Research advances in the anti-inflammatory effects of SGLT inhibitors in type 2 diabetes mellitus.

Diabetes mellitus is one of the most significant global burden diseases. It is well established that a chronic, systemic, low-grade inflammatory condition is strongly correlated with type 2 diabetes mellitus (T2D) and the development of target-organ damage (TOD). Sodium-glucose cotransporter inhibitors (SGLTis), novel oral drugs for the treatment of diabetes, act mainly by reducing glucose reabsorption in proximal renal tubules and/or the intestine. Several high-quality clinical trials and large observational studies have revealed that SGLTis significantly improve cardiovascular and renal outcomes in T2D patients. Increasing evidence suggests that this is closely related to their anti-inflammatory properties, which are mainly manifested by a reduction in plasma concentrations of inflammatory biomarkers. This review analyses the potential mechanisms behind the anti-inflammatory effects of SGLTis in diabetes and presents recent evidence of their therapeutic efficacy in treating diabetes and related TOD.

Effects of different light conditions on morphological, anatomical, photosynthetic and biochemical parameters of Cypripedium macranthos Sw.

In this study, the morphological (plant height, leaf length and width, stem diameter and leaf number), anatomical (epidermal cell density and thickness, Stomatal length and width), photosynthetic (net photosynthetic rate, transpiration rate, stomatal conductance, intercellular CO2 concentration, relative humidity, leaf temperature and chlorophyll fluorescence parameters) and biochemical parameters (the content of soluble sugar, soluble protein, proline, malondialdehyde and electrical conductivity) of Cypripedium macranthos Sw. in Changbai Mountain were determined under different light conditions (L10, L30, L50, L100). The results showed that morphological values including plant height, leaf area, stem diameter and leaf number of C. macranthos were smaller under the condition of full light at L100. The epidermal cell density and epidermal thickness of C. macranthos were the highest under L30 and L50 treatments, respectively. It had the highest net photosynthetic rate (Pn) and chlorophyll content under L50 treatment. Meanwhile, correlation analysis indicated that photosynthetically active radiation (PAR) and water use efficiency (WUE) were the main factors influencing Pn. C. macranthos accumulated more soluble sugars and soluble proteins under L100 treatment, while the degree of membrane peroxidation was the highest and the plant was severely damaged. In summary, the adaptability of C. macranthos to light conditions is ranked as follows L50 > L30 > L10 > L100. Appropriate light conditions for C. macranthos are 30%-50% of full light, which should be taken into account in protection and cultivation.

Methane mitigation via the nitrite-DAMO process induced by nitrate dosing in sewers.

Nitrate or nitrite-dependent anaerobic methane oxidation (n-DAMO) is a microbial process that links carbon and nitrogen cycles as a methane sink in many natural environments. This study demonstrates, for the first time, that the nitrite-dependent anaerobic methane oxidation (nitrite-DAMO) process can be stimulated in sewer systems under continuous nitrate dosing for sulfide control. In a laboratory sewer system, continuous nitrate dosing not only achieved complete sulfide removal, but also significantly decreased dissolved methane concentration by ∼50 %. Independent batch tests confirmed the coupling of methane oxidation with nitrate and nitrite reduction, revealing similar methane oxidation rates of 3.68 ± 0.5 mg CH4 L-1 h-1 (with nitrate as electron acceptor) and 3.57 ± 0.4 mg CH4 L-1 h-1 (with nitrite as electron acceptor). Comprehensive microbial analysis unveiled the presence of a subgroup of the NC10 phylum, namely Candidatus Methylomirabilis (n-DAMO bacteria that couples nitrite reduction with methane oxidation), growing in sewer biofilms and surface sediments with relative abundances of 1.9 % and 1.6 %, respectively. In contrast, n-DAMO archaea that couple methane oxidation solely to nitrate reduction were not detected. Together these results indicated the successful enrichment of n-DAMO bacteria in sewerage systems, contributing to approx. 64 % of nitrite reduction and around 50 % of dissolved methane removal through the nitrite-DAMO process, as estimated by mass balance analysis. The occurrence of the nitrite-DAMO process in sewer systems opens a new path to sewer methane emissions.

[Awareness of issues in research and educational activities and expectations for young researchers' activities and supporting].

OBJECTIVES: To understand the actual situation and needs of young researchers and to provide reference for the management of Young Researchers Association (YRA) and the Japanese Society for Hygiene activities in the future. METHODS: An Internet survey was conducted on 67 members registered in YRA of the Japanese Society for Hygiene. The questions included those on basic information, research content and impressions about the activities of the society. RESULTS: Although members of YRA differ in backgrounds, research method used, and years of research experience, the respondents rated the organization as highly useful and participated continuously. In particular, they considered that participation in the planning of academic conferences and summer gatherings of YRA not only helped improve interpersonal relationships and expertise, but also provided opportunities to consult regarding educational activities and collect information. Regarding the format of conferences, it was shown that the majority of requests were for a hybrid format. It was also shown that most of the respondents expected opportunities for collaboration and joint research through participation in YRA. CONCLUSION: Through YRA, we would like to contribute to the further revitalization of young researchers and the Japanese Society for Hygiene by understanding and responding to the needs of diverse young researchers.

Quantifying Methane Influx from Sewer into Wastewater Treatment Processes.

Wastewater treatment contributes substantially to methane (CH4) emissions, yet monitoring and tracing face challenges because the treatment processes are often treated as a "black box". Particularly, despite growing interest, the amount of CH4 carryover and influx from the sewer and its impacts on overall emissions remain unclear. This study quantified CH4 emissions from six wastewater treatment plants (WWTPs) across China, utilizing existing multizonal odor control systems, with a focus on Beijing and Guiyang WWTPs. In the Beijing WWTP, almost 90% of CH4 emissions from the wastewater treatment process were conveyed through sewer pipes, affecting emissions even in the aerobic zone of biological treatment. In the Guiyang WWTP, where most CH4 from the sewer was released at the inlet well, a 24 h online monitoring revealed CH4 fluctuations linked to neighborhood water consumption and a strong correlation to influent COD inputs. CH4 emission factors monitored in six WWTPs range from 1.5 to 13.4 gCH4/kgCODrem, higher than those observed in previous studies using A2O technology. This underscores the importance of considering CH4 influx from sewer systems to avoid underestimation. The odor control system in WWTPs demonstrates its potential as a cost-effective approach for tracing, monitoring, and mitigating CH4.

SERPINH1 promoted the proliferation and metastasis of colorectal cancer by activating PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Serpin peptidase inhibitor clade H member 1 (SERPINH1) was initially recognized as an oncogene implicated in various human malignancies. Nevertheless, the clinical relevance and functional implications of SERPINH1 in colorectal cancer (CRC) remain largely elusive. AIM: To investigate the effects of SERPINH1 on CRC cells and its specific mechanism. METHODS: Quantitative real-time polymerase chain reaction, western blotting analysis, The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues. A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC. RESULTS: SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues, manifested at both mRNA and protein tiers. Elevated SERPINH1 levels correlated closely with advanced T stage, lymph node involvement, and distant metastasis, exhibiting a significant association with poorer overall survival among CRC patients. Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation, invasion, and migration in vitro, while conversely, SERPINH1 knockdown elicited the opposite effects. Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation. Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation, thereby facilitating CRC cell invasion and migration. CONCLUSION: These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC, potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.

The preparation of gallic acid-grafted cationic chitosan as effective salt-tolerant flocculants.

In this work, gallic acid was successfully grafted onto quaternary aminated chitosan to prepare a high efficiency cationic flocculant. The mechanism of flocculation and different influencing factors were studied in detail. The prepared flocculant only needs 60 mg L-1 to achieve a 98.7% and 94.5% removal rate on methyl blue (MB) and Congo red (CR), respectively. The high removal rate (93.2%) of a CR-MB mixed dye also confirms the universality of flocculation. In addition, kaolin as a simulated suspended solid was removed at a rate of 97% in the experiment at a dosage of 3 mg L-1. A zeta potential test showed that it worked best when the potential of the flocculation system was zero; this was because an electrostatic balance was reached between the flocculant and pollutant. Importantly, the three-functional molecules can provide more possibilities to form hydrogen bonds with water molecules, which is conducive to the stretching of flocculant molecular chains in salt water. The flocculant maintained a high stability in four different salt environments and has a positive industrial application significance. Furthermore, the flocculation experiment of the actual wastewater of the printing and dyeing plant found that the dye wastewater changed obviously from turbidity to clarification, which proved the practical application potential of the flocculant. This work provides a feasible idea for the preparation of bio-based flocculants.

[Perioperative stroke after aortic valve replacement for aortic stenosis - incidence, risk factors and short-term outcome].

INTRODUCTION: One of the most serious complications of surgical aortic valve replacement (SAVR) is stroke that can result in increased rates of complications, morbidity and mortality postoperatively. The aim of this study was to investigate incidence, risk factors and short-term outcome in a well defined cohort of SAVR-patients. MATERIALS AND METHOD: A retrospective study on 740 consecutive aortic stenosis patients who underwent SAVR in Iceland 2002-2019. Patients with stroke were compared with non-stroke patients; including preoperative risk factors of cardiovascular disease, echocardiogram-results, rate of early postoperative complications other than stroke and 30 day mortality. RESULTS: Mean age was 71 yrs (34% females) with 57% of the patients receiving stented bioprosthesis, 31% a stentless Freestyle®-valve and 12% a mechanical valve. Mean EuroSCORE-II was 3.6, with a maximum preop-gradient of 70 mmHg and an estimated valvular area of 0.73 cm2. Thirteen (1.8%) patients were diagnosed with stroke where hemiplegia (n=9), loss of consciousness (n=3) and/or aphasia (n=4) were the most common presenting symptoms. In 70% of cases the neurological symptoms resolved or disappeared in the first weeks and months after surgery. Only one patient out of 13 died within 30-days (7.7%). Stroke-patients had significantly lower BMI than non-stroke patients, but other risk factors of cardiovascular diseases, intraoperative factors or the rate of other severe postoperative complications than stroke were similar between groups. Total length of stay was 14 days vs. 10 days median, including 2 vs. 1 days in the ICU, in the stroke and non-stroke-groups, respectively. CONCLUSIONS: The rate of stroke after SAVR was low (1.8%) and in line with other similar studies. Although a severe complication, most patients with perioperative stroke survived 30 days postoperatively and in majority of cases neurological symptoms recovered.

Methylated derivatives of polycyclic aromatic hydrocarbons in road dust, green belt soil and parking lot dust: occurrence, spatial distribution and emission sources.

Convenient transportation facilities not only bring the higher standard of living to big cities, but also bring some environmental pollution problems. In order to understand the presence and sources of methylated polycyclic aromatic hydrocarbons (Me-PAHs) in environmental samples and their association with total organic carbon (TOC), 49 Me-PAHs were analyzed in road dust, green belt soil and parking lot dust samples in Harbin. The results showed that the ranges of the total Me-PAHs (ΣMe-PAHs) content in road dust were 221-5826 ng/g in autumn and 697-7302 ng/g in spring, and those in green belt soil were 170-2509 ng/g and 155-9215 ng/g in autumn and spring, respectively. And ΣMe-PAHs content in parking lot dust ranged from 269 to 2515 ng/g in surface parking lots and from 778 to 10,052 ng/g in underground parking lots. In these samples, the composition profile of Me-PAHs was dominated by 4-ring Me-PAHs. The results of diagnostic ratios and principal component analysis (PCA) indicated that petrogenic and pyrogenic sources were the main sources of Me-PAHs in the samples. Spearman correlation analysis showed that there was no correlation for Me-PAHs in road dust and green belt soil on the same road. Furthermore, there was a significant positive relationship (0.12 ≤ R2 ≤ 0.67, P < 0.05) between Me-PAHs concentrations and the TOC content. This study demonstrated the presence of Me-PAHs with high concentrations in the road environment samples of Harbin.

Seasonal patterns, fate and ecological risk assessment of pharmaceutical compounds in a wastewater treatment plant with Bacillus bio-reactor treatment.

Pharmaceutical compounds (PhCs) pose a growing concern with potential environmental impacts, commonly introduced into the environment via wastewater treatment plants (WWTPs). The occurrence, removal, and season variations of 60 different classes of PhCs were investigated in the baffled bioreactor (BBR) wastewater treatment process during summer and winter. The concentrations of 60 PhCs were 3400 ± 1600 ng/L in the influent, 2700 ± 930 ng/L in the effluent, and 2400 ± 120 ng/g dw in sludge. Valsartan (Val, 1800 ng/L) was the main contaminant found in the influent, declining to 520 ng/L in the effluent. The grit chamber and BBR tank were substantially conducive to the removal of VAL. Nonetheless, the BBR process showcased variable removal efficiencies across different PhC classes. Sulfadimidine had the highest removal efficiency of 87 ± 17% in the final effluent (water plus solid phase). Contrasting seasonal patterns were observed among PhC classes within BBR process units. The concentrations of many PhCs were higher in summer than in winter, while some macrolide antibiotics exhibited opposing seasonal fluctuations. A thorough mass balance analysis revealed quinolone and sulfonamide antibiotics were primarily eliminated through degradation and transformation in the BBR process. Conversely, 40.2 g/d of macrolide antibiotics was released to the natural aquatic environment via effluent discharge. Gastric acid and anticoagulants, as well as cardiovascular PhCs, primarily experienced removal through sludge adsorption. This study provides valuable insights into the intricate dynamics of PhCs in wastewater treatment, emphasizing the need for tailored strategies to effectively mitigate their release and potential environmental risks.

Visible-Light-Driven Z-Type Pg-C3N4/Nitrogen Doped Biochar/BiVO4 Photo-Catalysts for the Degradation of Norfloxacin.

Antibiotics cannot be effectively removed by traditional wastewater treatment processes, and have become widespread pollutants in various environments. In this study, a Z-type heterojunction photo-catalyst Pg-C3N4 (PCN)/Nitrogen doped biochar (N-Biochar)/BiVO4 (NCBN) for the degradation of norfloxacin (NOR) was prepared by the hydrothermal method. The specific surface area of the NCBN (42.88 m2/g) was further improved compared to BiVO4 (4.528 m2/g). The photo-catalytic performance of the catalyst was investigated, and the N-Biochar acted as a charge transfer channel to promote carrier separation and form Z-type heterojunctions. Moreover, the NCBN exhibited excellent performance (92.5%) in removing NOR, which maintained 70% degradation after four cycles. The main active substance of the NCBN was •O2-, and the possible degradation pathways are provided. This work will provide a theoretical basis for the construction of heterojunction photo-catalysts.

Correlation of retrobulbar perfusion deficits with glaucomatous visual field defects.

PURPOSE: This study is to evaluate the correlation between retrobulbar perfusion deficits and glaucomatous visual field defects. METHODS: Eighty-four patients with glaucoma and 17 normal subjects serving as controls were selected. Color Doppler imaging (CDI) was used to measure the changes in blood flow parameters in the retrobulbar ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs). Visual field testing was performed using a Humphrey perimeter, categorizing the visual field deficits into four stages according to the Advanced Glaucoma Intervention Study (AGIS) scoring method. Subsequently, the correlation of retrobulbar hemodynamic parameter alterations among glaucomatous patients with varying visual field defects was examined. RESULTS: The higher the visual field stage, the lower the peak systolic velocity (PSV) of the OA, CRA, and SPCAs in glaucomatous patients. The CRA had the highest sensitivity to changes in its PSV. The PSV of the temporal SPCA (TSPCA-PSV) was lower in advanced glaucoma than in early-stage glaucoma. The PSVs of the OA, CRA, and TSPCA, as well as the resistance index of the CRA (CRA-RI), were positively correlated with the visual field index and the mean deviation. Except for that of OA, the PSV of the retrobulbar vessels was negatively correlated with the pattern standard deviation (PSD). The OA-PSV and end-diastolic velocity (EDV) of the CRA and TSPCA were lower in patients with superior visual field defects than in those with inferior visual field defects. CONCLUSIONS: Greater severity of visual field defects corresponded to poorer retrobulbar blood flow in glaucomatous patients. Patients suffered significant perfusion impairments in the CRA at the early stage, accompanied by SPCA perfusion disorder at the advanced stage. The presence of a bow-shaped defect in the superior or inferior region of the visual field in moderate-stage glaucoma was closely correlated with retrobulbar vascular EDV. TRIAL REGISTRATION: ChiCTR2200059048 (2022-04-23).

Reevaluating Adiponectin's impact on obesity hypertension: a Chinese case-control study.

BACKGROUND: Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This "adiponectin paradox" still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study. METHODS: A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. RESULTS: Serum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model. CONCLUSIONS: Our study reveals that adiponectin's role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the "adiponectin paradox".

Airborne antibiotic resistome and microbiome in pharmaceutical factories.

Antimicrobial resistance is considered to be one of the biggest public health problems, and airborne transmission is an important but under-appreciated pathway for the spread of antibiotic resistance genes (ARGs) in the environment. Previous research has shown pharmaceutical factories to be a major source of ARGs and antibiotic resistant bacteria (ARB) in the surrounding receiving water and soil environments. Pharmaceutical factories are hotspots of antibiotic resistance, but the atmospheric transmission and its environmental risk remain more concerns. Here, we conducted a metagenomic investigation into the airborne microbiome and resistome in three pharmaceutical factories in China. Soil (average: 38.45%) and wastewater (average: 28.53%) were major contributors of airborne resistome. ARGs (vanR/vanS, blaOXA, and CfxA) conferring resistance to critically important clinically used antibiotics were identified in the air samples. The wastewater treatment area had significantly higher relative abundances of ARGs (average: 0.64 copies/16S rRNA). Approximately 28.2% of the detected airborne ARGs were found to be associated with plasmids, and this increased to about 50% in the wastewater treatment area. We have compiled a list of high-risk airborne ARGs found in pharmaceutical factories. Moreover, A total of 1,043 viral operational taxonomic units were identified and linked to 47 family-group taxa. Different CRISPR-Cas immune systems have been identified in bacterial hosts in response to phage infection. Similarly, higher phage abundance (average: 2451.70 PPM) was found in the air of the wastewater treatment area. Our data provide insights into the antibiotic resistance gene profiles and microbiome (bacterial and non-bacterial) in pharmaceutical factories and reveal the potential role of horizontal transfer in the spread of airborne ARGs, with implications for human and animal health.

Enhanced multi-metals stabilization: Synergistic insights from hydroxyapatite and peroxide dosing strategies.

Sediment contamination by heavy metals is a pressing environmental concern. While in situ metal stabilization techniques have shown promise, a great challenge remains in the simultaneous immobilization of multi-metals co-existing in contaminated sediments. This study aims to address this challenge by developing a practical method for stabilizing multi-metals by hydroxyapatite and calcium peroxide (HAP/CaO2) dosing strategies. Results showed that dosing 15.12 g of HAP/CaO2 at a ratio of 3:1 effectively transformed labile metals into stable fractions, reaching reaction kinetic equilibrium within one month with a pseudo-second-order kinetic (R2 > 0.98). The stable fractions of Nickel (Ni), Chromium (Cr), and lead (Pb) increased by approximately 16.9 %, 26.7 %, and 21.9 %, respectively, reducing heavy metal mobility and ensuring leachable concentrations complied with the stringent environmental Class I standard. Mechanistic analysis indicated that HAP played a crucial role in Pb stabilization, exhibiting a high rate of 0.0176 d-1, while Cr and Ni stabilization primarily occurred through the formation of hydroxide precipitates, as well as the slowly elevated pH (>8.5). Importantly, the proposed strategy poses a minimal environmental risk to benthic organisms exhibits almost negligible toxicity towards Vibrio fischeri and the Chironomus riparius, and saves about 71 % of costs compared to kaolinite. These advantages suggest the feasibility of HAP/CaO2 dosing strategies in multi-metal stabilization in contaminated sediments.

Ammonium-based bioleaching of toxic metals from sewage sludge in a continuous bioreactor.

The broader reuse of sewage sludge as a soil fertilizer or conditioner is impeded by the presence of toxic metals. Bioleaching, a process that leverages microbial metabolisms and metabolites for metal extraction, is viewed as an economically and environmentally feasible approach for metal removal. This study presents an innovative bioleaching process based on microbial oxidation of ammonia released from sludge hydrolysis, mediated by a novel acid tolerant ammonia-oxidizing bacteria (AOB), Ca. Nitrosoglobus. Over a span of 1024 days, a laboratory-scale bioleaching reactor processing anaerobically digested (AD) sludge achieved an in-situ pH of 2.5 ± 0.3. This acidic environment facilitated efficient leaching of toxic metals from AD sludge, upgrading its quality from Grade C to Grade A (qualified for unrestricted use), according to both stabilization and contaminants criteria. The improved quality of AD sludge could potentially reduce sludge disposal expenses and enable a broader reuse of biosolids. Furthermore, this study revealed a pH-dependent total ammonia affinity of Ca. Nitrosoglobus, with a higher affinity constant at pH 3.5 (67.3 ± 20.7 mg N/L) compared to pH 4.5-7.5 (7.6 - 9.6 mg N/L). This finding indicates that by optimizing ammonium concentrations, the efficiency of this novel ammonium-based bioleaching process could be significantly increased.

Trophic Niche Differentiation in Two Sympatric Nuthatch Species (Sitta yunnanensis and Sitta nagaensis).

Sympatric closely related species may experience interspecific trophic competition due to ecological similarity; they may isolate in terms of diet or habitat use as a strategy to avoid competition. The body tissues of consumers contain stable isotope signatures information that can be applied to infer their dietary information. In this study, δ13C and δ15N stable isotopes were analyzed to determine the dietary information and trophic niches of sympatric coexisting Sitta yunnanensis and Sitta nagaensis. The results showed that the food sources of S. yunnanensis and S. nagaensis were from six orders, including Orthoptera, and the cumulative contribution rate was 99.97%, with the two species eating similar diets but at different rates. The larger δ13C of S. yunnanensis indicates that it had a wider range of habitats for feeding, while the difference in δ15N values was not significant (p > 0.05), indicating that both species feed on similar nutrient levels. As determined by Bayesian ellipses, the isotopic niches of S. yunnanensis and S. nagaensis were differentiated; the isotopic niche width of S. yunnanensis is 2.69‱2, which was larger than that of S. nagaensis (0.73‱2), indicates that differentiation between the two species in diet or habitat use reduced competition. Trophic niche differentiation and differences in foraging proportions may be the principal resource allocation mechanisms behind S. yunnanensis and S. nagaensis coexistence.

Antibiotic resistome in landfill leachate and impact on groundwater.

Landfill leachate is a hotspot in antibiotic resistance development. However, little is known about antibiotic resistome and host pathogens in leachate and their effects on surrounding groundwater. Here, metagenomic sequencing was used to explore profiles, host bacteria, environmental risks and influencing factors of antibiotic resistome in raw and treated leachate and surrounding groundwater of three landfills. Results showed detection of a total of 324 antibiotic resistance genes (ARGs). The ARGs conferring resistance to multidrug (8.8 %-25.7 %), aminoglycoside (13.1 %-39.2 %), sulfonamide (10.0 %-20.9 %), tetracycline (5.7 %-34.4 %) and macrolide-lincosamide-streptogramin (MLS, 5.3 %-29.5 %) were dominant in raw leachate, while multidrug resistance genes were the major ARGs in treated leachate (64.1 %-83.0 %) and groundwater (28.7 %-76.6 %). Source tracking analysis suggests non-negligible influence of leachate on the ARGs in groundwater. The pathogens including Acinetobacter pittii, Pseudomonas stutzeri and P. alcaligenes were the major ARG-carrying hosts. Variance partitioning analysis indicates that the microbial community, abiotic variables and their interaction contributed most to the antibiotic resistance development. Our results shed light on the dissemination and driving mechanisms of ARGs from leachate to the groundwater, indicating that a comprehensive risk assessment and efficient treatment approaches are needed to deal with ARGs in landfill leachate and nearby groundwater. ENVIRONMENTAL IMPLICATIONS: Antibiotic resistance genes are found abundant in the landfill sites, and these genes could be disseminated into groundwater via leaching of wastewater and infiltration of leachate. This results in deterioration of groundwater quality and human health risks posed by these ARGs and related pathogens. Thus measures should be taken to minimize potential negative impacts of landfills on the surrounding environment.

Causal effect of interleukin (IL)-6 on blood pressure and hypertension: A mendelian randomization study.

To examine whether circulating interleukin-6 (IL-6) levels (CirIL6) have a causal effect on blood pressure using Mendelian randomization (MR) methods. We used data from genome-wide association studies (GWAS) of European ancestry to obtain genetic instruments for circulating IL-6 levels and blood pressure measurements. We applied several robust MR methods to estimate the causal effects and to test for heterogeneity and pleiotropy. We found that circulating IL-6 had a significant positive causal effect on systolic blood pressure (SBP) and pulmonary arterial hypertension (PAH), but not on diastolic blood pressure (DBP) or hypertension. We found that as CirIL6 genetically increased, SBP increased using Inverse Variance Weighted (IVW) method (for ukb-b-20175, ß = 0.082 with SE = 0.032, P = 0.011; for ukb-a-360, ß = 0.075 with SE = 0.031, P = 0.014) and weighted median (WM) method (for ukb-b-20175, ß = 0.061 with SE = 0.022, P = 0.006; for ukb-a-360, ß = 0.065 with SE = 0.027, P = 0.014). Moreover, CirIL6 may be associated with an increased risk of PAH using WM method (odds ratio (OR) = 15.503, 95% CI, 1.025-234.525, P = 0.048), but not with IVW method. Our study provides novel evidence that circulating IL-6 has a causal role in the development of SBP and PAH, but not DBP or hypertension. These findings suggest that IL-6 may be a potential therapeutic target for preventing or treating cardiovascular diseases and metabolic disorders. However, more studies are needed to confirm the causal effects of IL-6 on blood pressure and to elucidate the underlying mechanisms and pathways.

A Streptococcus suis Strain Δcps/ssna-msly (P353L)-SC19 Provides Cross-Protection against Serotypes 2 and 9 Strain Challenges in a Mouse Model.

Streptococcus suis is an important zoonotic pathogen that mainly causes meningitis, septicemia, and arthritis. Due to the limited cross-protection between numerous serotypes, the existing inactive vaccines in clinical use fail to offer sufficient protection. In this study, a gene deletion-attenuated strain Δcps/ssna-msly (P353L)-SC-19 was constructed by deleting cps and ssna genes from the epidemic strain SC-19 with a mutation of SLY (P353L). The safety of Δcps/ssna-msly (P353L)-SC-19 was confirmed in both in vitro and in vivo experiments. We further demonstrated that immunization with Δcps/ssna-msly (P353L)-SC-19 induced significant cellular immunity and humoral immunity in mice and protected against infections caused by type 2 strain SC-19 (100% protection) and type 9 strain S29 (50% protection), while also preventing meningitis induced by S29. This study highlights the potential of using CPS-deficient strains to achieve cross-protection against different Streptococcus suis serotypes and develop a promising universal live vaccine.