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Abstract Influenza (Flu) is a severe health, medical, and economic problem, but no medication that has excellent outcomes and lowers the occurrence of these problems is now available. GanghuoQingwenGranules (GHQWG) is a common Chinese herbal formula for the treatment of influenza (flu). However, its methods of action remain unknown. We used network pharmacology, molecular docking, and molecular dynamics simulation techniques to investigate the pharmacological mechanism of GHQWG in flu. TCMSP and various types of literature were used to obtain active molecules and targets of GHQWG. Flu-related targets were found in the Online Mendelian Inheritance in Man (OMIM) database, the DisFeNET database, the Therapeutic Target Database (TTD), and the DrugBank database. To screen the key targets, a protein–protein interaction (PPI) network was constructed. DAVID was used to analyze GO and KEGG pathway enrichment. Target tissue and organ distribution was assessed. Molecular docking was used to evaluate interactions between possible targets and active molecules. For the ideal core protein–compound complexes obtained using molecular docking, a molecular dynamics simulation was performed. In total, 90 active molecules and 312 GHQWG targets were discovered. The PPI network's topology highlighted six key targets. GHQWG's effects are mediated via genes involved in inflammation, apoptosis, and oxidative stress, as well as the TNF and IL-17 signaling pathways, according to GO and KEGG pathway enrichment analysis. Molecular docking and molecular dynamics simulations demonstrated that the active compounds and tested targets had strong binding capabilities. This analysis accurately predicts the effective components, possible targets, and pathways involved in GHQWG flu treatment. We proposed a novel study strategy for future studies on the molecular processes of GHQWG in flu treatment. Furthermore, the possible active components provide a dependable source for flu drug screening.

Abstract Background Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. Methods The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. Results In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. Conclusions In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.

Adults with spinal cord injury (SCI), a destructive neurological injury, have a significantly higher incidence of osteoarthritis (OA), a highly prevalent chronic joint disorder. This study aimed to dissect the neuroimmune-related regulatory mechanisms of SCI and OA using bioinformatics analysis. Using microarray data from the Gene Expression Omnibus database, differentially expressed genes (DEGs) were screened between SCI and sham samples and between OA and control samples. Common DEGs were used to construct a protein-protein interaction (PPI) network. Weighted gene co-expression network analysis (WGCNA) was used to mine SCI- and OA-related modules. Shared miRNAs were identified, and target genes were predicted using the Human MicroRNA Disease Database (HMDD) database. A miRNA-gene-pathway regulatory network was constructed with overlapping genes, miRNAs, and significantly enriched pathways. Finally, the expression of the identified genes and miRNAs was verified using RT-qPCR. In both the SCI and OA groups, 185 common DEGs were identified, and three hub clusters were obtained from the PPI network. WGCNA revealed three SCI-related modules and two OA-related modules. There were 43 overlapping genes between the PPI network clusters and the WGCNA network modules. Seventeen miRNAs shared between patients with SCI and OA were identified. A regulatory network consisting of five genes, six miRNAs, and six signaling pathways was constructed. Upregulation of CD44, TGFBR1, CCR5, and IGF1, while lower levels of miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p in both SCI and OA were successfully verified using RT-qPCR. Our study suggests that a miRNA-gene-pathway network is implicated in the neuroimmune-related regulatory mechanisms of SCI and OA. CD44, TGFBR1, CCR5, and IGF1, and their related miRNAs (miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p) may serve as promising biomarkers and candidate therapeutic targets for SCI and OA.

Background and ObjectivePost-translational modifications of antibodies, with a specific focus on galactosylation, have garnered increasing attention in the context of understanding the pathogenesis and therapeutic implications of autoimmune diseases. However, the comprehensive scope and the clinical significance of antibody galactosylation in the context of Neuromyelitis Optica Spectrum Disorder (NMOSD) remain enigmatic.The primary aim of this research was to discern disparities in serum IgG galactosylation levels between individuals in the acute stage of NMOSD relapse and their age- and sex-matched healthy counterparts.MethodsA total of fourteen untreated NMOSD patients experiencing an acute relapse phase, along with thirteen patients under medication, were enrolled, and an additional twelve healthy controls of the same age and gender were recruited for this investigation. Western blot and lectin enzyme techniques were used to determine the level of IgG galactosylation in the serum samples from these subjects. The expression of CD45+, CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD16+CD56+ in peripheral blood leukocytes was measured by flow cytometry. The enzyme-linked immunosorbent assay (ELISA) was also used to quantify the amounts of IgG. Magnetic particle luminescence assays are used to detect cytokines. Robust statistical analysis was executed to ascertain the potential associations between IgG galactosylation and the aforementioned immune indices.ResultsIn the context of NMOSD relapses, serum IgG galactosylation exhibited a notable decrease in untreated patients (0.2482 ± 0.0261), while it remained comparatively stable in medicated patients when contrasted with healthy controls (0.3625 ± 0.0259) (p=0.0159). Furthermore, a noteworthy inverse correlation between serum IgG galactosylation levels and the Expanded Disability Status Scale (EDSS) score during NMOSD relapse was observed (r=-0.4142; p=0.0317). Notably, IgG galactosylation displayed an inverse correlation with NMOSD relapse among peripheral blood CD45+, CD3+, CD3+CD8+, CD19+ cells, as well as with IL-6 and IL-8. Nevertheless, it was not determined whether IgG galactosylation and CD3+CD4+ T cells or other cytokines are statistically significantly correlated.ConclusionOur research identified reduced IgG galactosylation in the serum of NMOSD patients during relapses, significantly correlated with disease severity, thereby providing a novel target for the diagnosis and treatment of NMOSD in the realm of medical research.

Crosstalk between nerves and bone is essential for bone repair, for which Schwann cells (SCs) are crucial in the regulation of the microenvironment. Considering that exosomes are critical paracrine mediators for intercellular communication that exert important effects in tissue repair, the aim of this study is to confirm the function and molecular mechanisms of Schwann cell-derived exosomes (SC-exos) on bone regeneration and to propose engineered constructs that simulate SC-mediated nerve–bone crosstalk. SCs promoted the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) through exosomes. Subsequent molecular mechanism studies demonstrated that SC-exos promoted BMSC osteogenesis by regulating the TGF-β signaling pathway via let-7c-5p. Interestingly, SC-exos promoted the migration and tube formation performance of endothelial progenitor cells. Furthermore, the SC-exos@G/S constructs were developed by bioprinting technology that simulated SC-mediated nerve–bone crosstalk and improved the bone regeneration microenvironment by releasing SC-exos, exerting the regulatory effect of SCs in the microenvironment to promote innervation, vascularization, and osteogenesis and thus effectively improving bone repair in a cranial defect model. This study demonstrates the important role and underlying mechanism of SCs in regulating bone regeneration through SC-exos and provides a new engineered strategy for bone repair.

Flatfoot is a common foot deformity, causing foot pain, osteoarthritis of the midfoot, and even knee and hip dysfunction. The elastic modulus of foot soft tissues and its association with gait biomechanics still remain unclear. For this study, we recruited 20 young individuals with flatfoot and 22 age-matched individuals with normal foot arches. The elastic modulus of foot soft tissues (posterior tibial tendon, flexor digitorum brevis, plantar fascia, heel fat pad) was obtained via ultrasound elastography. Gait data were acquired using an optical motion capture system. The association between elastic modulus and gait data was analyzed via correlation analysis. The elastic modulus of the plantar fascia (PF) in individuals with flatfoot was higher than that in individuals with normal foot arches. There was no significant difference in the elastic modulus of the posterior tibial tendon (PTT), the flexor digitorum brevis (FDB), or the heel fat pad (HFD), or the thickness of the PF, PTT, FDB, and HFD. Individuals with flatfoot showed greater motion of the hip and pelvis in the coronal plane, longer double-support phase time, and greater maximum hip adduction moment during walking. The elastic modulus of the PF in individuals with flatfoot was positively correlated with the maximum hip extension angle (r = 0.352, p = 0.033) and the maximum hip adduction moment (r = 0.429, p = 0.039). The plantar fascia is an important plantar structure in flatfoot. The alteration of the plantar fascia’s elastic modulus is likely a significant contributing factor to gait abnormalities in people with flatfoot. More attention should be given to the plantar fascia in the young population with flatfoot.

BackgroundParvimonas micra (P. micra), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for P. micra-related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to P. micra exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to P. micra, drawing insights from an extensive literature review of pertinent case reports.Case presentationA 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient’s symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to P. micra. Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where P. micra was identified as the causative agent.ConclusionThe literature analysis underscores the predilection of P. micra for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with P. micra infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, β-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of P. micra-associated infections.

Oxidative stress (OS) is regarded as the dominant theory for aging. While compelling correlative data have been generated to support the OS theory, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and aging has not been firmly established. Superoxide dismutase 1 (SOD1) is a primary antioxidant in all cells. It is, however, susceptible to oxidation due to OS and gains toxic properties to cells. This study investigates the role of oxidized SOD1 derived from amyotrophic lateral sclerosis (ALS) linked SOD1 mutations in cell senescence and aging. Herein, we have shown that the cell line NSC34 expressing the G93A mutation of human SOD1 (hSOD1G93A) entered premature senescence as evidenced by a decreased number of the 5-ethynyl-2′-deoxyuridine (EdU)-positive cells. There was an upregulation of cellular senescence markers compared to cells expressing the wild-type human SOD1 (hSOD1WT). Transgenic mice carrying the hSOD1G93A gene showed aging phenotypes at an early age (135 days) with high levels of P53 and P16 but low levels of SIRT1 and SIRT6 compared with age-matched hSOD1WT transgenic mice. Notably, the levels of oxidized SOD1 were significantly elevated in both the senescent NSC34 cells and 135-day hSOD1G93A mice. Selective removal of oxidized SOD1 by our CT4-directed autophagy significantly decelerated aging, indicating that oxidized SOD1 is a causal factor of aging. Intriguingly, mitochondria malfunctioned in both senescent NSC34 cells and middle-aged hSODG93A transgenic mice. They exhibited increased production of mitochondrial-derived vesicles (MDVs) in response to mild OS in mutant human SOD1 (hSOD1) transgenic mice at a younger age; however, the mitochondrial response gradually declined with aging. In conclusion, our data show that oxidized SOD1 derived from ALS-linked SOD1 mutants is a causal factor for cellular senescence and aging. Compromised mitochondrial responsiveness to OS may serve as an indicator of premature aging.

Tower cranes play a crucial role in the construction industry, facilitating the vertical and horizontal movement of materials and aiding in building construction, especially for high-rise structures. However, tower crane accidents can lead to severe consequences, highlighting the importance of effective safety management and inspection. This paper presents a novel approach to tower crane safety inspections using Unmanned Aerial Vehicles (UAVs) equipped with high-definition cameras and an intelligent inspection APP system. The system utilizes real-time kinematic (RTK) positioning and digital image processing to perform efficient and comprehensive inspections, reducing the reliance on manual labor and associated risks. A case study demonstrated the method’s practicality and effectiveness, with the UAV inspections capable of identifying 76.3% of major hazards, 64.8% of significant hazards, and 76.2% of general hazards within a 30-minute timeframe. Preliminary identification rates were also promising. Despite the initial requirement for manual drone piloting and the current manual review of images, the approach shows significant potential for enhancing safety in the construction industry. Future work will focus on integrating AI for hazard recognition and automating the inspection process further. The proposed method marks a step forward in tower crane safety management, offering a more efficient and accurate alternative to traditional inspection methods.

Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL−1β) along with verapamil at a concentration of 5 μM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 μM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL−1β. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.

BackgroundThere is increasing evidence pointing to a close relationship between sarcopenia and inflammatory bowel disease. However, it remains unclear whether or in which direction causal relationships exist, because these associations could be confounded.MethodsWe conducted a two-sample bidirectional mendelian randomization analysis using data from European genome-wide association studies of the appendicular lean mass(n = 450,243), walking pace(n = 459,915), grip strength (left hand, n = 461,026; right hand, n = 461,089), inflammatory bowel disease (25,042 patients and 34,915 controls), ulcerative colitis (12,366 patients and 33,609 controls), and Crohn’s disease (12,194 patients and 28,072 controls) to investigate the causal relationship between sarcopenia-related traits and inflammatory bowel disease and its subtypes on each other. The inverse-variance weighted method was used as the primary analysis method to assess the causality, and a comprehensive sensitivity test was conducted.ResultsGenetically predicted appendicular lean mass was significantly associated with inflammatory bowel disease (OR = 0.916, 95%CI: 0.853–0.984, P = 0.017), ulcerative colitis (OR =0.888, 95%CI: 0.813–0.971, P = 0.009), and Crohn’s disease (OR = 0.905, 95%CI: 0.820–0.999, P = 0.049). Similar results also revealed that the usual walking pace was causally associated with Crohn’s disease (OR = 0.467, 95%CI: 0.239–0.914, P = 0.026). Reverse mendelian randomization analysis results found that genetic susceptibility to inflammatory bowel disease, and Crohn’s disease were associated with lower appendicular lean mass. A series of sensitivity analyses ensured the reliability of the present research results.ConclusionThe mendelian randomization study supports a bidirectional causality between inflammatory bowel disease, Crohn’s disease and appendicular lean mass, but no such bidirectional causal relationship was found in ulcerative colitis. In addition, genetically predicted usual walking pace may reduce the risk of Crohn’s disease. These findings have clinical implications for sarcopenia and inflammatory bowel disease management.

Abstract Predicting future land system changes driven by anthropogenic and climactic impacts can help to explore adaptation and mitigation pathways for regional and global sustainable development. Here, we project land cover changes in China from 2030 to 2100 at a resolution of 1 km × 1 km under eight scenarios based on the Scenario Model Intercomparison Project (ScenraioMIP), which are extracted from Land Use Harmonization version 2 (LUH2). We use a rule‐based method to classify and map 9 land cover dynamic trajectories at patch scale to present land system changes. At the provincial scale we used hierarchical clustering to identify archetypes of land cover change, which can predict ecological risks for future management in western provinces. Our results reveal that anthropogenic mitigation policies under high mitigation pressure do not result in positive impacts on the land system, but rising temperatures will provide a great opportunity for ecological restoration in some regions.

Objective Carpal tunnel syndrome (CTS) is the most common peripheral entrapment neuropathy, and endoscopic carpal tunnel release (ECTR) is one of the minimally invasive procedures for the treatment of CTS. Based on the shortcomings of ECTR, we designed the “Modified Soft Tissue Release Kit” to assist the endoscopic operation. This study aimed to evaluate the effectiveness and safety of endoscopic treatment of CTS using this kit. Methods This retrospective review included 57 patients (86 wrists) who underwent ECTR using the “Modified Soft Tissue Release Kit” at our department between January 2017 and August 2019. Three scale scores (i.e., Quick–Disabilities of the Arm, Shoulder, and Hand [QDASH]; Boston Carpal Tunnel Syndrome Questionnaire [BCTSQ]: symptom severity [BCTSQ‐SS] and functional status [BCTSQ‐FS]) were recorded to assess hand function and symptoms preoperatively, 1 month postoperatively, 3 months postoperatively, and at the last follow‐up. We also asked patients to answer a satisfaction question during follow‐up. Pre‐ and post‐operation scores were compared using paired Wilcoxon signed‐rank test. Spearman's rank‐order correlation was used to evaluate the relationship between scale scores and patient satisfaction. Results A total of 55 patients (83 wrists) were followed up, with an average follow‐up of 27.2 ± 9.3 months. The median preoperative QDASH score was 45.5; the scores at 1 month postoperatively, 3 months postoperatively, and the last follow‐up were 4.5, 0, and 0, respectively, with a significant decrease noted compared with the preoperative scores (P

Objective Hallux valgus (HV) is a common foot deformity, and recurrence is one of the most serious complications after HV correction. As a result, the surgical technique with a lower recurrence rate is a dream. The purpose of the article should be to observe the correction effect of hallux valgus using a novel “V‐cut” osteotomy on the first metatarsal head combined with fixation in mortise‐shaped bone groove‐plasty technique. Methods Twenty‐three consecutive patients (40 feet) with HV were included from March 2019 to May 2020, who were all treated using single screw fixation with V‐cut osteotomy on the first metatarsal head combined with mortise‐shaped metatarsal bone groove‐plasty and Akin osteotomy on the first toe for hallux valgus correction. With a mean follow‐up time of 21.7 months, the visual analogue scale (VAS) score and American Orthopedic Foot and Ankle Society (AOFAS) forefoot score and the changes of the hallux valgus angle (HVA), intermetatarsal angle (IMA) and distal metatarsal articular angle (DMAA) were evaluated during the clinical follow‐up. The paired t test was used for analytical statistics. Results The VAS score improved from 6.78 ± 1.74 to 1.87 ± 1.45 and the AOFAS score improved from 53.9 ± 12.3 preoperatively to 94.7 ± 6.8 in the latest follow‐up postoperatively (P

BackgroundCoronavirus disease 2019 (COVID‐19) is a highly contagious respiratory disease that has posed a serious threat to people’s daily lives and caused an unprecedented challenge to public health and people’s health worldwide. Lung squamous cell carcinoma (LUSC) is a common type of lung malignancy with a highly aggressive nature and poor prognosis. Patients with LUSC could be at risk for COVID-19, We conducted this study to examine the potential for naringenin to develop into an ideal medicine and investigate the underlying action mechanisms of naringenin in COVID-19 and LUSC due to the anti-viral, anti-tumor, and anti-inflammatory activities of naringenin.MethodsLUSC related genes were obtained from TCGA, PharmGKB, TTD,GeneCards and NCBI, and then the transcriptome data for COVID-19 was downloaded from GEO, DisGeNET, CTD, DrugBank, PubChem, TTD, NCBI Gene, OMIM. The drug targets of Naringenin were revealed through CTD, BATMAN, TCMIP, SymMap, Chemical Association Networks, SwissTargetPrediction, PharmMapper, ECTM, and DGIdb. The genes related to susceptibility to COVID-19 in LUSC patients were obtained through differential analysis. The interaction of COVID-19/LUSC related genes was evaluated and demonstrated using STRING to develop a a COX risk regression model to screen and evaluate the association of genes with clinical characteristics. To investigate the related functional and pathway analysis of the common targets of COVID-19/LUSC and Naringenin, KEGG and GO enrichment analysis were employed to perform the functional analysis of the target genes. Finally, The Hub Gene was screened and visualized using Cytoscape, and molecular docking between the drug and the target was performed using Autodock.ResultsWe discovered numerous COVID-19/LUSC target genes and examined their prognostic value in LUSC patients utilizing a variety of bioinformatics and network pharmacology methods. Furthermore, a risk score model with strong predictive performance was developed based on these target genes to assess the prognosis of LUSC patients with COVID-19. We intersected the therapeutic target genes of naringenin with the LUSC, COVID-19-related targets, and identified 354 common targets, which could be used as potential target genes for naringenin to treat COVID-19/LUSC. The treatment of COVID-19/LUSC with naringenin may involve oxidative stress, anti-inflammatory, antiviral, antiviral, apoptosis, immunological, and multiple pathways containing PI3K-Akt, HIF-1, and VEGF, according to the results of the GO and KEGG enrichment analysis of these 354 common targets. By constructing a PPI network, we ascertained AKT1, TP53, SRC, MAPK1, MAPK3, and HSP90AA1 as possible hub targets of naringenin for the treatment of COVID-19/LUSC. Last but not least, molecular docking investigations showed that naringenin has strong binding activity in COVID-19/LUSC.ConclusionWe revealed for the first time the pharmacological targets and potential molecular processes of naringenin for the treatment of COVID-19/LUSC. However, these results need to be confirmed by additional research and validation in real LUSC patients with COVID-19.

Tendinopathy is a common disease in orthopaedics, seriously affecting tendon functions. However, the effects of non-surgical treatment on tendinopathy are not satisfactory and surgical treatments possibly impair the function of tendons. Biomaterial fullerenol has been proved to show good anti-inflammatory effects on various inflammatory diseases. For in vitro experiments, primary rat tendon cells (TCs) were treated by interleukin-1 beta (IL-1β) combined with aqueous fullerenol (5, 1, 0.3 μg/mL). Then inflammatory factors, tendon-related markers, migration and signaling pathways were detected. For in vivo experiments, rat tendinopathy model was constructed by local injection of collagenase into Achilles tendons of rats and fullerenol (0.5, 1 mg/mL) was locally injected 7 days after collagenase injection. Inflammatory factors and tendon-related markers were also investigated. Fullerenol with good water-solubility showed excellent biocompatibility with TCs. Fullerenol could increase expression of tendon-related factors (Collagen I and tenascin C) and decrease expression of inflammatory factors (matrix metalloproteinases-3, MMP-3, and MMP-13) and reactive oxygen species (ROS) level. Simultaneously, fullerenol slowed the migration of TCs and inhibited activation of Mitogen-activated protein kinase (MAPK) signaling pathway. Fullerenol also attenuated tendinopathy in vivo, including reduction of fiber disorders, decrease of inflammatory factors and increase of tendon markers. In summary, fullerenol is a promising biomaterial that can be used to treat tendinopathy.

Accurate inventories of grasslands are important for studies of greenhouse gas (GHG) dynamics, as grasslands store about one-third of the global terrestrial carbon stocks. This paper develops a framework for large-area grassland mapping based on the probability of grassland occurrence and the interactive pathways of fractional vegetation and soil-related endmember nexuses. In this study, grassland occurrence probability maps were produced based on data on bio-climate factors obtained from MODIS/Terra Land Surface Temperature (MOD11A2), MODIS/Terra Vegetation Indices (MOD13A3), and Tropical Rainfall Measuring Mission (TRMM 3B43) using the random forests (RF) method. Time series of 8-day fractional vegetation-related endmembers (green vegetation, non-photosynthetic vegetation, sand land, saline land, and dark surfaces) were generated using linear spectral mixture analysis (LSMA) based on MODIS/Terra Surface Reflectance data (MOD09A1). Time-series endmember fraction maps and grassland occurrence probabilities were employed to map grassland distribution using an RF model. This approach improved the accuracy by 5% compared to using endmember fractions alone. Additionally, based on the grassland occurrence probability maps, we identified extensive ecologically sensitive regions, encompassing 1.54 (104 km2) of desert-to-steppe (D-S) and 2.34 (104 km2) of steppe-to-meadow (S-M) transition regions. Among these, the D-S area is located near the threshold of 310 mm/yr in precipitation, an annual temperature of 10.16 °C, and a surface comprehensive drought index (TVPDI) of 0.59. The S-M area is situated close to the line of 437 mm/yr in precipitation, an annual temperature of 5.49 °C, and a TVPDI of 0.83.

Rope-driven robots are increasingly being applied for the efficiently cleaning of glass curtain walls. However, increasingly complex wall surfaces and the various shapes of obstacles may block the robot and reduce coverage. In this study, three-DOF rope-driven cleaning robots and a full-coverage path-planning algorithm were developed to achieve global operation. The robot adopts a five-rope parallel configuration, and four winches are mounted on the wall and one on the ground to produce 3D motion performance. We used a grid method to build the wall model to mark obstacles, and then we decomposed it according to the wall curvature to better access cleaning subareas. To further increase the cleaning coverage rate, a full-coverage path-planning algorithm based on an improved priority heuristic was designed, which does not ignore the inset area of U-shaped obstacles. By introducing two sets of priority criteria to judge the forward direction, the robot can switch directions to cover a whole area when encountering U-shaped obstacles. Furthermore, by planning a return route requiring the least amount of time when entering a dead zone, an escape strategy was developed to prevent the robot from being unable to choose a direction. The experimental results show that the robot, after applying the proposed path-planning algorithm, could complete the global cleaning of complex glass walls with various obstacles.

Background and Objectives: This study aimed to evaluate the effectiveness and safety of endoscopic gastrocnemius recession using the self-developed Modified Soft Tissue Release Kit. Materials and Methods: This retrospective review followed up 22 patients (34 feet) who underwent endoscopic surgery and 20 patients (30 feet) who received open surgery between January 2020 and January 2022. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the maximum ankle dorsiflexion angle were evaluated preoperatively and at the last follow-up. Postoperative complications were recorded. Patient satisfaction was surveyed at the last follow-up. The comparison between quantitative data was analyzed with the Wilcoxon signed-rank test. The comparison between qualitative data was analyzed with the chi-square test. Results: There was no significant difference in the baseline characteristics between the two groups. The AOFAS score in the endoscopic group increased from 50 (18) points preoperatively to 90 (13) points at the last follow-up; the maximum ankle dorsiflexion angle increased from −7.7 (2.8) degrees to 10.6 (3.6) degrees. The AOFAS score in the open group improved from 47 (15) points preoperatively to 90 (18) points at the last follow-up; the maximum ankle dorsiflexion angle increased from −7.6 (4.0) degrees to 10.7 (3.3) degrees. The change values of the AOFAS scores in the endoscopic and open groups were 39 (15) and 40.5 (11) points, respectively, and there was no significant difference between them. The change values of the maximum ankle dorsiflexion angles in the endoscopic and open groups were 19.5 (4.3) and 19.1 (4.9) degrees, respectively, and there was no significant difference between them. There were no complications, such as sural nerve injury, in both groups. There was no significant difference between the two groups in satisfaction with the surgical outcome. Conclusions: Endoscopic gastrocnemius recession using the Modified Soft Tissue Release Kit can significantly improve the foot function with significant mid-term efficacy and high safety.

Abstract Background Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC. Methods The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p 0.3 and p

Abstract The Middle Permian Lucaogou Formation in the Jimusar Sag, eastern Junggar Basin, NW China, was deposited in a salt lake within an intracontinental rift basin with intense hydrothermal activity. Hydrothermal-sedimentary dolomite in the form of three types of dolostones, namely, analcime-feldspar dolostone (AFD), silicic dolostone (SD) and buddingtonite-albite dolostone (BAD), related to syn-sedimentary hydrothermal activity at lake bottom was discovered. The characteristics and formation mechanism of the dolomite were studied based on micron-scale petrographic and isotopic geochemical research. The syn-depositional formation of these dolostones was indicated by their rock-mineral features and syn-sedimentary deformation stage. The dolomite was composed of relatively poorly ordered proto-dolomite crystals with micron-sized spherical or sub-spherical morphology and coexisted with hydrothermal minerals, including analcime, buddingtonite, albite and chalcedony. Albite clasts were replaced by the dolomite, indicating high-temperature conditions during formation. The remarkably low strontium isotopic compositions of the dolostones (87Sr/86Sr with an average of 0.705687) indicated that mantle-derived materials might have involved in the ore-forming fluid. The dolostones had positive δ13CPDB values (with an average of 6.94‰) and negative δ18OPDB values (with an average of − 8.12‰). Based on the δ18OPDB values, the formation temperatures of the dolomite were at least ~ 25 °C higher than those of the penecontemporaneous dolomite in the Lucaogou Formation in the study area. It is concluded that the dolomite precipitated from hydrothermal fluid erupting at the lake bottom. The possible genetic models are described. We suggest that the hydrothermal-sedimentary dolomite is an important genetic type, and this study may help increase the awareness of this understudied type of dolomite.

Soil organic matter (SOM) plays pivotal roles in characterizing dryland structure and function; however, remotely sensed spatially-detailed SOM mapping in these regions remains a challenge. Various digital soil mapping approaches based on either single-period remote sensing or spectral indices in other ecosystems usually produce inaccurate, poorly constrained estimates of dryland SOM. Here, a framework for spatially-detailed SOM mapping was proposed based on cross-wavelet transform (XWT) that exploits ecologically meaningful features from intra-annual fractional vegetation and soil-related endmember records. In this framework, paired green vegetation (GV) and soil-related endmembers (i.e., dark surface (DA), saline land (SA), sand land (SL)) sequences were adopted to extract 30 XWT features in temporally and spatially continuous domains of cross-wavelet spectrum. We then selected representative features as exploratory covariates for SOM mapping, integrated with four state-of-the-art machine learning approaches, i.e., ridge regression (RR), least squares-support vector machines (LS-SVM), random forests (RF), and gradient boosted regression trees (GBRT). The results reported that SOM maps from 13 coupled filtered XWT features and four machine learning approaches were consistent with soil-landscape knowledge, as evidenced by a spatially-detailed gradient from oasis to barren. This framework also presented more accurate and reliable results than arithmetically averaged features of intra-annual endmembers and existing datasets. Among the four approaches, both RF and GBRT were more appropriate in the XWT-based framework, showing superior accuracy, robustness, and lower uncertainty. The XWT synthetically characterized soil fertility from the consecutive structure of intra-annual vegetation and soil-related endmember sequences. Therefore, the proposed framework improved the understanding of SOM and land degradation neutrality, potentially leading to more sustainable management of dryland systems.

Fuel consumptions are measured by operating passenger car and tractor-trailer on two interstate roadway sites in Florida. Each site contains flexible pavement and rigid pavement with similar pavement, traffic and environmental condition. Field test reveals that the average fuel consumption differences between vehicle operating on flexible pavement and rigid pavement at given test condition are 4.04% for tractor-trailer and 2.50% for passenger car, with a fuel saving on rigid pavement. The fuel consumption differences are found statistically significant at 95% confidence level for both vehicle types. Test data are then used to calibrate the Highway Development and Management IV (HDM-4) fuel consumption model and model coefficients are obtained for three sets of observations. Field measurement and prediction by calibrated model shows generally good agreement. Nevertheless, verification and adjustment with more experiment or data sources would be expected in future studies.

Circadian rhythms are essential in a myriad of physiological processes to maintain homeostasis, especially the redox homeostasis. However, little is known about whether plasma H2S exhibits the physiological diurnal variation. The present study was performed to investigate the diurnal fluctuations of plasma H2S and explore the potential mechanisms. We found that the plasma H2S of the C57BL/6J mice was significantly higher at 19 o’clock than those at 7 o’clock which was not affected by the blood-collecting sequence and the concentrations of plasma cysteine (a precursor of H2S). No significant differences in mRNA or protein expression of the CSE, CBS, or MPST were observed between 7: 00 and 19: 00. There were also no significant differences in the CSE and CBS activities, while the activities of MPST in tissues were significantly higher at 19 o’clock. After treatment with AOAA (a CBS inhibitor) or PPG (a CSE inhibitor) for 14 days, plasma H2S concentrations at 19 o’clock were still significantly higher than those at 7 o’clock, although they were both significantly decreased as compared with controls. Identical findings were also observed in CSE KO mice. We also found the plasma H2O2 concentrations were significantly higher at 19 o’clock than those at 7 o’clock. However, H2O2 concentrations were significantly decreased at 19 o’clock than those at 7 o’clock when mice were exposed to continuous light for 24 h. Meanwhile, the diurnal fluctuations of plasma H2S levels and MPST activities in tissues were disappeared. After treatment with DTT for 14 days, there was no significant difference in plasma H2O2 concentrations between 7 o’clock and 19 o’clock. Meanwhile, the diurnal fluctuations of plasma H2S levels and MPST activities in tissues were disappeared. Identical findings were also observed in SOD2+/- mice. When heart tissues were incubated with increasing concentrations of H2O2in vitro, H2O2 could dose-dependently increase the activity of MPST within a certain concentration range. In conclusion, our studies revealed that plasma H2S concentration and tissue MPST activity exhibited diurnal fluctuations. Modulated by plasma H2O2 concentration, changes of MPST activity probably led to the diurnal fluctuations of plasma H2S.

Field experiments are performed in which Fuel Consumptions (FCs) are measured by operating passenger car over thirteen one-mile roadway sections at two highway speeds in Florida. The sections are composed of 6 flexible pavement sections and seven rigid pavement sections with varied pavement surface conditions and testing temperature. The first objective is to capture the fuel differences between flexible pavement and rigid pavement considering the effect of pavement roughness and pavement temperature. By ANalysis of COVAriance (ANCOVA), results show less fuel is consumed on rigid pavement opposed to flexible pavement by 2.25% at 93 km/h and 2.22% at 112 km/h. Fuel differences are found statistically significant at 95% Confidence Level (C.L.). Fuel savings on rigid pavement exhibits good agreement with authors’ Phase I direct comparison field study. Furthermore, fuel data from flexible pavement is applied to calibrate the Highway Development and Management IV (HDM-4) FC model in order to detect and quantify the impact of pavement deflection on FC. Calibrated models are evaluated and validated with experiment data. By results, the deflection-indhuced fuel effect is disclosed by the positive deflection adjustment coefficient generated from the calibration. It is also found that an increase of 0.1mm in pavement deflection at 25 °C (pavement temperature) would increase the FC by 1.53% at 93 km/h and 1.46% at 112 km/h. Results demonstrate good agreement with other findings.

Background and objective Epidermal growth factor receptor (EGFR) is closely correlated with the progression of lung cancer. Its activity is modulated by Casitas B-lineage lymphoma (Cbl) family. The aim of this study is to investigate the expression and clinical relevance of c-Cbl, Cbl-b and EGFR in non-small cell lung cancer (NSCLC). Methods Expressions of c-Cbl, Cbl-b and EGFR protein were detected with tissue microarrays and immunohistochemistry technique in 94 cases of NSCLC. The correlations between the expression of the three proteins and clinicopathological parameters were analyzed. Results The positive expression rates of EGFR, c-Cbl and Cbl-b were 60.6% (57/94), 30.9% (29/94) and 84.0% (79/94), respectively. The expression of EGFR, c-Cbl and Cbl-b was not associated with age, pathological type, TNM stage, lymph node metastasis, and smoking history. c-Cbl and Cbl-b status was not significantly correlated with overall survival. Subgroup analyses showed that c-Cbl-positive patients had longer survival than c-Cbl-negative patients in EGFR-positive group (P=0.014). Conclusion Detection of c-Cbl protein levels might contribute to the prognosis evaluation of EGFR-positive NSCLC.

This article proposes a novel adaptive switching control of hypersonic aircraft based on type-2 Takagi–Sugeno–Kang fuzzy sliding mode control and focuses on the problem of stability and smoothness in the switching process. This method uses full-state feedback to linearize the nonlinear model of hypersonic aircraft. Combining the interval type-2 Takagi–Sugeno–Kang fuzzy approach with sliding mode control keeps the adaptive switching process stable and smooth. For rapid stabilization of the system, the adaptive laws use a direct constructive Lyapunov analysis together with an established type-2 Takagi–Sugeno–Kang fuzzy logic system. Simulation results indicate that the proposed control scheme can maintain the stability and smoothness of switching process for the hypersonic aircraft.