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Abstract Background Distal radius fractures are a common orthopedic injury, particularly prevalent among elderly and osteoporotic patients. Although surgical treatment effectively restores fracture alignment and stabilizes the bone, Complex Regional Pain Syndrome (CRPS) can occur as a postoperative complication, severely impacting patients’ rehabilitation and quality of life. Therefore, assessing the risk factors for postoperative CRPS is crucial for early clinical intervention, aiming to improve recovery outcomes and overall patient well-being. Objective This study aims to dynamically evaluate the risk factors for CRPS following distal radius fracture surgery through a retrospective analysis. The goal is to provide scientific evidence for early clinical identification and intervention. Methods A retrospective analysis was conducted on 191 adult patients who underwent distal radius fracture surgery between January 2021 and December 2022, comprising 89 males and 102 females, with an average age of 59.7 ± 11.6(18–75) years. Baseline and follow-up data, including demographic information, clinical characteristics, and psychological assessments, were collected. Descriptive statistics, univariate, and multivariate logistic regression analyses were used to identify independent risk factors and assess their dynamic changes over time. Results Age, gender, occupation, fracture type, surgical method, osteoporosis, pain score (VAS), functional disability score (DASH), anxiety score (GAD-7), depression score (PHQ-9), physical therapy, and occupational therapy significantly affected the incidence of CRPS. Age and VAS scores were consistent risk factors. Female gender, internal fixation surgery, and high DASH scores posed higher risks in the early postoperative period but decreased over time. Occupation and fracture type were more significant in the mid to late postoperative period. Psychological factors were most significant in the midterm, while physical and occupational therapy were protective factors early on. Conclusion The occurrence of CRPS is the result of many factors. Elderly patients, females, and manual laborers had higher risks, with complex fractures and internal fixation surgery patients showing increased risk later on. Osteoporotic patients had higher risks in the mid to late postoperative period. VAS, DASH, GAD-7, and PHQ-9 scores were significantly associated with CRPS. Early physical and occupational therapy can effectively prevent CRPS, but further research is needed to evaluate their long-term effects.

Abstract Mid-infrared (MIR) Kerr microcombs are of significant interest for portable dual-comb spectroscopy and precision molecular sensing due to strong molecular vibrational absorption in the MIR band. However, achieving a compact, octave-spanning MIR Kerr microcomb remains a challenge due to the lack of suitable MIR photonic materials for the core and cladding of integrated devices and appropriate MIR continuous-wave (CW) pump lasers. Here, we propose a novel slot concentric dual-ring (SCDR) microresonator based on an integrated chalcogenide glass chip, which offers excellent transmission performance and flexible dispersion engineering in the MIR band. This device achieves both phase-matching and group velocity matching in two separated anomalous dispersion regions, enabling phase-locked, two-color solitons in the MIR region with a commercial 2-μm CW laser as the pump source. Moreover, the spectral locking of the two-color soliton enhances pump wavelength selectivity, providing precise control over soliton dynamics. By leveraging the dispersion characteristics of the SCDR microresonator, we have demonstrated a multi-octave-spanning, two-color soliton microcomb, covering a spectral range from 1156.07 to 5054.95 nm (200 THz) at a −40 dB level, highlighting the versatility and broad applicability of our approach. And the proposed multi-octave MIR frequency comb is relevant for applications such as dual-comb spectroscopy and trace-gas sensing. Graphical Abstract

Abstract Background This study aimed to develop a predictive model utilizing radiomics and body composition features derived from 18F-FDG PET/CT scans to forecast progression-free survival (PFS) and overall survival (OS) outcomes in patients with esophageal squamous cell carcinoma (ESCC). Methods We analyzed data from 91 patients who underwent baseline 18F-FDG PET/CT imaging. Radiomic features extracted from PET and CT images and subsequent radiomics scores (Rad-scores) were calculated. Body composition metrics were also quantified, including muscle and fat distribution at the L3 level from CT scans. Multiparametric survival models were constructed using Cox regression analysis, and their performance was assessed using the area under the time-dependent receiver operating characteristic (ROC) curve (AUC) and concordance index (C-index). Results Multivariate analysis identified Rad-scorePFS (P = 0.003), sarcopenia (P

Abstract Borayflo Haemostatic matrix is a new absorbable hemostatic gelatin matrix which can be used for intraoperative assisted hemostasis. In a prospective, multicenter, non-inferiority, randomized controlled trial, a total of 354 subjects were recruited from the departments of hepatobiliary surgery, obstetrics and gynaecology and orthopaedics of 4 hospitals and randomly allocated to test group (Borayflo Haemostatic matrix) or control group (Surgiflo Haemostatic matrix) in a 1:1 ratio. In the modified intention-to-treat population, 163 (93.14%) of 175 subjects in the test group versus 167 (94.89%) of 176 subjects in the control group successfully achieved hemostasis within 5 min (P > 0.05). Non-inferiority for effective rates of hemostasis at 5 min to Surgiflo Haemostatic matrix was shown in the study (treatment difference: -1.74% [95%CI, -6.70–3.22%] for modified intention-to-treat population). In terms of efficacy and safety, the new hemostatic gelatin matrix (Borayflo Haemostatic matrix) is equivalent to Surgiflo Haemostatic matrix. There was no significant difference in the incidence of AEs or SAEs between the test and control groups(P > 0.05). In addition, Borayflo Haemostatic matrix is a domestically produced haemostatic gelatin product, an advantage that will reduce the cost of surgical haemostasis for Chinese patients.

Abstract Background The association between serum triglyceride to high density lipoprotein cholesterol ratio (THR) in late pregnancy and adverse birth outcomes (ABO) remains controversial because of inconsistent results. The present study assessed the association between maternal serum THR and incidence of ABO [preterm birth (PTB), small and large for gestational age (SGA/LGA), low birth weight (LBW) and macrosomia] in a Chinese population. Methods A total of 11,553 consecutive participants from a real-world database with data on lipid profiles and birth outcomes were included. Logistic regression models were applied to assess the association between THR and incident ABO. Mediation analysis was performed to investigate the contribution of pregnancy complications [gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP) and pre-eclampsia (PE)] to this association. Results Approximately 6.6% (762/11,553), 8.9% (1023/11,553), 15.5% (1792/11,553), 4.3% (494/11,553), and 7.4% (851/11,553) of individuals developed PTB, SGA, LGA, LBW and macrosomia, respectively. Significant trends across the quintiles of THR toward decreasing incidence of SGA and LBW and increasing incidence of LGA and macrosomia were observed. The multivariate-adjusted odds ratios (OR) in the top quintile of serum THR (> 3.16) versus the bottom quintile (

Abstract Bovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen that infects cattle and causes significant economic losses. We generated a recombinant adenovirus called rHAd5-F + HN by expressing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein of BPIV3 using the human adenovirus serotype 5 (rHAd5). We evaluated its effects on humoral and cellular immune responses in mice (n = 45) and calves (n = 9). Serum antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI), and neutralising antibodies (NAb). After boosting immunity with rHAd5-F + HN, mice produced significantly higher levels of antibodies against the BPIV3 genotype A and genotype C strains. The production of antibodies exceeded those produced by adenoviruses rHAd5-F and rHAd5-HN, which express the F and HN glycoprotein, respectively. The percentages of splenic CD3+/CD8+T lymphocytes and IL-4+ cytokines in rHAd5-F + HN mice were considerably higher than those in the control group. Mice immunised with rHAd5-F + HN exhibited much lower viral loads in the lungs and tracheas compared to the control group. Additionally, the lungs of mice vaccinated with rHAd5-F + HN showed no notable histopathological changes. On the other hand, rHAd5-F + HN produced a humoral immune response in calves. Following the booster intramuscular injection with the rHAd5-F + HN, the serum antibody levels against BPIV3 genotype C strain were 1:20 452, 1:1024, and 1:426 in calves, as detected by ELISA, HI, and NAb, respectively. The HI and NAb levels against the BPIV3 genotype A strain were 1:213 and 1:85 in calves, respectively. These results indicate that rHAd5-F + HN effectively induced immunity against BPIV3 infection.

Microvascular changes are considered key factors in the process of intervertebral disk degeneration (IDD). Microvascular invasion and growth into the nucleus pulposus (NP) and cartilaginous endplates are unfavorable factors that trigger IDD. In contrast, the rich distribution of microvessels in the bony endplates and outer layers of the annulus fibrosus is an important safeguard for the nutrient supply and metabolism of the intervertebral disk (IVD). In particular, the adequate supply of microvessels in the bony endplates is the main source of the nutritional supply for the entire IVD. Microvessels can affect the progression of IDD through a variety of pathways. Many studies have explored the effects of microvessel alterations in the NP, annulus fibrosus, cartilaginous endplates, and bony endplates on the local microenvironment through inflammation, apoptosis, and senescence. Studies also elucidated the important roles of microvessel alterations in the process of IDD, as well as conducted in‐depth explorations of cytokines and biologics that can inhibit or promote the ingrowth of microvessels. Therefore, the present manuscript reviews the published literature on the effects of microvascular changes on IVD to summarize the roles of microvessels in IVD and elaborate on the mechanisms of action that promote or inhibit de novo microvessel formation in IVD.

Abstract The relative risk and benefits of Laparoscopic liver resection (LLR) are still controversial. This study aimed to evaluate perioperative and survival outcomes for three primary malignant liver tumors related outcomes following LLR. Data from three Homogeneous-High-Volume-Expert-Centers were collected. Multivariable logistic regression analysis was performed for the association between LLR, and major complications defined as Clavien-Dindo Classification grade ≥ II. Multivariable Cox proportional hazards regression was used to explore the impact of LLR on primary malignant liver tumor survival. Overall, 5886 patients underwent liver resection, of which 1991 underwent LLR. After adjusting for covariables, LLR had significantly lower rate of CDC grade ≥ II (OR = 0.56, 95% CI: 0.48–0.67, P 0.05). LLR was associated with lower rate of major complications, especially in women, non-drinkers, those without a history of abdominal surgery, and those with normal platelet. For primary malignant liver tumors, the survival outcomes did not differ significantly between LLR and OLR.

Abstract Background Integration of digital tools and resources in STEM instruction has garnered significant attention due to its high potential. Digital professional development is identified as a pivotal factor for equipping teachers with necessary digital skills to effectively orchestrate digital resources. Notably, the role of professional learning communities is considered critical. However, the intricate relationships among digital professional development, professional learning communities, and digital instructional integration among STEM teachers remain underexplored. Utilizing partial least-squares–structural equation models (PLS–SEM), the present study examined links in digital professional development, professional learning communities, and digital instructional integration among STEM teachers (N = 16,072) who participated in the Programme for International Student Assessment (PISA) 2022. Results Findings from the PLS–SEM analysis indicate that digital professional development exhibits a direct positive relationship with professional learning communities and digital instructional integration. Relatedly, professional learning communities is positively correlated with digital instructional integration. In terms of indirect effect, findings show that professional learning communities play a significant positive mediating role in linking digital professional development and digital instructional integration. Conclusions This study reports new evidence on the influence of digital professional development on digital instructional integration through professional learning communities among 16,072 STEM teachers and concludes that, when STEM teachers regularly immerse themselves in professional learning communities, they are more likely to benefit from their digital professional development by integrating digital technologies in classroom instruction. Policymakers and educational leaders should consider promoting digital professional development and professional learning communities among STEM teachers, along with efforts to encourage digital instructional integration.

Abstract Background Tobacco production faces ongoing challenges due to soil degradation, leading to a persistent decline in yield. Plant growth-promoting fungi (PGPF) have been recognized as an environmentally friendly agricultural strategy. However, many commercial PGPF products exhibit instability due to insufficient environmental compatibility. Results In this study, Penicillium sp. PQxj3 was isolated and assessed for its potential to enhance tobacco productivity under field conditions. The results demonstrated that Penicillium sp. PQxj3 treatment significantly promoted the tobacco growth and improved the crop yield. The height of tobacco in Penicillium sp. PQxj3 treatment group significantly increased by 50.19% and 24.05% compared with CK at exuberant and maturity period (P

Abstract Purpose Maintaining normothermia during the perioperative period is crucial for preventing complications, such as surgical site infections, prolonged hospital stays, and adverse cardiovascular events. This study aimed to elucidate methods of perioperative temperature management by integrating Western and traditional Chinese medicine (TCM) approaches. By combining advanced techniques of Western medicine with holistic and preventative practices of TCM, we aimed to provide a comprehensive strategy for effective perioperative thermal regulation. Methods And a comprehensive literature review was conducted to analyze the causes of perioperative hypothermia and methods of perioperative temperature management from both Western and traditional Chinese medicine (TCM) perspectives. Special emphasis was placed on evaluating the underlying factors contributing to perioperative hypothermia, as well as the effectiveness, selection criteria, indications, contraindications, adverse reactions, and potential complications associated with various temperature management techniques. Results Effective prevention and management strategies include preoperative risk assessment, physical warming measures, environmental temperature control, pharmacological interventions, perioperative temperature monitoring, comprehensive warming protocols, and postoperative warming and monitoring. Integrating traditional Chinese medicine provides additional methods to enhance overall effectiveness and patient outcomes. By combining these approaches, healthcare providers can significantly reduce the incidence of inadvertent perioperative hypothermia (IPH) and its associated complications, improving patient safety and recovery. Conclusion For IPH, a complex and challenging medical condition, both traditional Chinese medicine and Western medicine have established their own theoretical bases and developed corresponding prevention and treatment methods. However, it is important to note that although each of these methods has unique value and potential, they also have specific indications and unavoidable limitations. Therefore, by integrating and combining the complementary strengths and resources of traditional Chinese medicine and Western medicine, we can achieve a more comprehensive and effective prevention of IPH, ultimately improving the health and well-being of those affected.

Organic-rich shales from the Triassic Yanchang Formation in the Ordos Basin in China are mainly derived from aquatic organisms with type II kerogen. A reverse maturity trend, derived from the commonly used biomarker maturity parameter Ts/(Ts + Tm) occurs in the depth profiles of the Chang 73 submember and the Chang 8 member. In contrast, maturity proxies derived from aromatic compounds show a normal sequence for more deeply buried Chang 8 samples exhibiting higher maturity levels, as expected. To explain the abnormal phenomenon, multiple controlling factors—including the paleoredox condition, water salinity, the clay mineral content and composition, biodegradation, the primary migration fractionation effect, and organofacies—are considered. It was found that organofacies BC (HIo = 400-250) appear in the Chang 8 samples, while organofacies B (HIo = 400-650) appear in the Chang 73 submember. The results suggest that variation in organofacies has a significant impact on Ts/(Ts + Tm) values, even for samples with the same kerogen type and similar source input, and is primarily responsible for the reverse maturity trend in the depth profiles.

Abstract Background Radiation-induced skin injury (RISI) represents a significant complication in patients receiving radiotherapy and individuals exposed to nuclear accidents, characterized by a protracted wound-healing process relative to injuries from other etiologies. Current preventive and management approaches remain inadequate. Consequently, investigating efficacious intervention strategies that target the disease’s progression characteristics holds significant practical importance. Methods Small interfering RNA (siRNA) and overexpression plasmid were used to modulate the expression of Marvel domain containing 3 (Marveld3) and paired related homeobox 2 (PRRX2). Protein and mRNA levels were estimated by Western Blot and real-time PCR, respectively. Intracellular levels of Malondialdehyde (MDA), a terminal product of lipid peroxidation, were measured following the manufacturer’s protocol for MDA assay kit. Similarly, intracellular levels of ferrous iron (Fe2+) and reactive oxygen species (ROS) were determined using their respective assay kits. Lipid peroxidation status within the cells was evaluated via BODIPY staining. Immunohistochemistry was conducted to ascertain the expression of PRRX2 in skin tissues collected at various time points following irradiation of rats. The H-score method was used to evaluate the percentage of positively stained cells and staining intensity. RNA sequencing, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted by OE Biotech Company. Results In this study, our findings indicated that Marveld3 suppression could effectively inhibit lipid peroxidation levels in irradiated skin cells, concomitantly reducing intracellular Fe2+ content. Additionally, the silencing of Marveld3 effectively abrogated the impact of a ferroptosis agonist on cellular viability, resulting in the upregulation of 66 and 178 genes, as well as the downregulation of 188 and 31 genes in irradiated HaCaT and WS1 cells, respectively. Among the differentially expressed genes, the PRRX2 which was found to be involved in the process of ferroptosis, exhibited statistically significant upregulation. And the upregulation of PRRX2 expression may attenuate radiation-induced lipid peroxidation in skin cells, thereby functioning as a potential stress-responsive mechanism to counteract radiation effects. Conclusions This study elucidates the role of Marveld3 in radiation-induced ferroptosis in skin cells. Inhibition of Marveld3 led to the upregulation of PRRX2, which subsequently resulted in a reduction of Fe2+ and ROS levels, as well as the suppression of lipid peroxidation. These effects collectively mitigated the occurrence of ferroptosis.

Abstract Background Since chronic kidney disease is highly insidious in the early stages, most diagnosed patients have already developed irreversible renal failure. There is a lack of effective implementation and standardization of health education management for patients with chronic kidney disease, and the impact of health education management on health information literacy is not yet known. Methods This randomized controlled clinical trial was conducted from March 2022 to March 2023. A total of 130 patients with chronic kidney disease stage 3–4 were selected from a tertiary hospital in Zhuhai via a convenience sampling method and were then randomly assigned to intervention and control groups. The Health Information Literacy Questionnaire for Chronic Kidney Disease was used to assess the health literacy of the patients at month 0 and month 12. In addition, the renal function-related indices of the patients were measured before and after the intervention. The study adhered to SPIRIT guidelines. Results There was no significant difference between the two groups in health information literacy, platelet count, estimated glomerular filtration rate, or albumin level. However, the intervention group showed a significant improvement in health behavioral status such as information acquisition, checkups, and physical activity. Subgroup analysis revealed that hemoglobin was significantly higher in non-employed patients than in the intervention group. There was a significant improvement in hemoglobin level after receiving health guidance in patients with intermediate education, and acquisition capacity and estimated glomerular filtration rate in the intervention group were lower than in the control group for patients with elementary education. Conclusion Receiving health coaching helped to improve self-management behaviors and hemoglobin levels of patients with stage 3–4 chronic kidney disease. Education level is an important factor influencing the effectiveness of health coaching techniques. Trial registration This study was prospectively registered in the China Clinical Trial Registry on November 10, 2021, with registration number: ChiCTR2100053103.

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.

Based on the oil and gas exploration in western depression of the Qaidam Basin, NW China, combined with the geochemical, seismic, logging and drilling data, the basic geological conditions, oil and gas distribution characteristics, reservoir-forming dynamics, and hydrocarbon accumulation model of the Paleogene whole petroleum system (WPS) in the western depression of the Qaidam Basin are systematically studied. A globally unique ultra-thick mountain-style WPS is found in the western depression of the Qaidam Basin. Around the source rocks of the upper member of the Paleogene Lower Ganchaigou Formation, the structural reservoir, lithological reservoir, shale oil and shale gas are laterally distributed in an orderly manner and vertically overlapped from the edge to the central part of the lake basin. The Paleogene WPS in the western depression of the Qaidam Basin is believed unique in three aspects. First, the source rocks with low organic matter abundance are characterized by low carbon and rich hydrogen, showing a strong hydrocarbon generating capacity per unit mass of organic carbon. Second, the saline lake basinal deposits are ultra-thick, with mixed deposits dominating the center of the depression, and strong vertical and lateral heterogeneity of lithofacies and storage spaces. Third, the strong transformation induced by strike-slip compression during the Himalayan resulted in the heterogeneous enrichment of oil and gas in the mountain-style WPS. As a result of the coordinated evolution of source-reservoir-caprock assemblage and conducting system, the Paleogene WPS has the characteristics of “whole process” hydrocarbon generation of source rocks which are low-carbon and hydrogen-rich, “whole depression” ultra-thick reservoir sedimentation, “all direction” hydrocarbon adjustment by strike-slip compressional fault, and “whole succession” distribution of conventional and unconventional oil and gas. Due to the severe Himalayan tectonic movement, the western depression of the Qaidam Basin evolved from depression to uplift. Shale oil is widely distributed in the central lacustrine basin. In the sedimentary system deeper than 2 000 m, oil and gas are continuous in the laminated limy-dolomites within the source rocks and the alga limestones neighboring the source kitchen, with intercrystalline pores, lamina fractures in dolomites and fault-dissolution bodies serving as the effective storage space. All these findings are helpful to supplement and expand the WPS theory in the continental lake basins in China, and provide theoretical guidance and technical support for oil and gas exploration in the Qaidam Basin.

Abstract Background Cabbage (Brassica oleracea L. var. capitata) is an important crop within the Brassica oleracea species and is extensively cultivated worldwide. In recent years, outbreaks of downy mildew caused by Hyaloperonospora parasitica have resulted in substantial losses in cabbage production. Despite this, there have been limited studies on genes associated with resistance to downy mildew in cabbage. Results This study identified sister lines exhibiting significant differences in disease resistance and susceptibility. Using bulked segregant analysis followed by sequencing (BSA-seq) and linkage analysis, the cabbage resistance locus BoDMR2 was accurately mapped to an approximately 300 kb interval on chromosome 7. Among the candidate genes identified, several single nucleotide polymorphisms (SNPs) and a 3-bp insertion were found within the conserved domain of the Bo7g117810 gene, encoding a leucine-rich repeat domain protein, in susceptible genotypes. Additionally, real-time quantitative polymerase chain reaction (RT‒qPCR) analysis revealed that the expression level of Bo7g117810 in resistant specimens was 2.5-fold higher than that in susceptible specimens. An insertion‒deletion (InDel) marker was designed based on the identified insertion in susceptible materials, facilitating the identification and selection of downy mildew-resistant cabbage cultivars. Conclusions This study identifies Bo7g117810 as a potential candidate gene associated with adult-stage resistance to downy mildew in cabbage, supported by observed differences in gene sequence and expression levels. Furthermore, the development of an InDel marker I1-3, based on its mutation, provides valuable resources for breeding resistant cabbage cultivars.

Abstract Simplified rapid hydration has been proven to be non-inferior to standard hydration in preventing contrast-associated acute kidney injury among chronic kidney disease patients undergoing coronary angiography. The current investigation aimed to further confirm the feasibility and safety of the newly proposed hydration method-simplified rapid hydration (SH) in each risk stratification by Mehran risk score (MRS). Eligible patients (n = 954) randomized to the SH group and standard hydration group were allocated into 2 groups based on MRS: low to moderate-risk and high to very high-risk groups. Primary endpoints were the incidence of contrast-associated acute kidney injury (CA-AKI) and acute heart failure (AHF) (SH vs standard hydration). Secondary endpoints included serum creatinine (Scr), blood urea nitrogen (BUN), cystatin-C (Cys-C), and C-reactive protein (CRP) at 24 h, 48 h, and 72 h after PCI procedure, and the incidence of major adverse cardiac events (MACE). MRS was associated with a higher incidence of CA-AKI (OR = 1.101, 95%CI 1.049–1.156, P

Abstract Background Exposure of the hepatic artery is a fundamental step in many surgeries, during which iatrogenic hepatic artery injury may occur. Although the incidence of hepatic artery haemorrhage is low, its occurrence can lead to life-threatening haemorrhage. It is difficult and dangerous to accumulate clinical experience in laparoscopic hepatic artery repair in actual patients, and simulation training models for laparoscopic hepatic artery repair are currently lacking. In this study, a 3D printed model was designed to simulate the training curriculum for sudden hepatic artery haemorrhage, but whether training with the 3D printed model could yield superior skill improvement for surgeons remained to be determined. Methods A new 3D printed model was designed for this study. Surgeons from the General Surgery Department of Sir Run Run Shaw Hospital participated in this simulation training. The surgical performance of each model was compared, and the authenticity of the model was evaluated and mechanically tested. Results Experienced surgeons performed better on the 3D printed model. After repeated training, inexperienced surgeons showed significant improvement of their laparoscopic hepatic artery repair skills. The authenticity of the model was generally satisfactory, but shortcomings persisted in the mechanical testing of artery wall tearing, necessitating further improvement. Conclusions Few studies have investigated laparoscopic simulation training for sudden hepatic artery haemorrhage. This simulation model distinguishes surgeons with different levels of experience and allows those with less experience to improve their laparoscopic hepatic artery repair skills through training on the model.

Abstract Background and objectives Cauda equina syndrome with retention (CESR) is a severe lumbar condition characterized by painless urine retention due to cauda equina nerve injury. The standard treatment, posterior lumbar interbody fusion (PLIF), often yields suboptimal results. This study aims to compare the clinical safety and efficacy of a novel technique, capsule lumbar interbody fusion (CLIF), with PLIF in CESR patients, hypothesizing that CLIF can enhance neurological recovery by reducing nerve tension. Methods A single-center, retrospective study was conducted on 83 patients with CESR due to lumbar disc herniation, who underwent either PLIF (n = 44) or CLIF (n = 39). Patients were assessed preoperatively and at 3, 12, and 24 months postoperatively using the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), International Consultation on Incontinence Questionnaire Short Form (ICI-Q-SF), and Rintala score. Urodynamic studies and nerve tension measurements were also performed. Statistical analysis included t tests, Mann–Whitney U tests, and Spearman’s correlation. Results Both groups showed significant postoperative improvements, but the CLIF group had superior outcomes. At 12 months, the CLIF group had lower VAS scores (1.15 ± 0.84 vs. 1.68 ± 0.60, p = 0.001) and ODI scores (23.31 ± 7.51 vs. 28.30 ± 8.26, p = 0.005). At 24 months, the CLIF group continued to show better results with ODI scores (15.97 ± 6.43 vs. 22.11 ± 6.41, p

Abstract Topological photonics attract significant interests due to their intriguing fundamental physics and potential applications. Researchers are actively exploring various artificial platforms to realize novel topological phenomena, which provides promising pathways for the development of robust photonic devices. Among these platforms, femtosecond laser direct-written photonic waveguides show unique ability to visualize intricate light dynamics in 2 + 1 dimensions, which rendering them ideal tools for investigating topological photonics. By integrating topological concepts into these waveguides, researchers not only deepen their understanding of topological physics but also provide potential methodology for developing advanced topological photonic integrated devices. In this review, we discuss recent experimental implementations of different topological phases within femtosecond laser direct-written photonic waveguides, as well as the fascinating physical phenomena induced by the interplay of topology with non-Hermiticity, nonlinearity and quantum physics are also introduced. The exploration of topological waveguide arrays shows great promise in advancing the field of topological photonics, providing a solid foundation for further research and innovation in this rapidly developing domain.

Abstract The photothermal conversion properties of tellurium (Te) nanoparticles have been extensively investigated, rendering them a promising candidate for tumor photothermal therapy. However, there is still room for improvement in the development of efficient Te-based drug delivery systems. Here, Te nanoparticles are mineralized with bioactive molecules within attenuated Salmonella (S-Te), which are subsequently taken up by macrophages (RAW264.7) to construct a double-camouflaged delivery platform (RS-Te). Remarkably, RS-Te retains superior photothermal properties under near-infrared irradiation. The mineralization process eliminates bacterial proliferation potential, thereby mitigating the risk of excessive bacterial growth in vivo. Furthermore, the uptake of bacteria by macrophages not only polarizes them into M1 macrophages to induce an anti-tumor immune response but also circumvents any adverse effects caused by complex antigens on the bacterial surface. The results show that RS-Te can effectively accumulate and retain in tumors. RS-Te-mediated photothermal immunotherapy largely promotes the maturation of dendritic cells and priming of cytotoxic T cells induced by near-infrared laser irradiation. Moreover, RS-Te can switch the activation of macrophages from an immunosuppressive M2 phenotype to a more inflammatory M1 state. The double-camouflaged delivery system may offer highly efficient and safe cancer treatment.

Objective The C4 is the transition point between the upper and lower cervical vertebrae and plays a pivotal role in the middle of the cervical spine. Currently, there are limited reports on large‐scale sample studies regarding C4 anatomy in children, and a scarcity of experience exists in pediatric cervical spine surgery. The current study addresses the dearth of anatomical measurements of the C4 vertebral arch and lateral mass in a substantial sample of children. This study aims to measure the imaging anatomy of the C4 vertebral arch and lateral mass in children under 14 years of age across various age groups, investigate the growth and development of these structures. Methods We measured 12 indicators, including the size (D1, D2, D3, D4, D5, D6, D7, and D8) and angle (A, C, D, and E) of the C4 vertebral arch and lateral mass, in 513 children who underwent cervical CT examinations at our hospital. We employed the aggregate function for statistical analysis, conducted t‐tests for difference statistics, and utilized the least squares method for regression analysis. Results Overall, as age increased, there was a gradual increase in the size of the vertebral arch and lateral mass. Additionally, the medial inclination angle of the vertebral arch decreased, and the lateral mass flattened gradually. The rate of change decreased gradually with age. The mean value of D1 increased from 2.31 mm to 3.88 mm, of D2 from 16.75 mm to 29.2 mm, of D3 from 2.21 mm to 4.92 mm, and of D4 from 7.34 mm to 11.84 mm. Meanwhile, the mean value of D5 increased from 5.2 mm to 9.71 mm, of D6 from 10.19 mm to 16.16 mm, of D7 from 2.53 mm to 5.67 mm, and of D8 from 6.11 mm to 11.45 mm. Angle A ranged from 49.12° to 54.97°, angle C from 15.28° to 19.83°, angle D from 39.91° to 53.7°, and angle E from 18.63° to 28.08°. Conclusion Prior to cervical spine surgery in children, meticulous CT imaging anatomical measurements is essential. The imaging data serves as a reference for posterior C4 internal fixation, aids in designing posterior cervical screws for pediatric patients, and offer morphological anatomical references for posterior cervical spine surgery and screw design in pediatric patients.

Abstract Maintaining stillness is essential for accurate bioelectrical signal acquisition, but dynamic noise from breathing remains unavoidable. Isotropic adhesives are often used as bioelectronic interfaces to ensure signal fidelity, but they can leave irreversible residues, compromising device accuracy. We propose a hydrogel with selective frequency damping and asymmetric adhesion as a bioelectronic interface. This hydrogel mitigates dynamic noise from breathing, with a damping effect in the breathing frequency range 60 times greater than at other frequencies. It also exhibits an asymmetric adhesion difference of up to 537 times, preventing residues. By homogenizing ion distribution, extending Debye length, and densifying the electric field, the hydrogel ensures stable signal transmission over 10,000 cycles. Additionally, it can non-invasively diagnose otitis media with higher sensitivity than invasive probes and has been effective in clinical polysomnography monitoring, aiding in the diagnosis of obstructive sleep apnea.

Abstract Background Thoracic aortic dissection (TAD) is an irreversible cardiovascular disorder with high mortality and morbidity. However, the molecular mechanisms remain elusive. Thus, identifying an effective therapeutic target to prevent TAD is especially critical. The purpose of this study is to elucidate the potential mechanism of inflammation and vascular smooth muscle cell (VSMCs) phenotypic switch in β-aminopropionitrile fumarate (BAPN)-induced TAD. Methods A mouse model of TAD induced by BAPN and IL-1β -stimulated HVSMCs in vivo and in vitro models, respectively. ACE2 Knockdown mice treated with BAPN or without, and the TAD mouse model was treated with or without AAV-ACE2. Transthoracic ultrasound was conducted for assessment the maximum internal diameter of the thoracic aorta arch. RNA sequencing analysis was performed to recapitulate transcriptome profile changes. Western blot were used to detect the expression of MMP2, MMP9, ACE2, SIRT3, OPN, SM22α and other inflammatory markers. The circulating levels of ACE2 was measured by ELISA assay. Histological changes of thoracic aorta tissues were assessed by H&E, EVG and IHC analysis. Results We found that circulating levels of and the protein levels of ACE2 were increased in the TAD mouse model and in patients with TAD. For further evidence, ACE2 deficiency decelerated the formation of TAD. However, overexpression of ACE2 aggravated BAPN-induced aortic injury and VSMCs phenotypic switch via lowered SIRT3 expression and elevated inflammatory cytokine expression. Conclusion ACE2 deficiency prevented the development of TAD by inhibiting inflammation and VSMCs phenotypic switch in a SIRT3-dependent manner, suggesting that the ACE2/SIRT3 signaling pathway played a pivotal role in the pathological process of TAD and might be a potential therapeutical target.

Abstract Social isolation (SI) is a common phenomenon in the modern world, especially during the coronavirus disease 2019 pandemic, and causes lasting cognitive impairments and mental disorders. However, it is still unclear how SI alters molecules in the brain and induces behavioural dysfunctions. Here, we report that SI impairs cognitive function and induces depressive-like behaviours in C57BL/6 J mice, in addition to impairing synaptic plasticity and increasing the levels of APP cleavage-related enzymes, thereby promoting Aβ production. Moreover, we show that in APP/PS1 transgenic mice, SI accelerates pathological changes and behavioural deficits. Interestingly, downregulation of the expression of the BACE1 attenuates SI-induced Aβ toxicity and synaptic dysfunction. Furthermore, early intervention with BACE1 shRNA blocks SI-induced cognitive impairments. Together, our data strongly suggest that SI-induced upregulation of BACE1 expression mediates Aβ toxicity and induces behavioural deficits. Down-regulation of BACE1 may be a promising strategy for preventing SI-induced cognitive impairments.

Coal is a mixture of organic macerals and minerals. The presence of minerals can lead to differences in the macromolecular structure of coal, resulting in significant heterogeneity in its mechanical properties, which in turn affects the overall coalbed methane production, fracturing and transformation effects, and the large-scale application of mature technologies within the block. Taking typical anthracite and kaolinite minerals from the Qinshui Basin as the research object, the influence of kaolinite and its content on the mechanical properties of anthracite is quantitatively studied through molecular dynamics methods. The molecular structure and pore characteristics of anthracite under different mineral contents are analyzed, and its microscopic mechanism is revealed from the perspective of energy and ordering. The results indicate that: ① There are both van der Waals forces and hydrogen bonding forces during the binding process between coal organic matter and kaolinite, and the intensity of hydrogen bonding is higher than that of van der Waals forces. The probability, interaction strength, and orderliness of kaolinite molecules appearing around coal organic matter increase with the increase of mineral content. ② The porosity of anthracite decreases linearly with the increase of kaolinite content, with φ=−0.229 3a+9.629 5, while the bulk modulus, elastic modulus, and shear modulus of anthracite all increase linearly with the increase of kaolinite content. The Poisson’s ratio decreases exponentially with the increase of kaolinite content. ③ The degree of mechanical heterogeneity of anthracite increases overall with the increase of kaolinite content. The variability of bulk modulus, elastic modulus, and shear modulus under different kaolinite contents can be divided into five parts: very low, low, medium, high, and very high. The coefficient of variation of Poisson's ratio is all less than 0.1, indicating very low variability. ④ As the content of kaolinite increases, the interaction energy between coal organic matter and kaolinite shows a linear increase (Einteraction=4.558 5a+443.929). Compared with pure organic matter, when the content of kaolinite reaches 20%, the bond energy and van der Waals energy of anthracite increase by 63.86% and 48.06%, respectively. ⑤ The internal reason why kaolinite enhances the mechanical properties of coal is that it occupies a certain pore space after entering the coal organic matter and interacts with the aromatic carbon skeleton and different functional groups of the coal organic matter. The higher the content of kaolinite, the greater the degree of filling the pores of the coal macromolecular structure and the energy of the coal macromolecular structure, resulting in a decrease in the porosity of the coal macromolecular structure, an increase in orderliness, and an increase in mechanical strength and resistance to deformation.

Abstract Purpose To minimize radiation exposure to the small bowel (SB) in patients undergoing treatment for gynecological tumors by adopting a comfortable positioning method. Methods and patients All 76 women undergoing Intensity-Modulated Radiation Therapy (IMRT) were included in this study. Patients were immobilized in a supine position using a vacuum bag and thermoplastic cast formation. In the trial group (n = 36), patients raised their buttocks and a solid foam pad was placed under the sacral tail before immobilization. The control group (n = 40) received treatment in the standard supine position. The SB was delineated from the pubic symphysis to the total iliac bifurcation in computed tomography (CT) scans. Result In the trial group, a significant reduction in SB volume within the pelvic cavity was observed (mean 399.17 ± 158.7 cc) compared to the control group (mean 547.48 ± 166.9 cc), with a p-value less than 0.001. The trial group showed a statistically significant reduction in the absolute volume of irradiated SB at each dose, ranging from the low dose (10 Gy) to the high dose (45 Gy). In the control group, a negative correlation was found between SB and bladder volumes (R = -0.411, P = 0.008), whereas in the trial group, this correlation was weaker (R = -0.286, P = 0.091), with no significant relationship observed between bladder volume and SB. Conclusion The high buttocks supine position effectively reduces SB radiation exposure without the need for bladder distension. This positioning method holds promise for reducing SB irradiation in various pelvic tumors.

Abstract Objective The relationship between changes in Chinese visceral adiposity index (CVAI) and cardiometabolic diseases (CMD) in middle-aged and elderly individuals remains unclear. This study aimed to explore whether changes in the CVAI were associated with CMD incidence. Methods This study included 3,243 individuals aged over 45 years from the China Health and Retirement Longitudinal Study. The exposures were changes in the CVAI and cumulative CVAI from 2012 to 2015. Changes in the CVAI were classified using K-means clustering analysis, and the cumulative CVAI was calculated as follows: (CVAI2012 + CVAI2015)/2 × time (2015–2012). Multivariable logistic regression models were used to assess the relationship between different CVAI change classes and CMD incidence. Restricted cubic splines regression was used to assess the dose–response relationship between cumulative CVAI and CMD incidence. To investigate the relationship between combined exposure to each component of CAVI and CMD incidence, a weighted quantile sum regression analysis was employed. Results During the 5 years of follow-up, 776 (24%) incident CMD cases were identified. Changes in CVAI and cumulative CVAI were independently and positively associated with CMD. After adjusting for potential confounders, compared with Class 1, the adjusted ORs (95% CIs) for incident CMD were 1.18 (0.90–1.57) for Class 2, 1.40 (1.03–1.92) for Class 3, and 1.56 (1.04–2.34) for Class 4. When cumulative CVAI was categorized into quartiles, compared with Q1, the adjusted ORs (95% CIs) for incident CMD were 1.30 (1.00–1.70) for Q2, 1.34 (1.01–1.79) for Q3, and 1.63 (1.15–2.31) for Q4. In addition, cumulative CVAI in the overall population exhibited a linear association with CMD (P overall = 0.012, P non-linearity = 0.287), diabetes (P overall = 0.022, P non-linearity = 0.188), and stroke (P overall = 0.002, P non-linearity = 0.978), but showed no significant association with heart disease (P overall = 0.619, P non-linearity = 0.442). Conclusion Participants with higher baseline CVAI level and a change of elevating CVAI level may suffer an increased incidence of CMD. Furthermore, our findings elucidate the underlying mechanisms of the CVAI by highlighting TG as the primary contributor to the observed associations. Long-term CVAI monitoring is of significant importance for early identification and prevention of CMD, with significant implications for clinical practice.

Abstract Background The pathogenesis of osteoarthritis (OA) involves the progressive degradation of articular cartilage. Exosomes derived from mesenchymal stem cells (MSC-EXOs) have been shown to mitigate joint pathological injury by attenuating cartilage destruction. Optimization the yield and therapeutic efficacy of exosomes derived from MSCs is crucial for promoting their clinical translation. The preconditioning of MSCs enhances the therapeutic potential of engineered exosomes, offering promising prospects for application by enabling controlled and quantifiable external stimulation. This study aims to address these issues by employing pro-inflammatory preconditioning of MSCs to enhance exosome production and augment their therapeutic efficacy for OA. Methods The exosomes were isolated from the supernatant of infrapatellar fat pad (IPFP)-MSCs preconditioned with a pro-inflammatory factor, TNF-α, and their production was subsequently quantified. The exosome secretion-related pathways in IPFP-MSCs were evaluated through high-throughput transcriptome sequencing analysis, q-PCR and western blot analysis before and after TNF-α preconditioning. Furthermore, exosomes derived from TNF-α preconditioned IPFP-MSCs (IPFP-MSC-EXOsTNF−α) were administered intra-articularly in an OA mouse model, and subsequent evaluations were conducted to assess joint pathology and gait alterations. The expression of proteins involved in the maintenance of cartilage homeostasis within the exosomes was determined through proteomic analysis. Results The preconditioning with TNF-α significantly enhanced the exosome secretion of IPFP-MSCs compared to unpreconditioned MSCs. The potential mechanism involved the activation of the PI3K/AKT signaling pathway in IPFP-MSCs by TNF-α precondition, leading to an up-regulation of autophagy-related protein 16 like 1(ATG16L1) levels, which subsequently facilitated exosome secretion. The intra-articular administration of IPFP-MSC-EXOsTNF−α demonstrated superior efficacy in ameliorating pathological changes in the joints of OA mice. The preconditioning of TNF-α enhanced the up-regulation of low-density lipoprotein receptor-related protein 1 (LRP1) levels in IPFP-MSC-EXOsTNF−α, thereby exerting chondroprotective effects. Conclusion TNF-α preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of IPFP-MSCs derived exosomes in the treatment of OA. Graphical Abstract

Abstract Lettuce (Lactuca sativa L., Asteraceae) is one of the most important vegetable crops, known for its various horticultural types and significant morphological variation. The first reference genome of lettuce, a crisphead type (L. sativa var. capitata cv. Salinas), was previously released. Here, we reported a near-complete chromosome-level reference genome for looseleaf lettuce (L. sativa var. crispa). PacBio high-fidelity sequencing, Oxford Nanopore, and Hi-C technologies were employed to produce genome assembly. The final assembly is 2.59 Gb in length with a contig N50 of 205.47 Mb, anchored onto nine chromosomes, containing 14 recognizable telomeres and only 11 gaps. Repetitive sequences account for 77.11% of the genome, and 41,375 protein-coding genes were predicted, with 99.10% of these assigned functional annotations. This chromosome-level genome enriched genomic resources for various horticultural types of lettuce and will facilitate the characterization of morphological variation and genetic improvement in lettuce.

Abstract Alkoxycarbonylation reactions are common in the chemical industry, yet process sustainability is limited by the inefficient utilization of CO. In this study, we address this issue and demonstrate that significant improvements can be achieved by adopting a heterogeneously catalyzed process, using a Ru/NbOx catalyst. The Ru/NbOx catalyst enables the direct synthesis of methyl propionate, a key industrial commodity, with over 98% selectivity from CO, ethylene and methanol, without any ligands or acid/base promoters. Under ambient CO pressure, a high CO utilization efficiency (336 mmolestermolCO −1h−1) is achieved. Mechanistic investigations reveal that CO undergoes a methoxycarbonyl (COOCH3) intermediate pathway, attacking the terminal carbon atom of alkene and yielding linear esters. The origins of prevailing linear regioselectivity in esters are revealed. The infrared spectroscopic feature of the key COOCH3 species is observed at 1750 cm−1 (C=O vibration) both experimentally and computationally. The broad substrate applicability of Ru/NbOx catalyst for ester production is demonstrated. This process offers a sustainable and efficient approach with high CO utilization and atom economy for the synthesis of esters.

Early identification and treatment of stroke can greatly improve patient outcomes and quality of life. Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale (CPSS) and the Face Arm Speech Test (FAST) are commonly used for stroke screening, accurate administration is dependent on specialized training. In this study, we proposed a novel multimodal deep learning approach, based on the FAST, for assessing suspected stroke patients exhibiting symptoms such as limb weakness, facial paresis, and speech disorders in acute settings. We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements, facial expressions, and speech tests based on the FAST. We compared the constructed deep learning model, which was designed to process multi-modal datasets, with six prior models that achieved good action classification performance, including the I3D, SlowFast, X3D, TPN, TimeSformer, and MViT. We found that the findings of our deep learning model had a higher clinical value compared with the other approaches. Moreover, the multi-modal model outperformed its single-module variants, highlighting the benefit of utilizing multiple types of patient data, such as action videos and speech audio. These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke, thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

The ACP100 is a small modular reactor (SMR) designed and built in China, featuring an integrated primary loop and passive safety systems. In SMRs, the interaction between the reactor coolant system, containment vessel, and other systems is highly interdependent. Therefore, it is necessary to use high-precision analysis codes, which can be achieved by coupling multiple codes. This paper is the first part of a study which investigates the LOCA in the ACP100 using a coupled platform. In this paper, a coupling platform was developed for transient analysis of SMR accidents, based on the system code NUSOL-SYS and the Integrated Severe Accident Analysis (ISAA) code. An inter-process communication module was developed adopting shared memory and event objects to exchange data between the two codes. A coupling interface defining the data to be exchanged was proposed. Both NUSOL-SYS and ISAA were modified to perform synchronous time step control. The coupling platform were validated through a hypothetical scenario and Edwards’ pipe blowdown experiment, demonstrating exact consistency and high accuracy. This coupling platform offers a new method for SMR accident analysis, providing a foundation for future work.

Cochlear implantation (CI) offers a dependable treatment for sensorineural hearing loss, with precision electroacoustic stimulation parameters showing great potential in improving auditory outcomes in CI patients. Here, we report the attachment of MXene into CI systems which effectively mimic the neural electrode interface due to MXene's excellent electrical conductivity and biocompatibility. Low-frequency short-term biphasic electrical pulses emitted by the MXenes-based CI promoted the outgrowth of spiral ganglion neuron (SGN) neurites and growth cones, substantially boosting the calcium activity in SGNs. This study lays a theoretical foundation for the precision medicine approaches in CI patient care, and informs the selection of materials for cochlear implant electrode materials in the future.

Abstract NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. Although the underlying mechanisms remain unclear, this form of LTD cannot be induced by low-frequency stimulation (LFS) in adult mice. In this study, we found that LFS-induced LTD was not easily induced in adult animals and was age dependent. Interestingly, the level of the 5-HT1A receptor was correspondingly increased and exhibited an inverse correlation with the magnitude of LFS-LTD during development. Knockout or pharmacological inhibition of the 5-HT1A receptor reversed impaired LFS-LTD in adult mice (P60), while activation or inhibition of this receptor disturbed or enhanced LFS-LTD in adolescent mice (P21), respectively. Furthermore, the astrocytic 5-HT1A receptor in the hippocampus predominantly mediated age-dependent LFS-LTD through enhancing GABAergic neurotransmission. Finally, fear memory extinction differed among the above conditions. These observations enrich our knowledge of LTD at the cellular level and suggest a therapeutic approach for LTD-related psychiatric disorders.

Abstract Osteoarthritis (OA) is a chronic degenerative disease characterized by articular cartilage destruction and subchondral bone reconstruction in the early stages. Bergenin (Ber) is a cytoprotective polyphenol found in many medicinal plants. It has been proven to have anti-inflammatory, antioxidant, and other biological activities, which may reveal its potential role in the treatment of OA. This study aimed to determine the potential efficacy of Ber in treating OA and explore the possible underlying mechanism through network pharmacology and validation experiments. The potential co-targets and processes of Ber and OA were predicted by using network pharmacology, including a Venn diagram for intersection targets, a protein‒protein interaction (PPI) network to obtain key potential targets, and GO and KEGG pathway enrichment to reveal the probable mechanism of action of Ber on OA. Subsequently, validation experiments were carried out to investigate the effects and mechanisms of Ber in treating OA in vitro and vivo. Ber suppressed IL-1β-induced chondrocyte apoptosis and extracellular matrix catabolism by inhibiting the STAT3, NF-κB and Jun signalling pathway in vitro. Furthermore, Ber suppressed the expression of osteoclast marker genes and RANKL-induced osteoclastogenesis. Ber alleviated the progression of OA in DMM-induced OA mice model. These results demonstrated the protective efficacy and potential mechanisms of Ber against OA, which suggested that Ber could be adopted as a potential therapeutic agent for treating OA.

Abstract With the surge in Xinjiang jujube production, there has been a concurrent increase in storage losses, posing an ongoing challenge for farmers to preserve the freshness of the jujubes. To tackle this issue, a novel storage and freshness control system for jujubes, integrating Internet of Things technology, has been developed. The control system is centered around a programmable logic controller (PLC) and utilizes an HMI as the interface for human–computer interaction. It is structured with distinct layers, including equipment, transportation, and application layers. By integrating with the Internet of Things cloud platform, data transmission between the device layer and the cloud server is ensured through the use of the TCP/IP protocol over a 4G network. A mobile app enables remote control functionality for monitoring and managing the storage and preservation environment. Experimental results demonstrate the system's stable performance, enabling remote monitoring and convenient operation by management personnel during the jujube storage and preservation process. This contributes to enhancing automation levels in jujube storage, extending its storage cycle while maintaining quality standards, thus providing valuable insights into intelligent fruit and vegetable storage practices in Xinjiang.

Abstract Previous research has established associations between amygdala functional connectivity abnormalities and major depressive disorder (MDD). However, inconsistencies persist due to limited sample sizes and poorly elucidated transcriptional patterns. In this study, we aimed to address these gaps by analyzing a multicenter magnetic resonance imaging (MRI) dataset consisting of 210 first-episode, drug-naïve MDD patients and 363 age- and sex-matched healthy controls (HC). Using Pearson correlation analysis, we established individualized amygdala functional connectivity patterns based on the Automated Anatomical Labeling (AAL) atlas. Subsequently, machine learning techniques were employed to evaluate the diagnostic utility of amygdala functional connectivity for identifying MDD at the individual level. Additionally, we investigated the spatial correlation between MDD-related amygdala functional connectivity alterations and gene expression through Pearson correlation analysis. Our findings revealed reduced functional connectivity between the amygdala and specific brain regions, such as frontal, orbital, and temporal regions, in MDD patients compared to HC. Importantly, amygdala functional connectivity exhibited robust discriminatory capability for characterizing MDD at the individual level. Furthermore, we observed spatial correlations between MDD-related amygdala functional connectivity alterations and genes enriched for metal ion transport and modulation of chemical synaptic transmission. These results underscore the significance of amygdala functional connectivity alterations in MDD and suggest potential neurobiological mechanisms and markers for these alterations.

Abstract Roberts syndrome (RBS) is an autosomal recessive disorder with profound growth deficiency and limb reduction caused by ESCO2 loss-of-function variants. Here, we elucidate the pathogenesis of limb reduction in an Esco2 fl/fl;Prrx1-Cre Tg/0 mouse model using bulk- and single-cell-RNA-seq and gene co-expression network analyses during embryogenesis. Our results reveal morphological and vascular defects culminating in hemorrhage of mutant limbs at E12.5. Underlying this abnormal developmental progression is a pre-apoptotic, mesenchymal cell population specific to mutant limb buds enriched for p53-related signaling beginning at E9.5. We then characterize these p53-related processes of cell cycle arrest, DNA damage, cell death, and the inflammatory leukotriene signaling pathway in vivo. In utero treatment with pifithrin-α, a p53 inhibitor, rescued the hemorrhage in mutant limbs. Lastly, significant enrichments were identified among genes associated with RBS, thalidomide embryopathy, and other genetic limb reduction disorders, suggesting a common vascular etiology among these conditions.

Abstract Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.

Abstract Deep learning models have been developed for various predictions in glioma; yet, they were constrained by manual segmentation, task-specific design, or a lack of biological interpretation. Herein, we aimed to develop an end-to-end multi-task deep learning (MDL) pipeline that can simultaneously predict molecular alterations and histological grade (auxiliary tasks), as well as prognosis (primary task) in gliomas. Further, we aimed to provide the biological mechanisms underlying the model’s predictions. We collected multiscale data including baseline MRI images from 2776 glioma patients across two private (FAHZU and HPPH, n = 1931) and three public datasets (TCGA, n = 213; UCSF, n = 410; and EGD, n = 222). We trained and internally validated the MDL model using our private datasets, and externally validated it using the three public datasets. We used the model-predicted deep prognosis score (DPS) to stratify patients into low-DPS and high-DPS subtypes. Additionally, a radio-multiomics analysis was conducted to elucidate the biological basis of the DPS. In the external validation cohorts, the MDL model achieved average areas under the curve of 0.892–0.903, 0.710–0.894, and 0.850–0.879 for predicting IDH mutation status, 1p/19q co-deletion status, and tumor grade, respectively. Moreover, the MDL model yielded a C-index of 0.723 in the TCGA and 0.671 in the UCSF for the prediction of overall survival. The DPS exhibits significant correlations with activated oncogenic pathways, immune infiltration patterns, specific protein expression, DNA methylation, tumor mutation burden, and tumor-stroma ratio. Accordingly, our work presents an accurate and biologically meaningful tool for predicting molecular subtypes, tumor grade, and survival outcomes in gliomas, which provides personalized clinical decision-making in a global and non-invasive manner.

Abstract Background The interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) bulk blasts and leukemic stem cells (LSCs), but not on normal hematopoietic stem cells (HSCs), providing an opportunity to target and eliminate the disease, while sparing normal hematopoiesis. Herein, we report the activity of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE) in AML. Methods Antibodies to IL1RAP were isolated from CD138+ B cells collected from the immunized mice by optoelectric positioning and single cell sequencing. Individual mouse monoclonal antibodies (mAbs) were produced and characterized, from which we generated BIF002, an anti-human IL1RAP/CD3 TCE using Fab arm exchange. Mutations in human IgG1 Fc were introduced to reduce FcγR binding. The antileukemic activity of BIF002 was characterized in vitro and in vivo using multiple cell lines and patient derived AML samples. Results IL1RAP was found to be highly expressed on most human AML cell lines and primary blasts, including CD34+ LSC-enriched subpopulation from patients with both de novo and relapsed/refractory (R/R) leukemia, but not on normal HSCs. In co-culture of T cells from healthy donors and IL1RAPhigh AML cell lines and primary blasts, BIF002 induced dose- and effector-to-target (E:T) ratio-dependent T cell activation and leukemic cell lysis at subnanomolar concentrations. BIF002 administered intravenously along with human T cells led to depletion of leukemic cells, and significantly prolonged survival of IL1RAPhigh MOLM13 or AML patient-derived xenografts with no off-target side effects, compared to controls. Of note, BiF002 effectively redirects T cells to eliminate LSCs, as evidenced by the absence of disease initiation in secondary recipients of bone marrow (BM) from BIF002+T cells-treated donors (median survival not reached; all survived > 200 days) compared with recipients of BM from vehicle- (median survival: 26 days; p = 0.0004) or isotype control antibody+T cells-treated donors (26 days; p = 0.0002). Conclusions The novel anti-IL1RAP/CD3 TCE, BIF002, eradicates LSCs and significantly prolongs survival of AML xenografts, representing a promising, novel treatment for AML.

Abstract Sodium is crucial for maintaining cardiovascular health, especially in relation to heart failure. The impact of baseline serum sodium concentrations on the outcomes of newly diagnosed coronary heart disease (CHD) without heart failure remains unclear. This prospective cohort study included 681 patients who were newly diagnosed with CHD. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to assess the relationship between serum sodium concentrations and major adverse cardiovascular events. The improvement in traditional prediction models by the addition of serum sodium concentrations was assessed using changes in the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During a median follow-up of 51.04 months (IQR: 40.88–53.80 months), 131 events were recorded. Multivariate Cox proportional hazards models showed that the L2 group (136–138.9 mmol/L) had the highest MACE risk. Compared to L2, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the L1 (130–135.9 mmol/L), L3 (139–140.9 mmol/L), L4 (141–142.9 mmol/L), and L5 (143–147.0 mmol/L) groups were 0.31 (0.14–0.70, P = 0.005), 0.48 (030–0.78, P = 0.003), 0.56 (0.34–0.92, P = 0.022), and 0.37 (0.22–0.64, P

Abstract Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality, with many patients facing poor prognosis, particularly those with metastatic or drug-resistant tumors. Homologous recombination genes (HRGs) are crucial in tumor progression and therapy resistance, but their clinical significance in LUAD is not well understood. In this study, we systematically characterize key HRGs in LUAD patients, identifying two distinct HR subtypes associated with different outcomes and biological functions. We establish a 5-gene scoring system (XRCC2, RAD51, BRCA1, FANCA, and CHEK1) that reliably predicts patient outcomes and immunotherapy responses in LUAD. Bioinformatics analysis and clinical validation highlight XRCC2 as a crucial biomarker in LUAD. Functional investigations through in vivo and in vitro experiments reveal the role of XRCC2 in promoting lung cancer migration and invasion. Mechanistically, XRCC2 stabilizes vimentin (VIM) protein expression through deubiquitylation. We predict c-MYC as a potential regulator of XRCC2 and demonstrate that inhibiting c-MYC with compound 10058-F4 reduces XRCC2 and VIM expression. Preclinical studies show the synergistic inhibition of metastasis in vivo when combining 10058-F4 with doxorubicin (Dox). Our findings present a potential personalized predictive tool for LUAD prognosis, identifying XRCC2 as a critical biomarker. The c-Myc-XRCC2-VIM axis emerges as a promising therapeutic target for overcoming lung metastasis. This study provides valuable insights into LUAD, proposing a prognostic tool for further clinical validation and unveiling a potential therapeutic strategy for combating lung metastasis by targeting c-Myc-XRCC2-VIM.

Abstract Natural killer (NK) cell-based therapies have made great progress in treating both hematological and solid tumors. Their unique mechanism of action does not rely on antigen presentation to recognize and eliminate tumor cells, making them a promising approach for cancer immunotherapy. In this review, we present a comprehensive summary of the latest clinical data of the novel NK cell-based therapies from the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting the potential of these advancements to revolutionize the treatment of hematologic malignancies and solid tumors.

Abstract Cochlear implants can directly activate the auditory system’s primary sensory neurons, the spiral ganglion neurons (SGNs), via circumvention of defective cochlear hair cells. This bypass restores auditory input to the brainstem. SGN loss etiologies are complex, with limited mammalian regeneration. Protecting and revitalizing SGN is critical. Tissue engineering offers a novel therapeutic strategy, utilizing seed cells, biomolecules, and scaffold materials to create a cellular environment and regulate molecular cues. This review encapsulates the spectrum of both human and animal research, collating the factors contributing to SGN loss, the latest advancements in the utilization of exogenous stem cells for auditory nerve repair and preservation, the taxonomy and mechanism of action of standard biomolecules, and the architectural components of scaffold materials tailored for the inner ear. Furthermore, we delineate the potential and benefits of the biohybrid neural interface, an incipient technology in the realm of implantable devices. Nonetheless, tissue engineering requires refined cell selection and differentiation protocols for consistent SGN quality. In addition, strategies to improve stem cell survival, scaffold biocompatibility, and molecular cue timing are essential for biohybrid neural interface integration. Graphical Abstract