Heterogeneous effects of hospital competition on inpatient quality: an analysis of five common diseases in China.

BACKGROUND: Many countries has introduced pro-competition policies in the delivery of healthcare to improve medical quality, including China. With the increasing intensity of competition in China's healthcare market, there are rising concerns among policymakers about the impact of hospital competition on quality. This study investigated heterogeneous effects of hospital competition on inpatient quality. METHODS: We analyzed the inpatient discharge dataset and selected chronic obstructive pulmonary disease (COPD), ischemic stroke, pneumonia, hemorrhagic stroke, and acute myocardial infarction (AMI) as representative diseases. A total of 561,429 patients in Sichuan Province in 2017 and 2019 were included. The outcomes of interest were in-hospital mortality and 30-day unplanned readmissions. The Herfindahl-Hirschman Index was calculated using predicted patient flows to measure hospital competition. To address the spatial correlations of hospitals and the structure of the dataset, the multiple membership multiple classification model was employed for analysis. RESULTS: Amid intensifying competition in the hospital market, our study discerned no marked statistical variance in the risk of inpatient quality across most diseases examined. Amplified competition exhibited a positive correlation with heightened in-hospital mortality for both COPD and pneumonia patients. Elevated competition escalated the risk of 30-day unplanned readmissions for COPD patients, while inversely affecting the risk for AMI patients. CONCLUSIONS: There is the heterogeneous impact of hospital competition on quality across various diseases in China. Policymakers who intend to leverage hospital competition as a tool to enhance healthcare quality must be cognizant of the possible influences of it.

Isolation, identification, and optimization of conditions for the degradation of four sulfonamide antibiotics and their metabolic pathways in Pseudomonas stutzeri strain DLY-21.

Overuse of sulfonamides in aquaculture and agriculture leads to residual drugs that cause serious pollution of the environment. However, the residues of sulfonamides in the environment are not unique, and the existing microbial degradation technology has a relatively low degradation rate of sulfonamides. Therefore, in this study, a Pseudomonas stutzeri strain (DLY-21) with the ability to degrade four common SAs was screened and isolated from aerobic compost. Under optimal conditions, the DLY-21 strain degraded four sulfonamides simultaneously within 48 h, and the degradation rates were all over 90%, with the average degradation rates of SAs being sulfoxide (SDM) ≈ sulfachloropyridazine (SCP) > sulfa quinoxaline (SQ) > sulfadiazine (SQ). In addition, the main compounds of the strain DLY-21-degrading SAs were identified by LC-MS analysis. On this basis, four detailed reaction pathways for SA degradation were deduced. This is the first report of the use of a P. stutzeri strain to degrade four sulfonamide antibiotics (SQ, SDM, SCP, and SM1), which can improve the removal efficiency of sulfonamide antibiotic pollutants and thus ameliorate environmental pollution. The results showed that DLY-21 had a good degradation effect on four SAs (SQ, SDM, SCP, and SM1).

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Is low-dose computed tomography for lung cancer screening conveniently accessible in China? A spatial analysis based on cross-sectional survey.

BACKGROUND: Regular Low-Dose Computed Tomography (LDCT) for lung cancer high-risk population has been proved to improve health outcomes and relieve disease burden efficiently for both individual and society. With geographical impedance becoming the major barrier preventing patients from getting timely healthcare service, this study incorporated health seeking behavior in estimating spatial accessibility of relative scarce LDCT resource in China, thus to provide real-world evidence for future government investment and policy making. METHODS: Taking Sichuan Province in southwest China as the study area, a cross-sectional survey was first carried out to collect actual practice and preferences for seeking LDCT services. Using Computed Tomography (CT) registration data reported by owner institutions representing LDCT services capacity, and grided town-level high-risk population as demand, the Nearest Neighbor Method was then utilized to calculate spatial accessibility of LDCT services. RESULTS: A total of 2,529 valid questionnaires were collected, with only 34.72% of the high-risk populations (746 individuals) followed the recommended annual screening. Participants preferred to travel to municipal-level and above institutions within 60 min for LDCT services. Currently, every thousand high-risk populations own 0.0845 CT scanners in Sichuan Province, with 96.95% able to access LDCT within 60 min and over half within 15 min. Urban areas generally showed better accessibility than rural areas, and the more developed eastern regions were better than the western regions with ethnic minority clusters. CONCLUSIONS: Spatial access to LDCT services is generally convenient in Sichuan Province, but disparity exists between different regions and population groups. Improving LDCT capacity in county-level hospitals as well as promoting health education and policy guidance to the public can optimize efficiency of existing CT resources. Implementing mobile CT services and improving rural public transportation may alleviate emerging disparities in accessing early lung cancer detection.

Revealing spatiotemporal inequalities, hotspots, and determinants in healthcare resource distribution: insights from hospital beds panel data in 2308 Chinese counties.

BACKGROUND: Ensuring universal health coverage and equitable access to health services requires a comprehensive understanding of spatiotemporal heterogeneity in healthcare resources, especially in small areas. The absence of a structured spatiotemporal evaluation framework in existing studies inspired us to propose a conceptual framework encompassing three perspectives: spatiotemporal inequalities, hotspots, and determinants. METHODS: To demonstrate our three-perspective conceptual framework, we employed three state-of-the-art methods and analyzed 10 years' worth of Chinese county-level hospital bed data. First, we depicted spatial inequalities of hospital beds within provinces and their temporal inequalities through the spatial Gini coefficient. Next, we identified different types of spatiotemporal hotspots and coldspots at the county level using the emerging hot spot analysis (Getis-Ord Gi* statistics). Finally, we explored the spatiotemporally heterogeneous impacts of socioeconomic and environmental factors on hospital beds using the Bayesian spatiotemporally varying coefficients (STVC) model and quantified factors' spatiotemporal explainable percentages with the spatiotemporal variance partitioning index (STVPI). RESULTS: Spatial inequalities map revealed significant disparities in hospital beds, with gradual improvements observed in 21 provinces over time. Seven types of hot and cold spots among 24.78% counties highlighted the persistent presence of the regional Matthew effect in both high- and low-level hospital bed counties. Socioeconomic factors contributed 36.85% (95% credible intervals [CIs]: 31.84-42.50%) of county-level hospital beds, while environmental factors accounted for 59.12% (53.80-63.83%). Factors' space-scale variation explained 75.71% (68.94-81.55%), whereas time-scale variation contributed 20.25% (14.14-27.36%). Additionally, six factors (GDP, first industrial output, local general budget revenue, road, river, and slope) were identified as the spatiotemporal determinants, collectively explaining over 84% of the variations. CONCLUSIONS: Three-perspective framework enables global policymakers and stakeholders to identify health services disparities at the micro-level, pinpoint regions needing targeted interventions, and create differentiated strategies aligned with their unique spatiotemporal determinants, significantly aiding in achieving sustainable healthcare development.

METTL3-m6A-SIRT1 axis affects autophagic flux contributing to PM2.5-induced inhibition of testosterone production in Leydig cells.

Epidemiological studies have found that long-term inhalation of PM2.5 is closely related to spermatogenesis disorders and infertility, but the underlying molecular mechanism is still unidentified. Testosterone, an essential reproductive hormone produced by Leydig cells, whose synthesis is disrupted by multiple environmental pollutants. In the current study, we explored the role of METTL3-m6A-SIRT1 axis-mediated abnormal autophagy in PM2.5-induced inhibition of testosterone production in in vivo and in vitro models. Our in vivo findings shown that long-term inhalation of PM2.5 decreased sperm count, increased sperm deformity rates, and altered testicular interstitial morphology accompanied by reduced testosterone in serum and testes. Further, data from the in vitro model displayed that exposure to PM2.5 caused an increase in m6A modification and METTL3 levels, followed by a decrease in testosterone levels and autophagy dysfunction in Leydig cells. The knockdown of METTL3 promotes autophagy flux and testosterone production in Leydig cells. Mechanistically, PM2.5 increased METTL3-induced m6A modification of SIRT1 mRNA in Leydig cells, bringing about abnormal autophagy. Subsequently, administration of SRT1720 (a SIRT1 activator) enhanced autophagy and further promoted testosterone biosynthesis. Collectively, our discoveries indicate that METTL3-m6A-SIRT1 axis-mediated autophagic flux contributes to PM2.5-induced inhibition of testosterone biosynthesis. This research offers a novel viewpoint on the mechanism of male reproductive injury following PM2.5 exposure.

The Association of Allergy-Related and Non-Allergy-Related Olfactory Impairment with Cognitive Function in Older Adults: Two Cross-Sectional Studies.

BACKGROUND: Evidence on the association of Olfactory Impairment (OI) with age-related cognitive decline is inconclusive, and the potential influence of allergy remains unclear. OBJECTIVE: We aimed to evaluate the cross-sectional associations of allergy-related and non-allergy- related OI to cognitive function. METHODS: We included 2,499 participants from the Health and Retirement Study (HRS)-Harmonized Cognitive Assessment Protocol (HCAP) sub-study and 1,086 participants from the English Longitudinal Study of Ageing (ELSA)-HCAP. The Olfactory Function Field Exam (OFFE) using Sniffin' Stick odor pens was used to objectively assess olfactory function and an olfactory score <6/11 indicated OI. Mini-Mental Status Examination (MMSE) was used to assess global cognitive function and define cognitive impairment (<24/30). A neuropsychologic battery was used to assess five cognitive domains. RESULTS: Compared to non-OI participants, individuals with OI had lower MMSE z-score [ßHRS = -0.33, 95% Confidence Interval (CI): -0.41 to -0.24; ßELSA = -0.31, -0.43 to -0.18] and higher prevalence of cognitive impairment [Prevalence Ratio (PR)HRS = 1.46, 1.06 to 2.01; PRELSA = 1.63, 1.26 to 2.11]. The associations were stronger for non-allergy-related OI (ßHRS = -0.36; ßELSA = -0.34) than for allergy-related OI (ßHRS = -0.26; ßELSA = 0.13). Similar associations were observed with domain- specific cognitive function measures. CONCLUSION: OI, particularly non-allergy-related OI, was related to poorer cognitive function in older adults. Although the current cross-sectional study is subject to several limitations, such as reverse causality and residual confounding, the findings will provide insights into the OI-cognition association and enlighten future attention to non-allergy-related OI for the prevention of potential cognitive impairment.

Differences in physicochemical, rheological, and prebiotic properties of inulin isolated from five botanical sources and their potential applications.

This study compares the physicochemical and prebiotic properties of inulin isolated from five botanical sources. The average degree of polymerization (DP) for inulin ranged from 5.00 to 13.33. Notably, inulin from Dahlia tubers (DP = 13) and Platycodonis Radix (DP = 8) demonstrated granular, clustered morphology under SEM, semi-crystalline structures via X-ray diffraction, and exhibited shear-thinning behaviors from shear rate 1 s-1 to 500 s-1. In contrast, inulin from Jerusalem artichoke (DP = 5), chicory root (DP = 7), and Asparagi Radix (DP = 5) showcased rough flake morphologies under SEM, amorphous structures in X-ray patterns, and similar shear-thinning behaviors. All inulin types showed acid stability at pH levels below 2.0, with a reducing sugar conversion ratio (RRS) under 1 %. Furthermore, the isolated inulin from the different sources presented prebiotic capacity when added as a sole carbon source in the culture media of the probiotics Lactobacillus paracasei and Bifidobacterium longum. This study provides the properties of inulin from various sources, thereby offering a reference for the selection of appropriate inulin in industrial applications based on the desired characteristics of the final product.

In vitro assessment of the bacterial stress response and resistance evolution during multidrug-resistant bacterial invasion of the Xenopus tropicalis intestinal tract under typical stresses.

The intestinal microbiome might be both a sink and source of resistance genes (RGs). To investigate the impact of environmental stress on the disturbance of exogenous multidrug-resistant bacteria (mARB) within the indigenous microbiome and proliferation of RGs, an intestinal conjugative system was established to simulate the invasion of mARB into the intestinal microbiota in vitro. Oxytetracycline (OTC) and heavy metals (Zn, Cu, Pb), commonly encountered in aquaculture, were selected as typical stresses for investigation. Adenosine 5'-triphosphate (ATP), hydroxyl radical (OH·-) and extracellular polymeric substance (EPS) were measured to investigate their influence on the acceptance of RGs by intestinal bacteria. The results showed that the transfer and diffusion of RGs under typical combined stressors were greater than those under a single stressor. Combined effect of OTC and heavy metals (Zn, Cu) significantly increased the activity and extracellular EPS content of bacteria in the intestinal conjugative system, increasing intI3 and RG abundance. OTC induced a notable inhibitory response in Citrobacter and exerted the proportion of Citrobacter and Carnobacterium in microbiota. The introduction of stressors stimulates the proliferation and dissemination of RGs within the intestinal environment. These results enhance our comprehension of the typical stresses effect on the RGs dispersal in the intestine.

(3+1)-dimensional Pearcey-Gaussian wave packet with arbitrary velocity driven by flying focus.

The group velocity (GV) modulation of space-time wave packets (STWPs) along the transverse and longitudinal directions in free space is constrained by various factors. To surmount this limitation, a technique called "flying focus" has been developed, which enables the generation of laser pulses with dynamic focal points that can propagate at arbitrary velocities independent of GV. In this Letter, we propose a (3+1)-dimensional Pearcey-Gauss wave packet based on the "flying focus" technique, which exhibits superluminal propagation, transverse focus oscillation, and longitudinal periodic autofocusing. By selecting appropriate parameters, we can flexibly manipulate the position, the size, and the number of focal points- or make the wave packet follow a desired trajectory. This work may pave the way for the advancement of space-time structured light fields.

Adjuvant chemotherapy combined with immunotherapy in patients with cholangiocarcinoma after radical resection.

BACKGROUND: The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated. METHODS: Data from 101 patients with cholangiocarcinoma treated at the Sun Yat-sen University Cancer Center between 2015 and 2020 were studied. RESULTS: After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse-free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023). CONCLUSION: Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.

IL20RB signaling enhances stemness and chemotherapy resistance in pancreatic cancer.

OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness. MATERIALS AND METHODS: Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored. RESULTS: IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects. CONCLUSION: Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.

Morphological, Structural, Thermal, Pasting, and Digestive Properties of Starches Isolated from Different Varieties of Rice: A Systematic Comparative Study.

The aim of this study was to compare the properties of isolated starches from ten commonly consumed rice varieties in China and to investigate their possible association. In addition, principal component analysis (PCA) and correlation analysis were performed to demonstrate the weight or relevance of different properties. The starch granules had an irregular polyhedral structure. The crystalline structure had an orthogonal arrangement, which is characteristic of A-type starch with nanocrystals with an orthorhombic crystal structure. In addition, higher levels of rapidly digestible starch (72.43 to 74.32%) and resistant starch (2.27 to 2.3%) were found in glutinous rice starch. The highest content of slowly digestible starch (59.48%) was found in starch isolated from black rice, which may be an ideal rice variety for controlling blood glucose and weight. Starch isolated from red Hani terrace rice showed the highest thermal stability during cooking and the highest resistance to a high shear force treatment. In addition, the PCA suggests that the amylose content of starch largely determines the functional properties of starch and positively correlates with the peak viscosity and setback viscosity of the starch pasting. The results of this study will enrich the scientific knowledge of various rice starches and promote their application in the food industry and other industries.

Adjuvant chemotherapy in pancreatic cancer at different AJCC stages: a propensity score matching analysis.

OBJECTIVE: In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. MATERIALS AND METHODS: Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. RESULTS: 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). CONCLUSIONS: The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

Dual-band chirality-selective absorbing by plasmonic metasurfaces with breaking mirror and rotational symmetry.

In this work, we proposed a state-of-the-art metasurface model that breaks the mirror symmetry and rotation symmetry of the structure. It consists of two-layer rotating gold split rings, and has the capability of chirality-selective absorption for circularly polarized light (CPL) in two bands. The absorption peaks for left- and right- circularly polarized (LCP&RCP) light appeared at 989 nm and 1404 nm, respectively, with the maximum absorptivity of 98.5% and 96.3%, respectively. By changing the rotation angle of the two-layer gold split rings, it could also be designed as a single-band chiral metasurface absorber, which only absorbed RCP light but not LCP light, and the absorptivity of RCP light could be up to 97.4%. Furthermore, we found our designed absorbers had the characteristics of great circular dichroism (CD) and symmetric absorption. The physical mechanism of the selective absorption of CPL by the absorbers may be explained by the current vector analysis. In addition, the absorption peak could be tuned with the changing of the geometrical parameters of the structure. The proposed chirality-selective metasurface absorbers could be used in CD spectral detection, optical communication, optical filtering, and other fields.

Ambient particulate matter and in-hospital case fatality of acute myocardial infarction: A multi-province cross-sectional study in China.

The acute myocardial infarction (AMI) outcomes have been extensively linked with ambient particulate matter (PM). However, whether a smaller particle has greater impact and the consequent attributable burden associated with PM of different sizes remain unclear. We conducted a multi-province cross-sectional study among AMI patients using the inpatient discharge datasets from four Chinese provinces (Shanxi, Sichuan, Guangxi, and Guangdong) from 2014 to 2019. Ambient PM exposure for each patient was assessed using the ChinaHighAirPollutants dataset. We employed the mixed-effects logistic regression models to evaluate the association of PM of different sizes (PM1, PM2.5, PM10) on in-hospital case fatality. The potential reducible fractions in in-hospital case fatality were estimated through counterfactual analyses. Of 177,749 participants, 125,501 (70.6 %) were male and the in-hospital case fatality rate was 4.9%. For short-term (7-day average) exposure, the odds ratios (ORs) for PM1, PM2.5, and PM10 (per 10 µg/m3) were 1.052 (95 % confidence interval [CI], 1.032-1.071), 1.026 (95 % CI, 1.014-1.037), and 1.016 (95% CI, 1.008-1.024), respectively. The estimated ORs for long-term exposure (annual average) were 1.303 (95 % CI, 1.252-1.356) for PM1, 1.209 (95 % CI, 1.178-1.241) for PM2.5, 1.157 (95 % CI, 1.134-1.181) for PM10. Short-term exposure to PM1 showed the highest potential reducible fraction (8.5 %, 95 % CI, 5.0-11.7 %), followed by PM2.5 and PM10, while the greatest potential reducible fraction of long-term exposure was observed in PM10 (30.9 %, 95 % CI, 27.2-34.4%), followed by PM2.5 and PM1. In summary, PM with smaller size had a more pronounced impact on in-hospital AMI case fatality, with PM1 exhibiting greater effects than PM2.5 and PM10. Substantial health benefits for AMI patients could be achieved by mitigating ambient PM exposure.

Study on the Effect of AO-Coupled Constructed Wetlands on Conventional and Trace Organic Pollutant Treatment.

In this study, a pilot-scale integrated process was developed, which combined the integrated biological contact oxidation technology (AO) and the improved constructed wetland technology. The results showed significant removal efficiency for both conventional and trace organic pollutants. The average removal efficiencies for COD, NH4+-N, and TP were 78.52, 85.95, and 49.47%, respectively. For trace organic pollutants, triclocarban, triclosan, and sulfadiazine, the removal efficiencies reached 60.14, 57.42, and 84.29%, respectively. The AO stage played a crucial role in removing trace organic pollutants, achieving removal efficiencies of 37.28, 43.44, and 83.82% for triclocarban, triclosan, and sulfadiazine, respectively. Subsequent treatment using improved constructed wetland technology with coal slag + gravel fillers demonstrated the highest removal efficiency, with average efficiencies of 68.66, 63.38, and 81.32% for triclocarban, triclosan, and sulfadiazine, respectively. Correlation analysis revealed positive correlations between temperature, precipitation, and the removal efficiency of COD, NH4+-N, and TP, while negative correlations were observed with the removal efficiency of triclocarban, triclosan, and sulfadiazine. Furthermore, the influent concentrations of triclocarban and triclosan were significantly negatively correlated with the removal efficiency of COD and TP. The presence of triclocarban and triclosan potentially reduced the microbial diversity and hindered sludge sedimentation performance.

Organic anion transporting polypeptide 3a1 is a novel influx pump for Perfluorooctane sulfonate in Sertoli cells and contributes to its reproductive toxicity.

Persistent organic pollutant perfluorooctane sulfonate (PFOS) is strongly associated with male reproductive disorders, but the related mechanisms are still not fully understood. In this study, we used in vivo and in vitro models to explore the role of organic anion transporting polypeptide 3a1 (Oatp3a1) on PFOS-induced male reproductive injury. Thirty male C57BL/6 (B6) mice were orally given PFOS (0-10 mg/kg/bw) for 28 days. Body weight, organ index, sperm count, histology, and blood-testis barrier (BTB) integrity were evaluated. Primary Sertoli cells were used to describe the related molecular mechanisms of male reproductive injury caused by PFOS. Our results showed that PFOS induced a decrease in sperm count, morphological damage to testicular Sertoli cells, and disruption of BTB. In the in vitro model, exposure to PFOS significantly increased Oatp3a1 mRNA and protein levels and decreased miR-23a-3p expression in Sertoli cells, accompanied by reduced trans-epithelial electrical resistance (TEER) value. By performing the 14C-PFOS uptake experiment, we showed that 14C-PFOS uptake in HEK293-Oatp3a1 cells was apparently higher than in HEK293-MOCK cells. Meanwhile, treating Sertoli cells with Oatp3a1 siRNA significantly decreased Oatp3a1 expression and rescued PFOS-induced decreases in TEER value. As such, the present study highlights that Oatp3a1 may play an important role in the toxic effect of PFOS on Sertoli cells, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.

Study on toxicity responses and their mechanisms in Xenopus tropicalis long-term exposure to Shigella flexneri and ciprofloxacin.

The abuse and overuse of antibiotics increased not only the exposure of aquatic animals to antibiotics but also the development of resistance in pathogenic bacteria. To investigate the effects and mechanisms of exposure, a long-term experiment lasting 120 days was conducted in which Xenopus tropicalis was exposed to single and combined stress factors of multiresistant pathogenic Shigella flexneri and ciprofloxacin (CIP). The intestinal oxidative stress, immune factors and flora, as well as the brain-gut axis correlation factors of X. tropicalis, were tracked to account for the response of aquatic animals to the exogenous pollutants. SOD activity and MDA content were significantly increased in stressed X. tropicalis (p < 0.001), while the levels of proinflammatory factors (IL-1ß, IFN-γ) were significantly reduced (p < 0.01). The content of intestinal beneficial bacteria decreased and that of harmful bacteria increased in the intestinal flora of the stressed X. tropicalis (p < 0.001). These results suggested that S. flexneri and CIP disturbed the intestinal flora and caused oxidative damage in the host, and the body produced a series of responses, such as oxidative stress responses and regulation of the expression of immune factors, to maintain the balance of antioxidant inflammation. Significant changes in the expression of intestinal neurotransmitters (5-HT, CGRP) and brain peptides (BDNF, NCAM, NPY) (p < 0.05) also indicated that the brain-gut axis interaction was disrupted. In addition, although the coexisting CIP could reduce intestinal toxicity caused by S. flexneri, the amount of intestinal pathogenic bacteria Desulfovibrio increased significantly. Moreover, compared with the single exposure group, SOD activity, CAT activity and MDA content were significantly reduced in the dual exposure group. Therefore, the health risks of multiresistant pathogenic bacteria on the intestinal and brain-gut axis interaction should be given more attention, and the interaction of brain-gut axis is more important when antibiotics coexist.

Oxytetracycline and heavy metals promote the migration of resistance genes in the intestinal microbiome by plasmid transfer.

Horizontal gene transfer (HGT) has been considered the most important pathway to introduce antibiotic resistance genes (ARGs), which seriously threatens human health and biological security. The presence of ARGs in the aquatic environment and their effect on the intestinal micro-ecosystem of aquatic animals can occur easily. To investigate the HGT potential and rule of exogenous ARGs in the intestinal flora, a visual conjugative model was developed, including the donor of dual-fluorescent bacterium and the recipient of Xenopus tropicalis intestinal microbiome. Some common pollutants of oxytetracycline (OTC) and three heavy metals (Zn, Cu and Pb) were selected as the stressor. The multi-techniques of flow cytometry (FCM), scanning electron microscopy (SEM), atomic force microscopy (AFM), single-cell Raman spectroscopy with sorting (SCRSS) and indicator analysis were used in this study. The results showed that ARG transfer could occur more easily under stressors. Moreover, the conjugation efficiency mainly depended on the viability of the intestinal bacteria. The mechanisms of OTC and heavy metal stressing conjugation included the upregulation of ompC, traJ, traG and the downregulation of korA gene. Moreover, the enzymatic activities of SOD, CAT, GSH-PX increased and the bacterial surface appearance also changed. The predominant recipient was identified as Citrobacter freundi by SCRSS, in which the abundance and quantity of ARG after conjugation were higher than those before. Therefore, since the diversity of potential recipients in the intestine are very high, the migration of invasive ARGs in the microbiome should be given more attention to prevent its potential risks to public health.