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ABSTRACT Objective The failure rate of foot and ankle soft tissue defect reconstruction with flap is relatively high, often posing a significant burden on patients. The aim of this study is to explore the effectiveness of repeated stretch sutures in repairing skin and soft tissue defects of the ankle and foot. Methods Twenty‐three patients with ankle and foot skin and soft tissue defects were retrospectively analyzed between February 2016 and February 2019. Sutures were repeatedly stretched every 3–5 days. Local skin grafting was performed if necessary after wound surfaces disappeared or exposed tendons and bones were covered by soft tissue. Wound healing time, postoperative healing area, Vancouver Scar Assessment Scale, sensation, and function of the new skin were evaluated. Results Healing time was 17–35 (24.43 ± 5.29) days. Ten patients wholly healed, and 13 healed by approximately 70.08% ± 6.59%. The Vancouver Scar Assessment Scale average score was 2.83 ± 1.19 points, of which 15 cases were excellent (0–3 points) and 8 cases were good (4–7 points). The sensation and function of the new skin after repair were equivalent to those of normal skin after the last follow‐up. Conclusions Applying repeated tension sutures on the skin and soft defects of the ankle and foot reduced the skin graft area and decreased complex high‐risk surgical flaps' use and transplantation area.

Abstract Background Hippo‐avoidance prophylactic cranial irradiation (HA‐PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall‐off and compensate for setup errors. Most studies recommend a 5‐mm margin, while it could be optimized to a 2‐mm expansion. Here, we showed the details of optimized HA‐PCI for limited‐stage small cell lung cancer (LS‐SCLC). Methods This cohort study reviewed patients with LS‐SCLC receiving optimized HA‐PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo‐related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test—Revised (HVLT‐R) scores in different time points was conducted. The Kaplan–Meier method was used to calculate the survival rates. Results A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40–7.44) and 7.63 Gy (IQR: 7.14–8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric‐modulated arc therapy [VMAT]). The decline of HVLT‐R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow‐up of 52 months (95% CI: 47.2–56.7), the 2‐year overall survival and progression‐free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located

Objective The objective of this study was to unravel the genetic traits of Guanling cattle, pinpoint genes advantageous for muscle growth, and lay a foundation for the preservation of genetic diversity and further analysis of regulation mechanism of important economic traits in local cattle breed. Methods In this study, we sequenced the whole genome of 3 Guanling cattle in Guizhou province using the Illumina HiSeq cBo sequencing platform. And, high-multiplex polymerase chain reaction technology was employed to detect high-quality single nucleotide polymorphism (SNP) sites of other 55 Guanling cattle. Results Our study identified 166,411 non-synonymous SNPs (nsSNPs) and 42,423 insertions and deletions (indels). Through SNP annotation, gene function enrichment analysis, and comparing with Simmental, Angus, and Limousin cattle, we identified six genes (LEPR, AKAP9, SIX4, SPIDR, PRG4, FASN) which are potentially influential on meat quality traits, playing crucial roles in muscle growth, fat metabolism, and bodily support. We also examined polymorphisms at seven SNP sites in Guanling cattle and found that all seven were in Hardy–Weinberg equilibrium. Conclusion These findings suggested that these gene sites are stable and widespread in the Guanling cattle population. Our research lays the groundwork for future genetic enhancement and variety identification of Guanling cattle.

The artificial breeding of carp existed in China 8000 years ago. The breeding of carp played an important role in ancient Chinese history, and it still played a crucial role in modern aquaculture. The output of carp in China is very high, accounting for 8.42 % of the total output of freshwater products in 2023, ranking fifth in the total output of freshwater aquaculture fish. At the same time, carp is also the fish species with the highest number of new varieties bred in China. With the advent of the genomics era, breeding technologies have also made progress. This paper reviews the history and current status of carp farming, the germplasm resources of carp, and the application of fish genetic breeding technology in the germplasm innovation of carp.

Electric vehicles (EVs) have played a significant role in sustainability, and EVs fire accidents have raised doubts in recent years. To solve the mobile analytical equipment limitation in EVs fire accident and help staff receive prompt results at on-spot inspection, we provide a lightweight but accurate Transformer that can ideally adapt to the mobile environment. First, we built on the simple Segformer and extended it to aggregate the representations of amorphous objects, such as fire traces, in image recognition. Second, we used shunt-based self-attention (SSA) to enhance the model for capturing multi-scale contextual information and help distinguish the deformed level of EVs after combustion. Third, we redesigned a simple multi-level information aggregation (MIA) decoder to obtain the relationship between pixels in the channel dimensions by a weighted aggregation. Furthermore, to foster image trace recognition, we put forwards and evaluated the accuracy of models on electric vehicle fire traces (EVFTrace), a dataset of images of burnt EVs. On EVFTrace, the mean intersection over union (mIoU) achieves 72.24%. The float point operations (Flops) and parameters (Params) achieve 114.83 G and 89.5 M. Our model shows excellent efficiency and accuracy for burnt EVs segmentation tasks.

Gastric cancer (GC) is one of the most commonly diagnosed malignancies, threatening millions of lives worldwide each year. Importantly, GC is a heterogeneous disease, posing a significant challenge to the selection of patients for more optimized therapy. Over the last decades, extensive community effort has been spent on dissecting the heterogeneity of GC, leading to the identification of distinct molecular subtypes that are clinically relevant. However, so far, no tool is publicly available for GC subtype prediction, hindering the research into GC subtype-specific biological mechanisms, the design of novel targeted agents, and potential clinical applications. To address the unmet need, we developed an R package GCclassifier for predicting GC molecular subtypes based on gene expression profiles. To facilitate the use by non-bioinformaticians, we also provide an interactive, user-friendly web server implementing the major functionalities of GCclassifier. The predictive performance of GCclassifier was demonstrated using case studies on multiple independent datasets.

Endogenous benzoic acid causes detrimental effects on public health, but the underlying mechanisms often remain elusive. Benzoic acid (0.00–40.00 mg L−1) was detected from sixty fermented goat milk samples in six replicates, indicating the existence of endogenous benzoic acid. Herein, we investigated the effects of benzoic acid on the variations of metabolome and proteome signatures in fermented goat milk via integrative metabolomics (LOQ 2.39–98.98 μg L−1) and proteomics approach based on UHPLC-Q-Orbitrap HRMS. Explicitly, benzoic acid reduced the content of taurine (7.06–4.80 mg L−1) and hypotaurine (3.86–1.74 mg L−1) due to a significant decrease in the levels of glutamate decarboxylase 1 by benzoic acid. The reduction in lactose (7.13–5.31 mg L−1) and d-galactose (4.39–3.37 mg L−1) content was related to the decrease in α-lactalbumin and β-galactosidase levels, respectively, in fermented goat milk containing 40.00 mg L−1 benzoic acid. Meanwhile, the levels of maltose (22.84–16.53 mg L−1) and raffinose (4.19–3.10 mg L−1) progressively decreased with increasing benzoic acid concentrations (0.00–40.00 mg L−1), which had detrimental effects on the nutritional quality of fermented goat milk. Additionally, the concentration of benzoic acid and fermentation temperature are the most important factors to control the loss of nutrients in fermented dairy products.

Abstract Hydrogels are currently widely used in regenerative medicine and wound repair due to their superior biocompatibility, reliable mechanical strength, and good morphological memory. We aimed to prepare a self-expanding hydrogel that can be used as a skin expander for the repair of large soft skin tissue defects. Self-expanding hydrogels were prepared by chemical cross-linking, which consisted of water-soluble chitosan (CS), acrylamide (AM), methylene bisacrylamide (NMBA), etc. Five groups of in vitro experiments, including (CS-AM) of 0% (pure AM group), 13.9%, 27.8%, 41.7%, and 55.6%, were conducted to determine mechanical properties, swelling properties, cytotoxicity, etc. In the rat model, both a tight skin area (neck) and a loose skin area (back) were selected for expansion with hydrogels. A total of 27.8% of the CS-AM samples expanded stably under the skin of the rats, achieving 370% expansion in the tight zone and 490% expansion in the flaccid zone. Subcutaneous histopathological examination suggested that the inflammation index of the pericolloid tissue was lower in the CS-AM group than in the pure AM group. Our results demonstrate that self-expanding CS-AM hydrogels have great potential for application as skin expanders. Graphical Abstract

Abstract Spinal cord injury (SCI) involves a continuous and dynamic cascade of complex reactions, with mitochondrial damage and dysfunction-induced energy metabolism disorders playing a central role throughout the process. These disorders not only determine the severity of secondary injuries but also influence the potential for axonal regeneration. Given the critical role of energy metabolism disturbances in the pathology of SCI, strategies such as enhancing mitochondrial transport within axons to alleviate local energy deficits, or transplanting autologous or allogeneic mitochondria to restore energy supply to damaged tissues, have emerged as potential approaches for SCI repair. These strategies also aim to modulate local inflammatory responses and apoptosis. Preclinical studies have initially demonstrated that mitochondrial transplantation (MT) significantly reduces neuronal death and promotes axonal regeneration following spinal cord injury. MT achieves this by regulating signaling pathways such as MAPK/ERK and PI3K/Akt, promoting the expression of growth-associated protein-43 (GAP-43) in neurons, and inhibiting the expression of apoptosis-related proteins like Grp78, Chop, and P-Akt, thereby enhancing the survival and regeneration of damaged neurons. Additionally, MT plays a role in promoting the expression of vascular endothelial growth factor, facilitating tissue repair, and reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Furthermore, MT modulates neuronal apoptosis and inflammatory responses by decreasing the expression of p-JNK, a member of the MAPK family. In summary, by reviewing the detailed mechanisms underlying the cascade of pathological processes in SCI, we emphasize the changes in endogenous mitochondria post-SCI and the potential of exogenous MT in SCI repair. This review aims to provide insights and a basis for developing more effective clinical treatments for SCI. Graphical abstract

Abstract Background This study aimed to evaluate the ensiling characteristics, bacterial community structure, co-occurrence networks, and their predicted functionality and pathogenic risk in high-moisture oat (Avena sativa L.) silage. The oat harvested at heading stage (224 g/kg fresh weight) was spontaneously ensiled in plastic silos (10 L scale). Triplicate silos were opened after 1, 3, 7, 15, 30 and 60 days of fermentation, respectively. The bacterial community structure on day 3 and 60 were investigated using high-throughput sequencing technology, and 16S rRNA-gene predicted functionality and phenotypes were determined by PICRUSt2 and BugBase tools, respectively. Results After 60 days, the oat silage exhibited moderate fermentation quality, as indicated by large amounts of acetic acid (~ 50.4 g/kg dry matter (DM)) and lactic acid (~ 55.4 g/kg DM), relatively high pH (~ 4.79), acceptable levels of ammonia nitrogen (~ 75.2 g/kg total nitrogen) and trace amounts of butyric acid (~ 3.36 g/kg DM). Psychrobacter was prevalent in fresh oat, and Enterobacteriaceae and Lactobacillus dominated the bacterial community on day 3 and 60. Ensilage reduced the complexity of bacterial community network at the initial stage of fermentation. The bacterial functional pathways in fresh and ensiled oat are primarily characterized by the metabolism of carbohydrate and amino acid. During ensiling, the elevated pyruvate kinase and 1-phosphofructokinase levels were correlated with the lactic acid production, and the increased levels of 6-phosphogluconate dehydrogenase and ribulose-5-phosphate 3-epimerase may be responsible for the abundant acetic acid contents. Greater (P

Abstract Infectious disease is the result of interactions between host and pathogen and can depend on genetic variations in both. We conduct a genome-to-genome study of paired human and Mycobacterium tuberculosis genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR = 10.06, 95%CI: 4.87 − 20.77, P = 7.92 × 10−8) in the FLOT1 gene and a subclavaluee of Mtb Lineage 2. In a human macrophage infection model, we observe hosts with the rs3130660-A allele exhibited stronger interferon gene signatures. The interacting strains have altered redox states due to a thioredoxin reductase mutation. We investigate this association in a 2020 cohort of 699 patients recruited during the COVID-19 pandemic. While the prevalence of the interacting strain almost doubled between 2010 and 2020, its infection is not associated with rs3130660 in this recent cohort. These findings suggest a complex interplay among host, pathogen, and environmental factors in tuberculosis dynamics.

Abstract Hydrogen sulfide (H2S) is an important endogenous gasotransmitter, but the bioorthogonal reaction triggered H2S donors are still rare. Here we show one type of bioorthogonal H2S donors, sydnthiones (1,2,3-oxadiazol-3-ium-5-thiolate derivatives), which was designed with the aid of density functional theory (DFT) calculations. The reactions between sydnthiones and strained alkynes provide a platform for controllable, tunable and mitochondria-targeted release of H2S. We investigate the reactivity of sydnthiones‒dibenzoazacyclooctyne (DIBAC) reactions and their orthogonality with two other bioorthogonal cycloaddition pairs: tetrazine‒norbornene (Nor) and tetrazine‒monohydroxylated cyclooctyne (MOHO). By taking advantage of these mutually orthogonal reactions, we can realize selective labeling or drug release. Furthermore, we explore the role of H2S, which is released from the sydnthione-DIBAC reaction, on doxorubicin-induced cytotoxicity. The results demonstrate that the viability of H9c2 cells can be significantly improved by pretreating with sydnthione 1b and DIBAC for 6 h prior to exposure to Dox.

Abstract With the improvement of industry, the connectivity of electronic devices gradually shift from wired to wireless. As a solution for power delivery, the non-contact power transfer holds promising ways to charge for moving terminals, enabling battery-free sensing, processing, and communication. Based on a dual-band metasurface, this study proposes an adaptive wireless-powered network (AWPN) to realize the simultaneous wireless localization and non-contact power supply. It first achieves localization with 3 cm resolution on a single-input single-output (SISO) system, by combining space-time-coding (STC) and convolutional neural network (CNN). With precise position information, AWPN real-time aligns power beams to the terminals for stable energy transmission. Then, battery-free terminals enable to perceive the environmental data and uploads the results. From the measurement results, AWPN gets more than 98% CNN classification accuracy and can tolerate certain environmental changes. Thus, being adaptive and contactless, our study will propel the advancement in Internet of Things (IoT), intelligent metasurface, and the robot industry.

Abstract Background Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life. Methods This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life. Discussion If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications. Trial registration NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.

A novel equiatomic refractory AlNbTiVY high-entropy alloy containing rare earth elements was fabricated by vacuum arc melting. AlNbTiVY alloy possesses a dual-phase structure, consisting of a B2 ordered matrix and an Orthorhombic structured Y2Al second phase. The alloy has a dendritic microstructure with a density of only 5.18 g/cm3. As the testing temperature increases, the compressive yield strength of the alloy gradually decreases from 1104 MPa at room temperature to 321 MPa at 800 °C, with improved deformability and no fracture occurring in the 800 °C environment. Based on the insights of physics, a simple calculation was conducted on the temperature-dependent model of the alloy, and the theoretical application temperature of the alloy was predicted to exceed 600 °C.

Objective: This study aimed to review the relationship between job embeddedness and turnover intentions among nurses and explore the effects of the Job Embeddedness Scale, number of years in the career, education, and marital status on this relationship. Methods: The review was conducted by searching the China Knowledge Resource Integrated Database (CNKI), Weipu Database (CQVIP), China Biology Medicine (CBM), Wanfang Database, PubMed, Web of Science, Embase, CINAHL, and APA-PsycNet for articles on nurses’ job embeddedness and turnover from intention up to March 2024. The research quality was evaluated using the Agency for Healthcare Research and Quality (AHRQ) assessment criteria. The review protocol has been registered on PROSPERO [CRD42023483947]. Results: The results of this review included 47 studies consisting of 15,742 nurses from seven countries worldwide. A moderate negative correlation was found between job embeddedness and turnover intention (r = -0.487). Furthermore, on-the-job embeddedness (r = -0.527) was more negatively associated with turnover intention than off-the-job embeddedness (r = -0.234). The highest negative correlation was found between sacrifice and turnover intention (r = -0.460), while the lowest was for the link (r = -0.185). Furthermore, the relationship between job embeddedness and its dimensions with turnover intention was affected by different job embeddedness scales, number of years in the career, education, and marital status (P

Abstract Invasion and metastasis are the main reasons for the poor prognosis of patients with cervical cancer(CC). SYK is closely related to tumor development. However, the functions of its two isoforms, SYK (L) or SYK (S), are not fully understood to date. In this study, we investigated their biologic functions and possible prognostic values in CC. qRT-PCR was performed to detect the expression of SYK and two variant isoforms in cervical cancer tissues and cells. The association of SYK(L) and SYK(S) with Clinical pathological parameters were evaluated. The migration and invasion was detected by scratch assay and transwell. Western blot was conducted to measure the changes of epithelial mesenchymal transition (EMT)-related markers and PI3K/AKT signaling pathway proteins in cervical cancer cells. LY294002 (inhibitor of PI3K/AKT pathway) and IGF-1 (activator of PI3K/AKT pathway) were applied to evaluate the contribution of PI3K/AKT signaling pathway in cervical cancer cells. The expression of SYK(S) in cervical cancer tissues was significantly higher than that of SYK(L). SYK(L) and SYK(S) were correlated with muscular infiltration, SYK(L) high expression had a better prognosis, whereas SYK(S) high expression predicted a worse disease outcome. Cox multivariate regression analysis demonstrated that SYK(L) expression was an independent prognostic factor. SYK(L) significantly inhibited the proliferation, migration and invasion, while SYK(S) showed the opposite effects. LY294002 blocked SYK (L) knockdown-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas IGF-1 rescued the decreased migration, invasion and EMT induced by SYK (S) knockdown. The results suggest that SYK(L) and SYK(S) are involved in the progression of cervical cancer through PI3K/AKT signaling pathway, and may serve as potential targets for clinical treatment of advanced cervical cancer.

Abstract Background The value of endoscopic septoplasty for patients with deviated nasal septum and allergic rhinitis has not been systematically summarized. This study aims to assess the impact of surgical intervention on quality of life through a meta-analysis. Methods We conducted a comprehensive search of PubMed, CNKI, EMBASE, and the Cochrane Library for studies on the treatment of patients with deviated nasal septum and allergic rhinitis up to 2024. Studies that were duplicates, lacked full text, had incomplete data, or involved animal experiments, commentaries, or systematic reviews were excluded. Meta-analysis was performed using STATA 16.0. Results The total nasal symptom score (TNSS) in patients who received endoscopic surgery was considerably reduced compared to those treated with spray therapy alone, indicating a significant improvement (SMD = -21.29, 95% CI: -26.26, -116.33). Classic symptoms of allergic rhinitis, including rhinorrhea (SMD=-9.97, 95% CI: -16.97, -2.98), nasal obstruction (SMD=-27.25, 95% CI: -41.12, -13.38), nasal itching (SMD=-10.32, 95% CI: -13.16, -7.48), and sneezing (SMD=-12.66, 95% CI: -14.99, -10.34), showed significant improvement. There was no significant difference in the incidence of complications between the two treatments (OR = 1.01, 95% CI: 0.49, 2.10). Conclusion Patients with a deviated nasal septum and allergic rhinitis benefit more from septoplasty. However, the procedure should be performed cautiously by experienced clinicians, taking into account the specific condition of the nasal septum.

Abstract Understanding the evolution of cooperation in multi-player games is of vital significance for natural and social systems. An important challenge is that group interactions often lead to nonlinear synergistic effects. However, previous models mainly focus on deterministic nonlinearity, where synergy or discounting effects occur under specific conditions, not accounting for uncertainty and stochasticity in real-world systems. Here, we develop a probabilistic framework to study the cooperative behavior in stochastic nonlinear public goods games. Through both analytical treatment and Monte Carlo simulations, we provide a comprehensive understanding of social dilemmas with stochastic nonlinearity in both well-mixed and structured populations. We find that increasing the degree of nonlinearity makes synergy more advantageous when competing with discounting, thereby promoting cooperation. Furthermore, we show that network reciprocity loses effectiveness when the probability of synergy is small. Moreover, group size exhibits nonlinear effects on group cooperation regardless of the underlying structure. Our findings thus provide insights into how stochastic nonlinearity influences the emergence of prosocial behavior.

Abstract Understanding precise structures of two-/three- dimensional (2D/3D) covalent organic polymers (COPs) through single-crystal X-ray diffraction (SCXRD) analysis is important. However, how to grow high-quality single crystals for 2D/3D COPs is of challenge due to poor reversibility and difficult self-correction of covalent bonds. In addition, the success of introducing tellurium into the backbone to construct 2D/3D COPs and obtaining their single crystals is rare. Here, utilizing the strategy that a heavy element (e.g., tellurium) can form dynamic linkages with a self-correction function, we develop a fast and universal method for growing large-sized single crystals (up to 500 µm) for 2D/3D COPs, especially for 2D COPs. Three 2D COPs and one 3D COP are harvested through dynamic -Te-O-P- bonds in two days, with structures clearly uncovered via the SCXRD analysis. These 2D/3D COPs also show promising photocatalytic activities (nearly 100% selectivity and 100% yield) in superoxide anion radical-mediated coupling of (arylmethyl)amines.

Abstract X-ray imaging with a large field of view (FOV) and high resolution is extremely important for Rayleigh–Taylor instability measurement with a small amplitude and high spatial frequency in laser inertial confinement fusion. We developed an advanced Kirkpatrick–Baez (AKB) microscope based on the quadratic-aberration theory to realize a large FOV and high resolution. This microscope was assembled and tested in a laboratory, and it was then successfully applied for imaging the hydrodynamic instability of a perturbation target in implosion experiments at the Shenguang-III prototype laser facility. Imaging results demonstrate that the AKB microscope can achieve an optimal resolution of ~ 0.53 μm and ~ 0.40 μm and a spatial resolution of

Abstract Objectives This study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). Materials and methods Patients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models’ performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis. Results The study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766–0.959), sensitivity of 88% (95% CI: 73.9–100), and specificity of 78.4% (95% CI: 63.6–90.2) in the testing cohort. This model outperformed single-modality models and the clinical model. Conclusion A multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT. Critical relevance statement Our research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy. Key Points After neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%. The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy. The multimodality radiomics can be helpful in personalized treatment of esophageal cancer. Graphical Abstract

Abstract Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with an unmet clinical need, but its epigenetic regulation remains largely undefined. By performing multiomic profiling, we recently revealed distinct super-enhancer (SE) patterns in different subtypes of breast cancer and identified a number of TNBC-specific SEs that drive oncogene expression. One of these SEs, TCOF1 SE, was discovered to play an important oncogenic role in TNBC. However, the molecular mechanisms by which TCOF1 SE promotes the expression of the TCOF1 gene remain to be elucidated. Here, by using combinatorial approaches of DNA pull-down assay, bioinformatics analysis and functional studies, we identified FOSL1 as a key transcription factor that binds to TCOF1 SE and drives its overexpression. shRNA-mediated depletion of FOSL1 results in significant downregulation of TCOF1 mRNA and protein levels. Using a dual-luciferase reporter assay and ChIP-qPCR, we showed that binding of FOSL1 to TCOF1 SE promotes the transcription of TCOF1 in TNBC cells. Importantly, our data demonstrated that overexpression of FOSL1 drives the activation of TCOF1 SE. Lastly, depletion of FOSL1 inhibits tumor spheroid growth and stemness properties of TNBC cells. Taken together, these findings uncover the key epigenetic role of FOSL1 and highlight the potential of targeting the FOSL1-TCOF1 axis for TNBC treatment.

Abstract Introduction This study aims to compare sagittal condylar inclination (SCI) measurements derived from three workflows: intraoral scan (IOS) aligned with cone-beam computed tomography (CBCT), IOS aligned with facial scan (FS), and a jaw motion analyzer (JMA) system, in a cohort of young individuals with established normal occlusion. Additionally, the study aims to identify sources contributing to variance in these measurement approaches. Methods Twenty-four healthy individuals exhibiting normal occlusion were enrolled in this clinical trial. The SCI was delineated using a virtual articulator (VA) by aligning IOS with both CBCT and FS, creating two distinct workflows labeled CBCT-IOS and FS-IOS, respectively. Concurrently, SCI measurements were also acquired using a JMA. The normality of data distribution for the difference in bilateral SCI measurements within each workflow was tested using the Shapiro-Wilk test. Depending on the outcomes of this test, we utilized either a paired-sample T-test or Wilcoxon test for bilateral SCI comparisons. The inter-workflow differences were assessed using the Kruskal-Wallis H test. Bland-Altman plots were assess the interchangeability and consistency across each pair of digital methods and to evaluate the aggregate consistency among the trio of digital approaches. Results The analysis revealed that the CBCT-IOS workflow yielded the lowest average SCI measurements, whereas the JMA workflow produced the highest values. No significant differences were found in the SCI measurements between the left and right sides obtained by CBCT-IOS and JMA (P > .05), with the exception of the FS-IOS workflow (P = .002). Additionally, inter-flow comparisons revealed no significant differences in SCI measurements (P > .05), except when contrasting the SCI as measured by CBCT-IOS and JMA (P = .0131). The Bland-Altman plots demonstrated a high degree of consistency and 95% limits of agreement across the three digital workflows. Conclusion SCI measurements obtained from the three digital workflows exhibit a high degree of consistency and are interchangeable, affirming their clinical applicability for precise SCI assessment in young individuals with normal occlusion.

Abstract The role of collagen and its receptor, discoidin domain receptor 1 (DDR1) in immune response of colorectal cancer (CRC) remains unclear. We identified DDR1 as a promising target of immunotherapy resistance using a pooled in vivo CRISPR/sgRNA screening in microsatellite stable (MSS) CRC mouse models. Our findings demonstrated that knockdown or inhibition of DDR1 could enhance infiltration of CD8+ T cells and sensitize MSS CRC to PD-1 blockade. Furthermore, DDR1 was found to facilitate kinase domain phosphorylation, upregulate EZH2, consequently elevating H3K27me3 levels at the CXCL10 promotor, which led to the suppression of CXCL10 transcription once bound to collagen in ECM. Lastly, DDR1 was found positively correlated with collagen I expression in MSS CRC specimens. These findings indicated that targeting DDR1 or its inhibitor 7rh might be potential strategy for overcoming immunotherapy resistance in MSS CRC.

Abstract Background Stereotactic body radiation therapy (SBRT) has been widely used for pancreatic cancer. However, there is still a lack of studies comparing the latest SBRT techniques in terms of clinical efficacy and safety. Objectives: This study aims to evaluate three latest SBRT delivery platforms: CyberKnife (CK), Tomography Radixact (TOMO), and Halcyon volume rotation intensity modulation therapy (VMAT) for the treatment of pancreatic cancer. Methods Sixteen patients with pancreatic cancer treated with CK were retrospectively analyzed. SBRT plans were designed using Precision and Eclipse software. CK plans were optimized in two forms: fixed collimator (CK-Fixed) and multi-leaf grating collimator (CK-MLC). TOMO plans were designed with 2.5 cm Fixed Jaw, pitch 0.123–0.43 and 4.0 modulation factors in precision system. In Eclipse 15.6 system, photon optimizer (OP) algorithm was used to design the coplanar two-arc Halcyon VMAT. The median radiation dose was 40 Gy (35–45 Gy) in 5 fractions. The effectiveness of clinical treatment was evaluated by comparing the homogeneity index (HI), conformity index (CI), coverage of the planning target volume (PTV) and dose distribution parameters of organs at risk (OAR). Results All plans met the limits of clinical target dose and OAR. CK-MLC plans had the lowest maximum dose of 2 cm normal tissue from PTV margin (D2cm), indicating a low risk of peripheral radiation damage. Additionally, the CK-MLC plans had the lowest dose parameters and provided the best protection for the kidney, spinal cord, small intestine, and duodenum, with a paired t-test p

Abstract Electrocatalysts are extensively employed to suppress the shuttling effect in lithium-sulfur (Li-S) batteries. However, it remains challenging to probe the sulfur redox reactions and mechanism at the electrocatalyst/LiPS interface after the active sites are covered by the solid discharge products Li2S/Li2S2. Here, we demonstrate the intrinsic autocatalytic activity of the Li2S (100) plane towards lithium polysulfides on single-atom nickel (SANi) electrocatalysts. Guided by theoretical models and experimental data, it is concluded that LiPS dissociates into Li2S2 and short-chain LiPS on the Li2S (100) plane. Subsequently, Li2S2 undergoes further lithiation to Li2S on the Li2S (100) surface, generating a new Li2S (100) layer, thus enabling the autocatalytic formation of a new Li2S (100) surface. Benefiting from the autocatalytic growth of Li2S, the concentration of LiPS in the electrolyte remains at a lower level, enabling Li-S batteries under high loading and low electrolyte conditions to exhibit superior electrochemical performance.

Abstract Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

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

Abstract Background Whether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods. Methods Our sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods. Results 420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p

Abstract The strength of natural clay can be improved with epoxy resins. However, nanoscale curing mechanisms remain poorly understood, which is essential for enhancing stability. In this study, molecular dynamics simulation was employed to calculate the quantity of interface hydrogen bonds, adsorption energy, radius of gyration, and mechanical properties of clay cured by diglycidyl ether of bisphenol-A epoxy resin (DGEBA), diglycidyl ether 4,4’-dihydroxy diphenyl sulfone (DGEDDS), and Aliphatic epoxidation of olefin resin (AEOR). Adsorption behavior and mechanical properties of the clay cured by three epoxy resins were investigated: (1) The chain structure of AEOR led to 18.2% more hydrogen bonds than DGEBA and 59.1% more than DGEDDS. (2) The simulated adsorption energies for DGEBA, DGEDDS, and AEOR with kaolinite were 92.59, 98.25, and 116.87 kcal·mol−1, respectively. (3) The bulk and shear modulus of kaolinite increased by 4.93% and 4.80% when using AEOR. The interface stability and mechanical properties of kaolinite were also improved through strong hydrogen bonds and high adsorption energy. (4) The improvement in Young’s modulus of kaolinite was most significant with AEOR, followed by DGEDDS. AEOR excelled in the Z direction, while DGEDDS excelled in the X and Y directions. This research provided a theoretical foundation to effectively improve the properties of clay using epoxy resins.

Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrOx NCs) which enable photo-regulated ROS generation and scavenging using near infrared (NIR) laser. Upon NIR laser irradiation, BSA-IrOx NCs exhibit enhanced photodynamic therapy, destroying biofilms and killing bacteria. When the NIR laser is off, the nanoclusters' antioxidant enzyme-like activities prevent inflammation and repair damaged tissue through ROS clearance. Transcriptomic and metabolomic analyses revealed that BSA-IrOx NCs inhibit bacterial nitric oxide synthase, blocking bacterial growth and biofilm formation. Furthermore, the nanoclusters repair impaired skin by strengthening cell junctions and reducing mitochondrial damage in a fibroblast model. In vivo studies using rat infected wound models confirmed the efficacy of BSA-IrOx NCs. This study presents a promising strategy for treating biofilm-induced infected wounds by regulating the ROS microenvironment, addressing the challenges associated with current ROS-based antibacterial approaches.

The year 2023 has become the warmest year on global record. As the Antarctic and Arctic are sensitive regions to global warming, the climate changes in 2023 in these regions have attracted widespread attention. In this study, using observations, reanalysis and remote sensing data, we reported detailed polar climate changes in 2023, including warming, sea ice, atmospheric composition and extreme events. Antarctic exhibited large east‒west regional differences and the coexistence of extreme warm and cold events. In Coats Land, Queen Maud Land and the Antarctic Peninsula, three and seven stations recorded the second and third highest autumn air temperatures in history, respectively. The Amundsen–Scott station experienced extreme warming event in July, with the temperature increasing by 40 °C in one day. Abnormal cooling was evident in the Ross Sea and neighboring regions which were predominantly winter (June–August) cold anomalies, with Marylin Station reaching the lowest winter temperature in history. The Arctic experienced the warmest summer after 1979, with an overall distribution of ‘warm land‒cold sea’ on annual average. Compared with the 1991–2020 average, the annual air temperature anomalies reached more than 2 °C in northern Canada and the Barents Sea–Kara Sea coast. Abnormal high summer temperature caused most severe wildfires in Canada on record and second largest daily cumulative melt area over the Greenland ice Sheet daily post-1979. Polar sea ice continued to decrease rapidly, with minimum sea ice extent in Antarctic and Arctic ranking the first and sixth lowest post-1979. For melt season, Arctic Ocean sea ice began to melt later in 2023 than the 2011–2023 average, and freeze onset was delayed due to high temperatures in summer and autumn. Additionally, the status of polar atmospheric greenhouse gases remains bleak, and major greenhouse gas concentrations continue to increase. The Antarctic ozone hole in 2023 formed approximately 10 d earlier and lasted longer than the 1979–2023 average, with a maximum daily area of 2.6 × 107 km2 on 21 September. This summary of polar climate changes in 2023 will help people better understand global climate change and draw attention to polar regions.

Abstract Objective Ulcerative colitis (UC) and Hashimoto’s thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. Methods We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran’s Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Results Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36–69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Conclusion Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells.

Objective To explore the approach to establish a temporal lobe epilepsy model via intraperitoneal pilocarpine injection in C57BL/6J mice, and to summarize behavioral indicators predicting successful modeling during the acute phase of epileptic seizures after pilocarpine administration, aiming to offer a practical mice model for future epilepsy research.MethodsThirty C57BL/6J substrain mice (primary subjects) and forty C57BL/6N substrain mice (control subjects) were selected to establish a temporal lobe epilepsy model by inducing seizures through a single intraperitoneal injection of pilocarpine. The mice from the two substrains were each divided into 3 groups, and were injected intraperitoneally with 300 mg/kg, 330 mg/kg, or 360 mg/kg of pilocarpine, respectively. Motor seizure behaviors were observed and compared between the two substrains of C57BL/6 mice post pilocarpine injection, and the spontaneous recurrent seizures (SRS) were continuously monitored from the 7th day after injection. On the 28th day post-injection, the mice were euthanized and the histopathological changes in their hippocampi were examined. ResultsAfter pilocarpine administration, C57BL/6N mice displayed characteristic motor seizures followed by the onset of status epilepticus (SE). Conversely, C57BL/6J mice showed fewer instances of typical motor seizure behavior and the subsequent SE. Instead, they more often exhibited systemic tremors lasting several seconds to tens of seconds following limb twitching. This behavior is classified as “severe seizure (SS)” in current study. Following intraperitoneal injection of 330 mg/kg and 360 mg/kg pilocarpine, C57BL/6J mice displaying SS during the acute phase of seizure might exhibit SRS after a latency period. The percentage of spontaneous seizures observed in C57BL/6J mice post-modeling (70%) was comparable to that seen in C57BL/6N mice (75%) which developed SRS subsequent to SE. C57BL/6J mice displayed characteristic pathological alterations associated with temporal lobe epilepsy in the hippocampi after 28 d following pilocarpine injection, including increased mossy fiber sprouting and neuronal death. ConclusionsWhen inducing an epilepsy model via intraperitoneal pilocarpine injection in C57BL/6J mice, the behavioral criteria to predict the successful establishment of the model could be either the occurrence of SE or the manifestation of SS.

Abstract Prostate cancer is one of the most common cancers in men and poses a significant threat to global male health. Traditional prostate cancer assessment methods have certain limitations, necessitating the identification of new prognostic factors and treatment targets. Our study revealed that low expression of the cornichon family AMPA receptor auxiliary protein 2 (CNIH2) gene was associated with a better progression-free survival rate in prostate cancer patients. The area under the receiver operating characteristic (ROC) curve (AUC) showed that the prognostic ability of the CNIH2 gene was high at 1, 3, and 5 years. The gene was an independent prognostic factor according to multivariate analysis. Functional verification experiments showed that knocking down the CNIH2 gene could inhibit the proliferation, migration and invasion of prostate cancer cells and could also inhibit tumor growth in nude mice. Our study is the first to reveal the important role of the CNIH2 gene in prostate cancer. This discovery provides a new research direction for individualized treatment and prognostic evaluation of prostate cancer.

Abstract Background In mouse models of atherosclerosis, knockout of the PLA2G2A gene has been shown to reduce the volume of atherosclerotic plaques. Clinical trials have demonstrated the potential of using the sPLA2 inhibitor Varespladib in combination with statins to reduce lipid levels. However, this approach has not yielded the expected results in reducing the risk of cardiovascular events. Therefore, it is necessary to further investigate the mechanisms of PLA2G2A. Methods Single-cell transcriptome data from two sets of carotid plaques, combined with clinical patient information. were used to describe the expression characteristics of PLA2G2A in carotid plaques at different stages. In order to explore the mechanisms of PLA2G2A, we conducted enrichment analysis, cell–cell communication analysis and single-cell regulatory network inference and clustering analyses. We validated the above findings at the cellular level. Results Our findings indicate that PLA2G2A is primarily expressed in vascular fibroblasts and shows significant cell interactions with macrophages in the early-stage, especially in complement and inflammation-related pathways. We also found that serum sPLA2 levels have stronger diagnostic value in patients with mild carotid artery stenosis. Subsequent comparisons of single-cell transcriptomic data from early and late-stage carotid artery plaques corroborated these findings and predicted transcription factors that might regulate the progression of early carotid atherosclerosis (CA) and the expression of PLA2G2A. Conclusions Our study discovered and validated that PLA2G2A is highly expressed by vascular fibroblasts and promotes plaque progression through the activation of macrophage complement and coagulation cascade pathways in the early-stage of CA.

Abstract Background Cashmere, named as “soft gold”, derives from the secondary hair follicles (SHFs) of cashmere goat which is vital to Northwest China’s economy. The cytodifferentiation stage (E120), mirroring the complete hair follicle (HF) structure of adult goats and marking a critical phase in SHF development. Therefore, this study aims to enhance the understanding of SHF development and its impact on fiber quality, informing breeding strategies. Results From the scRNA-seq data analysis, the intricate processes and transcriptional dynamics of inner layer cell differentiation of HFs were unveiled in this study. we identified nine cell populations during cytodifferentiation and key structures such as the hair shaft and inner root sheath. And we discovered three main inner layer lineages and seven subpopulations, clarifying their roles in specialization and signaling. Pseudotime mapping analysis showed cell evolution from early stage to mature stages marked by unique gene expressions, and the intermediate stage on the differentiation of each lineage was revealed. The identification and spatial localization of specific transcription factors, such as GATA3, LEF1 and PRDM1, as well as keratin genes highlight regulatory pathways involved in HF development, which was further validated by immunofluorescence. These findings suggested the potential strategies to improve fiber quality, and the discovery of diverse cell types and their developmental molecular mechanisms, particularly in this species-specific context, offered a nuanced view of the regulatory mechanisms driving HF development in cashmere goats. Conclusion Overall, these findings provide a systematic molecular atlas of skin, defining three major branches and cell states of inner layer cells of HF, and determining how the branch-specific transcription factors, keratins, and signals coordinate HF morphogenesis during cytodifferentiation stage. This research not only advances skin tissue research in goats but also holds broader implications for the understanding of HF regeneration and development across various species.

Abstract Cell-derived extracellular vesicles (EVs), which carry diverse biomolecules such as nucleic acids, proteins, metabolites, and lipids reflecting their cell of origin, are released under both physiological and pathological conditions. EVs have been demonstrated to mediate cell-to-cell communication and serve as biomarkers. EV-associated DNA (EV-DNA) comprises genomic and mitochondrial DNA (i.e., gDNA and mtDNA) fragments. Some studies have revealed that EV-DNA can represent the full nuclear genome and mitochondrial genome of parental cells. Furthermore, DNA fragments loaded into EVs are stable and can be transferred to recipient cells to regulate their biological functions. In this review, we summarized and discussed EV-DNA research advances with an emphasis on EV-DNA detection at the population-EV and single-EV levels, gene transfer-associated biological functions, and clinical applications as biomarkers for disease liquid biopsy. We hope that this review will provide potential directions or guidance for future EV-DNA investigations.

Abstract Background Adequate sleep and rest are essential for patient recovery; however, lack of sleep has become a common problem faced by Chinese patients during hospital stays. Reduced sleep is often associated with a higher risk of disease progression and is strongly associated with increased hospital stay. However, there is no specific tool in China to assess short-term insomnia caused by hospitalization. This study aimed to translate the Hospital-acquired Insomnia Scale (HAIS) into Chinese, test its applicability to Chinese inpatients through reliability and validity indicators, and investigate the potential influencing factors of hospital-acquired insomnia. Methods Psychometric analysis from a sample of 679 hospitalized patients to whom the HAIS questionnaire was applied. The structural validity was assessed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and the content validity of the scale was assessed using the content validity index. Cronbach’s alpha coefficient, split-half reliability and test–retest reliability were calculated to evaluate the internal consistency of the scale. Multiple stepwise linear regression analysis was conducted to determine the potential correlates of hospital-acquired insomnia. Results EFA supported a four-factor structure with factor loadings for all dimensions greater than 0.40. CFA showed good indicators of model fit. The content validity index of the scale was 0.94. the Cronbach’s alpha of the scale was 0.915, the split-half reliability coefficient was 0.819, and the retest reliability was 0.844. Gender, age, total hours of sleep during the night, medical insurance, length of hospital stay, perceived stress level, and perceptions about sleep explained 46.2% of the variance in hospital-acquired insomnia. Conclusion The Chinese version of HAIS has good psychometric characteristics and is an effective instrument for evaluating hospital-acquired insomnia. In addition, hospital-acquired insomnia is more common in women, of younger age, less than 5 h of sleep a night, without medical insurance, stressed, and patients with more misconceptions about sleep.

Abstract Background Tumor cells develop multiple mechanisms to facilitate their immune evasion. Identifying tumor-intrinsic factors that support immune evasion may provide new strategies for cancer immunotherapy. We aimed to explore the function and the mechanism of the tumor-intrinsic factor NPM1, a multifunctional nucleolar phosphoprotein, in cancer immune evasion and progression. Methods The roles of NPM1 in tumor progression and tumor microenvironment (TME) reprogramming were examined by subcutaneous inoculation of Npm1-deficient tumor cells into syngeneic mice, and then explored by CyTOF, flow cytometry, immunohistochemistry staining, and RNA-seq. The in-vitro T-cell killing of OVA-presenting tumor cells by OT-1 transgenic T cells was observed. The interaction of NPM1 and IRF1 was verified by Co-IP. The regulation of NPM1 in IRF1 DNA binding to Nlrc5, Ciita promoter was determined by dual-luciferase reporter assay and ChIP-qPCR. Results High levels of NPM1 expression predict low survival rates in various human tumors. Loss of NPM1 inhibited tumor progression and enhanced the survival of tumor-bearing mice. Npm1-deficient tumors showed increased CD8+ T cell infiltration and activation alongside the reduced presence of immunosuppressive cells. Npm1 deficiency increased MHC-I and MHC-II molecules and specific T-cell killing. Mechanistically, NPM1 associates with the transcription factor IRF1 and then sequesters IRF1 from binding to the Nlrc5 and Ciita promoters to suppress IRF1-mediated expression of MHC-I and MHC-II molecules in tumor cells. Conclusions Tumor-intrinsic NPM1 promotes tumor immune evasion via suppressing IRF1-mediated antigen presentation to impair tumor immunogenicity and reprogram the immunosuppressive TME. Our study identifies NPM1 as a potential target for improving cancer immunotherapy.

Abstract Background To estimate and compare the association between metabolically healthy overweight/obesity (MHO) and the risk of type 2 diabetes (T2DM) among different ethnic groups in southwest China, while also exploring possible ethnic differences. Methods This is a prospective cohort study of 6,820 participants in Southwest China. MHO was defined as body mass index (BMI) ≥ 24 kg/m2 and the presence of ≤ 1 component of metabolic syndrome. Cox proportional risk models were utilized to analyze the association between MHO and the risk of T2DM. Results The median follow-up time was 6.58 years, during which 708 new cases of T2DM were diagnosed. In the total population, after adjusting for confounding factors, MHO was found to increase the risk of T2DM compared to metabolically healthy normal weight (MHNW) individuals (HR = 1.49, 95% CI: 1.15–1.93). Subgroup analysis by ethnicity revealed that, MHO increased the risk of T2DM in the Han population (HR = 1.64, 95% CI: 1.21–2.23), however, the difference was not statistically significant in the ethnic minority population.The results of sensitivity analysis further supported the robustness of these findings. Meanwhile, stratified by sex, age, and urban/rural, it was found that ethnic differences in the association between MHO and T2DM still existed, however, it is important to note that the association between MHO and T2DM was not statistically significant in the Han population subgroup aged ≥ 45 years (p > 0.05). Conclusion MHO was associated with an increased risk of T2DM compared to MHNW, and there are ethnic differences. Future interventions need to be strengthened for Han Chinese key populations to reduce the risk of T2DM.

Abstract Background Transfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors. Methods Adult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion. Results The analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion. Conclusion High WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Abstract Elaborating and understanding disparities in the burden of cardiovascular disease attributable to high fasting plasma glucose is important to improve diabetes prevention and promote cardiovascular health. In this study, we pool data on 791,373 people aged 25 years and older from three population-based surveys, and estimate the burden of cardiovascular disease attributable to high fasting plasma glucose between 2010 and 2018 in China by age, sex, region and socio-demographic index. In 2018, an estimated total of 498.61 thousand (95% uncertainty interval 463.93 to 534.12) cardiovascular disease-related deaths are attributable to high fasting plasma glucose in China. High fasting plasma glucose accounts for 1076.09 years of life lost per 100,000 people (95% uncertainty interval 1026.88–1129.04) due to cardiovascular disease in 2018, with substantial variation across provinces. In 2018, the higher age-standardised cardiovascular disease mortality rate attributable to high fasting plasma glucose is observed in the high-middle socio-demographic index region and the middle socio-demographic index region. Nationally, compared to 2010, exposure to high fasting plasma glucose and population aging in 2018 are the primary drivers of increased fasting plasma glucose-related deaths due to cardiovascular disease. Findings of this study emphasize the importance of developing population-specific tailored measures in China and other regions with similar condition.

Abstract Oats (Avena sativa L.) are rich in nutrients and bioactive compounds, serving as a roughage source for ruminants. This study investigated the impact of lactic acid bacteria (LAB), cellulase (M), and their combinations (LM) on the fermentation quality and metabolic compounds of oat silage. Results demonstrated that all additive treatments significantly increased lactic acid content compared to the control group (P

Abstract Background Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. Methods This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. Discussion This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. Trial registration Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023.

Abstract Background Quantifying the professional ethical challenges that nurses encounter is crucial for both theoretical insights and practical outcomes. The objective of this research is to assess the psychometric properties of the Chinese adaptation of the Moral Distress Scale for Healthcare Professionals (MD-APPS). Methods In 2024, a survey approach was utilized to engage with several tertiary-level healthcare institutions throughout China. A cohort of 448 nursing professionals who satisfied the specified selection benchmarks was consequently incorporated into the study. To evaluate the scale's reliability and validity, methods including the Content Validity Index (CVI), Factor Analysis—both Exploratory (EFA) and Confirmatory (CFA)—alongside assessments of internal consistency and test-retest reliability were employed. Results Expert evaluations yielded an I-CVI of 0.90, suggesting good content validity for the MD-APPS's Chinese adaptation. Exploratory Factor Analysis (EFA) revealed a bi-dimensional framework with 7 components, explaining 56.34% of the cumulative variance. Confirmatory Factor Analysis (CFA) outcomes displayed a χ-square/df ratio of 1.542. The estimate for Robust RMSEA was 0.054, and the SRMR was ascertained to be 0.041. Indices for both Robust TLI and Robust CFI surpassed the 0.9 threshold, indicating an acceptable fit; this aspect was supported by a P-value (Chi-square) of 0.094. The internal consistency, measured by Cronbach's α, was found to be 0.74, while the test-retest reliability over a two-week period reached 0.964. These findings provide initial evidence for the psychometric properties of the Chinese MD-APPS. Conclusion The Chinese adaptation of the MD-APPS demonstrates promising initial psychometric properties, suggesting its potential suitability for exploring nurses' professional ethical challenges within the Chinese cultural context. This scale may facilitate the identification of diverse elements influencing nurses' professional ethics and the assessment of the ethical climate in nursing practices. However, further validation studies are needed to fully establish its psychometric robustness across various healthcare settings in China.

Abstract Background The use of forced-air warming (FAW) blankets is widely recognized for preventing shivering and hypothermia in patients under general anesthesia. Various types of products are currently available for hospitals, and we have conducted a preliminary evaluation of insulation equipment based on expert opinions and initial parameters. However, we lack real-world experiments and accurate clinical data to validate these parameters and the accuracy of our decision-making results. This study aims to confirm the effectiveness of different FAW systems by assessing the thermal protection and operational characteristics of the equipment in both experimental and clinical settings, thereby enhancing our evaluation database. Methods In the manikin test, we conducted six tests including heat distribution and heating rate, heater outlet temperature stability, etc. In the clinical study, patients were randomly assigned to four groups [Group A (Bair Hugger Therapy, 3 M, St. Paul, MN, USA; 63500); Group B (EQUATOR® level I, Smith Medical ASD, MN, USA; Snuggle Warm, SW-2013); Group C (Jiang Men Da Cheng Medical Devices Co., Ltd, China; IOB-006); and Group D (Shang Hai Nest Tech Medical Materials Co., Ltd, China; BH-017)], with each group comprising 30 individuals. At the start of anesthesia induction, the FAW blanket was activated and set to 43 °C until the completion of surgery. The primary endpoint was the average core body temperature during surgery. Secondary endpoints included hemodynamic and surgical variables, adverse events, and recovery metrics. Results In the manikin test, the observed results of the experimental parameters (heat distribution, air pressure difference, and hole observation test) for Group A are superior to those of the other groups. In the clinical study, although the mean perioperative core body temperature remained above 36 °C across all groups [Group A: 36.31 ± 0.04; Group B: 36.26 ± 0.06; Group C: 36.17 ± 0.03; Group D: 36.25 ± 0.05], patients in Group A maintained higher temperatures compared to the other groups (p