A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

[Change Characteristics of Carbonaceous Aerosol in Chengdu from 2018 to 2021].

Carbonaceous aerosol is an important component of atmospheric fine particulates （PM2.5） that has an important effect on global climate change, atmospheric visibility, regional air quality, and human health. In order to investigate the long-term change characteristics of carbonaceous aerosols under the background of emission reduction, the concentrations of organic carbon （OC）, elemental carbon （EC） in PM2.5 samples, and volatile organic compounds （VOCs） in Chengdu from 2018 to 2021 and the corresponding meteorological factors were obtained through real-time online monitoring. The results showed that the average ρ（OC） and ρ（EC） during the monitoring period were （10.9 ±5.7） µg·m-3 and （2.6 ±1.9） µg·m-3, accounting for 25.2% and 6.0% of PM2.5, respectively, and the average ρ（SOC） was （5.7 ±3.3） µg·m-3, accounting for 52.9% of OC. The concentrations of OC, EC, and PM2.5 showed a downward trend from 2018 to 2020 [PM2.5： The concentration of average annual decrease was -7.1 µg·ï¼ˆm3·a） -1, with an average annual decrease of -14.6 %·a-1； OC： -1.7 µg·ï¼ˆm3·a）-1, -14.2 %·a-1； EC： -0.1 µg·ï¼ˆm3·a）-1, -4.4 %·a-1], and the concentrations of each pollutant in 2021 rebounded in different ranges compared with those in 2020. The concentrations of PM2.5 and OC were as follows： winter > spring > autumn > summer, and the concentrations of EC were as follows： winter > autumn > spring > summer. The proportions of OC and EC were higher in summer and autumn than in other seasons, with the average proportions of 26.8% and 6.9%, respectively. With the aggravation of the pollution level, OC, EC, and SOC concentrations gradually increased, but the proportions in PM2.5 showed a gradual downtrend, indicating that the control factor of PM2.5 pollution in Chengdu was not the carbon component. Source apportionment results showed that carbonaceous aerosols in Chengdu were mainly affected by motor vehicles, industrial sources, biomass combustion sources, and VOCs secondary reaction. From 2019 to 2021, EC was affected by the characteristic components of motor vehicles and decreased yearly. OC and EC were affected by VOCs more in spring and autumn than in other seasons. VOCs emission management should be increased in spring and autumn to reduce the impact of secondary reaction.

Far-infrared therapy promotes exercise capacity and glucose metabolism in mice by modulating microbiota homeostasis and activating AMPK.

The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.

The Effect of Oxidative Stress and Antioxidants Treatment on Gestational Diabetes Mellitus Outcome: A Scoping Review.

Diagnosing a pregnant woman's glucose intolerance is referred to as gestational diabetes mellitus (GDM). Diabetes has been linked to enhanced oxidative stress. In this condition, oxidative stress may damage nucleic acids, fats, and proteins, which in turn affects cell and tissue functions. The present study highlights the relationship between oxidative stress and GDM, with a particular focus on the role of hyperglycemia-induced processes during reactive oxygen species (ROS) oversupply, followed by it discusses the oxidative stress biomarkers and assesses the effects of antioxidant supplements on glycemic control, inflammatory processes, and oxidative stress among individuals with GDM. Two reviewers conducted a comprehensive literature search utilizing the PubMed®, Web of Science™, and Scopus® databases. Only items published in the English language up until June 2024 were taken into account. We conducted a thorough search of research databases to identify articles that had the terms "oxidative stress" or "antioxidant" and "GDM". From this search, we selected 55 relevant papers to be included in this narrative review. Pregnancy-induced hypertension, postpartum bleeding, lower birth weight, a higher risk of hyperbilirubinemia in their neonates, fetal growth retardation, and birth asphyxia were revealed to be outcomes of women enduring major oxidative stress during pregnancy. Furthermore, tight glycemic control both before and throughout pregnancy as well as oxidative stress treatment may help women highly prone to GDM.

Site-selective S-gem-difluoroallylation of unprotected peptides with 3,3-difluoroallyl sulfonium salts.

Bench-stable 3,3-difluoroallyl sulfonium salts (DFASs), featuring tunable activity and their editable C-ß and gem-difluoroallyl group, proved to be versatile fluoroalkylating reagents for site-selective S-gem-difluoroallylation of cysteine residues in unprotected peptides. The reaction proceeds with high efficiency under mild conditions (ambient temperature and aqueous and weak basic conditions). Various protected/unprotected peptides, especially bioactive peptides, are site-selectively S-gem-difluoroallylated. The newly added gem-difluoroallyl group and other functional groups derived from C-ß of DFASs are poised for ligation with bio-functional groups through click and radical chemistry. This stepwise "doubly orthogonal" modification of peptides enables the construction of bioconjugates with enhanced complexity and functionality. This proof of principle is successfully applied to construct a peptide-saccharide-biotin chimeric bioconjugate, indicating its great potential application in medicinal chemistry and chemical biology.

Rapid synthesis of aminal-linked covalent organic frameworks for CO2/CH4 separation.

As an emerging category of crystalline porous materials, covalent organic frameworks (COFs) are primarily synthesized via solvothermal methods. However, achieving rapid synthesis of COFs through this approach poses a significant challenge. To address the issue of slow synthesis, we studied the crystallization process of aminal-linked COFs via the condensation of a cost-effective aldehyde and secondary amine, and successfully expedited the synthesis of COFs within a one-hour duration. Furthermore, gram-scale aminal-linked COFs with abundant ultra-microporous channels demonstrated promising potential for CO2/CH4 separation. This study enables the rapid synthesis of aminal-linked COFs from cheap raw materials, which lays a foundation for their practical applications.

Course-based intra-articular injection of medical chitosan mitigates excessive deposition of triacylglycerides in the synovial tissue of the knee osteoarthritis.

BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: 60 patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), VAS, WOMAC scoring, and AKS scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the pre-surgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced a slightly more pronounced decline in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.

BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.

BACKGROUND: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. ß-Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti-inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms. METHODS: An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS-induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH-DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents. RESULTS: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF-α, IL-1ß, and IL-6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti-inflammatory cytokines (IL-10), while also inhibiting HS-induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF-α and IL-1ß) in mouse BV2 cells. CONCLUSION: ß-Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut-brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.

RHBDF1 modulates cisplatin sensitivity of small cell lung cancer through YAP1/Smad2 signaling pathway.

Small cell lung cancer (SCLC) is a fatal tumor type that is prone to drug resistance. In our previous study, we showed that human rhomboid-5 homolog-1 (RHBDF1) was differentially expressed in 5 intrinsic cisplatin-resistant SCLC tissues compared with 5 intrinsic cisplatin-sensitive SCLC tissues by RNA sequencing, which intrigued us. We performed gain- and loss-of-function experiments to investigate RHBDF1 function, bioinformatics analysis, qRT-PCR, western blotting, and immunoprecipitation to elucidate the molecular mechanisms as well as detect RHBDF1 expression in SCLC by immunohistochemistry. We found that RHBDF1 knockdown promoted cell proliferation and cisplatin chemoresistance and inhibited apoptosis in vitro and in vivo. These effects could be reversed by overexpressing RHBDF1 in vitro. Mechanistically, RHBDF1 interacted with YAP1, which increased the phosphorylation of Smad2 and transported Smad2 to the nucleus. Among clinical specimens, the RHBDF1 was a low expression in SCLC and was associated with clinicopathological features and prognosis. We are the first to reveal that RHBDF1 inhibited cell proliferation and promoted cisplatin sensitivity in SCLC and elucidate a novel mechanism through RHBDF1/YAP1/Smad2 signaling pathway which played a crucial role in cisplatin chemosensitivity. Targeting this pathway can be a promising therapeutic strategy for chemotherapy resistance in SCLC.

Rumen and hindgut microbiome regulate average daily gain of preweaning Holstein heifer calves in different ways.

BACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05). CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.

Incorporating physiological knowledge into correlative species distribution models minimizes bias introduced by the choice of calibration area.

Correlative species distribution models (SDMs) are important tools to estimate species' geographic distribution across space and time, but their reliability heavily relies on the availability and quality of occurrence data. Estimations can be biased when occurrences do not fully represent the environmental requirement of a species. We tested to what extent species' physiological knowledge might influence SDM estimations. Focusing on the Japanese sea cucumber Apostichopus japonicus within the coastal ocean of East Asia, we compiled a comprehensive dataset of occurrence records. We then explored the importance of incorporating physiological knowledge into SDMs by calibrating two types of correlative SDMs: a naïve model that solely depends on environmental correlates, and a physiologically informed model that further incorporates physiological information as priors. We further tested the models' sensitivity to calibration area choices by fitting them with different buffered areas around known presences. Compared with naïve models, the physiologically informed models successfully captured the negative influence of high temperature on A. japonicus and were less sensitive to the choice of calibration area. The naïve models resulted in more optimistic prediction of the changes of potential distributions under climate change (i.e., larger range expansion and less contraction) than the physiologically informed models. Our findings highlight benefits from incorporating physiological information into correlative SDMs, namely mitigating the uncertainties associated with the choice of calibration area. Given these promising features, we encourage future SDM studies to consider species physiological information where available. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00226-0.

Fabrication of cinnamon essential oil nanoemulsions with high antibacterial activities via microfluidization.

The high volatility and hydrophobicity of cinnamon essential oils (CiEO) limited their practical application. To enhance their stability and antibacterial activity, nanoemulsions encapsulating CiEO were prepared using hydroxypropyl-ß-cyclodextrin/lauroyl arginate (HPCD/LAE) inclusion complexes through high-pressure microfluidization (HPM). Effects of HPM parameters on the stability and antibacterial properties of nanoemulsion were investigated. Results revealed that increased processing pressure and cycle numbers were associated with reduced droplet size and greater homogeneity in CiEO distribution. Storage and thermal stability were optimized at 100 MPa and seven cycles. Moreover, the nanoemulsions showed strong synergistic antibacterial against E. coli (19.79 mm) and S. aureus (23.61 mm) compared with LAE (11.52 mm and 12.82 mm, respectively) and CiEO alone (13.26 mm and 17.68 mm, respectively). This study provided new information for constructing CiEO nanoemulsion, which is suitable for use in the food industry.

Copper Difluorocarbene Enables Catalytic Difluoromethylation.

Despite the synthetic versatility of difluorocarbene, its high reactivity severely regulates widespread applications of difluorocarbene in organic synthesis. Here, we report a copper difluorocarbene-involved catalytic coupling, representing a new mode of the difluoromethylation reaction. This method allows difluoromethylation of a wide range of readily available allyl/propargyl electrophiles with NaBH3CN and low-cost difluorocarbene precursor BrCF2CO2K, featuring high cost-efficiency, high stereo- and regioselectivities, and high functional group tolerance, even with complex drug-like molecules. Applying the method led to the efficient synthesis of deuterated difluoromethylated compounds of medicinal interest. The resulting difluoromethylated allyl and allenyl products can serve as versatile synthons for diverse transformations, rendering the approach attractive for synthesizing complex fluorinated structures. Experimental mechanistic studies and computational calculations reveal that the formation of a difluoromethylcopper(I) intermediate through the nucleophilic attack of boron hydride on the copper(I) difluorocarbene is the key step in the reaction.

A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries.

BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.

Magnetic-gold nanoparticle-mediated paper-based biosensor for highly sensitive colorimetric detection of food adulteration.

Food adulteration presents a significant challenge due to the evasion of legal oversight and the difficulty of identification. Addressing this issue, there is an urgent need for on-site, rapid, visually based small-scale equipment, along with large-scale screening technology, to enable prompt results without providing opportunities for dishonest traders to react. Colorimetric reactions offer advantages in terms of speed, visualization, and miniaturization. However, there is a scarcity of suitable colorimetric reactions for food adulteration detection, and interference from colored food impurities and easily comparable color results affects accuracy. To overcome limitations, this study introduces a novel approach utilizing polydopamine magnetic nanoparticles to enrich DNA in food samples, effectively eliminating interfering components. By employing gold nanoparticles to generate magnetic-gold nanoparticles, a single magnetic bead achieves simultaneous enrichment, impurity removal, and detection. The use of paper-based biosensors and visualization equipment allows for the visualization and digital analysis of results, achieving a low detection limit of 4.59 nmol mL-1. The method also exhibits high accuracy and repeatability, with a RSD ranging from 1.6 % to 4.0 %. This innovative colorimetric method addresses the need for rapid, miniaturized, and large-scale detection, thus providing a solution for food adulteration challenges.

The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.

The ß-secretase BACE1 is a central drug target for Alzheimer's disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. Here, we identify BACE2 as the protease shedding the lymphangiogenic vascular endothelial growth factor receptor 3 (VEGFR3). Inactivation of BACE2, but not BACE1, inhibited shedding of VEGFR3 from primary human lymphatic endothelial cells (LECs) and reduced release of the shed, soluble VEGFR3 (sVEGFR3) ectodomain into the blood of mice, non-human primates and humans. Functionally, BACE2 inactivation increased full-length VEGFR3 and enhanced VEGFR3 signaling in LECs and also in vivo in zebrafish, where enhanced migration of LECs was observed. Thus, this study identifies BACE2 as a modulator of lymphangiogenic VEGFR3 signaling and demonstrates the utility of sVEGFR3 as a pharmacodynamic plasma marker for BACE2 activity in vivo, a prerequisite for developing BACE1-selective inhibitors for a safer prevention of Alzheimer's disease.

Efficient Photocatalytic Activation of Peroxymonosulfate by Cobalt-Doped Oxygen-Vacancies-Rich BiVO4 for Rapid Tetracycline Degradation.

In this work, cobalt-doped oxygen-vacancies-rich BiVO4 (Co/BiVO4-Vo) was successfully synthesized for the degradation of tetracycline (TC) by activated peroxymonosulfate (PMS) under visible light. The morphologies, microstructures, and optical properties of the photocatalysts were analyzed in detail. Co/BiVO4-Vo exhibited significantly enhanced degradation, removing 92.3% of TC within 10 min, which was greater than those of pure BiVO4 (62.2%) and oxygen-vacancies-rich BiVO4 (BiVO4-Vo) (72.0%), respectively. The photogenerated charge separation and transport properties were explored through surface photovoltage (SPV), photoluminescence spectrum (PL), and UV-vis diffuse reflectance spectroscopy (UV-vis DRS) measurements. Additionally, an in-depth investigation was conducted on the photocatalytically assisted advanced oxidation processes based on SO4•- (SR-AOPs) for the degradation of organic pollutants. The experimental results showed that the introduction of oxygen vacancies and Co doping achieved an effective separation of photogenerated carriers, which could accelerate the cycling between Co3+ and Co2+ and further activate PMS. The results of free radical capture experiments and electron spin resonance (ESR) experiments showed that reactive oxygen species (ROSs) such as 1O2, •O2-, and SO4•- played a dominant role in the removal of pollutants. This work provides a novel insight into the further development of efficient and rapid PMS photoactivators for environmental remediation of water bodies.

Methane production from the biodegradation of lignite with different sizes by mixed fungi-methanogen microflora.

Biogenic coalbed methane (CBM) is a developing clean energy source. However, it is unclear how the mechanisms of bio-methane production with different sizes of coal. In this work, pulverized coal (PC) and lump coal (LC) were used for methane production by mixed fungi-methanogen microflora. The lower methane production from LC was observed. The aromatic carbon of coal was degraded slightly by 2.17% in LC, while 11.28% in PC. It is attributed to the proportion of lignin-degrading fungi, especially Penicillium, which was reached 67.57% in PC on the 7th day, higher than that of 11.38% in LC. The results suggested that the limited interaction area in LC led to microorganisms hardly utilize aromatics. It also led the accumulation of aromatic organics in the fermentation broth in PC. Increasing the reaction area of coal and facilitating the conversion of aromatic carbon are suggested means to increase methane production in situ.

Construction and evaluation of AuNPs enhanced electrochemical immunosensors with [Fe(CN)6]3-/4- and PPy probe for highly sensitive detection of human chorionic gonadotropin.

Human chorionic gonadotropin (HCG), a vital protein for pregnancy determination and a marker for trophoblastic diseases, finds application in monitoring early pregnancy and ectopic pregnancy. This study presents an innovative approach employing electrochemical immunosensors for enhanced HCG detection, utilizing Anti-HCG antibodies and gold nanoparticles (AuNPs) in the sensor platform. Two sensor configurations were optimized: BSA/Anti-HCG/c-AuNPs/MEL/e-AuNPs/SPCE with [Fe(CN)6]3-/4- as a redox probe (1) and BSA/Anti-HCG/PPy/e-AuNPs/SPCE using polypyrrole (PPy) as a redox probe (2). The first sensor offers linear correlation in the 0.10-500.00 pg∙mL-1 HCG range, with a limit of detection (LOD) of 0.06 pg∙mL-1, sensitivity of 32.25 µA∙pg-1∙mL∙cm-2, RSD <2.47 %, and a recovery rate of 101.03-104.81 %. The second sensor widens the HCG detection range (40.00 fg∙mL-1-5.00 pg∙mL-1) with a LOD of 16.53 fg∙mL-1, ensuring precision (RSD <1.04 %) and a recovery range of 94.61-106.07 % in serum samples. These electrochemical immunosensors have transformative potential in biomarker detection, offering enhanced sensitivity, selectivity, and stability for advanced healthcare diagnostics.