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Abstract The fusion of viruses with cellular membranes is a critical step in the life cycle of enveloped viruses. This process is facilitated by viral fusion proteins, many of which are conformationally pH-sensitive. The specifics of how changes in pH initiate this fusion have remained largely elusive. This study presents the cryo-electron microscopy (cryo-EM) structures of a prototype class III fusion protein, GP64, in its prefusion and early intermediate states, revealing the structural intermediates accompanying the membrane fusion process. The structures identify the involvement of a pH-sensitive switch, comprising H23, H245, and H304, in sensing the low pH that triggers the initial step of membrane fusion. The pH sensing role of this switch is corroborated by assays of cell-cell syncytium formation and dual dye-labeling. The findings demonstrate that coordination between multiple histidine residues acts as a pH sensor and activator. The involvement of a multi-histidine switch in viral fusion is applicable to fusogens of human-infecting thogotoviruses and other viruses, which could lead to strategies for developing anti-viral therapies and vaccines.

Abstract miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3’-untranslated regions (3’-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

Summary: Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

A cell line, termed ZFIN, was established from the caudal fin of zebrafish and was shown to be susceptible to spring viremia of carp virus (SVCV). The ZFIN cells are epithelial like cells and have a moderate plasmid transfection efficiency of 13.9%. Using an RNA-seq approach, differentially expressed genes (DEGs) regulated by SVCV were identified. Infection of SVCV gave rise to 3931 DEGs and up-regulated DEGs were mostly enriched into the biological regulation and cellular processes, among which pathways for the type I interferon signaling and the response to exogenous dsRNA were the top two GO terms. Several KEGG signaling pathways including TLR signaling pathway, RLR receptor signaling pathway, cytosolic DNA-sensing pathway, NLR signaling pathway, cytokine-cytokine receptor interaction and ferroptosis were significantly enriched. Antiviral genes including ifnφ1, isg15 and mx were significantly up-regulated. In addition, key DEGs involved in autophagy were identified. The results indicate that the ZFIN cell line provides a useful in vitro tool for study on the gene functions and cellular responses to viral infection in fish.

Abstract PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient‐derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.

Abstract Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4‐nitroquinoline 1‐oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single‐cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor‐promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor‐promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment‐associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.

The FUS::DDIT3 fusion protein, formed by the chromosomal translocation t (12;16) (q13;p11), is found in over 90% of myxoid liposarcoma (MLS) cases and is a crucial protein in its development. Many studies have explored the role of FUS::DDIT3 in MLS, and the prevailing view is that FUS::DDIT3 inhibits adipocyte differentiation and promotes MLS growth and invasive migration by functioning as an aberrant transcription factor that affects gene expression and regulates its downstream molecules. As fusion proteins are gradually showing their potential as targets for precision cancer therapy, FUS::DDIT3 has also been investigated as a therapeutic target. Drugs that target FUS::DDIT3 and its downstream molecules for treating MLS are widely utilized in both clinical practice and experimental studies, and some of them have demonstrated promising results. This article reviews the findings of relevant research, providing an overview of the oncogenic mechanisms of the FUS::DDIT3 fusion protein in MLS, as well as recent advancements in its therapy.

Abstract Osteoporosis (OP) is a systematic bone disease characterized by low bone mass and fragile bone microarchitecture. Conventional treatment for OP has limited efficacy and long‐term toxicity. Synthetic biology makes bacterial extracellular vesicle (BEVs)‐based therapeutic strategies a promising alternative for the treatment of OP. Here, we constructed a recombinant probiotics Escherichia coli Nissle 1917‐pET28a‐ClyA‐BMP‐2‐CXCR4 (ECN‐pClyA‐BMP‐2‐CXCR4), in which BMP‐2 and CXCR4 were overexpressed in fusion with BEVs surface protein ClyA. Subsequently, we isolated engineered BEVs‐BMP‐2‐CXCR4 (BEVs‐BC) for OP therapy. The engineered BEVs‐BC exhibited great bone targeting in vivo. In addition, BEVs‐BC had good biocompatibility and remarkable ability to promote osteogenic differentiation of BMSCs. Finally, the synthetic biology‐based BEVs‐BC significantly prevented the OP in an ovariectomized (OVX) mouse model. In conclusion, we constructed BEVs‐BC with both bone‐targeting and bone‐forming in one‐step using synthetic biology, which provides an effective strategy for OP and has great potential for industrialization.

Compared to conventional spoofing, emerging spoofing attacks pose a heightened threat to security applications within the global navigation satellite system (GNSS) due to their subtly designed signal structures. In response, a novel spoofing detection method entitled aggregated correlation residue likelihood analysis (A-CoRLiAn) is proposed in this study. Requiring only the addition of a pair of supplementary correlators, A-CoRLiAn harnesses correlation residues to formulate a likelihood metric, subsequently aggregating weighted decisions from all tracked satellites to ascertain the presence of spoofing. Evaluated under six diverse spoofing scenarios (including emerging challenges) in the Texas Spoofing Test Battery (TEXBAT) via Monte Carlo simulations, A-CoRLiAn yields a detection rate of 99.71%, demonstrating sensitivity, robustness, autonomy, and a lightweight architecture conducive to real-time implementation against spoofing threats.

To achieve cost-effective micro-/nano-displacement adjustment, this paper integrates the advantages of flexible hinge micro-/nano-displacement transmission. A linear stepper motor is utilized as the driving component to design and develop a high-precision, low-cost micro-/nano-positioning system. The structure, design, and working principles of the micro-/nano-positioning platform are introduced. The scaling factor model between micro-positioning platforms and nano-positioning platforms is analyzed. Static and dynamic models of flexible mechanisms have been established. The dimensions of the mechanical structure and the selection of motors are determined. The mechanical characteristics of the micro-/nano-positioning platform are validated through finite element analysis. To address the characteristic of increasing loads during the transmission process, an intelligent control system based on current feedback is designed and developed. The integration of drive and control provides a high level of system integration. Finally, experimental calibration was conducted to test the motion characteristics of the linear stepper motor-driven micro-/nano-positioning platform. It achieved a minimum displacement control resolution of 100 nm and demonstrated a certain level of stability.

In order to improve the accuracy of the transformer fault identification using nature-inspired algorithms, an identification method based on the GWO (Grey Wolf Optimizer)-optimized Dual-channel MLP (Multilayer Perceptron)-Attention is proposed. First, a Dual-channel model is constructed by combining the AM (Attention Mechanism) and MLP. Subsequently, the GWO algorithm is used to optimize the number and the nodes of the hidden layer in the Dual-channel MLP-Attention model. Typical transformer faults are simulated using DDRTS (Digital Dynamic Real-Time Simulator) system. Experiments showed that the GWO- optimized method has an accuracy rate of 95.3%-96.7% in identifying the transformer faults. Compared with BP, SVM, MLP, and single-channel M-A models, the proposed method improved the accuracy by14.1%, 9.6%, 9.3%, and 3.3% respectively. This result indicates the rationality and effectiveness of the proposed method in transformer fault identification.

Introduction: The application prospects of percutaneous endoscopic lumbar discectomy (PELD) as a minimally invasive spinal surgery method in the treatment of lumbar disc herniation are extensive. This study aims to find the optimal entry angle for the trephine at the L4/5 intervertebral space, which causes less lumbar damage and has greater postoperative stability. To achieve this, we conduct a three-dimensional simulated analysis of the degree of damage caused by targeted puncture-based trephine osteotomy on the lumbar spine.Methods: We gathered clinical CT data from patients to construct a lumbar model. This model was used to simulate and analyze the variations in trephine osteotomy volume resulting from targeted punctures at the L4/5 interspace. Furthermore, according to these variations in osteotomy volume, we created Finite Element Analysis (FEA) models specifically for the trephine osteotomy procedure. We then applied mechanical loads to conduct range of motion and von Mises stress analyses on the lumbar motion unit.Results: In percutaneous endoscopic interlaminar discectomy, the smallest osteotomy volume occurred with a 20° entry angle, close to the base of the spinous process. The volume increased at 30° and reached its largest at 40°. In percutaneous transforaminal endoscopic discectomy, the largest osteotomy volume was observed with a 50° entry angle, passing through the facet joints, with smaller volumes at 60° and the smallest at 70°. In FEA, M6 exhibited the most notable biomechanical decline, particularly during posterior extension and right rotation. M2 and M3 showed significant differences primarily in rotation, whereas the differences between M3 and M4 were most evident in posterior extension and right rotation. M5 displayed their highest stress levels primarily in posterior extension, with significant variations observed in right rotation alongside M4.Conclusion: The appropriate selection of entry sites can reduce lumbar damage and increase stability. We suggest employing targeted punctures at a 30° angle for PEID and at a 60° angle for PTED at the L4/5 intervertebral space. Additionally, reducing the degree of facet joint damage is crucial to enhance postoperative stability in lumbar vertebral motion units.

Oral squamous cell carcinoma (OSCC) stands as a prevalent subtype of head and neck squamous cell carcinoma, leading to disease recurrence and low survival rates. PPARγ, a ligand-dependent nuclear transcription factor, holds significance in tumor development. However, the role of PPARγ in the development of OSCC has not been fully elucidated. Through transcriptome sequencing analysis, we discovered a notable enrichment of ferroptosis-related molecules upon treatment with PPARγ antagonist. We subsequently confirmed the occurrence of ferroptosis through transmission electron microscopy, iron detection, etc. Notably, ferroptosis inhibitors could not completely rescue the cell death caused by PPARγ inhibitors, and the rescue effect was the greatest when disulfidptosis and ferroptosis inhibitors coexisted. We confirmed that the disulfidptosis phenotype indeed existed. Mechanistically, through qPCR and Western blotting, we observed that the inhibition of PPARγ resulted in the upregulation of heme oxygenase 1 (HMOX1), thereby promoting ferroptosis, while solute carrier family 7 member 11 (SLC7A11) was also upregulated to promote disulfidptosis in OSCC. Finally, a flow cytometry analysis of flight and multiplex immunohistochemical staining was used to characterize the immune status of PPARγ antagonist-treated OSCC tissues in a mouse tongue orthotopic transplantation tumor model, and the results showed that the inhibition of PPARγ led to ferroptosis and disulfidptosis, promoted the aggregation of cDCs and CD8+ T cells, and inhibited the progression of OSCC. Overall, our findings reveal that PPARγ plays a key role in regulating cell death in OSCC and that targeting PPARγ may be a potential therapeutic approach for OSCC.

In this paper, the design of an atmospheric turbulence simulation system for free-space optical (FSO) communication is proposed. The system can accurately simulate repeatable atmospheric turbulent fading channels. It has a dynamic execution range of 30 dB with an execution rate of 1 MHz. The execution accuracy of the system is higher than 0.1 dB. In addition, the reliable TCP/IP protocol is used for communication, which ensures the convenience and versatility of the system. Experiments are carried out to investigate the performance of the system, and the results prove its superiority. Hence, the atmospheric turbulence simulation system can effectively simulate the influence of atmospheric turbulence channels on FSO communication systems.

In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

The increasing uncertainty of wind power brings greater challenges to the control for mitigation of cascading failures. In order to minimize the risk of cascading failures in large-scale wind power systems at a lower economic cost, a multi-stage blocking control model is proposed based on sensitivity analysis. Firstly, the propagation mechanism of cascading failures in power systems with wind power integration is analyzed, and the propagation path of such failures is predicted. Subsequently, sensitive lines that are prone to failure are identified using the power sensitivity matrix, taking into account the effects of blocking control on the propagation path. By constraining the power flow of these sensitive lines, a multi-stage blocking control model for the predicted cascading failure path is proposed with the objective of minimizing the control cost and cascading failure probability. Based on probabilistic optimal power flow calculations, the constraints related to wind power uncertainty are transformed into opportunity constraints. To validate the effectiveness of the proposed model, the IEEE 39-node system is used as an example, and the results show that the obtained control method is able to balance economy and safety. In addition, the control costs for the same initial failure are higher as the wind power penetration rates and confidence levels increase.

Abstract Background The judgment of confidence (JOC) refers to the confidence in the accuracy of the target item individuals have just retrieved and is a typical retrospective metacognitive monitoring process. In the classical paradigm of JOC, JOC occurs after the recognition or recall task. While initially viewed as a single-stage monitoring process, recent research on JOC suggests its internal mechanisms may be more complex, potentially encompassing both retrieval and monitoring processes. This study aims to delve into these mechanisms concerning neural temporal processes. Methods In this study, event-related potential (ERP) was used to compare N400 and slow-wave ERPs of high and low JOCs at different time windows using a classic JOC paradigm. Results Behavioral results showed an inverted-U shaped relationship between response time (RT) and JOCs, peaking at magnitude 3 before declining. There were significantly longer RT for low JOCs compared with high JOCs, along with lower recognition scores. The ERP results showed that low JOCs induced larger N400 in the right frontal lobe and right central area, while high JOCs induced larger slow-wave components (500 ~ 700ms) in the right frontal lobe. Conclusions Based on these findings, the present study suggests that JOC involves two processing stages. N400 reflects the process of cue acquisition, while the slow-wave component reflects the process of cue application. Furthermore, a two-stage model was proposed and validated, enriching the study of metacognition monitoring mechanisms, offering insights into the processing mechanisms of retrospective metacognitive monitoring.

Abstract Background Physical exercise is an important method for both the physical and mental health of the senior population. However, excessive exertion can lead to increased risks of falls, severe injuries, and diminished quality of life. Therefore, simple and effective methods for fatigue monitoring during exercise are highly desirable, particularly in community settings. The purpose of this study was to explore the possibility of real-time detection of exercise-induced fatigue using surface Electromyogram (sEMG) features, including the kurtosis and skewness of the Probability Density Function (PDF) in the community settings to solve the issues of low sensitivity and high computational complexity of commonly used sEMG features. Methods sEMG signals from six forearm muscles were recorded during hand grip tasks at 20% maximal voluntary contraction (MVC) task-to-failure contractions from 30 healthy community-dwelling elders at their respective community centers. PDF shape features of the sEMG, namely kurtosis and skewness, were computed from 25 s of non-fatigue stable phase and 25 s of fatigue data for comparison. Statistical tests were conducted to compare and test for the significance of these features. We further proposed a novel fatigue indicator, Temporal-Mean-Kurtosis (TMK) of channel-averaged kurtosis, to detect fatigue with relatively low computational complexity and adequate sensitivity in community settings. ANOVA and post-hoc analyses were performed to examine the performance of TMK. Results Statistically significant differences were found between the non-fatigue period and the fatigue period for both kurtosis and skewness, with increasing values when approaching fatigue. TMK was shown to be sensitive in detecting fatigue with respect to time with lower computational complexity than the Sample Entropy. Conclusion This study investigated PDF shape features of sEMG signals during a handgrip exercise to identify muscle fatigue in older adults in community experiments. Results revealed significant changes in kurtosis upon fatigue, indicating that PDF shape features were suitable convenient detectors of muscle fatigue in community experiments. The proposed indicator, TMK, showed potential sensitivity in tracking muscle fatigue over time in community-based settings with limited computational complexity, highlighting the promise of sEMG’s PDF features in detecting muscle fatigue among the elderly.

Abstract Background Glechoma longituba, recognized as a medicinal plant, provides valuable pharmaceutical raw materials for treating various diseases. Saline-alkali stress may effectively enhance the medicinal quality of G. longituba by promoting the synthesis of secondary metabolites. To investigate the changes in the primary medicinal components of G. longituba under saline-alkali stress and improve the quality of medicinal materials, Na2CO3 was applied to induce short-term stress under different conditions and the biomass, physiologically active substances and primary medicinal components of G. longituba were measured in this study. Results Under alkaline salt stress, the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) were elevated in G. longituba, accompanied by increased accumulation of proline (Pro) and malondialdehyde (MDA). Furthermore, analysis of the medicinal constituents revealed that G. longituba produced the highest levels of soluble sugars, flavonoids, ursolic acid, and oleanolic acid under 0.6% Na2CO3 stress for 48 h, 0.2% Na2CO3 stress for 72 h, 0.4% Na2CO3 stress for 12 h, and 0.4% Na2CO3 stress for 8 h, respectively. Conclusions Short-term Na2CO3 stress enhances the synthesis of medicinal components in G. longituba. By manipulating stress conditions, the production of various medicinal substances could be optimized. This approach may serve as a basis for the targeted cultivation of G. longituba, offering potential applications in the treatment of diverse diseases.

Abstract Background As we delve into the intricate world of venetoclax combination therapy in relapsed or refractory acute myeloid leukemia (AML), our exploration not only aims to contribute to the current body of knowledge but also strives to inform future research directions, clinical decision-making, and the ongoing evolution of therapeutic strategies in the relentless pursuit of improved outcomes for patients facing this formidable hematologic malignancy. Methods We systematically searched PubMed, Embase, and Cochrane databases from inception to November 2023 for English-language studies on venetoclax combination therapy in relapsed/refractory AML. We excluded duplicate published studies, incomplete studies, those with incomplete data, animal experiments, literature reviews, and systematic studies. Meta-analysis was performed using STATA 15.1. Results Out of 58 identified articles, seven were included in the meta-analysis. The pooled complete remission (CR) rate was 15.4%, and the composite complete remission (CRc) rate was 35.7%. The partial remission (PR) rate was 2.6%, while the non-remission (NR) rate was 24.4%. The minimal residual disease status in CRc patients (MRD-CRc) rate was 39.4%, and the morphologic leukemia-free state (MLFS) rate was 10.3%. Incidence of adverse events included diarrhea (10.0%), nausea (4.3%), vomiting (2.6%), hypokalemia (16.4%), hypomagnesemia (0.8%), decreased appetite (4.2%), fatigue (9.1%), febrile neutropenia (39.6%), and thrombocytopenia (28.4%). Subgroup analysis based on combined drugs revealed varying CR and CRc rates. the combination of venetoclax and azacitidine + demonstrates superior outcomes, displaying the highest rates of CR at 31.3% and CRc at 62.7%. In contrast, venetoclax and idasanutlin exhibits a moderate CR rate of 6.1% and a CRc rate of 26.5%, while venetoclax and mivebresib shows the lowest CR rate at 3.3% and a moderate CRc rate of 8.0%. Conclusion In conclusion, while venetoclax combination therapies, particularly with azacitidine + , show promise in achieving favorable treatment responses in relapsed/refractory AML patients, a comprehensive evaluation of safety profiles is essential. Nevertheless, it is essential to underscore the markedly increased incidence rates of febrile neutropenia and thrombocytopenia observed among adverse events.

Abstract Skeletal editing of single-atom insertion to basic chemicals has been demonstrated as an efficient strategy for the discovery of structurally diversified compounds. Previous endeavors in skeletal editing have successfully facilitated the insertion of boron, nitrogen, and carbon atoms. Given the prevalence of oxygen atoms in biologically active molecules, the direct oxygenation of C-C bonds through single-oxygen-atom insertion like Baeyer-Villiger reaction is of particular significance. Herein, we present an approach for the skeletal modification of styrenes using O2 via oxygen insertion, resulting in the formation of aryl ether frameworks under mild reaction conditions. The broad functional-group tolerance and the excellent chemo- and regioselectivity are demonstrated in this protocol. A preliminary mechanistic study indicates the potential involvement of 1,2-aryl radical migration in this reaction.

Abstract Background Gesture recognition using surface electromyography (sEMG) has garnered significant attention due to its potential for intuitive and natural control in wearable human–machine interfaces. However, ensuring robustness remains essential and is currently the primary challenge for practical applications. Methods This study investigates the impact of limb conditions and analyzes the influence of electrode placement. Both static and dynamic limb conditions were examined using electrodes positioned on the wrist, elbow, and the midpoint between them. Initially, we compared classification performance across various training conditions at these three electrode locations. Subsequently, a feature space analysis was conducted to quantify the effects of limb conditions. Finally, strategies for group training and feature selection were explored to mitigate these effects. Results The results indicate that with the state-of-the-art method, classification performance at the wrist was comparable to that at the middle position, both of which outperformed the elbow, consistent with the findings from the feature space analysis. In inter-condition classification, training under dynamic limb conditions yielded better results than training under static conditions, especially at the positions covered by dynamic training. Additionally, fast and slow movement speeds produced similar performance outcomes. To mitigate the effects of limb conditions, adding more training conditions reduced classification errors; however, this reduction plateaued after four conditions, resulting in classification errors of 22.72%, 22.65%, and 26.58% for the wrist, middle, and elbow, respectively. Feature selection further improved classification performance, reducing errors to 19.98%, 19.75%, and 27.14% at the respective electrode locations, using three optimal features derived from single-condition training. Conclusions The study demonstrated that the impact of limb conditions was mitigated when electrodes were placed near the wrist. Dynamic limb condition training, combined with feature optimization, proved to be an effective strategy for reducing this effect. This work contributes to enhancing the robustness of myoelectric-controlled interfaces, thereby advancing the development of wearable intelligent devices.

Abstract Eukaryotic Argonaute proteins (eAgos) utilize short nucleic acid guides to target complementary sequences for RNA silencing, while prokaryotic Agos (pAgos) provide immunity against invading plasmids or bacteriophages. The Sir2-domain associated short pAgo (SPARSA) immune system defends against invaders by depleting NAD+ and triggering cell death. However, the molecular mechanism underlying SPARSA activation remains unknown. Here, we present cryo-EM structures of inactive monomeric, active tetrameric and active NAD+-bound tetrameric SPARSA complexes, elucidating mechanisms underlying SPARSA assembly, guide RNA preference, target ssDNA-triggered SPARSA tetramerization, and tetrameric-dependent NADase activation. Short pAgos form heterodimers with Sir2-APAZ, favoring short guide RNA with a 5′-AU from ColE-like plasmids. RNA-guided recognition of the target ssDNA triggers SPARSA tetramerization via pAgo- and Sir2-mediated interactions. The resulting tetrameric Sir2 rearrangement aligns catalytic residue H186 for NAD+ hydrolysis. These insights advance our understanding of Sir2-domain associated pAgos immune systems and should facilitate the development of a short pAgo-associated biotechnological toolbox.

Abstract Low back pain (LBP) is a highly prevalent disease. Among the various causes of LBP, one of the most frequent is myofascial pain syndrome (MPS) which affects the spinal stabilizer muscles. The aims of this study were to compare the differences in muscular electrical activity and biomechanical properties between the painful and non-painful sides in patients with unilateral MPS and to verify the feasibility of surface electromyography (sEMG) and MyotonPRO for assisting in MPS assessment. Forty patients with unilateral lumbar MPS were recruited via the Department of Rehabilitation Medicine Center of West China Hospital Sichuan University from October 2022 to October 2023. The electrical properties of the bilateral erector spinae muscles were characterized by sEMG signals during a trunk extension task. The following four time-domain features of sEMG were extracted: root mean square (RMS), mean absolute value (MAV), integrated EMG (iEMG), and waveform length (WL). And two frequency domain features were extracted: the median frequency (MDF) and mean power frequency (MPF). The mechanical properties of the muscles were assessed by MyotonPRO at rest. The following biomechanical parameters were acquired: oscillation frequency [Hz], dynamic stiffness [N/m], logarithmic decrement, relaxation time [ms], and Creep. The visual analog scale (VAS) was used to evaluate the pain severity, and the Oswestry Disability Index (ODI) was used to evaluate the severity of disability and disruption to lifestyle activities caused by LBP pain. The outcome measures were obtained prior to the Platelet-rich plasma (PRP) treatment and repeated two weeks after treatment. (1) Prior to the PRP treatment, all sEMG time-domain features on the painful side were significantly higher than those on the non-painful side (RMS, p 0.05). (2) Two weeks after the PRP treatment, statistically significant decreases were observed in both post-treatment VAS (p

Abstract Ancient Platycladus orientalis holds significant ecological, landscape, historical, and cultural value. In northern China, leaf blight has significantly impacted the growth and ornamental value of ancient P. orientalis. In this study, 26 blight leaf samples of ancient P. orientalis were collected in Beijing, China. Phylogenetic analysis based on the concatenated internal transcribed spacer (ITS), β-tubulin (tub2), and RNA polymerase second largest subunit (rpb2) DNA sequence data combined with fungal morphological characteristics revealed three taxa of Nothophoma, i.e. N. platycladus, N. spiraeae, and N. juglandis. Of which, N. platycladus is a species new to science. Koch’s postulates indicated that all these three species of Nothophoma could cause leaf blight of P. orientalis.

The genus Dendrostoma is known to inhabit tree barks associated with branch canker diseases in China and several countries of Europe. Previous studies indicated that species of Dendrostoma prefer inhabiting fagaceous hosts, especially species of Castanea. In the present study, we obtained four isolates from cankered branches of Chinese chestnut (C. mollissima) in Rizhao City, Shandong Province, China. Morphological comparisons and phylogenetical analyses of a combined ITS-tef1-rpb2 sequence matrix were conducted, which revealed two new species named Dendrostoma rizhaoense sp. nov. and D. tianii sp. nov. The new taxa are compared with other Dendrostoma species and comprehensive descriptions and illustrations are provided herein.

Diaporthe species are known as endophytes, saprobes and pathogens infecting a wide range of plants and resulting in important crop diseases. In the present study, four strains of Diaporthe were obtained from diseased leaves of Bauhinia variegata in Guangdong Province, China. Phylogenetic analyses were conducted to identify these strains using five gene regions: internal transcribed spacer (ITS), calmodulin (cal), histone H3 (his3), translation elongation factor 1-α (tef1) and β-tubulin (tub2). The results combined with morphology revealed two new species of Diaporthe named D. bauhiniicola in D. arecae species complex and D. guangzhouensis in D. sojae species complex.

To achieve efficient chitosan oligosaccharide preparation, chitosan oligosaccharide was prepared from chitosan through a pre-ultrasound-microwave assisted composite enzymatic method. The enzymatic hydrolysis process conditions were optimized using reducing sugar content as an indicator based on the response surface design method. In addition, the antioxidant capacity of chitosan oligosaccharide was examined. The results showed that the composite enzymes consisting α-amylase and chitosanase (1:1) possessed superior hydrolysis ability for chitosan than others. The optimum conditions of chitosan oligosaccharide preparation were as follows: A microwave power of 200 W, ultrasonic power of 200 W, 5 min pre-ultrasound-microwave time, 1% substrate concentration, pH5.8, temperature at 53.5 ℃, 0.24% composite enzyme additive amount, and 5.7 h enzymatic hydrolysis time. Under these conditions, the reducing sugar content reached the maximum (8.10 mg/mL). The prepared chitosan oligosaccharide contained 2~6 sugars with average molecular weight of 993.5 Da. The chitosan oligosaccharide had strong free radical scavenging activity, with the IC50 of DPPH and ABTS+ free radicals at 0.274 and 0.127 mg/mL, respectively, as well as the ferric reducing power reached the maximum value of 24.56 mmol/L at 1.5 mg/mL. The results show that the ultrasound-microwave pretreatment combined with composite enzymatic method has a good application prospect in the preparation of chitosan oligosaccharide.

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

Abstract The development of intracerebral hemorrhage (ICH) is a dynamic process and intervention during the acute phase of ICH is critical for subsequent recovery. Therefore, it is crucial to screen potential signature genes and therapeutic target genes in the acute phase of ICH. In this study, based on the results of mRNA sequencing in mouse ICH and mRNA sequencing of human ICH from online databases, top five potential signature genes after ICH, Tyrobp, Itgb2, Tlr2, Ptprc and Itgam, were screened. Quantitative PCR results showed higher mRNA expression of Tyrobp, Itgb2, Tlr2, Ptprc, and Itgam in the 1-, 3- and 5-day mouse ICH groups compared to the sham-operated group. Immune infiltration correlation analysis shows that the top-ranked signature gene, Tyrobp, is negatively correlated with M2 macrophages and plasma cells, and Western blot analysis shows higher expression of the Tyrobp protein in the 1-, 3-, and 5-day mouse ICH groups compared to the sham-operated group. Furthermore, immunohistochemistry revealed that TYROBP protein expression was significantly higher in human ICH tissues than in normal brain tissues. Our results suggest that Tyrobp is a signature gene in the acute phase of ICH and may be a potential target for the treatment of the acute phase of ICH.

After the underground coal gasification is completed, a hyperbolic shaped coal pillar is formed between the two cavities to support the overlying rock and ensure the safety and stability of the gasification area. The work aimed to study the bearing mechanical characteristics of hyperbolic shaped coal pillar. Based on the acoustic emission (AE) monitoring system and the XTDIC 3D full-field strain measure system, 6 sets of “hyperbolic” coal samples with different lateral arch heights (h=0, 3 mm, 7 mm, 10 mm, 13 mm, 17 mm) were tested for uniaxial compression. The influence of h on peak load, deformation damage, and AE characteristics of coal samples were analyzed to reveal the bearing failure mechanism. The results are as follows. ① The “hyperbolic” coal sample can be divided into rectangular structure (main load-bearing body) and lateral arch structure, and its load-bearing failure mechanism is related to the force form and lateral arch structure. As h increases, the bearing capacity of the coal sample decreases. Compared with h=0 mm coal samples, the peak load was reduced by 7.66, 13.56, 26.83, 35.28, and 62.75%. ② The overall force form of coal samples changed from pressure-based to pressure-bending with increased h. Stress concentration occurs in the middle region of the coal sample, forming a weak area. The corresponding horizontal displacement field migrates towards the middle and finally at the edge of the middle. The vertical displacement field changed from a horizontal strip to an inclined strip, and ultimately concentrated at the upper end of the lateral arch structure of the coal sample. ③ Under axial load, the lateral arch structure of the coal sample exerts an equivalent force on the middle area of its rectangular structure, and is affected by the heterogeneity of the coal sample, which exacerbates the damage degree of the weak area in the middle. The effect increases with the increase of h, the coal sample undergoes shear failure when the load does not exceed its tensile strength. The failure mode of the coal samples shifted from tensile-shear mixed failure to shear failure, and all typical coal samples have experienced varying degrees of peeling and local ejection failure. ④ The evolution of the cumulative count-time curve of coal AE can be divided into three types. When h is 0 mm and 3 mm, it can be divided into four stages: “upward convex” growth, relatively rapid growth, rapid growth, and “sudden” growth, and its evolutionary characteristics are consistent with conventional rock samples. When h is 7 mm and 10 mm, it can be divided into three stages: relatively rapid growth, rapid growth, and “sudden” growth. When h is 13 mm and 17 mm, it can be divided into two stages: rapid growth and “sudden” growth. The post-peak stage shows a “sudden” growth pattern, while the inconsistent growth pattern in the pre-peak stage is caused by the stable expansion of coal sample cracks and continuous damage in the central region.

Abstract Background Work-related musculoskeletal disorders (WMSDs) show a rapid growth trend. It has brought a huge economic burden to the society and become a serious occupational health problem that needs to be solved urgently. This study aimed to analyze the local muscle response under continuous ergonomic load, screen sensitive fatigue-related biomarkers and provide data support for the early prevention of local muscle damage and the exploration of early warning indicators. Methods Thirteen male college student volunteers were recruited to perform simulated repetitive manual lifting tasks in the laboratory. The lifting task was designed for 4 periods which lasted for 12 min in each, and then paused for 3 min for sampling. Local muscle fatigue is assesed by the Rating of perceived exertion (RPE) and the Joint analysis of sEMG spectrum and amplitude (JASA). Elbow venous blood was collected and 14 kinds of biomarkers were analyzed, which included Metabolic markers Ammonia (AMM), Lactic acid (LAC), Creatine kinase (CK), Lactate dehydrogenase (LDH), Cartilage oligomeric matrix protein (COMP), C-telopeptide of collagen I and II (CTX-I, CTX-II) and Calcium ion (Ca2+); Oxidative stress marker Glutathione (GSH); Inflammatory markers C-reaction protein (CRP), Prostaglandin E2 (PG-E2), Interleukin-6 (IL-6) and Tumor necrosis factor α (TNF-α); Pain marker Neuropeptide Y (NPY). Repeated measures analysis of variance (Repeated ANOVA), linear regression analysis, t-test and spearman correlation analysis were used to analyze the data. Results Both subjective and objective fatigue appeared at the same period. Serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+ and NPY after fatigue were significantly higher than those before fatigue (p

Abstract Background Higher education students exhibit heightened sensitivity to environmental changes as they navigate the critical transition from adolescence to adulthood. The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to universities worldwide, exemplifying a crisis that profoundly affects the learning outcomes and psychological status of college students. Although it is known that campus lockdown has triggered dramatic changes in lifestyles, learning outcomes, and psychological statuses, in-depth knowledge of the causal relationships among these changes remains largely unclear. Methods Here, we conducted a cross-sectional survey designed to assess the impact of campus closure during COVID-19 on lifestyle, educational performance, and anxiety levels among college students. We surveyed over 3,500 junior college, undergraduate and graduate participants from 94 colleges/universities across 30 provinces, municipalities, and autonomous regions in China.We employed structural equation modeling (SEM) to explore the relationships between changes in lifestyle, educational performance, and levels of anxiety associated with campus open or closure regulations during the COVID-19 pandemic. Results Our results discovered that sleep duration, physical activity involvement, and social connections were crucial for sustaining students' learning outcomes and mental health. The shift to online learning and campus lockdown exacerbated stressors, contributing to heightened anxiety (β = 0.066), disrupted sleep patterns, and enhanced physical activity (β = 0.070) and reduced learning effect (β = -0.059). Sleep patterns were disrupted by the campus lockdown, an effect mediated by the degradation of relationships among classmates. Nonetheless, the best-fitting SEM uncovered the intricate relationships among lifestyle changes, learning outcomes, and psychological status in response to sudden environmental changes (Fisher’s C = 80.949, P = 0.328). These results highlight the critical role of adaptable, supportive campus policies tailored to meet the diverse needs and interests of students during and beyond crises (Fisher’s C = 59.568, P = 0.809). Conclusions Our study advocates for a holistic approach that addresses the multifaceted aspects of student life to cultivate a resilient academic community. This approach contributes to a deeper understanding of the effects of sudden environmental changes on students' psychological well-being and academic performance in the post-pandemic era.

Abstract Objective To construct chimeric antigen receptor (CAR)-T cells targeting epithelial cell adhesion molecule (EpCAM) antigen (anti-EpCAM-CAR-T). Methods A third-generation CAR-T cell construct used a single-chain variable fragment derived from monoclonal antibody against human EpCAM. Peripheral blood mononuclear cells were extracted from volunteers. The proportion of cluster of differentiation 8 positive (CD8+) and CD4 + T cells was measured using flow cytometry. Western blot was used to detect the expression of EpCAM-CAR. The killing efficiency was detected using the MTT assay and transwell assay, and the secretion of killer cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was detected using the ELISA. The inhibitory effect of EpCAM-CAR-T on colorectal cancer in vivo was detected using xenografts. Results It was found that T cells expanded greatly, and the proportion of CD3+, CD8 + and CD4 + T cells was more than 60%. Furthermore, EpCAM-CAR-T cells had a higher tumour inhibition rate in the EpCAM expression positive group than in the negative group (P

Abstract Background Drug resistance, including Adriamycin-based therapeutic resistance, remains a challenge in breast cancer (BC) treatment. Studies have revealed that macrophages could play a pivotal role in mediating the chemoresistance of cancer cells. Accumulating evidence suggests that tRNA-Derived small RNAs (tDRs) are associated the physiological and pathological processes in multiple cancers. However, the underlying mechanisms of tDRs on chemoresistance of BC in tumor-associated macrophages remain largely unknown. Methods The high-throughput sequencing technique was used to screen tDRs expression profile in BC cells. Gain- and loss-of-function experiments and xenograft models were performed to verify the biological function of 3′tRF-Ala-AGC in BC cells. The CIBERSORT algorithm was used to investigate immune cell infiltration in BC tissues. To explore the role of 3′tRF-Ala-AGC in macrophages, M2 macrophages transfected with 3′tRF-Ala-AGC mimic or inhibitor were co-cultured with BC cells. Effects on Nuclear factor-κb (NF-κb) pathway were investigated by NF-κb nuclear translocation assay and western blot analysis. RNA pull-down assay was performed to identify 3′tRF-Ala-AGC interacting proteins. Results A 3′tRF fragment of 3′tRF-AlaAGC was screened, which is significantly overexpressed in BC specimens and Adriamycin-resistant cells. 3′tRF-AlaAGC could promote cell malignant activity and facilitate M2 polarization of macrophages in vitro and in vivo. Higher expression of M2 macrophages were more likely to have lymph node metastasis and deeper invasion in BC patients. Mechanistically, 3′tRF-AlaAGC binds Type 1-associated death domain protein (TRADD) in BC cells, and suppression of TRADD partially abolished the enhanced effect of 3′tRF-AlaAGC mimic on phenotype of M2. The NF-κb signaling pathway was activated in BC cells co-cultured with M2 macrophages transfected with 3′tRF-AlaAGC mimic. Conclusions 3′tRF-AlaAGC might modulate macrophage polarization via binding to TRADD and increase the effect of M2 on promoting the chemoresistance in BC cells through NF-κb signaling pathway.

Abstract Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit the development of synthetic chemistry, pharmaceutical research, and materials science. Substituted amines, especially nitrogen-containing alkyl heterocyclic compounds, are widely found in nature products and drugs. Generally, accessing these compounds requires multiple steps, which could result in low efficiency. In this work, a molecular editing strategy is used to realize the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials. Using derivatives of O-tosylhydroxylamine as the nitrogen source, this method enables precise nitrogen insertion into the Csp 2-Csp 3 bond of aryl alkanes. Notably, further synthetic applications demonstrate that this method could be used to prepare bioactive molecules with good efficiency and modify the molecular skeleton of drugs. Furthermore, a plausible reaction mechanism involving the transformation of carbocation and imine intermediates has been proposed based on the results of control experiments.

Abstract Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry, especially in most breeds of obese type pigs. The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear. Lysine 2-hydroxyisobutyrylation (Khib), is a novel protein post-translational modification (PTM), which play an important role in transcription, energy metabolism and metastasis of cancer cells, but its role in adipogenesis and fat accumulation has not been shown. Results In this study, we first analyzed the modification levels of acetylation (Kac), Khib, crotonylation (Kcr) and succinylation (Ksu) of fibro-adipogenic progenitors (FAPs), myogenic precursors (Myo) and mesenchymal stem cells (MSCs) with varied differentiation potential, and found that only Khib modification in FAPs was significantly higher than that in MSCs. Consistently, in parallel with its regulatory enzymes lysine acetyltransferase 5 (KAT5) and histone deacetylase 2 (HDAC2) protein levels, the Khib levels increased quadratically (P

BackgroundShoemaking industry workers are prone to work-related musculoskeletal disorders (WMSDs) due to long-term awkward postures during the work process. There is little research on the prevalence and influencing factors of WMSDs in the knee region of this industry, and it should be taken seriously. ObjectiveTo estimate the prevalence of work-related knee pain among shoemaking workers and analyze the related influencing factors. MethodsA total of 6982 shoemaking workers were selected from 26 shoemaking factories in Guangdong, Hubei, Fujian, Chongqing, Shandong, Zhejiang, and Jingxi by convenience sampling. Prevalence of work-related knee pain in past year, demographic characteristics, occupational related factors, and work posture were collected by a cross-sectional survey using the electronic version of Musculoskeletal Disorder Questionnaire. Logistic regression analysis was used to analyze the influencing factors that may lead to work-related knee pain.ResultsThis survey collected 6982 valid questionnaires with a recovery rate of 98.3%. The prevalence of work-related knee pain of shoemaking workers in the past 12 months was 13.0% (908/6982). According to the results of logistic regression analysis, compared with workers with less than 5 years of service, workers with 5-10 years of service (OR=1.21, 95%CI: 1.02, 1.45) and more than 10 years (1.53, 95%CI: 1.27, 1.83) showed a higher risk of knee WMSDs; sometimes, often and very frequent (reference : rarely or never) long-term standing (OR=1.33, 95%CI: 1.08, 1.64; OR=2.67, 95%CI: 2.10, 3.39; OR=2.75, 95%CI: 2.08, 3.63) and sometimes, often and very frequent (reference: rarely or never) long-term squatting or kneeling (OR=1.80, 95%CI: 1.47, 2.21; OR=2.43, 95%CI: 1.58, 3.75; OR=3.22, 95%CI: 1.66, 6.24) increased the risk of knee pain: long-term bending (OR=1.59, 95%CI: 1.34, 1.89) and often repeated movement of lower limbs and ankles (OR=1.48, 95%CI: 1.25, 1.75) were also risk factors for knee WMSDs among shoemaking industry workers (P

Abstract Purpose The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate. Methods We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted. Results A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = − 2.825, 95% CI − 3.343 to − 2.306, P

Abstract Time‐frequency analysis based on Wigner‐Ville distribution (WVD) plays a significant role in analysing non‐stationary signals, but it is susceptible to interference from cross‐terms (CTs) for multi‐component signals. To address this issue, a novel WVD enhancement method based on generative adversarial networks (namely WVD‐GAN) is proposed, to achieve highly‐concentrated time‐frequency (TF) representation. Specifically, a deep feature extraction module is designed with multiple residual connections in the generator of WVD‐GAN to leverage the latent information encoded in the shallow representations. Meanwhile, a simple and effective attention module is introduced to enhance auto‐term features. Moreover, a multi‐scale discriminator is proposed based on dilated convolutions to guide the generator to reconstruct high‐resolution TF images by discriminating CT. Finally, a comparative analysis is provided to demonstrate the effectiveness and robustness of the proposed method on different simulated and real‐life datasets. Extensive experiments demonstrate that the proposed method outperforms several state‐of‐the‐art methods.

Abstract Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.

BackgroundTime-resolved 3D cine phase-contrast cardiovascular magnetic resonance (4D flow CMR) enables the characterization of blood flow using basic and advanced hemodynamic parameters. However, different confounders, e.g., different field strength, scanner configurations, or sequences, might impact 4D flow CMR measurements. This study aimed to analyze the inter-site reproducibility of 4D flow CMR to determine the influence of said confounders.MethodsA cohort of 19 healthy traveling volunteers underwent 4D flow CMR at four different sites (Sites I–III: 3 T scanner; Site IV: 1.5 T scanner; all Siemens Healthineers, Erlangen, Germany). Two protocols of one 4D flow CMR research sequence were performed, one acquiring velocity vector fields in the thoracic aorta only and one in the entire heart and thoracic aorta combined. Basic and advanced hemodynamic parameters, i.e., forward flow volume (FFV), peak and mean velocities (Vp and Vm), and wall shear stress (3D WSS), at nine different planes across the thoracic aorta (P1–P2 ascending aorta, P3–P5 aortic arch, P6–P9 descending aorta) were analyzed. Based on a second scan at Site I, mean values and tolerance ranges (TOL) were generated for inter-site comparison. Equivalency was assumed when confidence intervals of Sites II–IV lay within such TOL. Additionally, inter- and intra-observer analysis as well as a comparison between the two protocols was performed, using an intraclass correlation coefficient (ICC).ResultsInter-site comparability showed equivalency in P1 and P2 for FFV, Vp, and Vm at all sites. Non-equivalency was present in various planes of P3–P9 and in P2 for 3D WSS in one protocol. In total, Site IV showed the most disagreements. Protocol comparison yielded excellent (>0.9) ICC in every plane for FFV, good (0.75–0.9) to excellent ICC for Vm and 3D WSS, good to excellent ICC in eight planes for Vp, and moderate (0.5–0.75) ICC in one plane for Vp. Inter- and intra-observer analysis showed excellent agreement for every parameter.ConclusionsBasic and advanced hemodynamic parameters revealed equivalency at different sites and field strength in the ascending aorta, a clinically important region of interest, under a highly controlled environment.

Stent(s) insertion is a common form of surgery for patients with cardiovascular diseases, and is associated with a high rate of hospital readmission. This study aims to investigate the acute association between PM2.5 exposure and hospital readmission for patients with cardiovascular disease and a history of stent(s) insertion. The records of hospital admission were collected from the Beijing Municipal Commission of Health and Family Planning Information Center between 1st January 2013 and 31st December 2017. Subsequent hospital readmission records for patients with a history of stent(s) insertion or without any surgery were extracted. The conditional logistic regression model was applied to investigate the association between PM2.5 concentration and cardiovascular disease readmission in patients who had undergone stent(s) insertion or without any surgery. A total of 81,468 patients who had a history of stent(s) insertion were included in this study. Of these, 17,224 patients (21.1 % of the total number of patients) were readmitted 27,749 times due to cardiovascular disease. The median daily PM2.5 concentration was 62.8 μg/m3 with an interquartile range (IQR) of 71.5 μg/m3. The excess risk (ER) associated 10 μg/m3 increase in PM2.5 concentration for readmission due to cardiovascular disease was 0.48 % (95 % CI: 0.09 %, 0.87 %) in patients with a history of stent(s) insertion. Patients who had stent(s) insertion at the vessel bifurcation site showed the highest risk of readmission for cardiovascular disease when exposed to PM2.5; the ER was 4.12 % (95 % CI: 1.60 %, 6.70 %). PM2.5 was significantly associated with angina pectoris and readmission for chronic ischemic heart disease in patients with a history of stent(s) insertion. PM2.5 had a significant association with cardiovascular readmission among patients with a history of insertion of stent(s). Patients who had vessel bifurcation treated showed the highest risk of readmission.

Depression and anxiety are serious psychiatric disorders with significant physical and mental health impacts, necessitating the development of safe and effective treatments. This study aimed to evaluate the efficacy of Jiangshi oligosaccharide (JSO), a type of inulin-based oligosaccharide, in alleviating anxiety and depression and to investigate the underlying molecular mechanisms. Using a mouse model of chronic restraint stress (CRS), JSO was administered orally at doses of 50, 100, and 200 mg/kg for 21 days. Behavioral tests, including the novelty-suppressed feeding test (NSFT), open field test (OFT), elevated plus maze test (EPMT), tail suspension test (TST), and forced swimming test (FST), demonstrated that JSO significantly improved anxiety- and depressive-like behaviors (P< 0.05). Notably, JSO reduced feeding latency in the NSFT, increased time spent in the center in the OFT, enhanced time and entries into open arms in the EPMT, and decreased immobility time in the TST and FST (P< 0.01). Histological and molecular analyses revealed that JSO treatment attenuated neuronal loss in the hippocampus (Hip) and medial prefrontal cortex (mPFC) and reduced the expression of inflammatory markers such as Iba-1 and GFAP in these regions. JSO significantly downregulated the mRNA and protein expression of pro-inflammatory factors (IL-1β, TNF-α, IL-6) while increasing anti-inflammatory markers (IL-10, TGF-β) (P< 0.05). Furthermore, JSO inhibited the c-GAS-STING-NLRP3 axis and apoptosis-related proteins (Bax/Bcl-2, Caspase-3/8/9) while promoting the expression of brain-derived neurotrophic factor (BDNF), PSD-95, and synaptophysin (SYP), indicating improved neuronal survival and synaptic plasticity (P< 0.01). These findings suggest that JSO exerts potent anti-anxiety and antidepressant effects by modulating neuroinflammation, synaptic function, and neuronal apoptosis in the Hip and mPFC of CRS mice. This study highlighted JSO as a potential therapeutic agent for stress-induced anxiety and depression.

BackgroundThe efficacy and acupoint selection of acupuncture in treating chemotherapy-induced peripheral neuropathy (CIPN) remain controversial. This study aims to explore the specific efficacy and acupoint selection of acupuncture in treating CIPN through a meta-analysis and data mining.MethodsSearching for clinical trials on acupuncture treatment for CIPN in 8 databases, evaluating its efficacy and safety through a meta-analysis, and exploring its acupoint selection through data mining.ResultsThe meta-analysis included 21 studies and 2,121 patients, showing that compared with the control group, the acupuncture group could significantly improve neuropathic pain intensity (SMD = −0.66, 95% CI [−1.07, −0.25], p = 0.002), significantly reduce the NCI-CTCAE (MD = −0.29, 95%CI [−0.50, −0.08], p