Systematic metabolic engineering enables highly efficient production of vitamin A in Saccharomyces cerevisiae.

Vitamin A is a micronutrient critical for versatile biological functions and has been widely used in the food, cosmetics, pharmaceutical, and nutraceutical industries. Synthetic biology and metabolic engineering enable microbes, especially the model organism Saccharomyces cerevisiae (generally recognised as safe) to possess great potential for the production of vitamin A. Herein, we first generated a vitamin A-producing strain by mining ß-carotene 15,15'-mono(di)oxygenase from different sources and identified two isoenzymes Mbblh and Ssbco with comparable catalytic properties but different catalytic mechanisms. Combinational expression of isoenzymes increased the flux from ß-carotene to vitamin A metabolism. To modulate the vitamin A components, retinol dehydrogenase 12 from Homo sapiens was introduced to achieve more than 90 % retinol purity using shake flask fermentation. Overexpressing POS5Δ17 enhanced the reduced nicotinamide adenine dinucleotide phosphate pool, and the titer of vitamin A was elevated by almost 46 %. Multi-copy integration of the key rate-limiting step gene Mbblh further improved the synthesis of vitamin A. Consequently, the titer of vitamin A in the strain harbouring the Ura3 marker was increased to 588 mg/L at the shake-flask level. Eventually, the highest reported titer of 5.21 g/L vitamin A in S. cerevisiae was achieved in a 1-L bioreactor. This study unlocked the potential of S. cerevisiae for synthesising vitamin A in a sustainable and economical way, laying the foundation for the commercial-scale production of bio-based vitamin A.

Dynamic alterations and ecological implications of rice rhizosphere bacterial communities induced by an insect-transmitted reovirus across space and time.

BACKGROUND: Cereal diseases caused by insect-transmitted viruses are challenging to forecast and control because of their intermittent outbreak patterns, which are usually attributed to increased population densities of vector insects due to cereal crop rotations and indiscriminate use of pesticides, and lack of resistance in commercial varieties. Root microbiomes are known to significantly affect plant health, but there are significant knowledge gaps concerning epidemics of cereal virus diseases at the microbiome-wide scale under a variety of environmental and biological factors. RESULTS: Here, we characterize the diversity and composition of rice (Oryza sativa) root-associated bacterial communities after infection by an insect-transmitted reovirus, rice black-streaked dwarf virus (RBSDV, genus Fijivirus, family Spinareoviridae), by sequencing the bacterial 16S rRNA gene amplified fragments from 1240 samples collected at a consecutive 3-year field experiment. The disease incidences gradually decreased from 2017 to 2019 in both Langfang (LF) and Kaifeng (KF). BRSDV infection significantly impacted the bacterial community in the rice rhizosphere, but this effect was highly susceptible to both the rice-intrinsic and external conditions. A greater correlation between the bacterial community in the rice rhizosphere and those in the root endosphere was found after virus infection, implying a potential relationship between the rice-intrinsic conditions and the rhizosphere bacterial community. The discrepant metabolites in rhizosphere soil were strongly and significantly correlated with the variation of rhizosphere bacterial communities. Glycerophosphates, amino acids, steroid esters, and triterpenoids were the metabolites most closely associated with the bacterial communities, and they mainly linked to the taxa of Proteobacteria, especially Rhodocyclaceae, Burkholderiaceae, and Xanthomonadales. In addition, the greenhouse pot experiments demonstrated that bulk soil microbiota significantly influenced the rhizosphere and endosphere communities and also regulated the RBSDV-mediated variation of rhizosphere bacterial communities. CONCLUSIONS: Overall, this study reveals unprecedented spatiotemporal dynamics in rhizosphere bacterial communities triggered by RBSDV infection with potential implications for disease intermittent outbreaks. The finding has promising implications for future studies exploring virus-mediated plant-microbiome interactions. Video Abstract.

Corosolic acid inhibits EMT in lung cancer cells by promoting YAP-mediated ferroptosis.

BACKGROUND: Corosolic acid (CA), a naturally occurring pentacyclic triterpenoid is renowned for its anticancer attributes. Previous studies have predominantly centered on the anticancer properties of CA in lung cancer, specifically its role in inducing apoptosis, however, investigations regarding its involvement in ferroptosis have been scarce. METHODS: The apoptotic and proliferative effects were evaluated by CCK8 and colony formation assay. Cell death and ROS generation were measured to assess the response of CA to iron death induction. Scratch and invasion assays were performed to verify the effect of CA on the invasive ability of lung cancer cells. Protein and mRNA expression were analyzed using Western blotting and qPCR. The CHX assay was carried out to detect protein half-life. Metabolite levels were measured with appropriate kits. Protein expression was detected through IF and IHC. A xenograft tumor model was established to investigate the inhibitory effect of CA on lung cancer in vivo. RESULTS: The current findings revealed that CA exerts its anticancer effect by inducing cell death, accompanied by the accumulation of lipid reactive oxygen species (ROS), hinting at the possible involvement of ferroptosis. Our experimental results further substantiated the significance of ferroptosis in the CA anticancer mechanism, as ferroptosis inhibitors were found to effectively rescue CA-induced cell death. Significantly, we demonstrated for the first time that CA could induce ferroptosis further by suppressing EMT in lung cancer cells. Additionally, CA could regulate GPX4 to induce ferroptosis, interestingly, CA downregulated GSH synthetase by inhibiting YAP rather than GPX4, thereby reducing GSH, inducing ferroptosis, and further suppressing EMT in lung cancer cells.We also discovered that GSS is a crucial downstream target of YAP in regulating GSH. Moreover, a xenograft mouse model indicated that CA could trigger ferroptosis in lung cancer cells by regulating YAP expression and GSH levels. CONCLUSION: CA inhibited lung cancer cell metastasis by inducing ferroptosis. Our data offer the first evidence that CA induces ferroptosis in lung cancer cells by regulating YAP/GSS to modulate GSH, thereby further suppressing EMT. These results imply the potential of CA as an inducer of ferroptosis to inhibit lung cancer metastasis.

Integrating deep phenotyping with genetic analysis: a comprehensive workflow for diagnosis and management of rare bone diseases.

Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.

A Recombinant Mosaic HAs Influenza Vaccine Elicits Broad-Spectrum Immune Response and Protection of Influenza a Viruses.

The annual co-circulation of two influenza A subtypes, H1N1 and H3N2, viruses in humans poses significant public health threats worldwide. However, the continuous antigenic drift and shift of influenza viruses limited the effectiveness of current seasonal influenza vaccines, necessitating the development of new vaccines against both seasonal and pandemic viruses. One potential solution to this challenge is to improve inactivated vaccines by including multiple T-cell epitopes. In this study, we designed stabilized trimeric recombinant mosaic HA proteins named HAm, which contain the most potential HA T-cell epitopes of seasonal influenza A virus. We further evaluated the antigenicity, hemagglutinin activity, and structural integrity of HAm and compared its immunogenicity and efficacy to a commercial quadrivalent inactivated influenza vaccine (QIV) in mice. Our results demonstrated that the HAm vaccine was able to induce broadly cross-reactive antibodies and T-cell responses against homologous, heterologous, and heterosubtypic influenza-naive mice. Additionally, the HAm antigens outperformed QIV vaccine antigens by eliciting protective antibodies against panels of antigenically drifted influenza vaccine strains from 2009 to 2024 and protecting against ancestral viruses' lethal challenge. These results suggest that the HAm vaccine is a promising potential candidate for future universal seasonal and pandemic influenza vaccine development.

Association of Aerobic and Muscle-Strengthening Activity with Chronic Low Back Pain: population-based study.

BACKGROUND CONTEXT: Chronic low back pain (CLBP) is a significant global health burden, primarily affecting the middle-aged and older; However, there is a lack of clear, evidence-based guidelines for leisure-time physical activity aimed at preventing CLBP. PURPOSE: This study sought to delineate the association between aerobic physical activity (APA) and muscle strengthening activities (MSA) and the prevalence of CLBP. STUDY DESIGN: This was a population-based study conducted across the United States. PATIENT SAMPLE: This nationwide study utilizes deidentified data from 22 consecutive rounds of the National Health Interview Survey (NHIS) from 1997 to 2018. OUTCOME MEASURES: The primary outcome was self-reported CLBP. METHODS: We analyzed the prevalence of CLBP in a representative sample of 324,793 middle-aged and older people. Among 263,871 individuals, we used multiple logistic regression to investigate individual and joint association between the amount of APA and MSA with CLBP. RESULTS: In total, 263,871 participants (mean age, 59.0 years; SD, 9.7) were included in the final analysis. From 1997 to 2018, the prevalence of CLBP was approximately 32%, with an annual increase. Engaging in APA for 75-150 minutes weekly was associated with a modest reduction in CLBP risk (OR (95% CI) = 0.97(0.97 to 0.98)). Similar benefits were seen with 150-225, 225-300, and >300 minutes. Engaging in MSA 2-3 times and 4-5 times weekly also reduced CLBP risk (0.98(0.98 to 0.99) and 0.98(0.97 to 0.99), respectively). Optimal reductions of CLBP risk may be associated with balanced levels of APA and MSA, with recommended amounts being 225-300 min/w of APA and 4-5 times/w of MSA (0.92(0.89 to 0.95)). CONCLUSIONS: The study found engaging in over 75 minutes of APA and 2-5 weekly MSA sessions is associated with a reduced risk of CLBP. Furthermore, a balanced combination of APA and MSA may correspond to the greatest reduction in CLBP risk.

How Do Socio-Demographic Factors, Health Status, and Knowledge Influence the Acceptability of Probiotics Products in Hong Kong?

In recent years, due to growing interest in gut health, the potential benefits of probiotics on the gut have received much attention. Probiotics, now readily available in both dietary supplements and a variety of foods, have become a focal point of consumer health choices. This study aims to explore the impact of consumer-related factors, including socio-demographic profiles, health status, and probiotics knowledge, on the acceptance of probiotics products in Hong Kong. A total of 385 participants engaged in a survey, providing data for an in-depth analysis of how these factors influence attitudes toward probiotics. Findings revealed a general confidence in the safety of probiotics products among respondents; however, there was a noticeable gap in probiotics understanding. The study highlighted a correlation between probiotics knowledge and specific socio-demographic attributes, with higher educational attainment positively linked to greater probiotics awareness. Furthermore, the research indicated that women exhibit higher health consciousness and a greater propensity for probiotics consumption compared to men. Consequently, promoting enhanced probiotics education and fostering increased health awareness are crucial steps to prevent the misuse of probiotics and optimize health outcomes.

Deep learning in Cobb angle automated measurement on X-rays: a systematic review and meta-analysis.

PURPOSE: This study aims to provide an overview of different deep learning algorithms (DLAs), identify the limitations, and summarize potential solutions to improve the performance of DLAs. METHODS: We reviewed eligible studies on DLAs for automated Cobb angle estimation on X-rays and conducted a meta-analysis. A systematic literature search was conducted in six databases up until September 2023. Our meta-analysis included an evaluation of reported circular mean absolute error (CMAE) from the studies, as well as a subgroup analysis of implementation strategies. Risk of bias was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). This study was registered in PROSPERO prior to initiation (CRD42023403057). RESULTS: We identified 120 articles from our systematic search (n = 3022), eventually including 50 studies in the systematic review and 17 studies in the meta-analysis. The overall estimate for CMAE was 2.99 (95% CI 2.61-3.38), with high heterogeneity (94%, p < 0.01). Segmentation-based methods showed greater accuracy (p < 0.01), with a CMAE of 2.40 (95% CI 1.85-2.95), compared to landmark-based methods, which had a CMAE of 3.31 (95% CI 2.89-3.72). CONCLUSIONS: According to our limited meta-analysis results, DLAs have shown relatively high accuracy for automated Cobb angle measurement. In terms of CMAE, segmentation-based methods may perform better than landmark-based methods. We also summarized potential ways to improve model design in future studies. It is important to follow quality guidelines when reporting on DLAs.

Assessing the impact of COVID-19 non-pharmaceutical interventions and relaxation policies on Class B respiratory infectious diseases transmission in China.

This study investigates the incidence of Class B respiratory infectious diseases (RIDs) in China under the Coronavirus disease 2019 (COVID-19) epidemic and examines variations post-epidemic, following the relaxation of non-pharmaceutical interventions (NPIs). Two-stage evaluation was used in our study. In the first stage evaluation, we established counterfactual models for the pre-COVID-19 period to estimate expected incidences of Class B RIDs without the onset of the epidemic. In the second stage evaluation, we constructed seasonal autoregressive integrated moving average intervention (SARIMA-Intervention) models to evaluate the impact on the Class B RIDs after NPIs aimed at COVID-19 pandemic were relaxed. The counterfactual model in the first stage evaluation suggested average annual increases of 10.015%, 78.019%, 70.439%, and 67.799% for tuberculosis, scarlet fever, measles, and pertussis respectively, had the epidemic not occurred. In the second stage evaluation, the total relative reduction in 2023 of tuberculosis, scarlet fever, measles and pertussis were - 35.209%, - 59.184%, - 4.481%, and - 9.943% respectively. The actual incidence declined significantly in the first stage evaluation. However, the results of the second stage evaluation indicated that a rebound occurred in four Class B RIDs after the relaxation of NPIs; all of these showed a negative total relative reduction rate.

Neutrophils in Atopic Dermatitis.

Neutrophils have a critical role in inflammation. Recent studies have identified their distinctive presence in certain types of atopic dermatitis (AD), yet their exact function remains unclear. This review aims to compile studies elucidating the role of neutrophils in AD pathophysiology. Proteins released by neutrophils, including myeloperoxidase, elastase, and lipocalin, contribute to pruritus progression in AD. Neutrophilic oxidative stress and the formation of neutrophil extracellular traps may further worsen AD. Elevated neutrophil elastase and high-mobility group box 1 protein expression in AD patients' skin exacerbates epidermal barrier defects. Neutrophil-mast cell interactions in allergic inflammation steer the immunological response toward Th2 imbalance and activate the Th17 pathway, particularly in response to allergens or infections linked to AD. Notably, drugs alleviating pruritic symptoms in AD inhibit neutrophilic inflammation. In conclusion, these findings underscore that neutrophils may be therapeutic targets for AD symptoms, emphasizing their inclusion in AD treatment strategies.

Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins.

Extracellular vesicles (EVs) are considered as promising candidates for predicting patients who respond to immunotherapy. Nevertheless, simultaneous detection of multiple EVs markers still presents significant technical challenges. In this work, we developed a high-throughput microdroplet-enhanced chip (MEC) platform, which utilizes thousands of individual microchambers (∼pL) as reactors, accelerating the detection efficiency of the CRISPR/Cas systems and increasing the sensitivity by up to 100-fold (aM level). Ten biomarkers (including 5 RNAs and 5 proteins) from patients' EVs are successfully detected on one chip, and the comprehensive markers show increased accuracy (AUC 0.911) than the individual marker for the efficacy prediction of immunotherapy. This platform provides a high-throughput yet sensitive strategy for screening immunotherapy markers in clinical.

High Capacitance Performance N, O Codoped Carbon Foams Synthesized via an All-In-One Step Carbonization of Molecular Salt Strategy.

The preparation of porous carbon is constrained by the extensive use and detrimental impact of activators and dopants. Therefore, developing green and efficient strategies that leverage the intrinsic properties and pretreatment of the materials to achieve self-activation and self-doping is particularly crucial for porous carbon materials. Herein, potassium histidine was utilized as the molecular salt precursor, attaining the efficient and streamlined preparation of porous carbon through a one-step carbonization process that enables self-activation, self-doping, and self-templating. More interestingly, the carbonization temperature significantly impacts the porous structure of the molecular salt precursors, the properties of the heteroatoms, and electrochemical performance. The designed electrodes exhibit high accessibility to electrolyte ions and effective ion-electron transport channels. Therefore, the optimal carbon material (KHis800) has an excellent mass-specific capacitance of 305.2 F g-1 at 0.2 A g-1, and a high capacitance retention rate of 115.6% (50,000 cycles at 5 A g-1). Notably, KHis800 also shows a maximum energy density of 19.6 Wh kg-1. This research is dedicated to exploring a more efficient preparation method for porous carbon material via molecular salts, offering insights for the sustainable development of carbon materials.

Application of MALDI-TOF mass spectrometry for identification of Nocardia species.

BACKGROUND: Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. RESULTS: Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement (P = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) (P = 0.016). An in-house library construction ensured accurate species identification for all isolates. CONCLUSIONS: The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis, with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia. Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis. For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes.

A carbon/oxygen calculation method to improve the response sensitivity of carbon/oxygen logging.

Carbon/Oxygen logging is an effective method to perform oil layer recognition and oil saturation calculation, which plays an important role in the evaluation of remaining oil after casing. At present, there are two main methods to calculate the ratio of carbon to oxygen (C/O). Compared with the energy window count method, the element yield method can avoid the influence of background count in the gamma spectrum and calculated carbon/oxygen value has the higher sensitivity and better accuracy, but it is still greatly affected by carbon and oxygen elements in the formation skeleton. Therefore, a new carbon/oxygen calculation method is proposed in this paper to overcome the influence of formation skeleton and improve the response sensitivity of Carbon/Oxygen logging. Based on Monte Carlo method, the inelastic gamma spectrum of pure sandstone and pure limestone skeletons are obtained. Based on spectrum analysis technology, the ratio relationship of carbon, oxygen yield and skeleton mark element (Si, Ca) yield in two skeletons are obtained. Using these ratio relationships, the carbon and oxygen yields from the sandstone and limestone reservoir skeletons are deducted from the total carbon and oxygen yield. A new carbon/oxygen parameter called the residual carbon/oxygen value (C/O)R is calculated to perform oil-water recognition and a set of oil saturation calculation model suitable for the residual carbon/oxygen value is proposed. The environment application of the residual carbon/oxygen value is also analyzed. The study shows that the residual carbon/oxygen value has higher sensitivity than original carbon/oxygen value in oil layer recognition and has a great accuracy in oil saturation calculation. In environment application aspect, the residual carbon/oxygen value is basically unaffected by formation water salinity and is affected by wellbore fluid and wellbore size obviously. This new carbon/oxygen value calculation method has an important significance to improve the application effect of Carbon/Oxygen logging.

Predicting the Time to Relapse Following Withdrawal from Different Biologics in Patients with Psoriasis who Responded to Therapy: A 12-Year Multicenter Cohort Study.

BACKGROUND: For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice. OBJECTIVE: We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics. METHODS: This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥ 50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI < 10 and ≥ 50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice-Williams-Peterson Gap time model) was used to predict relapse and generate a predictive model. RESULTS: This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability. CONCLUSIONS: These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases.

Removal of enrofloxacin as well as nutrients in mariculture water by Sesuvium portulacastrum system: Insights for biodegradation, ecotoxicity of enrofloxacin.

Antibiotic contamination and eutrophication in mariculture have become problems that cannot be ignored, and enrofloxacin (ENR), as an example, is especially widely used in mariculture. This study firstly revealed that Sesuvium portulacastrum, a plant with world-wide distribution in coastal zones, with its rhizosphere microorganisms, could remove ENR as well as nutrients. The S. portulacastrum system could degrade ENR to small-molecule products 1,2,3,4-tetrahydroquinolin-4-ol and (2,4-dihydroxyphenyl)-cyclopropylamine. And there were 81.3-39.2 % removals of ENR with 0.01-100 mg/L. Although ENR significantly influenced functions of rhizosphere microbial community, like decreasing nitrogen fixation, shifting trophic strategies from phototrophy to chemoheterotrophy, nutrients (NH4+-N, NO2--N, NO3--N and total dissolved phosphorus) removal of S. portulacastrum system was essentially unaffected at low ENR concentration (< 1 mg/L). The removal mechanism of S. portulacastrum system was explored. Neither of the isolated root exudates and rhizosphere bacteria could degrade ENR, however, without rhizosphere bacteria, ENR removal rate would decrease. Root proteins including oxidase, decarboxylase, dehydrogenase, such as laccase, isocitrate dehydrogenase, delta-1-pyrroline-5-carboxylate dehydrogenase were overexpressed. Additionally, endocytosis is a pathway for antibiotics to enter S. portulacastrum. This study demonstrated that S. portulacastrum system could be used for remediation of antibiotics-nutrients combined pollution, and deepened understanding the antibiotic removal mechanism of macrophytes in mariculture, moreover, provided new macroplant species and a theoretical basis for antibiotics removal in aquatic systems.

Follicle-stimulating hormone promotes atrial fibrosis in menopausal women with atrial fibrillation.

BACKGROUND: Postmenopausal women with atrial fibrillation (AF) exhibit a higher level of atrial fibrosis and a higher recurrence rate after ablation compared with men. However, the underlying mechanism remains unclear. OBJECTIVE: The purpost of this study was to investigate the mechanism through which menopause promotes atrial fibrosis. METHODS: In a prospective cohort of women with AF, regression analyses were conducted to assess the relationship between low-voltage area (LVA) and sex hormone levels. CREM-IbΔC-X mice, a spontaneous AF model, underwent bilateral ovariectomy (OVX). Electrocardiograms, echocardiograms, and Masson staining were performed. Follicle-stimulating hormone (FSH) stimulation was applied in male mice for 3 months. OVX was also applied in an angiotensin II (Ang II)-induced pressure overload mouse model, after programmed electrical stimulation and structural analyses. Bulk RNA sequencing (RNA-seq) was performed to elucidate potential mechanisms. RESULTS: Women demonstrated a significantly higher LVA burden than men (P < .001). A positive correlation was observed between LVA burden and FSH level (P = .002). Mice in the OVX group exhibited a significantly higher incidence of AF (P = .040) and atrial fibrosis (P = .021) compared with the Sham group, which could be attenuated by adeno-associated virus encoding small interfering RNA against Fshr. In male CREM-IbΔC-X mice, FSH stimulation promoted the occurrence of AF (P = .035) and atrial fibrosis (P = .002). In Ang II-induced female mice, OVX prompted atrial fibrosis, increased AF inducibility, and shortened atrial effective refractory period, which could be attenuated with knockdown of Fshr. RNA-seq indicated mitochondrial dysfunction. CONCLUSION: Postmenopausal women exhibited a higher LVA burden than men, which was positively correlated with FSH level. FSH promoted atrial fibrosis through oxidative stress.

CEP112 coordinates translational regulation of essential fertility genes during spermiogenesis through phase separation in humans and mice.

Spermiogenesis, the complex transformation of haploid spermatids into mature spermatozoa, relies on precise spatiotemporal regulation of gene expression at the post-transcriptional level. The mechanisms underlying this critical process remain incompletely understood. Here, we identify centrosomal protein 112 (CEP112) as an essential regulator of mRNA translation during this critical developmental process. Mutations in CEP112 are discovered in oligoasthenoteratospermic patients, and Cep112-deficient male mice recapitulate key phenotypes of human asthenoteratozoospermia. CEP112 localizes to the neck and atypical centrioles of mature sperm and forms RNA granules during spermiogenesis, enriching target mRNAs such as Fsip2, Cfap61, and Cfap74. Through multi-omics analyses and the TRICK reporter assay, we demonstrate that CEP112 orchestrates the translation of target mRNAs. Co-immunoprecipitation and mass spectrometry identify CEP112's interactions with translation-related proteins, including hnRNPA2B1, EEF1A1, and EIF4A1. In vitro, CEP112 undergoes liquid-liquid phase separation, forming condensates that recruit essential proteins and mRNAs. Moreover, variants in patient-derived CEP112 disrupt phase separation and impair translation efficiency. Our results suggest that CEP112 mediates the assembly of RNA granules through liquid-liquid phase separation to control the post-transcriptional expression of fertility-related genes. This study not only clarifies CEP112's role in spermatogenesis but also highlights the role of phase separation in translational regulation, providing insights into male infertility and suggesting potential therapeutic targets.

Comparison of Incidence of Metabolic Syndrome and Five Obesity- and Lipid-Linked Indicators for Predicting Metabolic Syndrome Among Normal-Weight and Overweight Adults.

Purpose: Metabolic syndrome (MetS) is an increasingly prevalent issue in China's public health landscape. Few studies have investigated the metabolic syndrome (MetS) in overweight people. We proposed to analyze and contrast the occurrence of MetS in normal-weight and overweight individuals and identify potential indicators for forecasting MetS in adults in Zhejiang Province. Methods: This cohort study included 359 adults aged 40-65 years and followed up for five years in Zhejiang Province. The study assessed the predictive capabilities of five indicators linked to obesity and lipid levels, namely body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-glucose index (TyGi), and their combined indices (TyG-BMI, TyG-WHtR). The evaluation was done employing the area under the Receiver Operating Characteristic (ROC) Curve (AUC). DeLong test was applied to compare area under different ROC curves.We evaluated the relationships between five variables and MetS using multivariate logistic regression. Results: In normal-weight individuals, the five-year cumulative incidence of MetS was 21.85%, but in overweight people, it was 60.33%. After adjusting for confounding factors, BMI, WHtR, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in normal-weight individuals, while BMI, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in overweight individuals. In normal-weight individuals, the WHtR (AUC=0.738 and optimal threshold value =0.469) and TyG-WHtR (AUC=0.731 and optimal threshold value =4.121) had the larger AUC, which was significantly greater than that of the different three indicators. The TyG-BMI (AUC=0.769 and optimal threshold value = 211.099) was the best predictor of MetS in overweight individuals. Conclusion: The five-year cumulative incidence of MetS in overweight people was approximately triple that of normal-weight people in Zhejiang Province. In the overweight population, the TyG-BMI performed better than the other indices in predicting MetS. WHtR and TyG-WHtR outperformed BMI, TyGi, and TyG-BMI in anticipating MetS in a normal-weight population.

Outcomes of Traditional Dual Growing Rods With Apical Control Techniques for the Treatment of Early-Onset Scoliosis: Comparison With Patients Treated With Traditional Dual Growing Rods Only With a Minimum 2-Year Follow-up After Graduation.

BACKGROUND AND OBJECTIVES: Correction with traditional dual growing rods (TDGR) might not be sufficient for severe and rigid spinal deformity. TDGR combines with apical control techniques (ACT) could theoretically improve curve correction and decrease the incidence of mechanical complications. However, long-term results for TDGR with ACT are limited. The aim of this study was to retrospectively review and compare the outcomes of patients who graduated from TDGR with or without ACT. METHODS: Patients who were treated by TDGR with or without ACT with a minimum 2-year follow-up after graduation were enrolled. According to the intervention for the apex, patients were further divided into the TDGR group, the TDGR + apical control pedicle screws group (without apical fusion), and the TDGR + hybrid technique group. Clinical outcomes, radiological parameters, pulmonary function, and complications were compared among the 3 groups. RESULTS: A total of 76 patients (51 patients in the TDGR group, 10 patients in the apical control pedicle screws group, and 15 patients in the hybrid technique group) were enrolled. Compared with TDGR, TDGR + ACT achieved better main curve correction, better control of apical vertebral translation and rotation, and lower incidence of complications and revision surgery (P < .05) while maintaining development of the spine and chest. Although the difference was not significant, patients in the TDGR + ACT group had better pulmonary function at the last follow-up (P > .05). The percentage of patients receiving final fusion in the TDGR + ACT group was significantly lower than that in the TDGR group (P < .05). CONCLUSION: Compared with TDGR, TDGR + ACT can achieve better curve correction and apical control and comparable clinical outcomes while maintaining the growth of the spine and chest. Patients may derive more benefits from treatment with TDGR + ACT, including a lower incidence of mechanical complications and revision surgery, better pulmonary function, and the avoidance of final fusion.