Phylogenetic analysis and divergence time estimation of Lycium species in China based on the chloroplast genomes.

BACKGROUND: Lycium is an economically and ecologically important genus of shrubs, consisting of approximately 70 species distributed worldwide, 15 of which are located in China. Despite the economic and ecological importance of Lycium, its phylogeny, interspecific relationships, and evolutionary history remain relatively unknown. In this study, we constructed a phylogeny and estimated divergence time based on the chloroplast genomes (CPGs) of 15 species, including subspecies, of the genus Lycium from China. RESULTS: We sequenced and annotated 15 CPGs in this study. Comparative analysis of these genomes from these Lycium species revealed a typical quadripartite structure, with a total sequence length ranging from 154,890 to 155,677 base pairs (bp). The CPGs was highly conserved and moderately differentiated. Through annotation, we identified a total of 128-132 genes. Analysis of the boundaries of inverted repeat (IR) regions showed consistent positioning: the junctions of the IRb/LSC region were located in rps19 in all Lycium species, IRb/SSC between the ycf1 and ndhF genes, and SSC/IRa within the ycf1 gene. Sequence variation in the SSC region exceeded that in the IR region. We did not detect major expansions or contractions in the IR region or rearrangements or insertions in the CPGs of the 15 Lycium species. Comparative analyses revealed five hotspot regions in the CPG: trnR(UCU), atpF-atpH, ycf3-trnS(GGA), trnS(GGA), and trnL-UAG, which could potentially serve as molecular markers. In addition, phylogenetic tree construction based on the CPG indicated that the 15 Lycium species formed a monophyletic group and were divided into two typical subbranches and three minor branches. Molecular dating suggested that Lycium diverged from its sister genus approximately 17.7 million years ago (Mya) and species diversification within the Lycium species of China primarily occurred during the recent Pliocene epoch. CONCLUSION: The divergence time estimation presented in this study will facilitate future research on Lycium, aid in species differentiation, and facilitate diverse investigations into this economically and ecologically important genus.

Current therapy in amyotrophic lateral sclerosis (ALS): A review on past and future therapeutic strategies.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.

Decreased inter-hemispheric cooperation in major depressive disorder and its association with neurotransmitter profiles.

BACKGROUND: Inter-hemispheric cooperation is a prominent feature of the human brain, and previous neuroimaging studies have revealed aberrant inter-hemispheric cooperation patterns in patients with major depressive disorder (MDD). Typically, inter-hemispheric cooperation is examined by calculating the functional connectivity (FC) between each voxel in one hemisphere and its anatomical (structurally homotopic) counterpart in the opposite hemisphere. However, bilateral hemispheres are actually asymmetric in anatomy. METHODS: In the present study, we utilized connectivity between functionally homotopic voxels (CFH) to investigate abnormal inter-hemispheric cooperation in 96 MDD patients compared to 173 age- and sex-matched healthy controls (HCs). In addition, we analyzed the spatial correlations between abnormal CFH and the density maps of 13 neurotransmitter receptors and transporters. RESULTS: The CFH values in bilateral orbital frontal gyri and bilateral postcentral gyri were abnormally decreased in patients with MDD. Furthermore, these CFH abnormalities were correlated with clinical symptoms. In addition, the abnormal CFH pattern in MDD patients was spatially correlated with the distribution pattern of 5-HT1AR. LIMITATIONS: drug effect; the cross-sectional research design precludes causal inferences; the neurotransmitter atlases selected were constructed from healthy individuals rather than MDD patients. CONCLUSION: These findings characterized the abnormal inter-hemispheric cooperation in MDD using a novel method and the underlying neurotransmitter mechanism, which promotes our understanding of the pathophysiology of depression.

Leukocyte counts and ratios as potential predictors of large vessel occlusion in acute ischemic stroke: A retrospective cohort study.

Leukocyte counts and ratios are independent biomarkers to determine the severity and prognosis of acute ischemic stroke (AIS). In AIS, the connection between leukocytes and large vessel occlusion (LVO) is uncertain. This study aims to determine the relationship between the existence of LVO and leukocyte counts and ratios on admission to AIS. Patients were retrospectively evaluated within six hours of AIS starting between January 2019 and April 2023. On admission, blood specimens were collected, and leukocyte subtype counts were promptly analyzed. Computed tomography or digital subtraction angiography were utilized to verify the existence of LVO. Regression analysis and receiver operating characteristic (ROC) curves were employed to investigate the connections between the counts and ratios of leukocytes and the existence of LVO, as well as the discriminatory ability of these variables in predicting LVO. Total white blood cell (WBC) count, neutrophil count, and neutrophil-to-lymphocyte ratio (NLR) were substantially higher in the LVO existence group compared to the LVO absence group, whereas the ratio of eosinophils to neutrophils (ENR × 102) was lower (P < .001, respectively). Significant associations were observed between total WBC counts, neutrophil counts, NLR, and ENR × 102 and the existence of LVO (P < .001, respectively). Total WBC counts, neutrophil counts, NLR, and ENR × 102 had respective areas under the curves (AUC) of 0.730, 0.748, 0.704, and 0.680 for identifying LVO. Our results show that in AIS patients, the existence of LVO is independently associated with elevated total WBC and neutrophil counts, high NLR, and low ENR × 102 levels. Neutrophil and total WBC counts, as well as NLR and levels of ENR × 102, may serve as potential biomarkers for predicting LVO. Neuroinflammation, based on the existence of LVO, should be given particular attention in future investigations.

First Report of Alternaria alternata Causing Leaf Spot on Catalpa bungei in China.

Catalpa bungei originates from China. It is fast-growing and possesses a vertically aligned trunk, rendering it a commendable construction material and a significant economic species. In July 2022, a serious leaf spot occurred in the LanLake farm (surveyed area of about 700 acres) in Nanyang (33°3'23" N, 112°28'50" E), Henan Province, China. The incidence rate of leaf disease reached 54% (n=100). The disease initially manifested as irregular round spots with a yellowish-brown hue, subsequently extending in all directions. Later, the lesion periphery exhibited a darkening effect, leading to yellowing. Twenty diseased leaves were randomly collected and cut into small pieces at the interfaces between infected and healthy tissues. The tissues were sterilized in a solution of 75% ethanol and 1% NaClO for 30 seconds and 1 minute, respectively. After rinsing in sterile water, the pieces were placed on potato dextrose agar (PDA) plates and incubated at 25°C for 5 days. A total of 29 purified fungal strains were acquired, exhibiting comparable phenotypes in terms of morphological characteristics. Three strains (QS1-1, QS1-2, and QS1-3) were isolated for subsequent investigations. The colony exhibited abundant aerial mycelium with shades ranging from dark green to grey-brown on the reverse side. To analyze the morphological characteristics of conidia, potato carrot agar (PCA) was used as the culture medium and incubated at 25°C with a 12-hour light/dark cycle. Conidia were obclavate or spheroidal, dark brown, with 3 to 5 transverse septa, and 1 to 4 longitudinal septa, measuring 12.4 to 36.7 × 4.4 to 9.0 µm (n=100), with conical beak lengths ranging from 0 to 4.3 µm. These morphological traits suggested that the pathogen shares similarities with the Alternaria species. The rDNA internal transcribed spacer (ITS), translation elongation factor 1-alpha gene (tef1), glyceraldehyde 3-phosphate dehydrogenase gene (gapdh), and RNA polymerase II second largest subunit (rpb2) were amplified for further molecular identification. The resultant sequences were submitted to GenBank with the following accession numbers: OR733559, OR742124, OR761873 (ITS), OR939796, OR939797, OR939798 (tef1), OR939801, OR939802, OR939803 (gapdh), and PP054846, PP054847, PP054848 (rpb2). A Phylogenetic tree was constructed of combined genes (ITS, tef1, gapdh, and rpb2) of sequences, alongside the sequences of the type strains by the neighbor-joining method. The three strains formed a clade with the strains CBS 121456 of Alternaria alternata in phylogenetic trees, being separated from other Alternaria spp. The morphological features and molecular analyses supported the strains as members of Alternaria alternata (Woudenberg et al. 2015). To validate pathogenicity, a conidial suspension (106 conidia ml-1) of all three strains was inoculated onto three healthy leaves of five seedlings, with 50 µl of inoculum absorbed with cotton balls. Another group of five plants received sterile water as a control. All plants were incubated in a climate chamber at 28°C and 90% relative humidity. Four days post-inoculation, lesions resembling natural phenomena were observed, whereas control plants showed no symptoms. Subsequent reisolation produced cultures that were morphologically and molecularly identical to the original strains, fulfilling Koch's postulates. Stem canker of C. bungei caused by Phytophthora nicotianae has been reported in China (Chang et al. 2022). This is the first report of A. alternata causing leaf spots on C. bungei in China. Further research is required on management options to control this disease and the host range still needs to be clarified for accurate disease management.

Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs.

BACKGROUND: Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is one of the causes of tumor immune tolerance and failure of cancer immunotherapy. Here, we found that bladder cancer (BCa)-derived exosomal circRNA_0013936 could enhance the immunosuppressive activity of PMN-MDSCs by regulating the expression of fatty acid transporter protein 2 (FATP2) and receptor-interacting protein kinase 3 (RIPK3). However, the underlying mechanism remains largely unknown. METHODS: BCa-derived exosomes was isolated and used for a series of experiments. RNA sequencing was used to identify the differentially expressed circRNAs. Western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, ELISA and Flow cytometry were performed to reveal the potential mechanism of circRNA_0013936 promoting the immunosuppressive activity of PMN-MDSC. RESULTS: CircRNA_0013936 enriched in BCa-derived exosomes could promote the expression of FATP2 and inhibit the expression of RIPK3 in PMN-MDSCs. Mechanistically, circRNA_0013936 promoted the expression of FATP2 and inhibited the expression of RIPK3 expression via sponging miR-320a and miR-301b, which directly targeted JAK2 and CREB1 respectively. Ultimately, circRNA_0013936 significantly inhibited the functions of CD8+ T cells by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway, and down-regulating RIPK3 through the circRNA_0013936/miR-301b/CREB1 pathway in PMN-MDSCs. CONCLUSIONS: BCa-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway and down-regulating RIPK3 through the circRNA_0013936/miR-301b-3p/CREB1 pathway in PMN-MDSCs. These findings help to find new targets for clinical treatment of human bladder cancer.

Bioelectricity and CO2-to-butyrate production using photobioelectrochemical cells with bio-hydrogel.

Bio-photoelectrochemical cell (BPEC) is an emerging technology that can convert the solar energy into electricity or chemicals. However, traditional BPEC depending on abiotic electrodes is challenging for microbial/enzymatic catalysis because of the inefficient electron exchange. Here, electroactive bacteria (Shewanella loihica PV-4) were used to reduce graphene oxide (rGO) nanosheets and produce co-assembled rGO/Shewanella biohydrogel as a basic electrode. By adsorbing chlorophyll contained thylakoid membrane, this biohydrogel was fabricated as a photoanode that delivered maximum photocurrent 126 µA/cm3 under visible light. Impressively, the biohydrogel could be served as a cathode in BPEC by forming coculture system with genetically edited Clostridium ljungdahlii. Under illumination, the BPEC with above photoanode and cathode yielded âˆ¼ 5.4 mM butyrate from CO2 reduction, 169 % increase compared to dark process. This work provided a new strategy (nanotechnology combined with synthetic biology) to achieve efficient bioelectricity and valuable chemical production in PBEC.

Artificial and Biosynthetic Nanoparticles Boost Bioelectrochemical Reactions via Efficient Bidirectional Electron Transfer of Shewanella loihica.

Bioelectrochemical reactions using whole-cell biocatalysts are promising carbon-neutral approaches because of their easy operation, low cost, and sustainability. Bidirectional (outward or inward) electron transfer via exoelectrogens plays the main role in driving bioelectrochemical reactions. However, the low electron transfer efficiency seriously inhibits bioelectrochemical reaction kinetics. Here, a three dimensional and artificial nanoparticles-constituent inverse opal-indium tin oxide (IO-ITO) electrode is fabricated and employed to connect with exoelectrogens (Shewanella loihica PV-4). The above electrode collected 128-fold higher cell density and exhibited a maximum current output approaching 1.5 mA cm-2 within 24 h at anode mode. By changing the IO-ITO electrode to cathode mode, the exoelectrogens exhibited the attractive ability of extracellular electron uptake to reduce fumarate and 16 times higher reverse current than the commercial carbon electrode. Notably, Fe-containing oxide nanoparticles are biologically synthesized at both sides of the outer cell membrane and probably contributed to direct electron transfer with the transmembrane c-type cytochromes. Owing to the efficient electron exchange via artificial and biosynthetic nanoparticles, bioelectrochemical CO2 reduction is also realized at the cathode. This work not only explored the possibility of augmenting bidirectional electron transfer but also provided a new strategy to boost bioelectrochemical reactions by introducing biohybrid nanoparticles.

Microbiological impact of long-term wine grape cultivation on soil organic carbon in desert ecosystems: a study on rhizosphere and bulk sandy soils.

The improvement of nutrients in soil is essential for using deserts and decertified ecosystems and promoting sustainable agriculture. Grapevines are suitable crops for desert soils as they can adapt to harsh environments and effectively impact soil nutrients; however, the mechanisms underlying this remain unclear. This study explored the impact of the different duration(3, 6, and 10 years) of grape cultivation on soil organic carbon, physicochemical properties, enzyme activities, microbial communities, and carbon cycle pathways in both rhizosphere and bulk soils. Partial least squares path modeling was used to further reveal how these factors contributed to soil nutrient improvement. Our findings indicate that after long-term grape cultivation six years, soil organic carbon, total nitrogen, total phosphorus, microbial biomass carbon and nitrogen, and enzyme activities has significantly increased in both rhizosphere and bulk soils but microbial diversity decreased in bulk soil. According to the microbial community assembly analysis, we found that stochastic processes, particularly homogenizing dispersal, were dominant in both soils. Bacteria are more sensitive to environmental changes than fungi. In the bulk soil, long-term grape cultivation leads to a reduction in ecological niches and an increase in salinity, resulting in a decrease in soil microbial diversity. Soil enzymes play an important role in increasing soil organic matter in bulk soil by decomposing plant litters, while fungi play an important role in increasing soil organic matter in the rhizosphere, possibly by decomposing fine roots and producing mycelia. Our findings enhance understanding of the mechanisms of soil organic carbon improvement under long-term grape cultivation and suggest that grapes are suitable crops for restoring desert ecosystems.

Efficacy, safety, and cost-effectiveness analysis of Cerebrolysin in acute ischemic stroke: A rapid health technology assessment.

This study conducts a rapid health technology assessment to systematically evaluate the effectiveness, safety, and cost-effectiveness of Cerebrolysin as an adjunctive therapy for acute ischemic stroke to provide evidence-based medicine for clinical decisions of Cerebrolysin. All systematic reviews/meta-analyses, pharmacoeconomic studies, and health technology assessment reports of Cerebrolysin for the treatment of acute ischemic stroke before August 17, 2023, were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Weipu, Sinomed database and the official website of health technology assessment. According to the inclusion and exclusion criteria, 2 researchers independently carried out screening, data extraction, and quality evaluation and descriptively analyzed the results of the included studies. A total of 14 pieces of literature were incorporated, comprising 8 systematic reviews/meta-analyses and 6 pharmacoeconomic studies. In terms of effectiveness, compared to control groups, the use of Cerebrolysin as a treatment for acute ischemic stroke demonstrates certain advantages, including enhancement in total efficacy rate, neurological function, upper limb motor dysfunction, and facilitation of the recovery of activities of daily living. Especially in patients with moderate to severe acute ischemic stroke, Cerebrolysin has demonstrated the ability to enhance neurological function recovery and ameliorate disabilities. Regarding safety, adverse reactions were mild or comparable to those in the control group. The primary findings of economic studies reveal that advocating for the use of Cerebrolysin offers certain cost-effectiveness advantages. Cerebrolysin contributes to improved clinical efficacy and evaluation indexes while demonstrating favorable safety and economic benefits.

LncRNAs associated with lymph node metastasis in thyroid cancer based on TCGA database.

OBJECTIVE: Long non-coding RNA (lncRNA), especially RNA associated with lymph node metastasis, plays an important role in the development of cancer. Identifying metastasis related lncRNAs and exploring their clinical significance can guide the treatment and prognosis of thyroid cancer patients. METHODS: RNA expression and clinical data of thyroid cancer was derived from The Cancer Genome Atlas (TCGA) database, while the survival data was obtained from the ULCAN database. R language and SPSS software were used to analyze the correlation between lncRNA and lymph node metastasis of thyroid cancer and the lncRNAs associated with lymph node metastasis were screened. RESULT: 10 lncRNAs showed significant differential expression in thyroid cancer with and without lymph node metastasis. Four lncRNAs (LRRC52-AS1, AP002358.1, AC004847.1, and AC254633.1) were overexpressed in metastatic thyroid cancer, while six lncRNAs (SLC26A4-AS1, LINC01886, LINC01789, AF131216.3, AC062015.1, and AL031710.1) were underexpressed. The expression levels of these lncRNAs were associated with the clinical staging of tumors. Cox regression analysis further showed that elevated expression levels of AP002358.1 and LRRC52-AS1 were associated with poor prognosis in patients with thyroid cancer. In addition, analysis of the UALCAN database indicated that these two lncRNAs were significantly overexpressed in thyroid cancer compared to other cancers, and the expression levels of AF131216.3 and AL031710.1 were associated with progression-free survival in thyroid cancer patients. CONCLUSION: These lncRNAs may play crucial roles in the development and progression of thyroid cancer and could serve as potential markers for predicting tumor metastasis, clinical stage, and patient prognosis.

Clinicopathological features of differentiated thyroid carcinoma as predictors of the effects of radioactive iodine therapy.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis; however, 5 %-15 % develop radioactive iodine-refractory (RAIR) DTC (RAIR-DTC), which has a poor prognosis and limited treatment options. The aim of the present study was to investigate the clinicopathological characteristics of RAIR-DTC in order to provide clinical evidence for timely prediction of the effects of iodine therapy. METHODS: Clinicopathological data for 44 patients with RAIR-DTC and 50 patients with radioiodine-avid DTC (RAIA-DTC) were retrospectively analyzed. The risk factors for RAIR-DTC were evaluated and a RAIR-DTC prediction model was established. RESULTS: RAIR-DTC showed unique clinicopathological features that differed from those of RAIA-DTC; these included age >55 years, a high-risk histological subtype, a large tumor size, a late TNM stage, calcification, distant metastasis, and more than six metastatic lymph nodes. Patients with RAIR-DTC also developed earlier tumor progression. Binary logistic regression analysis showed that distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm were independent risk factors for RAIR-DTC, and the specificity and sensitivity of a combination of these three parameters for the prediction of RAIR-DTC were 98.0 % and 56.8 %, respectively. Decision curve analysis and the calibration curve revealed that the combined prediction of these three parameters had good repeatability and accuracy. CONCLUSION: The clinicopathological features of DTC can effectively predict the effects of iodine therapy. A combination of distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm showed significantly higher prediction accuracy.

CD70-induced differentiation of proinflammatory Th1/17/22/GM lymphocytes associated with disease progression and immune reconstitution during HIV infection.

Immune overactivation is a hallmark of chronic HIV infection, which is critical to HIV pathogenesis and disease progression. The imbalance of helper T cell (Th) differentiation and subsequent cytokine dysregulation are generally considered to be the major drivers of excessive activation and inflammatory disorders in HIV infection. However, the accurate factors driving HIV-associated Th changes remained to be established. CD70, which was a costimulatory molecule, was found to increase on CD4+ T cells during HIV infection. Overexpression of CD70 on CD4+ T cells was recently reported to associate with highly pathogenic proinflammatory Th1/Th17 polarization in multiple sclerosis. Thus, the role of CD70 in the imbalance of Th polarization and immune overactivation during HIV infection needs to be investigated. Here, we found that the elevated frequency of CD70 + CD4+ T cells was negatively correlated with CD4 count and positively associated with immune activation in treatment-naïve people living with HIV (PLWH). More importantly, CD70 expression defined a population of proinflammatory Th1/17/22/GM subsets in PLWH. Blocking CD70 decreased the mRNA expression of subset-specific markers during Th1/17/22/GM polarization. Furthermore, we demonstrated that CD70 influenced the differentiation of these Th cells through STAT pathway. Finally, it was revealed that patients with a high baseline level of CD70 on CD4+ T cells exhibited a greater risk of poor immune reconstitution after antiretroviral therapy (ART) than those with low CD70. In general, our data highlighted the role of CD70 in Th1/17/22/GM differentiation during HIV infection and provided evidence for CD70 as a potential biomarker for predicting immune recovery.

Characterization of the complete chloroplast genome of Cynanchum acutum subsp. sibiricum (Apocynaceae).

In this study, we assembled the complete chloroplast (cp) genome of Cynanchum acutum subsp. sibiricum using high-throughput Illumina sequencing reads. The resulting chloroplast genome assembly displayed a typical quadripartite structure with a total length of 158,283 bp, which contained a pair of inverted repeat regions (IRs) of 24,459 bp. These two IRs were separated by a large single-copy region (LSC) and a small single-copy region (SSC) of 89,424 bp and 19,941 bp in length, respectively. The C. acutum subsp. sibiricum cp genome contained 130 genes, and its overall GC content was 37.87%. Phylogenetic analysis among C. acutum subsp. sibiricum and nine other Cynanchum species demonstrated that C. acutum subsp. sibiricum was closely related to C. chinense. The C. acutum subsp. sibiricum cp genome presented in this study lays a good foundation for further genetic and genomic studies of the Cynanchum as well as Apocynaceae.

Construction of an infectious cloning system of porcine reproductive and respiratory syndrome virus and identification of glycoprotein 5 as a potential determinant of virulence and pathogenicity.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection of pigs causes a variety of clinical manifestations, depending on the pathogenicity and virulence of the specific strain. Identification and characterization of potential determinant(s) for the pathogenicity and virulence of these strains would be an essential step to precisely design and develop effective anti-PRRSV intervention. In this study, we report the construction of an infectious clone system based on PRRSV vaccine strain SP by homologous recombination technique, and the rescue of a chimeric rSP-HUB2 strain by replacing the GP5 and M protein-coding region from SP strain with the corresponding region from a highly pathogenic strain PRRSV-HUB2. The two recombinant viruses were shown to be genetically stable and share similar growth kinetics, with rSP-HUB2 exhibiting apparent growth and fitness advantages. Compared to in cells infected with PRRSV-rSP, infection of cells with rSP-HUB2 showed significantly more inhibition of the induction of type I interferon (IFN-ß) and interferon stimulator gene 56 (ISG56), and significantly more promotion of the induction of proinflammatory cytokines IL-6, IL-8, ISG15 and ISG20. Further overexpression, deletion and mutagenesis studies demonstrated that amino acid residue F16 in the N-terminal region of the GP5 protein from HUB2 was a determinant for the phenotypic difference between the two recombinant viruses. This study provides evidence that GP5 may function as a potential determinant for the pathogenicity and virulence of highly pathogenic PRRSV.

Risk factors and clinical outcomes of basilar artery occlusion presenting with paroxysmal sympathetic hyperactivity as the initial manifestation: a prospective study.

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) has been linked to a worse clinical prognosis in patients with traumatic brain injury. We aimed to identify the risk factors and clinical features associated with basilar artery occlusion (BAO) presenting with PSH as the first clinical presentation. METHODS: This study recruited patients with acute BAO who received endovascular therapy (EVT) at two stroke centers in China. PSH Assessment Measure ≥8 was included in the PSH+ group, while those with a score below 8 were classified as the PSH- group. Clinical data and radiological findings were compared between the two groups. A binary logistic regression model was employed to identify independent risk factors for PSH. RESULTS: 101 participants were enrolled, of whom 19 (18.8%) presented with PSH as the initial manifestation of BAO. Worse prognosis (modified Rankin Scale score of 4-6) at day 90 occurred in 14 (73.7%) of the PSH+ patients and 42 (51.2%) of the PSH- patients (P=0.076). The 90-day mortality rate was higher in the PSH+ group with 12 (63.2%) participants, compared with 31 (37.8%) participants in the PSH- group (P=0.044). A significantly increased risk of PSH was found in patients with midbrain involvement (OR 6.53, 95% CI 1.56 to 27.30, P=0.01) and a high baseline National Institutes of Health Stroke Scale (NIHSS) score (OR 1.15, 95% CI 1.01 to 1.31, P=0.037). CONCLUSIONS: Patients with BAO presenting with PSH as the initial clinical manifestation experience a higher risk of 90-day mortality, despite undergoing EVT. Midbrain infarction and baseline NIHSS score may be significant risk factors for PSH following BAO.

The structural modification and biological evaluation of tetrahydrothienopyridine derivatives as selective BChE inhibitors.

A series of tetrahydrothienopyridine derivatives have been designed, synthesized, and evaluated as selective BChE inhibitors. Compounds were analyzed via HRMS, 1H NMR, and 13C NMR. The inhibitory effects were evaluated according to the method of Ellman et al. 6n was the most potent and selective inhibitor against BChE (eeAChE IC50 = 686.4 ± 478.6 µM, eqBChE IC50 = 10.5 ± 5.0 nM, SI = 6.5*104, hBChE IC50 = 32.5 ± 6.5 nM). Cell-based assays have confirmed the low neurotoxicity of 6a and 6n and their moderate neuroprotective effects. Compounds 6a and 6n provide novel chemical entities for the treatment of Alzheimer's disease.

Mechanistic Insights into Radical-Induced Selective Oxidation of Methane over Nonmetallic Boron Nitride Catalysts.

Boron-based nonmetallic materials (such as B2O3 and BN) emerge as promising catalysts for selective oxidation of light alkanes by O2 to form value-added products, resulting from their unique advantage in suppressing CO2 formation. However, the site requirements and reaction mechanism of these boron-based catalysts are still in vigorous debate, especially for methane (the most stable and abundant alkane). Here, we show that hexagonal BN (h-BN) exhibits high selectivities to formaldehyde and CO in catalyzing aerobic oxidation of methane, similar to Al2O3-supported B2O3 catalysts, while h-BN requires an extra induction period to reach a steady state. According to various structural characterizations, we find that active boron oxide species are gradually formed in situ on the surface of h-BN, which accounts for the observed induction period. Unexpectedly, kinetic studies on the effects of void space, catalyst loading, and methane conversion all indicate that h-BN merely acts as a radical generator to induce gas-phase radical reactions of methane oxidation, in contrast to the predominant surface reactions on B2O3/Al2O3 catalysts. Consequently, a revised kinetic model is developed to accurately describe the gas-phase radical feature of methane oxidation over h-BN. With the aid of in situ synchrotron vacuum ultraviolet photoionization mass spectroscopy, the methyl radical (CH3•) is further verified as the primary reactive species that triggers the gas-phase methane oxidation network. Theoretical calculations elucidate that the moderate H-abstraction ability of predominant CH3• and CH3OO• radicals renders an easier control of the methane oxidation selectivity compared to other oxygen-containing radicals generally proposed for such processes, bringing deeper understanding of the excellent anti-overoxidation ability of boron-based catalysts.