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Abstract Numerous myofibroblasts are arisen from endothelial cells (ECs) through endothelial to mesenchymal transition (EndMT) triggered by TGF-β. However, the mechanism of ECs transforms to a different subtype, or whether there exists an intermediate state of ECs remains unclear. In present study, we demonstrate Midkine (MDK) mainly expressed by CD31 + ACTA2+ECs going through partial EndMT contribute greatly to myofibroblasts by spatial and single-cell transcriptomics. MDK is induced in TGF-β treated ECs, which upregulates C/EBPβ and increases EndMT genes, and these effects could be reversed by siMDK. Mechanistically, MDK promotes the binding ability of C/EBPβ with ACTA2 promoter by stabilizing the C/EBPβ protein. In vivo, knockout of Mdk or conditional knockout of Mdk in ECs reduces EndMT markers and significantly reverses fibrogenesis. In conclusion, our study provides a mechanistic link between the induction of EndMT by TGF-β and MDK, which suggests that blocking MDK provides potential therapeutic strategies for renal fibrosis.

Abstract As a byproduct of manufacturing soybeans, okara is high in dietary fiber, protein, and fats, and it contains all of the essential amino acids. Wheat, the primary ingredient in noodles, will lose nutrients during manufacturing, creating an imbalance in nutrients. This experiment is for the purpose of studying the effects of okara on quality, antioxidant properties, amino acid content, resistant starch (RS) content, and microstructure of noodles. The results indicate that the addition of 9% okara noodles increased hardness and adhesiveness by 107.19% and 132.14%, respectively, and improved ABTS free radical scavenging activity by 60.78%. The addition of 12% okara noodles increased the DPPH free radical scavenging ability by 23.66%, reduced the rapidly digestible starch (RDS) content of the noodles to 21.21%, and the resistant starch content increased to 44.85% (p

Based on the engineering background of the ultra-close adjacent coal seam group in the deep part of Pingdingshan No.8 coal mine, this paper studies the reasonable layering of bottom pumping roadway under the mining condition of deep ultra-close seam. FLAC3D numerical model is used to simulate the evolution law of the plastic zone, stress field and displacement field of coal seam under different net rock distances between the roof of bottom pumping roadway and Ⅵ16-17 coal seam. The results show that when the net rock distance is 3 m or 5 m, the coal seam above the bottom drainage roadway can be divided into pressure relief zone, stress concentration zone and primary rock stress zone under the influence of mining. When the net rock distance is 8 m or more, the coal seam above the bottom drainage roadway can be divided into pressure relief zone and primary rock stress zone under the influence of mining. The optimal layout of bottom drainage roadway is 8-10 m distance from the retained net rock. After the bottom pumping roadway is mined, the position directly above the roadway has the best pressure relief effect, the coal body in this area is fully deformed, the gas control is easier, is conducive to the support and maintenance of the coal roadway in the later period, and is the best position to arrange the coal roadway. Field monitoring effectively verified the reliability of the bottom pumping roadway in the net rock distance to control the gas outburst risk of the working face near the deep seam group.

The Qixia Formation in the foothills of Longmen Mountain in the western Sichuan Basin is gaining attention for oil and gas exploration. However, exploration of the Qixia Formation in the middle Longmen Mountain is insufficient. Consequently, it is essential to understand its stratigraphic sedimentary characteristics for guiding natural gas exploration. This study focuses on the Beichuan Tongkou section, combines field measurements, thin-section observation and trace element analyses to investigate the sequence stratigraphy and sedimentary features of the Qixia Formation, thereby defining its sedimentary environment. Within the Beichuan Tongkou section, which spans from the Liangshan Formation to the Qixia Formation, researchers have identified two third-order and one fourth-order sequence boundaries, delineating one third-order sequence and two fourth-order sequences. The sedimentary facies found in this interval include shore-swamp, open platform, and platform edge environments, which are further classified into four subfacies including open sea, intertidal sea, intra-platform beach, and platform edge beach. Additionally, three microfacies are identified including intra-platform bioclastic beach, platform edge bioclastic beach, and platform edge sand debris and bioclastic beach. The Qi1 member and lower part of the Qi2 member is located on an open platform, while the upper-middle part of the Qi2 member is found at the platform edge. This setup defines a sedimentary model for a carbonate-rimmed platform in the Qixia Formation of the middle Longmen Mountain. During the sedimentary period of the Qixia Formation, a warm, humid, and oxygen-rich marine environment supported abundant ancient organisms. In the highstand system tract of the upper-middle part of the Qi2 member, the Sr/Ba ratio is lowest, while the MgO/CaO ratio is highest, indicating elevated ancient water temperatures and specific chemical compositions. The m value, reflective of paleosalinity, is notably high, suggesting a shallow, high-energy platform edge environment away from the mainland. Thick, high-energy platform edge sand debris and bioclastic beaches in this area promote the development of high-quality porous dolomite reservoirs of beach facies. The sedimentary facies and reservoir conditions of the Qi2 member in the middle Longmen Mountain are comparable to those in other sections, making it a promising target for oil and gas exploration within the Qixia Formation and a potential strategic replacement area for reservoir expansion.

Abstract Background Varicocele is the most prevalent correctable cause of male infertility. Currently, surgical treatment is the primary method to enhance fertility.For many young varicocele patients who have postponed surgery due to time constraints, daytime surgery is especially crucial. Thus, this study aims to investigate the clinical and nursing application value of the Plan-Do-Check-Act (PDCA) cycle in daytime varicocelectomy. Methods Retrospective collection of clinical data was conducted on 130 patients undergoing laparoscopic varicocelectomy in the Third Affiliated Hospital of Southern Medical University, Guangzhou,China.Among them, 65 patients who underwent daytime surgery were assigned to the observation group, while 65 patients who underwent routine hospital surgeries were assigned to the control group.The former also implemented PDCA cycle management.A comparison was made between the two groups regarding hospitalization time, hospitalization costs, and patient satisfaction. Results The observation group exhibited a shorter hospitalization time and lower hospitalization costs compared to the control group, with higher patient satisfaction and pre-discharge visual analog scale (VAS) scores noted (P 0.05). The implementation of the PDCA cycle in the observation group has demonstrated its effectiveness, ensuring the smooth conduct of the daytime varicocelectomy. Conclusion In conclusion,daytime varicocelectomy can reduce hospitalization time,lower hospitalization costs, improve patient satisfaction. The PDCA Cycle enhances the rationality and efficacy of the daytime varicocelectomy procedure and is highly recommended. Furthermore, it offers valuable reference for the application of the PDCA Cycle in various other diseases and nursing management approaches. Trial Registration The Trial Registration Number: ChiCTR2300077465;Date of registration: November 9, 2023.

Abstract Background Epigenetic remodeling at effector gene loci has been reported to be critical in regulating T cell differentiation and function. However, efforts to investigate underlying epigenetic mechanisms that control T cell behaviors have been largely hindered by very limited experimental tools, especially in humans. Results In this study, we employed a flow cytometric assay to analyze histone acetylation at single-cell level in human T cells. The data showed that histone acetylation was increased during T cell activation. Among T cell subsets, terminally differentiated effector memory T (TEMRA) cells robustly producing effector cytokines were hyper-acetylated. Conversely, these TEMRA cells had lower expression levels of TCF-1, a key transcription factor for maintaining stem cell features. Pharmaceutical inhibition of histone acetylation using a small molecule C646 restrained the production of effector molecules, but retained stem cell-like properties in T cells after expansion. Conclusions Per-cell histone acetylation is associated with terminal differentiation and poor stemness in human T cells. These observations suggest a new approach to enhance the stem cell-like properties of T cells and improve the efficacy of immunotherapy.

Recently, deep learning-based methods have emerged as the preferred approach for ultrasound data analysis. However, these methods often require large-scale annotated datasets for training deep models, which are not readily available in practical scenarios. Additionally, the presence of speckle noise and other imaging artifacts can introduce numerous hard examples for ultrasound data classification. In this paper, drawing inspiration from self-supervised learning techniques, we present a pre-training method based on mask modeling specifically designed for ultrasound data. Our study investigates three different mask modeling strategies: random masking, vertical masking, and horizontal masking. By employing these strategies, our pre-training approach aims to predict the masked portion of the ultrasound images. Notably, our method does not rely on externally labeled data, allowing us to extract representative features without the need for human annotation. Consequently, we can leverage unlabeled datasets for pre-training. Furthermore, to address the challenges posed by hard samples in ultrasound data, we propose a novel hard sample mining strategy. To evaluate the effectiveness of our proposed method, we conduct experiments on two datasets. The experimental results demonstrate that our approach outperforms other state-of-the-art methods in ultrasound image classification. This indicates the superiority of our pre-training method and its ability to extract discriminative features from ultrasound data, even in the presence of hard examples.

Graph contrastive learning (GCL) has emerged as a promising paradigm for learning graph representations. Recently, the idea of hard negatives is introduced to GCL, which can provide more challenging self-supervised objectives and alleviate over-fitting issues. These methods use different graphs in the same mini-batch as negative examples, and assign larger weights to true hard negative ones. However, the influence of such weighting strategies is limited in practice, since a small mini-batch may not contain any challenging enough negative examples. In this paper, we aim to offer a more flexible solution to affect the hardness of negatives by directly manipulating the representations of negatives. By assuming that (1) good negative representations should not deviate far from the representations of real graph samples, and (2) the computation process of graph encoder may introduce biases to graph representations, we first design a negative representation generator (NRG) which (1) employs real graphs as prototypes to perturb, and (2) introduces parameterized perturbations through the feed-forward computation of the graph encoder to match the biases. Then we design a generation loss to train the parameters in NRG and adaptively generate negative representations for more challenging contrastive objectives. Experiments on eight benchmark datasets show that our proposed framework ANGCL has 1.6% relative improvement over the best baseline, and can be successfully integrated with three types of graph augmentations. Ablation studies and hyper-parameter experiments further demonstrate the effectiveness of ANGCL.

Abstract Background Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression. Methods Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay. Results Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors. Conclusion Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.

Abstract Mounting attention has been focused on defects of the autophagy-lysosomal pathway in sepsis, however, the precise mechanisms governing the autophagy-lysosomal process in sepsis are poorly known. We have previously reported that Erbin deficiency aggravated the inflammatory response and organ injuries caused by sepsis. In the present study, we found that Erbin knockout impaired the autophagy process in both muramyl dipeptide (MDP)-induced bone marrow-derived macrophages (BMDMs) and sepsis mouse liver and lung, as detected by the accumulation of LC3-II and SQSTM1/p62, and autophagosomes. Pretreatment with autophagy inhibitor chloroquine (CQ) further aggravated inflammatory response and organ injuries in vivo and in vitro sepsis model. We also observed that the impaired lysosomal function mediated autophagic blockade, as detected by the decreased expression of ATP6V, cathepsin B (CTSB) and LAMP2 protein. Immunoprecipitation revealed that the C-terminal of Erbin (aa 391–964) interacts with the N-terminal of transcription factor EB (TFEB) (aa 1–247), and affects the stability of TFEB-14-3-3 and TFEB-PPP3CB complexes and the phosphorylation status of TFEB, thereby promote the nucleus translocation of TFEB and the TFEB target genes transcription. Thus, our study suggested that Erbin alleviated sepsis-induced inflammatory responses and organ injuries by rescuing dysfunction of the autophagy-lysosomal pathway through TFEB-14-3-3 and TFEB-PPP3CB pathway.

Many clinical conditions can cause fever of unknown origin (FUO) in children, but the etiological diagnosis remains challenging despite the variety of inspection methods available at present. This study aims to investigate the effectiveness of droplet digital polymerase chain reaction (ddPCR) in identifying pathogens in children with FUO as a novel application. A 7-month-old boy failed to obtain etiology evidence for his disease through various tests. After collecting peripheral blood for ddPCR analysis, Staphylococcus aureus and Escherichia coli were detected, and Sanger sequencing confirmed the pathogens. During the disease, the child developed septic arthritis and osteomyelitis in the femur. Despite the patient's fever being removed, his limb activity improving, and inflammatory biomarkers decreasing, avascular necrosis of the femoral head remained after targeted antibiotic treatment and surgery. If the patient had undergone ddPCR analysis at an early stage, it may be possible to avoid sequelae. ddPCR helps identify pathogens in the diagnosis of children with FUO and could be a promising complementary tool.

Idiopathic pulmonary fibrosis (IPF) is one of the most fatal chronic interstitial lung diseases with unknown pathogenesis, current treatments cannot truly reverse the progression of the disease. Pulmonary macrophages, especially bone marrow derived pro-fibrotic macrophages, secrete multiple kinds of profibrotic mediators (SPP1, CD206, CD163, IL-10, CCL18…), thus further promote myofibroblast activation and fibrosis procession. IL20Rb is a cell-surface receptor that belongs to IL-20 family. The role of IL20Rb in macrophage activation and pulmonary fibrosis remains unclear. In this study, we established a bleomycin-induced pulmonary fibrosis model, used IL4/13-inducing THP1 cells to induce profibrotic macrophage (M2-like phenotype) polarization models. We found that IL20Rb is upregulated in the progression of pulmonary fibrosis, and its absence can alleviate the progression of pulmonary fibrosis. In addition, we demonstrated that IL20Rb promote the activation of bone marrow derived profibrotic macrophages by regulating the Jak2/Stat3 and Pi3k/Akt signaling pathways. In terms of therapeutic strategy, we used IL20Rb neutralizing antibodies for animal administration, which was found to alleviate the progression of IPF. Our results suggest that IL20Rb plays a profibrotic role by promoting profibrotic macrophage polarization, and IL20Rb may become a potential therapeutic target for IPF. Neutralizing antibodies against IL20Rb may become a potential drug for the clinical treatment of IPF.

Intracranial aneurysm is a high-risk disease, with imaging playing a crucial role in their diagnosis and treatment. The rapid advancement of artificial intelligence in imaging technology holds promise for the development of AI-based radiomics predictive models. These models could potentially enable the automatic detection and diagnosis of intracranial aneurysms, assess their status, and predict outcomes, thereby assisting in the creation of personalized treatment plans. In addition, these techniques could improve diagnostic efficiency for physicians and patient prognoses. This article aims to review the progress of artificial intelligence radiomics in the study of intracranial aneurysms, addressing the challenges faced and future prospects, in hopes of introducing new ideas for the precise diagnosis and treatment of intracranial aneurysms.

Purpose: To investigate the regulatory effect and mechanism of Vitamin D receptor (VDR) on mitochondrial function in renal tubular epithelial cell under diabetic status. Methods: The diabetic rats induced by streptozotocin (STZ) and HK-2 cells under high glocose(HG)/transforming growth factor beta (TGF-β) stimulation were used in this study. Calcitriol was administered for 24 weeks. Renal tubulointerstitial injury and some parameters of mitochondrial function including mitophagy, mitochondrial fission, mitochondrial ROS, mitochondrial membrane potential (MMP), mitochondrial ATP, Complex V activity and mitochondria-associated ER membranes (MAMs) integrity were examined. Additionally, paricalcitol, 3-MA (an autophagy inhibitor), VDR over-expression plasmid, VDR siRNA and Mfn2 siRNA were applied in vitro. Results: The expression of VDR, Pink1, Parkin, Fundc1, LC3II, Atg5, Mfn2, Mfn1 in renal tubular cell of diabetic rats were decreased significantly. Calcitriol treatment reduced the levels of urinary albumin, serum creatinine and attenuated renal tubulointerstitial fibrosis in STZ induced diabetic rats. In addition, VDR agonist relieved mitophagy dysfunction, MAMs integrity, and inhibited mitochondrial fission, mitochondrial ROS. Co-immunoprecipitation analysis demonstrated that VDR interacted directly with Mfn2. Mitochondrial function including mitophagy, mitochondrial membrane potential (MMP), mitochondrial Ca2+, mitochondrial ATP and Complex V activity were decreased dramatically in HK-2 cells under HG/TGF-β ambience. In vitro pretreatment of HK-2 cells with autophagy inhibitor 3-MA, VDR siRNA or Mfn2 siRNA negated the activating effects of paricalcitol on mitochondrial function. Pricalcitol and VDR over-expression plasmid activated Mfn2 and then partially restored the MAMs integrity. Additionally, VDR restored mitophagy was partially associated with MAMs integrity through Fundc1. Conclusion: Activated VDR could contribute to restore mitophagy through Mfn2-MAMs-Fundc1 pathway in renal tubular cell. VDR could recover mitochondrial ATP, complex V activity and MAMs integrity, inhibit mitochondrial fission and mitochondrial ROS. It indicating that VDR agonists ameliorate renal tubulointerstitial fibrosis in diabetic rats partially via regulation of mitochondrial function.

Chronic viral infections cause T cell dysfunction in both animal models and human clinical settings, thereby affecting the ability of the host immune system to clear viral pathogens and develop proper virus-specific immune memory. However, the impact of chronic viral infections on the host's immune memory to other pathogens has not been well described. In this study, we immunized mice with recombinant Listeria monocytogenes expressing OVA (Lm-OVA) to generate immunity to Lm and allow analysis of OVA-specific memory T (Tm) cells. We then infected these mice with lymphocytic choriomeningitis virus (LCMV) strain Cl-13 which establishes a chronic infection. We found that chronically infected mice were unable to protect against Listeria re-challenge. OVA-specific Tm cells showed a progressive loss in total numbers and in their ability to produce effector cytokines in the context of chronic LCMV infection. Unlike virus-specific T cells, OVA-specific Tm cells from chronically infected mice did not up-regulate the expression of inhibitory receptors, a hallmark feature of exhaustion in virus-specific T cells. Finally, OVA-specific Tm cells failed to mount a robust recall response after bacteria re-challenge both in the chronically infected and adoptively transferred naïve hosts. These results show that previously established bacteria-specific Tm cells become functionally impaired in the setting of an unrelated bystander chronic viral infection, which may contribute to poor immunity against other pathogens in the host with chronic viral infection.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and PPARs are involved in its pathogenesis; however, the specific mechanisms by which changes in PPARδ impact the OA pathogenesis yet to be discovered. The purpose of this study was to ascertain how PPARδ affects the onset and development of OA. In vitro, we found that PPARδ activation ameliorated apoptosis and extracellular matrix (ECM) degradation in OA chondrocytes stimulated by IL-1β. In addition, PPARδ activation may modulate AKT/mTOR signaling to partially regulate chondrocyte autophagy and apoptosis. In vivo, injection of PPARδ agonist into the articular cavity improved ECM degradation, apoptosis and autophagy in rats OA models generated by destabilization medial meniscus (DMM), eventually delayed degeneration of articular cartilage. Thus, targeting PPARδ for OA treatment may be a possibility.

To improve automatic generation control (AGC) performance and reduce the wastage of regulation resources in interconnected grids including high-proportion renewable energy, a multi-area integrated AGC (MAI-AGC) framework is proposed to solve the coordination problem of secondary frequency regulation between different areas. In addition, a cocktail exploration multi-agent deep deterministic policy gradient (CE-MADDPG) algorithm is proposed as the framework algorithm. In this algorithm, the controller and power distributor of an area are combined into a single agent which can directly output the power generation command of different units. Moreover, the cocktail exploration strategy as well as various other techniques are introduced to improve the robustness of the framework. Through centralized training and decentralized execution, the proposed method can nonlinearly and adaptively derive the optimal coordinated control strategies for multiple agents and is verified on the two-area LFC model of southwest China and the four-area LFC model of the China Southern Grid (CSG).

Owing to the tremendous contribution for the carrier transport across the interface, the band alignment engineering in oxide semiconductor heterojunctions (OSHs) is of vital importance for developing oxide semiconductor optoelectronic devices. Here, we have deposited a series of ultra-wide bandgap GeO2 thin films on quartz substrates by the direct-current reactive magnetron sputtering method to construct the OSHs and described the effect of the flow rate ratios of O2 and Ar (O2:Ar) and substrate temperatures on the bandgap energies of GeO2 films and band alignments at the interface of OSHs. Based on the energy loss spectra of O 1 s peaks, the tunable bandgap energies ranging from 4.37 to 5.37 eV have been achieved for GeO2 films. An obvious variation of band alignments has been found in the OSHs, suggesting the dramatically influence of deposition conditions. The valence band offsets are determined to be ranging from 1.85 to 1.96 eV (from 1.88 to 1.95 eV) and the conduction band offsets are calculated to be ranging from 1.88 to 2.78 eV (from 1.74 to 2.19 eV) for the GeO2 films grown at different O2:Ar (substrate temperatures), respectively, due to the nonlocalization of the oxygen vacancies in valence band and the formation of single hexagonal phase in the GeO2 film. Our findings on the band alignment engineering in the GeO2/SiO2 heterointerfaces will open the way for developing GeO2-based optoelectronic devices.

The implementation of the Natural Forest Protection Project (NFPP) in Northeastern China (NC) has improved the ecological environment and the capacity of ecosystem services (ESs), and has also played a positive role in promoting ESs in NC. In the study, the spatial and temporal variation characteristics of Soil Conservation (SC), Water Yield (WY), Carbon Storage (CS) and Habitat Quality (HQ) were evaluated based on InVEST and RUSLE models from 2000 to 2020 in NC. Furthermore 11 scenarios were established based on the ordered weighted average (OWA) operator, and regional PCA were selected by comparing the conservation efficiency (CE) of the 11 scenarios. The results showed that the multi-year average values of SC, WY, CS and HQ in the study area were 2.38×108 t, 2.67×1011 m3, 1.45×1010 tC and 0.71 (dimensionless). From a spatial distribution perspective, the high values of HQ, CS and SC in the study area were mainly distributed in the northern part of Inner Mongolia region, northern and north-central Heilongjiang Province, eastern Jilin Province, and eastern Liaoning Province. The high values of WY were mainly distributed in southeastern Liaoning Province, and low values covered almost the whole study area in 2000. Lastly, scenario 2 had the highest PE among 11 scenarios and were therefore selected as the PCA in the study and the CE of this scenario for HQ, SC, CS and WY were 1.31, 2.17, 1.69 and 1.80. The protected area for scenario were 2.24×105 km2, and the mainly land use type were forest. By overlaying NC with NFPP, priority I was chosen as the scope for further implementation of NFPP. The study can provide decision support for forestry policy and the scope of NFPP implementation in the near future.

Abstract Emerging infectious diseases are a critical public health challenge in the twenty-first century. The recent proliferation of such diseases has raised major social and economic concerns. Therefore, early detection of emerging infectious diseases is essential. Subjects from five medical institutions in Beijing, China, which met the spatial-specific requirements, were analyzed. A quality control process was used to select 37,422 medical records of infectious diseases and 56,133 cases of non-infectious diseases. An emerging infectious disease detection model (EIDDM), a two-layer model that divides the problem into two sub-problems, i.e., whether a case is an infectious disease, and if so, whether it is a known infectious disease, was proposed. The first layer model adopts the binary classification model TextCNN-Attention. The second layer is a multi-classification model of LightGBM based on the one-vs-rest strategy. Based on the experimental results, a threshold of 0.5 is selected. The model results were compared with those of other models such as XGBoost and Random Forest using the following evaluation indicators: accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. The prediction performance of the first-layer TextCNN is better than that of other comparison models. Its average specificity for non-infectious diseases is 97.57%, with an average negative predictive value of 82.63%, indicating a low risk of misdiagnosing non-infectious diseases as infectious (i.e., a low false positive rate). Its average positive predictive value for eight selected infectious diseases is 95.07%, demonstrating the model's ability to avoid misdiagnoses. The overall average accuracy of the model is 86.11%. The average prediction accuracy of the second-layer LightGBM model for emerging infectious diseases reaches 90.44%. Furthermore, the response time of a single online reasoning using the LightGBM model is approximately 27 ms, which makes it suitable for analyzing clinical records in real time. Using the Knox method, we found that all the infectious diseases were within 2000 m in our case, and a clustering feature of spatiotemporal interactions (P

Abstract Background Gaming disorder is a new disease, which is included in the disease unit of disorder caused by addiction in the 11th revision of the International Classification of Diseases. This study examined the symptom characteristics of gaming disorders in Chinese adolescents using the latent profile analysis. Methods Totally, 5988 students (including 3285 boys and 2703 girls; aged 12–18 years) from junior high schools and senior high schools were enrolled. The Gaming Disorder Symptom Questionnaire-21 (GDSQ-21) was used to screen gaming disorder. A latent profile analysis was used for classifying the subgroups based on the extent of gaming usage. The relationship between adolescent gamers and demographic variables was analyzed by logistic regression. Results The results of latent profile analysis supported the models of four latent profiles, which were defined as healthy gamers (Profile 1, 56.83%), impaired control gamers (Profile 2, 26.09%), impaired control-game priority gamers (Profile 3, 9.72%) and gamers with disorder (Profile 4, 7.36%), respectively. Logistic regression analysis found that, compared with girls, boys were more likely to be classified into the group dominated by the impaired gamers, the impaired control-game priority gamers, and the gamers with disorder. Conclusions This study highlighted that the latent profile analysis identified four different groups of adolescent gamers, showing a clearer conceptualization of heterogeneous gamers. Gender and average weekly gaming time can predict the latent profile of adolescents. Our findings may facilitate the design of individualized assessment and early intervention programs for adolescent gamer users based on different gaming usage symptoms.

Objective As conventional plates require repeated pre‐bending during surgery with poor matching, this study aimed to explore the design and application of an acetabular integrative anatomical plate (AIAP) via the lateral‐rectus approach (LRA) in fresh complex acetabular fractures for the good reduction and fixation. Methods We designed an AIAP based on the anatomical morphology of the Chinese people. From March 2016 to September 2021, 178 patients with fresh complex acetabular fractures treated with an AIAP via the LRA were retrospectively analyzed. All patients were treated by the LRA under general anesthesia in a supine position. The fragments were well reduced and fixed by AIAPs. The operation time and intraoperative blood loss were recorded. All patients underwent reexamination of pelvic X‐rays and CT scans and were followed up for over 1 year postoperatively. The reduction quality of fracture was evaluated according to the Matta criteria. The postoperative functional recovery was evaluated by modified Merle d'Aubigne‐Postel scoring system. Statistics were analyzed by SPSS 25.0 (SPSS Inc., Chicago, IL, USA). Results All 178 patients went through the operation successfully. The time from injury to operation ranged from 5 to 21 days (8.7 ± 2.6 days). The operation time ranged from 35 to 150 min (75 ± 29 min). The intraoperative blood loss was from 250 to 1400 ml (440 ± 153 ml). According to the Matta score, the fracture reduction was evaluated as excellent in 131 cases, good in 31 cases, and poor in 16 cases, with an overall excellent and good rate of 91%. Four patients suffered wound fat liquefaction and healed after fresh dressing. All patients were followed up for 1 to 5 years without wound infection. All fractures were healed. At the last follow‐up, the modified Merle d'Aubigne‐Postel score results were evaluated as excellent in 125 cases, good in 26 cases, and fair in 27 cases, with an overall excellent and good rate of 84.8%. Postoperative complications included six cases of traumatic arthritis of the hips and two cases of femoral head necrosis. Conclusion The LRA with an AIAP can help expose, reduce, and fix anterior and posterior columns as well as the quadrilateral area of the acetabulum, which is capable of improving the reduction quality of complex acetabular fractures and shortening surgical time and blood loss, thus reaching a good clinical efficacy.

Abstract Water disinfection is conventionally achieved by oxidation or irradiation, which is often associated with a high carbon footprint and the formation of toxic byproducts. Here, we describe a nano-structured material that is highly effective at killing bacteria in water through a hydrodynamic mechanism. The material consists of carbon-coated, sharp Cu(OH)2 nanowires grown on a copper foam substrate. We show that mild water flow (e.g. driven from a storage tank) can efficiently tear up bacteria through a high dispersion force between the nanotip surface and the cell envelope. Bacterial cell rupture is due to tearing of the cell envelope rather than collisions. This mechanism produces rapid inactivation of bacteria in water, and achieved complete disinfection in a 30-day field test. Our approach exploits fluidic energy and does not require additional energy supply, thus offering an efficient and low-cost system that could potentially be incorporated in water treatment processes in wastewater facilities and rural communities.

Objective Anterior dislocation of the sacroiliac joint (ADSIJ) is caused by strong violence, and because of its low morbidity, there are no standardized diagnostic and therapeutical guidelines at this moment. This study aims to explore the surgical techniques and preliminary outcomes of the lateral‐rectus approach (LRA) for treating ADSIJ. Methods A retrospective study was conducted of 15 patients with ADSIJ from January 2016 to January 2021. The patients' age ranged from 1.8 years old to 57 years old (37 ± 18 years old). All patients underwent open reduction and internal fixation (ORIF) through the LRA. Eight patients were combined with lumbosacral plexus injury and underwent neurolysis during operation. Patients' fracture type, mechanism of injury, associated injuries, operation time and intraoperative bleeding volume were accessed by reviewing medical history. Quality of fracture reduction was evaluated with the Matta score. At 1‐year follow‐up, the functional rehabilitation was evaluated by the Majeed rehabilitation criteria. For those with lumbosacral plexus injury, the neuromotor function was evaluated using muscle strength grading proposed by the British Medical Research Council (BMRC) and recovery was recorded. Results All 15 patients underwent the operation successfully. The surgical time ranged from 70 to 220 min (126 ± 42 min), and the intraoperative blood loss ranged from 180 to 2000 mL (816 ± 560 mL). Eighty percent of the cohort (12/15) were rated as excellent and good in the Matta score for fracture reduction quality after operation without surgical incision‐related complications. At 1‐year follow‐up, the overall excellent and good rate was 73.3% (11/15) according to the Majeed criteria, the neuromotor function recovered completely in six cases and partially in two cases according to the BMRC muscle strength grading, and the recovery of sensory function was evaluated as excellent in six cases, good in one case and poor in one case, with an overall excellent and good rate of 87.5%. Conclusion The LRA can well expose the surrounding structures of the sacroiliac joint from the front, which helps surgeons reduce and fix the anterior dislocation of the sacroiliac joint under direct vision and effectively decompress the entrapment of the lumbosacral plexus to achieve better clinical efficacy.

Chondrosarcoma (CHS) is a malignant bone tumor with insensitivity to both radiotherapy and chemotherapy, and a high recurrence rate. However, the latent mechanism of recurrent CHS (Re-CHS) remains elusive. Here, we discovered that FBXO22 was highly expressed in clinical samples of Re-CHS. FBXO22 played a significant role in various cancers. However, the role of FBXO22 in Re-CHS remained unclear. Our research demonstrated that suppressing FBXO22 abated the proliferation and migration of CHS cells and facilitated their apoptosis. In addition, suppressing FBXO22 raised the expression of PD-L1 in Re-CHS. All these findings provide new evidence for using FBXO22 and PD-L1 as combined targets to prevent and treat Re-CHS, which may prove to be a novel strategy for immunotherapy of CHS, especially Re-CHS.

Abstract Interactions between oncogenic proteins contribute to the phenotype and drug resistance. Here, EZH2 (enhancer of zest homolog 2) is identified as a crucial factor that mediates HIF‐1 (hypoxia‐inducible factor) inhibitor resistance. Mechanistically, targeting HIF‐1 enhanced the activity of EZH2 through transcription activation of SUZ12 (suppressor of zest 12 protein homolog). Conversely, inhibiting EZH2 increased HIF‐1α transcription, but not the transcription of other HIF family members. Additionally, the negative feedback regulation between EZH2 and HIF‐1α is confirmed in lung cancer patient tissues and a database of cell lines. Moreover, molecular prediction showed that a newly screened dual‐target compound, DYB‐03, forms multiple hydrogen bonds with HIF‐1α and EZH2 to effectively inhibit the activity of both targets. Subsequent studies revealed that DYB‐03 could better inhibit migration, invasion, and angiogenesis of lung cancer cells and HUVECs in vitro and in vivo compared to single agent. DYB‐03 showed promising antitumor activity in a xenograft tumor model by promoting apoptosis and inhibiting angiogenesis, which could be almost abolished by the deletion of HIF‐1α and EZH2. Notably, DYB‐03 could reverse 2‐ME2 and GSK126‐resistance in lung cancer. These findings clarified the molecular mechanism of cross‐regulation of HIF‐1α and EZH2, and the potential of DYB‐03 for clinical combination target therapy.

Sintering lunar regolith simulants as building materials is an effective method to establish long-term lunar bases. However, the high energy consumption of conventional thermal sintering is a challenge for energy-scarce lunars. The cold sintering process (CSP), which densifies ceramics with the assistance of transient solvent, offers a solution to overcome the aforementioned problems. Utilizing the CSP at 150 °C, 200 MPa, and 15 wt% 10 mol NaOH for 90 min, the density and compressive strength of the samples reached 2.44 g/cm3 and 207 MPa, respectively. The energy consumption of CSP equipment is only 0.86 kW·h, which is 6.66 times lower than that of conventional thermal sintering (5.73 kW·h). Furthermore, the compressive strength of the samples after three cool-heat cycles temperature between −196 °C and 150 °C was 205 MPa, indicating that the samples maintained high reliability in a simulated lunar environment. This excellent performance is attributed to the NaOH solution dissolving the oxide clusters on the particle surface, and the precipitation-generated glass phase connecting adjacent particles, making the particles consolidated and densified. Therefore, the cold sintering process presents promising prospects for the energy-efficient fabrication of lunar construction materials with excellent mechanical strength and durability.

BackgroundThere is a growing amount of evidence suggesting that immunity and inflammation play an important role in the pathophysiology of schizophrenia. In this study, we aimed to examine the relationship between hematological and inflammatory markers with symptom severity in Han Chinese patients with drug-free schizophrenia.MethodsThis retrospective study was conducted at Chaohu Hospital of Anhui Medical University and data were extracted from the electronic medical record system over a 5-year period (May 2017 to April 2022), including participants’ general and clinical information as well as Brief Psychiatric Rating Scale (BPRS) scores and hematological parameters.ResultsA total of 2,899 patients with schizophrenia were identified through the initial search. After screening, 91 patients and 141 healthy controls (HCs) were included. The patients had a higher value of neutrophils/lymphocytes ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) than HCs (all P < 0.001). MLR was positively correlated with BPRS total score (r = 0.337, P = 0.001) and resistance subscale score (r = 0.350, P = 0.001). Binary logistic regression analyses revealed that severely ill was significantly associated with being male and a higher value of MLR (Natural Logaruthm, Ln) (all P < 0.05), and the receiver operating characteristic (ROC) analysis showed good performance of a regression model with an area under the curve (AUC) value of 0.787.ConclusionPatients with drug-free schizophrenia have an unbalanced distribution of peripheral blood granulocytes, and elevated NLR, MLR and PLR. Patients with higher value of MLR tend to have more psychotic symptoms, especially those symptoms of hostility, uncooperativeness, and suspiciousness. Our study gives a preliminary indication that MLR is a potential predictor of disease severity in patients with drug-free schizophrenia.

Baijiu is one of the six primary distilled spirits in the world. It is produced through the solid-state fermentation of grains in the open environment, so high-quality Baijiu brewing largely depends on terrior. Environmental microbes are one of the most important factors affecting the quality, quantity, and flavors of Baijiu. As atmosphere is a pool and transport pathway for microbes from the ambient environment to Baijiu brewing ecosystems, we explored the functional microbes of Baijiu brewing in five important regions. The regions fell into two topographical types, namely, plain and river-valley. In total, 41 functional microbes were identified rich (relative abundance >0.1%) in at least one of the regions, such as the fungi of Aspergillus, Candida, Cladosporium, Debaryomyces, Penicillium, Pichia, Rhizopus, Saccharomyces, and Wickerhamomyces and the bacteria of Acetobacter, Bacillus, Clostridium, Enterobacter, Lactobacillus, Methanosarcina, Methanobacterium, Methanobrevibacter, and Pseudomonas. However, some functional bacteria (e.g., Clostridia, Gluconacetobacter, and Weissella) and fungi (e.g., Dekkera, Eurotium, Issatchenkia, Mucor, and Phoma) were not rich or were not detected in the atmosphere. Airborne microbiomes and the Phylogenetic Diversity (PD) index were significantly different between the main brewing season (winter) and the summer break in each region, except for the fungi in one region. In winter, airborne microbiomes were significantly different among almost all the regions. The relative abundance of bacterial fermentation function in each region increased from summer to winter. The relative abundances of fungal yeast function were higher in winter for the plain regions but were higher in summer for the river-valley regions. In sum, our results suggested that: (1) atmosphere was one but not the sole important source of functional microbes for Baijiu brewing and (2) microbiomes in different regions might be quite different but they could share some major functions related to Baijiu brewing.

Esophageal cancer (EC) is a common and devastating tumor of the upper digestive tract. Unfortunately, by the time any symptoms have manifested, the disease has often progressed to an advanced stage and is accompanied by macro- and micrometastases, including in the bones. The treatment of esophageal cancer with bone metastases remains clinically challenging, given the poor prognosis associated with this condition. Effective prognostic biomarkers can help medical staff choose the appropriate operation and treatment plan, that is for most beneficial for making patients. Current treatments for esophageal cancer with bone metastases include pain-relieving drugs, surgical therapy, radiotherapy (RT), chemotherapy (CT, including molecular-targeted drug therapy), endocrine therapy (ET), bisphosphonates (BPs) and interventional therapy. Of these robust measures, radiotherapy has emerged as a particularly promising therapy for bone metastases from esophageal cancer. Substantial progress has been made in radiation therapy techniques since the discovery of X-rays by Roentgen in 1895. In its palliative capacity, the key goals of radiotherapy are to relieve the patients’ bone pain and debilitate effects, including relieving spinal cord compression, correcting the spinal deformity and restoring spinal stability. However, it is worth mentioning that RT for esophageal cancer has various side effects. Currently, the available studies focused exclusively on radiotherapy for ECBM are too small to draw any definitive conclusions, and each of these studies has significant limitations. In this review, in addition to the epidemiology described at the beginning, we will explore the current prognostic biomarkers and radiotherapy for esophageal cancer, with a particular focus on those with bone metastases.

One new dimeric cyclohexylethanoid derivative (1) and one new rearranged abietane diterpenoid (2) were isolated from Clerodendrum bungei and C. inerme, respectively, together with 11 known compounds. The structures of the isolated compounds were elucidated by detailed spectroscopic and ECD analyses. The absolute configuration of 2 was unequivocally determined using single-crystal X-ray diffraction analysis. Compound 1 showed the greatest inhibitory effect on NO production in RAW 264.7 murine macrophages induced by lipopolysaccharide (LPS) with the IC50 value of 6.328 µM. Compound 1 also suppressed the proinflammatory cytokines IFN-γ, TNF-α, IL-1β, iNOS and IL-6 mRNA expression, while increased the mRNA expression of the anti-inflammatory cytokines IL-4, IL-10 and Arg-1 through NF-κB signaling pathway. The further experiments confirmed that compound 1 demonstrated the strong in vivo anti-inflammatory effect by reducing mortality, the serum TNF-α, IL-6 and IFN-γ levels, and tissue toxicity in CLP-induced septic mice. Collectively, these findings suggested that compound 1 might serve as a potential anti-inflammatory agent candidate for the sepsis treatment.

Thioredoxin (TRX) proteins play essential roles in reactive oxygen species scavenging in plants. We executed an exhaustive analysis of the TRX gene family in Citrus sinensis (CsTRXs), encompassing identification, phylogenetic analysis, detection of conserved motifs and domains, gene structure, cis-acting elements, gene expression trends, and subcellular localization analysis. Our findings established that a total of 22 CsTRXs with thioredoxin domains were identified in the genome of C. sinensis. Phylogenetic analysis indicated that CsTRXs were divided into six subclusters. Conserved motifs analysis of CsTRXs indicated a wide range of conserved motifs. A significant number of cis-acting elements associated with both abiotic and biotic stress responses, inclusive of numerous phytohormone-related elements, were detected in the promoter regions of CsTRXs. The expression levels of CsTRXs including CsTRXf1, CsTRXh1, CsTRXm1, CsTRXo3, CsTRXx2 and CsTRXy1 were observed to be reduced upon pathogen infection. Subcellular localization analysis found that CsTRXf1, CsTRXm1, CsTRXo3, CsTRXx2 and CsTRXy1 were predominantly localized in chloroplasts, whereas CsTRXh1 was distributed indiscriminately. This research yields integral data on CsTRXs, facilitating future efforts to decipher the gene functions of CsTRXs.

Abstract Laser‐inducing provides a cost‐effective, easily‐manufacturable, and environment‐friendly approach to directly transfer carbon‐rich polymers into graphene materials, which attracts attention from various fields, such as sensors, electrocatalysts, micro‐supercapacitors, etc. Laser‐induced graphene (LIG) benefits from the intrinsic properties of graphene, for example, high conductivity, high electroactivity, and high specific area. In this work the potential of laser‐induced graphene in constructing an enzymatic electrochemical biosensing interface is evaluated. Here, a laminar‐structured laser‐induced graphene material is fabricated by laser engraving with polyimide. After deposition of the electron mediator ferrocene, a conjugated enzyme complex of bovine serum albumin‐glucose oxidase (BSA‐GOx) is modified on the laser‐induced graphene by cross‐linking. The fabricated glucose oxidase/ferrocene/LIG (GOx/Fc/LIG) biosensor achieves high sensitivity of 11.3 µA mM−1 cm−2), wide linear range of 0–11 mM, and low detection of limit of 0.04 µM. The LIG electrodes exhibit high flexibility with bending angle as high as 60° without observed conductivity change. The repeatability and robustness of the developed LIG biosensor in detection of real serum samples empower it with great potential in clinical implementation in the future.

Faced with the problem of sub-synchronous oscillation (SSO) caused by the interaction between permanent magnetic synchronous generator (PMSG)-based wind farms and weak AC grids, we construct a transient energy function model that follows the structure of a PMSG. The transient energy composition of a PMSG is analyzed, and the dissipation energy expression that can intuitively reflect the development trend of SSO is derived, reflecting the damping level of a grid-connected wind power system. Furthermore, in response to the problem of mutual coupling between the control links of the PMSG during the SSO process, which hinders oscillation characteristic assessment, a method based on oscillation energy is proposed to analyze the oscillation characteristics. Considering the dynamic changes in the output of the phase-locked loop during sub-synchronous oscillation, the transient energy dominated by various control links is derived, and the effects of the phase-locked loop, current inner loop, and voltage outer loop on transient energy and oscillation characteristics are analyzed. The simulation verifies the effectiveness of the analysis of the transient energy model.

Abstract Surveillance is an intricate challenge worldwide especially in those complicated environments such as nuclear plants, banks, crowded areas, barns, etc. Deploying self‐powered wireless sensor nodes can increase the system's event detection capabilities by collecting environmental changes, while the incompatibility among components (energy harvesters, sensors, and wireless modules) limits their application. Here, a broadly compatible self‐powered visualized platform (SPVP) is reported to construct a passive internet of events (IoE) network for surveillance systems. By encoding electric signals into reference and working LEDs, SPVP can visualize resistance change generated by commercial resistive sensors with a broad working range (

AbstractThe occurrence of the Ms6.8 Luding earthquake on 5 September 2022 filled the seismic gap in the southeastern segment of the Xianshuihe fault zone and transferred stress to the surrounding faults, which attracted much more attention to the seismic hazard. In this study, we calculate the coseismic Coulomb stress changes caused by the Ms6.8 Luding earthquake and analyze its relationship with the relocated aftershocks, and further explore the stress evolution before the Luding earthquake and seismic hazards on the surrounding faults after it. The results show significant coseismic Coulomb stress increases in the northern Anninghe fault zone and the coseismic unruptured section of the southeastern Xianshuihe fault zone. Aftershocks are highly correlated with the positive coseismic Coulomb stress change, wherein eight out of eleven aftershocks of M ≥ 3.0 occurred in areas with significant stress increases ranging from 0.03 MPa to 0.44 MPa, indicating the triggering effect. The Moxi fault experiences co- and post-seismic Coulomb stress changes due to historical M ≥ 7.0 strong earthquakes since 1515, which help understand the seismogenic mechanism of the Luding earthquake. Moreover, the Luding earthquake advanced the potential earthquakes in the northern section of the Anninghe fault zone by approximately 60 years, further highlighting the potential seismic hazards.

Aspect-based sentiment analysis (ABSA) aims to automatically identify the sentiment polarity of specific aspect words in a given sentence or document. Existing studies have recognised the value of interactive learning in ABSA and have developed various methods to precisely model aspect words and their contexts through interactive learning. However, these methods mostly take a shallow interactive way to model aspect words and their contexts, which may lead to the lack of complex sentiment information. To solve this issue, we propose a Lightweight Multilayer Interactive Attention Network (LMIAN) for ABSA. Specifically, we first employ a pre-trained language model to initialise word embedding vectors. Second, an interactive computational layer is designed to build correlations between aspect words and their contexts. Such correlation degree is calculated by multiple computational layers with neural attention models. Third, we use a parameter-sharing strategy among the computational layers. This allows the model to learn complex sentiment features with lower memory costs. Finally, LMIAN conducts instance validation on six publicly available sentiment analysis datasets. Extensive experiments show that LMIAN performs better than other advanced methods with relatively low memory consumption.

Over recent years, chronic wounds caused by various factors, including diabetics and burns, have represented the major challenge and financial burden for both physicians and patients. Traditional wound care strategies based on passive dressing are not capable of real-time monitoring and timely treatment, which may result in overaggressive or conservative therapeutic options. To address these drawbacks, smart bandages with the capabilities of monitoring biomarkers for diagnosing and even implementing approaches to achieve efficient healing of chronic wounds have attracted widespread research interest. The current research frontier is in the embryonic phase toward a “closed-loop” wound management style. In this review, not only technologies for wound environment monitoring but also various mechanisms, materials and characteristics of platforms that promote wound healing are discussed, while the research progress on the concept of “theranostics” is summarized. This review provides a fundamental understanding of the wound biology, and should be valuable for the desirable assessment of wound status, and timely medical intervention, which is expected to facilitate the evolution of a new generation of smart bandages for preferable wound care applications.

Strain hardening cementitious composites (SHCC) exhibit promising potential for pavement applications owing to their excellent crack control and self-healing ability. However, the high cement content and absence of coarse aggregates in SHCC lead to high shrinkage and poor wear resistance, limiting SHCC’s large-scale application. This study aims to develop a low-shrinkage SHCC containing coarse silica sand by incorporating MgO expansive agent (MEA), and compare its performance with SHCC incorporating shrinkage reducing agent (SRA). The effects of MEA and SRA with different contents on the shrinkage and mechanical properties of SHCC containing coarse silica sand were systematically investigated through shrinkage tests, abrasion tests, compression tests and tension tests. The results show that the incorporation of MEA and SRA both significantly reduces the shrinkage of SHCC, but the latter leads to a significant decrease in the mechanical properties of SHCC. The mechanism underlying the reduction of shrinkage by MEA and SRA, as well as their influence on mechanical properties, are investigated at the microscopic level through XRD and SEM analysis. Overall, this study provides valuable insights into the advantages of incorporating MEA in enhancing the properties of SHCC, thereby offering significant potential for practical pavement applications utilizing SHCC.

The spine is one of the most important structures in the human body, serving to support the body, organs, protect nerves, etc. Medical image segmentation for the spine can help doctors in their clinical practice for rapid decision making, surgery planning, skeletal health diagnosis, etc. The current difficulty is mainly the poor segmentation accuracy of skeletal Magnetic Resonance Imaging (MRI) images. To address the problem, we propose a spine MRI image segmentation method, Atrous Spatial Pyramid Pooling (ASPP)-U-shaped network (UNet), which combines an ASPP structure with a U-Net network. This approach improved the network feature extraction by introducing an ASPP structure into the U-Net network down-sampling structure. The medical image segmentation models are trained and tested on publicly available datasets and obtained the Dice coefficient and Mean Intersection over Union coefficients with 0.866 and 0.755, respectively. The experimental results show that ASPP-UNet has higher accuracy for spine MRI image segmentation compared with other mainstream networks.

Abstract Optical cavities are essential for enhancing the sensitivity of molecular absorption spectroscopy, which finds widespread high-sensitivity gas sensing applications. However, the use of high-finesse cavities confines the wavelength range of operation and prevents broader applications. Here, we take a different approach to ultrasensitive molecular spectroscopy, namely dual-comb optomechanical spectroscopy (DCOS), by integrating the high-resolution multiplexing capabilities of dual-comb spectroscopy with cavity optomechanics through photoacoustic coupling. By exciting the molecules photoacoustically with dual-frequency combs and sensing the molecular-vibration-induced ultrasound waves with a cavity-coupled mechanical resonator, we measure high-resolution broadband ( > 2 THz) overtone spectra for acetylene gas and obtain a normalized noise equivalent absorption coefficient of 1.71 × 10−11 cm−1·W·Hz−1/2 with 30 GHz simultaneous spectral bandwidth. Importantly, the optomechanical resonator allows broadband dual-comb excitation. Our approach not only enriches the practical applications of the emerging cavity optomechanics technology but also offers intriguing possibilities for multi-species trace gas detection.

Abstract Background Human adenoviruses (HAdV) have been known to cause a range of diseases, including respiratory tract infections (RTIs). However, there is limited information available regarding the genotype diversity and epidemiology of HAdV associated with RTIs in Nanning. Methods Between June 2019 and December 2021, throat swab, nasal swab, or nasopharyngeal swab samples were obtained from individuals hospitalized with respiratory tract infections (RTIs). Statistical software was used to analyze the epidemiological data. The highly conserved 132-bp gene region of the HAdV hexon was targeted for the detection of HAdV using a qPCR assay. An 875-bp hexon gene fragment was subjected to phylogenetic analysis. Results Significant variations were observed in the age and gender distribution of HAdV-positive patients (P = 0.004 and P = 0.025, respectively). The age distribution of HAdV-positive patients showed that 67.89% of those who tested positive were the age group of 0–6 years. Furthermore, the prevalence of HAdV detection was highest during spring and autumn, with a peak in February. Additionally, genotyping of the 36 HAdV-positive samples with 875-bp fragments identified the presence of circulating HAdV species B, C, and E in Nanning between 2019 and 2021. Conclusions This study identified an association between HAdV prevalence and age as well as season. Among hospitalized patients with RTIs in Nanning, HAdV-B, HAdV-C, and HAdV-E were found to be co-circulating. The most commonly detected genotypes were HAdV-C1, HAdV-C6, and HAdV-E4.

Abstract Poor survival and restricted function of transplanted stem cells are regarded as limiting their efficacy in wound recovery greatly. Consequently, it is necessary to identify innovative therapeutic strategies to solve these issues. Firstly, the biological effect of PF-127 hydrogel alone and in combination with SAP on the survival, and migration of cultured HUCMSCs was assessed by cell viability, apoptosis, and scratch wound assays. S. aureus and E. coli were used to evaluate the antibacterial activity of PF-127 plus SAP combination. Further, the ability of HUCMSCs-conditioned medium (HUCMSCs-CM) to promote the angiogenesis and migration of human umbilical vein endothelial cells (HUVECs) in vitro was evaluated using tube formation and transwell migration assays. Finally, the HUCMSCs embedded in PF-127 plus SAP scaffold were administered onto mice’s excisional cutaneous wound bed. Histological and immunohistochemical analyses were employed to investigate the wound healing capacity as well as cellular responses of PF-127/HUCMSCs/SAP hydrogel. PF-127 showed cytotoxicity on HUCMSCs, whereas the addition of SAP significantly promoted cell viability and alleviated apoptosis of HUCMSCs encapsulated in PF-127 hydrogel in vitro. SAP supplementation substantially abrogated the inhibiting effect of PF-127 on the migration of HUCMSCs in vitro. The combination of PF-127 and SAP exerted an obvious bacteriostatic function on S. aureus and E. coli. Moreover, the co-treatment with SAP could remarkably enhance the stimulative effect of HUCMSCs-CM on the angiogenesis and migration of HUVECs in vitro. PF-127 combined SAP-embedded HUCMSCs transplantation resulted in a potently accelerated wound healing process, promoted the number of proliferating cells and newly formed blood vessels, as well as enhanced expression of vascular endothelial growth factor. PF-127 coupled with SAP contributes to HUCMSCs-mediated traumatic wound closure in mice by promoting cell survival, antibacterial action, and angiogenesis. Our results offered a theoretical foundation for the clinical treatment of traumatic skin defects.

Abstract. Background. This study was performed to introduce a new wireless endoscopic system. Research and development were based on fifth-generation transmission technology. Eye symptoms and visual discomfort induced by the novel endoscopic system were compared with those induced by the conventional endoscopic system before and during laparoscopic pelvic surgery. Materials and methods. Twenty surgeons successfully conducted laparoscopic pelvic surgeries using a conventional endoscopic system and a wireless endoscopic system. Subjective and objective data were measured to evaluate visual discomfort before and 2 hours after surgery. Results. In the conventional endoscopic and wireless endoscopic system groups, no significant differences were found in the presurgical or postsurgical questionnaires. In both groups, tear film breakup times significantly decreased after surgery. However, after comparing the 2 groups, no statistically significant difference was found. Conclusions. Compared with the conventional endoscopic system, the novel wireless endoscopic system does not cause additional visual discomfort for experienced surgeons.

Abstract Background Total knee arthroplasty (TKA) is a surgical procedure primarily used to treat patients with end-stage knee osteoarthritis (KOA). Postoperative physical exercise is a critical part of the overall treatment of KOA and can bring significant benefits to the patients' recovery. Wearable devices can monitor patients' exercise data and upload it to the physician's workstation. This allows the rehabilitation physician to make timely adjustments based on the patients' movement feedback, and the surgeon can be informed of the patients' functional status. Overall, this study aims to evaluate the effectiveness of using wearable monitoring devices for rehabilitation exercise after TKA, with a focus on cost, time savings, and patient outcomes. Method/design This is a single-center, single-blinded, parallel randomized controlled trial conducted at Xi'an Honghui Hospital, a regional orthopedic medical center. Eligible patients will be recruited to participate in the study, and baseline data collection and clinical assessments will be conducted at the time of admission. Using the principle of random allocation, recruited patients will be divided into either the experimental or control group. Both groups will undergo a standard, widely promoted rehabilitation program. The patients in the experimental group will wear equipment to detect and track mobility in the lower limbs. All patients will return to the outpatient clinic for follow-up assessments at 2 weeks, 12 weeks, and 24 weeks after discharge, where outcome indicators will be measured. The primary outcome will be the cost and time after discharge, while secondary outcomes will include the 6-min walk test (6MWT), range of motion (ROM), visual analog scale (VAS), American Knee Society Score (KSS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Discussion We should encourage the adoption of novel, easy-to-use, supervised devices if they prove to be beneficial for patients in terms of cost, time, and effectiveness after TKA. This type of device is particularly important for people in remote rural areas, those with limited financial resources, and those who are reluctant to return to hospitals for follow-up care. Trial registration Chinese Clinical Trial Registry ChiCTR2300068418. Registered on 17 February 2023.

Abstract. Background:. Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. Methods:. The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. Results:. We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F lowTAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo. Conclusion:. Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Abstract Background Breed identification is useful in a variety of biological contexts. Breed identification usually involves two stages, i.e., detection of breed-informative SNPs and breed assignment. For both stages, there are several methods proposed. However, what is the optimal combination of these methods remain unclear. In this study, using the whole genome sequence data available for 13 cattle breeds from Run 8 of the 1,000 Bull Genomes Project, we compared the combinations of three methods (Delta, F ST, and I n) for breed-informative SNP detection and five machine learning methods (KNN, SVM, RF, NB, and ANN) for breed assignment with respect to different reference population sizes and difference numbers of most breed-informative SNPs. In addition, we evaluated the accuracy of breed identification using SNP chip data of different densities. Results We found that all combinations performed quite well with identification accuracies over 95% in all scenarios. However, there was no combination which performed the best and robust across all scenarios. We proposed to integrate the three breed-informative detection methods, named DFI, and integrate the three machine learning methods, KNN, SVM, and RF, named KSR. We found that the combination of these two integrated methods outperformed the other combinations with accuracies over 99% in most cases and was very robust in all scenarios. The accuracies from using SNP chip data were only slightly lower than that from using sequence data in most cases. Conclusions The current study showed that the combination of DFI and KSR was the optimal strategy. Using sequence data resulted in higher accuracies than using chip data in most cases. However, the differences were generally small. In view of the cost of genotyping, using chip data is also a good option for breed identification.

Introduction: Reducing the protein adsorption of nanoparticles (NPs) as drug carriers to slow their rapid clearance by macrophages uptake is a critical challenge for NPs clinical translational applications. Despite extensive research efforts to inhibit cellular uptake, including covering biological agents or surface chemical coatings to impart “stealth” properties to NPs, their stability remains insufficient. Objectives: Developed a novel surface modification technology based on a physical infusion engineering approach to achieve persistent inhibition of protein adhesion and cellular uptake by nanocarriers. Methods: The nanoparticles were prepared based on conventional drug carrier mesoporous silica NPs through a two-step process. A functional nanoscale slippery surface was formed by grafting “liquid-like” brushes on the particles surface, and then a lubricant-entrenched slippery surfaces (LESS) was formed by infusing silicone oil lubricant into the entire surface. Co-incubation with macrophages (in vitro and in vivo) was used to examine the anti-uptake properties of modified NPs. The anti-adhesion properties of LESS coating surfaces to various liquids, proteins and cells were used to analyze the anti-uptake mechanism. Loaded with drugs, combined with tumor models, to evaluate the drug utilization of modified NPs. Results: Relying on the stable and slippery LESS coating, the modified surface could prevent the adhesion of various liquids and effectively shield against the adhesion of proteins and cells, as well as remarkably reduce macrophage cellular uptake in vitro and in vivo. In addition, the LESS coating does not affect cell activity and allows NPs to be loaded with drugs, significantly improving the utilization of drugs in vitro and in vivo. This allows the NPs to reach to the target tumor site for drug delivery without active clearance by macrophages. Conclusion: Our research introduces a new nanocarrier technology to improve anti-biofouling performance and stealth efficiency that will facilitate the development of nanomedicines for clinical transformation applications.

A combined pretreatment method of “low temperature-ultrasound-papain” (LTUP) was proposed to remove the purine of pork loins. Compared with untreated pork loin, under optimal conditions (temperature 58 °C, ultrasound density 100 W/cm2, and papain concentration 0.085%), the purine removal rate of treated pork loin could reach 59.29 ± 1.39%. The meat quality of pork loin treated with the LTUP method such as hardness and chewiness decreased by 58.37% and 64.38%, respectively, and the in vitro protein digestibility was increased by 19.64%; the cooking loss was decreased by 15.45%, compared with the simulated household blanching process (HT). In view of the high purine removal rate, the losses of free amino acids and soluble peptides were acceptable and reasonable. SEM and LF-NMR results showed that low temperature and ultrasound combined with papain treatment opened a channel for purine transfer and promoted purine dissolution by affecting the protein structure of pork loin. In addition, the migration of water within the muscle tissue was also related to purine removal. In summary, LTUP is recommended as an efficient and green way for the meat industry to remove purine.