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Abstract Chemoresistance remains a major challenge in the effective treatment of colorectal cancer (CRC), contributing to poor patient outcomes. While the molecular mechanisms underlying chemoresistance are complex and multifaceted, emerging evidence suggests that altered mitochondrial function and hormone signaling play crucial roles. In this study, we investigated the role of CYP19A1, a key enzyme in estrogen biosynthesis, in regulating chemoresistance in CRC. Using a combination of in vitro functional assays, transcriptomic analysis, and clinical data mining, we demonstrate that CYP19A1 expression is significantly upregulated in CRC cells and patient-derived samples compared to normal controls. Mechanistically, we found that CYP19A1 regulates chemoresistance through modulation of mitochondrial function and complex I activity, which is mediated by CYP19A1-dependent estrogen biosynthesis. Notably, targeted inhibition of CYP19A1 and complex I using specific inhibitors effectively reversed the chemoresistance of CRC cells to chemotherapeutic drugs. Moreover, analysis of the TCGA CRC dataset revealed that high CYP19A1 expression correlates with poor overall survival in chemotherapy-treated patients. Taken together, our findings uncover a novel role for CYP19A1 in regulating chemoresistance in CRC through modulation of mitochondrial function and estrogen signaling, and highlight the potential of targeting the CYP19A1/estrogen/complex I axis as a therapeutic strategy to overcome chemoresistance and improve patient outcomes.

Abstract Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. Methods This trial compared two aspects of radiation treatment, total dose and field, using a two‐by‐two factorial design. The high‐dose (HD) group received 59.4 Gy radiation, and the standard‐dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression‐free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. Results The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80‐1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82–1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72–1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. Conclusions IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

Abstract Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems.

Abstract Objective The purpose of this study was to investigate the diagnostic value of circ_0013958 in acute myocardial infarction (AMI) patients and its influence on the prognosis of AMI patients. Methods The GSE160717 dataset was downloaded from the NCBI database and differentially expressed genes were analyzed between the control group and the AMI group. The up-regulated genes included circ_0013958. The expression of circ_0013958 in both groups was further verified by RT-qPCR. The Receiver Operating Characteristic curve was used to evaluate the diagnostic value of circ_0013958 in AMI. Pearson correlation analysis was used to examine the correlation between circ_0013958 levles and biochemical indicators. Binary logistic regression was used to analyze the risk factors affecting the occurrence of AMI. Prognostic analysis was performed using COX regression analysis and the Kaplan-Meier Curve. Results Compared to the control group, the level of circ_0013958 in AMI patients increased. Circ_0013958 can effectively distinguish AMI patients from non-AMI patients. Circ_0013958 levels were positively correlated with cTnI, LDH, CRP and TC levels. The elevated level of circ_0013958 was an independent risk factor for the occurrence of AMI. Higher circ_0013958 levels were also associated with the occurrence of major adverse cardiac events (MACEs) in AMI patients. Additionally, elevated circ_0013958 levels reduced the survival probability of AMI patients. Conclusion Circ_0013958 levels were up-regulated in AMI patients. It can be used as a diagnosis biomarker for AMI. The level of circ_0013958 was correlated with the disease severity and was an independent risk factor for the occurrence of AMI. Elevated circ_0013958 levels were associated with poor prognosis in AMI patients.

This study evaluated the effect of black soldier fly (Hermetia illucens) larvae oil (BO) produced by a novel technique, subcritical butane extraction, on the flesh quality, lipid nutrients and muscle growth of rainbow trout (Oncorhynchus mykiss) fillet, and investigated the alleviating mechanisms of dietary astaxanthin (AST) supplementation. Two hundred and forty fish (215.16 ± 2.30 g) were distributed to three groups with four replicates. Fish were fed three experimental diets for 8 weeks: the control diet (CD diet), total fish oil of the CD diet was replaced with BO to formulate the BO100 diet, and then 1 g/kg AST was supplemented with the BO100 diet to formulate the AST diet. Results showed that the final body weight and the sarcomere length of fillet were significantly increased and the protein phosphorylation levels of mammalian target of rapamycin (mTOR) and p70 S6 kinase were enhanced in the BO100 group compared to the CD group (P

This study aimed to compare the effects of dietary methionine (Met) and 2-hydroxy-4-(methylthio)-butanoate (HMTBA) on the eggshell quality of broiler breeder hens and elucidate the mechanism of Met in improving eggshell quality from the perspectives of eggshell microstructure and shell gland physiological function. A total of 720 WOD188 broiler breeder hens at 40 weeks old were assigned to 3 groups, with 8 replicates per group and 30 birds per replicate. Over 7 weeks, birds were fed a basal diet or the same diet supplemented with 0.15% Met or 0.17% HMTBA. Our findings revealed significant improvements in the Met group for egg shape index, shell thickness, breaking strength, and fracture toughness (P 0.05). Met supplementation increased calcium and phosphorus levels in both serum and shell gland tissue (P

Abstract This study aimed to investigate the knowledge, attitude, and practice (KAP) of non-emergency surgical patients toward anesthesia. This cross-sectional study was conducted between May and October 2023 at Zibo Central Hospital among non-emergency surgical patients. A total of 429 valid questionnaires were enrolled (mean age: 42.81 ± 13.17 years old; 227 (52.91%) females). The mean KAP scores were 7.79 ± 3.95 (possible range: 0–18), 32.35 ± 2.80 (possible range: 8–40), and 18.14 ± 3.96 (possible range: 6–24), respectively. Multivariate logistic regression analysis showed that knowledge (OR = 1.095, 95% CI 1.036–1.158, P = 0.001) and previous poor anesthesia experience (OR = 0.081, 95% CI 0.017–0.386, P = 0.002) were independently associated with practice. Non-emergency surgical patients had inadequate knowledge, positive attitude, and proactive practice towards anesthesia. It is crucial for healthcare professionals to implement targeted educational interventions to inform patients about the anesthesia process, potential risks, and benefits.

Abstract Autoreactive CD4+ T helper cells are critical players that orchestrate the immune response both in multiple sclerosis (MS) and in other neuroinflammatory autoimmune diseases. Ubiquitination is a posttranslational protein modification involved in regulating a variety of cellular processes, including CD4+ T cell differentiation and function. However, only a limited number of E3 ubiquitin ligases have been characterized in terms of their biological functions, particularly in CD4+ T cell differentiation and function. In this study, we found that the RING finger protein 213 (RNF213) specifically promoted regulatory T (Treg) cell differentiation in CD4+ T cells and attenuated autoimmune disease development in an FOXO1-dependent manner. Mechanistically, RNF213 interacts with Forkhead Box Protein O1 (FOXO1) and promotes nuclear translocation of FOXO1 by K63-linked ubiquitination. Notably, RNF213 expression in CD4+ T cells was induced by IFN-β and exerts a crucial role in the therapeutic efficacy of IFN-β for MS. Together, our study findings collectively emphasize the pivotal role of RNF213 in modulating adaptive immune responses. RNF213 holds potential as a promising therapeutic target for addressing disorders associated with Treg cells.

Abstract Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.

Abstract Assimilatory nitrate reduction and methane (CH4) oxidation by bacteria play important roles in carbon (C) and nitrogen (N) biogeochemical cycles. Here, an investigation of enzymatic assimilatory nitrate reduction and CH4 oxidation by Methylobacter sp. YHQ from the wetlands is presented, specifically concentrating on N and oxygen (O) isotope fractionation with various initial nitrate and oxygen concentrations. The N enrichment factors (15 ε assimilation) increased from 4.2 ± 0.7‰ to 6.9 ±1.3‰ and the O isotope enrichment factors (18 ε assimilation) increased from 2.7 ± 0.9‰ to 4.7 ± 0.8‰ during nitrate assimilation when initial nitrate concentrations increased from 0.9 mM to 2 mM. Similar 18 ε and 15 ε values were observed at different oxygen concentrations. The values of 18 ε and 15 ε provided vital parameters for the assessment of assimilatory nitrate reduction via the Rayleigh equation approach. The ratios of O and N isotope enrichment factors (18 ε:15 ε)assimilation ranged from 0.64 ± 0.15 to 0.74 ± 0.18 during nitrate assimilation by Methylobacter sp. YHQ with Nas, which were different from (18 ε:15 ε)assimilation for assimilatory eukaryotic nitrate reductase (eukNR) from literature data. Thus, N and O isotope fractionation could be useful tools to distinguish eukNR from Nas during nitrate assimilation. Additionally, the rates of CH4 oxidation and nitrate reduction were evaluated with a reaction-based kinetic model, and it quantitatively described the enzymatic reactions of nitrate assimilation. Combining dual N-O isotope analysis with kinetic modeling provides new insights into the microbially driven C-N interactions. Graphical Abstract

During the process of heating greenhouses, the phenomenon of inadequate heating installations is widespread. To address this issue, this paper proposed a solar air collector-air source heat pump (SAC-ASHP) system for greenhouses, combining solar technology with heat pump (HP) technology to provide sufficient heat during continuous cloudy days and winter. The heating capacities of the system on sunny, cloudy, and overcast days were 100.2 kWh, 112.3 kWh, and 157.8 kWh, respectively. The corresponding power was 30.1 kWh, 36.1 kWh, and 53.6 kWh. The coefficient of performance (COP) of the single air source heat pump (ASHP) for these days was 3.4, 3.2, and 3.0, respectively, while the COP of the solar heat pump (SHP) was 4.0, 3.5, and 3.1. Additionally, greenhouse employed heat and moisture recovery for humid air, aiming to provide a suitable environment for plant growth around the clock while conserving energy. The heat collection in the heat and moisture recovery combined HP mode was 66.7 % higher than in the heat exchanger (HE)-fan mode. This experimental study investigated the operational performance of the system in dynamic environments, revealing the stability of the system for greenhouse heating in cold regions, and providing new research ideas for greenhouse heating.

AimsTo investigate the prevalence and influencing factors of drug-related problems (DRPs) in inpatients with kidney disease to provide reference data for pharmaceutical care.MethodsThe basic information, diagnoses, and medication reconciliation (MR) of inpatients in the Department of Nephrology at our hospital between October 2020 and September 2021 were collected. The Chinese-modified DRP version based on the PCNE classification (Version 9.1) was used to assess, intervene and statistically analyze the results of the patients’ DRPs. The influence factor of DRPs in inpatients with kidney disease was analyzed by the multivariate binary logistic regression.ResultsOf 623 patients included in this study, 132 (21.80%) had DRPs. The prevalence of anemia was significantly higher in patients with DRPs than those without DRPs (43.18% vs. 28.72%, p < 0.05), the mean number of drug types consumed (7.25 ± 3.44 with DRPs vs. 5.93 ± 3.58 without DRPs, p < 0.05) and the proportion of ≥5 drugs (%) (79.55% with DRPs vs 58.04% without DRPs, p < 0.05) were significantly increased. In addition, the prevalence of hypertension (76.52% vs. 68.64%), diabetes (27.27% vs. 22.20%) and hyperuricemia (16.67% vs. 13.65%) in DRP patients were higher than those without DRPs, but there was no statistical difference (p > 0.05). The logistic regression analysis showed that patients with anemia (OR = 1.702, 95%CI: 1.146–2.529, p = 0.008), average number of medication types taken (OR = 1.089, 95%CI: 1.034–1.147, p = 0.001) significantly increased the risk of DRPs. The distribution of harm levels was as follows: 78 problems (59.09%) were level C, 29 (21.97%) were level B, 10 (7.58%) were level D, 7 (5.30%) were level A, 7 (5.30%) were level E, and 1 (0.76%) were level F. All DRPs were resolved after 128 interventions.ConclusionRenal anemia, the average number of drug varieties consumed, and the proportion of ≥5 drugs are associated with the occurrence of DRPs. Pharmacists conducting MR services can reduce DRPs of inpatients in the department of nephrology and ensure patient drug safety.

IntroductionInonotus hispidus, commonly referred to as the Sanghuang mushroom, is a species that is consumed as a tea. To date, this is the only species of the same fungus that has been successfully cultivated.MethodsA single-factor test was conducted using Inonotus hispidus MS-5 and MS-9 as test materials. The response surface methodology was adopted to design and optimise the liquid fermentation medium for them.ResultsAs indicated in the results, the optimum fermentation conditions for MS-5 include 24.09 g/L glucose, 7.88 g/L yeast extract, 0.99 g/L dandelion powder, 1.5 g MgSO4, 2 g KH2PO4, 0.01 g vitamin B1, and 1 L deionized water; the optimum fermentation conditions for MS-9 include 24.64 g/L glucose, 7.77 g/L yeast extract, 0.98 g/L dandelion powder, 1.5 g MgSO4, 2 g KH2PO4, 0.01 g vitamin B1, and 1 L deionized water. Under such conditions, the mycelial biomass (dry weight) values were able to reach 16.02 g/L and 14.91 g/L for MS-5 and MS-9, respectively, which were 1.6 and 1.54 times those measured before optimization.DiscussionAs revealed in the antioxidant and anticancer experiment, Inonotus hispidus exopolysaccharides has corresponding functional effects at the cellular level. This research optimised the liquid culture formulation of Inonotus hispidus and demonstrated that the function of it as a traditional Sanghuang herbal tea is well-documented.

Abstract Background The Xylogone ganodermophthora is a pathogenic bacterium that poses a significant challenge to the continuous cultivation of the Ganoderma lucidum fungus. This study aims to identify and investigate specific agents for the effective prevention and control of X. ganodermophthora, establishing a theoretical foundation for overcoming this persistent challenge in G. lucidum cultivation. Results Using different G. lucidum soil as materials to study the presence of X. ganodermophthora in the soil. Additionally, the plate confrontation test was employed to investigate the impact of X. ganodermophthora on G. lucidum growth. The impact of physical factors and antibacterial agents on pathogenic bacteria was successfully carried out, with a further exploration of the effectiveness of field control. PCR amplification experiment and sequencing analysis verified that X. ganodermophthora existed in G. lucidum continuous cropping obstacle soil. This pathogenic bacteria has a significant inhibitory effect on the growth of G. lucidum, with an inhibition rate of up to 52.23%. High temperature, low temperature, light and other physical factors have no obvious inhibitory effect on this pathogen. Further investigation revealed that specific drugs, such as low concentrations (10 μL/mL) of Acticide DB20 and Imazalil, could effectively inhibit X. ganodermophthora growth in G. lucidum. Among them, Imazalil has a notable inhibitory effect on the growth of X. ganodermophthora. Conclusions Indoor toxicity test and field control results showed that Imazalil could effectively control the growth of pathogen X. ganodermophthora in G. lucidum continuous cropping obstacle, and promote the growth of G. lucidum. Graphical Abstract

Introduction: Human papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. Objectives: We established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. Methods: We designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. Results: We successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. Conclusion: We highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis.

Microsatellite DNA (SSR) is extensively used as molecular markers in diverse fields, including molecular ecology, conservation biology, and molecular breeding. Nevertheless, the efficient and easy acquisition of high-quality SSR molecular markers for economically cultured marine animals remains a challenge. Holothuria leucospilota is an economically and ecologically important tropical sea cucumber. Recently, artificial breeding and cultivation of this species have been reported. However, there is still a lack of highly polymorphic SSR molecular markers for geographical population differentiation and genetic breeding. This study aims to develop and utilize SSR markers from genomic data to assess the genetic variation and population structure of H. leucospilota in the South China Sea. A comprehensive pipeline was created, integrating microsatellite discovery, primer design, and assessment into a single platform. Through this, 15 highly polymorphic microsatellite loci were identified and validated. The results revealed high genetic diversity and low genetic differentiation among H. leucospilota populations. Larval dispersal and ocean currents in the South China Sea were identified as the primary factors influencing genetic connectivity between populations. In addition, the artificial culture and releasing of H. leucospilota have influenced the genetic structure of their wild populations in the South China Sea. This study provides a pipeline for identifying SSR markers within genome data, and applies it to assess the genetic diversity and structure of H. leucospilota. The outcomes of this research are expected to be beneficial and applicable to the future aquaculture of tropical sea cucumbers.

Steel slag, as an industrial byproduct obtained from the steel manufacturing industry, may cause land occupation, resource waste, and environmental pollution. The application of steel slag as a material for soil reinforcement in road engineering is very popular due to its potential hydration activity. The unconfined compression strength, microstructure, and transport properties of loess soil with cement, lime and steel slag were investigated. The results show that the loess soil can be reinforced by cement, lime, and steel slag to varying degrees. The reinforcement mechanism of cement for loess soil is realized by pore filling by cement hydration products such as CH, C-S-H and AFt, and their unconfined compression strength is improved by reducing the porosity. The reinforcement mechanism of lime for loess soil is achieved by pore filling by hydration products such as CH and CaCO3, and their strength is improved by a refined pore structure where the porosity has not been significantly reduced. The reinforcement mechanism of steel slag for loess soil is a combined mechanism of cement and lime, including pore filling and refined pores. The pore structure of reinforced soil can be studied at different scales by the MIP, LF NMR, and X-CT test methods. The transport properties including diffusivity and permeability of reinforcing soil can be well explored by Avizo software based on the microstructure obtained from X-CT.

In China, steel slag as a solid waste caused land occupation and environmental pollution, and its utilization ratio is relatively low. To increase the utilization field and ratio of steel slag, hydration behavior and cementitious properties of three types of steel slag were investigated and compared based on test results from an early age to a long-term via multiple techniques. Experimental results suggested that steel slag showed a strong latent hydraulic activity at a later age, and the mechanical strength of steel slag paste specimens (w/b=0.3) could reach 15 MPa at 360 days. Cementitious properties of steel slag were primally depended on the hydration of calcium silicate (C3S and C2S), calcium aluminate (ferrite), glassy phase in steel slag, especially for calcium silicate. The sum amount of calcium silicate in used steel slag was approximately from 21% to 28%, and the amount of C2S was significantly greater than that of C3S. The hydration of C2S and glassy phase resulted in the continuous increase in bound water content of steel slag, and a certain content of C2S still existed in pastes at 360 days. The mechanical strength of steel slag pastes markedly increased at a later age due to more hydrates formed in the microstructure.

Abstract Self‐assembly processes triggered by physical or chemical driving forces have been applied to fabricate hierarchical materials with subtle nanostructures. However, various physicochemical processes often interfere with each other, and their precise control has remained a great challenge. Here, in this paper, a rational synthesis of 1D magnetite‐chain and mesoporous‐silica‐nanorod (Fe3O4&mSiO2) branched magnetic nanochains via a physical–chemical coupling coassembly approach is reported. Magnetic‐field‐induced assembly of magnetite Fe3O4 nanoparticles and isotropic/anisotropic assembly of mesoporous silica are coupled to obtain the delicate 1D branched magnetic mesoporous nanochains. The nanochains with a length of 2–3 µm in length are composed of aligned Fe3O4@mSiO2 nanospheres with a diameter of 150 nm and sticked‐out 300 nm long mSiO2 branches. By properly coordinating the multiple assembly processes, the density and length of mSiO2 branches can well be adjusted. Because of the unique rough surface and length in correspondence to bacteria, the designed 1D Fe3O4&mSiO2 branched magnetic nanochains show strong bacterial adhesion and pressuring ability, performing bacterial inhibition over 60% at a low concentration (15 µg mL−1). This cooperative coassembly strategy deepens the understanding of the micro‐nanoscale assembly process and lays a foundation for the preparation of the assembly with adjustable surface structures and the subsequent construction of complex multilevel structures.

Titanium (Ti)-based metal-organic frameworks (Ti-MOFs) have attracted intensive research attention due to their low toxicity and high abundance of titanium. However, limited by the high reactivity of titanium species in the reaction system, the construction of Ti-MOFs still faces great challenges. Herein, we successfully introduced Ti into MOF-74 using a one-pot method. Powder X-ray diffraction (PXRD) combined with X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma (ICP) spectroscopy confirmed that the Ti­(IV) ions were uniformly inserted into the MOF-74 structure. Our scanning electron microscopy (SEM)/energy-dispersive spectrometry (EDS) analysis showed that the Ti content was up to 44% with good sample homogeneity. The adsorption selectivity of Ti0.44/Ni0.56-MOF-74 at 1.0 bar and 298 K for C2H2/C2H4 and C2H2/CO2 (50/50, v/v) mixtures was 4.9 and 6.8, respectively, which are higher than that of pristine Ni-MOF-74. The results of our breakthrough simulation experiments revealed that the adsorption and separation performances of Ti0.44/Ni0.56-MOF-74 were greatly improved. This study provided insights for the construction of Ti-based bimetallic MOFs used for the separation of light hydrocarbons.

Objective(s): To investigate the effects and mechanisms of ivabradine (IVA) on isoprenaline-induced cardiac injury.Materials and Methods: Forty male C57BL/6 mice were randomly divided into control group, model group, high-dose IVA group, and low-dose IVA group. The control group was given saline, other groups were given subcutaneous injections of isoproterenol (ISO) 5 mg/kg/d to make the myocardial remodeling model. A corresponding dose of IVA (high dose 50 mg/kg/d, low dose 10 mg/kg/d) was given by gavage (30 days). A transthoracic echocardiogram was obtained to detect the structure and function of the heart. An electron microscope was used to explore the cardiomyocytes’ apoptosis and autophagy. HE staining and Masson’s trichrome staining were performed to explore myocardial hypertrophy and fibrosis. Western blot was used to detect Bax, Bcl-2, cleaved caspase-3, Becline-1, LC3, phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), phosphorylated extracellular regulated protein kinases1/2 (p-ERK1/2), phosphorylated c-Jun N-terminal kinase (p-JNK), and α-smooth muscle actin (α-SMA) in the myocardium.Results: Heart rate in the IVA groups was reduced, and the trend of heart rate reduction was more obvious in the high-dose group. Echocardiography showed that IVA improved the cardiac structure and function compared to the model group. IVA attenuated cardiac fibrosis, decreased cardiomyocyte apoptosis, and increased autophagy. The phosphorylated MAPK in the ISO-induced groups was increased. IVA treatment decreased the p-p38MAPK level. There were no differences in p-ERK and p-JNK levels.Conclusion: The beneficial effects of IVA on myocardial injury are related to blocking the p38MAPK signal pathway, decreasing cardiomyocyte apoptosis, and increasing cardiomyocyte autophagy.

Abnormal crops image data play crucial role in controlling crop diseases and pest for smart agriculture. However, current agricultural image acquisition methods suffer from low-value data. This article presents a new strategy for collect high-quality image data for abnormal crops. First, a novel agricultural Internet of Things (IoT) image acquisition system is proposed, that integrates edge intelligence, motion–static synergy, which enables both coarse and fine crop image acquisition. To enhance image acquisition efficiency and data value in the agricultural IoT, this article proposes an image acquisition method based on edge intelligence and static and motion collaboration, using banana plantations as the example object. The method comprises three phases. In the first phase, the edge server deploys the YOLO-FDAC target detection model to detect abnormal crops from the images captured by static nodes. In the second phase, the coordinate solution method of abnormal crops and the quantification method of the degree of abnormality is presented. In the third phase, based on the severity of abnormality and the ant colony optimization, a path optimization algorithm for the image acquisition robot is designed. Finally, this article evaluates the performance of each level of the proposed method by comparing it with traditional methods. The experimental results demonstrate that the proposed image acquisition strategy has high acquisition efficiency and high image data value.

Abstract Background Mechanical power (MP) is the total energy released into the entire respiratory system per minute which mainly comprises three components: elastic static power, Elastic dynamic power and resistive power. However, the energy to overcome resistance to the gas flow is not the key factor in causing lung injury, but the elastic power (EP) which generates the baseline stretch of the lung fibers and overcomes respiratory system elastance may be closely related to the ARDS severity. Thus, this study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients. Methods We retrieved patient data from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The retrieved data involved adults (≥ 18 years) diagnosed with ARDS and subjected to invasive mechanical ventilation for ≥ 48 h. We employed univariate and multivariate logistic regression analyses to investigate the correlation between EP and development of moderate-severe ARDS. Furthermore, we utilized restricted cubic spline models to assess whether there is a linear association between EP and incidence of moderate-severe ARDS. In addition, we employed a stratified linear regression model and likelihood ratio test in subgroups to identify potential modifications and interactions. Results Moderate-severe ARDS occurred in 73.4% (296/403) of the patients analyzed. EP and MP were significantly associated with moderate-severe ARDS (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.15–1.28, p

Abstract Background Cervical conization is a brief but painful procedure that can be performed under sufficient sedation with propofol and opioids. However, this sedation approach comes with a high risk of sedation-related adverse events (SRAEs). Esketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, causes less cardiorespiratory depression than opioids. The aim of this study was to assess the efficacy and safety of adding a low dose of esketamine to propofol and sufentanil sedation as an opioid-reduced regimen. Methods A total of 122 consecutive patients with ASA I-II, body mass index

Additive Manufacturing (AM) can rapidly fabricate and produce customized, large-scale components, thereby fully exploiting High-Entropy Alloys (HEAs)' performance and industrial value—their broad potential for application in extreme service environments such as nuclear energy and aerospace. Because HEAs have a vast composition space, researchers can accurately map their mechanical properties by HEAs phases to reduce time-consuming and intensive experimental work. However, it is still a considerable challenge to predict HEAs phases accurately. And machine learning (ML) can predict the phases to accelerate the study of HEAs.To accurately predict the HEAs phases, the study propose deep learning (DL) algorithms that rely on AM process parameters and data augmentation and do the following: (i) This study developed a more detailed phase classification strategy for HEAs to enable the model to predict the complex multiphase of HEAs; (ii) The process parameters of AM affect the formation of the HEAs phase. In this study, the process parameters of AM are added to the model features to improve the model's accuracy in predicting the HEAs phase; (iii) To alleviate the data scarcity dilemma of HEAs, this study use data augmentation to improve DL's performance further. The results show that after adding AM process parameters to the model and performing data augmentation, the DL model's accuracy to 91.23%. In addition, this study manufactured four new HEAs through AM experiments to verify the robustness and practicality of their algorithms.

Abstract Objective To compare force degradation of elastomeric chains and NiTi coil springs in vivo and in vitro, and evaluate the effects of pre-stretched and reused elastomeric chains in the oral cavity during the time. Methods In the in vitro groups, 4-unit elastomeric chains and NiTi coil springs with an initial force of 200 g were placed in dry air and artificial saliva. The volunteers wore clear retainers which were used to hold the sample of 4-unit chains, pre-stretched 4-unit chains, and NiTi coil springs with the initial force of 200 g in the in vivo groups. After the first 4 weeks, 4-unit specimens were stretched to 200 g again for another 4 weeks in vivo. The force value and the percentage of force degradation were recorded at each measurement time interval in the in vivo and in vitro groups. Results The force degradation of elastomeric chains was greatest within the initial 4 hours, followed by a more stable phase after 1 week. The average force degradation of 4-unit elastomeric chains after 4 weeks was in vivo (64.8%) > artificial saliva (55.0%) > dry air (46.42%) (P

Compared to traditional manual methods for assessing the cotton verticillium wilt (CVW) hazard level, utilizing deep learning models for foliage segmentation can significantly improve the evaluation accuracy. However, instance segmentation methods for images with complex backgrounds often suffer from low accuracy and delayed segmentation. To address this issue, an improved model, YOLO-VW, with high accuracy, high efficiency, and a light weight, was proposed for CVW hazard level assessment based on the YOLOv10n model. (1) It replaced conventional convolutions with the lightweight GhostConv, reducing the computational time. (2) The STC module based on the Swin Transformer enhanced the expression of foliage and disease spot boundary features, further reducing the model size. (3) It integrated a squeeze-and-excitation (SE) attention mechanism to suppress irrelevant background information. (4) It employed the stochastic gradient descent (SGD) optimizer to enhance the performance and shorten the detection time. The improved CVW severity assessment model was then deployed on a server, and a real-time detection application (APP) for CVW severity assessment was developed based on this model. The results indicated the following. (1) The YOLO-VW model achieved a mean average precision (mAP) of 89.2% and a frame per second (FPS) rate of 157.98 f/s in assessing CVW, representing improvements of 2.4% and 21.37 f/s over the original model, respectively. (2) The YOLO-VW model’s parameters and floating point operations per second (FLOPs) were 1.59 M and 7.8 G, respectively, compressed by 44% and 33.9% compared to the original YOLOv10n model. (3) After deploying the YOLO-VW model on a smartphone, the processing time for each image was 2.42 s, and the evaluation accuracy under various environmental conditions reached 85.5%, representing a 15% improvement compared to the original YOLOv10n model. Based on these findings, YOLO-VW meets the requirements for real-time detection, offering greater robustness, efficiency, and portability in practical applications. This model provides technical support for controlling CVW and developing cotton varieties resistant to verticillium wilt.

The Agrobacterium-based transgenic technique is commonly used for gene function validation and molecular breeding. However, it is not suitable for plants with a low regeneration capacity or a low transformation rate, such as Panax notoginseng (Burk) F.H. Chen and Lilium regale Wilson. In this study, a novel Agrobacterium transformation method based on injection in the meristems was developed using P. notoginseng and L. regale as experimental models. PCR analysis confirmed the successful integration of the reporter gene DsRed2 (Discosoma striata red fluorescence protein 2) into the genome of two experimental models. QRT-PCR and Western blot analysis demonstrated the transcriptional and translational expression of DsRed2. Additionally, laser confocal microscopy confirmed the significant accumulation of the red fluorescent protein in the leaves, stems, and roots of transformed P. notoginseng and L. regale. Most importantly, in the second year after injection, the specific bright orange fluorescence from DsRed2 expression was observed in the transgenic P. notoginseng and L. regale plants. This study establishes a fast, efficient, and tissue-culture-independent transgenic technique suitable for plants with a low regeneration capacity or a low transformation rate. This technique may improve the functional genomics of important medicinal and ornamental plants such as P. notoginseng and L. regale, as well as their molecular breeding.

Abstract Objective This study investigated the correlation between the pulsatility index (PI) of the middle cerebral artery with the total burden of cerebral small vessel disease and cognitive impairment. Method Information on patients hospitalized in the Department of Neurology was collected retrospectively. These patients had complete clinical and laboratory data. The middle cerebral artery PI was measured using transcranial Doppler, a Mini‐Mental State Examination (MMSE) was used to assess cognitive function, and the total cerebral small vessel disease burden was assessed using magnetic resonance imaging. Patients were grouped according to their scores for total imaging burden of cerebral small vessel disease and cognitive function. Logistic regression analysis assessed the association between the PI, total imaging burden, and cognitive impairment. Spearman analysis was used to evaluate the correlation between the PI and total imaging burden and cognitive impairment, and receiver operating characteristic (ROC) curves were used to determine the predictive value of the PI for cognitive function. Results The PI was higher in the cognitive impairment (CI) group than in the no‐CI group. Binary logistic regression analysis showed that increased PI was an independent risk factor for CI (OR = 1.582; 95% CI: 1.043–2.401; p = .031) and total imaging burden (OR = 1.842; 95% CI: 1.274–2.663; p = .001). Spearman analysis found that the PI correlated negatively with the MMSE score (r = −.627, p

Rationale and objectives: Postoperative pelvic radiographs remain a vital tool for assessing cup orientation after total hip arthroplasty (THA), with the accuracy influenced by various factors. The objective of this study is to investigate the accuracy of cup anteversion measurement in developmental dysplasia of the hip (DDH) patients and others based on postoperative pelvic radiographs conducted under the current heavy workload conditions. Materials and methods: Patients who underwent THA at our hospital with both postoperative X-ray and CT images from January 2020 to December 2022 were included in this retrospective cohort study. Virtual X-ray films were generated using digitally reconstructed radiographs (DRR) technology from CT images, with pelvic position perfectly controlled. Radiographic anteversion (RA) was measured on 3D-CT, virtual X-rays, and actual postoperative X-rays, abbreviated as RA_3D, RA_DRR, and RA_Xray, respectively. A repeated-measures analysis of covariance (ANCOVA) was utilized to evaluate the variations in RA within and between different groups across three methods. The Bland-Altman plot analysis showed the variations among methods in DDH and non-DDH patients, setting a clinically acceptable limits of agreement (LOA) at ±5°. Results: This study included 154 hip cases, with 63 DDH and 91 other diseases. Repeated-measures ANCOVA revealed a descending trend in RA across three methods, with differences of 2.64° (DDH) vs. 2.74° (others) from 3D to DRR, and 4.89° (DDH) vs. 1.07° (others) from DRR to X-ray. The group by methods interaction effect were significant (p = 0.002). Significant statistical differences in RA_Xray (P = 0.035) were observed between DDH and non-DDH patients, but not in RA_3D and RA_DRR. Bland-Altman plots showed 71.4 % of DDH patients exceeded the clinically acceptable LOA, compared to 36.3 % of other patients. Conclusion: Our study indicated that under the current intense workload, the reliability of assessing cup anteversion using postoperative pelvic radiographs is challenged, especially in patients with DDH.

Abstract Background The association between obstructive sleep apnea syndrome (OSAS) and mortality has not been extensively researched among individuals with varying diabetic status. This study aimed to compare the relationship of OSAS with all‐cause and cause‐specific mortality in US individuals with or without diabetes based on data from the National Health and Nutrition Examination Survey (NHANES). Methods The study included participants from the NHANES 2005–2008 and 2015–2018 cycles with follow‐up information. OSAS data (OSAS.MAP10) was estimated from the questionnaire. Hazard ratios (HRs) and the 95% confidence interval (CI) of OSAS for mortality were calculated by Cox regression analysis in populations with different diabetes status. The relationships between OSAS and mortality risk were examined using survival curves and restricted cubic spline curves. Results A total of 13 761 participants with 7.68 ± 0.042 follow‐up years were included. In the nondiabetic group, OSAS.MAP10 was positively associated with all‐cause, cardiovascular, and cancer mortality. In individuals with prediabetes, OSAS.MAP10 was positively related to all‐cause mortality (HR 1.11 [95% CI: 1.03–1.20]) and cardiovascular mortality (HR 1.17 [95% CI: 1.03–1.33]). The relationship between OSAS.MAP10 and the risk of all‐cause mortality and cancer mortality exhibited L‐shaped curves in diabetes patients (both with nonlinear p values

Abstract Background To examine standardized uptake valuemax of the primary lesion (pSUVmax) and tumor markers (TMs) for clinically predicting distant metastasis in novo lung adenocarcinoma. Methods The current retrospective observational study examined individuals diagnosed with de novo lung adenocarcinoma at Shanxi Cancer Hospital between February 2015 and December 2019. Results Totally, 532 de novo lung adenocarcinoma cases were included. They were aged 60.8 ± 9.7 years and comprised 224 women and 268 patients with distant metastasis. The areas under the curves (AUCs) of pSUVmax, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), cytokeratin‐19 fragment (CYFRA21‐1), carbohydrate antigen 125 (CA125), and Grade of TMs for predicting distant metastasis were 0.742, 0.601, 0.671, 0.700, 0.736, and 0.745, respectively. The combination of pSUVmax, LDH, CEA, CYFRA21‐1, CA125, and grade of TMs in predicting distant metastasis had an AUC value of 0.816 (95%CI: 0.781–0.851), with sensitivity of 89.2%, specificity of 58.7%, positive predictive value of 73.7%, and negative predictive value of 79.7%, respectively. Conclusions pSUVmax combined with serum levels of LDH, CEA, CYFRA21‐1, CA125, and the grade of TMs may have good performance in predicting distant metastasis of de novo lung adenocarcinoma.

Abstract Reprogramming metabolic flux is a promising approach for constructing efficient microbial cell factories (MCFs) to produce chemicals. However, how to boost the transmission efficiency of metabolic flux is still challenging in complex metabolic pathways. In this study, metabolic flux is systematically reprogrammed by regulating flux size, flux direction, and flux rate to build an efficient MCF for chondroitin production. The ammoniation pool for UDP‐GalNAc synthesis and the carbonization pool for UDP‐GlcA synthesis are first enlarged to increase flux size for providing enough precursors for chondroitin biosynthesis. Then, the ammoniation pool and the carbonization pool are rematched using molecular valves to shift flux direction from cell growth to chondroitin biosynthesis. Next, the adaptability of polymerization pool with the ammoniation and carbonization pools is fine‐tuned by dynamic and static valve‐based adapters to accelerate flux rate for polymerizing UDP‐GalNAc and UDP‐GlcA to produce chondroitin. Finally, the engineered strain E. coli F51 is able to produce 9.2 g L−1 chondroitin in a 5‐L bioreactor. This strategy shown here provides a systematical approach for regulating metabolic flux in complex metabolic pathways for efficient biosynthesis of chemicals.

AbstractWe assembled the complete mitochondrial genome (mitogenome) of Mastigias papua (Scyphozoa: Rhizostomeae: Mastigiidae) by the data generated from the next-generation sequencing platform. The complete mitogenome of M. papua was 16,560 bp in length, containing 14 protein-coding genes, two transfer RNA genes, and two ribosomal RNA genes. The base compositions were A 30.65%, C 15.16%, G 16.34%, and T 37.86%, with a gene arrangement similar to the mitogenomes derived from other representatives of Scyphozoa. Based on the 13 common protein-coding genes of 16 species within Scyphozoa, we constructed the phylogenetic tree and found that M. papua has a close relationship with Cassiopea andromeda and Cassiopea xamachana. All these species belong to an order of jellyfish Rhizostomeae, which have similar morphological characteristics. This is agreement with the conclusion we got by the phylogenetic relationship analysis using molecular data. This research has practical implications for advancing understanding of the phylogenetic relationships, taxonomic classifications, and phylogeography within Scyphozoa.

Abstract Background AD16 is a Class 1.1 new drug candidate for Alzheimer’s disease (AD), which has demonstrated potential benefits in AD by reducing neuroinflammation in preclinical studies. Herein, the pharmacokinetics (PK), safety, and tolerability of single and multiple-dose AD16 and the effect of food were assessed in healthy Chinese adults. Methods Single-center, randomized, placebo-controlled, double-blind studies were conducted for single and multiple ascending doses. A total of 62 subjects were enrolled in single-dose groups; 10 each in 5, 10, 20, 30, and 40 mg groups, and 6 each in 60 and 80 mg dose groups. Twenty subjects were divided equally into 30 and 40 mg groups for the multiple-dose study. To determine the effect of a high-fat diet on AD16, 16 subjects were administered a single 20 mg dose of AD16 under the fasted and fed condition in a single-center, randomized, open-label, two-cycle, two-crossover study. Moreover, safety and PK parameters were also assessed. Results Plasma exposure to a single oral dose of AD16 increased at an approximate dose-increasing rate. The pharmacodynamic dose of the AD16 can be maintained through the accumulation effect of the drug within the safety window. Compared to fasting, ingesting a high-fat meal decelerated the rate of AD16 absorption, albeit without effect on its overall absorption. No dose-related toxicities were seen in any of the studies, all treatment-emergent adverse events were grade I/II, and no serious adverse event occurred. Conclusions The present study exhibited favorable safety, tolerability, and PK profile of AD16, supporting its further research as a potential drug treatment for AD. Trial registration ClinicalTrials.gov; NCT05787028, NCT05787041, NCT05806177. The SAD and FE studies were retrospectively registered on 28 March 2023. The MAD study was retrospectively registered on 10 April 2023.

Abstract Background Chemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency. Results Herein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO2 nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO2 nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO2 nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO2 subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced ·OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as ~ 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform. Conclusions In general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.

The fluidity of powder has an important impact on the key production processes such as mixing, conveying and packaging. To solve the fluidity problem in the production of purified frocto-oligosaccharide (P-FOS) powder, the influence of different particle sizes and their proportions on the fluidity of P-FOS powder was investigated. The flow characteristic of P-FOS was analyzed by using the powder rheometer. Research on the mixing experiment based on the different particle sizes (180~250, 150~180, 120~150, and 0.05), but the fluidity of P-FOS dry powder with the reduction of particle size. P-FOS dry powders with different particle sizes exhibit fluidity across different regions. The flow indices of samples with particle sizes in the range of 180~250, 150~180 and 120~150 μm were 12.5, 7.7, and 6.6, respectively. Their flow features were in the zone of easy flow area. Meanwhile, the flow indices of samples with particle sizes of 109~120 and 96~109 μm were 2.9 and 3.3, respectively. Their flow characteristics were in the bonding region. The mixing ratio of particles of different particle sizes had a significant influence on fluidity. The relationship between the particle size and the flow index was consistent with the square regression model, and the R2 (adjusted) could reach to 99.43%. If the particle size distribution was known, the fluidity of the P-FOS powder could be predicted and regulated by this model, thus guaranteeing the continuity and stability of the transport and packing of the dry powder.

Abstract Polymer dielectrics with excellent thermal resistance and superior energy storage behaviour are extensively demanded with the increasing development of film capacitors applied in hostile environments. In this study, novel diamine with sulfonyl‐containing side chain was designed and synthesised. The corresponding polyimide (PI) dielectrics derived from the sulfonyl‐containing diamine were prepared, so were the polyimides possessing the same backbone but without side chains. Consequently, superior thermal resistance of glass transition temperature ranged from 162–208°C was obtained. Moreover, the polyimides presented permittivity of 3.34–5.89 at 1 kHz, Weibull breakdown strength of 377–538 MV/m and discharged energy density of 3.82–5.85 J/cm3. In particular, sulfonyl‐containing polyimide of SPI‐2 with flexible backbone and sulfonyl side chain indicates the highest discharged energy density and charge‐discharge efficiency simultaneously. The introduction of the strong polar sulfonyl group in the side chain enhances dielectric and energy storage properties effectively. In addition, it is found that the dipolar moment density (μ/Vvdw) calculated from molecular simulation is closely correlated to permittivity measured from experiments. The combined method of molecular simulation and experiments would offer an effective approach to assist in molecular design of high‐performance polymer dielectrics.

Abstract Objective To explore the feasibility, safety, and clinical application value based on the fusion image of 18 F-FDG PET/CT, for guiding retroperitoneal puncture biopsy technology and to determine the diagnosis of retroperitoneal masses in diagnosing malignant tumors. Methods From March 2019 to January 2023, 42 patients underwent 18 F-FDG PET/CT imaging and were found to have retroperitoneal lesions that required definite diagnosis; 22 were male, 20 were female, and the average age was(59.17 ± 13.23) years. According to the fused 18 F-FDG PET/CT tomographic image, the target point with the highest metabolic activity, the safest, and expected maximum sample size was selected. CT scans were acquired with the same machine and fused with 18 F-FDG PET, guiding the puncture biopsy needle to approach the expected target zone, enabling timely delivery of pathological and immunohistochemical examination of the biopsy. Success rate, total examination time, biopsy operation time, complications, CT radiation dose, pathological, and immunohistochemical results were recorded. Results All 42 patients were sampled successfully with the successful rate being 100%. The site of sampling of 42 patients accurately targeted the highest metabolic activity, the safest, and the expected maximum sample size. All 42 patients received clear diagnosis (25 cases of malignant tumors and cases of 17 benign tissues). 15 cases of patients had a change in clinical diagnosis, accounting for 35.7% of all patients, and affecting subsequent treatment plans. The average total examination time for patients was (41.3 ± 7.3) minutes, and the biopsy operation time was (29.1 ± 8.7) minutes. The effective radiation dose generated by the entire examination generated by CT guidance was (2.0 ± 0.5) mSv; no severe complications occurred in the patients. Conclusion Real-time-guided retroperitoneal puncture biopsy based on 18 F-FDG PET/CT fusion image is safe, accurate, and feasible, and can provide patients of retroperitoneal mass with clear pathological diagnosis and immunohistochemical evaluation.

A Y-type air-cooled structure has been proposed to improve the heat dissipation efficiency and temperature uniformity of battery thermal management systems (BTMSs) by reducing the flow path of air. By combining computational fluid dynamics (CFD) methods, the influence of the depths of the distribution and convergence plenums on the airflow velocity through battery cells was analyzed to improve heat dissipation efficiency. Adjusting the width of the first and ninth cooling channels can change the air velocity of these two channels, thereby improving the temperature uniformity of the BTMS. Further discussion was conducted regarding the influences of inlet and outlet depths. When the inlet width and outlet width were 20 mm, the maximum temperature and maximum temperature difference of the Y-type BTMS were 39.84 °C and 0.066 °C at a discharge rate of 2.5 °C, respectively; these temperatures were 1.537 °C (3.68%) and 0.059 °C (47.2%) lower than those of the T-type model. Meanwhile, the energy consumption of the sample also decreased by 13.1%. The results indicate that the heat dissipation performance of the proposed Y-type BTMS was improved, achieving excellent temperature uniformity, and the energy consumption was also reduced.

Microplastics (MPs) have emerged as a major environmental issue. They have been found to cause significant reproductive toxicity and lower testosterone levels in adult males, though the exact mechanisms remain unclear. In this study, C57bl/6 mice were orally exposed to saline or varying doses (0.25, 0.5, and 1 mg/day) of 5 μm polystyrene MPs (PS-MPs) for 4 weeks, and TM3 mouse Leydig cells were treated with different concentrations of PS-MPs. Our results found that exposure to PS-MPs significantly reduced testosterone levels and impaired the synthesis function of testicular steroids. In vitro, PS-MPs reduced steroid synthesis in Leydig cells. Treatment with PS-MPs significantly increased the apoptosis rate and BAX/BCL2 ratio in Leydig cells. Additionally, GSH-px and SOD activities decreased, while MDA levels increased, along with a rise in mitochondrial ROS. In conclusion, chronic PS-MP exposure reduced testosterone levels in mice through mitochondrial oxidative stress and BAX/BCL2-mediated apoptosis. This study offers new insights into the health risks posed by MPs.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. Meanwhile, doxorubicin, a chemotherapeutic agent for triple-negative breast cancer, has poor sensitivity. The objective of this study was to examine the effect of cordycepin on doxorubicin sensitivity and efficacy in the TNBC xenograft model and explore the relevant molecular pathways. The combination of the drugs in nude mice carrying MDA-MB-231 xenografts significantly reduced the volume, size, and weight of xenografts and improved the tumor inhibition rate. The drug combination was significantly more effective than cordycepin or doxorubicin alone, reflecting the fact that cordycepin enhanced the anti-tumor effects of doxorubicin in MDA-MB-231 xenografts. At the same time, the monitoring of several biological parameters failed to detect any obvious side effects associated with this treatment. After predicting the importance of the TNF pathway in inhibiting tumor growth using network pharmacology methods, we verified the expression of TNF pathway targets via immunohistochemistry and quantitative PCR. Furthermore, a TNF-α inhibitor was able to abrogate the beneficial effects of cordycepin and doxorubicin treatment in MDA-MB-231 cells. This clearly indicates the role of TNF-α, or related molecules, in mediating the therapeutic benefits of the combined treatment in animals carrying TNBC xenografts. The observations reported here may present a new direction for the clinical treatment of TNBC.

Storm surge is the most serious marine disaster in China, and the inundation characteristics of storm surge are the key indicators of disaster severity. Especially in the context of relative sea level rise (RSLR), it is very important to rapidly and accurately estimate the inundation characteristics of storm surge for the risk assessment and emergency management of storm surge disasters. Taking Taizhou city, Zhejiang Province, as the study area, this paper constructed an RSLR scenario library considering absolute sea level rise, land subsidence and storm surge water increase. The scenario library includes 72 scenarios, consisting of a combination of four absolute sea level rise scenarios, three land subsidence scenarios, three timescales (2030, 2050 and 2100) and two storm surge water increase scenarios. Then, an improved passive inundation method was used to predict and analyze the inundation characteristics of storm surge under each scenario. This improved method combines the advantages of the accurate active inundation method and the rapid passive inundation method, and is suitable for rapid and accurate estimation of the storm surge inundation characteristics, which can meet the needs of a storm surge disaster risk assessment and emergency response. The prediction and analysis results show that a minor RSLR can also cause a large-scale inundation in coastal areas of Taizhou. When the value of RSLR exceeds the critical value (0.6 m), it may significantly increase the expansion of the inundation area of storm surge. At a relative sea level rise of 1.57 m (extreme scenario in 2100), the inland storm surge inundation of low-risk areas may become high-risk areas. Finally, the quantitative measures for preventing storm surge disasters were put forward according to the current situation of the coast in Taizhou. Without considering storm surge and superimposed general surge, the existing 20-year return period standard seawall can effectively protect against storm surge under various scenarios. In the case of maximum water increase, it is expected that effective protection will remain until 2030, but the standard of the seawall defense will need to be improved in 2050 and 2100.

Abstract Background Depression has become a challenging public health problem, and the loss of a spouse is one of the main causes of depression in older adults. Social participation and psychological resilience are protective factors that reduce depressive symptoms in adults. The purpose of this study was to explore the influences of social participation and psychological resilience on the depression of Chinese widowed older adults. Methods We carried out a cross-sectional study on 790 community-dwelling widowed older adults in Shaanxi, China, in 2019. A structured face-to-face interview was used to collect data. We used the ordinary least squares model (OLS), the generalized propensity score matching (GPSM) and the mediation model to test the relationship between social participation, psychological resilience and depression. Results We find a U-shaped relationship between social participation and depression, with the increase in social participation scores, the average depression level decreased and then increased. The psychological resilience of the widowed older adults was negatively associated with depression. The higher their psychological resilience, the lower their depression level. Among the four factors of psychological resilience, factor 2 (optimism and positive acceptance of change) and factor 3 (secure relationships and tolerance of negative affect) of psychological resilience were protective factors for depression after adjusting for demographic variables and physical health conditions. Psychological resilience plays a mediating role, as evident in factor 2 and factor 3 mediating the relationship between social participation and depression. Conclusion An appropriate level of social participation will relieve the depression of widowed older adults. Social participation can reduce the depression level of widowed older adults by improving their psychological resilience. Community and family could reduce depression by intervening in the social participation of widowed older adults. Active social participation is crucial because it has a protective and resilient impact, which can help people recover from the stress of losing a spouse.

Abstract The construction of mesoporous Janus nanoparticles (mJNPs) with controllable components is of great significance for the development of sophisticated nanomaterials with synergistically enhanced functionalities and applications. However, the compositions of reported mJNPs are mainly the functionally inert SiO2 and polymers. The universal synthesis of metal-compound based mJNPs with abundant functionalities is urgently desired, but remains a substantial challenge. Herein, we present a hydrophilicity mediated interfacial selective assembly strategy for the versatile synthesis of metal-compound based mJNPs. Starting from the developed silica-based mJNPs with anisotropic dual-surface of hydrophilic SiO2 and hydrophobic organosilica, metal precursor can selectively deposit onto the hydrophilic SiO2 subunit to form the metal-compound based mJNPs. This method shows good universality and can be used for the synthesis of more than 20 kinds of metal-compound based mJNPs, including alkali-earth metal compounds, transition metal compounds, rare-earth metal compounds etc. Besides, the composition of the metal-compound subunit can be well tuned from single to multiple metal elements, even high-entropy complexes. We believe that the synthesis method and obtained new members of mJNPs provide a very broad platform for the construction and application of mJNPs with rational designed functions and structures.

This study investigated how different feedback sources, such as teacher and peer correction, affect students learning English as a foreign language (EFL) regarding speaking accuracy, fluency, and academic passion. The effects of online and face-to-face instruction and peer and teacher corrections were investigated in this study using a factorial design. Convenience sampling was used to choose six intact classes from Jinzhong University's Department of Foreign Languages. Academic passion and speaking tests were used before and after the treatment. The data were analyzed using ANOVA tests. The findings showed that peer correction outperformed teacher correction in improving speaking accuracy, fluency, and academic passion.Additionally, peer correction was more beneficial than receiving no correction at all. Furthermore, teacher correction positively influenced speaking accuracy compared to the non-correction group. The findings also demonstrated that feedback mechanisms have a significant overall impact on speaking accuracy and fluency independent of particular training and correction circumstances. The interaction between instruction and correction was not statistically significant. These findings highlight the crucial role that correction mechanisms play in enhancing speaking accuracy and naturalness, which has important ramifications for language teachers and curriculum designers.

In the era of digital intelligence empowerment, the data-driven approach to the mining and organization of humanistic knowledge has ushered in new development opportunities. However, current research on allusions, an important type of humanities data, mainly focuses on the adoption of a traditional paradigm of humanities research. Conversely, little attention is paid to the application of auto-computing techniques to allusive resources. In light of this research gap, this work proposes a model of allusive word sentiment recognition and application based on text semantic enhancement. First, explanatory texts of 36,080 allusive words are introduced for text semantic enhancement. Subsequently, the performances of different deep learning-based approaches are compared, including three baselines and two optimized models. The best model, ERNIE-RCNN, which exhibits a 6.35% improvement in accuracy, is chosen for the sentiment prediction of allusive words based on text semantic enhancement. Next, according to the binary relationships between allusive words and their source text, explanatory text, and sentiments, the overall and time-based distribution regularities of allusive word sentiments are explored. In addition, the sentiments of the source text are inferred according to the allusive word sentiments. Finally, the LDA model is utilized for the topic extraction of allusive words, and the sentiments and topics are fused to construct an allusive word-sentiment theme relationship database, which provides two modes for the semantic association and organization of allusive resources. The empirical results show that the proposed model can achieve the discovery and association of allusion-related humanities knowledge.

The deep integration of the digital economy and high-quality energy development is a vital breakthrough in promoting the digital transformation and upgrading of energy, and it is also a critical path to achieving green and low-carbon development. However, the degree of integration of the two has yet to be discovered. This article measures the coupling coordination degree of the digital economy and high-quality energy development using panel data from 30 provinces in China from 2013 to 2020, explores the spatiotemporal evolution characteristics of the coupling coordination degree, and further analyzes the driving factors of the coupling coordination degree. The results show that:(1) The coupling coordination degree shows an upward trend, but there are apparent gradient differences and spatial non-equilibrium features in the coupling coordination degree among provinces. (2) The coupling coordination degree shows a ''parabolic'' spatial trend of ''high east and low west'' in the east-west direction and an ''inverted U-shaped'' spatial trend in the north-south direction. (3) The center of gravity of the coupling coordination degree moves to the southwest, clustering in the northeast-southwest direction and showing a spreading trend in the southeast-northwest direction. (4) The coupling coordination degree has a significant positive spatial correlation, and the cold-hot spot gradually develops into a distribution pattern with the Yangtze River Delta in China as the agglomeration center. (5) Economic development, industrial structure, government behavior, environmental regulation, urbanization, technological innovation, and external openness significantly impact the coupling coordination degree. In addition, economic development and human capital have a positive spatial spillover effect on the coupling coordination degree. Urbanization level and technological innovation have a negative spatial spillover effect on the coupling coordination degree. Accordingly, to promote the coupling and interaction between the digital economy and high-quality energy development, the government should take effective measures in optimizing the industrial structure, scientifically promoting the urbanization process, and enhancing the scientific and technological innovation capacity.

IntroductionClinical observations have found that prolonged use of analgesics increases the incidence of infection. However, the direct causal relationship between prescription analgesic use (PAU) and risk of infection (ROI) remains unclear.MethodsThis study used Mendelian randomization (MR) design to estimate the causal effect of PAU on ROI, as well as their mediating factors. Genetic data on prescription analgesics use and immune cells were obtained from published GWAS. Additionally, data on ROI were extracted from the FinnGen database. Two-sample MR analysis and multivariate MR (MVMR) analysis were performed using inverse variance weighting (IVW) to ascertain the causal association between PAU and ROI. Finally, 731 immune cell phenotypes were analyzed for their mediating role between analgesics and infection.ResultsUsing two-sample MR, IVW modeling showed that genetically predicted opioid use was associated with increased risk of pulmonary infection (PI) (OR = 1.13, 95% CI: 1.05–1.21, p< 0.001) and upper respiratory infection (URI) (OR = 1.18, 95% CI: 1.08–1.30, p< 0.001); non-steroidal anti-inflammatory drugs (NSAIDs) were related to increased risk of skin and subcutaneous tissue infection (OR = 1.21, 95% CI: 1.05–1.39, p = 0.007), and antimigraine preparations were linked to a reduced risk of virus hepatitis (OR = 0.79, 95% CI: 0.69–0.91, p< 0.001). In MVMR, the association of opioids with URI and PI remained after accounting for cancer conditions. Even with a stricter threshold (p< 0.05/30), we found a significant causal association between opioids and respiratory infections (URI/PI). Finally, mediation analyses found that analgesics influence the ROI through different phenotypes of immune cells as mediators.ConclusionThis MR study provides new genetic evidence for the causal relationship between PAU and ROI, and the mediating role of immune cells was demonstrated.