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Abstract Small nucleolar RNAs (snoRNAs) were previously regarded as a class of functionally conserved housekeeping genes, primarily involved in the regulation of ribosome biogenesis by ribosomal RNA (rRNA) modification. However, some of them are involved in several biological processes via complex molecular mechanisms. DNA damage response (DDR) is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases. It has recently been revealed that snoRNAs are involved in DDR at multiple levels, indicating their relevant theoretical and clinical significance in this field. The present review systematically addresses four main points, including the biosynthesis and classification of snoRNAs, the mechanisms through which snoRNAs regulate target molecules, snoRNAs in the process of DDR, and the significance of snoRNA in disease diagnosis and treatment. It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.

Abstract Background Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. Results We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. Conclusions Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.

The combination of straw return and nitrogen (N) fertilization is an effective strategy for increasing farmland productivity and improving soil structure while mitigating climate change. However, although straw return practices are widely recommended in agroecosystems targeting sustainable agriculture, few studies have explored changes in grain yield, resource use efficiency, water productivity, and potential interactions between these variables. A field experiment was conducted during 2022–2023 in Northeast China to study the effects of straw return modes and N fertilizer input on maize grain yield and the efficient use of radiation, water, and N. We investigated two straw return tillage methods (rotary tillage with straw returning, RTS; plow tillage with straw returning, PTS) and five N fertilizer levels (0, 112, 187, 262, and 337 kg N ha−1) based on a field location experiment that started in 2015. Compared with RTS treatment, the PTS treatment resulted in a higher photosynthetic capacity by regulating the leaf area index and photosynthetic metabolism, resulting in increased dry matter accumulation and transportation. Such physiological improvements are conducive to increasing the nutrient use efficiency, water productivity, and grain yield. Specifically, PTS combined with the N3 treatment was an efficient tillage mode that increased radiation use efficiency of grain by 123.48 % and 207.41 % and by 153.44 % and 167.37 % in 2022 and 2023, respectively, compared with the PTS and N0 treatment. Together with partial least squares path modeling, regression analysis, and random forest, the variations in the above parameters led to high productivity in terms of N uptake, water productivity, leaf area index, radiation use efficiency, N use efficiency, and dry matter accumulation. Our results highlight the key roles of straw return methods in affecting grain yield, and further suggest that PTS combined with optimized N fertilizer input can enhance resource utilization, leading to a productive, efficient, and sustainable maize population.

BackgroundForest musk deer (FMD, Moschus Berezovskii) is a critically endangered species world-widely, the death of which can be caused by pulmonary disease in the farm. Pulmonary fibrosis (PF) was a huge threat to the health and survival of captive FMD. MicroRNAs (miRNAs) and messenger RNAs (mRNAs) have been involved in the regulation of immune genes and disease development. However, the regulatory profiles of mRNAs and miRNAs involved in immune regulation of FMD are unclear.MethodsIn this study, mRNA-seq and miRNA-seq in blood were performed to constructed coexpression regulatory networks between PF and healthy groups of FMD. The hub immune- and apoptosis-related genes in the PF blood of FMD were explored through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Further, protein–protein interaction (PPI) network of immune-associated and apoptosis-associated key signaling pathways were constructed based on mRNA-miRNA in the PF blood of the FMD. Immune hub DEGs and immune hub DEmiRNAs were selected for experimental verification using RT-qPCR.ResultsA total of 2744 differentially expressed genes (DEGs) and 356 differentially expressed miRNAs (DEmiRNAs) were identified in the PF blood group compared to the healthy blood group. Among them, 42 DEmiRNAs were negatively correlated with 20 immune DEGs from a total of 57 correlations. The DEGs were significantly associated with pathways related to CD molecules, immune disease, immune system, cytokine receptors, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, cytokine-cytokine receptor interaction, intestinal immune network for IgA production, and NOD-like receptor signaling pathway. There were 240 immune-related DEGs, in which 186 immune-related DEGs were up-regulated and 54 immune-related DEGs were down-regulated. In the protein-protein interaction (PPI) analysis of immune-related signaling pathway, TYK2, TLR2, TLR4, IL18, CSF1, CXCL13, LCK, ITGB2, PIK3CB, HCK, CD40, CD86, CCL3, CCR7, IL2RA, TLR3, and IL4R were identified as the hub immune genes. The mRNA-miRNA coregulation analysis showed that let-7d, miR-324-3p, miR-760, miR-185, miR-149, miR-149-5p, and miR-1842-5p are key miRNAs that target DEGs involved in immune disease, immune system and immunoregulation.ConclusionThe development and occurrence of PF were significantly influenced by the immune-related and apoptosis-related genes present in PF blood. mRNAs and miRNAs associated with the development and occurrence of PF in the FMD.

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 μM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 μM) promoted nuclear translocation of β-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the β-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Abstract Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.

ATG1/ATG13, a core kinase complex regulator in the macroautophagy/autophagy machinery during autophagosome formation, is modulated in a sophisticated manner by posttranslational ubiquitination to determine proper autophagy levels in eukaryotic cells. However, the mechanisms that regulate the stability and activity of this complex remain elusive. We recently identified two negative regulators of autophagy, 14-3-3λ and 14-3-3k, that help redundantly regulate autophagy by directly associating with SINAT and ATG13s. The specific interaction between the molecular adaptors 14-3-3λ and 14-3-3κ and phosphorylated ATG13a is crucial for SINAT-mediated ubiquitination and degradation of ATG13a, and for maintenance of the ATG1-ATG13 complex. Consistent with the function of 14-3-3s in autophagy, the 14-3-3λ 14-3-3κ double mutant exhibits enhanced tolerance to nutrient deprivation with constitutive induction of autophagy. These findings demonstrate that 14-3-3λ and 14-3-3k coordinate with SINATs to regulate both the homeostasis of ATG13 phosphorylation and the induction of autophagy in plants.

Abstract This study evaluated the long-term myopia control effect and safety in children wearing Defocus Incorporated Multiple Segments (DIMS) spectacle lenses. Participants who completed the 2-year RCT were followed for a total of 6 years; their cycloplegic refractions and axial length were measured. Group 1 (n = 36) wore DIMS spectacles for 6 years; Group 2 (n = 14) wore DIMS lens for the first 3.5 years and SV spectacles afterwards; Group 3 (n = 22) wore SV spectacles in the first 2 years and switched to DIMS; Group 4 (n = 18) wore SV spectacles in the first 2 years, switched to DIMS for 1.5 years and then SV spectacles again. Group 1 showed no significant differences in myopia progression (− 0.52 ± 0.66 vs. − 0.40 ± 0.72D) and axial elongation (0.32 ± 0.26 vs. 0.28 ± 0.28 mm, both p > 0.05) between the first and the later 3 years. In the last 2.5 years, DIMS lens groups (Groups 1 and 3) had less myopia progression and axial elongation than the single vision groups (Groups 2 and 4). There was no evidence of rebound after stopping the treatment. Post-wear visual functions in all groups were within norms. The results supported that DIMS lenses provided sustained myopia control without adverse effects over the 6-year study period. Trial registration: clinicaltrials.gov; NCT02206217.

Abstract Background The outcome of in vitro fertilization-embryo transfer (IVF) is often determined according to follicle and estradiol levels following gonadotropin stimulation. In previous studies, although most of them analyzed the estrogen level from ovaries or the average estrogen level of a single follicle, there was no study on the ratio of estrogen increase, which was also correlated with pregnancy outcomes in the clinic. This study aimed to make timely adjustments to follow-up medication to improve clinical outcomes based on the potential value of estradiol growth rate. Methods We comprehensively analyzed estrogen growth during the entire ovarian stimulation period. Serum estradiol levels were measured on the day of gonadotropin treatment (Gn1), five days later (Gn5), eight days later (Gn8), and on the trigger day (HCG). This ratio was used to determine the increase in estradiol levels. According to the ratio of estradiol increase, the patients were divided into four groups: A1 (Gn5/Gn1 ≤ 6.44), A2 (6.44 21.33); B1 (Gn8/Gn5 ≤ 2.39), B2 (2.39 3.84). We analyzed and compared the relationship between data in each group and pregnancy outcomes. Results In the statistical analysis, the estradiol levels of Gn5 (P = 0.029, P = 0.042), Gn8 (P

For improving the colour diversity and corrosion resistance of current zinc-copper-titanium alloys for the construction industry，the corrosion resistance of the surface film of Zn-Cu-Ti alloy after anodic oxidation treatment was analyzed and investigated by means of polarization curve，AC impedance，simulated seawater immersion experiment and salt spray test.Results showed that the quality of the anodic oxide film increased and then decreased with the increase of the current density and the concentration of NaOH in the electrolyte.When the current density was 10 A/dm2 and the NaOH concentration was 20 g/L，the as-obtained film had the most positive self-corrosion potential and the smallest self-corrosion current density.Additionally，the anodized film layer could significantly enhance its corrosion resistance in the simulated seawater corrosion test environment.

Recent advancements in next-generation sequencing (NGS) technology and bioinformatics tools have revealed a vast array of viral diversity in insects, particularly RNA viruses. However, our current understanding of insect RNA viruses has primarily focused on hematophagous insects due to their medical importance, while research on the viromes of agriculturally relevant insects remains limited. This comprehensive review aims to address the gap by providing an overview of the diversity of RNA viruses in agricultural pests and beneficial insects within the agricultural ecosystem. Based on the NCBI Virus Database, over eight hundred RNA viruses belonging to 39 viral families have been reported in more than three hundred agricultural insect species. These viruses are predominantly found in the insect orders of Hymenoptera, Hemiptera, Thysanoptera, Lepidoptera, Diptera, Coleoptera, and Orthoptera. These findings have significantly enriched our understanding of RNA viral diversity in agricultural insects. While further virome investigations are necessary to expand our knowledge to more insect species, it is crucial to explore the biological roles of these identified RNA viruses within insects in future studies. This review also highlights the limitations and challenges for the effective virus discovery through NGS and their potential solutions, which might facilitate for the development of innovative bioinformatic tools in the future.

Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue (cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.

Abstract Moving target detection performance is seriously affected by missing array elements for multichannel synthetic aperture radar (Multi‐SAR) systems. Meanwhile, there is a contradiction between the accuracy of data recovery and the computational burden in traditional methods. To solve the problems, a moving target detection method based on CUR‐RPCA for missing array elements is proposed in this paper. First, key nodes of the echo data are extracted and rearranged into a low‐rank matrix. Then we uses the low‐rank characteristic to complete key nodes of data. Subsequently, complete echo data is constructed by utilising recovered key nodes of data and CUR decomposition. Therefore using the ideas of CUR and RPCA, a novel optimization problem is constructed to achieve separation of moving targets and clutter while recovering data. In addition, only key nodes of the data is completed to achieve the performance of all data recovery, so that the disadvantage of low computational efficiency has been overcome for traditional matrix completion methods. Finally, the superior clutter suppression performance of the proposed method is verified by several numerical simulations and comparative studies.

Objective To analyze the characteristics of local coronavirus disease 2019 (COVID-19) cases aged ≥ 60 years in Zhejiang province during the epidemic period dominantly due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection for providing evidence to the improvement of COVID-19 prevention and control among the elderly. MethodsThe information on all local COVID-19 cases aged ≥ 60 years at the diagnosis reported in Zhejiang province from March through April, 2022 were extracted from the National Information System for Disease Control and Prevention and from the reports of field surveys on the cases. Descriptive statistics were conducted to analyze epidemiological characteristics of the cases. ResultsOf a total of 163 elderly local COVID-19 cases reported during the two months, 82 (50.31%) were confirmed cases and 81 (49.69%) were asymptomatic infections. Among the 82 confirmed cases, 69 (84.15%) were mild type and 13 (15.85%) were common type; no severe/critical case and mortality were reported. For all the cases, the male to female ratio was 0.92 : 1; the age ranged from 60 to 95 years, with a median age of 68 years. The majority (69.33%, n = 113) of the cases′ occupations were non-social workers. Nearly a half (46.01%, n = 75) of the cases had underlying diseases. More than a half (57.06%, n = 93) of the cases had full-dose COVID-19 vaccination with booster injection. Of the cases, 69.94% (114) were identified among the people under centralized medical observation. Among the cases with cardio-cerebrovascular diseases, the proportion of common type patients was significantly higher than that of asymptomatic infection compared with the cases without the diseases (P = 0.008). The proportion of common type COVID-19 was significantly lower than that of asymptomatic infection (P = 0.015) and mild type COVID-19 (P = 0.012) for the cases with booster COVID-19 vaccination in comparison with those without the booster vaccination. ConclusionThe clinical manifestation of local elderly COVID-19 cases was generally mild during the epidemic induced mainly by SARS-CoV-2 Omicron variant. The study results suggested that promoting COVID-19 vaccination and developing Omicron variant-specific vaccine are of significance for COVID-19 epidemic control and prevention in elderly population.

Objiective: In presence of measurement uncertainty evaluation, the detection methods, with water-sodium chloride pretreatment, for health food was evaluated. Methods: A mathematical model was established to analysis of uncertainty sources. Then the individual components of uncertainty were evaluated. Finally, the combined uncertainty and extended uncertainty were calculated. Results: The uncertainty caused by several factors, including the fitting of the standard curve, the preparation of solution and standard, the repeatability of measurement, and the weigh of sample.The contents of mevastatin, lovastatin and simvastatin were 0.099 2, 0.101 0, 0.099 5 mg/kg in health foods, respectively. The relative combined standard uncertainties were about 0.003 2, 0.005 6, 0.005 1 mg/kg, k=2. Conclusion: Water-sodium chloride pretreatmen can reduce the interference of matrix and the uncertainty introduced by repeatability.

Abstract Depression is a common and debilitating condition for which effective treatments are needed. Lepidium meyenii Walp (Maca) is a plant with potential medicinal effects in treating depression. Recently, there has been growing interest in plant‐derived extracellular vesicles (EVs) due to their low toxicity and ability to transport to human cells. Targeting the gut–brain axis, a novel strategy for depression management, may be achieved through the use of Maca‐derived EVs (Maca‐EVs). In this study, we successfully isolated Maca‐EVs using gradient ultracentrifugation and characterized their shape, size, and markers (CD63 and TSG101). The in vivo imaging showed that the Dil‐labeled Maca‐EVs crossed the brain–blood barrier and accumulated in the brain. The behavioral tests revealed that Maca‐EVs dramatically recovered the depression‐like behaviors of unpredictable chronic mild stress (UCMS) mice. UCMS mice fecal were characterized by an elevated abundance of g_Enterococcus, g_Lactobacillus, and g_Escherichia_Shigella, which were significantly restored by administration of Maca‐EVs. The effects of Maca‐EVs on the altered microbial and fecal metabolites in UCMS mice were mapped to biotin, pyrimidine, and amino acid (tyrosine, alanine, aspartate, and glutamate) metabolisms, which were closely associated with the serotonin (5‐HT) production. Maca‐EVs were able to increase serum monoamine neurotransmitter levels in UCMS mice, with 5‐HT showing the most significant changes. We further demonstrated that 5‐HT improved the expression of brain‐derived neurotrophic factor, a key regulator of neuronal plasticity, and its subsequent activation of TrkB/p‐AKT signaling by regulating the GTP‐Cdc42/ERK pathway. These findings suggest that Maca‐EVs enhance 5‐HT release, possibly by modulating the gut–brain axis, to improve depression behavior. Our study sheds light on a novel approach to depression treatment using plant‐derived EVs.

In the internal cooling channel forming of the blanket component for fusion reactor, the combination of Fe-Cr-Al ferritic steel with RAFM steel (reduced activation ferritic/martensitic steel) can form alumina film and then be served as tritium permeation barrier (TPB), which can inhibit the penetration of tritium into structural materials. To realize reliable joining between the two materials, Hot Isostatic Pressing (HIP) diffusion bonding, which is considered as the most promising fabrication technique for blanket component was used. The microstructure and mechanical properties of the joints were analyzed, and the results showed that Fe-Cr-Al/CLF-1 steel interfaces generated some large-size AlN, and the interfacial microvoids are not totally eliminated. While adding Ni interlayer between Fe-Cr-Al/CLF-1 steel could significantly reduce the size of AlN and promote interfacial microvoids closure. Fine NiAl and Ni3Al phases, as the strengthening phases in Nickel-based superalloys, were formed due to atom interdiffusion across the interfaces. Fe-Cr-Al/Ni/CLF-1 joints exhibited average tensile strength of 636 and 529 MPa, and elongation rate of 3% and 15% when tested at 25 and 300 °C, respectively. Microhardness test demonstrated Fe-Cr-Al/Ni/CLF-1 steel joints could be enhanced by precipitation-hardening of NixAly phases. These preliminary studies have laid a foundation for the preparation of TPB in the cooling channel of blanket components.

Many hosts utilize the ubiquitin system to defend against viral infection. As a key subunit of the ubiquitin system, the role of polyubiquitin in the viral infection of insects is unclear. Here, we identified the full-length cDNA of the polyubiquitin-C (UBC) gene in Laodelphax striatellus, the small brown planthopper (SBPH). LsUBC was expressed in various tissues and was highly expressed in salivary glands, midgut, and reproductive systems. Furthermore, the LsUBC expression profiles in the developmental stages showed that LsUBC was ubiquitously expressed in seven developmental stages and was highest expressed in female adults with SBPH. qRT-PCR analyses indicated that rice stripe virus (RSV) infection promoted the LsUBC expression. Knockdown of LsUBC mRNA via RNA interference increased RSV accumulation. These findings suggest that LsUBC inhibits RSV accumulation in L. striatellus.

In this study, sRNA libraries and mRNA libraries of HFs of FMD were constructed and sequenced using an Illumina HiSeq 2500, and the expression profiles of miRNAs and genes in the HFs of FMD were obtained at the anagen and catagen stages. In total, 565 differentially expressed unigenes (DEGs) were identified, 90 of which were upregulated and 475 of which were downregulated. In the BP category of GO enrichment, the DEGs were enriched in the processes related to HF development and differentiation, including the hair cycle regulation and processes, HF development, skin epidermis development, regulation of HF development, skin development, the Wnt signaling pathway, and the BMP signaling pathway. Through KEGG analysis it was found that DEGs were significantly enriched in pathways associated with HF development and growth. A total of 186 differentially expressed miRNAs (DEmiRNAs) were screened (p < 0.05) in the HFs of FMD at the anagen stage vs. the catagen stage, 33 of which were upregulated and 153 of which were downregulated. Through DEmiRNA–mRNA association analysis, we found DEmiRNAs and target genes that mainly play regulatory roles in HF development and growth. The enrichment analysis of DEmiRNA target genes revealed similarities with the enrichment results of DEGs associated with HF development. Notably, both sets of genes were enriched in key pathways such as the Notch signaling pathway, melanogenesis, the cAMP signaling pathway, and cGMP-PKG. To validate our findings, we selected 11 DEGs and 11 DEmiRNAs for experimental verification using RT-qPCR. The results of the experimental validation were consistent with the RNA-Seq results.

In response to the COVID-19, social media big data has played an important role in epidemic warning, tracking the source of infection, and public opinion monitoring, providing strong technical support for China’s epidemic prevention and control work. The paper used Sina Weibo posts related to COVID-19 hashtags as the data source, and built a BERT-CNN deep learning model to perform fine-grained and high-precision topic classificationon massive social media posts. Taking Shenzhen as a region of interest, we mined the “epidemic data bulletin” and “daily life impact” posts during the epidemic for spatial analysis. The results show that the confirmed communities and designated hospitals in Shenzhen as a whole present the characteristics of “sparse east and dense west”, and there is a strong positive spatial correlation between the number of confirmed cases and social media response. Specifically, Nanshan District, Futian District and Luohu District have more confirmed cases due to large population movements and dense transportation networks, and social media has responded more violently, and people’s lives have been greatly affected. However, Yantian District, Pingshan District and Dapeng New District showed opposite characteristics. The case study results further show that using deep learning methods to mine text information in social media is scientifically feasible for improving situational awareness and decision support during the COVID-19.

Type III polyketide synthases (PKSs) catalyze the formation of a variety of polyketide natural products with remarkable structural diversity and biological activities. Despite significant progress in structural and mechanistic studies of type III PKSs in bacteria, fungi, and plants, research on type III PKSs in cyanobacteria is lacking. Here, we report structural and mechanistic insights into CylI, a type III PKS that catalyzes the formation of the alkylresorcinol intermediate in cylindrocyclophane biosynthesis. The crystal structure of apo‐CylI reveals a distinct arrangement of structural elements that are proximal to the active site. We further solved the crystal structures of CylI in complexes with two substrate analogues at resolutions of 1.9 Å. The complex structures indicate that N259 is the key residue that determines the substrate preference of CylI. We also solved the crystal structure of CylI complexed with the alkylresorcinol product at a resolution of 2.0 Å. Structural analysis and mutagenesis experiments suggested that S170 functions as a key residue that determines cyclization specificity. On the basis of this result, a double mutant was engineered to completely switch the cyclization of CylI from aldol condensation to lactonization. This work elucidates the molecular basis of type III PKS in cyanobacteria and lays the foundation for engineering CylI‐like enzymes to generate new products. [ABSTRACT FROM AUTHOR]

Six new thiodiketopiperazine-class alkaloids lecanicilliums A–F were isolated from the mangrove sediment-derived fungus Lecanicillium kalimantanense SCSIO41702, together with thirteen known analogues. Their structures were determined by spectroscopic analysis. The absolute configurations were determined by quantum chemical calculations. Electronic circular dichroism (ECD) spectra and the structure of Lecanicillium C were further confirmed by a single-crystal X-ray diffraction analysis. Lecanicillium A contained an unprecedented 6/5/6/5/7/6 cyclic system with a spirocyclic center at C-2′. Biologically, lecanicillium E, emethacin B, and versicolor A displayed significant cytotoxicity against human lung adenocarcinoma cell line H1975, with IC50 values of 7.2~16.9 μM, and lecanicillium E also showed antibacterial activity against four pathogens with MIC values of 10~40 μg/mL. Their structure–activity relationship is also discussed.