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Osteoporosis, an age-related metabolic bone disease, is mainly caused by an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. At present, there are many osteoporosis drugs that can promote bone formation or inhibit bone resorption. However, there were few therapeutic drugs that can simultaneously promote bone formation and inhibit bone resorption. Oridonin (ORI), a tetracyclic diterpenoid compound isolated from Rabdosia rubescens, has been proved to have anti-inflammatory, anti-tumor effects. However, little is known about the osteoprotective effect of oridonin. Thioacetamide (TAA) is a common organic compound with significant hepatotoxicity. Recent studies have found that there was a certain association between TAA and bone injury. In this work, we investigated the effect and mechanism of ORI on TAA-induced osteoclastogenesis and inhibition of osteoblast differentiation. The results showed that TAA could promote the osteoclastogenesis of RAW264.7 by promoting the MAPK/NF-κB pathway, and also promoted p65 nuclear translocation and activated intracellular ROS generation, and ORI can inhibit these effects to inhibit TAA-induced osteoclastogenesis. Moreover, ORI can also promote the osteogenic differentiation pathway and inhibit adipogenic differentiation of BMSCs to promote bone formation. In conclusion, our results revealed that ORI, as a potential therapeutic drug for osteoporosis, could protect against TAA-induced bone loss and TAA-inhibited bone formation.

The search for wearable electronics has been attracted great efforts, and there is an ever-growing demand for all-solid-state flexible energy storage devices. However, it is a challenge to obtain both positive and negative electrodes with excellent mechanical strength and match positive and negative charges to achieve high energy densities and operate voltages to satisfy practical application requirements. Here, flexible MXene (Ti3C2Tx)/cellulose nanofiber (CNF) composite film negative electrodes (MCNF) were fabricated with a vacuum filtration method, as well as positive electrodes (CP) by combining polyaniline (PANI) with carbon cloth (CC) using an in-situ polymerization method. Both positive and negative free-standing electrodes exhibited excellent electrochemical behavior and bendable/foldable flexibility. As a result, the all-pseudocapacitance asymmetric device of MCNF//CP assembled with charge-matched between anode and cathode achieves an extended voltage window of 1.5 V, high energy density of 30.6 Wh·kg−1 (1211 W·kg−1), and 86% capacitance retention after 5000 cycles, and the device maintains excellent bendability, simultaneously. This work will pave the way for the development of all-pseudocapacitive asymmetric supercapacitors (ASC) with simultaneously preeminent mechanical properties, high energy density, and wide operating voltage window.

Pearl millet is an important cereal crop worldwide and shows superior heat tolerance. Here, we developed a graph-based pan-genome by assembling ten chromosomal genomes with one existing assembly adapted to different climates worldwide and captured 424,085 genomic structural variations (SVs). Comparative genomics and transcriptomics analyses revealed the expansion of the RWP-RK transcription factor family and the involvement of endoplasmic reticulum (ER)-related genes in heat tolerance. The overexpression of one RWP-RK gene led to enhanced plant heat tolerance and transactivated ER-related genes quickly, supporting the important roles of RWP-RK transcription factors and ER system in heat tolerance. Furthermore, we found that some SVs affected the gene expression associated with heat tolerance and SVs surrounding ER-related genes shaped adaptation to heat tolerance during domestication in the population. Our study provides a comprehensive genomic resource revealing insights into heat tolerance and laying a foundation for generating more robust crops under the changing climate.

The combination of idle computing resources in mobile devices and the computing capacity of mobile edge servers enables all available devices in an edge network to complete all computing tasks in coordination to effectively improve the computing capacity of the edge network. This is a research hotspot for 5G technology applications. Previous research has focused on the minimum energy consumption and/or delay to determine the formulation of the computational offloading strategy but neglected the cost required for the computation of collaborative devices (mobile devices, mobile edge servers, etc.); therefore, we proposed a cost-based collaborative computation offloading model. In this model, when a task requests these devices' assistance in computing, it needs to pay the corresponding calculation cost; and on this basis, the task is offloaded and computed. In addition, for the model, we propose an adaptive neighborhood search based on simulated annealing algorithm (ANSSA) to jointly optimize the offloading decision and resource allocation with the goal of minimizing the sum of both the energy consumption and calculation cost. The adaptive mechanism enables different operators to update the probability of selection according to historical experience and environmental perception, which makes the individual evolution have certain autonomy. A large number of experiments conducted on different scales of mobile user instances show that the ANSSA can obtain satisfactory time performance with guaranteed solution quality. The experimental results demonstrate the superiority of the mobile edge computing (MEC) offloading system. It is of great significance to strike a balance between maintaining the life cycle of smart mobile devices and breaking the performance bottleneck of MEC servers.

Purpose The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms. Methods Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red. Results It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells. Conclusion It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

Markers are needed to increase the diagnostic accuracy of prostate-specific antigen (PSA) in prostate cancer (PCa) screening. Mounting evidence has shown that plasma proteins can be hopeful biomarkers for cancer diagnosis.Tandem mass tag (TMT)-based proteomics and parallel reaction monitoring (PRM) analysis were used to screen the differential proteins and further validated in other independent studies (n = 539). Receiver-operating characteristic (ROC), decision curves and nomograms were applied to assess the diagnostic accuracy of biomarkers.Three candidate proteins (DBP, LCAT and ORM2) were preliminarily screened. Subsequent validation studies revealed significant upregulation of ORM2 in PCa patients across other independent cohorts. ORM2 yielded excellent discriminative power for PCa from benign prostatic hyperplasia (BPH) patients (AUC = 0.861 and 0.814 in validation phases 2a and 2b, respectively). Importantly, the combination of ORM2 and PSA gave better predictive accuracy than PSA alone. We incorporated age, PSA and ORM2 into a nomogram, which yielded C-index of 0.883 in validation phase 2a. A similar C-index of 0.879 was obtained in external validation phase 2b.In summary, our study suggests that ORM2 could be treated as a complementary biomarker for PSA in distinguishing PCa from BPH.

Electrochemical machining is widely used in biomedical, aerospace, automotive and other fields. The development of electrochemical machining (ECM) is restricted by many factors such as the difficulty of preparing micro-electrode, large machined gap and serious stray corrosion. In this paper, we present a method to fabricate micro-holes by combining micro-graphite electrode with hollow structure. Firstly, a sealed graphite electrode was proposed to guarantee that the sediment can be fully removed by the flowing electrolyte. Then, the effect of machined parameters such as the pulse frequency, machined voltage, electrode feeding speed and electrolyte concentration on machining quality were studied. By optimizing the machined parameters, the minimum value of micro-hole taper with 0.07 could be obtained. To improve the shape precision of workpiece, this paper designed the hollow structure inside the electrode. With the increasing of the pulse frequency, the machining accuracy of micro-holes increased. The results suggested that the pulse frequency of 100 KHz, the machined voltage of 18 V, the feeding speed of 1 µm/s and electrolyte concentration of 5% were more suitable for micro-holes machining with ECM.

Graphene oxide (GO) is an excellent membrane-forming material with unique two-dimensional transport channels and excellent adsorption properties for heavy metal contaminants. However, swelling under cross-flow conditions and long-term water immersion leads to poor separation performances. To improve the stability of GO membrane materials, we propose a PVA-integrated graphene oxide/attapulgite membrane (GOAP) with a 3D microstructural arrangement of "brick-mortar-brick." The addition of PVA as mortar reinforces the strength of the structures via induced hydrogen bonding within the 3D water transport network. Furthermore, the Al

Circular RNAs (circRNAs) have been demonstrated to play vital roles in cancer development and progression. However, studies on the association between circRNAs and prostate cancer (PCa) are still lacking. CircRNA sequencing of two pairs of PCa tissues and adjacent normal tissues was conducted in the present study, and qRT–PCR was performed to verify the results. Functional experiments were performed to investigate cellular functions after specific changes. Mass spectrometry analysis after RNA pull-down experiments and Co-IP assays were further conducted. Downstream target proteins were predicted via online databases and detected in vitro by Western blot analysis and in vivo by immunohistochemistry. Hsa_circ_0006156 (subsequently named circ_0006156) expresses at low levels in both PCa tissues and cells, and it significantly inhibits the migration and invasion of PCa cells. Circ_0006156 binds to and blocks the ubiquitination of S100A9. Moreover, functional assays revealed that circ_0006156 represses the malignant progression of PCa by binding to S100A9. Finally, in vivo experiments showed that circ_0006156 suppresses PCa migration and invasion by increasing S100A9, revealing circ_0006156 as a potential novel effective target for PCa treatment.

Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) is the first direct-acting antiviral (DAA) therapy approved for patients who have previously failed a DAA-containing regimen including NS5A inhibitors. In clinical trials, SOF/VEL/VOX was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. However, the effectiveness and safety of SOF/VEL/VOX in the real world remained uncertain. We aimed to perform a systematic review and meta-analysis to assess the real world effectiveness and safety of SOF/VEL/VOX.We systematically searched the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for relevant real world studies published before January 28, 2022. Patients with previous treatment failure who received SOF/VEL/VOX were included. The primary outcome was the percentage of patients achieving SVR12. Secondary outcome included adverse events (AEs) during treatment.Fifteen studies with a total of 1796 HCV-infected patients with previous treatment failure were included. SVR12 rates were 93% (95% CI 91-95) in the ITT populations (n = 1517, 11 cohorts) and 96% (95% CI 95-97) in the PP populations (n = 1187, 10 cohorts). SVR12 rates were significantly higher in non-GT3-infected patients (OR = 2.29, 95% CI 1.23-4.27, P = 0.009) and non-cirrhotic patients (OR = 2.22, 95% CI 1.07-4.60, P = 0.03) than in GT3-infected patients and cirrhotic patients. Furthermore, the SVR12 rates of previous treatment of SOF/VEL were significantly lower than those of other regimens in both ITT and PP populations (P ≤ 0.001). Adverse events (AEs) were reported in 30% (228/760) of patients. Serious AEs (SAEs) were reported in 3.82% (29/760) of patients. The most frequently reported AEs were headache, asthenia, nausea, fatigue, and diarrhea, which were mostly mild in severity. AE-related treatment discontinuations were reported in 0.66% (5/760) of patients.Consistent with clinical trials, the real world evidence indicates that SOF/VEL/VOX is a well-tolerated and highly effective salvage therapy for HCV-infected patients with previous treatment failure. However, there may still be a risk of treatment failure for patients with GT3 infection, cirrhosis, or SOF/VEL treatment failure. The protocol of this study was registered at PROSPERO, registration no. CRD 42022306828.

With the rapidly developing wireless communication technology, electromagnetic pollution problems have become more prominent. Electromagnetic pollution has caused great harm to wireless equipment, precision instruments, military safety, etc., which urgently requires the development of lightweight, high-efficiency, broadband electromagnetic waves (EMW) absorbing materials. MXene is an emerging two-dimensional (2D) material with the advantages of lamellar structure, excellent conductivity, and abundant surface groups. At the same time, conducting polymers (CPs) have excellent performance in terms of conductivity, surface activity, quality, and electromagnetic loss, making them have excellent potential in EMW absorbing direction. This article examines the preparation, structure, and performance of MXene and CPs-based radar absorbing materials (RAM). A comprehensive summary and objective analysis of the nowaday study progress on the EMW absorbing performances of MXene and CPs, and a comprehension of the absorbing mechanism are reviewed. Finally, the research direction of absorbing materials has been prospected.

Background Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. Methods CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography‑derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). Results Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014–2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066–4.261; P = 0.032). Conclusion TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

Humans need to accurately infer the intentions and feelings of others to engage in successful social interaction. However, the application of artificial intelligence technology in Education (AIEd) forms a human–machine collaborative environment which changed the interaction relationship of individuals, it may have an affect on them. This study aimed to explore whether AIEd affects adolescents’ emotional perception. Combined with the actual teaching situation and the result of the questionnaire, 1332 students recruited through random sampling from AI Curriculum Reform Demonstration Schools in Guangzhou participated in this study. Different emotional priming stimulative materials (sentences and situational pictures) were used in the experiments. The task was designed to investigate adolescents’ reaction time to emotional faces (positive, negative). After eliminating blank data and invalid data with response time greater than 150 ms, 977 and 962 valid data were included in the statistical analysis in experiment 1 and experiment 2 respectively. Results show that AIEd has a negative effect on adolescents’ emotional perception. Prior research has focused on theory to the exclusion of practical applications and the psychological impact of AIEd, thus this study makes an innovative contribution in exploring the impact of the application of artificial intelligence technology in education on adolescents’ physical and mental development by using empirical research methods.

Background Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, the relationship between radiographic and histopathological response remains unclear. Methods We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti–programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China. Radiographic response was evaluated using mRECIST. A pCR was defined as no viable tumor cells in resected samples. Results We included 35 eligible patients, of whom 15 (42.9%) achieved pCR after systemic therapy. After a median follow-up of 13.2 months, tumors recurred in 8 non-pCR and 1 pCR patient. Before resection, there were 6 complete responses, 24 partial responses, 4 stable disease cases, and 1 progressive disease case, per mRECIST. Predicting pCR by radiographic response yielded an area under the receiver operating characteristic curve (AUC) of 0.727 (95% CI: 0.558–0.902), with an optimal cutoff value of 80% reduction in the enhanced area in MRI (called major radiographic response), which had a 66.7% sensitivity, 85.0% specificity, and a 77.1% diagnostic accuracy. When radiographic response was combined with α-fetoprotein response, the AUC was 0.926 (95% CI: 0.785–0.999); the optimal cutoff value was 0.446, which had a 91.7% sensitivity, 84.6%, specificity, and an 88.0% diagnostic accuracy. Conclusions In patients with unresectable HCC receiving combined TKI/anti–PD 1 therapy, major radiographic response alone or combined with α-fetoprotein response may predict pCR.

Synthesis of capsular polysaccharide (CPS), an important virulence factor of pathogenic bacteria, is modulated by the CpsBCD phosphoregulatory system in Streptococcus. Serine/threonine kinases (STKs, e.g. Stk1) can also regulate CPS synthesis, but the underlying mechanisms are unclear. Here, we identify a protein (CcpS) that is phosphorylated by Stk1 and modulates the activity of phosphatase CpsB in Streptococcus suis, thus linking Stk1 to CPS synthesis. The crystal structure of CcpS shows an intrinsically disordered region at its N-terminus, including two threonine residues that are phosphorylated by Stk1. The activity of phosphatase CpsB is inhibited when bound to non-phosphorylated CcpS. Thus, CcpS modulates the activity of phosphatase CpsB thereby altering CpsD phosphorylation, which in turn modulates the expression of the Wzx-Wzy pathway and thus CPS production.

MXenes are under the spotlight due to their versatile physicochemical characteristics. Since their discovery in 2011, significant advancements have been achieved in their synthesis and application sectors. However, the spontaneous oxidation of MXenes, which is critical to its processing and product lifespan, has gotten less attention due to its chemical complexity and poorly understood oxidation mechanism. This perspective focuses on the oxidation stability of MXenes and addresses the most recent advancements in understanding and the possible countermeasures to limit the spontaneous oxidation of MXenes. A section is dedicated to the presently accessible methods for monitoring oxidation, with a discussion on the debatable oxidation mechanism and coherently operating factors that contribute to the complexity of MXenes oxidation. The current potential solutions for mitigating MXenes oxidation and the existing challenges are also discussed with prospects to prolong MXene’s shelf-life storage and expand their application scope. Graphical Abstract

Background Tissue-resident CD8+T cells (CD103+CD8+T cells) are the essential effector cell population of anti-tumor immune response in tissue regional immunity. And we have reported that IL-33 can promote the proliferation and effector function of tissue-resident CD103+CD8+T cells. As of now, the immunolocalization and the prognostic values of tissue-resident CD8+T cells in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) still remain to be illustrated. Methods In our present study, we used the tissue microarrays of HCC and ICC, the multicolor immunohistochemistry (mIHC), and imaging analysis to characterize the tissue-resident CD8+T cells in HCC and ICC tissues. The prognostic values and clinical associations were also analyzed. We also studied the biological functions and the cell–cell communication between tumor-infiltrating CD103+CD8+T cells and other cell types in HCC and ICC based on the published single-cell RNA sequencing (scRNA-seq) data. Results Our work unveiled the expressions of CD8 and CD103 and immunolocalization of tissue-resident CD8+T cells in human HCC and ICC. Elevated CD8+T cells indicated a better overall survival (OS) rate, implying that tumor-infiltrating CD8+T cells in HCC and ICC could serve as an independent prognostic factor. Moreover, the number of CD103+CD8+T cells was increased in HCC and ICC tissues compared with adjacent normal tissues. HCC patients defined as CD8highCD103high had a better OS, and the CD8lowCD103low group tended to have a poorer prognosis in ICC. Evaluation of the CD103+CD8+T-cell ratio in CD8+T cells could also be a prognostic predictor for HCC and ICC patients. A higher ratio of CD103+CD8+T cells over total CD8+T cells in HCC tissues was negatively and significantly associated with the advanced pathological stage. The percentage of higher numbers of CD103+CD8+T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In contrast, the higher ratio of CD103+CD8+T cells over total CD8+T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In addition, single-cell transcriptomics revealed that CD103+CD8+T cells were enriched in genes associated with T-cell activation, proliferation, cytokine function, and T-cell exhaustion. Conclusion The CD103+ tumor-specific T cells signified an important prognostic marker with improved OS, and the evaluation of the tissue-resident CD103+CD8+T cells might be helpful in assessing the on-treatment response of liver cancer.