PRMT6-mediated transcriptional activation of ythdf2 promotes glioblastoma migration, invasion, and emt via the wnt-ß-catenin pathway.

BACKGROUND: Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Glioblastoma (GBM; WHO Grade 4 glioma) is the most common and lethal primary brain tumor in adults, with a prognosis that is extremely poor, despite being less common than other systemic malignancies. Our current research finds PRMT6 upregulated in GBM, enhancing tumor malignancy. Yet, the specifics of PRMT6's regulatory processes and potential molecular mechanisms in GBM remain largely unexplored. METHODS: PRMT6's expression and prognostic significance in GBM were assessed using glioma public databases, immunohistochemistry (IHC), and immunoblotting. Scratch and Transwell assays examined GBM cell migration and invasion. Immunoblotting evaluated the expression of epithelial-mesenchymal transition (EMT) and Wnt-ß-catenin pathway-related proteins. Dual-luciferase reporter assays and ChIP-qPCR assessed the regulatory relationship between PRMT6 and YTHDF2. An in situ tumor model in nude mice evaluated in vivo conditions. RESULTS: Bioinformatics analysis indicates high expression of PRMT6 and YTHDF2 in GBM, correlating with poor prognosis. Functional experiments show PRMT6 and YTHDF2 promote GBM migration, invasion, and EMT. Mechanistic experiments reveal PRMT6 and CDK9 co-regulate YTHDF2 expression. YTHDF2 binds and promotes the degradation of negative regulators APC and GSK3ß mRNA of the Wnt-ß-catenin pathway, activating it and consequently enhancing GBM malignancy. CONCLUSIONS: Our results demonstrate the PRMT6-YTHDF2-Wnt-ß-Catenin axis promotes GBM migration, invasion, and EMT in vitro and in vivo, potentially serving as a therapeutic target for GBM.

PBX/Knotted 1 homeobox-2 (PKNOX2) is a novel regulator of myocardial fibrosis.

Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing. However, the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription factors. In this study, we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription factors. With this unbiased protocol, we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell subtypes. Particularly in fibroblasts, a novel regulator, PKNOX2, was identified as being associated with physiological fibroblast activation in healthy hearts. To validate the roles of these transcription factors in maintaining homeostasis, we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast remodelling. The trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast formation. Both gain- and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis remodelling. Moreover, fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis, respectively. In summary, this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart muscle. With this optimized protocol, we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies.

Interleukin-4 protects retinal ganglion cells and promotes axon regeneration.

BACKGROUND: The preservation of retinal ganglion cells (RGCs) and the facilitation of axon regeneration are crucial considerations in the management of various vision-threatening disorders. Therefore, we investigate the efficacy of interleukin-4 (IL-4), a potential therapeutic agent, in promoting neuroprotection and axon regeneration of retinal ganglion cells (RGCs) as identified through whole transcriptome sequencing in an in vitro axon growth model. METHODS: A low concentration of staurosporine (STS) was employed to induce in vitro axon growth. Whole transcriptome sequencing was utilized to identify key target factors involved in the molecular mechanism underlying axon growth. The efficacy of recombinant IL-4 protein on promoting RGC axon growth was validated through in vitro experiments. The protective effect of recombinant IL-4 protein on somas of RGCs was assessed using RBPMS-specific immunofluorescent staining in mouse models with optic nerve crush (ONC) and N-methyl-D-aspartic acid (NMDA) injury. The protective effect on RGC axons was evaluated by anterograde labeling of cholera toxin subunit B (CTB), while the promotion of RGC axon regeneration was assessed through both anterograde labeling of CTB and immunofluorescent staining for growth associated protein-43 (GAP43). RESULTS: Whole-transcriptome sequencing of staurosporine-treated 661 W cells revealed a significant upregulation in intracellular IL-4 transcription levels during the process of axon regeneration. In vitro experiments demonstrated that recombinant IL-4 protein effectively stimulated axon outgrowth. Subsequent immunostaining with RBPMS revealed a significantly higher survival rate of RGCs in the rIL-4 group compared to the vehicle group in both NMDA and ONC injury models. Axonal tracing with CTB confirmed that recombinant IL-4 protein preserved long-distance projection of RGC axons, and there was a notably higher number of surviving axons in the rIL-4 group compared to the vehicle group following NMDA-induced injury. Moreover, intravitreal delivery of recombinant IL-4 protein substantially facilitated RGC axon regeneration after ONC injury. CONCLUSION: The recombinant IL-4 protein exhibits the potential to enhance the survival rate of RGCs, protect RGC axons against NMDA-induced injury, and facilitate axon regeneration following ONC. This study provides an experimental foundation for further investigation and development of therapeutic agents aimed at protecting the optic nerve and promoting axon regeneration.

Neurotoxicity of Combined Exposure to the Heavy Metals (Pb and As) in Zebrafish (Danio rerio).

Lead (Pb) and arsenic (As) are commonly occurring heavy metals in the environment and produce detrimental impacts on the central nervous system. Although they have both been indicated to exhibit neurotoxic properties, it is not known if they have joint effects, and their mechanisms of action are likewise unknown. In this study, zebrafish were exposed to different concentrations of Pb (40 µg/L, 4 mg/L), As (32 µg/L, 3.2 mg/L) and their combinations (40 µg/L + 32 µg/L, 4 mg/L + 3.2 mg/L) for 30 days. The histopathological analyses showed significant brain damage characterized by glial scar formation and ventricular enlargement in all exposed groups. In addition, either Pb or As staining inhibited the swimming speed of zebrafish, which was enhanced by their high concentrations in a mixture. To elucidate the underlying mechanisms, we examined changes in acetylcholinesterase (AChE) activity, neurotransmitter (dopamine, 5-hydroxytryptamine) levels, HPI axis-related hormone (cortisol and epinephrine) contents and neurodevelopment-related gene expression in zebrafish brain. The observations suggest that combined exposure to Pb and As can cause abnormalities in swimming behavior and ultimately exacerbate neurotoxicity in zebrafish by interfering with the cholinergic system, dopamine and 5-hydroxytryptamine signaling, HPI axis function as well as neuronal development. This study provides an important theoretical basis for the mixed exposure of heavy metals and their toxicity to aquatic organisms.

Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer.

Breast cancer is one of the most common female malignant tumors, with triple-negative breast cancer (TNBC) being the most specific, highly invasive, metastatic and associated with a poor prognosis. Our previous study showed that the natural product ganoderic acid A (GAA) has a certain affinity for MDM2. In this study, two series of novel GAA PROTACs C1-C10 and V1-V10 were designed and synthesized for the treatment of breast cancer. The antitumor activity of these compounds was evaluated against four human tumor cell lines (MCF-7, MDA-MB-231, SJSA-1, and HepG2). Among them, V9 and V10 showed stronger anti-proliferative effects against breast cancer cells, and V10 showed the best selectivity in MDA-MB-231 cells (TNBC), which was 5-fold higher than that of the lead compound GAA. Preliminary structure-activity analysis revealed that V-series GAA PROTACs had better effects than C-series, and the introduction of 2O-4O PEG linkers could significantly improve the antitumor activity. Molecular docking, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and Western blot researches showed that both V9 and V10 could bind with MDM2, and degrade the protein through the ubiquitin-proteasome system. Molecular dynamics simulation (MD) revealed that V10 is a bifunctional molecule that can bind to von Hippel-Lindau (VHL) at one end and target MDM2 at the other. In addition, V10 promoted the upregulation of p21 in p53-mutant MDA-MB-231 cells, and induced apoptosis via down-regulation of the bcl-2/bax ratio and the expression of cyclin B1. Finally, in vivo experiments showed that, V10 also exhibited good tumor inhibitory activity in xenografted TNBC zebrafish models, with an inhibition rate of 27.2% at 50 µg/mL. In conclusion, our results suggested that V10 has anti-tumor effects on p53-mutant breast cancer in vitro and in vivo, and may be used as a novel lead compound for the future development of TNBC.

Impact of Pediococcus acidilactici GLP06 supplementation on gut microbes and metabolites in adult beagles: a comparative analysis.

There is growing interest in the potential health benefits of probiotics for both humans and animals. The study aimed to investigate the effects of feeding the canine-derived probiotic Pediococcus acidilactici GLP06 to adult beagles by analysing the microbiome and metabolome. Twenty-four healthy adult beagles were randomly assigned to four groups. The CK group received a standard diet, while the three probiotic groups, the LG group (2 × 108 CFU/day/dog), MG group (2 × 109 CFU/day/dog), and HG group (2 × 1010 CFU/day/dog), received the standard diet supplemented with varying amounts of probiotics. The results show that, compared to the CK group, total antioxidant capacity was significantly increased in the MG and HG groups (p < 0.05), and superoxide dismutase and catalase were significantly increased in the HG group (p < 0.05). Compared to the CK group, malondialdehyde and blood urea nitrogen content were significantly decreased in the MG and HG groups (p < 0.05). Additionally, secretory immunoglobulin A activity was significantly increased in the HG group compared to the CK and LG groups (p < 0.05), and immunoglobulin G activity was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). In addition, compared with the CK group, the abundance of Faecalitalea and Collinsella increased in the LG group, and the relative abundance of Tyzzerella and Parasutterella increased in the MG group. The α diversity and the relative abundances of beneficial bacteria (Faecalibacterium, Lachnospiraceae_NK4A1316, and Ruminococcaceae_UCG-005) were higher in the HG group than in the CK group. Furthermore, acetic acid content was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). Butyric acid, isobutyric acid, and the total SCFA content were significantly increased in the HG group compared to the CK group (p < 0.05). Moreover, metabolome analysis revealed 111 upregulated and 171 downregulated metabolites in the HG group. In conclusion, this study presents evidence that supplementing with P. acidilactici GLP06 can have a positive impact on antioxidant activity, immunoproteins, SCFAs, and gut microbiota in adult beagles. These findings highlight the potential of probiotics as a dietary intervention to enhance gut health and overall wellbeing in companion animals.

ZS-VAT: Learning Unbiased Attribute Knowledge for Zero-Shot Recognition Through Visual Attribute Transformer.

In zero-shot learning (ZSL), attribute knowledge plays a vital role in transferring knowledge from seen classes to unseen classes. However, most existing ZSL methods learn biased attribute knowledge, which usually results in biased attribute prediction and a decline in zero-shot recognition performance. To solve this problem and learn unbiased attribute knowledge, we propose a visual attribute Transformer for zero-shot recognition (ZS-VAT), which is an effective and interpretable Transformer designed specifically for ZSL. In ZS-VAT, we design an attribute-head self-attention (AHSA) that is capable of learning unbiased attribute knowledge. Specifically, each attribute head in AHSA first transforms the local features into attribute-reinforced features and then accumulates the attribute knowledge from all corresponding reinforced features, reducing the mutual influence between attributes and avoiding information loss. AHSA finally preserves unbiased attribute knowledge through attribute embeddings. We also propose an attribute fusion model (AFM) that learns to recover the correct category knowledge from the attribute knowledge. In particular, AFM takes all features from AHSA as input and generates global embeddings. We carried out experiments to demonstrate that the attribute knowledge from AHSA and the category knowledge from AFM are able to assist each other. During the final semantic prediction, we combine the attribute embedding prediction (AEP) and global embedding prediction (GEP). We evaluated the proposed scheme on three benchmark datasets. ZS-VAT outperformed the state-of-the-art generalized ZSL (GZSL) methods on two datasets and achieved competitive results on the other dataset.

Nodakenin Ameliorates Ovariectomy-Induced Bone Loss by Regulating Gut Microbiota.

Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using µCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.

Comparison of the Response to Neoadjuvant Therapy Between Immunohistochemistry HER2 (3+) and HER2 (2+)/ISH+ Early-Stage Breast Cancer: A Retrospective Multicenter Cohort Study.

BACKGROUND: According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. METHODS: We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. RESULTS: In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P < .001). HER2E showed increased PCR rates compared to non-HER2E (P = .004). CONCLUSIONS: Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential.

Metabolomics and Molecular Networking-Guided Screening of Bacillus-Derived Bioactive Compounds Against a Highly Lethal Vibrio Species.

Microorganisms are important sources of bioactive natural products. However, the complexity of microbial metabolites and the low abundance of active compounds render the isolation and purification process laborious and inefficient. During our search for active substances capable of inhibiting the newly discovered highly lethal Vibrio strain vp-HL, we found that the fermentation broth of multiple Bacillus strains exhibited antibacterial activity. However, the substances responsible for the activity remained unclear. Metabolomics, molecular networking (MN), and the Structural similarity Network Annotation Platform for Mass Spectrometry (SNAP-MS) were employed in conjunction with bioactivity screening to predict the antibacterial compounds from Bacillus strains. The analysis of fractions, and their isolation, NMR-based annotation, and bioactivity evaluation of an amicoumacin compound partially confirmed the prediction from these statistical analyses. This work presents the potential of marine Bacillus in producing active substances against Vibrio species. Additionally, it highlighted the significance and feasibility of metabolomics and MN in the dereplication of compounds and the determination of isolation targets.

Comammox and unknown ammonia oxidizers contribute to nitrite accumulation in an integrated A-B stage process that incorporates side-stream EBPR (S2EBPR).

A novel integrated pilot-scale A-stage high rate activated sludge, B-stage short-cut biological nitrogen removal and side-stream enhanced biological phosphorus removal (A/B-shortcut N-S2EBPR) process for treating municipal wastewater was demonstrated with the aim to achieve simultaneous and carbon- and energy-efficient N and P removal. In this studied period, an average of 7.62 ± 2.17 mg-N/L nitrite accumulation was achieved through atypical partial nitrification without canonical known NOB out-selection. Network analysis confirms the central hub of microbial community as Nitrospira, which was one to two orders of magnitude higher than canonical aerobic oxidizing bacteria (AOB) in a B-stage nitrification tank. The contribution of comammox Nitrospira as AOB was evidenced by the increased amoB/nxr ratio and higher ammonia oxidation activity. Furthermore, oligotyping analysis of Nitrospira revealed two dominant sub-clusters (microdiveristy) within the Nitrospira. The relative abundance of oligotype II, which is phylogenetically close to Nitrospira_midas_s_31566, exhibited a positive correlation with nitrite accumulation in the same operational period, suggesting its role as comammox Nitrospira. Additionally, the phylogenetic investigation suggested that heterotrophic organisms from the family Comamonadacea and the order Rhodocyclaceae embedding ammonia monooxygenase and hydroxylamine oxidase may function as heterotrophic nitrifiers. This is the first study that elucidated the impact of integrating the S2EBPR on nitrifying populations with implications on short-cut N removal. The unique conditions in the side-stream reactor, such as low ORP, favorable VFA concentrations and composition, seemed to exert different selective forces on nitrifying populations from those in conventional biological nutrient removal processes. The results provide new insights for integrating EBPR with short-cut N removal process for mainstream wastewater treatment.

Secondary metabolites from the deep-sea derived fungus Aspergillus terreus MCCC M28183.

Aspergillus fungi are renowned for producing a diverse range of natural products with promising biological activities. These include lovastatin, itaconic acid, terrin, and geodin, known for their cholesterol-regulating, anti-inflammatory, antitumor, and antibiotic properties. In our current study, we isolated three dimeric nitrophenyl trans-epoxyamides (1-3), along with fifteen known compounds (4-18), from the culture of Aspergillus terreus MCCC M28183, a deep-sea-derived fungus. The structures of compounds 1-3 were elucidated using a combination of NMR, MS, NMR calculation, and ECD calculation. Compound 1 exhibited moderate inhibitory activity against human gastric cancer cells MKN28, while compound 7 showed similar activity against MGC803 cells, with both showing IC50 values below 10 µM. Furthermore, compound 16 exhibited moderate potency against Vibrio parahaemolyticus ATCC 17802, with a minimum inhibitory concentration (MIC) value of 7.8 µg/mL. This promising research suggests potential avenues for developing new pharmaceuticals, particularly in targeting specific cancer cell lines and combating bacterial infections, leveraging the unique properties of these Aspergillus-derived compounds.

Side-Stream Enhanced Biological Phosphorus Removal (S2EBPR) enables effective phosphorus removal in a pilot-scale A-B stage shortcut nitrogen removal system for mainstream municipal wastewater treatment.

While the adsorption/bio-oxidation (A/B) process has been widely studied for carbon capture and shortcut nitrogen (N) removal, its integration with enhanced biological phosphorus (P) removal (EBPR) has been considered challenging and thus unexplored. Here, full-scale pilot testing with an integrated system combining A-stage high-rate activated sludge with B-stage partial (de)nitrification/anammox and side-stream EBPR (HRAS-P(D)N/A-S2EBPR) was conducted treating real municipal wastewater. The results demonstrated that, despite the relatively low influent carbon load, the B-stage P(D)N-S2EBPR system could achieve effective P removal performance, with the carbon supplement and redirection of the A-stage sludge fermentate to the S2EBPR. The novel process configuration design enabled a system shift in carbon flux and distribution for efficient EBPR, and provided unique selective factors for ecological niche partitioning among different key functionally relevant microorganisms including polyphosphate accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs). The combined nitrite from B-stage to S2EBPR and aerobic-anoxic conditions in our HRAS-P(D)N/A-S2EBPR system promoted DPAOs for simultaneous internal carbon-driven denitrification via nitrite and P removal. 16S rRNA gene-based oligotyping analysis revealed high phylogenetic microdiversity within the Accumulibacter population and discovered coexistence of certain oligotypes of Accumulibacter and Competibacter correlated with efficient P removal. Single-cell Raman micro-spectroscopy-based phenotypic profiling showed high phenotypic microdiversity in the active PAO community and the involvement of unidentified PAOs and internal carbon-accumulating organisms that potentially played an important role in system performance. This is the first pilot study to demonstrate that the P(D)N-S2EBPR system could achieve shortcut N removal and influent carbon-independent EBPR simultaneously, and the results provided insights into the effects of incorporating S2EBPR into A/B process on metabolic activities, microbial ecology, and resulted system performance.

Revisiting the role of Acinetobacter spp. in side-stream enhanced biological phosphorus removal (S2EBPR) systems.

We piloted the incorporation of side-stream enhanced biological phosphorus removal (S2EBPR) with A/B stage short-cut nitrogen removal processes to enable simultaneous carbon-energy-efficient nutrients removal. This unique configuration and system conditions exerted selective force on microbial populations distinct from those in conventional EBPR. Interestingly, effective P removal was achieved with the predominance of Acinetobacter (21.5 ± 0.1 %) with nearly negligible level of known conical PAOs (Ca. Accumulibacter and Tetrasphaera were 0.04 ± 0.10 % and 0.47 ± 0.32 %, respectively). Using a combination of techniques, such as fluorescence in situ hybridization (FISH) coupled with single cell Raman spectroscopy (SCRS), the metabolic tracing of Acinetobacter-like cells exerted PAO-like phenotypic profiling. In addition, comparative metagenomics analysis of the closely related Acinetobacter spp. revealed the EBPR relevant metabolic pathways. Further oligotyping analysis of 16s rRNA V4 region revealed sub-clusters (microdiversity) of the Acinetobacter and revealed that the sub-group (oligo type 1, identical (100 % alignment identity) hits from Acinetobacter_midas_s_49494, and Acinetobacter_midas_s_55652) correlated with EBPR activities parameters, provided strong evidence that the identified Acinetobacter most likely contributed to the overall P removal in our A/B-shortcut N-S2EBPR system. To the best of our knowledge, this is the first study to confirm the in situ EBPR activity of Acinetobacter using combined genomics and SCRS Raman techniques. Further research is needed to identify the specific taxon, and phenotype of the Acinetobacter that are responsible for the P-removal.

Short-term exposure to gaseous pollutants is neglected factors for knee osteoarthritis: evidence from a humid subtropical region of China.

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO2 (RR = 0.993, lag19 day) and O3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO2, O3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations.

Combined inhibitory effects of microcystin-LR and microcystin-RR on growth and development in zebrafish larvae.

Microcystins (MCs) are the most widespread, frequently found, and seriously toxic cyanobacterial toxins in aquatic environments. Microcystin-leucine-arginine (MCLR) and microcystin-arginine-arginine (MCRR) are the most studied MCs. Normally, their levels are low and they coexist in the environment; however, they may also interact with each other. The developmental toxicity of MCLR in the presence of MCRR in the early life stage of zebrafish (from 2 to 120 h post fertilization) was investigated for the first time in this study. Our findings revealed that MCRR treatment marginally elevated thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels, whereas MCLR treatment alone resulted in a significant increase in T3 and T4 levels, indicating a cooperative effect. Furthermore, clear changes in the expression levels of genes involved in growth and development, accompanied by growth inhibition, were observed after co-treatment with MCRR and MCLR. In addition, zebrafish larvae subjected to MCRR and/or MCLR treatment showed increased levels of superoxide dismutase, glutathione, and malondialdehyde, and decreased levels of catalase in the MCRR + MCLR group, indicating oxidative stress and lipid peroxidation. Thus, we investigated the synergistic developmental toxicity of MCRR and MCLR during the early life stages of zebrafish development.

Effect of Strontium-Substituted Calcium Phosphate Coatings Prepared by One-Step Electrodeposition at Different Temperatures on Corrosion Resistance and Biocompatibility of AZ31 Magnesium Alloys.

As potential degradable biomaterials, magnesium (Mg) alloys have development prospects in the field of orthopedic load-bearing, whereas the clinical application has encountered a bottleneck due to a series of problems caused by its rapid corrosion. In this study, strontium-substituted calcium phosphate (CaP) coatings with different structures were prepared on the surface of the Mg matrix by a simple one-step electrodeposition method at different temperatures, which enhanced the poor corrosion resistance of the Mg matrix. The coated sample prepared at 65 °C reduced the corrosion current density by 3 orders of magnitude and increased the impedance by nearly 2 orders of magnitude compared with bare Mg alloy, thanks to its dense fibrous structure similar to that of natural bones. Although the coating composition varies with different preparation temperatures, CaP, as an inorganic component similar to natural bone, has good cytocompatibility. Doping the right amount of strontium, which is a trace element in human bones, is beneficial to stimulate osteoblast differentiation, inhibit the activity of osteoclasts, and induce the formation of bone tissues. This provides a new option for modifying the Mg alloy with CaP coatings as a base.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 prevents SARS-CoV-2 infection: Two investigator-initiated postexposure prophylaxis trials.

HH-120, an IgM-like angiotensin converting enzyme 2 (ACE2) fusion protein, has been developed as a nasal spray against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently undergoing human trials. HH-120 nasal spray was assessed for postexposure prophylaxis (PEP) in two investigator-initiated (NS01 and NS02) trials with different risk levels of SARS-CoV-2 exposure. NS01 enrolled family caregiver participants who had continuous contacts with laboratory-confirmed index cases; NS02 enrolled participants who had general contacts (Part 1) or close contacts (Part 2) with index cases. The primary endpoints were safety and laboratory-confirmed and/or symptomatic SARS-CoV-2 infection. In NS01 trial (14 participants), the SARS-CoV-2 infection rates were 25% in the HH-120 group and 83.3% in the external control group (relative risk reduction [RRR]: 70.0%). In NS02-Part 1 (193 participants), the infection rates were 4% (HH-120) versus 11.3% (placebo), symptomatic infection rates were 0.8% versus 3.5%, hence with a RRR of 64.6% and 77.1%, respectively. In Part 2 (76 participants), the infection rates were 17.1% (HH-120) versus 30.4% (placebo), symptomatic infection rates were 7.5% versus 27.3%, with a RRR of 43.8% and 72.5%, respectively. No HH-120-related serious adverse effects were observed. The HH-120 nasal spray used as PEP was safe and effective in preventing laboratory-confirmed and symptomatic SARS-CoV-2 infection.

Pseudodonghicola flavimaris sp. nov. and Sedimentitalea xiamensis sp. nov., two novel species belonging to the family Roseobacteraceae.

Two Gram-stain-negative, chemoheterotrophic, aerobic bacteria, designated IC7T and JM2-8T, were isolated from seawater of the Yellow Sea of China and rhizosphere soil of mangroves in Xiamen, Fujian, respectively. Phylogenetic analyses based on 16S rRNA gene and genome sequences showed that these two novel strains belonged to the family Roseobacteraceae. Strain IC7T formed a coherent lineage within the genus Pseudodonghicola, showing 98.05 % 16S rRNA gene sequence similarity to Pseudodonghicola xiamenensis Y-2T. Strain JM2-8T was most closely related to members of the genus Sedimentitalea, showing 96.51 and 96.73 % 16S rRNA gene sequence similarities to Sedimentitalea nanhaiensis NH52FT and Sedimentitalea todarodis KHS03T, respectively. The two novel strains contained Q-10 as the major quinone, and phosphatidylethanolamine, aminophospholipid, phosphatidylglycerol and phosphatidylcholine as the principal polar lipids. The main fatty acid of strain IC7T was C19 : 0 cyclo ω8c, while the fatty acid profile JM2-8T was dominated by summed feature 8 containing C18 : 1 ω7c and/or C18 : 1 ω6c. The average nucleotide identity and digital DNA-DNA hybridization values between these two novel isolates and their closely related species were below the cut-off values of 95-96 and 70 %, respectively. The combined genotypic and phenotypic data show that strain IC7T represents a novel species of the genus Pseudodonghicola, for which the name Pseudodonghicola flavimaris sp. nov. is proposed, with the type strain IC7T (=MCCC 1A02763T=KCTC 82844T), and strain JM2-8T represents a novel species of the genus Sedimentitalea, for which the name Sedimentitalea xiamensis sp. nov. is proposed, with the type strain JM2-8T (=MCCC 1A17756T=KCTC 82846T).

Complete Genome Sequence and Probiotic Properties of Pediococcus acidilactici CLP03 Isolated from Healthy Felis catus.

Probiotics are available from various sources, including the gastrointestinal tract of healthy animals. In this study, Pediococcus acidilactici was isolated for the first time from Felis catus and evaluated for its functionality. The findings revealed that P. acidilactici CLP03 exhibited inhibitory properties against pathogenic bacteria (E. coli, Salmonella, S. aureus, P. aeruginosa, and L. monocytogenes). Then, survival of strains exposed to pH 2.5, 0.3% bile salts, 0.5% bile salts, and gastrointestinal fluids was 63.97%, 98.84%, 87.95%, and 52.45%, respectively. Also, P. acidilactici CLP03 demonstrated high hydrophobicity (69.63-82.03%) and self-aggregation (73.51-81.44%), negative for hemolytic, and was susceptible to clindamycin. Finally, the scavenging rates of DPPH, ABTS, and O2- were 53.55%, 54.81%, and 85.13%, respectively, which demonstrated that the strain CLP03 has good oxidation resistance. All these characteristics contribute to the survival, colonization, and functionality of the strain in the gastrointestinal tract, indicating their excellent probiotic potential. On the other hand, animal experiments (KM mice, randomly assigned to four groups) showed that the gavage of CLP03 had no toxic effects on mice, increased the serum SOD content, and decreased the MDA and BUN contents, which revealed gavage of CLP03 significantly increased the antioxidant capacity of mice in vivo. In addition, complete genome annotation showed that P. acidilactici CLP03 had 1976 CDS genes, and the numbers of CRISPR, gene islands, and phages were 8, 3, and 6, respectively. In conclusion, P. acidilactici CLP03 could be a candidate functional cat probiotic to enhance animal health and welfare.