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Abstract Large‐scale wildfires can significantly reduce the air gap insulation resistance of high‐voltage transmission lines and cause chain tripping incidents. To assess the resilience of the power transmission system during wildfire, this paper proposes a resilience assessment framework for transmission system that considers the entire process of wildfire disaster. Firstly, a wildfire spread model, considering multiple influencing factors, is developed based on the cellular automaton. Based on the air gap breakdown mechanism during wildfires, the trip‐out probability of transmission lines is calculated, and various failure scenarios are obtained by using the Monte Carlo sampling. Secondly, considering the geographical location of failures, maintenance personnel schedules and restoration time, a power transmission system restoration model is established. Thus, a resilience assessment method for power transmission system during wildfire disasters is proposed. Finally, IEEE RTS‐79 transmission system is taken as an example to demonstrate the effectiveness of the proposed resilience assessment method. The results show that the proposed method can effectively calculate the wildfire spread tendency and transmission line's trip‐out probability. Furthermore, three typical resilience improvement measures are quantitatively analysed, which provides a quantifiable reference for the power sector to formulate prevention and recovery strategies for extreme wildfire disasters.

Abstract As a crucial source of protein for humans, aquaculture provides societal benefits but also poses environmental costs making it pivotal to strike a balance between costs and benefits to ensure aquaculture sustainability. Here we developed a composite sustainability index integrating societal benefits and environmental costs of aquaculture. The results show that two-fifths of the 161 countries achieved a high sustainability score (score > 50) in 2018, indicating a considerable need for improvement in the sustainability of aquaculture worldwide. This was particularly true for Asian countries (average score 45.01 ± 11.44), while European countries outperformed other regions (60.15 ± 13.64). Moreover, a Boosted Regression Tree model revealed that 59.3% of the variance in aquaculture sustainability was supported by eight indicators, including social factors, geographical effects, and aquaculture structures. By focusing on bivalve production and maintaining an optimized choice of fishes and shrimp taxa, the sustainability of global aquaculture could be enhanced.

Abstract An imbalance between the adipogenesis and osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is considered the basic pathogenesis of osteoporosis. Although actin cytoskeleton remodelling plays a crucial role in the differentiation of BMSCs, the role of actin cytoskeleton remodelling in the adipogenesis of BMSCs and postmenopausal osteoporosis (PMOP) has remained elusive. Glia maturation factor-beta (GMFB) has a unique role in remodelling the polymerization/depolymerization cycles of actin. We observed that GMFB expression was increased in bone tissue from both ovariectomized (OVX) rats and PMOP patients. GMFB knockout inhibited the accumulation of bone marrow adipocytes and increased bone mass in the OVX rat model. The inhibition of adipocyte differentiation in GMFB knockout BMSCs was mediated via actin cytoskeleton remodelling and the Ca2+-calcineurin-NFATc2 axis. Furthermore, we found that GMFB shRNA treatment in vivo had favourable effects on osteoporosis induced by OVX. Together, these findings suggest a pathological association of the GMFB with PMOP and highlight the potential of the GMFB as a therapeutic target for osteoporosis patients.

In this article, a single-board integrated millimeter-wave (mm-Wave) asymmetric full-digital beamforming (AFDBF) array is developed for beyond-fifth-generation (B5G) and sixth-generation (6G) communications. The proposed integrated array effectively addresses the challenge of arranging a large number of ports in a full-digital array by designing vertical connections in a three-dimensional space and successfully integrating full-digital transmitting (Tx) and receiving (Rx) arrays independently in a single board. Unlike the traditional symmetric array, the proposed asymmetric array is composed of an 8 × 8 Tx array arranged in a square shape and an 8 + 8 Rx array arranged in an L shape. The center-to-center distance between two adjacent elements is 0.54λ0 for both the Tx and Rx arrays, where λ0 is the free-space wavelength at 27 GHz. The proposed AFDBF array possesses a more compact structure and lower system hardware cost and power consumption compared with conventional brick-type full-digital arrays. In addition, the energy efficiency of the proposed AFDBF array outperforms that of a hybrid beamforming array. The measurement results indicate that the operating frequency band of the proposed array is 24.25–29.50 GHz. An eight-element linear array within the Tx array can achieve a scanning angle ranging from −47° to +47° in both the azimuth and the elevation planes, and the measured scanning range of each eight-element Rx array is –45° to +45°. The measured maximum effective isotropic radiated power (EIRP) of the eight-element Tx array is 43.2 dBm at 28.0 GHz (considering the saturation point). Furthermore, the measured error vector magnitude (EVM) is less than 3% when 64-quadrature amplitude modulation (QAM) waveforms are used.

Abstract Liver transplantation is the definitive treatment for end-stage liver disease, yet T-cell mediated rejection (TCMR) remains a major challenge. This study aims to identify key genes associated with TCMR and their potential biological processes and mechanisms. The GSE145780 dataset was subjected to differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms to pinpoint key genes associated with TCMR. Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, and regulatory networks were constructed to ascertain the biological relevance of these genes. Expression validation was performed using single-cell RNA-seq (scRNA-seq) data and liver biopsy tissues from patients. We identified 5 key genes (ITGB2, FCER1G, IL-18, GBP1, and CD53) that are associated with immunological functions, such as chemotactic activity, antigen processing, and T cell differentiation. GSEA highlighted enrichment in chemokine signaling and antigen presentation pathways. A lncRNA-miRNA-mRNA network was delineated, and drug target prediction yielded 26 potential drugs. Evaluation of expression levels in non-rejection (NR) and TCMR groups exhibited significant disparities in T cells and myeloid cells. Tissue analyses from patients corroborated the upregulation of GBP1, IL-18, CD53, and FCER1G in TCMR cases. Through comprehensive analysis, this research has identified 4 genes intimately connected with TCMR following liver transplantation, shedding light on the underlying immune activation pathways and suggesting putative targets for therapeutic intervention.

Manganese is an important alloying element in iron and steel. Adding the appropriate amount of manganese can enhance the properties of steel. The manganese content directly influences steel quality in the converter steelmaking process. Too little manganese results in insufficient hardness and strength of steel products, whereas excessive manganese leads to increased embrittlement and production costs. Therefore, determining the appropriate amount of manganese is crucial for improving steel quality and reducing smelting costs. The quantity of manganese added during converter steelmaking primarily depends on the predicted final manganese content. However, this content is influenced by various factors, such as the oxidation reaction process and the addition of other alloying elements. These factors exhibit nonlinear effects on the manganese content, and the factors are highly interconnected, making accurate prediction of manganese content at the end point challenging. In response to the challenges posed by noise and strong coupling in predicting manganese content at the end point of converter steelmaking, a research framework was developed to address these issues and facilitate accurate predictions. Key influencing factors in the smelting process were identified through Pearson correlation coefficient analysis and mechanistic analysis. Subsequently, the relationship between these influencing factors and end-point manganese content was modeled using the long short-term memory network (LSTM). To mitigate the effects of high-frequency noise in nonlinear and nonstationary sequences, singular spectral analysis (SSA) was employed during the prediction process. This led to the development of a method known as SSA−LSTM for predicting end-point manganese content. The effects of different test sets and the number of neurons on the prediction results were investigated using converter steelmaking production data from Hebei Jingye Iron & Steel Co., Ltd. The proposed method achieved minimal prediction error when the test set comprised 10% of the data and the number of neurons was set to 85. At these parameters, the mean absolute error of the prediction method for end-point manganese was 1.19%, with a root-mean-square error of 1.48%. These results demonstrate that the proposed method effectively addresses issues related to large noise and nonlinear data. Moreover, compared with existing time series prediction methods, the proposed method, particularly after SSA treatment, showed reduced prediction errors. This validates the effectiveness of the method and provides a basis for accurate alloy addition in actual production processes.

Abstract The conversion of methanol over zeolites offers a sustainable alternative for fuels and chemicals production. However, a complete understanding of the competing reaction pathways, particularly those leading to C-C bond formation, remains elusive. This work presents a novel mechanism for selective methanol conversion in ZSM-5 zeolites, involving a Brønsted acid site (BAS)-mediated Meerwein–Ponndorf–Verley (MPV) reduction pathway. Employing a multidimensional solid-state NMR spectroscopy combined with isotopic labeling and theoretical calculations, we identify this pathway for acetaldehyde reduction with methanol, directly contributing to ethene formation. This mechanism, involving carbenium ion intermediates like 1-hydroxyethane or 1-methoxyethane ions, contrasts with the well-established Lewis acid-catalyzed MPV process. Based on reactant adsorption modes, we propose two distinct reaction routes for BAS-MPV reduction, bridging the gap between direct and hydrocarbon pool mechanisms in methanol conversion. We further demonstrate the applicability of this pathway to acetone, highlighting its broader role in the early stages of the reaction.

Abstract In this study, the corrosion electrochemistry and corrosion behavior of two steels were studied under the simulated alumina production conditions. The corrosion rate of 16Mn steel is greater than that of Q235 steel. The effect of S2− concentration on corrosion rate was significantly higher than that of S2O3 2−. The synergistic corrosion rates of Q235 and 16Mn steels increase at first and then decrease with the sulfur content, and the peak value appears when the concentration of S2− and S2O3 2− is 4 g/L and 3 g/L respectively. There are two main types of corrosion products: one is surface octahedral grain, which is composed of Fe2O3, Fe3O4 and Al2O3.The other is the interlayer corrosion between the surface layer and the matrix, which is composed of FeS, FeS2 and NaFeO2.The formation mechanism of the corrosion and corrosion mechanism were obtained by analyzing the phenomenon of ion competitive adsorption. Further validation and analysis of ion competition adsorption phenomenon were conducted using first-principles calculations based on density functional theory (DFT). The formation of corrosion products on the steel surface was investigated at an ion level, and the adsorption energies of OH− and S2− at the top site of Fe(110) surface were calculated. It was found that S2− is more likely to be adsorbed on the Fe(110) surface compared to OH−. The corrosion mechanism of steel is discussed preliminarily.

Abstract Evidence-based data regarding the timing of the application of invasive mechanical ventilation among adults with septic shock is insufficient. The guidelines fail to provide clear advice about the optimal time to initiate this support. Consequently, we aimed to investigate whether early intubation could improve survival rates in septic shock patients. We conducted a retrospective analysis of the MIMIC-IV database to evaluate the effectiveness of early intubation on mortality in a cohort of septic shock patients. Adults diagnosed with septic shock, according to the Sepsis-3 definition, were included. They were categorized into an early intubation group (first 8 h after vasopressor initiation) and a non-early intubation group (unexposed). A propensity score matching (PSM) analysis was used to balance the baseline characteristics between the two groups. The primary outcomes were 30-day and 90-day all-cause mortality rates. In addition, we employed the restricted cubic spline to analyze the potential non-linear relationship between the timing of intubation and 30-day or 90-day all-cause mortality. A total of 6864 adult patients, of whom 2048 were intubated in the first 8 h, were evaluated in the final cohort. Following a 1:1 PSM procedure, 2786 patients were successfully paired. At 30 days, 288 of 1393 patients (20.7%) in the early intubation group and 381 of 1393 patients (27.4%) in the non-early intubation group had died (hazard ratio [HR] 0.717; 95% confidence interval [CI] 0.616–0.836; p

Abstract The lower respiratory tract (LRT) microbiome impacts human health, especially among critically ill patients. However, comprehensive characterizations of the LRT microbiome remain challenging due to low microbial mass and host contamination. We develop a chelex100-based low-biomass microbial-enrichment method (CMEM) that enables deep metagenomic profiling of LRT samples to recover near-complete microbial genomes. We apply the method to 453 longitudinal LRT samples from 157 intensive care unit (ICU) patients in three geographically distant hospitals. We recover 120 high-quality metagenome-assembled genomes (MAGs) and associated plasmids without culturing. We detect divergent longitudinal microbiome dynamics and hospital-specific dominant opportunistic pathogens and resistomes in pneumonia patients. Diagnosed pneumonia and the ICU stay duration were associated with the abundance of specific antibiotic-resistance genes (ARGs). Moreover, CMEM can serve as a robust tool for genome-resolved analyses. MAG-based analyses reveal strain-specific resistome and virulome among opportunistic pathogen strains. Evolutionary analyses discover increased mobilome in prevailing opportunistic pathogens, highly conserved plasmids, and new recombination hotspots associated with conjugative elements and prophages. Integrative analysis with epidemiological data reveals frequent putative inter-patient strain transmissions in ICUs. In summary, we present a genome-resolved functional, transmission, and evolutionary landscape of the LRT microbiota in critically ill patients.

Abstract. Background:. Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic–clinical–radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism. Methods:. This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram. Results:. Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276–13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086–0.405, P

Due to environmental noise and human factors, magnetic data collected in the field often contain various noises and interferences that significantly affect the subsequent data processing and interpretation. Empirical Mode Decomposition (EMD), an adaptive multiscale analysis method for nonlinear and non-stationary signals, is widely used in geophysical and geodetic data processing. Compared with traditional EMD, Improved Complete Ensemble EMD with Adaptive Noise (ICEEMDAN) is more effective in addressing the problem of mode mixing. Based on the principles of 1D ICEEMDAN, this paper presents an alternative algorithm for 2D ICEEMDAN, extending its application to two-dimensional scenarios. The effectiveness of the proposed approach is demonstrated through synthetic signal experiments, which show that the 2D ICEEMDAN exhibits a weaker mode mixing effect compared to the traditional bidimensional EMD (BEMD) method. Furthermore, to improve the performance of the denoising method based on 2D ICEEMDAN and preserve useful signals in high-frequency components, an improved soft thresholding technique is introduced. Synthetic magnetic anomaly data testing indicates that our denoising method effectively preserves signal continuity and outperforms traditional soft thresholding methods. To validate the practical application of this improved threshold denoising method based on 2D ICEEMDAN, it is applied to ground magnetic survey data in the Yandun area of Xinjiang. The results demonstrate the effectiveness of the method in removing noise while retaining essential information from practical magnetic anomaly data. In particular, practical applications suggest that 2D ICEEMDAN can extract trend signals more accurately than the BEMD. In conclusion, as a potential tool for multi-scale decomposition, the 2D ICEEMDAN is versatile in processing and analyzing 2D geophysical and geodetic data.

Abstract Background Compost-bedded pack barns (CBP) are getting huge attention as an alternative housing system for dairy cows due to their beneficial impact on animal welfare. Effective microorganisms (EM) inoculums are believed to enhance compost quality, improve soil structure and benefit the environment. However, little information is available on the impact of incubation with external EM combinations on the barn environment, compost quality and microbial diversity in CBP. This experiment was carried out to investigate the effect of inoculating different combinations of EM [Lactobacillus plantarum (L), Compound Bacillus (B) and Saccharomyces cerevisiae (S)] on compost quality and microbial communities of CBP products, as well as the relationship with the heifers’ barn environment. CBP barns were subjected to the following four treatments: CON with no EM inoculum, LB/LS/LBS were Incubated with weight ratios of 1:2 (L: B), 1:2 (L: S), 1:1:1 (L: B: S), respectively. Results The EM inoculation (LB, LS, LBS) reduced the concentration of respirable particulate matter (PM10 and PM2.5) in the CBP, and decreased the serum total protein and total cholesterol levels in heifers. Notably, LBS achieved the highest content of high-density lipoprotein compared to other treatments. Microbiome results revealed that EM inoculation reduced the bacterial abundance (Chao1 index) and fungal diversity (Shannon & Simpson indexes), while increasing the relative abundance of various bacterial genera (Pseudomonas, Paracoccus, Aequorivita) and fungi (Pestalotiopsis), which are associated with cellulose decomposition that ultimately resulted in accelerating organic matter degradation and humification. Furthermore, high nutrient elements (TK&TP) and low mycotoxin content were obtained with EM inoculation, with LBS showing a particularly pronounced effect. Meanwhile, LBS contributed to a decline in the proportion of fungal pathogen categories but also led to an increase in fungal saprotroph categories. Conclusion Generally, EM inoculation positively impacted compost product quality as organic fertilizer and barn environment by modifying the abundance of cellulolytic bacteria and fungi, while inhibiting the reproduction of pathogenic microbes, especially co-supplementing with L, B and S achieved an amplifying effect.

Abstract CF2-containing compounds hold significant potential in drug discovery, organic synthesis, and materials science. However, synthesizing various CF2-containing building blocks from a single compound remains challenging. Here, we present a Cu-catalyzed, switchable defluoroborylation and hydrodefluorination of trifluoromethylated alkynes, yielding four types of CF2-containing compounds. The chemo- and regio-selective sp2/sp3 1,2-diborylation and sp2 monoborylation of 1-(trifluoromethyl)alkynes are controlled by adjusting the solvent and ligand quantity. Additionally, altering the base allows selective generation of gem-difluoroalkenes or difluoromethylalkenes. Notably, our method prevents over-defluorination of the CF3 group on unsaturated C-C bonds during nucleophilic additions, preserving the pharmaceutically valuable CF2 group. Experimental data and density functional theory (DFT) calculations elucidate the regioselectivities of Cu-Bpin addition and the regulatory role of the ligand in selective deborylation processes.

Cassia Semen, derived from the dried ripe seeds of leguminous plant Cassia obtusifolia Linn. or Cassia. tora Linn., exhibits a variety of pharmacological effects such as clearing heat to brighten the eyes, lubricating the intestine to relieve constipation, lowering blood pressure and lipids, hepatoprotection and anti-diabetes, etc. And due to its homology of medicine and food, it has broad development prospects in the fields of medicine and food. Based on the summary and analysis of the published literatures, this paper systematically reviews the integrated research progress of Cassiae Semen in recent years from the aspects of bioactive ingredients, pharmacological effects, toxicity and its applications in the food field. Additionally, the emerging challenges and possible development directions for the study of Cassiae Semen are discussed as well. In future research on Cassiae Semen, more attention should be paid to the pharmacological effects of naphthopyranones and polysaccharides and their mechanisms underlying improving eye diseases. Meanwhile, it is essential to focus on strengthening the researches on the pharmacokinetics of Cassiae Semen and the safety evaluation of its related functional foods. This article provides new basic information for further research, development, and utilization of Cassiae Semen.

Abstract To gain insights into the spatial distribution of non-penetrating cracks during the rock fracture process, a comprehensive uniaxial compression test is conducted on cubic gypsum specimens (100 mm × 100 mm × 100 mm) containing two non-penetrating cracks. The two pre-formed cracks are rectangular, with dimensions of 25 mm length, 2 mm width, and depths of 80 mm and 35 mm on adjacent sides of the specimen. The depth of the 80 mm crack can be adjusted from 0° to 150° in increments of 30°, while the other is fixed at a 45° angle. The results show that the spatial distribution of non-penetrating cracks can significantly influence the strength of the specimen. Initially, the strength of the specimen exhibits an upward trend and subsequently declines as the pre-crack inclination angle of the main rupture plane increases, ultimately reaching its pinnacle at 90°. The total percentage of tensile cracks in specimens with different inclinations are found to be 57%, 57%, 63%, 77%, 68%, and 61%, respectively. This change aligns seamlessly with the fluctuation in specimen strength as influenced by the angle of inclination. Non-penetrating cracks can also induce spalling on the specimen surface and give rise to anti-wing cracks, thereby exacerbating the spalling on the specimen surface. The inclinations of non-penetrating cracks can inevitably exert a certain influence on the propagation of neighboring non-penetrating cracks. Additionally, the macro-scale shear fracture of the specimen often occurs on the side of the non-penetrating crack that is deeper. The curved tensile fracture surface formed by the extension of the non-penetrating crack bears resemblance to the non-penetrating region in its ability to somewhat restrain the propagation of new cracks. Even under uniaxial compression, the spalling surface of the specimen containing spatial non-penetrating cracks frequently exhibits fracture characteristics belonging to I-III mode fracture, while its interior may display characteristics belonging to I-II-III mode fracture. These findings hold significant implications for comprehending and elucidating the genuine fracture process and three-dimensional fracture theory of rocks.

Abstract Transcription coupled-nucleotide excision repair (TC-NER) removes DNA lesions that block RNA polymerase II (Pol II) transcription. A key step in TC-NER is the recruitment of the TFIIH complex, which initiates DNA unwinding and damage verification; however, the mechanism by which TFIIH is recruited during TC-NER, particularly in yeast, remains unclear. Here, we show that the C-terminal domain (CTD) of elongation factor-1 (Elf1) plays a critical role in TC-NER in yeast by binding TFIIH. Analysis of genome-wide repair of UV-induced cyclobutane pyrimidine dimers (CPDs) using CPD-seq indicates that the Elf1 CTD in yeast is required for efficient TC-NER. We show that the Elf1 CTD binds to the pleckstrin homology (PH) domain of the p62 subunit of TFIIH in vitro, and identify a putative TFIIH-interaction region (TIR) in the Elf1 CTD that is important for PH binding and TC-NER. The Elf1 TIR shows functional, structural, and sequence similarities to a conserved TIR in the mammalian UV sensitivity syndrome A (UVSSA) protein, which recruits TFIIH during TC-NER in mammalian cells. These findings suggest that the Elf1 CTD acts as a functional counterpart to mammalian UVSSA in TC-NER by recruiting TFIIH in response to Pol II stalling at DNA lesions.

Abstract The injection of supercritical CO2 (ScCO2) into the enhanced geothermal systems (EGS) is a highly intricate thermohydromechanical (THM) coupled process. To improve the realism and accuracy of simulating convective heat transfer characteristics in CO2‐EGS, a coupled model based on discrete fracture network (DFN) theory is established. In this model, the dynamic evolution laws of reservoir porosity and permeability, as well as the nonlinear variations of thermophysical parameters for ScCO2 under the influences of temperature and pressure are considered. The validity of the numerical results was confirmed through a comparative analysis with the analytical solution. The result shows that the ScCO2 can rapidly extracts heat from both the fractures and the adjacent rock matrix. The heat of the rock matrix far away from the fractures cannot be compensated to the fractures immediately, resulting in the high temperature peak effect of the local rock matrix. The injection of ScCO2 can increase the porosity and permeability of reservoir, which is induced by the weakened thermal expansion effect of rock. The alteration of reservoir porosity and permeability also leads to the change of the flow characteristics of ScCO2. Additionally, the thermal parameters of ScCO2 changes with the temperature and pressure conditions of the reservoir. The change of flow rate and heat extraction rate of ScCO2 in EGS is dominated by the decrease of density, specific heat capacity, porosity, permeability, and thermal conductivity.

Mg-2.2Gd-0.4Zr sheets were prepared using transverse gradient extrusion (TGE) technology to improve their formability. The effects of different TGE processes (inclination angles of the die are 15°, 30°, 37°, 45° and 49°) on the microstructure, texture, mechanical properties, and formability of extruded sheets were researched. Furthermore, the flow behaviors of Mg-2.2Gd-0.4Zr sheets during extrusion were analyzed by the finite element simulation method. For comparison, Mg-2.2Gd-0.4Zr sheets were processed by conventional extrusion (CE) process. Results showed that the texture of TGE sheets was effectively altered. With the increase of the TGE dies tilt angle, the deviation of the basal pole in the center region of the extruded sheet towards the extrusion direction (ED) increased, while in the 1/4 edge region the basal pole deviated towards the transverse direction (TD) along the ED. The multi-type textures formed in TGE sheets are mainly attributed to the extra flow velocity along the TD and the flow gradient along the ED during extrusion. High elongation of 45.6% and low yield stress of 98.9 MPa are obtained for TGE-45 sheets. In addition, the Erichsen value (IE) of the TGE-45 sheet is 5.46 mm, which is about 47% higher than the 3.72 mm of the CE Mg-2.2Gd-0.4Zr sheet. The improved formability is due to the effective coordination of multi-directional strains during the Erichsen test for the TGE sheets.

Abstract Mutations in the Cockayne Syndrome group B (CSB) gene cause cancer in mice, but premature aging and severe neurodevelopmental defects in humans. CSB, a member of the SWI/SNF family of chromatin remodelers, plays diverse roles in regulating gene expression and transcription-coupled nucleotide excision repair (TC-NER); however, these functions do not explain the distinct phenotypic differences observed between CSB-deficient mice and humans. During investigating Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism that involves elongating RNA polymerase II (RNAPII) undergoing transient pauses at internal T-runs where CSB is required to propel RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, and when coupled with G-rich sequences upstream, exacerbates genome instability by promoting R-loop formation. These R-loop prone motifs are notably abundant in relatively long genes related to neuronal functions in the human genome, but less prevalent in the mouse genome. These findings provide mechanistic insights into differential impacts of CSB deficiency on mice versus humans and suggest that the manifestation of the Cockayne Syndrome phenotype in humans results from the progressive evolution of mammalian genomes.

Abstract The existing hypervalent I(III) reagents bearing ONO2 group are limited in types and their applications primarily focused on the nitrooxylation reactions featuring a fully-exo fashion. Herein, a benziodazole-type O2NO-I(III) compound was prepared and its reaction with β-monosubstituted enamines in the presence of CuI could trigger a radical nitration/cyclization/dehydration cascade to provide a series of less explored but biologically interesting furazan heterocycles. Mechanistically, the benziodazole-type O2NO-I(III) compound acts as a nitrating reagent and incorporates its NO moiety into the final furazan product in a fully-endo model, a process of which was proposed to involve nitration, cyclization and dehydration.

Abstract Background Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer’s disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. Methods This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aβ42, Aβ40, Aβ42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman’s correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aβ42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. Results The participants’ mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P

The purpose of this study was to comparative analyze the diagnostic efficiency of Thyroid Imaging Reporting and Data System proposed by Kwak, American College of Radiology, the European Thyroid Association and the Chinese Medical Association, respectively (Kwak TI-RADS, ACR TI-RADS, EU-TIRADS and C-TIRADS, respectively) for malignant risk stratification of thyroid nodules. A total of 1142 thyroid nodules confirmed by cytological or surgical pathologies were retrospectively classified according to Kwak TI-RADS, ACR TI-RADS, EU-TIRADS and C-TIRADS. The area under the receiver operating characteristic curve (AUC), the diagnostic sensitivity, specificity, Youden index, and accuracy of each TI-RADS for nodules was calculated and compared. The diagnostic sensitivity of ACR TI-RADS was 85.5%, which was lowest (all P 0.05). The AUC of C-TIRADS was highest among the four methods (all P

PurposeThe aim of this study was to develop a novel approach for predicting the expression status of Epidermal Growth Factor Receptor (EGFR) and its subtypes in patients with Non-Small Cell Lung Cancer (NSCLC) using a Three-Dimensional Convolutional Neural Network (3D-CNN) ConvNeXt, radiomics features and clinical features.Materials and methodsA total of 732 NSCLC patients with available CT imaging and EGFR expression data were included in this retrospective study. The region of interest (ROI) was manually segmented, and clinicopathological features were collected. Radiomic and deep learning features were extracted. The instances were randomly divided into training, validation, and test sets. Feature selection was performed, and XGBoost was used to create solo models and combined models to predict the presence of EGFR and subtypes mutations. The effectiveness of the models was assessed using ROC and PRC curves.ResultsWe established the following models: ModelCNN, Modelradiomic, Modelclinical, ModelCNN+radiomic, ModelCNN+clinical, Modelradiomic+clinical, and ModelCNN+radiomic+clinical, which were based on deep learning features, radiomic features, clinical data and combinations of these, respectively. In predicting EGFR mutations, ModelCNN+radiomic+clinical demonstrated superior performance compared to other prediction models, achieving an AUC of 0.801. For distinguishing between EGFR subtypes ex19del and L858R, ModelCNN+radiomic reached the highest AUC value of 0.775.ConclusionsBoth deep learning models and radiomic signature-based models offer reasonably accurate non-invasive predictions of EGFR status and its subtypes. Fusion models hold the potential to enhance noninvasive methods for predicting EGFR mutations and subtypes, presenting a more reliable prediction approach.

With the continuous application of new agricultural chemicals in agricultural systems, it is imperative to study the environmental fate and potential transformation products (TPs) of these chemicals to better assess their ecological and health risks, as well as guide scientific application. The dissipation of fluchloraminopyr was firstly evaluated under aerobic/anaerobic condition in four representative soils, with Dissipation Time 50 (DT50) values ranging from 0.107 to 4.76 days. Eight TPs generated by soil degradation were identified via Ultra-High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-QTOF/MS) and Density Functional Theory (DFT) calculations. The predominant transformation reactions of fluchloraminopyr in soil include oxidation, dechlorination, hydroxylation, and acetylation. The predictions from toxicological software indicated that the acute and chronic toxicity of TPs to aquatic organisms was significantly lower than that of fluchloraminopyr. Moreover, both M267 and M221 exhibited higher acute oral toxicity to terrestrial organisms compared to the parent compound. Consequently, these findings offer essential ecological risk evaluation data for the judicious application of fluchloraminopyr.

The photosystem II (PSII) Subunit P (PsbP) protein is a component of its oxygen-evolving complex, which can oxidize water to produce oxygen using light energy and is critical to the core components and stability of PSII. Using the whole-genome information, the PsbP genes of 10 plant species were comprehensively identified. The expression patterns of wheat PsbPs under Blumeria graminis f. sp. tritici (Bgt) infection were assessed using qRT-PCR, and the functions of TaPsbPs in wheat powdery mildew resistance were studied using barley stripe mosaic virus-induced gene silencing. In total, 122 PsbP genes were divided into 8 classes with similar gene structures. No tandem repeat events were identified in wheat PsbP, suggesting that the PsbP genes in common wheat were donated by its diploid progenitor species. The expression levels of TaPsbP2A-1, TaPsbP3A-1, TaPsbP4A-1, TaPsbP4A-2, and TaPsbP7A-2 were induced by Bgt. The silencing of TaPsbP4A-1 increased the resistance of common wheat ‘Bainong AK58’ to Bgt. This study provides valuable information for functional and evolutionary research on the PsbP gene family.

ObjectivePublic health emergencies pose a serious challenge to the ability of medical personnel to respond. We aimed to establish a scientific and effective resilience capability assessment scale for grassroots medical workers and explore the way to improve resilience.Research designDeveloped a resilience ability assessment scale and applied it on the medical personnel who worked in community health service centers for more than 1 year. Related indicators were identified through literature review and the Delphi method. The established scale was given weight using the attribute analytic hierarchy process, and the evaluation model was built through the grey correlation analysis.Principal findingsA three-level indicator scale was established, which included three first-level indicators [professional quality (weight 0.346), psychological capital (weight 0.614), and emergency attitude (weight 0.040)]. The second-level indicators had 13 contents and were further subdivided into 46 three-level indicators. The overall resilience ability assessment score of 347 medical workers in Guangzhou was only 0.787. However, steady scientific-exercise habits and relative training can help improve their public health emergency resilience ability (p

Early identification of sepsis in emergency room patients is critical for initiating timely interventions, highlighting the need for effective predictive scoring systems. A retrospective observational study was conducted using data from the CETAT database collected between December 2019 and October 2021. The study evaluated how well the SIRS, qSOFA, and NEWS scoring systems, along with logistic regression models, predict sepsis and high-risk sepsis in emergency room patients. The logistic regression models were further optimized by incorporating additional features based on local data.A total of 12,799 patients were analyzed, including 1,360 sepsis cases, of which 373 were classified as high-risk sepsis. The NEWS score demonstrated superior predictive performance compared to qSOFA and SIRS, with an AUC-ROC of 0.737 (95% CI 0.72–0.75) for sepsis and 0.653 (95% CI 0.62–0.69) for high-risk sepsis. After optimization, the NEWS-based model improved to an AUC-ROC of 0.756 (95% CI 0.74–0.77) for sepsis and 0.718 (95% CI 0.69–0.75) for high-risk sepsis. Further enhancement was observed with the inclusion of additional clinical variables, resulting in AUC-ROC values of 0.834 (95% CI 0.82–0.85) for sepsis and 0.756 (95% CI 0.73–0.78) for high-risk sepsis. Data from the MIMIC-IV database, which included sepsis status and relevant variables for SIRS, qSOFA, and NEWS score calculations, confirmed that the optimized NEWS-based model improved the sepsis prediction AUC-ROC from 0.690 (95% CI 0.68–0.70) to 0.708 (95% CI 0.70–0.72), and consistently outperformed qSOFA and SIRS in sepsis prediction.

Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. Methods To study the function of OTUB2 in IBD, we generated Otub2–/– mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. Results OTUB2 was highly expressed in colon‐infiltrating macrophages in both humans with IBD and mice with DSS‐induced experimental colitis. Colitis was significantly aggravated in Otub2–/– mice and bone marrow chimeric mice receiving Otub2–/– bone marrow. OTUB2‐deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48‐linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. Conclusion This study identified OTUB2 as a novel regulator of intestinal inflammation.

BackgroundBy using meta-analysis to evaluate the effects of exercise on adolescent body mass index (BMI), standing long jump, sit ups, lung capacity, sitting forward bending, 50 m running, and 800 m running, a large amount of literature will be reviewed to reveal the key role of exercise in the healthy development of adolescents. This study aims to promote the development of adolescent physical health and solve the common problem of declining physical fitness, comprehensively improve the physical fitness of adolescents, and provide decision-making support for policymakers. The research results will provide methodological references for precise and effective intervention practices, further improve adolescent physical fitness, and lay a solid physiological foundation for their comprehensive development.MethodsA literature search was conducted on China National Knowledge Infrastructure (CNKI) and PubMed, collecting randomized controlled trials (RCTs) that investigated the effects of physical activity on adolescent physical fitness according to predefined criteria. The quality of these studies was assessed, and their outcome data were analyzed using RevMan 5.4 software. The analysis encompassed 13 articles with a total of 4,633 participants, examining measures such as mean difference (MD) and heterogeneity, followed by subgroup analyses.ResultsThe meta-analysis revealed that physical activity had a moderate to high effect on adolescent performance in sit-ups (MD = 4.91, 95% CI = 3.41–6.41), vital capacity (MD = 120.66, 95% CI = 48.67–194.46), sit-and-reach test (MD = 0.82, 95% CI = 0.09–1.56), 50-meter dash (MD = −1.05, 95% CI = −1.48 to −0.62), and 800-meter run (MD = −18.48, 95% CI = −24.98 to −11.97). Conversely, its influence on BMI (MD = −0.31, 95% CI = −1.87 to 1.24) and standing long jump (MD = 0.1, 95% CI = 0.05–0.15) was relatively low.ConclusionEngaging in physical activities significantly improves adolescent physical fitness. The most effective regimen involves a combination of aerobic and anaerobic exercises, with each session lasting 30 min, performed three times per week for at least 2 months. The extent of improvement in various fitness indicators, reflecting different aspects of physical fitness, is influenced by factors such as the nature of the physical activity, intervention duration, exercise frequency, and age.Systematic Review RegistrationPROSPERO, identifier CRD42024568197

Non-native freshwater fish species are regarded as a key factor responsible for the degradation of freshwater ecosystems. Although research on China's non-native freshwater fish species has been conducted at the national scale, the spatial distribution and introduction pathways of these species in China remain unclear. To address this knowledge gap, this study compiled a dataset of non-native freshwater fish species across administrative regions in China. We first assessed the number of non-native freshwater fish species by taxonomy, geographical origin, introduction pathway, and province. There were 177 non-native freshwater fish species, belonging to 17 orders, 48 families, and 118 genera. The orders Cypriniformes (33.3%), Perciformes (28.2%), Siluriformes (10.2%), and Salmoniformes (6.2%) accounted for the largest proportion of non-native freshwater fish species. Eighty-nine non-native species were introduced from other countries or regions, mostly from North America (31 species; 34.8%), Asia (20 species; 22.5%), Africa (13 species; 14.6%), Europe (11 species; 12.4%), and South America (10 species; 11.2%). Aquaculture was the most common introduction pathway. Non-native freshwater fish species were more widely distributed in southwest China. Our study showed that there were obvious differences in the number and composition of non-native freshwater fish species across various provinces in China. The variation in the number of non-native freshwater fish species across provinces in China was attributed to distinct geographical features, development of the aquaculture industry, and efforts to study non-native freshwater fish species. Therefore, comprehensive surveys and studies of non-native freshwater fish species are needed, which are of great importance for the management and control of non-native species invasions.

BackgroundThe gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.Methods16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.ResultsThe composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.ConclusionSex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.

Diffusion magnetic resonance imaging (dMRI) allows non-invasive assessment of brain tissue microstructure. Current model-based tissue microstructure reconstruction techniques require a large number of diffusion gradients, which is not clinically feasible due to imaging time constraints, and this has limited the use of tissue microstructure information in clinical settings. Recently, approaches based on deep learning (DL) have achieved promising tissue microstructure reconstruction results using clinically feasible dMRI. However, it remains unclear whether the subtle tissue changes associated with disease or age are properly preserved with DL approaches and whether DL reconstruction results can benefit clinical applications. Here, we provide the first evidence that DL approaches to tissue microstructure reconstruction yield reliable brain tissue microstructure analysis based on clinically feasible dMRI scans. Specifically, we reconstructed tissue microstructure from four different brain dMRI datasets with only 12 diffusion gradients, a clinically feasible protocol, and the neurite orientation dispersion and density imaging (NODDI) and spherical mean technique (SMT) models were considered. With these results we show that disease-related and age-dependent alterations of brain tissue were accurately identified. These findings demonstrate that DL tissue microstructure reconstruction can accurately quantify microstructural alterations in the brain based on clinically feasible dMRI.

Summary: Early prediction of acute pancreatitis (AP) with acute kidney injury (AKI) using abdominal contrast-enhanced CT could effectively reduce the mortality and the economic burden on patients and society. However, this challenge is limited by the imaging manifestations of early-stage AP that are not clearly visible to the naked eye. To address this, we developed a machine learning model using imperceptible variations in the structural changes of pancreas and peripancreatic region, extracted by radiomics and artificial intelligence technology, to screen and stratify the high-risk AP patients at the early stage of AP. The results demonstrate that the machine learning model could screen the high-risk AP with AKI patients with an area under the curve (AUC) of 0.82 for the external cohort, superior to the human radiologists. This finding confirms the significant potential of machine learning in the screening of acute pancreatitis and contributes to personalized treatment and management for AP patients.

Waterbirds are often used as indicators of wetland biodiversity and ecosystem health due to their sensitivity to environmental changes. However, most studies have focused on long-term variations of waterbird communities, while the intra-annual changes have rarely been investigated. Here, we analyzed the seasonal dynamics of compositions and the intra-annual variations of species richness and abundance of waterbird communities among the nine major river basins of China, and focused on the effects of different residential types and taxonomic groups on the diversity variations. In most of the nine basins, the waterbird communities in spring and autumn showed high similarity, while those in summer and winter were quite different. Such a seasonal cycle of species composition was caused by the seasonal migration of waterbirds. The season with higher species richness shifted from summer to winter as the latitude of the basin decreased within China, but almost all basins had the lowest community abundance in summer. This was because the variation of richness was directly influenced by the variation in species composition, but the variation of abundance was more influenced by the population size of different waterbird assemblages. Our results emphasized the importance of seasonal dynamics of waterbird communities to the understanding of their migration patterns, and highlighted the impact of different waterbird assemblages on intra-annual community variations. Additionally, we also noted the potential effects of population size and behaviors at different parts of the waterbird life circle on the observations of them. The information gathered in this study will provide guidance for the conservation of waterbird species and their habitats.

BACKGROUND: Hemorrhagic shock (HS) causes severe organ damage, worsened by high-altitude conditions with lower oxygen and temperatures. Existing research lacks specific insights on brain and heart damage under these conditions. This study hypothesizes that high-altitude and cold (HAC) environments exacerbate HS-induced damage in the brain and heart, aiming to improve treatment strategies. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley (SD) rats (200–250 g of weight) were randomly assigned into sham, HS + normal, HS + HAC (4,000 m), and HS + HAC (6,000 m). The HS model was established in SD rats (35% loss of total blood volume), and histopathological injuries of the brain and heart were detected using hematoxylin and eosin staining, Sirius red staining, and immunohistochemistry. Apoptosis of the brain and heart tissues was detected by terminal transferase-mediated dUTP nick end labeling (TUNEL) immunofluorescence staining. To determine the levels of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (Mcp-1), BCL2-associated X (BAX), and myeloid cell leukemia-1 (Mcl-1) protein, western blotting assay was used. RESULTS: The HAC environment induced pathological damage to the brain and heart and aggravated the degree of cardiac fibrosis in HS rats. However, it did not cause apoptosis of the brain and heart. In addition, it upregulated TNF-α, IFN-γ, Mcp-1, and BAX protein levels, but downregulated Mcl-1 protein levels (P < 0.05). CONCLUSIONS: The HAC environment aggravated the degree of brain and heart damage in HS rats, which may be related to neuron nucleus pyknosis, myocardial fibrosis, and inflammatory and apoptosis activation.

Ovarian aging leads to endocrine disorders and systemic degeneration of tissue and organ structure and function, seriously affecting women's physical and mental health. Safe and effective treatments for this condition are lacking. Umbilical cord mesenchymal stem cells (UCMSCs), which have multidirectional differentiation potential, show strong self-renewal, secrete bioactive factors and release exosomes, can undergo homing, colonization, integration and differentiation into supporting and functional cells in tissues and organs through direct manipulation and can also improve the tissue microenvironment through paracrine action, promoting cell division, proliferation and microangiogenesis, inhibiting inflammation and apoptosis, reducing oxidative stress, and mediating two-way immune regulation. These processes activate dormant cells, repaired damaged cells, replace necrotic cells, and regenerate fresh cells, restoring the structure and function of the ageing ovary. Furthermore, with the increasing development of UCMSC research and technology, the therapeutic use of UCMSCs is expected to become an effective means for the treatment of ovarian ageing caused by tissue cell ageing, degeneration, and necrosis.

Abstract Algorithmic recommendation technology, including news apps, social networking services (SNSs), and video or short-video apps, and is widely embedded in various mobile applications (apps), has raised concerns about potential addiction. This study constructs a model linking the uses and gratifications of algorithmic recommendation apps with algorithmic dependence, with a particular focus on fatigue as a key mediator in explaining the psychological mechanism behind the formation of algorithmic app dependence. Snowball sampling was employed for data collection, and a total of 354 valid questionnaires were collected via the online survey tool (i.e., WJX platform). The results show that the use of algorithmic recommendation apps has a direct positive effect on algorithmic app dependence. While all three types of user gratification obtained (i.e., information gratification, entertainment gratification, and expression gratification) are positively related to algorithmic app dependence, the mediating role of fatigue varies: entertainment gratification indirectly reduces algorithmic app dependence by increasing fatigue, whereas expression gratification indirectly increases algorithmic app dependence by reducing fatigue. The theoretical contributions and practical implications of the research findings are discussed.

Abstract Ocular disorders can significantly lower patients’ quality of life and impose an economic burden on families and society. However, for the majority of these diseases, their prevalence and mechanisms are yet unknown, making prevention, management, and therapy challenging. Although connections between exposure factors and diseases can be drawn through observational research, it is challenging to rule out the interference of confounding variables and reverse causation. Mendelian Randomization (MR), a method of research that combines genetics and epidemiology, has its advantage to solve this problem and thus has been extensively utilized in the etiological study of ophthalmic diseases. This paper reviews the implementation of MR in the research of ocular diseases and provides approaches for the investigation of related mechanisms as well as the intervention strategies.

Abstract Objective This study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). Methods Retrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis. Results Twelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89–30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61–7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67–43.33 months) for Group 3 (n = 4), and 19 months (range 7.89–30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004). Conclusion Surgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.

Objective To investigate the binding and carrying effects of human serum albumin (HSA) from various sources on sphingosine-1-phosphate (S1P). Methods Utilizing human plasma-derived HSA (pHSA) and recombinant HSA (rHSA) samples as the focal points of our investigation, LC-MS/MS technology was employed to meticulously compare and analyze the disparities in S1P content among the aforementioned samples. Subsequently, under physiological concentration conditions, S1P was directly introduced to HSA samples for loading processing, facilitating a comprehensive comparison of the binding efficacy of HSA from different sources to S1P. Within a serum-free culture setting, HSA samples from various sources were co-cultured with HUVEC cells. The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed, allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was calculated using surface plasmon resonance (SPR) technology. Furthermore, leveraging AutoDock Vina software and the Molprophet platform, the molecular docking analysis of HSA and S1P was conducted, aiming to predict the key binding pocket domain of S1P within HSA. Results All pHSA samples exhibited detectable levels of S1P (ranging from 3.31±0.03 to 30.35±0.07 μg/L), with significant variations observed among pHSA samples from different manufacturers (P

Abstract Background Standardized corneal densitometry (CD) values in large samples of healthy Chinese individuals are scarce. Therefore, we aimed to determine the standard CD values using a Scheimpflug camera in healthy corneas, investigate the correlations of sex, age, and ocular parameters with corneal density, and explore the impact of corneal density on the forward scattering and optical quality of the eye. Methods This retrospective observational study involved 990 healthy Chinese individuals, including 494 males and 496 females (mean age: 23.88 ± 6.90 years). The CD values at various depths and radial areas of 0–12 mm were measured using a Scheimpflug camera. Densitometric measurements were expressed in standardized grayscale units (GSU). The optical scatter index (OSI), modulation transfer function cutoff values (MTFcutoff), and Strehl’s ratio (SR) were also determined using an optical quality analysis system. Results The average CD within a 12 mm diameter area was 16.26 ± 1.35 GSU. The highest and lowest optical densities at different depths were observed in the anterior (21.41 ± 2.16 GSU) and posterior (12.00 ± 1.01 GSU) layers, respectively (P 0.05). However, upon adjusting for age, central corneal thickness (CCT), corneal curvature, white-to-white (WTW) corneal diameter, and axial length, females exhibited a greater average CD within the 12 mm diameter and in the 6–10 mm and 10–12 mm circles than males. Age-related changes in CD were evident, except in the 2–6 mm circle. CCT, corneal curvature, WTW corneal diameter, and partial depth correlated with CD in the radial area, and CD in different areas correlated with the OSI, MTFcutoff, and SR (P

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype. Molecular stratification and target therapy bring clinical benefit for TNBC patients, but it is difficult to implement comprehensive molecular testing in clinical practice. Here, using our multi-omics TNBC cohort (N = 425), a deep learning-based framework was devised and validated for comprehensive predictions of molecular features, subtypes and prognosis from pathological whole slide images. The framework first incorporated a neural network to decompose the tissue on WSIs, followed by a second one which was trained based on certain tissue types for predicting different targets. Multi-omics molecular features were analyzed including somatic mutations, copy number alterations, germline mutations, biological pathway activities, metabolomics features and immunotherapy biomarkers. It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation, germline BRCA2 mutation and PD-L1 protein expression (area under the curve [AUC]: 0.78, 0.79 and 0.74 respectively). The molecular subtypes of TNBC can be identified (AUC: 0.84, 0.85, 0.93 and 0.73 for the basal-like immune-suppressed, immunomodulatory, luminal androgen receptor, and mesenchymal-like subtypes respectively) and their distinctive morphological patterns were revealed, which provided novel insights into the heterogeneity of TNBC. A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes (log-rank P < 0.001). Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA (N = 143) and appeared robust to the changes in patient population. For potential clinical translation, we built a novel online platform, where we modularized and deployed our framework along with the validated models. It can realize real-time one-stop prediction for new cases. In summary, using only pathological WSIs, our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making. It had the potential to be clinically implemented and promote the personalized management of TNBC.

Abstract Background Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. Methods We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. Results A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48–5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02–26.02; p

Abstract Background Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. Methods We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. Results Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. Conclusions This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.

Abstract Integrated circuit anti-counterfeiting based on optical physical unclonable functions (PUFs) plays a crucial role in guaranteeing secure identification and authentication for Internet of Things (IoT) devices. While considerable efforts have been devoted to exploring optical PUFs, two critical challenges remain: incompatibility with the complementary metal-oxide-semiconductor (CMOS) technology and limited information entropy. Here, we demonstrate all-silicon multidimensionally-encoded optical PUFs fabricated by integrating silicon (Si) metasurface and erbium-doped Si quantum dots (Er-Si QDs) with a CMOS-compatible procedure. Five in-situ optical responses have been manifested within a single pixel, rendering an ultrahigh information entropy of 2.32 bits/pixel. The position-dependent optical responses originate from the position-dependent radiation field and Purcell effect. Our evaluation highlights their potential in IoT security through advanced metrics like bit uniformity, similarity, intra- and inter-Hamming distance, false-acceptance and rejection rates, and encoding capacity. We finally demonstrate the implementation of efficient lightweight mutual authentication protocols for IoT applications by using the all-Si multidimensionally-encoded optical PUFs.

Abstract Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. The oncometabolites have been studied in OSCC, but the mechanism of metabolic reprogramming remains unclear. To identify the potential metabolic markers to distinguish malignant oral squamous cell carcinoma (OSCC) tissue from adjacent healthy tissue and study the mechanism of metabolic reprogramming in OSCC. We compared the metabolites between cancerous and paracancerous tissues of OSCC patients by 1HNMR analysis. We established OSCC derived cell lines and analyzed their difference of RNA expression by RNA sequencing. We investigated the metabolism of γ-aminobutyrate in OSCC derived cells by real time PCR and western blotting. Our data revealed that much more γ-aminobutyrate was produced in cancerous tissues of OSCC patients. The investigation based on OSCC derived cells showed that the increase of γ-aminobutyrate was promoted by the synthesis of glutamate beyond the mitochondria. In OSCC cancerous tissue derived cells, the glutamate was catalyzed to glutamine by glutamine synthetase (GLUL), and then the generated glutamine was metabolized to glutamate by glutaminase (GLS). Finally, the glutamate produced by glutamate-glutamine-glutamate cycle was converted to γ-aminobutyrate by glutamate decarboxylase 2 (GAD2). Our study is not only benefit for understanding the pathological mechanisms of OSCC, but also has application prospects for the diagnosis of OSCC.

Educational leadership theory is a dynamic and multifaceted subject that emerged from enterprise leadership perspectives, but it necessitates alignment with the practical aspects of educational management. To comprehensively grasp the evolution and present research status of this theory, content analysis is employed in this study to systematically analyze and quantify pertinent information. The key findings are as follows: Firstly, empirical research serves as the predominant research method in studying educational leadership theory. Within this field, qualitative and quantitative research methods are employed simultaneously. Moreover, case studies play a crucial role in advancing the development of issues and the construction of theories. Additionally, the distributed leadership theory has gained significant prominence within the realm of educational leadership. Current research methods employed in this theory are still in a stage of maturity, relying primarily on qualitative research to uncover underlying patterns among social phenomena through examination of specific cases. Finally, the primary focus of educational leadership theory lies in studying school managers and teachers. In light of the influence stemming from distributed leadership theory, teacher leadership has garnered increasing attention from scholars and has emerged as a burgeoning area of interest. This study contributes to the field by presenting a comprehensive framework for cognitive educational leadership theory through an extensive content analysis, thereby offering valuable insights into its overall developmental trajectory. These findings provide a macro-level perspective on educational leadership theory, particularly beneficial for subsequent researchers, especially those new to the field, seeking to grasp the broader landscape of this discipline.

Abstract Ripretinib, a broad‐spectrum inhibitor of the KIT and PDGFRA receptor tyrosine kinases, is designated as a fourth‐line treatment for gastrointestinal stromal tumor (GIST). It is tailored for patients resistant to imatinib, sunitinib, and regorafenib. As its increasing use, instances of resistance to ripretinib are becoming more frequent. Unfortunately, there are currently no scientifically mature treatment options available for patients resistant to ripretinib. Posttranslational modifications (PTMs) such as ubiquitination, in conjunction with its interplay with other modifications, play a collective role in regulating tumor initiation and progression. However, the specific association between ubiquitination and ripretinib resistance is not reported. Through proteome–ubiquitinome sequencing, increased levels of the USP5 protein and decreased ubiquitination in ripretinib‐resistant GISTs are detected. Subsequent examination of the mass spectrometry findings validated the interaction through which TRIM21 governs USP5 expression via ubiquitination, and USP5 regulates MDH2 expression through deubiquitination, consequently fostering ripretinib resistance in GIST. Moreover, ZDHHC18 can palmitoylate MDH2, preventing its ubiquitination and further increasing its protein stability. The research underscores the correlation between posttranslational modifications, specifically ubiquitination, and drug resistance, emphasizing the potential of targeting the USP5‐MDH2 axis to counteract ripretinib resistance in GIST.

Purpose This study investigated the topological structural characteristics of systemic lupus erythematosus (SLE) with and without neuropsychiatric symptoms (NPSLE and non-NPSLE), and explore their clinical implications.Methods We prospectively recruited 50 patients with SLE (21 non-NPSLE and 29 NPSLE) and 32 age-matched healthy controls (HCs), using MRI diffusion tensor imaging. Individual structural networks were constructed using fibre numbers between brain areas as edge weights. Global metrics (eg, small-worldness, global efficiency) and local network properties (eg, degree centrality, nodal efficiency) were computed. Group comparisons of network characteristics were conducted. Clinical correlations were assessed using partial correlation, and differentiation between non-NPSLE and NPSLE was performed using support vector classification.Results Patients with oth non-NPSLE and NPSLE exhibited significant global and local topological alterations compared with HCs. These changes were more pronounced in NPSLE, particularly affecting the default mode and sensorimotor networks. Topological changes in patients with SLE correlated with lesion burdens and clinical parameters such as disease duration and the systemic lupus international collaborating clinics damage index. The identified topological features enabled accurate differentiation between non-NPSLE and NPSLE with 87% accuracy.Conclusion Structural networks in patients SLE may be altered at both global and local levels, with more pronounced changes observed in NPSLE, notably affecting the default mode and sensorimotor networks. These alterations show promise as biomarkers for clinical diagnosis.