Integrating network pharmacology and transcriptomic omics reveals that akebia saponin D attenuates neutrophil extracellular traps-induced neuroinflammation via NTSR1/PKAc/PAD4 pathway after intracerebral hemorrhage.

Neutrophils and their production of neutrophil extracellular traps (NETs) significantly contribute to neuroinflammation and brain damage after intracerebral hemorrhage (ICH). Although Akebia saponin D (ASD) demonstrates strong anti-inflammatory activities and blood-brain barrier permeability, its role in regulating NETs formation and neuroinflammation following ICH is uncharted. Our research focused on unraveling the influence of ASD on neuroinflammation mediated by NETs and the mechanisms involved. We found that increased levels of peripheral blood neutrophils post-ICH are correlated with worse prognostic outcomes. Through network pharmacology, we identified ASD as a promising therapeutic target for ICH. ASD administration significantly improved neurobehavioral performance and decreased NETs production in neutrophils. Furthermore, ASD was shown to upregulate the membrane protein NTSR1 and activate the cAMP signaling pathway, confirmed through transcriptome sequencing, western blot, and immunofluorescence. Interestingly, the NTSR1 inhibitor SR48692 significantly nullified ASD's anti-NETs effects and dampened cAMP pathway activation. Mechanistically, suppression of PKAc via H89 negated ASD's anti-NETs effects but did not affect NTSR1. Our study suggests that ASD may reduce NETs formation and neuroinflammation, potentially involving the NTSR1/PKAc/PAD4 pathway post-ICH, underlining the potential of ASD in mitigating neuroinflammation through its anti-NETs properties.

Transcriptome disclosure of hormones inducing stigma exsertion in Nicotiana tabacum by corolla shortening.

BACKGROUND: Stigma exsertion is an essential agricultural trait that can promote cross-pollination to improve hybrid seed production efficiency. However, the molecular mechanism controlling stigma exsertion remains unknown. RESULTS: In this study, the Nicotiana tabacum cv. K326 and its two homonuclear-heteroplasmic lines, MSK326 (male-sterile) and MSK326SE (male-sterile and stigma exserted), were used to investigate the mechanism of tobacco stigma exsertion. A comparison of the flowers between the three lines showed that the stigma exsertion of MSK326SE was mainly due to corolla shortening. Therefore, the corollas of the three lines were sampled and presented for RNA-seq analysis, which found 338 candidate genes that may cause corolla shortening. These genes were equally expressed in K326 and MSK326, but differentially expressed in MSK326SE. Among these 338 genes, 15 were involved in hormone synthesis or signal transduction pathways. Consistently, the content of auxin, dihydrozeatin, gibberellin, and jasmonic acid was significantly decreased in the MSK326SE corolla, whereas abscisic acid levels were significantly increased. Additionally, seven genes involved in cell division, cell cycle, or cell expansion were identified. Protein-protein interaction network analysis identified 45 nodes and 79 protein interactions, and the largest module contained 20 nodes and 52 protein interactions, mainly involved in the hormone signal transduction and pathogen defensive pathways. Furthermore, a putative hub gene coding a serine/threonine-protein kinase was identified for the network. CONCLUSIONS: Our results suggest that hormones may play a key role in regulating tobacco stigma exsertion induced by corolla shortening.

Overexpression of the WRKY transcription factor gene NtWRKY65 enhances salt tolerance in tobacco (Nicotiana tabacum).

BACKGROUND: Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. RESULTS: This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. CONCLUSIONS: Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.

A machine learning approach for predicting perihematomal edema expansion in patients with intracerebral hemorrhage.

OBJECTIVES: Preventing the expansion of perihematomal edema (PHE) represents a novel strategy for the improvement of neurological outcomes in intracerebral hemorrhage (ICH) patients. Our goal was to predict early and delayed PHE expansion using a machine learning approach. METHODS: We enrolled 550 patients with spontaneous ICH to study early PHE expansion, and 389 patients to study delayed expansion. Two imaging researchers rated the shape and density of hematoma in non-contrast computed tomography (NCCT). We trained a radiological machine learning (ML) model, a radiomics ML model, and a combined ML model, using data from radiomics, traditional imaging, and clinical indicators. We then validated these models on an independent dataset by using a nested 4-fold cross-validation approach. We compared models with respect to their predictive performance, which was assessed using the receiver operating characteristic curve. RESULTS: For both early and delayed PHE expansion, the combined ML model was most predictive (early/delayed AUC values were 0.840/0.705), followed by the radiomics ML model (0.799/0.663), the radiological ML model (0.779/0.631), and the imaging readers (reader 1: 0.668/0.565, reader 2: 0.700/0.617). CONCLUSION: We validated a machine learning approach with high interpretability for the prediction of early and delayed PHE expansion. This new technique may assist clinical practice for the management of neurocritical patients with ICH. KEY POINTS: • This is the first study to use artificial intelligence technology for the prediction of perihematomal edema expansion. • A combined machine learning model, trained on data from radiomics, clinical indicators, and imaging features associated with hematoma expansion, outperformed all other methods.

Ventriculoperitoneal shunt for tuberculous meningitis-associated hydrocephalus: long-term outcomes and complications.

BACKGROUND: Hydrocephalus is a frequent complication of tuberculous meningitis (TBM), and ventriculoperitoneal shunt (VPS) has been shown to improve short-term prognosis for patients with TBM-associated hydrocephalus. However, questions remain about long-term prognosis and shunt-related complications. This study aims to provide a comprehensive assessment of both long-term prognosis and shunt-related complications in patients with TBM-induced hydrocephalus who have undergone VPS treatment. METHODS: This retrospective study analyzed the clinical data of TBM patients with hydrocephalus treated with VPS at Peking Union Medical College Hospital between December 1999 and February 2023. Both short-term outcomes at discharge and long-term outcomes during follow-up were examined. Prognosis and shunt-related complications were assessed using the modified Rankin Scale (mRS) and the Activity of Daily Living (ADL) score to evaluate neurological function and autonomic living ability, respectively. RESULTS: A total of 14 patients with TBM-associated hydrocephalus were included in this study. Of these, 92.9% (13/14) exhibited favorable short-term outcomes, while 57.1% (8/14) showed positive long-term outcomes. Initial results indicated 6 complete recoveries (CR), 7 partial recoveries (PR), and 1 treatment failure. No catheter-related complications were observed initially. Long-term results included 4 CRs, 4 PRs, and 6 treatment failures. A variety of shunt surgery-related complications were noted, including three instances of catheter obstruction, one of incision infection, one of catheter-related infection, one of acute cerebral infarction, and one of transient peritoneal irritation accompanied by diarrhea. CONCLUSIONS: VPS appears to be an effective and well-tolerated treatment for TBM-associated hydrocephalus, efficiently alleviating acute intracranial hypertension. Nonetheless, continuous long-term monitoring and proactive management are essential to mitigate the risk of catheter-related complications.

Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1ß, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software. RESULTS: A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1ß: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9). CONCLUSIONS: This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS. PROSPERO REGISTRATION NUMBER: CRD42022368744.

Hydrogel-potassium humate composite alleviates cadmium toxicity of tobacco by regulating Cd bioavailability.

Cadmium (Cd) removal from soil to reduce Cd accumulation in plants is essential for agroecology, food safety, and human health. Cd enters plants from soil and affects plant growth and development. Hydrogels can easily combine with Cd, thereby altering its bioavailability in soil. However, few studies have evaluated the effects of hydrogel on the complex phytotoxicity caused by Cd uptake in plants and the microbial community structure. Herein, a new poly (acrylic acid)-grafted starch and potassium humate composite (S/K/AA) hydrogel was added to soil to evaluate its impact on tobacco growth and the soil microenvironment. The results indicate that the addition of S/K/AA hydrogel can significantly improve the biomass, chlorophyll (Chl) content, and photosynthetic capacity of tobacco plants during Cd stress conditions, and decrease Cd concentration, probably by affecting Cd absorption through the expression of Cd absorption transporters (e.g., NRAMP5, NRAMP3, and IRT1). Moreover, the application of S/K/AA hydrogel not only reduced the accumulation of reactive oxygen species (ROS), but also reduced the antioxidant activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), suggesting that S/K/AA hydrogel alleviates Cd toxicity via a non-antioxidant pathway. Notably, we further analyzed the effectiveness of the hydrogel on microbial communities in Cd-contaminated soil and found that it increased the Cd-tolerant microbial community (Arthrobacter, Massilia, Streptomyces), enhancing the remediation ability of Cd-contaminated soil and helping tobacco plants to alleviate Cd toxicity. Overall, our study provides primary insights into how S/K/AA hydrogel affects Cd bioavailability and alleviates Cd toxicity in plants.

Evaluation and comparison of the benthic and microbial indices of biotic integrity for urban lakes based on environmental DNA and its management implications.

With the intensification of human disturbance in urban lakes, the loss of eukaryotic biodiversity (macroinvertebrates, etc.) reduces the accuracy of the index of biotic integrity (IBI) assessment. Therefore, how to accurately evaluate the ecological status of urban lakes based on IBI has become an important issue. In this study, 17 sampling sites from four lakes in Wuhan City, China were selected to analyze the composition and diversity characteristics of benthic and microbial communities and their relationship with environmental factors based on eDNA high-throughput sequencing, and compare the application effects of the benthic index of biotic integrity (B-IBI) and the microbial index of biotic integrity (M-IBI). Canonical correspondence analysis showed that the key environmental factors affecting benthic family/genus composition were temperature, conductivity, total phosphorus (TP), and total nitrogen (TN). Redundancy analysis showed that pH, TP, conductivity, and ammonia nitrogen had the greatest impact on microbial phyla/genera. After screening, four and six core metrics were determined from candidate parameters to establish B-IBI and M-IBI. The B-IBI evaluation results showed that healthy, sub-heathy, and poor accounted for 58.8%, 35.3%, and 5.9%, respectively, in the sites. The results of the M-IBI evaluation showed that 29.4% of the sites were healthy, 47.1% were sub-healthy, and 23.5% were common. M-IBI was positively correlated with water quality (r = 0.74, P < 0.001), whereas B-IBI was not. Further results showed that M-IBI was negatively correlated with the relative abundance of bloom-forming cyanobacteria Planktothrix (r = -0.54, P < 0.05). Therefore, M-IBI is more sensitive than B-IBI and can better reflect the actual water pollution status. This study can provide a new perspective for ecological assessment and management of urban lakes strongly disturbed by human activities.

Competitive adsorption of heavy metals between Ca-P and Mg-P products from wastewater during struvite crystallization.

Wastewater usually contains high concentration of calcium (Ca), posing a competitive reaction with magnesium (Mg) on phosphorus (P) recovery during the struvite crystallization. The differences in the adsorption of heavy metals by Ca-P and Mg-P (struvite) generated are still unclear. Herein, we analyzed the residues of four kinds of common heavy metals (Cu, Zn, Cd, Pb) in Ca-P and Mg-P (struvite) under varying conditions (solution pH, N/P ratio, Mg/Ca ratio) in the swine wastewater and explored their possible competitive adsorption mechanisms. The experiments using synthetic wastewater and real wastewater have similar experimental patterns. However, under the same conditions, the metal (Pb) content of struvite recovered from the synthetic wastewater (16.58 mg/g) was higher than that of the real wastewater (11.02 mg/g), as predicted by the Box-Behnken Design of Response Surface Methodology (BBD-RSM). The results demonstrated that Cu was the least abundant in the precipitates compared to Zn, Cd, and Pb of almost all experimental groups with an N/P ratio greater than or equal to 10. The fact might be mainly attributed to the its stronger binding capacity of Cu ion with NH3 and other ligands. Compared with struvite, the Ca-P product had a higher adsorption capacity for heavy metals and a lower P recovery rate. In addition, the higher solution pH and N/P ratio were favorable to obtain qualified struvite with lower heavy metal content. It can be applied to reduce the incorporation of heavy metals by modulating pH and N/P ratio through RSM, which is suitable for different Mg/Ca ratios. It is anticipated that the results obtained would offer support for the safe utility of struvite from wastewater containing Ca and heavy metals.

Validation of perihematomal edema expansion as a new imaging biomarker to predict clinical outcome in patients with intracerebral hemorrhage.

OBJECTIVES: The use of hematoma expansion (HE) in intracerebral hemorrhage (ICH) patients is limited due to its low sensitivity. Perihematomal edema (PHE) has been considered an important marker of secondary brain injury after ICH. Enrolling PHE expansion to redefine traditional ICH expansion merits exploration. MATERIALS AND METHODS: This study analyzed a cohort of patients with spontaneous ICH. The hematoma and PHE were manually segmented. Logistic regression analysis was utilized to identify risk factors for poor outcomes. Receiver operating characteristic curve analysis was performed to calculate the predictive values of PHE expansion and HE. Poor neurological outcome was defined as a modified Rankin Scale score of 4-6 at 90 days. RESULTS: Overall, 223 target patients were enrolled in the study. Multivariable analysis showed the larger PHE expansion is the independent risk factors for poor prognosis. The predictive value of absolute PHE expansion (AUC=0.776, sensitivity=67.9%, specificity=77.0%) was higher than that of absolute HE (AUC=0.573, sensitivity=41.7%, specificity=87.1%) and HE (>6 ml) (AUC=0.594, sensitivity=23.8%, specificity=95.0%). The best cutoff for early absolute/relative PHE expansion resulting in a poor outcome was 5.96 ml and 31%. CONCLUSIONS: Early PHE expansion was associated with a poor outcome, characterized by a better predictive value than HE.

Effects of heavy metals and hyporheic exchange on microbial community structure and functions in hyporheic zone.

The responses of microbial communities in hyporheic zone to the eco-hydrological process have been a hotspot in river ecological health research. However, the impact of different metal pollution levels and hyporheic exchange on the microbial communities are still unclear. In this study, we further explored the effects of different degrees of heavy metals pollution and the strength of hyporheic exchange on the structures and functions of microbial community in hyporheic zone sediment ecosystem. Sediments were collected from the Weihe River to determine the concentrations of heavy metals, grain size distribution, and hydraulic conductivity, and the microbial information were obtained by eDNA technology. The comprehensive pollution status of the study area was at the slight and moderate level. The hydraulic conductivity (Kv) varied between 0.20 and 3.65 (m/d). The microbial community structures had complex temporal and spatial heterogeneity. The microbial molecular ecological network had modular characteristics and significant differences in different periods (p < 0.05). Metabolic functional genes in microbial communities had the highest relative abundance. In particular, there is a significant negative correlation between heavy metals and microorganisms (p < 0.05), with Cu and Zn contributing the most to microbial community changes (p < 0.05). Moreover, grain size had a significant impact on microorganisms, heavy metals and grain size significantly affect the predictive functions of microbial communities. Our in-depth research on microorganisms in the hyporheic zone provides references for monitoring and bioremediation of aquatic ecosystems.

Assessing the Evolution of Intracranial Hematomas by using Animal Models: A Review of the Progress and the Challenges.

Stroke has become the second leading cause of death in people aged higher than 60 years, with cancer being the first. Intracerebral hemorrhage (ICH) is the most lethal type of stroke. Using imaging techniques to evaluate the evolution of intracranial hematomas in patients with hemorrhagic stroke is worthy of ongoing research. The difficulty in obtaining ultra-early imaging data and conducting intensive dynamic radiographic imaging in actual clinical settings has led to the application of experimental animal models to assess the evolution of intracranial hematomas. Herein, we review the current knowledge on primary intracerebral hemorrhage mechanisms, focus on the progress of animal studies related to hematoma development and secondary brain injury, introduce preclinical therapies, and summarize related challenges and future directions.

Capturing response differences of species distribution to climate and human pressures by incorporating local adaptation: Implications for the conservation of a critically endangered species.

Considering local adaptation has been increasingly involved in forecasting species distributions under climate change and the management of species conservation. Herein, we take the critically endangered Chinese giant salamander (Andrias davidianus) that has both a low dispersal ability and distinct population divergence in different regions as an example. Basin-scale models that represent different populations in the Huanghe River Basin (HRB), the Yangtze River Basin (YRB), and the Pearl River Basin (PRB) were established using ensemble species distribution models. The species ranges under the future human population density (HPD) and climate change were predicted, and the range loss was evaluated for local basins in 2050 and 2070. Our results showed that the predominant factors affecting species distributions differed among basins, and the responses of the species occurrence to HPD and climate factors were distinctly different from northern to southern basins. Future HPD changes would be the most influential factor that engenders negative impacts on the species distribution in all three basins, especially in the HRB. Climate change will likely be less prominent in decreasing the species range, excluding in the YRB and PRB under the highest-emissions scenario in 2050. Overall, the high-emissions scenario would more significantly aggravate the negative impacts produced by HPD change in both 2050 and 2070, with maximum losses of species ranges in the HRB, YRB, and PRB of 83.4%, 60.0%, and 53.5%, respectively, under the scenarios of the combined impacts of HPD and climate changes. We proposed adapted conservation policies to effectively protect the habitat of this critically endangered animal in different basins based on the outcomes. Our research addresses the importance of incorporating local adaptation into species distribution modeling to inform conservation and management decisions.

Diagnosis and treatment of low T3 syndrome in neurocritical patients.

WHAT IS KNOWN AND OBJECTIVE: Low levels of serum triiodothyronine (T3) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. The application of hormone replacement therapy (HRT) in the treatment of neurocritical patients with low T3 syndrome remains controversial. We studied the role of low T3 state as a predictor of outcomes in neurocritical patients and examined the effect of HRT on prognosis. METHODS: A retrospective analysis was performed on the data of 32 neurocritical patients with low T3 syndrome who were admitted to the neuro-intensive care unit of Peking Union Medical College Hospital between January 2012 and October 2018. While 18/32 (56.25%) patients received HRT (HRT group; n = 18), 14/32 (43.75%) patients did not receive HRT (non-HRT group; n = 14). Patients were followed up for periods ranging from 3 months to 72 months. Baseline clinical and laboratory data were compared between the two groups using Mann-Whitney U tests or the t tests. Overall survival was assessed by Kaplan-Meier curve and compared by log-rank tests. Univariate and multivariate regression analyses were performed to identify the factors associated with prognosis and estimate the effect of HRT. We also assessed the influence of HRT on final neurological function, using the Glasgow Coma Scale (GCS) and the Glasgow Outcome Scale (GOS) scores. RESULTS AND DISCUSSION: The neurocritical events in our cohort included post-operative complications (n = 18), traumatic brain injury (n = 8) and spontaneous intracerebral haemorrhage (n = 6). Mean GCS score in the cohort was 6.41 (6.44 ± 3.14 in HRT group vs 6.36 ± 2.06 in non-HRT group). A total of 15/32 (46.87%) deaths were recorded (7 in the HRT group, 8 in the non-HRT group). In the HRT group, 15 patients underwent repeat thyroid function tests after completion of HRT; the low T3 situation was corrected in only 5/15 (33.3%) patients. Overall survival was significantly shorter in the non-HRT group than in the HRT group (16.45 months vs 47.47 months; P = .034). In univariate regression analysis, the HRT group has the lower mortality risk than the non-HRT group (HR = 0.301, 95% Cl: 0.094-0.964; P = .043). However, multivariate regression analysis showed no significant difference in mortality risk between the two groups (HR = 0.340 95% CI: 0.099-1.172; P = .087). There was no significant difference in effects of HRT on the short- and long-term neurological function between the groups. WHAT IS NEW AND CONCLUSION: Low T3 syndrome may influence the prognosis of neurocritical patients, attention should be paid to the changes in serum T3 levels during treatment. Although it is unclear to what extent HRT can improve the short or long-term outcomes of neurological function, it can significantly improve the survival rates of neurocritical patients.

Bromadiolone poisoning leading to subarachnoid haemorrhage: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Many cases of rodenticide poisoning have been reported. Bromadiolone, often called a super-warfarin, is a second-generation dicoumarin rodenticide with long half-life. The main clinical manifestations of bromadiolone poisoning are excessive or inappropriate bleeding of skin mucosa, digestive tract and urinary tract. However, the phenomenon of central nervous system (CNS) toxicity is an uncommon medical emergency. We present a case of SAH and intracerebral haematoma mediated by bromadiolone intoxication, revealing that bromadiolone poisoning might cause intracerebral haematoma. CASE DESCRIPTION: A 44-year-old woman presented with skin mucosa haemorrhage and haematuresis initially. The patient developed lethargy, headache, nausea and vomiting. The toxicology test result revealed that the presence of bromadiolone in her blood. Coagulation test results showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). SAH, frontal lobe haematoma, midline shift and brain oedema were discovered by skull CT examination. The coagulation disorders were addressed after the treatment of vitamin K and fresh frozen plasma. The intracranial symptoms were relieved after surgery and the treatment with mannitol. WHAT IS NEW AND CONCLUSION: This case suggests that bromadiolone poisoning should be diagnosed and treated as early as possible. Bromadiolone poisoning might cause SAH and intracerebral haematoma, which is rare but potentially lethal. It is important to strengthen the diagnosis and post-treatment monitoring.

Monitoring seasonal distribution of an endangered anadromous sturgeon in a large river using environmental DNA.

Monitoring dynamic distribution is crucial to conservation management of anadromous sturgeons, but traditional survey methods are less efficient for low-density populations in a large river. Natural propagation of Chinese sturgeon has been monitored annually mainly at the spawning ground using netting for eggs and hydroacoustics for broodstock. However, absence of spawning was observed sporadically in recent years, indicating further crises for the declining population. We analyzed eDNA of water samples collected from 24 sites across 1360 km of the migratory route of anadromous Chinese sturgeon in the middle and lower reaches of the Yangtze River. Chinese sturgeon was detected at 9 sites during the spawning season and 14 sites after the spawning season. We found that positive eDNA detection rates remained constant in the middle reaches but dramatically changed in the lower reaches, reflecting seasonal migration pattern of Chinese sturgeon. Invasive sturgeons were detected in the river, indicating their possible escape from aquaculture facilities. This study established a protocol for the use of eDNA to monitor distribution of Chinese sturgeon and could be valuable in making better policies for the conservation of this endangered species.

The Impact of Impoundment on Mercury Bioaccumulation in Fish Downstream from a Newly Constructed Reservoir, Wujiang River, Southwest China.

Mercury concentrations in fish were investigated downstream from a newly impounded subtropical reservoir in August 2008. After 6-7 months of reservoir impoundment, mean mercury concentration in fish from downstream is significantly increased by 1.9 times. Not only carnivorous fish but also benthic fish had significantly higher total mercury concentrations than others. No significant correlation was found between total mercury concentrations and body length or weight of 13 fish species. Compared with the pre-impoundment, total mercury in fish from downstream is significantly increased by reservoir impoundment, but the increased rate is lower than those in subarctic and temperate areas. Fish samples surpassed the Chinese hygienic standard for tolerances of mercury in foods increased by 4.3%. More attention should be given to fish mercury levels from downstream sites to prevent possible adverse effects on the health of local people.

Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy of late luteal phase clomiphene citrate (CC) administration relative to early follicular phase CC for ovulation induction for polycystic ovary syndrome (PCOS). STUDY DESIGN: Review. MATERIALS AND METHODS: A complete electronic databases including PubMed, Embase, The Cochrane Library, Web of Science, and CBM were searched for relevant randomized controlled trials (RCTs). The search was not restricted by language and publication time. Two reviewers selected trials and assessed trial quality by the Cochrane Handbook 5.1.0 independently. RESULTS: Four eligible RCT studies involving 708 women (934 cycles) were included. The results of the Meta-analysis: Late luteal phase group was associated with a number of higher total follicles (MD 1.82; 95% CI 0.86-2.78, p < 0.00001) and significant higher endometrial thickness on the day of HCG (MD 0.88; 95% CI 0.78-0.99, p < 0.00001) compared with early follicular group. There were no significant differences in the rate of pregnancy (RR 1.29; 95% CI 0.83-2.01, p = 0.26), ovulation rate (RR 0.99; 95% CI 0.86-1.14, p = 0.87), and abortion rate (RR 1.12; 95% CI 0.38 to 3.29, p = 0.84) between the two groups. CONCLUSION: It appeared that late luteal phase CC for ovulation induction might be an effective method for ovulation induction in women with PCOS compared to conventional CC administration. Further intensive randomized-controlled studies should be warranted to define the efficacy of CC used in late luteal phase.

Population genomic analysis reveals genetic divergence and adaptation in Brachymystax lenok.

Studying how populations in various environments differ genetically is crucial for gaining insights into the evolution of biodiversity. In order to pinpoint potential indicators of divergence and adaptation to diverse environments, we conducted a comprehensive analysis of 3,491,868 single nucleotide polymorphisms (SNPs) derived from five populations of Brachymystax lenok. We discovered significant geographic divergence among these 5 populations, which lack evidence of gene flow among them. Our results further demonstrated that the current distribution pattern of Brachymystax lenok are driven by geographical isolation and changes in oceans and rivers. We also performed genome-wide scan and identified the genes evolved to adapt the different environments, including stress response. In general, these results provide genomic support for high-level genetic divergence and the genetic basis of adaptation to different environments.

Overexpression of NtDOGL4 improves cadmium tolerance through abscisic acid signaling pathway in tobacco.

The DELAY OF GERMINATION1-LIKE (DOGL) genes play an essential role in diverse biological processes in plants. However, their exact involvement in the response to cadmium (Cd) stress via the ABA pathway remains unclear. Here, we focused on NtDOGL4, a tobacco DOGL gene whose expression is highly induced upon exposure to Cd. Overexpression of NtDOGL4 in tobacco resulted in elevated endogenous ABA levels, reduced Cd accumulation, and increased tolerance to Cd. Moreover, NtDOGL4 overexpression led to decreased accumulation of reactive oxygen species (ROS) and improved ROS scavenging capacity under Cd stress. Further analyses revealed the direct binding of the transcription factor ABSCISIC ACID-INSENSITIVE 5 (ABI5) to the NtDOGL4 promoter, positively regulating its expression in tobacco. Notably, NtDOGL4 overexpression promoted suberin formation and deposition, while suppressing the expression of Cd transporter genes in tobacco roots, as evidenced by histochemical staining, suberin fraction determination, and qRT-PCR assays. Collectively, our results demonstrate that NtDOGL4 overexpression reduces Cd accumulation, thereby improving Cd stress tolerance through the modulation of antioxidant system, transcription of Cd transporters, and suberin deposition. Notably, the NtABI5-NtDOGL4 module functions as a positive regulator in tobacco's Cd tolerance, underscoring its potential as a molecular target for developing low-Cd crops to ensure environmental safety.