Observations on the efficacy of edaravone dexborneol in preventing post-stroke depression and its inflammatory mechanism: a prospective, randomized, control trial.

Objective: This study aimed to observe the effect of edaravone dexborneol (EDB) on the incidence of early post-stroke depression (PSD) and explore its inflammatory mechanisms. Methods: A prospective, randomized controlled study was conducted from January 2022 to June 2023, involving patients with acute ischemic stroke (AIS) at the Neurology Department of the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine. The control group received routine treatment, while the experimental group received routine combined EDB treatment. The main outcome measures included PSD incidence, Patient Health Questionnaire (PHQ-9) and Hamilton Depression Scale (HAMD) scores on days 14 and 30, and inflammatory factor levels on day 14. Results: A total of 93 patients were included in the study, 51 in the experimental group and 42 in the control group. On day 14, the PSD incidence was 13.7% in the experimental group, lower than 31.0% in the control group (95%CI 0.127-0.996; p = 0.044). Compared to the control group, the experimental group showed significantly lower concentrations of pro-inflammatory cytokines IL-1ß (95%CI 3.353-5.184), IL-6 (95%CI 2.694-3.426), TNF-α (95%CI 4.985-12.196), IFN-γ (95%CI 0.163-0.451), MCP-1 (95%CI 0.335-0.787), IL-17A (95%CI 0.543-1.024), and IL-23p19 (95%CI 1.677-1.959) (all p < 0.001), and higher levels of anti-inflammatory cytokines IL-4 (95%CI -1.087 to -0.941), IL-10 (95%CI -6.125 to -1.662), and IL-13 (95%CI -6.078 to -2.953) (all p ≤ 0.001). On day 30, the PSD incidence in the experimental group was 15.7%, lower than 40.5% in the control group (95%CI 0.103-0.725; p = 0.007). Compared with the control group, the experimental group had lower PHQ-9 scores on day 14 (95%CI 0.034-1.577; p = 0.041) and day 30 (95%CI 0.018-1.573; p = 0.045), and also had lower HAMD scores on day 14 (95% CI 0.281-2.856; p = 0.018) and day 30 (95% CI 0.647-3.482; p = 0.005). Conclusion: EDB could reduce the incidence of early PSD, reduce pro-inflammatory cytokine levels, and elevate anti-inflammatory cytokine levels, which was possibly related to the anti-inflammatory mechanism of EDB. Clinical trial registration: http://www.chictr.org.cn/, identifier [ChiCTR2300067750].

Targeting cell death in NAFLD: mechanisms and targeted therapies.

Nonalcoholic fatty liver disease (NAFLD) is a group of chronic liver disease which ranges from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and is characterized by lipid accumulation, inflammation activation, fibrosis, and cell death. To date, a number of preclinical studies or clinical trials associated with therapies targeting fatty acid metabolism, inflammatory factors and liver fibrosis are performed to develop effective drugs for NAFLD/NASH. However, few therapies are cell death signaling-targeted even though the various cell death modes are present throughout the progression of NAFLD/NASH. Here we summarize the four types of cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis in the NAFLD and the underlying molecular mechanisms by which the pathogenic factors such as free fatty acid and LPS induce cell death in the pathogenesis of NAFLD. In addition, we also review the effects of cell death-targeted therapies on NAFLD. In summary, our review provides comprehensive insight into the roles of various cell death modes in the progression of NAFLD, which we hope will open new avenues for therapeutic intervention.

Decoupling of strain- and intrastrain-level interactions of microbiomes in a sponge holobiont.

Holobionts are highly organized assemblages of eukaryotic hosts, cellular microbial symbionts, and viruses, whose interactions and evolution involve complex biological processes. It is largely unknown which specific determinants drive similarity or individuality in genetic diversity between holobionts. Here, we combine short- and long-read sequencing and DNA-proximity-linkage technologies to investigate intraspecific diversity of the microbiomes, including host-resolved viruses, in individuals of a model marine sponge. We find strong impacts of the sponge host and the cellular hosts of viruses on strain-level organization of the holobiont, whereas substantial overlap in nucleotide diversity between holobionts suggests frequent exchanges of microbial cells and viruses at intrastrain level in the local sponge population. Immune-evasive arms races likely restricted virus-host co-evolution at the intrastrain level, generated holobiont-specific genome variations, and linked virus-host genetics through recombination. Our work shows that a decoupling of strain- and intrastrain-level interactions is a key factor in the genetic diversification of holobionts.

Coronary artery segmentation in CCTA images based on multi-scale feature learning.

BACKGROUND: Coronary artery segmentation is a prerequisite in computer-aided diagnosis of Coronary Artery Disease (CAD). However, segmentation of coronary arteries in Coronary Computed Tomography Angiography (CCTA) images faces several challenges. The current segmentation approaches are unable to effectively address these challenges and existing problems such as the need for manual interaction or low segmentation accuracy. OBJECTIVE: A Multi-scale Feature Learning and Rectification (MFLR) network is proposed to tackle the challenges and achieve automatic and accurate segmentation of coronary arteries. METHODS: The MFLR network introduces a multi-scale feature extraction module in the encoder to effectively capture contextual information under different receptive fields. In the decoder, a feature correction and fusion module is proposed, which employs high-level features containing multi-scale information to correct and guide low-level features, achieving fusion between the two-level features to further improve segmentation performance. RESULTS: The MFLR network achieved the best performance on the dice similarity coefficient, Jaccard index, Recall, F1-score, and 95% Hausdorff distance, for both in-house and public datasets. CONCLUSION: Experimental results demonstrate the superiority and good generalization ability of the MFLR approach. This study contributes to the accurate diagnosis and treatment of CAD, and it also informs other segmentation applications in medicine.

Association of coagulation markers with the severity of white matter hyperintensities in cerebral small vessel disease.

Background and purpose: This study aimed to explore the correlation and causal relationship between fibrinogen, D-dimer, and the severity of cerebral white matter hyperintensity (MMH). Methods: A retrospective analysis of 120 patients with cerebral small vessel disease (CSVD) confirmed by head MRI attending the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine from August 2021 to February 2023 was performed. According to the Fazekas scale score, the patients were divided into 42 cases in the mild group, 44 cases in the moderate group, and 34 cases in the severe group. The levels of fibrinogen and D-dimer were compared among the three groups; the correlations between fibrinogen, D-dimer, and WMH severity were further analyzed; and independent risk factors for WMH severity were explored using the multivariate ordered logistic regression analysis. Furthermore, a two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of fibrinogen and D-dimer on WMH. Results: As the severity of WMH increased, the levels of D-dimer and fibrinogen also gradually increased, and the results showed a positive correlational association, with significant differences within the groups (all p < 0.05); the multivariate ordered logistic regression model showed that after adjusting for the relevant covariates, D-dimer (OR = 5.998, 95% CI 2.213-16.252, p < 0.001) and fibrinogen (OR = 9.074, 95% CI 4.054-20.311, p < 0.001) remained independent risk factors for the severity of WMH. In the MR study, the random-effect inverse variance weighted (IVW) model showed that increased levels of genetically predicted D-dimer (OR, 1.01; 95% confidence interval 0.95-1.06; p = 0.81) and fibrinogen (OR, 1.91; 95% confidence interval 0.97-3.78; p = 0.06) were not associated with increased risk of WMH. The authors did not obtain strong evidence of a direct causal relationship between D-dimer, fibrinogen, and WMH. Conclusion: In this retrospective-based study, the authors found possible associations between D-dimer, fibrinogen, and WMH, but there was no obvious causal evidence. Further efforts are still needed to investigate the pathophysiology between D-dimer, fibrinogen, and WMH.

Gene inversion led to the emergence of brackish archaeal heterotrophs in the aftermath of the Cryogenian Snowball Earth.

Land-ocean interactions greatly impact the evolution of coastal life on earth. However, the ancient geological forces and genetic mechanisms that shaped evolutionary adaptations and allowed microorganisms to inhabit coastal brackish waters remain largely unexplored. In this study, we infer the evolutionary trajectory of the ubiquitous heterotrophic archaea Poseidoniales (Marine Group II archaea) presently occurring across global aquatic habitats. Our results show that their brackish subgroups had a single origination, dated to over 600 million years ago, through the inversion of the magnesium transport gene corA that conferred osmotic-stress tolerance. The subsequent loss and gain of corA were followed by genome-wide adjustment, characterized by a general two-step mode of selection in microbial speciation. The coastal family of Poseidoniales showed a rapid increase in the evolutionary rate during and in the aftermath of the Cryogenian Snowball Earth (∼700 million years ago), possibly in response to the enhanced phosphorus supply and the rise of algae. Our study highlights the close interplay between genetic changes and ecosystem evolution that boosted microbial diversification in the Neoproterozoic continental margins, where the Cambrian explosion of animals soon followed.

Novel order-level lineage of ammonia-oxidizing archaea widespread in marine and terrestrial environments.

Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant archaea on Earth, widely distributed in marine, terrestrial, and geothermal ecosystems. However, the genomic diversity, biogeography, and evolutionary process of AOA populations in subsurface environments are vastly understudied compared to those in marine and soil systems. Here, we report a novel AOA order Candidatus (Ca.) Nitrosomirales which forms a sister lineage to the thermophilic Ca. Nitrosocaldales. Metagenomic and 16S rRNA gene-read mapping demonstrates the abundant presence of Nitrosomirales AOA in various groundwater environments and their widespread distribution across a range of geothermal, terrestrial, and marine habitats. Terrestrial Nitrosomirales AOA show the genetic capacity of using formate as a source of reductant and using nitrate as an alternative electron acceptor. Nitrosomirales AOA appear to have acquired key metabolic genes and operons from other mesophilic populations via horizontal gene transfer, including genes encoding urease, nitrite reductase, and V-type ATPase. The additional metabolic versatility conferred by acquired functions may have facilitated their radiation into a variety of subsurface, marine, and soil environments. We also provide evidence that each of the four AOA orders spans both marine and terrestrial habitats, which suggests a more complex evolutionary history for major AOA lineages than previously proposed. Together, these findings establish a robust phylogenomic framework of AOA and provide new insights into the ecology and adaptation of this globally abundant functional guild.

GSK2606414 Sensitizes ABCG2-Overexpressing Multidrug-Resistant Colorectal Cancer Cells to Chemotherapeutic Drugs.

Colorectal cancer is a common malignant tumor. A major factor in the high mortality rate of colorectal cancer is the emergence of multidrug resistance (MDR). Overexpression of the ABCG2 gene in cancer cells directly leads to MDR. Finding new inhibitors of ABCG2 may be an effective way to overcome drug resistance. We found that the compound GSK2606414 enhanced the sensitivity of the ABCG2 substrate to the chemotherapeutic drugs mitoxantrone and doxorubicin in ABCG2-overexpressing multidrug-resistant colorectal cancer cells by increasing their intracellular accumulation without affecting the protein expression of ABCG2. Molecular docking experiments predicted that GSK2606414 could stably bind in the drug-binding pocket of ABCG2. In conclusion, GSK2606414 can sensitize ABCG2-overexpressed multidrug-resistant colorectal cancer cells to chemotherapy drugs and can be used as a potential inhibitor of ABCG2.

BDH1-mediated ßOHB metabolism ameliorates diabetic kidney disease by activation of NRF2-mediated antioxidative pathway.

A ketogenic diet (KD) and ß-hydroxybutyrate (ßOHB) have been widely reported as effective therapies for metabolic diseases. ß-Hydroxybutyrate dehydrogenase 1 (BDH1) is the rate-limiting enzyme in ketone metabolism. In this study, we examined the BDH1-mediated ßOHB metabolic pathway in the pathogenesis of diabetic kidney disease (DKD). We found that BDH1 is downregulated in the kidneys in DKD mouse models, patients with diabetes, and high glucose- or palmitic acid-induced human renal tubular epithelial (HK-2) cells. BDH1 overexpression or ßOHB treatment protects HK-2 cells from glucotoxicity and lipotoxicity by inhibiting reactive oxygen species overproduction. Mechanistically, BDH1-mediated ßOHB metabolism activates NRF2 by enhancing the metabolic flux of ßOHB-acetoacetate-succinate-fumarate. Moreover, in vivo studies showed that adeno-associated virus 9-mediated BDH1 renal expression successfully reverses fibrosis, inflammation, and apoptosis in the kidneys of C57 BKS db/db mice. Either ßOHB supplementation or KD feeding could elevate the renal expression of BDH1 and reverse the progression of DKD. Our results revealed a BDH1-mediated molecular mechanism in the pathogenesis of DKD and identified BDH1 as a potential therapeutic target for DKD.

Multi-constraint point set registration with redundant point removal for the registration of coronary arteries.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. The registration of the coronary artery at different phases can help radiologists explore the motion patterns of the coronary artery and assist in the diagnosis of CAD. However, there is no automatic and easy-to-execute method to solve the missing data problem that occurs at the endpoints of the coronary artery tree. This paper proposed a non-rigid multi-constraint point set registration with redundant point removal (MPSR-RPR) algorithm to tackle this challenge. METHODS: Firstly, the MPSR-RPR algorithm roughly registered two coronary artery point sets with the pre-set smoothness regularization parameter and Gaussian filter width value. The moving coherent, local feature, and the corresponding relationship between bifurcation point pairs were exploited as the constraints. Next, the spatial geometry information of the coronary artery was utilized to automatically recognize the vessel endpoints and to delete the redundant points of the coronary artery. Finally, the algorithm continued carrying out the multi-constraint registration with another group of the pre-set parameters to improve the alignment performance. RESULTS: The experimental results demonstrated that the MPSR-RPR algorithm achieved a significantly lower mean value of the modified Hausdorff distance (MHD) compared to the other state-of-the-art methods for addressing the serious missing data in the left and right coronary arteries. CONCLUSION: This study demonstrated the effectiveness of the proposed algorithm in aligning coronary arteries, providing significant value in assisting in the diagnosis of coronary artery and myocardial lesions.

The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.

Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.

A moderately thermophilic origin of a novel family of marine group II euryarchaeota from deep ocean.

Marine group II (MGII) is the most abundant planktonic heterotrophic archaea in the ocean. The evolutionary history of MGII archaea is elusive. In this study, 13 new MGII metagenome-assembled genomes were recovered from surface to the hadal zone in Challenger Deep of the Mariana Trench; four of them from the deep ocean represent a novel group. The optimal growth temperature (OGT) of the common ancestor of MGII has been estimated to be at about 60°C and OGTs of MGIIc, MGIIb, and MGIIa at 47°C-50ºC, 37°C-44ºC, and 30°C-37ºC, respectively, suggesting the adaptation of these species to different temperatures during evolution. The estimated OGT range of MGIIc was supported by experimental measurements of cloned ß-galactosidase that showed optimal enzyme activity around 50°C. These results indicate that MGIIc may have originated from a common ancestor that lived in warm or even hot marine environment, such as hydrothermal vents.

siRNA targeting Atp5a1 gene encoding ATPase α, the ligand of Peg fimbriae, reduced Salmonella Enteritidis adhesion.

Salmonella enterica serovar Enteritidis (S. Enteritidis) is a zoonotic pathogen that can infect both humans and animals. Among the 13 types of fimbrial operons in S. Enteritidis, the highly conserved Peg fimbriae play a crucial role in the adhesion and invasion of S. Enteritidis into host cells but are not well studied. In this study, we identified the ATP synthase subunit alpha (ATPase α) as a ligand of Peg fimbriae using ligand blotting and mass spectrometry techniques. We confirmed the in vitro binding of ATPase α to the purified adhesion protein (PegD). Furthermore, we used siRNA to suppress the expression of ATPase α gene Atp5a1 in Leghorn male hepatoma (LMH) cells, which resulted in a significant reduction in the adhesion rate of S. Enteritidis to the cells (P < 0.05). The findings in this study provide insight into the mechanism of S. Enteritidis infection through Peg fimbriae and highlight the importance of ATPase α in the adhesion process.RESEARCH HIGHLIGHTS Ligand blotting was performed to screen the ligand of S. Enteritidis Peg fimbriae.Binding assay confirmed that ATPase α is the ligand of the Peg fimbriae.siRNA targeting ATPase α gene (Atp5a1) significantly reduced S. Enteritidis adhesion.

Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade.

PURPOSE: Radiation-induced sarcomas (RIS) have a poor prognosis and lack effective treatments. Its genome and tumor microenvironment are not well characterized and need further exploration. EXPERIMENTAL DESIGN: Here, we performed whole-exome sequencing (WES) and mRNA sequencing (mRNA-seq) on patients with RIS and primary sarcomas (WES samples 46 vs. 48, mRNA-seq samples 16 vs. 8, mainly in head and neck), investigated the antitumor effect of programmed cell death protein 1 (PD-1) blockade in RIS patient-derived xenograft models, and analyzed clinical data of patients with RIS treated with chemotherapy alone or combined with an anti-PD-1 antibody. RESULTS: Compared with primary sarcomas, RIS manifested different patterns of copy-number variations, a significantly higher number of predicted strong MHC-binding neoantigens, and significantly increased immune cell infiltration. Clinical data showed that the combinatorial use of chemotherapy and PD-1 blockade achieved a higher objective response rate (36.67% vs. 8.00%; P = 0.003), longer overall survival (31.9 months vs. 14.8 months; P = 0.014), and longer progression-free survival (4.7 months vs. 9.5 months; P = 0.032) in patients with RIS compared with single chemotherapy. CONCLUSIONS: Elevated genomic instability and higher immune cell infiltrations were found in RIS than in primary sarcomas. Moreover, higher efficacy of chemotherapy plus PD-1 blockade was observed in animal experiments and clinical practice. This evidence indicated the promising application of immune checkpoint inhibitors in the treatment of RIS.

Diversity, distribution, and functional potentials of magroviruses from marine and brackish waters.

Marine group II (MGII) archaea (Ca. Poseidoniales) are among the most abundant microbes in global oceanic surface waters and play an important role in driving marine biogeochemical cycles. Magroviruses - the viruses of MGII archaea have been recently found to occur ubiquitously in surface ocean. However, their diversity, distribution, and potential ecological functions in coastal zones especially brackish waters are unknown. Here we obtained 234 non-redundant magroviral genomes from brackish surface waters by using homology searches for viral signature proteins highlighting the uncovered vast diversity of this novel viral group. Phylogenetic analysis based on these brackish magroviruses along with previously reported marine ones identified six taxonomic groups with close evolutionary connection to both haloviruses and the viruses of Marine Group I archaea. Magroviruses were present abundantly both in brackish and open ocean samples with some showing habitat specification and others having broad spectrums of distribution between different habitats. Genome annotation suggests they may be involved in regulating multiple metabolic pathways of MGII archaea. Our results uncover the previously overlooked diversity and ecological potentials of a major archaeal virial group in global ocean and brackish waters and shed light on the cryptic evolutionary history of archaeal viruses.

Spatiotemporal Shift of T4-Like Phage Community Structure in the Three Largest Estuaries of China.

Estuaries are one of the most highly productive and economically important ecosystems at the continent-ocean interface. Estuary productivity is largely determined by the microbial community structure and activity. Viruses are major agents of microbial mortality and are key drivers of global geochemical cycles. However, the taxonomic diversity of viral communities and their spatial-temporal distribution in estuarine ecosystems have been poorly studied. In this study, we investigated the T4-like viral community composition at three major Chinese estuaries in winter and in summer. Diverse T4-like viruses, which were divided into three main clusters (Clusters I to III), were revealed. The Marine Group of Cluster III, with seven identified subgroups, was the most dominant (averaging 76.5% of the total sequences) in the Chinese estuarine ecosystems. Significant variations of T4-like viral community composition were observed among estuaries and seasons, with higher diversity occurring in winter. Among various environmental variables, temperature was a main driver of the viral communities. This study demonstrates viral assemblage diversification and seasonality in Chinese estuarine ecosystems. IMPORTANCE Viruses are ubiquitous but largely uncharacterized members of aquatic environments that cause significant mortality in microbial communities. Recent large-scale oceanic projects have greatly advanced our understanding of viral ecology in marine environments, but those studies mostly focused on oceanic regions. There have yet to be spatiotemporal studies of viral communities in estuarine ecosystems, which are unique habitats that play a significant role in global ecology and biogeochemistry. This work is the first comprehensive study that provides a detailed picture of the spatial and seasonal variation of viral communities (specifically, T4-like viral communities) in three major estuarine ecosystems in China. These findings provide much-needed knowledge regarding estuarine viral ecosystems, which currently lags in oceanic ecosystem research.

Study on the intervention effect of SMG health management in patients with ischemic stroke.

INTRODUCTION: The aim of the study was to explore the clinical effect of brain and heart health managers combined with the "SMG" health management mode on nursing intervention in ischemic stroke patients. MATERIAL AND METHODS: A total of 187 ischemic stroke patients divided into 96 patients in the observation group and 91 patients in the control group with the random number table method. The control group conducted the routine care intervention, and the observation group used the brain and heart health managers combined with the "SMG" health management model for the nursing intervention. The control of stroke risk factors was explored by comparing blood pressure, blood glucose and blood lipid and other indicators between the two groups before and after treatment. RESULTS: Compared with that before the intervention, the Stroke Self-Efficacy Questionnaire (SSEQ) score of both the observation group and the control group were significantly higher ( p < 0.05), and the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were all decreased ( p < 0.05). The proportion of patients with treatment adherence did not differ significantly before and after the intervention in the control group ( p > 0.05), and it increased significantly in the observation group after the intervention ( p < 0.05). The observation group had higher SSEQ score and lower HAMA, HAMD, NIHSS, and mRS scores after the intervention compared with the control group, with statistically significant differences. CONCLUSIONS: The combination of brain and heart health managers and "SMG" is more conducive to improving the selfefficacy of ischemic stroke patients, alleviating patient anxiety and depression, improving patient treatment compliance, controlling stroke risk factors, and promoting neurological function recovery.

Effect of Cluster Nursing on Recovery Effect and Hospitalization Time of Patients with Acute Cerebral Infarction After Thrombectomy.

Objective: To explore the effects of cluster nursing on self-care ability, length of hospital stay, complications and neurological function of patients with mechanical thrombectomy of large vessel occlusion in acute cerebral infarction. Methods: A total of 83 patients with acute cerebral infarction who underwent thrombolectomy in a tertiary hospital in Anhui Province from June 2019 to March 2021 were randomly divided into observation group and control group. The observation group was treated with cluster nursing intervention mode, and the control group was treated with routine nursing mode. Barthel index scores and National Institute of Health Stroke Scale (NIHSS) scores were compared between the two groups at admission and at 1 week, 1 month and 3 months of nursing intervention. The length of stay and incidence of complications were compared between the two groups. Results: There was no significant difference in baseline data, Barthel index and NIHSS score between the two groups at admission (P>0.05). The Barthel index at 1 week, 1 month and 3 months after operation in the observation group was significantly higher than that in the control group (P<0.05), while the NIHSS score, incidence of complications and length of hospital stay were significantly lower than those of the control group (P<0.05). Conclusion: Cluster nursing can improve the neurological function, improve the self-care ability, reduce the incidence of complications, shorten the hospitalization period, improve the prognosis and promote the recovery of patients with acute cerebral infarction thrombolysis.

Ecological dynamics and impacts of viruses in Chinese and global estuaries.

Estuaries are important ecosystems providing irreplaceable services for humankind and, in turn, are extensively influenced by human activities and climate changes. Microbial processes, which are largely controlled by viruses, are always responsible for the ecological function and environmental problems in estuaries. However, we know little about the ecology and importance of viruses in estuarine systems. Here, we investigated viral ecological dynamics in estuarine systems on local (four largest estuaries in China in different seasons) and global scales. Viral production varied by almost 20-fold in Chinese estuaries with significant seasonality, being responsible for the removal of 1.41%-21.45% of the bacterioplankton standing stock each day, and contributed directly to the organic carbon pool by releasing an average of 3.57 µg of cellular carbon per liter per day. By compiling data from 21 estuaries across the world, we found for the first time that viral population size peaked at mid-latitude and viral production increased towards the equator in estuarine ecosystems. The results indicated the higher viral impact on microbial mortality and dissolved organic matter cycling in tropical estuaries. Our field investigation and global synthesized analysis provide compelling evidence of spatiotemporal variations in estuarine viral dynamics. The global view of viral impacts on estuarine microbial mortality offers important insight for incorporating viruses into ecological models and understanding the environmental implications of the tropicalization of temperate aquatic ecosystems under a scenario of climate warming.

Ectopic pregnancy and failed oocyte retrieval during in vitro fertilization stimulation: Two case reports.

BACKGROUND: Due to a slight rise in beta-human chorionic (ß-hCG) levels that are undetectable, and vaginal bleeding that is similar to regular menstruation, ectopic pregnancy (EP) that occurs during the expected menstrual cycle prior to ovulation induction as part of in vitro fertilization (IVF) is likely to be undiagnosed. We present two cases of unexpected EP and emphasize the importance of the ß-hCG assay when an unexplained increase in progesterone is present prior to the triggering of ovulation during controlled ovarian stimulation (COS). CASE SUMMARY: A 26-year-old woman with primary infertility and a 31-year-old woman with secondary infertility. Both patients sought IVF treatment due to fallopian tube obstruction and underwent COS using the gonadotropin-releasing-hormone (GnRH)-antagonist protocol. In the late stage of COS, progesterone levels in both patients significantly increased, and luteinizing hormone levels decreased, followed by oocyte retrieval failure. A right salpingectomy was performed and tubal ectopic pregnancy was diagnosed by pathology in the first patient, and the second patients was diagnosed with a suspected EP abortion because her ß-hCG levels declined to 12.5 mIU/mL. After full recovery for 2 mo, the first patient entered a new IVF treatment cycle with a GnRH-antagonist regimen and successfully achieved eight oocytes and three viable embryos. After 6 mo, the second patient received another COS treatment with a progestin-primed ovarian stimulation protocol and successfully achieved nine oocytes and five viable embryos. CONCLUSION: ß-hCG levels in the initial and midterm phases of COS must be considered in patients with unusual hormone dynamics.