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Background: Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma. Methods: TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry. Results: TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP−/− CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP−/− mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP−/− mice and PYCR1−/− mice. Similar to TREMP−/− mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1−/− mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients. Conclusions: The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases.

Abstract Weakly supervised video anomaly detection aims to detect anomalous events with only video-level labels. In the absence of boundary information for anomaly segments, most existing methods rely on multiple instance learning. In these approaches, the predictions for unlabeled video snippets are guided by the classification of labeled untrimmed videos. However, these methods do not account for issues such as video blur and visual occlusion, which can hinder accurate anomaly detection. To address these issues, we propose a novel weakly supervised video anomaly detection method that fuses multimodal and multiscale features. Firstly, RGB and optical flow snippets are input into pre-trained I3D to extract appearance and motion features. Then, we introduce an Attention De-redundancy (AD) module, which employs an attention mechanism to filter out task-irrelevant redundancy in these appearance and motion features. Next, to mitigate the effects of video blurring and visual occlusion, we propose a Multi-scale Feature Learning module. This module captures long-term and short-term temporal dependencies among video snippets to provide global and local guidance for blurred or occluded video snippets. Finally, to effectively utilize the discriminative features of different modalities, we propose an Adaptive Feature Fusion module. This module adaptively fuses appearance and motion features based on their respective feature weights. Extensive experimental results demonstrate that our proposed method outperforms mainstream unsupervised and weakly supervised methods in terms of AUC. Specifically, our proposed method achieves 97.00% AUC and 85.31% AUC on two benchmark datasets, i.e., ShanghaiTech and UCF-Crime, respectively.

Abstract A multiscale regulation strategy has been demonstrated for synthetic energy storage enhancement in a tetragonal tungsten bronze structure ferroelectric. Grain refining and second-phase precipitation (perovskite phase) are introduced in the BaSrTiNb2-xTaxO9 ceramics by regulating the composition and sintering process. Disordered polarization and distribution, chemical inhomogeneity, and insulating boundary layers are achieved to provide the fundamental structural origin of the relaxation characteristic, high breakdown strength, and superior energy storage performance. Thus, an ultrahigh energy storage density of 12.2 J cm−3 with an low energy consumption was achieved at an electric field of 950 kV cm−1. This is the highest known energy storage performance in tetragonal tungsten bronze-based ferroelectric. Notably, this ceramic shows remarkable stability over frequency, temperature, and cycling electric fields. This work brings new material candidates and structure design for developing of energy storage capacitors apart from the predominant perovskite ferroelectric ceramics.

Abstract Background Early dissemination to distant organs accounts for the dismal prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Chronic, dysregulated, persistent and unresolved inflammation provides a preferred tumor microenvironment (TME) for tumorigenesis, development, and metastasis. A better understanding of the key regulators that maintain inflammatory TME and the development of predictive biomarkers to identify patients who are most likely to benefit from specific inflammatory-targeted therapies is crucial for advancing personalized cancer treatment. Methods This study identified cell-specific expression of CALB2 in human PDAC through single-cell RNA sequencing analysis and assessed its clinicopathological correlations in tissue microarray using multi-color immunofluorescence. Co-culture systems containing cancer-associated fibroblasts (CAFs) and patient-derived organoids (PDOs) in vitro and in vivo were employed to elucidate the effects of CALB2-activated CAFs on PDAC malignancy. Furthermore, CUT&RUN assays, luciferase reporter assays, RNA sequencing, and gain- or loss-of-function assays were used to unravel the molecular mechanisms of CALB2-mediated inflammatory reprogramming and metastasis. Additionally, immunocompetent KPC organoid allograft models were constructed to evaluate CALB2-induced immunosuppression and PDAC metastasis, as well as the efficacy of inflammation-targeted therapy. Results CALB2 was highly expressed both in CAFs and cancer cells and correlated with an unfavorable prognosis and immunosuppressive TME in PDAC patients. CALB2 collaborated with hypoxia to activate an inflammatory fibroblast phenotype, which promoted PDAC cell migration and PDO growth in vitro and in vivo. In turn, CALB2-activated CAFs upregulated CALB2 expression in cancer cells through IL6-STAT3 signaling-mediated direct transcription. In cancer cells, CALB2 further activated Ca2+-CXCL14 inflammatory axis to facilitate PDAC metastatic outgrowth and immunosuppression. Genetic or pharmaceutical inhibition of CXCL14 significantly suppressed CALB2-mediated metastatic colonization of PDAC cells in vivo and extended mouse survival. Conclusions These findings identify CALB2 as a key regulator of inflammatory reprogramming to promote PDAC metastatic progression. Combination therapy with αCXCL14 monoclonal antibody and gemcitabine emerges as a promising strategy to suppress distant metastasis and improve survival outcomes in PDAC with CALB2 overexpression.

Background The global prevalence of low back pain is gradually increasing, and it is the main cause of disability, sick leave, and unemployment, posing a heavy burden on individuals and society. Assessing the degree of disability in patients with chronic low back pain is crucial for evaluating the efficacy of clinical interventions and clinical epidemiology. The Roland-Morris Disability Questionnaire (RMDQ) is currently the main tool for evaluating disability in patients with low back pain, but the applicability of its measurement performance in the Chinese population remains unclear. Objective To evaluate the applicability of RMDQ in the Chinese population with low back pain and provide evidence for clinical practice and research application. Methods CNKI, Wanfang Data Knowledge Service Platform, SinoMed, PubMed, Embase and Web of Science were searched from inception to 2023-10-01, to establish a literature base for the performance of the low back pain scale, and then select research on the measurement performance of RMDQ from it. The measurement performance of the RMDQ scale was evaluated according to the COSMIN system evaluation guidelines, and the evidence evaluation level was used to grade the evidence. Results A total of six RMDQ documents were included, with insufficient methodological quality for RMDQ content validity and adequate measurement performance. The quality of internal consistency methodology was very good with uncertainty and measurement performance was adequate; the methodological quality of retesting was uncertain, and the measurement performance was sufficient; the methodological quality of measurement error was uncertain, and the measurement performance was sufficient; the methodological quality of criterion validity was uncertain, and the measurement performance was insufficient; hypothesis testing methodological quality was very good with uncertain, and the measurement performance was sufficient and uncertain; the quality of reactivity methodology was very good, with sufficient and insufficient, while the measurement performance was sufficient with insufficient. According to the GRADE evidence quality rating results, there is low quality evidence to prove uncertainty in content validity, and moderate quality evidence to prove sufficient retesting reliability and internal consistency; there is sufficient evidence of low quality to prove the measurement error and reactivity. There is very low quality evidence of insufficient calibration validity when using the Oswestry Dysfunction Index (ODI) and the Visual Analog Scale (VAS) as calibrators; hypothesis testing had moderate quality evidence of uncertainty. Conclusion The methodological quality of the RMDQ scale is not high, with acceptable measurement performanceand low quality of evidence, and needs to be used cautiously in clinical practice or trials of low back pain in China. Although there is sufficient evidence of moderate quality to prove the reliability and internal consistency of retesting, the research content and methods are not standardized. In future research, attention should be paid to standardization to more accurately assess its applicability in the Chinese population.

Abstract Atomically dispersed single atom (SA) and atomic cluster (AC) metallic materials attract tremendous attentions in various fields. Expanding monometallic SA and AC to multimetallic SA/AC composites opens vast scientific and technological potentials yet exponentially increasing the synthesis difficulty. Here, we present a general energy-selective-clustering methodology to build the largest reported library of carbon supported bi-/multi-metallic SA/AC materials. The discrepancy in cohesive energy results into selective metal clustering thereby driving the symbiosis of multimetallic SA or/and AC. The library includes 23 bimetallic SA/AC composites, and expanded compositional space of 17 trimetallic, quinary-metallic, septenary-metallic SA/AC composites. We chose bimetallic M1 SAM2 AC to demonstrate the electrocatalysis utility. Unique decoupled active sites and inter-site synergy lead to 8/47 mV overpotential at 10 mA cm−2 for alkaline/acidic hydrogen evolution and over 1000 h durability in water electrolyzer. Moreover, delicate modulations towards composition and configuration yield high-performance catalysts for multiple electrocatalysis systems. Our work broadens the family of atomically dispersed materials from monometallic to multimetallic and provides a platform to explore the complex composition induced unconventional effects.

Abstract The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Ae. albopictus, with Ae. aegypti being more competent. However, the underlying mechanisms remain unclear. Here, we find Ae. albopictus shows comparable vector competence to ZIKV/DENV with Ae. aegypti by blood-feeding after antibiotic treatment or intrathoracic injection. This suggests that midgut microbiota can influence vector competence. Enterobacter hormaechei_B17 (Eh_B17) is isolated from field-collected Ae. albopictus and conferred resistance to ZIKV/DENV infection in Ae. aegypti after gut-transplantation. Sphingosine, a metabolite secreted by Eh_B17, effectively suppresses ZIKV infection in both Ae. aegypti and cell cultures by blocking viral entry during the fusion step, with an IC50 of approximately 10 μM. A field survey reveals that Eh_B17 preferentially colonizes Ae. albopictus compared to Ae. aegypti. And field Ae. albopictus positive for Eh_B17 are more resistant to ZIKV infection. These findings underscore the potential of gut symbiotic bacteria, such as Eh_B17, to modulate the arbovirus vector competence of Aedes mosquitoes. As a natural antiviral agent, Eh_B17 holds promise as a potential candidate for blocking ZIKV/DENV transmission.

Abstract Systemic infection with Candida albicans poses a significant risk for people with weakened immune systems and carries a mortality rate of up to 60%. However, current therapeutic options have several limitations, including increasing drug tolerance, notable off-target effects, and severe adverse reactions. Over the past four decades, the progress in developing drugs to treat Candida albicans infections has been sluggish. This comprehensive review addresses the limitations of existing drugs and summarizes the efforts made toward redesigning and innovating existing or novel drugs through nanotechnology. The discussion explores the potential applications of nanomedicine in Candida albicans infections from four perspectives: nano-preparations for anti-biofilm therapy, innovative formulations of “old drugs” targeting the cell membrane and cell wall, reverse drug resistance therapy targeting subcellular organelles, and virulence deprivation therapy leveraging the unique polymorphism of Candida albicans. These therapeutic approaches are promising to address the above challenges and enhance the efficiency of drug development for Candida albicans infections. By harnessing nano-preparation technology to transform existing and preclinical drugs, novel therapeutic targets will be uncovered, providing effective solutions and broader horizons to improve patient survival rates. Graphical abstracts

Piezoelectric materials， as important functional materials， have been widely used in various fields of the national economy for the preparation of structural health detection devices. With the development of modern industrial technology， especially aerospace， nuclear energy， and intelligent manufacturing， various high-temperature conditions have put forward higher requirements for the performance of piezoelectric materials. Therefore， the development of high-temperature piezoelectric materials with excellent comprehensive performance and their application in sensor devices with higher service temperatures have received widespread attention from researchers. Fresnoite （Ba2TiSi2O8， BTS） crystal is a kind of promising piezoelectric material for high-temperature sensing applications due to its high electrical resistivity， low dielectric loss， and excellent piezoelectric properties. The preparation process of BTS crystal by Czochralski method， characterization of single crystal electro-elastic properties， phase transition regulation， and the research progress of surface acoustic wave sensors and high-temperature vibration sensors based on BTS piezoelectric crystal were introduced in this paper. Finally， the research and development of new high-temperature piezoelectric crystals and their sensors were summarized and presented.

To master the heat transfer performance of the condensers， a model based on convolutional neural network and bidirectional gated recurrent unit with attention mechanism （CNN-BiGRU-AT） is adopted to predict their heat transfer coefficients. Taking the condenser of a 1，000 MW unit in a power plant as the research subject， the condenser characteristics are first analyzed， and a theoretical model for calculating its heat transfer coefficients is constructed. Then， CNN is employed to extract the data features of factors influencing the heat transfer characteristics， while BiGRU is utilized to capture the long and short-term dependencies between the data. Finally， AT is used to highlight the important parts of the features， thereby constructing a prediction model for heat transfer coefficients based on CNN-BiGRU-AT. The analysis of the computational results indicates that compared to traditional theoretical calculations and BP （backpropagation） networks， as well as GRU networks， the computational results obtained using the CNN-BiGRU-AT model are more accurate and exhibit better regularity.

Abstract Rabbit meat is tender, high in protein, low in fat and cholesterol, and offers several nutritional benefits. However, it has a stronger taste and can be challenging to cook. The global rabbit industry has been developing steadily, and China's total rabbit meat production has exceeded half of the world's total production in 2021. Along with the progress of the production process, the meat of the nutrition and taste at the same time, to improve smell also can get better control, solved the problems met in rabbit meat production. This article discusses the attributes of rabbit meat and outlines the deodorization, texture adjustment, and water retention techniques currently used in rabbit meat processing, aiming to offer a theoretical foundation for the advancement of rabbit meat processing technology.

Abstract Background Osteo-sarcopenia (OS) has become a global public health problem and a frontier research problem, as a combination of sarcopenia (SP) and osteoporosis (OP) diseases. The clinical performances include muscle weakness, systemic bone pain, standing difficulty, even falls and fractures, etc., which seriously affect the patient’s life and work. The pathological mechanism of the OS may be the abnormal metabolism which disrupts the equilibrium stability of the musculoskeletal system. Therefore, this study combined vitamin D (Vit. D) and whole-body vibration training (WBVT) to intervene in subjects of OS, aiming to evaluate the effectiveness and safety of the diagnosis and treatment protocol and to explore the efficacy mechanism. Methods We propose a multicenter, parallel-group clinical trial to evaluate the efficacy and safety of Vit. D combined with WBVT intervention in OS. Subjects who met the inclusion or exclusion criteria and signed the informed consent form would be randomly assigned to the WBVT group, Vit. D group, or WBVT+ Vit. D group. All subjects will be treated for 1 month and followed up after 3 and 6 months. The primary outcomes are lumbar bone mineral density (BMD) and appendicular skeletal muscle mass (ASM) measured by dual-energy X-ray absorptiometry (DXA) and handgrip strength measured by grip strength meter. Secondary outcomes include serum markers of myostatin (MSTN), irisin and bone turnover markers (BTM), SARC-CalF questionnaire, 1-min test question of osteoporosis risk, patient health status (evaluated by the SF-36 health survey), physical performance measurement that includes 5-time chair stand test, 6-m walk, and the short physical performance battery (SPPB). Discussion If Vit. D combined with WBVT can well relieve OS symptoms without adverse effects, this protocol may be a new treatment strategy for OS. After therapeutic intervention, if the serum marker MSTN/irisin is significant, both have the potential to become sensitive indicators for screening OS effective drugs and treatments, which also indicates that WBVT combined with Vit. D plays a role in improving OS by regulating MSTN/irisin. Trial registration Chinese Clinical Trial Registry ChiCTR2400082269 . Registered on March 26, 2024.

Abstract We conducted a retrospective, observational study among acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis or talaromycosis to assess AmB formulations-related adverse events (AEs). Total 205 eligible patients were enrolled. Of them, 139 received AmB therapy, 51 received liposomal AmB (L-AmB) therapy, and 15 received AmB cholesteryl sulfate complex (ABCD) therapy. The incidences of total AEs between the AmB, L-AmB and ABCD group had no significant differences. The ABCD group had significantly higher incidences of hepatotoxicity and hematological toxicity than the AmB and L-AmB groups. The incidence of grade 3–4 hematological toxicity in the ABCD group was significantly higher than that in the AmB and L-AmB groups. Multinomial logistic regression models showed that compared with AmB, ABCD had a higher risk for the occurrence of grade 3–4 hematological toxicity (aOR = 43.924, 95%CI 6.296-306.418; p

Abstract Treatment of Mycobacterium abscessus (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti‐Mab drugs. In this study, we explored an intrinsic resistance mechanism through which Mab resists echinomycin (ECH). ECH showed activity against Mab at a minimum inhibitory concentration (MIC) of 2 µg/ml. A ΔembC strain in which the embC gene was knocked out showed hypersensitivity to ECH (MIC: 0.0078–0.0156 µg/ml). The MICs of ECH‐resistant strains screened with reference to ΔembC ranged from 0.25 to 1 µg/ml. Mutations in EmbB, including D306A, D306N, R350G, V555I, and G581S, increased the Mab's resistance to ECH when overexpressed in ΔembC individually (MIC: 0.25–0.5 µg/ml). These EmbB mutants, edited using the CRISPR/Cpf1 system, showed heightened resistance to ECH (MIC: 0.25–0.5 µg/ml). The permeability of these Mab strains with edited genes and overexpression was reduced, as evidenced by an ethidium bromide accumulation assay, but it remained significantly higher than that of the parent Mab. In summary, our study demonstrates that ECH exerts potent anti‐Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH. Mutation in EmbB may partially compensate for a loss of EmbC function.

Abstract Protein Disulfide-Isomerase A2 (PDIA2) is a gene that encodes proteins, responsible for protein folding and modification within cells. The development and course of many disorders are intimately linked to the aberrant expression of PDIA2. Nevertheless, more research is necessary to fully understand PDIA2’s biological significance in pan-cancer, notably in prostate cancer (PCa). PDIA2 expression is elevated in various tumors and closely related to patient prognosis. Patients with prostate cancer who express PDIA2 high in particular have a bad prognosis in terms of progression-free survival. In addition, the upregulation of PDIA2 expression in prostate cancer patients is accompanied by higher Gleason scores, advanced tumor staging, lymph node metastasis, and elevated PSA levels. Detailed experiments further demonstrate that PDIA2 is a carcinogenic gene affecting prostate cancer cells’ response to dasatinib therapy. For patients with prostate cancer, there is a clear positive connection between the expression level of PDIA2 and a bad prognosis. The prostate cancer treatment efficacy of dasatinib is hampered by PDIA2, which is intimately linked to the growth, invasion, and metastasis of PCa cells. In summary, our research highlights the potential of PDIA2 as a biomarker for the diagnosis and management of PCa.

Abstract Chemical derivatization is a powerful strategy to enhance sensitivity and selectivity of liquid chromatography-mass spectrometry for non-targeted analysis of chemicals in complex mixtures. However, it remains impossible to obtain large sets of reference spectra for chemically derived molecules (CDMs), representing a major barrier in real-world applications. Herein, we describe a deep learning approach that enables accurate prediction of electrospray ionization tandem mass spectra for CDMs (DeepCDM). DeepCDM is established by transfer learning from a generic spectrum predicting model using a small set of experimentally acquired tandem mass spectra of CDMs, which converts a generic model with low predictability for CDMs into a specialized model with high predictability. We demonstrate DeepCDM by predicting electrospray ionization tandem mass spectra of dansylated molecules. The success in establishing Dns-MS further enables the development of DnsBank, a dansylation-specialized in silico spectral library. DnsBank achieves significant increases of accurate annotation rates of dansylated molecules, facilitating discovery of new hazardous pollutants from an environmental study of leather industrial wastewater. DeepCDM is also highly versatile for other classes of CDMs. Therefore, we envision that DeepCDM will pave a way for high-throughput identification of CDMs in non-targeted analysis to dig unknowns with potential health impacts from emerging anthropogenic chemicals.

Abstract Background Qin-Yu-Qing-Chang decoction (QYQC), an herbal formula from China, is extensively employed to manage ulcerative colitis (UC) and exhibits potential benefits for colonic function. Nevertheless, the fundamental molecular mechanisms of QYQC remain largely uncharted. Methods The primary constituents of QYQC were determined utilizing UHPLC-MS/MS analysis and the effectiveness of QYQC was assessed in a mouse model of colitis induced by dextran sulfate sodium. Evaluations of colon inflammatory responses and mucosal barrier function were thoroughly assessed. RNA sequencing, molecular docking, colonic energy metabolism, and 16S rRNA sequencing analysis were applied to uncover the complex mechanisms of QYQC in treating UC. Detect the signal transduction of the peroxisome proliferator-activated receptor-γ (PPAR-γ) both in the nucleus and cytoplasm. Furthermore, a PPAR-γ antagonist was strategically utilized to confirm the functional targets that QYQC exerts. Results Utilizing UHPLC-MS/MS, the principal constituents of the nine traditional Chinese medicinal herbs comprising QYQC were systematically identified. QYQC treatment substantially ameliorated colitis in mice, as evidenced by the improvement in symptoms and the reduction in colonic pathological injuries. Besides, QYQC treatment mitigated the inflammatory response and improved mucosal barrier function. Furthermore, QYQC enhanced the mitochondria citrate cycle (TCA cycle) by triggering PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus. This prevented the unconstrained expansion of facultative anaerobes, particularly pathogenic Escherichia coli (E. coli, family Enterobacteriaceae) and thus improved colitis. Results of molecular docking indicated that the representative chemical components of QYQC including Baicalin, Paeoniflorin, Mollugin, and Imperatorin bound well with PPAR-γ. The impact of QYQC on colitis was diminished in the presence of a PPAR-γ antagonist. Conclusions In summary, QYQC ameliorates UC by activating PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus, which enhances the energy metabolism of intestinal epithelial cells and thereby preventing the uncontrolled proliferation of facultative anaerobes.

Abstract Background The transition of family caregivers of patients with end-of-Life cancer receiving palliative care from hospital to home is a complex and challenging process. This phase of care involves not only the physical and psychological health of the patient but also the role adaptation and emotional support of the family caregivers. To gain a deeper understanding of the various experiences and feelings during this process, we conducted a qualitative study. Methods This study employed a descriptive phenomenological research method. The interviews focused on the specific experiences, challenges faced, support received, and coping strategies of family caregivers of patients with end-of-life cancer during the transition from hospital to home palliative care. All data were treated with strict confidentiality, and recordings and transcriptions were made with the participants’ consent. Results A total of 15 family caregivers participated. Four main themes and nine sub-themes were identified: complex transition process (anxiety about uncertainty, resistance to transition), discontinuity in care (insufficient discharge guidance, lack of continuous communication mechanisms), post-discharge continuous care needs (need for home care knowledge and skills, social and emotional support, grief counselling and death education), and personal growth and gains (enhanced coping ability, increased psychological resilience). Conclusion Family caregivers face numerous emotional, cognitive, practical, and social support challenges during the transition from hospital to home care. To improve the caregiving experience and quality of life, appropriate training and support should be provided to better meet the caregivers’ needs.

Abstract Hydrogels, characterised as highly hydrophilic three‐dimensional polymer networks, have gained increasing attention due to their unique physicochemical properties, finding applications in various fields. Natural polymer hydrogels exhibit higher biocompatibility and biodegradability compared to traditional synthetic polymer hydrogels. Proteins, being the principal materials of natural polymer hydrogels, bear numerous modifiable functional groups. The resultant hydrogel possesses responsiveness, adjustable degradability, and underway as an excellent biomaterial. Seven common raw materials used to construct protein hydrogels are introduced. In terms of comparing natural polymer hydrogels with traditional synthetic polymer hydrogels, the authors conduct a detailed analysis and comparison, highlighting the advantages of natural polymer hydrogels in terms of biocompatibility and biodegradability, and summarising their characteristics. The authors also address the limitations of various protein hydrogels and list existing strengthening cross‐linking strategies, proposing new insights to overcome the application limits of protein hydrogels. Additionally, the applications of protein hydrogels in drug delivery, biosensing, bio‐inks and tissue engineering are discussed. The authors conclude by summarising the current challenges faced by protein hydrogels and prospecting its future development.

Abstract Objective and methods To ascertain the connection between cuproptosis-related genes (CRGs) and the prognosis of hepatocellular carcinoma (HCC) via single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data, relevant data were downloaded from the GEO and TCGA databases. The differentially expressed CRGs (DE-CRGs) were filtered by the overlaps in differentially expressed genes (DEGs) between HCC patients and normal controls (NCs) in the scRNA-seq database, DE-CRGs between high- and low-CRG-activity cells, and DEGs between HCC patients and NCs in the TCGA database. Results Thirty-three DE-CRGs in HCC were identified. A prognostic model (PM) was created employing six survival-related genes (SRGs) (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) via univariate Cox regression analysis and LASSO. The predictive ability of the model was validated via a nomogram and receiver operating characteristic curves. Research has employed tumor immune dysfunction and exclusion as a means to examine the influence of PM on immunological heterogeneity. Macrophage M0 levels were significantly different between the high-risk group (HRG) and the low-risk group (LRG), and a greater macrophage level was linked to a more unfavorable prognosis. The drug sensitivity data indicated a substantial difference in the half-maximal drug-suppressive concentrations of idarubicin and rapamycin between the HRG and the LRG. The model was verified by employing public datasets and our cohort at both the protein and mRNA levels. Conclusion A PM using 6 SRGs (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) was developed via bioinformatics research. This model might provide a fresh perspective for assessing and managing HCC.

Abstract This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.

Abstract Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Abstract Among the fascinating phenomena observed in two-dimensional (2D) magnets, the magneto-exciton effect stands out as a pivotal link between optics and magnetism. Although the excitonic effect has been revealed and exhibits a considerable correlation with the spin structures in certain 2D magnets, the underlying mechanism of the magneto-exciton effect remains underexplored, especially under high magnetic fields. Here we perform a systematic investigation of the spin-exciton coupling in 2D antiferromagnetic NiPS3 under high magnetic fields. When an in-plane magnetic field is applied, the exceptional sharp excitonic emission at ~1.4756 eV exhibits a Zeeman-like splitting with g ≈ 2.0, experimentally identifying the exciton as an excitation of dominant triplet-singlet character. By examining the polarization of excitonic emission and simulating the spin evolution, we further verify the correlation between excitonic emission and Néel vector in NiPS3. Our work elucidates the mechanism behind the spin-exciton coupling in NiPS3 and establishes a strategy for optically probing the spin evolutions in 2D magnets.

Abstract BAP1, BRCA1-Associated Protein 1, serves as a novel tumor suppressor through the deubiquitination of monoubiquitination of H2A and subsequent gene transcriptional regulation. Regulated cell death like apoptosis or ferroptosis is considered an essential mechanism mediating tumor suppression. Previous reports, including ours, have demonstrated that BAP1 could promote apoptosis and ferroptosis to inhibit tumor development. Whether BAP1 regulated additional types of cell death remains unclear. Disulfidptosis is a recently identified novel cell death mode characterized by aberrant accumulation of intracellular disulfide (e.g., cystine) and depletion of NADPH. In this study, we first demonstrated that BAP1 could significantly protect disulfidptosis induced by glucose starvation, which is validated by various cell death inhibitors and the accumulation of disulfide bonds in the cytoskeleton proteins. BAP1 is known to inhibit SLC7A11 expression. We found that the protective effect of BAP1 against disulfidptosis was counteracted when overexpressing SLC7A11 or adding additional cystine. Conversely, BAP1-mediated suppression of disulfidptosis was largely abrogated when SLC7A11-mediated cystine uptake was inhibited by the knockout of SLC7A11 or erastin treatment. Besides, high BAP1 expression showed lower NADP+/NADPH levels, which might confer resistance to disulfidptosis. Consistent with these observations, the expression level of BAP1 was also positively correlated with NADPH-related genes in KIRC patients, though the underlying mechanism mediating NADPH regulation remains further investigation. In summary, our results revealed the role of BAP1 in the regulation disulfidptosis and provided new insights into the understanding of disulfidptosis in tumor development.

Rattus tanezumi (Niethammer, 1975) is one of the commensal rodent species in South China. With the development of transportation and climate change, R. tanezumi has gradually migrated north and become the dominant rat species for the past few years. In this study, we assembled a complete mitochondrial genome of R. tanezumi, captured from North China. The mitogenome contains 16,307 nucleotide pairs, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, as well as one non-coding control region. Based on whole mitogenome phylogenetical analysis showed that R. tanezumi captured from North China had a close phylogenetic relationship with that from Japan and South Korea. These findings are valuable for further studies on the evolution, genetic diversity, and taxonomy of Asian commensal rodent.

In this paper, the highland barley moisture, β-glucan, amylopectin and protein content rapid detection model was established based on the 4000~10000 cm−1 near-infrared spectrum and actual contents of 76 highland barleys. The results showed that SG convolution smoothing was the optimal spectral preprocessing method for the partial least squares (PLS) prediction model of moisture, amylopectin and β-glucan contents, while SG convolution smoothing+multiplicative scatter correction (MSC) was the optimal spectral preprocessing method for the PLS prediction model of protein content. In order to further improve the accuracy of the prediction model, the different characteristic wavelength selection algorithms including competitive adaptive reweighted sampling (CARS), successive projections algorithm (SPA) and variables combination population analysis and iterative retained information variable (VCPA-IRIV) were used on the prediction results of the model. The results showed that VCPA-IRIV treatment could effectively improve the determination coefficient of prediction of moisture, amylose and protein content prediction model, and reduce the root mean square error of prediction. The treatment of CARS had a remarkable effect on the prediction accuracy for the β-glucan content. Ultimately, the established prediction models of moisture, β-glucan, amylopectin and protein content for highland barley had good prediction accuracy with the appropriate Rp (0.9868, 0.9808, 0.9701 and 0.9879) and RMSEP (0.2042, 0.1846, 0.8135 and 0.2095) value, respectively. In conclusion, the rapid detection model of highland barley characteristic nutrient content based on near infrared spectroscopy established in this study had high accuracy, which would have certain guiding significance for processing enterprises to quickly understand the quality of raw materials and efficiently screen qualified raw materials.

The pitting mechanism of 7 series high-strength aluminum (Al) alloys (7xxx) is investigated experimentally and numerically (finite element method, FEM) by comparing the characteristics of passive films and pitting kinetics of two types of 7xxx Al alloys. The point defect model (PDM) is used to evaluate the passive film properties in the two varieties of 7xxx Al alloy, and the FEM is employed to calculate the point defect diffusion process in detail. The results reveal that the two 7xxx Al alloys exhibit various microstructures, particularly the 7xxx-1, characterized by a robust (111) fiber texture and a lower proportion of low-angle grain boundaries than the 7xxx-2. The diffusivity D of point defects in 7xxx-1 (3.85 × 10−18–52.74 × 10−18 cm2 s−1) is lower than that in 7xxx-2 (5.47 × 10−18–66.61 × 10−18 cm2 s−1) and the diffusion duration of 7xxx-1 is longer than 7xxx-2, which is closely associated with the rupture of passive film. Additionally, FEM proved that the initial shapes of pits dictate the progression of pitting, manifesting that the shallow dish shape grows laterally while the deep hole shape grows longitudinally.

Short chain fatty acids (SCFA) exist in dietary foods and are produced by the fermentation of gut microbiota, and are considered an important element for regulating host health. Through blood circulation, SCFA produced in the gut and obtained from foods have an impact on the intestinal health as well as vital organs of the host. It has been recognized that the gut is the “vital organ” in the host. As the gut microbial metabolites, SCFA could create an “axis” connecting the gut and to other organs. Therefore, the “gut-organ axes” have become a focus of research in recent years to analyze organism health. In this review, we summarized the sources, absorption properties, and the function of SCFA in both gut and other peripheral tissues (brain, kidney, liver, lung, bone and cardiovascular) in the way of “gut-organ axes”. Short chain fatty acids exert both beneficial and pathological role in gut and other organs in various ways, in which the beneficial effects are more pronounced. In addition, the beneficial effects are reflected in both preventive and therapeutic effects. More importantly, the mechanisms behinds the gut and other tissues provided insight into the function of SCFA, assisting in the development of novel preventive and therapeutic strategies for maintaining the host health.

Abstract In forensic genetics, utilizing massively parallel sequencing (MPS) to analyze short tandem repeats (STRs) has demonstrated several advantages compared to conventional capillary electrophoresis (CE). Due to the current technical limitations, although flanking region polymorphisms had been mentioned in several previous studies, most studies focused on the core repeat regions of STRs or the variations in the adjacent flanking regions. In this study, we developed an MPS system consisting of two sets of multiplex PCR systems to detect not only the STR core repeat regions but also to observe variants located at relatively distant positions in the flanking regions. The system contained 42 commonly used forensic STRs, including 21 autosomal STRs (A-STRs) and 21 Y-chromosomal STRs (Y-STRs), and a total of 350 male individuals from a Chinese Han population were genotyped. The length and sequence variants per locus were tallied and categorized based on length (length-based, LB), sequence without flanking region (core repeat regions sequence-based, RSB), and sequence with flanking region (core repeat and flanking regions sequence-based, FSB), respectively. Allele frequencies, Y-haplotype frequencies, and forensic parameters were calculated based on LB, RSB, and FSB, respectively, to evaluate the improvement in discrimination power, heterozygosity, and effectiveness of forensic systems. The results suggested the sequence variations have more influence on A-STRs and could improve the identification ability of MPS-STR genotyping. Concordance between MPS and CE methods was confirmed by using commercial CE-based STR kits. The impact of flanking region variations on STR genotype analysis and potential factors contributing to discordances were discussed. A total of 58 variations in the flanking regions (53 SNPs/SNVs and 5 InDels) were observed and most variations (48/58) were distributed in A-STRs. In summary, this study delved deeper into the genetic information of forensic commonly used STR and advanced the application of massively parallel sequencing in forensic genetics.

Abstract Background Wheat (Triticum aestivum L.) is an important grain crops in the world, and its growth and development in different stages is seriously affected by saline-alkali stress, especially in seedling stage. Therefore, nondestructive detection of wheat seedlings under saline-alkali stress can provide more comprehensive technical support for wheat breeding, cultivation and management. Results This research focused on moisture signal prediction and classification of saline-alkali stress in wheat seedlings using fusion techniques. After collecting and analyzing transverse relaxation time and Multispectral imaging (MSI) information of wheat seedlings, four regression models were used to predict the moisture signal. K-Nearest Neighbor (KNN) and Gaussian-Naïve Bayes (GNB) models were combined with fivefold cross validation to classify the prediction of wheat seedling stress. The results showed that wheat seedlings would increase the bound water content through a certain mechanism to enhance their saline-alkali stress. Under the same Na concentration, the effect of alkali stress on moisture, growth and spectrum of wheat seedlings is stronger than salt stress. The Gradient Boosting Decision Regression Tree model performs the best in predicting wheat moisture signals, with a coefficient of determination (R2P) of 0.98 and a root mean square error of 109.60. It also had a short training time (1.48 s) and an efficient prediction speed (1300 obs/s). The KNN and GNB demonstrated significantly enhanced predictive performance when classifying the fused dataset, compared to using single datasets individually. In particular, the GNB model performing best on the fused dataset, with Precision, Recall, Accuracy, and F1-score of 90.30, 88.89%, 88.90%, and 0.90, respectively. Conclusions Under the same Na concentration, the effects of alkali stress on water content, spectrum, and growth of wheat were stronger than that of salt stress, which was more unfavorable to the growth of wheat. The fusion of low-field nuclear magnetic resonance and MSI technology can improve the classification of wheat stress, and provide an effective technical method for rapid and accurate monitoring of wheat seedlings under saline-alkali stress. Graphical Abstract

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

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

Abstract Objective The aim of this study is to assess the use of machine learning methodologies in the diagnosis of endometriosis (EM). Methods This study included a total of 106 patients with EM and 203 patients with non-EM conditions (like simple cysts and simple uterine fibroids), all admitted to the Shunyi Women’s and Children’s Hospital of Beijing Children’s Hospital between January 2017 and September 2022. All participants were free of comorbidities and their diagnoses were confirmed via postoperative pathology. Comparative analysis was conducted between the EM and non-EM groups. Baseline data were assessed, including white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, mean platelet volume, hemoglobin, carbohydrate antigen 125 (CA125), carbohydrate antigen 199, coagulation parameters, and other serologic indicators. An optimal predictive model was developed using an artificial intelligence algorithm to determine the presence of EM. The objective is to provide new insights for the clinical diagnosis and treatment of EM. Results The random forest algorithm demonstrated superior performance when compared to decision trees, LogitBoost, artificial neural networks, naïve Bayes, support vector machines, and linear regression in machine learning methods. Combining CA125 with the NLR yielded a better prediction of EM than using CA125 alone when applying the random forest algorithm. The accuracy of predicting EM with CA125 combined with NLR was 78.16%, with a sensitivity of 86.21% and an area under the curve (AUC) of 0.85 (P

Abstract Background To establish and validate the criterion-referenced standards of functional fitness in predicting physical independence in 80 + years. Methods A group of 2,749 older community dwellers (60–84 years) were recruited, and 2,050 were identified with moderate-to-high independent living ability according to the proposed minimum composite physical function score. The Senior Fitness Test battery was applied to measure functional fitness at five-year intervals. The declining rate for each fitness dimension was calculated based on the differences between any two adjacent age groups and was adjusted according to the reported degradation rate differences between the cross-sectional and longitudinal studies. Results The age-and-sex-specific criterion-referenced standards were identified for muscle strength, cardiovascular endurance, and dynamic balance that older adults should possess at 60–79 to maintain independent living abilities. Moderate to high consistency (k = 0.622–0.650) and associations (φ = 0.641–0.694) were found between the predicted physical independence by criterion-referenced standards of functional fitness and the results from the composite physical function scale. Moreover, the predicted independent living abilities in later years from the criterion-referenced standards of functional fitness showed high test-retest reliability (P a = 0.90–0.96). Conclusion The criterion-referenced standards for functional fitness are valid and reliable to predict independent living abilities in later years, and provide the threshold to identify the limitations in physical fitness and detect the risks of functional disabilities among older adults in an early stage.

Objective To ensure the successful implementation of metro shield tunnel parallel under-passing through the existing open-cut highway tunnel project under deformation joint condition, it is necessary to analyze the deformation situation and stress characteristics of the mentioned highway tunnel under this working condition. Method A refined model of Jinan Rail Transit Line S2 left/right shield tunnel parallel under-passing of the existing open-cut highway tunnel in Jiluo Road Yellow River Tunnel project is established. The z-direction(vertical) settlement, x-direction (horizontal) displacement, and stress change of this highway tunnel structure bottom plate are analyzed. Through establishing two working conditions with and without deformation joint, changes of the z-direction settlement and x-direction displacement of the mea-sured line are compared. By selecting No.2 deformation joint in the project, the settlement difference and stress state development history on both sides of No.2 deformation joint are further analyzed. Result & Conclusion Compared to the working condition without deformation joint, that with deformation joint reduces the structural integrity of existing open-cut highway tunnels and changes its deformation and force characteristics. Deformation joints are always subject to tensile and shear stresses. Under deformation joint working condition, settlement on both sides of the deformation joint shows significant changes with the tunneling of metro shield, and reaches its maximum value when the tunneling is directly beneath the deformation joint.

Abstract Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Al–Fe alloy is a kind of high thermal conductivity alloy, which are widely utilized in the communication and automobile industries. The thermal conductivity is greatly affected by the morphology, size, and distribution of iron-rich intermetallic phases (Fe-rich phases), pores, and Al grains. The evolution of microstructure and thermal conductivity of Al–Fe alloys by adding Sc2O3 particles and adjusting cooling rates are systematically studied by optical and scanning electron microscopy, and synchrotron X-ray imaging. The results show that Sc2O3 addition reduces the size and increases the number of primary Fe-rich phases, while increasing the grain size of Al matrix. The Sc2O3 promote their nucleation of primary Fe-rich phases and partial Sc solutes inhibit their growth, resulting in the improvement of thermal conductivity and mechanical properties. The remaining Sc2O3 particles have large lattice misfit with Al, led to the formation of coarsen size Al. The highest thermal conductivity is 214 W/(m·K) in the alloy with Sc2O3 and slow cooling rate. Sc2O3 addition increase the thermal conductivity of the studied alloys, i.e., an increment of 3 W/(m K) (by 1.1 %) at slow cooling rate by and an increment of 11 W/(m K) (by 6.2 %) at fast cooling rate. This study provides a new strategy to improving thermal conductivity of Al alloy for both academia and industry.

In general, the Ti–6.5Al–2Zr–1Mo–1V (TA15) components fabricated via laser powder bed fusion (L-PBF) exhibit high strength and low ductility. Herein, we report a novel approach to enhance the comprehensive mechanical properties of L-PBF TA15 alloy by adjusting the laser power. Samples processed using the optimal laser power exhibit a grid structure of alternating wide and narrow prior-β grains (PBGs), the inside of which is composed of a fully martensitic microstructure. The paper discusses in detail the alterations in the microstructure of samples processed at both low and high laser powers, clarifying the relationship between microstructure and mechanical properties. Thinner martensite contributes to higher strength, while a homogenous microstructure improves ductility. These findings provide valuable insights for controlling microstructure and achieving strength-ductility synergy in L-PBF additive manufacturing of titanium alloys.

Plumbagin (PLB), a naphthoquinone compound, has been proven to have anti-cancer properties in different types of cancers. However, the anti-tumor actions as well as molecular processes in osteosarcoma (OS) remain unclear. This study investigates the underlying mechanisms of PLB in human OS cells in vitro. Our study showed that PLB significantly inhibited the proliferation of human OS cells in a time- and dosage-dependent manner. RNA sequencing data revealed that the efficacy of PLB is related to cell cycle, cell death, and p38 MAPK signaling pathway in KHOS-240S cells. Further studies indicated that PLB triggers G2/M phase arrest, mitochondrial-dependent apoptosis, as well as ferroptosis in human OS cells. Mechanistically, PLB treatment increased ROS generation that activates the p38 MAPK signaling pathway. BIRB 796, a p38 MAPK inhibitor, partly reversed PLB-induced phase arrest of G2/M and cell death. Furthermore, N-acetylcysteine (NAC), a ROS scavenger, significantly decreased G2/M phase arrest and cell death and reversed p38 MAPK activation caused by PLB. In conclusion, PLB induces arrest G2/M arrest, apoptosis as well as ferroptosis in human OS cells via ROS generation and p38 MAPK activation. There is potential for PLB to be an effective treatment for OS.

Background In recent years, physical impairment (PI) combined with cognitive impairment (CI) is a common comorbidity in the elderly. An early detection of PI combined with CI in the elderly and timely interventions may help to improve the quality of life of the elderly and reduce the burden on their families and society. However, relevant studies on the comorbidity of PI and CI in the elderly and its influencing factors have been rarely reported. Objective To observe the clinical characteristics of the comorbidity of PI and CI in the elderly and the influencing factors. Methods Elderly patients hospitalized in Peking University People's Hospital from September 2018 to November 2019 were selected. A total of eligible 244 subjects meeting the inclusion criteria were surveyed for the physical function and cognitive function using the Short Physical Performance Battery (SPPB) and the Mini-mental State Examination (MMSE), respectively. PI was diagnosed with lower than 10 points of the SPPB, and CI was diagnosed with lower than 27 points of the MMSE. Patients were divided into non-PI+non-CI, PI+non-CI, non-PI+CI, PI+CI. Social demographic, anthropometric, laboratory examination and other indicators of patients were collected, and Logistic regression analysis was used to explore the influencing factors for PI combined with CI in the elderly. Results Among the 244 patients, there were 102 (41.80%), 64 (26.23%), 26 (10.66%) and 52 (21.31%) cases of non-PI+non-CI, PI+non-CI, non-PI+CI and PI+CI, respectively. Multivariate binary Logistic regression analysis showed that compared with non-PI+non-CI cases, age (P

Abstract Background Many studies have demonstrated the association between intestinal microbiota and joint diseases. The “gut-joint axis” also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. Results CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. Conclusion Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract

Abstract Carboxy-terminal domain small phosphatase like 2 (CTDSPL2), one of the haloacid dehalogenase phosphatases, is associated with several diseases including cancer. However, the role of CTDSPL2 and its regulatory mechanism in lung cancer remain unclear. Here, we aimed to explore the clinical implications, biological functions, and molecular mechanisms of CTDSPL2 in non-small cell lung cancer (NSCLC). CTDSPL2 was identified as a novel target of the tumor suppressor miR-193a-3p. CTDSPL2 expression was significantly elevated in NSCLC tissues. Database analysis showed that CTDSPL2 expression was negatively correlated with patient survival. Depletion of CTDSPL2 inhibited the proliferation, migration, and invasion of NSCLC cells, as well as tumor growth and metastasis in mouse models. Additionally, silencing of CTDSPL2 enhanced CD4+ T cell infiltration into tumors. Moreover, CTDSPL2 interacted with JAK1 and positively regulated JAK1 expression. Subsequent experiments indicated that CTDSPL2 activated the PI3K/AKT signaling pathway through the upregulation of JAK1, thereby promoting the progression of NSCLC. In conclusion, CTDSPL2 may play an oncogenic role in NSCLC progression by activating PI3K/AKT signaling via JAK1. These findings may provide a potential target for the diagnosis and treatment of NSCLC.

Abstract Achieving the United Nations’ Sustainable Development Goals (SDGs) requires an overall and well-balanced achievement of all SDGs rather than cherry-picking a few. While it is vital to assess the evenness of SDGs achievement, such analysis, particularly on a global scale, is still evidently absent from the existing literature. To remedy such a scholarly gap, this paper measures the evenness of SDGs achievement for 193 countries from 2010 to 2019 by adapting the evenness assessment method originating from ecology and biodiversity literature. Our analyses regarding the country-level SDG evenness index scores (EIS) indicate a significant heterogeneity across countries. Global South countries usually underperform in the evenness of 17 goals, while a significant portion of Global North countries also suffer from the unbalanced developments in SDGs. By integrating the evenness measures into the conventional global SDG monitoring framework, this study identifies six development paths in pursuing the SDGs and shows that maintaining the overall SDGs improvements while balancing the development of each goal is practical but has not taken place in at least 35% of countries. We estimate that the SDG evenness and average performance could further increase by 3.5 p.p. and 2.1 p.p., or 74 percent and 50 percent of the growth in the baseline continue past paths scenario, respectively, if each country could follow the effective development path of frontier counterparts with similar income levels. Our SDG evenness measures, complemented by inter-temporal cross-country analyses, could inform policies and cooperation strategies to identify the weaknesses in sustainable development, boost effective growth, and protect unevenly developed countries. Future research could further develop these measures to provide deeper insights into achieving rapid and well-balanced development of SDGs at various levels.

Abstract RNase H1 has been acknowledged as an endoribonuclease specializing in the internal degradation of the RNA moiety within RNA–DNA hybrids, and its ribonuclease activity is indispensable in multifaceted aspects of nucleic acid metabolism. However, the molecular mechanism underlying RNase H1-mediated hybrid cleavage remains inadequately elucidated. Herein, using single-molecule approaches, we probe the dynamics of the hybrid cleavage by Saccharomyces cerevisiae RNase H1. Remarkably, a single RNase H1 enzyme displays 3′-to-5′ exoribonuclease activity. The directional RNA degradation proceeds processively and yet discretely, wherein unwinding approximately 6-bp hybrids as a prerequisite for two consecutive 3-nt RNA excisions limits the overall rate within each catalytic cycle. Moreover, Replication Protein A (RPA) reinforces RNase H1’s 3′-to-5′ nucleolytic rate and processivity and stimulates its 5′-to-3′ exoribonuclease activity. This stimulation is primarily realized through the pre-separation of the hybrids and consequently transfers RNase H1 to a bidirectional exoribonuclease, further potentiating its cleavage efficiency. These findings unveil unprecedented characteristics of an RNase and provide a dynamic view of RPA-enhanced processive hybrid cleavage by RNase H1.

Abstract Au@Pt nanozyme, a bimetallic core–shell structure Au and Pt nanoparticle, has attracted significant attention due to its excellent catalytic activity and stability. Here, we propose that Au@Pt improves glucose tolerance and reduces TG after four weeks administration. The transcriptomic analysis of mouse liver tissues treated with Au@Pt nanozyme showed changes in genes related to glucose and lipid metabolism signaling pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, PPAR signaling, and insulin signaling. Moreover, analysis of fecal samples from mice treated with Au@Pt nanozyme showed significant changes in the abundance of beneficial gut microbiota such as Dubosiella, Parvibacter, Enterorhabdus, Monoglobus, Lachnospiraceae_UCG-008, Lachnospiraceae_UCG-006, Lachnospiraceae_UCG-001, and Christensenellaceae_R-7_group. Combined multi-omics correlation analyses revealed that the modulation of glucose and lipid metabolism by Au@Pt was strongly correlated with changes in hepatic gene expression profiles as well as changes in gut microbial profiles. Overall, our integrated multi-omics analysis demonstrated that Au@Pt nanozyme could modulate glucose and lipid metabolism by regulating the expression of key genes in the liver and altering the composition of gut microbiota, providing new insights into the potential applications of Au@Pt nanozyme in the treatment of metabolic disorder. Graphical Abstract

Abstract In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple “wisdom” by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

Abstract Background Medical device-related pressure injures (MDRPIs) are common in critically ill patients and associated with negative clinical outcomes and elevated healthcare expenses. We aim to estimate worldwide incidence of MDRPI and explore associated factors through systemic review and meta-analysis. Methods The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were systematically queried to identify relevant studies published from Jan 1, 2010 up until June 30, 2024. Studies were included if they provided data on the incidence or prevalence of MDRPI. Random-effect models were utilized to calculate the overall or domain-specific aggregated estimates of MDRPI. A meta-regression analysis was additionally performed to investigate the heterogeneity among studies. Results We included 28 observational studies on 117,624 patients in the meta-analysis. The overall incidence of MDRPI was 19.3% (95% confidence interval (CI) 13.5–25.2%). The incidence of MDRPI in Europe, North America, Asia, South America, and Oceania was 17.3% (95% CI 12.7–21.9%), 3.6% (95% CI 0.0–8.5%), 21.9% (95% CI 14.3–29.6%), 48.3% (95% CI 20.8–75.7%), and 13.0% (95% CI 5.0–21.1%), respectively (p

Abstract Intermetallic compounds (IMCs) with ordered atomic structure have gained great attention as nanocatalysts for its enhanced activity and stability. Although the reliance of IMC preparation on high-temperature annealing is well known, a comprehensive understanding of the formation mechanisms of IMCs in this process is currently lacking. Here, we employ aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) to track the formation process of IMCs on carbon supports during in-situ annealing, by taking PtFe as a case study within an industry-relevant impregnation synthesis framework. We directly discern five different stages at the atomic level: initial atomic precursors; Pt cluster formation; Pt-Fe disordered alloying; structurally ordered Pt3Fe formation, and final Pt3Fe-PtFe IMC conversion. In particular, we find that the crucial role of high-temperature annealing resides in facilitating the diffusion of Fe towards Pt, enabling the creation of alloys with the targeted stoichiometric ratio, which in turn provides the thermodynamic driving force for the disorder-to-order transition.

Abstract The Wnt receptor Frizzled3 (FZD3) is important for brain axonal development and cancer progression. We report structures of FZD3 in complex with extracellular and intracellular binding nanobodies (Nb). The crystal structure of Nb8 in complex with the FZD3 cysteine-rich domain (CRD) reveals that the nanobody binds at the base of the lipid-binding groove and can compete with Wnt5a. Nb8 fused with the Dickkopf-1 C-terminal domain behaves as a FZD3-specific Wnt surrogate, activating β-catenin signalling. The cryo-EM structure of FZD3 in complex with Nb9 reveals partially resolved density for the CRD, which exhibits positional flexibility, and a transmembrane conformation that resembles active GPCRs. Nb9 binds to the cytoplasmic region of FZD3 at the putative Dishevelled (DVL) or G protein-binding site, competes with DVL binding, and inhibits GαS coupling. In combination, our FZD3 structures with nanobody modulators map extracellular and intracellular interaction surfaces of functional, and potentially therapeutic, relevance.