an advanced Bias Correction and Spatial Disaggregation (BCSD) method is employed, using the China Meteorological Forcing Dataset (CMFD) as a reference. HiCPC offers detailed daily precipitation and temperature data across China at an enhanced spatial resolution of 0.1° × 0.1°. It covers both the historical period (1979–2014) and future projections (2015–2100) based on four CMIP6 Shared Socioeconomic Pathways (SSPs) scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). Upon validation, HiCPC demonstrates good performance, surpassing CMIP6 GCMs across the historical period. This reinforces its significance for essential research in climate change evaluation and its associated implications within China.

Abstract Little is known about biological processes controlling inorganic phosphate (PO4) in groundwater ecosystems. Here we present analyses of groundwater samples from the Hetao Basin, China that show an increasing contribution of microbial cycling to groundwater PO4 from oxic to anoxic conditions along a flow path with phosphate-bound oxygen isotopes (δ18OPO4). Under oxic conditions, although 25–47% of the dissolved PO4 inherited the initial source signal of igneous apatite, groundwater δ18OPO4 reflected a pronounced impact of intracellular enzymatic cycling. Under anoxic conditions, dissolved PO4 carried a nearly exclusive equilibrium isotope signal, which was probably due to (i) release of PO4 with an equilibrium δ18OPO4 from Fe(III) oxides, as a result of Fe(III) reduction in the presence of Fe(III)- and sulfate-reducing bacteria; and/or (ii) cumulative microbial cycling of dissolved PO4 with increasing groundwater residence time. Our study highlights that PO4 in groundwater is tightly microbially cycled under a wide range of redox conditions and microbial cycling contributes to the release of PO4 in groundwater.

ABSTRACTBackground Male infertility is a worldwide population health concern, but its etiology remains poorly understood. Tortoise-shell glue (TSG) is widely utilized as a pharmaceutical or dietary supplement for various health ailments. This study aimed to evaluate the effects of TSG on male infertility in obese rats.Methods A male infertility with obesity rat model was established after a high-fat diet (HFD) and cyclophosphamide (CTX) treatment. The body weight, testis weight, and weight of adipose tissues around the epididymis were detected. We then evaluated spermatozoon motility and concentration and testis pathological changes. Next, we assessed the hypothalamic-pituitary-gonadal (HPG) axis. Moreover, serum metabolomics was used to identify differential metabolites. The Spearman correlation analysis was employed to assess the correlation between differential metabolites and sex hormone levels.Results Here, we demonstrated that TSG alleviated obesity and male infertility. Meanwhile, TSG restored the function of the HPG axis in obese infertility rats, including mRNA levels of GnRH, GnRHR, RFRP-3, and kisspeptin in the hypothalamus and pituitary and sex hormone levels in the serum. In addition, 16 potentially significant metabolites, such as Quinapril and Malabaricone C, were identified as significant in the therapeutic effects of TSG on male infertility. The majority of these differential metabolites exhibited recovery following TSG treatment. The further Spearman analysis demonstrated the close correlation between differential metabolites and sex hormones, especially Kamahine C.Conclusion TSG attenuated obesity and male infertility in rats through the HPG axis by regulating serum metabolites. It shows potential as a viable treatment option for male infertility.

Abstract Remote sensing technology has the potential to enhance the lake’s large-scale and long-term dynamic monitoring capabilities significantly. High-quality in-situ datasets are essential for improving the accuracy and reliability of remote sensing retrieval of lake ecosystems. This dataset provides satellite-ground synchronized in-situ data on water multi-parameters for typical lakes in China spanning the period between 2020 and 2023. It includes quality-checked water optical parameters (remote sensing reflectance (Rrs), chlorophyll-a (Chl-a), total suspended matter (TSM) and Secchi disk depth (SDD)), and water surface temperature (WST) data. It encompasses 586 sampling points across 18 lakes. The dataset exhibits two significant highlights: Firstly, synchronous observations from multiple satellites are coordinated during the data collection effectively supporting the retrieval and validation of water remote sensing products. Secondly, it encompasses diverse data types, collecting synchronous measurements of Rrs and various parameters. This dataset will continuously update, substantially enhancing regional and global lake monitoring capabilities through satellite remote sensing data.

Abstract Background Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. Methods Age-specific mortality data for cervical and breast cancers among Chinese women aged 20–84 years were obtained from China’s National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban–rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. Results From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35–64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5–7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: − 0.7%, 95% CI − 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI − 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: − 2.7%, 95% CI − 4.6 to − 0.7%, P = 0.007) in urban areas. Urban–rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35–54 age group across urban and rural areas, periods, and regions in China. Conclusions Special attention should be given to women aged 35–54 years due to mortality trends and rural–urban disparities. Focusing on vulnerable age groups and addressing rural–urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.

Objective The application of sprayed waterproof membranes can enable composite action between the shotcrete and the waterproof membrane in metro tunnel linings. However, there is currently no design guidance or reference literature for analyzing waterproof single-layer lining composite structures. A design method is proposed to determine the thickness of the tunnel single-layer lining composite structure and to allocate bending moments according to stiffness based on intermediate layer theory. Method The theoretical derivation of equivalent thickness and bending moment distribution is first conducted. The Qingdao Metro Line 1 Xizhen Station is selected for calculating the equivalent thickness and bending moment distribution of each layer, yielding theoretical analytical solutions. To verify the accuracy of the theory, numerical simulation analysis is performed using the finite element Ansys, comparing and discussing the equivalent thickness and bending moment distribution for different second layer shotcrete thicknesses in tunnels. Finally, indoor experiments are conducted to perform four-point beam tests comparing structures with and without a sprayed waterproof membrane. The equivalent thickness of the composite structure is calculated through the reverse deduction of the bending strength reduction ratio of the intermediate layer structure. Result & Conclusion The proposed design method can accurately determine the equivalent thickness and bending moment distribution, proving to be both reasonable and feasible.

ObjectiveTo investigate the levels of seven organophosphorus esters （OPEs） and six indicator polychlorinated biphenyls （PCBs） in pig liver from Hubei Province， the risk of exposure to OPEs and PCBs in Hubei residents through dietary intake of pig liver were assessed.MethodsA total of 51 pig liver samples were collected from Hubei Province in 2022. By isotope dilution method， OPEs and PCBs in pig liver samples were determined by ultra-high performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS） and high resolution gas chromatography high resolution magnetic mass spectrometry （HRGC-HRMS）， respectively. The source of pollution was explored by analyzing the fingerprint characteristics. Based on the estimation dietary intake （EDI） and hazard index （HI） of Hubei residents， the risk of exposure to OPEs and PCBs through dietary intake of pig liver was assessed.ResultsThe levels of seven OPEs （∑7OPEs） in pig liver ranged from 15.6 to 262 ng/g， with an average of 89.7 ng/g （P50=88.4 ng/g）. The levels of six PCBs （∑6PCBs） ranged from 3.67 to 19.5 pg/g， with an average of 9.02 pg/g （P50=8.21 pg/g）. Tris （1，3-Dichloro-2-Propyl） Phosphate （TDCPP） and PCB 52 was the main characteristic pollutant of OPEs and PCBs in pig liver， respectively. Some OPEs were positively correlated with each other （r=0.278-0.841， P

Objective To investigate the expression levels of platelet microparticles(PMPs) in patients with diabetic nephropathy (DN) and their relationship with renal injury. Methods Thirty DN patients, 30 T2DM patients without DN and 30 healthy controls were enrolled. Flow cytometry was used to detect the quantity and phenotype of PMPs, and ELISA was used to measure the levels of plasma renin, angiotensin Ⅱ (angiotoninⅡ, AngⅡ), vascular endothelial growth factor (vascular endothelial growth factor, VEGF) and transforming growth factor-β1(transforming growth factor-β1, TGF-β1). Kidney function was determined by blood biochemistry. Results The quantity of PMPs in the DN group was (1 564±346) particles/μL, which was significantly higher than that in the non-DN group (1 246±312) particles/μL and the control group (1 223±299) particles/μL (P

Abstract Female urethral caruncle is the most common urethral mass in postmenopausal women, yet there is a lack of studies on its imaging. The aim of this study was to provide a summary of the clinical and ultrasound features as well as the precise location of female urethral caruncle. This study reviewed the clinical and ultrasonographic records of 20 consecutive women with pathologically confirmed urethral caruncle. Data on patient demographics, symptoms, and transperineal and transrectal ultrasound imaging features, including location, shape, margin, size, blood flow, and inner echo of the caruncle, were extracted. Each patient presented with only one mass at the urethral meatus. Most caruncles were located on the posterior lip (75%) of the urethra, presenting as oval (80%), mixed-echoic (50%), or hypo-echoic (40%) nodules with abundant linear (40%) or dendritic (60%) blood flow. The average distance between the bladder neck and the cranial end of the masses was 28 mm. Hyper-echogenic spots, cystic echo areas, and macrocalcifications were detected in thirteen caruncles (70%). This study shows that transperineal combined with transrectal ultrasound can be used to assess female urethral caruncle, and its relative location to the urethra can be accurately described, which is helpful for surgeons making preoperative localization and conversations.

Abstract Background The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique. Methods A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models. Results The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p

Abstract Background Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. Objective To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. Methods Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. Results All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). Conclusion The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

This study focuses on producing polyurethane dispersion (PUD)/carboxylated nitrile butadiene rubber (XNBR) blends with different types of crosslinkers without both accelerators and sulphur. Two types of crosslinkers: epoxide crosslinker and organo-modified siloxane, are introduced in the PUD/XNBR (blending ratio of 80:20). The zeta potential and particle size of the PUD/XNBR blends were determined using a dynamic light-scattering nanoparticle analyser. The chemical interaction and surface roughness of the PUD/XNBR blends were evaluated using Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). The zeta potential and particle size of the PUD were influenced by XNBR blending and the types of crosslinkers. FTIR observations indicate that the XNBR and the crosslinkers facilitated intermolecular hydrogen bonding and different extents of ordered hydrogen bonding. A higher degree of ordered hydrogen bonding can be associated with a higher surface roughness of the PUD/XNBR blends. Nevertheless, the hybrid crosslinkers can be used to achieve reasonable surface roughness for the easier donning of latex gloves. The research findings can be applied to design glove products with desirable surface roughness and intermolecular bonding.

Noncontact optical thermometers have attracted widespread attention, but existing problems such as single-mode and low-sensitivity thermometers still urgently need to be solved. Herein, a novel multiple-mode thermometer was designed for the polymorphism LaSc3(BO3)4:Eu2+/3+,Li+. X-ray diffraction (XRD) patterns revealed a slight transition between α- and β-phases with the concentrations of the dopants, which is further proved by structure refinements and first-principles calculations. The coexistence of Eu2+ and Eu3+ in the phosphors and their relative percentages were confirmed by X-ray absorption near-edge structure (XANES) spectra. Benefiting from appropriate emissions from Eu2+ and Eu3+ without obvious energy transfer and their opposite changing trends with temperatures under 307 nm excitation, a triple-mode optical thermometer is obtained for this material within the temperature range of 150–450 K. The highest sensitivities of 27.65, 14.05, and 7.68 %·K−1 are achieved based on two fluorescence intensity ratio (FIR) modes of Eu2+ and Eu3+ (5d–4f/5D0–7F2,4) and the fluorescence lifetime (FL) mode of Eu2+, respectively. To the best of our knowledge, the former is almost the highest in Eu2+ and Eu3+ co-doped thermometers. These results indicate that this material may be used as an excellent multiple-mode optical thermometer.

Abstract This report presents liquid metal-based infrared-modulating materials and systems with multiple modes to regulate the infrared reflection. Inspired by the brightness adjustment in chameleon skin, shape-morphing liquid metal droplets in silicone elastomer (Ecoflex) matrix are used to resemble the dispersed “melanophores”. In the system, Ecoflex acts as hormone to drive the deformation of liquid metal droplets. Both total and specular reflectance-based infrared camouflage are achieved. Typically, the total and specular reflectances show change of ~44.8% and 61.2%, respectively, which are among the highest values reported for infrared camouflage. Programmable infrared encoding/decoding is explored by adjusting the concentration of liquid metal and applying areal strains. By introducing alloys with different melting points, temperature-dependent infrared painting/writing can be achieved. Furthermore, the multi-layered structure of infrared-modulating system is designed, where the liquid metal-based infrared modulating materials are integrated with an evaporated metallic film for enhanced performance of such system.

Abstract Background Tyrosine phosphorylation of intracellular proteins is a post‐translational modification that plays a regulatory role in signal transduction during cellular events. Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases (PTPs) contributed their role as a convergent node to mediate cross‐talk between signaling pathways. In the context of cancer, PTP‐mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy. This is achieved by the promotion of constitutive activation of growth‐stimulatory signaling pathways or modulation of the immune‐suppressive tumor microenvironment. Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors, reversing drug resistance that was responsible for clinical failures during cancer therapy. Areas covered This review aimed to elaborate recent insights that supported the involvement of PTP‐mediated pathways in the development of resistance to targeted therapy and immune‐checkpoint therapy. Expert opinion This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long‐term tumor regression. Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced‐stage tumors.

Abstract Background Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation. Methods Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis. Results Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria. Conclusion This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.

Abstract Stomatal movement is vital for plants to exchange gases and adaption to terrestrial habitats, which is regulated by environmental and phytohormonal signals. Here, we demonstrate that hydrogen peroxide (H2O2) is required for light-induced stomatal opening. H2O2 accumulates specifically in guard cells even when plants are under unstressed conditions. Reducing H2O2 content through chemical treatments or genetic manipulations results in impaired stomatal opening in response to light. This phenomenon is observed across different plant species, including lycopodium, fern, and monocotyledonous wheat. Additionally, we show that H2O2 induces the nuclear localization of KIN10 protein, the catalytic subunit of plant energy sensor SnRK1. The nuclear-localized KIN10 interacts with and phosphorylates the bZIP transcription factor bZIP30, leading to the formation of a heterodimer between bZIP30 and BRASSINAZOLE-RESISTANT1 (BZR1), the master regulator of brassinosteroid signaling. This heterodimer complex activates the expression of amylase, which enables guard cell starch degradation and promotes stomatal opening. Overall, these findings suggest that H2O2 plays a critical role in light-induced stomatal opening across different plant species.

Abstract Corrosion of electrocatalysts during electrochemical operations, such as low potential - high potential cyclic swapping, can cause significant performance degradation. However, the electrochemical corrosion dynamics, including structural changes, especially site and composition specific ones, and their correlation with electrochemical processes are hidden due to the insufficient spatial-temporal resolution characterization methods. Using electrochemical liquid cell transmission electron microscopy, we visualize the electrochemical corrosion of Pd@Pt core-shell octahedral nanoparticles towards a Pt nanoframe. The potential-dependent surface reconstruction during multiple continuous in-situ cyclic voltammetry with clear redox peaks is captured, revealing an etching and deposition process of Pd that results in internal Pd atoms being relocated to external surface, followed by subsequent preferential corrosion of Pt (111) terraces rather than the edges or corners, simultaneously capturing the structure evolution also allows to attribute the site-specific Pt and Pd atomic dynamics to individual oxidation and reduction events. This work provides profound insights into the surface reconstruction of nanoparticles during complex electrochemical processes.

BackgroundLarge language models (LLMs) demonstrated advanced performance in processing clinical information. However, commercially available LLMs lack specialized medical knowledge and remain susceptible to generating inaccurate information. Given the need for self-management in diabetes, patients commonly seek information online. We introduce the Retrieval-augmented Information System for Enhancement (RISE) framework and evaluate its performance in enhancing LLMs to provide accurate responses to diabetes-related inquiries. ObjectiveThis study aimed to evaluate the potential of the RISE framework, an information retrieval and augmentation tool, to improve the LLM’s performance to accurately and safely respond to diabetes-related inquiries. MethodsThe RISE, an innovative retrieval augmentation framework, comprises 4 steps: rewriting query, information retrieval, summarization, and execution. Using a set of 43 common diabetes-related questions, we evaluated 3 base LLMs (GPT-4, Anthropic Claude 2, Google Bard) and their RISE-enhanced versions respectively. Assessments were conducted by clinicians for accuracy and comprehensiveness and by patients for understandability. ResultsThe integration of RISE significantly improved the accuracy and comprehensiveness of responses from all 3 base LLMs. On average, the percentage of accurate responses increased by 12% (15/129) with RISE. Specifically, the rates of accurate responses increased by 7% (3/43) for GPT-4, 19% (8/43) for Claude 2, and 9% (4/43) for Google Bard. The framework also enhanced response comprehensiveness, with mean scores improving by 0.44 (SD 0.10). Understandability was also enhanced by 0.19 (SD 0.13) on average. Data collection was conducted from September 30, 2023 to February 5, 2024. ConclusionsThe RISE significantly improves LLMs’ performance in responding to diabetes-related inquiries, enhancing accuracy, comprehensiveness, and understandability. These improvements have crucial implications for RISE’s future role in patient education and chronic illness self-management, which contributes to relieving medical resource pressures and raising public awareness of medical knowledge.

As the mechanical performance of 3D printed polymers advances, there arises an urgent demand for enhanced methodologies to ensure their structural integrity. In this work, magnetostrictive polymer composites (MPCs) are investigated utilizing an ultraviolet (UV) curable epoxy resin through direct ink writing (DIW) for internal stress detection. A strong correlation between stress and magnetic flux change was observed within the printed MPCs. Impact from the inclusion of fumed silica (FS) as a rheological filler in the matrix were identified and investigated. The tensile strengths of the MPCs were in the range of 31 MPa–34 MPa. The changes in magnetic flux density (ΔB) of the MPCs under quasistatic loading were within the interval of 0.5 to 5.4 Gauss. A similar sensing behavior was obtained for the MPCs during cyclic loading. A similar sensing behavior was obtained for the MPCs during cyclic loading. Furthermore, it was found that incorporating the MPCs into specific layers further increased the tensile strength to over 40 MPa while still showing a significant ΔB response. Additionally, localized deposition of magnetostrictive particles at known stress concentrations emerged as a promising strategy for future stress-sensing endeavors.

BackgroundThe global prevalence of Metabolic Syndrome (MetS) is increasing, primarily characterized by abdominal obesity, which significantly heightens the risk of cardiovascular diseases, gastrointestinal disorders, and cancers. Constipation is a common gastrointestinal issue that impacts both physiological and psychological health and worsens with age. Calcium, an essential mineral vital for human health, has been proven to be crucial not only for bone health but also beneficial for gastrointestinal health. However, the results regarding its impact on constipation are inconsistent. This study aimed to investigate the relationship between dietary calcium intake and constipation in individuals with MetS.MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Participants were assessed for MetS based on the International Diabetes Federation (IDF) criteria. Dietary calcium intake was evaluated through 24-h dietary recalls, and constipation was defined based on the frequency of bowel movements recorded in the bowel health questionnaire. The relationship between calcium intake and constipation was explored using logistic regression models with adjustment for covariates, and restricted cubic spline analyses were also used to investigate nonlinear relationships.ResultsThe study included 4,838 adult participants with MetS. Adjusted logistic regression revealed that an increase in dietary calcium intake was significantly associated with a reduced risk of constipation (OR: 0.562, 95% CI: 0.379 to 0.835, p = 0.006). Compared to the lowest quartile, the highest quartile of dietary calcium intake significantly decreased the risk of constipation (OR: 0.282, 95% CI: 0.115 to 0.691, p = 0.008). Results from the restrictive cubic spline analysis indicated a negative linear association between dietary calcium intake and constipation risk (non-linearity p = 0.704).ConclusionThe findings suggested that increased dietary calcium intake is associated with a decreased risk of constipation among MetS patients, emphasizing dietary calcium as a potentially modifiable factor for managing gastrointestinal symptoms in this population.

IntroductionLung cancer is a leading cause of cancer-related deaths, with its incidence continuing to rise. Chromatin remodeling, a crucial process in gene expression regulation, plays a significant role in the development and progression of malignant tumors. However, the role of chromatin regulators (CRs) in lung adenocarcinoma (LUAD) remains underexplored.MethodsThis study developed a chromatin regulator-related signature (CRRS) using a 429-combination machine learning approach to predict survival outcomes in LUAD patients. The CRRS model was validated across multiple independent datasets. We also investigated the impact of CRRS on the immune microenvironment, focusing on immune cell infiltration. To identify potential therapeutic targets, TFF1, a chromatin regulator, was knocked down using siRNA in LUAD cells. We assessed its impact through apoptosis analysis, proliferation assays, and in vivo tumor growth studies. Additional validation was performed using Ki67 expression and TUNEL assays.ResultsThe CRRS accurately predicted survival outcomes and was shown to modulate immune cell infiltration in the tumor microenvironment. High-risk patients demonstrated increased activity in cell cycle regulation and DNA repair pathways, along with distinct mutation profiles and immune responses compared to low-risk patients. TFF1 emerged as a key therapeutic target. Knockdown of TFF1 significantly inhibited LUAD cell proliferation, induced apoptosis, and suppressed in vivo tumor growth. Ki67 and TUNEL assays confirmed the role of TFF1 in regulating tumor growth and cell death.DiscussionThese findings highlight the potential of chromatin regulators in prognostic modeling and immune modulation in LUAD. TFF1 was identified as a promising therapeutic target, suggesting that targeting TFF1 could provide new treatment strategies. Further research is warranted to explore its full potential and therapeutic applicability.

Oxidative stress during sepsis could play a crucial role in the pathogenesis of several diseases, especially cardiovascular disorders. In fact, myocardial dysfunction during sepsis is caused by a number of chemicals, one of which is hydrogen peroxide (H2O2). Therefore, sepsis‐induced cardiomyopathy can be controlled through modulation of oxidative stress. Despite the encouraging pharmacological activities demonstrated by inorganic nanostructures, the mechanisms behind their blood protein interaction and antioxidant activity remain unclear. In order to advance the investigation for fabricating nanostructure platforms and studying their antioxidant effects as well as blood protein binding affinities, we explored the synthesis of manganese oxide (Mn3O4) nanorods via hydrothermal method and subsequent characterization using various techniques. The antioxidant effects against H2O2-induced oxidative stress in AC16 cardiomyocytes were then evaluated by different cellular and molecular assays. Additionally, the interaction of Mn3O4 nanorods with hemoglobin was investigated by experimental and and docking analyses. The results showed that synthesized Mn3O4 nanorods had an absorption peak in the range of 260 to 420 nm, vibration bands centered at 510 cm−1, 629 cm−1 and 410 cm−1, 13 distinct XRD peaks, a rod-like morphology with a diameter range of 10 to 75 nm, a hydrodynamic size of 371.7 nm, and a zeta potential of −43.3 mV. Moreover, the antioxidant assays indicated that synthesized Mn3O4 nanorods can trigger a protective effect against H2O2-induced oxidative stress in AC16 cardiomyocytes through inhibition of reactive oxygen species (ROS) overproduction, increased content of superoxide dismutase (SOD) and catalase and glutathione (GSH), and reduction of caspase-3 activity. Furthermore, the fluorescence quenching mechanism of hemoglobin by Mn3O4 nanorods was determined to be controlled by a spontaneous and static quenching process, involvement of hydrogen bonds, a binding affinity (Kb) value of 104 M−1, and number of binding site (n) of around 1.03. Additionally, it was found that Mn3O4 nanorods induced a slight conformational change in the hemoglobin structure, where Tyr35 and Trp37 move to a hydrophilic microenvironment. In conclusion, it can be suggested that Mn3O4 nanorods with a reasonable plasma protein binding affinity can be used as an antioxidant co-therapy in cardiac dysfunction during sepsis.

BackgroundMandibular defects pose significant challenges in reconstructive surgery, and scaffold materials are increasingly recognized for their potential to address these challenges. Among various scaffold materials, Beta-tricalcium phosphate (β-TCP) is noted for its exceptional osteogenic properties. However, improvements in its biodegradation rate and mechanical strength are essential for optimal performance.MethodsIn this study, we developed a novel β-TCP-based scaffold, CFBB, by calcining fetal bovine cancellous bone. To enhance its properties, we modified CFBB with Chitosan (CS) and Zinc (Zn), creating three additional scaffold materials: CFBB/CS, CFBB/Zn2+, and CFBB/Zn2+/CS. We conducted comprehensive assessments of their physicochemical and morphological properties, degradation rates, biocompatibility, osteogenic ability, new bone formation, and neovascularization both in vitro and in vivo.ResultsOur findings revealed that all four materials were biocompatible and safe for use. The modifications with CS and Zn2+ significantly improved the mechanical strength, osteogenic, and angiogenic properties of CFBB, while concurrently decelerating its resorption rate. Among the tested materials, CFBB/Zn2+/CS demonstrated superior performance in promoting bone regeneration and vascularization, making it a particularly promising candidate for mandibular reconstruction.ConclusionThe CFBB/Zn2+/CS scaffold material, with its enhanced mechanical, osteogenic, and angiogenic properties, and a controlled resorption rate, emerges as a highly effective alternative for the repair of oral mandible defects. This study underscores the potential of combining multiple bioactive agents in scaffold materials to improve their functionality for specific clinical applications in bone tissue engineering.

A strategy for the synthesis of α-carboline derivatives from indole-3-carboxaldehydes and 3-aminocyclohex-2-enones under metal-free conditions has been developed. The combination use of phenyliodine (III) diacetate (PIDA) and benzoic acid could significantly facilitate the corresponding [3 ​+ ​3] annulation process. This newly developed strategy featured unextraordinary chemoselectivity, good functional group tolerance and the preservation of the carbonyl group of the ketone substrates, which offers the possibility for further transformation of the products.

Abstract Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

Abstract As the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between m6A and cancers has garnered substantial attention in recent years. An increasing number of small molecules have emerged as potential agents to target m6A regulators for cancer treatment. These molecules target the epigenetic level, enabling precise intervention in RNA modifications and efficiently disrupting the survival mechanisms of tumor cells, thus paving the way for novel approaches in cancer treatment. However, there is currently a lack of a comprehensive review on small molecules targeting m6A regulators for anti-tumor. Here, we have comprehensively summarized the classification and functions of m6A regulators, elucidating their interactions with the proliferation, metastasis, drug resistance, and immune responses in common cancers. Furthermore, we have provided a comprehensive overview on the development, mode of action, pharmacology and structure–activity relationships of small molecules targeting m6A regulators. Our aim is to offer insights for subsequent drug design and optimization, while also providing an outlook on future prospects for small molecule development targeting m6A.

On February 6, 2023, the doublet earthquake including two main shocks with magnitudes MW7.8 and MW7.5, occurred near the western side of the East Anatolian Fault at the southeast boundary of the Anatolian Plateau in Turkey. Based on the WGM2012 Bouguer gravity anomaly data and the Etopo1 topography data, this study first introduced a joint inversion of admittance and coherence functions and used the Bayesian optimal parameter estimation method to obtain the effective elastic thickness Te and loading ratio F of the lithosphere for various tectonic units in the Anatolian Plateau. Secondly, we discussed the characteristics and influencing factors of the lithospheric mechanical strength and analyzed its relationship with seismic activity. The lithospheric mechanical strength of the Anatolian Plateau showed clear lateral heterogeneity and a ''weak-strong-weak'' spatial pattern from east to west, reflecting various tectonic processes. At last, the strong seismic activity was found where the lithospheric strength was low in the Anatolian Plate. We also incorporated GPS strain rate and other results to investigate the tectonic background and primary causes of the MW7.8 and MW7.5 doublet earthquakes in Turkey. The results have a good insight into urban safety design in the Turkish region, including post-disaster rehabilitation, earthquake hazard assessment, and loss reduction.

Abstract Background It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. Main body Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1β (IL-1β) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. Conclusion Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Abstract Background Unidentified heart failure occurs in patients with multiple myeloma when their heart was involved. CMR with late gadolinium enhancement (LGE) and T1 mapping can identify myocardial amyloid infiltrations. Purpose To explore the role of CMR with late gadolinium enhancement (LGE) and T1 mapping for detection of multiple myeloma patients’heart. Material and methods A total of 16 MM patients with above underwent CMR (3.0-T) with T1 mapping (pre-contrast and post-contrast) and LGE imaging. In addition, 26 patients with non-obstructive hypertrophic cardiomyopathy and 26 healthy volunteers were compared to age- and sex-matched healthy controls without a history of cardiac disease, diabetes mellitus, or normal in CMR. All statistical analyses were performed using the statistical software GraphPad Prism. The measurement data were represented by median (X) and single sample T test was adopted. Enumeration data were represented by examples and Chi-tested was adopted. All tests were two-sided, and P values 0.05). Pre-contrast T1 values of MM group were obviously higher than those of healthy controls and non-obstructive hypertrophic cardiomyopathy group (ms:1462.0 ± 71.3vs. 1269.3 ± 42.3, 1324.0 ± 45.1, all P

Abstract Background Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. Methods Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. Results PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. Conclusion Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.

Abstract Background Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. Methods A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. Results The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p

Abstract Background The interdisciplinary realm of medical humanities explores narratives and experiences that can enhance medical education for physicians through perspective-taking and reflective practice. However, there is a gap in comprehension regarding its appropriateness at the postgraduate level, especially when utilising art therapists as faculty. This study aims to assess the acceptability of an innovative art therapy-focused educational initiative among junior doctors during a palliative care rotation, with the goal of cultivating empathy and promoting well-being. Methods A qualitative research project was conducted at the Division of Supportive and Palliative Care (DSPC) in the National Cancer Centre Singapore (NCCS). The study involved the recruitment of junior doctors who had successfully completed a three-month palliative care rotation program, spanning from January 2020 to April 2021. In a single small-group session lasting 1.5 h, with 3 to 4 participants each time, the individuals participated in activities such as collage making, group reflection, and sharing of artistic creations. These sessions were facilitated by an accredited art therapist and a clinical psychologist, focusing on themes related to empathy and wellbeing. To assess the acceptability of the program, two individual interviews were conducted three months apart with each participant. An independent research assistant utilised a semi-structured question guide that considered affective attitude, burden, perceived effectiveness, coherence, and self-efficacy. Thematic analysis of the transcribed data was then employed to scrutinise the participants’ experiences. Results A total of 20 individual interviews were completed with 11 participants. The three themes identified were lack of pre-existing knowledge of the humanities, promotors, and barriers to program acceptability. Conclusions The participants have mixed perceptions of the program’s acceptability. While all completed the program in its entirety, the acceptability of the program is impeded by wider systemic factors such as service and manpower needs. It is vital to address these structural limitations as failing to do so risks skewing current ambivalence towards outright rejection of future endeavours to integrate humanities programs into medical education.

Abstract Altermagnetism represents an emergent collinear magnetic phase with compensated order and an unconventional alternating even-parity wave spin order in the non-relativistic band structure. We investigate directly this unconventional band splitting near the Fermi energy through spin-integrated soft X-ray angular resolved photoemission spectroscopy. The experimentally obtained angle-dependent photoemission intensity, acquired from epitaxial thin films of the predicted altermagnet CrSb, demonstrates robust agreement with the corresponding band structure calculations. In particular, we observe the distinctive splitting of an electronic band on a low-symmetry path in the Brilliouin zone that connects two points featuring symmetry-induced degeneracy. The measured large magnitude of the spin splitting of approximately 0.6 eV and the position of the band just below the Fermi energy underscores the significance of altermagnets for spintronics based on robust broken time reversal symmetry responses arising from exchange energy scales, akin to ferromagnets, while remaining insensitive to external magnetic fields and possessing THz dynamics, akin to antiferromagnets.

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.

ABSTRACT: Avian arthritis is a common disease in the poultry industry, and the etiology is complex. Bacterial arthritis is usually caused by Staphylococcus aureus (S. aureus) infection. This study explored the minimum inhibitory concentration (MIC) of different organic acids against S. aureus MRSA85 and found that vanillic acid, suberic acid, itaconic acid, salicylic acid, and other organic acids had significant inhibitory effects on this strain, especially cinnamic acid, which exhibited the best inhibitory effect. The Fractional Inhibitory Concentration Index (FICI) test further revealed the synergistic effect among some compound organic acids, which can significantly enhance the antibacterial efficiency against MRSA85 while reducing the risk of bacterial resistance. Under the low concentrations (1/2 or 1/4 MIC) conditions, the MIC of the compound organic acids against S. aureus remains unchanged, and it can even enhance the sensitivity of antibiotic-resistant S. aureus to Oxacillin. Furthermore, the compound organic acids could effectively promote the recovery of S. aureus-induced arthritis in broiler models, reduce inflammatory responses, and lower down bacterial loads and inflammatory cytokine levels in joints, which indicated that the effects of the Compound 2 is comparable to that of the trimethoprim-sulfamethoxazole group. These results support the potential and application value of organic acids and their compounds, including Compound 1 to 3, as novel antibacterial agents in the treatment of S. aureus infections.

Background Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored.Aims To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3.Methods Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated β-galactosidase (SA-β-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification.Results The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process.Conclusions Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.

Methods In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model’s discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation.Results AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894–0.934) and 0.923 (95% CI, 0.895–0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model’s favorable clinical applicability.Conclusion We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

Nutritional status significantly impacts linear bone growth. We aimed to determine the relationship between the trajectories of four body composition indicators and pubertal advanced bone age. Trajectories of body mass index z-score (BMI z-score), visceral fat area z-score (VFA z-score), fat mass index z-score (FMI z-score), and fat-free mass index z-score (FFMI z-score) were identified based on three body composition measurements conducted from October 2018 to April 2023 within a pediatric cohort (the PROC study). We assessed pubertal bone age using the Tanner-Whitehouse 3-Chinese Radius-Ulna-Short (TW3-C RUS) method among 1402 primary school children. Children with a trajectory of higher BMI z-score, VFA z-score, FMI z-score, and FFMI z-score since childhood were more likely to have advanced bone age. The risk of advanced bone age was higher in children who were consistently in the high VFA z-score group (odds ratio [OR] = 6.73) or consistently in the high BMI z-score group (OR = 5.57), as compared to those in the low VFA z-score and low BMI z-score groups. Regular monitoring and maintenance of normal VFA during childhood may reduce the risk of advanced bone age at puberty. Furthermore, BMI monitoring is optional, especially in cases where specialized body composition equipment is not available.

PurposeWe investigated the capability and imaging criteria of T1 mapping and arterial spin labeling (ASL) MRI to identify renal injury in patients with liver cirrhosis.MethodsWe recruited 27 patients with cirrhosis and normal renal function (cirrhosis-NR), 10 with cirrhosis and renal dysfunction (cirrhosis-RD) and 23 normal controls (NCs). All participants were examined via renal T1 mapping and ASL imaging. Renal blood flow (RBF) derived from ASL was measured from the renal cortex, and T1 values were measured from the renal parenchyma (cortex and medulla). MRI parameters were compared between groups. Diagnostic performances for detecting renal impairment were statistically analyzed.ResultsCortical T1 (cT1) and medullary T1 (mT1) were significantly lower in the NCs than in the cirrhosis-NR group. The cortical RBF showed no significant changes between the NCs and cirrhosis-NR group but was markedly decreased in the cirrhosis-RD group. The areas under the curve (AUCs) for discriminating cirrhosis-NR from NCs were 0.883 and 0.826 by cT1 and mT1, respectively. Cortical RBF identified cirrhosis-RD with AUC of 0.978, and correlated with serum creatinine (r = −0.334) and the estimated glomerular filtration rate (r = 0.483). A classification and regression tree based on cortical RBF and cT1 achieved 85% accuracy in detecting renal impairment in the cirrhosis.ConclusionRenal T1 values might be sensitive predictors of early renal impairment in patients with cirrhosis-NR. RBF enabled quantifying renal perfusion impairment in patients with cirrhosis-RD. The diagnostic algorithm based on cortical RBF and T1 values allowed detecting renal injury during cirrhosis.

ABSTRACT: Infectious bronchitis virus (IBV) is one of the most widely spread RNA viruses, causing respiratory, renal, and intestinal damage, as well as decreased reproductive performance in hens, leading to significant economic losses in the poultry industry. In this study, a new IBV strain designated as CK/CH/GX/LA/071423 was successfully isolated from the 60-day-old Three-Yellow chicken vaccinated with H120 and QXL87 vaccines. The complete genome sequence analysis revealed that the CK/CH/GX/LA/071423 strain shared a high similarity of 96.7% with the YX10 strain belonging to the GI-19 genotype. Genetic evolution analysis based on the IBV S1 gene showed that the CK/CH/GX/LA/071423 isolate belonged to the GI-19 genotype. Recombination analysis of the virus genome using RDP and Simplot software indicated that CK/CH/GX/LA/071423 was derived from recombination events between the YX10 and 4/91 vaccine strains, which was supported by phylogenetic analysis using gene sequences from the 3 regions. Furthermore, the S1 protein tertiary structure differences were observed between the CK/CH/GX/LA/071423 and the QXL87 and H120 vaccine strains. Pathogenicity studies revealed that the CK/CH/GX/LA/071423 caused death and led to pale and enlarged kidneys with abundant urate deposits, indicative of a nephropathogenic IBV strain. High virus titers were detected in the trachea, kidneys, and cecal tonsils, demonstrating broad tissue tropism. Throughout the experimental period, the virus positive rate in throat swabs of the infected group reached to 100%. These findings highlight the continued predominance of the QX genotype IBV in Guangxi of China and the ongoing evolution of different genotypes through genetic recombination, raising concerns about the efficacy of current IBV vaccines in providing effective protection to poultry.

In the food field, a large number of phenomena and problems that are difficult to be macroscopically explained by traditional experimental methods occur during the process of research and development in upstream laboratories to production in downstream factories. Molecular simulation techniques are not only efficient and cost-effective, but also an important tool for connecting micro and macro scales, because molecular models can be used to study molecular behaviors at the atomic level, and thus predict and explain experimental results. This review summarized the commonly used software and databases for molecular simulation techniques, and introduced their applications in recent years in the fields of food safety, food processing and storage, and screening of food functional factors and their mechanisms.

Abstract Human–wildlife conflict has become a significant challenge for conservationists, particularly in areas where endangered species, such as large carnivores, are recovering. If we fail to keep a balance between the interests of humans and wildlife, the human–wildlife conflict can have adverse outcomes. However, the drivers of human–wildlife conflict, and how to mitigate conflict, are often poorly understood. In this study, we aimed to explore the possible causes for and potential mitigating approaches to human–tiger conflict risks through spatiotemporal niche partitioning. Based on data from the reports of Amur tiger (Panthera tigris altaica) preying on cattle and camera trap detection data from 2014 to 2019 in Hunchun, Northeast China, we predicted Amur tiger occurrence and created risk maps of human–tiger potential encounters. We found that Amur tiger occurrence was positively driven by prey distribution and negatively by the distribution of pastures used for domestic cattle grazing. Livestock was increasingly predated in areas with limited preferred prey, that is, wild pig (Sus scrofa) and sika (Cervus nippon), and in closer proximity to cattle‐grazing land. On the basis of our models, we divided areas utilized by human and Amur tigers into low‐, medium‐, and high‐risk areas across multiple spatiotemporal scales. We suppose that multiple spatiotemporal scale niche partitioning management might effectively reduce the risk of human–tiger encounters, prompt harmonized coexistence between humans and tigers, and provide new solutions to other areas experiencing human–wildlife conflicts.

IntroductionBody dissatisfaction significantly impacts depression among adolescents with polycystic ovary syndrome (PCOS). This relationship is compounded by various factors. Our study aims to explore the roles of self-esteem and self-compassion in the relationship between body dissatisfaction and depression in adolescent with PCOS.MethodsA cross-sectional study was conducted at the Shanghai First Maternity and Infant Hospital, involving 287 adolescents diagnosed with PCOS from January 2020 to December 2021. Participants completed validated questionnaires covering body dissatisfaction, self-esteem, self-compassion and depression. We utilized correlation and mediation analyses to examine the relationships and mediating effects among these variables.ResultsBody dissatisfaction had a significant positive effect on depression (β = 4.254, p < 0.001). Conversely, self-esteem (β = −0.944, p < 0.001) and self-compassion (β = −0.318, p < 0.001) were negative predictors of depression. Both self-esteem [β = 3.405, 95% CI = (0.151, 0.305)] and self-compassion [β = 1.525, 95% CI = (0.045, 0.165)] were shown to partially mediate the relationship between body dissatisfaction and depression, explaining 37.07% and 16.61% of the total effect, respectively.ConclusionThis study highlights the importance of fostering self-esteem and self-compassion among adolescents with PCOS to buffer the depressive effects of body dissatisfaction. Interventions aimed at promoting accurate and positive body perceptions, enhancing self-esteem, fostering a supportive attitude toward personal challenges, and maintaining positive emotional states are recommended to decrease the incidence of depression.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA β-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

Abstract Background Multiple myeloma (MM) is a prevalent hematological tumor, and recent clinical data have highlighted the significance of atrial fibrillation (AF) as a crucial complication affecting the prognosis of MM. This review aims to consolidate findings from published clinical studies, focusing on the epidemiological characteristics of AF in MM patients and the associated risks arising from MM treatments such as autologous hematopoietic stem cell transplantation, proteasome inhibitors, and immunomodulatory agents. Main body While existing data partially demonstrate a strong correlation between MM and AF, further clinical studies are necessary to comprehensively investigate their association. These studies should encompass various aspects, including the risk of AF resulting from MM treatment, the impact of AF-induced embolic events and heart failure on MM prognosis, as well as the influence of AF management methods like catheter ablation or left atrial appendage closure on MM prognosis. Conclusions The supplementation of future data will provide more precise guidance for managing MM patients. By incorporating information regarding AF risk associated with MM treatment and examining the effects of AF management strategies on MM prognosis, healthcare professionals can enhance their decision-making process when caring for individuals with MM.