Search

【Objective】Based on the micro-nano fiber coupler, this paper proposes a micro-nano fiber coupled ring mirror structure. Theoretical simulations and experimental studies are conducted to investigate the relationship between its spectrum and the polarization state of light within the ring mirror, the length of the micro-nano fiber in the tapered region, and the refractive index of the surrounding medium.【Methods】Theoretically, the basic principle of micro-nano fiber coupler is analyzed, and the optical field distribution of micro-nano fiber coupling and the spectral polarization of micro-nano fiber ring mirror are simulated. Experimentally, the spectral controllability is verified.【Results】The results show that when the half-wave plate angle of the circular polarization controller is adjusted at －90～90°, the period and the peak wavelength remains constant. The extinction ratio changes regularly with the angle and reaches the minimum at 45°, as well as the maximum at 90°. As the length of the waist cone increases, the channel interval and the free spectral range of the ring mirror comb spectrum presents gradually decrease. As the surrounding refractive index varies in the range of 1.332 0 to 1.335 5, the output interference wavelength is red-shift with 18 350 nm / RIU sensitivity.【Conclusion】In summary, by adjusting the polarization state of the coupled light inside the micro-nano fiber coupler, the length of the micro-nano tapered region, and the refractive index surrounding the coupler structure, corresponding changes in the output spectrum can be achieved. This provides a new approach for constructing novel all-fiber devices. These devices can not only be used as wavelength selection and regulation components in lasers to optimize laser output characteristics, but also applied in sensing fields such as biomedicine for high-precision detection of liquid components.

Abstract Background The Caprini risk assessment model (RAM) is a classical score that evaluates the risk of developing venous thromboembolism (VTE) aimed at patients with lower extremity fractures (LEF). However, the influencing factors of RAM pay more attention to clinical characteristic variables and recognized thrombophilia markers such as prothrombin, while ignoring the influence of other laboratory indicators on thrombosis. This is the first paper to screen predictive risk factors associated with VTE to modify the Caprini model and determine its diagnostic value. Results and methods We included 953 LEF patients from January 2019 to December 2021 and randomized them in a 7:3 ratio into a training set (n = 667) and a validation set (n = 286). Logistic regression and LASSO regression were used to screen for independent predictors of patients in the training set. Logistic regression screened for: age (OR 1.04, 95% CI 1.02—1.06), D-dimer (OR 1.06, 95% CI 1.03—1.08), Caprini (OR 1.17, 95% CI 1.08—1.27) and fasting blood glucose (FBG) (OR 1.18, 95% CI 1.03—1.35), which also appeared in the LASSO seven-factor model. In addition to Caprini and age, FBG and D-dimer may be important predictors of deep vein thrombosis in patients with LEF. Therefore, we constructed three models. caprini + D-dimer, caprini + FBG, and caprini + D-dimer + FBG. We compared them with caprini alone. Caprini + FBG + D-dimer showed the greatest ROC (0.784, 95% CI 0.730–0.837, Delong test P = 0.002 vs. Caprini’s ROC). D-dimer and FBG have a significant increase in the predictive effect for predicting DVT in terms of NRI (59.98% improvement, P

Abstract Background Mitochondrial permeability transition (MPT)-driven necrosis (MPTDN) is a non-apoptotic mode of cell death triggered by oxidative stress and cytosolic Ca2+ overload. Recent evidence suggests that activation of MPTND can effectively induce cancer cell death and may represent a novel therapeutic strategy for cancer. Yet, the role of MPTDN-related genes in non-small cell lung cancer (NSCLC) remains unrevealed. This study aimed to identify MPTDN-related biomarkers for predicting prognosis and guiding treatment in NSCLC. Methods Gene expression profiles and clinical information of NSCLC were collected from public databases, and MPTDN-related genes were obtained from published article. Differential expressed MPTDN-related genes in NSCLC and control were screened, and molecular clusters were obtained. Based on the differentially expressed genes (DGEs) between clusters, univariate Cox and LASSO regression analyses were performed to screen biomarkers, followed by nomogram construction. Correlations between these biomarkers and immune cell infiltration, immune checkpoints, and chemotherapeutic agents were observed. Expression levels of MPTDN-related biomarkers were detected using RT-qPCR in NSCLC tissues and cells. Moreover, the biological function of ARL14 in NSLCL was verified in vitro. Results Thirty-five differential MPTDN-related genes were identified, and two molecular clusters were obtained. Three biomarkers with prognostic values were finally screened, including ARL14, ZDHHC11B, and HLF. Among them, ARL14 was significantly upregulated in tumor samples, while ZDHHC11B and HLF were downregulated. Nomogram containing three genes exhibited predictive accuracy in 1, 3, and 5-year survival rates. Three gene were strongly associated with most immune cells, immune checkpoints, and drugs sensitivity. RT-qPCR confirmed that expression levels of three genes in tissues or cells were consistent with the results of bioinformatics analysis. Finally, ARL14 knockdown inhibited the malignant phenotype of NSCLC cells. Conclusion We first performed the comprehensive analysis of MPTDN in NSCLC and screened three NSCLC-related biomarkers as promising biomarkers. ARL14 might be a new potential target for therapy of NSCLC.

Abstract Background To determine the optimal treatment modality for intracranial germinoma (IG). Materials and methods A search of Medline, Embase, Web of Science and Cochrane Library was conducted up to April, 2024. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated. Subgroup analysis was applied according to radiotherapy (RT) alone or with chemotherapy (CTx). Results Total 37 studies were included in systematic review. Most IG patients were treated with biopsy or resection followed by RT with or without CTx. Prognosis of IG patients with different surgical resection is similar. Meta-analyses demonstrated focal field RT were with higher recurrence rate compared with craniospinal irradiation (CSI) [RR = 7.128, 95% CI (5.083, 9.995)], whole-brain RT (WBRT) [RR = 4.094, 95% CI (2.923, 5.735)] or whole-ventricle RT (WVRT) [RR = 3.361, 95% CI (2.126, 5.312)]; both WBRT and WVRT were also with higher recurrence compared with CSI; but no significant difference in recurrence and mortality between WVRT and WBRT. Total 24 studies reported treatment-related acute and/or late toxicity, combination CTx increased acute toxic, and expanded RT field and/or dose increased late toxicity. Conclusion Based on our findings, focal field RT is not recommended regardless of whether combined with CTx for intracranial pure germinoma. Although CSI is associated with better local control than other reduced-field RT, considering the potential toxicity and pattern of relapse, whole ventricles irradiation is more reasonable for localized or nonmetastatic germinoma. Reduced-dose CSI with or without chemotherapy is effective in metastatic or disseminated IG.

Sleep health is a novel concept, a multidimensional sleep-wakefulness pattern that adapts to individual, social, and environmental demands to promote physical and mental well-being. Current research has found that sleep health is not only associated with physiological health issues such as diabetes, overweight/obesity, and cardiovascular risks but also has significant impacts on mental health issues such as anxiety and depression. Previous sleep-related studies have primarily focused on identifying and treating sleep disorders and problems, with less attention to the positive attributes of sleep health. This review summarizes studies on sleep health, including its definition, measurement tools, and correlations with health outcomes, aiming to foster a more comprehensive understanding of sleep health and provide a reference for research on sleep health among Chinese residents.

Abstract The allocation of communication resources is extremely important for the device-to-device (D2D) communication network with unmanned aerial vehicle (UAV) relays, but this field currently mainly focuses on the communication between UAVs and ground devices. While neglecting the comprehensive optimization of air-to-ground communication and internal ground communication. This paper studies the optimization problem of communication for ground D2D devices based on UAV relays in urban environment. We study the comprehensive optimization considering the air-to-ground communication and the mobile ground communication devices. We construct the D2D communication neighbor table, and the terrestrial D2D devices will sort and select the best D2D link for pairing based on the Euclidean distance and gain set around them. We construct a communication model for this scenario and propose an improved Dual-Actor Network Softmax Twin Delayed Deep Deterministic Policy Gradient algorithm based on deep reinforcement learning. We perform transmit power optimization to address the interference caused by D2D communication using frequency division multiplexing technology. By designing the reward function and training mechanism, we can achieve good power control and reduce communication interference. The results of the simulation analysis performed in this scenario show an effective reduction in communication latency and an increase in D2I (device-to-infrastructure) channel capacity, D2D connectivity success, and energy efficiency. The feasibility and effectiveness of the algorithm is verified by comparing the baseline algorithm.

Objective To investigate the effect and prognosis of early enteral nutrition (EEN) combined with probiotics on patients with severe multiple injuries. Methods A total of 110 patients with multiple injuries who scored＞16 points on the trauma severity score in the Intensive Care Unit of Dazhou Central Hospital from July 2022 to July 2023 were collected and divided into control group (55 cases) and observation group (55 cases) using a random number table method. The control group received EEN support, while the observation group received EEN combined with probiotic nutritional support. Serum diamine oxidase (DAO), D-lactic acid (D-La), total protein (PB), prealbumin (PAB), C-reactive protein (CRP), and white blood cell count (WBC) were compared between the two groups before and after treatment. The length of ICU stay, incidence of gastrointestinal adverse events, and 28-day mortality rate were statistically analyzed for both groups. Results After treatment, serum DAO, D-La, CRP, and WBC levels in both groups were lower than before treatment, with the observation group having lower levels than the control group ［(7.77±1.03) ng/L vs (8.84±0.63) ng/L, (48.25±7.23) mg/L vs (53.85±6.44) mg/L, (33.43±17.28) mg/L vs (43.44±19.13) mg/L, (7.48±1.56)×109/L vs (9.77±1.30)×109/L］, with a significant difference (P＜0.05); post-treatment TP and PAB levels in both groups were higher than before treatment, with the observation group having higher levels than the control group ［(58.80±2.83) g/L vs (54.43±2.06) g/L, (175.93±5.78) g/L vs (159.16±8.06) g/L］, with a significant difference (P＜0.05); the incidence of gastrointestinal adverse events in the observation group was lower than that in the control group (26.1% vs 46.5%), with a significant difference (P＜0.05); however, there was no significant difference in ICU stay or 28-day mortality rate between the two groups (P＞0.05). Conclusion EEN combined with probiotics can effectively protect the intestinal mucosal barrier of patients with severe multiple injuries, improve their nutritional status, and reduce the incidence of gastrointestinal adverse events, but it has no significant impact on the ICU stay or 28-day mortality rate of patients with severe multiple injuries.

Reproductive isolation (RI) refers to the phenomena that different populations cannot mate to produce offsprings under natural conditions, or the produced offsprings cannot survive or are sterile. It plays an important role in speciation and maintaining species stability, and is the core scientific issue of evolutionary biology. There are extensive interspecific and intersubspecific RI in rice, which is an ideal model to study RI. Additionally, interspecific and intersubspecific hybrids display strong heterosis in rice due to the distant genetic relationship, but they suffer from serious RI which restricts the effective utilization of distant heterosis. The scientists have made great progress in cloning the causal genes and expounding the molecular genetic basis of RI in rice, which not only deepen our theoretical understanding of the rice evolutionary biology, but also greatly promote the development of distant hybrid rice breeding. To date, more than 60 RI loci have been identified, and the related genes of 15 RI loci have been cloned in rice. The scientists have proposed five molecular genetic models of RI in rice, including one-locus killer-protector model, one-locus killer-target model, one-locus sporophytic interaction model, two-locus duplicate gametic lethal model and two-locus sporophytic interaction model. According to these findings, several strategies and methods such as developing wide compatibility lines, breeding intersubspecific introgression rice and establishing artificial hybrid compatible lines by genome editing have been proposed to overcome RI in rice. Based on the rice model, this review summarizes the advances of RI in rice, including RI types, molecular genetic basis and overcoming strategies, and provides a forward-looking perspective on the development trend and challenges in the field of rice RI, with an aim to provide ideas and references for further study of molecular genetic mechanism of plant RI and distant crop hybrid breeding.

Abstract Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by multilineage immune dysregulation, which subsequently causes inflammation, fibrosis, and even cirrhosis of liver. Due to the limitation of traditional assays, the local hepatic immunopathogenesis of PBC has not been fully characterized. Here, we utilize single-cell RNA sequencing technology to depict the immune cell landscape and decipher the molecular mechanisms of PBC patients. We reveal that cholangiocytes and hepatic stellate cells are involved in liver inflammation and fibrosis. Moreover, Kupffer cells show increased levels of inflammatory factors and decreased scavenger function related genes, while T cells exhibit enhanced levels of inflammatory factors and reduced cytotoxicity related genes. Interestingly, we identify a liver-resident Th1-like population with JAK-STAT activation in the livers of both PBC patients and murine PBC model. Finally, blocking the JAK-STAT pathway alleviates the liver inflammation and eliminates the liver-resident Th1-like cells in the murine PBC model. In conclusion, our comprehensive single-cell transcriptome profiling expands the understanding of pathological mechanisms of PBC and provides potential targets for the treatment of PBC in patients.

Abstract Our previous research revealed a close association between the acetylation of peroxisome proliferator-activated receptor γ (PPARγ) histone H3K27 and the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). We preliminarily explored the epigenetic mechanism of steroid-induced avascular necrosis of the femoral head (SANFH) development, but the specific histone deacetylase (HDAC) involved in this regulatory process remains unknown. In this study, we combined cell, animal, and clinical specimen experiments to screen for specific HDAC genes that could regulate BMSC adipogenic differentiation and to explore their roles. The results showed that dexamethasone (DEX) significantly exacerbated the imbalance between the adipogenic and osteogenic differentiation of BMSCs, and there were differences in HDAC expression in the adipogenic differentiation cell models, with histone deacetylase 10 (HDAC10) showing the most significant decrease in expression. Subsequent use of a chromatin immunoprecipitation assay kit and quantitative polymerase chain reaction (ChIP‒qPCR) revealed a decrease in HDAC10 expression at predicted potential sites within the PPARγ promoter, indicating a significant decrease in HDAC10 enrichment in the PPARγ promoter region of BMSCs, thereby promoting sustained PPARγ expression. Additionally, immunohistochemistry of samples collected from mice and humans with SANFH and normal femoral heads revealed an imbalance between adipogenic and osteogenic differentiation in the necrotic area of femoral heads, with a significant decrease in the relative expression of HDAC10 in the necrotic area of femoral heads with SANFH. In summary, we speculate that HDAC10 affects the progression of SANFH by regulating BMSC adipogenic differentiation, a process possibly related to PPARγ histone acetylation. These findings provide a promising direction for the treatment of SANFH. Graphical abstract

Abstract The study presents an arthroscopic transosseous suture bridge technique for repairing avulsion fractures of the tibial insertion of the anterior cruciate ligament (ACL), specifically tailored for adolescent patients. The technique utilizes two mini tunnels, integrating the principles of transosseous tunneling and suture bridging to ensure stable fixation while minimizing the impact on the bone bed. Over a seven-year period, 39 patients with Meyers-Mckeever types II, III, and IV tibial avulsion fractures underwent this procedure. The surgery had an average duration of 52.7 min and resulted in decreased swelling and pain within two months postoperatively. All patients achieved full knee extension and over 120° of flexion. X-rays confirmed complete fracture healing within six to 12 months, and negative anterior drawer test and Lachman test indicated stable fixation. Significant improvements were seen in Lysholm and IKDC scores. This technique offers several advantages: it is effective, stable, and particularly suitable for adolescents due to the reduced impact on the bone bed and successful avoidance of epiphyseal plate injury.

Emodin has shown certain anti-rheumatoid arthritis (RA) activity in preliminary studies. However, the precise mechanisms of emodin’s anti-RA effects, particularly its direct targets, remain unclear. This study aimed to evaluate the anti-RA activity of emodin and elucidate its potential mechanisms, with a specific focus on identifying its molecular targets. Employing a collagen-induced arthritis (CIA) rat model, along with transcriptomic analysis, thermal proteome profiling (TPP) and TNF-α-induced L929 cell model, the anti-RA activity of emodin was confirmed, identifying TNF-α as a potential target. Techniques such as drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), Affinity ultrafiltration-liquid chromatography/mass spectrometry (AUF-LC/MS), surface plasmon resonance (SPR) and bio-layer interferometry (BLI) validated the direct binding of emodin to TNF-α. Molecular dynamics simulation, ELISA and BLI further revealed that emodin stabilizes the asymmetric trimeric structure of TNF-α, disrupting the TNF-α-TNFR1 interaction. In vitro assays, including luciferase reporter gene assay and TNF-α-induced MH7A cell model, demonstrated that this disruption inhibits TNF-α-induced NF-κB activation, leading to the downregulation of inflammatory mediators such as IL-6, IL-1β, and COX2. In conclusion, emodin directly targets TNF-α, stabilizing its structure and blocking TNF-α-TNFR1 interaction, which subsequently suppresses downstream NF-κB pathway activation and contributes to its potent anti-RA properties.

Background: Patients with advanced hepatocellular carcinoma have poor prognosis. We aimed to investigate the efficacy of sorafenib combined with transarterial chemoembolization in patients with advanced hepatocellular carcinoma. Method: SELECT was a randomized, multi-centre, controlled, phase 3 trial done at twelve centres in China. Eligible patients were aged 18 years or older and had advanced-stage hepatocellular carcinoma, Barcelona Clinic Liver Cancer stage C diseases, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group (ECOG) performance statuses of 0 or 1. Participants were randomly assigned (1:1) with a computer-generated random sequence to sorafenib combined with transarterial chemoembolization or sorafenib alone. The primary endpoint was overall survival. Secondary endpoints were time to progression, tumor response rate, disease control rate and safety. Efficacy was analyzed in the intention-to-treat, per-protocol and as-treated populations. Safety outcomes were analyzed in the safety population. This trial is registered with ClinicalTrials.gov, number NCT01906216. Findings: Between September 7, 2013, and Dec 4, 2019, 199 patients were randomly assigned, 99 to the combination group and 100 to the sorafenib alone group. Protocol adherence was 86% (85 of 99 patients) in the combination group and 56% (56 of 100 patients) in the sorafenib alone group. The most common reason for discontinuation was disease progression (68 [69%] in the combination group and 80 [80%] in the sorafenib alone group). The median age was 55 years (IQR 46-63). 164 (82.4%) of 199 were male and 35 (17.6%) were female. At a median follow-up of 13.6 months (IQR 6.8-28.2), in the intention-to-treat population, median overall survival was 14.9 months (95%CI 10.5-19.3 months) in the combination group versus 11.9 months (95%CI 9.0-14.8 months) in the sorafenib alone group (HR 0.862 [95%CI 0.645-1.150]; P=0.312). Median time to progression survival was significantly longer in the combination group than the sorafenib alone group (10.0 months [95%CI 6.4-13.6 months] vs 5.9 months [95%CI 3.1-8.7 months]; HR 0.686 [95%CI 0.515-0.954]; P=0.016). In the per-protocol and as-treated analyses, both median overall survival and time to progression was significantly improved in the combination group compared with sorafenib alone group. Interpretation: In SELECT trial, sorafenib combined with TACE did not show overall survival benefit over sorafenib alone in intention-to-treat analysis; however, significantly longer overall survival benefit and improved time to progression was observed in both per-protocol and as-treated analyses.

Three new species of the genus Vacrothele Tang & Yang, 2022 are described in detail from China: Vacrothele fuyuanensis sp. nov., Vacrothele jiangkouensis sp. nov. and Vacrothele baiseensis sp. nov. Two described species of the Macrothele are transferred to the genus, i.e., Vacrothele emei (Lin & Li, 2021) comb. nov. and Vacrothele taiwanensis (Shimojana & Haupt, 1998) comb. nov. A key to species of Vacrothele and a geographic distribution map are given.

Background & Aims: Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification. Methods: Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets. The novel model was developed using a Cox multivariable regression analysis and compared with our original 6-and-12 model (the largest tumor size [ts, centimetres] + tumor number [tn]) and other available models in terms of predictive accuracy. Results: The proposed model, named the ‘6-and-12 model 2.0’, was generated as ‘ts + tn + 1.5×log10 alpha-fetoprotein (AFP)’, showed good discrimination (C-index 0.674) and calibration (Hosmer–Lemeshow test p = 0.147), and outperformed current existing models. An easy-to-use stratification was proposed according to the different AFP levels (≤100, 100–400, 400–2,000, 2,000–10,000, 10,000–40,000, and >40,000 ng/ml) along with the corresponding tumor burden cutoffs (8/14, 7/13, 6/12, 5/11, 4/10, and any tumor burden); that is, if the AFP level was 400–2,000 ng/ml, the stratification should be low-(≤6)/intermediate-(6–12)/high-risk (>12) strata. Hence, it could divide the patients into three distinct risk categories with a median overall survival of 45.0 (95% CI, 40.1–49.9), 30.0 (95% CI, 26.1–33.9), and 15.4 (95% CI, 13.4–17.4) months (p

Abstract Background A 3.0-mm ultrathin bronchoscope (UTB) with a 1.7-mm working channel provides better accessibility to peripheral bronchi. A 4.0-mm thin bronchoscope with a larger 2.0-mm working channel facilitates the use of a guide sheath (GS), ensuring repeated sampling from the same location. The 1.1-mm ultrathin cryoprobe has a smaller diameter, overcoming the limitation of the size of biopsy instruments used with UTB. In this study, we compared the endobronchial ultrasound localization rate and diagnostic yield of peripheral lung lesions by cryobiopsy using UTB and thin bronchoscopy combined with GS. Methods We retrospectively evaluated 133 patients with peripheral pulmonary lesions with a diameter less than 30 mm who underwent bronchoscopy with either thin bronchoscope or UTB from May 2019 to May 2023. A 3.0-mm UTB combined with rEBUS was used in the UTB group, whereas a 4.0-mm thin bronchoscope combined with rEBUS and GS was used for the thin bronchoscope group. A 1.1-mm ultrathin cryoprobe was used for cryobiopsy in the two groups. Results Among the 133 patients, peripheral pulmonary nodules in 85 subjects were visualized using r-EBUS. The ultrasound localization rate was significantly higher in the UTB group than in the thin bronchoscope group (96.0% vs. 44.6%, respectively; P

Abstract Background Patients with mucopolysaccharidosis (MPS) often face delayed diagnoses, limited treatment options and high healthcare costs, that may significantly affect patients' quality of life. The objective of this study was to understand medical service utilization related to diagnosis and treatment, economic burden during diagnosis period, and health-related quality of life among MPS patients in China. Methods A series of patients diagnosed with MPS registered in the national patient organization were recruited for a cross-sectional survey from May to July 2019. Information were collected from patients or their parents via phone interview, including demographic data, utilization of services related to diagnosis and treatment, total cost during the period of MPS diagnosis and health-related quality of life (HRQoL). HRQoL was assessed by PedsQL 4.0 Generic Core Scale (PedsQL) and 36-item short-form health survey (SF-36) depending on the age of patients with MPS and compared with the general Chinese population. Results A total of 180 MPS patients (50, 67, 15, 46, 1 and 1 for type I, II, III, IV, VI and VII), with a mean age of 9.54 years and 137 (76.11%) males, were included in analysis. The mean age at first visit to a medical doctor for MPS related symptoms was 3.65 ± 2.58 years old, while only 12 patients (6.67%) were diagnosed on their first visit. The mean diagnostic delay, which is defined as the time between the first visit to a medical doctor for MPS related symptoms and the final diagnosis, was 9.42 months, with no significant difference between types. The average number of misdiagnosis was 4.56. Before the confirmed diagnosis, the patients made an average of 6.31 visits and visited 4.3 hospitals. During diagnosis period, the mean of ¥81,086.72 direct medical costs accounted for 63.75% of the total cost. Only 32.78% of the patients had ever received specific treatments. The mean scores of PedsQL and SF-36 of patients were significantly lower than the Chinese norms. Household annual income per person, specific treatment use and MPS subtype were significantly associated HRQoL of patients. Conclusion The results highlight challenges faced by MPS patients in terms of diagnosis, access to specific treatments, economic burden and low HRQoL. There is an urgent need to improve early detection and diagnosis, create fair and consistent mechanisms to increase access to specialized treatment and reduce the economic burden of MPS patients in China.

Objectives: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. Methods: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. Results: In total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. Conclusions: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

Abstract Abnormalities in ether lipid metabolism as well as the formation of neutrophil extracellular traps have recently been recognized as detrimental factors affecting tumorigenesis and progression. However, the role of abnormal ether lipid metabolism in colorectal cancer (CRC) evolution has not been reported. Here we show that the lipid metabolism-related gene enoyl-CoA δ-isomerase 2 (ECI2) plays a tumor-suppressor role in CRC and is negatively associated with poor prognosis in CRC patients. We mechanistically demonstrate that ECI2 reduces ether lipid-mediated Interleukin 8 (IL-8) expression leading to decreased neutrophil recruitment and neutrophil extracellular traps formation for colorectal cancer suppression. In particular, ECI2 inhibits ether lipid production in CRC cells by inhibiting the peroxisomal localization of alkylglycerone phosphate synthase (AGPS), the rate-limiting enzyme for ether lipid synthesis. These findings not only deepen our understanding of the role of metabolic reprogramming and neutrophil interactions in the progression of CRC, but also provide ideas for identifying potential diagnostic markers and therapeutic targets for CRC.

IntroductionThe emergence of the wide variety of novel tigecycline resistance tet(X) variants, including tet(X3), tet(X4), tet(X5), and tet(X6), has raised a serious threat to global public health and posed a significant challenge to the clinical treatment of multidrug-resistant bacterial infections.MethodsIn this study, we evaluated the synergism of tigecycline combining with other antibiotics as a means of overcoming the tet(X)-mediated resistance in Acinetobacter spp. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments, time-kill assays and dose–response curves. The in vivo synergistic effect of the combination was confirmed in a mouse model of thigh with neutrophilic granulocyte reduction. Additionally, combinations were tested for their ability to prevent high-level tigecycline-resistant mutants.ResultsWe found that the combinations of tigecycline with apramycin exhibited synergistic activity against tet(X)-harboring Acinetobacter spp. with FICI of 0.088. The MICTGC decreased more than 5 times in the presence of subinhibitory levels of apramycin. The combination showed in vitro synergism in time-kill assays and in vivo therapeutic effectiveness in the mouse thigh infection model.DiscussionThis study shed light on the synergism of tigecycline in combination with apramycin which offers a viable therapeutic alternative for infections caused by tet(X)-harboring Acinetobacter spp.

ABSTRACT Chromosomal trisomy syndrome is associated with diverse clinical phenotypes, including intellectual disability. Partial trisomy of the distal 17q is a rare anomaly with similar clinical features, including psychomotor and growth deficits, facial dysmorphism, and microcephaly. Here, we describe three patients from two unrelated families with terminal trisomy 17q. We performed G‐banding karyotype and chromosomal microarray analyses. The child in Family 1 had a 31.3 Mb mosaic duplication on chromosome 17. Family 2 comprised dizygotic twins with a 263 kb deletion on chromosome 15 and a 9.2 Mb duplication on chromosome 17; however, normal karyotyping results were obtained for both parents. We also analyzed the genetic mechanisms underlying the occurrence of these chromosomal aberrations and summarized the literature describing known genotype–phenotype correlations. Given the rarity of partial trisomy of terminal 17q, these cases will provide new insights into the diagnosis of this condition and genotype–phenotype correlations, which can aid in the detection of such conditions and genetic counseling.

Abstract The accumulation of lactate is a rising risk factor for patients after flap transplantation. Endothelial‐to‐mesenchymal transition (EndoMT) plays a critical role in skin fibrosis. Nevertheless, whether lactate overproduction directly contributes to flap necrosis and its mechanism remain unknown. The current study reveals that skin flap mice exhibit enhanced PKM2 and fibrotic response. Endothelial‐specific deletion of PKM2 attenuates flap necrosis and ameliorates flap fibrosis in mice. Administration of lactate or overexpressing PKM2 promotes dysfunction of endothelial cells and stimulates mesenchymal‐like phenotype following hypoxia. Mechanistically, glycolytic‐lactate induces a correlation between Twist1 and p300/CBP, leading to lactylation of Twist1 lysine 150 (K150la). The increase in K150la promotes Twist1 phosphorylation and nuclear translocation and further regulates the transcription of TGFB1, hence inducing fibrosis phenotype. Genetically deletion of endothelial‐specific PKM2 in mice diminishes lactate accumulation and Twist1 lactylation, then attenuates EndoMT‐associated fibrosis following flap ischemia. The serum lactate levels of flap transplantation patients are elevated and exhibit predictive value for prognosis. This findings suggested a novel role of PKM2‐derived lactate in mediating Twist1 lactylation and exacerbates flap fibrosis and ischemia. Inhibition of glycolytic‐lactate and Twist1 lactylation reduces flap necrosis and fibrotic response might become a potential therapeutic strategy for flap ischemia.

Background The effect of microwave ablation (MWA) for the renal cell carcinoma (RCC) in Von Hippel-Lindau (VHL) disease is unclear.Objective To assess the safety, Technique efficacy, renal function and oncological outcome of MWA for RCC in VHL patients.Methods Consecutive patients with RCCs in VHL disease treated by MWA were retrospectively collected from November 2009 to October 2020. The technical efficacy rate and complications were assessed. The outcomes of pre- and post-ablative eGFR were compared. The local recurrent-free survival (LRFS), renal-cancer-free survival (RCFS), cancer-specific survival (CSS), overall survival (OS) and complications were presented.Results A total of 10 patients (mean age, 39.0 years ± 10.7 [SD]; 3 women) with 28 RCCs (mean tumor size, 3.0 cm ± 0.34; mean tumor volume, 20.7 mL ± 43.3) treated with MWA were included. Th median follow-up time was 52 months(IQR:27-80). The overall technical efficacy rate was 100% with no major complications occurred. No significant statistical difference between pre-ablative and postablative creatinine level (102.0 µmol/L ± 30.4 vs 112.3 µmol/L ± 38.7, p = 0.06), but the pre-ablative eGFR level was significantly higher than the post-ablative eGFR (78.0 mL/(min*1.73m2) ± 28.6 vs 72 mL/(min*1.73m2) ± 31.4, p = 0.04), with the mean decrease of 5.86 ml/(min*1.73m2). The local recurrent-free survival(LRFS) and renal-cancer-free survival (RCFS) were 100% and 60%, respectively. The cancer specifical survival (CSS) and overall survival (OS) were 95.5% and 100%, respectively.Conclusion Microwave ablation is a safe and feasible method for the treatment of RCC in VHL disease, preserving renal function and yielding satisfactory oncological outcomes.

BackgroundPerioperative ischemic stroke is a rare but devastating complication. Mechanical thrombectomy is a promising therapeutic method, but very little data is available on its efficacy and safety. This study aims to answer this question by comparing the clinical outcomes of perioperative and community-onset stroke patients after endovascular therapy.MethodsA retrospective cohort study was conducted on a total of 35 perioperative and 584 community-onset acute ischemic stroke patients who underwent endovascular thrombectomy at our hospital over the past 3.5 years. The recanalization rate, clinical recovery and cerebral hemorrhage within 90 days after therapy were compared between these two patient groups.ResultsEndovascular thrombectomy provided perioperative and community-onset ischemic stroke patients with comparable rates of successful reperfusion (mTICI ≥2b grade) (97.1% vs. 97.3%; p = 0. 967) and favorable functional recovery (mRS ≤ 2) (51.4% vs. 43.3%, p = 0.348), with no increase in severe intracranial hemorrhage (0% vs. 2.6 and 1.0%, for hematoma ≥30% of infarcted tissue and intraventricular hemorrhage, respectively) within 90 days. In addition, perioperative stroke patients had higher prevalence of atrial fibrillation (42.9% vs. 26.7%; p = 0.038) and intracranial cerebral artery stenosis without clear embolism (17.1% vs. 3.8%; p

Huanglongbing (HLB) and citrus canker, arising from Candidatus Liberibacter asiaticus (CaLas) and Xanthomonas citri pv. Citri (Xcc), respectively, have been imposing tremendous losses to the global citrus industry. Systemic acquired resistance (SAR) has been shown to be crucial for priming defense against pathogen in citrus. Salicylic acid (SA) binding protein 2 (SABP2), which is responsible for converting methyl salicylate (MeSA) to SA, is essential for full SAR establishment. Here, we characterized the functions of four citrus SABP2 genes (CsSABP2-1, CsSABP2-1V18A, CsSABP2-2 and CsSABP2-3) against HLB and citrus canker. In vitro enzymatic assay revealed that all four proteins had MeSA esterase activities, and CsSABP2-1 and CsSABP2-1V18A has the strongest activity. Their activities were inhibited by SA except for CsSABP2-1V18A. Four genes controlled by a strong promoter 35S were induced into Wanjincheng orange (Citrus sinensis Osbeck) to generate transgenic plants overexpressing CsSABP2. Overexpressing CsSABP2 increased SA and MeSA content and CsSABP2-1V18A had the strongest action on SA. Resistance evaluation demonstrated that only CsSABP2-1V18A had significantly enhanced tolerance to HLB, although all four CsSABP2s had increased tolerance to citrus canker. The data suggested the amino acid Val-18 in the active site of CsSABP2 plays a key role in protein function. Our study emphasized that balancing the levels of SA and MeSA is crucial for regulating SAR and conferring broad-spectrum resistance to HLB and citrus canker. This finding offers valuable insights for enhancing resistance through SAR engineering.

Background Risk factors for recovery from oculomotor nerve palsy (ONP) after aneurysm surgery explored by meta-analysis. Methods The PubMed, Embase, web of science, Cochrane library, China Knowledge, Wan fang, and VIP databases were searched for case-control or cohort studies on risk factors of oculomotor nerve palsy recovery after aneurysm surgery, with a cut-off date of 14 February 2024, and data were analyzed using Stata 15. Result A total of 12 articles involving 866 individuals were included, meta-analysis results suggesting that gender (OR = 0.75, 95% CI [0.51–1.10]), age (OR = 1.00, 95% CI [0.93–1.07]), aneurysm size (OR = 0.85, 95% CI [−0.71 to 1.01]), treatment time (OR = 1.01, 95% CI [0.91–1.13]) is not a risk factor for recovery of motor nerve palsy after aneurysm surgery. Preoperative complete ONP (OR = 2.27, 95% CI [1.07–4.81]), surgery (OR = 9.88, 95% CI [2.53–38.57]), subarachnoid hemorrhage (OR = 1.29, 95% CI [1.06–1.56]) is a risk factor for recovery of motor nerve palsy after aneurysm surgery. Conclusion Based on the results of the studies we included, we found that complete ONP before surgery led to poorer recovery, but patients with post-operative and subarachnoid hemorrhage had better recovery.

Prenatal diagnosis is crucial for pregnancies from couples with a carrier of a balanced translocation. We retrospectively reviewed 195 pregnancies from 189 couples with a balanced translocation carrier. Of these, 126 were from natural conception, while 69 were conceived through assisted reproductive technology (ART) with preimplantation genetic diagnosis (PGD). Both single nucleotide polymorphism (SNP) array analysis and conventional karyotyping were conducted on all pregnancies, and karyotype-visible imbalances and pathogenic/likely pathogenic copy number variations (CNVs) were categorized as clinically significant abnormalities. In natural conception group, couples with a female carrier experiencing more than two miscarriages accounted for 30.2 %, significantly higher than the 14.0 % in male carrier couples (p

Abstract In this paper, we prove that for certain class of initial data, the corresponding solutions to the 3-D viscous primitive equations blow up in finite time. Specifically, we find a special solution to simplify the 3-D systems, assuming that the pressure function p ( x , y , t ) $p(x,y,t)$ is a concave function. We also consider the equations on the line x = 0 $x=0$ , y = 0 $y=0$ .

Background: The obesity paradox in patients with coronary artery disease is well established, but the role of the metabolic syndrome associated with obesity is not well studied. Our study aims to evaluate the in-hospital outcomes of percutaneous coronary intervention (PCI) in metabolically healthy individuals with obesity (MHO) and metabolically unhealthy (MUHO) individuals with obesity over 65 years of age with acute coronary syndrome (ACS) between 2016 and 2020. Methods: This was a retrospective and observational study. Patients were identified through utilizing the National Inpatient Sample (NIS) Database (2016–2020) and ICD-10 codes. By employing a t-test and Pearson's Chi-square test, we assessed and contrasted the initial attributes, concurrent conditions, and results pertaining to all-cause mortality (ACM), cardiogenic shock (CS), length of stay (LOS), and hospitalization expense. Moreover, propensity score matching was conducted in a 1:1 ratio with respect to age, gender, and race. We also utilized multivariable logistic regression to compare MHO and MUHO in terms of the impact on all-cause mortality. Results: Out of a total of 135,395 patients identified, 2995 patients with MUHO were matched with 2995 MHO patients. Patients in the MUHO group had a higher prevalence of chronic pulmonary disease (24.9 % vs. 19.5 %), peripheral vascular disease (9.3 % vs. 6.7 %), hypothyroidism (16 % vs. 11.5 %), prior myocardial infarction (15.9 % vs. 6.2 %), and prior stroke (7.5 % vs. 2.8 %). Patients in the MHO group had a higher ACM (12.4 % vs. 2.8 %, p

BackgroundAlthough the emerging NGS-based assays, metagenomic next-generation sequencing (mNGS) and targeted next-generation sequencing (tNGS), have been extensively utilized for the identification of pathogens in pulmonary infections, there have been limited studies systematically evaluating differences in the efficacy of mNGS and multiplex PCR-based tNGS in bronchoalveolar lavage fluid (BALF) specimens.MethodsIn this study, 85 suspected infectious BALF specimens were collected. Parallel mNGS and tNGS workflows to each sample were performed; then, we comparatively compared their consistency in detecting pathogens. The differential results for clinically key pathogens were confirmed using PCR.ResultsThe microbial detection rates of BALF specimens by the mNGS and tNGS workflows were 95.18% (79/83) and 92.77% (77/83), respectively, with no significant difference. mNGS identified 55 different microorganisms, whereas tNGS detected 49 pathogens. The comparative analysis of mNGS and tNGS revealed that 86.75% (72/83) of the specimens were complete or partial concordance. Particularly, mNGS and tNGS differed significantly in detection rates for some of the human herpesviruses only, including Human gammaherpesvirus 4 (P

Miura origami's reconfigurable characteristic and structural asymmetry, combined with electromagnetic (EM) wave manipulation, crashed a unique spark. However, the complexity of the three‐dimensional (3D) origami structure after folding makes it challenging to study the phase regulation mechanism. Here, we propose a reconfigurable phase gradient metasurface based on Miura origami and derive the underlying mechanism of phase modulation in detail under linearly and circularly polarized (LP and CP) incidence. We adopt the one‐dimensional (1D) gradient design along the x direction to verify the idea. The phase calculation formulas are given under LP and CP incidence through the Jones matrix's derivation. The beam deflector angles corresponding to LP and CP waves are identical in the planar state. As the folding angle increases, the phase evolution rules corresponding to the LP and CP waves are discrepant, leading to differential beam steering. Finally, the origami sample is processed for verification, and the experimental data are consistent with the simulation and theoretically calculated values. We believe this work can help analyze the EM behavior of complex 3D origami structures and lay a foundation for designing a multifunctional EM origami metasurface.

BackgroundBile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks.MethodsIn this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology.Results(1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets.ConclusionThis study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

BackgroundTumor microenvironment (TME) represents the key factor inducing leukemia development. As stromal cells within the leukemia microenvironment, Bone Marrow Mesenchymal Stem Cells (BM-MSCs) can trigger leukemia progression under certain conditions. As a critical transcription factor, nuclear factor erythroid related factor 2 (Nrf2) can modulate antioxidant response and antioxidant enzyme gene expression, and prevent various oxidative changes. We previously identified a novel mechanism by which Nrf2 promotes leukemia resistance, providing a potential therapeutic target for the treatment of drug-resistant/refractory leukemias. However, the role of Nrf2 in BM-MSCs from B-cell acute lymphoblastic leukemia (B-ALL) patients has not been clearly reported. The present work focused on investigating the effect of Nrf2 overexpression within MSCs on leukemia cell invasion, extramedullary infiltration and proliferation as well as its downstream pathway.MethodsThrough clinical sample detection, in vitro cell experiments and in vivo animal experiments, the role of Nrf2 within MSCs within adult B-ALL cell migration and invasion and its potential molecular mechanism was explored through transcriptome sequencing analysis, RT-PCR, Western blot, cell migration, cell invasion, lentivirus transfection and other experiments.ResultsNrf2 was highly expressed in BM-MSCs from patients with B-ALL as well as in BM-MSCs co-cultured with leukemia cells. Overexpression of Nrf2 within MSCs significantly promoted leukemia cell migration, invasion and proliferation. The extramedullary organ infiltration rate in B-ALL model mice receiving the combined infusion of both cell types dramatically increased relative to that of leukemia cells alone, accompanied by the significantly shortened survival time. Mechanism study found that Nrf2 overexpression within MSCs promoted PI3K-AKT/ERK1/2 phosphorylation in the downstream pathway by activating SDF-1/CXCR4 axis, ultimately leading to extramedullary infiltration of leukemia cells.ConclusionHigh Nrf2 expression with in MSCs enhances leukemia cell invasion and migration, which then accelerates infiltration in leukemic extramedullary organs. Targeting Nrf2 or inhibiting its downstream signal molecules may be the effective interventions for B-ALL patients treatment.

Abstract Background Multiple myeloma (MM) is the second most common refractory hematologic cancer. Searching for new targets and prognostic markers for MM is significant. Methods GSE39754, GSE6477 and GSE24080 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in MM versus healthy people from GSE39754 and GSE6477 were screened using limma package, and MM-related module genes were chosen with the use of Weighted gene co-expression network analysis (WGCNA), and the two were intersected using ggVennDiagram for obtaining MM-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Then, protein–protein interactions (PPI) analysis in String database was used to obtain hub genes, while prognosis was analyzed by survival package in GSE24080. Receiver operating characteristic (ROC) curve was adopted for evaluating diagnostic value of hub genes. Besides, univariable/multivariable Cox regression were employed to screen independent prognostic biomarkers. Gene set enrichment analysis (GSEA) was used to find possible mechanism. Finally, western-blotting and reverse transcription-polymerase chain reaction (RT-PCR) verify TYROBP expression within MM and healthy people. We performed cell adhesion and transwell assays for investigating TYROBP function in MM cell adhesion and migration. Results Through differential analyses, 92 MM-related DEGs were obtained. 10 hub genes were identified by PPI and CytoHubba. Their diagnostic and prognostic significance was analyzed. Down-regulation of genes like TYROBP, ELANE, MNDA, and MPO related to dismal MM prognosis. Upon univariable/multivariable Cox regression, TYROBP independently predicted MM prognosis. GSEA pathway was enriched, indicating that TYROBP expression affected MM development via cell adhesion molecular pathway. Upon Western-blotting and RT-PCR assays, TYROBP expression among MM patients decreased relative to healthy donors. Cell adhesion and transwell migration assays revealed increased MM cell adhesion and decreased migration upon TYROBP up-regulation. Conclusion In summary, TYROBP is a potential prognostic marker for MM.

Food intake disorders are costly to treat, with an increasing prevalence over the years, and a higher risk of mortality compared to other psychiatric disorders. Avoidant/restrictive food intake disorder (ARFID) , as a relatively new type of food intake disorder, is more prevalent in children and adolescents than in other age groups, affecting their normal growth and development, as well as psychosocial functioning. Currently, there are more foreign studies, while domestic studies are still in the initial stage. Therefore, this paper reviews assessment tools, influencing factors and treatment approaches for ARFID in children and adolescents, with the aim of providing a reference for related research in China.

Background Pulmonary hypertension (PH) is often caused by left heart disease (group 2 PH) , which is difficult to diagnose early and with a high mortality rate. Potassium channel dysfunction is a marker of PH, however, the epidemiological data of the disease and the effect of potassium ions on PH still remain unclear. Objective To investigate the correlation of serum potassium level with myocardial markers, echocardiographic indicators and length of hospital stay in patients with group 2 PH, and evaluate the predictive value of serum potassium levels for the severity of group 2 PH, so as to provide the oretical basis for clinical diagnosis and treatment. Methods The clinical data of 400 adult inpatients diagnosed with group 2 PH in the First Hospital of Shanxi Medical University from January 2020 to December 2021 were retrospectively collected as follows: (1) general data: gender, age, BMI, length of hospital stay, smoking status, smoking index (SI) and drinking history; (2) underlying diseases (diabetes mellitus, hypertension) ; (3) laboratory data: serum potassium level, myocardial markers[procalcitonin, N-terminal pro-brain natriuretic peptide (NT-proBNP) , cardiac troponin I, cardiac troponin T, creatine kinase-MB], echocardiographic indicators (left atrial diameter, right ventricular diameter, right atrial area, left ventricular ejection fraction, shortening fraction, peak tricuspid regurgitation velocity, pulmonary artery systolic pressure) . The patients were divided into 5.5 mmol/L group (n=3) according to the serum potassium level. Spearman correlation analysis was used to explore the correlation of serum potassium level with myocardial markers and echocardiographic indicators. Log-rank (Mantel-Cox) test was used to compare the discharge rate of patients with different serum potassium levels. Receiver operating characteristic curve (ROC curve) was plotted to evaluate the predictive value of serum potassium level for the severity of group 2 PH. Results Procalcitonin and NT-proBNP levels of patients in the >5.5 mmol/L group were significantly higher than the 5.5 mmol/L to investigate its relationship with length of hospital stay in depth. Log-rank (Mantel-Cox) testresults showed that for group 2 PH patients greater than average hospitalization levels, there was a significant difference in cumulative hospitalization rates among patients with different serum potassium levels (5.5 mmol/L) (P=0.022) . ROC analysis showed that the diagnostic value of serum potassium level for non-mild PH (AUC=0.577, cut-off value=3.91 mmol/L, sensitivity=64.7%, specificity=52.5%) was similar to that of NT-proBNP (AUC=0.585, cut-off value=1 070.69 pg/mL, sensitivity=78.1%, specificity=39.6%) , which can effectively predict the severity of group 2 PH. Conclusion Serum potassium level can predict the severity of group 2 PH and the length of hospital stay. Intervention of serum potassium levels may be one of the new approach to prevent and treat PH.

Abstract Tumor necrosis factor receptor‐associated factor 5 (TRAF5) has been implicated in the pathogenesis of human malignancies. This work aimed to clarify the role of TRAF5 in lung adenocarcinoma (LUAD) progression. Herein, we uncovered that TRAF5 level was reduced in LUAD tissues. Low TRAF5 expression correlated with dismal prognosis in LUAD patients. Moreover, upregulated TRAF5 impeded cell viability, migration, and invasion, induced apoptosis in vitro, as well as impaired tumorigenicity in vivo. However, depletion of TRAF5 revealed opposing results. Moreover, TRAF5 was identified as the downstream target of methyltransferase‐like 3 (METTL3)‐elicited N6‐methyladenosine (m6A) modification. METTL3 stabilized TRAF5 mRNA and positively modulated TRAF5 level. Further, TRAF5 depletion relieved the repressive phenotype caused by METTL3 addition. In addition, it was manifested that the METTL3/TRAF5 axis served as an inhibitor in LUAD through the PI3K/AKT/Nuclear Factor‐Kappa B (NF‐κB) signaling. Collectively, we propose that METTL3‐mediated TRAF5 m6A modification exerted as a vital tumor inhibitory function in LUAD development. The METTL3/TRAF5 axis may be a critical effector of LUAD progression.

To propose a sensory evaluation method suitable for Qingzhuan tea, a representative Qingzhuan tea produced in Hubei was soak or spray boiled in order to analyze the effects of different boiling conditions on the sensory quality and the leaching rate of major chemical components of Qingzhuan tea. The sensory quality and chemical components of the tea infusions were compared with those of tea infusion obtained by the brewing method specified in the Chinese national standard. The results showed that the sensory quality of the boiled tea infusion was significantly better than that of the brewed tea infusion; the leaching rates of major quality components such as water extract, tea polyphenols, amino acids, soluble sugars and tea pigments were much higher in the former than in the latter. From the perspectives of sensory quality and the leaching rate of major quality components, tea infusion prepared by boiling for 2 min with a tea/water ratio of 1:80 and then standing for 2–4 min tasted moderate and had good internal quality. Further correlation analysis showed high correlation coefficients between the leaching rates of soluble sugars, theabrownine and water extract and taste quality. The results of this study provide a reference for the objective evaluation of the sensory quality of Qingzhuan tea and other types of compressed tea.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Drought is one of the most serious abiotic stresses in citrus plantations. It is thus imperative to fully understand the drought-resistant mechanisms in these plants. Here, RNA-seq was used to analyze the transcriptomic changes in the roots of Poncirus trifoliata, a widely used rootstock in citrus plantations, under a 72-day soil drought and a 7-day recovery stage. Our results showed that the genes upregulated under drought were only enriched in the galactose metabolism and protein processing in endoplasmic reticulum pathways. In the galactose metabolism pathway, four genes related to the synthesis of raffinose family oligosaccharides, which act as osmoprotectants and ROS scavengers, were significantly upregulated under long-term drought. Several heat-shock protein (HSP) family genes were significantly upregulated under drought, leading to increased levels of HSPs to alleviate the endoplasmic reticulum-associated degradation of misfolded proteins induced by drought stress. Some other upregulated genes under drought, like late embryogenesis-abundant family genes and lipid transfer protein family genes, might also be crucial to the drought resistance of P. trifoliata roots. MSYJ196370 (heat-shock factor family gene) was the top hub gene in the protein–protein interaction analysis of upregulated genes under drought. These findings supplement the transcriptomic response of P. trifoliata root under long-term drought stress.

The digital economy enhances economic efficiency and improves economic structure, driving economic growth through transformations in efficiency, momentum, and quality. It has become a new driving force for advancing common prosperity. This study uses SDM, SDID, and SPSTR models to explore the impact of digital economy on common prosperity, which constructs the index system to evaluate the common prosperity from process index and outcome index. According to the panel data of 76 cities in the Yellow River Basin from 2011 to 2021, and the findings are as follows: (1) The digital economy exhibits a development pattern characterized by high activity downstream and lower activity upstream, and the development trend is stable. The development pattern of common prosperity has changed from sporadic distribution to regional agglomeration, and the level of common prosperity in most cities has improved. (2) The digital economy has a significant positive spatial effect on common prosperity. And the findings are robust after introducing the “Big Data” exogenous policy impact, dynamic SDM model, and other methods. Moreover, spatial heterogeneity exists. The promotion effect in the upper and lower reaches is stronger, while the middle reaches are weakly affected by the digital economy. (3) The spatial spillover effect of the digital economy on common prosperity has a boundary, and the positive spillover reaches a maximum value at 600–650 km. (4) Nonlinear analysis confirms that the digital economy provides momentum for common prosperity industrial structure optimization that can effectively stimulate the “endogenous” growth mechanism, strengthen the marginal increasing effect of the digital economy driving common prosperity and enhance the effect of “making a bigger pie”. The digital economy makes effective use of digital resources and technologies, promotes the equalization of public services, exerts a positive impact on the realization of common prosperity, and consolidates the effect of “dividing a better cake”.

Sound is an important medium of communication among insects. Some longhorn beetles produce sounds during their daily activities, and these sounds play a role in courtship, predation, and defense. However, whether there are differences in the sounds emitted by longhorn beetles and how to distinguish and recognize these sounds have not been investigated in detail. Here, the sounds of Glenea cantor (Fabricius), Moechotypa diphysis (Pascoe), and Psacothea hilaris (Pascoe) were collected, and the differences in their stridulatory organs were observed and compared using scanning electron microscopy (SEM). The characteristics of their sounds were analyzed using MATLAB. Linear prediction cepstral coefficients (LPCC) and Mel frequency cepstral coefficients (MFCC) were used to extract the sound features, and the support vector machine (SVM) model was used to identify the sounds of three species. The results showed that the stridulatory organs of three species of longhorn beetles differed in morphology and time domain, and the combination of MFCC and SVM had a better recognition ability. The difference in the stridulatory organs of longhorn beetles may be an important reason for the differences in the sounds they produce, and we discussed the application of insect sounds in insect classification.

Objective To explore the mediating role of coping methods between the parental care burden and quality of survival in school-aged asthma children.Methods Using the method of convenient sampling, the parents of school-age asthmatic children in pediatric clinics of three first-class hospitals in Sichuan Province from January 2021 to July 2021 were selected as the research objects. The general information questionnaire, the parents' coping style scale, the caregiver's burden questionnaire, and the short form of the quality of life measurement scale were used to investigate. Structural equation modeling was used to examine the mediating relationship among coping style, caregiver burden, and quality of life.Results A total of 380 questionnaires were collected in this study, of which 366 were valid questionnaires, with an effective rate of 96.3%. The average age of parents was (34.37±5.08) years old, and the average age of children was (7.71±1.70) years old. The average total scores of the caregiver burden scale, coping style scale, and quality of life measurement scale of parents of school-age asthmatic children were (29.56±17.42) points, (163.58±26.47) points, and (88.81±13.29) points; the caregiver burden of parents of school-age asthmatic children There is a pairwise correlation with coping style and quality of life (P < 0.05). Coping style (seeking social support, maintaining self-esteem and psychological stability) plays a partial mediating role in the relationship between caregiver burden and quality of life, with a mediating effect value of 15.1%.Conclusion School-age asthma children parents quality of survival is not optimistic, caregivers burden overall low burden, overall response in the medium level, coping (seek social support, maintain self-esteem and psychological stability) in school-age asthma parents intermediary burden and quality of survival, suggested that based on this path intervention children parents coping and caregivers burden, to improve the quality of survival.

Abstract Objective The purpose of this study is to reduce the spread of the vanA gene by curing the vanA-harboring plasmid of vancomycin-resistant using the CRISPR-Cas9 system. Methods Two specific spacer sequence (sgRNAs) specific was designed to target the vanA gene and cloned into plasmid CRISPR-Cas9. The role of the CRISPR-Cas system in the plasmid elimination of drug-resistance genes was verified by chemically transformation and conjugation delivery methods. Moreover, the elimination efficiency in strains was evaluated by plate counting, PCR, and quantitative real-time PCR (qPCR). Susceptibility testing was performed by broth microdilution assay and by Etest strips (bioMérieux, France) to detect changes in bacterial drug resistance phenotype after drug resistance plasmid clearance. Results In the study, we constructed a specific prokaryotic CRISPR-Cas9 system plasmid targeting cleavage of the vanA gene. PCR and qPCR results indicated that recombinant pCas9-sgRNA plasmid can efficiently clear vanA-harboring plasmids. There was no significant correlation between sgRNA lengths and curing efficiency. In addition, the drug susceptibility test results showed that the bacterial resistance to vancomycin was significantly reduced after the vanA-containing drug-resistant plasmid was specifically cleaved by the CRISPR-Cas system. The CRISPR-Cas9 system can block the horizontal transfer of the conjugated plasmid pUC19-vanA. Conclusion In conclusion, our study demonstrated that CRISPR-Cas9 achieved plasmid clearance and reduced antimicrobial resistance. The CRISPR-Cas9 system could block the horizontal transfer of plasmid carrying vanA. This strategy provided a great potential to counteract the ever-worsening spread of the vanA gene among bacterial pathogens and laid the foundation for subsequent research using the CRISPR-Cas9 system as adjuvant antibiotic therapy.

Abstract Radar target detection with fewer echo pulses in non-Gaussian clutter background is a challenging problem. In this instance, the conventional detectors using coherent accumulation are not very satisfactory. In contrast, the matrix detector based on Riemannian manifolds has shown potential on this issue since the covariance matrix of radar echo data during one coherent processing interval(CPI) has a smooth manifold structure. The Affine Invariant (AI) Riemannian distance between the cell under test (CUT) and the reference cells has been used as a statistic to achieve improved detection performance. This paper uses the Bures–Wasserstein (BW) distance and Generalized Bures–Wasserstein (GBW) distance on Riemannian manifolds as test statistics of matrix detectors, and propose relevant target detection method. Maximizing the GBW distance is formulated as an optimization problem and is solved by the Riemannian trust-region (RTR) method to achieve enhanced discrimination for target detection. Our evaluation of simulated data and measured data show that the matrix detector based on GBW distance leads to a significant performance gain over existing methods.

Introduction: Osteoporosis is the most common bone disorder where the hyperactive osteoclasts represent the leading role during the pathogenesis. Targeting hyperactive osteoclasts is currently the primary therapeutic strategy. However, concerns about the long-term efficacy and side effects of current frontline treatments persist. Alternative therapeutic agents are still needed. Objectives: Obacunone (OB) is a small molecule with a broad spectrum of biological activities, particularly antioxidant and anti-inflammatory effects. This study aims to examine OB’s therapeutic potential on osteoporosis and explore the rudimentary mechanisms. Methods: Osteoclast formation and osteoclastic resorption assays were carried out to examine OB’s inhibitory effects in vitro, followed by the in-vivo studies of OB’s therapeutic effects on ovariectomy-induced osteoporotic preclinical model. To further study the underlying mechanisms, mRNA sequencing and analysis were used to investigate the changes of downstream pathways. The molecular targets of OB were predicted, and in-silico docking analysis was performed. Ligand-target binding was verified by surface plasmon resonance (SPR) assay and Western Blotting assay. Results: The results indicated that OB suppressed the formation of osteoclast and its resorptive function in vitro. Mechanistically, OB interacts with macrophage migration inhibitory factor (MIF) which attenuates receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced signaling pathways, including reactive oxygen species (ROS), NF-κB pathway, and mitogen-activated protein kinases (MAPKs). These effects eventually caused the diminished expression level of the master transcriptional factor of osteoclastogenesis, nuclear factor of activated T cells 1 (NFATc1), and its downstream osteoclast-specific proteins. Furthermore, our data revealed that OB alleviated estrogen deficiency-induced osteoporosis by targeting MIF and thus inhibiting hyperactive osteoclasts in vivo. Conclusion: These results together implicated that OB may represent as a therapeutic candidate for bone disorders caused by osteoclasts, such as osteoporosis.

Heavy metal contamination has been regarded as an environmental variable that affects the efficiency of pest biological control, but the parasitic fitness of parasitoids under heavy metal stress is poorly understood. Herein, the effect of Cd exposure through the host pupa of Hyphantria cunea on the parasitic fitness of Chouioia cunea was investigated, and the mechanism by which Cd exposure affects the interaction between H. cunea and C. cunea from the perspective of innate immunity in host insect and the oxidative status in the parasitoid offspring was explored. Our results indicated that Cd can be transferred from the H. cunea pupae to the parasitoid offspring, and the transfer coefficient reflected biological amplification. There were no significant differences in the rates of parasitism success and offspring emergence between the untreated and Cd-treated groups. However, after parasitizing Cd-accumulated pupae, the parasitic fitness of offspring wasps (e.g., the number, individual size and life span) decreased significantly. Under Cd exposure, the cellular and humoral immunity of H. cunea pupae decreased significantly. Compared with the untreated group, the H2O2 content of parasitoid offspring in the Cd-treated group was significantly increased. Cd exposure significantly inhibited superoxide dismutase activity in parasitoid offspring, but the contents of ascorbic acid and glutathione were significantly increased by Cd stress. Taken together, these results indicate that Cd exposure reduces the cyclic utilization efficiency of C. cunea on H. cunea pupae. The oxidative status of parasitoid offspring triggered by Cd exposure could be responsible for the reduced parasitic fitness of C. cunea on Cd-accumulated H. cunea pupae.

Abstract Mounting evidence indicate that cuproptosis, a novel form of programmed cell death, contributes to cancer development and progression. However, a comprehensive analysis regarding the expressions, functions, and regulatory network of cuproptosis-related genes is still lacking. In the present work, cuproptosis-related genes, upstream miRNAs and lncRNAs, and clinical data of breast cancer from TCGA database were analyzed by R language including Cox regression analysis, correlation calculation, ROC curve construction, and survival evaluation, and were further verified by public-available databases. Chemosensitivity and immune infiltration were also evaluated by online tools. SLC31A1 was significantly increased in breast cancer samples than those in normal tissues. SLC31A1 was negatively related to a favorable outcome in breast cancer, and the AUC value increased with the prolongation of follow-up time. LINC01614 and miR-204-5p were potential upstream regulators of SLC31A1. Moreover, SLC31A1 was significantly positively correlated with different immune cells infiltration, immune cell biomarkers, and immune checkpoints in breast cancer. SLC31A1 was a potential cuproptosis-related gene in breast cancer, which was significantly upregulated and was able to predict diagnosis, prognosis, chemosensitivity, and immune infiltration. LINC01640/miR-204-5p/SLC31A1 might be a significant and promising axis during cuproptosis in breast cancer.

Abstract The WUSCHEL-related homeobox (WOX) family members are plant-specific transcriptional factors, which function in meristem maintenance, embryogenesis, lateral organ development, as well as abiotic stress tolerance. In this study, 14 MsWOX transcription factors were identified and comprehensively analyzed in the cultivated alfalfa cv. Zhongmu No.1. Overall, 14 putative MsWOX members containing conserved structural regions were clustered into three clades according to phylogenetic analysis. Specific expression patterns of MsWOXs in different tissues at different levels indicated that the MsWOX genes play various roles in alfalfa. MsWUS, MsWOX3, MsWOX9, and MsWOX13-1 from the three subclades were localized in the nucleus, among which, MsWUS and MsWOX13-1 exhibited strong self-activations in yeast. In addition, various cis-acting elements related to hormone responses, plant growth, and stress responses were identified in the 3.0 kb promoter regions of MsWOXs. Expression detection of separated shoots and roots under hormones including auxin, cytokinin, GA, and ABA, as well as drought and cold stresses, showed that MsWOX genes respond to different hormones and abiotic stress treatments. Furthermore, transcript abundance of MsWOX3, and MsWOX13-2 were significantly increased after rhizobia inoculation. This study presented comprehensive data on MsWOX transcription factors and provided valuable insights into further studies of their roles in developmental processes and abiotic stress responses in alfalfa.