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Abstract Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan–Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan–Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P

Abstract This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer’s Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4’s role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aβ and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.

Abstract Artificial intelligence (AI) decision support systems in pediatric healthcare have a complex application background. As an AI decision support system (AI-DSS) can be costly, once applied, it is crucial to focus on its performance, interpret its success, and then monitor and update it to ensure ongoing success consistently. Therefore, a set of evaluation indicators was explicitly developed for AI-DSS in pediatric healthcare, enabling continuous and systematic performance monitoring. The study unfolded in two stages. The first stage encompassed establishing the evaluation indicator set through a literature review, a focus group interview, and expert consultation using the Delphi method. In the second stage, weight analysis was conducted. Subjective weights were calculated based on expert opinions through analytic hierarchy process, while objective weights were determined using the entropy weight method. Subsequently, subject and object weights were synthesized to form the combined weight. In the two rounds of expert consultation, the authority coefficients were 0.834 and 0.846, Kendall's coordination coefficient was 0.135 in Round 1 and 0.312 in Round 2. The final evaluation indicator set has three first-class indicators, fifteen second-class indicators, and forty-seven third-class indicators. Indicator I-1(Organizational performance) carries the highest weight, followed by Indicator I-2(Societal performance) and Indicator I-3(User experience performance) in the objective and combined weights. Conversely, 'Societal performance' holds the most weight among the subjective weights, followed by 'Organizational performance' and 'User experience performance'. In this study, a comprehensive and specialized set of evaluation indicators for the AI-DSS in the pediatric outpatient clinic was established, and then implemented. Continuous evaluation still requires long-term data collection to optimize the weight proportions of the established indicators.

Abstract Background Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis. Method All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots. Result The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p

Abstract Background Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. Methods A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. Results 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. Conclusion The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.

Abstract Early insulin therapy is capable to achieve glycemic control and restore β-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

Abstract Femoral head varus is an important complication in intertrochanteric fracture patients treated with proximal femoral nail anti-rotation (PFNA) fixation. Theoretically, extending the length of the intramedullary nail could optimize fixation stability by lengthening the force arm. However, whether extending the nail length can optimize patient prognosis is unclear. In this study, a review of imaging data from intertrochanteric fracture patients with PFNA fixation was performed, and the length of the intramedullary nail in the femoral trunk and the distance between the lesser trochanter and the distal locking screw were measured. The femoral neck varus status was judged at the 6-month follow-up. The correlation coefficients between nail length and femoral neck varus angle were computed, and linear regression analysis was used to determine whether a change in nail length was an independent risk factor for femoral neck varus. Moreover, the biomechanical effects of different nail lengths on PFNA fixation stability and local stress distribution have also been verified by numerical mechanical simulations. Clinical review revealed that changes in nail length were not significantly correlated with femoral head varus and were also not an independent risk factor for this complication. In addition, only slight biomechanical changes can be observed in the numerical simulation results. Therefore, commonly used intramedullary nails should be able to meet the needs of PFNA-fixed patients, and additional procedures for longer nail insertion may be unnecessary.

Abstract Rapeseed (Brassica napus L.), accounts for nearly 16% of vegetable oil, is the world’s second produced oilseed. However, pod shattering has caused significant yield loses in rapeseed production, particularly during mechanical harvesting. The GH28 genes can promote pod shattering by changing the structure of the pod cell wall in Arabidopsis. However, the role of the GH28 gene family in rapeseed was largely unknown. Therefore, a genome-wide comprehensive analysis was conducted to classify the role of GH28 gene family on rapeseed pod shattering. A total of 37 BnaGH28 genes in the rapeseed genome were identified. These BnaGH28s can be divided into five groups (Group A-E), based on phylogenetic and synteny analysis. Protein property, gene structure, conserved motif, cis-acting element, and gene expression profile of BnaGH28 genes in the same group were similar. Specially, the expression level of genes in group A-D was gradually decreased, but increased in group E with the development of silique. Among eleven higher expressed genes in group E, two BnaGH28 genes (BnaA07T0199500ZS and BnaC06T0206500ZS) were significantly regulated by IAA or GA treatment. And the significant effects of BnaA07T0199500ZS variation on pod shattering resistance were also demonstrated in present study. These results could open a new window for insight into the role of BnaGH28 genes on pod shattering resistance in rapeseed.

Abstract Objective To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. Methods A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. Results High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P

Abstract Background Bactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology . Results The ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth. Conclusions Generally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Abstract Background EGFR and/or HER2 expression in pancreatic cancers is correlated with poor prognoses. We generated homodimeric (EGFRxEGFR or HER2xHER2) and heterodimeric (EGFRxHER2) T cell-engaging bispecific antibodies (T-BsAbs) to direct polyclonal T cells to these antigens on pancreatic tumors. Methods EGFR and HER2 T-BsAbs were constructed using the 2 + 2 IgG-[L]-scFv T-BsAbs format bearing two anti-CD3 scFvs attached to the light chains of an IgG to engage T cells while retaining bivalent binding to tumor antigens with both Fab arms. A Fab arm exchange strategy was used to generate EGFRxHER2 heterodimeric T-BsAb carrying one Fab specific for EGFR and one for HER2. EGFR and HER2 T-BsAbs were also heterodimerized with a CD33 control T-BsAb to generate ‘tumor-monovalent’ EGFRxCD33 and HER2xCD33 T-BsAbs. T-BsAb avidity for tumor cells was studied by flow cytometry, cytotoxicity by T-cell mediated 51Chromium release, and in vivo efficacy against cell line-derived xenografts (CDX) or patient-derived xenografts (PDX). Tumor infiltration by T cells transduced with luciferase reporter was quantified by bioluminescence. Results The EGFRxEGFR, HER2xHER2, and EGFRxHER2 T-BsAbs demonstrated high avidity and T cell-mediated cytotoxicity against human pancreatic ductal adenocarcinoma (PDAC) cell lines in vitro with EC50s in the picomolar range (0.17pM to 18pM). They were highly efficient in driving human polyclonal T cells into subcutaneous PDAC xenografts and mediated potent T cell-mediated anti-tumor effects. Both EGFRxCD33 and HER2xCD33 tumor-monovalent T-BsAbs displayed substantially reduced avidity by SPR when compared to homodimeric EGFRxEGFR or HER2xHER2 T-BsAbs (∼150-fold and ∼6000-fold respectively), tumor binding by FACS (8.0-fold and 63.6-fold), and T-cell mediated cytotoxicity (7.7-fold and 47.2-fold), while showing no efficacy against CDX or PDX. However, if either EGFR or HER2 was removed from SW1990 by CRISPR-mediated knockout, the in vivo efficacy of heterodimeric EGFRxHER2 T-BsAb was lost. Conclusion EGFR and HER2 were useful targets for driving T cell infiltration and tumor ablation. Two arm Fab binding to either one or both targets was critical for robust anti-tumor effect in vivo. By engaging both targets, EGFRxHER2 heterodimeric T-BsAb exhibited potent anti-tumor effects if CDX or PDX were EGFR+HER2+ double-positive with the potential to spare single-positive normal tissue.

Abstract Background and purpose Effective evaluation of rotator cuff tear residual tendon quality is the key to surgical repair. However, until now, the evaluation of rotator cuff tissue by ultrasonic shear wave elasticity (SWE) has been controversial. This prospective study analyzed the association between preoperative SWE and arthroscopic residual tendon quality scores. Methods The shear wave velocity (SWV) of the deltoid muscle, the supraspinatus tendon, and the supraspinatus muscle were measured in full-thickness rotator cuff tear patients. Tendon quality was scored according to tear size, tendon margin, tendon thickness, and footprint coverage during arthroscopy. The arthroscopic scores were used as the gold standard, and the SWV ratio of tendon and muscle (supraspinatus tendon/deltoid and supraspinatus muscle/deltoid) were calculated and correlated with the arthroscopic scores. Result Eighty-nine patients (129 shoulders) were enrolled, including 89 operation shoulders and 40 control shoulders. In the group of operation shoulders, both the SWV ratios of tendon (SWV-RT) and the SWV ratio of muscle (SWV-RM) were negatively correlated with arthroscopic scores (The correlation coefficient (R) ranged from -0.722 to -0.884 and -0.569 to -0.689). The SWV-RT and SWV-RM of the operation shoulders were significantly lower than that of the control shoulders (p

Abstract Opportunistic spectrum access (OSA), a promising technology to resolve radio spectrum scarcity, is still faced with some challenges, of which one is potentially frequent channel handoff (CH) even handoff blocking (HB) for secondary user (SU) to avoid primary user (PU). Reaccess is a direct way to resolve HB. However, multiple handoff blocking‐then‐reaccess (H‐BTR) are time consuming. Whether it is worthwhile to make multiple H‐BTR, is an interesting but hardly mentioned issue. To this end, the multiple H‐BTR‐based OSA are focused on here. Three key indices, the average transmission probability, handoff delay, and average reaccess times of SU in the H‐BTR‐based OSA, are deduced as close form first. Then, the effects of H‐BTR frequency and service traffic rate of SU on OSA are discussed. Finally, the H‐BTR‐based OSA is compared to two other schemes, the handoff without BTR (HWBTR)‐based OSA and the stop‐and‐waiting (SW)‐based OSA. Theoretical and simulated results show that the H‐BTR‐based OSA performs best among three schemes. Making H‐BTR in moderate frequency according to service traffic rate can increase transmission opportunity while additional delay of SU is tolerable, thus the performance of OSA can be well improved.

Abstract Background The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. Methods A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein–Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. Results A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value 1.5 or HR/N

As a key material for lithium metal batteries (LMBs), lithium metal is one of the most promising anode materials to break the bottleneck of battery energy density and a commonly used active material for reference electrodes. Although lithium anodes are regarded as the holy grail of lithium batteries, decades of exploration have not led to the successful commercialization of LMBs, due mainly to the challenges related to the inherent properties of lithium metal. To pave the way for further investigation, herein, a comprehensive review focusing on the fundamental science of lithium are provided. Firstly, the natures of lithium atoms and their isotopes, lithium clusters and lithium crystals are revisited, especially their structural and energetic properties. Subsequently, the electrochemical properties of lithium metal are reviewed. Numerous important concepts and scientific questions, including the electronic structure of lithium, influence of high pressure and low temperature on the properties of lithium, factors influencing lithium deposition, generation of lithium dendrites, and electrode potential of lithium in different electrolytes, are explained and analyzed in detail. Approaches to improve the performance of lithium anodes and thoughtfulness about the electrode potential in lithium battery research are proposed.

Introduction: Forming a bridge made of functional axons to span the lesion is essential to reconstruct the motor circuitry following spinal cord injury (SCI). Dorsal root ganglion (DRG) axons are robust in axon growth and have been proved to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. However, whether DRG transplantation affects the axon outgrowth of spinal motor neurons (SMNs) that play crucial roles in motor circuitry remains unclear. Methods: We investigated the axonal growth patterns of co-cultured DRGs and SMN aggregates (SMNAs) taking advantage of a well-designed 3D-printed in vitro system. Chondroitin sulphate proteoglycans (CSPG) induced inhibitory matrix was introduced to imitate the inhibitory environment following SCI. Axonal lengths of DRG, SMNA or DRG & SMNA cultured on the permissive or CSPG induced inhibitory matrix were measured and compared. Results: Our results indicated that under the guidance of full axonal connection generated from two opposing populations of DRGs, SMNA axons were growth-enhanced and elongated along the DRG axon bridge to distances that they could not otherwise reach. Quantitatively, the co-culture increased the SMNA axonal length by 32.1 %. Moreover, the CSPG matrix reduced the axonal length of DRGs and SMNAs by 46.2 % and 17.7 %, respectively. This inhibitory effect was antagonized by the co-culture of DRGs and SMNAs. Especially for SMNAs, they extended the axons across the CSPG-coating matrix, reached the lengths close to those of SMNAs cultured on the permissive matrix alone. Conclusions: This study deepens our understanding of axon-facilitated reconstruction of the motor circuitry. Moreover, the results support SCI treatment utilizing the enhanced outgrowth of axons to restore functional connectivity in SCI patients.

Abstract Background The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. Methods Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. Results The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24–123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). Conclusion The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

Abstract Bacteria have evolved various response systems to adapt to environmental stress. A protease-based derepression mechanism in response to DNA damage was characterized in Deinococcus, which is controlled by the specific cleavage of repressor DdrO by metallopeptidase PprI (also called IrrE). Despite the efforts to document the biochemical, physiological, and downstream regulation of PprI-DdrO, the upstream regulatory signal activating this system remains unclear. Here, we show that single-stranded DNA physically interacts with PprI protease, which enhances the PprI-DdrO interactions as well as the DdrO cleavage in a length-dependent manner both in vivo and in vitro. Structures of PprI, in its apo and complexed forms with single-stranded DNA, reveal two DNA-binding interfaces shaping the cleavage site. Moreover, we show that the dynamic monomer-dimer equilibrium of PprI is also important for its cleavage activity. Our data provide evidence that single-stranded DNA could serve as the signal for DNA damage sensing in the metalloprotease/repressor system in bacteria. These results also shed light on the survival and acquired drug resistance of certain bacteria under antimicrobial stress through a SOS-independent pathway.

Abstract Traditional methods for developing new materials are no longer sufficient to meet the needs of the human energy transition. Machine learning (ML) artificial intelligence (AI) and advancements have caused materials scientists to realize that using AI/ML to accelerate the development of new materials for batteries is a powerful potential tool. Although the use of certain fixed properties of materials as descriptors to act as a bridge between the two separate disciplines of AI and materials chemistry has been widely investigated, many of the descriptors lack universality and accuracy due to a lack of understanding of the mechanisms by which AI/ML operates. Therefore, understanding the underlying operational mechanisms and learning logic of AI/ML has become mandatory for materials scientists to develop more accurate descriptors. To address those challenges, this paper reviews previous work on AI, machine learning and materials descriptors and introduces the basic logic of AI and machine learning to help materials developers understand their operational mechanisms. Meanwhile, the paper also compares the accuracy of different descriptors and their advantages and disadvantages and highlights the great potential value of accurate descriptors in AI/machine learning applications for battery research, as well as the challenges of developing accurate material descriptors. Graphical Abstract

Highlights The poly(1,3-dioxolane) (PDOL) electrolyte demonstrates promising potential for practical application due to its advantages in in-situ polymerization process, high ionic conductivity, and long cycle life. This review focuses on the polymerization mechanism, composite innovation, and application of PDOL electrolytes. This review provides a comprehensive summary of the challenges associated with the PDOL electrolyte and makes forward-looking recommendations.

Abstract Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.

Time Domain Coding Metasurface (TDCM) is an emerging technology enabling dynamic modulation of electromagnetic waves. In response to the control characteristics of this technology, this paper presents a radar jamming method based on TDCM intrapulse and interpulse coding optimization. First, optimization models are established in fast and slow time domains. By optimizing intrapulse and interpulse phase coding, the energy redistribution of targets is achieved, thereby generating deceptive interference on the range-Doppler two-dimensional plot. Subsequently, a genetic algorithm is employed to solve this discrete optimization problem. Furthermore, this paper analyzes the effect of various modulation factors on interference effectiveness in terms of TDCM coding strategies, providing guidance for achieving optimal strategies for deceptive interference.

BackgroundTo explore the relationship between body mass index (BMI), age, sex, and blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP) in children during COVID-19, providing reference for the prevention and screening of hypertension in children.MethodsThis study adopted a large-scale cross-sectional design to investigate the association between BMI and blood pressure in 7-17-year-old students in City N, China, during COVID-19. Thirty-six primary and secondary schools in City N were sampled using a stratified cluster sampling method. A total of 11,433 students aged 7–17 years in City N, China, were selected for blood pressure (Diastolic blood pressure, DBP, Systolic blood pressure, SBP), height, and weight, Resting heart rate (RHR), chest circumference, measurements, and the study was written using the STROBE checklist. Data analysis was conducted using SPSS 26.0, calculating the mean and standard deviation of BMI and blood pressure for male and female students in different age groups. Regression analysis was employed to explore the impact of BMI, age, and sex on SBP and DBP, and predictive models were established. The model fit was evaluated using the model R2.ResultsThe study included 11,287 primary and secondary school students, comprising 5,649 boys and 5,638 girls. It was found that with increasing age, BMI and blood pressure of boys and girls generally increased. There were significant differences in blood pressure levels between boys and girls in different age groups. In regression models, LC, Age, BMI, and chest circumference show significant positive linear relationships with SBP and DBP in adolescents, while RHR exhibits a negative linear relationship with SBP. These factors were individually incorporated into a stratified regression model, significantly enhancing the model’s explanatory power. After including factors such as Age, Gender, and BMI, the adjusted R2 value showed a significant improvement, with Age and BMI identified as key predictive factors for SBP and DBP. The robustness and predictive accuracy of the model were further examined through K-fold cross-validation and independent sample validation methods. The validation results indicate that the model has a high accuracy and explanatory power in predicting blood pressure in children of different weight levels, especially among obese children, where the prediction accuracy is highest.ConclusionDuring COVID-19, age, sex, and BMI significantly influence blood pressure in children aged 7–17 years, and predictive models for SBP and DBP were established. This model helps predict blood pressure in children and reduce the risk of cardiovascular diseases. Confirmation of factors such as sex, age, and BMI provide a basis for personalized health plans for children, especially during large-scale infectious diseases, providing guidance for addressing health challenges and promoting the health and well-being of children.

ChaCha is a well-known stream cipher that has been used in many network protocols and software. In this paper, we study the security of reduced round ChaCha. First, by considering the differential-linear hull effect, we improve the correlation of a four-round differential-linear distinguisher proposed at FSE 2023 by providing other intermediate linear masks. Then, based on the four-round differential-linear distinguisher and the PNB method, by using the assignment 100 ··· 00 for consecutive PNBs, higher backward correlation is obtained and improved key recovery attacks of 7-round and 7.25-round ChaCha are obtained with time complexity 2189.7 and 2223.9, which improve the previously best-known attacks by 217.1 and 214.44, respectively. Finally, we consider the equivalence of the security between (R + 0.25)-round and (R + 0.5)⊕-round ChaCha, and show that (R + 0.25)-round and (R + 0.5)⊕-round ChaCha provide the same security against chosen(known) plaintext attacks. As a result, improved differential-linear cryptanalysis of 7.5⊕-round ChaCha can also be obtained similarly to that of 7.25-round ChaCha, which improves the previously best-known attack by 219.

IntroductionTravel satisfaction as experienced by rural residents is closely related to personal physical and mental health, as well as rural economic conditions. An improved rural road environment can be expected to enhance villagers’ satisfaction with regards to visits to markets, but to date this has not been established empirically.MethodsIn this study, a questionnaire was designed to obtain local residents’ evaluations of road environment characteristics for periodic market travel. And we use an Oprobit regression model and Importance-Performance Map Analysis (IPMA) to explore the heterogeneity of the 14 key elements of the “home-to-market” road environment impact on villagers’ satisfaction under different modes of travel.ResultsThe results of the study reveal that villagers expressed dissatisfaction with the current lack of sidewalks and non-motorized paths, and except for road traffic disturbances and road deterioration, which did not significantly affect mode of travel, other factors proved significant. Significantly, bus services are associated with a significant positive effect on walking, non-motorized and bus travel satisfaction, while distance travel also affects walking, non-motorized and motorized travel satisfaction. It is worth noting that greening and service facilities negatively affect motorized travel satisfaction. In summary, road width, sidewalks, bus service, and road deterioration, are among the elements most in need of urgent improvement for all modes of travel.DiscussionThe characteristics of the road environment that influence satisfaction with travel to the periodic market vary by travel mode, and this study is hoped to provide data support and optimization recommendations for the improvement of the rural road environment in China and other countries.

Inorganic arsenic is a well-established environmental toxicant linked to acute liver injury, fibrosis, and cancer. While oxidative stress, pyroptosis, and ferroptosis are known contributors, the role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in arsenic-induced hepatic immunotoxicity remains underexplored. Our study revealed that acute arsenic exposure prompts differentiation of hepatic dendritic cells (DCs) and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells, alongside increased transcription factors and cytokines. Inorganic arsenic triggered liver redox imbalance, leading to elevated alanine transaminase (ALT), hydrogen peroxide (H2O2), malondialdehyde (MDA), and activation of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway. PINK1-mediated mitophagy was initiated, and its inhibition exacerbates H2O2 accumulation while promoting DCs/Th1/Th2/Treg differentiation in the liver of arsenic-exposed mice. Mitoquinone (MitoQ) pretreatment relieved arsenic-induced acute liver injury and immune imbalance by activating Nrf2/HO-1 and PINK1-mediated mitophagy. To our knowledge, this is the first report identifying PINK1-mediated mitophagy as a protective factor against inorganic arsenic-induced hepatic DCs/Th1/Th2 differentiation. This study has provided new insights on the immunotoxicity of inorganic arsenic and established a foundation for exploring preventive and therapeutic strategies targeting PINK1-mediated mitophagy in acute liver injury. Consequently, the application of mitochondrial antioxidant MitoQ may offer a promising treatment for the metalloid-induced acute liver injury.

Lotus (Nelumbo nucifera Gaertn.) seed, a traditional Chinese herbal medicine, exhibits good hypoglycemic activities. However, the bioactive components that are responsible for the biological effects and their underlying mechanisms remain obscure. This study aimed to identify the bioactive components of lotus seed skin phenolic-rich extract (LSSE) and investigate their α-glucosidase inhibitory activity. In vivo study showed that LSSE could significantly decrease the fasting blood glucose levels and the area under the curves with dose-dependent manners in diabetes mellitus mice. And the α-glucosidase activity was decreased by 39.4% after intervention with LSSE. The results also demonstrated that LSSE possessed up to 77.53% rat intestinal maltase inhibitory activity and general sucrase and isomaltase inhibitory activity. A total of 38 phenolic compounds were first quantified in LSSE. Molecular docking analysis further revealed that the bioactive components in LSSE bind with α-glucosidase by hydrogen bonding Van der Waals and hydrophobic interactions. These results indicate the potential use of LSSE for natural hypoglycemic functional foods.

Graphene-based warm uterus acupoint paste (GWUAP) is an emerging non-drug alternative therapy for the treatment of primary dysmenorrhea (PD), but the underlying mechanism is still unclear. SD female rats were randomly divided into control group, model group and treatment group to explore the mechanism of GWUAP in the treatment of PD. Combined with 16S rDNA and fecal metabolomics, the diversity of microbiota and metabolites in each group was comprehensively evaluated. In this study, GWUAP reduced the torsion score of PD model rats, improved the pathological morphology of uterine tissue, reduced the pathological damage score of uterine tissue, and reversed the expression levels of inflammatory factors, pain factors and sex hormones. The 16 S rDNA sequencing of fecal samples showed that the abundance of Lactobacillus in the intestinal flora of the model group decreased and the abundance of Romboutsia increased, while the abundance of Lactobacillus in the intestinal flora of the treatment group increased and the abundance of Romboutsia decreased, which improved the imbalance of flora diversity in PD rats. In addition, 32 metabolites related to therapeutic effects were identified by metabolomics of fecal samples. Moreover, there is a close correlation between fecal microbiota and metabolites. Therefore, the mechanism of GWUAP in the treatment of PD remains to be further studied.

Osteoarthritis (OA) is a common degenerative joint disease in the elderly, while oxidative stress-induced chondrocyte degeneration plays a key role in the pathologic progression of OA. One possible reason is that the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which acts as the intracellular defense factor against oxidative stress, is significantly inhibited in chondrocytes. Spinosin (SPI) is a potent Nrf2 agonist, but its effect on OA is still unknown. In this study, we found that SPI can alleviate tert-Butyl hydroperoxide (TBHP)-induced extracellular matrix degradation of chondrocytes. Additionally, SPI can effectively activate Nrf2, heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) in chondrocytes under the TBHP environment. When Nrf2 was silenced by siRNA, the cartilage protective effect of SPI was also weakened. Finally, SPI showed good alleviative effects on OA in mice. Thus, SPI can ameliorate oxidative stress-induced chondrocyte dysfunction and exhibit a chondroprotective effect through activating the Nrf2/HO-1 pathway, which may provide a novel and promising option for the treatment of OA.

ABSTRACTInoculation with plant growth-promoting rhizobacteria (PGPR) strains has promoted plant growth and decreased nitrous oxide (N₂O) emissions from agricultural soils simultaneously. However, limited PGPR strains can mitigate N₂O emissions from agricultural soils, and the microbial ecological mechanisms underlying N₂O mitigation after inoculation are poorly understood. In greenhouse pot experiments, the effects of inoculation with Stutzerimonas stutzeri NRCB010 and NRCB025 on tomato growth and N₂O emissions were investigated in two vegetable agricultural soils with contrasting textures. Inoculation with NRCB010 and NRCB025 significantly promoted tomato growth in both soils. Moreover, inoculation with NRCB010 decreased the N₂O emissions from the fine- and coarse-textured soils by 38.7% and 52.2%, respectively, and inoculation with NRCB025 decreased the N₂O emissions from the coarse-textured soil by 76.6%. Inoculation with NRCB010 and NRCB025 decreased N₂O emissions mainly by altering soil microbial community composition and the abundance of nitrogen-cycle functional genes. The N₂O-mitigating effect might be partially explained by a decrease in the (amoA + amoB)/(nosZI + nosZII) and (nirS + nirK)/(nosZI + nosZII) ratios, respectively. Soil pH and organic matter were key variables that explain the variation in abundance of N-cycle functional genes and subsequent N₂O emission. Moreover, the N₂O-mitigating effect varied depending on soil textures and individual strain after inoculation. This study provides insights into developing biofertilizers with plant growth-promoting and N₂O-mitigating effects.IMPORTANCEPlant growth-promoting rhizobacteria (PGPR) have been applied to mitigate nitrous oxide (N₂O) emissions from agricultural soils, but the microbial ecological mechanisms underlying N₂O mitigation are poorly understood. That is why only limited PGPR strains can mitigate N₂O emissions from agricultural soils. Therefore, it is of substantial significance to reveal soil ecological mechanisms of PGPR strains to achieve efficient and reliable N₂O-mitigating effect after inoculation. Inoculation with Stutzerimonas stutzeri strains decreased N₂O emissions from two soils with contrasting textures probably by altering soil microbial community composition and gene abundance involved in nitrification and denitrification. Our findings provide detailed insight into soil ecological mechanisms of PGPR strains to mitigate N₂O emissions from vegetable agricultural soils.

Abstract Rapeseed (Brassica napus L.) with short or no dormancy period are easy to germinate before harvest (pre-harvest sprouting, PHS). PHS has seriously decreased seed weight and oil content in B. napus. Short-chain dehydrogenase/ reductase (SDR) genes have been found to related to seed dormancy by promoting ABA biosynthesis in rice and Arabidopsis. In order to clarify whether SDR genes are the key factor of seed dormancy in B. napus, homology sequence blast, protein physicochemical properties, conserved motif, gene structure, cis-acting element, gene expression and variation analysis were conducted in present study. Results shown that 142 BnaSDR genes, unevenly distributed on 19 chromosomes, have been identified in B. napus genome. Among them, four BnaSDR gene clusters present in chromosome A04、A05、C03、C04 were also identified. These 142 BnaSDR genes were divided into four subfamilies on phylogenetic tree. Members of the same subgroup have similar protein characters, conserved motifs, gene structure, cis-acting elements and tissue expression profiles. Specially, the expression levels of genes in subgroup A, B and C were gradually decreased, but increased in subgroup D with the development of seeds. Among seven higher expressed genes in group D, six BnaSDR genes were significantly higher expressed in weak dormancy line than that in nondormancy line. And the significant effects of BnaC01T0313900ZS and BnaC03T0300500ZS variation on seed dormancy were also demonstrated in present study. These findings provide a key information for investigating the function of BnaSDRs on seed dormancy in B. napus.

Abstract Over the long history of evolution, nature has developed a variety of biological systems with switchable recognition functions, such as the ion transmissibility of biological membranes, which can switch their ion selectivities in response to diverse stimuli. However, developing a method in an artificial host-guest system for switchable recognition of specific guests upon the change of external stimuli is a fundamental challenge in chemistry because the order in the host-guest affinity of a given system hardly varies along with environmental conditions. Herein, we report temperature-responsive recognition of two similar gaseous guests, CO2 and C2H2, with selectivities switched by temperature change by a diffusion-regulatory mechanism, which is realized by a dynamic porous crystal featuring ultrasmall pore apertures with flip-flop locally-motive organic moiety. The dynamic local motion regulates the diffusion process of CO2 and C2H2 and amplifies their rate differences, allowing the crystal to selectively adsorb CO2 at low temperatures and C2H2 at high temperatures with separation factors of 498 (CO2/C2H2) and 181 (C2H2/CO2), respectively.

Abstract Background Lip squamous cell carcinoma (LSCC) was one of the most common cancer types of head and neck tumors. This study aimed to find more predictors of the prognosis in postoperative LSCC patients. Methods A total of 147 LSCC patients between June 2012 and June 2018 were collected from two tertiary care institutions. There were 21 clinicopathological factors included and analyzed in our study. The univariate and multivariate Cox regression analyses were performed to find the independent prognostic factors for predicting progression-free survival (PFS) and overall survival (OS) in postoperative LSCC patients. The role of adjuvant radiotherapy in various subgroups was displayed by Kaplan–Meier plots. Results The 1-, 3-, and 5-year PFS of postoperative LSCC patients were 88.4%, 70.1%, and 57.8%, respectively. Similarly, the 1-, 3-, and 5-year OS of postoperative LSCC patients were 94.6%, 76.9%, and 69.4%, respectively. The results suggested that postoperative LSCC patients with age at diagnosis ≥ 70 years, grade with moderate or poor differentiate, the American Joint Committee on Cancer (AJCC) stage IV, higher systemic immune-inflammation index (SII), surgical margin

Abstract Background Major depressive disorder (MDD) is a common mental illness that affects millions of people worldwide and imposes a heavy burden on individuals, families and society. Previous studies on MDD predominantly focused on neurons and employed bulk homogenates of brain tissues. This paper aims to decipher the relationship between oligodendrocyte lineage (OL) development and MDD at the single-cell resolution level. Methods Here, we present the use of a guided regularized random forest (GRRF) algorithm to explore single-nucleus RNA sequencing profiles (GSE144136) of the OL at four developmental stages, which contains dorsolateral prefrontal cortex of 17 healthy controls (HC) and 17 MDD cases, generated by Nagy C et al. We prioritized and ordered differentially expressed genes (DEGs) based on Nagy et al., which could predominantly discriminate cells in the four developmental stages and two adjacent developmental stages of the OL. We further screened top-ranked genes that distinguished between HC and MDD in four developmental stages. Moreover, we estimated the performance of the GRRF model via the area under the curve value. Additionally, we validated the pivotal candidate gene Malat1 in animal models. Results We found that, among the four developmental stages, the onset development of OL (OPC2) possesses the best predictive power for distinguishing HC and MDD, and long noncoding RNA MALAT1 has top-ranked importance value in candidate genes of four developmental stages. In addition, results of fluorescence in situ hybridization assay showed that Malat1 plays a critical role in the occurrence of depression. Conclusions Our work elucidates the mechanism of MDD from the perspective of OL development at the single-cell resolution level and provides novel insight into the occurrence of depression.

In X-ray fluorescence spectroscopy analysis, high intensity X-ray is usually used to irradiate the sample for obtaining stable energy spectrum quickly, which also leads to serious pulse pile-up, count rate loss and energy resolution degradation. It is effective for improving energy spectrum performance to recognize and reject pile-up pulses. Fast shaping discrimination technology (FSDT) and pulse feature time discrimination technology (FTDT) are popular methods for identifying pile-up pulses. It is impossible for FSDT to identify pile-up pules with intervals shorter than the fast pulse resolution time. The measured feature time is subject to pulse-height variation and ADC sampling frequency, which limits FTDT detection capability. In this paper, a pulse shape discrimination method was proposed. An original digital pulse was shaped to a triangular pulse and a trapezoidal pulse. The amplitude ratio, which is also known as time-invariant pulse-shape signature (TIPS), is a pulse shape feature for recognizing pile-up pulse. It is not necessary to measure the pulse arrival time. TIPS is not dependent on ADC sampling frequency and pulse amplitude, but only on ballistic deficit and noise fluctuations. The triangular pulse shaper is a bandpass filter that can suppress high-frequency noise, which can reduce TIPS broadening. The trapezoidal pulse shaping algorithm can be immune to ballistic deficit, while the triangular pulse shaping algorithm cannot. Generally, there are higher TIPS value in pile-up pules because of ballistic deficit. A threshold can be used to determine whether the pulse is pile-up. The TIPS value of some piled pulses is less than that of non-piled pulses. If the threshold is set relatively low, many non-piled pulses will be misjudged. Conversely, a lot of pile-up pulses will be missed. The loss rate of the non-piled pulses can be determined by its TIPS distribution. A copper sample is used for the test experiment. When the tube current is set to 3.9 μA, the measured count rate is only 6 500 s-1 in the fast shaper so that the pile-up can be almost ignored. The measured TIPS distribution can be regarded as the TIPS distribution of non-piled pulses. When the tube current is set to 1 mA, the measured count rate reaches 1.22×106 s-1 in the fast shaper. When α is the same, the accuracy, recall rate and F1 score are all improved by using the proposed method to identify pile-up pulses. For example, when α is 15%, the accuracy, recall rate and F1 score are increased to 73.55%, 78.75% and 76.06% respectively. The peak-to-total ratio of the Kα peak of Cu is increased to 76.6%. The proposed method can effectively identify pile-up pulses.

Abstract Backgroud Laparoscopic adenomyomectomy combined with intraoperative placement of levonorgestrel-releasing intrauterine device (LNG-IUS) is a novel conservative surgical procedure for adenomyosis. Our study aimed to compare the efficacy of surgery with or without intraoperative placement of LNG-IUS treatment in adenomyosis. Methods We retrospectively reviewed the medical records of adenomyosis patients who received laparoscopic adenomyomectomy from January 2014 to April 2020, finally including 70 patients undergoing surgery-LNG-IUS as group A and 69 patients undegoing surgery only as group B. Risk factors for three-year relapse were analyzed using Cox’s multivariate proportional hazard analysis. Results Visual analog scale and Mansfield-Voda-Jorgensen Menstrual Bleeding Scale scores of group A at 3, 6, 12, 24, and 36 months were significantly lower than those of group B at the corresponding points (P