In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing.

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.

DNMT1 regulates human erythropoiesis by modulating cell cycle and endoplasmic reticulum stress in a stage-specific manner.

The dynamic balance of DNA methylation and demethylation is required for erythropoiesis. Our previous transcriptomic analyses revealed that DNA methyltransferase 1 (DNMT1) is abundantly expressed in erythroid cells at all developmental stages. However, the role and molecular mechanisms of DNMT1 in human erythropoiesis remain unknown. Here we found that DNMT1 deficiency led to cell cycle arrest of erythroid progenitors which was partially rescued by treatment with a p21 inhibitor UC2288. Mechanically, this is due to decreased DNA methylation of p21 promoter, leading to upregulation of p21 expression. In contrast, DNMT1 deficiency led to increased apoptosis during terminal stage by inducing endoplasmic reticulum (ER) stress in a p21 independent manner. ER stress was attributed to the upregulation of RPL15 expression due to the decreased DNA methylation at RPL15 promoter. The upregulated RPL15 expression subsequently caused a significant upregulation of core ribosomal proteins (RPs) and thus ultimately activated all branches of unfolded protein response (UPR) leading to the excessive ER stress, suggesting a role of DNMT1 in maintaining protein homeostasis during terminal erythroid differentiation. Furthermore, the increased apoptosis was significantly rescued by the treatment of ER stress inhibitor TUDCA. Our findings demonstrate the stage-specific role of DNMT1 in regulating human erythropoiesis and provide new insights into regulation of human erythropoiesis.

Comprehensive analysis of thalassemia alleles (CATSA) based on third-generation sequencing is a comprehensive and accurate approach for neonatal thalassemia screening.

Thalassemia is one of the most common and damaging monogenic diseases in the world. It is caused by pathogenic variants of α- and/or ß-globin genes, which disrupt the balance of these two protein chains and leads to α-thalassemia or ß-thalassemia, respectively. Patients with α-thalassemia or ß-thalassemia could exhibit a severe phenotype, with no simple and effective treatment. A three-tiered strategy of carrier screening, prenatal diagnosis and newborn screening has been established in China for the prevention and control of thalassemia, of which the first two parts have been studied thoroughly. The implementation of neonatal thalassemia screening is lagging, and the effectiveness of various screening programs has not yet been demonstrated. In this study, hemoglobin capillary electrophoresis (CE), hotspot testing method, and third-generation sequencing (TGS) were used in the variant detection of 2000 newborn samples, to assess the efficacy of these methods in neonatal thalassemia screening. Compared with CE (249, 12.45 %) and hotspot analysis (424, 21.2 %), CATSA detected the largest number of thalassemia variants (535, 26.75 %), which included 24 hotspot variants, increased copy number of α-globin gene, rare pathogenic variants, and three unreported potentially disease-causing variants. More importantly, CATSA directly determined the cis-trans relationship of variants in three newborns, which greatly shortens the clinical diagnosis time of thalassemia. CATSA showed a great advantage over other genetic tests and could become the most powerful technical support for the three-tiered prevention and control strategy of thalassemia.

Enhancing glucaric acid production from myo-inositol in Escherichia coli by eliminating cell-to-cell variation.

Glucaric acid (GA) is a value-added chemical and can be used to manufacture food additives, anticancer drugs, and polymers. The non-genetic cell-to-cell variations in GA biosynthesis are naturally inherent, indicating the presence of both high- and low-performance cells in culture. Low-performance cells can lead to nutrient waste and inefficient production. Furthermore, myo-inositol oxygenase (MIOX) is a key rate-limiting enzyme with the problem of low stability and activity in GA production. Therefore, eliminating cell-to-cell variations and increasing MIOX stability can select high-performance cells and improve GA production. In this study, an in vivo GA bioselector was constructed based on GA biosensor and tetracycline efflux pump protein TetA to continuously select GA-efficient production strains. Additionally, the upper limit of the GA biosensor was improved to 40 g/L based on ribosome-binding site optimization, achieving efficient enrichment of GA high-performance cells. A small ubiquitin-like modifier (SUMO) enhanced MIOX stability and activity. Overall, we used the GA bioselector and SUMO-MIOX fusion in fed-batch GA production and achieved a 5.52-g/L titer in Escherichia coli, which was 17-fold higher than that of the original strain.IMPORTANCEGlucaric acid is a non-toxic valuable product that was mainly synthesized by chemical methods. Due to the problems of non-selectivity, inefficiency, and environmental pollution, GA biosynthesis has attracted significant attention. The non-genetic cell-to-cell variations and MIOX stability were both critical factors for GA production. In addition, the high detection limit of the GA biosensor was a key condition for performing high-throughput screening of GA-efficient production strains. To increase GA titer, this work eliminated the cell-to-cell variations by GA bioselector constructed based on GA biosensor and TetA, and improved the stability and activity of MIOX in the GA biosynthetic pathway through fusing the SUMO to MIOX. Finally, these approaches improved the GA production by 17-fold to 5.52 g/L at 65 h. This study represents a significant step toward the industrial application of GA biosynthetic pathways in E. coli.

Insights into Euphorbia diversity: Probing the contrasts between Euphorbia fischeriana Steud and Euphorbia ebracteolata Hayata.

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A physiologically based pharmacokinetic/pharmacodynamic model to determine dosage regimens and withdrawal intervals of aditoprim against Streptococcus suis.

Introduction: Streptococcus suis (S. suis) is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against S. suis. In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against S. suis and withdrawal intervals. Methods: The PBPK model of ADP injection can predict drug concentrations in plasma, liver, kidney, muscle, and fat. A semi-mechanistic pharmacodynamic (PD) model, including susceptible subpopulation and resistant subpopulation, is successfully developed by a nonlinear mixed-effect model to evaluate antibacterial effects. An integrated PBPK/PD model is conducted to predict the time-course of bacterial count change and resistance development under different ADP dosages. Results: ADP injection, administrated at 20 mg/kg with 12 intervals for 3 consecutive days, can exert an excellent antibacterial effect while avoiding resistance emergence. The withdrawal interval at the recommended dosage regimen is determined as 18 days to ensure food safety. Discussion: This study suggests that the PBPK/PD model can be applied as an effective tool for the antibacterial effect and safety evaluation of novel veterinary drugs.

Oridonin exerts anticonvulsant profile and neuroprotective activity in epileptic mice by inhibiting NLRP3-mediated pyroptosis.

BACKGROUND: Epilepsy is a chronic disabling disease poorly controlled by available antiseizure medications. Oridonin, a bioactive alkaloid with anti-inflammatory properties and neuroprotective effects, can inhibit the increased excitability of neurons caused by glutamate accumulation at the cellular level. However, whether oridonin affects neuronal excitability and whether it has antiepileptic potential has not been reported in animal models or clinical studies. METHOD: Pentylenetetrazol was injected into mice to create a model of chronic epilepsy. Seizure severity was assessed using the Racine scale, and the duration and latency of seizures were observed. Abnormal neuronal discharge was detected using electroencephalography, and neuronal excitability was assessed using calcium imaging. Damage to hippocampal neurons was evaluated using Hematoxylin-Eosin and Nissl staining. The expression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and other pyroptosis-related proteins was determined using western blotting and immunofluorescence. A neuronal pyroptosis model was established using the supernatant of BV2 cells treated with lipopolysaccharide and adenosine triphosphate to stimulate hippocampal neurons. RESULTS: Oridonin (1 and 5 mg/kg) reduced neuronal damage, increased the latency of seizures, and shortened the duration of fully kindled seizures in chronic epilepsy model mice. Oridonin decreased abnormal discharge during epileptic episodes and suppressed increased neuronal excitability. In vitro experiments showed that oridonin alleviated pyroptosis in hippocampal HT22 neurons. CONCLUSION: Oridonin exerts neuroprotective effects by inhibiting pyroptosis through the NLRP3/caspase-1 pathway in chronic epilepsy model mice. It also reduces pyroptosis in hippocampal neurons in vitro, suggesting its potential as a therapy for epilepsy.

Comparative study on the activation of peroxymonosulfate and peroxydisulfate by Ar plasma-etching CNTs for sulfamethoxazole degradation: Efficiency and mechanisms.

Sulfamethoxazole (SMX), a widely utilized antibiotic, was continually detected in the environment, causing serious risks to aquatic ecology and water security. In this study, carbon nanotubes (CNTs) with abundant defects were developed by argon plasma-etching technology to enhance the activation of persulfate (PS, including peroxymonosulfate (PMS) and peroxydisulfate (PDS)) for SMX degradation while reducing environmental toxicity. Obviously, the increase of ID/IG value from 0.980 to 1.333 indicated that Ar plasma-etching successfully introduced rich defects into CNTs. Of note, Ar-90-CNT, whose Ar plasma-etching time was 90 min with optimum catalytic performance, exhibited a significant discrepancy between PMS activation and PDS activation. Interestingly, though the Ar-90-CNT/PDS system (kobs = 0.0332 min-1) was more efficient in SMX elimination than the Ar-90-CNT/PMS system (kobs = 0.0190 min-1), Ar plasma-etching treatment had no discernible enhancement in the catalytic efficiency of MWCNT for PDS activation. Then the discrepancy on activation mechanism between PMS and PDS was methodically investigated through quenching experiments, electron spin resonance (ESR), chemical probes, electrochemical measurements and theoretical calculations, and the findings unraveled that the created vacancy defects were the ruling active sites for the production of dominated singlet oxygen (1O2) in the Ar-90-CNT/PMS system to degrade SMX, while the electron transfer pathway (ETP), originated from PDS activation by the inherent edge defects, was the central pathway for SMX removal in the Ar-90-CNT/PDS system. Based on the toxicity test of Microcystis aeruginosa, the Ar-90-CNT/PDS system was more effective in alleviating environmental toxicity during SMX degradation. These findings not only provide insights into the discrepancy between PMS activation and PDS activation via carbon-based materials with controlled defects regulated by the plasma-etching strategy, but also efficiently degrade sulfonamide antibiotics and reduce the toxicity of their products.

Enhancing rutin accumulation in Tartary buckwheat through a novel flavonoid transporter protein FtABCC2.

Tartary buckwheat (Fagopyrum tataricum) is an annual coarse cereal from the Polygonaceae family, known for its high content of flavonoid compounds, particularly rutin. But so far, the mechanisms of the flavonoid transport and storage in Tartary buckwheat (TB) remain largely unexplored. This study focuses on ATP-binding cassette transporters subfamily C (ABCC) members, which are crucial for the biosynthesis and transport of flavonoids in plants. The evolutionary and expression pattern analyses of the ABCC genes in TB identified an ABCC protein gene, FtABCC2, that is highly correlated with rutin synthesis. Subcellular localization analysis revealed that FtABCC2 protein is specifically localized to the vacuole membrane. Heterologous expression of FtABCC2 in Saccharomyces cerevisiae confirmed that its transport ability of flavonoid glycosides such as rutin and isoquercetin, but not the aglycones such as quercetin and dihydroquercetin. Overexpression of FtABCC2 in TB hairy root lines resulted in a significant increase in total flavonoid and rutin content (P < 0.01). Analysis of the FtABCC2 promoter revealed potential cis-acting elements responsive to hormones, cold stress, mechanical injury and light stress. Overall, this study demonstrates that FtABCC2 can efficiently facilitate the transport of rutin into vacuoles, thereby enhancing flavonoids accumulation. These findings suggest that FtABCC2 is a promising candidate for molecular-assisted breeding aimed at developing high-flavonoid TB varieties.

Insight into N2O emission and denitrifier communities under different aeration intensities in composting of cattle manure from perspective of multi-factor interaction analysis.

Nitrous oxide (N2O) emission from composting is a significant contributor to greenhouse effect and ozone depletion, which poses a threat to environment. To address the challenge of mitigating N2O emission during composting, this study investigated the response of N2O emission and denitrifier communities (detected by metagenome sequencing) to aeration intensities of 6 L/min (C6), 12 L/min (C12), and 18 L/min (C18) in cattle manure composting using multi-factor interaction analysis. Results showed that N2O emission occurred mainly at mesophilic phase. Cumulative N2O emission (QN2O, 9.79 mg·kg-1 DW) and total nitrogen loss (TN loss, 16.40 %) in C12 composting treatment were significantly lower than those in the other two treatments. The lower activity of denitrifying enzymes and the more complex and balanced network of denitrifiers and environmental factors might be responsible for the lower N2O emission. Denitrification was confirmed to be the major pathway for N2O production. Moisture content (MC) and Luteimonas were the key factors affecting N2O emission, and nosZ-carrying denitrifier played a significant role in reducing N2O emission. Although relative abundance of nirS was lower than that of nirK significantly (P < 0.05), nirS was the key gene influencing N2O emission. Community composition of denitrifier varied significantly with different aeration treatments (R2 = 0.931, P = 0.001), and Achromobacter was unique to C12 at mesophilic phase. Physicochemical factors had higher effect on QN2O, whereas denitrifying genes, enzymes and NOX- had lower effect on QN2O in C12. The complex relationship between N2O emission and the related factors could be explained by multi-factor interaction analysis more comprehensively. This study provided a novel understanding of mechanism of N2O emission regulated by aeration intensity in composting.

Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair.

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

Construction and mechanistic insights of a novel ZnO functionalized rGO composite for efficient adsorption and reduction of Cr(VI).

A series of ZnO decorated reduced graphene oxide (rGO) (ZnrGOx) with different doping ratios were synthesized by the alkaline hydrothermal method using graphene oxide (GO) and Zn(NO3)2·6H2O as precursors, and subsequently used for the adsorption study of Cr(VI) in water. The morphology, crystalline phase structure, and surface elemental properties of ZnrGOx composites were revealed by XRD, SEM, BET, FT-IR, and XPS characterizations. The results showed that ZnO nanoparticles can be clearly seen on the surface of layered rGO. Meanwhile, as the doping rate increased, the C = C double bonds were broken and more carboxylic acid groups formed in ZnrGOx. In addition, the ZnrGO0.1 composite had the most excellent adsorption performance and good stability, and reusability. The adsorption removal rate of Cr(VI) can reach 99%, and the maximum adsorption amount of Cr(VI) was 68.9655 mg/g in 3 h. The isothermal and kinetic model simulations showed that Cr(VI) adsorption on ZnrGO0.1 composite is a chemical adsorption process, spontaneous and endothermic. Based on the concentrations of different valence states of Cr in the solid and liquid phases, 40% of Cr(VI) was reduced to Cr(III) on the surface of ZnrGO0.1 composite. Moreover, the adsorption-reduction mechanisms of Cr(VI) on ZnrGO0.1 composite were further elucidated. The ZnrGO0.1 composite manifested great potential as an efficient adsorbent for Cr(VI) removal.

Two Novel Alkaliphilic Species Isolated from Saline-Alkali Soil in China: Halalkalibacter flavus sp. nov., and Halalkalibacter lacteus sp. nov.

The degradation of farmland in China underscores the need for developing and utilizing saline-alkali soil. Soil health relies on microbial activity, which aids in the restoration of the land's ecosystem, and hence it is important to understand microbial diversity. In the present study, two Gram-stain-positive strains HR 1-10T and J-A-003T were isolated from saline-alkali soil. Preliminary analysis suggested that these strains could be a novel species. Therefore, the taxonomic positions of these strains were evaluated using polyphasic analysis. Phylogenetic and 16S rRNA gene sequence analysis indicated that these strains should be assigned to the genus Halalkalibacter. Cell wall contained meso-2,6-diaminopimelic acid. The polar lipids present in both strains were diphosphatidyl-glycerol, phosphatidylglycerol, and an unidentified phospholipid. The major fatty acids (>10%) were anteiso-C15:0, C16:0 and iso-C15:0. Average nucleotide identity and digital DNA#x2013;DNA hybridization values were below the threshold values (95% and 70%, respectively) for species delineation. Based on the above results, the strains represent two novel species of the genus Halalkalibacter, for which the names Halalkalibacter flavus sp. nov., and Halalkalibacter lacteus sp. nov., are proposed. The type strains are HR 1-10T (=GDMCC 1.2946T = MCCC 1K08312T = JCM 36285T), and J-A-003T (=GDMCC 1.2949T = MCCC 1K08417T = JCM 36286T).

Efficacy and safety of transcranial pulse stimulation in young adolescents with attention-deficit/hyperactivity disorder: a pilot, randomized, double-blind, sham-controlled trial.

Background: This is the first study to evaluate the efficacy and safety of transcranial pulse stimulation (TPS) for the treatment of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Hong Kong. Methods: This double-blind, randomized, sham-controlled trial included a TPS group and a sham TPS group, encompassing a total of 30 subjects aged 12-17 years who were diagnosed with ADHD. Baseline measurements SNAP-IV, ADHD RS-IV, CGI and executive functions (Stroop tests, Digit Span) and post-TPS evaluation were collected. Both groups were assessed at baseline, immediately after intervention, and at 1-month and 3-month follow-ups. Repeated-measures ANOVAs were used to analyze data. Results: The TPS group exhibited a 30% reduction in the mean SNAP-IV score at postintervention that was maintained at 1- and 3-month follow-ups. Conclusion: TPS is an effective and safe adjunct treatment for the clinical management of ADHD. Clinical trial registration: ClinicalTrials.Gov, identifier NCT05422274.

Study on the influence of rock bridge angle on the size effect of rock uniaxial compression.

As a basic parameter of rock, the rock bridge angle plays an important role in maintaining the stability of rock masses. To study the size effect of rock bridge angle on the uniaxial compressive strength of rocks, this paper adopts the principle of regression analysis and combines numerical simulation to carry out relevant research. The research results indicate that: (1) the uniaxial compressive strength decreases with the increase of the rock bridge angle, showing a power function relationship; (2) The uniaxial compressive strength decreases with the increase of rock size and tends to stabilize when the rock size is greater than 350 mm, showing a significant size effect. (3) The fluctuation coefficient of compressive strength increases with the increase of rock bridge angle and decreases with the increase of rock size; When the rock size is 350 mm, the fluctuation coefficient is less than 5%; (4) The characteristic compressive strength and characteristic size both increase with the increase of the rock bridge angle.

High Tartronic Acid Content Germplasms Screening of Cucumber and Its Response to Exogenous Agents.

Tartronic acid is known for its potential to inhibit sugar-to-lipid conversion in the human body, leading to weight loss and fat reduction. This compound is predominantly found in cucumbers and other cucurbit crops. Therefore, cultivating cucumbers with high tartronic acid content holds significant health implications. In this study, we assessed the tartronic acid content in 52 cucumber germplasms with favorable overall traits and identified 8 cucumber germplasms with elevated tartronic acid levels. Our investigation into factors influencing cucumber tartronic acid revealed a decrease in content with fruit development from the day of flowering. Furthermore, tartronic acid content was higher in early-harvested fruits compared to late-harvested ones, with the rear part of the fruit exhibiting significantly higher content than other parts. Foliar spraying of microbial agents increased tartronic acid content by 84.4%. This study provides valuable resources for breeding high tartronic acid cucumbers and offers practical insights for optimizing cucumber production practices.

Dosimetric comparison of HyperArc and InCise MLC-based CyberKnife plans in treating single and multiple brain metastases.

BACKGROUND AND PURPOSE: This study aimed to compare the dosimetric attributes of two multi-leaf collimator based techniques, HyperArc and Incise CyberKnife, in the treatment of brain metastases. MATERIAL AND METHODS: 17 cases of brain metastases were selected including 6 patients of single lesion and 11 patients of multiple lesions. Treatment plans of HyperArc and CyberKnife were designed in Eclipse 15.5 and Precision 1.0, respectively, and transferred to Velocity 3.2 for comparison. RESULTS: HyperArc plans provided superior Conformity Index (0.91 ± 0.06 vs. 0.77 ± 0.07, p < 0.01) with reduced dose distribution in organs at risk (Dmax, p < 0.05) and lower normal tissue exposure (V4Gy-V20Gy, p < 0.05) in contrast to CyberKnife plans, although the Gradient Indexes were similar. CyberKnife plans showed higher Homogeneity Index (1.54 ± 0.17 vs. 1.39 ± 0.09, p < 0.05) and increased D2% and D50% in the target (p < 0.05). Additionally, HyperArc plans had significantly fewer Monitor Units (MUs) and beam-on time (p < 0.01). CONCLUSION: HyperArc plans demonstrated superior performance compared with MLC-based CyberKnife plans in terms of conformity and the sparing of critical organs and normal tissues, although no significant difference in GI outcomes was noted. Conversely, CyberKnife plans achieved a higher target dose and HI. The study suggests that HyperArc is more efficient and particularly suitable for treating larger lesions in brain metastases.

Abundant Edge Active Sites-Modified High-Crystalline g-C3N5 for Hydrogen Peroxide Production from Pure-Water via a Quasi-Homogeneous Photocatalytic Process.

Ultrathin carbon nitride pioneered a paradigm that facilitates effective charge separation and acceleration of rapid charge migration. Nevertheless, the dissociation process confronts a disruption owing to the proclivity of carbon nitride to reaggregate, thereby impeding the optimal utilization of active sites. In response to this exigency, the adoption of a synthesis methodology featuring alkaline potassium salt-assisted molten salt synthesis is advocated in this work, aiming to craft a nitrogenated graphitic carbon nitride (g-C3N5) photocatalyst characterized by thin layer and hydrophilicity, which not only amplifies the degree of crystallization of g-C3N5 but also introduces a plethora of abundant edge active sites, engendering a quasi-homogeneous photocatalytic system. Under visible light irradiation, the ultra-high H2O2 production rate of this modified high-crystalline g-C3N5 in pure water attains 151.14 µm h-1. This groundbreaking study offers a novel perspective for the innovative design of highly efficient photocatalysts with a quasi-homogeneous photocatalytic system.

Novel biaryloxazolidinone derivatives with broad-spectrum antibacterial activity, favorable drug-like profiles and in vivo efficacy against linezolid-resistant Staphylococcusaureus.

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC = 0.06 µg/mL), MSSA (MIC = 0.125 µg/mL), MRSA (MIC = 0.06 µg/mL), LRSA (MIC = 0.125 µg/mL) and LREFa (MIC = 0.5 µg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2 cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49 h, high peak plasma concentration (Cmax = 2320 ng/mL), high plasma exposure (AUC0-t = 8310 h ng/mL), and superior oral bioavailability (F = 68.1 %) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.