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Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13+) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.
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Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.
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Purpose: This study investigates the prevalence and progression of myopia among primary and secondary school students in Xuzhou City, China, during one academic year. Methods: The study employed a prospective research design and utilized a whole-group sampling method to conduct non-cycloplegic spot photo screenings on 37,938 students from 44 primary and secondary schools in Xuzhou City, China. A one-year study was conducted to gather spherical equivalent refraction (SER), and subsequent analysis was carried out to explore the disparities in myopia prevalence among primary and secondary school students within the same academic year, as well as the progression of myopia. Results: During the 2022 academic year, the overall prevalence of myopia in the first and second semesters was 62.6 and 64.2% respectively, indicating an increasing trend. Particularly in primary school (Grades 1-6), the prevalence of myopia increased with higher grade levels, and significant variations in myopia prevalence were observed mainly in grades 1-3 and 7 (p < 0.05). The incidence rate of myopia in middle school remained stable, while in primary school, there was a positive correlation between myopia incidence and the grade level, with the highest rate of 20.1% in grade 6. Among the myopic population, the median value of spherical equivalent refraction slightly decreased between the two semesters. The proportion of high myopia increased among students in grades 5-8. Conclusion: Our study revealed that within one academic year, the prevalence of myopia and the severity of myopia have significantly increased in Xuzhou City, China, accompanied by an increase in the proportion of high myopia. For different grade levels, we should adopt personalized prevention and control measures, with a particular focus on lower grade levels and students who have just entered a new grade.
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Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.
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BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.
Subject(s)
Antigens, CD19 , Fever , Immunotherapy, Adoptive , Humans , Female , Male , Middle Aged , Immunotherapy, Adoptive/methods , Adult , Antigens, CD19/metabolism , Infections/blood , Aged , ROC Curve , Young Adult , Retrospective StudiesABSTRACT
OBJECTIVE: To evaluate the effectiveness of low-level red light (LRL) in controlling the progression of myopia in children and adolescents. METHODS: A randomized controlled trial was conducted from March 2022 to June 2022 at the Xuzhou First People's Hospital. A total of 73 children and adolescents with myopia, between the ages of 6 and 14, and meeting the inclusion criteria, were randomly divided into two groups. The experimental group wore single vision spectacles with LRL intervention, while the control group wore single vision spectacles alone. Spherical equivalent refraction (SER), axial length (AL), subfoveal choroidal thickness (SFCT), and best-corrected visual acuity (BCVA) were measured for the participants. Data analysis was performed using chi-square test, independent samples t-test, and Mann-Whitney U test. To compare the changes in SER and AL between groups, we utilized the Generalized Estimating Equations (GEE) model. RESULTS: The experimental group was composed of 36 individuals, while the control group had 37. The mean age of the participants was 8.9 ± 2.0 years. No statistically significant distinctions in SER, AL and SFCT were observed between the two groups at baseline (P > 0.05). After 6 months of intervention, the experimental group's increase in SER (-0.01D; 95 % CI: -0.09, 0.06) was higher than that of the control group (-0.41D; 95 % CI: -0.51, -0.32), with a significance level of P < 0.001. Furthermore, the changes over time revealed significant differences between the two groups (Wald χ2group×time: 31.576, P < 0.001). The experimental group's AL increase (-0.02 mm; 95 % CI: -0.07, 0.03) was less than the control group's (0.22 mm; 95 % CI: 0.19, 0.25) (P < 0.001), with a significant difference over time between them (wald χ2group×time: 62.305, P < 0.001). SFCT change after 6 months in the experimental group was significantly greater (29.19 µm; 95 % CI: 18.48, 39.91) compared to that of the control group (-6.59 µm; 95 % CI: -14.28, 1.09) (P < 0.001). No adverse events were observed, and there was no evidence of fundus structural damage on OCT imaging. CONCLUSIONS: The findings suggest that low-level red light can effectively control myopia progression in children and adolescents within 6 months. No adverse reactions were observed.
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Exploring low-cost visible light photocatalysts for CO2 reduction to produce proportionally adjustable syngas is of great significance for meeting the needs of green chemical industry. A S-Scheme CeO2/g-C3N4 (CeO2/CN) heterojunction was constructed by using a simple two-step calcination method. During the photocatalytic CO2 reduction process, the CeO2/CN heterojunction can present a superior photocatalytic performance, and the obtained CO/H2 ratios in syngas can be regulated from 1 : 0.16 to 1 : 3.02. In addition, the CO and H2 production rate of the optimal CeO2/CN composite can reach 1169.56 and 429.12â µmol g-1 h-1, respectively. This superior photocatalytic performance is attributed to the unique S-Scheme photogenerated charge transfer mechanism between CeO2 and CN, which facilitates rapid charge separation and migration, while retaining the excellent redox capacity of both semiconductors. Particularly, the variable valence Ce3+/Ce4+ can act as electron mediator between CeO2 and CN, which can promote electron transfer and improve the catalytic performance. This work is expected to provide a new useful reference for the rational construction of high efficiency S-Scheme heterojunction photocatalyst, and improve the efficiency of photocatalytic reduction of CO2, promoting the photocatalytic reduction of CO2 into useful fuels.
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Background: Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research. Purpose: This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma. Methods: We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models. Results: The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; p<0.001), bipolar disorder (aOR=2.97; p<0.001), depression (aOR=4.44; p<0.001), and sleep disorder (aOR=1.83; p<0.001) than the controls. Conclusion: The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma.
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INTRODUCTION: Brain dysfunction in sepsis is known as sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Neuron specific enolase (NSE) may serve as an important neurocritical biomarker for detection and longitudinal monitoring in SAE patients. Our systematic review and meta-analysis will aim to explore the diagnostic and prognostic value of serum NSE in SAE patients. Currently, no systematic review and meta-analysis have been assessed that NSE as a biomarker of SAE. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of serum NSE for the diagnostic and prognostic value of SAE patients. The primary objective is to evaluate the diagnostic accuracy of serum NSE as an independent biomarker for SAE. The secondary objective is to determine the prognostic strength of serum NSE as an independent biomarker of mortality in septic patients determine. We will perform a systematic search and descriptive review using the MEDLINE database and the PubMed interface. We will assign two independent reviewers to review all collected titles and associated abstracts, review full articles, and extract study data. We will use the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2) assessment tool according to the recommendation by the Cochrane Collaboration to evaluate quality and risk of bias of the selected studies. Subgroup and sensitivity analyses will also be used to assess heterogeneity. Review Manager version 5.4 and Stata16.0. will be used for statistical analysis. ETHICS AND DISSEMINATION: The meta-analysis will provide ICU physicians with the most current information to predict which patients are at risk of SAE and take corresponding intervention measures to reduce morbidity and ameliorate neurological outcomes. There is no need for ethics approval for this review. The findings will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42023398736.
Subject(s)
Biomarkers , Meta-Analysis as Topic , Phosphopyruvate Hydratase , Sepsis-Associated Encephalopathy , Systematic Reviews as Topic , Humans , Sepsis-Associated Encephalopathy/blood , Sepsis-Associated Encephalopathy/diagnosis , Phosphopyruvate Hydratase/blood , Biomarkers/blood , PrognosisABSTRACT
Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.
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Endoplasmic reticulum exit sites (ERESs) are tubular outgrowths of endoplasmic reticulum that serve as the earliest station for protein sorting and export into the secretory pathway. How these structures respond to different cellular conditions remains unclear. Here, we report that ERESs undergo lysosome-dependent microautophagy when Ca2+ is released by lysosomes in response to nutrient stressors such as mTOR inhibition or amino acid starvation in mammalian cells. Targeting and uptake of ERESs into lysosomes were observed by super-resolution live-cell imaging and focus ion beam scanning electron microscopy (FIB-SEM). The mechanism was ESCRT dependent and required ubiquitinated SEC31, ALG2, and ALIX, with a knockout of ALG2 or function-blocking mutations of ALIX preventing engulfment of ERESs by lysosomes. In vitro, reconstitution of the pathway was possible using lysosomal lipid-mimicking giant unilamellar vesicles and purified recombinant components. Together, these findings demonstrate a pathway of lysosome-dependent ERES microautophagy mediated by COPII, ALG2, and ESCRTS induced by nutrient stress.
Subject(s)
COP-Coated Vesicles , Calcium-Binding Proteins , Endoplasmic Reticulum , Endosomal Sorting Complexes Required for Transport , Lysosomes , Microautophagy , Vesicular Transport Proteins , Lysosomes/metabolism , Endoplasmic Reticulum/metabolism , Humans , Endosomal Sorting Complexes Required for Transport/metabolism , Endosomal Sorting Complexes Required for Transport/genetics , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/genetics , COP-Coated Vesicles/metabolism , Vesicular Transport Proteins/metabolism , Vesicular Transport Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Protein Transport , HeLa Cells , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , Autophagy/physiology , TOR Serine-Threonine Kinases/metabolism , Calcium/metabolismABSTRACT
INTRODUCTION: Brain dysfunction in sepsis is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Neuron specific enolase (NSE) may serve as an important neurocritical biomarker for detection and longitudinal monitoring in SAE patients. Our Meta-analysis aimed to explore the diagnostic and prognostic value of serum NSE in SAE patients. Currently, no systematic Review and Meta-analysis have been assessed that NSE as a biomarker of SAE. METHODS: The study protocol was registered in the PROSPERO database (CRD42023398736) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic review and Meta-analysis to evaluate the serum NSE's diagnostic accuracy for SAE and prognostic strength for probability of death of septic patients. We systematic searched electronic bibliographic databases from PubMed, MEDLINE, Web of Science, Embase, Cochrane databases, CNKI, CQVIP, and WFSD. QUADAS-2 assessment tool was used to evaluate quality and risk of bias of the selected studies. Subgroup analyses, funnel plots, sensitivity analyses were also carried out. Review Manager version 5.4 and Stata16.0. was used for statistical analysis. RESULTS: This Meta-analysis included 22 studies with 1361 serum samples from SAE patients and 1580 serum samples from no-encephalopathy septic (NE) patients. The Meta-analysis showed that individuals with SAE had higher serum NSE level than NE controls (SMD 1.93 (95 % CI 1.51-2.35), P < 0.00001). In addition, there are 948 serum samples from survival septic patients and 446 serum samples from non-survival septic patients, septic patients with survival outcomes had lower serum NSE levels than those with death outcomes (SMD -1.87 (95 % CI -2.43 to -1.32), P < 0.00001). CONCLUSION: Our Meta-analysis reveals a significant association between elevated NSE concentrations and the increased likelihood of concomitant SAE and mortality during septic patients. This comprehensive analysis will equip ICU physicians with up-to-date insights to accurately identify patients at risk of SAE and implement appropriate intervention strategies to mitigate morbidity and improve neurological outcomes. However, it is important to note that the presence of substantial heterogeneity among studies poses challenges in determining the most effective discrimination cutoff values and optimal sampling collection time.
Subject(s)
Brain Diseases , Sepsis-Associated Encephalopathy , Sepsis , Humans , Sepsis-Associated Encephalopathy/diagnosis , Sepsis/diagnosis , Biomarkers , Prognosis , Brain Diseases/diagnosis , Phosphopyruvate HydrataseABSTRACT
The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.
Subject(s)
Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck , Retrospective Studies , Prognosis , CD8-Positive T-Lymphocytes , Tumor MicroenvironmentABSTRACT
The most toxic of the ochratoxins is ochratoxin A (OTA), which is primarily produced by species of Aspergillus and Penicillium that can be found in maize, wheat, coffee, red wine, and various grains. OTA induces immunotoxicity, nephrotoxicity, hepatotoxicity, teratogenicity, and carcinogenicity in both animals and humans. Thus, there is a need to identify mycotoxin detoxification agents that can effectively decontaminate OTA. Seeds of basil (Ocimum basilicum L.), chan (Hyptis suaveolens L.), and chia (Salvia hispanica L.) are functional foods capable of eliminating harmful substances. Despite this potential, the impact of these seeds on OTA detoxification remains unclear. This study reveals that milled basil, chan, and chia seeds adsorb significant levels of OTA, with chia demonstrating the highest adsorption capacity, followed by chan and basil seeds showing the least efficiency. Furthermore, milled basil, chan, and chia seeds effectively reduced OTA residues in artificial gastric and intestinal fluids, where they achieved up to 93% OTA adsorption in the former. In addition, these milled seeds were able to remove OTAs from canned, drip, and instant coffee. This study is the first to report the OTA elimination potential of basil, chan, and chia seeds.
Subject(s)
Ochratoxins , Ocimum basilicum , Humans , Animals , Ochratoxins/analysis , Coffee/chemistry , Seeds/chemistryABSTRACT
PURPOSE: To compare the efficacy and safety of low-level red light (LRL) in controlling myopia progression at 3 different powers: 0.37 mW, 0.60 mW, and 1.20 mW. DESIGN: Single-center, single-masked, randomized controlled trial. PARTICIPANTS: Two hundred children aged 6-15 with myopia of -0.50 diopter (D) or more and astigmatism of -2.50 D or less were enrolled from April to May 2022. Follow-up ended in December 2022. METHODS: Participants were assigned randomly to 3 intervention groups and 1 control group (1:1:1:1). All participants wore single-vision spectacles. Moreover, the intervention group randomly received LRL at 3 different powers twice daily for 3 minutes per session, with a minimum 4-hour interval. MAIN OUTCOME MEASURES: Changes in spherical equivalent (SE), axial length (AL), and subfoveal choroidal thickness (SFCT) were measured. RESULTS: After 6 months, SE progression was significantly lower in the 0.37-mW group (0.01 D; 95% confidence interval [CI], -0.12 to 0.15), 0.60-mW group (-0.05 D; 95% CI, -0.18 to 0.07), and 1.20-mW group (0.16 D; 95% CI, 0.03 to 0.30) compared to the control group (-0.22 D; 95% CI, -0.50 to 0.30; adjusted P < 0.001 for all). AL changes in the 0.37-mW group (0.04 mm; 95% CI, -0.01 to 0.08), 0.60-mW group (0.00 mm; 95% CI, -0.05 to 0.05), and 1.20-mW group (-0.04 mm; 95% CI, -0.08 to 0.01) were significantly smaller than the control group (0.27 mm; 95% CI, 0.22 to 0.33; adjusted P < 0.001 for all). Similarly, increases in SFCT were significantly greater in the 0.37-mW group (22.63 µm; 95% CI, 12.13 to 33.34 µm), 0.60-mW group (36.17 µm; 95% CI, 24.37 to 48.25 µm), and 1.20-mW group (42.59 µm; 95% CI, 23.43 to 66.24 µm) than the control group (-5.07 µm; 95% CI, -10.32 to -0.13 µm; adjusted P < 0.001 for all). No adverse events were observed. CONCLUSIONS: LRL effectively controlled myopia progression at 0.37 mW, 0.60 mW, and 1.20 mW. Further research is required. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Subject(s)
Astigmatism , Myopia , Child , Humans , Red Light , Myopia/prevention & control , Refraction, Ocular , Choroid , Disease ProgressionABSTRACT
Background: Hydrotherapy can improve the motor and non-motor symptoms of Parkinson's disease (PD), but the long-term effects of hydrotherapy on PD are still unclear. Objective: The purpose of this systematic evaluation and meta-analysis was to explore the long-term effects of hydrotherapy on balance function in PD patients. Methods: A systematic search of five databases was conducted to identify appropriate randomized controlled trials (RCTs) according to the established inclusion and exclusion criteria. The general characteristics and outcome data (balance, exercise, mobility, quality of life, etc.) of the included studies were extracted, and the quality of the included studies was evaluated using the Cochrane risk of bias assessment tool. Finally, the outcome data were integrated for meta-analysis. Results: A total of 149 articles were screened, and 5 high-quality RCTs involving 135 PD patients were included. The results of the meta-analysis showed positive long-term effects of hydrotherapy on balance function compared to the control group (SMD = 0.69; 95% CI = 0.21, 1.17; p = 0.005; I2 = 44%), However, there were no significant long-term effects of hydrotherapy on motor function (SMD = 0.06; 95% CI = -0.33, 0.44; p = 0.77; I2 = 0%), mobility and quality of life (SMD = -0.21; 95% CI = -0.98, 0.57; p = 0.6; I2 = 71%). Interestingly, the results of the sensitivity analysis performed on mobility showed a clear continuation effect of hydrotherapy on mobility compared to the control group (SMD = -0.80; 95% CI = -1.23, -0.37; p < 0.001; I2 = 0%). Conclusion: The long-term effects of hydrotherapy on PD patients mainly focus on balance function, and the continuous effects on motor function, mobility, and quality of life are not obvious.
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Purpose: Burkholderia cepacia complex (Bcc) is a known significant opportunistic pathogen causing morbidity and mortality, particularly in those with cystic fibrosis, chronic granulomatous disease, or immunocompromising host. Mortality of Bcc bloodstream infections among non-cystic fibrosis patients remained high. The antibiotic treatment for Bcc infection is quite challenging due to its intrinsic resistance to most antibiotics, and the resistance to carbapenems was the biggest concern among them. We aimed to realize the mechanism of carbapenem resistance in Bcc. Patients and Methods: Ten strains of Bcc were identified by the MALDI-TOF MS, and the drug susceptibility test was using VITEK 2 system. The Burkholderia cepacia complex genomes were sequenced via Nanopore GridIon. We also downloaded another ninety-five strains of Bcc from the National Center for Biotechnology Information database to evaluate the divergence between carbapenem-resistance and carbapenem-sensitive strains. Results: The genetic organization between carbapenem-sensitive and carbapenem-resistant strains of Bcc showed no difference. However, in the carbapenem-sensitive strain, E151V substitution in PenR was detected. In addition, a novel specific OXA family subgroup, blaOXA-1043 in Burkholderia cenocepacia was discovered. Conclusion: The E151V substitution in PenR may be associated with carbapenem-sensitive in Bcc. Moreover, the V151E mutation in PenR may be related to the activation of PenB, leading to Bcc resistance to carbapenems. Besides, a novel OXA family subgroup, blaOXA-1043, was found in Burkholderia cenocepacia, which differs from the previous OXA family.
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SIGNIFICANCE: Changes in behavior and lifestyle during the post-coronavirus disease 2019 (COVID-19) epidemic may have some impact on myopia rates in preschoolers, and exploring the changes in myopia rates in preschool children may inform the formulation of myopia prevention and control policies. PURPOSE: This study aimed to investigate the prevalence of myopia in preschool children during the post-COVID-19 epidemic period in Xuzhou, China. METHODS: A series of cross-sectional school-based studies was conducted. A total of 117,632 preschool children aged 3 to 6 years were subjected to annual vision screening from 2019 to 2021. Spot photo screening was used to record the spherical equivalent refraction for each child and to analyze the prevalence of myopia by age, sex, and region during the post-COVID-19 epidemic period. RESULTS: A total of 113,979 preschool children were included in the analysis, of whom 60,784 (53.3%) were male and 53,195 (46.7%) were female. For all children, the mean ± standard deviation spherical equivalent refraction in 2019, 2020, and 2021 was +0.32 ± 0.50, +0.34 ± 0.55, and +0.34 ± 0.54 D, respectively (all P < .05), indicative of a very slight hyperopic shift. In all age groups, the change in mean spherical equivalent refraction and its distribution were relatively stable. From 2019 to 2021, the overall prevalence of myopia in preschool children was 3.1, 3.3, and 3.5%, respectively. The rise in myopia rates was minimal. The largest increase in the annual prevalence of myopia was seen among children aged 6 years, at 0.5%, followed by those aged 5 years (0.4%) and aged 3 years (0.4%). The prevalence was higher in boys than girls and in urban versus rural areas. CONCLUSIONS: During the post-COVID-19 epidemic period, the refractive status of Xuzhou preschool children remained stable.
Subject(s)
COVID-19 , Myopia , Child, Preschool , Humans , Male , Female , Prospective Studies , Prevalence , Cross-Sectional Studies , COVID-19/epidemiology , Myopia/epidemiology , Refraction, OcularABSTRACT
One-third of the mammalian proteome is comprised of transmembrane and secretory proteins that are synthesized on endoplasmic reticulum (ER). Here, we investigate the spatial distribution and regulation of mRNAs encoding these membrane and secretory proteins (termed "secretome" mRNAs) through live cell, single molecule tracking to directly monitor the position and translation states of secretome mRNAs on ER and their relationship to other organelles. Notably, translation of secretome mRNAs occurred preferentially near lysosomes on ER marked by the ER junction-associated protein, Lunapark. Knockdown of Lunapark reduced the extent of secretome mRNA translation without affecting translation of other mRNAs. Less secretome mRNA translation also occurred when lysosome function was perturbed by raising lysosomal pH or inhibiting lysosomal proteases. Secretome mRNA translation near lysosomes was enhanced during amino acid deprivation. Addition of the integrated stress response inhibitor, ISRIB, reversed the translation inhibition seen in Lunapark knockdown cells, implying an eIF2 dependency. Altogether, these findings uncover a novel coordination between ER and lysosomes, in which local release of amino acids and other factors from ER-associated lysosomes patterns and regulates translation of mRNAs encoding secretory and membrane proteins.