Hippocampal subfield morphology from first episodes of bipolar disorder type II and major depressive disorder in a drug naïve Chinese cohort.

Introduction: Symptoms during the onset of major depressive disorder [MDD] and bipolar disorder type II [BD-II] are similar. The difference of hippocampus subregion could be a biological marker to distinguish MDD from BD-II. Methods: We recruited 61 drug-naïve patients with a first-episode MDD and BD-II episode and 30 healthy controls (HC) to participate in a magnetic resonance imaging [MRI] study. We built a general linear model (one-way analysis of covariance) with 22 hippocampal subfields and two total hippocampal volumes as dependent variables, and the diagnosis of MDD, BD-II, and HC as independent variables. We performed pair-wise comparisons of hippocampal subfield volumes between MDD and HC, BD-II and MDD, BD-II and HC with post hoc for primary analysis. Results: We identified three regions that differed significantly in size between patients and controls. The left hippocampal fissure, the hippocampal-amygdaloid transition area (HATA), and the right subiculum body were all significantly larger in patients with MDD compared with the HC. In the onset of first-episode of MDD, the hippocampal volume increased significantly, especially on the left side comparing to HC. However, we found differences between MDD and BD-II were not statistically significant. The volume of the left HATA and right subiculum body in BD-II was larger. Conclusions: The sample size of this study is relatively small, as it is a cross-sectional comparative study. In both MDD and BD-II groups, the volume of more left subregions appeared to increase. The left subregions were severely injured in the development of depressive disorder.

Differences in male Aedes aegypti and Aedes albopictus hearing systems facilitate recognition of conspecific female flight tones.

When Aedes albopictus mosquitoes invade regions predominated by Aedes aegypti, either the latter can be displaced or the species can coexist, with potential consequences on disease transmission. Males from both species identify females by listening for her flight sounds. Comparing male hearing systems may provide insight into how hearing could prevent interspecific mating. Here, we show that species-specific differences in female wing beat frequencies are reflected in differences in male ear mechanical tuning frequencies and sound response profiles. Though Aedes albopictus males are attracted to sound, they do not readily display abdominal bending, unlike Aedes aegypti. We observed interspecific differences in male ear mechanical, but not electrical, tuning, suggesting a conserved primary auditory processing pathway. Our work suggests a potential role for hearing in the premating isolation of Aedes aegypti and Aedes albopictus, with implications for predicting future dynamics in their sympatric relationships and our understanding of mosquito acoustic communication.

Transcription factor FoAce2 regulates virulence, vegetative growth, conidiation, and cell wall homeostasis in Fusarium oxysporum f. sp. cubense.

Fusarium wilt of banana, caused by the fungus Fusarium oxysporum f. sp. cubense (Foc), is a serious fungal disease that affects banana plants globally. To explore the virulence mechanisms of this pathogen, we created a null mutation of the transcription factor gene FoAce2 (encoding F. oxysporum angiotensin converting enzyme 2). Deletion of FoAce2 resulted in slower growth, decreased aerial mycelia and conidiation, and a significant decrease in fungal virulence against banana hosts relative to those of the wild-type (WT) fungus. Additionally, transmission electron microscopy showed that the cell wall was thicker in the FoAce2 deletion mutants. Consistent with this finding, the cell wall glucose level was decreased in the ΔFoAce2 mutants compared with that in the WT and complemented strain, ΔFoAce2-C1. Complementation with the WT FoAce2 gene fully reversed the mutant phenotypes. Analysis of the transcriptome of ΔFoAce2 and the WT strain showed alterations in the expression levels of many genes associated with virulence and growth. Thus, FoAce2 appears to be essential for Foc virulence, cell wall homeostasis, conidiation, and vegetative growth.

Association between nutrition-related indicators with the risk of chronic obstructive pulmonary disease and all-cause mortality in the elderly population: evidence from NHANES.

Background: This study aims to use six nutrition-related indicators to assess the relationship between nutritional status and the risk of COPD as well as the all-cause mortality rate, and to determine the most reliable predictive indicators. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2013 to 2018 were extracted. Nutritional status was evaluated using Controlling nutritional status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), Advanced Lung Cancer Inflammation Index (ALI), Prognostic Nutritional Index (PNI), Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI), and Albumin-to-Globulin Ratio (AGR) nutritional-related indicators. Multivariate weighted logistic and Cox regression models were employed to assess the correlation between the six nutritional-related indicators and the risk of COPD and as all-cause mortality. The restricted cubic spline tests were applied to explore potential nonlinear relationships, and ROC curves and C-index analyses were conducted to compare the predictive capabilities of different indicators. Stratified analysis and propensity score matching (PSM) to assess the robustness of the results. Results: In this study, Lower ALI, lower GNRI, and higher CONUT scores were positively correlated with an increased risk of COPD (OR: 1.77, 95% CI: 1.10-2.84) (OR: 8.66, 95% CI: 2.95-25.5), and (OR: 5.11, 95% CI: 1.72-15.2), respectively. It was found that ALI and GNRI had a non-linear relationship with the risk of COPD. After propensity score matching (PSM), the associations between ALI, GNRI, CONUT scores, and COPD remained consistent. Lower ALI, PNI, and GNRI scores were positively associated with all-cause mortality in COPD patients (HR: 2.41, 95% CI: 1.10-5.27), (HR: 3.76, 95% CI: 1.89-7.48), and (HR: 4.55, 95% CI: 1.30-15.9), respectively, with GNRI displaying a non-linear relationship with all-cause mortality. ROC curve and C-index analyses indicated that ALI had the best predictive ability for both COPD risk and all-cause mortality. Conclusion: ALI, GNRI, and CONUT scores are correlated with the risk of COPD, while ALI, PNI, and GNRI scores are associated with all-cause mortality in COPD patients. Compared to other nutritional scores, ALI may provide more effective predictive value for both risk and all-cause mortality.

The metabolites mainly composed of lipids in tongue coating are non-invasive potential biomarkers for chronic gastritis.

The changes in tongue coating metabolites in patients with chronic gastritis (CG) under different gastroscopy indicators were analyzed, and these metabolites were screened for potential non-invasive biomarkers to assist in the diagnosis of chronic gastritis. The technology of gas chromatography and liquid chromatography combined with mass spectrometry has been used to more comprehensively detect tongue coating metabolites of 350 CG patients. Spearman correlation analysis and random forest algorithm were used to screen metabolites that can serve as potential biomarkers. Compared with healthy individuals, CG group showed significant changes in the content of 101 metabolites, with an increase in the content of 54 metabolites and a decrease in the content of 47 metabolites. These differential metabolites are mainly composed of 47 lipids and lipid like substances. 1 metabolite was associated with bile reflux, 1 metabolite was associated with gastric mucosal erosion, 10 metabolites were associated with atrophy, 10 metabolites were associated with intestinal metaplasia, and 3 metabolites were associated with Helicobacter pylori infection. The ROC model composed of 5 metabolites can distinguish between CG group and healthy individuals, with an accuracy of 95.4%. The ROC model composed of 5,6-Dihydroxyindole can distinguish between chronic superficial gastritis group and chronic atrophic gastritis group, with an accuracy of 75.3%. The lipids and lipid like metabolites were the main abnormal metabolites in patients with chronic gastritis. It was worth noting that the content of Sphinganine 1-phase, 4-Ipomenol, and Nervonic acid in tongue coating increased, and the content of 1-Methyladenosine and 3-Hydroxycapric acid decreased, which helped to identify CG patients. The decrease in the content of 5,6-dihydroxyindole reminded patients that the development trend of CG was shifting from superficial to atrophic or even intestinal metaplasia. The detection of these metabolic markers of tongue coating was expected to be developed as a non-invasive and convenient technology in the future to assist us in monitoring and diagnosing the occurrence and development of CG.

Sex differences in the combined influence of inflammation and nutrition status on depressive symptoms: insights from NHANES.

Background: Both nutrition and inflammation are associated with depression, but previous studies have focused on individual factors. Here, we assessed the association between composite indices of nutrition and inflammation and depression. Methods: Adult participants selected from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were chosen. The exposure variable was the Advanced Lung Cancer Inflammation Index (ALI) integrating nutrition and inflammation, categorized into low, medium, and high groups. The outcome variable was depression assessed using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression model was employed to evaluate the relationship between ALI and the risk of depression. Results: After extensive adjustment for covariates, in the overall population, participants with moderate and high levels of ALI had a decreased prevalence of depression compared to those with low ALI levels, with reductions of 17% (OR, 0.83; 95% CI: 0.72-0.97) and 23% (OR, 0.77; 95% CI: 0.66-0.91), respectively. Among females, participants with moderate and high ALI levels had a decreased prevalence of depression by 27% (OR, 0.73; 95% CI: 0.60-0.88) and 21% (OR, 0.79; 95% CI: 0.64-0.98), respectively, compared to those with low ALI levels, whereas no significant association was observed among males. Subgroup analyses based on females and males yielded consistent results. Conclusion: In this study, we observed a negative correlation between moderate to high levels of ALI and the prevalence of depression, along with gender differences. Specifically, in females, greater attention should be given to the nutritional and inflammatory status.

Altered nucleocytoplasmic export of adenosine-rich circRNAs by PABPC1 contributes to neuronal function.

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

Genetic correlation between smoking behavior and gastroesophageal reflux disease: insights from integrative multi-omics data.

BACKGROUND: Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior-specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD. METHODS: Firstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared "pleiotropic SNPs" between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD. RESULTS: Consistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel "pleiotropic SNPs" (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk. CONCLUSION: We identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD.

Optimizing ciprofloxacin removal through regulations of trophic modes and FNA levels in a moving bed biofilm reactor performing sidestream partial nitritation.

The performance of partial nitritation (PN)-moving bed biofilm reactor (MBBR) in removal of antibiotics in the sidestream wastewater has not been investigated so far. In this work, the removal of ciprofloxacin was assessed under varying free nitrous acid (FNA) levels and different trophic modes. For the first time, a positive correlation was observed between ciprofloxacin removal and FNA levels, either in the autotrophic PN-MBBR or in the mixotrophic PN-MBBR, mainly ascribed to the FNA-stimulating effect on heterotrophic bacteria (HB)-induced biodegradation. The maximum ciprofloxacin removal efficiency (∼98 %) and removal rate constant (0.021 L g-1 SS h-1) were obtained in the mixotrophic PN-MBBR at an average FNA level of 0.056 mg-N L-1, which were 5.8 and 51.2 times higher than the corresponding values in the autotrophic PN-MBBR at 0 mg FNA-N L-1. Increasing FNA from 0.006 to 0.056 mg-N L-1 would inhibit ammonia oxidizing bacteria (AOB)-induced cometabolism and metabolism from 10.2 % and 6.9 % to 6.2 % and 6.4 %, respectively, while HB-induced cometabolism and metabolism increased from 31.2 % and 22.7 % to 41.9 % and 34.5 %, respectively. HB-induced cometabolism became the predominant biodegradation pathway (75.9 %-85.8 %) in the mixotrophic mode. Less antimicrobial biotransformation products without the piperazine or fluorine were newly identified to propose potential degradation pathways, corresponding to microbial-induced metabolic types and FNA levels. This work shed light on enhancing antibiotic removal via regulating both FNA accumulation and organic carbon addition in the PN-MBBR process treating sidestream wastewater.

The Contribution of Mosaic Chromosomal Alterations to Schizophrenia.

BACKGROUND: Mosaic chromosomal alterations are implicated in neuropsychiatric disorders, but the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages has not been fully established. METHODS: We analyzed blood-derived genotype arrays from 9715 patients with SCZ and 28,822 control participants of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mosaic chromosomal alterations. We focused on probable early developmental sCNVs through stringent filtering. We assessed the burden of sCNVs across varying cell fraction cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the PGC (Psychiatric Genomics Consortium) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 participants (449 cases and 487 controls). RESULTS: Patients with SCZ had a significantly higher somatic losses detection rate than control participants (1.00% vs. 0.52%; odds ratio = 1.91; 95% CI, 1.47-2.49; two-sided Fisher's exact test, p = 1.49 × 10-6). Further analysis indicated that the odds ratios escalated proportionately (from 1.91 to 2.78) with the increment in cell fraction cutoffs. Recurrent sCNVs associated with SCZ (odds ratio > 8; Fisher's exact test, p < .05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, and some regions were validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2. CONCLUSIONS: The study highlights the significant impact of mosaic chromosomal alterations on SCZ, suggesting their pivotal role in the disorder's genetic etiology.

The relationship between dietary intake of ω-3 and ω-6 fatty acids and frailty risk in middle-aged and elderly individuals: a cross-sectional study from NHANES.

Background: Frailty is a complex clinical syndrome characterized by a decline in the functioning of multiple body systems and reduced adaptability to external stressors. Dietary ω-3 fatty acids are considered beneficial dietary nutrients for preventing frailty due to their anti-inflammatory and immune-regulating properties. However, previous research has yielded conflicting results, and the association between ω-6 fatty acids, the ω-6: ω-3 ratio, and frailty remains unclear. This study aims to explore the relationship between these factors using the National Health and Nutrition Examination Survey (NHANES) database. Materials and methods: Specialized weighted complex survey design analysis software was employed to analyze data from the 2005-2014 NHANES, which included 12,315 participants. Multivariate logistic regression models and restricted cubic splines (RCS) were utilized to assess the relationship between omega intake and frailty risk in all participants. Additionally, a nomogram model for predicting frailty risk was developed based on risk factors. The reliability of the clinical model was determined by the area under the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Results: In dietary ω-3 intake, compared to the T1 group (≤1.175 g/d), the T3 group's intake level (>2.050 g/d) was associated with approximately 17% reduction in frailty risk in model 3, after rigorous covariate adjustments (odds ratio (OR) = 0.83, 95% confidence interval (CI): (0.70, 0.99)). In dietary ω-6 intake, the T2 group's intake level (>11.423, ≤19.160 g/d) was associated with a 14% reduction in frailty risk compared to the T1 group (≤11.423 g/d) (OR: 0.86, 95% CI: 0.75, 1.00, p = 0.044). RCS results indicated a non-linear association between ω-3 and ω-6 intake and frailty risk. Both ROC and DCA curves demonstrated the stability of the constructed model and the effectiveness of an omega-rich diet in reducing frailty risk. However, we did not find a significant association between the ω-6: ω-3 ratio and frailty. Conclusion: This study provides support for the notion that a high intake of ω-3 and a moderate intake of ω-6 may contribute to reducing frailty risk in middle-aged and elderly individuals.

The impact of childhood trauma on Adolescent Depressive Symptoms: the Chain Mediating role of borderline personality traits and self-control.

BACKGROUND: The adolescent depression associated with childhood trauma has been confirmed, but the underlying mechanisms remain unclear. This study aims to explore the chain-mediated role of borderline personality traits and self-control in the relationship between childhood trauma and adolescent depression. METHODS: A cross-sectional study was conducted on 2,664 students from a senior high school through online questionnaires from October to December 2022 in Henan, China. Childhood Trauma Questionnaire-Short Form, Borderline Personality Dimension of Personality Diagnostic Questionnaire-4, Self-Control Scale, and Children's Depression Inventory were used to measure childhood trauma, borderline personality traits, and self-control. RESULTS: The prevalence of depression in adolescents was 21.17%, while the prevalence of borderline personality was 12.00%. childhood trauma (r = 0.50, p < 0.001) and borderline personality traits (r = 0.60, p < 0.001) were positively correlated with adolescent depressive symptoms, while self-control was negatively correlated with depressive symptoms (r = - 0.50, p < 0.001). Borderline personality traits and Self-control both play a mediating role in childhood trauma and depressive symptoms, and the mediating effect values are 0.116 (95%CI = [0.098, 0.137]), and 0.022 (95%CI = [0.012, 0.032]) respectively. The chain mediating effect of borderline personality traits and self-control on the relationship between childhood trauma and depressive symptoms was significant (effect value: 0.034, 95%CI = [0.028, 0.042]). CONCLUSIONS: Childhood trauma can predict depressive symptoms in adolescents due to the formation of borderline personality traits and the reduction of self-control. These findings are important for understanding the formation of personality traits, self-control abilities and coping strategies shaped by traumatic experiences in adolescents.

Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

Causal effects of neuroticism on postpartum depression: a bidirectional mendelian randomization study.

PURPOSE: Postpartum depression (PPD) brings adverse and serious consequences to both new parents and newborns. Neuroticism affects PPD, which remains controversial for confounding factors and reverse causality in cross-sectional research. Therefore, mendelian randomization (MR) study has been adopted to investigate their causal relationship. METHODS: This study utilized large-scale genome-wide association study genetic pooled data from three major databases: the United Kingdom Biobank, the European Bioinformatics Institute, and the FinnGen databases. The causal analysis methods used inverse variance weighting (IVW). The weighted median, MR-Egger method, MR-PRESSO test, and the leave-one-out sensitivity test have been used to examine the results' robustness, heterogeneity, and horizontal pleiotropy. The fixed effect model yielded the results of meta-analysis. RESULTS: In the IVW model, a meta-analysis of the MR study showed that neuroticism increased the risk of PPD (OR, 1.17; 95% CI, 1.11-1.25, p < 0.01). Reverse analysis showed that PPD could not genetically predict neuroticism. There was no significant heterogeneity or horizontal pleiotropy bias in this result. CONCLUSION: Our study suggests neuroticism is the risk factor for PPD from a gene perspective and PPD is not the risk factor for neuroticism. This finding may provide new insights into prevention and intervention strategies for PPD according to early detection of neuroticism.

Inorganic carbon limitation decreases ammonium removal and N2O production in the algae-nitrifying bacteria symbiosis system.

Ammonium removal by a symbiosis system of algae (Chlorella vulgaris) and nitrifying bacteria was evaluated in a long-term photo-sequencing batch reactor under varying influent inorganic carbon (IC) concentrations (15, 10, 5 and 2.5 mmol L-1) and different nitrogen loading rate (NLR) conditions (270 and 540 mg-N L-1 d-1). The IC/N ratios provided were 2.33, 1.56, 0.78 and 0.39, respectively, for an influent NH4+-N concentration of 90 mg-N L-1 (6.43 mmol L-1). The results confirmed that both ammonium removal and N2O production were positively related with IC concentration. Satisfactory ammonium removal efficiencies (>98 %) and rates (29-34 mg-N gVSS-1 h-1) were achieved regardless of NLR levels under sufficient IC of 10 and 15 mmol L-1, while insufficient IC at 2.5 mmol L-1 led to the lowest ammonium removal rates of 0 mg-N gVSS-1 h-1. The ammonia oxidation process by ammonia oxidizing bacteria (AOB) played a predominant role over the algae assimilation process in ammonium removal. Long-time IC deficiency also resulted in the decrease in biomass and pigments of algae and nitrifying bacteria. IC limitation led to the decreasing N2O production, probably due to its negative effect on ammonia oxidation by AOB. The optimal IC concentration was determined to be 10 mmol L-1 (i.e., IC/N of 1.56, alkalinity of 500 mg CaCO3 L-1) in the algae-bacteria symbiosis reactor, corresponding to higher ammonia oxidation rate of ∼41 mg-N gVSS-1 h-1 and lower N2O emission factor of 0.13 %. This suggests regulating IC concentrations to achieve high ammonium removal and low carbon emission simultaneously in the algae-bacteria symbiosis wastewater treatment process.

Favipiravir biotransformation by a side-stream partial nitritation sludge: Transformation mechanisms, pathways and toxicity evaluation.

Information on biotransformation of antivirals in the side-stream partial nitritation (PN) process was limited. In this study, a side-stream PN sludge was adopted to investigate favipiravir biotransformation under controlled ammonium and pH levels. Results showed that free nitrous acid (FNA) was an important factor that inhibited ammonia oxidation and the cometabolic biodegradation of favipiravir induced by ammonia oxidizing bacteria (AOB). The removal efficiency of favipiravir reached 12.6% and 35.0% within 6 days at the average FNA concentrations of 0.07 and 0.02 mg-N L-1, respectively. AOB-induced cometabolism was the sole contributing mechanism to favipiravir removal, excluding AOB-induced metabolism and heterotrophic bacteria-induced biodegradation. The growth of Escherichia coli was inhibited by favipiravir, while the AOB-induced cometabolism facilitated the alleviation of the antimicrobial activities with the formed transformation products. The biotransformation pathways were proposed based on the roughly identified structures of transformation products, which mainly involved hydroxylation, nitration, dehydrogenation and covalent bond breaking under enzymatic conditions. The findings would provide insights on enriching AOB abundance and enhancing AOB-induced cometabolism under FNA stress when targeting higher removal of antivirals during the side-stream wastewater treatment processes.

Developing antibiotics-based strategies to efficiently enrich ammonia-oxidizing archaea from wastewater treatment plants.

The effects of five antibiotics (i.e., ampicillin, streptomycin, carbenicillin, kanamycin and tetracycline) on ammonia-oxidizing archaea (AOA) enrichment from anoxic activated sludge were investigated. The combined use of five antibiotics during 90-day cultivation could selectively inhibit nitrite-oxidizing bacteria (NOB) and ammonia-oxidizing bacteria (AOB) with AOA unaffected, as evidenced by the nitrite accumulation ratio of 100 % and the proportion of AOA in ammonia-oxidizing microbes over 91 %. The alternative use of five antibiotics was the optimal approach to screening for AOA during 348-day cultivation, which inhibited AOB growth at a level equivalent to the combined use of five antibiotics (the AOB-amoA gene decreased by over 99.90 %), further promoted AOA abundance (the much higher AOA-amoA to AOB-amoA gene copy number ratio (1453.30) than that in the groups with the combined use of five antibiotics (192.94)), eliminated bacterial adaptation to antibiotics and reduced antibiotic-resistant bacteria to form Nitrocosmicus-dominant community (42.35 % in abundance).

Warming enhances the negative effects of shrub removal on phosphorus mineralization potential.

Shrubs have developed various mechanisms for soil phosphorus utilization. Shrub encroachment caused by climate warming alters organic phosphorus mineralization capability by promoting available phosphorus absorption and mediating root exudates. However, few studies have explored how warming regulates the effects of dominant shrubs on soil organic phosphorus mineralization capability. We provide insights into warming, dominant shrub removal, and their interactive effects on the soil organic phosphorus mineralization potential in the Qinghai-Tibetan Plateau. Real-time polymerase chain reaction was used to quantify the soil microbial phosphatase genes (phoC and phoD), which can characterize the soil organic phosphate mineralization potential. We found that warming had no significant effect on the soil organic phosphate-mineralized components (total phosphate, organic phosphate, and available phosphate), genes (phoC and phoD), or enzymes (acid and alkaline phosphatases). Shrub removal negatively influenced the organic phosphate-mineralized components and genes. It significantly decreased soil organic phosphate mineralization gene copy numbers only under warming conditions. Warming increased fungal richness and buffered the effects of shrub removal on bacterial richness and gene copy numbers. However, the change in the microbial community was not the main factor affecting organic phosphate mineralization. We found only phoC copy number had significant correlation to AP. Structural equation modelling revealed that shrub removal and the interaction between warming and shrub removal had a negative direct effect on phoC copy numbers. We concluded that warming increases the negative effect of shrub removal on phosphorus mineralization potential, providing a theoretical basis for shrub encroachment on soil phosphate mineralization under warming conditions.

Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus: dual evidence from NHANES database and Mendelian randomization analysis.

Background: Low levels of high-density lipoprotein cholesterol (HDL-C) are commonly seen in patients with type 2 diabetes mellitus (T2DM). However, it is unclear whether there is an independent or causal link between HDL-C levels and T2DM. This study aims to address this gap by using the The National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analysis. Materials and methods: Data from the NHANES survey (2007-2018) with 9,420 participants were analyzed using specialized software. Logistic regression models and restricted cubic splines (RCS) were used to assess the relationship between HDL-C and T2DM incidence, while considering covariates. Genetic variants associated with HDL-C and T2DM were obtained from genome-wide association studies (GWAS), and Mendelian randomization (MR) was used to evaluate the causal relationship between HDL-C and T2DM. Various tests were conducted to assess pleiotropy and outliers. Results: In the NHANES study, all groups, except the lowest quartile (Q1: 0.28-1.09 mmol/L], showed a significant association between HDL-C levels and reduced T2DM risk (all P < 0.001). After adjusting for covariates, the Q2 [odds ratio (OR) = 0.67, 95% confidence interval (CI): (0.57, 0.79)], Q3 [OR = 0.51, 95% CI: (0.40, 0.65)], and Q4 [OR = 0.29, 95% CI: (0.23, 0.36)] groups exhibited average reductions in T2DM risk of 23%, 49%, and 71%, respectively. In the sensitivity analysis incorporating other lipid levels, the Q4 group still demonstrates a 57% reduction in the risk of T2DM. The impact of HDL-C levels on T2DM varied with age (P for interaction = 0.006). RCS analysis showed a nonlinear decreasing trend in T2DM risk with increasing HDL-C levels (P = 0.003). In the MR analysis, HDL-C levels were also associated with reduced T2DM risk (OR = 0.69, 95% CI = 0.52-0.82; P = 1.41 × 10-13), and there was no evidence of pleiotropy or outliers. Conclusion: This study provides evidence supporting a causal relationship between higher HDL-C levels and reduced T2DM risk. Further research is needed to explore interventions targeting HDL-C levels for reducing T2DM risk.

A high-fidelity, dual site-specific integration system in CHO cells by a Bxb1 recombinase.

Site-specific integration (SSI) via recombinase mediated cassette exchange (RMCE) has shown advantages over random integration methods for expression of biotherapeutics. As an extension of our previous work developing SSI host cells, we developed a dual-site SSI system having two independent integration sites at different genomic loci, each containing a unique landing pad (LP). This system was leveraged to generate and compare two RMCE hosts, one (dFRT) compatible with the Flp recombinase, the other (dBxb1) compatible with the Bxb1 recombinase. Our comparison demonstrated that the dBxb1 host was able to generate stable transfectant pools in a shorter time frame, and cells within the dBxb1 transfectant pools were more phenotypically and genotypically stable. We further improved process performance of the dBxb1 host, resulting in desired fed batch performance attributes. Clones derived from this improved host (referred as 41L-11) maintained stable expression profiles over extended generations. While the data represents a significant improvement in the efficiency of our cell line development process, the dual LP architecture also affords a high degree of flexibility for development of complex protein modalities.