The aging of microplastics exacerbates the damage to photosynthetic performance and bioenergy production in microalgae (Chlorella pyrenoidosa).

The toxicity of microplastics (MPs) on freshwater plants has been widely studied, yet the influence of aged MPs remains largely unexplored. Herein, we investigated the influence of polyvinyl chloride (PVC) MPs, both before and after aging, at different environmentally relevant concentrations on Chlorella pyrenoidosa, a freshwater microalgae species widely recognized as a valuable biomass resource. During a 96-h period, both virgin and aged MPs hindered the growth of C. pyrenoidosa. The maximum growth inhibition rates were 32.40 % for virgin PVC at 250 mg/L and 44.72 % for aged PVC at 100 mg/L, respectively. Microalgae intracellular materials, i.e., protein and carbohydrate contents, consistently decreased after MP exposure, with more pronounced inhibition observed with aged PVC. Meanwhile, the MP aging significantly promoted the nitrogen uptake of C. pyrenoidosa, i.e., 1693.45 ± 42.29 mg/L (p < 0.01), contributing to the production of humic acid-like substances. Additionally, aged PVC induced lower chlorophyll a and Fv/Fm when compared to virgin PVC, suggesting a more serious inhibition of the photosynthesis process of microalgae. The toxicity of MPs to C. pyrenoidosa was strongly associated with intercellular oxidative stress levels. The results indicate that MP aging exacerbates the damage to photosynthetic performance and bioenergy production in microalgae, providing critical insights into the toxicity analysis of micro(nano)plastics on freshwater plants.

Generation and Fate of Nanoplastics in the Intestine of Plastic-Degrading Insect (Tenebrio molitor Larvae) during Polystyrene Microplastic Biodegradation.

The insect Tenebrio molitor exhibits ultrafast efficiency in biodegrading polystyrene (PS). However, the generation and fate of nanoplastics (NPs) in the intestine during plastic biodegradation remain unknown. In this study, we investigated the biodegradation of PS microplastics (MPs) mediated by T. molitor larvae over a 4-week period and confirmed biodegradation by analyzing Δδ13C in the PS before and after biotreatment (-28.37‰ versus -24.88‰) as an effective tool. The ·OH radicals, primarily contributed by gut microbiota, and H2O2, primarily produced by the host, both increased after MP digestion. The size distribution of residual MP particles in excrements fluctuated within the micrometer ranges. PS NPs were detected in the intestine but not in the excrements. At the end of Weeks 1, 2, 3, and 4, the concentrations of PS NPs in gut tissues were 3.778, 2.505, 2.087, and 2.853 ng/lava, respectively, while PS NPs in glands were quantified at 0.636, 0.284, and 0.113 ng/lava and eventually fell below the detection limit. The PS NPs in glands remained below the detection limit at the end of Weeks 5 and 6. This indicates that initially, NPs generated in the gut entered glands, then declined gradually and eventually disappeared or possibly biodegraded after Week 4, associated with the elevated plastic-degrading capacities of T. molitor larvae. Our findings unveil rapid synergistic MP biodegradation by the larval host and gut microbiota, as well as the fate of generated NPs, providing new insights into the risks and fate associated with NPs during invertebrate-mediated plastic biodegradation.

Novel Insights into Alkyl Polyglucoside Biosurfactant Promoting Anaerobic Dark Fermentation for Hydrogen Production in Sludge.

Anaerobic fermentation of excess sludge (ES) for hydrogen production is a crucial strategy for resource utilization and environmentally friendly treatment. However, the low hydrolysis efficiency of ES and the depletion of produced hydrogen have become the limiting factors for low hydrogen yield. This study innovatively applied the bio-based surfactant alkyl polyglucoside (APG) to enhance the efficiency of dark fermentation for hydrogen production from ES. When the APG content was 100 mg/g (calculated based on total suspended solids), the maximum hydrogen production reached 17.8 mL/g VSS, approximately 3.7 times that in the control group. Mechanistic analysis revealed that APG promoted the release of organic matter from ES. APG also facilitated the release of soluble protein and soluble polysaccharide, increasing the organic matter reduction rate to 34.8%, significantly higher than other groups. APG enhanced the accumulation of volatile fatty acids and promoted the proportion of small molecular carboxylic acids. Enzyme activity analysis revealed that APG promoted the activity of hydrolytic enzymes but inhibited the activity of hydrogen-consuming enzymes. The research results provide a green and environmentally friendly strategy for the efficient resource utilization of ES.

Exploring Impact of Probiotic-Fermented Soymilk on Dextran-Sulfate-Sodium-Induced Ulcerative Colitis via Modulating Inflammation and Gut Microbiota Profile.

SCOPE: Lactic acid bacteria with probiotic functions and their fermentation products play a role in regulating ulcerative colitis (UC). This study investigates the potential role of fermented soymilk (FSM4) rich in isoflavones on DSS-induced UC. METHODS AND RESULTS: Mice received 3% DSS and are supplemented daily once for 1 week by NFSM and FSM4. DSS usually causes intestinal inflammation and alters the gut microbiota. FSM4 intervention improves the UC-related inflammation and gut microbiota alteration. It considerably decreases pro-inflammatories such as TNF-α, IL-1ß, and IL-6 in serum and COX-2 and MPO in colon tissues and pathogenic bacteria (Escherichia-Shigella). This facilitates gut-healthy bacteria growth. These healthy bacteria negatively correlat with pro-inflammatory factors but positively associated with acetic acid, butyric acid, and propionic acid, which may act for PPAR-γ pathway activating and NF-κB p65 pathway inhibiting, lowering the risk of UC. Overall, FSM4 might alleviate UC and significantly reverse the dysbiosis of gut microbiota via the PPAR-γ activation. It could be a good alternative for developing functional food to protect against UC. CONCLUSION: FSM4 attenuates intestinal inflammation and modulates the SCFA-producing bacteria growth, which enable the PPAR-γ activation to alleviate the UC target, which could be a dietary intervention strategy for gut health.

Effects of fermentation with Lactiplantibacillus plantarum NCU116 on the antihypertensive activity and protein structure of black sesame seed.

Effects of fermentation by Lactobacillus Plantarum NCU116 on the antihypertensive potential of black sesame seed (BSS) and structure characteristics of fermented black sesame seed protein (FBSSP) were investigated. Angiotensin-I-converting enzyme (ACE) inhibition and zinc chelating ability of fermented black sesame seed hydrolysate (FBSSH) reached the highest of 60.78 ± 3.67 % and 2.93 ± 0.04 mg/mL at 48 h and 60 h of fermentation, respectively. Additionally, the antioxidant activities of FBSSH and surface hydrophobicity of FBSSP were increased noticeably by fermentation. The α-helix and ß-rotation of FBSSP tended to decrease and increase, respectively, during fermentation. Correlation analysis indicated strong positive relationships between ß-turn and ACE inhibition activity as well as zinc chelating ability with correlation coefficients r of 0.8976 and 0.8932. Importantly, novel ACE inhibitory peptides LLLPYY (IC50 = 12.20 µM) and ALIPSF (IC50 = 558.99 µM) were screened from FBSSH at 48 h using in silico method. Both peptides showed high antioxidant activities in vitro. Molecular docking analysis demonstrated that the hydrogen bond connected with zinc ions of ACE mainly attributed to the potent ACE inhibitory activity of LLLPYY. The findings indicated that fermentation by Lactobacillus Plantarum NCU116 is an effective method to enhance the antihypertensive potential of BSS.

Biodegradation of polyvinyl chloride, polystyrene, and polylactic acid microplastics in Tenebrio molitor larvae: Physiological responses.

It is widely understood that microplastics (MPs) can induce various biological stresses in macroinvertebrates that are incapable of biodegrading plastics. However, the biodegradation and physiological responses of plastic-degrading macroinvertebrates toward MPs of different degradability levels remain unexplored. In this study, Tenebrio molitor larvae (mealworms) were selected as a model of plastics-degrading macroinvertebrate, and were tested against three common plastics of different degradability rankings: polyvinyl chloride (PVC), polystyrene (PS), and polylactic acid (PLA) MPs (size <300 µm). These three MPs were biodegraded with the rate sequence of PLA > PS > PVC, resulting in a reversed order of negative physiological responses (body weight loss, decreased survival, and biomass depletion) of mealworms. Simultaneously, the levels of reactive oxygen species (ROS), antioxidant enzyme activities, and lipid peroxidation were uniformly increased as polymer degradability decreased and intermediate toxicity increased. PVC MPs exhibited higher toxicity than the other two polymers. The oxidative stresses were effectively alleviated by supplementing co-diet bran. The T. molitor larvae fed with PLA plus bran showed sustainable growth without an increase in oxidative stress. The results provide new insights into the biotoxicity of MPs on macroinvertebrates and offer comprehensive information on the physiological stress responses of plastic-degrading macroinvertebrates during the biodegradation of plastics with different degradability levels.

Effects of enzyme treatment on the antihypertensive activity and protein structure of black sesame seed (Sesamum indicum L.) after fermentation pretreatment.

Effects of enzyme treatment on the hypertensive potential and protein structure of black sesame seed (BSS) were investigated. Compared with BSS, Angiotensin-converting enzyme (ACE) inhibition of fermented black sesame seed (FBSS) has significantly improved after acid protease processing and reached 75.39% at 2 U/g in 3 h. Meanwhile, the zinc chelating ability and antioxidant activity of FBSS hydrolysate as well as surface hydrophobicity, free sulfhydryl content, and peptide content of FBSS protein, were significantly increased. The results illustrated that this strategy promoted the protein unfolding and exposure of hydrophobic residues, thus contributing toward enzymatic hydrolysis. Secondary structure results indicated that the α-helix of FBSS protein and ß-sheet of BSS protein decreased after hydrolyzing. The differences in ACE inhibition may also result from the difference in peptide sequence except for peptide content. In conclusion, the combination of fermentation pretreatment and enzyme treatment is an effective method to enhance the antihypertensive potential of BSS.

Unveiling the residual plastics and produced toxicity during biodegradation of polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC) microplastics by mealworms (Larvae of Tenebrio molitor).

Evidence for plastic degradation by mealworms has been reported. However, little is known about the residual plastics derived from incomplete digestion during mealworm-mediated plastic biodegradation. We herein reveal the residual plastic particles and toxicity produced during mealworm-mediated biodegradation of the three most common microplastics, i.e., polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC). All three microplastics are effectively depolymerized and biodegraded. We discover that the PVC-fed mealworms exhibit the lowest survival rate (81.3 ± 1.5%) and the highest body weight reduction (15.1 ± 1.1%) among the experimental groups by the end of the 24-day experiment. We also demonstrate that the residual PVC microplastic particles are more difficult to depurate and excrete for the mealworms compared to the residual PE and PS particles by using laser direct infrared spectrometry. The levels of oxidative stress responses, including reactive oxygen species, antioxidant enzyme activities, and lipid peroxidation, are also highest in the PVC-fed mealworms. Sub-micron microplastics and small microplastics are found in the frass of mealworms fed with PE, PS, and PVC, with the smallest particles detected at diameters of 5.0, 4.0, and 5.9 µm, respectively. Our findings provide insights into the residual microplastics and microplastic-induced stress responses in macroinvertebrates under micro(nano)plastics exposure.

RBM3 interacts with Raptor to regulate autophagy and protect cardiomyocytes from ischemia-reperfusion-induced injury.

Acute myocardial infarction (AMI) is a common disease with high morbidity and mortality worldwide. However, postinfarction pathogenesis remains unclear, and it is particularly important to identify new therapeutic targets. The RNA-binding motif protein RBM3 (also known as cold-inducible protein) is known to promote translation and is associated with tumor proliferation and neuroprotection. However, little is known about the biological effects of RBM3 on myocardial infarction. In the present study, we found that RBM3 expression was significantly upregulated in ischemia-reperfusion (I/R) condition and downregulation of RBM3 inhibited autophagy and promoted apoptosis in cardiomyocytes. We confirmed that RBM3 interacts with Raptor to regulate the autophagy pathway. Taken together, these findings illustrate the protective effects of RBM3 against I/R-induced myocardial apoptosis through the autophagy pathway.

Moxifloxacin Derivatives with Potential Antibacterial Activity against Methicillin- Resistant Staphylococcus Aureus (MRSA).

BACKGROUND: Methicillin-resistant S. aureus (MRSA) has already tormented humanity and the environment for a long time and is responsible for many difficult-to-treat infections. Unfortunately, there are limited therapeutic options, and MRSA isolates with complete resistance to vancomycin, the first-line drug for the treatment of MRSA infections, have already emerged in recent years. Moxifloxacin retained activity against mutant bacterial strains with various levels of fluoroquinolones resistance and had a lower potential to select for resistant mutants. Isatin is a versatile structure, and its derivatives are potent inhibitors of many enzymes and receptors. The fluoroquinolone- isatin derivatives demonstrated excellent antibacterial activity against both drug-sensitive and drug-resistant organisms. The structure-activity relationship elucidated that incorporation of 1,2,3-triazole moiety into the C-7 position of fluoroquinolone skeleton was favorable to the antibacterial activity. Accordingly, fluoroquinolone derivatives with isatin and 1,2,3-triazole fragments at the side chain on the C-7 position are promising candidates to fight against drug-resistant bacteria. OBJECTIVE: To explore more active moxifloxacin derivatives to fight against MRSA and enrich the structure-activity relationships. METHODS: The synthesized moxifloxacin derivatives 7a-i and 14a-f were evaluated for their antibacterial activity against a panel of MRSA strains by means of standard two-fold serial dilution method. RESULTS: The majority of the synthesized moxifloxacin derivatives were active against most of the tested MRSA strains with MIC values in a range of 1 to 64 µg/mL. The mechanistic investigations revealed that topoisomerase IV was one of the targets for antibacterial activity. CONCLUSION: These derivatives are useful scaffolds for the development of novel topoisomerase IV inhibitors.

Catalyst-Free Self-Healing Bio-Based Polymers: Robust Mechanical Properties, Shape Memory, and Recyclability.

The poor mechanical properties and disadvantages of catalysts limit the application of self-healing materials. To address these issues, catalyst-free self-healing bio-based polymers (AESO-EMPA polymers) with robust mechanical properties were prepared using epoxidized maleopimaric anhydride (EMPA) and aminated epoxidized soybean oil (AESO). The AESO-EMPA polymers are recyclable and exhibit self-healing and shape memory because of the dual-dynamic network of multiple H-bonds and dynamic ester bonds in the structure. Under the synergistic catalysis of the tertiary amines and hydroxyl groups originated from the polymers, the polymers in this study achieve network rearrangement without the need for additional catalysts. The polymers also exhibit excellent mechanical properties with a tensile strength of 29.1 ± 0.25 MPa and a Tg of 80.2 °C owing to the unique rigid backbone of rosin and the dual-dynamic network. The AESO-EMPA polymers can be used as reusable adhesives and exhibit excellent shear strength and repair rates.

A novel PGAM5 inhibitor LFHP-1c protects blood-brain barrier integrity in ischemic stroke.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate Macaca fascicularis model with tMCAO. Thus, our study identifies compound LFHP-1c as a firstly direct PGAM5 inhibitor showing amelioration of ischemia-induced BBB disruption in vitro and in vivo, and provides a potentially therapeutics for brain ischemic stroke.

UBE2D3 contributes to myocardial ischemia-reperfusion injury by regulating autophagy in dependence of p62/SQSTM1.

The impairment of autophagic flux has been widely recognized in myocardial ischemia-reperfusion (I/R) injury, but its underlying mechanism contributing to impaired autophagic flux is poorly understood. As celluar major degradation systems, autophagy and ubiquitin proteasome system (UPS) participate in the multitudinous progression of disease by interactive relationship. Especially UBE2D3, one of the ubiquitin-binding enzyme E2 family, is closely related to the regulation impairment of autophagic flux under I/R in our study. Therefore, this study aims to further explore the regulatory mechanism of UBE2D3 in I/R induced autophagy. We determined interference with UBE2D3 alleviated injury of myocardial cells both in vivo and in vitro. Conversely, when inhibiting proteasome function by injecting MG-132, myocardial infarct size of rats became increasingly enhanced, along with the high expression levels of LDH and CK-MB in serum, compared with myocardial I/R injury without treatment of MG-132. This had been caused by UBE2D3 promoting p62/SQSTM1(p62) ubiquitination(Ub), which lead to worsen the impairment of autophagic flux induced by myocardial I/R injury. In addition, UBE2D3 could also participate in the regulation of autophagy by negatively regulating mTOR. But more surprisingly, this mechanism was independent of the known mTOR-beclin1 pathway. These results suggested that in myocardial I/R injury, UBE2D3 promoted p62 ubiquitination to aggravate the impairment of autophagic flux. Moreover, mTOR was also involved in its regulation of autophagic flux in a way escaped from beclin1.

Metatranscriptomics reveals the gene functions and metabolic properties of the major microbial community during Chinese Sichuan Paocai fermentation.

Chinese Sichuan Paocai (CSP) is one of the world's best-known fermented vegetables with a large presence in the Chinese market. The dynamic microbial community is the main contributor to Paocai fermentation. However, little is known about the ecological distribution and functional importance of these community members. In this study, metatranscriptomics was used to comprehensively explore the active microbial community members and key transcripts with significant functions in the Paocai fermentation process. Enterobacter, Leuconostoc, and Lactobacillus dominated the three-fermentation stages (Pre-, Mid- and Lat-), respectively. Carbon metabolism was the most abundant pathway. GH (glycoside hydrolase) and GT (lycosyl transferase) were the two most highly expressed carbohydrate-active enzymes. The most highly differentially expressed genes were grouped in the biosynthesis of amino acids, followed by glycolysis. Meta-pathways in the Sichuan Paocai fermentation ecosystem were reconstructed, Lactobacillaceae and Enterobacteriaceae were the two most important metabolic contributors. In addition, the nrfA and nirB were two genes referred to distinct nitrite reductase enzymes and 9 specialized genes, such as eclo, ron and ent were expressed to produce autoinducer 2 (AI-2) kinase in response to population density. The present study revealed functional enzymes and meta-pathways of the active microbial communities, which provide a deeper understanding of their contribution to CSP products.

Sex differences in immune responses to SARS-CoV-2 in patients with COVID-19.

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.

A General Electrodeposition Strategy for Fabricating Ultrathin Nickel Cobalt Phosphate Nanosheets with Ultrahigh Capacity and Rate Performance.

Transition-metal phosphates/phosphides possess promising theoretical electrochemical characteristics and exhibit great potential in advanced supercapacitors. Unfortunately, limited by the processing techniques and overall structure, their specific capacity and rate performance are still unsatisfactory. Herein, we report the fabrication of transition-metal phosphate electrodes with an ultrathin sheetlike array structure by one-step electrodeposition at room temperature. As a proof-of-concept, a transition-metal phosphate member of NiCo(HPO4)2·3H2O with an ultrathin nanosheet structure (thickness ∼2.3 nm) was synthesized and investigated. The as-prepared NiCo(HPO4)2·3H2O electrode showcases an ultrahigh specific capacity of 1768.5 C g-1 at 2 A g-1 (the highest value for transition-metal phosphates/phosphides reported to date), superb rate performance of 1144.8 C g-1 at 100 A g-1, and excellent electrochemical stability. Moreover, the transition-metal phosphate nanosheet array can be uniformly deposited on various conductive substrates, demonstrating the generality of our strategy. Therefore, this simple electrodeposition strategy provides an opportunity to fabricate ultrathin transition-metal phosphate nanosheet materials that can be used for energy storage/conversion, electrocatalysis, and other electrochemical energy-related devices.

Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation.

OBJECTIVE: We aimed to find crucial microRNAs (miRNAs) associated with the development of atrial fibrillation (AF), and then try to elucidate the possible molecular mechanisms of miRNAs in AF. METHODS: The miRNA microarray, GSE68475, which included 10 right atrial appendage samples from patients with persistent AF and 11 samples from patients with normal sinus rhythm, was used for the analysis. After data preprocessing, differentially expressed miRNAs were screened using limma. Target genes of miRNAs were predicted using miRWalk2.0. We then conducted functional enrichment analyses for miRNA and target genes. Protein-protein interaction (PPI) network and module analyses for target genes were performed. Finally, transcription factors (TFs)-target genes regulatory network was predicted and constructed. RESULTS: Seven genes, including CAMK2D, IGF2R, PPP2R2A, PAX6, POU3F2, YWHAE, and AP2A2, were targeted by TFs. Among these seven genes, CAMK2D (targeted by miR-31-5p), IGF2R (targeted by miR-204-5p), PAX6 (targeted by miR-223-3p), POU3F2 (targeted by miR-204-5p), YWHAE (targeted by miR-31-5p), and AP2A2 (targeted by miR-204-5p) belonged to the top 10 degree genes in the PPI network. Notably, MiR-204-5p, miR-31-5p, and miR-223-3p had more target genes. Besides, CAMK2D was enriched in some pathways, such as adrenergic signaling in cardiomyocytes pathway and cAMP signaling pathway. YWHAE was enriched in the Hippo signaling pathway. CONCLUSION: miR-31-5p played a crucial role in cardiomyocytes by targeting CAMK2D and YWHAE via cAMP and Hippo signaling pathways. miR-204 was involved in the progression of AF by regulating its target genes IGF2R, POU3F2, and AP2A2. On the other hand, miR-223-3p functioned in AF by targeting PAX6, which was associated with the regulation of apoptosis in AF. This study would provide a theoretical basis and potential therapeutic targets for the treatment of AF. (Anatol J Cardiol 2020; 23: 324-33).

Defervescent dengue patients might be a potential source of infection for vector mosquitoes.

BACKGROUND: Dengue is a re-emerging public health problem and mosquito-borne infectious disease that is transmitted mainly by Aedes aegypti and Ae. albopictus. Early diagnosis, isolation, and treatment of patients are critical steps for dengue epidemic control, especially to prevent secondary transmission of dengue virus (DENV). However, little is known about defervescent dengue patients as a source of infection. METHODS: This case study describes 1268 dengue patients hospitalized at Guangzhou Eighth People's Hospital from June 2013 to December 2014. The viral loads of each individual were measured using real-time reverse transcription-polymerase chain reaction. Ae. aegypti and Ae. albopictus were exposed to blood meal with gradated dengue viral loads to characterize the relationship between viremia in dengue patients and the vector competence of vector mosquitoes. RESULTS: The viral numbers in the blood were measured, ranging from 108 to 103 copies/ml from day 1 to day 12 after fever onset. Vector competence analysis of Ae. aegypti and Ae. albopictus indicated that viremia > 104 copies/ml can still infect vector mosquitoes, which implied that the defervescent dengue patients might be a source of infection. CONCLUSIONS: The results of this study indicate that some defervescent dengue patients still have sufficient viral load to infect vector mosquitoes. Therefore, the protection against mosquito biting for these people should be extended to prevent secondary transmission events.

Author Correction: The natural product 4,10-aromadendranediol induces neuritogenesis in neuronal cells in vitro through activation of the ERK pathway.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Synthesis and Target Identification of Benzoxepane Derivatives as Potential Anti-Neuroinflammatory Agents for Ischemic Stroke.

Benzoxepane derivatives were designed and synthesized, and one hit compound emerged as being effective in vitro with low toxicity. In vivo, this hit compound ameliorated both sickness behavior through anti-inflammation in LPS-induced neuroinflammatory mice model and cerebral ischemic injury through anti-neuroinflammation in rats subjected to transient middle cerebral artery occlusion. Target fishing for the hit compound using photoaffinity probes led to identification of PKM2 as the target protein responsible for anti-inflammatory effect of the hit compound. Furthermore, the hit exhibited an anti-neuroinflammatory effect in vitro and in vivo by inhibiting PKM2-mediated glycolysis and NLRP3 activation, indicating PKM2 as a novel target for neuroinflammation and its related brain disorders. This hit compound has a better safety profile compared to shikonin, a reported PKM2 inhibitor, identifying it as a lead compound in targeting PKM2 for the treatment of inflammation-related diseases.