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Bacterial infections remain a significant global health concern, necessitating a comprehensive understanding of the intricate host−pathogen interactions that play a critical role in the outcome of infectious diseases. Recent investigations have revealed that noncoding RNAs (ncRNAs) are key regulators of these complex interactions. Among them, long noncoding RNAs (lncRNAs) have gained significant attention because of their diverse regulatory roles in gene expression, cellular processes and the production of cytokines and chemokines in response to bacterial infections. The host utilizes lncRNAs as a defense mechanism to limit microbial pathogen invasion and replication. On the other hand, some host lncRNAs contribute to the establishment and maintenance of bacterial pathogen reservoirs within the host by promoting bacterial pathogen survival, replication, and dissemination. However, our understanding of host lncRNAs in the context of bacterial infections remains limited. This review focuses on the impact of host lncRNAs in shaping host−pathogen interactions, shedding light on their multifaceted functions in both host defense and bacterial survival, and paving the way for future research aimed at harnessing their regulatory potential for clinical applications.

BackgroundChimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL.MethodsRelevant observational studies pertaining to the purpose of the meta-analysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between-study heterogeneity.ResultsFifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I2 = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I2 = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all < 0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05).ConclusionA high MTV at baseline is associated with a poor survival of NHL patients after CAR-T.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY (INPLASY202450069).

ObjectiveThis research aims to investigate the impact of omega-3 fatty acids supplementation on the lipid levels of pregnant women who have experienced pregnancy losses.MethodsThis retrospective study analyzed data from pregnant women with previous pregnancy losses from two medical centers. Their lipid profiles were measured at least twice during pregnancy. According to the use of omega-3 soft gel capsules, participants were divided into the omega-3 group and the control group. We assessed the relationship between omega-3 fatty acids supplementation and longitudinal lipid levels during pregnancy using generalized estimating equations (GEE). Subsequently, we conducted subgroup analyses to delineate the profile of beneficiaries who received omega-3 fatty acids based on body mass index (BMI), age, menstrual regularity, number of previous pregnancy losses, number of previous live births, and educational level.ResultsThe omega-3 group included 105 participants, while the control group comprised 274 participants. Women in the omega-3 group started supplementation between 3.43 and 17.14 weeks of gestation. According to GEE analysis, supplementing omega-3 fatty acids significantly reduced triglyceride (TG) levels during pregnancy (adjusted β = −0.300, 95% CI -0.445 to −0.154, p

BackgroundThe stress hyperglycemia ratio (SHR) has emerged as a potential prognostic indicator for various critical illnesses. However, its role in determining outcomes in patients with atrial fibrillation (AF) within the intensive care unit (ICU) remains unclear. This study aimed to elucidate the association between SHR and all-cause mortality in this clinical setting.MethodsWe conducted a retrospective cohort study utilizing data from a large, retrospective database. Critically ill patients with documented AF were stratified based on quartiles of SHR. The primary outcome was 365-day all-cause mortality, with secondary outcomes including 90-day and 28-day mortality. COX proportional hazards models adjusted for confounders and Kaplan-Meier curve analyses were used to explore the relationship between SHR and mortality.Results2,679 patients with critical AF were enrolled in the final study. Among the patients studied, those in the highest SHR quartiles exhibited an increased risk of 365-day all-cause mortality (HR:1.32, 95%CI=1.06-1.65). Notably, in subgroup analyses, the prognostic value of SHR was particularly pronounced in patients with hypertension. Sensitivity analyses confirmed the persistence of these findings after excluding cohorts with malignant tumors, and heart failure.ConclusionsOur research discerns a positive association between SHR and all-cause mortality in critically ill patients with AF, highlighting the significance of acute glycemic dysregulation on patient outcomes. Longer follow-up is still needed in the future to study the association between SHR and all-cause mortality in critically ill patients with AF.

Dairy mastitis is one of the most common diseases in dairy farming, and the formation of pathogenic bacteria biofilms may be an important reason why traditional antibiotic therapy fails to resolve some cases of dairy mastitis. We isolated and identified three strains of A. lwoffii were with strong biofilm forming ability from dairy cow mastitis samples from Chongqing dairy farms in China. In order to investigate the effect of novel anti-biofilm peptide CRAMP-34 on A.lwoffii biofilms, the anti-biofilm effect was evaluated by crystal violet staining, biofilms viable bacteria counting and confocal laser scanning microscopy (CLSM). In addition, transcriptome sequencing analysis, qRT-PCR and phenotypic verification were used to explore the mechanism of its action. The results showed that CRAMP-34 had a dose-dependent eradicating effect on A. lwoffii biofilms. Transcriptome sequencing analysis showed that 36 differentially expressed genes (11 up-regulated and 25 down-regulated) were detected after the intervention with the sub-inhibitory concentration of CRAMP-34. These differentially expressed genes may be related to enzyme synthesis, fimbriae, iron uptake system, capsular polysaccharide and other virulence factors through the functional analysis of differential genes. The results of subsequent bacterial motility and adhesion tests showed that the motility of A.lwoffii were enhanced after the intervention of CRAMP-34, but there was no significant change in adhesion. It was speculated that CRAMP-34 may promote the dispersion of biofilm bacteria by enhancing the motility of biofilm bacteria, thereby achieving the effect of eradicating biofilms. Therefore, these results, along with our other previous findings, suggest that CRAMP-34 holds promise as a new biofilm eradicator and deserves further research and development.

Objective: The purpose of this study is to analyze the inherent relationship between the score values and the biomechanical characteristics of the forward kicking motion, we aim to identify the fundamental variables influencing the score values of the forward kicking motion and establish the key biomechanical factors that effectively trigger scoring in the forward kicking motion.Methods: The DaeDo electronic scoring system was used with the Vicon optical motion capture system and the Kistler 3D force platform to obtain kinematic and kinetic variables of the front roundhouse kick motion. Linear bivariate correlation analysis and principal component analysis were used to analyze the associations between kinematic, kinetic variables, and scoring values, and summarize key biomechanical factors for effectively scoring.Results: The peak ankle plantar flexion angle and knee extension torque of the kicking leg showed a significant negative correlation with scoring values (r < 0, p < 0.05), while other variables showed no statistical significance. The peak knee flexion angle and hip extension angular velocity of the supporting leg showed a significant positive correlation with scoring values (r > 0, p < 0.01), while the peak ankle plantar flexion torque showed a significant negative correlation with scoring values (r < 0, p < 0.05), and other variables showed no statistically significant correlation. The absolute values of eigenvectors of the first and second principal components, which included hip angular velocity, ankle angle, knee torque, and hip torque, were relatively large, indicating their strong influence on effective scoring triggering.Conclusion: Maintaining ankle dorsiflexion and a larger knee flexion angle in the kicking leg is favorable for triggering scoring. Higher knee flexion angle and hip extension angular velocity in the supporting leg are also advantageous for triggering scoring. “Body posture” and “Strength” are key factors that effectively trigger scoring.

ObjectiveTo investigate self-stigma’s influence on schizophrenia patients’ quality of life and its mediated impact by various factors.MethodsThis study adopted a cross-sectional design and randomly selected 170 hospitalized patients with schizophrenia for evaluation. The assessment tools included the Positive and Negative Syndrome Scale (PANSS), Internalized Stigma of Mental Illness Scale (ISMI), Schizophrenia Quality of Life Scale (SQLS), and Coping Questionnaire for Schizophrenia Patients (CQSP), among others. Correlation analysis, regression analysis, and mediation analysis were used to test the correlation and mediation effects.ResultsSelf-stigma had a significant impact on quality of life (T = 8.13, p = 0.00). When self-stigma is used as a mediator, the problem-solving factor in coping strategies has an indirect effect on quality of life, which is significant (AB = -0.16, P = 0.02), while the avoidance factor in coping strategies has a direct effect on quality of life, which is significant (C’ = 0.54, p < 0.001), and an indirect effect, which is also significant (AB = 0.25, p < 0.001).ConclusionThe study highlights the significant impact of self-stigma on the quality of life of schizophrenia patients, emphasizing the crucial roles of self-esteem and coping strategies. These findings suggest clinical interventions to improve quality of life should focus on reducing self-stigma, especially enhancing self-esteem and promoting adaptive coping strategies. By addressing these factors, we can better support the mental health and well-being of those with schizophrenia, offering an effective approach to rehabilitation.

Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a multifactorial disease characterized by significant deterioration of bone microstructure and bone loss. Mg deficiency can affect bone structure in an indirect way through the two main regulators of calcium homeostasis (parathyroid hormone and vitamin D). In human osteoblasts (OBs), parathyroid hormone regulates the expression of receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) to affect osteoclast (OC) formation. In addition, Mg may also affect the vitamin D3 -mediated bone remodeling activity. vitamin D3 usually coordinates the activation of the OB and OC. The unbalanced activation OC leads to bone resorption. The RANK/RANKL/OPG axis is considered to be a key factor in the molecular mechanism of osteoporosis. Mg participates in the pathogenesis of osteoporosis by affecting the regulation of parathyroid hormone and vitamin D levels to affect the RANK/RANKL/OPG axis. Different factors affecting the axis and enhancing OC function led to bone loss and bone tissue microstructure damage, which leads to the occurrence of osteoporosis. Clinical research has shown that Mg supplementation can alleviate the symptoms of osteoporosis to some extent.

ObjectiveTo explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA).MethodsA child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition.ResultsA ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils.ConclusionThe diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

BackgroundThere are many problems of psychological burden in patients with tumor implanted in port of intravenous infusion. However, more attention is paid to its complications in the literature, and psychological problems are seldom concerned. The purpose of this study was to explore the psychological state and needs of tumor patients after implantation of an intravenous infusion port and provide valuable references for psychological interventions.MethodA semi-structured interview was conducted with 11 patients with intravenous infusion ports. Colaizzi’s 7-step analysis was used to analyze the interview data.ResultsAccording to the primary information, four themes and nine sub-themes were extracted: (1) lack of self-worth, (2) multiple emotional experiences (guilt, doubt, worry, and gain). (3) Poor self-management and self-maintenance awareness (over-reliance on medical staff, unchanged family roles, lack of related knowledge). (4) Expectations and suggestions for the future (inner expectations, suggestions for infusion ports).ConclusionThe patient’s psychological state should be carefully monitored during tube implantation, to relieve the patient’s tension and anxiety and improve nursing satisfaction and patient outcomes.

This study investigated whether abnormal peak inversion spontaneous potentials (PISPs) recorded at resting myofascial trigger points (MTrPs) stem from the discharge of muscle spindles. Forty-eight male Sprague-Dawley rats were randomly divided into six groups. Five groups underwent MTrP modeling intervention, whereas one group did not receive intervention and was duly designated as the blank control. After model construction, five rat models were randomly subjected to ramp-and-hold stretch tests, succinylcholine injection, eperisone hydrochloride injection, saline injection, and blank drug intervention. By contrast, the rats in the blank control group were subjected to ramp-and-hold stretch tests as a control. Frequencies and amplitudes of PISPs were recorded pre- and post-interventions and compared with those of the blank group. Stretch tests showed that the depolarization time and amplitude of PISPs ranged from 0.4 ms to 0.9 ms and from 80 uV to 140 μV, respectively. However, no PISPs were observed in the control rats. The frequency of PISPs in the ramp and hold phases and the first second after the hold phase was higher than that before stretching (p < 0.01). Succinylcholine and eperisone exerted excitatory and inhibitory effects on PISPs, respectively. In the group injected with 0.9% saline, no considerable differences of the PISPs were observed during the entire observation period. In conclusion, PISPs recorded at resting MTrPs are closely related to muscle spindles. The formation of MTrPs may be an important factor that regulate dysfunctional muscle spindles.

Kashin-Beck disease (KBD) is an endochondral osteogenesis disorder characterised by epiphysis damage and secondary deformable arthropathy induced by multiple external factors, among which selenium (Se) and iodine deficiency are important influencing factors. Iodine deficiency is usually accompanied by a low Se content in the soil in the KBD areas of China. Se can reverse oxidative damage to chondrocytes. In addition, Se is related to the bone conversion rate and bone mineral density. Low Se will hinder growth and change bone metabolism, resulting in a decrease in the bone conversion rate and bone mineral density. Thyroid hormone imbalance caused by thyroid dysfunction caused by iodine deficiency can damage bone homeostasis. Compared with Se deficiency alone, Se combined with iodine deficiency can reduce the activity of glutathione peroxidase more effectively, which increases the vulnerability of chondrocytes and other target cells to oxidative stress, resulting in chondrocyte death. Clinical studies have shown that supplementation with Se and iodine is helpful for the prevention and treatment of KBD.

BackgroundThe progress in Colorectal cancer (CRC) screening and management has resulted in an unprecedented caseload for histopathological diagnosis. While artificial intelligence (AI) presents a potential solution, the predominant emphasis on slide-level aggregation performance without thorough verification of cancer in each location, impedes both explainability and transparency. Effectively addressing these challenges is crucial to ensuring the reliability and efficacy of AI in histology applications.MethodIn this study, we created an innovative AI algorithm using transfer learning from a polyp segmentation model in endoscopy. The algorithm precisely localized CRC targets within 0.25 mm² grids from whole slide imaging (WSI). We assessed the CRC detection capabilities at this fine granularity and examined the influence of AI on the diagnostic behavior of pathologists. The evaluation utilized an extensive dataset comprising 858 consecutive patient cases with 1418 WSIs obtained from an external center.ResultsOur results underscore a notable sensitivity of 90.25% and specificity of 96.60% at the grid level, accompanied by a commendable area under the curve (AUC) of 0.962. This translates to an impressive 99.39% sensitivity at the slide level, coupled with a negative likelihood ratio of

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

BackgroundThe number of people with dementia is soaring. Cognitive reserve has been thought to be associated with dementia risk. It is not clear at which period in the life course and which cognitive reserve proxies contribute to the reduced risk of dementia.MethodsBy scanning four databases (PubMed, Embase, Web of Science, and MEDLINE) up to Jun 3, 2023, longitudinal studies of life-course cognitive reserve and risk of dementia were found. The HRs and 95% CIs for each study were summarized using random effects models. Subgroup analyses and sensitivity analyses were conducted. Utilizing funnel plots, Begg and Egger tests, publication bias was investigated.ResultsA total of 27 studies were included, containing 10 in early-life, 10 in middle-life, and 13 in late-life. All studies used validated questionnaires to measure cognitive reserve, and dementia diagnosis followed recognized worldwide guidelines. All included studies were of medium or low risk. Cognitive reserve in early-life (Hazard ratio (HR): 0.82; 95% confidence interval (CI): 0.79–0.86), middle-life (HR: 0.91; 95% CI: 0.84–0.98) and late-life (HR: 0.81; 95% CI: 0.75–0.88) all have protective effects on dementia risk. Multiple sensitivity analyses showed consistent results.ConclusionDementia risk is reduced by the buildup of cognitive reserves during life-course. Accumulation of proxies for cognitive reserve in early and late life had the greatest effect on dementia risk reduction. Social connection may be an effective approach to lower dementia risk.

PurposeThe debate over the causal and longitudinal association between cystatin C and stroke in older adults persists. Our aim was to assess the link between cystatin C levels, both measured and genetically predicted, and stroke risk.MethodsThis study employed a retrospective cohort design using samples of the China Health and Retirement Longitudinal Study (CHARLS), which is a nationally representative cohort recruiting individuals aged 45 years or above. A multivariate logistic model and the two-sample Mendelian randomization framework were used to investigate the longitudinal and genetically predicted effect of serum cystatin C on stroke.ResultsThe study population had a mean age of 59.6 (SD ±9.5), with 2,996 (46.1%) women. After adjusting for confounding factors, compared to those in the first quartile of cystatin C, those in the last quartile had the greatest risk of stroke incidence [odds ratio (OR), 1.380; 95% confidence interval (CI), 1.046–1.825]. The Mendelian randomization analysis showed that a genetically predicted cystatin C level was positively associated with total stroke (OR by inverse variance-weighted method, 1.114; 95% CI, 1.041–1.192).ConclusionsThis national cohort study suggests that higher serum cystatin C is associated with an increased risk of total stroke, which is further supported by Mendelian randomization.

IntroductionWith the help of robot technology, intelligent rehabilitation of patients with lower limb motor dysfunction caused by stroke can be realized. A key factor constraining the clinical application of rehabilitation robots is how to realize pattern recognition of human movement intentions by using the surface electromyography (sEMG) sensors to ensure unhindered human-robot interaction.MethodsA multilayer CNN-LSTM prediction network incorporating the self-attention mechanism (SAM) is proposed, in this paper, which can extract and learn the periodic and trend characteristics of the sEMG signals, and realize the accurate autoregressive prediction of the human motion information. Firstly, the multilayer CNN-LSTM network utilizes the CNN layer for initial feature extraction of data, and the LSTM network is used to improve the enhancement of the historical time-series features. Then, the SAM is used to improve the global feature extraction performance and parallel computation speed of the network.ResultsIn comparison with existing test is carried out using actual data from five healthy subjects as well as a clinical hemiplegic patient to verify the superiority and practicality of the proposed algorithm. The results show that most of the model’s prediction R > 0.9 for different motion states of healthy subjects; in the experiments oriented to the motion characteristics of patient subjects, the angle prediction results of R > 0.99 for the untrained data on the affected side, which proves that our proposed model also has a better effect on the angle prediction of the affected side.DiscussionThe main contribution of this paper is to realize continuous motion estimation of ankle joint for healthy and hemiplegic individuals under non-ideal conditions (weak sEMG signals, muscle fatigue, high muscle tension, etc.), which improves the pattern recognition accuracy and robustness of the sEMG sensor-based system.

Introduction:Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery.Methods:Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).Results:Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target.Conclusion:Unraveling DDIT4’s involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Melanoma is the most lethal type of skin cancer with an increasing incidence. Cuproptosis is the most recently identified copper-dependent form of cell death that relies on mitochondrial respiration. The hippocampal (Hippo) pathway functions as a tumor suppressor by regulating Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) activity. However, its role in cuproptosis remains unknown. In addition, the correlation of cuproptosis-related genes and Hippo pathway-related genes with tumor prognosis warrants further investigation. In the present study, we explored the correlation of cuproptosis-related genes and Hippo pathway-related genes with the prognosis of melanoma through analysis of data from a public database and experimental verification. We found eight Hippo pathway-related genes that were downregulated in melanoma and exhibited predictive value for prognosis. There was a significant positive correlation between cuproptosis-related genes and Hippo pathway-related genes in skin cutaneous melanoma. YAP1 expression was positively correlated with ferredoxin 1 (FDX1) expression in the GSE68599 dataset and A2058 cells. Moreover, YAP1 was positively and negatively correlated with M2 macrophages and regulatory T cell infiltration, respectively. In conclusion, the present study demonstrated the prognostic value of Hippo pathway-related genes (particularly YAP1) in melanoma, revealing the correlation between the expression of Hippo pathway-related genes and immune infiltration. Thus, the present findings may provide new clues on the prognostic assessment of patients with melanoma and a new target for the immunotherapy of this disease.

As the upstream region of the Asian summer monsoon, the Bay of Bengal summer monsoon (BOBSM) system has impacts on rainfall patterns in East Asia. In this study, we investigate the impact of the interannual variability of the BOBSM retreat on China precipitation in early summer (June) of the following year. When the BOBSM retreat occurs earlier in the previous year, we find enhanced rainfall in both the northeastern and eastern parts of China. Conversely, when the retreat of the BOBSM is delayed in the previous year, there is a tendency for decreased rainfall in most of northeastern and eastern China, while rainfall in the northern part of the Taiwan island region tends to increase. Statistical analysis demonstrates the co-variability between China’s June precipitation anomalies and preceding wind anomalies in the eastern Bay of Bengal. The results indicate a strong relationship between the preceding BOBSM retreat and China precipitation anomalies in the following June. Furthermore, the analysis suggests that the BOBSM retreat is more of an independent signal rather than modulated by an Indian Ocean Dipole event.

Background and objectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has broad tissue tropism and high transmission, which are likely to perpetuate the pandemic. The study aim to analyze the clinicopathogenic characteristics in paediatric patients.MethodsIn this single-centre study, we retrospectively included all confirmed cases infected by SARS-CoV-2 infection at Xi’an Children's Hospital, China, from 1 December to 31 December 2022. The demographic, clinical, laboratory, and radiological features of the patients were analysed.ResultsA total of 4,520 paediatric patients with SARS-CoV-2 omicron variant infections were included. Of these, 3,861 (85.36%) were outpatients, 659 (14.64%) were hospitalised patients, and nine patients (0.20%) died. Of the nine patients who died, five were diagnosed with acute necrotising encephalopathy (ANE). The most common symptoms were fever in 4,275 (94.59%) patients, cough in 1,320 (29.20%) patients, convulsions in 610 (13.50%) patients, vomiting in 410 (9.07%) patients, runny nose/coryza in 277 (6.13%) patients, hoarseness of voice in 273 (6.04%) patients. A blood cell analysis showed a slight elevation of monocytes (mean: 11.14 ± 0.07%). The main diagnoses for both outpatients and inpatients were respiratory infection with multisystem manifestations.ConclusionsA high incidence of convulsions is a typical characteristic of children infected with SARS-CoV-2. Five of the nine COVID-19 fatalities were associated with ANE. This indicates that nervous system damage in children with SARS-CoV-2 infection is more significant.

IntroductionThe risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (

BackgroundThe prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients’ leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients.MethodsPatients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model.ResultsThere are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts.ConclusionsThe CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

Objective: To explore the inherent relationship between lower limb biomechanical indicators and effective scoring values of double roundhouse kick (DRK) by taekwondo athletes, and to find key biomechanical factors that trigger effective scoring.Methods: Using the DAEDO Protector and Scoring System (PSS) in conjunction with the Vicon optical motion capture system and Kistler 3D force plate, kinematic and dynamic indicators of the front kicking motion were obtained from 12 professional taekwondo athletes (18.00 ± 2.20 years, 182.15 ± 8.62 cm and 70.00 ± 14.82 kg). The correlation between kinematics, dynamics, and scoring values was initially analyzed using bivariate linear correlation. Subsequently, based on the results of the linear correlation analysis, a stepwise regression analysis was performed to establish a stepwise regression equation.Results: The results reveal that during the First Hit, there is a significant positive correlation (r > 0, p < 0.05) between peak hip flexion angular velocity of the dominant leg, knee abduction angle, and peak foot horizontal plane linear velocity of the non-dominant leg with effective score. On the other hand, peak ankle flexion angular velocity of the non-dominant leg, peak foot sagittal plane linear velocity, peak hip abduction angle, and peak hip flexion angle of the dominant leg exhibit a significant negative correlation (r < 0, p < 0.05) with effective score. These correlations hold statistical significance (DW> 1.023). During the Second Hit, there is a significant positive correlation (r > 0, p < 0.05) between peak ankle internal rotation angular velocity of the dominant leg, foot coronal plane linear velocity, hip adduction angular velocity, and peak ankle internal rotation moment of the non-dominant leg with effective score. Conversely, peak hip flexion angle of the dominant leg shows a significant negative correlation (r < 0, p < 0.05) with effective score. All these variables have a statistically significant impact on effective score (DW > 1.023).Conclusion: Explosive power, body posture, adequate terminal velocity, and body rotation have an association with effective scoring of the electronic protector. The peak angular velocity of the ankle joint of the dominant leg and the peak linear velocity of the foot horizontal plane of the non-dominant leg significantly contribute to the effectiveness score of the electronic protector.

Nocardia species are gram-positive, acid-fast, saprophytic, aerobic bacilli, predominantly resulting in opportunistic infections in immunocompromised individuals. Here, we reported a case of Nocardia infection in a 27-year-old woman with normal immunocompetence, who presented as a solitary neoplasm in the left principal bronchus with a chief complaint of postural dyspnea. By electrotomy via bronchoscopy, the neoplasm was successfully removed, and it was further identified as Nocardia farcinica by metagenomic next-generation sequencing.

BackgroundThe relationship between weight change patterns and arthritis onset, specifically rheumatoid arthritis (RA) and osteoarthritis (OA), is unclear. We examined the association between weight changes from young adulthood to midlife and arthritis onset.MethodsUsing data from NHANES 1999–2018, participants with self-reported arthritis were selected. Age at diagnosis determined arthritis onset. Weight change patterns were based on BMI at age 25 and 10 years before the survey. Patterns were categorized as stable non-obese, non-obese to obese, obese to non-obese, and stable obese. Cox regression models and restricted cubic spline (RCS) analysis were employed, calculating hazard ratios (HRs) and 95% confidence intervals (CIs) considering covariates.ResultsOut of 20,859 participants (male 11,017, 52.82%), 4922 developed arthritis over a mean 8.66-year follow-up. Compared to stable non-obese individuals, the HRs for arthritis were 1.55 (95% CI=1.45 to 1.66, P < 0.0001) for non-obese to obese and 1.74 (95% CI=1.56 to 1.95, P < 0.0001) for stable obese. Those gaining 10-20 kg had a HR of 1.33 (95% CI=1.22 to 1.46, P < 0.0001), and gains >20 kg had a HR of 1.56 (95% CI=1.42 to 1.71, P < 0.0001), compared to stable weight (change within 2.5 kg). Identical results observed for OA and RA. RCS showed a nonlinear relationship between weight change and arthritis (all P < 0.01).ConclusionsStable obesity and weight gain during adulthood increase arthritis risk. Maintaining a non-obese weight throughout adult years might reduce arthritis risk in later life.

Objective: To compare the morphological and quantitative changes in pathological myopia (PM) and the perioperative changes in posterior scleral reinforcement (PSR) using three-dimensional magnetic resonance images (3D MRI).Methods: A total of 49 patients with high myopia (HM; 98 eyes), 15 with pathological myopia (PM; 19 eyes), and 10 without high myopia (NORM; 20 eyes) were recruited between September 2019 and July 2021. The patients underwent measurements of refractive error and axial length, as well as 3D MRI of the eyeball. Python was used to analyze the 3D MRI images, calculate the vitreous volume, establish a topography of the height of the eyeball posterior surface, and calculate the rate of change in height (H). For the PM group undergoing PSR, changes in vitreous volume and the highest point of the eyeball posterior surface in four quadrants (temporal, subtemporal, nasal, and subnasal) were compared before and after PSR.Results: The vitreous volume was smaller in the NORM group compared to the HM and PM groups (p < 0.01). The PM group had a larger volume than the HM group (p < 0.01). The H for the PM group was higher than that of the NORM and HM groups (p < 0.01). After PSR in the PM group, the total vitreous volume, as well as the volume in the subnasal and supratemporal quadrants, decreased (p < 0.05). Additionally, the highest point of the eyeball’s posterior surface was generally shifted to the upper nasal side. Finally, the shape and position of the scleral band after PSR were plotted.Conclusion: 3D MRI is capable of a quantitative description of the eyeball morphology in PM and PSR. It allows for precise calculations of changes in vitreous volume and the H of the posterior surface. It also facilitates a meticulous analysis of the specific details of the scleral band following PSR.

Metabolic reprogramming at a cellular level contributes to many diseases including cancer, yet few assays are capable of measuring metabolic pathway usage by individual cells within living samples. Here, autofluorescence lifetime imaging is combined with single-cell segmentation and machine-learning models to predict the metabolic pathway usage of cancer cells. The metabolic activities of MCF7 breast cancer cells and HepG2 liver cancer cells were controlled by growing the cells in culture media with specific substrates and metabolic inhibitors. Fluorescence lifetime images of two endogenous metabolic coenzymes, reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD), were acquired by a multi-photon fluorescence lifetime microscope and analyzed at the cellular level. Quantitative changes of NADH and FAD lifetime components were observed for cells using glycolysis, oxidative phosphorylation, and glutaminolysis. Conventional machine learning models trained with the autofluorescence features classified cells as dependent on glycolytic or oxidative metabolism with 90%–92% accuracy. Furthermore, adapting convolutional neural networks to predict cancer cell metabolic perturbations from the autofluorescence lifetime images provided improved performance, 95% accuracy, over traditional models trained via extracted features. Additionally, the model trained with the lifetime features of cancer cells could be transferred to autofluorescence lifetime images of T cells, with a prediction that 80% of activated T cells were glycolytic, and 97% of quiescent T cells were oxidative. In summary, autofluorescence lifetime imaging combined with machine learning models can detect metabolic perturbations between glycolysis and oxidative metabolism of living samples at a cellular level, providing a label-free technology to study cellular metabolism and metabolic heterogeneity.

BackgroundIn vitro fertilization (IVF) is the main technique to address the infertility issue in the patient-oriented strategy encompassing individualized oocyte number (POSEIDON) population. Adopting appropriate protocols for assisted reproduction technologies (ART) cycles in the POSEIDON group may attain more favorable pregnancy outcomes.ObjectivesThis study aimed to compare the effectiveness of modified long gonadotropin-releasing hormone agonist protocol and non-downregulation protocol in POSEIDON patients undergoing ART, and to identify the factors affecting the pregnancy outcomes in this group.DesignThis study was designed as a propensity score-matched (PSM) retrospective analysis.ParticipantsThe study cohort consisted of 910 patients diagnosed with ovarian hyporesponsiveness and treated by IVF from January 2020 to June 2022. They were followed up until the transfer of the last embryo of the IVF cycle and/or pregnancy at 12 weeks. The study was conducted at the Center of Reproductive Medicine, Tongji Medical College, Wuhan Union Hospital, Huazhong University of Science and Technology.MethodsThe patients were divided into Group I and Group II. Group I was treated with modified long gonadotropin-releasing hormone agonist protocol while Group II was put on a non-downregulation protocol. Propensity score matching (PSM) was used to select patients for each group. The subjects were compared in terms of the baseline level, process of controlled ovarian hyperstimulation, and pregnancy outcomes. Binary logistic regression analysis was performed to assess the difference in the cumulative pregnancy rate between the two groups.ResultsOf the 910 POSEIDON patients who underwent IVF, 213 received the modified long gonadotropin-releasing hormone agonist protocol and 697 were subjected to the non-downregulation protocol. From the original cohort, PSM matched 174 pairs of patients. No statistically significant difference was found in total gonadotropin (Gn) dose between the two PSM groups, but the average daily Gn dose was lower in Group I and the duration of Gn lasted longer. The number of retrieved oocytes, the number of metaphase II (MII) ooctyes retrieved, normal fertilization, and normal cleavage embryos was significantly higher in Group I than in Group II, but there existed no significant difference in the number of high-quality embryos between the two groups. The single-cycle CPR (cumulative pregnancy rate) was higher in Group I than in Group II (for Group I: before PSM, CPR = 52.6%; after PSM, CPR = 51.7%; for Group II: before PSM, CPR = 34.0%; after PSM, CPR = 34.5%), and the difference was statistically significant. A binary logistic regression analysis in the unmatched patients showed that the CPR of Group II was 0.486 times that of Group I (95% CI: 0.303 to 0.779).ConclusionsThe modified long gonadotropin-releasing hormone agonist protocol can be used as an optimal protocol for IVF or ICSI (Intracytoplasmic sperm injection) in POSEIDON patients.Level of evidenceLevel III

ObjectiveThe immune response assumes a pivotal role in the underlying mechanisms of urticaria pathogenesis. The present study delves into an investigation of the genetic causal connections between urticaria and prevalent autoimmune afflictions, notably rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn’s disease (CD).MethodsA bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationships involving four autoimmune diseases and urticaria. The genome-wide association study (GWAS) summary data of four autoimmune disease were sourced from the IEU OpenGWAS database. The GWAS summary data for urticaria were derived from the Finnish consortium dataset. The principal analytical approach employed in this study was the random-effects inverse variance weighted (IVW) method. Subsequently, a series of sensitivity analyses were performed, encompassing assessments of heterogeneity, horizontal pleiotropy, outliers, “Leave-one-out” analyses, and tests for adherence to the assumption of normal distribution.ResultsThe random-effects IVW analysis indicate a positive genetic causal association between RA and urticaria (P < 0.001, OR 95% CI = 1.091 [1.051-1.133]). Conversely, SLE, UC, and CD do not exhibit a significant genetic causal relationship with urticaria. The reverse MR analysis reveals a positive genetic causal linkage between urticaria and SLE (P = 0.026, OR 95% CI = 1.289 [1.031-1.612]). However, the analysis demonstrates no substantial genetic causal relationship between urticaria and RA, UC, or CD. Importantly, the genetic causal assessment absence of heterogeneity, horizontal pleiotropy, and outliers. Furthermore, it remains unaffected by any individual single nucleotide polymorphism (SNP), demonstrating adherence to a normal distribution.ConclusionThis investigation establishing RA as a predisposing factor for urticaria. Moreover, urticaria as a plausible risk determinant for SLE. Heightened vigilance is recommended among RA patients to monitor the manifestation of urticaria within clinical settings. Similarly, individuals afflicted by urticaria should duly acknowledge the prospective susceptibility to SLE.

Rationale & objectiveA causal relationship concerning diabetic retinopathy (DR) and diabetic nephropathy (DN) has been studied in many epidemiological observational studies. We conducted a two-sample mendelian randomization study from the perspective of genetics to assess these associations.Methods20 independent single nucleotide polymorphisms (SNPs) associated with diabetic retinopathy were selected from the FinnGen consortium. Summary-level data for diabetic nephropathy were obtained from the publicly available genome-wide association studies (GWAS) database, FinnGen and CKDGen consortium. Inverse variance weighted (IVW) was selected as the primary analysis. MR-Egger, weighted median (WM), simple mode and weighted mode were used as complementary methods to examine causality. Additionally, sensitivity analyses including Cochran’s Q test, MR-Egger, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analyses were conducted to guarantee the accuracy and robustness of our MR analysis.ResultsOur current study demonstrated positive associations of genetically predicted diabetic retinopathy with diabetic nephropathy (OR=1.32; P=3.72E-11), type 1 diabetes with renal complications (OR=1.96; P= 7.11E-11), and type 2 diabetes with renal complications (OR=1.26, P=3.58E-04). Further subtype analysis and multivariate mendelian randomization (MVMR) also reached the same conclusion. A significant casualty with DN was demonstrated both in non-proliferative DR (OR=1.07, P=0.000396) and proliferative DR (OR=1.67, P=3.699068E-14). All the findings were robust across several sensitivity analyses.ConclusionConsistent with previous clinical studies, our findings revealed a positive correlation between DR and DN, providing genetic evidence for the non-invasive nature of DR in predicting DN.

The COVID-19 pandemic, caused by SARS-CoV-2 virus, has been one of the top public health threats across the world over the past three years. Mycobacterium bovis BCG is currently the only licensed vaccine for tuberculosis, one of the deadliest infectious diseases in the world, that is caused by Mycobacterium tuberculosis. In the past decades, recombinant M.bovis BCG has been studied as a novel vaccine vector for other infectious diseases in humans besides tuberculosis, such as viral infections. In the current study, we generated a recombinant M. bovis BCG strain AspikeRBD that expresses a fusion protein consisting of M. tb Ag85A protein and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using synthetic biology technique. Our results show that the recombinant M. bovis BCG strain successfully expressed this fusion protein. Interestingly, the recombinant M. bovis BCG strain AspikeRBD significantly induced SARS-CoV-2 spike-specific T cell activation and IgG production in mice when compared to the parental M.bovis BCG strain, and was more potent than the recombinant M.bovis BCG strain expressing SARS-CoV-2 spike RBD alone. As expected, the recombinant M. bovis BCG strain AspikeRBD activated an increased number of M. tb Ag85A-specific IFNγ-releasing T cells and enhanced IgG production in mice when compared to the parental M.bovis BCG strain or the BCG strain expressing SARS-CoV-2 spike RBD alone. Taken together, our results indicate a potential application of the recombinant M. bovis BCG strain AspikeRBD as a novel dual vaccine against SARS-CoV-2 and M. tb in humans.

This study employs a Bayesian panel vector autoregressive model to examine the impact of economic uncertainty on public health, using an annual, country-level panel dataset of 103 emerging markets and developing countries spanning the years 1995 through 2019. The results from the full sample suggest that the immediate effects of heightened economic uncertainty on health are marginal, yet it may engender prolonged life expectancy and lowered mortality rates. The analysis unveils considerable heterogeneities among various country classifications. The health-enhancing effects of economic uncertainty are predominantly discernible in emerging markets, low-income and upper-middle-income countries. Additionally, a diminution in suicide rates, attributed to escalated economic uncertainty, is uniquely detected in upper-middle-income countries. Furthermore, economic growth and healthcare expenditure emerge as paramount determinants in bolstering overall population health, particularly in lower-middle-income countries. The detrimental effect of environmental pollution on health is more pronounced in emerging markets and middle-income nations. Excluding high-income countries, it is essential to emphasize the beneficial health outcomes resulting from financial development and globalization, as well as the deleterious effects of environmental pollution. Lastly, several policy implications aligned with the findings are outlined, providing a roadmap for decision-makers in these diverse economies to promote better health outcomes.

Cationic lead/cadmium and anionic arsenic exhibit opposite geochemical behaviors in soils, which makes the synchronous remediation of As, Cd, and Pb challenging. In this study, we developed an iron-manganese modified biochar (BC-Fe-Mn) that prepared from straw with iron (Fe) and manganese (Mn) loading at a pyrolysis temperature of 550 °C. After BC-Fe-Mn immobilization for 90 days, the simultaneous immobilization efficiency of Pb, Cd, and As reached 57%, 51%, and 35%, respectively. Speciation distributions shows that As transformed from specific bound state into weakly low crystallinity iron bound state. Cd transformed from carbonate fraction into Fe-Mn oxide bound fraction, and Pb transformed from carbonate fraction into residual state. During the procedure, simultaneous immobilization mechanisms might involve heavy metal morphological transformation, precipitation/co-precipitation, and surface complexation. Cd and Pb absorbed onto BC-Fe-Mn. Then the increased free iron oxides (Fed) reacted with the dissolved As to form iron-arsenic precipitation. The results show that BC-Fe-Mn is a promising material for the simultaneous immobilization of Pb, Cd, and As in multi-metal contaminated soil.

IntroductionStreptococcus pneumoniae is an important human pathogen that may cause severe invasive pneumococcal diseases (IPDs) in young children and the elderly. A comprehensive comparative whole-genome analysis of invasive and non-invasive serotype strains offers great insights that are applicable to vaccine development and disease control.MethodsIn this study, 58 invasive (strains isolated from sterile sites) and 71 non-invasive (serotypes that have not been identified as invasive in our study) pneumococcal isolates were identified among the 756 pneumococcal isolates obtained from seven hospitals in Zhejiang, China (2010–2022). Serotyping, antimicrobial resistance tests, and genomic analyses were conducted to characterize these strains.Results and discussionThe three most invasive serotypes were 23F, 14, and 6B. The invasive pneumococcal isolates' respective resistance rates against penicillin, ceftriaxone, tetracycline, and erythromycin were 34.5%, 15.5%, 98.3%, and 94.7%. Whole-genome sequencing indicated that the predominant invasive clonal complexes were CC271, CC876, and CC81. The high rate of penicillin non-susceptible Streptococcus pneumoniae (PNSP) is related to the clonal distribution of resistance-conferring penicillin-binding proteins (PBP). Interestingly, we found a negative correlation between invasiveness and resistance in the invasive pneumococcal serotype strains, which might be due to the proclivity of certain serotypes to retain their β-lactam resistance. Moreover, the mutually exclusive nature of zmpC and rrgC+srtBCD suggests their intricate and potentially redundant roles in promoting the development of IPD. These findings reveal significant implications for pneumococcal vaccine development in China, potentially informing treatment strategies and measures to mitigate disease transmission.

PurposeThyroid hormones sensitivity is a newly proposed clinical entity closely related with metabolic health. Prior studies have reported the cross-sectional relationship between thyroid hormones sensitivity and diabetes; however, the longitudinal association is unclear to date. We aimed to explore the relationship between impaired thyroid hormone sensitivity at baseline and diabetes onset using a cohort design.MethodsThis study enrolled 7283 euthyroid participants at the first visit between 2008 and 2009, and then annually followed until diabetes onset or 2019. Thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured to calculate thyroid hormone sensitivity by thyroid feedback quantile-based index (TFQI), Chinese-referenced parametric thyroid feedback quantile-based index (PTFQI), thyrotropin index (TSHI), thyrotroph thyroxine resistance index (TT4RI) and FT3/FT4 ratio. Cox proportional hazard model and cross-lagged panel analysis were used.ResultsThe mean baseline age was 44.2 ± 11.9 years, including 4170 (57.3%) male. During a median follow-up of 5.2 years, 359 cases developed diabetes. There was no significant association between thyroid hormones sensitivity indices and diabetes onset, and adjusted hazard ratios per unit (95% CIs) were 0.89 (0.65-1.23) for TFQI, 0.91 (0.57-1.45) for PTFQI, 0.95 (0.70-1.29) for TSHI, 0.98 (0.70-1.01) for TT4RI and 2.12 (0.17-5.78) for FT3/FT4 ratio. Cross-lagged analysis supported the temporal association from fasting glucose to impaired thyroid hormones sensitivity indices.ConclusionsOur findings could not demonstrate that thyroid hormones sensitivity status is a predictor of diabetes onset in the euthyroid population. Elevated fasting glucose (above 7.0 mmol/L) appeared to precede impaired sensitivity indices of thyroid hormones.

The cone is a crucial component of the whole life cycle of gymnosperm and an organ for sexual reproduction of gymnosperms. In Pinus koraiensis, the quantity and development process of male and female cones directly influence seed production, which in turn influences the tree’s economic value. There are, however, due to the lack of genetic information and genomic data, the morphological development and molecular mechanism of female and male cones of P. koraiensis have not been analyzed. Long-term phenological observations were used in this study to document the main process of the growth of both male and female cones. Transcriptome sequencing and endogenous hormone levels at three critical developmental stages were then analyzed to identify the regulatory networks that control these stages of cones development. The most significant plant hormones influencing male and female cones growth were discovered to be gibberellin and brassinosteroids, according to measurements of endogenous hormone content. Additionally, transcriptome sequencing allowed the identification of 71,097 and 31,195 DEGs in male and female cones. The synthesis and control of plant hormones during cones growth were discovered via enrichment analysis of key enrichment pathways. FT and other flowering-related genes were discovered in the coexpression network of flower growth development, which contributed to the growth development of male and female cones of P. koraiensis. The findings of this work offer a cutting-edge foundation for understanding reproductive biology and the molecular mechanisms that control the growth development of male and female cones in P. koraiensis.

Myxobacteria are widely distributed in various habitats of soil and oceanic sediment. However, it is unclear whether soil-dwelling myxobacteria tolerate a saline environment. In this study, a salt-tolerant myxobacterium Myxococcus sp. strain MxC21 was isolated from forest soil with NaCl tolerance >2% concentration. Under 1% salt-contained condition, strain MxC21 could kill and consume bacteria prey and exhibited complex social behaviors such as S-motility, biofilm, and fruiting body formation but adopted an asocial living pattern with the presence of 1.5% NaCl. To investigate the genomic basis of stress tolerance, the complete genome of MxC21 was sequenced and analyzed. Strain MxC21 consists of a circular chromosome with a total length of 9.13 Mbp and a circular plasmid of 64.3 kb. Comparative genomic analysis revealed that the genomes of strain MxC21 and M. xanthus DK1622 share high genome synteny, while no endogenous plasmid was found in DK1622. Further analysis showed that approximately 21% of its coding genes from the genome of strain MxC21 are predominantly associated with signal transduction, transcriptional regulation, and protein folding involved in diverse niche adaptation such as salt tolerance, which enables social behavior such as gliding motility, sporulation, and predation. Meantime, a high number of genes are also found to be involved in defense against oxidative stress and production of antimicrobial compounds. All of these functional genes may be responsible for the potential salt-toleration. Otherwise, strain MxC21 is the second reported myxobacteria containing indigenous plasmid, while only a small proportion of genes was specific to the circular plasmid of strain MxC21, and most of them were annotated as hypothetical proteins, which may have a direct relationship with the habitat adaptation of strain MxC21 under saline environment. This study provides an inspiration of the adaptive evolution of salt-tolerant myxobacterium and facilitates a potential application in the improvement of saline soil in future.

Background/objectiveThe outbreak of COVID-19 in China since 2019 has had a significant impact on the mental health of people in Hubei Province during the three-year pandemic period. Therefore, studying the prevalence of depression among the population of Hubei Province since the pandemic is of great significance.MethodsBased on opportunity and stress theory, we collected provincial-level data from Hubei (N = 3,285) to examine the impact of declining economic status on depressive symptoms and to investigate the moderating effect of psychological resilience during the period of economic adjustment.ResultsWe used propensity score matching to estimate the treatment effect of economic status decline on depression severity and confirmed the moderating effect of psychological resilience. We found that the more that an individual’s economic status declines, the more severe that his or her depressive symptoms become. Specifically, each unit decrease in economic status is associated with an increase of approximately 0.117 units in depression level. In addition, our results indicated that psychological resilience significantly moderated the relationship between economic decline and depression (−0.184*).Conclusions and implicationsOur study confirms the role of economic status in depressive symptoms. Compared with traditional research on the relationship between economic status and mental illness, this paper expands the research regarding the two in the context of a major public health emergency. Furthermore, we suggest ways to improve people’s mental health following the pandemic.

BackgroundConfidence and appropriate care approach toward dementia among nursing staff (nurses and care assistants) are crucial manifestations of competency to deal with the complexity of dementia care in long-term care facilities (LTCFs). The purpose of this study was to investigate the confidence in dementia care and care approach among nursing staff in LTCFs in mainland China.MethodsA cross-sectional study design was utilized in LTCFs in Shandong Province, mainland China. A convenient sample included of 317 nursing staff drawn from 15 LTCFs. Survey questions included (a) demographics, (b) dementia knowledge, (c) dementia care confidence, and (d) approach to care for people with dementia. Data were analyzed with descriptive statistics. Factors associated with confidence and care approach for people with dementia were examined using Pearson’s correlation and multivariate regression analyses.ResultsDementia care confidence was generally moderate. Factors affecting confidence to care for people with dementia included educational level, months of caring dementia patients, and dementia knowledge. Most nursing staff did not use a person-centered care approach which was significantly associated with their age, dementia-learning experience, and knowledge and confidence toward caring for people with dementia.ConclusionA positive correlation was identified between confidence to care for people with dementia and nursing staff care approach. Clinical recommendations are provided to further develop education strategies tailored for nursing staff to meet the growing demand for dementia care services.

PurposeTo assess the usefulness of amide proton transfer-weighted (APTw) imaging in the differentiation of parotid gland tumors.Materials and methodsPatients with parotid gland tumors who underwent APTw imaging were retrospectively enrolled and divided into groups according to pathology. Two radiologists evaluated the APTw image quality independently, and APTw images with quality score ≥3 were enrolled. The maximum and average values of APTw imaging for tumor lesions (APTmax and APTmean) were measured. The differences in APTmax and APTmean were compared between malignant tumors (MTs) and benign tumors (BTs), as well as between MTs and pleomorphic adenomas (PAs) and between MTs and Warthin tumors (WTs). Independent-samples t-test, Kruskal–Wallis H test, and receiver operating characteristic (ROC) curve analyses were used for statistical analysis.ResultsSeventy-three patients were included for image quality evaluation. In this study, 32/73 and 29/73 parotid tumors were scored as 4 and 3, respectively. After excluding lesions with quality score ≤2 (12/73), the APTmean and APTmax of MTs were 4.15% ± 1.33% and 7.43% ± 1.61%, higher than those of BTs 2.74% ± 1.04% and 5.25% ± 1.54%, respectively (p < 0.05). The areas under the ROC curve (AUCs) of the APTmean and APTmax for differentiation between MTs and BTs were 0.819 and 0.821, respectively. MTs indicated significantly higher APTmean and APTmax values than those of PAs (p < 0.05) and WTs (p < 0.05). The AUCs of the APTmean and APTmax for differentiation between MTs and PAs were 0.830 and 0.815 and between MTs and WTs were 0.847 and 0.920, respectively.ConclusionMost APTw images for parotid tumors had acceptable image quality for APTw value evaluation. Both APTmax and APTmean can be used to differentiate MTs from BTs and to differentiate MTs from subtype parotid gland tumors.

Alzheimer’s disease (AD), one of the leading diseases of the nervous system, is accompanied by symptoms such as loss of memory, thinking and language skills. Both mild cognitive impairment (MCI) and very mild cognitive impairment (VMCI) are the transitional pathological stages between normal aging and AD. While the changes in whole-brain structural and functional information have been extensively investigated in AD, The impaired structure–function coupling remains unknown. The current study employed the OASIS-3 dataset, which includes 53 MCI, 90 VMCI, and 100 Age-, gender-, and education-matched normal controls (NC). Several structural and functional parameters, such as the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and The ALFF/VBM ratio, were used To estimate The whole-brain neuroimaging changes In MCI, VMCI, and NC. As disease symptoms became more severe, these regions, distributed in the frontal-inf-orb, putamen, and paracentral lobule in the white matter (WM), exhibited progressively increasing ALFF (ALFFNC

The garbage classification recycling policy is proposed to curb the waste of recyclable and land resources to reduce the environmental pollution caused by garbage. This paper establishes a tripartite evolutionary game model with governments, recycling companies, and citizens as stakeholders to discuss their corresponding strategic behaviors. Through the stability analysis, we draw a conclusion that only when governments choose to regulate the classification, while both recycling companies and citizens take an active part in the classification, can the environmental benefit be maximized. In addition, the government and recycling companies are advised to increase the rate at which the evolutionary game model converges to a steady state by reducing their own operating costs during the implementation of garbage classification. On this basis, we also recommend an appropriate increase in the benefits given to citizens, which will have a significantly positive impact on citizens and even also on the government and the recycling companies themselves.

BackgroundEpidemiological studies have linked various circulating cytokines to cardiovascular disease (CVD), which however remains uncertain whether these relationships represent causality or are due to bias. To address this question, we conducted a Mendelian randomization (MR) analysis to systematically investigate the causal effects of circulating cytokine levels on CVD development.MethodsThis study leveraged the summary statistic from respective genome-wide association study (GWAS) of 47 cytokines and four types of CVD. The cis-quantitative trait locus (cis-QTL) definition, derived from a GWAS meta-analysis comprising 31,112 participants of European descent, served as instruments for cytokines. A two-sample MR design was employed, followed by comprehensive sensitivity analyses to validate the robustness of results.ResultsThe results of inverse-variance weighted method using cis-protein QTL (cis-pQTL) instruments, showed the causal effects of four cytokines (i.e., IL-1ra, MCSF, SeSelectin, SCF) on the risk of coronary artery disease (CAD). We also identified causal relationships between two cytokines (i.e., IL-2ra, IP-10) and heart failure (HF), as well as two cytokines (i.e., MCP-3, SeSelectin) and atrial fibrillation (AF), after controlling for false discovery rate (FDR). The use of cis-expression QTL (cis-eQTL) revealed additional causal associations between IL-1a, MIF and CAD, between IL-6, MIF, and HF, as well as between FGFBasic and AF. No significant sign was survived for stroke with FDR applied. Results were largely consistent across sensitivity analyses.ConclusionThe present study provides supportive evidence that genetic predisposition to levels of certain cytokines causally affects the development of specific type of CVD. These findings have important implications for the creation of novel therapeutic strategies targeting these cytokines as a means of preventing and treating CVD.

IntroductionOvarian aging has steadily grown to be a significant health issue for women as a result of the increase in average life expectancy and the postponement of reproductive age. One of the important pathological foundations of ovarian aging is formed by mitochondrial dysfunction, which causes decreases in follicle quantity and oocyte quality. In recent years, brown adipose tissue (BAT) transplantation has been proven as an effective treatment for aging-related diseases, such as ovarian aging. However, BAT transplantation is an invasive operation with long-term risks. Therefore, we need to find an alternative strategy.MethodsWe injected BAT-derived exosomes into eight-month-old C57BL/6 female mice. The fertility was detected by the estrous cycle and mating test. The changes of ovary and oocyte were measured by ovarian volume, organ coefficient, follicle counting, and oocyte maturation rate. ROS level, mitochondrial membrane potential and ATP level were measured to analyze the mitochondrial function of oocytes. The changes in metabolism were explored by cold stimulation test, body weight and blood sugar. The possible molecular mechanism was further investigated by RNA sequencing.ResultsIn terms of fertility, the estrous cycle of aging mice after BAT-derived exosome intervention was more regular, and the number of progenies and litters was increased. At the tissue level, the ovaries in the BAT-exosome group were larger, and the number of primordial follicles, secondary follicles, antral follicles and total follicles increased. At the cellular level, BAT-derived exosomes improved the maturation of oocytes in vivo and in vitro, increased the mitochondrial membrane potential and ATP levels of oocytes, and decreased ROS levels. Besides, BAT-derived exosomes ameliorated the metabolism and viability of aging mice. Furthermore, mRNA sequencing showed that BAT exosomes altered the expression levels of genes related to metabolism and the quality of oocytes.ConclusionBAT-derived exosomes enhanced mitochondrial function, promoted follicle survival, improved fertility, and extended ovarian lifespan in aging mice.

Objectives: Patient-reported outcomes (PROs) provide a global perspective of patient health status which plays an enormous role in evaluating clinical efficacy. However, the application of PROs in traditional Chinese medicine (TCM) was still insufficiently studied in mainland China.Methods: This cross-sectional study was performed based on interventional clinical trials of TCM that were conducted in mainland China from 1 January 2010, to 15 July 2022. Data was retrieved from the ClinicalTrials.gov and Chinese Clinical Trial Registry. We included interventional clinical trials of TCM for which the country of the primary sponsors or recruitment settings in mainland China. For each included trial, data including clinical trial phases, study settings, participant’s age, sex, diseases, and the patient-reported outcome measures (PROMs) were extracted. Trials were categorized into four categories according to 1) listed PROs as primary endpoints, 2) listed PROs as secondary endpoints, 3) listed PROs as coprimary outcomes (both primary and secondary endpoints), and 4) did not mention any PROMs.Results: Among a total of 3,797 trials, 680 (17.9%) trials listed PROs as primary endpoints, 692 (18.2%) trials listed PROs as secondary endpoints, and 760 (20.0%) trials listed PROs as coprimary endpoints. Among 675,787 participants included in the registered trials, 448,359 (66.3%) patients’ data were scientifically collected by PRO instruments. Neurological diseases (11.8%), musculoskeletal symptoms (11.5%), mental health conditions (9.1%) were the most common conditions evaluated by PROMs. Disease-specific symptoms related concepts were used most frequently (51.3%), followed by health-related quality of life concepts. Visual analog scale, 36-item Short-Form Health Questionnaire, and TCM symptom score were the most common PROMs in these trials.Conclusion: In this cross-sectional study, the use of PROs increased in the past decades according to clinical trials of TCM conducted in mainland China. Considering that the application of PROs in clinical trials of TCM has some existing issues including uneven distribution and lack of normalized PROs of TCM, further study should be focused on the standardization and normalization of TCM-specific scales.

To improve the economic benefits of engineered cementitious composites and control the repair cycle, repair materials were designed, with the key components of the mixture being low-cost polypropylene (PP) fibers and fast-setting sulfoaluminate cement. The effects of water/binder ratio, fiber content, and aggregate particle size on the flowability, mechanical properties, and toughness of the polypropylene fiber-reinforced sulfoaluminate cementitious composite (PP-SACC) were explored. Based on experimentally measured axial tensile stress–strain curves, a constitutive model of PP-SACC was derived in terms of fiber content and water/binder ratio. Additionally, the correlation coefficients representing the relationships of the mixture indices with the tensile properties were explored based on revised gray relational analysis. Test results indicated that fiber content and water/binder ratio were the most important factors affecting the mechanical properties, toughness, and fluidity of the material; in contrast, the influence of aggregate size was slight. The PP-SACC mixture with an aggregate size of 75 µm, a water/binder ratio of 0.30, and a fiber content of 3.0% demonstrated an excellent degree of toughness and exhibited a flexural hardening phenomenon under bending load.

The tumor microenvironment (TME) is the internal environment that tumors depend on for survival and development. Tumor-associated macrophages (TAMs), as an important part of the tumor microenvironment, which plays a crucial role in the occurrence, development, invasion and metastasis of various malignant tumors and has immunosuppressant ability. With the development of immunotherapy, eradicating cancer cells by activating the innate immune system has yielded encouraging results, however only a minority of patients show a lasting response. Therefore, in vivo imaging of dynamic TAMs is crucial in patient-tailored immunotherapy to identify patients who will benefit from immunotherapy, monitor efficacy after treatment, and identify alternative strategies for non-responders. Meanwhile, developing nanomedicines based on TAMs-related antitumor mechanisms to effectively inhibit tumor growth is expected to become a promising research field. Carbon dots (CDs), as an emerging member of the carbon material family, exhibit unexpected superiority in fluorescence imaging/sensing, such as near infrared imaging, photostability, biocompatibility and low toxicity. Their characteristics naturally integrate therapy and diagnosis, and when CDs are combined with targeted chemical/genetic/photodynamic/photothermal therapeutic moieties, they are good candidates for targeting TAMs. We concentrate our discussion on the current learn of TAMs and describe recent examples of macrophage modulation based on carbon dot-associated nanoparticles, emphasizing the advantages of their multifunctional platform and their potential for TAMs theranostics.

Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7-/- C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7-/- mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7.

Purpose: To compare the effects of whole-body vibration training (WBVT) with different frequencies on the balance ability of older adults.Methods: Randomized controlled trials (RCTs) on the WBVT interventions on balance ability in older adults were searched through PubMed, Web of Science, The Cochrane Library, ProQuest, Embase, Opengrey, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database (CSTJ) databases from the establishment of the database to August 2022, and all literature that met the PICOS (Participants, Intervention, Comparison, Outcomes, Study design) criteria were enrolled. Two reviewers screened and assessed the methodological quality of the included literature according to the physiotherapy evidence database (PEDro) scale criteria. Statistical analysis was performed using Stata 14.0 software after data extraction.Results: Twenty-five RCTs with a total of 1267 subjects were finally included. The results of the pairwise comparison of the Network Meta-analysis showed that the Timed Up and Go Test (TUGT) values of Low-frequency whole-body vibration training (LF-WBVT) was lower than the placebo and traditional rehabilitation groups, and the difference was statistically significant [WMD = −1.37, 95% CI (−2.53, −0.20)] [WMD = −1.84, 95% CI(-3.17,-0.51)]. The Five-repetition Sit-to-Stand Test (5STS) values of LF-WBVT, Medium-frequency whole-body vibration training (MF-WBVT), and High-frequency whole-body vibration training (HF-WBVT) were lower than the placebo and traditional rehabilitation groups, but none of them were statistically significant. In addition, the TUGT and 5STS values of HF-WBVT had a tendency to be lower than those of LF-WBVT and MF-WBVT, but neither of them was statistically different. The cumulative probability ranking results of both TUGT and 5STS showed that HF-WBVT was the best protocol.Conclusion: Current evidence shows that HF-WBVT may be the best protocol for improving balance in older adults. Due to the study’s limitations, the conclusion obtained in this study still needs to be further confirmed by more high-quality studies.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021250405].