Dynamics of bacterioplankton communities in the estuary areas of the Taihu Lake: Distinct ecological mechanisms of abundant and rare communities.

As the crucial confluences of rivers and lakes, the estuary areas with varied hydrodynamic exchanges intensively affect the bacterioplankton communities, whereas the ecological characteristics of the bacterioplankton in the areas have not been well understood. Here, the distribution patterns and assembly mechanisms of bacterioplankton communities in the estuary areas of the Taihu Lake were investigated using high-throughput sequencing and multivariate statistical analyses. Our results showed obvious seasonal variations in bacterioplankton diversity and community composition, which had significant correlations with water temperature. Neutral and null models together revealed that stochastic processes (especially dispersal limitation) were the major processes in shaping the communities across different seasons. By contrast, heterogeneous selection in deterministic processes exhibited increased impacts on community assembly during summer and autumn, which was significantly related to the comprehensive water quality index (WQI) rather than any single factor. In this study, rare communities displayed more pronounced seasonal dynamics compared to abundant communities, likely due to their sensitivity towards environmental factors. Accordingly, the heterogeneous selection of deterministic processes largely shaped the rare communities. These results enriched our understanding of the assembly mechanisms of bacterioplankton communities in estuary areas and emphasized the specific co-occurrence patterns of abundant and rare communities.

Pilot-scale investigation of performance and microbial community in a novel system combining fixed and suspended activated sludge.

The conventional activated sludge (CAS) process is a widely used method for wastewater treatment due to its effectiveness and affordability. However, it can be prone to sludge abnormalities such as sludge bulking/foaming and sludge loss, which can lead to a decrease in treatment efficiency. To address these issues, a novel bag-based fixed activated sludge (BBFAS) system utilizing mesh bags to contain the sludge was developed for low carbon/nitrogen ratio wastewater treatment. Pilot-scale experiments demonstrated that the BBFAS system could successfully avoid the sludge abnormalities. Moreover, it was not affected by mass transfer resistance and exhibited significantly higher nitrogen removal efficiency, surpassing that of the CAS system by up to 78%. Additionally, the BBFAS system demonstrated comparable organic matter removal efficiency to CAS system. 16S rRNA gene high-throughput sequencing revealed that the bacterial community structure within the BBFAS system was significantly different from that of the CAS system. The bacteria associated with ammonium removal were more abundant in the BBFAS system than in the CAS system. The abundance of Nitrospira in the BBFAS could reach up to 6% and significantly higher than that in the CAS system, and they were likely responsible for both ammonia-oxidizing and nitrite-oxidizing functions. Clear stratification of microbial communities was observed from the outer to inner layers of the bag components due to the gradients of dissolved oxygen and other substrates. Overall, this study presents a promising approach for avoiding activated sludge abnormalities while maintaining high pollutant removal performance.

Temporal differentiation in the adaptation of functional bacteria to low-temperature stress in partial denitrification and anammox system.

Despite reliable nitrite supply through partial denitrification, the adaptation of denitrifying bacteria to low temperatures remains elusive in partial denitrification and anammox (PDA) systems. Here, temporal differentiations of the structure, activity, and relevant cold-adaptation mechanism of functional bacteria were investigated in a lab-scale PDA bioreactor at decreased temperature. Although distinct denitrifying bacteria dominated after low-temperature stress, both short- and long-term stresses exerted differential selectivity towards the species with close phylogenetic distance. Species Azonexus sp.149 showed high superiority over Azonexus sp.384 under short-term stress, and long-term stress improved the adaptation of Aquabacterium sp.93 instead of Aquabacterium sp.184. The elevated transcription of nitrite reductase genes suggested that several denitrifying bacteria (e.g., Azonexus sp.149) could compete with anammox bacteria for nitrite. Species Rivicola pingtungensis and Azonexus sp.149 could adapt through various adaptation pathways, such as the two-component system, cold shock protein (CSP), membrane alternation, and electron transport chain. By contrast, species Zoogloea sp.273 and Aquabacterium sp.93 mainly depended on the CSP and oxidative stress response. This study largely deepens our understanding of the performance deterioration in PDA systems during cold shock and provides several references for efficient adaptation to seasonal temperature fluctuation.

Comparative evaluation of SPE methods for biotoxicity assessment of water and wastewater: Linkage between chemical extracting efficiency and biotoxicity outcome.

Biotoxicity assessment results of environmental waters largely depend on the sample extraction protocols that enrich pollutants to meet the effect-trigger thresholds of bioassays. However, more chemical mixture does not necessarily translate to higher combined biotoxicity. Thus, there is a need to establish the link between chemical extracting efficiency and biotoxicity outcome to standardize extraction methods for biotoxicity assessment of environmental waters. This study compares the performance of five different extraction phases in solid phase extraction (SPE), namely HLB, HLB+Coconut, C18 cartridge, C18 disk and Strata-X, and evaluated their chemical extracting efficiencies and biotoxicity outcomes. We quantitatively assessed cytotoxicity, acute toxicity, genotoxicity, estrogenic activity, and neurotoxicity of the extracts using in vitro bioassays and characterized the chemical extracting efficiencies of the SPE methods through chemical recoveries of 23 model compounds with different polarities and total organic carbon. Using Pareto ranking, we identified HLB+Coconut as the optimal SPE method, which exhibited the highest level of water sample biotoxicity and recovered the most chemicals in water samples. We found that the biotoxicity outcomes of the extracted water samples significantly and positively correlated with the chemical extracting efficiencies of the SPE methods. Moreover, we observed synchronous changing patterns in biotoxicity outcome and chemical extracting efficiencies in response to increasing sample volumes per cartridge (SVPC) during SPE. Our findings underscore that higher chemical extracting efficiency of SPE corresponds to higher biotoxicity outcome of environmental water samples, providing a scientific basis for standardization of SPE methods for adequate assessment of biotoxicities of environmental waters.

Highly Sensitive and Selective Detection of Inorganic Phosphates in the Water Environment by Biosensors Based on Bioluminescence Resonance Energy Transfer.

The accurate detection of phosphate in water is very important to prevent water eutrophication and ensure the health of water quality. However, traditional phosphomolybdenum blue spectrophotometry is not sensitive, is time-consuming, and demands large amounts of chemical reagents. Therefore, highly sensitive, rapid, and environmentally friendly Pi detection methods are urgently needed. Here, we developed a bioluminescence resonance energy transfer (BRET)-based biosensor, which can detect Pi in water quickly, highly sensitively, and highly selectively. The NanoLuc and the Venus fluorescent protein were selected as the bioluminescence donor and energy acceptor, respectively. The best-performing BRET sensor variant, VenusΔC10-PΔC12-ΔN4Nluc, was identified by Pi-specific binding protein (PiBP) screening and systematic truncation. Single-factor experiments optimized the key parameters affecting the detection performance of the sensor. Under the optimal detection conditions, the detection limit of this method was 1.3 µg·L-1, the detection range was 3.3-434 µg·L-1, and it had excellent selectivity, repeatability, and stability. This low-cost and environment-friendly BRET sensor showed a good application prospect in real water quality detection.

Protocol of a Multicenter Cohort Observational Study of Cerebral Venous Thrombosis in China Mainland.

Epidemiological data on cerebral venous thrombosis in China are still lacking at present on the aspects of incidence, recurrence, risk factors, and so on. Herein, we aimed to fill the gap, based on the result of this multicenter prospective cohort study. A total of 26 top tertiary hospitals distributed in China Mainland will take part in this study. For the first time, a dataset of cerebral venous thrombosis cohort (including multiethnic patients of all ages in almost all regions of Mainland China, regardless of gender) will be built. Inclusion criteria were as follows: (1) aged ≥14 years, (2) neuroimaging-confirmed cerebral venous thrombosis, (3) symptom onset was within 30 days prior to enrollment, (4) signed the informed consent form. Demographic data, risk factors, clinical and neuroimaging features, ophthalmologic and aural results, blood tests, cerebrospinal fluid examination, therapeutic strategies, and adverse events were analyzed. Two milliliters of fasting venous blood and 2 mL of cerebrospinal fluid will be collected and stored. Furthermore, patients will be followed up at months 1, 3, 6, and 12 after baseline assessment. Primary outcome will be all-cause mortality. Secondary outcomes: (1) cerebrospinal fluid pressure and Frisen grade; (2) recanalization rate on imaging; (3) rating scales such as GCS, NIHSS, mRS, Mini-Mental State Examination, Montreal Cognitive Assessment, Patient Health Questionnaire 9-item, HIT-6, and Tinnitus Handicap Index. This study will for the first time provide strong evidence on the incidence rate, recurrence rate, and demographic data, as well as special risk factors, clinical outcomes, symptomatic and imaging features of cerebral venous thrombosis in Chinese population. The results of this study will also provide an important reference on prevention, early diagnosis, and customized treatment of cerebral venous thrombosis in Chinese patients.

Tertiary Wastewater Treatment Processes Can Be a Double-Edged Sword for Water Quality Improvement in View of Mitigating Antimicrobial Resistance and Pathogenicity.

Despite the high removal efficiency for chemical pollutants by tertiary wastewater treatment processes (TWTPs), there is no definite conclusion in terms of microbial risk mitigation yet. This study utilized metagenomic approaches to reveal the alterations of antibiotic resistance genes (ARGs), virulence factor genes (VFGs), their co-occurrence, and potential hosts during multiple TWTPs. Results showed that the TWTPs reduced chemical pollutants in wastewater, but the denitrifying biofilter (DB) significantly increased the absolute abundances of selected antibiotic-resistant bacteria and ARGs, and simultaneously elevated the relative abundances of ARGs and VFGs through the enrichment of multidrug resistance and offensive genes, respectively. Moreover, the co-occurrence of ARGs and VFGs (e.g., bacA-tapW, mexF-adeG) was only identified after the DB treatment and all carried by Pseudomonas. Then, the ultraviolet and constructed wetland treatment showed good complementarity for microbial risk reduction through mitigating antibiotic resistance and pathogenicity. Network and binning analyses showed that the shift of key operational taxonomic units affiliating to Pseudomonas and Acinetobacter may contribute to the dynamic changes of ARGs and VFGs during the TWTPs. Overall, this study sheds new light on how the TWTPs affect the antibiotic resistome and VFG profiles and what TWTPs should be selected for microbial risk mitigation.

PBT assessment of chemicals detected in effluent of wastewater treatment plants by suspected screening analysis.

Wastewater treatment plants (WWTPs) are the major sources of contaminants discharged into downstream water bodies. Profiling the contaminants in effluent of WWTPs is crucial to assess the potential eco-risks toward downstream organisms. To this end, this study investigated the contaminants in effluent of 10 WWTPs locating in 10 cities of Yangtze River delta region of China by suspected screening analysis. Further, the persistence, bioaccumulation, toxicity (PBT) and the characteristics sub-structures of PBT-like chemicals were analyzed. Totally, 704 chemicals including 155 chemical products, 31 food additives, 52 natural substances, 112 personal care products, 123 pesticides, 192 pharmaceuticals, 17 hormones and 22 others were found. The results of PBT analysis suggested that 42 chemicals (5.97% among the detected chemicals in WWTPs) were with PBT property. Among them, 31 contaminants were not reported previously. 9 characteristics sub-structures (N-methyleneisobutylamine, 1-naphthaldehyde, 2,3,3-trimethylcyclohexene, cyclohexanol, N-sec-butyl-n-propylamine, (5E)-2,6-dimethylocta-1,5-diene, 2-ethylphenol, pentadecane and 6-methoxyhexane) were found for PBT-like chemicals. The sub-structures of highly linear alkyl partially explained the significantly higher PBT score for personal care products. Present study provides fundamental information on PBT properties of contaminants in effluent of WWTPs, which will benefit to prioritize contaminants with high concerns in effluent of WWTPs.

Evaluation of peripapillary retinal nerve fiber layer thickness in intracranial atherosclerotic stenosis.

PURPOSE: To evaluate the peripapillary retinal nerve fiber layer thickness (pRNFL) in patients with intracranial atherosclerotic stenosis (ICAS). METHODS: A cross-sectional study was performed in a general hospital. The intracranial atherosclerotic stenosis was evaluated by digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA). High-definition optical coherence tomography (HD-OCT) was used to evaluate the peripapillary retinal nerve fiber layer thickness. RESULTS: A total of 102 patients, including 59(57.8%) patients with ICAS and 43(42.2%) patients without ICAS, were finally analysed in the study. The peripapillary retinal nerve fiber layer thickness (pRNFL) was reduced significantly in the average, the superior and the inferior quadrants of the ipsilateral eyes and in the superior quadrant of the contralateral eyes in patients with ICAS compared with patients without ICAS. After multivariate analysis, only the superior pRNFL thickness in the ipsilateral eyes was significantly associated with ICAS (OR,0.968; 95% CI,0.946-0.991; p = 0.006). The area under receiver operator curve was 0.679 (95% CI,0.576-0.782) for it to identify the presence of ICAS. The cut-off value of the superior pRNFL was 109.5 µm, and the sensitivity and specificity were 50.8% and 83.7%, respectively. CONCLUSION: The superior pRNFL in the ipsilateral eye was significantly associated with ICAS in this study. Larger studies are needed to explore the relation between pRNFL and ICAS further.

Intra-arterial Thrombolysis for Acute Retinal Ischemia: A Retrospective, Observational, Cohort Study.

BACKGROUND: To determine whether intra-arterial thrombolysis (IAT) within 16 hours after the onset of symptoms is feasible and associated with better visual outcomes in patients with acute retinal ischemia (ARI). METHODS: The retrospective cohort study was performed from January 2014 to December 2021 in the Xuanwu Hospital of Capital Medical University. Patients with ARI who initially presented visual acuity of 20/100 or worse were screened in the study. Visual end points were evaluated at one week and at final visit after treatment. Serious adverse events were recorded during operation and within 1 week after IAT treatment. RESULTS: The amount of clinically significant visual improvement (≥0.3 logarithm of the minimum angle of resolution) in the IAT group was significantly higher than that in the conservative treatment group at one week after the treatment (47.8% vs 16.7%; P = 0.014) and at final visit (52.2% vs 20%; P = 0.014). After controlling confounding factors, ARI treatment was the only factor significantly associated with the amount of clinically significant visual improvement (OR, 4.364; 95 CI, 1.298-14.667; P = 0.017). A patient (4.3%) experienced retinal hemorrhage without symptom within 1 week after IAT treatment. No patients experienced new symptomatic cerebral infarction, intracranial hemorrhage, TIA, artery dissection, vascular perforation, and distal embolization during operation and within 1 week after IAT treatment. CONCLUSIONS: IAT may be associated with better visual improvement within 16 hours after the onset of symptoms. Besides, IAT is feasible and associated with a low risk of periprocedural complications for ARI. This study will aid in feasibility testing and sample size calculations in advance of future, fully-powered efficacy studies for ARI.

Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-ß1 and CST3.

Microcystin-LR (MC-LR) is a toxic secondary metabolite produced by cyanobacteria that has been demonstrated to promote colorectal cancer (CRC). However, the mechanism by which MC-LR enhances CRC in the tumor microenvironment (TME) is poorly understood. To elucidate its role in TME, a co-culture system was established using CRC cells and M2 macrophages in a Transwell chamber. The study found that MC-LR promotes CRC cell migration by upregulating TGF-ß1 expression and secretion in M2 macrophages and downregulating CST3 in CRC cells. Neutralizing TGF-ß1 increased CST3 expression in CRC cells, while overexpressing CST3 in CRC cells suppressed TGF-ß1 expression in M2 macrophages, both of which weakened MC-LR-induced cellular motility in the co-culture system. In vivo, the mice in the MC-LR/AOM/DSS group had more tumor nodules, deeper tumor invasion, and higher M2 macrophage infiltration compared to the AOM/DSS group, and the expression of TGF-ß1 and CST3 in tumors was consistent with the cellular level. Overall, this study provides insights into the regulatory mechanism of MC-LR on TME, revealing that MC-LR upregulates the expression and secretion of TGF-ß1 in M2 macrophages, which in turn inhibits the expression of CST3 in CRC cells to promote migration.

Risk and risk factor of ischemic stroke after acute retinal arterial ischemia.

PURPOSES: We aimed to confirm the risk and risk factor for ischemic stroke after acute retinal arterial ischemia (ARAI). METHODS: A retrospective cohort study of patients with a diagnosis of acute retinal arterial ischemia (ARAI) and completing 2-year follow-up was conducted from January 2015 to December 2021 at a general hospital. RESULTS: A total of 69 patients including 43(62.3%) patients of central retinal artery occlusion (CRAO), 11(15.9%) patients of branch retinal artery occlusion (BRAO) and 15(21.7%) patients of ophthalmic artery occlusion (OAO) were included in the study. Patients age was 58.2 ± 13.0(years), male patients accounting for 51 (73.9%) and 22 (31.9%) patients having at least 70% ipsilateral carotid artery stenosis (ICAS). During the 2-years follow-up period, 11(15.9%) patients of ARAI experienced ischemic stroke. Among them, 3(20%) patients of OAO, 6(14%) patients of CRAO and 2(18.2%) patients of BRAO had ischemic stroke. The cumulative probabilities of ischemic stroke were 13.0% at 12.9 months and 15.9% at 24 months after ARAI. In addition, patients with at least 70% ICAS were more likely than patients without it to have ischemic stroke (p = 0.002). After Cox regression analysis, ICAS (≥ 70%) or occlusion was significantly associated with a high risk of ischemic stroke after ARAI during the 2-years follow-up time (HR,6.769,95%CI [1.792-25.578], p = 0.005). CONCLUSION: Patients have a high risk of ischemic stroke, particularly those with a diagnosis of ICAS (≥ 70%) or occlusion after the onset of ARAI. Clinical management of ARAI should focus on vascular risk factors control and secondary prevention for stroke.

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study.

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

The difference of the retinal structural and microvascular characteristics in patients with MOGAD-ON and AQP4-ON.

BACKGROUND: Antibodies against myelin-oligodendrocyte-glycoprotein (MOG-Abs) associated disease (MOGAD) has been recognized as a disease entity. Optic neuritis (ON) is the most common symptom in MOGAD. To demonstrate the differences in retinal microvascular characteristics between patients with MOGAD-ON and aquaporin-4 antibody (AQP4-Ab) positive ON. METHODS: In a prospective study, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were used to measure retinal and microvascular parameters. RESULTS: Twenty-six MOGAD-ON eyes, 40 AQP4-ON eyes, and 60 control eyes were included in the study. The thickness of RNFL and GCC in MOGAD-ON eyes was significantly lower than that of HC (p < 0.001, respectively), but comparable to AQP4-ON eyes. The vessel density in retina capillary plexus (RCP) was reduced significantly in MOGAD-ON than that in AQP4-ON (p < 0.05, respectively). The visual accuracy was positively correlated with vessel density of superficial RCP in MOG-ON (p = 0.001) and positively correlated with the thickness of the inner retina layer in AQP4-ON (p < 0.001). CONCLUSION: The retinal neuro-axonal damages between MOGAD-ON and AQP4-ON were comparable. Unlike AQP4-ON eyes, microvascular densities were significantly reduced in MOGAD-ON and were positively correlated with the deterioration of visual acuity in MOGAD-ON. TRIAL REGISTRATION: Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE, NCT: 04106830).

Bioaccumulation and biomagnification effects of nano-TiO2 in the aquatic food chain.

The increasing production of nano-TiO2 has attracted extensive concerns about the ecological consequence and health risk of these compounds in natural ecosystem. However, little is known about its toxicity on zooplankton, especially its possibility to access to the food chain via dietary exposure. To address this concern, the toxic and cumulative effects of nano-TiO2 on an aquatic food chain were explored through two trophic levels independently or jointly including producer and consumer. The results revealed that exposure to suspensions of nanomaterials had negative effects on both producers and consumers. Specifically, nanoparticles reduced the density of algal cells in a concentration-dependent way, and hatching life expectancy, average lifespan, net reproductive rate, and population intrinsic growth rate of rotifers decreased significantly with the concentration of nanomaterials increased (P < 0.05). Notably, nanoparticles accumulated in algal cells and were transferred to consumers through dietary exposure. Biomagnification of nano-TiO2 was observed in this simplified food chain, as many of the biomagnification factor (BMF) values in this study were >1. Exposure concentration, exposure time and their interactions play a strong part in the accumulation of nanoparticles in algae and rotifers. Overall, the present findings confirmed that nano-TiO2 was deleterious to plankton, posing a significant environmental threat to aquatic ecosystems. Graphical abstract.

Predictive values of systemic inflammatory responses index in early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Acute ischemic stroke (AIS) is the main cause of worldwide death and disability. Early neurological deterioration (END) can further increase the probability of death and disability in patients with ischemic stroke. Therefore, it is essential to find biomarkers to predict END early. Inflammatory response plays a crucial role in determining the course, outcome, and prognosis of END. Earlier studies focused on the relationship between routine hematological inflammatory markers and END, which limited the results. At present, relatively new and comprehensive markers of inflammatory response are relatively scarce. In this study, we investigate the predictive value of inflammatory markers in acute ischemic stroke cases for END which include systemic inflammatory response index (SIRI), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), and then to establish a nomogram model. METHODS: A total of 375 patients with AIS were analyzed who were admitted to the Second Affiliated Hospital of Harbin Medical University from September 2019 to June 2021. The associations between END and inflammatory markers were studied by employing the analysis of univariate. Following that, through regression models of the least absolute shrinkage and selection operator, the END risk model's feature selection was optimized. The development of the model of prediction was carried out by applying the multivariable logistic regression analysis. The calibration, discrimination, and clinical efficacy of the prediction model were studied via calibration plot, C-index, and decision curve analysis (DCA). The bootstrapping validation method was used for the evaluation of internal validation. RESULTS: We constructed a nomogram consisting of CRP, monocytes, NIHSS and SIRI. This model had desirable calibration and discrimination, with a C-index of 0.757 (95% confidence interval: 0.702-0.805). Interval validation could still achieve the higher C-index value of 0.747. When the risk threshold for END was greater than 13% but less than 84%, DCA proved to be clinically useful. CONCLUSIONS: Our research shows that SIRI can be used as a new predictor of END, as well as a monitor of treatment response. Compared with the traditional single inflammatory indicator, the integration of SIRI nomogram can predict the occurrence of END more objectively and reliably.

MiR-26a regulated adipogenic differentiation of ADSCs induced by insulin through CDK5/FOXC2 pathway.

OBJECTIVE: Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes, since insulin can induce adipogenic differentiation of human adipose-derived stem cells (ADSCs). MiR-26a was reported to be highly expressed in ADSCs under induction and Forkhead box C2 (FOXC2), as a key substrate of cyclin-dependent kinase 5 (CDK5) could inhibit white adipocyte differentiation, which was mediated by miR-26a. However, the relationship between miR-26a and CDK5/FOXC2 during ADSCs differentiation remains unknown. We want to verify the regulated mechanism of miR-26a/CDK5/FOXC2 axis participating in the adipogenic differentiation of ADSCS. METHODS: ADSCs were isolated and verified by flow cytometry. Oil Red O staining was performed to assess the capacity for adipogenic differentiation of ADSCs. The proliferation ability of ADSCs was verified by MTT assay. The expression of miR-26a, peroxisome proliferator-activated receptors γ (PPARγ), CDK5, and FOXC2 were tested by qRT-PCR and Western blot, and the relationship between miR-26a and CDK5 was verified by dual-luciferase reporter gene assay. RESULTS: MiR-26a and PPARγ were upregulated and CDK5 and FOXC2 were downregulated during adipogenic differentiation of ADSCs. Knockdown of miR-26a or overexpression of CDK5 could inhibit adipogenic differentiation of ADSCs induced by insulin. MiR-26a could directly target CDK5 and the effect of miR-26a inhibitor on adipogenic differentiation of ADSCs could be blocked by si-CDK5. CONCLUSION: We demonstrated that miR-26a regulated insulin-induced adipogenic differentiation of ADSCs by regulating CDK5/FOXC2 pathway, which could provide the key to a comprehensive mechanistic understanding of obesity and type 2 diabetes.

Iron Minerals Mediated Interfacial Hydrolysis of Chloramphenicol Antibiotic under Limited Moisture Conditions.

Iron minerals are important soil components; however, little information is available for the transformation of antibiotics on iron mineral surfaces, especially under limited moisture conditions. In this study, we investigated the catalytic performance of four iron minerals (maghemite, hematite, goethite, and siderite) for the hydrolysis of chloramphenicol (CAP) antibiotic at different moisture conditions. All the iron oxides could efficiently catalyze CAP hydrolysis with the half-lives <6 days when the surface water content was limited, which was controlled by the atmospheric relative humidity of 33-76%. Different minerals exhibited distinctive catalytic processes, depending on the surface properties. H-bonding or Lewis acid catalysis was proposed for surface hydrolytic reaction on iron oxides, which however was almost completely inhibited when the surface water content was >10 wt % due to the competition of water molecules for surface reactive sites. For siderite, the CAP hydrolysis was resistant to excessive surface water. A bidentate H-bonding interaction mechanism would account for CAP hydrolysis on siderite. The results of this study highlight the importance of surface moisture on the catalytic performance of iron minerals. The current study also reveals a potential degradation pathway for antibiotics in natural soil, which has been neglected before.

The role of genetics in Parkinson's disease: a large cohort study in Chinese mainland population.

This study aimed to determine the mutational spectrum of familial Parkinson's disease and sporadic early-onset Parkinson's disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson's disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson's disease, 242 probands from families with autosomal-dominant Parkinson's disease, and 1242 sEOPD patients (age at onset ≤ 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson's disease-associated genes occurred more frequently in the autosomal-recessive Parkinson's disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson's disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/p.P144Qfs*2) were identified in our cohort. Furthermore, the age at onset of the 132 probands with genetic diagnoses (median, 31.5 years) was about 14.5 years earlier than that of patients without molecular diagnoses (i.e. non-carriers, median 46.0 years). Specifically, the age at onset of Parkinson's disease patients with pathogenic/likely pathogenic variants in ATP13A2, PLA2G6, PRKN, or PINK1 was significantly lower than that of non-carriers, while the age at onset of carriers with other gene pathogenic/likely pathogenic variants was similar to that of non-carriers. The clinical spectrum of Parkinson's disease-associated gene carriers in this mainland Chinese population was similar to that of other populations. We also detected 61 probands with GBA possibly pathogenic variants (3.64%) and 59 probands with GBA p.L444P (3.52%). These results shed insight into the genetic spectrum and clinical manifestations of Parkinson's disease in mainland China and expand the existing repertoire of pathogenic or likely pathogenic variants involved in known Parkinson's disease-associated genes. Our data highlight the importance of genetic testing in Parkinson's disease patients with age at onset < 40 years, especially in those from families with a recessive inheritance pattern, who may benefit from early diagnosis and treatment.

Integrated metagenomic and metatranscriptomic analyses of ultraviolet disinfection effects on antibiotic resistance genes and bacterial communities during wastewater treatment.

Ultraviolet (UV) disinfection is now widely implemented in wastewater treatment plants (WWTPs) worldwide, but its effect on antibiotic resistome of the surviving bacteria remains unclear. In this study, we employed high-throughput sequencing-based metagenomic and metatranscriptomic approaches to comprehensively elucidate the effects of UV disinfection on the shifts of bacterial community and antibiotic resistance genes (ARGs) on both DNA and mRNA levels in one WWTP. Metagenomic analyses revealed an insignificant change in the bacterial community after UV disinfection, while metatranscriptomic analyses showed that UV disinfection significantly changed the abundance of 13.79% of phyla and 10.32% of genera. In total, 38 ARG-like open reading frames (ORFs) and 327 ARG-like transcripts were identified in the DNA and RNA samples, respectively. The relative abundances of the total ARGs, each ARG type, and each ARG subtype also varied after UV disinfection. Additionally, UV disinfection significantly reduced the expression of total ARGs from 49.40 transcripts per kilobase of exon model per million mapped reads (TPM) to 47.62 TPM, and significantly changed the expression of 10.75% of ARG subtypes in wastewater (p < 0.05). Notably, the significant increase in the expression and obvious increase in the relative abundance of macrolide-lincosamide-streptogramin B (MLSB) resistance genes revealed that UV disinfection increases the potential health risk of MLSB resistance genes in wastewater. Moreover, potential host analyses of ARGs revealed the different preferences of antibiotic resistant bacteria (ARB) to ARGs. This study may shed new light on the underlying mechanism of the UV disinfection effect on antibiotic resistance.