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Abstract Background Blocking cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) shows substantial antitumor efficacy. Here, we report the preclinical data and outcomes of a first-in-human phase 1a trial of JS007, a novel anti-CTLA-4 antibody, in advanced solid tumors. Methods In preclinical studies, both in vitro characteristics and in vivo characteristics of JS007 were investigated. The clinical trial included a dose escalation phase and a dose expansion phase. Eligible patients with previously treated advanced solid tumors were enrolled. In the dose escalation phase, JS007 was administered intravenously every 3 weeks at doses of 0.03, 0.3, 1, 3, and 10 mg/kg. Then, 3 and 10 mg/kg were chosen for the dose expansion phase. The primary endpoints included the maximum tolerated dose (MTD) of JS007 based on dose-limiting toxicities (DLTs) and safety. Results JS007 could effectively bind to CTLA-4 and induce an immune response in vitro. Potent in vivo antitumor activity of JS007 was observed. Increased T cell infiltration and T regulatory (Treg) cell depletion in tumor microenvironment of cancer cell xenografts were detected after treated with JS007. Pharmacological analysis in experimental animals showed a dose-proportional increase in exposure. In the clinical trial, a total of 28 patients were treated with JS007 across 5 dose levels. No DLTs occurred. The MTD did not reach at the highest dose tested (10 mg/kg). Twenty-three (82.1%) patients experienced at least one treatment-related adverse event (TRAE). The incidence of Grade ≥ 3 TRAEs was 28.6% (8/28) with alanine aminotransferase increase (7.1%, 2/28) being the most frequently reported TRAE. No severe immune-related adverse event (irAE) occurred. Pharmacological profiles of JS007 in patients were similar to those in animal models. Serum concentration of JS007 showed a dose-dependent escalation, and the half-life of JS007 was 9.4 ~ 12.2 days. Treatment-induced anti-drug antibody was detected in 2 patients. The disease control rate was 50% (14/28), and the median overall survival was 14.7 months. Conclusions JS007 preliminarily demonstrates good tolerance and encouraging antitumor activity in patients with previously treated advanced solid tumors. Trial registration ClinicalTrials.gov identifier: NCT05049265 (Sep 20, 2021).

Calcium–magnesium–alumina–silicate (CMAS) corrosion has attracted special attention in the thermal barrier coating (TBC) field. At high temperatures, when CMAS melts, it adheres to the coating surface and penetrates the interior, severely destroying the TBC. In this study, a promising CMAS-phobic and infiltration-inhibiting material, GdPO4, on which molten CMAS is difficult to wet and penetrate, was proposed. These desirable attributes are explained by analyzing the material characteristics of GdPO4 and its interfacial reaction with CMAS. GdPO4 is demonstrated to have low surface energy, making it difficult for molten CMAS to wet and adhere to the surface. When in contact with molten CMAS, a double-layer structured reaction layer consisting of an acicular upper sublayer and a compact lower sublayer is formed on the GdPO4 surface, which can effectively impede molten CMAS spreading and penetration. First-principles calculation results revealed that the reaction layer has low surface energy and low adhesion to CMAS, which are favorable for molten CMAS phobicity. Additionally, the formation of the reaction layer increases the viscosity of the molten CMAS, which can increase melt wetting and penetration. Hence, GdPO4, which exhibits excellent CMAS-phobicity and infiltration-inhibiting ability, is a promising protective layer material for TBCs against CMAS adhesion and attack.

Background The key task in China's medical and health field during the "14th Five-Year Plan" period is to realize treatment-prevention integration and innovate the mechanism of treatment-prevention integration. Objective This paper analyzes the implementation mechanism of treatment-prevention integration under the background of integrated service system construction, and provides reference for exploring the path of medical and prevention integration adapting to the strategy of "Healthy China". Methods Taking 2018 as the time node, relevant literature was searched on CNKI and Wanfang Data Knowledge Service Platform with keywords of "treatment-prevention integration" "medical and prevention coordination" "combination of prevention and treatment" and literatures on case policies, measures and implementation effects of integrated service systems such as medical alliance. Finally, 18 literatures and 15 cases were selected. Based on the rainbow model, system integration, organizational integration, professional integration, service integration, functional integration and normative integration were determined as condition variables from macro, meso and micro levels and supporting factors, and the effect of treatment-prevention integration was determined as result variable. QCA was adopted to explore the implementation mechanism of medical and preventive integration under the background of integrated service system construction. Results There were four configuration paths that could effectively improve the effect of treatment-prevention integration, and the four paths were in line with the multi-layer integrated path and the medium-micro integrated path respectively. The following results were obtained: (1) It was more effective to carry out treatment-prevention integration relying on the integrated service system, and there are multiple paths that can effectively improve the effect of treatment-prevention integration under the integrated service system; (2) Service integration plays a fundamental role in improving the effect of medical and preventive integration; (3) The setting of relevant policy indicators for improving the system integration, professional integration and functional integration of treatment-prevention integration is not perfect. Conclusion (1) Relying on the construction of integrated service system to promote the improvement of treatment-prevention integration effect; (2) Give full play to the basic guarantee role of service integration; (3) Make reference to the successful experience of multi-level integration cases, set policy indicators at macro, meso and micro levels in a balanced manner, and improve the integration of system integration, professional integration and supporting elements.

High-temperature-resistant adhesives are critical materials in the aerospace field. The zirconium-modified aluminum phosphate-based adhesives developed in this work had the advantage of adjustable thermal expansibility, achieving a high matching of coefficient of thermal expansion (CTE) with alumina. The introduction of zirconium can significantly improve the thermal stability of the adhesive matrix, and the Zr/Al ratio substantially affects the various reaction processes inside the adhesive, especially the types of zirconium-containing compounds. Most of the zirconium-containing compounds in the A7Z3 adhesive were ZrO2 only when the mass ratio of zirconium hydroxide to aluminum hydroxide was 3 : 7, which was the key reason why it had the highest CTE. The room-temperature bonding strength of A7Z3 after heat treatment at 1500 °C reached 67.2 MPa. After pretreatment at 1500 °C, the high-temperature bonding strength of A7Z3 was greater than 50 MPa in the range of (room temperature) RT–1000 °C. After 40 thermal cycles between RT and 1500 °C, the bonding strength still reached 10 MPa. Physical bonding occurred at temperatures below 1000 °C, while chemical bonding dominated above 1000 °C based on the generation of Al5BO9 and mullite at the interfaces.

Background: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment. Methods: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Results: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67 %) patients' itching symptoms completely disappeared, 10 of 36 (27.78 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients' symptoms were not significantly relieved. 16 of 36 (44.4 %) patients' itching symptoms completely disappeared, 9 of 36 (25 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31 ± 1.67 vs 3.67 ± 1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were “satisfied” or “very satisfied” with the results of the treatment. Conclusions: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus.

Iris domestica is a widely used ornamental garden and important medicinal plant. Our previous studies have shown that it exhibits significant uptake and translocation capacity under Cd stress compared to other Iris species. Gene expression is studied using RT-qPCR; however, there are no reference genes have been found for I. domestica under Cd stress. In this investigation, thirteen possible reference genes from previous studies and our transcriptome were screened using RT-qPCR in the leaves and roots of Cd-stressed plants. The findings revealed that UBC9 and ACT were the best reference genes for roots with and without Cd stress, whereas YLS8 and ACT7 were the best reference genes for leaves. Among the different tissues without Cd stress, UBC9 and UBC28 exhibited the best results, whereas PP2C06 and UBC9 exhibited the best results under Cd stress. The most stable reference genes in the leaves and roots were UBC9 and UBC28, respectively, under and without Cd stress, and GADPH was the most unstable. Finally, three metal ion response genes, NRAMP2, YSL9 and CYP81Q32 were detected using RT-qPCR and compared with the transcriptome data to further confirm the reliability of the chosen genes. This study identified suitable reference genes for I. domestica under Cd-stress conditions.

Abstract Background Retinal ischemia/reperfusion (RIR) is implicated in various forms of optic neuropathies, yet effective treatments are lacking. RIR leads to the death of retinal ganglion cells (RGCs) and subsequent vision loss, posing detrimental effects on both physical and mental health. Apigenin (API), derived from a wide range of sources, has been reported to exert protective effects against ischemia/reperfusion injuries in various organs, such as the brain, kidney, myocardium, and liver. In this study, we investigated the protective effect of API and its underlying mechanisms on RGC degeneration induced by retinal ischemia/reperfusion (RIR). Methods An in vivo model was induced by anterior chamber perfusion following intravitreal injection of API one day prior to the procedure. Meanwhile, an in vitro model was established through 1% oxygen and glucose deprivation. The neuroprotective effects of API were evaluated using H&E staining, spectral-domain optical coherence tomography (SD-OCT), Fluoro-Gold retrograde labeling, and Photopic negative response (PhNR). Furthermore, transmission electron microscopy (TEM) was employed to observe mitochondrial crista morphology and integrity. To elucidate the underlying mechanisms of API, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry assay, western blot, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, JC-1 kit assay, dichlorofluorescein-diacetate (DCFH-DA) assay, as well as TMRE and Mito-tracker staining were conducted. Results API treatment protected retinal inner plexiform layer (IPL) and ganglion cell complex (GCC), and improved the function of retinal ganglion cells (RGCs). Additionally, API reduced RGC apoptosis and decreased lactate dehydrogenase (LDH) release by upregulating Bcl-2 and Bcl-xL expression, while downregulating Bax and cleaved caspase-3 expression. Furthermore, API increased mitochondrial membrane potential (MMP) and decreased extracellular reactive oxygen species (ROS) production. These effects were achieved by enhancing mitochondrial function, restoring mitochondrial cristae morphology and integrity, and regulating the expression of OPA1, MFN2, and DRP1, thereby regulating mitochondrial dynamics involving fusion and fission. Conclusion API protects RGCs against RIR injury by modulating mitochondrial dynamics, promoting mitochondrial fusion and fission.

Abstract In power systems with a high proportion of renewable energy resources (RES), the inherent stochasticity and volatility of RES necessitate careful consideration in power system planning. Scenario analysis is commonly employed to address the stochastic nature in power system planning. Existing studies generally adopt an open‐loop structure, where representative days are selected first and planning decisions are subsequently made. However, this method may not accurately represent the operating status of a system owing to changes in the power generation structure during the planning process. To address this limitation, this paper introduces a closed‐loop framework for representative day selection within the context of generation and transmission expansion planning (G&TEP), incorporating demand response (DR). The framework comprises three layers: representative day selection, planning decisions, and long‐term operational simulation. Initially, an approach for selecting representative days is proposed by combining the clustering and optimization‐based methods. Subsequently, a G&TEP model that incorporates DR is presented in the second layer. Lastly, the framework encompasses a three‐layer closed‐loop structure, enabling dynamic adjustments and enhancements to the representative day selection process to ensure optimality. Case studies on the reliability and operational test system of a power grid with large‐scale renewable integration (XJTU‐ROTS) demonstrate the effectiveness of our proposed framework.

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median −12.12%, interquartile ranges (IQRs) −18.62 to −5.626) and creatine (median −46.91 μmol/L, IQR −64.70 to −29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03–25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.

Abstract Background Gastric cancer (GC), particularly for advanced stage of GC, commonly undergoes peritoneal metastasis (PM), which is the leading cause of GC‐related death. However, there currently has no reliable biomarker to predict the onset of GCPM. It is well known that the imbalance of gut microbiota contributes to the development and metastasis of gastrointestinal tumors. Unfortunately, little is known about how the alternation in gut microbiota is associated with the onset of GCPM. Methods Our current study analyzed structural characteristics and functional prediction of gut microbiota in GC patients with PM (PM group) and without PM (non‐PM group). Fresh fecal samples were collected from a discovery cohort (PM = 38, non‐PM = 54) and a validation cohort (PM = 15, non‐PM = 21) of GC patients and their 16S ribosomal RNA (16s rRNA) gene amplicons were sequenced, followed by bioinformatics. Results The results indicated an increase in the biodiversity of gut microbiota in the non‐PM group of the discovery cohort, compared with the PM group. Moreover, LEfSe analysis found 31 significantly different microorganisms, of which the Roseburia ranked the fifth in the random forest (RF) model. The characteristics of intestinal microbiota in GCPM patients were changed, and the abundance of Roseburia in gut microbiota from the GCPM patients was reduced and receiver operating characteristic (ROC) analysis revealed that the reduced abundance of gut Roseburia effectively predicted the onset of GCPM. Conclusion This signature was also observed in the validation cohort. Therefore, Roseburia is a protective microbial marker and the reduced abundance of Roseburia in gut microbiota may help early diagnosis of GCPM.

ABSTRACT: Lipid metabolic capacity, feed utilization, and the diversity of gut microbiota are reduced in the late laying stage for laying hens. This experiment aimed to investigate the effects of different levels of dietary metabolizable energy (ME) on hepatic lipid metabolism and cecal microbiota in late laying hens. The 216 Peking Pink laying hens (57-wk-old) were randomly assigned to experimental diets of 11.56 (HM = high ME), 11.14 (MM = medium ME), or 10.72 (LM = low ME) MJ of ME/kg, with each dietary treatment containing 6 replicates per group and 12 chickens per replicate. The HM group showed higher triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) concentrations in the liver compared with the LM group; second, the HM group showed higher TG concentration and the LM group showed lower T-CHO concentration compared with MM group; finally, the HM group showed a lower hepatic lipase (HL) activity compared with the MM and LM groups (P < 0.05). There was a significant difference in the microbial community structure of the cecum between the HM and MM groups (P < 0.05). The decrease of dietary ME level resulted in a gradual decrease relative abundance of Proteobacteria. At the genus level, beneficial bacteria were significantly enriched in the LM group compared to the MM group, including Faecalibacterium, Lactobacillus, and Bifidobacterium, (linear discriminant analysis [LDA] >2, P 2, P < 0.05). The HM group had a higher abundance of Sutterella spp. compared to the LM group (LDA>2, P

Introduction Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in China. The combination of immune checkpoint inhibitors (ICIs) and antiangiogenic drugs, such as bevacizumab and tyrosine kinase inhibitors, has been recommended as first-line treatment for advanced HCC. However, two-thirds of patients did not benefit from this form of immunotherapy. Currently, data on the subsequent regimen for patients previously treated with ICIs are lacking. Studies have shown that the combination of radiotherapy (RT) and ICIs is a potentially effective second-line therapy for HCC. This study aims to assess the efficacy and safety of combined therapy with stereotactic body RT (SBRT), sintilimab and IBI305 (a biosimilar of bevacizumab) in patients with HCC following the progression of first-line ICI therapy.Methods and analysis This study is an open-label, single-arm, single-centre, phase 2 trial of 21 patients with advanced HCC in whom previous ICI therapy has failed. Participants will receive approximately 30–40 Gy/5–8F SBRT, followed by 200 mg sintilimab and 15 mg/kg IBI305 intravenously every 3 weeks. Treatment will continue until the development of unacceptable toxicity or disease progression. We will use Simon’s two-stage design, with the objective response rate (ORR) as the primary endpoint. Secondary endpoints include ORR of lesions without RT, disease control rate, progression-free survival, overall survival and safety.Ethics and dissemination The study was authorised by the Medical Ethics Committee. Dissemination of results will occur via a peer-reviewed publication and other relevant media.Trial registration number ChiCTR2200056068.

BackgroundNurse turnover has become a salient issue in healthcare system worldwide and seriously compromises patient outcomes. Social support is considered an effective contributor to alleviate nurse turnover intention (TI). However, the degree of correlation between social support and nurse TI remains elusive.AimsThis study aims to evaluate the strength of the effectiveness of social support on TI among nurses as well as its potential moderators.DesignThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.MethodsTo obtained qualified studies, two researchers searched Embase, PubMed, Web of science, CINAHL, CNKI, WanFang, and Chinese Medical Journal Full Text Database from inception to January 6, 2024. Meta-analysis, publication bias, and sensitivity analysis were carried out on the included studies using CMA 3.0 software, and the moderating effect was verified through meta-analysis of variance (ANOVA).ResultsA total of 38 studies were obtained, involving 63,989 clinical nurses. The comprehensive effect size of the random effect model showed a significant medium negative correlation between social support and TI among nurses (p

Purposes With the continuous promotion of the dual carbon goal, new energy has ushered in explosive development, and the capacity and space for new energy consumption have become a concern for all sectors of society. In the research on existing new energy consumption capacity and space, the consumption measures are relatively single and focus more on theoretical research, which is not applicable, propose specific methods and processes. Methods In this article the time series production simulation method was adopted to build a new energy consumption capacity and consumption space method and process for large-scale new energy grid connection on the Panoramic Power System Operation Simulation Analysis Platform. Findings The new energy consumption capacity of Shanxi Province during the 14th and 15th Five Year Plans was estimated. On the basis. Based on this, comprehensive consumption measures were taken to increase its new energy utilization rate to over 95%, improving the new energy consumption capacity. On the basis of a new energy utilization rate of 95%, the new energy consumption space under various scenarios was calculated for different proportion of newly added wind and solar power, different production timing, different new energy utilization rates, and different years, guiding the new energy planning of Shanxi Province and assisting in the implementation of the dual carbon target.

Three-dimensional object detection has been substantially improved with the use of expensive LiDAR and stereo vision systems in intelligent driving. The less-expensive and more scalable solution of monocular 3D object detection, however, remains a key challenge. This study primarily explores real-time pseudo 3D object detection with monocular vision and designs a single-shot RPN model, VKP-P3D, which relies purely on visual feature extraction. Through a multiscale feature fusion and an attention mechanism module, this model obtains high-dimensional feature representations during the feature extraction phase. In the detection head of the VKP-P3D model, the pseudo 3D object detection is obtained by regressing 2D bounding box and the visible key points within the image coordinate of the 3D box from the camera’s perspective. Finally, assuming flat ground and considering geometric parameters of the camera, the object’s 3D information can be extracted. To verify the effectiveness of the proposed algorithm, we constructed two pseudo 3D object detection datasets based on visible key points and compared with current state-of-the-art real-time object detector. Results showed that the proposed model has high detection accuracy and speed.

Weeping forsythia (Forsythia suspensa, Oleaceae) is a deciduous broad-leaved tree species distributed in the warm temperate zone of China. However, the species still lacks a chromosome-level genome. In this study, the former draft genome (Accession No. WIPI00000000) of weeping forsythia was assembled into 14 chromosomes with a 712.9 Mb genome size. Weeping forsythia underwent α and β whole-genome duplication events. After the divergence between weeping forsythia and Olea europaea, 1 453 gene families had a significant expansion, and 1 146 gene families had a significant contraction. The enrichment pathways and ontologies of expanded genes suggested that the tillering, photosynthesis and growth capacity of weeping forsythia were enhanced after the divergence of weeping forsythia and O. europaea. The contracted genes suggested that the resistance of weeping forsythia to cold and drought was weakened. The last glacial period led to a significant decline in the effective population size of weeping forsythia. Forty-six candidate genes were identified for the synthesis of the forsythin and forsythoside A by genomic and transcriptomic data. In this study, we improved the previous draft genome of weeping forsythia. Our genome will provide genomic resources for the subsequent evolution and breeding research of weeping forsythia.

Abstract The fluctuation and stochastic characteristics of renewable energy resources challenge the secure system operation and also impose significant financial risks for the market participating renewable energy plants (REPs). Energy storage systems (ESSs) can serve as effective tools in enhancing the operating flexibility of REPs, thus improving their profitability while making them grid‐friendly. However, current studies focussing on the energy market participation of ESS‐equipped REPs neglect ESSs' frequency regulation performance. Moreover, power output deviation and power curtailment of REPs bring difficulties to the integration of renewable energy. To address these challenges, an optimal ESS configuration method for REPs participating in the joint energy‐regulation market is proposed first. A method considering constraints on frequency regulation performance is applied. Then, to reduce power output deviation and power curtailment of REPs, an incentive mechanism based on the excess revenue recovery is implemented to induce the grid‐friendly power outputs of REPs. Numerical analysis on XJTU‐ROTS2017 systems demonstrates that the optimal ESS configuration results obtained from the proposed method could promote the profitability of ESS‐equipped REPs. The results also verify the effectiveness of the excess revenue recovery mechanism in facilitating the grid‐friendly operation behaviours of the ESS‐equipped REPs.

Dust and air pollution events are increasingly occurring around the Taklimakan Desert in southern Xinjiang and in the urban areas of northern Xinjiang. Predicting such events is crucial for the advancement, growth, and prosperity of communities. This study evaluated a dust and air pollution forecasting system based on the Weather Research and Forecasting model coupled with the China Meteorological Administration Chemistry Environment (WRF-CUACE) model using ground and satellite observations. The results showed that the forecasting system accurately predicted the formation, development, and termination of dust events. It demonstrated good capability for predicting the evolution and spatial distribution of dust storms, although it overestimated dust intensity. Specifically, the correlation coefficient (R) between simulated and observed PM10 was up to 0.85 with a mean absolute error (MAE) of 721.36 µg·m−3 during dust storm periods. During air pollution events, the forecasting system displayed notable variations in predictive accuracy across various urban areas. The simulated trends of PM2.5 and the Air Quality Index (AQI) closely aligned with the actual observations in Ürümqi. The R for simulated and observed PM2.5 concentrations at 24 and 48 h intervals were 0.60 and 0.54, respectively, with MAEs of 28.92 µg·m−3 and 29.10 µg·m−3, respectively. The correlation coefficients for simulated and observed AQIs at 24 and 48 h intervals were 0.79 and 0.70, respectively, with MAEs of 24.21 and 27.56, respectively. The evolution of the simulated PM10 was consistent with observations despite relatively high concentrations. The simulated PM2.5 concentrations in Changji and Shihezi were notably lower than those observed, resulting in a lower AQI. For PM10, the simulation–observation error was relatively small; however, the trends were inconsistent. Future research should focus on optimizing model parameterization schemes and emission source data.

c-Src is involved in multiple signaling pathways and serves as a critical target in various cancers. Growing evidence suggests that prolonging a drug’s residence time (RT) can enhance its efficacy and selectivity. Thus, the development of c-Src antagonists with longer residence time could potentially improve therapeutic outcomes. In this study, we employed molecular dynamics simulations to explore the binding modes and dissociation processes of c-Src with antagonists characterized by either long or short RTs. Our results reveal that the long RT compound DAS-DFGO-I (DFGO) occupies an allosteric site, forming hydrogen bonds with residues E310 and D404 and engaging in hydrophobic interactions with residues such as L322 and V377. These interactions significantly contribute to the long RT of DFGO. However, the hydrogen bonds between the amide group of DFGO and residues E310 and D404 are unstable. Substituting the amide group with a sulfonamide yielded a new compound, DFOGS, which exhibited more stable hydrogen bonds with E310 and D404, thereby increasing its binding stability with c-Src. These results provide theoretical guidance for the rational design of long residence time c-Src inhibitors to improve selectivity and efficacy.

In the original publication [...]

Introduction: Sexually transmitted infections (STIs) are among the most common infectious diseases worldwide, often leading to coinfections. Timely detection of genital tract pathogens in at-risk populations is crucial for preventing STIs. We evaluated the NAP-Fluo Cycler System, an innovative microfluidic nucleic acid detection platform, for its ability to simultaneously identify Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Ureaplasma urealyticum (UU), Mycoplasma genitalium (MG), and Mycoplasma hominis (MH) in urethral or cervical secretions. Materials and methods: The limits of detection (LODs), repeatability, specificity, and interference resistance of the system were evaluated using standard strains, a panel of 24 pathogens, and seven interferents. We used the system to analyze 302 clinical samples and compared the results with those of five approved commercial reference kits. Results: The system achieved LODs of 500 IFU/mL, 500 CFU/mL, and 500 CCU/mL for CT, NG, and UU/MG/MH, respectively, demonstrating high stability (coefficient of variation

Objective: Rece nt studies ha ve revealed that hemoglobin beta (HBB) plays an important role not only in blood disorders but also in malignancies. The aim of this study is to investigate the clinical significance, diagnostic value, and biological function of HBB in lung cancer. Methods: HBB expression was examined in lung cancer tissues and plasma samples using quantitative real-time polymerase chain reaction, and its relationship with clinical pathological characteristics was analyzed. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of HBB in lung cancer. The proliferation of A549 and SPCA1 cells was analyzed using a cell counting kit-8 assay and protein expressions were detected by western blot. Results: The expressions of HBB were found to be down-regulated in both lung cancer tissues and plasma samples. Notably, plasma HBB levels were significantly elevated in postoperative samples when compared to their preoperative counterparts. Across 66 cases of lung cancer tissues, a correlation was observed between HBB levels and both gender and tumor, node, metastasis staging. ROC curve analysis further confirmed the high diagnostic potential of HBB expression in lung cancer. Moreover, the combination of HBB and carcinoembryonic antigen (CEA) had greater significance than HBB or CEA alone in the diagnosis of lung cancer. Knocking out or overexpressing HBB could affect lung cancer cell proliferation through the ERK1/2 signaling pathway. Conclusion: HBB can serve as a novel biomarker for the diagnosis and monitoring of lung cancer, regulating cell proliferation via the ERK1/2 pathway and playing a pivotal role in the oncogenesis and progression of the disease.

With the rapid development of urbanization in China, urban energy consumption increases rapidly, leading to energy shortages and environmental pollution, of which building operational energy consumption carbon emissions (BECCE) account for a large proportion. It has a vital impact on global warming and urban green and sustainable development. Chengdu city in Sichuan Province is taken as the research area in this paper. First, basic information and power data on four types of single buildings, including large-sized buildings, small- and medium-sized buildings, government agencies, and residential buildings, are collected. Second, the characteristics of the four types of buildings are extracted, and the calculation model of BECCE (“electricity-carbon” model) based on particle swarm optimization algorithm–support vector machine (PSO–SVM) is constructed, and the model is trained and verified using the method of five-fold cross-validation. Then, according to the mean absolute error (MAE), root mean square error (RMSE), and R2 evaluation indicators, the constructed “electricity-carbon” model is compared and evaluated. Finally, the generalization ability of the “electricity-carbon” model is verified. The research results show that (1) the “electricity-carbon” model constructed in this paper has a high accuracy rate, and the fitting ability of the PSO–SVM model is significantly better than that of the support vector regression (SVR) model; (2) in the testing stage, the fitting situation of large buildings is the best, and MAE, RMSE, and R2 are 858.7, 1108.6, and 0.91, respectively; and (3) the spatial distribution map of regional BECCE can be quickly obtained using the “electricity-carbon” model constructed in this paper. The “electricity-carbon” model constructed in this paper can provide a scientific reference for building emission reduction.

INTRODUCTION: In an in-depth study of the application of sustainable energy in cross-border e-commerce, a comprehensive assessment and model optimization of its life cycle are conducted to promote the practical application of sustainable development in e-commerce. With the increasing global concern for renewable energy and environmental protection, e-commerce, as an international business model, has attracted much attention in terms of the environmental and social impacts of its sustainability. OBJECTIVES: The aim is to provide scientific assessment methods and effective model optimization strategies to promote the feasibility and sustainability of cross-border e-commerce for sustainable energy. METHODS: A comprehensive life cycle assessment (LCA) model was constructed using the system life cycle assessment (SLCA) methodology by collecting data from various aspects of sustainable energy cross-border e-commerce. The model considers the entire life cycle process from energy production, logistics, transportation, and product manufacturing to final consumption and integrates various factors such as resource utilization, environmental emissions, and social responsibility. Based on the assessment, a series of model optimization strategies are proposed, including suggestions for improving supply chain efficiency, promoting green energy applications, and strengthening social responsibility. RESULTS: This study achieved significant life cycle assessment and model optimization results. In terms of energy use, promoting the application of renewable energy significantly reduces carbon emissions; in terms of supply chain management, optimization leads to an overall efficiency improvement and a reduction in resource wastage; and in terms of social responsibility, the enterprise strengthens employee training and community involvement, which enhances its social image. These results show that sustainable energy cross-border e-commerce can better achieve sustainable development goals through systematic assessment and optimization. CONCLUSION: Life cycle assessment and model optimization provide scientific assessment methods and practical suggestions for sustainable energy cross-border e-commerce. In global sustainable development, the e-commerce industry should actively adopt sustainable energy and minimize its negative impacts on the environment and society by optimizing production and supply chain management. Future research can continue to expand the assessment model and deeply explore the potential of sustainable energy in e-commerce to provide more precise guidance for the industry's sustainable development.

Tumor vascular normalization profoundly affects the advancement of cancer therapy. Currently, with the rapid increase in research on tumor vascular normalization, few analytical and descriptive studies have investigated the trends in its development, key research power, present research hotspots, and future outlooks. In this study, articles and reviews published between January 1, 2003, and October 29, 2022 were retrieved from Web of Science database. Subsequently, published research trends, countries/regions, institutions, authors, journals, references, and keywords were analyzed based on traditional bibliometric laws (such as Price's exponential growth, Bradford's, Lotka's, and Zipf's). Our results showed that the last two decades have seen an increase in tumor vascular normalization research. USA emerged as the preeminent contributor to the field, boasting the highest H-index and accruing the greatest quantity of publications and citations. Among institutions, Massachusetts General Hospital and Harvard University made significant contributions, and Professor RK Jain was identified as a key leader in this field. Out of 583 academic journals, Cancer Research and Clinical Cancer Research published the most articles on vascular normalization. The research focal points in the field primarily include immunotherapy, tumor microenvironments, nanomedicine, and emerging frontier themes such as metabolism and mechanomedicine. Concurrently, the challenges of vascular normalization in cancer are discussed as well. In conclusion, the study presented a thorough analysis of the literature covering the past 20 years on vascular normalization in cancer, highlighting leading countries, institutions, authors, journals, and the emerging research focal points in this field. Future studies will advance the ongoing efforts in the field of tumor vascular normalization, aiming to enhance our ability to effectively manage and treat cancer.

Rationale & Objective: Long pentraxin-3 (PTX-3) serves as a biomarker for prognosticating adverse clinical outcomes in individuals with chronic kidney disease (CKD). The objective of the current meta-analysis was to evaluate the prognostic efficacy of PTX-3 in patients with CKD. In addition, we compared the prognostic effectiveness of PTX-3 and the short pentraxin C-reactive protein (CRP) in the identical cohort of patients with CKD. Study Design: A systematic review and meta-analysis. Setting & Participants: Patients with CKD treated with or without dialysis. Selection Criteria for Studies: A cohort study with a minimum 1-year follow-up. Data Extraction: Risk measurements, adjusted hazard risk with 95% CI, and modified variables. Analytical Approach: To aggregate the adjusted effect estimates, a fixed-effects or random-effects model was employed. Results: Nine studies covering 1,825 patients with CKD were selected in the present review. Six of the 9 studies exclusively included patients receiving hemodialysis. The collected findings indicated that patients with CKD in the highest tertile of PTX-3 demonstrated significantly higher risks of all-cause mortality (HR, 1.92; 95% CI, 1.44-2.56), cardiovascular death (HR, 1.98; 95% CI, 1.28-3.05), infectious death (HR, 5.26; 95% CI, 1.60-17.31), and fatal and nonfatal cardiovascular events (HR, 1.81; 95% CI, 1.35-2.42), as compared with those in the lowest tertile. These significant associations with risk were also observed when effect estimates were presented as per unit change in the PTX-3. Moreover, when comparing the prognostic value of PTX-3 and CRP in the same individuals (5 studies covering 904 patients), PTX-3 proved to be a satisfactory predictor of adverse events in these patients, whereas CRP failed to exhibit such predictive capability, regardless of the type of effect estimate used. Limitations: A relatively small sample size and some heterogeneity. Conclusions: Pentraxin 3 is associated with adverse events in individuals with CKD and may be a more reliable predictor of adverse clinical events than CRP in this population. Plain-Language Summary: Systemic inflammatory markers are useful in predicting the prognosis of patients with CKD. Pentraxin-3 (PTX-3) is an emerging biomarker of inflammation compared with other members of the pentraxin family, such as C-reactive protein (CRP). This meta-analysis evaluated the prognostic value of PTX-3 in predicting adverse outcomes in patients with CKD. Also, we compared the prognostic values between PTX-3 and CRP in the subset of studies with data on CRP. We found that patients with CKD with higher circulating PTX-3 levels had a significantly heightened risk of adverse outcomes compared with those with lower PTX-3 levels. By contrast, CRP did not appear to be a good predictor of adverse events. Pentraxin-3 might be a more reliable prognostic marker than CRP in patients with CKD.

Abstract Background RNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5–methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined. Methods In the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis. Results A total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10–5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells. Conclusion In conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target.

Abstract Background The hepatopancreas of crustaceans serves as a significant organ for both the synthesis and secretion of digestive enzymes, as well as energy storage. In the event of food shortage, the hepatopancreas can provide energy for survival. To investigate the potential regulatory mechanisms of the hepatopancreas in response to starvation in Eriocheir Sinensis, transcriptome analysis, histological study and qRT-PCR were performed. Results The results showed that starvation caused a decrease in the hepatopancreas index of E. sinensis, which had certain effects on the tissue structure, metabolism and angiogenesis in the hepatopancreas. In addition, WGCNA and linear regression analysis showed that the genes significantly related to the hepatopancreas index were mainly enriched in the angiogenesis pathway, in which AKT signaling played an important role. Starvation may inhibit AKT signaling pathway by reducing the expression of TGFBI, HSP27, HHEX, and EsPVF1, thereby hindering angiogenesis, promoting apoptosis, and leading to hepatopancreas atrophy. Conclusion These results indicate that AKT plays an important role in the angiogenesis pathway and apoptosis of the starvation induced hepatopancreas index reduction, which is beneficial to further understand the effect of starvation stress on hepatopancreas of Chinese mitten crab.

Introduction: The gut microbiome is vital for providing resistance against colonized pathogenic bacteria. Recently, specific commensal species have become recognized as important mediators of host defense against microbial infection by a variety of mechanisms. Objectives: To examine the contribution of live and pasteurized A. muciniphila to defend against the intestinal pathogen Salmonella Typhimurium in a streptomycin-treated mouse model of infection. Methods: C57B6J mice were pretreated with phosphate-buffered saline (PBS), live Akkermansia muciniphila (AKK), and pasteurized A. muciniphila (pAKK) for two weeks, then mice were infected by S. Typhimurium SL 1344. 16S rRNA-based gut microbiota analysis was performed before and after infection. Bacterial counts in feces and tissues, histopathological analysis, gut barrier-related gene expression, and antimicrobial peptides were examined. Co-housing was performed to examine the role of microbiota in the change of susceptibility of mice to infection. Results: AKK and pAKK markedly decreased Salmonella fecal and systemic burdens and reduced inflammation during infection. Notably, further characterization of AKK and pAKK protective mechanisms revealed different candidate protective pathways. AKK promoted gut barrier gene expression and the secretion of antimicrobial peptides, and co-housing studies suggested that AKK-associated microbial community played a role in attenuating infection. Moreover, pAKK had a positive effect on NLRP3 in infected mice. We verified that pretreatment of pAKK could promote the expression of NLRP3, and enhance the antimicrobial activity of macrophage, likely through increasing the production of reactive oxygen (ROS), nitric oxide (NO), and inflammatory cytokines. Conclusion: Our study demonstrates that live or pasteurized A. muciniphila can be effective preventive measures for alleviating S. Typhimurium-induced disease, highlighting the potential of developing Akkermansia-based probiotics or postbiotics for the prevention of Salmonellosis.

Due to the rapid development of renewable energy (RE), the power transmission and transformation equipment of some renewable energy gathering stations are congested especially at noon. Therefore, an operation simulation method considering energy storage system (ESS) is proposed, and some evaluation indices of source-network-storage are given. This paper proposes two solutions to alleviate the contradiction between renewable energy utilization and equipment congestion: expanding equipment and configuring ESS. To compare the utilization rate of renewable energy and the investment cost of the power grid, the cost of two schemes of expanding key gathering station equipment and configuring ESS under the condition of increasing the same utilization rate of renewable energy are compared, to give suggestions for the coordinated development of renewable energy and power transmission and transformation investment. ROTS system is used to compare two schemes of equipment expansion and ESS configuration in some renewable energy gathering stations with transmission and transformation congestion. The appropriate scheme is selected according to the indices proposed.

Neural interfaces are crucial conduits between neural tissues and external devices, enabling the recording and modulation of neural activity. However, with increasing demand, simple neural interfaces are no longer adequate to meet the requirements for precision, functionality, and safety. There are three main challenges in fabricating advanced neural interfaces: sensitivity, heat management, and biocompatibility. The electrical, chemical, and optical properties of 2D nanomaterials enhance the sensitivity of various types of neural interfaces, while the newly developed interfaces do not exhibit adverse reactions in terms of heat management and biocompatibility. Additionally, 2D nanomaterials can further improve the functionality of these interfaces, including magnetic resonance imaging (MRI) compatibility, stretchability, and drug delivery. In this review, we examine the recent applications of 2D nanomaterials in neural interfaces, focusing on their contributions to enhancing performance and functionality. Finally, we summarize the advantages and disadvantages of these nanomaterials, analyze the importance of biocompatibility testing for 2D nanomaterials, and propose that improving and developing composite material structures to enhance interface performance will continue to lead the forefront of this field.

Due to the large-scale integration of renewable energy and the rapid growth of peak load demand, it is necessary to comprehensively consider the construction of various resources to increase the acceptance capacity of renewable energy and meet power balance conditions. However, traditional grid planning methods can only plan transmission lines, often resulting in low utilization rates of newly constructed lines. Additionally, static planning methods can only address single-target scenarios and cannot cope with dynamic growth in load and renewable energy. To address these issues, this paper proposes a multi-stage collaborative planning method for transmission networks and energy storage. This method considers the non-line substitution effect of energy storage resources and their characterization methods. It establishes the coupling relationship between resources across different planning stages to achieve coordinated multi-stage planning for transmission networks and energy storage. Based on the IEEE-24 node system and a case study in a northern province of China, the results show that the proposed method reduces investment costs by approximately 30% compared to static planning methods and by about 7.79% compared to conventional grid planning methods. Furthermore, this method can accommodate more renewable energy.

As renewable energy becomes more widespread, the uncertainty of its output poses serious challenges for peak and frequency regulation of the power system. Evaluating a grid’s capacity to integrate renewable energy sources can provide an early-warning and decision-making basis for grid operation and scheduling. This paper presents a method for evaluating the hosting capacity of renewable energy, considering frequency security constraints. Introducing the system frequency nadir constraint into a system ensures that the frequency does not drop to a dangerous level in the event of power disturbances. The analytical characterization relation equation for the system frequency nadir constraint is constructed based on polynomial chaos expansion (PCE) theory. Furthermore, with the goal of minimizing the reduction in renewable energy, considering multiple flexible resources, like demand response (DR), Combined Heat and Power (CHP), energy storage, and Power-to-Gas (P2G), a renewable energy hosting capacity evaluation model that considers frequency security and flexibility resources is established. Finally, based on the concept of the feasible region, the maximum hosting capacity of a system’s renewable energy is visualized using the progressive vertex enumeration method. It identifies the safe operating region for renewable energy output that meets the safety constraints of power grid operations. The simulation results were validated using a modified IEEE 39 bus system.

In adapting to the double-high development trend of high-voltage direct current (HVDC) receiving-end power systems and solving optimization problems in emergency frequency control (EFC) supporting virtual power plants (VPPs) in large-scale power systems, a parameter estimation method for a VPP frequency response model based on a successive linear programming (SLP) method is proposed. First, a “centralized/decentralized” hierarchical control architecture for VPP participation in EFC is designed. Second, the frequency response characteristics of multiple flexible resources are scientifically analyzed, and the system frequency response (SFR) model and equivalent model of VPP are constructed. Subsequently, parameter estimation of the VPP frequency response model is carried out based on the SLP method, aiming to balance the accuracy and computational efficiency of the model. Finally, the effectiveness of the proposed methodology is verified by using PSD-BPA to simulate and test the three-zone HVDC recipient area grid.

Abstract Background Soybean is one of the most important oil crops in the world. The domestication of wild soybean has resulted in significant changes in the seed oil content and seed size of cultivated soybeans. To better understand the molecular mechanisms of seed formation and oil content accumulation, WDD01514 (E1), ZYD00463 (E2), and two extreme progenies (E23 and E171) derived from RILs were used for weighted gene coexpression network analysis (WGCNA) combined with transcriptome analysis. Results In this study, both seed weight and oil content in E1 and E171 were significantly higher than those in E2 and E23, and 20 DAF and 30 DAF may be key stages of soybean seed oil content accumulation and weight increase. Pathways such as “Photosynthesis”, “Carbon metabolism”, and “Fatty acid metabolism”, were involved in oil content accumulation and grain formation between wild and cultivated soybeans at 20 and 30 DAF according to RNA-seq analysis. A total of 121 oil content accumulation and 189 seed formation candidate genes were screened from differentially expressed genes. WGCNA identified six modules related to seed oil content and seed weight, and 76 candidate genes were screened from modules and network. Among them, 16 genes were used for qRT-PCR and tissue specific expression pattern analysis, and their expression-levels in 33-wild and 23-cultivated soybean varieties were subjected to correlation analysis; some key genes were verified as likely to be involved in oil content accumulation and grain formation. Conclusions Overall, these results contribute to an understanding of seed lipid metabolism and seed size during seed development, and identify potential functional genes for improving soybean yield and seed oil quantity.

Abstract Objective The study explored improvements in pulmonary inflammation and fibrosis in a bovine type II collagen-induced rheumatoid arthritis-associated interstitial lung disease mouse model after treatment with baricitinib and the possible mechanism of action. Methods A rheumatoid arthritis-associated interstitial lung disease mouse model was established, siRNA Jak2 and lentiviral vectors were transfected with human embryonic lung fibroblast cells. And the levels of relevant proteins in mouse lung tissue and human embryonic lung fibroblasts were detected by Western blotting. Results The levels of JAK2, p-JAK2, p-STAT3, p-SMAD3, SMA, TGFβR2, FN and COL4 were increased in the lung tissues of model mice (P

Abstract The Dunhuang Mogao Grottoes are a significant cultural heritage site in the Silk Road, famous for its wonderful murals and statues. The rainfall causes the changes of humidity in the caves, which can easily activate the salts diseases of murals. In order to prevent the deterioration of the murals, the environmental monitoring tests were conducted to analyze the microclimate changes of the cave in rainfall weather, and proposed the risk prevention measures and suggestions. The results indicate that the temperature of caves has small change, but the humidity shows a clear trend of increase. The humidity and the duration of high humidity increases with the increase of the rainfall grade and frequency. The optimal starting time for environment control in the cave is when a atm and a cave are consistent, and the relative humidity is controlled below 62%. The caves with lower layer, larger degree of openness and small volume are most vulnerable to water vapour diffusion. The environment monitoring should pay more attention to the continuous rainfall weather and the vulnerable caves. The research has great significance for the prevention of ancient mural deterioration.

Only a handful of massive starless core candidates have been discovered so far, but none of them have been fully confirmed. Within the MM1 clump in the filamentary infrared dark cloud G34.43+0.24 that was covered by the Atacama Large Millimeter/submillimeter Array (ALMA) ATOMS survey at Band 3 (∼2″, 6000 au) and the ALMA-QUARKS survey at Band 6 (∼0.″3, 900 au), two prestellar core candidates MM1-C and E1 with masses of 71 and 20 M _⊙ and radii of 2100–4400 au were discovered. The two cores show no obvious sign of star formation activities. In particular, MM1-C is a very promising massive prestellar core candidate with a total gas mass of 71 M _⊙ . Within MM1-C, we detected two extremely dense substructures, C1 and C2, as characterized by their high densities of ${n}_{{{\rm{H}}}_{2}}\sim {10}^{8\mbox{--}9}\,{\mathrm{cm}}^{-3}$ . Moreover, evidence of further fragmentation in C2 was also revealed. We have detected the primordial fragmentation in the earliest stage of massive star formation, and we speculate that MM1-C would be the birthplace of a massive multiple system. However, we cannot fully rule out the possibility that the massive prestellar core MM1-C will just form a cluster of low-mass stars if it undergoes further fragmentation.

Machine vision has been used to grade the potted anthurium plant in large-scale production recently. Images are taken to measure the number and size of anthurium spathes. However, due to the limitation of the shooting angle, the occlusion problem reduces the accuracy of measurement. It is necessary to segment the overlapping spathes and repair the incomplete ones. The traditional image completion model has good performance on missing small areas, but it is not satisfactory for missing large areas. In this article, a multi-scale fusion Recurrent Feature Reasoning (RFR) network was proposed to repair the spathe images. Unlike the traditional RFR, a multi-layer component was used in the feature reasoning module. This network can combine multi-scale features to complete the learning task and obtain more details of the spathe, which makes the network more advantageous in image completion when missing large areas of spathes. In this study, a comparison experiment between this network and the widely used image completion network was performed, and the results showed that this network performed well in all types of image completion, especially with large-area incomplete images.

Backgrounds The available literature on the correlation between serum amyloid A (SAA) and prognosis of chronic kidney disease (CKD) are limited, and the findings from existing studies are inconclusive. This meta-analysis aimed to evaluate the available evidence regarding the link between SAA and risks of all-cause and cardiovascular mortality in CKD patients. Additionally, we aimed to investigate the potential dose-response relationships, provided that adequate data is accessible.Methods Pubmed and Embase were searched for related literature (last update: 12 July 2023). The pooled effect estimates were calculated using random- or fixed-effects models depending on heterogeneity among studies.Results This meta-analysis incorporated 8 studies encompassing 2331 CKD patients. The findings revealed an 85% increase in all-cause mortality risk [hazard risk (HR) 1.85, 95% confidence interval (CI) 1.29–2.65] and a 39% increase in cardiovascular mortality risk (HR 1.07, 95% CI 1.07–1.80) when comparing the highest tertile of baseline SAA levels to the lowest tertile. Furthermore, a positive linear relationship between SAA and all-cause mortality risk was observed (Pnon-linearity = 0.959), with a 17.7% increase in risk for each 10 mg/L SAA increase (HR 1.177, 95% CI 1.055–1.313). Similarly, a linear relationship between SAA and cardiovascular mortality risk was identified (Pnon-linearity = 0.477) with a 19.3% increase in risk for each 10 mg/L SAA increase (HR 1.193, 95% CI 1.025–1.388).Conclusions This meta-analysis provided evidence that SAA levels are positively and linearly associated with risks of all-cause and cardiovascular mortality among CKD patients.

Highlights A mixed GAI and MAI (MGM) treatment modulating the bulk and interfacial defects simultaneously is reported. The devices’ performance is enhanced to ~24.5% in 0.12 cm2 and ~18.7% in 64 cm2 with improved stability. The MGM treatment can be applied to a wide range of perovskite compositions.

Abstract KDM4C, which is a histone lysine demethylase, has been proposed to participate in the malignant transformation and progression of several types of cancer. However, its roles in hepatocellular carcinoma (HCC) remain poorly understood. Here, we find that KDM4C protein expression is increased in HCC and promotes HCC cell growth, proliferation and migration. Furthermore, we provide evidence that depletion of KDM4C leads to a defective G2/M checkpoint, increases radiation-induced DNA damage, impairs DNA repair and enhances radiosensitivity in HCC cells. Using RNA sequencing, we identify that the chemokine CXCL2 is a downstream effector of KDM4C. KDM4C knockdown increases the binding of H3K36me3 to the promoter of CXCL2, thus upregulating CXCL2 expression and promoting CXCL2 secretion in HCC cells. Importantly, the observed effects of KDM4C depletion in HCC cells can be partially rescued by CXCL2 silencing. Thus, our findings reveal that KDM4C is involved in cell migration and radiosensitivity by modulating CXCL2 transcription, indicating that KDM4C may be a potential therapeutic target in HCC.

Abstract Background The discrepancy between the results of cytogenetics and the results of chromosome microarray analysis (CMA) has often led to confusion over genetic counselling for prenatal diagnosis. Case presentation The prenatal ultrasound results of a congenital heart defect (CHD) foetus displayed an apartial endocardial pad defect and permanently dilated coronary sinus and left superior vena cava at 21 weeks of gestation. Cytogenetic analysis, CMA, fluorescent in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) with foetal cord blood samples were used to detect the genetic aetiology. Routine G-binding cytogenetic analysis showed normal karyotypes in both the foetus’ and parents’ blood samples. CMA results demonstrated that there were 53.973-Mb recurrent CNVs at Xp22.33-p11.22, as confirmed by MLPA assay. Conclusions Herein, we described the CNV of six duplications at Xp22.33-p11.22 and the 53.973 Mb duplication CNV that was not found in foetal cord blood samples by conventional cytogenetic methods, and it was confirmed by CMA and MLPA. Our novel findings will provide helpful information for prenatal diagnosis and genetic counselling for foetal CHDs.

This study sought to explore the antimicrobial activity of punicalagin against V. parahaemolyticus and its potential modes of action. V. parahaemolyticus ATCC 17802 and RIMD 2210633Sm were exposed to punicalagin, and the energy production, membrane potential, and envelope permeability, as well as the interaction with cell biomolecules, were measured using a variety of fluorescent probes combined with electrophoresis and Raman spectroscopy. Punicalagin treatment disrupted the envelope integrity and induced a decrease in intracellular ATP and pH. The uptake of 1-N-phenyl-naphtylamine (NPN) demonstrated that punicalagin weakened the outer membrane. Punicalagin damaged the cytoplasmic membrane, as indicated by the membrane depolarization and the leakage of intracellular potassium ions, proteins, and nucleic acids. Electronic microscopy observation visualized the cell damage caused by punicalagin. Further, gel electrophoresis coupled with the Raman spectrum assay revealed that punicalagin affected the protein expression of V. parahaemolyticus, and there was no effect on the integrity of genomic DNA. Therefore, the cell envelope and proteins of V. parahaemolyticus were the assailable targets of punicalagin treatment. These findings suggested that punicalagin may be promising as a natural bacteriostatic agent to control the growth of V. parahaemolyticus.