Search

Abstract Background Intervertebral disc degeneration (IVDD) is a common spine disease with inflammation as its main pathogenesis. Mulberroside A (MA), isolated from herbal medicine, possesses anti-inflammatory characteristics in many diseases. Whereas, there is little exploration of the therapeutic potential of MA on IVDD. This study aimed at the therapeutic potential of MA on IVDD in vivo and in vitro and the mechanism involved. Methods In vitro, western blotting, RT-qPCR, and immunofluorescence analysis were implemented to explore the bioactivity of MA on interleukin-1 beta (IL-1β)-induced inflammation nucleus pulposus cells (NPCs) isolated from Sprague-Dawley male rats. In vivo, X-ray and MRI were applied to measure the morphological changes, and histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disc sections on puncture-induced IVDD rat models. Results In vitro, MA up-regulated the expression level of anabolic-related proteins (Aggrecan and Collagen II) and decreased catabolic-related proteins (Mmp2, Mmp3, Mmp9, and Mmp13) in IL-1β-induced NPCs. Furthermore, MA inhibits the production of pro-inflammatory factors (Inos, Cox-2, and Il-6) stimulated by IL-1β. Mechanistically, MA inhibited the signal transduction of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways in IL-1β-induced NPCs. Moreover, MA might bind to Ppar-γ and then suppress the NF-kB pathway. In vivo experiment illustrated that MA mitigates the IVDD progression in puncture-induced IVDD model. X-ray and MRI images showed MA restore the disc height and T2-weighted signal intensity after puncturing. H&E and Safranin O/Fast Green also showed MA also alleviated morphological changes caused by acupuncture. In addition, MA reversed the expression level of Mmp13, Aggrecan, Collagen II, and Ppar-γ induced in IVDD models. Conclusions MA inhibited degenerative phenotypes in NPCs and alleviated IVDD progression via inhibiting the MAPK and NF-κB pathways; besides, MA suppressed the NF-κB pathway was attributed to activating Ppar-γ, those supported that MA or Ppar-γ might be a potential drug or target for IVDD.

Abstract BCL-2 inhibitors such as venetoclax offer therapeutic promise in acute myeloid leukemia (AML) and other cancers, but drug resistance poses a significant challenge. It is crucial to understand the mechanisms that regulate venetoclax response. While correlative studies have identified numerous genes linked to venetoclax sensitivity, their direct impact on the drug response remains unclear. In this study, we targeted around 1400 genes upregulated in venetoclax-sensitive primary AML samples and carried out a CRISPR knockout screen to evaluate their direct effects on venetoclax response. Our screen identified the transcription factor ZNF740 as a critical regulator, with its expression consistently predicting venetoclax sensitivity across subtypes of the FAB classification. ZNF740 depletion leads to increased resistance to ventoclax, while its overexpression enhances sensitivity to the drug. Mechanistically, our integrative transcriptomic and genomic analysis identifies NOXA as a direct target of ZNF740, which negatively regulates MCL-1 protein stability. Loss of ZNF740 downregulates NOXA and increases the steady state protein levels of MCL-1 in AML cells. Restoring NOXA expression in ZNF740-depleted cells re-sensitizes AML cells to venetoclax treatment. Furthermore, we demonstrated that dual targeting of MCL-1 and BCL-2 effectively treats ZNF740-deficient AML in vivo. Together, our work systematically elucidates the causal relationship between venetoclax response signature genes and establishes ZNF740 as a novel transcription factor regulating venetoclax sensitivity.

Abstract Dielectric capacitors are highly desired for electronic systems owing to their high-power density and ultrafast charge/discharge capability. However, the current dielectric capacitors suffer severely from the thermal instabilities, with sharp deterioration of energy storage performance at elevated temperatures. Here, guided by phase-field simulations, we conceived and fabricated the self-assembled metadielectric nanostructure with HfO2 as second-phase in BaHf0.17Ti0.83O3 relaxor ferroelectric matrix. The metadielectric structure can not only effectively increase breakdown strength, but also broaden the working temperature to 400 oC due to the enhanced relaxation behavior and substantially reduced conduction loss. The energy storage density of the metadielectric film capacitors can achieve to 85 joules per cubic centimeter with energy efficiency exceeding 81% in the temperature range from 25 °C to 400 °C. This work shows the fabrication of capacitors with potential applications in high-temperature electric power systems and provides a strategy for designing advanced electrostatic capacitors through a metadielectric strategy.

Objectives: TANK-binding kinase 1 (TBK1) is pivotal in autoimmune and inflammatory diseases, yet its role in osteoarthritis (OA) remains elusive. This study sought to elucidate the effect of the TBK1 inhibitor BX795 on OA and to delineate the underlying mechanism by which it mitigates OA. Methods: Interleukin-1 Beta (IL-1β) was utilized to simulate inflammatory responses and extracellular matrix degradation in vitro. In vivo, OA was induced in 8-week-old mice through destabilization of the medial meniscus surgery. The impact of BX795 on OA was evaluated using histological analysis, X-ray, micro-CT, and the von Frey test. Additionally, Western blot, RT-qPCR, and immunofluorescence assays were conducted to investigate the underlying mechanisms of BX795. Results: Phosphorylated TBK1 (P-TBK1) levels were found to be elevated in OA knee cartilage of both human and mice. Furthermore, intra-articular injection of BX795 ameliorated cartilage degeneration and alleviated OA-associated pain. BX795 also counteracted the suppression of anabolic processes and the augmentation of catabolic activity, inflammation, and senescence observed in the OA mice. In vitro studies revealed that BX795 reduced P-TBK1 levels and reversed the effects of anabolism inhibition, catabolism promotion, and senescence induction triggered by IL-1β. Mechanistically, BX795 inhibited the IL-1β-induced activation of the cGAS–STING and TLR3–TRIF signaling pathways in chondrocytes. Conclusions: Pharmacological inhibition of TBK1 with BX795 protects articular cartilage by inhibiting the activation of the cGAS–STING and TLR3–TRIF signaling pathways. This action attenuates inflammatory responses and cellular senescence, positioning BX795 as a promising therapeutic candidate for OA treatment. The translational potential of this article: This study furnishes experimental evidence and offers a potential mechanistic explanation supporting the efficacy of BX795 as a promising candidate for OA treatment.

Abstract Background The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. Methods A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. Results After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P

Accurate delineation of agricultural parcels is crucial for ensuring food security and implementing precision agriculture practices. However, one of the primary challenges in parcel delineation revolves around the accurate extraction of parcel edges due to the diverse morphologies of these parcels. Current deep learning models for agricultural parcel delineation often produce unclosed or incomplete edges, highlighting the need to enhance the edge-awareness of the model. In this study, we proposed a refined edge-aware U-Net (REAUNet) to extract accurate agricultural parcel boundaries from Sentinel-2 images and GF-2 images. REAUNet integrates four innovative components for edge enhancement, i.e., the deep supervision, the edge detection block, the dual attention block and the refine module. The edge detection block and the dual attention block strengthen the ability of capturing spatial contextual information, and the deep supervision constrains parcel delineation across multiple scales, and the refine module further refines the parcel edges. Together, these components enhance the edge-awareness of the model, resulting in more accurate agricultural parcel delineation. From the ablation experiment, REAUNet with all four components reached the higher accuracy than the scenarios that only three out of four components were retained, which suggested that the inclusion of all four components was essential. The comparative evaluation showed that our proposed model surpassed the representative deep learning models for both thematic and geomantic accuracy. REAUNet demonstrated an increase of 2.0 % in F1-score and a decrease of 3.4 % in GTC (Global Total-Classification) compared to the SEANet, and exhibited a 0.8 % increase in IoU and a 2 % decrease in GTC relative to the MPSPNet. We also assessed the capability of the REAUNet model transferred for a new geographic region, and reported that a pre-train REAUNet model with only a small number of local samples could achieve a satisfactory accuracy. To conclude, the newly proposed REAUNet model reaches a high mapping accuracy for delineating agricultural parcels from the high-resolution images. With the powerful edge-aware capability, REAUNet can effectively utilize limited training samples to transfer a deep learning model for a new region, facilitating the generation of agricultural parcel products and a large-scale agricultural parcel mapping in practical applications.

Abstract The development of in situ techniques to quantitatively characterize the heterogeneous reactions is essential for understanding physicochemical processes in aqueous phase. In this work, a new approach coupling in situ UV–vis spectroscopy with a two‐step algorithm strategy is developed to quantitatively monitor heterogeneous reactions in a compact closed‐loop incorporation. The algorithm involves the inverse adding‐doubling method for light scattering correction and the multivariate curve resolution‐alternating least squares (MCR‐ALS) method for spectral deconvolution. Innovatively, theoretical spectral simulations are employed to connect MCR‐ALS solutions with chemical molecular structural evolution without prior information for reference spectra. As a model case study, the aqueous adsorption kinetics of bisphenol A onto polyamide microparticles are successfully quantified in a one‐step UV–vis spectroscopic measurement. The practical applicability of this approach is confirmed by rapidly screening a superior adsorbent from commercial materials for antibiotic wastewater adsorption treatment. The demonstrated capabilities are expected to extend beyond monitoring adsorption systems to other heterogeneous reactions, significantly advancing UV–vis spectroscopic techniques toward practical integration into automated experimental platforms for probing aqueous chemical processes and beyond.

Background: The significant rebound of influenza A (H1N1) virus activity, particularly among children, with rapidly growing number of hospitalized cases is of major concern in the post-COVID-19 era. The present study was performed to establish a prediction model of severe case in pediatric patients hospitalized with H1N1 infection during the post-COVID-19 era. Methods: This is a multicenter retrospective study across nine public tertiary hospitals in Yunnan, China, recruiting pediatric H1N1 inpatients hospitalized at five of these centers between February 1 and July 1, 2023, into the development dataset. Screening of 40 variables including demographic information, clinical features, and laboratory parameters were performed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to determine independent risk factors of severe H1N1 infection, thus constructing a prediction nomogram. Receiver operating characteristic (ROC) curve, calibration curve, as well as decision curve analysis (DCA) were employed to evaluate the model's performance. Data from four independent cohorts comprised of pediatric H1N1 inpatients from another four hospitals between July 25 and October 31, 2023, were utilized to externally validate this nomogram. Results: The development dataset included 527 subjects, 122 (23.1 %) of whom developed severe H1N1 infection. The external validation dataset included 352 subjects, 72 (20.5 %) of whom were eventually confirmed as severe H1N1 infection. The LASSO regression identified 19 candidate predictors, with logistic regression further narrowing down to 11 independent risk factors, including underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). By integrating these 11 factors, a predictive nomogram was established. In terms of prediction of severe H1N1 infection, excellent discriminative capacity, favorable accuracy, and satisfactory clinical usefulness of this model were internally and externally validated via ROC curve, calibration curve, and DCA, respectively. Conclusion: Our study successfully established and validated a novel nomogram model integrating underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, NLR, ESR, LDH, IL-10, and TNF-α. This nomogram can effectively predict the occurrence of serious case in pediatric H1N1 inpatients during the post-COVID-19 era, facilitating the early recognition and more efficient clinical management of such patients.

IntroductionOff-season upsurge of respiratory syncytial virus (RSV) infection with changed characteristics and heightened clinical severity during the post-COVID-19 era are raising serious concerns. This study aimed to develop and validate a nomogram for predicting the risk of severe acute lower respiratory tract infection (SALRTI) in children hospitalized for RSV infection during the post-COVID-19 era using machine learning techniques.MethodsA multicenter retrospective study was performed in nine tertiary hospitals in Yunnan, China, enrolling children hospitalized for RSV infection at seven of the nine participating hospitals during January–December 2023 into the development dataset. Thirty-nine variables covering demographic, clinical, and laboratory characteristics were collected. Primary screening and dimension reduction of data were performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by identification of independent risk factors for RSV-associated SALRTI using Logistic regression, thus finally establishing a predictive nomogram model. Performance of the nomogram was internally evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) based on the development dataset. External validation of our model was conducted using same methods based on two independent RSV cohorts comprising pediatric RSV inpatients from another two participating hospitals between January–March 2024.ResultsThe development dataset included 1102 patients, 239 (21.7%) of whom developed SALRTI; while the external validation dataset included 249 patients (142 in Lincang subset and 107 in Dali subset), 58 (23.3%) of whom were diagnosed as SALRTI. Nine variables, including age, preterm birth, underlying condition, seizures, neutrophil-lymphocyte ratio (NLR), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, and co-infection, were eventually confirmed as the independent risk factors of RSV-associated SALRTI. A predictive nomogram was established via integrating these nine predictors. In both internal and external validations, ROC curves indicated that the nomogram had satisfactory discrimination ability, calibration curves demonstrated good agreement between the nomogram-predicted and observed probabilities of outcome, and DCA showed that the nomogram possessed favorable clinical application potential.ConclusionA novel nomogram combining several common clinical and inflammatory indicators was successfully developed to predict RSV-associated SALRTI. Good performance and clinical effectiveness of this model were confirmed by internal and external validations.

Abstract Syringa oblata is an important garden plant whose leaf colour turns from green to red in autumn when air temperature and daylength decrease. This study explored the reasons for leaf reddening by detecting phenotypic characteristics and pigment types and contents. With leaf reddening, luminance L* increased and chrominance a* decreased significantly. Chlorophyll and carotenoid contents significantly decreased in accordance with the distribution change of green pigment in leaf cells. Conversely, the red pigment distribution increased and the total polyphenol, total flavonoid and total anthocyanin contents evidently increased. Anthocyanin accumulation was the important reason for leaf reddening. Of the anthocyanins detected in leaves, cyanidin and delphinidin-3-O-rutinoside contents gradually increased with leaf reddening and were negatively correlated with L*. They were considered key anthocyanins influencing leaf colour. Apigenin and syringic acid were correlated with delphinidin-3-O-rutinoside and cyanidin, and they could be the anthocyanin co-pigments. Cyanidin-3-O-arabinoside and taxifolin were more abundant polyphenols in leaves. In summary, anthocyanin accumulation and chlorophyll degradation occurred along with leaf reddening. Temperature, light, and other co-pigments influenced the anthocyanin and chlorophyll contents. This study provides evidence for applications of S. oblata as a coloured-leaf plant in gardens and as a source of active ingredients in the commercial market.

Background ELMSAN1 (ELM2‐SANT domain‐containing scaffolding protein 1) is a newly identified scaffolding protein of the MiDAC (mitotic deacetylase complex), playing a pivotal role in early embryonic development. Studies on Elmsan1 knockout mice showed that its absence results in embryo lethality and heart malformation. However, the precise function of ELMSAN1 in heart development and formation remains elusive. To study its potential role in cardiac lineage, we employed human‐induced pluripotent stem cells (hiPSCs) to model early cardiogenesis and investigated the function of ELMSAN1. Methods and Results We generated ELMSAN1‐deficient hiPSCs through knockdown and knockout techniques. During cardiac differentiation, ELMSAN1 depletion inhibited pluripotency deactivation, decreased the expression of cardiac‐specific markers, and reduced differentiation efficiency. The impaired expression of genes associated with contractile sarcomere structure, calcium handling, and ion channels was also noted in ELMSAN1‐deficient cardiomyocytes derived from hiPSCs. Additionally, through a series of structural and functional assessments, we found that ELMSAN1‐null hiPSC cardiomyocytes are immature, exhibiting incomplete sarcomere Z‐line structure, decreased calcium handling, and impaired electrophysiological properties. Of note, we found that the cardiac‐specific role of ELMSAN1 is likely associated with histone H3K27 acetylation level. The transcriptome analysis provided additional insights, indicating maturation reduction with the energy metabolism switch and restored cell proliferation in ELMSAN1 knockout cardiomyocytes. Conclusions In this study, we address the significance of the direct involvement of ELMSAN1 in the differentiation and maturation of hiPSC cardiomyocytes. We first report the impact of ELMSAN1 on multiple aspects of hiPSC cardiomyocyte generation, including cardiac differentiation, sarcomere formation, calcium handling, electrophysiological maturation, and proliferation.

Under the new educational philosophy, the comprehensive quality evaluation of students in sports colleges is increasingly receiving attention from educators and society. Because comprehensive quality not only covers professional knowledge and skills, but also includes moral qualities, innovative spirit, teamwork ability, etc., which are all urgent needs for talents in sports colleges and universities in society. However, the comprehensive quality evaluation system for students in sports colleges and universities seems to be unable to fully meet this demand, and there are some problems that cannot be ignored, such as excessive emphasis on grades, fixed evaluation systems, lack of student participation in the evaluation process, and fuzzy evaluation standards. The existence of these problems not only affects the fairness and effectiveness of evaluation, but also hinders the comprehensive development of students and the process of educational reform. Therefore, how to optimize the comprehensive quality evaluation system of students in sports colleges and universities to better adapt to the needs of social development has become an important topic in current sports education research. The comprehensive quality evaluation of physical education institutions is multi-attribute decision-making (MADM). Exponential TODIM (ExpTODIM) and improved grey relational analysis (IGRA) approaches were used to address MADM issues in this context. Hesitant Triangular Fuzzy Sets (HTFSs) have been employed as a tool for characterizing the uncertain information inherent in the comprehensive quality evaluation of physical education institutions. In this paper, we develop a Hesitant Triangular Fuzzy Number Exponential TODIM-IGRA (HTFN-ExpTODIM-IGRA) approach to illustrate the MADM problem under the framework of HTFSs. Finally, numerical study for the comprehensive quality evaluation of physical education institutions, along with comparative analysis, is provided to validate the HTFN-ExpTODIM-IGRA approach.

Abstract Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non‐invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)‐coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte‐derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte‐derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury.

Summary: Signal-regulatory protein alpha (SIRPα) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its immunoregulatory function in podocytes remains elusive. Here, we report that SIRPα controls podocyte antigen presentation in specific T cell activation via inhibiting spleen tyrosine kinase (Syk) phosphorylation. First, podocyte SIRPα under lupus nephritis (LN) conditions is strongly downregulated. Second, podocyte-specific deletion of SIRPα exacerbates renal disease progression in lupus-prone mice, as evidenced by an increase in T cell infiltration. Third, SIRPα deletion or knockdown enhances podocyte antigen presentation, which activates specific T cells, via enhancing Syk phosphorylation. Supporting this, Syk inhibitor GS-9973 prevents podocyte antigen presentation, resulting in a decrease of T cell activation and mitigation of renal disease caused by SIRPα knockdown or deletion. Our findings reveal an immunoregulatory role of SIRPα loss in promoting podocyte antigen presentation to activate specific T cell immune responses in LN.

Abstract Background Takotsubo syndrome (TTS), which is frequently secondary to severe emotional (fear, anxiety, etc.) or physical stress, is an acute reversible heart failure syndrome characterized by temporary left ventricular regional systolic dysfunction. Nevertheless, TTS after percutaneous coronary intervention (PCI) is rare, and its clinical characteristics are easily confused with complications after PCI. Case presentation This article reports a case of TTS induced by psychological and physical pressure after successful PCI in our institution. The patient had symptoms comparable to complications after PCI, including V1-V5 ST segment elevation and T wave changes of electrocardiogram (ECG) and troponin elevation. Coronary angiogram, left ventricle opacification (LVO), and cardiac magnetic resonance (CMR) were performed to exclude postoperative complications. Diagnosis of TTS was eventually achieved. Conclusion We cannot dismiss the risk of TTS in patients who have unexplained V1-V5 ST segment elevation and T wave changes of ECG and troponin elevation following successful PCI. Meanwhile, medical personnel should provide mental, cultural, and emotional services to patients in addition to essential diagnostic and treatment technical services during the perioperative period.

Abstract Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb) and B cell differentiation are tightly regulated by T follicular help (TFH) cells. However, the longevity and functional role of TFH cell subsets in COVID-19 convalescents and vaccine recipients remain poorly defined. Here, we show that SARS-CoV-2 infection and inactivated vaccine elicited both spike-specific CXCR3+ TFH cell and CXCR3− TFH cell responses, which showed distinct response patterns. Spike-specific CXCR3+ TFH cells exhibit a dominant and more durable response than CXCR3− TFH cells that positively correlated with antibody responses. A third booster dose preferentially expands the spike-specific CXCR3+ TFH cell subset induced by two doses of inactivated vaccine, contributing to antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells have a greater ability to induce spike-specific antibody secreting cells (ASCs) differentiation compared to spike-specific CXCR3− TFH cells. In conclusion, the persistent and functional role of spike-specific CXCR3+ TFH cells following SARS-CoV-2 infection and vaccination may play an important role in antibody maintenance and recall response, thereby conferring long-term protection. The findings from this study will inform the development of SARS-CoV-2 vaccines aiming to induce long-term protective immune memory.

The physicochemical indexes and microbial diversity were investigated to compare the altered quality properties of the abdomen and cheliped muscle in swimming crab (Portunus trituberculatus) during 100 days of frozen storage at −20℃. Over the extended duration of frozen storage, the sensory evaluation, moisture content, water activity (Aw), and water-holding capacity (WHC) in the abdomen and cheliped muscles of swimming crab decreased, while the pH, total volatile basic nitrogen (TVB-N), and trimethylamine (TMA) increased. The increase and decrease rates of these indicators were smaller in the abdomen than those in the cheliped muscle. High-throughput sequencing results indicated a reduction in the microbial richness and diversity in the abdomen and cheliped muscles of the swimming crab as frozen storage time extended. Proteobacteria, Actinobacteriota, and Firmicutes, Achromobacter, Kocuria, and Staphylococcus were the dominant phylum and genus in both muscle tissues, respectively. Furthermore, the correlation analysis between the composition of the microbiota and physiochemical properties revealed that the growths of Kocuria, Vibrio, Staphylococcus, and Aliiroseovarius were closely related to the physiochemical factors. The study provides a theoretical reference for quality deterioration and develops new products of different parts in the swimming crab during frozen storage.

IntroductionSince December 2019, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has presented considerable public health challenges. Multiple vaccines have been used to induce neutralizing antibodies (nAbs) and memory B-cell responses against the viral spike (S) glycoprotein, and many essential epitopes have been defined. Previous reports have identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-reactive naïve B cells and preexisting memory B cells in unexposed individuals. However, the role of these spike-reactive B cells in vaccine-induced immunity remains unknown.MethodsTo elucidate the characteristics of preexisting SARS-CoV-2 S-reactive B cells as well as their maturation after antigen encounter, we assessed the relationship of spike-reactive B cells before and after vaccination in unexposed human individuals. We further characterized the sequence identity, targeting domain, broad-spectrum binding activity and neutralizing activity of these SARS-CoV-2 S-reactive B cells by isolating monoclonal antibodies (mAbs) from these B cells.ResultsThe frequencies of both spike-reactive naïve B cells and preexisting memory B cells before vaccination correlated with the frequencies of spike-reactive memory B cells after vaccination. Isolated mAbs from spike-reactive naïve B cells before vaccination had fewer somatic hypermutations (SHMs) than mAbs isolated from spike-reactive memory B cells before and after vaccination, but bound SARS-CoV-2 spike in vitro. Intriguingly, these germline-like mAbs possessed broad binding profiles for SARS-CoV-2 and its variants, although with low or no neutralizing capacity. According to tracking of the evolution of IGHV4-4/IGKV3-20 lineage antibodies from a single donor, the lineage underwent SHMs and developed increased binding activity after vaccination.DiscussionOur findings suggest that spike-reactive naïve B cells can be expanded and matured by vaccination and cocontribute to vaccine-elicited antibody responses with preexisting memory B cells. Selectively and precisely targeting spike-reactive B cells by rational antigen design may provide a novel strategy for next-generation SARS-CoV-2 vaccine development.

Abstract Ligamentum flavum hypertrophy (LFH) is the main physiological and pathological mechanism of lumbar spinal canal stenosis (LSCS). The specific mechanism for LFH has not been completely clarified. In this study, bioinformatic analysis, human ligamentum flavum (LF) tissues collection and analysis, and in vitro and in vivo experiments were conducted to explore the effect of decorin (DCN) on LFH pathogenesis. Here, we found that TGF-β1, collagen I, collagen III, α-SMA and fibronectin were significantly upregulated in hypertrophic LF samples. The DCN protein expression in hypertrophic LF samples was higher than that in non-LFH samples, but the difference was not significant. DCN inhibited the expression of TGF-β1-induced fibrosis-associated proteins in human LF cells, including collagen I, collagen III, α-SMA, and fibronectin. ELISAs showed that TGF-β1 can upregulate PINP and PIIINP in the cell supernatant, and this effect was inhibited after DCN administration. Mechanistic studies revealed that DCN suppressed TGF-β1-induced fibrosis by blocking the TGF-β1/SMAD3 signaling pathway. In addition, DCN ameliorated mechanical stress-induced LFH in vivo. In summary, our findings indicated that DCN ameliorated mechanical stress-induced LFH by antagonizing the TGF-β1/SMAD3 signaling pathway in vitro and in vivo. These findings imply that DCN is a potential therapeutic candidate for ligamentum flavum hypertrophy.

Background and aim: Recent studies show that combination of apoptosis and oxidative stress forms a “vicious circle” in the process of premature ovarian failure (POF). Pearl extract has a good effect for anti-oxidation and anti-aging in vitro and vivo and can be used to treat various aging diseases. However, reports about effect and mechanism of pearl on ovarian function of premature ovarian failure (POF)are limited. Experimental procedure: The effect and mechanism of pearl on ovarian function of rats with POF were evaluated using rats with premature ovarian failure induced by tripterygium glycosides. The estrous cycle, contents of serum reproductive hormones, tissue structure, oxidative stress level, autophagy and apoptotic protein expression, and MAPK signaling pathway of ovary were assessed to characterise pearl. Result and conclusion: Low, medium and high-dose pearl improved the estrous cycle in POF rats, and high-dose pearl was the best in terms of recovery effect; high-dose pearl significantly increased (P

Compared to the southern Tibetan Plateau, the northern part has been regarded as relatively lacking geothermal resources. However, there is no lack of natural hot springs exposed in beads along large-scale fracture systems, and research on them is currently limited to individual hot springs or geothermal systems. This paper focuses on the Wahongshan-Wenquan Fracture Zone (WWFZ), analyzes the formation of five hydrothermal activity zones along the fracture zone in terms of differences in hot water hydrochemical and isotopic composition, and then explores the hot springs’ hydrothermal control in the fracture zone. The results show that the main fractures of the WWFZ are the regional heat control structures, and its near-north–south- and near-east–west-oriented fractures form a fracture system that provides favorable channels for deep hydrothermal convection. Ice and snow meltwater from the Elashan Mountains, with an average elevation of more than 4,500 m above sea level, infiltrates along the fractures, and is heated by deep circulation to form deep geothermal reservoirs. There is no detectable mantle contribution source heat to the hot spring gases, and the heat source is mainly natural heat conduction warming, but the “low-velocity body (LVB)” in the middle and lower crust may be the primary heat source of the high geothermal background in the area. The hot springs’ hydrochemical components show a certain regularity, and the main ionic components, TDS, and water temperature tend to increase away from the main rupture, reflecting the WWFZ controlling effect on hydrothermal transport. In the future, the geothermal research in this area should focus on the hydrothermal control properties of different levels, the nature of fractures, and the thermal contribution of the LVB in the middle and lower crust.

Abstract Background Omega-3 polyunsaturated fatty acids (n-3 PUFAs) confers anti-inflammatory efficacy, which has been suggested to be effective for patients with osteoarthritis (OA). However, previous studies evaluating the influence of n-3 PUFAs supplementation in patients with OA showed inconsistent results. We performed a systematic review and meta-analysis to comprehensively evaluate the influence of n-3 PUFAs on symptom and joint function of patients with OA. Methods Relevant randomized controlled trials (RCTs) were obtained by searching PubMed, Embase, and Cochrane Library databases. A random-effects model was employed to combine the results. Results Nine RCTs with 2070 patients with OA contributed to the meta-analysis. Pooled results showed that n-3 PUFAs supplementation could significantly relieve the arthritis pain as compared to placebo (standardized mean difference [SMD]: − 0.29, 95% confidence interval [CI] − 0.47 to − 0.11, p = 0.002, I 2 = 60%). Besides, supplementation with n-3 PUFAs was also associated with improved joint function (SMD: − 0.21, 95% CI − 0.34 to − 0.07, p = 0.002, I 2 = 27%). Subgroup analysis showed consistent results of studies with arthritis pain and joint function evaluated by the Western Ontario-McMaster University Osteoarthritis Index and other scales (p for subgroup difference = 0.33 and 0.34, respectively). No severe treatment-related adverse events (AEs) were observed in the included patients, and the incidence of overall AEs was similar between groups (odds ratio: 0.97, 95% CI 0.64–1.45, p = 0.86, I 2 = 0%). Conclusions Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with OA.

Aims: Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods: In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results: DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion: We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273.

BackgroundThe SARS-CoV-2 Omicron variant was reported to be linked to febrile seizures (FSs), but studies on FSs in children with Omicron infection remain relatively scarce, especially in the Chinese population. This study aimed to investigate the characteristics of children diagnosed with Omicron infection with FSs in Yunnan, China, and evaluate the potential association between FSs and Omicron infection.MethodsThis study was conducted at four hospitals in Yunnan from December 8, 2022, to January 8, 2023, and consisted of 590 pediatric subjects. According to clinical characteristics, 85, 129 and 376 subjects were divided into the FS-only, Omicron-FS, and Omicron-only groups, respectively. Demographic, clinical and laboratory data were retrospectively collected for analysis.ResultsThe incidence of FSs in children with Omicron infection was 25.5% (129/505). Older age, stronger male predominance, as well as lower proportions of prior history and family history of seizures were observed in Omicron-FS and Omicron-only groups than in FS-only group, but there were no differences in these four above-mentioned events between these two Omicron-related groups. Compared to FS-only group, Omicron-FS group also had a shorter fever-to-seizure onset duration and more frequent seizures during a single course of fever. Moreover, higher levels of IL-6, TNF-α and ferritin as well as decreased counts of leukocytes and lymphocytes were confirmed in Omicron-FS group than in FS-only and Omicron-only groups. Regarding COVID-19 vaccination status, Omicron-FS group revealed a higher proportion of unvaccinated children and a lower proportion of three-dose vaccination than Omicron-only group. As for clinical outcomes, proportions of mechanical ventilation and intensive care unit admission observed in the two Omicron-related groups were notably higher than those in FS-only group. Meanwhile, Omicron-FS group showed the longest length of hospital stay, followed by Omicron-only group and FS-only group, in order. Finally, all patients but one who died of fulminant myocarditis had been successfully discharged.ConclusionsThe incidence of FSs in children with Omicron infection was 25.5% in Yunnan. FSs might be a clinical sign deserving more attention in children with Omicron infection. Furthermore, COVID-19 vaccination is likely to provide effective protection against Omicron-related FSs in children.

Ag nanoparticles (AgNPs) are toxic and can accumulate in the human body or the environment, resulting in biotoxic effects. Ti3C2Tx, a new class of graphene-like 2D nanomaterials, is used in numerous applications due to its special physicochemical properties. There is great concern about the potential damage that this material may cause to the environment and human health. In this study, the interaction mechanisms of Ti3C2Tx, AgNPs and Ti3C2Tx/AgNPs materials with human serum albumin (HSA) were characterized using multispectral analysis and zeta potential measurements, respectively. The results showed that the effects of the three materials on the conformational changes of HSA were AgNPs > Ti3C2Tx/AgNPs > Ti3C2Tx in order. Hydrogen bonding and electrostatic interaction forces played an important role in the binding process of Ti3C2Tx and its complexes with HSA. Ag nanoparticles have a comparatively high level of biotoxicity and have a more significant effect on the conformational changes of proteins. Ti3C2Tx itself has biocompatibility and a large specific surface area. The biotoxicity of Ti3C2Tx/AgNPs complex is lower than that of AgNPs, indicating that the addition of Ti3C2Tx can reduce the biotoxicity of Ag nanoparticles, and Ti3C2Tx may be used as a carrier substance for Ag nanoparticles, which can reduce the toxicity of AgNPs while giving it unique properties similar to those of Ti3C2Tx, thus improve the biosafety of Ag nanoparticles in the application process.

Soil health has gained increasing attention under the rapid development of industrialization and the requirement for green agriculture. Therefore, up-to-date soil information related to soil health is urgently needed to ensure food security and biodiversity protection. Previous studies have shown the potential of proximal soil sensing in measuring soil information, while it remains challenging to get cost-efficient and robust estimates of multiple soil health indicators simultaneously via sensor fusion. In this study, we investigated the potential of visible near-infrared (vis-NIR), and mid-infrared (MIR) spectroscopy as well as three model averaging methods in predicting three soil health properties, including soil organic matter (SOM), pH, cation exchange capacity (CEC). The model averaging methods are not only used for model fusion but also for high-level sensor fusion, which include Granger-Ramanathan (GR), Bayesian Model Averaging and Spectral-Guided Ensemble Modelling (S-GEM). Here, S-GEM is a recently proposed algorithm that can improve soil spectroscopic prediction by including spectral information in ensemble modelling. Four widely used prediction models were evaluated, including partial least square regression, Cubist, memory based learning and convolutional neural network. For SOM, sensor fusion based on model averaging algorithms was comparable to that of Sensorsingle + Modelmultiple (MIR singly based on S-GEM) with R2 of 0.86. However, MIR only with S-GEM performed the best among all methods (LCCC of 0.92, RMSE of 3.66 g kg−1 and RPIQ of 3.68). The 10-fold cross-validation results indicated that Sensorsingle + Modelmultiple (MIR singly based on S-GEM) performed best among all methods for pH, with R2 of 0.84, LCCC of 0.90, RMSE of 0.45 and RPIQ of 3.65. For CEC, Sensormultiple + Modelmultiple based on GR performed best with R2 of 0.66, LCCC of 0.80, RMSE of 3.48 cmol + kg−1 and RPIQ was 2.22. Our results also showed that sensor fusion failed to improve spectral prediction of soil information when the performance among sensors differed a lot (△R2 > 0.2), and the use of a single best sensor is therefore suggested in this case. When the sensors have a close model performance (△R2

The effects of land use/cover change (LUCC) on the spatial distribution and change of ecosystem service value (ESV) are still ambiguous, and cannot effectively guide the formulation of land use (LU) management policies based on the concept of harmonious development. Therefore, based on LUCC data from 1980 to 2020, this study adopted the MCE-CA-Markov model to simulate and predict the LUCC under the Business As Usual (BAU) and Ecological Development Priority (EDP) scenarios in 2030 and 2050. The historical and future ESVs as well as the effects of LUCC on ESV change were calculated in Gansu province, Northwest China. The results showed that the LU and ESV of Gansu province changed greatly between 1980 and 2020, with an increase in Forest (568.62 km2), medium- and high-coverage grassland (1517.58 km2), and Construction land (2264.58 km2), and a decrease in Farmland (-730.17 km2) and Unused land (-2858.58 km2), resulting in an increase of 8.162 billion CNY in total ESV. From 2020 to 2050, the LUCC under the EDP scenario will be more conducive to the increase in ESV, with the increment (52.765 billion CNY) being much higher than that under the BAU scenario (3.885 billion CNY). The growth of ESV will mainly result from the expansion of Forest, Water, and Grassland, accounting for 55.4%, 48.6%, and 19.1% of the total ESV increment, respectively, while the decrease in ESV will be attributed to the changes in Farmland and Unused land, accounting for −16.2% and −10.8% of the total ESV increment, respectively. The results have a certain reference for the future LU structure optimization and ecological benefit growth in northwest China.

Abstract To investigate the long-term deformation properties of unbound granular materials (UGM) that are ordinarily adopted to construct subgrade for high-speed railway, a series of medium-sized cyclic triaxial tests were performed to obtain the relationship between permanent strain and loading cycles under different cyclic stress levels. Moreover, DEM analysis was conducted for the samples to reveal the deformation mechanism and verify the strain developing tendency. It is found that the UGM samples present different long-term deformation properties under different cyclic stress levels. As cyclic stress increases, the permanent strain of UGM sample transfers from rapid stabilization to tardy stabilization, then to tardy failure and finally to rapid failure. Furthermore, the exponent in a power law function was selected as the critical indicator of deformation developing tendency. With the exponent obtained precisely in accordance with the strain rate, the deformation tendency can be analyzed quantitatively. Finally, the characteristics of interparticle force chains induced by different cyclic stress levels were obtained by DEM analysis, which provided evidences for the classification of long-term deformation properties of UGM samples. The achievements have guiding significance for the design of subgrade of both ballasted and unballasted high-speed railway.

Abstract Background Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. Methods Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. Results A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. Conclusion Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM.

Background: The incidence of intervertebral disc degeneration (IVDD) is a common degenerative disease with inflammation, decreased autophagy, and progression of fibrosis as its possible pathogenesis. Physalin A (PA) is a widely studied anti-inflammatory drug. However, its therapeutic effects on IVDD remain unexplored. Therefore, we aimed to explore the therapeutic potential of PA in IVDD progression. Materials and methods: In vivo, we investigated PA bioactivity using a puncture-induced IVDD rat model. IVDD signals and height changes were detected using X-ray, micro-CT, and MRI, and structural and molecular lesions using histological staining and immunohistochemistry of intervertebral disc sections. In vivo, interleukin-1 beta (IL-1β) and TGF-β1 were employed to establish inflammation fibrotic nucleus pulposus (NP) cells. The PA effect duration, concentration, influence pathways, and pathological changes in IVDD treatment were elucidated using western blotting, real-time PCR, and immunofluorescence. Results: PA exerted significant effects on IVDD remission due to anti-inflammation, fibrosis reduction, and autophagy enhancement. In vitro, PA improved inflammation by blocking the NF-κB and MAPK pathways, whereas it promoted autophagy via the PI3K/AKT/mTOR pathway and affected fibrotic progression by regulating the SMAD2/3 pathway. Moreover, PA improved the disc degeneration process in IVDD model. Conclusions: PA exhibited significant anti-inflammatory and anti-fibrotic effects and improved autophagy in vivo and in vitro IVDD models, thus effectively relieving IVDD progression, indicating it is a promising agent for IVDD treatment. The translational potential of this article: This study successfully reveals that PA, a natural bioactive withanolide, effectively relieved IVDD progression via inflammation inhibition, fibrosis reduction, and autophagy enhancement, indicating it is a promising agent for IVDD treatment.

Aims: Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods: After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. Results: In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. Conclusion: Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA. Cite this article: Bone Joint Res 2023;12(2):121–132.

In a medium voltage (MV) solid state transformer(SST), the isolated bidirectional DC/DC converter (IBDC) is the core circuit for controlling power flow and galvanic isolation. Current research works on MV single-cell IBDC mainly focus on two directions: resonant and non-resonant topologies. However, for different scenarios with various voltage regulation ranges and power ranges, which topology should be adopted to achieve better efficiency performance is unclear. To effectively illustrate the two IBDCs’ respective benefits, a comparison between the two IBDCs is conducted in this study along with the optimization design method. For resonant IBDC, a complex objective optimization-based parameter design strategy is developed to realize rapid automatic design under various operating conditions. For non-resonant IBDC, a multi-phase modulation scheme aimed at minimizing the current stress under different voltage and power ranges is introduced. The optimal operating range of the two IBDCs has been derived. A 4 kV/1 kV 200 kW non-resonant IBDC experimental prototype has been built and its efficiency is tested under various operating conditions. The test data were compared with the established power loss model to derive the converter's full range efficiency, and the efficiency of the converter over a wider power range could then be projected.

As the key module of programmable switches or the SmartNIC card, the packet processing pipeline undertakes the task of packet forwarding and processing. However, the current pipeline for the FPGA-based SmartNIC is inflexible, and the related reconfigurable commercial device designs are closed-source. To solve this problem, this paper proposes a high-performance reconfigurable pipeline design, which has fully reconfigurable match-action units, supporting various network functions by its flexible reconfiguration. The fields of the match key and the size of the match table can be reconfigured without recompiling the HDL code or modifying the hardware. The processing rules and action instructions for the pipeline can be dynamically installed by the configuration module at runtime. We implement our design on the Xilinx Alveo U200 board with a Virtex UltraScale+ XCU200-2FSGD2104E FPGA and show that the designed pipeline supports fast reconfiguration to implement new network functions and that the throughput of the designed pipeline reaches 100 Gbps with low latency.

Summary: Endosymbiosis with chemosynthetic Gammaproteobacteria is widely recognized as an adaptive mechanism of siboglinid tubeworms, yet evolution of these endosymbionts and their driving forces remain elusive. Here, we report a finished endosymbiont genome (HMS1) of the cold-seep tubeworm Sclerolinum annulatum. The HMS1 genome is small in size, with abundant prophages and transposable elements but lacking gene sets coding for denitrification, hydrogen oxidization, oxidative phosphorylation, vitamin biosynthesis, cell pH and/or sodium homeostasis, environmental sensing, and motility, indicative of early genome erosion and adaptive evolution toward obligate endosymbiosis. Unexpectedly, a prophage embedded in the HMS1 genome undergoes lytic cycle. Highly expressed ROS scavenger and LexA repressor genes indicate that the tubeworm host likely activates the lysogenic phage into lytic cycle through the SOS response to regulate endosymbiont population and harvest nutrients. Our findings indicate progressive evolution of Sclerolinum endosymbionts toward obligate endosymbiosis and expand the knowledge about phage-symbiont-host interaction in deep-sea tubeworms.

Highlights Surgical treatment of chondrosarcoma of the scapula can achieve good oncologic and functional outcomes. Prosthetic reconstruction of the scapula after scapulectomy does not provide better functional results than humeral suspension, and both are feasible treatment modalities.

Brazzein has excellent potential for use as a sweetener because of its high level of sweetening potency and stability against extreme temperature and pH. It is extracted from the tropical and difficult—to‐cultivate African plant Pentadiplandra brazzeana, which hampers its commercial viability. Here we report the mammary‐specific expression of wildtype or triple mutational (H31R/E36D/E41A) des‐pGlu brazzeins in the milk of transgenic mice. Using enzyme‐linked immunoassay (ELISA), western blot, and sweetness intensity testing, we confirmed that the triple mutation made the des‐pGlu brazzein molecule 10,000 times sweeter than sucrose in a weight base, even after 10 min of incubation at 100 °C; in addition, the triple mutant was also significantly sweeter than the wildtype des‐pGlu brazzein. This study provides new insights for producing brazzein or brazzein‐sweetened milk from animals for use in food and healthcare applications.

BackgroundLower psychological wellbeing is associated with poor outcomes in a variety of diseases and healthy populations. However, no study has investigated whether psychological wellbeing is associated with the outcomes of COVID-19. This study aimed to determine whether individuals with lower psychological wellbeing are more at risk for poor outcomes of COVID-19.MethodsData were from the Survey of Health, Aging, and Retirement in Europe (SHARE) in 2017 and SHARE's two COVID-19 surveys in June–September 2020 and June–August 2021. Psychological wellbeing was measured using the CASP-12 scale in 2017. The associations of the CASP-12 score with COVID-19 hospitalization and mortality were assessed using logistic models adjusted for age, sex, body mass index, smoking, physical activity, household income, education level, and chronic conditions. Sensitivity analyses were performed by imputing missing data or excluding cases whose diagnosis of COVID-19 was solely based on symptoms. A confirmatory analysis was conducted using data from the English Longitudinal Study of Aging (ELSA). Data analysis took place in October 2022.ResultsIn total, 3,886 individuals of 50 years of age or older with COVID-19 were included from 25 European countries and Israel, with 580 hospitalized (14.9%) and 100 deaths (2.6%). Compared with individuals in tertile 3 (highest) of the CASP-12 score, the adjusted odds ratios (ORs) of COVID-19 hospitalization were 1.81 (95% CI, 1.41–2.31) for those in tertile 1 (lowest) and 1.37 (95% CI, 1.07–1.75) for those in tertile 2. As for COVID-19 mortality, the adjusted ORs were 2.05 (95% CI, 1.12–3.77) for tertile 1 and 1.78 (95% CI, 0.98–3.23) for tertile 2, compared with tertile 3. The results were relatively robust to missing data or the exclusion of cases solely based on symptoms. This inverse association of the CASP-12 score with COVID-19 hospitalization risk was also observed in ELSA.ConclusionThis study shows that lower psychological wellbeing is independently associated with increased risks of COVID-19 hospitalization and mortality in European adults aged 50 years or older. Further study is needed to validate these associations in recent and future waves of the COVID-19 pandemic and other populations.

Compared to a stateless data plane, a stateful data plane offloads part of state information and control logic from a controller to a data plane to reduce communication overhead and improve packet processing efficiency. However, existing methods for implementing stateful data planes face challenges, particularly maintaining state consistency during packet processing and improving throughput performance. This paper presents a high-performance, FPGA (Field Programmable Gate Array)-based stateful packet processing approach, which addresses these challenges utilizing the PHV (Packet Header Vector) dynamic scheduling technique to ensure flow state consistency. Our experiments demonstrate that the proposed method could operate at 200 MHz while adding 3–12 microseconds latency. The method we proposed also provides a considerable degree of programmability.

Cell fate commitment involves transcription factor activity and changes in chromatin architecture. Here the authors show that CAF-1 maintains lineage fidelity by controlling chromatin accessibility at specific sites; suppressing CAF-1 triggers differentiation of myeloid stem and progenitor cells into a mixed lineage state.

The Natural Heritage Site of the Coast of Yellow Sea-Bohai Gulf of China plays a prominent role in the conservation of global biodiversity. However, with the increase in the number of species inhabiting here, the problem of competition in the habitat space of species within the heritage site has gradually emerged, which has become an important bottleneck restricting the sustainable development of the heritage site. Therefore, this study selected the typical wetland wildlife in this area, red crowned crane (Grus japonensis) and Chinese water deer (Hydropotes inermis), as the study objects. This study used their continuous GPS tracking data to reveal the seasonal laws of habitat selection and suitability of two typical wetland species, and analyze their spatial competition and coexistence relationship. The study results showed that the distribution of home range of the crane and the deer in spring and summer was significantly larger than that in autumn and winter. The area of the sub and most suitable area of the deer in spring was larger than that of the crane. In autumn and winter, the area of the sub and most suitable areas for the deer was small, while the area of the most suitable area for the crane was more than 50 hm2. Except in spring, the two species kept a certain distance from each other in other seasons, and their habitat selection was stable. The optimal threshold range of the crane for D_ree variable was 0–202 m in spring and 0–1200 m in summer and autumn. The deer was affected by vegetation factors in the four seasons. The threshold range of D_ree variable in spring, autumn and winter was 0–80 m, the suitable vegetation height of the deer was 2.31–2.92 m. Finally, this study proposed a refined management pattern of habitat with multiple species coexist.

BackgroundTo assess the clinical and radiographical outcomes of 3-level anterior cervical discectomy and fusion (ACDF) with a 3D-printed titanium cage in treating degenerative cervical spondylosis.MethodsIn this study, 25 patients with degenerative cervical spondylosis who underwent 3-level ACDF using a 3D-printed titanium cage from March 2019 to June 2021 were retrospectively enrolled. The patient-reported outcome measures (PROMs) were evaluated by visual analog scale (VAS) for the neck (VAS-neck) and arm pain (VAS-arm), Neck Disability Index (NDI) score, Japanese Orthopedic Association (JOA) score, SF-12 concise health survey, and the Odom criteria. The radiographical parameters, including C2-C7 lordosis, segmental angle, segmental height, and subsidence, were assessed. The mean duration of follow-up was 25.6 months.ResultsBony fusion was achieved in all patients (100%). In three patients (12%) mild dysphagia was observed during the follow-up. The VAS-neck, VAS-arm, NDI score, JOA score, SF-12 score, C2-C7 lordosis, and segmental angle improved noticeably at the latest follow-up. Based on the Odom criteria, 22 patients (88%) reported satisfactory (excellent or good). The mean loss of C2-C7 lordosis and segmental angle between the immediate postoperative and the latest follow-up values were 1.6° ± 0.5° and 1.1° ± 0.5°, respectively. The mean subsidence was 0.9 ± 0.6 mm.ConclusionIn patients with multi-level degenerative cervical spondylosis, 3-level ACDF using the 3D-printed titanium cage can effectively relieve the symptoms, stabilize the spine, and restore segmental height and cervical curvature. It is proven to be a reliable option for patients with 3-level degenerative cervical spondylosis. However, a future comparative study involving a larger population and longer follow-up time may be required to further evaluate the safety, efficacy and outcomes of our preliminary results.

Summary: Osteoarthritis (OA) is a trauma-/age-related degenerative disease characterized by chronic inflammation as one of its pathogenic mechanisms. Mulberroside A (MA), a natural bioactive withanolide, demonstrates anti-inflammatory properties in various diseases; however, little is known about the effect of MA on OA. We aim to examine the role of MA on OA and to identify the potential mechanisms through which it protects articular cartilage. In vitro, MA improved inflammatory response, anabolism, and catabolism in IL-1β-induced OA chondrocytes. The chondroprotective effects of MA were attributed to suppressing the MAPK, NF-κB, and PI3K-AKT-mTOR signaling pathways, as well as promoting the autophagy process. In vivo, intra-articular injection of MA reduced the cartilage destruction and reversed the change of anabolic and catabolic-related proteins in destabilized medial meniscus (DMM)-induced OA models. Thus, the study indicates that MA exhibits a chondroprotective effect and might be a promising agent for OA treatment.

Abstract Background This study sought to define the risk factors for lymph node metastasis (LNM) of soft tissue sarcomas (STS) of the head, neck, and extremities, and the clinical significance of negative lymph node dissection (NLND). Methods STS patient data in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2015 were extracted and pooled. Logistics regression analysis was used to identify risk factors for LNM, Cox proportional hazards and Fine–Grey’s models were used for survival analysis, and Propensity score matching analysis (PSM) was used to assess the impact of NLND on patient prognosis. Results A total of 3276 patients were enrolled in the study, of whom 283 (8.6%) developed LNM. Rhabdomyosarcoma had the highest rate of LNM (25.3%), followed by clear cell sarcoma (16.8%) and epithelioid sarcoma (12.4%), while leiomyosarcoma had the lowest rate of LNM (1.3%). Sex, tumor size, grade, histology, and site were significantly associated with LNM. For specific histologic subtypes of STS, NLND significantly improves overall survival (HR: 0.718, 95%CI 0.535–0.962; P = 0.026) and cancer-specific survival (HR: 0.699, 95%CI 0.506–0.967; P = 0.031) and reduces cancer-specific mortality (Gray’s test, P = 0.017). However, NLND did not improve overall survival (P = 0.46) or reduce cancer-specific mortality (Gray’s test, P = 0.772) of patients with leiomyosarcoma. Conclusions Histology is an independent risk factor for LNM in STS of the head, neck, and extremities. Prophylactic NLND treatment was necessary and had a clinical benefit for patients with STS who were at high risk for LNM but had no significant impact on the prognosis of patients with leiomyosarcoma.

To better recover a sparse image signal carrying redundant information from many fewer measurements than the Nyquist-Shannon sampling theorem suggested, convolutional neural networks (CNNs) can be used to emulate a compressed sensing (CS) process. However, the existing CS methods based on CNNs have the problems of high computational complexity and unsatisfactory reconstruction effect. This study aims to present a faster algorithm based on CNNs to obtain reconstructed images with finer texture details from CS measurements. A tree-structured dilated conventional network (TDCN) for image CS is proposed. To extract the image multi-scale features as much as possible for better image reconstruction, the TDCN combines tree-structured residual blocks made of three dilation convolution layers with different dilation factors; the output of each dilated convolution layer is directed to fusion layer to eliminate information loss due to the multiple cascading dilated convolutions. Moreover, L1 loss is employed as an objective optimization function instead of L2 loss to improve training results of the network and achieve better convergence. Extensive CS experiments in the study demonstrate that the proposed TDCN outperforms existing state-of-the-art methods in terms of both PSNR and SSIM at different sampling rates while maintaining a fast computational speed. Our code and the trained model are available at https://github.com/UHADS/TDCN.

The recalcitrance of lignocellulosic biomass is the major limitation for the production of natural gas. Here the authors develop a catalytic-drive approach with Ni2Al3 alloy catalyst to enable nearly complete conversion of various agricultural and forestry residues into natural gas.

Seasons are the important influencing factor for gut microbiota, which in turn affects the ecology and evolution of the host. The seasonal variation in gut microbiota has increasingly attracted the attention of researchers and professionals worldwide. However, studies of seasonal variations in gut microbiota have not been systematically analyzed by bibliometrics or visual analysis. This study is based on 271 publications from 2012 to 2022 in the Web of Science Core Collection database (WOSCC) to analyze hot spots and trends in this field. The collaborations between different countries, institutions, authors, journals, and keywords were bibliometrically analyzed using Excel, CiteSpace (Version 6.2. R4), and VOSviewer (version 1.6.19) software. The number of publications has been increasing rapidly and shows a general upward trend. China and the Chinese Academy of Sciences are the country and institution contributing the most, respectively. The research hotspots and trends mainly include the diversity of gut microbiota communities in different seasons, the relationship between diet and gut microbiota in seasonal changes, and the relationship between gut microbiota and evolutionary adaptation in seasonal changes. This is the first bibliometric and visualization analysis of seasonal variations in gut microbiota, which may advance this field and lay the foundation for future research.

Screening novel narrow-band phosphors inspired by natural mineral structures is urgently demanded for improving the performance of phosphor-converted light-emitting diodes. In this work, a novel narrow-band deep-blue-emitting tungsten bronze-type KCaAl2F9:Eu2+ phosphor with superior thermal stability is successfully synthesized. Structural analysis shows that the representative KCaAl2F9:0.013Eu2+ phosphor crystallizes in an orthorhombic space group C2221 with a rigid network. The rigid [AlF6]3− octahedrons are linked together by sharing corners to build endless [AlF6]3−∞ chains, further stacking with each other in a highly cross–linked way to establish the rigid network of the KCaAl2F9 host. Benefiting from the rigid microenvironment, the developed phosphor not only shows a narrow-band deep-blue emission with a full width at half maximum of 45 nm and a high color purity of 92%, but it also exhibits the superior thermal stability with an emission loss of only 10% at 423 K, demonstrating its application potential in bridging the deep-blue spectral cavity toward sunlight-like full-spectrum lighting. In addition, the concentration/temperature quenching behaviors of KCaAl2F9:Eu2+ phosphor are systematically investigated. By revealing the specific structure–property relationship of tungsten bronze-type KCaAl2F9:Eu2+ phosphor, the present study provides a significant guide for identifying the novel narrow-band deep-blue-emitting component applicable to full-spectrum warm white light-emitting diode devices.

BackgroundOsteoarthritis (OA) is a common aging-related degenerative joint disease with chronic inflammation as its possible pathogenesis. Oroxin B (OB), a flavonoid isolated from traditional Chinese herbal medicine, possesses anti-inflammation properties which may be involved in regulating the pathogenesis of OA, but its mechanism has not been elucidated. Our study was the first to explore the potential chondroprotective effect and elucidate the underlying mechanism of OB in OA.MethodsIn vitro, primary mice chondrocytes were stimulated with IL-1β along with or without the administration of OB or autophagy inhibitor 3-methyladenine (3-MA). Cell viability assay was measured with a cell counting kit-8 (CCK-8). The phenotypes of anabolic-related (Aggrecan and Collagen II), catabolic-related (MMP3, MMP13, and ADAMTS5), inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1β), and markers of related signaling pathways in chondrocytes with different treatment were detected through western blot, RT-qPCR, and immunofluorescent staining. In vivo, the destabilized medial meniscus (DMM) operation was performed to establish the OA mice model. After knee intra-articular injection with OB for 8 weeks, the mice’s knee joints were obtained for subsequent histological staining and analysis.ResultsOB reversed the expression level of anabolic-related proteins (Aggrecan and Collagen II) and catabolic-related (MMP3, MMP13, and ADAMTS5) in IL-1β-induced chondrocytes. Mechanistically, OB suppressed the inflammatory response stimulated by IL-1β, as the inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1β) markers were downregulated after the administration of OB in IL-1β-induced chondrocytes. Besides, the activation of PI3K/AKT/mTOR signaling pathway induced by IL-1β could be inhibited by OB. Additionally, the autophagy process impaired by IL-1β could be rescued by OB. What’s more, the introduction of 3-MA to specifically inhibit the autophagic process impairs the protective effect of OB on cartilage. In vivo, histological staining revealed that intra-articular injection of OB attenuated the cartilage degradation, as well as reversed the expression level of anabolic and catabolic-related proteins such as Aggrecan, Collagen II, and MMP13 induced in DMM-induced OA models.ConclusionsThe study verified that OB exhibited the chondroprotective effect by anti-inflammatory, inhibiting the PI3K/AKT/mTOR signaling pathway, and enhancing the autophagy process, indicating that OB might be a promising agent for the treatment of OA.

Study region: Upper reach of the Heihe River basin (UHRB) Study focus: We quantified the potential changes in future climate and streamflow, as well as their corresponding contribution to the annual variations. And the dominant factors of streamflow change were explored in further. Robust multivariate bias correction was applied to correct the outputs of the general circulation method (GCMs) before applying the climate projection. The Soil and Water Assessment Tool model was applied to explore streamflow characteristics under the climate projection of bias-corrected GCMs under four representative emission scenarios (SSP1–2.6, SSP2–4.5, SSP3–7.0, and SSP5–8.5). New hydrological insights for the region: By the end of the 21st century, climate will follow a warming and wetting trend within the basin; the annual streamflow is projected to increase by > 18 % in the 2030 s, and > 36 % in the 2050 s and 2090 s. Overall, the minimum temperature had a positive impact on streamflow in the cold seasons, especially in spring, contributing the most to the annual streamflow increment. When the temperature increase is greater than 5.42 °C, the peak streamflow will shift forward from May to April. Moreover, evapotranspiration will increase with temperature, leading to a decrease in summer streamflow. The results enable us to better understand the climate and streamflow changes at different time scales and provide guidance for the development of climate change response strategies and water resource management planning.