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Highlights 1. This is the first report identifying SCUBE1 and RNF103-CHMP3 as therapeutic targets for diabetic foot ulcers (DFU). 2. Our study found that SCUBE1 and RNF103-CHMP3 were significantly downregulated in patients who were cured of DFU. 3. This study discovered that SCUBE1 and RNF103-CHMP3 are associated with extracellular interactions. 4. Our findings indicate that SCUBE1 and RNF103-CHMP3 are related to immune cell infiltration. 5. This study provides new theoretical foundations and molecular targets for the diagnosis and treatment of DFU.

Abstract Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer’s disease (AD) patients show potential as biomarkers for brain degeneration. To investigate AD-specific PLR and its underlying neuromodulatory sources, we combine high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( $${P}_{c}$$ P c ) and post-illumination pupil dilation recovery (amplitude, $${P}_{d}$$ P d , and time, T). The $${P}_{c}$$ P c -driven differential analysis reveals altered visual signal processing and reduced thalamocortical activation in AD mice in comparison with wild-type (WT) control mice. In contrast, the post-illumination pupil dilation recovery-based fMRI highlights multiple brain areas associated with AD brain degeneration, including the cingulate cortex, hippocampus, septal area of the basal forebrain, medial raphe nucleus, and pontine reticular nuclei (PRN). Additionally, the brain-wide functional connectivity analysis highlights the most significant changes in PRN of AD mice, which serves as the major subcortical relay nuclei underlying oculomotor function. This work integrates non-invasive pupil-fMRI measurements in preclinical models to identify pupillary biomarkers based on brain-wide functional changes, including neuromodulatory dysfunction coupled with AD brain degeneration.

Laser welding process involves three-dimensional (3D) highly dynamic spatial thermal cycling that results in intricate microstructure evolution in different zones. Understanding of the 3D topological evolution of microstructure under spatial thermal cycling is crucial for effective control in solidification processes. In this paper, a 3D multiphase-field model combined with accelerated methods and multi-scale coupling algorithms was developed for high-precision prediction of the dynamic microstructure evolution in laser welding. The heat flow distribution during laser welding varied significantly, with the cooling rates of 1.7–1.9 × 104 K/s at the middle region and 7.5–9.0 × 104 K/s at the bottom region. Considering the effects of 3D heat flow, a large angle may appear between the grains' primary growth direction and the cross-sectional plane, thereby the ultimate morphology through 2D analysis may lead to distortion from reality. The simulation of 3D microstructure evolution during distinct regions results showed that the grains at the bottom region exhibited larger characteristic dimensions (Length/Height >2.5, Length/Width >2.0) and columnar shape, while the middle region tended to form equiaxed structures. The grain size statistics revealed that the grains in the middle region exhibited larger scale due to their smaller GR (G: temperature gradient, R: growth rate) values. The simulation results were in good agreement with the electro-back-scattered diffraction testing results and the theoretical analysis.

Abstract Toxoplasma gondii is a significant zoonotic pathogen of toxoplasmosis in humans and animals. Here a live attenuated Toxoplasma vaccine of WH3 Δrop18 was developed. The results showed that all mice vaccinated with WH3 Δrop18 were able to survive when challenge with various strains of Toxoplasma, including RH (type I), ME49 (type II), WH3 or WH6 (type Chinese 1). No cysts, if few, in the brain of the vaccinated animals were seen after challenge with cyst forming strains of ME49 or WH6. Vaccination with the WH3 Δrop18 triggered a strong immune response, including significantly increased level of the cytokines (IFN-γ, IL-12, TNF-α and IL-10) and the activation of CD4+ and CD8+ T-lymphocytes and long term of specific antibodies against Toxoplasma. Our results strongly indicate that vaccine of WH3 Δrop18 might provide effective immune protection against a wide range strains of Toxoplasma infections and be a promising live attenuated vaccine candidate.

Abstract TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet’s disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide, with high incidence and poor survival rates. RBP1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the relationship between RBP1 and HNSCC were analyzed based on The Cancer Genome Atlas (TCGA) database. Materials and methods RBP1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. Tumor tissue and adjacent normal tissue of 6 HNSCC patients were collected to analyze the RBP1 mRNA expression level by quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of RBP1 and clinical data in HNSCC. A nomogram was also established to predict the impact of RBP1 on prognosis based on Cox multivariate results. The methylation level of RBP1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of RBP1 were investigated using gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA). Results The mRNA expression levels of RBP1 were highly expressed in HNSCC tissue. The Cox analyses demonstrate that highly-expressed RBP1 is an independent prognosis marker(P

Abstract Background Cytomegalovirus (CMV) is the most common congenital infection in pregnancy with potential long-term adverse effects on the fetus. There is limited data on CMV seroprevalence in pregnant women in Singapore, with last reported study dating back over two decades. We look at the latest CMV seroprevalence in antenatal population in Singapore. Methods Between January 2021 and August 2021, 385 pregnant women receiving antenatal care at Singapore General Hospital were randomly selected for CMV IgG test to be performed on their blood samples collected during the first trimester of their pregnancies. Positivity for CMV IgG represents past exposure prior to pregnancy. Results Overall CMV seroprevalence was 71.7% (276/385) (95% CI 067, 0.76, p value

Abstract Mental health is deteriorating far and fast globally post-COVID. Though there were already over one billion people living with mental disorders pre-pandemic, in the first year of COVID-19 alone, the prevalence of anxiety and depression soared by 25% worldwide. In light of the chronic shortages of mental health resources and talents, along with disruptions of available health services caused by pandemic-related restrictions, technology is widely believed to hold the key to addressing the rising mental health crises. However, hurdles such as fragmented and oftentimes suboptimal patient protection measures substantially undermine technology’s potential to address the global mental health crises reliably and at scale. To shed light on these issues, this paper aims to discuss the post-pandemic mental health challenges and opportunities, and the strategies and solutions the global mental health community could leverage to protect and elevate society’s mental health in the long run.

Abstract Background Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer. Its epidemiological features, treatment principles, and prognostic factors remain controversial. Objective This study aimed to develop an improved machine learning-based model to predict the prognosis of patients with invasive micropapillary carcinoma. Methods A total of 1123 patients diagnosed with IMPC after surgery between 1998 and 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database for survival analysis. Univariate and multivariate analyses were performed to explore independent prognostic factors for the overall and disease-specific survival of patients with IMPC. Five machine learning algorithms were developed to predict the 5-year survival of these patients. Results Cox regression analysis indicated that patients aged > 65 years had a significantly worse prognosis than those younger in age, while unmarried patients had a better prognosis than married patients. Patients diagnosed between 2001 and 2005 had a significant risk reduction of mortality compared with other periods. The XGBoost model outperformed the other models with a precision of 0.818 and an area under the curve of 0.863. Conclusions A machine learning model for IMPC in patients with breast cancer was developed to estimate the 5-year OS. The XGBoost model had a promising performance and can help clinicians determine the early prognosis of patients with IMPC; therefore, the model can improve clinical outcomes by influencing management strategies and patient health care decisions.

Abstract Background This report investigated the expression, prognostic and biological implications of hsa_circ_0079929 in lung adenocarcinoma, which was based on clinical and experimental data. Methods Patients with lung adenocarcinoma were screened and their clinical data and tissues (including cancerous tissues and adjacent normal tissues) were collected. The total RNA in tissues and cell lines was analyzed to obtained hsa_circ_0079929 level. The clinical significance was examined using the Chi-square test, Multi-variate Cox proportional hazards regression, and Kaplan-Meier curve. Cell malignant features were evaluated from three aspects (proliferation, migration, and invasion), detected by CCK-8 and Transwell methods. Results Hsa_circ_0079929 raised in expression level in lung adenocarcinoma. This upregulation of hsa_circ_0079929 was correlated with adverse clinical parameters and poor outcome in terms of overall survival, resulting in an independent prognostic purpose molecular for overall survival. Overexpression of hsa_circ_0079929 could contribute to cell proliferation/migration/invasion, whereas its knockdown could inhibit these malignant features. Hsa_circ_0079929 was a molecular decoy for miR-1184 in lung adenocarcinoma cells. Conclusions Hsa_circ_0079929 could promote the malignant features of lung adenocarcinoma cells and may aid the follow up and therapeutic target discovery of lung adenocarcinoma.

Abstract Background Crohn’s disease (CD), a prominent manifestation of chronic gastrointestinal inflammation, and breast cancer (BC), seemingly disparate in the medical domain, exhibit a shared characteristic. This convergence arises from their involvement in chronic inflammation and immune responses, an aspect that has progressively captivated the attention of investigators but remain controversial. Methods We used two-sample Mendelian Randomization (MR) and transcriptomics to explore the relationship between CD and BC. MR assessed causality of CD on different BC subtypes and reverse causality of BC on CD. We identified CD-related differentially expressed genes and their prognostic impact on BC, and developed a new molecular BC classification based on these key genes. Results MR revealed a causal link between CD and increased BC risk, especially in estrogen receptor-positive (ER+) patients, but not in ER-negative (ER-) cases. BC showed no causal effect on CD. Transcriptomics pinpointed genes like B4GALNT2 and FGF19 that affected BC prognosis in CD patients. A nomogram based on these genes predicted BC outcomes with high accuracy. Using these genes, a new molecular classification of BC patients was proposed. Conclusions CD is a risk factor for ER + BC but not for ER- BC. BC does not causally affect CD. Our prognostic model and new BC molecular classifications offer insights for personalized treatment strategies.

A novel reference signal scheme, E DFT-s-OFDM DMRS was proposed for high-mobility scenarios in the Terahertz band. The proposed scheme involved segmenting the reference signal sequence with cyclic prefix and cyclic suffix into a head and tail reference signal sequence. These sequences were then embedded into the tail and head of each OFDM symbol, respectively. The scheme had the advantage of using a complete reference signal sequence formed by the tail of the preceding OFDM symbol and the head of the following OFDM symbol. This allowed the receiver to perform channel estimation in each OFDM symbol interval, improving the accuracy and real-time performance of channel estimation. Furthermore, adjacent OFDM symbols share identical head and tail reference signal sequences, eliminating the traditional cyclic prefix for each OFDM symbol and improving spectral efficiency. Simulation results demonstrate that this scheme provides more precise channel estimation and greater spectral efficiency than DMRS scheme with 5G NR DFT-s-OFDM waveform for high-mobility scenarios in the Terahertz band.

In the rapidly evolving domain of finance, quantitative stock selection strategies have gained prominence, driven by the pursuit of maximizing returns while mitigating risks through sophisticated data analysis and algorithmic models. Yet, prevailing models frequently neglect the fluid dynamics of asset relationships and market shifts, a gap that undermines their predictive and risk management efficacy. This oversight renders them vulnerable to market volatility, adversely affecting investment decision quality and return consistency. Addressing this critical gap, our study proposes the Graph Learning Spatial–Temporal Encoder Network (GL-STN), a pioneering model that seamlessly integrates graph theory and spatial–temporal encoding to navigate the intricacies and variabilities of financial markets. By harnessing the inherent structural knowledge of stock markets, the GL-STN model adeptly captures the nonlinear interactions and temporal shifts among assets. Our innovative approach amalgamates graph convolutional layers, attention mechanisms, and long short-term memory (LSTM) networks, offering a comprehensive analysis of spatial–temporal data features. This integration not only deciphers complex stock market interdependencies but also accentuates crucial market insights, enabling the model to forecast market trends with heightened precision. Rigorous evaluations across diverse market boards—Main Board, SME Board, STAR Market, and ChiNext—underscore the GL-STN model’s exceptional ability to withstand market turbulence and enhance profitability, affirming its substantial utility in quantitative stock selection.

Abstract Central nervous system Infections (CNSIs) is a disease characterized by complex pathogens, rapid disease progression, high mortality rate and high disability rate. Here, we evaluated the clinical value of metagenomic next generation sequencing (mNGS) in the diagnosis of central nervous system infections and explored the factors affecting the results of mNGS. We conducted a retrospective study to compare mNGS with conventional methods including culture, smear and etc. 111 suspected CNS infectious patients were enrolled in this study, and clinical data were recorded. Chi-square test were used to evaluate independent binomial variables, taking p 300*106/L), the positive rate of CSF mNGS is higher. To sum up, conventional microbiologic testing is insufficient to detect all neuroinvasive pathogens, and mNGS exhibited satisfactory diagnostic performance in CNSIs and with an overall detection rate higher than culture (p

Abstract Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal ‘trajectory’ of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Owing to the significant development in graphene, an increasing number of studies have been conducted to identify novel two-dimensional (2D) organic materials with Dirac cones and topological properties. Although a series of toy models based on specific lattice patterns has been proposed and demonstrated to possess a Dirac cone, realistic materials corresponding to the lattice models must be identified to achieve excellent properties for practical applications. To understand factors contributing to the rarity of 2D organic Dirac materials and provide guidance for identifying novel organic Dirac systems, we review recent theoretical studies pertaining to various 2D Dirac models and their corresponding organic Dirac materials, including the Haldane, Kagome, Libe, line-centered honeycomb, and Cairo pentagonal models. Subsequently, the corresponding structural and topological electronic properties are summarized. Additionally, we investigate the relationship between the existence of Dirac cones and their structural features, as well as the manner by which Dirac points emerge and propagate in these systems.

Abstract Background Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. Methods In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. Results Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency. Conclusions In summary, our findings demonstrate that the H19/let-7 g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.

Abstract The Yangtze River (hereafter referred to as the YZR), the largest river in China, is of paramount importance for ensuring water resource security. The Yangtze River Basin (hereafter referred to as the YRB) is one of the most densely populated areas in China, and complex human activities have a significant impact on the ecological security of water resources. Therefore, this paper employs theories related to ecological population evolution and the Driving Force-Pressure-State-Impact-Response (DPSIR) model to construct an indicator system for the ecological security of water resources in the YRB. The report evaluates the ecological security status of water resources in each province of the YRB from 2010 to 2019, clarifies the development trend of its water resource ecological security, and proposes corresponding strategies for regional ecological security and coordinated economic development. According to the results of the ecological population evolution competition model, the overall indicator of the ecological security of water resources in the YRB continues to improve, with the safety level increasing annually. Maintaining sound management of water resources in the YRB is crucial for sustainable socioeconomic development. To further promote the ecological security of water resources in the YRB and the coordinated development of the regional economy, this paper proposes policy suggestions such as promoting the continuous advancement of sustainable development projects, actively adjusting industrial structure, continuously enhancing public environmental awareness, and actively participating in international ecological construction and seeking cooperation among multiple departments.

With the aggravation of energy shortage and ecological deterioration, it becomes more and more essential for China to improve energy efficiency and realize the targets of energy conservation and emission reduction. This paper focuses on the measurement of the total factor energy efficiency (TFEE), the potentials of energy conservation and emission reduction, and the influencing factors of TFEE in China. Firstly, the model of Gray Weight Slack-Based Measure (GW-SBM) is established, with the weights of the indicators obtained via the grey relational analysis method, to calculate the TFEE of thirty provinces and six regions in China from 2009 to 2019. Then, the potentials of energy conservation and emission reduction are analyzed on the basis of TFEE measurements. Finally, the influencing factors of TFEE are identified via the truncated bootstrap model. The findings show that the TFEE values of 30 provinces fluctuate in the range of 0.20 and 1.0, varying significantly among provinces. Energy conservation potential reached 8.7490 million tons of standard coal (potential 39.06%), which means that more than one-third of energy consumption is inefficient. The top two factors in the TFEE measurement identified by the truncated bootstrap model, are energy consumption structure and environmental protection expenditure. Based on the research conclusions, this paper puts forward some countermeasures and suggestions.

Abstract Background Diabetic sarcopenia is a disease‐related skeletal muscle disorder that causes progressive symptoms. The complete understanding of its pathogenesis is yet to be unravelled, which makes it difficult to develop effective therapeutic strategies. This study investigates how MFG‐E8 affects mitophagy and the protective role of D‐pinitol (DP) in diabetic sarcopenia. Methods In vivo, streptozotocin‐induced diabetic SAM‐R1 (STZ‐R1) and SAM‐P8 (STZ‐P8) mice (16‐week‐old) were used, and STZ‐P8 mice were administrated of DP (150 mg/kg per day) for 6 weeks. Gastrocnemius muscles were harvested for histological analysis including transmission electron microscopy. Proteins were evaluated via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) assay. In vitro, advanced glycation end products (AGEs) induced diabetic and D‐galactose (DG) induced senescent C2C12 models were established and received DP, MFG‐E8 plasmid (Mover)/siRNA (MsiRNA), or 3‐MA/Torin‐1 intervention. Proteins were evaluated by IF and WB assay. Immunoprecipitation (IP) and co‐immunoprecipitation (CO‐IP) were used for hunting the interacted proteins of MFG‐E8. Results In vivo, sarcopenia, mitophagy deficiency, and up‐regulated MFG‐E8 were confirmed in the STZ‐P8 group. DP exerted protective effects on sarcopenia and mitophagy (DP + STZ‐P8 vs. STZ‐P8; all P

The increase in bacterial antibiotic resistance poses a significant threat to the effectiveness of antibiotics, and there is growing evidence suggesting that global warming may speed up this process. However, the direct influence of temperature on the development of antibiotic resistance and the underlying mechanisms is not yet fully understood. Here we show that antibiotic resistance exhibits a nonlinear response to elevated temperatures under the combined stress of temperatures and antibiotics. We find that the effectiveness of gatifloxacin against Escherichia coli significantly diminishes at 42 °C, while resistance increases 256-fold at 27 °C. Additionally, the increased transcription levels of genes such as marA, ygfA, and ibpB with rising temperatures, along with gene mutations at different sites, explain the observed variability in resistance patterns. These findings highlight the complexity of antibiotic resistance evolution and the urgent need for comprehensive studies to understand and mitigate the effects of global warming on antibiotic resistance.

BackgroundThis is the first case report describing a patient with non-small cell lung cancer (NSCLC) harboring two rare human epidermal growth factor receptor 2 (HER2) exon 21 insertion mutations, who responded to furmonertinib treatment. Furmonertinib maybe one effective and economical treatment for NSCLC patients harboring HER2 mutations with minor side effects.Case descriptionWe present a case report of a 49-year-old female diagnosed with stage IV lung adenocarcinoma who complained of irritating dry cough symptoms followed by chest tightness. Firstly, we describe the patient’s treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient’s fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed. After that, comprehensive genomic profiling revealed two HER2 exon 21 insertion mutations. Subsequently, the patient received targeted therapy with furmonertinib and achieved 11 months of progression-free survival. The patient received pyrrotinib therapy for 2 months after disease progression, but the disease continued to progress. In October 2023, the patient received therapy with furmonertinib again, and a month later, the disease went into partial remission. However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023.ConclusionFurmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.

ABSTRACT Background Tremor‐dominant (TD) and nontremor‐dominant (NTD) Parkinson's disease (PD) showed different responses to rehabilitation. However, the neural mechanism behind this remains unclear. Methods This cohort study explores changes in motor function, brain activation, and functional connectivity following 2 weeks of rehabilitation in TD‐PD and NTD‐PD patients, respectively. A total of 11 TD‐PD patients, 24 NTD‐PD patients, and 21 age‐matched healthy controls (HCs) were included. At baseline, all participants underwent functional magnetic resonance imaging (fMRI) while performing the foot tapping task. Motor symptoms, gait, balance, and task‐based fMRI were then evaluated in patients before and after rehabilitation. Results Compared to HCs, TD‐PD patients showed increased activity in the left inferior frontal gyrus and the right insula, and NTD‐PD patients showed increased activations in the left postcentral gyrus and decreased within‐cerebellar connectivity at baseline. Rehabilitation improved motor function in PD patients regardless of motor subtype. TD‐PD patients showed increased recruitments of the sensorimotor cortex and the bilateral thalamus after rehabilitation, and NTD‐PD patients showed increased cerebellar activation and within‐cerebellar connectivity that was associated with better motor performance. Conclusions This study demonstrated that rehabilitation‐induced brain functional reorganization varied by motor subtypes in PD, which may have important implications for making individualized rehabilitation programs. Trial Registration ClinicalTrials.gov identifier: ChiCTR1900020771

BackgroundMesenchymal stem cells (MSCs) are safe and effective in treating myocardial infarction (MI) and have broad application prospects. However, the heterogeneity of MSCs may affect their therapeutic effect on the disease. We recently found that MSCs derived from different segments of the same umbilical cord (UC) showed significant difference in the expression of genes that are related to heart development and injury repair. We therefore hypothesized that those MSCs with high expression of above genes are more effective to treat MI and tested it in this study.MethodsMSCs were isolated from 3 cm-long segments of the maternal, middle and fetal segments of the UC (maternal-MSCs, middle-MSCs and fetal-MSCs, respectively). RNA-seq was used to analyze and compare the transcriptomes. We verified the effects of MSCs on oxygen-glucose deprivation (OGD)-induced cardiomyocyte apoptosis in vitro. In vivo, a rat MI model was established by ligating the left anterior descending coronary artery, and MSCs were injected into the myocardium surrounding the MI site. The therapeutic effects of MSCs derived from different segments of the UC were evaluated by examining cardiac function, histopathology, cardiomyocyte apoptosis, and angiogenesis.ResultsCompared to fetal-MSCs and middle-MSCs, maternal-MSCs exhibited significantly higher expression of genes that are associated with heart development, such as GATA-binding protein 4 (GATA4), and myocardin (MYOCD). Coculture with maternal-MSCs reduced OGD-induced cardiomyocyte apoptosis. In rats with MI, maternal-MSCs significantly restored cardiac contractile function and reduced the infarct size. Mechanistic experiments revealed that maternal-MSCs exerted cardioprotective effects by decreasing cardiomyocyte apoptosis, and promoting angiogenesis.ConclusionOur data demonstrated that maternal segment-derived MSCs were a superior cell source for regenerative repair after MI. Segmental localization of the entire UC when isolating hUCMSCs was necessary to improve the effectiveness of clinical applications.

Geometries, stabilities, bonding nature, and vibrational properties of bimetallic KMgn0/– (n = 2–12) clusters have been comprehensively studied by CALYPSO code within DFT calculations. The results reveal the structural transition from 2D to 3D at n = 3. From n ≥ 8, the geometry of KMgn0/– transfers a hollow framework with a six-atom triangular prism unit. By comparing the geometry of neutral and anionic KMgn0/– clusters, most of them are structurally different. In all doped clusters, the K atoms tend to localize on the convex positions of the skeleton and play the role of electron donors. Two highly stable clusters KMg9 and KMg9– have been found, and studies showed that the prominent stability benefits from their compact magnesium structural motifs and quasi-full/full shell electronic configurations. Additionally, bonding nature analysis reflects there is much weak K-Mg interaction than Mg-Mg interaction in the KMg90/– clusters. The spectroscopic properties based on the PES, IR and Raman spectra have also been discussed.

To research the impact of oxygen consistency on the thermal dynamic characteristics and the change of gas products of weakly caking coal oxidation, differential scanning calorimetry and temperature programmed experiments were used to study, and the correlation between the intensity of heat release at distinct consistencies of oxygen and concentration of gas products was computed applying grey correlation method. The outcomes indicated that the coal low-temperature oxidation process can be categorized into three phases: speedy endothermic, slow endothermic, and exothermic. The apparent activation energy in the slow heat absorption phase exceeded the speedy endothermic stage, and the apparent activation energy in the heat release phase increased by 20.83 kJ/mol. The concentration of gas products generated at the spontaneous combustion process of coal growth when temperature went up. However, CH4 concentration increased with the temperature rising after 120 °C. C2H6 gas does not appear until 100 °C. C2H4 gas appeared after 90 °C. At various O2 consistencies, the correlation between exothermic intensity and CO2 remained the largest, the correlation between exothermic intensity and CO and CH4 was larger at lower oxygen consistencies. As concentration of oxygen increased, the correlation between exothermic intensity and C2H4 and C2H6 increased first and then decreased.

X-linked hereditary Alport syndrome (XLAS) type 1 (OMIM: 301050) results from a pathogenic variant in the collagen type IV alpha 5 chain (COL4A5) gene.A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells of a 7-year-old male patient with XLAS using non-integrating episomal vector technique. The male donor had a heterozygous variant in the COL4A5 gene. The resulting iPSC line has a standard karyotype, can express pluripotent biomarkers, and is able to create germ layers in vivo. It can serve as a valuable cellular model for investigating the underlying mechanisms of XLAS.

Purpose: In breast cancer (BC) patients with clinical axillary lymph node metastasis (cN+) undergoing neoadjuvant therapy (NAT), precise axillary lymph node (ALN) assessment dictates therapeutic strategy. There is a critical demand for a precise method to assess the axillary lymph node (ALN) status in these patients. Materials and methods: A retrospective analysis was conducted on 160 BC patients undergoing NAT at Fujian Medical University Union Hospital. We analyzed baseline and two-cycle reassessment dynamic contrast-enhanced MRI (DCE-MRI) images, extracting 3668 radiomic and 4096 deep learning features, and computing 1834 delta-radiomic and 2048 delta-deep learning features. Light Gradient Boosting Machine (LightGBM), Support Vector Machine (SVM), RandomForest, and Multilayer Perceptron (MLP) algorithms were employed to develop risk models and were evaluated using 10-fold cross-validation. Results: Of the patients, 61 (38.13 %) achieved ypN0 status post-NAT. Univariate and multivariable logistic regression analyses revealed molecular subtypes and Ki67 as pivotal predictors of achieving ypN0 post-NAT. The SVM-based “Data Amalgamation” model that integrates radiomic, deep learning features, and clinical data, exhibited an outstanding AUC of 0.986 (95 % CI: 0.954–1.000), surpassing other models. Conclusion: Our study illuminates the challenges and opportunities inherent in breast cancer management post-NAT. By introducing a sophisticated, SVM-based “Data Amalgamation” model, we propose a way towards accurate, dynamic ALN assessments, offering potential for personalized therapeutic strategies in BC.

Stroke is recognized as a network communication disorder. Advances in neuroimaging technologies have enhanced our comprehension of dynamic cerebral alterations. However, different levels of motor function impairment after stroke may have different patterns of brain reorganization. Abnormal and adaptive patterns of brain activity in mild-to-moderate motor function impairments after stroke remain still underexplored. We aim to identify dynamic patterns of network remodeling in stroke patients with mild-to-moderate impairment of motor function. fMRI data were obtained from 30 stroke patients and 31 healthy controls to establish a spatiotemporal multilayer modularity model. Then, graph-theoretic measures, including modularity, flexibility, cohesion, and disjointedness, were calculated to quantify dynamic reconfiguration. Our findings reveal that the post-stroke brain exhibited higher modular organization, as well as heightened disjointedness, compared to HCs. Moreover, analyzing from the network level, we found increased disjointedness and flexibility in the Default mode network (DMN), indicating that brain regions tend to switch more frequently and independently between communities and the dynamic changes were mainly driven by DMN. Notably, modified functional dynamics positively correlated with motor performance in patients with mild-to-moderate motor impairment. Collectively, our research uncovered patterns of dynamic community reconstruction in multilayer networks following stroke. Our findings may offer new insights into the complex reorganization of neural function in post-stroke brain.

The plant-specific INDETERMINATE DOMAIN (IDD) gene family is important for plant growth and development. However, a comprehensive analysis of the IDD family in orchids is limited. Based on the genome data of Phalaenopsis equestris, the IDD gene family was identified and analyzed by bioinformatics methods in this study. Ten putative P. equestris IDD genes (PeIDDs) were characterized and phylogenetically classified into two groups according to their full amino acid sequences. Protein motifs analysis revealed that overall structures of PeIDDs in the same group were relatively conserved. Its promoter regions harbored a large number of responsive elements, including light responsive, abiotic stress responsive elements, and plant hormone cis-acting elements. The transcript level of PeIDD genes under cold and drought conditions, and by exogenous auxin (NAA) and abscisic acid (ABA) treatments further confirmed that most PeIDDs responded to various conditions and might play essential roles under abiotic stresses and hormone responses. In addition, distinct expression profiles in different tissues/organs suggested that PeIDDs might be involved in various development processes. Furthermore, the prediction of protein-protein interactions (PPIs) revealed some PeIDDs (PeIDD3 or PeIDD5) might function via cooperating with chromatin remodeling factors. The results of this study provided a reference for further understanding the function of PeIDDs.

IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1–6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K–Akt and TGF-β signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.

A deep understanding of the effects of the inorganic characteristics of Xinjiang coals on combustion particulate generation is of great significance for their clean and efficient utilization. This work investigated the inorganic characteristics of Wucaiwan coal (WCW), Wanxiang coal (WX), Tianchi coal (TC), and Xiheishan coal (XHS) and the their relationship with the production of ultrafine particulates during combustion. The results show that the four Xinjiang coals are mainly lignites with low ash and sulfur contents. Coal ashes are enriched in basic elements. Among them, the content of Na2O (3.58%−7.13%) is commonly higher than that of conventional utility coals. The ashes of WCW and WX coals have higher contents of CaO (> 33%), but low contents of SiO2 and Al2O3. WX coal is particularly characterized by high Na and Cl. The Na in coal is primarily water soluble(62.3%−90.6%). The K is mainly HCl insoluble. The Fe occurs primarily as HCl soluble and insoluble forms. And the distribution of Ca and Mg in different forms varies according to coal types. The composition of ultrafine particulate matter from Xinjiang coal combustion is dominated by Na, K, Cl, and S. The particle size range of the ultrafine particulate matter is accurately defined by using the condition that the mass fraction of Na2O+K2O+Cl+SO3 is higher than 50%. The ultrafine particulate matter of WCW, TC and XHS coals has similar particle size ranges (≤0.07 μm); while the ultrafine particulate matter of WX coal, which has the highest content of Na in the water-soluble form, has a wider particle size range (≤0.76 μm). The generation of ultrafine particulate matter (y) is found to be highly linearly and positively correlated with the total amount of water-soluble (Na+K) (x) in the coal, with the relationship equation y = 0.528x−0.239 and the correlation coefficient of 0.948.

Abstract Background To explore the application effect of 3D printing surgical training models in the preoperative assessment of robot-assisted partial nephrectomy. Methods Eighty patients who underwent robot-assisted partial nephrectomy surgery between January 2022 and December 2023 were selected and divided into two groups according to the chronological order. The control group (n = 40) received preoperative assessment with verbal and video education from January 2022 to December 2022, while the observation group (n = 40) received preoperative assessment with 3D printing surgical training models combined with verbal and video education from January 2023 to December 2023. The preoperative anxiety, information demand score, and surgical awareness were compared between the two groups. The physiological stress indicators, including interleukin-6 (IL-6), angiotensin II (AT II), adrenocorticotropic hormone (ACTH), cortisol (Cor), mean arterial pressure (MAP), and heart rate (HR), were also measured at different time points before and after surgery.They were 6:00 am on the day before surgery (T0), 6:00 am on the day of the operation (T1), 6:00 am on the first day after the operation (T2), and 6:00 am on the third day after the operation (T3).The preparation rate before surgery was compared between the two groups. Results The anxiety and surgical information demand scores were lower in the observation group than in the control group before anesthesia induction, and the difference was statistically significant (P

Abstract The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.

Abstract In this study, we investigate the influence of global innovation networks (GINs) on the innovation output of semiconductor firms. Utilizing negative binomial regression and network analysis, we assess how network positions, specifically degree, betweenness, and closeness centrality, affect firms’ innovation performance, revealing significant positive impacts. Moreover, our results identify a positive U-shaped relationship between structural holes in GINs and innovation performance, suggesting that while moderate network engagement aids innovation, too much can be detrimental. This research provides key insights into optimizing GIN participation for better innovation results in the competitive semiconductor sector.

Abstract Background Syndrome coronavirus-2 (SARS-CoV-2) has developed various strategies to evade the antiviral impact of type I IFN. Non-structural proteins and auxiliary proteins have been extensively researched on their role in immune escape. Nevertheless, the detailed mechanisms of structural protein-induced immune evasion have not been well elucidated. Methods Human alveolar basal epithelial carcinoma cell line (A549) was stimulated with polyinosinic-polycytidylic acid (PIC) and independently transfected with four structural proteins expression plasmids, including nucleocapsid (N), spike (S), membrane (M) and envelope (E) proteins. By RT-qPCR and ELISA, the structural protein with the most pronounced inhibitory effects on IFN-β induction was screened. RNA-sequencing (RNA-Seq) and two differential analysis strategies were used to obtain differentially expressed genes associated with N protein inhibition of IFN-β induction. Based on DIANA-LncBase and StarBase databases, the interactive competitive endogenous RNA (ceRNA) network for N protein-associated genes was constructed. By combining single-cell sequencing data (GSE158055), lncRNA-miRNA-mRNA axis was further determined. Finally, RT-qPCR was utilized to illustrate the regulatory functions among components of the ceRNA axis. Results SARS-CoV-2 N protein inhibited IFN-β induction in human alveolar epithelial cells most significantly compared with other structural proteins. RNA-Seq data analysis revealed genes related to N protein inhibiting IFNs induction. The obtained 858 differentially expressed genes formed the reliable ceRNA network. The function of LINC01002-miR-4324-FRMD8 axis in the IFN-dominated immune evasion was further demonstrated through integrating single-cell sequencing data. Moreover, we validated that N protein could reverse the effect of PIC on LINC01002, FRMD8 and miR-4324 expression, and subsequently on IFN-β expression level. And LINC01002 could regulate the production of FRMD8 by inhibiting miR-4324. Conclusion SARS-CoV-2 N protein suppressed the induction of IFN-β by regulating LINC01002 which was as a ceRNA, sponging miR-4324 and participating in the regulation of FRMD8 mRNA. Our discovery provides new insights into early intervention therapy and drug development on SARS-CoV-2 infection.

Abstract Background Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. Methods To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. Results We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. Conclusion Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

Abstract In this paper, we present a continuous-time algorithm with a dynamic event-triggered communication (DETC) mechanism for solving a class of distributed convex optimization problems that satisfy a metric subregularity condition. The proposed algorithm addresses the challenge of limited bandwidth in multi-agent systems by utilizing a continuous-time optimization approach with DETC. Furthermore, we prove that the distributed event-triggered algorithm converges exponentially to the optimal set, even without strong convexity conditions. Finally, we provide a comparison example to demonstrate the efficiency of our algorithm in communication resource-saving.

Abstract Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.

Abstract Background Male breast cancer constitutes a minority of breast cancer diagnoses, yet its incidence has been on the rise in recent decades. However, elderly male breast cancer patients have been inadequately represented in clinical trials, posing challenges in treatment decisions. This study seeks to clarify the efficacy of chemotherapy in this demographic and identify the population most likely to benefit from such intervention. Methods We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 1900 male breast cancer patients aged 70 years or older. Among them, 1652 were categorized in the no-chemotherapy group, while 248 were in the chemotherapy group. A multifactorial logistic regression model was employed to investigate the determinants influencing the administration of chemotherapy in elderly male breast cancer patients. Additionally, the multivariate Cox proportional hazards regression model was applied to identify factors associated with outcomes, with overall survival (OS) as the primary endpoint. Results Multivariate logistic regression analysis revealed that grade, tumor size, and nodal status were robust predictors for elderly male breast cancer patients receiving chemotherapy. Furthermore, the multivariate analysis demonstrated that chemotherapy conferred benefits compared to the no-chemotherapy group (HR = 0.822, 95% CI: 0.682–0.991, p = 0.040). Stratified analyses indicated that individuals with N+, poorly/undifferentiated grade, and stage II/III disease could derive benefits from chemotherapy. Upon further investigation of progesterone receptor (PR) positive patients, it was found that only stage III patients experienced significant benefits from chemotherapy (HR = 0.571, 95% CI: 0.372–0.875, p = 0.010). Conversely, in PR negative patients, both stage II (HR = 0.201, 95% CI: 0.051–0.792, p = 0.022) and stage III patients (HR = 0.242, 95% CI: 0.060–0.972, p = 0.046) derived benefits from chemotherapy. Conclusion Adjuvant chemotherapy may benefit certain elderly male breast cancer patients, specifically those with positive lymph node status, poorly/undifferentiated grade, and PR-positive in stage III, as well as PR-negative expression in stage II/III. Given favorable physical tolerance, it is advisable not to hastily dismiss chemotherapy for these elderly male breast cancer patients.

Objective: To investigate the contribution of YWHAZ gene on the radioresistance and metastasis ability of oral squamous cell carcinoma (OSCC) cells. Methods: The relationship between the expression level of YWHAZ gene and the survival of head and neck squamous cell carcinoma (HNSC) patients was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistance cell line (CAL-27R) was constructed by irradiating CAL-27 ​cells with fractional doses. Cell survival was measured by colony formation assay. Cell migration and invasion were detected by transwell assay. The formation of γH2AX foci was detected by immunofluorescence assay. The protein expressions were detected by Western blot assay. In some experiments, CAL-27R cells were effectively transferred with siRNA YWHAZ (siYWHAZ). Results: GEPIA database showed that the expression level of YWHAZ in HNSC tumors was higher than that in adjacent normal tissues, and the HNSC patients with higher level of YWHAZ had a shorter survival. In vitro experiments demonstrated that the expression of YWHAZ protein in CAL-27 ​cells was lower than HSC-3 ​cells (t ​= ​18.89, P ​

Abstract Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an “epitope-focused” vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design.

Abstract Background Intravenous leiomyomatosis (IVL), pulmonary benign metastatic leiomyomatosis (PBML), and leiomyomatosis peritonealis disseminata (LPD) are leiomyomas with special growth patterns and high postoperative recurrence rates. We report the safety and efficacy of a pilot study of sirolimus in the treatment of recurrent IVL, PBML, and recurrent LPD. Methods This was a pilot study to evaluate the safety and efficacy of sirolimus in the treatment of leiomyomatosis (ClinicalTrials.gov identifier NCT03500367) conducted in China. Patients received oral sirolimus 2 mg once a day for a maximum of 60 months or until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. The primary end point of this study was the objective response rate. Secondary end points included safety and tolerability, disease control rate, and progression-free survival. Results A total of 15 patients with leiomyomatosis were included in the study, including five with recurrent IVL, eight with PBML and two with recurrent LPD. The median follow-up time was 15 months (range 6–54 months), nine patients (60%) had treatment-related adverse events (including all levels), and two patients had treatment-related grade 3 or 4 adverse events. The objective response rate was 20.0% (95% CI, 7.1–45.2%), and the disease control rate was 86.7% (95% CI, 62.1–96.3%). Partial response was achieved in three patients. The median response time in the three partial response patients was 33 months (range 29–36 months), and the sustained remission time of these three patients reached 0, 18, and 25 months, respectively. Conclusions Sirolimus was safe and effective in the treatment of recurrent IVL, PBML, and recurrent LPD. Trial registration ClinicalTrials.gov identifier NCT03500367. Registered on 18 April 2018.

Abstract Introduction Psittacosis is a zoonosis caused by Chlamydia psittaci, the clinical manifestations of Psittacosis range from mild illness to fulminant severe pneumonia with multiple organ failure. This study aimed to evaluate the clinical characteristics of Chlamydia psittaci infection diagnosed based on metagenomic next-generation sequencing(mNGS), as well as the risk factors affecting the progress of Chlamydia psittaci infection, in order to improve the effect of therapeutics. Methods We retrospectively analyzed the clinical data of patients infected with chlamydia psittaci in the First Affiliated Hospital of Nanchang University from January 2021 to December 2021. The patient’s past medical history, clinical manifestations, laboratory examinations, chest CT results, treatment status, and prognosis data were collected. we also investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of patients with Chlamydia psittaci pneumonia using mNGS. Results All cases of Chlamydia psittaci in our research have been confirmed by mNGS. Among 46 cases of Chlamydia psittaci pneumonia, Poultry exposure was reported in 35 cases. In severe cases of Chlamydia psittaci pneumonia, Neutrophils, Procalcitonin (PCT), Lactate Dehydrogenase (LDH), Hydroxybutyrate Dehydrogenase (HBDH), Creatine Kinase Isoenzymes-B (CK-MB) and D-Dimer levels were remarkably higher than that of non-severe cases, except for lymphocytes (all P

Abstract Background Oral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer. However, few studies investigated the potential role of oral and gastric microbiota in early-stage intramucosal esophageal squamous carcinoma (EIESC). Method A total of 104 samples were collected from 31 patients with EIESC and 21 healthy controls. The compositions of oral and gastric microbiota were analyzed using 16 S rRNA V3-V4 amplicon sequencing. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. The correlation between oral microbiota and clinicopathological factors was evaluated using Spearman correlation analysis. Additionally, co-occurrence networks were established and random forest models were utilized to identify significant microbial biomarkers for distinguishing between the EIESC and control groups. Results A total of 292 oral genera and 223 species were identified in both EIESC and healthy controls. Six oral genera were remarkably enriched in EIESC groups, including the genera Porphyromonas, Shigella, Subdoligranulum, Leptotrichia, Paludibacter, and Odoribacter. LEfSe analysis identified genera Porphyromonas and Leptotrichia with LDA scores > 3. In the random forest model, Porphyromonas endodontalis ranked the top microbial biomarker to differentiate EIESC from controls. The elimination rate of Porphyromonas endodontalis from the oral cavity to the stomach was also dramatically decreased in the EIESC group than controls. In the microbial co-occurrence network, Porphyromonas endodontalis was positively correlated with Prevotella tannerae and Prevotella intermedia and was negatively correlated with Veillonella dispar. Conclusion Our study potentially indicates that the dysbacteriosis of both the oral and gastric microbiome was associated with EIESC. Larger scale studies and experimental animal models are urgently needed to confirm the possible role of microbial dysbacteriosis in the pathogenesis of EIESC. (Chinese Clinical Trial Registry Center, ChiCTR2200063464, Registered 07 September 2022, https://www.chictr.org.cn/showproj.html?proj=178563)

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture. Methods/design This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. Discussion This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Abstract Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1β and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1β, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.

A series of experiments was conducted to study the performance and mechanisms of Cemented Ultrafine Tailings Backfill (CUTB). Firstly, the optimum fiber type was selected by single factor multilevel test. Secondly, the effects of cement content, rice husk ash content, fiber content and fiber length on backfill properties were analyzed by orthogonal test and microstructure test, and the influence mechanism of fiber and rice husk ash content was revealed. Finally, fuzzy mathematics theory is used to optimize the ratio parameters. The results show, compared to glass and basalt fiber, polypropylene fiber yields the most substantial enhancement in backfill strength. The increase of cement content, polypropylene fiber content and length can reduce slump, but the change of rice husk ash content has no obvious effect. Increased cement or fiber content effectively restrained the formation of primary fractures in CUTB, thus enhancing its integrity. Adding an optimal dosage range of 0–4 % of rice husk ash boosted the early compressive strength, albeiting at the expense of later compressive strength. Fiber addition with the optimum content range between 0.1 and 0.4 % enhanced the strengthening effect of cement content on compressive strength. Fiber primarily enhances the macroscopic strength of backfill through the dispersion and co-loading of forces, whereas rice husk ash enhances strength by optimizing void structure distribution. The optimal ratio parameters of a cement content of 310 kg/m³, rice husk ash content of 8.0 %, fiber content of 0.4 %, and fiber length of 9 mm were proposed finally.

Background: Anhedonia is a deficit of dynamic reward process, and a large proportion of schizophrenia patients continue to experience anhedonia even during the stable phase. However, few studies have examined the multiple aspects of performance in reward processing in patients with stable schizophrenia and evidence suggests that physical and cognitive effort may involve different neural mechanisms. Methods: Parallel measures of effort-based expenditure for reward tasks (EEfRT) and self-report questionnaires of pleasure were applied in 61 patients with stable schizophrenia (SSZ) and 46 healthy controls (HCs), and percentages of hard task choices (HTC%) were used to assess motivation in reward processing. Negative symptoms, neurocognitive and social function were evaluated in SSZ patients, and associations with performance in reward tasks were explored. Results: SSZ patients reported more severe consummatory and anticipatory anhedonia and social anhedonia. HTC% in reward tasks of SSZ patients were significantly lower than that of HCs, especially in cognitive-effort tasks. HTC% in cognitive tasks were correlated with motivation and pleasure dimension of negative symptoms, whereas HTC% in physical tasks were associated with expression dimension. Anticipatory anhedonia and negative symptoms were correlated with Personal and Social Performance Scale (PSP) scores. Conclusion: Patients with stable schizophrenia have social anhedonia, physically consummatory and anticipatory anhedonia and reduced reward motivation. They are less willing to make cognitive effort than physical effort for reward. The different associations of physical and cognitive effort with negative symptoms indicate physical and cognitive effort may represent disparate neuropsychological processes. Anticipatory anhedonia is closely related to social functioning.