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Heat shock proteins (HSPs), also known as heat stress proteins, can be divided into five main families, including HSP100, HSP90, HSP70, HSP60, and small heat shock proteins (sHSPs), according to their molecular weight. Further studies have shown that HSPs represent a class of highly conserved proteins that widely exist in the subcellular compartments of prokaryotic and eukaryotic cells. They have many functions, such as protein folding, repair, and immunity, and play important roles in organism growth and development. For example, Dmhsp70-A and Dmhsp70-B showed similar trends in the development of asexual embryos in Daphnia magna. However, they exhibited different trends in the development of sexual embryos despite high expression in both embryo types. Penaeus japonicus is one of the most important commercial shrimp species in China, Japan, and Southeast Asian countries. Relevant studies have shown that hsp genes widely exist in P. japonicus and play important roles in growth and development. For example, hsp10 and hsp60 were expressed in all tissues of P. japonicus, and the differential expression of hsp60 was identified in the early development stages. However, previous studies were based on single genes, and more systematic studies based on the role of the hsp gene family in the growth and development of P. japonicus have not been published. Our laboratory has completed the genome sequence of P. japonicus, which provides basic data for analyzing the molecular mechanism of hsp in the growth and development of P. japonicus. To further study the characteristics of the hsp gene family in P. japonicus and the expression characteristics of hsp genes during different development stages, the hsp gene family of P. japonicus was identified and analyzed using bioinformatics methods, and variation in its expression during the development of P. japonicus was measured using reverse transcription and quantitative real-time (RT-qPCR). Fifteen members of the hsp gene family were identified from the whole genome of P. japonicus via bioinformatics analysis, and their gene structures, motif compositions, chromosome localizations, and phylogenetic characteristics were analyzed. The expression of hsp genes in maternal-to-zygotic cells, blastocysts, gastrulae, limb buds, intramembranous nauplii, stage 1 nauplii, stage 1 zoeae, stage 1 myses, and stage 1 post-larval juveniles of P. japonicus was measured using qPCR. A total of 15 hsp genes were identified, including 1 hsp10, 2 hsp20, 2 hsp40, 1 hsp60, 6 hsp70, and 3 hsp90 genes. The physicochemical properties of seven proteins were stable, with instability coefficients less than 40. Subcellular localization results showed that most of the hsp gene family members were located in the cytoplasm, as seven hsp genes were localized to the cytoplasm, two to the nucleus, two to the extracellular region, two to the endoplasmic reticulum, and two to the mitochondria. Isoelectric point (pI) is related to the number and proportion of acidic and basic amino acids contained in a protein. Most HSPs exhibited a pI < 7, suggesting they were acidic proteins. The 15 hsp genes were located on 11 chromosomes. Phylogenetic tree analysis showed that most of the HSP family members were first clustered with HSP family members from species such as Penaeus monodon, Litopenaeus vannamei, and Fenneropenaeus chinensis and then with HSP family members of other species, which was consistent with the traditional taxonomic status. A few HSP family members were clustered first with HSP family members from Eriocheir sinensis, D. melanogaster, and other insects, and then with HSP family members from other species. Motif analysis showed that the hsp gene family was highly conserved; however, the functions of different families were quite different. Structural domain analysis showed that the HSP family included cpn10-, metazoan ACD-, DnaJ bact superfamily-, GroEL-, PTZ00009 superfamily-, dnaK-, HSP70 superfamily-, HSP90 superfamily-, PRK14083 superfamily-, and HATpase_HSP90-like domains. Each gene family contained corresponding domains and was important in molecular chaperone processes. hsp genes were expressed in different developmental stages of P. japonicus and played important roles in growth and development. The trend of Pjhsp10-19.517 was similar to that of Pjhsp60-19.518, which was highly expressed during embryonic development and significantly downregulated during larval development. This is consistent with the conclusion of previous studies that HSP60 and HSP10 are molecular chaperones for each other to ensure the correct folding of the target protein. The hsp genes such as Pjhsp40-15.349, Pjhsp70-39.287, Pjhsp70-1.298, and Pjhsp90 were highly expressed in the embryonic period; Pjhsp20, Pjhsp70-3.662, Pjhsp70-15.369, Pjhsp70-32.916, and Pjhsp90-12.759 were highly expressed during the larval period. The hsp genes expressed at high levels during the embryonic period satisfy the high protein requirements of embryos by playing the role of molecular chaperone and regulating the transcription of vitellogenin to meet the embryonic need for vitellin. The hsp genes expressed at high levels during the larval period protect the body from environmental pressure, pathogens, and xenobiotics through a synergistic immune effect. The authors believe that hsp genes play important roles in the growth and development of P. japonicus, and the specific pathways and mechanisms should be further studied. This study provides basic data for further investigations of the role of hsp genes in the growth and development of P. japonicus.

The ridgetail white shrimp (Exopalaemon carinicauda), belonging to the Palaemonidae family of crustaceans, is an economically important small-to-medium-sized shrimp in China that is naturally distributed on the coasts of the Yellow and Bohai Seas. Due to its rapid growth and high tolerance for environmental stress, the scale at which E. carinicauda is cultured has expanded in recent years. The reproductive performance of broodstock is crucial to the yield and quality of larvae, as the egg production of E. carinicauda is much lower than that of other economically important shrimps. Meanwhile, E. carinicauda seedling production mainly relies on wild shrimp or breeding parents, resulting in low fertility and poor seed quality, such that the cultivation of E. carinicauda is often hindered by a slow growth rate and poor disease resistance, seriously limiting the development of the E. carinicauda farming industry. Optimizing growth and reproductive traits is vital for the animal aquaculture industry, as these traits are crucial for developing high-quality seedlings and are directly related to yield. Cultivating new varieties with high fertility and fast growth rates can effectively improve the aquaculture of E. carinicauda. In this study, we estimated the genetic parameters of growth and reproduction traits in E. carinicauda. We constructed 40 full-sibling lines of E. carinicauda and 25 half-sibling lines by pairing one male with two females. Thirty shrimps were randomly selected from each line at 50 d and 80 d of age, and the body length, total abdominal length, and body weight were measured to calculate the genetic parameters. The number of eggs, body length, body weight, and incubation time of the first spawning were measured to ensure that the culture conditions for each line were consistent. The main baits used during incubation were folded brachyuran rotifers (Brachinonus plicatilis) and brine shrimp (Artemia sinica). The heritability, phenotypic correlations, and genetic correlations of body weight, body length, total abdominal length traits, time of first spawning, absolute egg count, egg count per unit of body length, and egg count per unit of body weight in E. carinicauda were estimated at the ages of 50 and 80 d using a general linear model. The results showed that the heritability estimate values for body length, total abdominal length, and body weight at 50 d were approximately 0.27–0.69, 0.31–0.44, and 0.20–0.65, respectively, and those for body length, total abdominal length, and body weight at 80 d were approximately 0.39–0.54, 0.31–0.47, and 0.33–0.71, respectively. The heritability estimate values for the number of eggs, the number of eggs per unit of body length, the number of eggs per unit of body weight, and the time of the first spawning were approximately 0.45–0.52, 0.30–0.49, 0.43–0.48, and 0.33–0.77, respectively. The heritability estimate values for all three growth-related traits and four reproduction traits almost reached the level of medium-high heritability. The heritability estimate values for growth and reproduction traits based on full siblings reached a highly significant level according to t-tests. Therefore, the unbiased estimates of narrow-sense heritability for growth and reproduction traits were those estimated by the full-sibling variance component. The phenotypic and genetic correlations for growth and reproduction traits were approximately 0–0.756 9 and –0.006 5–0.951 4, respectively. The genetic correlation coefficients of body weight with body length and egg count were 0.951 4 and 0.205 8, respectively. The phenotypic correlation coefficients of body weight with body length and egg count were 0.742 0 and 0.212 4, respectively. However, the genetic and phenotypic correlations between body length and egg count were poor. Therefore, we suggest that body length and egg count be set as two different targets in breeding programs. The results indicate that the heritability estimate values for body length, total abdominal length, and body weight at 50 and 80 d and for reproduction traits including egg count, egg count per unit length or weight, and time of first spawning almost reached the level of medium-high heritability. The growth and reproductive traits of E. carinicauda can be selected through individual or population-phenotypic selection. The above results provide important basic data to support the breeding of E. carinicauda and have considerable application value for future breeding programs.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a Priority 1 (Critical) pathogen urgently requiring new antibiotics. Polymyxins are a last-line option against CRAB-associated infections. This transcriptomic study utilized a CRAB strain to investigate mechanisms of bacterial killing with polymyxin B, colistin, colistin B, and colistin/sulbactam combination therapy. After 4 h of 2 mg/L polymyxin monotherapy, all polymyxins exhibited common transcriptomic responses which primarily involved disruption to amino acid and fatty acid metabolism. Of the three monotherapies, polymyxin B induced the greatest number of differentially expressed genes (DEGs), including for genes involved with fatty acid metabolism. Gene disturbances with colistin and colistin B were highly similar (89 % common genes for colistin B), though effects on gene expression were generally lower (0–1.5-fold in most cases) with colistin B. Colistin alone (2 mg/L) or combined with sulbactam (64 mg/L) resulted in rapid membrane disruption as early as 1 h. Transcriptomic analysis of this combination revealed that the effects were driven by colistin, which included disturbances in fatty acid synthesis and catabolism, and inhibition of nutrient uptake. Combination therapy produced substantially higher fold changes in 72 % of DEGs shared with monotherapy, leading to substantially greater reductions in fatty acid biosynthesis and increases in biofilm, cell wall, and phospholipid synthesis. This indicates synergistic bacterial killing with the colistin/sulbactam combination results from a systematic increase in perturbation of many genes associated with bacterial metabolism. These mechanistic insights enhance our understanding of bacterial responses to polymyxin mono- and combination therapy and will assist to optimize polymyxin use in patients.

Cadmium (Cd) exposure can induce follicular atresia and laying performance reduction in hens, which is linked to autophagy within the granulosa cells. Selenium (Se) can influence autophagy and counteract Cd toxicity. This study aimed to investigate the protective effect of Se on Cd-induced follicular atresia in laying hens. Sixty-four laying hens were randomly allocated into 4 treatments: control group: basal diet; Se group: basal diet + 0.4 mg/kg Se from selenized yeast; Cd group: basal diet + 25 mg/kg Cd from CdCl2; and Cd+Se group: basal diet + 25 mg/kg Cd + 0.4 mg/kg Se. Compared to the Cd group, Se supplementation alleviated the ovarian pathological changes and oxidative stress in the follicles, serum, liver, and ovary, increased daily laying production, ovarian weight and F5–F1 follicle amounts, serum levels of progesterone and oestradiol, and up-regulated mTOR expression (p < 0.05), while decreasing the count of autophagic vacuoles, ovarian atresia follicle numbers, and Cd deposition, and down-regulated expression levels of autophagy-related mRNAs, including ATG5, LC3-I, and LC3-II, Beclin1, and Dynein in the follicles (p < 0.05). In conclusion, 0.4 mg/kg Se supplementation protected against Cd-induced laying performance reduction and follicular atresia, which were achieved via decreasing oxidative stress and inhibiting mTOR pathways of autophagy.

Abstract Osteosarcoma (OSA) is a primary bone malignancy characterized by its aggressive nature and high propensity for metastasis. Despite advancements in multimodal therapies, the clinical outcomes for OSA patients remain suboptimal, necessitating deeper molecular insights for improved therapeutic strategies. Here, we employed single-cell RNA sequencing (scRNA-seq) to elucidate the cellular heterogeneity and transcriptional dynamics of OSA tumors. Our study identified eleven distinct tumor cell subpopulations, including osteoblastic, chondroblastic, and myeloid lineages, each exhibiting unique transcriptional profiles associated with disease progression and metastasis. Epithelial-mesenchymal transition (EMT) emerged as a critical process driving aggressive phenotypes, supported by gene set enrichment analyses (GSVA) and transcription factor regulatory network analyses. Integration of copy number variation (CNV) data highlighted genomic alterations in osteoblastic and chondroblastic cells, implicating potential therapeutic targets. Furthermore, immune cell infiltration analyses revealed distinct immune profiles across OSA subtypes, correlating with tumor mutational burden (TMB) and clinical outcomes. Our findings underscore the complexity of OSA biology and provide a foundation for developing personalized treatment strategies targeting tumor heterogeneity and immune interactions.

Abstract The phosphoethanolamine transferase EptA utilizes phosphatidylethanolamine (PE) in the bacterial cell membrane to modify the structure of lipopolysaccharide, thereby conferring antimicrobial resistance on Gram-negative pathogens. Previous studies have indicated that excessive consumption of PE can disrupt the cell membrane, leading to cell death. This implies the presence of a regulatory mechanism for EptA catalysis to maintain a balance between antimicrobial resistance and bacterial growth. Through microsecond-scale all-atom molecular dynamics simulations, we demonstrate that membrane lipid homeostasis modulates the conformational transition and catalytic activation of EptA. The conformation of EptA oscillates between closed and open states, ensuring the precise spatiotemporal sequence of substrates binding. Interestingly, the conformation of EptA is significantly influenced by its surrounding lipid microenvironment, particularly the PE proportion in the membrane. PE-rich membrane conditions initiate and stabilize the open conformation of EptA through both orthosteric and allosteric effects. Importantly, the reaction mediated by EptA gradually depletes PE in the membrane, ultimately hindering its conformational transition and catalytic activation. These findings collectively establish a self-promoted model, illustrating the regulatory mechanism of EptA during the development of antibiotic resistance.

Abstract Background The extensive use of antibiotics in the global livestock industry in recent decades has accelerated the accumulation and dissemination of antibiotic-resistance genes (ARGs) within terrestrial ecosystems. This occurs due to the limited absorption of most antibiotics, leading to their release into the environment through feces and urine. This poses a significant threat to both the environment and human health. However, the response of antibiotic-resistant microorganisms and their ARGs in grasslands to prolonged grazing, as well as the primary microbial taxa driving the ARG distribution, remain poorly understood, especially within various microhabitats. In this study, we characterized ARGs in the phyllosphere, litter, and soil after decades of livestock grazing in a meadow steppe. We particularly focused on identifying the major members of the microbial community influencing ARGs and the distinction between microbial generalists and specialists. Results Our findings indicate that a core set of ARGs accounted for 90% of the abundance in this plant-soil ecosystem. While the soil exhibited the highest ARG abundance, the phyllosphere, and litter displayed higher ARG diversity and diverse distribution patterns after overgrazing. Grazing increased ARG abundance by elevating the proportion of core ARGs and suppressing stochastic ARGs in the phyllosphere and litter, while it had little effect on the ARGs in the soil. Additionally, microbial generalist abundance increased, but specialist abundance decreased in the phyllosphere and litter, with no effect in the soil, under grazed conditions. Ultimately, microbial microhabitats and grazing influenced ARG community characteristics through direct (i.e., feces and other exogenous ARG input) and indirect (i.e., trampling and selective feeding) effects on nutrient availability, microbial community composition, and mobile genetic elements. The generalist community, with its broad ecological niches and phylogenetic composition, made the most significant contribution to the ARG characteristics. Conclusions This study underscores the impact of environmental disturbances on the distributional patterns of ARGs in ecosystems, mediated by the regulation of microbial generalized species. These insights enhance our understanding of microbial control over ARGs and facilitate predictions regarding the dynamics and risk of ARGs in diverse ecological niches subjected to anthropogenic disturbances. Video Abstract

MnCoGe-based alloys represent promising candidates for magnetic refrigeration due to their advantageous Curie temperature and structural transition temperature near room temperature, coupled with exceptional magnetocaloric effect (MCE). However, the practical application of these materials is constrained by their inferior mechanical properties. Although resin bonding enhanced these properties, it simultaneously detracted from the MCE. In order to overcome this challenge, a novel synthesis method combining arc melting and hot press sintering is proposed. This approach led to an enhancement in the mechanical properties of MnCoGe-based alloys without compromising their MCE. The results of our investigation indicated that the Mn1·16Co0.84Ge alloy has achieved an unprecedented compressive stress of 367 MPa. At room temperature, this alloy undergoes a first-order martensitic phase transformation characterized by a mixed crystal structure comprised of hexagonal austenite and orthorhombic martensite. Furthermore, the Mn0·91Co1.09Ge alloy demonstrated a maximum isothermal entropy change of 19.5 J/kg K under a 7 T magnetic field. This study establishes a robust framework for designing high-performance magnetic refrigeration materials that integrate excellent mechanical properties with superior MCE.

Objective: To investigate the bactericidal mechanism of a composite sol made of carbon nitride and chitosan on Salmonella typhimurium by studying its effects on lipid metabolism. Methods: Transmission electron microscopy and protein leakage concentration were utilized to evaluate the magnitude of cell membrane damage induced by carbon nitride-chitosan composite sol at a cellular level. In addition, lipid metabolomics was employed to investigate the bactericidal process by examining several metabolite functions and regulatory networks associated with bacterial lipid metabolism. Results: The composite sol of carbon nitride-chitosan caused more extensive damage to the cell membrane of Salmonella typhimurium. In lipid metabolism, the significantly up-regulated in 203 metabolites and down-regulated in 95 metabolites. These metabolites were particularly involved in the metabolism of fatty acids, glycerophospholipids, and glycolipids. Metabolite function analysis showed that the composite sol treatment disrupted various metabolic pathways in bacteria. These pathways included fatty acid biosynthesis, glycerol phospholipid metabolism, linoleic acid metabolism, tetraenoic acid metabolism, as well as pathways related to cell energy metabolism, material transport, and signal conduction. These disturbances finally resulted in the demise of the bacteria. Conclusion: This study revealed from the perspective of lipid metabolism that the combination of carbon nitride and chitosan disrupts the metabolic pathways of Salmonella, especially those related to lipid metabolism, leading to bacterial metabolic disruption and death. It provides a theoretical basis for comprehending the mechanisms by which photocatalytic materials exert their antibacterial properties.

Abstract Topological pumps reveal topological insights of adiabatic mode evolution, in which adiabaticity plays a crucial role. However, the adiabatic infimum, i.e., the possible shortest evolution duration of an adiabatic topological pumping process, has remained elusive. In this study, we report the approach of adiabatic infimum in topological pumps in photonic waveguides based on the lithium niobate-on-insulator (LNOI) platform. Besides the most common way to achieve adiabaticity by slowing down the evolution of the system, the adiabaticity of a topological pump is also contingent on an effective Berry connection between instant eigenstates, which can be controlled by the selection of specific pump loops. Specifically, we develop a strategy to identify a pump loop with a minimized effective Berry connection, corresponding to the adiabatic infimum of a topological pump. As such, it is experimentally demonstrated that topological pumps can happen even with rapid evolution speed, at which the conventional pump would completely fail. The adiabatic infimum accelerates the topological pumps from the constraints of slow evolution and facilitates the design of compact topological devices.

Abstract The capacity to discern and locate positions in three-dimensional space is crucial for human-machine interfaces and robotic perception. However, current soft electronics can only obtain two-dimensional spatial locations through physical contact. In this study, we report a non-contact position targeting concept enabled by transparent and thin soft electronic skin (E-skin) with three-dimensional sensing capabilities. Inspired by the active electrosensation of mormyroidea fish, this E-skin actively ascertains the 3D positions of targeted objects in a contactless manner and can wirelessly convey the corresponding positions to other devices in real-time. Consequently, this E-skin readily enables interaction with machines, i.e., manipulating virtual objects, controlling robotic arms, and drones in either virtual or actual 3D space. Additionally, it can be integrated with robots to provide them with 3D situational awareness for perceiving their surroundings, avoiding obstacles, or tracking targets.

Abstract Background There have been emerging clinical trials investigating the efficacy of synthetic-graft-augmented autografts in anterior cruciate ligament reconstruction (ACLR) in recent years. Hamstring tendon and Ligament Augmentation and Reconstruction System (LARS) are both widely discussed graft choices for ACLR. Purpose To compare the clinical efficacy of hamstring tendon grafts with LARS-augmented hamstring tendon grafts in ACLR. Study Design Systematic review and meta-analysis. Method A systematic literature search was performed in PubMed, Embase and the Cochrane Library to identify primary evidence related to the comparison of ACLR with a hamstring tendon (HT) versus a hamstring tendon with LARS (HT + LARS). Quality assessment of the included studies was conducted using Newcastle–Ottawa Scale for non-RCTs. Quantitative analysis was conducted with Reviewer Manager 5.4. The primary outcomes compared were the Lysholm scale, Tegnar activity scale, International Knee Documentation Committee (IKDC) evaluation, KT-1000-based laxity, complication/retear rate and rate of return-to-sports. The secondary outcomes were the Knee Injury and Osteoarthritis Outcomes Score (KOOS), Global Rating of Change (GRC) scale, hop tests, isokinetic knee strength tests and radiographic and arthroscopic evaluations. Results Six cohort studies with 710 participants were included in this study. Compared with the HT group, the HT + LARS group had better Lysholm scores at the 1-year follow-up (P = 0.0007) and at the final follow-up (P = 0.04). HT + LARS group had better IKDC scores at the 1-year follow-up (P = 0.003). The HT + LARS group had a better return-to-sports rate in short term. No significant difference in complications or re-surgery was observed. The secondary results revealed superior or non-inferior outcomes in the HT + LARS group. Conclusions As grafts for ACLR, the use of hamstring tendons with LARS augmentation, compared with the use of hamstring tendons alone, in the short term, has significantly superior overall functional results and better early sports participation and non-inferior results in other comparisons. In the long term, the use of hamstring tendon with LARS augmentation demonstrated non-inferior results in terms of functional scores, knee stability, knee strength, complications and re-tear rate, etc.

Abstract Objective This study aimed to compare the efficacy and cost-utility of unilateral biportal endoscopy (UBE) versus percutaneous endoscopic interlaminar discectomy (PEID) for the treatment of single-level lumbar disc herniation (LDH). Methods A retrospective analysis was conducted on 99 patients who underwent either UBE (n = 33) or PEID (n = 66) between July 2022 and December 2023 at the Second Xiangya Hospital. Patients were matched 1:2 based on age, sex, and surgery level to ensure comparability. Clinical outcomes were assessed using Visual Analog Scale (VAS), European Quality of Life-5 Dimensions (EQ-5D), and Oswestry Disability Index (ODI) scores, with quality-adjusted life years (QALYs) calculated for cost-utility analysis. Hospitalization costs were analyzed, and the incremental cost-utility ratio (ICER) was determined. Results Both UBE and PEID groups demonstrated significant postoperative improvements in VAS, EQ-5D, and ODI scores (p

Abstract Background Ticks are vectors of numerous pathogens, with their bacterial composition, abundance, diversity, and interaction influencing both their growth and disease transmission efficiency. Despite the abundance of ticks in Inner Mongolia, China, comprehensive data on their microbial communities are lacking. This study aims to analyze the microbial communities within ticks from Inner Mongolia to inform innovative control strategies for interrupting pathogen transmission. Methods Tick samples were collected from animals and vegetation in multiple locations across Inner Mongolia and stored at − 80 °C. Ticks were identified using morphological keys and molecular biology methods. Full-length 16S rRNA gene sequencing was performed on collected samples. Bacterial community composition and diversity were mainly analyzed using bioinformatic tools such as QIIME, phyloseq, and DESeq2. Alpha diversity was assessed using Chao1, ACE, and Shannon indices, while beta diversity was evaluated using Bray-Curtis dissimilarity matrices. LEfSe analysis was applied to identify taxa associated with ecological and biological variables. Results A total of 5,048,137 high-quality read counts were obtained, forming an average of 789.3 OTUs per sample. Proteobacteria, Firmicutes, and Bacteroidetes were the most dominant phyla. Bacterial community composition varied significantly with geography, with Dermacentor nuttalli showing a higher abundance of Rickettsia in Xilingol League, while other regions had different dominant genera. The microbial community also differed based on the feeding status of ticks. Additionally, the microbiota of engorged ticks showed organ specificity. Pathogen detection efforts revealed the presence of nine pathogens across all three tick species. D. nuttalli was found to carry a significantly higher burden of pathogenic bacteria, making it the most potentially threatening tick species in Inner Mongolia. Conclusions The study highlights significant variations in tick microbiomes influenced by geographic location, feeding status, and tick species. It underscores the importance of enhancing tick and tick-borne disease surveillance in Inner Mongolia for early detection and control of emerging pathogens. Graphical Abstract

Abstract This untargeted metabolomics study investigated the synergistic antibacterial activity of polymyxin B and Leu10-teixobactin, a depsipeptide inhibitor of cell wall biosynthesis. Checkerboard microdilution assays revealed a significant synergy against polymyxin-susceptible and -resistant A. baumannii, excluding lipopolysaccharide-deficient variants. Time-kill assays confirmed bactericidal synergy, reducing bacterial burden by approximately 4-6-log10CFU/mL. The combination (2xMIC polymyxin B and 0.5xMIC Leu10-teixobactin) prevented bacterial regrowth after 24 h, indicating sustained efficacy against the emergence of resistant mutants. The analysis of A. baumannii ATCC™ 19606 metabolome demonstrated that the polymyxin B–Leu10-teixobactin combination produced more pronounced perturbation compared to the individual antibiotics across all time points (1, 3 and 6 h). Pathway analysis revealed that lipid metabolism, cell envelope biogenesis, and cellular respiration were predominantly impacted by the combination, and to a lesser extent by polymyxin B monotherapy. Leu10-teixobactin treatment alone had only a minor impact on the metabolome, primarily at the 6 h time point. Peptidoglycan assays confirmed the combination’s concerted deleterious effects on bacterial cell envelope integrity. Electron microscopy further substantiated these findings, revealing pronounced cell envelope damage, membrane blebbing, and vacuole formation. These findings highlight the potential of the polymyxin B–Leu10-teixobactin combination as an effective treatment in preventing resistance in A. baumannii.

Abstract Diffuse axonal injury (DAI) results in aberrant functional connectivity and is significantly linked to cognitive impairment. Nevertheless, the network mechanisms influencing neurocognitive function following DAI remain unclear. This study aimed to examine the characteristics of static and dynamic functional network connectivity (FNC) in patients with DAI. Resting-state functional magnetic resonance imaging data were collected from 26 patients with DAI and 27 healthy controls. Resting-state networks were extracted using independent component analysis. We evaluated the connectivity strength through spatial maps and static FNC, and then further dynamic properties were identified using a sliding time-window approach and k-means clustering, and investigated their associations with clinical variables. Patients with DAI showed stronger intra-network spatial maps in the default mode network and subcortical network than healthy controls, but static inter-network functional connectivity remained stable. Furthermore, three recurring states for dynamic connectivity were identified in all participants, and state 1 occurred most frequently in patients with DAI and exhibited higher fractional time, and as well as longer mean dwell time, which was positively associated with MMSE scores. Meanwhile, patients with DAI exhibited mostly increased functional connectivity strength of dynamic FNC in all states, particularly within the default mode network and visual network. These findings suggest that patients with DAI are characterized by altered dynamic FNC and temporal properties, which provide distinct complementary information different from static functional connectivity, and new insights into the neural pathophysiology of DAI associated with cognitive impairment.

Abstract Purposes Whether patients with early-onset colorectal cancer (EOCRC) receive chemotherapy has been controversial, so our study aimed to screen patients with EOCRC who benefit from chemotherapy. Methods A total of 2166 EOCRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into chemotherapy and non-chemotherapy groups, propensity score matching (PSM) was performed to balance the differences between the groups, and the Kaplan–Meier method was used to calculate the cancer-specific survival (CSS) of EOCRC patients. Multifactorial COX regression analysis was used to identify independent prognostic factors for CSS and to construct a nomogram for predicting CSS in EOCRC patients. The overall risk score was calculated based on Nomogram, and EOCRC patients were classified into high-risk and low-risk groups to assess further chemotherapy's therapeutic effect on patients with different risk stratification. Results Before PSM, patients in the chemotherapy group had poorer CSS (p

Abstract The procedure of anterior cruciate ligament (ACL) allograft preparation can be divided into fresh-frozen method (FF-allograft) or freeze-dried method (FD-allograft). This study aims to biomechanically and histologically compare the graft to bone tunnel integration between the two allografts. In-vitro results indicated that FF-allograft and FD-allograft showed excellent biocompatibility and biomechanics, while FD-allograft showed a denser collagen fiber arrangement than FF-allograft and autograft. Then, in-vivo preformation of the FF-allograft, FD-allograft, and autograft on bone tunnel integration was evaluated via a canine ACL reconstruction model. In-vivo results indicated that no signs of infection or osteoarthritis were shown in the femur-graft-tibia complexes, but more vascularity and synovitis formed around the implanted FF-allograft. Micro-computed tomography showed that peri-graft bone in the FF-allograft group was significantly increased and remodeled compared with the FD-allograft group; Histologically, the FF-allograft group exhibited similar graft-bone tunnel healing to the FD-allograft group. Tartrate-resistant acid phosphatase (TRAP) staining showed significantly more osteoclasts presented in the FD-allograft group compared to the FF-allograft group. Meanwhile, a significantly higher failure load was shown in the FF-allograft group when compared with the FD-allograft group (P

Objective Diffuse‐type tenosynovial giant cell tumors (Dt‐TGCTs) commonly occur in the knee joint and tend to recur postoperatively. However, limited clinical data are available on ankle joint involvement especially associated multiportal arthroscopic treatment outcomes. The purpose of this study was to report the clinical results of multiportal arthroscopy‐assisted resection of Dt‐TGCTs of the ankle. Methods We retrospectively reviewed the clinical data of 33 patients with Dt‐TGCT of the ankle who underwent multiportal arthroscopic treatment between August 2011 and December 2020. Clinical follow‐up included the visual analogue scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, Kofoed score, and recurrence rate to assess surgical outcomes. The number of patients who achieved the patient acceptable symptom state (PASS) based on the AOFAS score was also examined. Additionally, the patients were categorized into two groups based on the final surgical approach: Group A who underwent multiportal arthroscopic synovectomy and Group AO who underwent combined arthroscopic and open surgical excision. Intergroup comparisons were conducted. Intraoperative characteristics, such as the number of patients with involvement of the tarsal tunnel and fibularis tendon and the Outerbridge grading of cartilage damage, were recorded to assess the selection of surgical procedures. Results Among the 33 patients, 15 were assigned to Group A, and 18 were in Group AO. The median follow‐up duration for the 33 patients was 77 months (range, 28–142 months). The median VAS score was 1 (range, 0–4), the AOFAS score was 96 (range, 65–100), and the Kofoed score was 96 (range, 67–100). A total of 27 patients (82%) achieved PASS based on AOFAS scores, while five patients (15%) had recurrence. No statistically significant difference was observed between the two groups in recurrence rate, follow‐up VAS score, AOFAS score, Kofoed score, or number of patients who reached the PASS (p > 0.05). In the AO group, 16 cases of Dt‐TGCT involved the tarsal tunnel, and 11 cases involved the fibularis tendon. All these patients exhibited extension beyond the joint. In contrast, only one patient in Group A had involvement of the tarsal tunnel. Statistically significant differences were observed between the groups (p

Obtaining high-performance cathodes is critical for protonic ceramic fuel cells (PCFCs), as cathode performance significantly impacts fuel cell performance. A full understanding of the interactions among the diverse properties of cathode materials would benefit cathode design. In this study, PrBaFe2O6−δ (PBF) was doped with various dopants, including cobalt (Co), Ni, Cu, Zn, and Mn. Experiments and first-principles calculations are used to study the key properties of dopant-modified PrBaFe2O6−δ, including oxygen vacancy (VO) creation, hydration ability, proton mobility, and oxygen reduction reaction (ORR) activity. There is no perfect dopant that can improve every property to its full potential. Instead, different dopants can impact different properties of the material. Co-dopant has the best cathode performance since it balances the material’s instinctive properties, even though it does not provide a significant advantage in the formation of VO. PCFC utilizing Co-doped PrBaFe2O6−δ cathode has a high performance of 1680 mW·cm−2 at 700 °C, which is greater than that of the other dopant-tailored PrBaFe2O6−δ cathodes reported in this study and is one of the largest ever recorded for PrBaFe2O6−δ-based cathodes for PCFCs. Co-doped PrBaFe2O6−δ cathode is further demonstrated to be robust, with excellent operational stability. This study not only provides a potential cathode candidate for PCFCs but also suggests an intriguing approach to cathode design by carefully examining and balancing different vital properties of the material.

Abstract Staphylococcus aureus (S. aureus) is a significant Gram-positive opportunistic pathogen behind many debilitating infections. β-lactam antibiotics are conventionally prescribed for treating S. aureus infections. However, the adaptability of S. aureus in evolving resistance to multiple β-lactams contributed to the persistence and spread of infections, exemplified in the emergence of methicillin-resistant S. aureus (MRSA). In the present study, we investigated the efficacies of the synthetic teixobactin analogue, Leu10-teixobactin, combined with the penicillinase-resistant cephalosporin cefepime against MRSA strains. The Leu10-teixobactin and cefepime combination exerted synergism against most strains tested in broth microdilution assay. Time-kill profiles showed that both Leu10-teixobactin and cefepime predominantly exhibited synergistic activity, with > 2.0-log10CFU decrease compared to monotherapy at 24 h. Moreover, biofilm assays revealed a significant inhibition of biofilm production in ATCC™43300 cells treated with sub-MICs of Leu10-teixobactin and cefepime. Subsequent electron microscopy studies showed more extensive damage with the combination therapy compared to monotherapies, including aberrant bacterial morphology, vesicle formation and substantial lysis, indicating combined damage to the cell wall. Quantitative real-time PCR revealed marked perturbation of genes mecA, sarA, atlA, and icaA, substantiating the apparent mode of combined antibacterial action of both antibiotics against peptidoglycan synthesis and initial biofilm production. Hence, the study highlights the prospective utility of the Leu10-teixobactin-cefepime combination in treating MRSA infections via β-lactam potentiation.

Abstract The Southeastern Siberia (SES) region has recently experienced increasingly extensive wildfires in spring, which have threatened its large carbon sequestration capacity from vast forests and peatlands. However, the underlying mechanisms propelling the increased fires and their potential responses to future climate change remain unclear. Here, by using reanalysis data and climate model output together with a deep learning model, we explore the relationship between positive-phase North Atlantic Tripole (NAT) sea-surface temperature anomalies and SES wildfire increases and project the future trend in SES wildfire intensities under climate change. We found that the positive-phase April NAT enhances the Siberian anticyclone, causing increased temperatures and snowmelt via strengthened transport of warm-air advection into the SES region. The latter process heightens the exposure of local high-density peatlands to favorable conditions for fire ignition and leads to more intensive wildfire incidents. We further demonstrate that the projected NAT variations can drive interdecadal changes in future April SES wildfires. With future phase shifting of NAT modes under global warming, the regionally averaged burned area in SES could be increased by 47–62% under different warming scenarios from 1982–2014 to 2015–2100. Our findings reveal the climate-driven escalation of future wildfires in SES in the context of global warming and call for active and urgent fire management strategies to mitigate the fire risk.

Abstract Two-dimensional conjugated coordination polymers exhibit remarkable charge transport properties, with copper-based benzenehexathiol (Cu-BHT) being a rare superconductor. However, the atomic structure of Cu-BHT has remained unresolved, hindering a deeper understanding of the superconductivity in such materials. Here, we show the synthesis of single crystals of Cu3BHT with high crystallinity, revealing a quasi-two-dimensional kagome structure with non-van der Waals interlayer Cu-S covalent bonds. These crystals exhibit intrinsic metallic behavior, with conductivity reaching 103 S/cm at 300 K and 104 S/cm at 2 K. Notably, superconductivity in Cu3BHT crystals is observed at 0.25 K, attributed to enhanced electron-electron interactions and electron-phonon coupling in the non-van der Waals structure. The discovery of this clear correlation between atomic-level crystal structure and electrical properties provides a crucial foundation for advancing superconductor coordination polymers, with potential to revolutionize future quantum devices.

Abstract Surface flashover is a crucial issue for the miniaturisation of electronic facilities in military, industrial, and aerospace engineering. The oriented hexagonal boron nitride (hBN) composites, due to excellent thermal and electrical insulating properties, show a potential application in high‐voltage power equipment, while the surface flashover performance of hBN composites dependent on oriented hBN texture is rarely reported. The effects of hBN orientation and contents on the surface flashover performances of oriented hBN composites are investigated. The isothermal surface potential decay of the oriented hBN composites was also studied. It is found that the charge transportation could be adjusted by the hBN orientation, thus regulating surface flashover strength. The DC flashover voltage of the in‐plane oriented hBN composites with a thickness of 15 μm reached the maximum of 27.6 kV at the hBN loading of 20 wt%, 14.5% higher than that of the pure resin. The carrier mobility of out‐of‐plane oriented hBN composites is about three times greater than that of the in‐plane oriented composites, indicating that the charges are easily transported along the hBN basal plane. The larger carrier mobility causes charge dissipation in composites near the electrode at the hBN basal plane parallel to the axis of electrodes and inhibits the distortion of the surface electric field on the composites, thus enhancing the surface flashover. Consequently, developing oriented insulators for high‐voltage applications and enabling an optimum insulation design would be beneficial because of the compactness and high reliability of power apparatus for use in power grids.

Helium is a globally scarce strategic resource that is relevant to national economies and the development of high-tech industries, and China primarily depends on imported helium for its industrial applications. Therefore, there is an urgent demand for clarifying helium formation and enrichment patterns, searching for helium-rich fields, and realizing China's helium resource inventory and development potential. This article analyzes the reservoir characteristics and accumulation conditions of typical helium-rich fields in China, and clarifying the origin and source of helium as well as the main controlling factors of helium enrichment. It was recognized that helium in natural gas in China mainly comes from crustal sources. Relatively shallow buried ancient U–Th-rich granite basement or intrusion, large and stable ancient uplift or submarine formed in the early period, good overburden of huge thick paste-salt rock or mudstone cover, and channels connecting the basement and reservoir, were the main controlling factors of helium enrichment. Four types of helium-rich gas reservoirs, namely helium-rich conventional gas, helium-rich shale gas, helium-rich non-hydrocarbon gas, and helium-rich water-soluble gas, have been modeled and predicted to be helium-rich favorable exploration areas. Based on this analysis, the prospect of helium resource development in China has been analyzed. It was proposed that the exploration of helium-rich fields and the comprehensive development and utilization of medium- and low-abundance helium resources are important ways to increase the domestic helium production in China in the future.

Abstract Temperature is an important limiting factor in the counter-seasonal cultivation of pepper. Currently, there are no studies on transcriptomic analysis of ‘cold stress memory’ in pepper. In this study, in order to understand the mechanism of ‘cold stress memory’ in pepper (Capsicum annuum L.), seedlings were subjected to the following treatments: normal temperature treatment (P0), the first cold treatment for 3 days (P3), the recovery temperature treatment for 3 days (R3), and another cold treatment for 3 days (RP3). The results showed that P3 plants wilted the most, RP3 the second and R3 the least. Leaf reactive oxygen species (ROS) and electrolyte leakage were the most in P3, the second in RP3 and the least in R3. In addition, RP3 had the highest accumulation of zeaxanthin, violaxanthin and β-cryptoxanthin, followed by P3, and R3 had the least. These results suggest that pepper seedlings are characterized by ‘cold stress memory’. Transcriptomics was used to analyze the key genes and transcription factors involved in the biosynthesis of zeaxanthin, violaxanthin and β-cryptoxanthin during the formation of ‘cold stress memory’. This study provides candidate genes and transcription factors for an in-depth study of the cold tolerance mechanism in pepper.

Abstract. Background:. Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods:. Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results:. NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions:. Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Abstract Recent years have witnessed an increasing number of manipulated online reviews in e-commerce platforms. Previous research has provided substantial evidence that vendor manipulation of online reviews has a significant negative impact on the stakeholders involved in the e-commerce business. Many platforms take various governance measures to filter manipulated reviews. Nevertheless, the effectiveness of these measures still remains unknown to a large extent. To bridge this research gap, this paper investigates the effect of differentiated platform governance, including defined as interventions to counterattack manipulation intensity, manipulation duration, and perceived quality manipulated, on the probability of future review manipulation. We develop a game theoretical model that incorporates the strategic interactions between the platform and vendors, which yield several testable hypotheses. We then conduct an empirical analysis of platform governance and review manipulation by using the review manipulation data collected from Amazon.com. Results of the analytical model and empirical analysis show that platform governance that targets manipulation intensity and manipulation duration can both effectively mitigate review manipulation probability. On the contrary, platform governance to counterattack manipulating perceived product quality exhibits an inverted U-shape relationship with review manipulation probability. This study provides novel insights into how to better mitigate online review manipulation for e-commerce platforms.

Abstract The outbreak of COVID-19 had a significant impact on the psychological and behavioral health of college students. However, few studies have systematically explored the relationship between COVID-19 and psychological and behavioral health among college students worldwide. Therefore, the purpose of this study was to explore the impact of COVID-19 on college students’ psychological and behavioral health using a knowledge-mapping approach. In total, 796 publications were selected and analyzed to clarify the publication volume and time distribution, core authors, major journals, research institutions, country distributions, research hotspots, and core themes. Since the outbreak of the COVID-19 pandemic in 2019, studies focused on the impact of COVID-19 on college students’ psychological and behavioral health showed an increasing trend year by year. The three countries with the highest centrality were Britain (0.34), the United States (0.24), and Mexico (0.13). The five major topics of research were mental health, academic pressure, physical health risks, college students’ majors, and daily living habits, with most research concerned with college students’ mental health. The visualized burst detection results were combined to identify three cutting-edge research topics in this field: the sustained impact of COVID-19 on college students’ mental health, the sustained impact of COVID-19 on medical college students, and the mediating role of college students’ mental resilience during COVID-19. We conclude by discussing the implications of our findings.

Abstract Background Stevens–Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens–Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens–Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature. Case presentation A previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens–Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient’s condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae. Conclusion We should be aware that coronavirus disease 2019 infection is associated with the development of Stevens–Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens–Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.

Abstract The rapid expansion of the oncology field has revealed new insights into cell death processes, with a particular emphasis on the role of ferroptosis. Characterized by iron dependency and the accumulation of lipid peroxides and iron within cells, ferroptosis stands out as a unique form of programmed cell demise. This in-depth analysis delves into the pivotal role of IGF2BP3, an RNA-binding protein, in the complex regulatory network of ferroptosis in cancerous cells. By exerting post-transcriptional control over genes associated with iron equilibrium, IGF2BP3 is demonstrated to manage cellular iron concentrations and reactive oxygen species (ROS) equilibrium, thus affecting the destiny of the cell. The correlation between aberrant IGF2BP3 expression and increased aggressiveness, metastatic capacity, and poor prognosis in various cancers is further clarified. The potential of IGF2BP3 as a biomarker for prognosis and a therapeutic agent to enhance cancer cells’ vulnerability to ferroptosis is also examined, heralding new strategies in cancer treatment.

Abstract Background Sarcopenia and osteoarthritis are prevalent age-related diseases that mutually exacerbate each other, creating a vicious cycle that worsens both conditions. Exercise is key to breaking this detrimental cycle. Facing increasing demand for rehabilitation services within this patient demographic, ChatGPT-4 and wearable device may increase the availability, efficiency and personalization of such health care. Aim To evaluate the clinical efficacy and cost-effectiveness of a rehabilitation system implemented on mobile platforms, utilizing the integration of ChatGPT-4 and wearable devices. Methods The study design is a prospective randomized open blinded end-point (PROBE) non-inferiority trial. 278 patients diagnosed with osteoarthritis and sarcopenia will be recruited and randomly assigned to the intervention group and the control group. In the intervention group patients receive mobile phone-based rehabilitation service where ChatGPT-4 generates personalized exercise therapy, and wearable device guides and monitor the patient to implement the exercise therapy. Traditional clinic based face-to-face exercise therapy will be prescribed and implemented in the control group. All patients will receive three-months exercise therapies following the frequency, intensity, type, time, volume and progression (FITT-VP) principle. The patients will be assessed at baseline, one month, three months, and six months after initiation. Outcome measures will include ROM, gait patterns, Visual Analogue Scale (VAS) for pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) for functional assessment, Short-Form Health Survey 12 (SF-12) for quality of life, Minimal Clinically Important Difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) for clinically significant measures. Discussion A rehabilitation system combining the capabilities of ChatGPT-4 and wearable devices potentially enhance the availability and efficiency of professional rehabilitation services, thus enhancing the therapeutic outcomes for a substantial population concurrently afflicted with sarcopenia and osteoarthritis.

Abstract Background During the development of disease-modifying intervertebral disc degeneration (IDD) drugs, the rat model of IDD is frequently used for disease progression assessment. The aim of this study was to describe a magnetic resonance (MRI) scoring system for the assessment of different disc conditions in puncture-induced IDD, allowing standardization and comparison of results obtained by different investigators. Methods A total of 36 Sprague-Dawley rats were utilized in the present study. The animals were divided into two groups: a sham group and an IDD group caused by puncture. The rats in the IDD group were subsequently divided into six categories based on time frames, with five rats in each category. The sham group was divided into two sub-groups (n = 3) for 28 and 56 days, respectively. T2-weighted images of rats consecutively studied with MRI of the coccygeal discs were classified according to the time course using the corresponding histological data. Additional scoring of the micro-CT was employed to identify the progression of bone destruction of the rat model of IDD. Results A comparison of the MRI results between the sham group and the IDD group revealed a significant reduction in NP height, area, T2WI value, and DHI in the latter group (P

In order to improve the quality and nutritional value of yogurt and evaluate the effect of Lactobacillus on the quality of pig skin hydrolyzed collagen yogurt, milk and pig skin hydrolyzed collagen were used as raw materials, and Lactobacillus plantarum, Lactobacillus casei, Lactobacillus rhamnosus and Bifidobacterium breve were used to prepare collagen yogurt, and its pH, acidity, color, texture, total bacterial count and sensory properties were measured. Results showed that compared with yogurt without added hydrolyzed collagen, collagen yogurt fermented by Lactobacillus casei significantly (P

Objective Postmenopausal changes in bone mass and structure compromise the mechanical properties of proximal humerus, predisposing it to low‐energy fractures with complex morphology. The aim of the study is to investigate associations of bone quality and estimated bone strength of the surgical neck with age after menopause. Methods A total of 122 healthy postmenopausal women were recruited from December 2016 to December 2022 and assigned to three groups: the 50–59 years group, the 60–69 years group, and the older than 70 years group. Bone properties of the surgical neck, including volumetric bone mineral density (vBMD), cortical thickness (CTh), the periosteal and medullary size, and estimated indices of bone strength were evaluated by quantitative computed tomography. Results Compared to the 50–59 years group, postmenopausal women aged over 70 years were characterized by lower cortical thickness (13.9%) and vBMD (6.65%), as well as reduced strength indices including the minimum and maximum section modulus (Zmin 18.11%, Zmax 21.71%), polar section modulus (Zpol 20.21%), and the minimum and maximum second moments of area (Imax 21.01%, Imin 21.43%). Meanwhile, the difference in periosteal diameter and perimeter, total area in three groups did not reach statistical significance. Both cortical thickness and vBMD value were inversely associated with age, showing 10.56% and 23.92% decline. Imax showed the greatest age‐related decrease between age of 54 and 86 years (39.08%), followed by Zmax (−35.77%), Imin (−35.73%), Zpol (−34.90%) and Imin (−23.92%).The strength indices had stronger correlations with cortical thickness than with bone size or density. Conclusion In postmenopausal women, aging is associated with a significant decline in cortical bone thickness and mechanical strength of the proximal humerus, especially over the age of 70 years.

Abstract Glutaraldehyde (GTA) crosslinking is commonly used to improve the thermal stability and mechanical strength of collagen casings. The aim of this research was to determine the optimal pH of the crosslinking between GTA and collagen as well as the crosslinking mechanisms. The weakly alkaline environment could facilitate the generation of GTA polymerization through the rapid generation of -C = C-C = O and -N = C-C = C- conjugated structures, and enhance the crosslinking reaction of GTA polymers with collagen amino groups. In the pH range of 8–10, the fibril diameter and d-space value declined significantly in the self-assembled collagen fibril-GTA system. Meanwhile, collagen casing films crosslinked with GTA in weakly alkaline conditions exhibited higher mechanical strength and thermal stability. These results suggest that the crosslinking of collagen casings and GTA can be improved by adjusting the pH. Possible crosslinking mechanisms related to the formation of conjugated long chains have also been proposed. This study could provide guidance on the appropriate use of GTA in the production process of collagen casings. Graphical Abstract

Abstract Autoimmune disorders are characterized by aberrant T cell and B cell reactivity to the body’s own components, resulting in tissue destruction and organ dysfunction. Autoimmune diseases affect a wide range of people in many parts of the world and have become one of the major concerns in public health. In recent years, there have been substantial progress in our understanding of the epidemiology, risk factors, pathogenesis and mechanisms of autoimmune diseases. Current approved therapeutic interventions for autoimmune diseases are mainly non-specific immunomodulators and may cause broad immunosuppression that leads to serious adverse effects. To overcome the limitations of immunosuppressive drugs in treating autoimmune diseases, precise and target-specific strategies are urgently needed. To date, significant advances have been made in our understanding of the mechanisms of immune tolerance, offering a new avenue for developing antigen-specific immunotherapies for autoimmune diseases. These antigen-specific approaches have shown great potential in various preclinical animal models and recently been evaluated in clinical trials. This review describes the common epidemiology, clinical manifestation and mechanisms of autoimmune diseases, with a focus on typical autoimmune diseases including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and sjögren’s syndrome. We discuss the current therapeutics developed in this field, highlight the recent advances in the use of nanomaterials and mRNA vaccine techniques to induce antigen-specific immune tolerance.

Abstract Textile dyeing requires optimizing combinations of ingredients and process parameters to achieve target colour properties. Modelling the complex relationships between these factors and the resulting colour is challenging. In this case, a physics-informed approach for multi-output regression to model CIELAB colour values from dyeing ingredient and process inputs is proposed. Leveraging attention mechanisms and multi-task learning, the model outperforms baseline methods at predicting multiple colour outputs jointly. Specifically, the Transformer model’s attention mechanism captures the complex interactions between dyeing ingredients and process parameters, while the multi-task learning framework exploits the intrinsic correlations among the L*, a*, and b* dimensions of the CIELAB colour space. In addition, the incorporation of physical knowledge through a physics-informed loss function integrates the CMC colour difference formula. This loss function, along with the attention mechanisms, enables the model to learn the nuanced relationships between the dyeing process variables and the final colour output, thereby improving the overall prediction accuracy. This reduces trial-and-error costs and resource waste, contributing to environmental sustainability by minimizing water and energy consumption and chemical emissions.

Polyols such as 1,5-pentadiol, 1,6-hexanediol, and 1,2,6-hexanetriol are crucial chemicals, traditionally derived from non-renewable fossil sources. In the pursuit of sustainable development, exploring renewable and environmentally benign routes for their production becomes imperative. Furfural and 5-hydroxymethylfurfural are C5 and C6 biomass-derived platform molecules, which have potential in the synthesis of various polyols through hydrogenation and hydrogenolysis reactions. Currently, there is an extensive body of literature exploring the transformation of biomass-derived furan compounds. However, a comprehensive review of the transformation of furan compounds to polyols is lacking. We summarized the literature from recent years about the ring-opening reaction involved in converting furan compounds to polyols. This article reviews the research progress on the transformation of furfural, furfuryl alcohol, and 2-methylfuran to 1,2-pentadiol, 1,4-pentadiol, 1,5-pentadiol, and 1,2,5-pentanetriol, as well as the transformation of 5-hydroxymethylfurfural to 1,2-hexanediol, 1,6-hexanediol, and 1,2,6-hexanetriol. The effects of the supported Pd, Pt, Ru, Ni, Cu, Co, and bimetallic catalysts are discussed through examining the synergistic effects of the catalysts and the effects of metal sites, acidic/basic sites, hydrogen spillover, etc. Reaction parameters like temperature, hydrogen pressure, and solvent are considered. The ring opening catalytic reaction of furan rings is summarized, and the catalytic mechanisms of single-metal and bimetallic catalysts and their catalytic processes and reaction conditions are discussed and summarized. It is believed that this review will act as a key reference and inspiration for researchers in this field.

Abstract Quantum networks can establish End-to-End (E2E) entanglement connections between two arbitrary nodes with desired entanglement fidelity by performing entanglement purification to support quantum applications reliably. The existing works mainly focus on link-level purification scheduling and lack consideration of purifications at network-level, which fails to offer an effective solution for concurrent requests, resulting in low throughput. However, efficiently allocating scarce resources to purify entanglement for concurrent requests remains a critical but unsolved problem. To address this problem, we explore the purification resource scheduling problem from a network-level perspective. We analyze the cost of purification, design the E2E fidelity calculation method in detail, and propose an approach called Purification Scheduling Control (PSC). The basic idea of PSC is to determine the appropriate purification through jointly optimizing purification and resource allocation processes based on conflict avoidance. We conduct extensive experiments that show that PSC can maximize throughput under the fidelity requirement.

Abstract Purpose We aimed to develop and externally validate a CT-based deep learning radiomics model for predicting overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients, and investigate the association of radiomics with tumor heterogeneity and microenvironment. Methods The clinicopathological data and contrast-enhanced CT images of 512 ccRCC patients from three institutions were collected. A total of 3566 deep learning radiomics features were extracted from 3D regions of interest. We generated the deep learning radiomics score (DLRS), and validated this score using an external cohort from TCIA. Patients were divided into high and low-score groups by the DLRS. Sequencing data from the corresponding TCGA cohort were used to reveal the differences of tumor heterogeneity and microenvironment between different radiomics score groups. What’s more, univariate and multivariate Cox regression were used to identify independent risk factors of poor OS after operation. A combined model was developed by incorporating the DLRS and clinicopathological features. The SHapley Additive exPlanation method was used for interpretation of predictive results. Results At multivariate Cox regression analysis, the DLRS was identified as an independent risk factor of poor OS. The genomic landscape of different radiomics score groups was investigated. The heterogeneity of tumor cell and tumor microenvironment significantly varied between both groups. In the test cohort, the combined model had a great predictive performance, with AUCs (95%CI) for 1, 3 and 5-year OS of 0.879(0.868–0.931), 0.854(0.819–0.899) and 0.831(0.813–0.868), respectively. There was a significant difference in survival time between different groups stratified by the combined model. This model showed great discrimination and calibration, outperforming the existing prognostic models (all p values

Abstract Nitrous oxide (N₂O) emissions from forest soils are typically intensified under elevated anthropogenic nitrogen (N) deposition, likely due to increased N availability. However, the extent to which these emissions are linked to N availability across different timescales remains poorly understood. Here we investigated the temporal-scale-dependent mechanisms of N₂O emissions in a subalpine forest under N-addition, using hourly-resolved N₂O measurements. Our findings revealed that N-addition induced both pulse emissions and a long-lasting effect on soil N₂O emissions. The pulse emissions occurred immediately after each N-addition, indicating a strong linkage between the pulse events and elevated N availability. However, variations in annual N₂O emissions were not directly regulated by N availability but were instead explained by denitrifying microbial functional genes ratio. A global meta-analysis further confirmed the importance of microbial functional genes in regulating N2O emissions in natural terrestrial ecosystems. Our results suggest a crucial role of microbial functional genes in predicting annual N2O emissions from forest soils.

Background/Aims: Ketogenic diet (KD) may benefit patients with liver cancer, but the underlying mechanism of its anti-cancer effect remains an open issue. This work aimed to explore the influence of simulated KD on the proliferation and migration of cultured hepatoma cells. Materials and Methods: The low-glucose medium supplemented with β-hydroxybutyrate (BHB-Glow) was utilized to simulate clinical KD treatment. Western blot was utilized for detecting the expression of glycolysis-related proteins, Seahorse XF96 for oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), and ELISA for insulin content. Expression of FOXC2 in liver cancer cells was analyzed by bioinformatics and qPCR. Cell Count Kit-8 (CCK-8) testing kit was utilized for testing cell viability. Results: KD treatment significantly reduced the expression of glycolysis-related proteins in Huh-7 cells, inhibited insulin production in β islet cells, reduced ECAR, and increased OCR. FOXC2 was significantly up-regulated in Huh-7 cell line, and sh-FOXC2 hindered the proliferation and migration of Huh-7 cells. The exogenous addition of insulin promoted the malignant progression of Huh-7 cells. Together, the medium simulating KD environment strengthened the protection of liver cancer cells by reducing insulin production and down-regulating FOXC2 expression. Conclusion: This study confirmed through in vitro cell experiments that KD could inhibit the proliferation and migration of liver cancer cells by targeting down regulation of insulin and FOXC2 expression, providing new theoretical basis for the treatment of liver cancer patients.

Abstract Acenaphthylene-containing polycyclic aromatic hydrocarbons (AN-PAHs) are noteworthy structural motifs for organic functional materials due to their non-alternant electronic structure, which increases electron affinity. However, the synthesis of AN-PAHs has traditionally required multiple sequential synthetic steps, limiting structural diversity. Herein, we present a tandem C−H penta- and hexaannulation reaction of aryl alkyl ketone with acetylenedicarboxylate. This integrated approach enhances overall efficiency and selectivity, marking a significant advancement in AN-PAH synthesis. Mechanistic studies unveil an orchestrated extension of five- and six-membered rings through C−H activation-annulation and Diels–Alder reaction. Additionally, the tandem annulation reaction can be performed stepwise, further validating the proposed mechanism and increasing the structural diversity of AN-PAHs.

Abstract On-chip metasurface for guided wave radiation works as an upgrade of conventional grating couplers, enriching the interconnection between guided wave and free-space optical field. However, the number of controllable parameters in equivalent Jones matrix of on-chip metasurface is limited that restricts the channels for multiplexing. Here, a supercell design based on detour phase and geometric phase has been proposed to reach full-parametric modulation of Jones matrix. As proof of concept, four independent sets of amplitude-phase channels have been experimentally demonstrated through a single on-chip metasurface. Moreover, through joint modulation of three phase mechanisms including detour phase, geometric phase and propagation phase, the Jones matrix could be decoupled from forward- and backward-propagating guided waves for direction multiplexing. This work paves the way for guided wave radiation towards high-capacity multiplexing and may further extend its application in optical communications, optical displays and augmented/virtual reality.

Abstract The increasing amount of coal gasification fine slag (CGFS) necessitates its resource utilization. CGFS, mainly composed of porous carbonaceous particles and partially fused spherical or agglomerated ash particles, is an inexpensive and high-quality raw material for preparing adsorbent materials. However, the challenge remains in developing a simple, low-cost, and environmentally friendly method to produce high-performance porous materials from CGFS. In this study, a one-step treatment method using 2 mol/L nitric acid under hydrothermal conditions was proposed for CGFS. The adsorbent material (CGFS-2 M) prepared under a solid–liquid ratio of 2:5 and an initial concentration of 200 mg/L methylene blue (MB) exhibited an equilibrium adsorption capacity as high as 210.20 mg/g. The excellent adsorption performance of CGFS-2 M can be attributed to several factors: acid leaching for mineral removal and pore formation, resulting in a specific surface area and total pore volume 2.2 and 1.6 times that of untreated CGFS, respectively, and an optimized mesoporous pore size distribution favorable for MB adsorption; optimal mineral removal and a well-defined carbon microcrystal structure providing more space for MB adsorption; nitric acid treatment increasing the surface oxygen content and hydrophilicity, enhancing its ability to remove MB. The synergistic effect of pore structure improvement and surface modification indicates a feasible research direction for enhancing the performance of CGFS-based adsorbent materials. These results provide theoretical support for the development of efficient CGFS-based adsorbents.

Abstract Objective Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate obesity predictor of reproductive outcomes. The aim of this study was to investigate the discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS. Methods A total of 998 women with PCOS from PCOSAct were included. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence interval (95% CIs) to assess the effect of anthropometric measures, including body mass index (BMI), waist circumference (WC), hip circumference (HC), the waist‒hip ratio (WHR) and the waist‒height ratio (WHtR), on reproductive outcomes. The discrimination abilities of the models were assessed and compared based on the area under the receiver operating characteristic curve (AUC), Akaike’s information criterion (AIC) and integrated discrimination improvement (IDI). Results Among PCOS women, there was a graded association between anthropometric measures and predicted reproductive outcomes across quintiles of anthropometric measures, including a linear association among WHR, BMI and reproductive outcomes and among waist circumference, WHtR and live birth, pregnancy, and ovulation. However, only a linear association was noted between the hip and ovulation. C-statistic comparisons and IDI analyses revealed a trend towards a significant superiority of BMI for ovulation and WHR for live birth, pregnancy and conception in the models. Combining obesity variables improved discrimination in the multivariable models for reproductive outcomes. Conclusions Our findings support that BMI is a better predictor of ovulation and that the WHR is a better predictor of live birth, pregnancy and conception, whereas the combination of obesity variables contributes to the discrimination of reproduction.

Abstract Background N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. Objectives This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. Methods m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. Results m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. Conclusions The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.