Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach.

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.

Optimal time point for neutrophil-to-lymphocyte ratio to predict stroke-associated pneumonia.

PURPOSE: This study aimed at the population receiving thrombolytic therapy and to explore the optimal time point for neutrophil-to-lymphocyte ratio (NLR) in predicting stroke-associated pneumonia (SAP). METHODS: We assessed patients undergoing intravenous thrombolysis (IVT) for acute ischemic stroke. Blood parameters were sampled before thrombolysis (within 30 min after admission) and within 24-36 h after thrombolysis, respectively. The primary outcome measure was the occurrence of SAP. Multivariate logistic regression analysis was performed to analyze the association between admission blood parameters and the event of SAP. We also used receiver operating characteristic (ROC) curve analysis to assess the discriminative ability of blood parameters measured at different times in predicting SAP. RESULTS: Among the 388 patients, SAP occurred in 60 (15%) patients. Multivariate logistic regression analysis showed that NLR was significantly associated with SAP (NLR before IVT: aOR = 1.288; 95%CI = 1.123-1.476; p < 0.001; NLR after IVT: (aOR = 1.127, 95%CI = 1.017-1.249; p = 0.023). The ROC curve showed that the predictive ability of NLR after IVT was better than NLR before IVT, not only in predicting the occurrence of SAP but also in predicting short-term and long-term functional outcomes, hemorrhagic transformation, and 1-year mortality. CONCLUSION: Increased NLR measured within 24-36 h after IVT has a significant predictive effect on the occurrence of SAP and can be used to predict short-term and long-term poor functional outcomes, hemorrhagic transformation, and 1-year mortality.

Regulation of Heat Stress in Physcomitrium (Physcomitrella) patens Provides Novel Insight into the Functions of Plant RNase H1s.

RNase H1s are associated with growth and development in both plants and animals, while the roles of RNase H1s in bryophytes have been rarely reported. Our previous data found that PpRNH1A, a member of the RNase H1 family, could regulate the development of Physcomitrium (Physcomitrella) patens by regulating the auxin. In this study, we further investigated the biological functions of PpRNH1A and found PpRNH1A may participate in response to heat stress by affecting the numbers and the mobilization of lipid droplets and regulating the expression of heat-related genes. The expression level of PpRNH1A was induced by heat stress (HS), and we found that the PpRNH1A overexpression plants (A-OE) were more sensitive to HS. At the same time, A-OE plants have a higher number of lipid droplets but with less mobility in cells. Consistent with the HS sensitivity phenotype in A-OE plants, transcriptomic analysis results indicated that PpRNH1A is involved in the regulation of expression of heat-related genes such as DNAJ and DNAJC. Taken together, these results provide novel insight into the functions of RNase H1s.

Microbial quantities and enzyme activity in soil irrigated with sewage for different lengths of time.

Sewage is widely used on agricultural soils in peri-urban areas of developing countries to meet shortages of water resource. Although sewage is a good source of plant nutrients, it also increases the heavy metals loads to soils. Microbial responses to these contaminants may serve as early warning indicators of adverse effects of sewage irrigation on soil quality. The purpose of this study was to assess the effect of time of sewage irrigation on soil microbial indicators. Soil samples were collected from seven soil sites (S1-S7) irrigated with 0 years, 16 years, 23 years, 25 years, 27 years, 32 years and 52 years, respectively in Shijiazhuang of China and analyzed. For each soil sample, we determined the quantities of bacteria, fungi and actinomycete, and enzyme activities of urease, sucrase, phosphatase, dehydrogenase and catalase. Our results showed that the soils of S2-S7 irrigated with sewage effluents for different times (ranged between 16 and 52 years) exhibited higher densities of bacteria, actinomycete, urease, sucrase and phosphatase but lower densities of fungi when compared with S1 irrigated with sewage effluents for 0 years. The soil S7 irrigated with sewage effluents for longest times (52 years) contained lowest activities of catalase when compared with the soils of S1-S6. The densities of bacteria (R = 0.877, p < 0.01), actinomycete (R = 0.875, p < 0.01), sucrase (R = 0.858, p < 0.01) and phosphatase (R = 0.804, p < 0.05) were significantly correlated in a positive manner with time of sewage irrigation. Soil fungi quantities and urease, dehydrogenase and catalase activities did not change significantly with irrigation time. This study confirms that sewage irrigation had negative effects on microbial properties including fungi, catalase and dehydrogenase in the long term, so there is a need for continuous monitoring for sustainable soil health.

Renal function affects the safety and efficacy of tirofiban in acute ischemic stroke thrombectomy patients.

BACKGROUND: Acute ischemic stroke poses a significant health threat, and thrombectomy has become a routine treatment. Tirofiban has emerged as a promising adjunct therapy to minimize reocclusion after thrombectomy. We aimed to investigate whether renal function influences the safety and efficacy of tirofiban in patients undergoing endovascular therapy. METHODS: Patients' clinical data collected from the stroke unit were analyzed. The modified Rankin scale score and symptomatic intracranial hemorrhage (sICH) were used as outcome measures. RESULTS: A total of 409 patients (mean age: 66.5 years, 292 males [71.4%]) were included. Tirofiban significantly improved 3-month functional outcomes (adjusted odds ratio [aOR] = 2.408, 95% confidence interval [CI] 1.120-5.175), reduced 3-month mortality (aOR = 0.364, 95% CI 0.155-0.856), and decreased the incidence of sICH (aOR = 0.339, 95% CI 0.149-0.767) in patients with estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m². However, no significant improvement in prognosis was observed with tirofiban in patients with eGFR < 90 mL/min/1.73 m². Interaction analysis suggested a potential influence of renal function on tirofiban efficacy. CONCLUSION: Renal function may impact the efficacy of tirofiban. Administration of tirofiban in direct thrombectomy patients with normal renal function is safe and improves prognosis. However, the prognostic benefits of tirofiban are limited in patients with impaired renal function.

The Influence of Patent Foramen Ovale on the Clinical Features of Migraine without Aura: A Cross-Sectional Study.

Objective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA). Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann-Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test. Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores. Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.

Driving factors influencing spatiotemporal variation of natural organic chlorine in Shennongjia forest soil.

Studying the geochemical behavior of chlorine is the basis of understanding the chlorine cycle in nature. To explore the spatiotemporal distribution of natural organic chlorine (Clorg), L layer (litter fall), F-H layer (humification zone), topsoil layer (0-20 cm), and deep soil layer (20-40 cm) samples were collected from 18 sampling sites at different altitudes (851-2918 m) in Shennongjia Forest in May, August, and December. Clorg content was analyzed, and the Clorg stocks were calculated. The major factors affecting the distribution of Clorg were explored. The results revealed that the sum of Clorg content in four layers varied from 7.958 to 184.686 mg/kg, and the highest value was observed in August. Clorg accounted for 46%-77% of total chlorine, with the highest mean ratio in soil layer (0-20 cm). Clorg content exhibited the following trend: F-H layer > L layer > topsoil layer (0-20 cm) > deep soil layer (20-40 cm). The seasonal patterns of Clorg in soil layers were different from that in L and F-H layers, which were mainly controlled by the content and humification degree of organic matter. Clorg storage was much higher in soil layers (61-246 kg/ha) than those in F-H layer (1.1-7.1 kg/ha) and in L layer (0.1-0.8 kg/ha) because of the large thickness of the soil layers. Overall, the Clorg content exhibited an increasing trend with altitude, except at an altitude of approximately 1800 m. Clorg content in L and F-H layers varied more obviously with altitude than that in soil layers. When inorganic chlorine (Clin) was not a limiting factor for the chlorination process, Clorg content in L and F-H layers was significantly affected by climate and organic matter controlled by altitude, while Clorg content in soil layers was also mediated by metal ions and pH, and soil particle size. This study could provide a scientific basis for assessing the chlorine cycle in nature.

Predictors of functional dependence at one year in acute ischemic stroke with large vessel occlusion.

BACKGROUND: In China, the current status of clinical treatment of eLVO and the factors affecting its long-term prognosis are unclear. OBJECTIVE: This study aims to explore the predictive factors of functional outcomes at one year in patients of acute ischemic stroke with emergent large vessel occlusion (eLVO). METHODS: We retrospectively collected 536 patients who underwent treatments for eLVO. Primary outcomes included one-year functional outcomes and delayed functional independence (DFI). The logistic regression was performed to predict the primary outcome. RESULTS: 431 (85%) survivors participated in the one-year follow-up. In the multivariate logistic analysis adjusted for baseline characteristics, the following factors were found to be significant predictors of functional dependence at one year: old age (aOR = 1.042, 95% CI=1.01-1.076, p = 0.011), low Alberta stroke program early CT score (ASPECTS) (aOR = 0.791, 95% CI=0.671-0.933, p = 0.005), unsuccessful reperfusion (aOR = 0.168, 95% CI=0.048-0.586, p = 0.005), poor medication compliance (aOR = 0.022, 95% CI=0.007-0.072, p < 0.001), and complicated with stroke-associated pneumonia (SAP) (aOR = 2.269, 95% CI=1.103-4.670, p = 0.026). We also found that men (aOR = 3.947, 95% CI=1.15-13.549, p = 0.029) had better medication adherence (aOR = 14.077, 95% CI=1.736-114.157, p = 0.013), and going to rehabilitation centers (aOR = 5.197, 95% CI=1.474-18.327, p = 0.010) were independent predictors of DFI. CONCLUSION: The significant predictors of functional dependence at one year were: old age, low ASPECTS, unsuccessful reperfusion, poor medication adherence, and combination with SAP. Men, good medication adherence, and going to rehabilitation centers contributed to getting delayed functional independence.

Characteristics of dissolved organic matter in surface water and sediment and its ecological indication in a typical mining-affected river-Le'an River, China.

Dissolved organic matter (DOM) plays an important role in the cycling and toxicity of heavy metals in aquatic systems. However, most studies have focused only on DOM in either water or sediments. This study aimed to analyze the source, composition, and structural characteristics of DOM in both surface water and bottom sediments of the Le'an River and its major tributaries. In addition, the potential ecological risks of three typical heavy metals (Cu, Pb, and Zn) were quantitatively evaluated based on the characteristics of DOM and in situ data. The results showed that sediment DOM is more aromatic and hydrophobic than surface water DOM. Although humic-like components dominated the DOM pool in both surface water and sediments, their sources were different. Surface water DOM is mainly autochthonous, while sediment DOM is controlled by both autochthonous and allochthonous sources. Risk prediction results based on DOM characteristics show that surface water has a higher potential risk of heavy metal release than sediments. Comprehensively considering the ecological risk of water and sediments, high-risk areas were found to be mainly distributed in the upper and middle reaches of the Le'an River. This distribution is attributable to the developed mining and smelting industries in these areas and consistent with the risk assessment results of measured concentrations of heavy metals. This study established a new technique for predicting the ecological risk of aquatic systems based on the characteristics of DOM in surface water and sediments.

High fibrinogen to albumin ratio is associated with hematoma enlargement in spontaneous intracerebral hemorrhage.

BACKGROUND: We investigate whether fibrinogen to albumin ratio could predict hematoma enlargement in patients suffered with spontaneous intracerebral hemorrhage. MATERIALS AND METHODS: A total of 149 patients met the entry criteria and received 1-month follow-up after discharge were divided into tertiles based on fibrinogen to albumin ratio levels (Tertile 1 [<8.06], Tertile 2 [8.06-10.33], Tertile 3 [>10.33]). Univariate analysis and binary logistic regression analysis was performed to explore the relationship between fibrinogen to albumin ratio and hematoma enlargement occurrence. RESULTS: There was a significant difference in fibrinogen to albumin ratio between hematoma enlargement group and non-hematoma enlargement group (10.11 (8.37-11.73) vs 8.81 (7.61-10.39), p = .017). In binary logistic regression analysis, the highest tertile (>10.33) was independently related to hematoma enlargement (OR = 3.152, 95% CI = 1.326-7.493, p = .009). CONCLUSION: Fibrinogen to albumin ratio on admission might be an independent predictor of hematoma enlargement after intracerebral hemorrhage.

Current trends and insights on EMS mutagenesis application to studies on plant abiotic stress tolerance and development.

Ethyl methanesulfonate (EMS)-induced mutagenesis is a powerful tool to generate genetic resource for identifying untapped genes and characterizing the function of genes to understand the molecular basis of important agronomic traits. This review focuses on application of contemporary EMS mutagenesis in the field of plant development and abiotic stress tolerance research, with particular focuses on reviewing the mutation types, mutagenesis site, mutagen concentration, mutagenesis duration, the identification and characterization of mutations responsible for altered stress tolerance responses. The application of EMS mutation breeding combined with genetic engineering in the future plant breeding and fundamental research was also discussed. The collective information in this review will provide good insight on how EMS mutagenesis is efficiently applied to improve abiotic stress tolerance of crops with the utilization of Next-generation sequencing (NGS) for mutation identification.

Improving PM2.5 predictions during COVID-19 lockdown by assimilating multi-source observations and adjusting emissions.

The Coronavirus Disease 2019 (COVID-19) outbreak caused a suspension of almost all non-essential human activities, leading to a significant reduction of anthropogenic emissions. However, the emission inventory of the chemistry transport model cannot be updated in time, resulting in large uncertainty in PM2.5 predictions. This study adopted a three-dimensional variational approach to assimilate multi-source PM2.5 data from satellite and ground observations and jointly adjusted emissions to improve PM2.5 predictions of the WRF-Chem model. Experiments were conducted to verify the method over Hubei Province, China, during the COVID-19 epidemic from Jan 21st to Mar 20th, 2020. The results showed that PM2.5 predictions were improved at almost all the validation sites, and the benefit of data assimilation (DA) can last for 48 h. However, the benefits of DA diminished quickly with the increase of the forecast time. By adjusting emissions, the PM2.5 predictions showed a much slower error accumulation along forecast time. At 48Z, the RMSE still has an 8.85 µg/m3 (19.49%) improvement, suggesting the effectiveness of emissions adjustment based on the improved initial conditions via DA.

Differential Influence of the COVID-19 Pandemic on Mechanical Thrombectomy and Bridging Therapy for Acute Ischemic Stroke.

Background: The coronavirus disease 2019 (COVID-19) pandemic is having a dramatic impact on acute stroke care. Its effects may accompany stroke care for a long time. We compared the treatment, short-term and long-term functional outcomes of patients with AIS from 2019 to 2020. Our objective was to evaluate the effect of COVID-19 epidemic on mechanical thrombectomy (MT) in patients in our hospital. Methods: We collected information on subjects treated with MT in 2019-2020, including age, sex, time from the onset to arterial sheath insertion, time from the onset to recanalization, the rate of lung infection and hemorrhagic transformation, modified Rankin scale (mRS), NHISS, and ASPECTS. Results: The number of patients with MT decreased significantly by 26.6% in 2020 (p = 0.025). The pretreatment ASPECTS score for 2020 was significantly higher than 2019 (p = 0.004). Besides, the patients were more likely to develop lung infection (65 vs. 54.1%, p = 0.042) and had a higher risk of hemorrhagic transformation (47.4% vs. 30.4%, p = 0.005) in 2019. The discharged mRS reflected the worse short-term functional prognosis of patients with MT in 2019 (66 vs. 44.9%, p = 0.046). In the subgroup analysis of bridging thrombolysis (BT), more patients with BT are expected to have a poor short-term functional prognosis in 2020, according to the discharged mRS (62.5 vs. 37.5%, p = 0.024). However, there was no difference in mRS at 180 days between the two groups (p = 0.094). Conclusion: For patients with MT, both short- and long-term functional outcomes were not significantly affected due to the mild condition of patients admitted to hospital in 2020. For patients with BT, the COVID-19 pandemic has prolonged the green channel time of stroke, leading to a poor short-term functional prognosis of patients with stroke in the pandemic period. There was no difference in the effectiveness of direct MT and BT during the COVID-19 pandemic.

Decrease in intravenous thrombolysis and poor short-term functional prognosis for acute ischemic stroke during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: Since the outbreak of the coronavirus pandemic in 2019 (COVID-19), healthcare systems around the world have been hit to varying degrees. As a neurologist team, for patients with acute ischemic stroke (AIS), we compared the situations of intravenous thrombolysis (IVT) treatment from 2019 to 2020 to investigate the influence of COVID-19 pandemic on the attendance and prognosis of the IVT patients. METHODS: We collected the messages of objects who had received IVT (Bridging surgery was ruled out) during 2019-2020. We analyzed differences in age, gender, time from onset to start IVT, door to needle time (DNT), pretreatment NIHSS score, postoperative NIHSS score, and so on. Statistical tests were also performed to respectively compare the discharged modified Rankin score (mRS) and discharged NIHSS score between two years. RESULTS: Since the onset of COVID-19 restrictions in Wenzhou, we observed a significant reduction of 24.7% (p = 0.023) from 267(2019) to 201(2020) of received IVT on hospital admission. We compared the DNT between two years and it reflected that the DNT (min) in 2020 was obviously longer than in 2019 (51.60 ± 23.80 vs 46.80 ± 21.90, p = 0.026). We also compared the discharged mRS, which reflected much more IVT patients in 2020 during the COVID-19 pandemic had a poor short-term functional prognosis (38.2% vs 29.2%, p = 0.043). CONCLUSIONS: The COVID-19 pandemic caused the decrease of admissions and prolonged the time of the green channel for stroke, which led to the worse short-term prognosis of AIS patients during the pandemic. It's necessary to ensure an effective green channel and provide adequate medical resources during the pandemic period to reduce the damage caused by COVID-19.

Health risks associated with multiple metal(loid)s in groundwater: A case study at Hetao Plain, northern China.

To compare the health risks of multiple metal(loid)s in groundwater, and discuss the feasibility of drinking water standards, 66 groundwater samples were collected from the Hetao Plain in October 2017. Eighteen metal(loid) species (boron (B), manganese (Mn), iron (Fe), strontium (Sr), barium (Ba), lithium (Li), scandium (Sc), titanium (Ti), vanadium (V), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), rubidium (Rb), molybdenum (Mo), uranium (U)) were analyzed, and the related non-carcinogenic risks were assessed. The results showed that 83.3% of the groundwater samples had As and Fe contents above the maximum allowed contaminant levels (MCLs) in drinking water standards, followed by Mn (70.2%), B (65.2%), Se (60.6%), U (18.2%), Ni (18.2%) and Mo (1.50%). Compared with the dermal exposure pathway, oral ingestion made a risk contribution of more than 99% for all target metal(loid)s. Site-specific hazard quotient (HQ) values ranged from 2.30E+00 to 1.75E+02, indicating that multiple metal(loid)s in the drinking groundwater cause a serious non-carcinogenic risk to the local people. The risk contributions (mean value) were ranked as As (55.2%) > U (25.5%) > Li (10.8%) > other total metal(loid)s (8.60%), and the contributions of U and Li could reach 91.7% (site 20) and 69.8% (site 56), respectively. The calculation of specific health risks further indicated that the MCLs of metal(loid)s do not match the corresponding health risk well. Some metal(loid)s such as Li that showed high exposure risks in this study, still have no MCL values until now. Therefore, current drinking water standards need to be updated.

Comparison of the health risks associated with different exposure pathways of multiple volatile chlorinated hydrocarbons in contaminated drinking groundwater.

A total of 152 groundwater samples were collected around a contaminated site to evaluate the carcinogenic and noncarcinogenic risks of exposure to twelve volatile chlorinated hydrocarbons (VCHs) by oral ingestion, dermal contact and inhalation absorption during showering. Although toxicity data of some VCHs are fragmentary, the results showed that the carcinogenic and noncarcinogenic risks of exposure to VCHs in contaminated drinking groundwater for local residents needs immediate attention. The main risk contributors for the carcinogenic and noncarcinogenic risks are carbon tetrachloride and 1,1,2-trichloroethane through inhalation exposure pathway, respectively. The health risk contribution rates associated with three exposure pathways for a specific VCH were intrinsic to the compound, and the dermal contact corresponded to a negligible contribution for almost every VCH species. Although most of the evaluated VCHs had a higher risk contribution by inhalation than by oral ingestion pathway, the integrated multi-VCH health risk contributions of the three exposure pathways were mainly dependent on the VCH compositions. Drinking boiled water not only decreased the exposure risk but also affected the risk contribution rates of three exposure pathways, which indicates that it is feasible to reduce the risk of VCH exposure during daily activities based on the risk contribution of the exposure pathways. In addition to the VCHs included in the drinking water standards, species such as 1,1,2,2-tetrachloroethane and hexachloroethane also showed a remarkable exposure health risk according to the standardized health risk calculation, which implied that improved drinking water standards are urgently required.

Significance of stable carbon and bromine isotopes in the source identification of PBDEs.

Typical brominated organic pollutants poly brominated diphenyl ethers (PBDEs) might be characterized by their stable carbon and bromine isotopic compositions. Currently, there are no published reports concerning the two-dimensional isotopic (δ13C and δ81Br) values of PBDEs. To assess the significance of carbon and bromine isotopes in the source identification of PBDEs, EA-IRMS and off-line-IRMS methods were employed to measure the δ13C and δ81Br values of the typical PBDE congeners, 2,2',4,4'-tetrabromodiphenyl ethers (BDE-47) and decabromodiphenyl ether (BDE-209) from different suppliers. The results show that individual PBDE congeners (three BDE-47 samples and three BDE-209 samples) have unique δ13C and δ81Br values, possibly due to differences in the precursors and manufacturing processes, indicating that the isotope composition is a promising probe to determine the source of PBDEs in the environment. While it is worth noting that some challenges might exist during practical application of this method, such as the similar isotopic compositions of PBDEs from different source. Thus, source identification associated with isotopic signatures should be used cautiously. This study provides a basis for further research into the source identification of PBDEs in the environment by examining their isotopic characteristics.