Cytosolic stress granules relieve the ubiquitin-proteasome system in the nuclear compartment.

The role of cytosolic stress granules in the integrated stress response has remained largely enigmatic. Here, we studied the functionality of the ubiquitin-proteasome system (UPS) in cells that were unable to form stress granules. Surprisingly, the inability of cells to form cytosolic stress granules had primarily a negative impact on the functionality of the nuclear UPS. While defective ribosome products (DRiPs) accumulated at stress granules in thermally stressed control cells, they localized to nucleoli in stress granule-deficient cells. The nuclear localization of DRiPs was accompanied by redistribution and enhanced degradation of SUMOylated proteins. Depletion of the SUMO-targeted ubiquitin ligase RNF4, which targets SUMOylated misfolded proteins for proteasomal degradation, largely restored the functionality of the UPS in the nuclear compartment in stress granule-deficient cells. Stress granule-deficient cells showed an increase in the formation of mutant ataxin-1 nuclear inclusions when exposed to thermal stress. Our data reveal that stress granules play an important role in the sequestration of cytosolic misfolded proteins, thereby preventing these proteins from accumulating in the nucleus, where they would otherwise infringe nuclear proteostasis.

Systematic Optimization of Universal Real-Time Hypersensitive Fast Detection Method for HBsAg in Serum Based on SERS.

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.

Associations of long-term exposure to air pollution and greenness with incidence of chronic obstructive pulmonary disease in Northern Europe: The Life-GAP project.

BACKGROUND: Prolonged exposure to air pollution has been linked to adverse respiratory health, yet the evidence concerning its association with chronic obstructive pulmonary disease (COPD) is inconsistent. The evidence of a greenness effect on chronic respiratory diseases is limited. OBJECTIVE: This study aimed to investigate the association between long-term exposure to particulate matter (PM2.5 and PM10), black carbon (BC), nitrogen dioxide (NO2), ozone (O3) and greenness (as measured by the normalized difference vegetation index - NDVI) and incidence of self-reported chronic bronchitis or COPD (CB/COPD). METHODS: We analyzed data from 5355 adults from 7 centers participating in the Respiratory Health in Northern Europe (RHINE) study. Mean exposures to air pollution and greenness were assessed at available residential addresses in 1990, 2000 and 2010 using air dispersion models and satellite data, respectively. Poisson regression with log person-time as an offset was employed to analyze the association between air pollution, greenness, and CB/COPD incidence, adjusting for confounders. RESULTS: Overall, there were 328 incident cases of CB/COPD during 2010-2023. Despite wide statistical uncertainty, we found a trend for a positive association between NO2 exposure and CB/COPD incidence, with incidence rate ratios (IRRs) per 10 µg/m³ difference ranging between 1.13 (95% CI: 0.90-1.41) in 1990 and 1.18 (95% CI: 0.96-1.45) in 2000. O3 showed a tendency for inverse association with CB/COPD incidence (IRR from 0.84 (95% CI: 0.66-1.07) in 2000 to 0.88 (95% CI: 0.69-1.14) in 2010. No consistent association was found between PM, BC and greenness with CB/COPD incidence across different exposure time windows. CONCLUSION: Consistent with prior research, our study suggests that individuals exposed to higher concentrations of NO2 may face an elevated risk of developing COPD, although evidence remains inconclusive. Greenness was not associated with CB/COPD incidence, while O3 showed a tendency for an inverse association with the outcome.

Meta-analysis of the SARS-CoV-2 positivity rate in municipal wastewater.

The aim of this study is to conduct a systematic analysis of the SARS-CoV-2 levels in urban sewage and evaluate the associated positivity rates, thereby developing comprehensive insights into the epidemic situation and providing valuable inputs for the development of effective disease prevention and control strategies. The PubMed, Scopus, Embase, China National Knowledge Infrastructure, Wanfang Database, and VIP databases were systematically searched based on the predefined retrieval strategy. The literature published up to February 2023 was meticulously screened according to the predetermined inclusion and exclusion criteria, and the relevant data were extracted for subsequent integration. The quality assessment of the included studies adhered to the rigorous Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement guidelines. The meta-analysis was conducted using Stata 17.0 software. The meta-analysis included a total of 34 studies, encompassing 8429 municipal wastewater samples. A random effects model was employed for the analysis, revealing an overall SARS-CoV-2 positivity rate of 53.7% in the municipal wastewater samples. The subgroup analyses demonstrated significant regional variations in the SARS-CoV-2 positivity rate in municipal wastewater, with Africa exhibiting the highest rate at 62.5% (95% confidence interval [CI] 47.4 ~ 76.0%) and Oceania displaying the lowest at 33.3% (95% CI 22.0 ~ 46.3%). However, the subgroup analyses based on the sampling site, strain prevalence period, and laboratory testing method did not yield any statistically significant differences. The SARS-CoV-2 positivity rate in wastewater is relatively high globally, although it exhibits regional disparities. Regions with larger populations and lower economic levels demonstrate higher viral detection rates in sewage. Different types of wastewater sampling sites can be employed to monitor distinct aspects of the COVID-19 pandemic. Continuous surveillance of SARS-CoV-2 in wastewater plays a pivotal role in complementing clinical data, helping to track outbreak progression across diverse regions.

Multi-Level Information Encryption/Decryption of Fluorescent Hydrogels Based on Spatially Programmed Crystal Phases.

The growing urgence of information protection promotes continuously the development of information-encryption technique. To date, hydrogels have become an emerging candidate for advanced information-encryption materials, because of their unique stimulus responsiveness. However, current methods to design multi-level information-encrypted hydrogels usually need sophisticated chemistry or experimental setup. Herein, a novel strategy is reported to fabricate hydrogels with multi-level information encryption/decryption functions through spatially programming the polymorphic crystal phases. As homocrystalline and stereocomplex crystal phases in fluorescent hydrogels have different solvent stabilities, the transparency and fluorescence of the hydrogels can be regulated, thereby enabling the multi-level encryption/decryption processes. Moreover, the structural origins behind these processes are discussed. It is believe that this work will inspire future research on developing advanced information-encryption materials upon programming the polymer crystal structure.

Targeting choroidal vasculopathy via up-regulation of tRNA-derived fragment tRF-22 expression for controlling progression of myopia.

BACKGROUND: Myopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has gradually been recognized as a critical trigger of myopic pathology. However, the precise mechanism controlling choroidal vasculopathy remains unclear. Transfer RNA-derived fragments (tRFs) are known as a novel class of small non-coding RNAs that plays important roles in several biological and pathological processes. In this study, we investigated the role of tRF-22-8BWS72092 (tRF-22) in choroidal vasculopathy and myopia progression. METHODS: The tRF-22 expression pattern under myopia-related stresses was detected by qRT-PCR. MTT assays, EdU incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of tRF-22 in choroidal endothelial cell function in vitro. Isolectin B4 staining and choroidal sprouting assay ex vivo were conducted to detect the role of tRF-22 in choroidal vascular dysfunction in vivo. Immunofluorescent staining, western blot assays and ocular biometric parameters measurement were performed to examine whether altering tRF-22 expression in choroid affects scleral hypoxia and ECM remodeling and myopia progression in vivo. Bioinformatics analysis and luciferase activity assays were conducted to identify the downstream targets of tRF-22. RNA-sequencing combined with m6A-qPCR assays were used to identify the m6A modified targets of METTL3. Gain-of-function and Loss-of-function analysis were performed to reveal the mechanism of tRF-22/METTL3-mediated choroidal vascular dysfunction. RESULTS: The results revealed that tRF-22 expression was significantly down-regulated in myopic choroid. tRF-22 overexpression alleviated choroidal vasculopathy and retarded the progression of myopia in vivo. tRF-22 regulated choroidal endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, tRF-22 interacted with METTL3 and blocked m6A methylation of Axin1 and Arid1b mRNA transcripts, which led to increased expression of Axin1 and Arid1b. CONCLUSIONS: Our study reveals that the intervention of choroidal vasculopathy via tRF-22-METTL3- Axin1/Arid1b axis is a promising strategy for the treatment of patients with myopic pathology.

Comparison of acknowledged hepatocellular carcinoma risk scores in high-risk hepatitis C patients with sustained virological response.

Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC) even after sustained virological response (SVR). Several HCC risk scores have been developed but which one is most suitable for this population is unclear. In this study, we compared the prediction ability of the aMAP model, THRI model, PAGE-B model and Models of HCV in a prospective hepatitis C cohort in order to propose better model(s) to clinical practice. Adult hepatitis C patients with baseline advanced fibrosis (141 cases), compensated cirrhosis (330 cases) and decompensated cirrhosis (80 cases) were included and followed up every 6 months for about 7 years or until HCC development. Demographic data, medical history and laboratory results were recorded. HCCs were diagnosed by radiography, AFP or liver histology. The median follow-up period was 69.93(60.99-74.93) months, during which 53 (9.62%) patients developed HCC. The areas under the receiver operating characteristic curve of aMAP, THRI, PAGE-B and Models of HCV scores were 0.74, 0.72, 0.70 and 0.63 respectively. The predictive power of the aMAP model score was comparable to that of THRI, PAGE-Band higher than that of Models of HCV (p < 0.05). Dividing patients into non-high-risk and high-risk groups, the cumulative incidence rates of HCC based on aMAP, THRI, PAGE-B and Models of HCV was 5.57% vs. 24.17%, 1.10% vs. 13.90%, 5.80% vs. 15.90% and 6.41% vs. 13.81% (all p < 0.05). The AUC of the four models were all below 0.7 in male while all were higher than 0.7 in female. The performance of all the models was not influenced by fibrosis stage. aMAP, THRI model and PAGE-B model were all performed well while THRI model and PAGE-B model were easier to calculate. There was no need to select score according to fibrosis stage but should be caution when explain the results in male patients.

Decreased ubiquitin modifying enzyme A20 associated with hyper-responsiveness to ovalbumin challenge following intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) is strongly correlated with an increased risk of asthma later in life. Farm dust protects mice from developing house dust mite-induced asthma, and loss of ubiquitin modifying enzyme A20 in lung epithelium would abolish this protective effect. However, the mechanisms of A20 in the development of asthma following IUGR remains unknown. METHODS: An IUGR rat model induced by maternal nutrient restriction was used for investigating the role of A20 in the response characteristics of IUGR rats to ovalbumin (OVA) challenge. The ubiquitination of proteins and N6-methyladenosine (m6A) modifications were used to further assess the potential mechanism of A20. RESULTS: IUGR can reduce the expression of A20 protein in lung tissue of newborn rats and continue until 10 weeks after birth. OVA challenging can increase the expression of A20 protein in lung tissue of IUGR rats, but its level was still significantly lower than the control OVA group. The differentially ubiquitinated proteins in lung tissues were also observed in IUGR and normal newborn rats. Furthermore, this ubiquitination phenomenon continued from the newborn to adulthood. In the detected RNA methylations, m6A abundance of the motif GGACA was the highest. The higher abundances of m6A modification of A20 mRNA from IUGR were negatively correlated with the trend of A20 protein levels. CONCLUSION: These findings indicate A20 as a key regulator during the development of asthma following IUGR, providing further insight into the prevention of asthma induced by environmental factors.

Development of a Prediction Score for Evaluation of Extubation Readiness in Neurosurgical Patients with Mechanical Ventilation.

BACKGROUND: There is no widely accepted consensus on the weaning and extubating protocols for neurosurgical patients, leading to heterogeneity in clinical practices and high rates of delayed extubation and extubation failure-related health complications. METHODS: In this single-center prospective observational diagnostic study, mechanically ventilated neurosurgical patients with extubation attempts were consecutively enrolled for 1 yr. Responsive physicians were surveyed for the reasons for delayed extubation and developed the Swallowing, Tongue protrusion, Airway protection reflected by spontaneous and suctioning cough, and Glasgow Coma Scale Evaluation (STAGE) score to predict the extubation success for neurosurgical patients already meeting other general extubation criteria. RESULTS: A total of 3,171 patients were screened consecutively, and 226 patients were enrolled in this study. The rates of delayed extubation and extubation failure were 25% (57 of 226) and 19% (43 of 226), respectively. The most common reasons for the extubation delay were weak airway-protecting function and poor consciousness. The area under the receiver operating characteristics curve of the total STAGE score associated with extubation success was 0.72 (95% CI, 0.64 to 0.79). Guided by the highest Youden index, the cutoff point for the STAGE score was set at 6 with 59% (95% CI, 51 to 66%) sensitivity, 74% (95% CI, 59 to 86%) specificity, 90% (95% CI, 84 to 95%) positive predictive value, and 30% (95% CI, 21 to 39%) negative predictive value. At STAGE scores of 9 or higher, the model exhibited a 100% (95% CI, 90 to 100%) specificity and 100% (95% CI, 72 to 100%) positive predictive value for predicting extubation success. CONCLUSIONS: After a survey of the reasons for delayed extubation, the STAGE scoring system was developed to better predict the extubation success rate. This scoring system has promising potential in predicting extubation readiness and may help clinicians avoid delayed extubation and failed extubation-related health complications in neurosurgical patients.

The role of flexible bronchoscopy in children with Mycoplasma pneumoniae pneumonia.

PURPOSE: To explore the effectiveness of flexible bronchoscopy in pediatric Mycoplasma pneumoniae pneumonia (MPP). METHODS: This retrospective cohort study included children with MPP admitted between 2016 and 2019 in Shanghai. Tracheobronchial manifestations, etiologic findings, therapeutic effect, and health-economic indicators were assessed in bronchoscopy (plus bronchoalveolar lavage (BAL)) and non-bronchoscopy group. We used propensity-score matching and multivariable logistic regression to investigate the effect of bronchoscopy and BAL on disease recovery. RESULTS: In 900 children with MPP, 24/278 (8.6%) of those who underwent bronchoscopy had sputum plugs. Coinfection rate was four-fold enhanced by BAL (19.6% vs. 4.5%, p < 0.01) in patients with severe MPP (SMPP) and nearly doubled (10.8% vs. 5.9%, p = 0.03) in those without SMPP, compared with no BAL. Total of 224 (24.9%) patients had multilobar consolidation; after BAL, a significantly shorter lesion-resolution duration was observed on imaging (OR: 0.2, 95% CI: 0.0-0.7). However, longer fever duration (OR: 2.8, 95% CI: 1.7-4.8), hospital stay (OR: 3.1, 95% CI: 1.9-5.1), and higher costs were found in the bronchoscopy group than in the non-bronchoscopy group. CONCLUSIONS: Through BAL, coinfection may explain one-fifth of causes for SMPP. Bronchoscopy with BAL may increase the detection rate of pathogen and resolve pulmonary lesions in patients with multilobar consolidation. IMPACT: Flexible bronchoscopy with bronchoalveolar lavage is of great assistance in the timely detection of coinfection, sputum plug and inflammatory polyps in children with Mycoplasma pneumoniae pneumonia (MPP), and improves the recovery of lung damage in MPP patients with multilobar consolidation. This study provides new insights into the indications of flexible bronchoscopy for the diagnosis and treatment of pediatric patients with MPP.

Thermomonas mangrovi sp. nov., isolated from soil of a mangrove nature reserve.

A Gram-stain-negative, non-motile, aerobic and ovoid-rod-shaped bacterial strain, designated as 2C3345T, was isolated from soil of a mangrove nature reserve in Shenzhen, PR China and its taxonomic position was investigated. The 16S rRNA gene sequence of strain 2C3345T exhibited the highest similarity value to that of the type strains Thermomonas aquatica NBRC 113114T (98.4 %), Thermomonas carbonis KCTC 42013T (98.1 %), Thermomonas brevis DSM 15422T (98.0 %) and Thermomonas haemolytica DSM 13605T (97.9 %). Strain 2C3345T grew optimally at 28-30 °C, pH 7.0 and without NaCl. The predominant ubiquinone in 2C3345T was identified as Q-8. The major fatty acids of 2C3345T were iso-C15 : 0, iso-C16 : 0 and summed feature 9 (is0-C17:1ω9c and/or 10-methyl C16:0). The major polar lipids of 2C3345T were phosphatidylcholine (PC), phosphatidylglycerol (PG), diphosphatidglycerol (DPG), phosphatidylethanolamine (PE), an unidentified phospholipid, an unidentified aminolipid and two unidentified lipids. The DNA G+C content of strain 2C3345T was 69.9 %. The draft genome sequence of 2C3345T included 2 888 645 bp in total (N50=310 730 bp) with a medium read coverage of 388.6×and 21 scaffolds. In silico DNA-DNA hybridisation with type strains of species of the genus Thermomonas showed 24.4, 22.4, 24.1 and 23.2% relatedness to T. aquatica NBRC 113114T, T. carbonis KCTC 42013T, T. brevis DSM 15422T and T. haemolytica DSM 13605T, respectively. And the average nucleotide identity by blast (ANIb) values between 2C3345T and these four reference strains were 81.9, 80.0, 81.2 and 80.6 %, respectively, lower than the 95-96% threshold value for dividing prokaryotic species. On the basis of its phenotypic, chemotaxonomic, phylogenetic and phylogenomic properties, strain 2C3345T is considered to represent a novel species within the genus Thermomonas, for which the name Thermomonas mangrovi sp. nov. is proposed. The type strain is 2C3345T (=KCTC 92730T =MCCC 1K08335T).

Effect of appropriate empirical antimicrobial therapy on mortality of patients with Gram-negative bloodstream infections: a retrospective cohort study.

BACKGROUND: Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs. METHODS: This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality. RESULTS: We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35-0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15-1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86-1.02], p = 0.047). CONCLUSIONS: Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs.

Yunpi Tongbian Fang alleviates slow transit constipation induced by loperamide by regulating intestinal microbiota and short-chain fatty acids in rats.

Slow transit constipation (STC) is a prevalent chronic colonic dysfunction disease that significantly impairs the quality of life for affected individuals. Yunpi Tongbian Fang (YPTBF), a traditional Chinese medicine compound, has demonstrated promising clinical efficacy; however, its underlying mechanism remains elusive. In order to assess the laxative properties of YPTBF, which encompasses the influence on gut microbiota, gut metabolites, gut neurotransmitters, and colon histology, an oral administration of YPTBF was conducted for a duration of two consecutive weeks on STC rats induced by loperamide hydrochloride. The results showed that YPTBF improved the symptoms of STC, alleviated the decrease in total fecal volume and fecal water content caused by loperamide-induced constipation, restored intestinal transport function, and HE staining showed the recovery of pathological damage to the colon mucosa. In addition, YPTBF increased the concentrations of 5-HT and ACHE, while reducing the concentrations of VIP and NO. YPTBF adjusted the diversity and abundance of gut microbiota in STC rats, enabling the recovery of beneficial bacteria and promoting the production of acetic acid, propionic acid, and butyric acid. We found that YPTBF can improve constipation in STC rats, possibly by regulating the intestinal microbiota structure and improving SCFAs metabolism.

Paracoccus onchidii sp. nov., a moderately halophilic bacterium isolated from a marine invertebrate from the South China Sea.

A novel moderately halophilic bacterial strain, designated Z330T, was isolated from the egg of a marine invertebrate of the genus Onchidium collected in the South China Sea. The 16S rRNA gene sequence of strain Z330T exhibited the highest similarity value to that of the type strain Paracoccus fistulariae KCTC 22803T (97.6%), Paracoccus seriniphilus NBRC 100798T (97.6%) and Paracoccus aestuarii DSM 19484T (97.6%). Phylogenomic and 16S rRNA phylogenetic analysis showed that strain Z330T was most closely related to P. seriniphilus NBRC 100798T and P. fistulariae KCTC 22803T. Strain Z330T grew optimally at 28-30 °C, pH 7.0-8.0 with the presence of 5.0-7.0% (w/v) NaCl. In addition, growth of strain Z330T occurred at 0.5-16% NaCl, indicated strain Z330T was a moderately halophilic and halotolerant bacterium of genus Paracoccus. The predominant respiratory quinone in strain Z330T was identified as ubiquinone-10. The major polar lipids of strain Z330T were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, glycolipid and six unidentified polar lipids. The major fatty acids of strain Z330T was summed feature 8 (C18:1 ω6c and/or C18:1 ω7c). The draft genome sequence of strain Z330T includes 4,084,570 bp in total (N50 = 174,985 bp) with a medium read coverage of 463.6 × and 83 scaffolds. The DNA G + C content of strain Z330T was 60.5%. In silico DNA-DNA hybridization with the four type strains showed 20.5, 22.3, 20.1 and 20.1% relatedness to Paracoccus fistulariae KCTC 22803T, Paracoccus seriniphilus NBRC 100798T, Paracoccus aestuarii DSM 19484T and Paracoccus denitrificans 1A10901T, respectively. And the average nucleotide identity (ANIb) values between strain Z330T and these four type strains were 76.2, 80.0, 75.8 and 73.8%, respectively, lower than the 95-96% threshold value for dividing prokaryotic species. On the basis of the phenotypic, phylogenetic, phylogenomic and chemotaxonomic properties, a novel species of the genus Paracoccus, Paracoccus onchidii sp. nov. is proposed with the type strain Z330T (= KCTC 92727T = MCCC 1K08325T).

Ultrasensitive detection of SARS-CoV-2 S protein with aptamers biosensor based on surface-enhanced Raman scattering.

A rapid and accurate diagnostic modality is essential to prevent the spread of SARS-CoV-2. In this study, we proposed a SARS-CoV-2 detection sensor based on surface-enhanced Raman scattering (SERS) to achieve rapid and ultrasensitive detection. The sensor utilized spike protein deoxyribonucleic acid aptamers with strong affinity as the recognition entity to achieve high specificity. The spherical cocktail aptamers-gold nanoparticles (SCAP) SERS substrate was used as the base and Au nanoparticles modified with the Raman reporter molecule that resonates with the excitation light and spike protein aptamers were used as the SERS nanoprobe. The SCAP substrate and SERS nanoprobes were used to target and capture the SARS-CoV-2 S protein to form a sandwich structure on the Au film substrate, which can generate ultra-strong "hot spots" to achieve ultrasensitive detection. Analysis of SARS-CoV-2 S protein was performed by monitoring changes in SERS peak intensity on a SCAP SERS substrate-based detection platform. This assay detects S protein with a LOD of less than 0.7 fg mL-1 and pseudovirus as low as 0.8 TU mL-1 in about 12 min. The results of the simulated oropharyngeal swab system in this study indicated the possibility of it being used for clinical detection, providing a potential option for rapid and accurate diagnosis and more effective control of SARS-CoV-2 transmission.

The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change.

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014-2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

Research on the relationship between common metabolic syndrome and meteorological factors in Wuhu, a subtropical humid city of China.

As climate conditions deteriorate, human health faces a broader range of threats. This study aimed to determine the risk of death from metabolic syndrome (MetS) due to meteorological factors. We collected daily data from 2014 to 2020 in Wuhu City, including meteorological factors, environmental pollutants and death data of common MetS (hypertension, hyperlipidemia and diabetes), as well as a total number of 15,272 MetS deaths. To examine the relationship between meteorological factors, air pollutants, and MetS mortality, we used a generalized additive model (GAM) combined with a distributed delay nonlinear model (DLNM) for time series analysis. The relationship between the above factors and death outcomes was preliminarily evaluated using Spearman analysis and structural equation modeling (SEM). As per out discovery, diurnal temperature range (DTR) and daily mean temperature (T mean) increased the MetS mortality risk notably. The ultra low DTR raised the MetS mortality risk upon the general people, with the highest RR value of 1.033 (95% CI: 1.002, 1.065) at lag day 14. In addition, T mean was also significantly associated with MetS death. The highest risk of ultra low and ultra high T mean occured on the same day (lag 14), RR values were 1.043 (95% CI: 1.010, 1.077) and 1.032 (95% CI: 1.003, 1.061) respectively. Stratified analysis's result showed lower DTR had a more pronounced effect on women and the elderly, and ultra low and high T mean was a risk factor for MetS mortality in women and men. The elderly need to take extra note of temperature changes, and different levels of T mean will increase the risk of death. In warm seasons, ultra high RH and T mean can increase the mortality rate of MetS patients.

Hsa_circ_0001361 facilitates cell progression and glycolytic metabolism in neuroblastoma via interacting with mir-490-5p to induce TRIM2 upregulation.

Circular RNAs (circRNAs) can regulate the progression of neuroblastoma (NB) via miRNA/mRNA axis. This study aimed to investigate the functional mechanism of hsa_circ_0001361 in NB. Hsa_circ_0001361, miR-490-5p and tripartite motif 2 (TRIM2) were detected through reverse transcription-quantitative polymerase chain reaction. The proliferation ability was examined using cell counting kit-8 assay, colony formation assay and ethynyl-2'-deoxyuridine assay. Cell migration and invasion were assessed via transwell assay and wound healing assay. The protein levels were measured by western blot. Glycolysis was analyzed via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed for target analysis. Hsa_circ_0001361 research in vivo was performed using xenograft tumor assay. Hsa_circ_0001361 was overexpressed in NB tissues and cells. Hsa_circ_0001361 downregulation suppressed cell proliferation, metastasis and glycolysis. Hsa_circ_0001361 served as a miR-490-5p sponge. The functions of hsa_circ_0001361 in NB cells were associated with miR-490-5p sponging effect. Hsa_circ_0001361 resulted in TRIM2 expression change via targeting miR-490-5p. MiR-490-5p acted as a tumor inhibitor in NB by downregulating TRIM2. Hsa_circ_0001361 knockdown reduced tumor growth in vivo through mediating miR-490-5p/TRIM2 axis. Our results suggested that hsa_circ_0001361 upregulated TRIM2 by absorbing miR-490-5p, thereby promoting cell malignant behaviors and glycolytic metabolism in NB.

Predictive models for sepsis in children with Staphylococcus aureus bloodstream infections: a retrospective cohort study.

BACKGROUND: The presence of Staphylococcus aureus in the bloodstream can lead to the development of sepsis; however, the severity and risk factors of the systemic inflammatory response to Staphylococcus aureus bloodstream infections were unclear. This study is aimed to build a model to predict the risk of sepsis in children with Staphylococcus aureus bloodstream infections. METHODS: A retrospective analysis of hospitalized pediatric patients diagnosed with Staphylococcus aureus bloodstream infections was performed between January 2013 and December 2019. Each patient was assessed using the pediatric version of the Sequential Organ Failure Assessment score (pSOFA) within 24 h of blood culture collection. A nomogram based on logistic regression models was constructed to predict the risk factors for sepsis in children with Staphylococcus aureus bloodstream infections. It was validated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Of the 94 patients included in the study, 35 cases (37.2%) developed sepsis. The pSOFA scores ranged from 0 to 8, with 35 patients having a pSOFA score of ≥ 2. Six children (6.4%) died within 30 days, who were all from the sepsis group and had different pSOFA scores. The most common organs involved in sepsis in children with staphylococcal bloodstream infections were the neurologic system (68.6%), respiratory system (48.6%), and coagulation system (45.7%). Hospital-acquired infections (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3-7.2), implanted catheters (aOR, 10.4; 95% CI, 3.8-28.4), procalcitonin level ≥ 1.7 ng/mL (aOR, 15.4; 95% CI, 2.7-87.1), and underlying diseases, especially gastrointestinal malformations (aOR, 14.0; 95% CI, 2.9-66.7) were associated with Staphylococcus aureus sepsis. However, methicillin-resistant Staphylococcus aureus infection was not a risk factor for sepsis. The nomogram had high predictive accuracy for the estimation of sepsis risk, with an AUC of 0.85. CONCLUSIONS: We developed a predictive model for sepsis in children with Staphylococcus aureus infection.

Three-Dimensional Printed Poly (Lactic-co-Glycolic Acid)-Magnesium Composite Scaffolds for the Promotion of Osteogenesis Through Immunoregulation.

Scaffolds play an important role in bone tissue engineering. The ideal engineered scaffold needs to be biocompatible, bioactive, and able to regulate immune cells to enhance bone regeneration. In this study, magnesium (Mg)-contained poly(lactic-co-glycolic acid) (PLGA) scaffolds (hereinafter, referred to as PLGA-2Mg) were fabricated by 3-dimensional printing using a mixture of PLGA and MgSO 4 powder. Poly(lactic-co-glycolic acid) scaffolds (hereinafter, referred to as PLGA) were also fabricated by 3-dimensional printing and were used as control. The biocompatibility, immunoregulatory ability, and osteogenic properties of PLGA-2Mg were analyzed and compared with those of PLGA. The results indicate that the incorporation of Mg increased the Young modulus and surface roughness of the scaffold, but did not affect its degradation. The PLGA-2Mg further promoted the adhesion and proliferation of MC3T3-E1 cells compared with PLGA, which indicates its improved biocompatibility and bioactivity. In addition, PLGA-2Mg inhibited the polarization of RAW 264.7 cells toward the M1 phenotype by down-regulating the IL-1ß , IL-6 , and iNOs gene expression when challenged with lipopolysaccharide stimulation. In contrast, it promoted the polarization of RAW 264.7 cells toward the M2 phenotype by up-regulating the TGF-ß , IL-10 , and Arg-1 gene expression without lipopolysaccharide stimulation. Finally, MC3T3-E1 cells were cocultured with RAW 264.7 cells and scaffolds using a transwell system. It was found that the expression level of osteogenic-related genes ( ALP , COL-1 , BMP2 , and BSP ) was significantly upregulated in the PLGA-2Mg group compared with that in the PLGA group. Consequently, PLGA-2Mg with increased biocompatibility and bioactivity can promote osteogenesis through immunoregulation and has the potential to be used as a novel scaffold in bone tissue engineering.