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Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.

Photoluminescence lifetime imaging of upconverting nanoparticles is increasingly featured in recent progress in optical thermometry. Despite remarkable advances in photoluminescent temperature indicators, existing optical instruments lack the ability of wide-field photoluminescence lifetime imaging in real time, thus falling short in dynamic temperature mapping. Here, we report video-rate upconversion temperature sensing in wide field using single-shot photoluminescence lifetime imaging thermometry (SPLIT). Developed from a compressed-sensing ultrahigh-speed imaging paradigm, SPLIT first records wide-field luminescence intensity decay compressively in two views in a single exposure. Then, an algorithm, built upon the plug-and-play alternating direction method of multipliers, is used to reconstruct the video, from which the extracted lifetime distribution is converted to a temperature map. Using the core/shell NaGdF 4 :Er 3+ ,Yb 3+ /NaGdF 4 upconverting nanoparticles as the lifetime-based temperature indicators, we apply SPLIT in longitudinal wide-field temperature monitoring beneath a thin scattering medium. SPLIT also enables video-rate temperature mapping of a moving biological sample at single-cell resolution. Photoluminescence lifetime imaging of upconverting nanoparticles is useful for optical thermometry, but is limited for dynamic samples. Here, the authors present a wide-field and single shot approach based on compressive sensing, for video-rate upconversion temperature sensing of moving samples.

Synchronization, which has been a common natural phenomenon, occurs frequently in complex financial systems and is an important contagion mechanism for systemic financial risks and even financial crises. In view of this, we construct a coupled stochastic volatility model and its volatility synchronization analysis framework and combine machine learning methods and rolling cycle window to propose a prediction method for dynamic volatility synchronization. Taking the Shanghai Composite Index (SSEC) and Shenzhen Component Index (SZI) as binary synchronization examples, we analyze the dynamic forecasting performance of the proposed method in an in-sample and out-of-sample empirical comparison by combining multiple loss functions and Superior Predictive Ability (SPA) tests for high-frequency data. It is found that the in-sample estimates of our proposed model are highly consistent with the market behavior and that the model outperforms other models in predicting stock market volatility synchronization accuracy. In addition, by combining dynamic simulation with multivariate empirical mechanism analysis, our methodology not only explores synchronization dynamics but also identifies significant risk events, providing a comprehensive framework for understanding complex system behaviors.

Multimodal transportation is getting more and more attention due to its economical and efficient characteristics. Choosing a reasonable transportation plan can effectively control transportation costs. Considering that there are fixed schedules for railway and waterway transportation in real life, this article will establish a multimodal transportation route optimization model with the goal of minimizing the total transportation cost consisting of transportation cost, transit cost, waiting cost and carbon emission cost. The genetic algorithm based on preservation strategy and immigration strategy is used to solve the model. The effectiveness of the model is proved by the case study, and it can provide decision support for the choice of multimodal transportation scheme.

Glofitamab offers a promising option for the treatment of diffuse large B-cell lymphoma. It is crucial to gather comprehensive safety information of glofitamab through large-scale post market monitoring. This study conducted a comprehensive analysis of glofitamab-related adverse events (AEs) based on FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to mining the significant signals. The clinical characteristics of all AE and cytokine release syndrome reports were analyzed. Sensitivity analyses were performed to exam the potential bias. The differences in AE signals among different subgroups were investigated. A total of 641 reports and 1,542 AEs with glofitamab were identified. Cytokine release syndrome was the most significant signal. Notably, American and European reporters demonstrated higher cytokine release syndrome reporting frequency. Cytokine release syndrome was often reported by professionals and occurred within 30 days, especially with glofitamab at a dose of 2.5 mg. Hypogammaglobulinaemia was discovered as a new significant AE signal. The findings suggest potential reporting differences in glofitamab-related AEs across different continents. Educating consumers on how to recognize the early symptoms of cytokine release syndrome is essential to improve safety. Close monitoring of cytokine release syndrome is recommended within 30 days of administration of glofitamab, especially at a dose of 2.5 mg. Furthermore, it is essential to stay vigilant about the emergence of the newly identified AE. These findings contribute to a broader understanding of the AE profiles of glofitamab.

Background In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions. Results In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn ) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data ( n = 11,647) and cultured 24 “most-wanted” and “medium priority” taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially “dark taxa” that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the “most wanted” functionally unknown proteins in the FUnkFams database. Conclusions A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. 6-6epGnHGpob5sGsfPZJHQ Video abstract

The human gastrointestinal (GI) tract harbors diverse microbes, and the family Lachnospiraceae is one of the most abundant and widely occurring bacterial groups in the human GI tract. Beneficial and adverse effects of the Lachnospiraceae on host health were reported, but the diversities at species/strain levels as well as their metabolites of Lachnospiraceae have been, so far, not well documented. In the present study, we report on the collection of 77 human‐originated Lachnospiraceae species (please refer hLchsp, https://hgmb.nmdc.cn/subject/lachnospiraceae) and the in vitro metabolite profiles of 110 Lachnospiraceae strains (https://hgmb.nmdc.cn/subject/lachnospiraceae/metabolites). The Lachnospiraceae strains in hLchsp produced 242 metabolites of 17 categories. The larger categories were alcohols (89), ketones (35), pyrazines (29), short (C2–C5), and long (C > 5) chain acids (31), phenols (14), aldehydes (14), and other 30 compounds. Among them, 22 metabolites were aromatic compounds. The well‐known beneficial gut microbial metabolite, butyric acid, was generally produced by many Lachnospiraceae strains, and Agathobacter rectalis strain Lach‐101 and Coprococcus comes strain NSJ‐173 were the top 2 butyric acid producers, as 331.5 and 310.9 mg/L of butyric acids were produced in vitro, respectively. Further analysis of the publicly available cohort‐based volatile‐metabolomic data sets of human feces revealed that over 30% of the prevailing volatile metabolites were covered by Lachnospiraceae metabolites identified in this study. This study provides Lachnospiraceae strain resources together with their metabolic profiles for future studies on host–microbe interactions and developments of novel probiotics or biotherapies. The human‐originated Lachnospiraceae biobank included 77 species was constructed. In vitro metabolite profiling of 110 Lachnospiraceae strains yielded 242 metabolites of 17 categories. Many Lachnospiraceae strains produce short‐chain fatty acids, and Agathobacter rectalis strain Lach‐101 and Coprococcus comes strain NSJ‐173 are the top two butyric acid producers in vitro. Highlights The human‐originated Lachnospiraceae biobank included 77 species was constructed. In vitro metabolite profiling of 110 Lachnospiraceae strains yielded 242 metabolites of 17 categories. Many Lachnospiraceae strains produce SCFAs, and Agathobacter rectalis strain Lach‐101 and Coprococcus comes strain NSJ‐173 are the top two butyric acid producers in vitro.

Background Selpercatinib, a highly selective tyrosine kinase inhibitor, has emerged as an excellent treatment option for patients with rearranged during transfection-altered cancer. However, there is limited comprehensive safety information available for selpercatinib through large-scale post-marketing monitoring. Methods This study conducted a comprehensive analysis of selpercatinib-related adverse events (AEs) using the FDA Adverse Event Reporting System database. Four disproportionality methods were employed to identify potential AEs associated with selpercatinib. Specifically, this study investigated the differences in AEs of selpercatinib with respect to reporter continent, indication, sex, age, weight, dose, frequency, and onset time. Results A total of 464 reports and 1,007 selpercatinib-related AEs were identified. Three new significant AEs were discovered, including dysphagia, pericardial effusion, and hemiparesis. Notably, Asia reported hepatic function abnormal more frequently, especially in patient administered doses exceeding 160 mg. Furthermore, hypersensitivity was reported more frequently by Asia and in individuals weighing less than 50 kg. Conclusions It is paramount to stay vigilant concerning the potential emergence of three newly identified AEs. Significant differences were found in selpercatinib-related AEs concerning reporter continent, sex, weight, dose, frequency, and onset time, which deserved clinical attention. These findings contribute to a broader understanding of the AE profiles of selpercatinib. Highlight • Three new significant adverse events were discovered, including dysphagia, pericardial effusion, and hemiparesis. • Asia reported hepatic function abnormal more frequently, especially in patient administered single doses exceeding 160 mg. • Hypersensitivity was reported more frequently by Asia and in individuals weighing less than 50 kg.

As the major component of cell membranes, phosphatidylcholine (PC) is synthesized de novo in the Kennedy pathway and then undergoes extensive deacylation-reacylation remodeling via Lands’ cycle. The re-acylation is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT) and among the four LPCAT members in human, the LPCAT3 preferentially introduces polyunsaturated acyl onto the sn-2 position of lysophosphatidylcholine, thereby modulating the membrane fluidity and membrane protein functions therein. Combining the x-ray crystallography and the cryo-electron microscopy, we determined the structures of LPCAT3 in apo-, acyl donor-bound, and acyl receptor-bound states. A reaction chamber was revealed in the LPCAT3 structure where the lysophosphatidylcholine and arachidonoyl-CoA were positioned in two tunnels connected near to the catalytic center. A side pocket was found expanding the tunnel for the arachidonoyl CoA and holding the main body of arachidonoyl. The structural and functional analysis provides the basis for the re-acylation of lysophosphatidylcholine and the substrate preference during the reactions. During phosphatidylcholine (PC) remodeling re-acylation is catalyzed by lysophosphatidylcholine acyltransferases (LPCAT). Here, the authors present crystal and cryo-EM structures of chicken LPCAT3 in the apo-, acyl donor-bound and acyl receptor-bound states, and based on the structures and further functional analysis they discuss the mechanism of the enzyme.

Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman–Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N , N ′-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline). Chiral vicinal amino alcohols are found in many bioactive compounds and may serve as chiral ligands. Here, the authors report a photocatalytic enantioselective cross-coupling of nitrones with aromatic aldehydes with a chiral ligand-coordinated rare earth ion synergistically producing enantiopure vicinal amino alcohols.