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The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene‐related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type‐H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES‐enhanced osteoporotic fracture healing. This proof‐of‐concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration. Electrical stimulation (ES) at dorsal root ganglions (DRGs) triggers calcium influx and activates the Ca2+/CaMKII/CREB signaling cascade, resulting in the transcription of calcitonin gene‐related peptide (CGRP). After synthesized in DRGs, CGRP is transported to peripheral nerve terminals and released following depolarization by ES. The released CGRP and subsequently increased type‐H vessel formation promote osteoporotic fracture healing.

Identifying pathogens in patients with lower respiratory tract infections (LRTIs) has always been a major challenge. Metagenomic next-generation sequencing (mNGS) technology is a new diagnostic tool that can assist clinicians in the etiological diagnosis of LRTIs. This study focuses on the clinical value of mNGS in the diagnosis of suspected LRTIs. A total of 400 patients with suspected LRTIs admitted at the First Affiliated Hospital of Nanchang University from July 2020 to February 2023 were enrolled in this retrospective study. Bronchoalveolar lavage fluid (BALF) samples were analyzed using both mNGS and culture methods. The diagnostic accuracy of two approaches was systematically compared against the final clinical diagnosis, which served as the gold-standard reference. Of the 400 enrolled cases, 82.3% (329/400) were diagnosed with LRTIs. From these cases, mNGS identified 76.8% (307/400) truepositive cases, 8.0% (32/400) falsepositive cases, 9.8% (39/400) truenegative cases, and 5.5% (22/400) falsenegative cases. mNGS demonstrated significantly higher sensitivity [93.3% (307/329) vs. 55.6(183/329)%] alongside greater negative predictive values [63.9% (39/61) vs.25.9%(51/197)], whereas culture offered higher specificity [54.9%(39/71) vs. 71.8%(51/71)]. The area under the receiver-operating curve (AUC) of mNGS[0.744(95%CI: 0.67–0.82)]was significantly higher than that of cultures[0.636(95%CI: 0.57–0.71)]. Specifically, mNGS detected more Streptococcus pneumoniae (7.0% vs. 0%), Haemophilus influenzae (6.7% vs. 0%), Aspergillus (9.4% vs. 3.5%), Pneumocystis jirovecii (11.9% vs. 0%) and other intracellular pathogens. Of the 329 patients with LRTIs, antibiotic treatment was modified based on the mNGS results in more than half of the patients(50.5%,166/329), including 20 cases of adjusted antimicrobial regimens, 70 cases de-escalated the empirical antibiotic treatment, and 76 patients escalated the treatment by increasing dosage or medication. 60.8%(101/166) of patients responded to modified antibiotic treatment. Significant benefits of mNGS have been shown in pathogen identification and antimicrobial treatment stewardship in patients with LRTIs. For those with suboptimal therapeutic responses, physicians should be alert to some emerging intracellular pathogens, including Chlamydia psittaci , Mycobacterium tuberculosis , and Pneumocystis jirovecii .

The height of the water-flow fracture zone (WFZ) is an important reference for designing the size of a waterproof crown pillar. Once the WFZ is connected with the sea, there will be catastrophic consequences, especially for undersea mining. This study suggests using a rotating forest (RoF) model to predict the height of the WFZ for the evaluation of the size of a waterproof crown pillar. To train and test the RoF model, five indicators with major influencing factors on undersea safety mining were determined, 107 field-measured mining datasets were collected, 75 (70%) datasets were used for training, and 32 (30%) datasets were used for model testing. At the same time, the random forest ensemble algorithm (RFR) and support vector machine (SVM) models were introduced for comparison and verification; in the end, the tested results were evaluated by RMSE (root-mean-square error) and R2. The comparison shows that the predicted results from the RoF model are significantly better than those from the RFR and SVM models. An importance analysis of the impact indicators shows that the mining height and depth have significant impacts on the prediction results. The development height of the WFZ in undersea safety mining was predicted via the RoF model. The predicted results via the RoF model were verified by field observations using panoramic borehole televiewers. The RoF prediction results are consistent with the observation results at all depths. Compared with the other two models, the RoF model has the smallest average absolute error at 2.87%. The results show that the RoF model can be applied to predict the height of the WFZ in undersea mining, which could be an effective way of minimizing the mineral resource waste in the study area and in other similar areas in the world under the premise of mine safety.

Long noncoding RNAs (lncRNAs) have been reported to play pivotal roles in a variety of cancers. However, lncRNAs involved in hepatocellular carcinoma (HCC) initiation and progression remain largely unclear. In this study, we identified an lncRNA gradually increased during hepatocarcinogenesis (lncRNA-GIHCG) using publicly available microarray data. Our results further revealed that GIHCG is upregulated in HCC tissues in comparison with adjacent non-tumor tissues. High GIHCG expression is correlated with large tumor size, microvascular invasion, advanced BCLC stage, and poor survival of HCC patients. Functional experiments showed that GIHCG promotes HCC cells proliferation, migration, and invasion in vitro, and promotes xenografts growth and metastasis in vivo. Mechanistically, we demonstrated that GIHCG physically associates with EZH2 and the promoter of miR-200b/a/429 , recruits EZH2 and DNMT1 to the miR-200b/a/429 promoter regions, upregulates histone H3K27 trimethylation and DNA methylation levels on the miR-200b/a/429 promoter, and dramatically silences miR-200b/a/429 expression. Furthermore, the biological functions of GIHCG on HCC are dependent on the silencing of miR-200b/a/429. Collectively, our results demonstrated the roles and functional mechanisms of GIHCG in HCC, and indicated GIHCG may act as a prognostic biomarker and potential therapeutic target for HCC. Key Message lncRNA-GIHCG is upregulated in HCC and associated with poor survival of patients. GIHCG significantly promotes tumor growth and metastasis of HCC. GIHCG physically associates with EZH2. GIHCG upregulates H3K27me3 and DNA methylation levels on the miR-200b/a/429 promoter. GIHCG epigenetically silences miR-200b/a/429 expression.

The aim of this study was to investigate how the cholangiocarcinoma cell lines RBE and HCCC-9810 responded to NCOA4 downregulation in terms of proliferation, migration and invasive.First,we analyzed the differential expression and survival prognosis of the NCOA4 gene using a bioinformatic approach,as well as validation using clinical samples.Next,cholangiocarcinoma cells were cultured and the NCOA4 gene was down-regulated with siRNA,and then NCOA4 and GPX4 expression was detected using qPCR and Western blot.Cell was measured using CCK8, cell cloning, wound healing, and transwell migration and invasion.Levels of changes in indicators related to ferroptosis were measured after induction of iron metamorphosis by Erastin. Data from TCGA showed that NCOA4 shows greater downgrade in tumor tissues than in non-tumor tissues and the overall survival (OS) of patients with low NCOA4 expression was significantly shorter than that of patients with high NCOA4 expression.The qPCR results showed that NCOA4 was expressed at low levels in cholangiocarcinoma tissue specimens; the mRNA expression of NCOA4 decreased after knocking down NCOA4 in cells. Western blot (WB) analysis showed that NCOA4 downregulation led to an increase in GPX4 expression. The cell cloning assay confirmed that downregulation of NCOA4 significantly increased cell viability. The transwell and wound healing assays demonstrated that the proliferation rate increased after downregulation of NCOA4. After NCOA4 silencing, ferroptosis indicators such as Fe 2+ , MDA, and ROS expression were lowered;GSH expression was increased.Our findings indicated the regulatory effects of NCOA4 on GPX4 protein and its contribution to malignant progression in CCA, which could provide a potential therapeutic target for CCA.

In this paper, to achieve attitude tracking and disturbance rejection of micro quodrotor in the presence of uncertain external disturbances, the output regulation technique is utilized. First of all, the model that established regarding micro quadrotor is transformed to a stabilization problem of the second-order augmented system by employing the internal model. Second, an adaptive internal model is designed via exosystem information. The nonlinear unknown functions of the system are approximated by fuzzy logic systems, and the fuzzy adaptive laws are designed to tackle the uncertainty parameters. Then the new adaptive fuzzy state controllers and adaptive control laws are proposed by combining the backstepping technique and the adaptive control method. Unlike the traditional controller design method, the proposed controllers and adaptive control laws are designed respectively for roll angle, pitch angle, yaw angle and the height of the four-channel helicopter. Moreover, the new algorithm can perform well in attitude tracking and disturbance rejection of the closed-loop systems. Finally simulation results have demonstrated the effectiveness of the proposed approach.

The management of wound exudate is of vital importance for wound healing. Exudate accumulation around wound prolongs inflammation and hinders healing. Although traditional dressings can absorb wound exudate, they are unable to drain exudate in time, often resulting in a poor feature with wound healing. In recent years, the appearance of asymmetric wettability dressings has shown great potential in exudate management. Here, we summarize the latest progress of 3 kinds of asymmetric wettability wound dressings in exudate management, including Janus structure, sandwich structure, and gradient structure. The most common Janus structural dressing among asymmetric wettability dressings is highlighted from 2 aspects: single-layer modified Janus structure and double-layer Janus structure. The challenges faced by asymmetric wettability wound dressings are discussed, and the developing trends of smart wound dressings in this field are prospected.

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks 1 . Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOR OXT ) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvl OXTR ) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvl OXTR cells minimally respond to aggressor cues. During defeat, aVMHvl OXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvl OXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity. In mice, the neural mechanisms underlying aversive social learning, specifically avoidance and fear after defeat, involve oxytocin signalling in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part.

In the fabrication of soft magnetic composites, the lattice mismatch between the inorganic insulation layer and the iron matrix often leads to the formation of cracks during the molding process, which significantly impairs the operational performance of the materials. Consequently, it is imperative to develop novel strategies for inorganic insulation coatings that offer high electrical resistivity and thermal stability and are less susceptible to cracking during formation. This paper presents a new structure for soft magnetic composites that incorporates FePO4 as an intermediate transition layer between the iron-based soft magnetic particles and the inorganic ceramic insulation layer. This configuration is designed to provide insulation coatings with superior voltage and thermal resistance, as well as high electrical resistivity. The research details the processes forming the FePO4 intermediate transition layer and the SiO2 insulation layer on the iron powder surface, along with their interaction mechanisms. An analysis comparing the scenarios with and without the FePO4 intermediate transition layer shows its beneficial impact on the magnetic properties and mechanical strength of the soft magnetic composites. Further investigations reveal that at a phosphoric acid concentration of 1 wt.%, the FePO4 layer significantly enhances the interface compatibility between the Fe powder matrix and the SiO2 insulation layer. Under these conditions, the Fe@ FePO4/SiO2 soft magnetic composites demonstrate outstanding overall performance: the saturation magnetization stands at 215.60 emu/g, effective permeability at 83.2, resistivity at 57.42 Ω·m, power loss at 375.0 kW/m3 under 30 mT/100 kHz, and radial compressive strength at 15.95 Kgf. These findings offer novel insights and practical approaches for advancing inorganic insulation coating strategies and provide vital scientific support for further enhancing the magnetic and mechanical properties of soft magnetic composites.

Recent evidence suggests that innate and adaptive immunity play a crucial role in Parkinson’s disease (PD). However, studies regarding specific immune cell classification in the peripheral blood in PD remain lacking. Therefore, we aimed to explore the different immune status in patients with PD at different ages of onset. We included 22 patients; among them were 10 who had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 young healthy controls (YHCs) and 8 elder HCs (EHCs). Mass cytometry staining technology was used to perform accurate immunotyping of cell populations in the peripheral blood. Motor symptoms and cognitive function were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III score and Mini-mental State Examination (MMSE) score, respectively. T test and ANOVA statistical analysis were performed on the frequency of annotated cell population. Linear regression model was used to analyze the correlation between clusters and clinical symptoms. We characterized 60 cell clusters and discovered that the immune signature of PD consists of cluster changes, including decreased effector CD8 + T cells, lower cytotoxicity natural killer (NK) cells and increased activated monocytes in PD patients. In summary, we found that CD8 + T cells, NK cells, and monocytes were associated with PD. Furthermore, there may be some differences in the immune status of patients with EOPD and LOPD, suggesting differences in the pathogenesis between these groups.