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Abstract SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed. Using a differential staining strategy with a rationally designed SARS-CoV-2 Receptor Binding Domain (RBD) – ACE2 fusion protein and a native Omicron RBD protein, we developed a recombinant human monoclonal antibody (hmAb) from a convalescent individual following SARS-CoV-2 Omicron infection. The resulting hmAb, 1301B7 potently neutralized a wide range of SARS-CoV-2 variants including the original Wuhan-1, the more recent Omicron JN.1 strain, and SARS-CoV. 1301B7 contacts the ACE2 binding site of RBD exclusively through its VH1-69 heavy chain. Broad specificity is achieved through 1301B7 binding to many conserved residues of Omicron variants including Y501 and H505. Consistent with its extensive binding epitope, 1301B7 is able to potently diminish viral burden in the upper and lower respiratory tract and protect mice from challenge with Omicron XBB1.5 and Omicron JN.1 viruses. These results suggest 1301B7 has broad potential to prevent or treat clinical SARS-CoV-2 infections and to guide development of RBD-based universal SARS-CoV-2 prophylactic vaccines and therapeutic approaches.

Abstract Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and EGFR-TKI combination treatments have become the standard first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC) patients. However, the best option has yet to be determined. This study compares the efficacy and safety of various first-line EGFR-TKI monotherapies and combination treatments for advanced EGFR-mutated NSCLC. Methods We searched PubMed, Embase, the Cochrane Central Register of Controlled Clinical Trials databases, and several international conferences to identify randomized controlled trials reporting on first-line EGFR-TKI treatments for patients with advanced EGFR-mutated NSCLC. The study quality was assessed using the revised tool for risk of bias in randomized trials. The efficacy and safety outcomes of the included treatments were compared by network meta-analysis based on a frequentist approach. Results We identified 26 trials (8,359 patients) investigating 14 treatment groups, including first, second, and third-generation EGFR-TKIs and their combination treatments. Osimertinib plus chemotherapy and lazertinib plus amivantamab showed the highest efficacy in improving progression-free survival. New third-generation EGFR-TKIs demonstrated comparable efficacy to osimertinib alone but did not surpass it. Subgroup analyses revealed slight variation in treatment efficacy based on mutation types and patient demographics. Combination treatments were associated with a higher incidence of adverse events. Conclusion These results reveal that osimertinib plus chemotherapy and lazertinib plus amivantamab are superior first-line options for patients with advanced EGFR-mutated NSCLC. However, these combinations are associated with higher adverse event rates.

Abstract The pharmacokinetics of vancomycin exhibit significant inter-individual variability, particularly among elderly patients. This study aims to develop a predictive model that integrates machine learning with population pharmacokinetics (popPK) to facilitate personalized medication management for this demographic. A retrospective analysis incorporating 33 features, including popPK parameters such as clearance and volume of distribution. A combination of multiple algorithms and Shapley Additive Explanations was utilized for feature selection to identify the most influential factors affecting drug concentrations. The performance of each algorithm with popPK parameters was superior to that without popPK parameters. Our final ensemble model, composed of support vector regression, light gradient boosting machine, and categorical boosting in a 6:3:1 ratio, included 16 optimized features. This model demonstrated superior predictive accuracy compared to models utilizing all features, with testing group metrics including an R2 of 0.656, mean absolute error of 3.458, mean square error of 28.103, absolute accuracy within ± 5 mg/L of 81.82%, and relative accuracy within ± 30% of 76.62%. This study presents a rapid and cost-effective predictive model for estimating vancomycin plasma concentrations in elderly patients. The model offers a valuable tool for clinicians to accurately determine effective plasma concentration ranges and tailor individualized dosing regimens, thereby enhancing therapeutic outcomes and safety.

Abstract The high energy consumption of Carbon Capture Utilization and Storage(CCUS) promotes the research of integrated absorption and mineralization technology. A novel DEEA/AEP biphasic absorbent is used to absorb $$\hbox {CO}_{2}$$ . After phase separation, only one phase enriched with the absorption product is sent into the mineralization system, then reacts with $$\hbox {Ca(OH)}_{2}$$ to produce $$\hbox {CaCO}_{3}$$ at normal temperature and pressure. The effects of temperature, Ca/C and dispersion of the system were investigated, and cyclic utilization experiment was also conducted. The process was characterized and analyzed by Thermal gravimetric analysis (TGA), X-ray diffraction (XRD), and nuclear magnetic resonance (13C NMR). The results showed that at 50 $$^{\circ }$$ C, Ca/C = 1, the extent of mineralization of $$\hbox {CO}_{2}$$ -enriched phase mineralization was 95.73% after ultrasonic treatment for 30 min. During 6 cycles, the volume percentage of $$\hbox {CO}_{2}$$ -enriched phase could be maintained at 52–55%, and the $$\hbox {CO}_{2}$$ load was 11.92mol/L. The results above indicate that the $$\hbox {CO}_{2}$$ -enriched phase mineralization technology after absorption by biphasic absorbent can effectively capture $$\hbox {CO}_{2}$$ , realize recycling, and reduce CCUS energy consumption.

Abstract The trade-off between rapid growth and other important physiological traits (e.g., survival and adaptability) poses a fundamental challenge for microbes to achieve fitness maximization. Studies on Bacillus subtilis biology often use strains derived after a process of lab ‘domestication’ from an ancestral strain known as Marburg strain. The domestication process led to loss of a large plasmid (pBS32) encoding a phosphatase (RapP) that dephosphorylates the Spo0F protein and thus regulates biofilm formation and sporulation. Here, we show that plasmid pBS32, and more specifically rapP, enhance growth rates by preventing premature expression of the Spo0F-Spo0A-mediated adaptive response during exponential phase. This results in reallocation of proteome resources towards biosynthetic, growth-promoting pathways without compromising long-term fitness during stationary phase. Thus, RapP helps B. subtilis to constrain physiological trade-offs and economize cellular resources for fitness improvement.

Abstract Background Neuropsychiatric manifestations, such as cognitive impairment, are relatively prevalent in systemic sclerosis (SSc) patients. This study aimed to investigate the resting state (RS) functional alternations of SSc patients and the potential influenced factors. Methods Forty-four SSc patients (mean age, 46.3 ± 11.4 years; 40 females) and 19 age and sex comparable healthy volunteers (mean age, 42.6 ± 11.3 years; 16 females) were recruited and underwent RS functional MR imaging (fMRI) and neuropsychological assessments. Functional segregation analysis was performed to calculate the amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo). Functional integration analysis was conducted using group independent component analysis to calculate intra-network and inter-network functional connectivity (FC). The fMRI measurements were compared between SSc patients and healthy volunteers using voxel-based pairwise two-sample t-tests. The correlations between clinical characteristics and fMRI measurements were also analyzed. Results Compared to healthy volunteers, SSc patients exhibited significantly decreased ALFF and increased ReHo (all P 30; inter-network FC: P

Abstract Background As the incidence of gastric cancer increases sharply in adults aged over 45 years, a better understanding of gastric cancer screening knowledge and practice is crucial to promote cancer-screening services. This study aimed to evaluate knowledge of early gastric cancer screening, adherence to screening, and perceived barriers hindering screening practices among adults aged ≥ 45 years in China. Methods A multi-center, face-to-face, cross-sectional study was conducted in community sites in Shijiazhuang, China, through the distribution of structured questionnaires from August to September, 2022. Results Of the 1053 respondents, only 13.4% demonstrated a good understanding of early gastric cancer screening. While 64.0% knew that gastroscopy is the gold standard for screening (“how to screen”), only 19.9% were aware of the recommended starting age (“when to screen”). Moreover, less than half could correctly identify high-risk groups (“whom to screen”), with awareness ranging from 20.5% for those infected with H. pylori to 47.8% for those with gastric diseases. Independent factors related to higher screening knowledge included female sex (OR = 1.55, 95% CI = 1.01–2.38), higher education level (OR = 4.03, 95% CI = 2.68–6.06), being with a personal/family experience of gastric diseases (OR = 1.68, 95% CI = 1.12–2.52). In addition, only 23.4% of respondents underwent GC screening. The dominant barrier to early screening was the “absence of symptoms or signs”, followed by “fearing procedural discomfort”. Conclusion This study highlights significant gaps in early gastric cancer screening knowledge and participation among middle-aged and elderly individuals in China. Addressing these gaps through culturally tailored health education campaigns is a critical strategy for increasing public awareness and participation.

Objective: This study aimed to investigate the application value of fractional bolus injection of a contrast agent combined with double-layer detector spectral CT 50 keV virtual monoenergetic imaging (VMI) in combined imaging of computed tomography urography (CTU) and aortic CT angiography (CTA). Methods: The experimental group included 32 patients who underwent spectral CTU with a Philips IQon dual-layer detector at Beijing Tongren Hospital, Capital Medical University, between March and April 2024. Using fractional bolus injection of a contrast agent and bolus tracking technology, the conventional 120 kVp mixed energy image was reconstructed after scanning for group A1; the 50 keV VMI obtained by spectral reconstruction was group A2. The control group included 32 patients who underwent CTU examination between December 2023 and March 2024 using the same equipment, and the contrast agent split bolus and group injection tracking techniques were used. After scanning, the conventional 120 kVp mixed energy image was reconstructed for group B. The objective evaluation included the CT value, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of the abdominal aorta and bilateral renal arteries, which were compared among the three groups. The Kruskal–Wallis and Nemenyi tests were used to compare the average CT values of the initial, middle, and lower parts of the ureter. Wilcoxon test was used to compare the effective radiation dose between the experimental and control groups. Subjective evaluation was performed by two senior radiologists on the three groups of CTU and CTA images using the 4- and 3-point methods, respectively. The consistency of the subjective scores of the two radiologists was analyzed using the Kappa test. Results: Among the objective evaluation indices, there were statistically significant differences among groups A2, A1, and B. There was a significant difference in the SNR of the bilateral renal arteries between groups A1 and B. The effective radiation dose of the experimental group was 15.1% lower than that of the control group, which was significantly different. There was no significant difference in the subjective evaluation of the CTA and CTU images among the three groups. The consistency of the CTA and CTU image scoring results between the two physicians was excellent and good, respectively. Conclusion: If CTU examination was performed by fractional injection of a contrast agent, fusion images of the urinary system and aorta were obtained, which not only had a clear anatomical relationship and the same image quality, but also reduced the effective radiation dose. The 50keV virtual monoenergetic image obtained by spectral reconstruction optimizes the image quality of CTU and CTA and has clinical value.

To understand the effects of fractured formation on the responses of array sonic logging, the wave propagation of array acoustic logging was simulated based on the staggered grid finite difference method and poroelastic theory. Methods of velocity dispersion analysis and attenuation estimation were carried out on simulated sonic waveforms, and the differences of velocity dispersion and wave amplitude attenuation among these wave modes were summarized. First, the velocity-stress equation in cylindrical coordinates was deduced for the Biot poroelastic model. Next, the velocity-stress wave equation was discretized by using the staggered grid finite difference method. Furthermore, the higher order finite difference format and nearly perfect match layer (NPML) were adopted to improve the efficiency and accuracy of the finite difference method. Finally, simulated sonic waveforms in formation models with a tilted fracture zone and collapsed interval were applied to the velocity dispersion analysis by using forward and back amplitudes and the phase estimation method. The results show that the time difference of the P and S wave field in the low-velocity fracture zone increases and that the attenuation amplitude changes with the dip angle of the fracture zone. The attenuation of Stoneley waves and pseudo-Rayleigh waves is enhanced when the shaft collapse expands in the radial and axial directions. The time difference of acoustic waves, velocity dispersion, and amplitude attenuation can reflect the characteristics of the fracture zone, which is of great significance to the evaluation and development of fractured reservoirs.

The joining of dissimilar titanium and aluminum alloys has potential applications in railway and aerospace industries, owing to substantial weight reduction and better economic viability. In this study, the residual stress distribution and local mechanical performance of ultrasonic-assisted resistance spot welding (UaRSW) welds were investigated. The welding current, welding time, and electrode force of the RSW process were set as 9.0 kA, 350 ms, and 1.0 kN respectively, and the frequency and power of ultrasonic vibration were 20 kHz and 800 W. The residual stress was evaluated by X-ray diffraction (XRD) method and numerical simulation, and these methods showed a reasonable match. There was tensile residual stress distributed on RSW welds and UaRSW welds, but the value of residual stress was reduced by about 30% at welding nugget and 20% at heat affected zone (HAZ) with the ultrasonic vibration, the reduction of residual stress in UaRSW welds was attributed to the more uniform temperature distribution and lower plastic deformation resistant of AA6061. The welding peak temperature was decreased from 1673.4 °C to 1584.2 °C with the ultrasonic vibration, resulted from the modified Al/Ti contact surface and reduced contact resistance. The miniature tensile test results showed the improvement of mechanical performance by ultrasonic vibration. The maximum load of welding nugget region increased from 19.6 N to 22.3 N, and the elongation obtained 10% increase. This hybrid welding technique shows a potential to improve the quality of welds with ensured efficiency, which is also simple to realize automation in the manufacturing industry.

Abstract The global aging population has led to a rise in age-related health issues, such as malnutrition, metabolic disorders, and even immune decline. Among these concerns, periodontitis holds particular significance for the well-being of the elderly. This study aimed to investigate the impact of aging on inflammatory resorption of alveolar bone in mice with periodontitis, with a specific focus on alterations in the intestinal microenvironment. To achieve this, we established a D-galactose (D-gal)-induced aging mouse model with periodontitis and employed histopathological staining, oxidative stress, and inflammatory factors analyses to assess the severity of periodontitis and the health status. Additionally, the 16S rRNA sequencing and untargeted metabolomics analysis were employed to investigate alterations in the intestinal microbiota and metabolites. Our results showed that D-gal-induced aging mice with periodontitis experienced more pronounced alveolar bone inflammatory resorption and disruptions in the gut barrier, accompanied by an overall decline in physical condition. The microbial composition and structure of aged mice also underwent significant modifications, with a decreased Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, metabolomics analysis demonstrated that D-gal-induced aging primarily influenced lipids and lipid-like molecules metabolism, and enrichment observed in the rheumatoid arthritis and histidine metabolism pathways. These findings provide further evidence that the aging process exacerbates age-related alveolar bone loss (ABL) through disturbances in intestinal homeostasis.

Abstract Brain damage caused by acute hypoxia is associated with the physiological activities of mitochondria. Although mitochondria being dynamically regulated, our comprehensive understanding of the response of specific brain cell types to acute hypoxia remains ambiguous. Tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial-based molecular chaperone, plays a role in controlling mitochondrial movements. Herein, we demonstrated that acute hypoxia significantly alters mitochondria morphology and functionality in both in vivo and in vitro brain injury experiments. Summary-data-based Mendelian Randomization (SMR) analyses revealed possible causative links between mitochondria-related genes and hypoxia injury. Advancing the protein-protein interaction network and molecular docking further elucidated the associations between TRAP1 and mitochondrial dynamics. Furthermore, it was shown that TRAP1 knockdown levels variably affected the expression of key mitochondrial dynamics proteins (DRP1, FIS1, and MFN1/2) in primary hippocampal neurons, astrocytes, and BV-2 cell, leading to changes in mitochondrial structure and function. Understanding the function of TRAP1 in altering mitochondrial physiological activity during hypoxia-induced acute brain injury could help serve as a potential therapeutic target to mitigate neurological damage.

Abstract Background Coronary artery bypass grafting (CABG) is often performed with hypothermic cardiopulmonary bypass (CPB) to reduce metabolic demands and protect the myocardium. However, hypothermia can increase bleeding risks and other complications. Methods This is a prospective, multi-center, randomized controlled trial. From September 2023 to December 2024, a total of 336 eligible patients planning to undergo on-pump CABG will be enrolled. All participants will be randomly divided into mild hypothermia CPB group (target oxygenator arterial outlet blood temperature at 32–33℃) or normothermia CPB group (target oxygenator arterial outlet blood temperature at 35–36℃). The primary endpoint is Universal Definition of Perioperative Bleeding (UDPB) class 2–4. Secondary endpoints are class of UDPB, levels of coagulation and inflammatory factors, in-hospital mortality, perioperative related complications, ICU length of stay, and hospital length of stay. Discussion This clinical trial aims to compare the effects of different target temperature during CPB on postoperative bleeding and to explore optimal temperature strategy to provide new clinical evidence. Trial registration Chictr.org.cn : ChiCTR2300075405. The trial was prospectively registered on 4 September 2023.

Abstract This study aimed to elucidate the role and underlying mechanisms of Peroxisome proliferator-activated receptor gamma (PPARγ) and its m6A methylation in renal ischemia-reperfusion (I/R) injury and ferroptosis of tubular epithelial cells (TECs). High-throughput transcriptome sequencing was performed on renal tissue samples from I/R injury models and sham-operated mice, complemented by in vivo and in vitro experiments focusing on the PPARγ activator Rosiglitazone and the manipulation of METTL14 and IGF2BP2 expression. Key evaluations included renal injury assessment, ferroptosis indicator measurement, and m6A methylation analysis of PPARγ. Our findings highlight the critical role of the PPARγ pathway and ferroptosis in renal I/R injury, with Rosiglitazone ameliorating renal damage and TEC ferroptosis. METTL14-mediated m6A methylation of PPARγ, dependent on IGF2BP2, emerged as a pivotal regulator of PPARγ expression, renal injury, and ferroptosis. This study reveals that PPARγ m6A methylation, orchestrated by METTL14 through an IGF2BP2-dependent mechanism, plays a crucial role in mitigating renal I/R injury and TEC ferroptosis. These insights offer promising avenues for therapeutic strategies targeting acute kidney injury.

Abstract This paper aims to propose a faster and more accurate network for human spatiotemporal action localization tasks. Like the YOWO model, we also use convolutional neural networks (CNNs) for feature extraction, but our model differs from YOWO in three significant ways: firstly, we don’t use the feature fusion strategy, we only use spatial features extracted by 2D CNNs for action localization and spatiotemporal features extracted by 3D CNNs for action recognition; secondly, we make an improvement to the 2D CNNs network by introducing a coordinate attention mechanism and utilize the CIoU loss instead of the coordinate offset loss for bounding box regression; thirdly, we provide a more lightweight and faster spatiotemporal action localization architecture, which reduces the number of parameters by 21.76 million and achieves a speed of 39 fps on 16-frame input clips compared to the YOWO model. We test our model’s performance on three public datasets: UCF-Sports, JHMDB-21 and UCF101-24. Compared with the YOWO model, we improve frame-mAP (@IoU 0.5) by 17.09% and 7.15% on the UCF-Sports and JHMDB-21 datasets, and for video-mAP, we improve by 2.7%, 8.7% and 14.4% at IoU thresholds of 0.2, 0.5 and 0.75 on the JHMDB-21 dataset.

Owing to their exceptional piezoelectric effects, piezoelectric materials play a crucial role in high-end technologies and contribute significantly to the national economy. Bismuth layer-structured ferroelectrics (BLSFs) possess high Curie temperatures, making them a focal point of research in high-temperature piezoelectric sensor devices. However, their poor piezoelectric performance and low direct-current (DC) electrical resistivity hinder their effective deployment in high-temperature applications. To overcome these shortcomings, we employed composition optimization by partially substituting bismuth ions with rare-earth praseodymium ions. This approach enhances the piezoelectric performance and improves the DC electrical resistivity by preventing the loss of volatile bismuth ions and stabilizing the bismuth oxide layer (Bi2O2)2+, thereby reducing the concentration of oxygen vacancies. Consequently, we achieved a large piezoelectric constant d33 of 23.5 pC/N in praseodymium-substituted Bi5Ti3FeO15, which is three times higher than that of pure Bi5Ti3FeO15 (7.1 pC/N), along with a high Curie temperature TC of 778 °C. Additionally, the optimal composition of 4 mol% praseodymium-substituted Bi5Ti3FeO15 exhibits good thermal stability of electromechanical coupling characteristics up to 300 °C. This study holds promise for a wide array of high-temperature piezoelectric applications and has the potential to accelerate the development of high-temperature piezoelectric sensor technologies.

Radioactive TBP/kerosene(OK) organic waste liquid is produced in the process of uranium purification and spent fuel retreatment. In order to avoid the safety risks caused by the accumulation of radioactive organic waste liquid over the years, it is urgent to treat it. In this paper, the conventional Fenton oxidation method and microwave synergistic Fenton method were used to treat simulated radioactive TBP/OK waste liquid, and the effects of mass fraction of Fenton’s reagent ρ(\begin{document}$ {\text{Fe}}^{\text{2+}} $\end{document}) and ρ(\begin{document}$ {\text{H}}_{\text{2}}{\text{O}}_{\text{2}} $\end{document}), initial pH and oxidation time(t) on the removal of chemical oxygen demand(COD) was experimentally investigated. The results of the conventional Fenton oxidation method show that: at the optimal process conditions, ρ(\begin{document}$ {\text{Fe}}^{\text{2+}} $\end{document})=20 mg/L，ρ(\begin{document}$ {\text{Fe}}^{\text{2+}} $\end{document})/ρ(\begin{document}$ {\text{H}}_{\text{2}}{\text{O}}_{\text{2}} $\end{document})=1∶10, initial pH=1.90，t=15 min, the COD removal can reach up to 72.01%; the most important factor is the ratio of ρ(\begin{document}$ {\text{Fe}}^{\text{2+}} $\end{document})/ρ(\begin{document}$ {\text{H}}_{\text{2}}{\text{O}}_{\text{2}} $\end{document}), followed by ρ(\begin{document}$ {\text{Fe}}^{\text{2+}} $\end{document}), initial pH, and oxidation time. The microwave synergistic Fenton method is superior to the conventional heating Fenton method, and even better than the conventional Fenton oxidation method, when under the same optimal reaction conditions. As for the microwave synergistic Fenton method, the COD removal can be increased to 95.80%. The dosage of Fenton reagent is also reduced from ρ(\begin{document}$ {\text{Fe}}^{\text{2+}} $\end{document})=20 mg/L，ρ(\begin{document}$ {\text{H}}_{\text{2}}{\text{O}}_{\text{2}} $\end{document})=200 mg/L to ρ(\begin{document}$ {\text{Fe}}^{\text{2+}} $\end{document})=10 mg/L，ρ(\begin{document}$ {\text{H}}_{\text{2}}{\text{O}}_{\text{2}} $\end{document})=100 mg/L. It can be seen that the microwave synergistic Fenton method not only further improves the COD removal, but also reduces the dosage of Fenton reagent.

Abstract Semen Ziziphi Spinosae (SZS) is a traditional Chinese herbal medicine widely used to treat insomnia and anxiety in clinical practice. Currently, the demand for SZS is increasing every year, but the production of wild SZS is unstable due to environmental factors. Grafting sour jujube scions onto sour jujube or jujube tree stocks can achieve a high production rate within a short period of time. However, the effects of grafting on the quality of SZS have not been reported. This study investigated the differences between wild-type and grafted SZS from three aspects: phenotype, chemical composition, and molecular mechanism. The findings revealed that the grafted specimens were generally larger in morphology and lighter in color than the wild-type samples. The dimensions of both the grafted specimens were generally larger than those of the wild specimens. The HPLC-ELSD results revealed that the three main chemical components in the grafted SZS, namely, spinosin, jujuboside A, and jujuboside B, had higher contents than their wild-type counterparts. Comprehensive transcriptome sequencing analysis and KEGG annotation revealed that DEG enrichment between grafted and wild-type SZS occurred mainly during stress resistance and rootstock scion healing. There were 23 DEGs that may encode enzymes involved in the biosynthetic pathway of flavonoids and 21 genes encoding terpenoid saponins. Further investigation revealed that the expression of the genes C4H, CHS, CHI, and F3’5’H in the flavonoid biosynthesis pat.hway and HMGR, MVK, MVD, and FPPS in the saponin biosynthesis pathway accounted for the difference in quality between grafted and wild SZS. Furthermore, WGCNA identified 15 core genes related to medicinal ingredients between grafted and wild SZS. These results provide support for further research on the differences in the quality of medicinal ingredients between grafted and wild SZS.

Abstract Background Keratin-15 (KRT15) involves in the progression and owns prognostic values in several solid cancers, whose clinical role in epithelial ovarian cancer (EOC) is rarely reported. This study aimed to identify the association of KRT15 expression with tumor features and survival of surgical EOC patients. Methods Formalin-fixed paraffin-embedded tumor tissues of 140 EOC patients who underwent tumor resection were retrieved for KRT15 determination using immunohistochemistry (IHC) assay. Results The median (interquartile range) KRT15 IHC score was 0.0 (0.0–1.0), ranging from 0.0 to 12.0. Among all, 36.4% of patients had positive KRT15 expression (IHC score > 0) and 15.0% of patients had high KRT15 expression (IHC score > 3). KRT15 was positively related to lymph node metastasis incidence (P = 0.027), and showed a tendency to correlate to FIGO stage but without statistical significance (P = 0.052), while it was not correlated with age, other tumor features, and tumor markers. Positive KRT15 expression was linked with poor disease-free survival (DFS) (P = 0.009) and overall survival (OS) (P = 0.032). Notably, high KRT15 expression showed an even stronger relationship with worse DFS (P = 0.001) and OS (P

Abstract MYCN amplification predicts poor prognosis in childhood neuroblastoma. To identify MYCN oncogenic signal dependencies we performed N-ethyl-N-nitrosourea (ENU) mutagenesis on the germline of neuroblastoma-prone TH-MYCN transgenic mice to generate founders which had lost tumorigenesis. Sequencing of the mutant mouse genomes identified the Ring Finger Protein 121 (RNF121 WT ) gene mutated to RNFM158R associated with heritable loss of tumorigenicity. While the RNF121WT protein localised predominantly to the cis-Golgi Complex, the RNF121 M158R mutation in Helix 4 of its transmembrane domain caused reduced RNF121 protein stability and absent Golgi localisation. RNF121WT expression markedly increased during TH-MYCN tumorigenesis, whereas hemizygous RNF121 WT gene deletion reduced TH-MYCN tumorigenicity. The RNF121WT-enhanced growth of MYCN-amplified neuroblastoma cells depended on RNF121WT transmembrane Helix 5. RNF121WT directly bound MYCN protein and enhanced its stability. High RNF121 mRNA expression associated with poor prognosis in human neuroblastoma tissues and another MYC-driven malignancy, laryngeal cancer. RNF121 is thus an essential oncogenic cofactor for MYCN and a target for drug development.

Abstract Branching enzymes (BEs) confer to α-glucans, the primary energy-storage reservoir in nature, a variety of features, like slow digestion. The full catalytic cycle of BEs can be divided in six steps, namely two covalent catalytic steps involving glycosylation and transglycosylation, and four noncatalytic steps involving substrate binding and transfers (SBTs). Despite the ever-growing wealth of biochemical and structural information on BEs, clear mechanistic insights into SBTs from an industrial-performance perspective are still missing. Here, we report a Rhodothermus profundi BE (RpBE) endowed with twice as much enzymatic activity as the Rhodothermus obamensis BE currently used in industry. Furthermore, we focus on the SBTs for RpBE by means of large-scale computations supported by experiment. Engineering of the crucial positions responsible for the initial substrate-binding step improves enzymatic activity significantly, while offering a possibility to customize product types. In addition, we show that the high-efficiency substrate-transfer steps preceding glycosylation and transglycosylation are the main reason for the remarkable enzymatic activity of RpBE, suggestive of engineering directions for the BE family.

Abstract Physiotherapies play a crucial role in noninvasive tissue engineering for wound healing. However, challenges such as the implementation of complex interventions and unsatisfactory treatment outcomes impede widespread application. Here, we proposed a stretchable and wirelessly-powered optoelectronic synergistic patch with a dual-layer serpentine wireless receiver circuit to drive the optoelectronic modulation component. Optimized structure and impedance matching enable the patch to seamlessly attach to irregular skin surfaces and operate robustly over a 30% tensile strain range. Based on Sprague-Dawley rat wound model. The wound closure rate of the optoelectronic synergistic group significantly outperformed both monointervention and blank control groups. Mechanistically, optoelectronic synergistic intervention enhances the secretion of vascular endothelial marker proteins and growth factors, and stabilizes mitochondrial function during oxidative stress. Overall, the scalable amalgamation of flexible electronics, wireless transmission, and synergistic interventions promise to improve wound care.

Abstract Background Lung phenotypes have been extensively utilized to assess lung injury and guide precise treatment. However, current phenotypic evaluation methods rely on CT scans and other techniques. Although lung ultrasound (LUS) is widely employed in critically ill patients, there is a lack of comprehensive and systematic identification of LUS phenotypes based on clinical data and assessment of their clinical value. Methods Our study was based on a retrospective database. A total of 821 patients were included from September 2019 to October 2020. 1902 LUS examinations were performed in this period. Using a dataset of 55 LUS examinations focused on lung injuries, a group of experts developed an algorithm for classifying LUS phenotypes based on clinical practice, expert experience, and lecture review. This algorithm underwent validation and refinement with an additional 140 LUS images, leading to five iterative revisions and the generation of 1902 distinct LUS phenotypes. Subsequently, a validated machine learning algorithm was applied to these phenotypes. To assess the algorithm’s effectiveness, experts manually verified 30% of the phenotypes, confirming its efficacy. Using K-means cluster analysis and expert image selection from the 1902 LUS examinations, we established seven distinct LUS phenotypes. To further explore the diagnostic value of these phenotypes for clinical diagnosis, we investigated their auxiliary diagnostic capabilities. Results A total of 1902 LUS phenotypes were tested by randomly selecting 30% to verify the phenotypic accuracy. With the 1902 LUS phenotypes, seven lung ultrasound phenotypes were established through statistical K-means cluster analysis and expert screening. The acute respiratory distress syndrome (ARDS) exhibited gravity-dependent phenotypes, while the cardiogenic pulmonary edema exhibited nongravity phenotypes. The baseline characteristics of the 821 patients included age (66.14 ± 11.76), sex (560/321), heart rate (96.99 ± 23.75), mean arterial pressure (86.5 ± 13.57), Acute Physiology and Chronic Health Evaluation II (APACHE II)score (20.49 ± 8.60), and duration of ICU stay (24.50 ± 26.22); among the 821 patients, 78.8% were cured. In severe pneumonia patients, the gravity-dependent phenotype accounted for 42% of the cases, whereas the nongravity-dependent phenotype constituted 58%. These findings highlight the value of applying different LUS phenotypes in various diagnoses. Conclusions Seven sets of LUS phenotypes were established through machine learning analysis of retrospective data; these phenotypes could represent the typical characteristics of patients with different types of critical illness.

Abstract Background Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. Methods We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. Results A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband’s parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. Conclusions WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

Abstract To assess the safety and efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapeutic intervention for IgA nephropathy (IgAN). Fifteen patients with IgA nephropathy were recruited based on inclusion and exclusion criteria and underwent FMT using enteric microbial capsules. Clinical indicators, intestinal microbiota and metabolomic profiles, as well as changes in serum immune cells and cytokines, were monitored before and after FMT. No severe adverse reactions were observed in the subjects. After FMT, there was a reduction in the 24-h urinary protein quantification in subjects. The relative abundances of Phocaeicola_vulgatus, Bacteroides_uniformis, Prevotella_copri, Phocaeicola_dorei, Bacteroides_ovatus, Bacteroides_xylanisolvens, Parabacteroides _distasonis, Bifidobacterium_pseudocatenulatum, Bacteroides_sp._HF-162, and Bifidobacterium_longum changed after FMT. In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine (PC. (18:3e/22:6)), serotonin, and fumagillin showed significant changes. Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites. This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN. No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.

Abstract Cadmium (Cd) is an unessential and pervasive contaminant in agricultural soil, eventually affecting the food and instigating health issues. The implication of nanocomposites in agriculture attained significant attention to drive food security. Nanocomposites possess exceptional characteristics to stun the challenges of chemical fertilizers that can enhance plant yield and better nutrient bioavailability. Similarly, biochar has the ability to immobilize Cd in soil by reducing mobility and bioavailability. Rice husk biochar is produced at high temperature pyrolysis under anoxic conditions and a stable carbon-rich material is formed. To strive against this issue, rice plants were subjected to Cd (15, 20 mg kg− 1) stress and treated with alone/combined Ca + Mg (25 mg L− 1) nanocomposite and rice husk biochar. In our study, growth and yield traits showed the nurturing influence of Ca + Mg nanocomposite and biochar to improve rice defence mechanism by reducing Cd stress. Growth parameters root length 28%, shoot length 34%, root fresh weight 19%, shoot fresh weight 16%, root dry weight 9%, shoot dry weight 8%, number of tillers 32%, number of grains 20%, and spike length 17% were improved with combined application of Ca + Mg and biochar, with Cd (20 mg kg− 1), rivalled to alone biochar. Combined Ca + Mg and biochar application increased the SPAD 23%, total chlorophyll 26%, a 19%, b 18%, and carotenoids 15%, with Cd (20 mg kg− 1), rivalled to alone biochar. MDA 15%, H2O2 13%, and EL 10% were significantly regulated in shoots with combined Ca + Mg and biochar application with Cd (20 mg kg− 1) compared to alone biochar. POD 22%, SOD 17%, APX 18%, and CAT 9% were increased in shoots with combined Ca + Mg and biochar application with Cd (20 mg kg− 1) compared to alone biochar. Cd uptake in roots 13%, shoots 14%, and grains 21% were minimized under Cd (20 mg kg− 1) with combined Ca + Mg and B. pumilus application, compared to alone biochar. Subsequently, combined Ca + Mg and biochar application is a sustainable solution to boost crop production under Cd stress.

Abstract Background The global rise in developmental delays underscores the critical need for a thorough understanding and timely interventions during early childhood. Addressing this issue, the Chinese Baby Connectome Project (CBCP)’s behavior branch is dedicated to examining language acquisition, social-emotional development, and environmental factors affecting Chinese children. The research framework is built around three primary objectives: developing a 0–6 Child Development Assessment Toolkit, implementing an Intelligent Coding System, and investigating environmental influence. Methods Utilizing an accelerated longitudinal design, the CBCP aims to enlist a minimum of 1000 typically developing Chinese children aged 0–6. The data collected in this branch constitutes parental questionnaires, behavioral assessments, and observational experiments to capture their developmental milestones and environmental influences holistically. The parental questionnaires will gauge children’s developmental levels in language and social-emotional domains, alongside parental mental well-being, life events, parenting stress, parenting styles, and family relationships. Behavioral assessments will involve neurofunctional developmental evaluations using tools such as the Griffiths Development Scales and Wechsler Preschool and Primary Scale of Intelligence. Additionally, the assessments will encompass measuring children’s executive functions (e.g., Head-Toe-Knee-Shoulder), social cognitive abilities (e.g., theory of mind), and language development (e.g., Early Chinese Vocabulary Test). A series of behavior observation. experiments will be conducted targeting children of different age groups, focusing primarily on aspects such as behavioral inhibition, compliance, self-control, and social-emotional regulation. To achieve the objectives, established international questionnaires will be adapted to suit local contexts and devise customized metrics for evaluating children’s language and social-emotional development; deep learning algorithms will be developed in the observational experiments to enable automated behavioral analysis; and statistical models will be built to factor in various environmental variables to comprehensively outline developmental trajectories and relationships. Discussion This study’s integration of diverse assessments and AI technology will offer a detailed analysis of early childhood development in China, particularly in the realms of language acquisition and social-emotional skills. The development of a comprehensive assessment toolkit and coding system will enhance our ability to understand and support the development of Chinese children, contributing significantly to the field of early childhood development research. Trial registration This study was registered with clinicaltrials.gov NCT05040542 on September 10, 2021.

Clematis serratifolia has high medicinal and ornamental value. In this study, we characterize and report, for the first time, the complete chloroplast genome sequence of C. serratifolia based on high-throughput sequence dates. The whole chloroplast genome of C. serratifolia is a circular molecule of 159,648 bp in length, consisting of a large single-copy (LSC) region of 79,394 bp, a small single-copy (SSC) region of 18,112 bp, and two inverted repeat (IR) regions of 31,071 bp. The overall GC content of the chloroplast genome is 38%, while that in the LSC, SSC, and IR regions is 36.3%, 31.3%, and 42.1%, respectively. The chloroplast genome of C. serratifolia contains 133 genes, including 89 coding genes, 8 ribosomal RNAs, and 36 transfer RNAs. Among them, 14 protein-coding genes have a single intron, and 2 genes have two introns. The phylogenetic analysis showed a close relationship between C. serratifolia and C. heracleifolia.

Androgen‐regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone‐sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)‐homology splicing regulatory protein known as far upstream element‐binding protein 2 (KHSRP) is an RNA‐binding protein that can attach to AU‐rich elements in the 3′ untranslated region (3′‐UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen‐regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP‐regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA‐seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD‐dependent protein deacetylase sirtuin‐7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP‐regulated mRNA decay of the DDR‐related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration‐resistant PCa.

Abstract Background HIV-related stigma continues to hinder optimal HIV care, and its determinants should be understood at multiple levels. Based on the social-ecological model, this study aimed to explore factors associated with HIV-related stigma among women living with HIV in Guangdong Province, China. Methods A cross-sectional study was conducted from July to August 2022 to recruit newly reported women living with HIV with a history of pregnancy or current pregnancy in 2021 in 21 cities in Guangdong Province. HIV-related stigma was assessed using an abbreviated Chinese version of Berger's HIV Stigma Scale. Univariate and multivariable hierarchical regression analyses based on the social-ecological model were conducted to explore factors associated with HIV-related stigma and its four dimensions (personalized stigma, disclosure concerns, negative self-image and concerns about public attitudes) at the community/hospital, interpersonal, and individual levels. Results A moderate level of HIV-related stigma was found among the 360 participants included, with a mean score of 45.26. Multivariable hierarchical regression analysis showed that at the community/hospital-level, individuals were more likely to experience high levels of HIV-related stigma if they had experienced the discriminatory behaviors from health care workers (aOR = 2.34, 95%CI: 1.48–3.70) and if they rated serostatus disclosure services as less helpful (aOR = 0.69, 95%CI: 0.48–0.98). At the interpersonal-level, individuals with an HIV-positive partner (aOR = 1.71, 95%CI: 1.01–2.90) were more likely to experience high levels of HIV-related stigma than those with an HIV-negative or unknown partner. Individuals with high resilience (aOR = 0.22, 95%CI: 0.13–0.35) had lower levels of HIV-related stigma at the individual-level. In addition, ever experiencing discriminatory behaviors from health care workers, thinking serostatus disclosure services helpful, having ever seen publicity about personal interest protection services and complaint channels for people living with HIV(PLHIV), knowing about care and support services for PLHIV from social organizations at the community/hospital-level, partner notification and support at the interpersonal-level, and violations of personal interests, resilience at the individual-level were also associated with different dimensions of HIV-related stigma. Conclusions HIV-related stigma was moderate among women living with HIV. The social-ecological model can facilitate a better understanding of factors associated with HIV-related stigma. Multilevel intervention strategies need to be tailored to reduce HIV-related stigma.

Abstract Low back pain (LBP) is a highly prevalent disease. Among the various causes of LBP, one of the most frequent is myofascial pain syndrome (MPS) which affects the spinal stabilizer muscles. The aims of this study were to compare the differences in muscular electrical activity and biomechanical properties between the painful and non-painful sides in patients with unilateral MPS and to verify the feasibility of surface electromyography (sEMG) and MyotonPRO for assisting in MPS assessment. Forty patients with unilateral lumbar MPS were recruited via the Department of Rehabilitation Medicine Center of West China Hospital Sichuan University from October 2022 to October 2023. The electrical properties of the bilateral erector spinae muscles were characterized by sEMG signals during a trunk extension task. The following four time-domain features of sEMG were extracted: root mean square (RMS), mean absolute value (MAV), integrated EMG (iEMG), and waveform length (WL). And two frequency domain features were extracted: the median frequency (MDF) and mean power frequency (MPF). The mechanical properties of the muscles were assessed by MyotonPRO at rest. The following biomechanical parameters were acquired: oscillation frequency [Hz], dynamic stiffness [N/m], logarithmic decrement, relaxation time [ms], and Creep. The visual analog scale (VAS) was used to evaluate the pain severity, and the Oswestry Disability Index (ODI) was used to evaluate the severity of disability and disruption to lifestyle activities caused by LBP pain. The outcome measures were obtained prior to the Platelet-rich plasma (PRP) treatment and repeated two weeks after treatment. (1) Prior to the PRP treatment, all sEMG time-domain features on the painful side were significantly higher than those on the non-painful side (RMS, p 0.05). (2) Two weeks after the PRP treatment, statistically significant decreases were observed in both post-treatment VAS (p

Abstract Computer-aided diagnosis (CAD) has advanced medical image analysis, while large language models (LLMs) have shown potential in clinical applications. However, LLMs struggle to interpret medical images, which are critical for decision-making. Here we show a strategy integrating LLMs with CAD networks. The framework uses LLMs’ medical knowledge and reasoning to enhance CAD network outputs, such as diagnosis, lesion segmentation, and report generation, by summarizing information in natural language. The generated reports are of higher quality and can improve the performance of vision-based CAD models. In chest X-rays, an LLM using ChatGPT improved diagnosis performance by 16.42 percentage points compared to state-of-the-art models, while GPT-3 provided a 15.00 percentage point F1-score improvement. Our strategy allows accurate report generation and creates a patient-friendly interactive system, unlike conventional CAD systems only understood by professionals. This approach has the potential to revolutionize clinical decision-making and patient communication.

Abstract Despite recent work linking mixed phenotype acute leukemia (MPAL) to certain genetic lesions, specific driver mutations remain undefined for a significant proportion of patients and no genetic subtype is predictive of clinical outcomes. Moreover, therapeutic strategy for MPAL remains unclear, and prognosis is overall poor. We performed multiomic single cell profiling of 14 newly diagnosed adult MPAL patients to characterize the inter- and intra-tumoral transcriptional, immunophenotypic, and genetic landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. Despite this, we find that MPAL blasts express a shared stem cell-like transcriptional profile indicative of high differentiation potential. Patients with the highest differentiation potential demonstrate inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in the most stem-like MPAL cells, is applicable to bulk RNA sequencing data and is predictive of survival in an independent patient cohort, suggesting a potential strategy for clinical risk stratification.

Background: Consistent use of effective contraceptives is directly associated with a lower risk of unintended pregnancies, a significant public health burden in the U.S. The Asian American population is heterogeneous and fast-growing. However, patterns and disparities in contraceptive use among Asian American women, particularly within racial/ethnic subgroups, have been understudied, hindering effective family planning. Objectives: This study aimed to identify the prevalence of contraceptive use and its pattern in Asian American women using the 2015–2016 California Health and Interview Survey (CHIS) data, with a focus on different Asian ethnic subgroups. Study Design: A composite score of acculturation level (0–5) was created based on place of birth, years in the U.S., and language spoken at home. Data on demographics, self-rated health, contraceptive use, and related information were collected from women aged 18–44 years who were at risk of unintended pregnancy. Adjusted multivariable logistic regressions were conducted to examine contraceptive use and patterns in relation to race/ethnicity and other factors. Results: Over 18.20% of the overall sample (pop estimated N = 16,177,759) were Asian Americans, and among them, 24.62% were Chinese, followed by other Asian subgroups (28.83%), Filipina (25.49%), Korean (11.25%), and Vietnamese (9.80%). Overall, Filipina, Korean, and Vietnamese women were less likely to use contraception compared to their non-Hispanic White (NHW) peers, whereas acculturation level was positively associated with contraceptive use. Among different types of contraceptives, Filipina, Korean, and Vietnamese women were less likely to use long-acting reversible contraceptives compared to NHW. Such racial/ethnic disparities were not observed with less or moderately effective contraceptives. Conclusions: Patterns of contraceptive use and associated disparities varied among Asian American subgroups. Providers working with Asian American women should be aware of these racial disparities in contraceptive use and seek ways to address barriers to effective contraception use in this diverse population in order to provide culturally competent family planning services.

Abstract Background Controlled ovarian stimulation is a common skill of assisted reproductive technologies (ARTs). In the clinic, some females would undergo more than one controlled ovarian stimulation cycle. However, few studies have focused on the influence of multi-superovulation on oocytes and offspring. Results Here, we found that multi-superovulation disrupted the transcriptome of oocytes and that the differentially expressed genes (DEGs) were associated mainly with metabolism and fertilization. The disruption of mRNA degradation via poly (A) size and metabolism might be a reason for the reduced oocyte maturation rate induced by repeated superovulation. Multi-superovulation results in hypo-genomic methylation in oocytes. However, there was an increase in the methylation level of CGIs. The DMRs are not randomly distributed in genome elements. Genes with differentially methylated regions (DMRs) in promoters are enriched in metabolic pathways. With increasing of superovulation cycles, the glucose and insulin tolerance of offspring is also disturbed. Conclusions These results suggest that multi-superovulation has adverse effects on oocyte quality and offspring health.

Abstract Siberian wildrye (Elymus sibiricus) is a xero-mesophytic forage grass with high nutritional quality and stress tolerance. Among its numerous germplasm resources, some possess superior drought resistance. In this study, we firstly investigated the physiological differences between the leaves of drought-tolerant (DT) and drought-sensitive (DS) genotypes under different field water contents (FWC) in soil culture. The results showed that, under drought stress, DT maintained a lower leaf water potential for water absorption, sustained higher photosynthetic efficiency, and reduced oxidative damage in leaves by efficiently maintaining the ascorbic acid-glutathione (ASA-GSH) cycle to scavenge reactive oxygen species (ROS) compared to DS. Secondly, using RNA sequencing (RNA-seq), we analyzed the gene expression profiles of DT and DS leaves under osmotic stress of hydroponics induced by PEG-6000. Through differential analysis, we identified 1226 candidate unigenes, from which we subsequently screened out 115/212 differentially expressed genes (DEGs) that were more quickly induced/reduced in DT than in DS under osmotic stress. Among them, Unigene0005863 (EsSnRK2), Unigene0053902 (EsLRK10) and Unigene0031985 (EsCIPK5) may be involved in stomatal closure induced by abscisic acid (ABA) signaling pathway. Unigene0047636 (EsCER1) may positively regulates the synthesis of very-long-chain (VLC) alkanes in cuticular wax biosynthesis, influencing plant responses to abiotic stresses. Finally, the contents of wax and cutin were measured by GC–MS under osmotic stress of hydroponics induced by PEG-6000. Corresponding to RNA-seq, contents of wax monomers, especially alkanes and alcohols, showed significant induction by osmotic stress in DT but not in DS. It is suggested that limiting stomatal and cuticle transpiration under drought stress to maintain higher photosynthetic efficiency and water use efficiency (WUE) is one of the critical mechanisms that confer stronger drought resistance to DT. This study provides some insights into the molecular mechanisms underlying drought tolerance in E. sibiricus. The identified genes may provide a foundation for the selection and breeding of drought-tolerant crops.

Abstract The sensor that simultaneously perceives bending strain and magnetic field has the potential to detect the finger bending state and hand position of the human and robot. Based on unique magneto-mechanical coupling effect of magnetostrictive materials, the proposed a bi-perceptive flexible sensor, consisting of the Co–Fe film and magnetic sensing plane coils, can realize dual information perception of strain/magnetic field through the change of magnetization state. The sensor structure and interface circuit of the sensing system are designed to provide high sensitivity and fast response, based on the input–output characteristics of the simulation model. An asynchronous multi-task deep learning method is proposed, which takes the output of the position task as the partial input of the bending state task to analyze the output information of the sensor quickly and accurately. The sensing system, integrating with the proposed model, can better predict the bending state and approach distance of human or robot hand.

Abstract Background Previous studies indicated that excessive engagement in digital devices could lead to negative psychological impacts in general population. We aimed to determine the association of electronic screen exposure with depression among women in early pregnancy. Methods A cross-sectional study was conducted from June 2021 to June 2022. A total of 665 women in early pregnancy were recruited and the information included socio-demographic characteristics, screen exposure and Patient Health Questionnaire − 9 depression scale. Results Among the women in early pregnancy, the total daily smartphone viewing time was the longest (median [P25-P75], 5 [3–6] hours/day) in the three types of electronic screen exposure. The total daily smartphone viewing time (P = 0.015, OR[95%CI] = 1.09[1.11–1.18]), smartphone (P = 0.016, OR[95%CI] = 1.24[1.04–1.47]) and television viewing time (P = 0.006, OR[95%CI] = 1.35[1.09–1.67]) before nocturnal sleep were significantly associated with depression among women in early pregnancy. The thresholds calculated by receiver operator characteristic curves were 7.5 h/day, 1.5 h/day and 1.5 h/day, respectively. In addition, women with higher scores of smartphone addiction were more susceptible to depression (P

Abstract Lymphocyte receptors independently evolved in both jawed and jawless vertebrates with similar adaptive immune responses. However, the diversity of functional subtypes and molecular architecture in jawless vertebrate lymphocytes, comparable to jawed species, is not well defined. Here, we profile the gills, intestines, and blood of the lamprey, Lampetra morii, with single-cell RNA sequencing, using a full-length transcriptome as a reference. Our findings reveal higher tissue-specific heterogeneity among T-like cells in contrast to B-like cells. Notably, we identify a unique T-like cell subtype expressing a homolog of the nonlymphoid hematopoietic growth factor receptor, MPL-like (MPL-L). These MPL-L+ T-like cells exhibit features distinct from T cells of jawed vertebrates, particularly in their elevated expression of hematopoietic genes. We further discovered that MPL-L+ VLRA+ T-like cells are widely present in the typhlosole, gill, liver, kidney, and skin of lamprey and they proliferate in response to both a T cell mitogen and recombinant human thrombopoietin. These findings provide new insights into the adaptive immune response in jawless vertebrates, shedding new light on the evolution of adaptive immunity.

Abstract Elucidating cellular architecture and cell-type evolution across species is central to understanding immune system function and susceptibility to disease. Adaptive immunity is a shared trait of the common ancestor of cartilaginous and bony fishes. However, evolutionary features of lymphocytes in these two jawed vertebrates remain unclear. Here, we present a single-cell RNA sequencing atlas of immune cells from cartilaginous (white-spotted bamboo shark) and bony (zebrafish and Chinese tongue sole) fishes. Cross-species comparisons show that the same cell types across different species exhibit similar transcriptional profiles. In the bamboo shark, we identify a phagocytic B cell population expressing several pattern recognition receptors, as well as a T cell sub-cluster co-expressing both T and B cell markers. In contrast to a division by function in the bony fishes, we show close linkage and poor functional specialization among lymphocytes in the cartilaginous fish. Our cross-species single-cell comparison presents a resource for uncovering the origin and evolution of the gnathostome immune system.

Abstract Collagen posttranslational processing is crucial for its proper assembly and function. Disruption of collagen processing leads to tissue development and structure disorders like osteogenesis imperfecta (OI). OI-related collagen processing machinery includes prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP), with their structural organization and mechanism unclear. We determine cryo-EM structures of the P3H1/CRTAP/PPIB complex. The active sites of P3H1 and PPIB form a face-to-face bifunctional reaction center, indicating a coupled modification mechanism. The structure of the P3H1/CRTAP/PPIB/collagen peptide complex reveals multiple binding sites, suggesting a substrate interacting zone. Unexpectedly, a dual-ternary complex is observed, and the balance between ternary and dual-ternary states can be altered by mutations in the P3H1/PPIB active site and the addition of PPIB inhibitors. These findings provide insights into the structural basis of collagen processing by P3H1/CRTAP/PPIB and the molecular pathology of collagen-related disorders.

Abstract Background People with epilepsy (PWE) frequently experience sleep disturbances that can severely affect their quality of life. Depression is also a common symptom in the PWE population and can aggravate sleep problems. However, the interplay between epilepsy, depression, and sleep disturbances is not yet fully understood. Our study was designed to investigate the association between epilepsy and sleep disturbances in US adults and to determine whether depressive symptoms play a mediating role in this relationship. Methods We examined data from the National Health and Nutrition Examination Survey (NHANES) spanning January 1, 2015, to March 2020, before the pandemic.A total of 10,093 participants aged ≥ 20 years with complete data on epilepsy and sleep disturbance were included. Weighted multiple logistic regression and mediation analysis were used to explore the associations among depression, epilepsy, and sleep disturbance. Interaction effects of epilepsy with various covariates were also investigated. Results Epilepsy was associated with depression and sleep disturbances. Weighted logistic regression analysis revealed a significant association between epilepsy and sleep disturbances (OR = 3.67, 95% CI = 1.68–8.04). Depression partially mediated this relationship, demonstrating a mediation effect of 23.0% (indirect effect = 0.037, P

Suppressing corporate financialization exacerbated by rising labor costs is an important micro-level issue for revitalizing the manufacturing industry. This research investigates the interaction mechanism among labor costs and financialization, using panel data of Chinese listed companies from 2007 to 2022 in the context of the disappearance of the demographic dividend. The results of the moderated mediation model show that rising labor costs worsen financialization by reducing corporate profitability and increase financialization through negative earnings manipulation, whereas digitization suppresses both the direct and indirect effect of labor costs. Therefore, measures should be taken to enhance the profitability and accounting transparency of companies undergoing the process of accelerating digitization.

Objective This study aimed to identify and characterize a novel endo-β-glucanase, IDSGLUC9-4, from the rumen metatranscriptome of Hu sheep. Methods A novel endo-β-glucanase, IDSGLUC9-4, was heterologously expressed in Escherichia coli and biochemically characterized. The optimal temperature and pH of recombinant IDSGLUC9-4 were determined. Subsequently, substrate specificity of the enzyme was assessed using mixed-linked glucans including barley β-glucan and Icelandic moss lichenan. Thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), matrix assisted laser desorption ionization time of flight mass spectrometry analyses were conducted to determine the products released from polysaccharides and cello-oligosaccharides substrates. Results The recombinant IDSGLUC9-4 exhibited temperature and pH optima of 40°C and pH 6.0, respectively. It exclusively hydrolyzed mixed-linked glucans, with significant activity observed for barley β-glucan (109.59±3.61 μmol/mg min) and Icelandic moss lichenan (35.35±1.55 μmol/mg min). TLC and HPLC analyses revealed that IDSGLUC9-4 primarily released cellobiose, cellotriose, and cellotetraose from polysaccharide substrates. Furthermore, after 48 h of reaction, IDSGLUC9-4 removed most of the glucose, indicating transglycosylation activity alongside its endo-glucanase activity. Conclusion The recombinant IDSGLUC9-4 was a relatively acid-resistant, mesophilic endo-glucanase (EC 3.2.1.4) that hydrolyzed glucan-like substrates, generating predominantly G3 and G4 oligosaccharides, and which appeared to have glycosylation activity. These findings provided insights into the substrate specificity and product profiles of rumen-derived GH9 glucanases and contributed to the expanding knowledge of cellulolytic enzymes and novel herbivore rumen enzymes in general.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

In the process of resistance spot welding of advanced high-strength steel (AHSS), the development of heat-affected zones (HAZs) considerably modifies the mechanical properties of the weld region. However, the limited reporting in the study of shear behavior in the HAZ hinders the accurate prediction of joint fracture and failure behavior. This study focused on the shear fracture behavior of resistance spot-welded AHSS. Given the limited extent of the HAZ, a miniature shear test was designed and shear fracture tests were conducted on JSC590, JSC980, and JSC1180. These tests facilitated the acquisition and compilation of data regarding the shear mechanical properties of diverse steel grades and their respective HAZs. A hardness-based empirical model for the strength coefficient and the strain-hardening exponent in Hollomon's law was introduced, and this model was subsequently integrated into finite element method calculations. The accuracy of the model was validated by shear strength reproductions, exhibiting errors within the range of 5.4%–13.5% and the averaged error was less than 10%. Further analyses confirmed that stress triaxiality at critical positions varied from 0 to 0.33, indicative of shear-dominant stress conditions. Moreover, the evolution of stress states revealed a notable association between the fracture surfaces across different stress states and steel grades. These findings fill the gap regarding the shear behavior of localized HAZs and expand the understanding of their mechanical behavior under various stress states. It will contribute to accurate fracture prediction by stress triaxiality based fracture criteria, such as Modified Mohr-Coulomb (MMC) model, applied to AHSS.

Climate crisis mitigation roadmaps, policies and directives have increasingly declared that a key element for the facilitation of sustainable urban development is on-site decentralized renewable energy generation. A technology with enhanced capabilities, able of promoting the integration of renewable energy into buildings, for energy independent and resilient communities, is Photovoltaic Thermal (PVT) systems. Ongoing research has potential yet displays a lack in unified methodology. This limits its influence on future decision-making in building and city planning levels. In this investigation, the often overlooked air-based PVT technology is put on the spotlight and their suitability for integration with energy systems of buildings is assessed. The aim of this study is to highlight vital performance and integration roadblocks in PVT research and offer suggestions for overcoming them. The methodology of reviewed literature is examined in detail with the goal of contributing to a unified approach for more impactful research.