The Association between Cardiac Arrest and Mortality in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Background: The impact of cardiac arrest (CA) at admission on the prognosis of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains a subject of debate. Methods: We conducted a retrospective study at West China Hospital from 2018 to 2021, enrolling 247 patients with AMI complicated by CS (AMI-CS). Patients were categorized into CA and non-CA groups based on their admission status. Univariate and multivariate Cox regression analyses were performed, with 30-day and 1-year mortality as the primary endpoints. Kaplan-Meier plots were constructed, and concordance (C)-indices of the Global Registry of Acute Coronary Event (GRACE) score, Intra-aortic Balloon Pump in Cardiogenic Shock (IABP-SHOCK) II score, and IABP-SHOCK II score with CA were calculated. Results: Among the enrolled patients, 39 experienced CA and received cardiopulmonary resuscitation at admission. The 30-day and 1-year mortality rates were 40.9% and 47.0%, respectively. Neither univariate nor multivariate Cox regression analyses identified CA as a significant risk factor for 30-day and 1-year mortality. In C-statistics, the GRACE score exhibited a moderate effect (C-indices were 0.69 and 0.67, respectively), while the IABP-SHOCK II score had a better predictive performance (C-indices were 0.79 and 0.76, respectively) for the 30-day and 1-year mortality. Furthermore, CA did not enhance the predictive value of the IABP-SHOCK II score for 30-day (p = 0.864) and 1-year mortality (p = 0.888). Conclusions: Cardiac arrest at admission did not influence the survival of patients with AMI-CS. Active resuscitation should be prioritized for patients with AMI-CS, regardless of the presence of cardiac arrest.

Label-Aware Dual Graph Neural Networks for Multi-Label Fundus Image Classification.

Fundus disease is a complex and universal disease involving a variety of pathologies. Its early diagnosis using fundus images can effectively prevent further diseases and provide targeted treatment plans for patients. Recent deep learning models for classification of this disease are gradually emerging as a critical research field, which is attracting widespread attention. However, in practice, most of the existing methods only focus on local visual cues of a single image, and ignore the underlying explicit interaction similarity between subjects and correlation information among pathologies in fundus diseases. In this paper, we propose a novel label-aware dual graph neural networks for multi-label fundus image classification that consists of population-based graph representation learning and pathology-based graph representation learning modules. Specifically, we first construct a population-based graph by integrating image features and non-image information to learn patient's representations by incorporating associations between subjects. Then, we represent pathologies as a sparse graph where its nodes are associated with pathology-based feature vectors and the edges correspond to probability of the co-occurrence of labels to generate a set of classifier scores by the propagation of multi-layer graph information. Finally, our model can adaptively recalibrate multi-label outputs. Detailed experiments and analysis of our results show the effectiveness of our method compared with state-of-the-art multi-label fundus image classification methods.

Characterization, expression and functional analysis of Hsp40 during LPS challenge in blood parrot Amphilophus citrinellus ×Vieja melanura.

Heat shock protein 40 belonging to heat shock protein family plays an important role in the immune responses of organisms. In this study, the full length cDNA of Hsp40 was 2426 bp including a 1368 bp open reading frame (ORF) encoding 455 amino acids with a molecular weight of 49.16 kDa and a theoretical isoelectric point of 9.34 in blood parrot Vieja synspila ♀ × Amphilophus citrinellus ♂, an important ornamental fish in China. It had three conserved domains DnaJ, CRR and DnaJ_C. Phylogenetic analysis showed that the sequence of Hsp40 among species was conserved, and the blood parrot Hsp40 was closely related to Neolamprologus brichardi. Blood parrot Hsp40 mRNA could be detected in all of the tissues examined and mainly distributed in the cytoplasm. The expression of Hsp40 was upregulated during lipopolysaccharide (LPS) challenge. Upregulated Hsp40 inhibited the activity of nuclear factor κB (NF-κB) and activated protein 1 (AP-1) and reduced the ratio of Bax/Bcl-2 mRNA expression. This study provides a theoretical basis for further exploring the role of Hsp40 gene in the anti-bacterial immunity of blood parrot.

Epigenetic modification of Castor zinc finger 1 (CASZ1) is associated with tumor microenvironments and prognosis of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) represents the predominant and remarkably diverse form of renal cell carcinoma. The involvement of the Castor zinc finger 1 (CASZ1) gene in adverse prognostic outcomes has been observed across different cancer types. Nevertheless, the specific altered activities and associated multi-omics characteristics of CASZ1 in ccRCC remain unelucidated. METHOD: In order to explore the expression of CASZ1, evaluate its prognostic significance, and aid in the therapeutic decision-making process for patients with ccRCC, the The Cancer Genome Atlas(TCGA), Gene expression omnibus (GEO), and The Human Protein Atlas (HPA) databases were utilized to gather data on clinicopathological data, prognostic information, genomic, methylomic and immunomic data. Additionally, the Genomics of drug sensitivity in cancer (GDSC) database provided information on drug sensitivity. RESULTS: CASZ1 expression was found to be significantly reduced in ccRCC and was associated with unfavorable pathological characteristics and a bleak prognosis. Diminished CASZ1 mRNA levels were notably correlated with heightened cytosine-phosphate-guanine (CpG) methylation , indicating a poorer prognosis for patients with increased methylation. Examination of RNA-seq data from TCGA indicated that the CASZ1-high expression subgroup displayed heightened immune cell infiltration and increased expression of immune checkpoint markers, potentially suggesting a more favorable response to immunotherapy. Furthermore, data from the GDSC database indicated that the CASZ1-low expression subgroup might exhibit greater sensitivity to anti-angiogenetic treatments, such as Sunitinib and Axitinib. CONCLUSIONS: These results indicate that CASZ1 may function as a biomarker for distinguishing various tumor microenvironment phenotypes, predicting prognosis, and assisting in treatment decisions for individuals with ccRCC.

Macrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints.

Sphk1 regulates HMGB1 via HDAC4 and mediates epithelial pyroptosis in allergic rhinitis.

Background: Allergic rhinitis (AR) is a global health issue affecting millions of individuals worldwide. Pyroptosis has emerged as a major player in the development of AR, and targeting its inhibition with specific drugs holds promise for AR treatment. However, a comprehensive understanding of the precise mechanisms underlying pyroptosis in AR remains to be explored, warranting further investigation. Objective: This study aims to elucidate the roles of HMGB1, Sphk1, and HDAC4 in regulating human nasal epithelial cell (hNEC) pyroptosis and AR. Methods: An in vitro AR cell culture model and an in vivo AR mouse model were established. Western blot, ELISA, histological staining, and flow cytometry were utilized to confirm the gene and protein expression. The interactions among Sphk1, HDAC4, and HMGB1 were validated through ChIP, Co-IP, and Dual-luciferase assay. Results and conclusion: We identified that the expression levels of Sphk1, HMGB1, and inflammasome components, including IL-18, and IL-1ß were elevated in AR patients and mouse models. Knockdown of Sphk1 inhibited hNEC pyroptosis induced by dust mite allergen. Overexpression of HDAC4 suppressed HMGB1-mediated pyroptosis in hNECs. In addition, HDAC4 was found to mediate the transcriptional regulation of HMGB1 via MEF2C, a transcription factor. Additionally, Sphk1 was shown to interact with CaMKII-δ, promoting the phosphorylation of HDAC4 and inhibiting its cytoplasmic translocation. Knockdown of HDAC4 reversed the effect of Sphk1 knockdown on pyroptosis. These discoveries offer a glimpse into the molecular mechanisms underlying AR and suggest potential therapeutic targets for the treatment of this condition.

A CD25×TIGIT bispecific antibody induces anti-tumor activity through selective intratumoral Treg cell depletion.

Intratumoral regulatory T cells (Tregs) express high levels of CD25 and TIGIT, which are also recognized as markers of effector T cell (Teff) activation. Targeting these molecules each alone with monoclonal antibodies (mAbs) poses a risk of concurrently depleting both Teffs and peripheral Tregs, thereby compromising the effectiveness and selectivity of intratumoral Treg depletion. Here, leveraging the increased abundance of CD25+ TIGIT+ double-positive Tregs in the solid tumor microenvironment (but not in peripheral tissues), we explore the feasibility of using a CD25×TIGIT bispecific antibody (bsAb) to selectively deplete intratumoral Tregs. We initially constructed a bsAb co-targeting mouse CD25 and TIGIT, NSWm7210, and found that NSWm7210 conferred enhanced intratumoral Treg depletion, Teff activation, and tumor suppression as compared to the parental monotherapies in mouse models. We subsequently constructed a bsAb co-targeting human CD25 and TIGIT (NSWh7216), which preferentially eliminated CD25+ TIGIT+ double-positive cells over single-positive cells in vitro. NSWh7216 exhibited enhanced anti-tumor activity without toxicity of peripheral Tregs in CD25 humanized mice compared to the parental monotherapies. Our study illustrates the use of CD25×TIGIT bsAbs as effective agents against solid tumors based on selective depletion of intratumoral Tregs.

Unraveling how hydrogen-bonding networks affect the capture of amphetamine-type stimulants by polymerized deep eutectic solvent modified magnetic biochar: Coupling quantum chemical calculations with experiment.

The abuse of amphetamine-type stimulants (ATSs) has caused irreversible harm to public safety and ecosystems. A novel polymerized deep eutectic solvent modified magnetic pomelo peel biochar (PMBC) was prepared, and the differences in adsorption of four abused amphetamine-type stimulants (ATSs: AMP, MAMP, MDA and MDMA) were due to varying hydrogen bonds quantities and strengths. PMBC showed excellent chemical reactivity to MDMA, with a maximum adsorption capacity of 926.13 µg g-1, which was 3.25, 2.52 and 1.15 times higher than that of AMP, MAMP and MDA, respectively. Modern spectral analysis showed that there were a series of active centers (-COOH, -NH2 and -OH) on the PMBC, which could form hydrogen bond networks with the nitrogen and oxygen functional groups of ATSs. In various chemical environments: pH level (4-11), inorganic ion and organic matter (humic acid), PMBC maintained high activity towards four ATSs. Additionally, the quantum chemical calculations revealed that the methylenedioxy bridge of ATSs can increase the active sites, and the -NH- and -NH2 groups had different hydrogen bond formation capabilities, which together resulted in the adsorption order of PMBC on the four ATSs: MDMA > MDA > MAMP > AMP. Moreover, the hydrogen-bonding binding energies of several common hydrogen-bonding types were compared, including O-H····O, N-H····O/O-H····N and N-H···N. This study laid an empirical and theoretical foundation for the efficient capture of ATSs in water and contributed to the innovative design of materials.

Preoperative gut microbiota of POCD patients induces pre- and postoperative cognitive impairment and systemic inflammation in rats.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD. METHODS: Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1ß and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1. RESULTS: Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1ß in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1ß and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus. CONCLUSIONS: Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.

Cardiovascular disease in connective tissue disease-associated interstitial lung disease: A systematic review and meta-analysis of observational studies.

OBJECTIVES: We performed a systematic review and meta-analysis to assess whether patients with connective tissue disease (CTD)-associated interstitial lung diseases (ILD) have an increased prevalence of cardiovascular (CV) disease and to validate associated risk factors. METHODS: The PRISMA guidelines and PICO model were followed. We searched PubMed, Embase, Cochrane Library databases, Scopus, and Directory of Open Access Journals from inception to April 2024. RESULTS: Thirteen studies comprising of 12,520 patients were included. Patients with CTD-ILD had a significantly increased risk of CV disease than patients with CTD (relative risk [RR] = 1.65, 95 % confidence interval [CI]: 1.41, 1.93), which are related to the proportion of men (P = 0.001) and the proportion of smokers (P = 0.045). Subgroup analysis found that patients with CTD-ILD had a higher risk of heart failure (RR = 2.84, 95 % CI: 1.50, 5.39), arrhythmia (RR = 1.55, 95 % CI: 1.22, 1.97) than patients with CTD. Another subgroup analysis showed that RA-ILD and SSc-ILD were associated with an increased risk of CV disease, but not IIM-ILD and MCTD-ILD (RA-ILD: RR = 2.19, 95 % CI: 1.27, 3.80; SSc-ILD: RR = 1.53, 95 % CI: 1.29, 1.82). Besides, patients with CTD-ILD had a higher prevalence of pulmonary arterial hypertension (RR = 2.48, 95 % CI: 1.69, 3.63) than patients with CTD. CONCLUSIONS: Patients with CTD-ILD had a 1.65 times increased risk of CV than patients with CTD-non-ILD, with increased prevalence of heart failure and arrhythmia. The risk of CV disease in SSc-ILD and RA-ILD is increased and we should pay more attention to male smokers. In addition, compared with CTD patients, CTD-ILD patients had a higher risk of pulmonary arterial hypertension.

Baffled flow constructed wetland-microbial fuel cell coupling systems for combined secondary and tertiary wastewater treatment with simultaneous bioelectricity generation.

Baffled flow constructed wetland-microbial fuel cell (BFCW-MFC) coupling systems were constructed with baffles embedded in cathode chamber. The performance of BFCW-MFCs operated at different hydraulic retention times (HRTs) was evaluated. At the representative HRT of 48 h, embedding 1 or 2 baffles (i.e., BFCW-MFC1 and BFCW-MFC2) produced 32.9 % (29.5 mW/m3) and 53.2 % (34.0 mW/m3) more power density than control system (22.2 mW/m3), respectively. Comparable organics biodegradation efficiencies were observed in BFCW-MFCs at the same HRTs. BFCW-MFC1 and BFCW-MFC2 had higher ammonium and total nitrogen removal efficiency. All systems had decreased nitrogen removal performance as shortening HRT from 72 to 12 h. Multiple nitrogen removal processes were involved, including ammonium oxidation, anammox, and heterotrophic and autotrophic denitrification. The predominant bacteria on electrodes were identified for analyzing bioelectricity generation and wastewater treatment processes. Generally, simultaneous wastewater treatment and bioelectricity generation were obtained in BFCW-MFCs, and embedding 1 or 2 baffles was preferable.

Exploration on cold adaptation of Antarctic lichen via detection of positive selection genes.

Lichen as mutualistic symbiosis is the dominant organism in various extreme terrestrial environment on Earth, however, the mechanisms of their adaptation to extreme habitats have not been fully elucidated. In this study, we chose the Antarctic dominant lichen species Usnea aurantiacoatra to generate a high-quality genome, carried out phylogenetic analysis using maximum likelihood and identify genes under positive selection. We performed functional enrichment analysis on the positively selected genes (PSGs) and found that most of the PSGs focused on transmembrane transporter activity and vacuole components. This suggest that the genes related to energy storage and transport in Antarctic U. aurantiacoatra were affected by environmental pressure. Inside of the 86 PSGs screened, two protein interaction networks were identified, which were RNA helicase related proteins and regulator of G-protein signaling related proteins. The regulator of the G-protein signaling gene (UaRGS1) was chosen to perform further verification by the lichen genetic manipulation system Umbilicaria muhlenbergii. Given that the absence of UmRgs1 resulted in elevated lethality to cold shock, the role for UaRgs1 in Antarctic U. aurantiacoatra resistance to cold can be inferred. The investigation of lichen adaptation to extreme environments at the molecular level will be opened up.

Association between Healthy Eating Index-2015 and prostate enlargement: A cross-sectional study of the National and Nutrition Examination Survey 2001-2008.

Background: Benign prostate hyperplasia (BPH) occurs in elder men globally with high prevalence. Human diet and lifestyle aroused great attention in the prevalence of BPH. Prostate enlargement (PE) is a major symptom of BPH. Objectives: To elaborate the effect of total diet quality for adults from the United States, we investigated the association between Health Eating Index (HEI)-2015 and the risk of PE in adults from the National Health and Nutrition Examination Survey (NHANES). Methods: This cross-sectional study was conducted based on NHANES 2001-2008. Participants who reported a PE history were included. We conducted a logistic regression analysis to investigate the association between HEI-2015 and PE. Results: A total of 4,866 male participants aged 40 and above were enrolled. Compared with Q1 of HEI-2015, no significant differences were found in adjusted models. Higher vegetables intake (Odds ratio [OR] = 1.073; 95% confidence interval [95%CI] 1.015 to 1.134, P = 0.02) and higher total dairy intake (OR = 1.034; 95%CI 1.009 to 1.061, P = 0.01) were significantly related with higher risk of PE. Conclusions: There was no significant difference between HEI-2015 and PE after full adjustment. Total vegetables and dairy product might be associated with higher risk of PE and needed further validation.

Long-term outcomes of left bundle branch area pacing compared to right ventricular pacing in TAVI patients.

BACKGROUND: New-onset permanent pacemaker implantation (PPMI) is still a common complication after transcatheter aortic valve implantation (TAVI) with adverse clinical outcomes. OBJECTIVE: To investigate whether left bundle branch area pacing (LBBAP) improves long-term clinical results compared to traditional right ventricular pacing (RVP) in patients requiring PPMI following TAVI. METHODS: A total of 237 consecutive patients undergoing RVP (N=117) or LBBAP (N=120) following TAVI were retrospectively included. Long-term outcomes including all-cause death, heart failure rehospitalization (HFH) and left ventricular ejection fraction (LVEF) change compared to baseline were obtained until 5 years post-TAVI. RESULTS: The mean age of the overall population was 74 years with a mean surgical risk score as 4.4%. The paced QRS duration was significantly longer in RVP group compared to LBBAP group (151 ± 18 vs. 122 ± 12 ms, P<0.001). There was no difference between two groups in all-cause death (13.7% vs. 13.3%, adjusted HR: 0.76; 95% CI: 0.37 to 1.58; P=0.466) or the composite endpoint of death and HFH (29.9% vs. 19.2%, adjusted HR: 1.22; 95% CI: 0.70 to 2.13; P=0.476), however, the risk of HFH was significantly higher in RVP group at 5 years after TAVI (21.4% vs. 7.5%, adjusted HR: 2.26; 95% CI: 1.01 to 5.08; P=0.048). There was a greater improvement of LVEF over time in LBBAP group (P=0.046 for LVEF changes over time between groups). CONCLUSIONS: LBBAP improved long-term clinical outcomes compared to RVP in patients undergoing PPMI after TAVI in terms of less HFH and better LVEF improvement.

Application of real-time shear wave elastography to Achilles tendon hardness evaluation in older adults.

BACKGROUND: Real-time shear wave elastography (SWE) is a non-invasive imaging technique used to measure tissue stiffness by generating and tracking shear waves in real time. This advanced ultrasound-based method provides quantitative information regarding tissue elasticity, offering valuable insights into the mechanical properties of biological tissues. However, the application of real-time SWE in the musculoskeletal system and sports medicine has not been extensively studied. AIM: To explore the practical value of real-time SWE for assessing Achilles tendon hardness in older adults. METHODS: A total of 60 participants were enrolled in the present study, and differences in the elastic moduli of the bilateral Achilles tendons were compared among the following categories: (1) Age: 55-60, 60-65, and 65-70-years-old; (2) Sex: Male and female; (3) Laterality: Left and right sides; (4) Tendon state: Relaxed and tense state; and (5) Tendon segment: Proximal, middle, and distal. RESULTS: There were no significant differences in the elastic moduli of the bilateral Achilles tendons when comparing by age or sex (P > 0.05). There were, however, significant differences when comparing by tendon side, state, or segment (P < 0.05). CONCLUSION: Real-time SWE plays a significant role compared to other examination methods in the evaluation of Achilles tendon hardness in older adults.

Human umbilical cord mesenchymal stem cells derived extracellular vesicles ameliorate kidney ischemia-reperfusion injury by suppression of senescent tubular epithelial cells - Experimental Study.

BACKGROUND: Human umbilical cord mesenchymal stem cells derived extracellular vesicles (HUMSC-EVs) have drawn much interest in kidney transplantation, mainly because of their renoprotection by alleviating cell injury and stimulating tissue repair. Cellular senescence has been proven to play a dual regulatory role in kidney ischemia-reperfusion injury (IRI), and the regulation of HUMSC-EVs on tubular epithelial cell senescence may be a potential therapeutic target. MATERIALS AND METHODS: In vitro, the hypoxia-reoxygenation of human kidney-2 cells was used to simulate kidney IRI, and the regulation of HUMSC-EVs on human kidney-2 cells was detected. Transcriptome sequencing of human kidney-2 cells was used to explore the potential regulatory mechanism. In vivo, adult male mice were divided into five groups: control group, IRI group, HUMSC-EVs treatment group, senolytics treatment group (dasatinib + quercetin), and combined treatments group (HUMSC-EVs and senolytics). Kidney function, senescent features of tubular epithelial cells, acute kidney injury, and chronic interstitial fibrosis in mice were detected to explore the renoprotection effects of HUMSC-EVs. RESULTS: Kidney IRI significantly up-regulated expressions of LaminB1, p53, p21, p16, senescence-associated beta-galactosidase, and apoptosis of tubular epithelial cells. In the mouse kidney IRI model, kidney subcapsular injection of HUMSC-EVs significantly improved kidney function, reducing the senescent features of tubular epithelial cells and alleviating acute kidney injury and chronic interstitial fibrosis. HUMSC-EVs mainly achieved renoprotection by regulating Bax/Bcl-2-dependent apoptosis during acute kidney injury and mostly reduced tubular atrophy and kidney interstitial fibrosis by regulating Ras-pERK-Ets1-p53 pathway-dependent cell senescence. Oral administration of senolytics also alleviated kidney injury induced by IRI, while the combined treatments of HUMSC-EVs and senolytics had better renoprotection effects. CONCLUSIONS: The combination of HUMSC-EVs and senolytics alleviated acute kidney injury and chronic interstitial fibrosis by dynamic regulation of cell senescence and apoptosis, which provides a therapeutic potential strategy for organ preservation and tissue repair in kidney transplantation.

Burden of Voice Use and Voice Disorders in Early Childhood Educators in Singapore.

It is well established that teachers are prone to voice-related problems. Much of existing literature focuses on grade-school teachers, and early childhood educators are an understudied demographic. This study aims to determine the burden of voice use and prevalence of voice disorders in early childhood educators in Singapore. METHODS: A cross-sectional survey was performed in 2022. This was sent via email to all registered preschools/kindergartens in Singapore. RESULTS: There were a total of 413 responses. Mean age of respondents was 37.4years (range 28-46years) and 99.0% were female. 67.0% were Chinese, 14.8% Malay, 9.5% Indian, and 8.7% Others. Regarding burden of voice use, 81.4% of respondents reported talking for extended periods of time (>30 minutes) and 74.5% reported having to sing on >1 occasion a day. 321/413 respondents (77.9%) had to shout or raise their voice at least once a day, whereas 128 of out 413 respondents (31.1%) reported having to scream at least once a day. Point prevalence of voice disorder (defined by VHI-10 >11 was 37.5% and sVHI-10 >12) was 47.2%. Over the preceding 12months, 72.2% of respondents experienced hoarseness on at least 4-7 occasions, with 41.4% losing their voice. While 52.5% of respondents have taken at least 1 sick day off due to an issue with their voice, only 38% has consulted a GP and 13.6% consulted an ENT specialist on at least one occasion. 45.8% have considered leaving the profession on at least one occasion. Factors significantly associated with both point prevalence and year-long prevalence of voice disorders include large class size of >20 students and needing to shout and/or scream >1 time/day.