The epidemic characteristics of Mycoplasma pneumoniae infection among children in Anhui, China, 2015-2023.

The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and to provide evidence for the prevention and control strategies of M. pneumoniae in children in this region. A total of 66,488 pediatric patients with respiratory tract infection were enrolled from January 2015 to November 2023 in this study. The results of this study exhibited that M. pneumoniae infection in the Anhui region was characterized by a high positive rate during 2021-2023, especially this year is considered a year of pandemic for M. pneumoniae infection. Moreover, the positive rate of M. pneumoniae in female children is significantly higher than in male children, and the infection rate of M. pneumoniae in children increases significantly with age, particularly in school-aged children. IMPORTANCE: The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and provide evidence for the prevention and control strategies of M. pneumoniae in children in this region.

Trends on Prevalence, All-Cause Mortality, and Survival Status of Dementia Patients in Rural China Based on Pooling Analysis.

Objectives: No study has reported secular trends in dementia prevalence, all-cause mortality, and survival status in rural China. Methods: We established two cohorts (XRRCC1 and XRRCC2) in the same region of China, 17 years apart, to compare dementia prevalence, all-cause mortality, and survival status, and performed regression analysis to identify associated factors. Results: Dementia prevalence was 3.49% in XRRCC1 and 4.25% in XRRCC2, with XRRCC2 showing a significantly higher prevalence (OR = 1.79, 95%CI: 1.2-2.65). All-cause mortality rates for dementia patients were 62.0% in XRRCC1 and 35.7% in XRRCC2. Mortality in the normal population of XRRCC2 decreased by 66% compared to XRRCC1, mainly due to improved survival rates in women with dementia. Dementia prevalence was positively associated with age >65, spouse-absent status, and stroke, and negatively associated with ≥6 years of education. Conclusion: Dementia prevalence in rural China increased over 17 years, while mortality decreased. Major risk factors include aging, no spouse, and stroke, with higher education offering some protection.

Clinical value of transperineal ultrasound in evaluating the diagnostic grade of rectocele in Chinese women with obstructed defecation syndrome: An observational study.

We aimed to evaluate the effectiveness of transperineal ultrasound (TPUS) in diagnosing rectocele, rectal intussusception (RI), enterocele, perineal descent (PD), and cystocele in Chinese women with obstructed defecation syndrome (ODS), and to determine the grading of rectocele via TPUS. Between January 2019 and December 2021, 107 obstructed defecation syndrome patients, with a mean age of 49.76 years, received TPUS and defecation proctography (DEP). Both methods were used to diagnose anorectal angle, rectocele, RI, enterocele, and PD, while cystocele and uterine prolapse were diagnosed only through TPUS. Agreement between DEP and TPUS diagnostic results was compared using Cohen kappa statistics. Seventy-six rectoceles were reported following DEP and 72 after TPUS. DEP detected 7 enteroceles, 6 of which were diagnosed simultaneously by TPUS. 43 patients presented dyssynergic defecation (DD) upon DEP, while 51 upon TPUS. DEP and TPUS detected PD in 13 and 11 patients respectively, and RI in 82 and 73, respectively. Rectocele (kappa = 0.738), RI (kappa = 0.711), DD (kappa = 0.774), enterocele (kappa = 0.847), and PD (kappa = 0.625) were obtained by Cohen kappa statistics, which indicated a good agreement between DEP and TPUS. The cutoff values for the diagnosis of moderate and severe rectocele with TPUS were 12.05 mm (AUC: 0.941) and 18.50 mm (AUC: 0.977), respectively. The DEP-determined and TPUS-determined anorectal angles were significantly correlated in the resting and Valsalva states (P < .01). Compared with DEP, while maintaining good agreement in detecting rectocele, RI, DD, enterocele, and PD, TPUS is a repeatable and noninvasive alternative. Threshold values of 12.05 mm and 18.50 mm on TPUS may diagnose moderate and severe rectocele, respectively.

Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.

Ovarian cancer is a common cancer for females, and the incidence and mortality rates are on the rise. Many treatment strategies have been developed for ovarian cancer, including chemotherapy and immunotherapy, but they are often ineffective and prone to drug resistance. Protein ubiquitination is an important class of post-translation modifications that have been found to be associated with various human diseases and cancer development. Recent studies have revealed that protein ubiquitination is involved in the progression of ovarian cancer and plays an important role in the tumor immune process. Moreover, the combination of ubiquitinase/deubiquitinase inhibitors and cancer immunotherapy approaches can effectively reduce treatment resistance and improve treatment efficacy, which provides new ideas for cancer treatment. Herein, we review the role of protein ubiquitination in relation to ovarian cancer immunotherapy and recent advances in the use of ubiquitinase/deubiquitinase inhibitors in combination with cancer immunotherapy.

A phase I drug-drug interaction study to assess the effect of futibatinib on P-gp and BCRP substrates and of P-gp inhibition on the pharmacokinetics of futibatinib.

Futibatinib, an inhibitor of fibroblast growth factor receptor 1-4, is approved for the treatment of patients with advanced cholangiocarcinoma with FGFR2 fusions/rearrangements. In this phase I drug-drug interaction study, the effects of futibatinib on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates, and of P-gp inhibition on futibatinib pharmacokinetics (PK) were investigated in healthy adults aged 18-55 years. In part 1, 20 participants received digoxin (P-gp substrate) and rosuvastatin (BCRP substrate). Following a ≥10-day washout, futibatinib was administered for 7 days, with digoxin and rosuvastatin coadministered on the third day. In part 2, 24 participants received futibatinib. Following a ≥3-day washout, quinidine (P-gp inhibitor) was administered for 4 days, with futibatinib coadministered on day 4. Blood samples were collected predose and for 24 (futibatinib), 72 (rosuvastatin), and 120 h (digoxin) postdose. Urine samples (digoxin) were collected predose and for 120 h postdose. PK parameters were compared between treatments using analysis of variance. Coadministration with futibatinib had no effect on the PK of digoxin and rosuvastatin, and coadministration with quinidine had minimal effects on the PK of futibatinib. Differences in Cmax and AUC with and without futibatinib and quinidine, respectively, were <20%. The most common treatment-emergent adverse events were diarrhea (80%) and increased blood phosphorous (75%) in part 1 and prolonged electrocardiogram QT interval (38%) in part 2. The data show that futibatinib has no clinically meaningful effects on the PK of P-gp or BCRP substrates and that the effect of P-gp inhibition on futibatinib PK is not clinically relevant.

Early-stage postoperative depression and anxiety following orthognathic surgery: a cross-sectional study.

BACKGROUND: The objective of this study was to observe the incidence and potential risk factors of postoperative depression and anxiety in patients during the early period after undergoing orthognathic surgery. METHODS: From March 7 to September 7, 2023, patients ≥ 18 years of age who were scheduled for elective orthognathic surgery under general anesthesia in Peking University School and Hospital of Stomatology were included in this study. We prospectively evaluated their degrees of pre- and postoperative depression and anxiety using the Patient Health Questionnaire-9 and the State Trait Anxiety Inventory. Associations between the perioperative factors and occurrences of postoperative anxiety and depression were evaluated using a multivariate logistic regression model. RESULTS: A total of 371 patients were included in the analysis. Within five days after surgery, we observed the occurrence of depression in 32% (116) of the patients and anxiety in 72.8% (270) of them. Their preoperative depression score on the Pain Catastrophizing Scale and intraoperative urine output were significantly associated with a higher risk of postoperative depression. The presence of preoperative anxiety, postoperative moderate-to-severe pain, postoperative nausea and vomiting and postoperative insomnia were significantly associated with a higher risk of postoperative anxiety. Furthermore, a monthly income ≥ ¥10000 was found to be significantly associated with a lower risk of postoperative anxiety. CONCLUSIONS: Postoperative depression and anxiety are common among patients who undergo orthognathic surgery. Moreover, preoperative psychological status and incidence of postoperative adverse events were associated with an increased risk of depression and anxiety after surgery. The results of the present study suggest that careful psychological assessment and appropriate management are necessary to improve patients' recovery following orthognathic surgery.

Non-invasive in vivo imaging of changes in Collagen III turnover in myocardial fibrosis.

Heart failure (HF) affects 64 million people globally with enormous societal and healthcare costs. Myocardial fibrosis, characterised by changes in collagen content drives HF. Despite evidence that collagen type III (COL3) content changes during myocardial fibrosis, in vivo imaging of COL3 has not been achieved. Here, we discovered the first imaging probe that binds to COL3 with high affinity and specificity, by screening candidate peptide-based probes. Characterisation of the probe showed favourable magnetic and biodistribution properties. The probe's potential for in vivo molecular cardiac magnetic resonance imaging was evaluated in a murine model of myocardial infarction. Using the new probe, we were able to map and quantify, previously undetectable, spatiotemporal changes in COL3 after myocardial infarction and monitor response to treatment. This innovative probe provides a promising tool to non-invasively study the unexplored roles of COL3 in cardiac fibrosis and other cardiovascular conditions marked by changes in COL3.

Self-Supervised Contrastive Learning on Attribute and Topology Graphs for Predicting Relationships Among lncRNAs, miRNAs and Diseases.

Exploring potential association between long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and diseases is an essential part of prevention, diagnosis and treatment of diseases. Since determining these relationships experimentally is resource-intensive and time-consuming, therefore computational methods have emerged as an attractive way to address this issue. However, existing computational approaches for inferring lncRNA-disease associations (LDA), miRNA-disease associations (MDA) and lncRNA-miRNA interactions (LMI) tend to focus on single task, neglecting the benefits of leveraging multiple biomolecular interactions and domain-specific knowledge for multi-task prediction. Furthermore, labeled data for LDA, MDA and LMI is scarce and costly in real-word applications, making it challenging for models to learn comprehensive node embedding patterns. Building on our previous work, this paper proposes a multi-task prediction model (called SSCLMD) that employs self-supervised contrastive learning on attribute and topology graphs to identify potential LDAs, MDAs and LMIs. Specifically, firstly, domain knowledge of lncRNAs, miRNAs and diseases as well as their interactions are exploited to construct attribute graph and topology graph, respectively. Then, the nodes are encoded in the attribute and topology spaces to extract the specific and common feature. Meanwhile, the attention mechanism is performed to adaptively fuse the embedding from different views. SSCLMD incorporates a contrastive self-supervised learning task as a regularize to guide the learning of node embeddings in both attribute and topology space without relying on labels. Severing as a regularize in multi-task learning paradigm, it to improves the model's generalization capabilities. Extensive experiments on 2 manually curated datasets demonstrate that SSCLMD significantly outperforms other baseline methods in LDA, MDA and LMI prediction tasks. Additionally, case studies on both new and old datasets further supported the ability of SSCLMD to uncover novel disease-related lncRNAs and miRNAs. The source codes and supplementary file of this work are publicly available on \url{https://github.com/sheng-n/SSCLMD}.

Tracking the evolution of the morphology and stress distribution of SIS thermoplastic elastomers under tension using atomic force microscopy.

Styrene-based ABA-type triblock copolymers and their blends are widely investigated thermoplastic elastomers (TPEs). The design of tough TPE materials with high strength and resilience requires further clarification of the relationship between microstructure and macroscopic properties of stretched samples. Here, we applied atomic force microscopy (AFM)-based quantitative nanomechanical mapping to study the deformation behavior of poly(styrene-b-isoprene-b-styrene) blends under tension. The results indicated that the glassy polystyrene (PS) domains deformed and inhomogeneous stress distributions developed in the initial stretching stage. At 200% strain, the glassy PS domains started to crack. The change in the peak value in the JKR Young's modulus diagram during stretching was consistent with the stress - strain curve. Analysis of the particles before and after stretching suggested that the glassy domains separated and reorganized during stretching.

A tough thermoplastic elastomer (TPE) with high strength and resilience was developed using styrene-based triblock copolymers and their blends, with its high-performance mechanism analyzed through AFM-based quantitative nanomechanical mapping.

Perceived stress and prenatal depression symptoms among couples with gestational diabetes mellitus: The mediating role of dyadic coping.

PROBLEM: No studies have been conducted to examine the relationships between perceived stress, positive/negative dyadic coping, and prenatal depression symptoms in Chinese couples with gestational diabetes mellitus (GDM). BACKGROUND: GDM is a stressful event for pregnant women and their partners, which may result in clinically significant prenatal depression symptoms in couples. AIM: This study aims to examine the relationships and differences in perceived stress, positive/negative dyadic coping, and prenatal depression symptoms between Chinese pregnant women with GDM and their partners and to explore the mediating role of positive/negative dyadic coping. METHODS: A cross-sectional study was conducted in Guangzhou, China, from January to October 2021. 402 pairs of GDM couples completed the questionnaires, including the Edinburgh Postnatal Depression Scale, the Chinese version of the Dyadic Coping Inventory, and the Perceived Stress Scale. Dyadic data was analyzed using the actor-partner interdependence mediation model. FINDINGS: 37.6 % of pregnant women with GDM and 24.6 % of their partners experienced clinically significant prenatal depression symptoms. Depression symptoms in couples mutually influence each other. Perceived stress was directly or indirectly related to their and partners' prenatal depression symptoms in GDM couples, with negative dyadic coping acting as a mediator. Maternal negative dyadic coping was also a partner-mediator. DISCUSSION: The findings of the present study may provide healthcare professionals with a better understanding of the effect of the interpersonal interaction between the couples as a dyad on prenatal depression symptoms in Chinese context. CONCLUSION: There were intrapersonal and interpersonal associations among perceived stress, negative dyadic coping, and prenatal depression symptoms in pregnant women with GDM and their partners. It suggests a need for screening clinically significant prenatal depression symptoms and decreasing perceived stress and negative dyadic coping among couples with GDM with a focus on pregnant women with GDM.

Comparing the diagnostic performance of lung ultrasonography and chest radiography for detecting pneumothorax in patients with trauma: a meta-analysis.

INTRODUCTION: To compare the diagnostic performance of ultrasonography (US) and chest radiography for detecting pneumothorax in patients with trauma using a meta-analytic approach. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically searched to identify eligible studies until March 2023. The diagnostic performance of US and chest radiography was assessed using sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC). RESULTS: Overall, 21 studies involving 4,087 patients with trauma were included. The overall sensitivity, specificity, PLR, NLR, diagnostic score, DOR, and AUC of US for detecting pneumothorax were 0.83, 0.99, 73.72, 0.17, 6.06, 427.80, and 0.99, respectively. The corresponding values of chest radiography for detecting pneumothorax were 0.37, 1.00, 175.59, 0.63, 5.63, 279.97, and 0.86. US was associated with a higher sensitivity (ratio: 2.24; 95% confidence interval [CI]: 1.70-2.95; P < 0.001) or AUC (ratio: 1.15; 95% CI: 1.11-1.19; P < 0.001) and lower NLR (ratio: 0.27; 95% CI: 0.17-0.43; P < 0.001) compared with chest radiography. CONCLUSION: Lung US was associated with better diagnostic performance than chest radiography for detecting pneumothorax in patients with trauma.

Mutations and Differential Transcription of Mating-Type and Pheromone Receptor Genes in Hirsutella sinensis and the Natural Cordyceps sinensis Insect-Fungi Complex.

Sexual reproduction in ascomycetes is controlled by the mating-type (MAT) locus. (Pseudo)homothallic reproduction has been hypothesized on the basis of genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). However, the differential occurrence and differential transcription of mating-type genes in the MAT1-1 and MAT1-2 idiomorphs were found in the genome and transcriptome assemblies of H. sinensis, and the introns of the MAT1-2-1 transcript were alternatively spliced with an unspliced intron I that contains stop codons. These findings reveal that O. sinensis reproduction is controlled at the genetic, transcriptional, and coupled transcriptional-translational levels. This study revealed that mutant mating proteins could potentially have various secondary structures. Differential occurrence and transcription of the a-/α-pheromone receptor genes were also found in H. sinensis. The data were inconsistent with self-fertilization under (pseudo)homothallism but suggest the self-sterility of H. sinensis and the requirement of mating partners to achieve O. sinensis sexual outcrossing under heterothallism or hybridization. Although consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis insect-fungi complexes, the mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in N-terminal or middle-truncated proteins with significantly altered overall hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction because of the co-occurrence of multiple genomically independent genotypes of O. sinensis and >90 fungal species in natural C. sinensis.

Does Bullying Victimization Accelerate Adolescents' Non-suicidal Self-injury? The Mediating Role of Negation Emotions and The Moderating Role of Submissive Behavior.

Based on general strain theory, the current study examined whether bullying victimization was significantly related to adolescents' non-suicidal self-injury and whether negation emotions mediated this association and submissive behavior moderated this mediation process. A total of 1,984 adolescents completed a series of anonymous questionnaires regarding bullying victimization, negative emotions, non-suicidal self-injury, and submissive behavior. Results showed that bullying victimization was significantly and positively associated with non-suicidal self-injury and this relation was partially mediated by negative emotions. Submissive behavior moderated the relation between bullying victimization and non-suicidal self-injury as well as negation emotions and non-suicidal self-injury. Specifically, the victims of bullying with high submissive behavior were more likely to develop non-suicidal self-injury. Adolescents who had higher negative emotions were at greater risk of engaging in non-suicidal self-injury when they also had high submissive behavior. The positive association between negative emotions and non-suicidal self-injury was stronger in females than males.

Anti-HIV activity in traditional Chinese medicine: clinical implications of monomeric herbal remedies and compound decoctions.

With the global spread of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), the pursuit of potent treatments has ascended as a paramount concern in global healthcare. Traditional Chinese medicine (TCM) has been used for thousands of years in China and other East Asian countries and it offers remedies for an extensive array of ailments, including HIV and AIDS. This review focuses on the clinical significance of single herbs and composite tonics in TCM with antiviral activity against HIV. Initially, the anti-HIV activity of single herbs was analyzed in detail. Many herbs have been shown to have significant anti-HIV activity. The active ingredients of these herbs exhibit their anti-HIV effects through various mechanisms, such as inhibiting viral replication, preventing viral binding to host cells, and interfering with the viral lifecycle. Furthermore, we delved into the clinical significance of HIV-associated formulations provided as a result of Chinese compound prescription. These combinations of herbal ingredients are designed to amplify therapeutic efficacy and minimize adverse effects. Clinical trials have demonstrated the therapeutic benefits of these prescriptions for individuals infected with HIV. The intricate composition of these prescriptions potentially augments their anti-HIV activity through synergistic effects. Additionally, this review underscores the clinical importance of TCM in the context of HIV treatment. While numerous herbs and prescriptions exhibit anti-HIV activity, their safety and efficacy in clinical applications warrant further investigation. When combined with contemporary antiretroviral drugs, TCM may serve as an adjunctive therapy, assisting in reducing side effects, and enhancing patients' quality of life. To optimally harness these natural resources, further exploration is imperative to ascertain their efficacy, safety, and optimal utilization, thereby offering a broader spectrum of therapeutic options for HIV-afflicted individuals.

Targeted lipidomics-based study of radiation-induced metabolite profiles changes in plasma of total body irradiation cases.

PURPOSE: Lipidomics is an important tool for triaging exposed individuals, and helps early adoption of prevention and control strategies. The purpose of this study was to screen significantly perturbed lipids between pre- and post-irradiation of human plasma samples after total body irradiation (TBI) and explore potential radiation biomarkers for early radiation classification. METHODS: Plasma samples were collected before and after irradiation from 22 hospitalized cases of acute myeloid leukemia (AML) prepared for bone marrow transplantation. Acute total-body γ irradiation was performed at doses of 0, 4, 8, and 12 Gy. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with multiple reaction monitoring (MRM) method was utilized. Self-paired studies before and after irradiation were performed to screen potential lipid categorization markers and markers of dose-response relationships for radiation perturbation in humans. Based on the screened potential markers, a human TBI dose estimation model was developed. RESULTS: In total, 426 individual lipids from 14 major classes were quantified and 152 potential biomarkers with categorical characteristics were screened. A total of 80 lipids (32 TGs, 29 SMs, 9 FAs, 5 CEs, 5 PIs) were upregulated at 4 Gy, and a total of 91 lipids (39 SMs, 18 TGs, 15 HexCers, 7 CEs, 6 Cers, 3 LacCers, 2 LPEs, 1 PI) were upregulated at 12 Gy. Comparison of the ROC curves between the non-exposed and exposed groups at different doses showed AUC values ranging from 0.807 to 0.876. The metabolic pathways of potential lipid markers are mainly sphingolipid and glycerolipid metabolism, unsaturated fatty acid biosynthesis, fatty acid degradation and biosynthesis. Among the 13 dose-dependent radiosensitive lipids, CE (20:5), CE (18:1) and PI (18:2/18:2) were gradually incorporated into the TBI dose estimation model. CONCLUSION: This study suggested that it was feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage. Lipidomics strategies for radiation biodosimetry in humans were established with lipid biomarkers with good dose-response relationship.

Synthesis and evaluation of isothiazolo[4,5-b]pyridines as cyclin G-associated kinase (GAK) inhibitors.

Isothiazolo[4,3-b]pyridines have been extensively explored as inhibitors of cyclin G-associated kinase (GAK). In order to expand the structure-activity relationship study and to discover other chemotypes that act as GAK inhibitors, the closely related isothiazolo[4,5-b]pyridine scaffold was explored. An easy and efficient synthetic procedure to access 3,5- and 3,6-dihalogenated isothiazolo[4,5-b]pyridines as key building blocks was developed. Regioselective functionalization with various substituents was performed. None of the newly synthesized isothiazolo[4,5-b]pyridines were active as GAK inhibitors. Molecular modeling was applied to rationalise their inactivity as GAK binders.

The clinicopathological significance and prognostic value of PD-L1 in oral squamous cell carcinoma.

OBJECTIVE: To investigate the relationship between the expression of PD-L1 in OSCC and the clinicopathological features and prognosis of patients. METHODS: We retrospectively analyzed the clinicopathological data and prognosis of 381 OSCC patients. Immunohistochemical staining was performed on OSCC tumor specimens, and the expression level of PD-L1 was evaluated according to the combined positive score (CPS). Kaplan-Meier analysis was used to identify the effect of PD-L1 expression and clinicopathological features on the prognosis of patients. Univariate and multivariate Cox regression analyses were conducted to determine the hazard factors affecting the prognosis of patients. RESULTS: PD-L1 overexpression was significantly associated with cervical lymph node metastasis (p = 0.018), worse clinical stage (p = 0.022), worse tumor differentiation (p = 0.046), and worse depth of invasion (DOI) (p = 0.003). Poorer clinical stage and degree of tumor differentiation were significantly associated with poorer OS and DSS in patients. PD-L1 expression was not associated with prognosis in patients with OSCC. CONCLUSIONS: High PD-L1 expression was significantly associated with higher tumor malignancy in OSCC patients. Poorer clinical stage and degree of tumor differentiation were associated with poor prognosis in OSCC patients. Our results may help clinicians develop more appropriate individualized treatment strategies for their patients, thus improving their outcomes.

Estimating visibility and understanding factors influencing its variations at Bangkok airport using machine learning and a game theory-based approach.

In this study, six individual machine learning (ML) models and a stacked ensemble model (SEM) were used for daytime visibility estimation at Bangkok airport during the dry season (November-April) for 2017-2022. The individual ML models are random forest, adaptive boosting, gradient boosting, extreme gradient boosting, light gradient boosting machine, and cat boosting. The SEM was developed by the combination of outputs from the individual models. Furthermore, the impact of factors affecting visibility was examined using the Shapley Additive exPlanation (SHAP) method, an interpretable ML technique inspired by the game theory-based approach. The predictor variables include different air pollutants, meteorological variables, and time-related variables. The light gradient boosting machine model is identified as the most effective individual ML model. On an hourly time scale, it showed the best performance across three out of four metrics with the ρ = 0.86, MB = 0, ME = 0.48 km (second lowest), and RMSE = 0.8 km. On a daily time scale, the model performed the best for all evaluation metrics with ρ = 0.92, MB = 0.0 km, ME = 0.3 km, and RMSE = 0.43 km. The SEM outperformed all the individual models across three out of four metrics on an hourly time scale with ρ = 0.88, MB = 0.0 km, (second lowest), and RMSE = 0.75 km. On the daily scale, it performed the best with ρ = 0.93, MB = 0.02 km, ME = 0.27 km, and RMSE = 0.4 km. The seasonal average original (VISorig) and meteorologically normalized visibility (VISnorm) decrease from 2017 to 2021 but increase in 2022. The rate of decrease in VISorig is double than rate of decrease in VISnorm which suggests the effect of meteorology visibility degradation. The SHAP analysis identified relative humidity (RH), PM2.5, PM10, day of the season year (i.e., Julian day) (JD), and O3 as the most important variables affecting visibility. At low RH, visibility is not sensitive to changes in RH. However, beyond a threshold, a negative correlation between RH and visibility is found potentially due to the hygroscopic growth of aerosols. The dependence of the Shapley values of PM2.5 and PM10 on RH and the change in average visibilities under different RH intervals also suggest the effect of hygroscopic growth of aerosol on visibility. A negative relationship has been identified between visibility and both PM2.5 and PM10. Visibility is positively correlated with O3 at lower to moderate concentrations, with diminishing impact at very high concentrations. The JD is strongly negatively related to visibility during winter while weakly associated positively later in summer. Findings from this research suggest the feasibility of employing machine learning techniques for predicting visibility and understanding the factors influencing its fluctuations.

Repeat administration of human umbilical cord mesenchymal stem cells improves left ventricular diastolic function in mice with heart failure with preserved ejection fraction.

Currently, no therapy is proven to effectively improve heart failure with preserved ejection fraction (HFpEF). Although stem cell therapy has demonstrated promising results in treating ischemic heart disease, the effectiveness of treating HFpEF with human umbilical cord mesenchymal stem cells (hucMSCs) remains unclear. To answer this question, we administered hucMSCs intravenously (i.v.), either once or repetitively, in a mouse model of HFpEF induced by a high-fat diet and NG-nitroarginine methyl ester hydrochloride. hucMSC treatment improved left ventricular diastolic dysfunction, reduced heart weight and pulmonary edema, and attenuated cardiac modeling (inflammation, interstitial fibrosis, and hypertrophy) in HFpEF mice. Repeat hucMSC administration had better outcomes than a single injection. In vitro, hucMSC culture supernatants reduced maladaptive remodeling in neonatal-rat cardiomyocytes. Ribonucleic acid sequencing and protein level analysis of left ventricle (LV) tissues suggested that hucMSCs activated the protein kinase B (Akt)/forkhead box protein O1 (FoxO1) signaling pathway to treat HFpEF. Inhibition of this pathway reversed the efficacy of hucMSC treatment. In conclusion, these findings indicated that hucMSCs could be a viable therapeutic option for HFpEF.