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Abstract We have developed a new universal influenza B vaccination strategy based on inactivated influenza B viruses displaying mosaic hemagglutinins (mHAs). Recombinant mHA viruses were constructed by replacing the four major antigenic sites of influenza B virus HAs, with those from exotic avian influenza A virus HAs. Sequential vaccination of naïve mice with mHA-based vaccines elicited higher immune responses towards the immuno-subdominant conserved epitopes of the HA than vaccination with wildtype viruses. Among the different preparations tested, mHA split vaccines were less immunogenic than their whole inactivated virus counterparts. This lower immunogenicity was overcome by the combination with adjuvants. mHA split vaccines adjuvanted with a Toll-like receptor-9 agonist (CpG 1018) increased Th1 immunity and in vivo cross-protection, whereas adjuvanting with an MF59-like oil-in-water nano-emulsion (AddaVax) enhanced and broadened humoral immune responses and antibody-mediated cross-protection. The mHA vaccines with or without adjuvant were subsequently evaluated in mice that were previously immunized to closely mimic human pre-existing immunity to influenza B viruses and the contribution of innate and cellular immunity was evaluated in this model. We believe these preclinical studies using the mHA strategy represent a major step toward the evaluation of a universal influenza B virus vaccine in clinical trials.

Abstract Due to simultaneous horizontal and vertical displacement during vertical evacuation, the consequences of stampede congestion accidents can be more severe. Generally, pedestrians trigger a synchronization mechanism at some point during the vertical evacuation process. This synchronization behavior helps prevent stampede congestion and improves evacuation efficiency. This paper designs a well-controlled single-file vertical evacuation experiment. After the experiment, the video footage is imported into the TRACKER system to extract the coordinates of pedestrian step movements, after which the experimental data undergo calculations and visual analysis. The research findings indicate the following: Firstly, when the crowd coordinates trigger the synchronization mechanism, this behavior remains stable as long as pedestrian speed and direction are unchanged; Secondly, the variation in footstep speed over time is not directly related to the footstep synchronization rate of the crowd; Lastly, this study calculated the characteristic density value most likely to trigger the synchronization mechanism during vertical evacuation. This research deepens our understanding of crowd dynamics, reveals the characteristics of pedestrian movement during vertical evacuation, and proposes evacuation guidance strategies based on these features.

Abstract Objectives Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy. Methods Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine. Results A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068–1.975; p = 0.018), focal and focal to bilateral tonic–clonic seizures (OR = 1.583, 95% CI: 1.090–2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282–3.063; p = 0.002) were the influencing factors for migraine. However,

Abstract While many countries employed digital contact tracing to contain the spread of SARS-CoV-2, the contribution of cospace-time interaction (i.e., individuals who shared the same space and time) to transmission and to super-spreading in the real world has seldom been systematically studied due to the lack of systematic sampling and testing of contacts. To address this issue, we utilized data from 2230 cases and 220,878 contacts with detailed epidemiological information during the Omicron outbreak in Beijing in 2022. We observed that contact number per day of tracing for individuals in dwelling, workplace, cospace-time interactions, and community settings could be described by gamma distribution with distinct parameters. Our findings revealed that 38% of traced transmissions occurred through cospace-time interactions whilst control measures were in place. However, using a mathematical model to incorporate contacts in different locations, we found that without control measures, cospace-time interactions contributed to only 11% (95%CI: 10%–12%) of transmissions and the super-spreading risk for this setting was 4% (95%CI: 3%–5%), both the lowest among all settings studied. These results suggest that public health measures should be optimized to achieve a balance between the benefits of digital contact tracing for cospace-time interactions and the challenges posed by contact tracing within the same setting.

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in Prdx1-overexpression (Prdx1-OE) mice. Besides, S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production. Due to the limited druggability of S14 with low bioavailability (2.6%) and poor renal distribution, a pH-sensitive kidney-targeting dodecanamine-chitosan nanoparticle system is constructed to load S14 for precise treatment of AKI. l-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1 (Kim-1)-overexpressed cells. The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly. By encapsulation with micelles, the AUC0‒t, half-life time, and renal distribution of S14 increase 2.5-, 1.8-, and 3.1-fold, respectively. The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDP-glycosyltransferase (UGT)-mediated biotransformation. In summary, this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology, thereby driving advancements in marine drug development for AKI.

ABSTRACTPreviously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain–Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016–2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1–34]; adults, 25 years [range, 0–183]) and intensive care unit (children, 16 years [range, 1–30]; adults, 17 years [range, 0–102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Abstract Natural stilbenes have shown significant potential in the prevention and treatment of diseases due to their diverse pharmacological activities. Here we present a mild and effective Ti-catalyzed intermolecular radical-relay [2σ + 2π] cycloaddition of bicyclo[1.1.0]-butanes and 1,3-dienes. This transformation enables the synthesis of bicyclo[2.1.1]hexane (BCH) scaffolds containing aryl vinyl groups with excellent regio- and trans-selectivity and broad functional group tolerance, thus offering rapid access to structurally diverse stilbene bioisosteres.

Abstract N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC–MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. With a favorable bioavailability of 24.0%, N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs. Graphical Abstract

In response to problems of poor sampling quality, low sensitivity, and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) oropharyngeal (OP) swab sampling used in China, we aimed to evaluate the diagnostic performance and acceptability of saliva-based nucleic acid amplification tests (NAATs) in China. The results showed that, using nasopharyngeal (NP) swab results as the gold standard, the overall sensitivities for saliva specimens and OP swabs were 93.3 % and 85.0 %, the specificities were 92.6 % and 93.8 %, respectively. The results of an acceptability survey showed that the scores for saliva, OP, and NP samples were 9.46 ± 1.69, 8.11 ± 2.42, and 4.58 ± 3.82 out of 10, respectively, with significant differences among the three groups (P

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients.

Accurate information on microwave land surface emissivity (MLSE) is important for satellite data assimilation. In this article, a new random forest (RF) algorithm is developed for retrieving MLSE under all-sky conditions. Using Level-1 brightness temperature data from the FengYun-3D (FY-3D) microwave radiation imager in 2022, two global MLSE daily product datasets, clear-sky (FY-3D1) and clear/cloudy (FY-3D2), were obtained by using one-dimensional variational method and microwave radiative transfer method, respectively. Based on the global spatiotemporal consistency assessment, a high-quality daily MLSE training dataset for the Tibetan Plateau was selected from the two datasets. Then, ten land surface parameters from routine observation were chosen as input features to the RF model to simulate the MLSE under all-sky conditions in the Tibetan Plateau. The results show that both FY-3D1 and FY-3D2 MLSE datasets are comparable to the international mainstream MLSE products in quality, while the clear sky FY-3D1 is likely to be better than the clear/cloudy FY-3D2 MLSE. Land surface roughness, vegetation optical thickness, normalized vegetation index, and land cover type are identified as the most important factors affecting MLSE in the Tibetan Plateau. The RF model can effectively simulate the MLSE in the frequency range of 10.65–89.0 GHz under all-sky conditions. The coefficients of determination (R2) for horizontal polarization and vertical polarization range from 0.86 (10.65 GHz) to 0.91 (18.7 GHz) and from 0.60 (10.65 GHz) to 0.74 (89.0 GHz), respectively. The root mean square errors for horizontal polarization and vertical polarization range from 0.017 (23.8 GHz) to 0.023 (10.65 GHz) and from 0.016 (10.65 GHz) to 0.019 (89.0 GHz), respectively. These results indicate that machine learning is likely to be an effective method for future all-sky simulation of MLSE.

Three new 24-membered macrolactines, amylomacrolactines A–C (1–3), along with two known compounds 4 and 5, were isolated from the Arctic bacteria Bacillus amyloliquefaciens SCSIO 41392. The configurations of 1–3 were assigned by a combination of coupling constants, NOESY, and analysis of MM2-optimized conformation, as well as by comparison with reports in the literature. Compounds 1 and 2 showed quorum sensing (QS) inhibitory activities against the Pseudomonas aeruginosa (P. aeruginosa) PQS system and suppressed PQS-regulated virulence factor pyocyanin synthesis. In addition, compounds 3–5 affected the production of another essential virulence factor, siderophore of pyoverdine (PVD), in P. aeruginosa. More importantly, compound 5 showed an anti-biofilm activity against P. aeruginosa. Altogether, the isolated compounds displayed multiple bacterial virulence inhibition activities, which is worthy of further exploration for novel analogues in antimicrobial drug development.

Abstract Background Genetic generalized epilepsy (GGE) accounts for nearly one-third of all epilepsies. The feature of status epilepticus (SE) in patients with GGE has been rarely studied. We aimed to determine the electroclinical characteristics of SE in patients with GGE. Methods In this retrospective study, nine patients with GGE were enrolled at Xijing Hospital, Xi’an, China from May 2014 to May 2020. SE was confirmed by 24-h video-EEG recording. The demography, clinical manifestation, brain MRI and SE pattern were analyzed. Results Of the nine patients in the study, seven were female. The mean age of the patients at the time of inclusion was 16.8 years (range 7–31 years), and the mean age at the onset of epilepsy was 10.9 years (range 6–17 years). The follow-up time ranged from 3 months to 6 years. Myoclonic absence status was identified in four patients showing eyelid myoclonia with absence and one patient showing perioral myoclonia with absences. Myoclonic SE was identified in three patients showing juvenile myoclonic epilepsy. Autonomic SE was found in one patient with eyelid myoclonia with absence. SE was terminated by oral midazolam in four patients. In the other five patients, SE terminated spontaneously. Conclusions The seizure type of SE in patients with GGE is often consistent with their major symptoms. Oral midazolam may be an option to terminate SE in patients with GGE.

Abstract The search-engine-based surveillance methods for the early warning and prediction of infectious diseases cannot achieve search engine keywords automatic filtering and real-time updating, lead to powerless for the early warning of emerging infectious diseases. The aim of this study is to develop an artificial intelligence (AI) method for search-engine-based surveillance to improve the early warning ability for emerging infectious diseases. The 32 keywords (444 million search queries) that may be related to the coronavirus disease (COVID-19) outbreak was collected from December 18, 2019 to February 11, 2020 from Baidu’s search engine database. The graph convolution network (GCN) model was used to select search engine keywords automatically, and then, multiple linear regression was performed to explore the relationship between the daily query frequencies of keywords and daily new cases. The GCN model was used to automatically select keywords. The prediction trend of the GCN model was highly consistent with the true curve with a mean absolute error of 81.65. Three keywords including “epidemic”, “mask” and “coronavirus” were selected. The selection keywords in the search queries were highly correlated with the daily number of confirmed cases (r = 0.96, 0.94, and 0.89; P

In order to explore the antibacterial activity of endophytic fungi derived from Aegiceras corniculatum, antibacterial activity of ferment extract of endophytic fungi was used as evaluation index to screen active strains, the chemical constituents were separated on the basis of bioactivity-guiding method combined with various chromatographic techniques and identified by spectral technique together with comparison with literature data, and the antibacterial activity of pure compounds was determined by microplate method. The results were as follows: (1) Sixteen taxa of endophytic fungi isolated from A. corniculatum were distributed in 2 classes, 7 orders, 10 families and 10 genera. Fusarium was dominant genus. The ferment extract of endophytic fungi GXIMD02029 and GXIMD02039 displayed different levels of inhibitory effects on Bacillus subtilis, Staphylococcus epidermidis, methicillin-resistant S. aureus, Micrococcus luteus, Actinomyces viscosity, and Staphylococcus aureus when that of GXIMD02038 against methicillin-resistant S. aureus, Micrococcus luteus, and Staphylococcus aureus. (2) Seven pure compounds were isolated from endophytic fungi Phomopsis sp. GXIMD02029 and identified as (15R)-acetoxydothiorelone A (1), cytosporone B (2), pestalotiopsone H (3), pestalotiopsone B (4), p-hydroxybenzaldehyde (5), p-hydroxybenzoic acid (6), N-(2-phenylethyl)acetamide (7). (3) Compounds 1 and 2 showed different levels of antibacterial effects. Compound 1 exhibited inhibitory effect on Bacillus subtilis, Staphylococcus epidermidis and methicillin-resistant S. aureus with MIC value of 15.625 g·mL-1, Micrococcus luteus and Actinomyces viscosity with MIC value of 7.812 5 g·mL-1, and Staphylococcus aureus with MIC value of 31.25 g·mL-1. Compound 2 displayed inhibitory effect on Micrococcus luteus with MIC value of 62.5 g·mL-1, Bacillus subtilis, Staphylococcus epidermidis, methicillin-resistant S. aureus and Actinomyces viscosity with MIC values of 125 g·mL-1, and Staphylococcus aureus with MIC value of 250 g·mL-1. Three active strains were reported in the project. It is reported that Compound 1 shows the antibacterial activity for the first time. The result provides the basis for the antibacterial values of endophytic fungi of Aegiceras corniculatum.

Bruguiera gymnorhiza hypocotyl is a common marine herbal medicine of the Jing people used in the treatment of hepatitis B. Firstly, MTT and real-time fluorescence quantitative PCR methods were used to determine the anti-HBV activity of different extracted parts of B. gymnorhiza hypocotyl, the chemical constituents of the active extraction parts were isolated and identified using modern chromatographic techniques and spectroscopic methods, and in vitro screening model was employed to test the anti-HBV activity of obtained compounds. The results were as follows: (1) The n-butanol phase of the hypocotyl exhibited anti-HBV activity; (2) A total of 11 compounds were isolated and structurally identified, namely uridine (1), thymidine (2), adenosine (3), oryzalactam (4), n-butyl-O-D-fructopyranoside (5), nortetillapyrone (6), (4R,6S)-4-methoxyl-2,3-dihydroaquilegiolide (7), (4R,6S)-2-dihydromenisdaurilide (8), gallcatechin (9), 1-(4-hydroxy-3-methoxy)-phenyl-2-［4-(1,2,3-trihydroxypropyl)-2-methoxy］-phenoxy-1,3-propandiol(10), and (-)-lyoniresinol-9-O-β-D-xylopyrano-side (11), among them, compounds 4, 5, 7 and 8 were firstly obtained from B. gymnorhiza, and Compound 4 showed anti-HBV activity with an inhibition rate of 23.59%. The study clarify the chemical composition of the anti-HBV of B. gymnorhiza hypocotyl.

In order to find culturable bacteria resources and antibacterial activity strain in the rhizosphere soil of mangrove plants from the Maowei Sea, the rhizosphere soil of five mangrove plants(Rhizophora stylosa, Talipariti tiliaceum, Sonneratia apetala, Aegiceras corniculatum, and Pluchea indica) was cultured by enrichment media and then isolated the culturable bacteria. The culturable bacteria were purified by six different isolation media. The diversity of culturable bacteria was analyzed by the 16S rRNA gene sequence information. Antimicrobial activities (Staphylococcus epidermidis, methicillin-resistant S. aureus, and Pseudomonas aeruginosa) of the culturable bacteria were analyzed by disk diffusion method. The results were as follows: (1) A total of 120 strains were isolated from seven rhizosphere soil samples of mangrove plants which could be classified into 35 families and 47 genera, among which five potential new species were obtained. The dominant genus was Streptomyces (14.2%). (2) It was found that the crude extracts of nine strains had antibacterial activity against at least one pathogen. The results indicate that there are abundant culturable bacteria and potential new antibiotics resources in the mangrove rhizosphere soils from the Maowei Sea.

Four new sesquiterpenoids, talaroterpenes A–D (1–4), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1–4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1–4 were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A–D (1–4) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 μM, 1, 3 and 4 exhibited varying degrees of activation on ABCA1 and PPARα, while 4 showed the strongest activities. Furthermore, 4 induced significant alterations in the expression of downstream target genes CLOCK and BMAL1 of RORα, and the in silico molecular docking analysis supported the direct binding interactions of 4 with RORα protein. This study revealed that talaroterpene D (4) was a new potential non-toxic modulator of nuclear receptors.

Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021–2023). Approximately 252 anti-inflammatory compounds, including 129 new ones, were predominantly obtained from marine fungi and they are structurally divided into polyketides (51.2%), terpenoids (21.0%), alkaloids (18.7%), amides or peptides (4.8%), and steroids (4.3%). This review will shed light on the development of marine microbial secondary metabolites as potential anti-inflammatory lead compounds with promising clinical applications in human health.

Marine-derived fungi are assuming an increasingly central role in the search for natural leading compounds with unique chemical structures and diverse pharmacological properties. However, some gene clusters are not expressed under laboratory conditions. In this study, we have found that a marine-derived fungus Aspergillus sp. SYPUF29 would survive well by adding an exogenous nitric oxide donor (sodium nitroprusside, SNP) and nitric oxide synthetase inhibitor (L-NG-nitroarginine methyl ester, L-NAME) in culture conditions. Moreover, using the LC-MS/MS, we initially assessed and characterized the difference in metabolites of Aspergillus sp. SYPUF29 with or without an additional source of nitrogen. We have found that the metabolic pathway of Arginine and proline metabolism pathways was highly enriched, which was conducive to the accumulation of alkaloids and nitrogen-containing compounds after adding an additional source of nitrogen in the cultivated condition. Additionally, the in vitro anti-neuroinflammatory study showed that the extracts after SNP and L-NAME were administrated can potently inhibit LPS-induced NO-releasing of BV2 cells with lower IC50 value than without nitric oxide. Further Western blotting assays have demonstrated that the mechanism of these extracts was associated with the TLR4 signaling pathway. Additionally, the chemical investigation was conducted and led to nine compounds (SF1–SF9) from AS1; and six of them belonged to alkaloids and nitrogen-containing compounds (SF1–SF6), of which SF1, SF2, and SF8 exhibited stronger activities than the positive control, and showed potential to develop the inhibitors of neuroinflammation.

Three new polyketides, including three ester derivatives (1, 3, and 5) and a new natural product, which was a benzoquinone derivative, embelin A (4), together with nine known ones (2 and 6–13), were isolated from the mangrove-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by detailed NMR and MS spectroscopic analyses. The X-ray single-crystal diffraction analysis of 4 was described for the first time. Compound 9 displayed obvious inhibition against PDE4 with an inhibitory ratio of 40.78% at 10 μM. Compound 12 showed DPPH radical scavenging activity, with an EC50 of 16.21 µg/mL, compared to the positive control (ascorbic acid, EC50, 11.22 µg/mL). Furthermore, compound 4 exhibited cytotoxicity against PC-3 and LNCaP with IC50 values of 18.69 and 31.62 µM, respectively.

Two new C23-steroids derivatives, cyclocitrinoic acid A (1) and cyclocitrinoic acid B (2), and a new isocoumarin metabolite, (3R,4S)-6,8-dihydroxy-3,4,5-trimethyl-7-carboxamidelisocoumarin (10), together with 12 known compounds (3–9, 11–15) were isolated from the mangrove-sediment fungus Penicillium sp. SCSIO 41429. The structures of the new compounds were comprehensively characterized by 1D and 2D NMR, HRESIMS and ECD calculation. All isolates were evaluated for pancreatic lipase (PL) inhibitory and antioxidant activities. The biological evaluation results revealed that compounds 2, 14 and 15 displayed weak or moderate inhibition against PL, with IC50 values of 32.77, 5.15 and 2.42 µM, respectively. In addition, compounds 7, 12 and 13 showed radical scavenging activities against DPPH, with IC50 values of 64.70, 48.13, and 75.54 µM, respectively. In addition, molecular docking results indicated that these compounds had potential for PL inhibitory and antioxidant activities, which provided screening candidates for antioxidants and a reduction in obesity.

Wire and arc additively manufactured aluminum alloys are prone to porosity, leading to poor mechanical properties in samples, which hinders their broad industrial application. Laser and arc hybrid processes have garnered increasing attention for their potential to reduce porosity, stabilize the arc, and enhance deposition efficiency. This paper investigates the porosity, element distribution, microstructure evolution, and mechanical properties of 2319 aluminum alloy produced through the laser and cold metal transfer (laser-CMT) hybrid additive manufacturing process. In comparison with the as-deposited samples, the laser-CMT hybrid process decreases porosity, enhances element distribution, mitigates Cu element segregation, and results in increased θ′′ phase precipitation. Following T6 heat treatment, the ultimate tensile strength (UTS), yield strength (YS), and elongation of the x-direction specimens from the laser-CMT hybrid process are 450.0 MPa, 318.1 MPa, and 10.0%, respectively. These values are 11.27%, 7.03%, and 36.65% higher than those of the as-deposited samples. To validate the findings, a large-scale load-carrying frame for a commercial aircraft was fabricated, demonstrating the efficacy of the process. The paper also presents a detailed analysis of the strengthening mechanism. Samples deposited using the laser-CMT method exhibit reduced porosity and excellent mechanical properties, making this process promising for a wide range of applications.

Abstract Background Tillage measures have been effectively adopted for mitigating waterlogging damage in field crops, yet little is known about the role of tillage measures in crop responses to waterlogging. A field experiment was performed to investigate the effect of conventional planting (CK), small ridge planting (SR), big ridge planting (BR) and film side planting (FS) on soil available nutrients and enzymatic activity, chlorophyll contents, leaf nutrients, soluble protein, soluble sugar, nitrate reductase, antioxidant enzyme activity, lipid peroxidation, agronomic traits and yield of rapeseed under waterlogging stress conditions. Results Tillage measures remarkably improved rapeseed growth and yield parameters under waterlogging stress conditions. Under waterlogging conditions, rapeseed yield was significantly increased by 33.09 and 22.70% in the SR and BR groups, respectively, compared with CK. Correlation analysis showed that NO3 −-N, NH4 +-N, and urease in soils and malonaldehyde (MDA), superoxide dismutase (SOD), and nitrate reductase in roots were the key factors affecting rapeseed yield. The SR and BR groups had significantly increased NO3 −-N by 180.30 and 139.77%, NH4 +-N by 115.78 and 66.59%, urease by 41.27 and 26.45%, SOD by 6.64 and 4.66%, nitrate reductase by 71.67 and 26.67%, and significantly decreased MDA content by 14.81 and 13.35% under waterlogging stress, respectively, compared with CK. In addition, chlorophyll and N content in leaves, soluble sugar and POD in roots, and most agronomic traits were also significantly enhanced in response to SR and BR under waterlogging conditions. Conclusion Overall, SR and BR mitigated the waterlogging damage in rapeseed mainly by reducing the loss of soil available nitrogen, decreasing the MDA content in roots, and promoting urease in soils and SOD and nitrate reductase in roots. Finally, thorough assessment of rapeseed parameters indicated that SR treatment was most effective followed by BR treatment, to alleviate the adverse effects of waterlogging stress.

Mangrove habitat is rich in microbial flora and its secondary metabolites have novel structure, which is an important source for mining new drugs. This study preliminarily evaluated the culturable bacterial diversity of sediments, roots, leaves and hypocotyls of Bruguiera gymnorhiza and the biological activity of bacterial metabolites, and looked for anti-HBV drug source strains. Pure culture technique and 16S rRNA molecular biology technique were employed to determine the species of bacteria and analyze the species diversity. Using HepG2.2.15 cell line as a model, the anti-HBV activity of bacterial metabolites was tested by MTT and PCR techniques. The secondary metabolites of active bacteria were preliminary analyzed by LC-HRMS technique. The results were as follows: (1) A total of 59 species of bacteria were obtained, belonging to 4 phyla, 5 classes, 14 orders, 23 families, and 36 genera, among which Bacillus was the dominant genus. Strains GXIMD07402, GXIMD07665 and GXIMD07384 were potential new species of Pseudooceanicola, Thioclava and Aestuariibaculum, respectively. (2) The results of anti-HBV activity showed that GXIMD07366, GXIMD07616, GXIMD07384, GXIMD07550 and GXIMD07445X could significantly reduce the level of HBV DNA in the supernatant of HepG2.2.15 cells (P

Sleep quality is an important issue of public concern. This study, combined with sensor application, aims to explore the determinants of perceived comfort when using smart bedding to provide empirical evidence for improving sleep quality. This study was conducted in a standard sleep laboratory in Quanzhou, China, from March to April of 2023. Perceived comfort was evaluated using the Subjective Lying Comfort Evaluation on a seven-point rating scale, and body pressure distribution was measured using a pressure sensor. Correlation analysis was employed to analyze the relationship between perceived comfort and body pressure, and multiple linear regression was used to identify the factors of perceived comfort. The results showed that body pressure was partially correlated with perceived comfort, and sleep posture significantly influenced perceived comfort. In addition, height, weight, and body mass index are common factors that influence comfort. The findings highlight the importance of optimizing the angular range of boards based on their comfort performance to adjust sleeping posture and equalize pressure distribution. Future research should consider aspects related to the special needs of different populations (such as height and weight), as well as whether users are elderly and whether they have particular diseases. The design optimization of the bed board division and mattress softness, based on traditional smart bedding, can improve comfort and its effectiveness in reducing health risks and enhancing health status.

Four new cyclic pentapeptides, avellanins D–G (1–4), together with four known compounds (5–8), were isolated from a mangrove-derived Aspergillus fumigatus GXIMD 03099 fungus from Acanthus ilicifolius L. Their structures were elucidated by analysis of HRESIMS, NMR, and ESI-MS/MS data. Their absolute configurations were determined by X-ray diffraction analysis and Marfey’s method. Compounds 1–8 were screened for insecticidal and antibacterial activities. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with an LC50 value of 86.6 µM; compound 4 had weak activity against Vibrio harveyi with an MIC value of 5.85 µM.

Two new cytochalasin derivatives, peniotrinins A (1) and B (2), three new citrinin derivatives, peniotrinins C–E (4, 5, 7), and one new tetramic acid derivative, peniotrinin F (12), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 μM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer.

Background and objectiveSudden unexpected death in epilepsy (SUDEP) has been regarded as a leading cause of premature death in patients with epilepsy (PWE). Although patients, relatives and caregivers have the right to be informed of SUDEP, neurologists prefer not to release the facts for fear of associated anxiety. In the study, a Chinese questionnaire survey was carried out to elucidate effect of SUDEP disclosure on anxiety in PWE and variables determining the anxiety of patients and provided suggestions for SUDEP disclosure.MethodsA survey study in China was conducted. We recruited 305 PWE from 3 tertiary epilepsy centers who attended outpatient clinic from December 2021 to February 2022. Two hundred and thirty-two PWE completed the screening evaluation, survey and Hamilton anxiety rating scale (HAMA) twice with 171 PWE completing third HAMA at follow-up. HAMA scores at baseline, T1, T2 were compared using analysis of variance and dependent samples t-test. The variables related to anxiety were screened out by univariate analysis and used for multivariate logistic regression.ResultWe found 127 (54.7%) among the 232 participants experienced anxiety after SUDEP disclosure. HAMA scores at T1 were significantly higher than at baseline and T2, while there was no statistical difference between baseline and T2. Medical insurance, seizure severity, and whether the PWE supported SUDEP being disclosed to their relatives and caregivers only were associated with the occurrence of anxiety.ConclusionSUDEP disclosures may cause short-term acute anxiety, but have no long-term effects in PWE. Acute anxiety caused by SUDEP disclosure may be more common in PWE with NCMI and severe seizures. Meanwhile, compared with indirect SUDEP disclosure to their relatives and caregivers, direct SUDEP disclosure to PWE reduces the risk of anxiety. Recommendations are provided to avoid anxiety caused by SUDEP disclosure.

IntroductionFungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties.MethodsAn organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening.ResultsOut of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a −10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain.DiscussionWe concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.

Abstract Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson’s disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (P combined = 1.47 × 10−9) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P

Abstract This study provides an accurate method for evaluating the fit of earphones, which could be used for establishing a linkage between interference/gap values with human perception. Seven commercial CAD software tools stood out and were explored for the analysis of the deviation between earphone and ear. However, the current deviation analysis method remains to be improved for earphone fit evaluation due to excessive points in the calculation (Geomagic Wrap and Siemens NX), lack of value on interference (Geomagic Control X), computation boundary required (Rapidform XOR/Redesign), repetitive computation with same points and inclined calculation line segment or even invalid calculation (Solidworks, Creo). Therefore, an accurate deviation analysis algorithm was promoted, which calculated the deviation between earphone and ear exactly and classified the interference set and gap set precisely. There are five main procedures of this algorithm, which are point cloud model pre-processing, the generation of distance vectors, the discrimination of interference set and gap set, the discrimination of validity, and statistical analysis and visualization. Furthermore, the usability and validity of the deviation analysis algorithm were verified through statistical analysis and comparing visual effects based on the earphone-wearing experiment. It is certified that the deviation analysis algorithm is appropriate for earphone fit evaluation and the eight indexes of this algorithm were proved to be related to subjective comfort scores. It is meaningful for ear-worn product fit analysis, design, and development phases.

China had conducted some of the most stringent public health measures to control the spread of successive SARS-CoV-2 variants. However, the effectiveness of these measures and their impacts on the associated disease burden have rarely been quantitatively assessed at the national level. To address this gap, we developed a stochastic age-stratified metapopulation model that incorporates testing, contact tracing and isolation, based on 419 million travel movements among 366 Chinese cities. The study period for this model began from September 2022. The COVID-19 disease burden was evaluated, considering 8 types of underlying health conditions in the Chinese population. We identified the marginal effects between the testing speed and reduction in the epidemic duration. The findings suggest that assuming a vaccine coverage of 89%, the Omicron-like wave could be suppressed by 3-day interval population-level testing (PLT), while it would become endemic with 4-day interval PLT, and without testing, it would result in an epidemic. PLT conducted every 3 days would not only eliminate infections but also keep hospital bed occupancy at less than 29.46% (95% CI, 22.73-38.68%) of capacity for respiratory illness and ICU bed occupancy at less than 58.94% (95% CI, 45.70-76.90%) during an outbreak. Furthermore, the underlying health conditions would lead to an extra 2.35 (95% CI, 1.89-2.92) million hospital admissions and 0.16 (95% CI, 0.13-0.2) million ICU admissions. Our study provides insights into health preparedness to balance the disease burden and sustainability for a country with a population of billions.

Background: Depression and anxiety are the most common psychiatric comorbidities in patients with epilepsy (PWE). However, they are often unrecognized and consequently untreated. Objective: The study was conducted to evaluate the prevalence and risk factors of anxiety and depression among Chinese adult PWE. Design: Cross-sectional study. Methods: Adult PWE were recruited from 13 tertiary epilepsy centers from February to September 2022. Generalized Anxiety Disorder-7 and Neurological Disorders Depression Inventory for Epilepsy were applied to evaluate anxiety and depression, respectively. Both univariate and multivariate logistic regression analyses models were performed to explore the risk factors of anxiety and depression. Results: A total of 1326 PWE were enrolled in this study. The prevalence of anxiety and depression was 31.45% and 27.30%, respectively. Being female [odds ratio (OR) = 1.467, 95% CI: 1.134–1.899; p = 0.004], focal and focal to bilateral tonic-clonic seizures (TCSZ) (OR = 1.409, 95% CI: 1.021–1.939; p = 0.036), and seizure occurrence in the last 3 months (OR = 1.445, 95% CI: 1.026–2.044; p = 0.036) were the risk factors for anxiety. Focal and focal to bilateral TCSZ (OR = 1.531, 95% CI: 1.094–2.138; p = 0.013) and seizure occurrence in the last 3 months (OR = 1.644, 95% CI: 1.130–2.411; p = 0.010) were the risk factors for depression. In addition, for every 1-year increment of age, the odds of developing depression were decreased by 3.8% ( p = 4.12e −5 ). Nevertheless, up to 70% of PWE did not receive any treatment for comorbidity. Conclusion: There were approximately 30% of PWE screened positive for anxiety or depression. Both focal and focal to bilateral TCSZ and seizure occurrence in the last 3 months were estimated as risk factors for anxiety and depression. However, the current status of treatment was not optimal.

The early prediction of epileptic seizures holds paramount significance in patient care and medical research. Extracting useful spatial-temporal features to facilitate seizure prediction represents a primary challenge in this field. This study proposes GAMRNN, a novel methodology integrating a dual-layer gated recurrent unit (GRU) model with a convolutional attention module. GAMRNN aims to capture intricate spatial-temporal characteristics by highlighting informative feature channels and spatial pattern dynamics. We employ the Lion optimization algorithm to enhance the model's generalization capability and predictive accuracy. Our evaluation of GAMRNN on the widely utilized CHB-MIT EEG dataset demonstrates its effectiveness in seizure prediction. The results include an impressive average classification accuracy of 91.73%, sensitivity of 88.09%, specificity of 92.09%, and a low false positive rate of 0.053/h. Notably, GAMRNN enables early seizure prediction with a lead time ranging from 5 to 35 min, exhibiting remarkable performance improvements compared to similar prediction models.

Abstract It is important for territorial spatial planning to master meteorological disaster risk under the conditions of climate change and then carry out risk adaptation planning according to local conditions. Taking Beijing, a large city in China, as an example, a meteorological disaster risk assessment model was established based on the framework of hazard factors, disaster‐bearing body exposure, and vulnerability of underlying surface. Combined with 11 years of observation data from 293 high‐density weather stations, the rainstorm and high‐temperature risks of urban, agriculture, and ecological spaces were studied. The results show that (1) rainstorms and high‐temperature are mainly distributed in the built‐up areas of plain towns, which are the climate risk factors that need to be considered. (2) The central city of Beijing is at a high risk of rainstorms and high temperature, indicating that the underlying surface and disaster‐bearing body are highly vulnerable to meteorological disasters. (3) In suburbs with agricultural land, there is a certain rainstorm risk in Fangshan and Daxing districts, and a risk of high temperatures in the southern part of Tongzhou and Daxing. (4) The risk of high temperatures in the ecological space (eco‐zone) is relatively low, but the rainstorm risk is relatively high in Pinggu and Miyun. (5) The strategies of coping with rainstorm and high‐temperature disaster risk in Beijing's territorial space planning were discussed.

Sargassaceae, the most abundant family in Fucales, was recently formed through the merging of the two former families Sargassaceae and Cystoseiraceae. It is widely distributed in the world’s oceans, notably in tropical coastal regions, with the exception of the coasts of Antarctica and South America. Numerous bioactivities have been discovered through investigations of the chemical diversity of the Sargassaceae family. The secondary metabolites with unique structures found in this family have been classified as terpenoids, phlorotannins, and steroids, among others. These compounds have exhibited potent pharmacological activities. This review describes the new discovered compounds from Sargassaceae species and their associated bioactivities, citing 136 references covering from March 1975 to August 2023.

Acremonium fungi is one of the greatest and most complex genera in Hyphomycetes, comprising 130 species of marine and terrestrial sources. The past decades have witnessed substantial chemical and biological investigations on the diverse secondary metabolites from the Acremonium species. To date, over 600 compounds with abundant chemical types as well as a wide range of bioactivities have been obtained from this genus, attracting considerable attention from chemists and pharmacologists. This review mainly summarizes the sources, chemical structures, and biological activities of 115 recently reported new compounds from the genus Acremonium from December 2016 to September 2023. They are structurally classified into terpenoids (42%), peptides (29%), polyketides (20%), and others (9%), among which marine sources are predominant (68%). Notably, these compounds were primarily screened with cytotoxic, antibacterial, and anti-inflammatory activities. This paper provides insights into the exploration and utilization of bioactive compounds in this genus, both within the scientific field and pharmaceutical industry.

Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (1–4), along with seven known analogs (5–11), were isolated from the fermentation broth of the mangrove strain Streptomyces hiroshimensis GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against Talaromyces marneffei with minimum inhibitory concentration (MIC) values being in the range of 2–128 μg/mL except compound 2. This is the first report of polyene derivatives produced by S. hiroshimensis as bioactive compounds against T. marneffei. In vitro studies showed that compound 1 exerted a significantly stronger antifungal activity against T. marneffei than other new compounds, and the antifungal mechanism of compound 1 may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound 1 preventing and controlling talaromycosis.

For generalizations of concepts of different fields fractional derivative operators as well as fractional integral operators are useful notions. Our aim in this paper is to discuss boundedness of the integral operators which contain Mittag-Leffler function in their kernels. The results are obtained for strongly (α,h−m)-convex functions which hold for different kinds of convex functions at the same time. They also give improvements/refinements of many already published results.

Abstract Background Macrolactins, a type of macrolide antibiotic, are toxic to the producer strains. As such, its level is usually maintained below the lethal concentration during the fermentation process. To improve the production of macrolactins, we applied adaptive laboratory evolution technology to engineer a saline-resistant mutant strain. The hypothesis that strains with saline resistance show improved macrolactins production was investigated. Results Using saline stress as a selective pressure, we engineered a mutant strain with saline resistance coupled with enhanced macrolactins production within 60 days using a self-made device. As compared with the parental strain, the evolved strain produced macrolactins with 11.93% improvement in non-saline stress fermentation medium containing 50 g/L glucose, when the glucose concentration increased to 70 g/L, the evolved strain produced macrolactins with 71.04% improvement. RNA sequencing and metabolomics results revealed that amino acid metabolism was involved in the production of macrolactins in the evolved strain. Furthermore, genome sequencing of the evolved strain revealed a candidate mutation, hisD D41Y, that was causal for the improved MLNs production, it was 3.42 times higher than the control in the overexpression hisD D41Y strain. Results revealed that saline resistance protected the producer strain from feedback inhibition of end-product (macrolide antibiotic), resulting in enhanced MLNs production. Conclusions In the present work, we successfully engineered a mutant strain with enhanced macrolactins production by adaptive laboratory evolution using saline stress as a selective pressure. Based on physiological, transcriptomic and genetic analysis, amino acid metabolism was found to benefit macrolactins production improvement. Our strategy might be applicable to improve the production of other kinds of macrolide antibiotics and other toxic compounds. The identification of the hisD mutation will allow for the deduction of metabolic engineering strategies in future research.

Repetitive electrical nerve stimulation can induce a long-lasting perturbation of the axon's membrane potential, resulting in unstable stimulus-response relationships. Despite being observed in electrophysiology, the precise mechanism underlying electrical stimulation-dependent (ES-dependent) instability is still an open question. This study proposes a model to reveal a facet of this problem: how threshold fluctuation affects electrical nerve stimulations. This study proposes a new method based on a Circuit-Probability theory (C-P theory) to reveal the interlinkages between the subthreshold oscillation induced by neurons' resonance and ES-dependent instability of neural response. Supported by in-vivo studies, this new model predicts several key characteristics of ES-dependent instability and proposes a stimulation method to minimize the instability. This model provides a powerful tool to improve our understanding of the interaction between the external electric field and the complexity of the biophysical characteristics of axons.

This study evaluated the feasibility of domesticating the bioflocs with activated sludge as inoculum at high salinity. By using the gradually increase salinity from 0.2 to 4.0%, the study evaluated the effectiveness of bioflocs in sustaining the water quality of aquaculture, the biofloc morphology characteristics and microbial community structure of bioflocs in order to discover the influence of salinity. From the perspective of sustaining the water quality of bioflocs, the COD removal efficiency dropped sharply from 63.9% to 3.7%, the NO3−-N was maintained below 0.5 mg/L but the NH4+-N exceeded the safety threshold of aquaculture at the salinity of 2.5–4.0%. From the pespective of flocculation of flocs, the biofloc volume index and content were maintained at about 30 ml/g and 7 g/L, while the floc particle size (45–200 um) tended to increase cumulatively, showing good agglomeration, sedimentation and stability. From the pespective of floc microbial community structure, Arenibacter, Thauera, Paracoccus and Denitromonas became the dominant genera with relative abundances of 4.8–7.5%, 4.9–17.1%, 3.0–4.7% and 5.3–14.1% at 3.0–4.0% salinity, respectively, however, the relative abundance of Candidatus Competibacter rapidly decreased from 15.0% to 2.5% with the increasing salinity from 1.0% to 4.0%. Furthermore, Redundancy analysis (RDA) indicated that salinity was a key environmental factor affecting floc community, and Functional Annotation of Prokaryotic Taxa (FAPROTAX) confirmed the promoted flocs denitrification as well as inhibited nitrification and hydrocarbon cycling in higher salinity to some extent. This study demonstrated the feasibility of using freshwater activated sludge as a base nucleus for biofloc formation for salinity up to 2% – 2.5%, which provided a useful reference for improving the taste and nutritional value of fish cultured by Biofloc Technology (BFT).

There are various secondary flow types in turbodrill’s blade cascades, and all kinds of secondary flow have a significant effect on flow loss. In this paper, the stator cascade of φ160 mm turbodrill is taken as the research object, and the CFD method is used to analyze the secondary flow and its evolution. The origin and evolution mechanism of secondary flow is explained from the flow mechanism. The results show that when the working rotary speed is lower than the design rotary speed, the secondary flows are composed of suction surface separation vortex, horseshoe vortex, and passage vortex coexisting. The intensity of secondary flows increases with the decrease of rotary speed. When the working rotary speed is near the design rotary speed, the secondary flows include horseshoe vortex, passage vortex, and corner vortex. When the working rotary speed is higher than the design rotary speed, the secondary flows consist of pressure surface separation vortex and suction surface trailing edge separation vortex. Regardless of rotary speed, secondary flow intensity in the shroud region is greater than the hub region, which has a greater influence on the mainstream. In addition, compared with high rotary speeds, secondary flow intensity is greater at low rotary speeds, resulting in greater flow losses.

The Mycobacterium tuberculosis (MTB) infection causes tuberculosis (TB) and has been a long-standing public-health threat. It is urgent that we discover novel antitubercular agents to manage the increased incidence of multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains of MTB and tackle the adverse effects of the first- and second-line antitubercular drugs. We previously found that gliotoxin (1), 12, 13-dihydroxy-fumitremorgin C (2), and helvolic acid (3) from the cultures of a deep-sea-derived fungus, Aspergillus sp. SCSIO Ind09F01, showed direct anti-TB effects. As macrophages represent the first line of the host defense system against a mycobacteria infection, here we showed that the gliotoxin exerted potent anti-tuberculosis effects in human THP-1-derived macrophages and mouse-macrophage-leukemia cell line RAW 264.7, using CFU assay and laser confocal scanning microscope analysis. Mechanistically, gliotoxin apparently increased the ratio of LC3-II/LC3-I and Atg5 expression, but did not influence macrophage polarization, IL-1β, TNF-a, IL-10 production upon MTB infection, or ROS generation. Further study revealed that 3-MA could suppress gliotoxin-promoted autophagy and restore gliotoxin-inhibited MTB infection, indicating that gliotoxin-inhibited MTB infection can be treated through autophagy in macrophages. Therefore, we propose that marine fungi-derived gliotoxin holds the promise for the development of novel drugs for TB therapy.

Montmorillonite clay was modified by pillaring with AlMn oxides in different Al/Mn ratios and intercalation of two kinds of N-containing polymers (i.e., chitosan (CS) and polyvinyl pyrrolidinone (PVP)) chains. The modified pillared montmorillonite clay (PM) showed a rich two-dimensional layered porous structure with tunable parameters, such as large interlayer spacing, high specific area, and large porous volume. They were then used as supports for Pd nanoparticles. As applied in coupling reactions of aryl halides with terminal alkynes, Pd@CS/AlMn-PM showed better comprehensive catalytic performance than Pd@PVP/AlMn-PM. This was mainly attributed to its higher specific area, stronger chelation to Pd species, and better solvent resistance.

The coral-derived fungus Aspergillus austwickii SCSIO41227 from Beibu Gulf yielded four previously uncharacterized compounds, namely asperpentenones B–E (1–4), along with twelve known compounds (5–16). Their structures were elucidated using HRESIMS and NMR (1H and 13C NMR, HSQC, HMBC), among which the stereo-structure of compounds 1–3 was determined by calculated ECD. Furthermore, compounds 1–16 were evaluated in terms of their enzyme (acetylcholinesterase (AChE), pancreatic lipase (PL), and neuraminidase (NA)) inhibitory activities. These bioassay results revealed that compounds 2 and 14 exerted noticeable NA inhibitory effects, with IC50 values of 31.28 and 73.64 μM, respectively. In addition, compound 3 exhibited a weak inhibitory effect against PL. Furthermore, these compounds showed the potential of inhibiting enzymes in silico docking analysis to demonstrate the interactions between compounds and proteins.

Five new fusarin derivatives, steckfusarins A–E (1–5), and two known natural products (6, 7), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC50 value of 74.5 µg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 µM.

Tian et al. use mathematical modelling to estimate the impact of various interventions on malaria incidence on Hainan Island, also taking into account climate change. They find that although malaria transmission has been exacerbated by climate change, insecticide-treated bed nets and other interventions were effective in controlling the disease.