Development and validation of a scoring system to predict the mortality of hospitalized patients with SARS-CoV-2 Omicron: a nationwide, multicentre study.

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.

Antibiofilm Metabolites from Marine-derived Streptomyces sp. ZS-A31.

A novel compound streptothiomycin F (1), and a new natural product, N-(5-nitropentyl)acetamide (2), were discovered alongside ten previously identified compounds (3-12) through solid fermentation of marine-derived Streptomyces sp. ZS-A31 based on rice. The chemical structures of compounds 1-2 were elucidated using 1D and 2D NMR, as well as HRESIMS data analysis. Evaluation of all isolated compounds for their antibiofilm and antibacterial activities against P. aeruginosa was carried out using microdilution and crystal violet staining methods. Results highlighted the weak potency of the known compounds lumichrome (3) and vanillic acid (7) in inhibiting biofilm formation.

Enhanced Catalytic Oxidation Reactivity over Atomically Dispersed Pt/CeO2 Catalysts by CO Activation.

The elevation of the low-temperature oxidation activity for Pt/CeO2 catalysts is challenging to meet the increasingly stringent requirements for effectively eliminating carbon monoxide (CO) from automobile exhaust. Although reducing activation is a facile strategy for boosting reactivity, past research has mainly concentrated on applying H2 as the reductant, ignoring the reduction capabilities of CO itself, a prevalent component of automobile exhaust. Herein, atomically dispersed Pt/CeO2 was fabricated and activated by CO, which could lower the 90% conversion temperature (T90) by 256 °C and achieve a 20-fold higher CO consumption rate at 200 °C. The activated Pt/CeO2 catalysts showed exceptional catalytic oxidation activity and robust hydrothermal stability under the simulated working conditions for gasoline or diesel exhausts. Characterization results illustrated that the CO activation triggered the formation of a large portion of Pt0 terrace sites, acting as inherent active sites for CO oxidation. Besides, CO activation weakened the Pt-O-Ce bond strength to generate a surface oxygen vacancy (Vo). It served as the oxygen reservoir to store the dissociated oxygen and convert it into active dioxygen intermediates. Conversely, H2 activation failed to stimulate Vo, but triggered a deactivating transformation of the Pt nanocluster into inactive PtxOy in the presence of oxygen. The present work offers coherent insight into the upsurging effect of CO activation on Pt/CeO2, aiming to set up a valuable avenue in elevating the efficiency of eliminating CO, C3H6, and NH3 from automobile exhaust.

Trajectories of anxiety and depression among Chinese men who have sex with men on pre-exposure prophylaxis: a group-based trajectory model approach.

BACKGROUND: Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. METHODS: From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. RESULTS: A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18-30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. CONCLUSIONS: Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.

Sulphated Fucooligosaccharide from Sargassum Horneri: Structural Analysis and Anti-Alzheimer Activity.

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.

Approaches for Performance Verification Toward Standardization of Peripheral Blood Regulatory T-Cell Detection by Flow Cytometry.

CONTEXT.­: Regulatory T-cell (Treg) detection in peripheral blood, based on flow cytometry, is invaluable for diagnosis and treatment of immune-mediated diseases. However, there is a lack of reliable methods to verify the performance, which is pivotal towards standardization of the Tregs assay. OBJECTIVE.­: To conduct standardization studies and verify the performance of 3 commercially available reagent sets for the Tregs assay based on flow cytometry and agreement analysis for Treg detection across the different reagent sets. DESIGN.­: The analytical performance of Tregs assay using reagent sets supplied by 3 manufacturers was evaluated after establishing the gating strategy and determining the optimal antibody concentration. Postcollection sample stability was evaluated, as well as the repeatability, reproducibility, reportable range, linearity, and assay carryover. Agreement between the different assays was assessed via Bland-Altman plots and linear regression analysis. The relationship between the frequency of CD4+CD25+CD127low/- Tregs and CD4+CD25+Foxp3+ Tregs was evaluated. RESULTS.­: The postcollection sample stability was set at 72 hours after collection at room temperature. The accuracy, repeatability, reproducibility, and accuracy all met the requirements for clinical analysis. Excellent linearity, with R2 ≥0.9 and no assay carryover, was observed. For reportable range, a minimum of 1000 events in the CD3+CD4+ gate was required for Tregs assay. Moreover, the results for Tregs labeled by antibodies from the 3 manufacturers were in good agreement. The percentage of CD4+CD25+CD127low/- Tregs was closely correlated with CD4+CD25+Foxp3+ Tregs. CONCLUSIONS.­: This is the first study to evaluate systematically the measurement performance of Tregs in peripheral blood by flow cytometry, which provides a practical solution to verifying the performance of flow cytometry-based immune monitoring projects in clinical practice.

PSCK9 inhibitors reduced early recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis.

BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) is prone to cause early recurrent stroke (ERS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels and prevent cardiovascular events. This multicentre, hospital-based prospective cohort study was designed to investigate whether PCSK9 inhibitors would prevent ERS in patients with symptomatic ICAS. METHODS: From 1 October 2020 to 30 September 2022, consecutive patients with acute ischaemic stroke attributed to ICAS admitted within 1 week after onset were enrolled and followed up for 1 month. Patients were divided into two groups, the PCSK9 inhibitors group receiving PCSK9 inhibitors add-on therapy, and the control group receiving statins and/or ezetimibe. The primary outcome was ERS. Cox proportional hazard models and Kaplan-Meier survival curve were used to estimate the association between PCSK9 inhibitors and ERS. RESULTS: At the end of follow-up, the LDL-C levels were further lowered by PCSK9 inhibitors add-on therapy (n=232, from 3.06±1.16 mmol/L to 2.12±1.19 mmol/L) than statins and/or ezetimibe treatment (n=429, from 2.91±1.05 mmol/L to 2.64±0.86 mmol/L, p<0.001). The Kaplan-Meier survival curves showed that PCSK9 inhibitors add-on therapy significantly reduced ERS (5.59%, 24/429, vs 2.16%, 5/232; log-rank test, p=0.044). The multivariate Cox regression analysis revealed that, after adjusting for confounders with a p value less than 0.05 in univariate analysis or of particular importance, the HR was 0.335 (95% CI 0.114 to 0.986, p=0.047), compared with the control group. CONCLUSIONS: In our study, PCSK9 inhibitors add-on therapy further reduced LDL-C levels and ERS in patients with symptomatic ICAS.

New Alpiniamide-Type Polyketide with Antibiofilm Activities from the Marine-Derived Streptomyces sp. ZS-A65.

Two new alpiniamide-type polyketides, alpiniamides H-I (1-2), in addition to four recognized compounds, were discovered in Streptomyces sp. ZSA65 derived from the marine sediments. The planar structure and absolute configuration of alpiniamides H-I were elucidated using a combination of 1D, 2D NMR, HRESIMS data analysis, Mosher's method and ECD calculations. The antibiofilm and antibacterial activities against P. aeruginosa were evaluated using the microdilution method. Notably, Compound 2 exhibited strong antibiofilm property.

Cytotoxic and Antifungal Staurosporine Derivatives from Marine-Derived Actinomycete Streptomyces sp. ZS-A121.

A novel staurosporine derivate, streptomholyrine A (1), along with 6 known compounds were identified from the rice-based solid fermentation of marine-derived Streptomyces sp. ZS-A121. The planar structure and absolute configuration of streptomholyrine A were elucidated using a combination of 1D, 2D NMR, HRESIMS data analysis, chemical transformation, ECD and NMR calculations. Screening of all these compounds revealed their cytotoxic activity against HCT-116 cell lines, with IC50 values ranging from 0.012 to 11.67 µM, except for the known 1H-indole-3-hydroxyacetyl, which showed no inhibition activity. Furthermore, streptomholyrine A, along with two known staurosporine derivatives, k252d and staurosporine, exhibited activities against Candida albicans, with MICs of 12.5, 25.0 and 50.0 µg/ml, respectively.

Willingness to take long-acting injectable pre-exposure prophylaxis among men who have sex with men who participated in the CROPrEP study: a cross-sectional online study.

INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Inhibitory receptor CD47 binding to plasma TSP1 suppresses NK-cell IFN-γ production via activating the JAK/STAT3 pathway during HIV infection.

BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.

Online distribution of HIV self-testing kits to promote HIV testing among men who have sex with men discontinuing pre-exposure prophylaxis after demonstration project completion in China: a multicentre open-label randomized controlled trial.

Background: HIV self-testing (HIVST) offers potential solutions to challenges associated with site-based HIV testing (SBHT). However, the effectiveness of HIVST as an HIV prevention strategy for men who have sex with men (MSM) discontinuing pre-exposure prophylaxis (PrEP) after the completion of PrEP demonstration project has rarely been assessed. Methods: The China Real-world Study of Oral PrEP (CROPrEP) project was conducted in four cities in China. Participants were directed to community resources to continue their PrEP medication after the discontinuation of project-provided PrEP at the last CROPrEP visit. We conducted a multicentre open-label randomized controlled trial among MSM who had discontinued PrEP induced by the completion of CROPrEP. Eligible participants were randomly assigned to either the intervention group or the control group (1:1). Participants received regular health education and behavioural interventions throughout the trial. The intervention group was given a link to order free HIVST kits online, while the control group received information about free SBHT. Both groups completed internet-based follow-up surveys at three and six months. The primary outcome was the proportion of participants who underwent HIV testing during the six-month follow-up period. This trial was registered at chictr.org.cn (ChiCTR2000038416). Findings: Between November 2020 and January 2021, we recruited a total of 620 participants (300 in the intervention group and 320 in the control group). The follow-up completion rates were 99·0% and 95·0% in the intervention and control groups, respectively. At baseline, the median age of participants was 32 (interquartile range: 26-37), and 77·7% underwent HIV testing in the past three months. The proportion of participants who underwent HIV testing in the past three months was higher in the intervention group than in the control group at both the three-month (adjusted risk difference [RD]: 36·7, 95% confidence interval [CI]: 35·1-38·5, p < 0·001) and six-month (RD: 26·7, 95% CI: 24·6-28·7 p < 0·001) follow-up periods. Interpretation: Our study suggests that providing online distribution of HIVST kits for MSM with PrEP discontinuation induced by completion of the PrEP project effectively promoted HIV testing. This digital approach improves access to HIV testing for MSM and can be applicable to other settings where MSM turn to online public health services. Funding: The study was funded by the Fund of National Natural Science Foundation of China; the Mega-Projects of National Science Research for the 13th Five-Year Plan; and the Liaoning Revitalization Talents Program, China.

Recovery of carbon from spent carbon cathode by alkaline and acid leaching and thermal treatment and exploration of its application in lithium-ion batteries.

The spent carbon cathode (SCC) is a hazardous solid waste from aluminum production. It has an abundant carbon source and a unique graphitic carbon layer structure, making it a valuable waste for recycling. This paper uses alkaline and acid leaching methods to report a straightforward way of extracting recovered carbon (RC) from SCC as anode material for lithium-ion batteries (LIBs). The results show that alkaline and acid leaching conditions at 70 °C with 1 M NaOH and HCl solution individually in 6 h and a liquid-solid ratio of 20:1 can result in RC with up to 94.63% carbon content than 49.38% in SCC, exhibiting a typical graphite structure. SCC and RC materials are obtained after calcination at 400 °C in an inert atmosphere and used as anode materials (SCC-400 and RC-400). In this paper, The initial charging specific capacities are 490.0 mA h g-1, 195.4 mA h g-1, and 423.2 mA h g-1and initial coulombic efficiencies (ICE) are 67.8%, 78.9%, and 72.0% of RC-400, SCC, and SCC-400. RC-400 also shows excellent capacity retention and impedance values. This exciting finding provides a viable, non-hazardous, and resourceful method for treating and disposing of SCC from aluminum electrolysis.

Selected Bacteria Are Critical for Karst River Carbon Sequestration via Integrating Multi-omics and Hydrochemistry Data.

Recalcitrant dissolved organic carbon (RDOC) produced by microbial carbon pumps (MCPs) in the ocean is crucial for carbon sequestration and regulating climate change in the history of Earth. However, the importance of microbes on RDOC formation in terrestrial aquatic systems, such as rivers and lakes, remains to be determined. By integrating metagenomic (MG) and metatranscriptomic (MT) sequencing, we defined the microbial communities and their transcriptional activities in both water and silt of a typical karst river, the Lijiang River, in Southwest China. Betaproteobacteria predominated in water, serving as the most prevalent population remodeling components of dissolved organic carbon (DOC). Binning method recovered 45 metagenome-assembled genomes (MAGs) from water and silt. Functional annotation of MAGs showed Proteobacteria was less versatile in degrading complex carbon, though cellulose and chitin utilization genes were widespread in this phylum, whereas Bacteroidetes had high potential for the utilization of macro-molecular organic carbon. Metabolic remodeling revealed that increased shared metabolites within the bacterial community are associated with increased concentration of DOC, highlighting the significance of microbial cooperation during producing and remodeling of carbon components. Beta-oxidation, leucine degradation, and mevalonate (MVA) modules were significantly positively correlated with the concentration of RDOC. Blockage of the leucine degradation pathway in Limnohabitans and UBA4660-related MAGs were associated with decreased RDOC in the karst river, while the Fluviicola-related MAG containing a complete leucine degradation pathway was positively correlated with RDOC concentration. Collectively, our study revealed the linkage between bacteria metabolic processes and carbon sequestration. This provided novel insights into the microbial roles in karst-rivers carbon sink.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

Silver and Copper Dual Single Atoms Boosting Direct Oxidation of Methane to Methanol via Synergistic Catalysis.

Rationally constructing atom-precise active sites is highly important to promote their catalytic performance but still challenging. Herein, this work designs and constructs ZSM-5 supported Cu and Ag dual single atoms as a proof-of-concept catalyst (Ag1 -Cu1 /ZSM-5 hetero-SAC (single-atom catalyst)) to boost direct oxidation of methane (DOM) by H2 O2 . The Ag1 -Cu1 /ZSM-5 hetero-SAC synthesized via a modified co-adsorption strategy yields a methanol productivity of 20,115 µmol gcat -1 with 81% selectivity at 70 °C within 30 min, which surpasses most of the state-of-the-art noble metal catalysts. The characterization results prove that the synergistic interaction between silver and copper facilitates the formation of highly reactive surface hydroxyl species to activate the C-H bond as well as the activity, selectivity, and stability of DOM compared with SACs, which is the key to the enhanced catalytic performance. This work believes the atomic-level design strategy on dual-single-atom active sites should pave the way to designing advanced catalysts for methane conversion.

In Situ and Emerging Transmission Electron Microscopy for Catalysis Research.

Catalysts are the primary facilitator in many dynamic processes. Therefore, a thorough understanding of these processes has vast implications for a myriad of energy systems. The scanning/transmission electron microscope (S/TEM) is a powerful tool not only for atomic-scale characterization but also in situ catalytic experimentation. Techniques such as liquid and gas phase electron microscopy allow the observation of catalysts in an environment conducive to catalytic reactions. Correlated algorithms can greatly improve microscopy data processing and expand multidimensional data handling. Furthermore, new techniques including 4D-STEM, atomic electron tomography, cryogenic electron microscopy, and monochromated electron energy loss spectroscopy (EELS) push the boundaries of our comprehension of catalyst behavior. In this review, we discuss the existing and emergent techniques for observing catalysts using S/TEM. Challenges and opportunities highlighted aim to inspire and accelerate the use of electron microscopy to further investigate the complex interplay of catalytic systems.

GABAergic neurons differentiated from BDNF- and Dlx2-modified neural stem cells restore disrupted neural circuits in brainstem stroke.

BACKGROUND: Brainstem stroke causes severe and persistent neurological impairment. Due to the limited spontaneous recovery and regeneration of the disrupted neural circuits, transplantation of exogenous neural stem cells (NSCs) was an alternative, while there were limitations for primitive NSCs. METHODS: We established a mouse model of brainstem stroke by injecting endothelin in the right pons. Brain-derived neurotrophic factor (BDNF)- and distal-less homeobox 2 (Dlx2)-modified NSCs were transplanted to treat brainstem stroke. Transsynaptic viral tracking, immunostaining, magnetic resonance imaging, behavioral testing, and whole-cell patch clamp recordings were applied to probe the pathophysiology and therapeutic prospects of BDNF- and Dlx2-modified NSCs. RESULTS: GABAergic neurons were predominantly lost after the brainstem stroke. No endogenous NSCs were generated in situ or migrated from the neurogenesis niches within the brainstem infarct region. Co-overexpressions of BDNF and Dlx2 not only promoted the survival of NSCs, but also boosted the differentiation of NSCs into GABAergic neurons. Results from transsynaptic virus tracking, immunostaining, and evidence from whole-cell patch clamping revealed the morphological and functional integration of the grafted BDNF- and Dlx2-modified NSCs-derived neurons with the host neural circuits. Neurological function was improved by transplantation of BDNF- and Dlx2-modified NSCs in brainstem stroke. CONCLUSIONS: These findings demonstrated that BDNF- and Dlx2-modified NSCs differentiated into GABAergic neurons, integrated into and reconstituted the host neural networks, and alleviated the ischemic injury. It thus provided a potential therapeutic strategy for brainstem stroke.

Complete genome sequence of Streptomyces sp. HNA39, a new cyclizidine producer isolated from a South China Sea sediment.

Streptomyces sp. HNA39 is a promising candidate for the production of antineoplastic metabolites screened from a collection of 448 actinomycetes derived from coastal sediments. The complete genome sequence of HNA39 comprises a 7,351,753-bp linear chromosome with a GC content of 71.94%. Whole genome analysis reveals the presence of 29 putative biosynthetic gene clusters (BGCs) encoding secondary metabolites. Among them, a type I PKS BGC shows an 82% similarity with the cyclizidine (CLD) BGC identified from Streptomyces NCIB 11649. LC-MS profiles further supported the production of new CLD congeners. Bafilomycins were also found produced in abundance, corresponding to another type I PKS BGC highly homologous to that of bafilomycin B1 from S. lohii. CLDs are indolizidine alkaloids consisting a fused five- and six-membered ring system with an intriguing cyclopropane terminal linked by a trans-dienic chain. The cyclization mechanism of the cylopropyl ring, one of its pharmacophores, is still unknown. Genome sequencing of the new CLD producer and subsequent comparative analysis of their gene clusters would further our understanding of the chemistry behind cyclopropane formation.