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Abstract Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.

Abstract Objective An increasing number of studies shown that inadequate energy intake causes an increase in adverse incidents in chronic kidney disease (CKD) patients on low-protein diets (LPD). The study aimed to investigate the relationship between energy intake and cardiovascular mortality in CKD patients on a LPD. Methods This was a cross-sectional study, a total of 4264 CKD patients were enrolled from the NHANES database between 2009 and 2018. Restricted cubic spline plots and Cox regression analysis were used to analyze the association between energy intake and cardiovascular mortality in CKD patients on a LPD. Additionally, a nomogram was constructed to estimate cardiovascular survival in CKD patients on a LPD. Results Among CKD patients on a LPD in the United States, 90.05% had an energy intake of less than 25 kcal/kg/day, compared to 36.94% in CKD patients on a non-LPD. Energy intake and cardiovascular mortality showed a linear relationship in CKD patients on a LPD, while a ‘U-shaped’ relationship was observed in CKD patients on a non-LPD. Multifactorial Cox regression models revealed that for Per-standard deviation (Per-SD) decrement in energy intake, the risk of cardiovascular mortality increased by 41% (HR: 1.41, 95% CI: 1.12, 1.77; P = 0.004) in CKD patients on a LPD. The concordance index of the nomogram was 0.79 (95% CI, 0.75, 0.83). Conclusion CKD patients, especially those on a LPD, have significantly inadequate energy intake. Lower energy intake is associated with higher cardiovascular mortality in CKD patients on a LPD.

Abstract Purpose To compare the efficacy and safety of cortical bone trajectory (CBT) screw and pedicle screw (PS) internal fixation in the treatment of adjacent segment degeneration (ASD) after lumbar fusion. Methods This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023484937). We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and Wei Pu Database by computer to collect controlled clinical studies on the efficacy and safety of cortical bone trajectory (CBT) screw and pedicle screw (PS) internal fixation in the treatment of adjacent segment degeneration (ASD) after lumbar fusion from database establishment to November 2023. Two researchers screened the literature, extracted data and evaluated the risk of bias of the included studies, recorded the authors, and sample size, and extracted the intraoperative blood loss, operation time, Oswestry disability index (ODI), Visual analogue scale (VAS), disc height (DH), hospital length stay and complications in each study. Meta-analysis was performed using Revman 5.4 software provided by Cochrane Library. Results A total of 6 cohort studies (CS) and 1 randomized controlled study with a total of 420 patients were included in this study, including 188 patients in the CBT group and 232 patients in the PS group. The CBT group had lower intraoperative blood loss than the PS group [mean difference (MD) = -129.38, 95% CI (-177.22, -81.55), P

Abstract Background Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective. Methods Vascular endothelial growth factor (VEGFA) was used to treat bone marrow-derived mesenchymal stem cells (BM-MSCs), and their cell migration rates were determined by Transwell assays. The expression of the von Willebrand Factor (vWF)VE-cadherin, and endothelial nitric oxide synthase(eNOS) endothelial markers was determined by qRT‒PCR and Western blot analyses. The MALAT1-induced differentiation of BM-MCs to ECs via the CDC42/PAK1/paxillin pathway was explored by transfecting VEGFA-induced BM-MSC with si-MALAT1 and overexpressing CDC42 and PAK1. The binding capacity between CDC42, PAK1, and paxillin in VEGFA-treated and non-VEGFA-treated BM-MSCs was examined by protein immunoprecipitation. MiR-206 was overexpressed in VEGFA-induced BM-MSC, and the binding sites of MALAT1, miR-206, and CDC42 were identified using a luciferase assay. Sixty male Sprague‒Dawley rats were divided into six groups (n = 10/group). DMED modelling was demonstrated by APO experiments and was assessed by measuring blood glucose levels. Erectile function was assessed by measuring the intracavernosa pressure (ICP) and mean arterial pressure (MAP). Penile erectile tissue was analysed by qRT‒PCR, Western blot analysis, and immunohistochemical staining. Results MALAT1 under VEGFA treatment conditions regulates the differentiation of BM-MSCs into ECs by modulating the CDC42/PAK1/paxillin axis. In vitro experiments demonstrated that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs. CDC42 binds to PAK1, and PAK1 binds to paxillin. In addition, CDC42 in the VEGFA group had a greater ability to bind to PAK1, whereas PAK1 in the VEGFA group had a greater ability to bind to paxillin. Overexpression of miR-206 in VEGFA-induced BM-MSCs demonstrated that MALAT1 competes with the CDC42 3’-UTR for binding to miR-206, which in turn is involved in the differentiation of BM-MSCs to ECs. Compared to the DMED model group, the ICP/MAP ratio was significantly greater in the three BM-MSCs treatment groups. Conclusions MALAT1 facilitates BM-MSC differentiation into ECs by regulating the miR-206/CDC42/PAK1/paxillin axis to improve ED. The present findings revealed the vital role of MALAT1 in the repair of BM-MSCs for erectile function and provided new mechanistic insights into the BM-MSC-mediated repair of DMED.

The Vehicle On-Board Controller (VOBC) is a core component of urban rail transit trains, with high maintenance costs and serious consequences in case of failure. Ensuring long-term VOBC operation while minimizing maintenance costs is of paramount importance. This paper proposes a multi-objective preventive maintenance (PM) strategy and optimization considering system unavailability and maintenance costs. Firstly, we provide a statement of the problem and analyze the impact of different maintenance actions on VOBC. Next, the decreasing process parameter is introduced to adjust the PM interval dynamically. The mathematical models of system unavailability and maintenance costs are derived to construct a multi-objective PM strategy. Then, we develop a hybrid heuristic algorithm including multi-objective particle swarm optimization and genetic algorithm (MOPSO-GA), which is used to obtain the optimal Pareto frontier for maintenance strategies. In the study, we select maintenance strategies by introducing an aversion factor to fulfill the preferences of different decision-makers. A comprehensive sensitivity analysis is performed to illustrate the impact of several critical parameters on the multi-objective PM strategy. The case study on Beijing subway’s VOBC is also executed. The outcomes indicate that the proposed method can dynamically adjust to match the preferences of diverse decision-makers and the MOPSO-GA algorithm has excellent robustness on most parameters. This approach allows for creating field maintenance strategies catering to the varied maintenance requirements of urban rail transit VOBC.

This research examines the function of protein associated with topoisomerase II homolog 1 (PATL1) in nasal-type natural killer/T-cell lymphoma (NKTCL) and head and neck squamous cell carcinoma (HNSCC). We analyzed bulk RNA-seq data from NKTCL, nasal polyps, and normal nasal mucosa, identifying 439 differentially expressed genes. Machine learning algorithms highlighted PATL1 as a hub gene. PATL1 exhibited significant upregulation in NKTCL and HNSCC tumor samples in comparison to normal tissues, showing high diagnostic accuracy (AUC = 1.000) for NKTCL. Further analysis of local hospital data identified PATL1 as an independent prognostic risk factor for NKTCL. Data analysis of TCGA and GEO datasets revealed that high PATL1 expression correlated with poorer prognosis in HNSCC patients (p

Abstract Chronic spontaneous urticaria (CSU) comes with gut dysbiosis, but its relevance remains elusive. Here we use metagenomics sequencing and short-chain fatty acids metabolomics and assess the effects of human CSU fecal microbial transplantation, Klebsiella pneumoniae, Roseburia hominis, and metabolites in vivo. CSU gut microbiota displays low diversity and short-chain fatty acids production, but high gut Klebsiella pneumoniae levels, negatively correlates with blood short-chain fatty acids levels and links to high disease activity. Blood lipopolysaccharide levels are elevated, link to rapid disease relapse, and high gut levels of conditional pathogenic bacteria. CSU microbiome transfer and Klebsiella pneumoniae transplantation facilitate IgE-mediated mast cell(MC)-driven skin inflammatory responses and increase intestinal permeability and blood lipopolysaccharide accumulation in recipient mice. Transplantation of Roseburia hominis and caproate administration protect recipient mice from MC-driven skin inflammation. Here, we show gut microbiome alterations, in CSU, may reduce short-chain fatty acids and increase lipopolysaccharide levels, respectively, and facilitate MC-driven skin inflammation.

The strong multipath and long delay extensions can lead to large errors in the timing offset estimation and carrier frequency offset estimation of the Orthogonal Frequency Division Multiplexing (OFDM) underwater communication system, resulting in significant performance degradation. Therefore, this paper proposes a robust time-frequency synchronization method for OFDM systems. First, a new preamble based on Constant Amplitude Zero Autocorrelation (CAZAC) sequence is designed, and a new signal timing offset estimation method is developed based on the time domain characteristics of the preamble. Secondly, a two-stage frequency offset estimation (CFO) method is designed in the time domain followed by the frequency domain, which achieves a wide range of high-accuracy frequency offset estimation. Finally, an adaptive threshold signal first-arrival path detection method is proposed to achieve reliable detection of the position of the signal first-arrival path under complex multipath channels. The simulation, pool, and lake experiment results are provided to verify the reliability and effectiveness of this method. Compared with the traditional methods, the proposed method can more accurately obtain the signal timing position and estimate the CFO in complex multipath channels, and at the same time greatly expand the estimation range of the CFO.

Abstract Background Previous research has shown that lymphocytes and cytokines can mediate bone metabolism. This study explored the clinical association and predictive ability of lymphocytes and cytokines levels for bone metabolism. Methods A total of 162 patients were enrolled in this study. The levels of N-terminal propeptide of type I procollagen (P1NP), β-collagen degradation product (β-CTX), total T lymphocytes, immature T lymphocytes, suppressor/cytotoxic T lymphocytes, helper/inducer T lymphocytes, B lymphocytes, natural killer (NK) cells, Interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), IFN-α, interleukin-1 beta (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL12p70 were evaluated. The relationship between these lymphocyte subsets and cytokines with bone metabolic status was examined and their predictive ability for bone metabolic status was assessed. Results The principal component analysis (PCA) and correlation analysis results varied on differences in lymphocyte subsets and cytokines in various bone metabolism states. Differential analysis revealed significant differences in the absolute counts of B lymphocytes (P

ObjectivesTo assess the effect of total sleep deprivation (TSD) on spontaneous brain activity in medical staff during routine clinical practice.MethodsA total of 36 medical staff members underwent resting-state functional MRI (rs-fMRI) scans and neuropsychological tests twice, corresponding to rested wakefulness (RW) after normal sleep and 24 h of acute TSD. The rs-fMRI features, including the mean fractional amplitude of low-frequency fluctuation (mfALFF), z-score transformed regional homogeneity (zReHo), and functional connectivity (zFC), were compared between RW and TSD. Correlation coefficients between the change in altered rs-fMRI features and the change in altered scores of neuropsychological tests after TSD were calculated. Receiver operating characteristic (ROC) and logistic regression analyses were performed to evaluate the diagnostic efficacy of significantly altered rs-fMRI features in distinguishing between RW and TSD states.ResultsBrain regions, including right superior temporal gyrus, bilateral postcentral gyrus, left medial superior frontal gyrus, left middle temporal gyrus, right precentral gyrus, and left precuneus, showed significantly enhanced rs-fMRI features (mfALFF, zReHo, zFC) after TSD. Moreover, the changes in altered rs-fMRI features of the right superior temporal gyrus, bilateral postcentral gyrus, left middle temporal gyrus, and left precuneus were significantly correlated with the changes in several altered scores of neuropsychological tests. The combination of mfALFF (bilateral postcentral gyrus) and zFC (left medial superior frontal gyrus and left precuneus) showed the highest area under the curve (0.870) in distinguishing RW from TSD.ConclusionSpontaneous brain activity alterations occurred after TSD in routine clinical practice, which might explain the reduced performances of these participants in neurocognitive tests after TSD. These alterations might be potential imaging biomarkers for assessing the impact of TSD and distinguishing between RW and TSD states.

ObjectiveThis study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).MethodsThe study enrolled patients with diagnosis of T2D between 2009 and 2018 from the National Nutrition and Health Examination Survey (NHANES) database. Demographic information, laboratory test, and diagnostic data were collected. Restricted cubic spline (RCS) plots were used to assess the dose-effect relationship between LDH levels and the risk of DKD in patients with T2D. Based on LDH levels, individuals were divided into higher and lower groups using dichotomy, and multivariate logistic regression analysis was conducted to explore the relationship between different LDH levels and the risk of DKD in T2D patients. Stratified analysis was performed to assess the consistency of the result.ResultsA total of 4888 patients were included in the study, with 2976 (60.9%) patients without DKD and 1912 (39.1%) patients with DKD. RCS plots showed that the risk of DKD increased with increasing LDH levels. Multifactorial logistic regression analysis revealed that T2D patients with higher LDH levels had a 45% increased risk of DKD compared to those with lower LDH levels (OR=1.45; 95% CI: 1.11-1.89). Furthermore, each standard deviation increase in LDH level was associated with a 24% increase in DKD incidence among T2D patients (OR=1.24; 95% CI: 1.07-1.44). Stratified analysis consistently supported these findings.ConclusionsLDH can serve as a valuable biomarker for screening DKD in patients with T2D.

The study was designed to evaluate the antiproliferative effects of Nigella sativa plant ethanol extract against MDA-MB-231 triple-negative breast cancer cells. DAPI and annexin V/propidium iodide staining assays were used to examine apoptosis. Results showed that N. sativa extract significantly (p

Multi-scalar multiplication (MSM) is an important building block in most of elliptic-curve-based zero-knowledge proof systems, such as Groth16 and PLONK. Recently, Lu et al. proposed cuZK, a new parallel MSM algorithm on GPUs. In this paper, we revisit this scheme and present a new GPU-based implementation to further improve the performance of MSM algorithm. First, we propose a novel method for mapping scalars into Pippenger’s bucket indices, largely reducing the number of buckets compared to the original Pippenger algorithm. Second, in the case that memory is sufficient, we develop a new efficient algorithm based on homogeneous coordinates in the bucket accumulation phase. Moreover, our accumulation phase is load-balanced, which means the parallel speedup ratio is almost linear growth as the number of device threads increases. Finally, we also propose a parallel layered reduction algorithm for the bucket aggregation phase, whose time complexity remains at the logarithmic level of the number of buckets. The implementation results over the BLS12-381 curve on the V100 graphics card show that our proposed algorithm achieves up to 1.998x, 1.821x and 1.818x speedup compared to cuZK at scales of 221, 222, and 223, respectively.

Background Ferroptosis plays an important role in enhancing the efficacy of anti-programmed cell death 1 (PD-1) immunotherapy; however, the molecular mechanisms by which tumor ferroptosis sensitizes melanoma and lung cancer to anti-PD-1 immunotherapy have not been elucidated.Methods Cytotoxicity assays, colony formation assays, flow cytometry and animal experiments were used to evaluate the effects of mefloquine (Mef) on survival and ferroptosis in melanoma and lung cancer. RNA sequencing, Real-time quantitative PCR (qRT-PCR), western blotting, chromatin immunoprecipitation-qPCR and flow cytometry were used to determine the molecular mechanisms by which Mef regulates lysophosphatidylcholine acyltransferase 3 (LPCAT3). The relationship between LPCAT3 and the efficacy of anti-PD-1 immunotherapy was verified via a clinical database and single-cell RNA sequencing (ScRNA-Seq).Results In this study, we discovered that Mef induces ferroptosis. Furthermore, treatment with Mef in combination with T-cell-derived interferon-γ (IFN-γ) enhanced tumor ferroptosis and sensitized melanoma and lung cancer cells to anti-PD-1 immunotherapy. Mechanistically, Mef upregulated the expression of LPCAT3, a key gene involved in lipid peroxidation, by activating IFN-γ-induced STAT1-IRF1 signaling, and knocking down LPCAT3 impaired the induction of ferroptosis by Mef+IFN-γ. Clinically, analysis of the transcriptome and single-cell sequencing results in patients with melanoma showed that LPCAT3 expression was significantly lower in patients with melanoma than in control individuals, and LPCAT3 expression was positively correlated with the efficacy of anti-PD-1 immunotherapy.Conclusions In conclusion, our study demonstrated a novel mechanism by which LPCAT3 is regulated, and demonstrated that Mef is a highly promising new target that can be utilized to enhance the efficacy of anti-PD-1 immunotherapy.

The study aims to investigate the multiple mediating roles of core self-evaluation and sense of school belonging in the relationship between father-child attachment and academic burnout in college students. A sample of 418 college students completed the father-child attachment scale, the scale of sense of school belonging, core self-evaluation scale, and academic burnout scale. After controlling for variables such as mother–child attachment, gender, age, and grade, the results showed: (1) father-child attachment was significantly and negatively correlated with academic burnout, and positively correlated with core self-evaluation and sense of school belonging; both core self-evaluation and sense of school belonging were significantly and negatively correlated with academic burnout. (2) The multiple mediating model of father-child attachment influencing academic burnout in college students was established. Both core self-evaluation and sense of school belonging played a partial mediating role between father-child attachment and academic burnout. The direct effect of father-child attachment on academic burnout accounts for 33.3% of the total effect. The indirect effects of core self-evaluation and sense of school belonging between father-child attachment and academic burnout account for 50.0 and 16.7% of the total effect, respectively. These findings identify the internal mechanisms through which father-child attachment affects academic burnout in college students from personal traits and interpersonal perspectives.

Abstract Objective To compare the efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in lumbar degenerative diseases. Methods This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023432460). We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Database, and Wei Pu Database by computer to collect controlled clinical studies on the efficacy and safety of unilateral BE-TLIF and MIS-TLIF in lumbar degenerative diseases from database establishment to May 2023. Two researchers screened the literature, extracted data and evaluated the risk of bias of the included studies, recorded the authors, and sample size, and extracted the intraoperative blood loss, operation time, postoperative drainage, Oswestry disability index, Visual analogue scale, lumbar lordosis, disk height, hospital length stay, fusion rate, and complications in each study. Meta-analysis was performed using Revman 5.4 software provided by Cochrane Library. Results A total of 14 cohort studies with a total of 1007 patients were included in this study, including 472 patients in the BE-TLIF group and 535 patients in the MIS-TLIF group. The BE-TLIF group had lower intraoperative blood loss than the MIS-TLIF group [mean difference (MD) = − 78.72, 95% CI (− 98.47, − 58.97), P

As high-energy cathode materials, conversion-type metal fluorides provide a prospective pathway for developing next-generation lithium-ion batteries. However, they suffer from severe performance decay owing to continuous structural destruction and active material dissolution upon cycling, which worsen at elevated temperatures. Here, we design a novel FeF2 cathode with in situ polymerized solid-state electrolyte systems to enhance the cycling ability of metal fluorides at 60 ​°C. Novel FeF2 with a mesoporous structure (meso-FeF2) improves Li+ diffusion and relieves the volume change that typically occurs during the alternating conversion reactions. The structural stability of the meso-FeF2 cathode is strengthened by an in situ polymerized solid-state electrolyte, which prevents the pulverization and ion dissolution that are inevitable for conventional liquid electrolytes. Under the double action of this in situ polymerized solid-state electrolyte and the meso-FeF2's mesoporous structure, the active material maintains an intact SEI layer and part of the mesoporous structure after long charge–discharge cycling, showing excellent cycling stability at high temperatures.

The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic reprogramming places aerobic glycolysis in a dominant position, the TCA cycle remains indispensable for tumor cells as a hub for the metabolic linkage and interconversion of glucose, lipids, and certain amino acids. TCA intermediates such as citrate, α-ketoglutarate, succinate, and fumarate are altered in tumors, and they regulate the tumor metabolism, signal transduction, and immune environment to affect tumorigenesis and tumor progression. This article provides a comprehensive review of the modifications occurring in tumor cells in relation to the intermediates of the TCA cycle, which affects tumor pathogenesis and current therapeutic strategy for therapy through targeting TCA cycle in cancer cells.

AbstractObjective There is a paucity of research on the association between bile acids (BAs) levels and all-cause death in patients with diabetes mellitus (DM) on maintenance hemodialysis (MHD). This study aimed to investigate the clinical characteristics of patients with DM on MHD according to different BAs levels and their impact on prognosis.Methods A retrospective cohort of 1,081 patients on hemodialysis at Xindu People’s Hospital and the First Affiliated Hospital of Chengdu Medical College were enrolled. Demographic and clinical characteristics were collected. The relationship between BAs and all-cause death risk was fitted using restricted cubic splines (RCS), and the BAs cutoff value was calculated. Patients were divided into low and high BAs groups based on the cutoff value. The primary endpoint was all-cause death and the secondary outcomes were deaths from cardiovascular events.Results Finally, 387 patients with DM on MHD were included. The median BAs level of all patients was 4.0 μmol/L. The RCS-based BAs cutoff value was 3.5 μmol/L. The BAs levels correlated negatively with total cholesterol, low-density lipoprotein, and blood calcium levels. During the follow-up, 21.7% of the patients died. The multivariate Cox regression analysis demonstrated that patients with DM on MHD with higher BAs were associated independently with a decreased risk of all-cause death (HR =0.55; 95% CI, 0.35–0.81, p = 0.01) compared to those with lower BAs levels.Conclusions Higher BAs levels were associated with lower lipid levels in patients with DM on MHD. BAs is an independent risk factor for all-cause death in patients with DM on MHD.

In this paper, the effect of a buffer layer created using different hydrogen-containing ratios of reactive gas on the electrical properties of a top-gate In-Ga-Zn-O thin-film transistor was thoroughly investigated. The interface roughness between the buffer layer and active layer was characterized using atomic force microscopy and X-ray reflection. The results obtained using Fourier transform infrared spectroscopy show that the hydrogen content of the buffer layer increases with the increase in the hydrogen content of the reaction gas. With the increase in the hydrogen-containing materials in the reactive gas, field effect mobility and negative bias illumination stress stability improve nearly twofold. The reasons for these results are explained using technical computer-aided design simulations.

Rotary kiln has been widely used in hazardous waste treatment because of its strong adaptability to raw materials, high productivity, and simple processing technology. However, the formation of deposits reduces its performance period and profitability. This study characterized the deposit mineralogy and thermodynamically and experimentally investigated its formation mechanism. The results show that the main phases of the deposit are magnetite, monolithic iron, olivine, and yellow feldspar. They indicate that the deposit formation process was accompanied by the participation of alkaline and iron oxides. The intermediate product Ca2SiO4 can promote the generation of low melting point phases, such as CaFeSiO4 and Ca2Al2SiO7, which are the main phases of deposit materials. Additionally, the reduction intermediate product FeO facilitated the generation of a liquid ferrous mixture (Fe3O4-FeO and Fe3O4-FeO-Fe mixture), which in turn further promoted the growth of the initial deposit phase. The solid deposit formed and attached to the kiln inner wall, along with a decrease in temperature. These results are expected to provide an idea or approach for fundamentally solving the problem of deposits in the rotary kiln.

Abstract Objective To investigate the feasibility of diagnosing osteoporosis (OP) in women through magnetic resonance image compilation (MAGiC). Methods A total of 110 patients who underwent lumbar magnetic resonance imaging and dual X-ray absorptiometry examinations were collected and divided into two groups according bone mineral density: osteoporotic group (OP) and non-osteoporotic group (non-OP). The variation trends of T1 (longitudinal relaxation time), T2 (transverse relaxation time) and BMD (bone mineral density) with the increase of age, and the correlation of T1 and T2 with BMD were examined by establishing a clinical mathematical model. Results With the increase of age, BMD and T1 value decreased gradually, while T2 value increased. T1 and T2 had statistical significance in diagnosing OP (P

Abstract Constitutive activation of RAS-RAF-MEK-ERK signaling pathway (MAPK pathway) frequently occurs in many cancers harboring RAS or RAF oncogenic mutations. Because of the paradoxical activation induced by a single use of BRAF or MEK inhibitors, dual-target RAF and MEK treatment is thought to be a promising strategy. In this work, we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases, thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS mutations. KinaseProfiler enzyme profiling, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), cellular thermal shift assay, computational docking, and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/2. Kinase assay, luminescent ADP detection assay, and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase activity. Notably, erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase activity. Moreover, erianin attenuated melanoma and colorectal cancer in vivo. Overall, we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.

Heavy metal contamination from coal mining calls for advanced bioremediation, i.e., using sulfate-reducing bacteria (SRB) technology. Yet, the interaction of SRB with native soil microbiota during metal sequestration, especially in the presence of plants, remains ambiguous. In this study, we assessed the metal sequestration capabilities, ecological network interactions, and enzymatic functions in soils treated with a predominant SRB consortium, mainly Desulfovibrio (14 OTUs, 42.15%) and Desulfobulbus (7 OTUs, 42.27%), alongside Acacia dealbata (AD) and Pisum sativum (PS) plants. The SRB consortium notably enhanced the immobilization of metals such as Zn, Cu, As, and Pb in soil, with the conversion of metals to residual forms rising from 23.47 to 75.98%. Plant inclusion introduced variability, potentially due to changes in root exudates under metal stress. While AD flourished, PS demonstrated significant enhancement in conjunction with SRB, despite initial challenges. Comprehensive microbial analyses revealed the pivotal role of SRB in influencing microbial networking, underpinning critical ecological links. This interplay between plants and SRB not only enhanced microbial diversity but also enriched soil nutrients. Further, enzymatic assessments, highlighting enzymes like NADH:ubiquinone reductase and non-specific serine/threonine protein kinase, reinforced contribution of SRB to energy metabolism and environmental resilience of the entire soil microbial community. Overall, this research underscores the potential of SRB-driven bioremediation in revitalizing soils affected by coal mining.

Abstract Lithium (Li) metal anodes have attracted extensive attention due to their ultrahigh theoretical capacity and low potential. However, the uneven deposition of Li near the unstable electrode/electrolyte interfaces leads to the growth of Li dendrites and the degradation of active electrodes. Herein, we directly fluorinate alkyne‐containing conjugated microporous polymers (ACMPs) microspheres with fluorine gas (F2) to introduce a novel fluorinated interlayer as an interfacial stabilizer in lithium metal batteries. Using density functional theory methods, it is found that as‐prepared fluorinated ACMP (FACMP) has abundant partially ionic C–F bonds. The C–F bonds with electrochemical lability yield remarkable lithiophilicity during cycling. The in situ reactions between the active C–F bonds and Li ions enable transfer of lithium fluoride microcrystals to the solid electrolyte interphase (SEI) layers, guaranteeing effective ionic distribution and smooth Li deposition. Consequently, Li metal electrodes with the fluorinated interlayers demonstrate excellent cycling performances in both half‐batteries and full cells with a lithium bis(trifluoromethanesulfonyl)imide electrolyte as well as a nonfluorinated lithium bis(oxalate)borate electrolyte system. This strategy is highly significant in customizable SEI layers to stabilize electrode interfaces and ensure high utilization of Li metal anodes, especially in a nonfluorinated electrolyte.

Background anti-Programmed Death-1 (anti-PD-1) immunotherapy has shown promising manifestation in improving the survival rate of patients with advanced melanoma, with its efficacy closely linked to Programmed cell death-Ligand 1 (PD-L1) expression. However, low clinical efficacy and drug resistance remain major challenges. Although the metabolic alterations from tricarboxylic acid (TCA) cycle to glycolysis is a hallmark in cancer cells, accumulating evidence demonstrating TCA cycle plays critical roles in both tumorigenesis and treatment.Methods The plasma levels of metabolites in patients with melanoma were measured by nuclear magnetic resonance (NMR) spectroscopy. The effect of pyruvate dehydrogenase subunit 1 (PDHA1) and oxoglutarate dehydrogenase (OGDH) on immunotherapy was performed by B16F10 tumor-bearing mice. Flow cytometry analyzed the immune microenvironment. RNA sequencing analyzed the global transcriptome alterations in CPI613-treated melanoma cells. The regulation of PD-L1 and glycolysis by PDHA1/OGDH-ATF3 signaling were confirmed by Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, dual-luciferase reporter gene, Chromatin immunoprecipitation (ChIP)-quantitative PCR and Seahorse assay. The relationship between PDHA1/OGDH-ATF3-glycolysis and the efficacy of melanoma anti-PD-1 immunotherapy was verified in the clinical database and single-cell RNA-seq (ScRNA-Seq).Results In our study, the results showed that significant alterations in metabolites associated with glycolysis and the TCA cycle in plasma of patients with melanoma through NMR technique, and then, PDHA1 and OGDH, key enzymes for regulation TCA cycle, were remarkable raised in melanoma and negatively related to anti-PD-1 efficacy through clinical database analysis as well as ScRNA-Seq. Inhibition of PDHA1 and OGDH by either shRNA or pharmacological inhibitor by CPI613 dramatically attenuated melanoma progression as well as improved the therapeutic efficacy of anti-PD-1 against melanoma. Most importantly, suppression of TCA cycle remarkably raises PD-L1 expression and glycolysis flux through AMPK-CREB-ATF3 signaling.Conclusions Taken together, our results demonstrated the role of TCA cycle in immune checkpoint blockade and provided a novel combination strategy for anti-PD-1 immunotherapy in melanoma treatment.

Abstract Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG’s function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.

Adaptor signature is extended from the standard digital signature, which conceals a secret value in the “pre-signature”. The one who knows the secret value can transform it into a completed signature. Adaptor signatures are useful in addressing blockchain scalability issues, and have been used to build blockchain scaling protocols, such as payment channels or atomic swaps. Recently, someone propose two-party adaptor signature to enhance the privacy in application of adaptor signatures. However, we notice that there is no identity-based two-party adaptor signature scheme so far. Based on IEEE P1363 standard identity-based signature scheme, a secure two-party adaptor signature is constructed in this paper. Moreover, under the random oracle model, we analyze the security of our proposed P1363-based two-party adaptor signature. Finally, we make a comparison between our scheme and other adaptor signature schemes in computation and communication overheads, the result shows the costs of our scheme are acceptable.

Adaptor signature, as a new emerging cryptographic primitive, has become one promising method to mitigate the scalability issue on blockchain. It can transform an incomplete signature into a complete signature by revealing the witness of a pre-set hard relation, which can be applied to atomic swap, payment channel, payment hub, and other blockchain scenarios. Recently, a general transformation for constructing adaptor signatures has been proposed for some signature schemes with specific structures, e.g., Schnorr, ECDSA, SM2 signatures. However, we note that there is no identity-based adaptor signature method so far. In this article, we put forward an adaptor signature scheme for the identity-based signature scheme in the IEEE P1363 standard. Then, we formally prove the security of our scheme under the random oracle model. We also present the computation and communication costs, compared with other adaptor signatures. Finally, we show our scheme's potential use in atomic swaps and payment channel networks of blockchain.

Online social networks (OSNs) are becoming more and more popular in people's lives as the demand for online interaction continues to grow. Current OSNs are using centralized identity management system (IDM), which has some problems of single point of failure and privacy data leakage. The emergence of decentralized identity (DID) can solve these problems. However, most existing DID systems have some privacy issues that a user's attributes value are disclosed while accessing service. In this paper, we design a DID protocol to solve these challenges. The proposed protocol includes a range proof protocol to provide attribute privacy. The range proof protocol works with anonymous credentials and does not need a trusted setup. Moreover, the identity model behind the DID protocol is extended from an existing model, which achieves identity revocation. Finally, we implement a system prototype on the blockchain for evaluation. The security analysis shows that our protocol provides stronger privacy protection. The performance evaluation indicates that the computation cost and blockchain overheads of our protocol are acceptable in OSNs.

Abstract Background The 5-year survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remains

Abstract Objective To evaluate the efficacy and safety of tranexamic acid (TXA) in hemostasis in patients undergoing posterior lumbar interbody fusion (PLIF) by meta-analysis. Methods This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42022354812). The databases PubMed, Cochrane Library, Web of Science, and Embase were searched for randomized controlled trial (RCT) papers on the use of TXA in patients with PLIF from database establishment to August 2022. Two researchers screened the literature, extracted data, evaluated the risk of bias of the included studies, recorded the authors, sample size, type of study design, and TXA dose of each study, and extracted the intraoperative blood loss, number of blood transfusions, total blood loss, drainage volume, operation time, and incidence of deep venous thrombosis in each study. Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Library. Results A total of 14 RCTs with a total of 1681 patients were included in this study, including 836 patients in the TXA group and 845 patients in the control group. The intraoperative blood loss [mean difference (MD) = − 125.97, 95% confidence interval (CI) (− 138.56, − 113.37), P

Abstract Background C-Jun, a critical component of AP-1, exerts essential functions in various tumors, including melanoma, and is believed to be a druggable target for cancer therapy. Unfortunately, no effective c-Jun inhibitors are currently approved for clinical use. The advent of immune checkpoint inhibitor (ICI) has brought a paradigm shift in melanoma therapy, but more than half of patients fail to exhibit clinical responses. The exploration of new combination therapies has become the current pursuit of melanoma treatment strategy. This study aims to screen out Chinese herbal monomers that can target c-Jun, explore the combined effect of c–Jun inhibitor and ICI, and further clarify the related molecular mechanism. Methods We adopted a combinatorial screening strategy, including molecular docking, ligand-based online approaches and consensus quantitative structure-activity relationship (QSAR) model, to filter out c-Jun inhibitors from a traditional Chinese medicine (TCM) library. A mouse melanoma model was used to evaluate the therapeutic efficacy of monotherapy and combination therapy. Multicolor flow cytometry was employed to assess the tumor microenvironment (TME). Multiple in vitro assays were performed to verify down-streaming signaling pathway. CD4 + T-cell differentiation assay was applied to investigate Treg differentiation in vitro. Results Ailanthone (AIL) was screened out as a c-Jun inhibitor, and inhibited melanoma cell growth by directly targeting c-Jun and promoting its degradation. Surprisingly, AIL also facilitated the therapeutic efficacy of anti-programmed death ligand-1 (PD-L1) in melanoma cells by reducing the infiltration of Tregs in TME. Additionally, AIL treatment inhibited c-Jun-induced PD-L1 expression and secretion. As a consequence, Treg differentiation was attenuated after treatment with AIL through the c-Jun/PD-L1 axis. Conclusion Our findings identified AIL as a novel c-Jun inhibitor, and revealed its previously unrecognized anti-melanoma effects and the vital role in regulating TME by Treg suppression, which provides a novel combination therapeutic strategy of c-Jun inhibition by AIL with ICI. Graphical Abstract AIL down-regulates c-Jun by reducing its stability, and inhibits the function of Tregs via AIL-c-Jun-PD-L1 pathway, ultimately suppressing melanoma progression and enhancing the efficacy of anti-PD-L1.

For rotor–bearing systems, their dynamic vibration models must be built to simulate the vibration responses that affect the safe and reliable operation of rotating machinery under different operating conditions. Single physics-based modeling methods can be used to produce sufficient but inaccurate vibration samples at the cost of computational complexity. Moreover, single data-driven modeling methods may be more accurate, employing larger numbers of measured samples and reducing computational complexity, but these methods are affected by the insufficient and imbalanced samples in engineering applications. This paper proposes a physics-informed hybrid modeling method for simulating the dynamic responses of rotor–bearing systems to vibration under different rotor speeds and bearing health statuses. Firstly, a three-dimensional model of a rolling bearing and its supporting force are introduced, and a physics-based dynamic vibration model that couples flexible rotors and rigid bearings is constructed using multibody dynamics simulation. Secondly, combining the simulation vibration data obtained using the physics-based model with measured vibration data, algorithms are designed to learn vibration generation and data mapping networks in series connection to form a physics-informed hybrid model, which can quickly and accurately output the vibration responses of a rotor–bearing system. Finally, a case study on the single-span rotor platform is provided. By comparing the signal output by the proposed physics-informed hybrid modeling method with the measured signal in the time and frequency domains, the effectiveness of proposed method under both constant- and variable-speed operating conditions are illustrated.

Abstract In the wave of the Internet era created by computer and communication technology, flexible sensors play an important role in accurately collecting information owing to their excellent flexibility, ductility, freeform bending or folding, and versatile structural shapes. By endowing elastomeric polymers with conductivity, researchers have recently devoted extensive efforts toward developing high‐performance flexible sensors based on elastomeric conductive layers and exploring their potential applications in diverse fields ranging from project manufacturing to daily life. This review reports the recent advancements in elastomeric polymers used to make conductive layers, as well as the relationships between elastomeric polymers and the performance and application of flexible sensors are comprehensively summarized. First, the principles and methods for using elastomeric polymers to construct conductive layers are provided. Then, the fundamental design, unique properties, and underlying mechanisms in different flexible sensors (pressure/strain, temperature, humidity) and their related applications are revealed. Finally, this review concludes with a perspective on the challenges and future directions of high‐performance flexible sensors.

Abstract Autophagy and apoptosis are essential processes that participate in cell death and maintain cellular homeostasis. Dysregulation of these biological processes results in the development of diseases, including cancers. Therefore, targeting the interaction between apoptosis and autophagy offers a potential strategy for cancer therapy. Melanoma is the most lethal skin cancer. We previously found that tumor necrosis factor receptor‐associated factor 6 (TRAF6) is overexpressed in melanoma and benefits the malignant phenotype of melanoma cells. Additionally, TRAF6 promotes the activation of cancer‐associated fibroblasts in melanoma. However, the role of TRAF6 in autophagy and apoptosis remains unclear. In this study, we found that knockdown of TRAF6 induced both apoptosis and autophagy in melanoma cells. Transcriptomic data and real‐time PCR analysis demonstrated reduced expression of autophagy related 16 like 2 (ATG16L2) in TRAF6‐deficient melanoma cells. ATG16L2 knockdown resulted in increased autophagy and apoptosis. Mechanism studies confirmed that TRAF6 regulated ATG16L2 expression through c‐Jun. Importantly, targeting TRAF6 with cinchonine, a TRAF6 inhibitor, effectively suppressed the growth of melanoma cells by inducing autophagy and apoptosis through the TRAF6/c‐Jun/ATG16L2 signaling pathway. These findings highlight the pivotal role of TRAF6 in regulating autophagy and apoptosis in melanoma, emphasizing its significance as a novel therapeutic target for melanoma treatment.

This study explored the role of replacing fish meal protein with fermented soybean meal (FSBM) protein on the growth performance and intestinal morphology, immunity, and microbiota of the pearl gentian grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂). Three isonitrogenous and isolipidic diets with increasing levels of FSBM (0%, 20% and 40%; referred to as FM, FSBM20 and FSBM40 diets, respectively) as a replacement for fish meal were selected for this study. The pearl gentian grouper were fed these diets for 10 weeks. The findings revealed that the growth of fish fed the FSBM diets (FSBM20 and FSBM40) were remarkably lower than the fish fed the FM diet. Pathological manifestations of intestinal inflammation, such as shortened intestinal mucosal folds and thickened lamina propria, were observed in the fish fed the FSBM diets. Moreover, the gene expression levels of IL1β, IL12, IL17, and TNFα were remarkably upregulated in fish fed the FSBM40 diet, in contrast to the gene expression levels of IL4, IL5, IL10, and TGFβ1, which were remarkably downregulated (p < 0.05). The FSBM diets significantly affected the stability of the fish gut microbiota. Photobacterium was the dominant phylum in all experimental groups, and the proportion of these bacteria gradually decreased with increasing FSBM substitution. The composition of intestinal flora at the genus level was not the same in the three experimental groups, with a richer composition of intestinal bacteria detected in the FSBM20 and FSBM40 groups (p < 0.05). The correlation between intestinal flora balance and immune gene expression revealed that only Photobacterium was negatively correlated with the above upregulated genes, while other bacteria were positively correlated with these pro-inflammatory factors (p < 0.05). Photobacterium was positively correlated with the above downregulated genes, while other bacteria were negatively correlated with these anti-inflammatory factors (p < 0.05). In conclusion, high levels of substitution of FSBM for fish meal causes intestinal inflammation in pearl gentian grouper. This is likely associated with changes to the intestinal flora. More attention should be paid to the negative role of dietary FSBM on intestinal flora.

In order to investigate the main factors that caused the Nitrate increasement in Huixian Wetland, 15N-NO3 and 18O-NO3 analysis were conducted. SIAR model was applied to quantitatively test the contribution proportions of kinds of pollutants. Health risk assessment (HRA) was taken to study ten heavy metals of 96 groups samples in the four main waters in Huixian Wetland: Surface River, Subterranean Stream, Blue Hole and Well Water. The main sources of Nitrate were domestic sewage and animal feces, chemical fertilizer, and soil, with the contribution proportions of 39.1%, 32.2%, and 28.5%, respectively. The heavy metals concentration order is that of Mn > Al > Cr > Zn > As > Pb > Cu > Fe > Cd > Hg. The HRA showed that the average annual total health risks-through drinking and skin penetration-order was: Well Water > Blue Hole > Subterranean Stream > Surface River. The drinking water from Well and Blue Hole can cause the cancer risks in children of 7.08 × 10−5 a−1 and 7.01 × 10−5 a−1, respectively. Both were higher than the recommendation standard (5.0 × 10−5 a−1) from ICRP. As the main element contributed to the health risk of adults and children, the Cr in all the four waters were also over the standard (1 × 10−6 a−1) recommended by the Swedish Environmenta1 Protection Agency and the Dutch Ministry of Construction and Environment and the British Royal Society. The health risk levels of non-carcinogenic metals were 1 × 10−16–1 × 10−10, which were 5–11 order of magnitude lower than the acceptable level.

Abstract Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4+ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4+ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4+ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957

Abstract Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout (EpiCD147-OE or EpiCD147-KO) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis (EpiCD147-OE) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in EpiCD147-OE transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in EpiCD147-OE transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of CD147D207-230. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway.

In this study, a novel method to recover copper, zinc and iron from copper slag by SO2–O2 roasting-leaching-magnetic separation was proposed. The effect of roasting experiment conditions were roasting temperature of 900 °C, holding time of 120 min, and φSO2 (The volume fraction of SO2 in the mixed gas of SO2 and O2) of 90%. Under the leaching conditions of leaching temperature 80 °C, leaching time 1 h, liquid–solid ratio 14:1, and pH 7, 91.03% of copper and 85.04% of zinc can be recycled respectively. The iron in the leaching residue can be enriched and recovered by magnetic separation at a magnetic field strength of 3000 Gs for 40 min. The iron recovery rate is 85.88% with 53.86% of the iron grade in the concentrate.

Abstract Background Sacroiliac joint tuberculous arthritis is a relatively rare site of tuberculosis infection, but it can lead to severe sacroiliac joint destruction and dysfunction. Since there are few studies on the surgical methods of sacroiliac joint tuberculosis (SJT), we adopted three different surgical methods based on different degrees of destruction of sacroiliac joint tuberculous arthritis. While revealing its clinical symptoms to improve the diagnostic accuracy, and to determine the safety and feasibility of this surgical approach in the treatment of sacroiliac joint tuberculous arthritis. Methods We retrospectively analyzed 17 patients with tuberculous arthritis of the sacroiliac joint treated by anterior debridement. All these patients underwent anterior debridement of tuberculosis with or without bone graft fusion. Mean postoperative follow-up was 17.2 months (12–25 months). The erythrocyte sedimentation rate (ESR) was used to judge the general situation after surgery, and the fusion of sacroiliac joints was observed by X-ray films and CT scans. And VAS and ODI were used to score to observe postoperative functional recovery. Results Anterior approach debridement is an effective surgical approach for sacroiliac joint tuberculous arthritis. All patients achieved effective relief of lower back and hip pain. The pain was significantly relieved 3 months after the operation, and the pain basically disappeared 6 months after the operation. The erythrocyte sedimentation rate was also significantly reduced after the operation, and it can basically return to the normal level 3 months after the operation. The VAS score and ODI index of the other 16 patients after surgery were significantly lower than those before surgery, except for 1 patient who died of severe type I respiratory failure and septic shock 3 months after surgery, The surviving patients were basically able to achieve stable fusion of the sacroiliac joint at 12 months postoperatively. None of the patients reported significant pain until the last follow-up visit. Conclusions The anterior approach is a very effective surgical method for the treatment of sacroiliac joint tuberculous arthritis, and it is safe and feasible. A clear operative field of view facilitates complete debridement and reduces recurrence, and its function recovers well with stable arthrodesis.

Abstract Background The most commonly used approach for distal radius fractures is the traditional Henry approach. However, it requires an intraoperative incision of the pronator quadratus (PQ) muscle, which results in a series of complications if the repair of the PQ fails. Aim The objective of this study was to investigate the efficacy of sparing the pronator quadratus for volar plating of the distal radius fractures. Methods Seventy-six patients who suffered from distal radius fractures of types 23-B, 23-C1, and 23-C2 as per the AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification were treated with volar locking plate fixation using either the PQ muscle incision and repair (group A, n = 39) or the PQ muscle preservation approach (group B, n = 37). Intraoperative index, postoperative efficacy and complications of patients were recorded and evaluated. Results All patients were followed up for more than one year after surgery. All fractures achieved union. There were significant differences in mean operative time, mean intraoperative blood loss, and mean fracture healing time between the two groups. Still, there were no significant differences in limb function scores between the two groups at the 12-month postoperative follow-up. Outcomes assessed at 1 week, 1 month, and 3 months after surgery demonstrated significant differences in the mean range of motion and pain-related visual analog scale (VAS) between the two groups. As the range of motion and grip strength increased, the VAS scores decreased, and there was no significant difference between the two groups at 12 months postoperatively. Although tendon irritation and delayed carpal tunnel syndrome were more common in group A than in group B (7.6% vs. 0% and 5.1% vs. 0%, respectively), the differences were not statistically significant. Conclusion The modified Henry approach with sparing pronator quadratus muscle has no significant advantage in the range of wrist motion and upper limb function in the late stage. Nevertheless, the intraoperative placement of the plate under the pronator quadratus muscle can shorten the operation time, reduce intraoperative bleeding, reduce early postoperative pain, promote early activity, and improve the patient's quality of life. It is recommended that the pronator be preserved at the time of surgery.

The Multi-receiver Encryption (MRE) scheme can meet the secure data transmission requirements in multicast and broadcast scenarios. To meet compliance, critical information infrastructure in China should be protected with Chinese national commercial cryptographic algorithms. Designing an MRE scheme based on Elliptic Curve Cryptography (ECC) is one of the current design methods with better flexibility and performance. However, the research on MRE schemes based on SM2 elliptic curve public-key cryptography is still in a blank state. This paper proposes a Certificateless SM2-based Multi-receiver Encryption (CL-SM2-MRE) scheme. We prove the security of the CL-SM2-MRE scheme under the Random Oracle Model (ROM) and analyze the performance.

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal cells. Although elevated glycolysis flux has been reported in psoriasis, the molecular mechanisms underlying its pathogenesis remain unclear. We investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis, observing its high expression in psoriatic skin lesions of humans and imiquimod (IMQ)-induced mouse models. In mouse models, genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic inflammation. We found that CD147 interacted with glucose transporter 1 (Glut1). Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in vivo. In CD147-knockout mice and keratinocytes, oxidative phosphorylation was increased in the epidermis, indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of psoriasis. Using non-targeted and targeted metabolic techniques, we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid (α-KG). Depletion of CD147 also increased transcriptional expression and activity of γ-butyrobetaine hydroxylase (γ-BBD/BBOX1), a crucial molecule for carnitine metabolism, by inhibiting histone trimethylations of H3K9. Our findings demonstrate that CD147 is critical in metabolic reprogramming through the α-KG–H3K9me3–BBOX1 axis in the pathogenesis of psoriasis, indicating that epidermal CD147 is a promising target for psoriasis treatment.

Natural killer (NK) cells, as key immune cells, play essential roles in tumor cell immune escape and immunotherapy. Accumulating evidence has demonstrated that the gut microbiota community affects the efficacy of anti-PD1 immunotherapy and that remodeling the gut microbiota is a promising strategy to enhance anti-PD1 immunotherapy responsiveness in advanced melanoma patients; however, the details of the mechanism remain elusive. In this study, we found that Eubacterium rectale was significantly enriched in melanoma patients who responded to anti-PD1 immunotherapy and that a high E. rectale abundance was related to longer survival in melanoma patients. Furthermore, administration of E. rectale remarkably improved the efficacy of anti-PD1 therapy and increased the overall survival of tumor-bearing mice; moreover, application of E. rectale led to a significant accumulation of NK cells in the tumor microenvironment. Interestingly, conditioned medium isolated from an E. rectale culture system dramatically enhanced NK cell function. Gas chromatography–mass spectrometry/ultrahigh performance liquid chromatography–tandem mass spectrometry-based metabolomic analysis showed that l-serine production was significantly decreased in the E. rectale group; moreover, administration of an l-serine synthesis inhibitor dramatically increased NK cell activation, which enhanced anti-PD1 immunotherapy effects. Mechanistically, supplementation with l-serine or application of an l-serine synthesis inhibitor affected NK cell activation through Fos/Fosl. In summary, our findings reveal the role of bacteria-modulated serine metabolic signaling in NK cell activation and provide a novel therapeutic strategy to improve the efficacy of anti-PD1 immunotherapy in melanoma.

Background The EROSION (Effective Anti‐Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography‐Based Management in Plaque Erosion) study demonstrated that antithrombotic therapy without stenting was safe and feasible in selected patients with acute coronary syndrome caused by plaque erosion. However, the factors related to the prognosis of these patients are not clear. This study aimed to explore the predictors of an adverse prognosis of a nonstent strategy in a larger sample size. Methods and Results A total of 252 (55 patients were from the EROSION study) patients with acute coronary syndrome with plaque erosion who met the inclusion criteria of the EROSION study and completed clinical follow‐up were enrolled. Patients were divided into 2 groups according to the occurrence of major adverse cardiovascular events (MACE), which were defined as the composite of cardiac death, recurrent myocardial infarction, ischemia‐driven target lesion revascularization, rehospitalization because of unstable or progressive angina, major bleeding, and stroke. Among 232 patients with acute coronary syndrome included in the final analysis, 50 patients (21.6%) developed MACE at a median follow‐up of 2.9 years. Compared with patients without MACE, patients with MACE were older and had a higher degree of percentage of area stenosis (72.2%±9.4% versus 64.2%±15.7%, P

Abstract Background The purpose of this study was to evaluate the outcomes of bifocal bone transport in the treatment of femoral bone defects caused by infections. Methods Clinical and radiographic data of patients with infected femoral nonunion treated by the bifocal bone transport at our hospital were analyzed retrospectively, from January 2008 to December 2019. Depending on the location of bone defects, the patients were divided into three groups (proximal, intermediate, and distal). The Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria was applied to assess the bone and functional outcomes. Postoperative complications of three groups were documented and compared. Results Seventy-six cases of infected femoral bone defects (31 cases of proximal, 19 cases of intermediate, and 26 cases of distal) were managed by bifocal bone transport successfully with a mean follow-up time of 30.8 months (range, 23 to 41 months). There were 58 men (76.3%) and 18 women (23.6%), with a mean age of 38.8 years (range, 23 to 60 years). The bone union was received in 76 cases with a mean of 6.9 months (range, 5 to 8 months). Pin tract infection was observed in twenty-nine cases (38.1%), 7 cases (9.2%) of muscle contractures, 3 cases (7.9%) of joint stiffness, 13 cases (17.1%) of axial deviation, 2 cases (2.6%) of delayed union, one case (1.3%) of nonunion, and none (0%) of transport gap re-fracture. One patient (1.3%) was scheduled for knee arthroplasty when bone transport treatment ended. Conclusions Bone transport using an external rail fixator was a practical method to treat the femoral bone defects, since the satisfactory rate of bone union and limb function recovery. Complications of distal femoral bone transport were more severe than the proximal and intermedia, but the rate of complication was the least of the three groups. Soft-tissue-related complications were more likely to occur in the intermediate bone transport.

Despite acral melanoma being the most common melanoma subtype in non-White individuals, its molecular drivers remain unknown. Here, the authors integrate genomic and clinical data from 104 patients and identify late-arising focal amplifications of chr22q11.21 and LZTR1 as a key tumour promoter in this region.