An intellectual disability-related MED23 mutation dysregulates gene expression by altering chromatin conformation and enhancer activities.

Transcriptional Mediator controls diverse gene programs for various developmental and pathological processes. The human Mediator MED23/R617Q mutation was reported in a familial intellectual disability (ID) disorder, although the underlying mechanisms remain poorly understood. Constructed by gene editing, the Med23/R617Q knock-in mutant mice exhibited embryonic lethality due to the largely reduced Med23/R617Q protein level, but the R617Q mutation in HEK293T cells didn't change its expression and incorporation into Mediator Complex. RNA-seq revealed that MED23/R617Q mutation disturbed gene expression, related to neural development, learning and memory. Specifically, R617Q mutation reduced the MED23-dependent activities of ELK1 and E1A, but in contrast, upregulated the MAPK/ELK1-driven early immediate genes (IEGs) JUN and FOS. ChIP-seq and Hi-C revealed that the MED23 R617Q mutation reprogramed a subset of enhancers and local chromatin interactions, which correlated well with the corresponding gene expression. Importantly, the enhancers and chromatin interactions surrounding IEGs were unchanged by the R617Q mutation, but DACH1, an upstream repressor of IEGs, showed reduced enhancer-promoter interactions and decreased expression in mutant cells, thus relieving its inhibition to the intellectual-related IEGs. Overall, unraveling the MED23-DACH1-IEG axis provides a mechanistic explanation for the effects of the MED23/R617Q mutation on gene dysregulation and inherited ID.

A multiethnic whole genome sequencing study to identify novel loci for bone mineral density.

At present, there have only been a few DNA sequencing-based studies to explore the genetic determinants of bone mineral density (BMD). We carried out the largest whole genome sequencing analysis to date for femoral neck and spine BMD (n = 4981), with one of the highest average sequencing depths implemented thus far at 22×, in a multiethnic sample (58% Caucasian and 42% African American) from the Louisiana Osteoporosis Study (LOS). The LOS samples were combined with summary statistics from the GEFOS consortium and several independent samples of various ethnicities to perform GWAS meta-analysis (n = 44 506). We identified 31 and 30 genomic risk loci for femoral neck and spine BMD, respectively. The findings substantiate many previously reported susceptibility loci (e.g. WNT16 and ESR1) and reveal several others that are either novel or have not been widely replicated in GWAS for BMD, including two for femoral neck (IGF2 and ZNF423) and one for spine (SIPA1). Although we were not able to uncover ethnicity specific differences in the genetic determinants of BMD, we did identify several loci which demonstrated sex-specific associations, including two for women (PDE4D and PIGN) and three for men (TRAF3IP2, NFIB and LYSMD4). Gene-based rare variant association testing detected MAML2, a regulator of the Notch signaling pathway, which has not previously been suggested, for association with spine BMD. The findings provide novel insights into the pathophysiological mechanisms of osteoporosis.

Different levels of prepulse inhibition among patients with first-episode schizophrenia, bipolar disorder and major depressive disorder.

BACKGROUND: Deficits in prepulse inhibition may be a common feature in first-episode schizophrenia, bipolar disorder (BD) and major depressive disorder (MDD). We sought to explore the levels and viability of prepulse inhibition to differentiate first-episode schizophrenia, BD and MDD in patient populations. METHODS: We tested patients with first-episode schizophrenia, BD or MDD and healthy controls using prepulse inhibition paradigms, namely perceived spatial co-location (PSC-PPI) and perceived spatial separation (PSS-PPI). RESULTS: We included 53 patients with first-episode schizophrenia, 30 with BD and 25 with MDD, as well as 82 healthy controls. The PSS-PPI indicated that the levels of prepulse inhibition were smallest to largest, respectively, in the first-episode schizophrenia, BD, MDD and control groups. Relative to the healthy controls, the prepulse inhibition deficits in the first-episode schizophrenia group were significant (p < 0.001), but the prepulse inhibitions were similar between patients with BD and healthy controls, and between patients with MDD and healthy controls. The receiver operating characteristic curve analysis showed that PSS-PPI (area under the curve [AUC] 0.73, p < 0.001) and latency (AUC 0.72, p < 0.001) were significant for differentiating patients with first-episode schizophrenia or BD from healthy controls. LIMITATIONS: The demographics of the 4 groups were not ideally matched. We did not perform cognitive assessments. The possible confounding effect of medications on prepulse inhibition could not be eliminated. CONCLUSION: The level of prepulse inhibition among patients with first-episode schizophrenia was the lowest, with levels among patients with BD, patients with MDD and healthy controls increasingly higher. The PSS-PPI paradigm was more effective than PSC-PPI to recognize deficits in prepulse inhibition. These results provide a basis for further research on biological indicators that can assist differential diagnoses in psychosis.

Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy.

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.

Targeting the glutamine-arginine-proline metabolism axis in cancer.

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.

Association of urinary and seminal plasma vanadium concentrations with semen quality: A repeated-measures study of 1135 healthy men.

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had - 11.3% (-16.4%, -5.9%), - 11.1% (-19.1%, -2.4%), and - 20.9% (-29.0%, -11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.

Melittin Treats Periprosthetic Osteolysis in a Rat Model by Inhibiting the NF-kB Pathway and Regulating the Ratio of Receptor Activator of Nuclear Factor Kappa B Ligand/Osteoprotegerin.

BACKGROUND: Aseptic loosening around the prosthesis is a common cause of failure in total joint arthroplasty. Polyethylene wear particles trigger the release of inflammatory factors by macrophages. Key mediators involved in osteoclastogenesis include interleukin-6, tumor necrosis factor-α, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and bone protection hormone (Osteoprotegerin [OPG]). The purpose of our experiment was to see whether melittin can slow down the release of inflammatory mediators through the NF-kB pathway, regulate the RANKL/OPG ratio, reduce osteoclast formation, and delay the onset of arthritis in rats. METHODS: A total of 20 male Sprague-Dawley rats (10 months, Specific Pathogen Free, 350 g ± 20 g) were randomly divided into 5 groups: sham group, model group, melittin concentration 1 group (0.2 mg/kg), concentration 2 group (0.4 mg/kg), and concentration 3 group (0.6 mg/kg). All rats were implanted with TA2 high-purity titanium rods. A drill was used to create a bone canal along the long axis of the femur in the intercondylar notch. The model group and experimental groups were exposed to polyethylene particles, while the sham group did not receive any particles. RESULTS: The melittin group exhibited significantly increased serum levels of serum P, calcium-phosphorus product, OPG, PINP, PINP/CTX-I, and OPG/RANKKL (P < .05). In the experimental group, micro computed tomography scanning results revealed a decrease in the amount of bone defect around the prosthesis. Immunofluorescence analysis demonstrated a decrease in the expression of IKKα and P65, while the expression of OPG showed an upward trend. Both Hematoxylin-Eosin and Tartrate-Resistant Acid Phosphatase staining revealed less osteoclast and inflammatory cell infiltration in bone resorption pits. CONCLUSIONS: Our study demonstrates that melittin has the ability to inhibit the NF-kB pathway in a rat model, and reduce the impact of RANKL/OPG, thereby delaying osteoclast activity and alleviating periprosthetic osteolysis.

Design and properties of ternary alkali-activated binder based on blast furnace slag, recycled powder and waste glass powder.

Ternary alkali-activated binder was prepared by blast furnace slag (GGBS), recycled powder (RP) and waste glass powder (WGP) using simplex centroid design method. By measuring the fluidity, setting time, drying shrinkage and mechanical property of specimen, the complementary effect of GGBS, RP and WGP was discussed. The reaction mechanism and microstructure were explored by X-ray diffraction and scanning electron microscopy. The results reveal that the addition of RP could significantly reduce the fluidity and setting time of paste, while WGP can obviously improve the rheological property and play a retarding role. The workability of paste can be effectively regulated by mixing RP and WGP together. Whether added alone or in combination, RP and WGP can effectively improve the shrinkage performance. In the ternary system, GGBS can be rapidly activated and form a skeleton structure. The fine RP particles can play a good role in filling the structure, and the pozzolanic reaction of WGP gradually occurs, which makes the microstructure more compact. The incorporation of GGBS, RP and WGP can promote the growth of hydration products, improve the density of microstructure, and form a certain complementary effect.

Revealing the Antiperspirant Components of Floating Wheat and Their Mechanisms of Action through Metabolomics and Network Pharmacology.

Floating wheat is a classical herbal with potential efficacy in the treatment of hyperhidrosis. Aiming at revealing the main components and potential mechanisms of floating wheat, a comprehensive and unique phytopharmacology profile study was carried out. First, common wheat was used as a control to look for chemical markers of floating wheat. In the screening analysis, a total of 180 shared compounds were characterized in common wheat and floating wheat, respectively. The results showed that floating wheat and common wheat contain similar types of compounds. In addition, in non-targeted metabolomic analysis, when taking the contents of the constituents into account, it was found that there indeed existed quite a difference between floating wheat and common wheat and 17 potential biomarkers for floating wheat. Meanwhile, a total of seven components targeted for hyperhidrosis were screened out based on network pharmacology. Seven key differential components were screened, among which kaempferol, asiatic acid, sclareol, enoxolone, and secoisolariciresinol had higher degree values than the others. The analysis of interacting genes revealed three key genes, namely, MAP2K1, ESR1, and ESR2. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses showed that various signaling pathways were involved. Prolactin signaling, thyroid cancer, endocrine resistance, gonadotropin secretion, and estrogen signaling pathways were the main pathways of the intervention of floating wheat in excessive sweating, which was associated with the estrogenic response, hormone receptor binding, androgen metabolism, apoptosis, cancer, and many other biological processes. Molecular docking showed that the screened key components could form good bindings with the target proteins through intermolecular forces. This study reveals the active ingredients and potential molecular mechanism of floating wheat in the treatment of hyperhidrosis and provides a reference for subsequent basic research.

Virtual water flows and drivers in the international trade of agricultural products of the regional comprehensive economic partnership.

The regional comprehensive economic partnership (RCEP) is today the largest free trade area in the world. This paper examines agricultural trade in the RCEP from 2010 to 2019 through the perspective of virtual water. And the drivers of the virtual water flow between China and the RCEP are also explored. The results are as follows: the virtual water flow during the study period was 2,576.51 billion m3. From a temporal perspective, the annual virtual water flow over the study period is characterized by a slow rise-significant fall-slow rise. It has the characteristics of concentration in spatial distribution and water resources and product structure. However, the concentration degree showed a downward trend during the study period. Then, we have divided the major trading into four categories based on whether there is a shortage of water on both sides of the trade. In terms of the drivers of virtual water flows between China and the RCEP, we have used the gravity model to arrive at the following findings: crop yields, bilateral economic scale, and agricultural labor resources are the main drivers. Our research results have reference values for adjusting bilateral agricultural trade and water conservation.

[Multi-index evaluation of different parts of Amomum villosum].

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.

Higher reliability and validity of Wavelet-ALFF of resting-state fMRI: From multicenter database and application to rTMS modulation.

Amplitude of low-frequency fluctuation (ALFF) has been widely used for localization of abnormal activity at the single-voxel level in resting-state fMRI (RS-fMRI) studies. However, previous ALFF studies were based on fast Fourier transform (FFT-ALFF). Our recent study found that ALFF based on wavelet transform (Wavelet-ALFF) showed better sensitivity and reproducibility than FFT-ALFF. The current study aimed to test the reliability and validity of Wavelet-ALFF, and apply Wavelet-ALFF to investigate the modulation effect of repetitive transcranial magnetic stimulation (rTMS). The reliability and validity were assessed on multicenter RS-fMRI datasets under eyes closed (EC) and eyes open (EO) conditions (248 healthy participants in total). We then detected the sensitivity of Wavelet-ALFF using a rTMS modulation dataset (24 healthy participants). For each dataset, Wavelet-ALFF based on five mother wavelets (i.e., db2, bior4.4, morl, meyr and sym3) and FFT-ALFF were calculated in the conventional band and five frequency sub-bands. The results showed that the reliability of both inter-scanner and intra-scanner was higher with Wavelet-ALFF than with FFT-ALFF across multiple frequency bands, especially db2-ALFF in the higher frequency band slow-2 (0.1992-0.25 Hz). In terms of validity, the multicenter ECEO datasets showed that the effect sizes of Wavelet-ALFF with all mother wavelets (especially for db2-ALFF) were larger than those of FFT-ALFF across multiple frequency bands. Furthermore, Wavelet-ALFF detected a larger modulation effect than FFT-ALFF. Collectively, Wavelet db2-ALFF showed the best reliability and validity, suggesting that db2-ALFF may offer a powerful metric for inspecting regional spontaneous brain activities in future studies.

Integrative analysis of multi-omics data to detect the underlying molecular mechanisms for obesity in vivo in humans.

BACKGROUND: Obesity is a complex, multifactorial condition in which genetic play an important role. Most of the systematic studies currently focuses on individual omics aspect and provide insightful yet limited knowledge about the comprehensive and complex crosstalk between various omics levels. SUBJECTS AND METHODS: Therefore, we performed a most comprehensive trans-omics study with various omics data from 104 subjects, to identify interactions/networks and particularly causal regulatory relationships within and especially those between omic molecules with the purpose to discover molecular genetic mechanisms underlying obesity etiology in vivo in humans. RESULTS: By applying differentially analysis, we identified 8 differentially expressed hub genes (DEHGs), 14 differentially methylated regions (DMRs) and 12 differentially accumulated metabolites (DAMs) for obesity individually. By integrating those multi-omics biomarkers using Mendelian Randomization (MR) and network MR analyses, we identified 18 causal pathways with mediation effect. For the 20 biomarkers involved in those 18 pairs, 17 biomarkers were implicated in the pathophysiology of obesity or related diseases. CONCLUSIONS: The integration of trans-omics and MR analyses may provide us a holistic understanding of the underlying functional mechanisms, molecular regulatory information flow and the interactive molecular systems among different omic molecules for obesity risk and other complex diseases/traits.

Exogenous Metals Atlas in Spermatozoa at Single-Cell Resolution in Relation to Human Semen Quality.

While exogenous metal/metalloid (metal) exposure has been associated with reduced human semen quality, no study has assessed the associations of exogenous metals in human spermatozoa with semen quality. Here, we developed a strategy to explore the associations between exogenous metals in spermatozoa at single-cell resolution and human semen quality among 84 men screened as sperm donors, who provided 266 semen samples within 90 days. A cellular atlas of exogenous metals at the single-cell level was created with mass cytometry (CyTOF) technology, which concurrently displayed 18 metals in more than 50 000 single sperm. Exogenous metals in spermatozoa at single-cell resolution were extremely heterogeneous and diverse. Further analysis using multivariable linear regression and linear mixed-effects models revealed that the heterogeneity and prevalence of the exogenous metals at single-cell resolution were associated with semen quality. The heterogeneity of lead (Pb), tin (Sn), yttrium (Y), and zirconium (Zr) was negatively associated with sperm concentration and count, while their prevalence showed positive associations. These findings revealed that the heterogeneous properties of exogenous metals in spermatozoa were associated with human semen quality, highlighting the importance of assessing exogenous metals in spermatozoa at single-cell resolution to evaluate male reproductive health risk precisely.

Cloning and functional identification of pmKPI cDNA in Poecilobdella manillensis.

BACKGROUND: Kazal-type serine protease inhibitors play a role in physiological processes such as blood coagulation and fibrinolysis. The amino acid residues at the P1 site are different, and they inhibit different types of proteases. The inhibitory mechanism of the protease in the salivary glands of Poecilobdella manillensis is still unclear. METHODS AND RESULTS: Based on cloning, prokaryotic expression and bioinformatics analysis, we studied the role of Kazal-type serine protease inhibitors in P. manillensis and analyzed their expression by quantitative real-time PCR. The results suggested that the recombinant protein was successfully expressed in the supernatant when a prokaryotic expression vector was constructed and induced with 0.2 mmol/L IPTG at 37 °C for 4 h, and the enzymatic activity was determined. The mature protein encodes 91 amino acids and has a relative molecular weight of 9929.32 Da, and after removing the signal peptide, the theoretical isoelectric point was 8.79. It is an unstable protein without a transmembrane domain. The mature protein contains two Kazal-type domains, in which all P1 residues are Lys, consisting of an α helix and three antiparallel ß sheets. The upregulated expression of the mRNA was induced after a meal was provided, and the results showed an increasing and then decreasing trend. CONCLUSIONS: Taken together, the results indicate that mature proteins from P. manillensis inhibit thrombin activity, laying the foundation for the subsequent in-depth study of the function of genes encoding Kazal-type serine protease inhibitors.

CircDUS2L (circ_0039908) promotes lung adenocarcinoma progression by upregulating PGAM1 by acting as a miR-590-5p molecular sponge.

Lung adenocarcinoma (LUAD) is usually found at the metastatic stage. Circular RNA dihydrouridine synthase 2-like (DUS2L) (circDUS2L) has been discovered to be upregulated in LUAD. Nevertheless, the function of circDUS2L in LUAD has not been verified. Levels of circDUS2L, microRNA-590-5p (miR-590-5p), and phosphoglycerate mutase 1 (PGAM1) mRNA were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, metastasis, and invasion were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), colony formation, 5-ethynyl-2'-deoxyuridine (Edu), flow cytometry, and transwell assays. Protein levels were detected by western blotting. Cell glycolysis was analyzed by measuring cell glucose consumption, lactate production, and extracellular acidification rate (ECAR). The regulatory mechanism of circDUS2L in LUAD cells was analyzed by bioinformatics analysis, dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. Xenograft assay was conducted to confirm the function of circDUS2L in vivo. CircDUS2L was highly expressed in LUAD tissues and cells. CircDUS2L silencing constrained xenograft tumor growth in vivo. CircDUS2L knockdown induced apoptosis, repressed viability, colony formation, proliferation, metastasis, invasion, and glycolysis of LUAD cells in vitro by releasing miR-590-5p via functioning as a miR-590-5p sponge. MiR-590-5p was lowly expressed in LUAD tissues and cells, and miR-590-5p mimic curbed malignant behaviors and glycolysis of LUAD cells by targeting PGAM1. PGAM1 was overexpressed in LUAD tissues and cells, and circDUS2L sponged miR-590-5p to regulate PGAM1 expression. CircDUS2L elevated PGAM1 expression through functioning as a miR-590-5p sponge, thus driving malignant behaviors and glycolysis of LUAD cells.

Cold-resistant performance and the promoted development of functional community with flexible metabolic patterns in a Biofilm Bio-Nutrient Removal (BBNR) system amended with supplementary carbon source for phosphorus recovery.

The need for recovery of phosphorus (P) from wastewater has accelerated the retrofitting of existing bio-nutrient removal (BNR) processes into bio-nutrient removal-phosphorus recovery processes (BNR-PR). A periodical carbon source supplement is needed to facilitate the P-recovery. But the impact of this amendment on the cold resistances of the reactor and the functional microorganisms (for nitrogen and phosphorus (P) removal/recovery) are still unknown. This study presents the performances of a biofilm BNR process with a carbon source regulated the P recovery (BBNR-CPR) process operating at different temperatures. When the temperature was decreased from 25 ± 1 °C to 6 ± 1 °C, the system total nitrogen and total phosphorus removals and the corresponding kinetic coefficients decreased moderately. The indicative genes of the phosphorus-accumulating organisms (e.g., Thauera spp. and Candidatus Accumulibacter spp.) increased significantly. An increase of Nitrosomonas spp. genes aligned to polyhydroxyalkanoates (PHAs), glycine, and extracellular polymeric substance synthesis were observed, which was probably related to cold resistance. The results provide a new vision for understanding the advantages of P recovery-targeted carbon source supplementation for constructing a new type of cold-resistant BBNR-CPR processes.

Blood trihalomethane concentrations in relation to sperm mitochondrial DNA copy number and telomere length among 958 healthy men.

BACKGROUND: In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood. OBJECTIVE: To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men. METHODS: We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0-9, 10-14, 15-69, or >69 days) to explore potential windows of susceptibility. RESULTS: After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend≤0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15-69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations. CONCLUSION: Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction.

Impact of the COVID-19 pandemic and corresponding control measures on long-term care facilities: a systematic review and meta-analysis.

BACKGROUND: Long-term care facilities (LTCFs) were high-risk settings for COVID-19 outbreaks. OBJECTIVE: To assess the impacts of the COVID-19 pandemic on LTCFs, including rates of infection, hospitalisation, case fatality, and mortality, and to determine the association between control measures and SARS-CoV-2 infection rates in residents and staff. METHOD: We conducted a systematic search of six databases for articles published between December 2019 and 5 November 2021, and performed meta-analyses and subgroup analyses to identify the impact of COVID-19 on LTCFs and the association between control measures and infection rate. RESULTS: We included 108 studies from 19 countries. These studies included 1,902,044 residents and 255,498 staff from 81,572 LTCFs, among whom 296,024 residents and 36,807 staff were confirmed SARS-CoV-2 positive. The pooled infection rate was 32.63% (95%CI: 30.29 ~ 34.96%) for residents, whereas it was 10.33% (95%CI: 9.46 ~ 11.21%) for staff. In LTCFs that cancelled visits, new patient admissions, communal dining and group activities, and vaccinations, infection rates in residents and staff were lower than the global rate. We reported the residents' hospitalisation rate to be 29.09% (95%CI: 25.73 ~ 32.46%), with a case-fatality rate of 22.71% (95%CI: 21.31 ~ 24.11%) and mortality rate of 15.81% (95%CI: 14.32 ~ 17.30%). Significant publication biases were observed in the residents' case-fatality rate and the staff infection rate, but not in the infection, hospitalisation, or mortality rate of residents. CONCLUSION: SARS-CoV-2 infection rates would be very high among LTCF residents and staff without appropriate control measures. Cancelling visits, communal dining and group activities, restricting new admissions, and increasing vaccination would significantly reduce the infection rates.

Exposure to okadaic acid could disrupt the colonic microenvironment in rats.

Okadaic acid (OA) is one of the most prevalent marine phycotoxin with complex toxicity, which can lead to toxic symptoms such as diarrhea, vomiting, nausea, abdominal pain, and gastrointestinal discomfort. Studies have shown that the main affected tissue of OA is digestive tract. However, its toxic mechanism is not yet fully understood. In this study, we investigated the changes that occurred in the epithelial microenvironment following OA exposure, including the epithelial barrier and gut bacteria. We found that impaired epithelial cell junctions, mucus layer destruction, cytoskeletal remodeling, and increased bacterial invasion occurred in colon of rats after OA exposure. At the same time, the gut bacteria decreased in the abundance of beneficial bacteria and increased in the abundance of pathogenic bacteria, and there was a significant negative correlation between the abundance of pathogenic bacteria represented by Escherichia/Shigella and animal body weight. Metagenomic analysis inferred that Escherichia coli and Shigella spp. in Escherichia/Shigella may be involved in the process of cytoskeletal remodeling and mucosal layer damage caused by OA. Although more evidence is needed, our results suggest that opportunistic pathogens may be involved in the complex toxicity of OA during OA-induced epithelial barrier damage.