Nonlinear association between remnant cholesterol and reversion from impaired fasting glucose to normoglycemia: a multicenter cohort study.

BACKGROUND: Remnant cholesterol (RC), a potent atherogenic lipid, has been shown to be strongly correlated with insulin resistance and the pathogenesis of diabetes mellitus. However, the relationship between RC and normoglycemia reversal in individuals with impaired fasting glucose (IFG) is crucial and remains unclear. This investigation, which aimed to clarify this association, is important for understanding and potentially improving the management of diabetes. METHOD: This study, which included 15,019 IFG participants from 11 Chinese cities between 2010 and 2016, was conducted with a rigorous research process. Cox regression analysis revealed intriguing findings regarding the relationship between RC and normoglycemia reversal in individuals with IFG. Potential nonlinear associations were further explored via smooth curve-fitting techniques and 4-knot restricted cubic spline functions, ensuring a comprehensive analysis. To examine the validity of the results, an array of subgroup and sensitivity analyses were conducted, further bolstering the robustness of the findings. RESULTS: By the end of the 2.89-year median follow-up period, 6,483 of the 15,019 IFG participants (43.17%) had reverted to normoglycemia. The findings, which reveal that increased RC levels are inversely associated with the likelihood of normoglycemia reversal, are novel and significant. According to the fully adjusted Cox proportional hazards model analysis, an increase of one standard deviation in RC was associated with a 20% decrease in the likelihood of normoglycemia reversal among IFG participants (HR: 0.80, 95% CI: 0.77-0.82). A nonlinear association between RC and normoglycemia reversal was observed, with an inflection point at 41.37 mg/dL. This suggests that the growth rate of the likelihood of reversion decreased and stabilized after the inflection point was reached. Moreover, significant interactions were observed between the age groups, providing a more nuanced understanding of this complex relationship. CONCLUSION: Among Chinese adults with IFG, RC exhibited a negative nonlinear relationship with the probability of normoglycemia reversal. When RC levels reached or exceeded 41.38 mg/dL, the probability of achieving normoglycemia progressively diminished and subsequently stabilized. Maintaining RC levels below 41.38 mg/dL can significantly improve the probability of normoglycemia reversal among individuals with IFG, especially those aged 60 years or older.

Cs2CO3 Promoted [4 + 2] Cycloaddition of 1,6-Enynes: An Approach to Tetrahydro-1H-benzo-f-isoindole Isomers.

A Cs2CO3-promoted [4 + 2] cycloaddition of 1,6-enynes under mild reaction conditions has been developed. This protocol provides a facile approach to a series of tetrahydro-1H-benzo[f]isoindole isomerized products promoted by Cs2CO3 with moderate to high yields. By simply switching the reaction solvent and controlling the reaction time, two isomerization products could be obtained, both with good selectivity.

Effects of Dietary Ursolic Acid on Growth Performance and Intestinal Health of Largemouth Bass (Micropterus salmoides).

This study aimed to investigate the effects of ursolic acid (UA) on the growth performance and intestinal health of largemouth bass (Micropterus salmoides). Four diets were formulated with UA supplementation at 0, 250, 500, and 1000 mg/kg, defined as the control (CON), UA250, UA500, and UA1000, respectively. After an 8-week feeding experiment, the results showed that, in the UA500 group, the final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) increased, and the feed conversion ratio (FCR) and hepatosomatic index decreased. Total superoxide dismutase (T-SOD) activity exhibited a significant increase, and malondialdehyde (MDA) content decreased. An intestinal histological analysis revealed an improvement in the intestinal structural integrity of the UA500 group. The mRNA relative expression levels of physical barrier-related genes [occludin, claudin-1, and zonula occluden-1 (zo-1)] were upregulated. The mRNA relative expression of interlenkin 10 (il-10) increased, and the mRNA relative expression of interlenkin 1ß (il-1ß) and tumor necrosis factor-α (tnf-α) significantly decreased. The abundance of Firmicutes and Proteobacteria decreased, and the abundance of Tenericutes increased. The abundance of Mycoplasma, Cyanobium, and Staphylococcus decreased, while the abundance of Clostridium increased. In conclusion, dietary supplementation of UA significantly enhanced the growth performance and antioxidant capacity of largemouth bass while improving intestinal barrier function through its influence on the abundance of intestinal flora, such as Tenericutes, Firmicutes, and Mycoplasma. Optimal dietary UA levels for largemouth bass were determined to be between 498 and 520 mg/kg based on quadratic regression analyses of WGR, SGR, and FCR or T-SOD and MDA content.

Upregulation of ZMAT3 is Associated with the Poor Prognosis of Breast Cancer.

Background: Breast cancer is the leading cause of cancer-related deaths among women worldwide. Identifying robust biomarkers for predicting outcomes is essential for improving patient care and reducing fatalities. ZMAT3, a zinc finger protein with potential carcinogenic properties, has been associated with various cancers. However, its role in breast cancer prognosis remains unclear. Methods: We investigated the expression level of ZMAT3 in breast cancer tissues and its association with clinical outcomes through bioinformatics analysis and experimental validation. We examined the correlation between ZMAT3 expression and immune characteristics. ZMAT3 mRNA expression data from The Cancer Genome Atlas (TCGA) were analysed in relation to overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in patients with breast cancer. Immunohistochemistry (IHC) was performed on breast cancer tissues to assess ZMAT3 protein levels, with findings validated using qPCR and cell experiments. Results: ZMAT3 mRNA levels were significantly upregulated in breast cancer samples compared to normal tissues. High ZMAT3 expression was significantly correlated with the poor OS, DSS and PFI. A significant positive correlation was observed between high ZMAT3 mRNA levels and the abundance of tumour-infiltrating lymphocytes (TILs), especially CD8+T cells and regulatory T cells (Tregs). Multivariate Cox regression analysis identified ZMAT3 as an independent prognostic factor for breast cancer. IHC staining confirmed increased ZMAT3 protein expression in breast cancer tissues, which was further validated by qPCR and cell function tests. Conclusion: Our findings suggest that ZMAT3 is a prognostic biomarker linked to immune invasion in breast cancer. Elevated ZMAT3 expression correlates with adverse clinical outcomes, indicating its potential role in disease progression.

[Characteristics of soybean climate potential productivity in frigid region and its response to climate change]. / å¯’åœ°å¤§è±†æ°”å€™ç”Ÿäº§æ½œåŠ›ç‰¹å¾åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

A comprehensive understanding of the evolution of soybean climate potential productivity and its response to climate change in Heilongjiang Province can offer reference and basis for further tapping soybean production potential and realizing stable and high yield of soybean in the frigid region. Based on meteorological data from 80 meteorological stations in Heilongjiang Province from 1961 to 2020, we estimated photosynthesis, light temperature, and climate potential productivity of soybean by the stepwise correction method, examined the spatiotemporal variations by spatial interpolation and statistical analysis methods, and analyzed the impact of changes in climate factors such as radiation, temperature, and precipitation on climate potential productivity. The results showed that during the study period, the average values of photosynthesis potential productivity (YQ), light-temperature potential productivity (YT), and climate potential productivity (YW) of soybean in Heilongjiang Province were 7533, 6444, and 3515 kg·hm-2, respectively. The temporal changes of those variables showed significant increasing trends, with increases of 125.9, 182.9, and 116.1 kg·hm-2·(10 a)-1, respectively. For the spatial distribution, YQ, YT, YW were characterized by high values in plains and lower in the mountains, and gradually decreased from southwest to northeast. Compared with that during 1961-1990, the high value zone of YW in period 1991-2020 expanded by 7.1%, and the low value zone decreased by 5.1%. YW showed a significant response to climate change. The potential temperature growth period was extended due to climate warming. The continuous increase in thermal resources, combined with relatively sufficient precipitation, effectively alleviated the negative impact of the decline in light resources on soybean production in Heilongjiang Province. The projected "warm and humid" climate would comprehensively boost climate potential productivity of soybean in Heilongjiang Province.

The JA-to-ABA signaling relay promotes lignin deposition for wound healing in Arabidopsis.

Plants are frequently exposed to herbivory and mechanical damage that results in wounding. Two fundamental strategies, regeneration and healing, are employed by plants upon wounding. It is not fully understood how plants make different decisions, and how wound healing is sustained until the damaged tissues recover. In this study, we find that the local auxin accumulation patterns, determined by wounding modes, may activate different recovery programs in wounded tissues. Wounding triggers a transient jasmonic acid (JA) signaling that promotes lignin deposition in the first few hours after wounding occurs. This early response is subsequently relayed to ABA signaling via MYC2. The induced JA signaling promotes ABA biosynthesis to maintain the expression of RAP2.6, a key factor for sustained lignin biosynthesis and the later wound healing process. Our findings provide mechanistic insights into how plants heal from wounding and elucidate the molecular mechanisms underlying the prolonged healing process following wounding.

Genome-wide characterization of dynamic DNA 5-hydroxymethylcytosine and TET2-related DNA demethylation during breast tumorigenesis.

BACKGROUND: Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous. RESULTS: DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA). CONCLUSIONS: Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.

Positron emission tomography probes for stem cell monitoring: a review.

Stem cells possess unique self-renewal and differentiation capacities, that are central to cell replacement and tissue regeneration. The therapeutic potential of stem cell applications has garnered increasing attention in recent years for a spectrum of human diseases, from ischemic disorders to oncological challenges. Despite their potential, a comprehensive understanding of the biological behavior, efficacy, and safety of these cells remains elusive, hindering their clinical adoption. This review focuses on the use of positron emission tomography (PET) imaging as a cutting-edge tool for bridging this knowledge gap. PET imaging, a noninvasive diagnostic method, has been highlighted for its ability to monitor cellular dynamics after stem cell transplantation. A variety of molecular probes within the PET framework enable the longitudinal and quantitative evaluation of post-transplant cellular behavior. This discourse systematically delineates various PET probes specifically designed for the in vivo tracking of the stem cell life cycle. These probes offer a pathway to a deeper understanding and more precise evaluation of stem cell behavior post-transplantation. Implementing PET imaging probes can revolutionize the clinical understanding of stem cell behavior, advancing and widening clinical therapeutic applications.

Extrachromosomal circular DNA orchestrates genome heterogeneity in urothelial bladder carcinoma.

Rationale: Extrachromosomal circular DNA is a hallmark of cancer, but its role in shaping the genome heterogeneity of urothelial bladder carcinoma (UBC) remains poorly understood. Here, we comprehensively analyzed the features of extrachromosomal circular DNA in 80 UBC patients. Methods: We performed whole-genome/exome sequencing (WGS/WES), Circle-Seq, single-molecule real-time (SMRT) long-read sequencing of circular DNA, and RNA sequencing (RNA-Seq) on 80 pairs of tumor and AT samples. We used our newly developed circular DNA analysis software, Circle-Map++ to detect small extrachromosomal circular DNA from Circle-Seq data. Results: We observed a high load and significant heterogeneity of extrachromosomal circular DNAs in UBC, including numerous single-locus and complex chimeric circular DNAs originating from different chromosomes. This includes highly chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. We also found that large tumor-specific extrachromosomal circular DNAs could influence genome-wide gene expression, and are detectable in time-matched urinary sediments. Additionally, we found that the extrachromosomal circular DNA correlates with hypermutation, copy number variation, oncogene amplification, and clinical outcome. Conclusions: Overall, our study provides a comprehensive extrachromosomal circular DNA map of UBC, along with valuable data resources and bioinformatics tools for future cancer and extrachromosomal circular DNA research.

Phosphatidylserine-functional polydimethylsiloxane substrates regulate macrophage M2 polarization via modulus-dependent NF-κB/PPARγ pathway.

Macrophages, highly plastic innate immune cells, critically influence the success of implantable devices by responding to biochemical and physical cues. However, the mechanisms underlying their synergistic regulation of macrophage polarization on implant surfaces remain poorly understood. Therefore, we constructed anti-inflammatory phosphatidylserine (PS) modified polydimethylsiloxane (PDMS) substrates with low, medium, and high modulus (1-100 kPa) to investigate the combined effects and underlying mechanisms of substrate modulus and biochemical signal on macrophage polarization. The introduction of PS on the PDMS surface not only significantly enhanced the polarization of M0 to M2 but also potently suppressed lipopolysaccharide (LPS)-induced M1 activation, with this effect further potentiated by a reduction in substrate modulus. In vivo subcutaneous implantation experiments also corroborated the synergistic effect of PS functionalization and low modulus PDMS in inhibiting M1 activation and promoting M2 polarization. Notably, reduced modulus led to decreased integrin αV/ß3 clustering and cytoskeletal protein aggregation, ultimately diminishing YAP activation and nuclear translocation. Concomitantly, this disruption of the Piezo1-cytoskeletal protein positive feedback loop resulted in reduced p65/IκB phosphorylation and inflammation, while concurrently promoting PPARγ expression. Overall, our findings underscore the pivotal role of substrate modulus in modulating PS-mediated biomaterial-cell interactions, synergistically potentiating PS-induced M2 macrophage polarization, thus paving the way for the design of advanced immunomodulatory biomaterials.

Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused by ptxP3 macrolide-resistant Bordetella pertussis MT28 clone in China.

OBJECTIVES: China has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis. Here, we present a genomic epidemiological investigation of these events. METHODS: We performed a retrospective observational study using culture-positive B pertussis isolated in Shanghai, China, from 2016 to 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. RESULTS: From pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The macrolide-resistant Bordetella pertussis prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. Although MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symptoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations, including a novel prn150 allele, and has been detected across multiple regions in China. In addition, 26% (50/195) of MR-MT28 has evolved into predicted Pertactin (PRN)-deficient strains, with an IS481 insertion being the predominant mechanism. DISCUSSION: We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3-MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving + pertussis upsurge, age shift, and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance.

Hydrofluoric Acid-Free Broadband Near-Infrared Phosphors K2LiMF6:Cr3+ with Zero-Thermal Quenching: Structure, Luminescence, and Application.

Near-infrared (NIR) phosphor-converted light-emitting diodes (pc-LEDs) are considered promising light sources for night vision, food analysis, biomedicine, and plant growth. Yet, the application potential of this technology is vulnerable to the function degradation of the phosphors used, such as thermal quenching, which needs to be addressed urgently. Herein, the NIR phosphors K2LiMF6:Cr3+ (M = Al, Ga, In) with a cubic double-perovskite structure synthesized by a green hydrofluoric acid-free hydrothermal method exhibit outstanding thermal stability. Under 450 nm excitation, the as-synthesized K2LiMF6:Cr3+ phosphors all exhibited broadband NIR emission covering 650-1000 nm peaking at 755-780 nm. The prepared K2LiAlF6:Cr3+ phosphor shows a unique zero-thermal quenching performance (I423 K/I298 K = 102%). The comprehensive effects of a wide band gap, large thermal energy barrier, weak electron-phonon coupling effect, and high structural rigidity are responsible for the suppression of thermal quenching in this material. The output power of the NIR pc-LED device reached 285 mW at 100 mA. This series of phosphors has promise in night vision and bioimaging applications.

Encapsulated stretchable amphibious strain sensors.

Soft and stretchable strain sensors have found wide applications in health monitoring, motion tracking, and robotic sensing. There is a growing demand for strain sensors in amphibious environments, such as implantable sensors, wearable sensors for swimmers/divers, and underwater robotic sensors. However, developing a sensitive, stretchable, and robust amphibious strain sensor remains challenging. This work presents an encapsulated stretchable amphibious strain sensor. The conductive layer, made of silver nanowires embedded below the surface of polydimethylsiloxane, was sandwiched by two layers of thermoplastic polyurethane. Periodic sharp cuts were introduced to change the direction of flow from across the sensor to along the conductive path defined by the opening cracks. The crack advancing and opening is controlled by a unique combination of weak/strong interfaces within the sandwich structure. The cut design and the interfacial interactions between the layers were investigated. The strain sensor exhibited a high gauge factor up to 289, a linear sensing response, a fast response time (53 ms), excellent robustness against over-strain, and stability after 16 000 loading cycles and 20 days in an aqueous saline solution. The functionality of this amphibious strain sensor was demonstrated by tracking the motion of a robotic fish, undertaking language recognition underwater, and monitoring the blood pressure of a porcine aorta. This illustrates the promising potential for this strain sensor for both underwater use and surgically implantable applications.

Hypoxia-related signature to risk stratify patients for the benefit of immune checkpoint inhibitors therapy in head and neck squamous cell carcinoma: An experimental study.

BACKGROUND: Increasing evidence has shown that hypoxia is a biomarker of tumor proliferation and metastasis. This research aimed to identify a hypoxia-associated gene prognostic index (HAGPI) in head and neck squamous cell carcinoma (HNSCC) and based on HAGPI-defined subgroups to predict prognosis and response to immune checkpoint inhibitors therapy. METHODS: RNA-sequencing transcriptomic data for patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA). Protein-protein interaction network analysis was performed to select hypoxia-related hub genes. Univariate and multivariate cox regression analyses were used to identify hub genes to develop the HAGPI. Afterward expression data were imported into CIBERSORT to evaluate the relative proportion of 22 immune cells and compared the relative proportions of immune cells between the 2 HAGPI subgroups. The relationship between immunopheno score (IPS) and HAGPI was validated for immune checkpoint inhibitors (ICIs) response in TCGA cohorts. RESULTS: The HAGPI was constructed based on HS3ST1, HK1, PGK1, STC2, SERPINE1, PKLR genes. In high-HAGPI patients, the primary and secondary endpoint events in TCGA and GEO cohorts were significantly lower than low-HAGPI groups (P < .05). HAGPI-high patients exhibited a poorer prognosis than HAGPI-low patients did. The abundance of M2 macrophages and NK cell were significantly enhanced in the high-HAGPI while T cells regulatory and T cells CD8, were markedly elevated in the low-HAGPI. Meanwhile, patients in the low-HAGPI patients had higher levels of immunosuppressant expression and less aggressive phenotypes. Furthermore, IPS analysis showed that the low-HAGPI group with higher IPS represented a more immunogenic phenotype. CONCLUSION: The current study developed and verified a HAPGI model that can be considered as an independent prognostic biomarker and elucidated the tumor immune microenvironment of HNSCC.

Pulmonary neuroendocrine cells: crucial players in respiratory function and airway-nerve communication.

Pulmonary neuroendocrine cells (PNECs) are unique airway epithelial cells that blend neuronal and endocrine functions, acting as key sensors in the lung. They respond to environmental stimuli like allergens by releasing neuropeptides and neurotransmitters. PNECs stand out as the only lung epithelial cells innervated by neurons, suggesting a significant role in airway-nerve communication via direct neural pathways and hormone release. Pathological conditions such as asthma are linked to increased PNECs counts and elevated calcitonin gene-related peptide (CGRP) production, which may affect neuroprotection and brain function. CGRP is also associated with neurodegenerative diseases, including Parkinson's and Alzheimer's, potentially due to its influence on inflammation and cholinergic activity. Despite their low numbers, PNECs are crucial for a wide range of functions, highlighting the importance of further research. Advances in technology for producing and culturing human PNECs enable the exploration of new mechanisms and cell-specific responses to targeted therapies for PNEC-focused treatments.

A Fluorescent Lateral Flow Immunoassay for the Detection of Skeletal Muscle Troponin I in Serum for Muscle Injury Monitoring at the Point of Care.

Exercise-induced muscle injury is one of the most common types of sports injuries. Skeletal muscle troponin I (skTnI) serves as an ideal biomarker in assessing such injuries, facilitating timely detection and evaluation. In this study, we develop a fluorescent sandwich lateral flow immunoassay (LFIA) combined with a desktop analyzer for rapid detection of skTnI. Through optimizing the reaction system, the assay achieves a satisfying detection performance, reaching a limit of detection (LOD) of 0.5 ng/mL with a turnaround time of 15 min. The proposed detection platform offers portability, ease of use, and high sensitivity, which facilitates the monitoring of exercise-induced muscle injuries at the point of care. This feature is particularly advantageous for end users, enabling timely detection of sports-related injuries and ultimately enhancing prognosis and sports life.

The Application of Artificial Intelligence in Atrial Fibrillation Patients: From Detection to Treatment.

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. Although the guidelines for AF have been updated in recent years, its gradual onset and associated risk of stroke pose challenges for both patients and cardiologists in real-world practice. Artificial intelligence (AI) is a powerful tool in image analysis, data processing, and for establishing models. It has been widely applied in various medical fields, including AF. In this review, we focus on the progress and knowledge gap regarding the use of AI in AF patients and highlight its potential throughout the entire cycle of AF management, from detection to drug treatment. More evidence is needed to demonstrate its ability to improve prognosis through high-quality randomized controlled trials.

Rapid and extensive SARS-CoV-2 Omicron variant infection wave revealed by wastewater surveillance in Shenzhen following the lifting of a strict COVID-19 strategy.

Wastewater-based epidemiology (WBE) has emerged as a promising tool for monitoring the spread of COVID-19, as SARS-CoV-2 can be shed in the faeces of infected individuals, even in the absence of symptoms. This study aimed to optimize a prediction model for estimating COVID-19 infection rates based on SARS-CoV-2 RNA concentrations in wastewater, and reveal the infection trends and variant diversification in Shenzhen, China following the lifting of a strict COVID-19 strategy. Faecal samples (n = 4337) from 1204 SARS-CoV-2 infected individuals hospitalized in a designated hospital were analysed to obtain Omicron variant-specific faecal shedding dynamics. Wastewater samples from 6 wastewater treatment plants (WWTPs) and 9 pump stations, covering 3.55 million people, were monitored for SARS-CoV-2 RNA concentrations and variant abundance. We found that the viral load in wastewater increased rapidly in December 2022 in the two districts, demonstrating a sharp peak in COVID-19 infections in late-December 2022, mainly caused by Omicron subvariants BA.5.2.48 and BF.7.14. The prediction model, based on the mass balance between total viral load in wastewater and individual faecal viral shedding, revealed a surge in the cumulative infection rate from <0.1 % to over 70 % within three weeks after the strict COVID-19 strategy was lifted. Additionally, 39 cryptic SARS-CoV-2 variants were identified in wastewater, in addition to those detected through clinical surveillance. These findings demonstrate the effectiveness of WBE in providing comprehensive and efficient assessments of COVID-19 infection rates and identifying cryptic variants, highlighting its potential for monitoring emerging pathogens with faecal shedding.

Copper mediated follicular atresia: Implications for granulosa cell death.

3-nitropropanoic acid is a potent oxidative stress inducer that is conventionally regarded as a regulator of follicular atresia by regulating granulosa cells (GCs) death through the apoptosis pathway. There has been no research investigating the impact of copper metal overload induced Cuproptosis in ovarian GCs as a factor contributing to hindered follicular development.To elucidate whether 3-NP-induced oxidative stress plays a contributory role in promoting Cuproptosis, and discuss the role of Cuproptosis in the development of ovarian follicles.We conducted an analysis of cuproptosis occurrence in murine GCs and C57BL/6 J mice under the influence of 3-NP and 3-NP with added exogenous copper.The results revealed that 3-NP serving as a robust facilitator of exogenous copper uptake by upregulating the expression of copper transporter 1 (CTR1). In turn, culminated in the accumulation of intracellular copper within mouse granulosa cells (mGCs). Furthermore, 3-NP promoted mitochondrial permeability transition pore opening and concurrently reduced the stability of lipoic acid proteins. These actions collectively induced the oligomerization of Dihydrolipoamide S-Acetyltransferase (DLAT), ultimately leading to cuproptosis in GCs and consequent follicular atresia. Heavy metal copper and fungal decomposition product 3-NP, induce ovarian atresia via cuproptosis, modulating the reproductive performance of female animals.

Association between adherence to life's simple 7 metrics and risk of obstructive sleep apnea among adults in the United States.

BACKGROUND: We aimed to explore the impact of adherence to Life's Simple 7 (LS7) metrics on risk of obstructive sleep apnea (OSA), and the impact of inflammation on the association, in adults in the United States. METHODS: Data from 13,825 community-dwelling adults aged ≥ 20 years recruited in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008, 2015-2018 was analyzed. The LS7 score was calculated based on the AHA definition of LS7 metrics. The diagnosis of OSA was based on self-reported symptoms of sleep disturbance using a standard questionnaire. The Multivariable Apnea Prediction (MAP) Index score was also calculated to assess the risk of OSA. Log-binominal regression and negative binomial regression were performed to estimate the associations between LS7 and OSA and MAP index, with odds ratios (ORs) and prevalence ratios (PRs) and their 95% confidence intervals (CIs) calculated. Mediation analysis was performed to estimate the mediating effects of inflammatory indicators on the associations. RESULTS: A total of 4473 participants (32.4%) had OSA, and the mean MAP index was 0.39. In fully adjusted log-binominal regression models, with total score < 6 as the reference, the ORs (95% CIs) for risk of OSA were 0.90 (0.73, 1.10), 0.76 (0.65, 0.89), 0.78 (0.64, 0.95), and 0.45 (0.38, 0.54) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). When LS7 score was analyzed as a continuous variable, each 1-point increase in LS7 score was associated with a 15% decrease in OSA risk (P < 0.001). In negative binominal regression models, the adjusted PRs (95% CIs) for the MAP index were 0.93 (0.90, 0.97), 0.87 (0.84, 0.91), 0.80 (0.77, 0.84), and 0.55 (0.53, 0.57) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). For each 1-point increase in LS7 score, the risk of OSA decreased by 13% (P < 0.001). Consistent results were observed in subgroup analysis. Mediation analysis indicated that inflammatory factors, including blood cell count, neutrophil count, and C-reactive protein, positively mediated the association of LS7 with OSA, with a mediation proportion of 0.022 (P = 0.04), 0.02 (P = 0.04), and 0.02 (P = 0.02), respectively. CONCLUSIONS: In a nationally representative sample of US adults, adherence to LS7 metrics was independently associated with reduced OSA risk. Inflammation plays a mediating role in the association between LS7 and OSA.