Exercise-induced α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation.

Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here, we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in mice. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate α-ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.

Real-Time Study of the Specific Interactions of Lactoferrin with Mimicked Heparan Sulfate Meshes Using Ordered Porous Layer Interferometry.

Heparan sulfate (HS) meshes within the glycocalyx on cell surfaces have protein recognition ability and have been crucial for gaining insights into vital bioprocesses, such as viral infection, cancer development, and inflammation. The protein recognition ability is determined by the mesh property and compositions of HS, although little attention has been paid to the effect of the mesh property on the recognition. An in-depth specificity study of protein-HS-mesh recognition is essential to illustrate related biological functions. Here, ordered porous layer interferometry is applied to study the interaction behavior between mimicked HS meshes and lactoferrin (LF). Our work aimed at mimicking HS meshes with heparin, a widely used substitute of HS, and analyzing the specific LF-heparin-mesh interaction mechanism by inhibiting the nonspecific interaction in a blended sample. We found that the counterion release-based electrostatic interaction is dominant in the specific LF-heparin-mesh recognition. Furthermore, we detail the contributions of nonspecific and specific interactions to the recognition. We illustrate that the concentrated charge distribution of the proteins appears to be primarily related to this robust, specific recognition.

Development of a Methodology Based on Optical Interferometry for Measuring Fibrinolytic Activity.

Fibrinolytic activity assay is particularly important for the detection, diagnosis, and treatment of cardiovascular disease and the development of fibrinolytic drugs. A novel efficacious strategy for real-time and label-free dynamic detection of fibrinolytic activity based on ordered porous layer interferometry (OPLI) was developed. Fibrin or a mixture of fibrin and plasminogen (Plg) was loaded into the highly ordered silica colloidal crystal (SCC) film scaffold to construct a fibrinolytic response interference layer to measure fibrinolytic activity with different mechanisms of action. Fibrinolytic enzyme-triggered fibrinolysis led to the migration of interference fringes in the interferogram, which could be represented by optical thickness changes (ΔOT) tracked in real time by the OPLI system. The morphology and optical property of the fibrinolytic response interference layer were characterized, and the Plg content in the fibrinolytic response interference layer and experimental parameters of the system were optimized. The method showed adequate sensitivity for the fibrinolytic activity of lumbrokinase and streptokinase, with wide linear ranges of 12-6000 and 10-2000 U/mL, respectively. Compared with the traditional fibrin plate method, it has a lower detection limit and higher linearity. The whole kinetic process of fibrinolysis by these two fibrinolytic drug models was recorded in real time, and the Michaelis constant and apparent kinetic parameters were calculated. Importantly, some other blood proteins were less interfering with this system, and it showed reliability in fibrin activity detection in real whole blood samples. This study established a better and more targeted research method of in vitro fibrinolysis and provided dynamic monitoring data for the analysis of fibrinolytic activity of whole blood.

Production of 1,4-Butanediol from Succinic Acid Using Escherichia Coli Whole-Cell Catalysis.

The widespread attention towards 1,4-butanediol (BDO) as a key chemical raw material stems from its potential in producing biodegradable plastics. However, the efficiency of its biosynthesis via current bioprocesses is limited. In this study, a dual-pathway approach for 1,4-BDO production from succinic acid was developed. Specifically, a double-enzyme catalytic pathway involving carboxylic acid reductase and ethanol dehydrogenase was proposed. Optimization of the expression levels of the pathway enzymes led to a significant 318 % increase in 1,4-BDO titer. Additionally, the rate-limiting enzyme MmCAR was engineered to enhance the kcat/KM values by 50 % and increase 1,4-BDO titer by 46.7 %. To address cofactor supply limitations, an NADPH and ATP cycling system was established, resulting in a 48.9 % increase in 1,4-BDO production. Ultimately, after 48 hours, 1,4-BDO titers reached 201 mg/L and 1555 mg/L in shake flask and 5 L fermenter, respectively. This work represents a significant advancement in 1,4-BDO synthesis from succinic acid, with potential applications in the organic chemical and food industries.

Efficient production of protocatechuic acid using systems engineering of Escherichia coli.

Protocatechuic acid (3, 4-dihydroxybenzoic acid, PCA) is widely used in the pharmaceuticals, health food, and cosmetics industries owing to its diverse biological activities. However, the inhibition of 3-dehydroshikimate dehydratase (AroZ) by PCA and its toxicity to cells limit the efficient production of PCA in Escherichia coli. In this study, a high-level strain of 3-dehydroshikimate, E. coli DHS01, was developed by blocking the carbon flow from the shikimate-overproducing strain E. coli SA09. Additionally, the PCA biosynthetic pathway was established in DHS01 by introducing the high-activity ApAroZ. Subsequently, the protein structure and catalytic mechanism of 3-dehydroshikimate dehydratase from Acinetobacter pittii PHEA-2 (ApAroZ) were clarified. The variant ApAroZR363A, achieved by modulating the conformational dynamics of ApAroZ, effectively relieved product inhibition. Additionally, the tolerance of the strain E. coli PCA04 to PCA was enhanced by adaptive laboratory evolution, and a biosensor-assisted high-throughput screening method was designed and implemented to expedite the identification of high-performance PCA-producing strains. Finally, in a 5 L bioreactor, the final strain PCA05 achieved the highest PCA titer of 46.65 g/L, a yield of 0.23 g/g, and a productivity of 1.46 g/L/h for PCA synthesis from glucose using normal fed-batch fermentation. The strategies described herein serve as valuable guidelines for the production of other high-value and toxic products.

Med3-mediated NADPH generation to help Saccharomyces cerevisiae tolerate hyperosmotic stress.

Hyperosmotic stress tolerance is crucial for Saccharomyces cerevisiae in producing value-added products from renewable feedstock. The limited understanding of its tolerance mechanism has impeded the application of these microbial cell factories. Previous studies have shown that Med3 plays a role in hyperosmotic stress in S. cerevisiae. However, the specific function of Med3 in hyperosmotic stress tolerance remains unclear. In this study, we showed that the deletion of the mediator Med3 impairs S. cerevisiae growth under hyperosmotic stress. Phenotypic analyses and yeast two-hybrid assays revealed that Med3 interacts with the transcription factor Stb5 to regulate the expression of the genes gnd1 and ald6, which are involved in NADPH production under hyperosmotic stress conditions. The deletion of med3 resulted in a decrease in intracellular NADPH content, leading to increased oxidative stress and elevated levels of intracellular reactive oxygen species under hyperosmotic stress, thereby impacting bud formation. These findings highlight the significant role of Med3 as a regulator in maintaining NADPH generation and redox homeostasis in S. cerevisiae during hyperosmotic stress.IMPORTANCEHyperosmotic stress tolerance in the host strain is a significant challenge for fermentation performance in industrial production. In this study, we showed that the S. cerevisiae mediator Med3 is essential for yeast growth under hyperosmotic conditions. Med3 interacts with the transcription factor Stb5 to regulate the expression of genes involved in the NADPH-generation system during hyperosmotic stress. Adequate NADPH ensures the timely removal of excess reactive oxygen species and supports bud formation under these conditions. This work highlights the crucial role of Med3 as a regulator in maintaining NADPH generation and redox homeostasis in S. cerevisiae during hyperosmotic stress.

Synthesis of C-N bonds by nicotinamide-dependent oxidoreductase: an overview.

Compounds containing chiral C-N bonds play a vital role in the composition of biologically active natural products and small pharmaceutical molecules. Therefore, the development of efficient and convenient methods for synthesizing compounds containing chiral C-N bonds is a crucial area of research. Nicotinamide-dependent oxidoreductases (NDOs) emerge as promising biocatalysts for asymmetric synthesis of chiral C-N bonds due to their mild reaction conditions, exceptional stereoselectivity, high atom economy, and environmentally friendly nature. This review aims to present the structural characteristics and catalytic mechanisms of various NDOs, including imine reductases/ketimine reductases, reductive aminases, EneIRED, and amino acid dehydrogenases. Additionally, the review highlights protein engineering strategies employed to modify the stereoselectivity, substrate specificity, and cofactor preference of NDOs. Furthermore, the applications of NDOs in synthesizing essential medicinal chemicals, such as noncanonical amino acids and chiral amine compounds, are extensively examined. Finally, the review outlines future perspectives by addressing challenges and discussing the potential of utilizing NDOs to establish efficient biosynthesis platforms for C-N bond synthesis. In conclusion, NDOs provide an economical, efficient, and environmentally friendly toolbox for asymmetric synthesis of C-N bonds, thus contributing significantly to the field of pharmaceutical chemical development.

Systems engineering Escherichia coli for efficient production p-coumaric acid from glucose.

P-coumaric acid (p-CA), a pant metabolite with antioxidant and anti-inflammatory activity, is extensively utilized in biomedicine, food, and cosmetics industry. In this study, a synthetic pathway (PAL) for p-CA was designed, integrating three enzymes (AtPAL2, AtC4H, AtATR2) into a higher l-phenylalanine-producing strain Escherichia coli PHE05. However, the lower soluble expression and activity of AtC4H in the PAL pathway was a bottleneck for increasing p-CA titers. To overcome this limitation, the soluble expression of AtC4H was enhanced through N-terminal modifications. And an optimal mutant, AtC4HL373T/G211H, which exhibited a 4.3-fold higher kcat/Km value compared to the wild type, was developed. In addition, metabolic engineering strategies were employed to increase the intracellular NADPH pool. Overexpression of ppnk in engineered E. coli PHCA20 led to a 13.9-folds, 1.3-folds, and 29.1% in NADPH content, the NADPH/NADP+ ratio and p-CA titer, respectively. These optimizations significantly enhance p-CA production, in a 5-L fermenter using fed-batch fermentation, the p-CA titer, yield and productivity of engineered strain E. coli PHCA20 were 3.09 g/L, 20.01 mg/g glucose, and 49.05 mg/L/h, respectively. The results presented here provide a novel way to efficiently produce the plant metabolites using an industrial strain.

Nanoporous Polystyrene Inverse Opal Materials with Optical Interference Properties for Label-Free Biosensing.

Colloidal crystal nanomaterials have been proven to be valuable substrates for optical-based biosensing due to their ordered macroporous nanostructure and brilliant optical properties. In this work, silica colloidal crystal (SCC) thin films, as well as polystyrene-SCC composite films and inverse opal (IO) polystyrene films fabricated using SCC as templates, are investigated for their application as substrate materials in optical interferometric biosensors. The SCC films formed by the self-assembly of silica colloidal crystals have the most densely packed nano-3D structure, also known as the opal structure. IO films are fabricated by filling the opal pores of SCC with polystyrene and then removing the template, resulting in an interconnected nano-3D ordered macroporous structure, as indicated by the name inverse opal. The performance of the three materials was compared and discussed based on an ordered porous layer interferometry optical platform, focusing on refractive index response, protein adsorption response, and biomolecular interaction response. These results could potentially offer innovative material support for the advancement of label-free optical biosensors, which can be used for more biological/biochemical/biomolecular reaction monitoring studies.

Four novel Acinetobacter lwoffii strains isolated from the milk of cows in China with subclinical mastitis.

BACKGROUND: Acinetobacter lwoffii (A. lwoffii) is a Gram-negative bacteria common in the environment, and it is the normal flora in human respiratory and digestive tracts. The bacteria is a zoonotic and opportunistic pathogen that causes various infections, including nosocomial infections. The aim of this study was to identify A. lwoffii strains isolated from bovine milk with subclinical mastitis in China and get a better understanding of its antimicrobial susceptibility and resistance profile. This is the first study to analyze the drug resistance spectrum and corresponding mechanisms of A. lwoffii isolated in raw milk. RESULTS: Four A. lwoffii strains were isolated by PCR method. Genetic evolution analysis using the neighbor-joining method showed that the four strains had a high homology with Acinetobacter lwoffii. The strains were resistant to several antibiotics and carried 17 drug-resistance genes across them. Specifically, among 23 antibiotics, the strains were completely susceptible to 6 antibiotics, including doxycycline, erythromycin, polymyxin, clindamycin, imipenem, and meropenem. In addition, the strains showed variable resistance patterns. A total of 17 resistance genes, including plasmid-mediated resistance genes, were detected across the four strains. These genes mediated resistance to 5 classes of antimicrobials, including beta-lactam, aminoglycosides, fluoroquinolones, tetracycline, sulfonamides, and chloramphenicol. CONCLUSION: These findings indicated that multi-drug resistant Acinetobacter lwoffii strains exist in raw milk of bovine with subclinical mastitis. Acinetobacter lwoffii are widespread in natural environmental samples, including water, soil, bathtub, soap box, skin, pharynx, conjunctiva, saliva, gastrointestinal tract, and vaginal secretions. The strains carry resistance genes in mobile genetic elements to enhance the spread of these genes. Therefore, more attention should be paid to epidemiological surveillance and drug resistant A. lwoffii.

Whole-genome sequencing of multidrug-resistant Klebsiella pneumoniae with capsular serotype K2 isolates from mink in China.

BACKGROUND: Klebsiella pneumoniae is a zoonotic opportunistic pathogen, and also one of the common pathogenic bacteria causing mink pneumonia. The aim of this study was to get a better understanding of the whole-genome of multi-drug resistant Klebsiella pneumoniae with K2 serotype in China. This study for the first time to analyze Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, resistance and virulence genes of Klebsiella pneumoniae in mink. RESULTS: The isolate was Klebsiella pneumoniae with serotype K2 and ST6189 by PCR method. The string test was positive and showed high mucus phenotype. There was one plasmid with IncFIB replicons in the genome. The virulence factors including capsule, lipopolysaccharide, adhesin, iron uptake system, urease, secretory system, regulatory gene (rcsA, rcsB), determinants of pili adhesion, enolase and magnesium ion absorption related genes. The strain was multi-drug resistant. A total of 26  resistance genes, including beta-lactam, aminoglycosides, tetracycline, fluoroquinolones, sulfonamides, amide alcohols, macrolides, rifampicin, fosfomycin, vancomycin, diaminopyrimidines and polymyxin. Multidrug-resistant efflux protein AcrA, AcrB, TolC, were predicted in the strain. CONCLUSION: It was the first to identify that serotype K2 K. pneumonia with ST6189 isolated from mink in China. The finding indicated that hypervirulent and multi-drug resistant K. pneumoniae was exist in Chinese mink. The whole-genome of K. pneumoniae isolates have importance in mink farming practice.

Altered leptin level in autism spectrum disorder and meta-analysis of adipokines.

BACKGROUND: Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis. METHODS: Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies. RESULTS: Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis. CONCLUSIONS: These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.

Health economics study of paliperidone palmitate in the treatment of schizophrenia: a 12-month cohort study.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05). CONCLUSION: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

Functional knee phenotypes appear to be more suitable for the Chinese OA population compared with CPAK classification: A study based on 3D CT reconstruction models.

PURPOSE: The aim of this study was to investigate the distribution of coronal plane alignment of the knee (CPAK) classification and functional knee phenotypes in a Chinese osteoarthritis (OA) population and to compare different lower limb alignment targets according to the distribution characteristics to find suitable total knee arthroplasty (TKA) bone cut strategies for the Chinese OA patients. METHODS: The computed tomography (CT) images were retrospectively collected and the three-dimensional (3D) models were reconstructed from 434 Chinese OA patients, including 93 males and 341 females, with a mean age of 66.4 ± 9.3 years. Femoral mechanical angle (FMA), tibial mechanical angle (TMA) and mechanical hip-knee-ankle angle (mHKA) were measured on the 3D models. Arithmetic hip-knee-ankle angle (aHKA) was calculated using FMA plus TMA, and joint line obliquity was calculated as 180 + TMA-FMA. The CPAK according to MacDessi and the functional knee phenotypes according to Hirschmann were performed. In addition, the suitable TKA bone cut strategies were explored according to the phenotypes and based on the characteristics of different alignment targets, such as mechanical alignment, anatomic alignment (AA), kinematic alignment, restricted KA (rKA) and adjusted MA (aMA). Statistical differences were determined using the independent-samples t-test or the two independent-samples Wilcoxon test, with p < 0.05 considered statistically significant. RESULTS: The Chinese OA population showed a varus alignment tendency (mHKA = 172.1° ± 7.2°), to which the TMA was a major contributor (TMA = 84.7° ± 4.4° vs. FMA = 91.3° ± 3.2°). The mHKA was on average 3.9° more varus than the aHKA. A total of 140 functional knee phenotypes were found and 45.6% were concentrated in VARFMA3°-NEUFMA0° to VARTMA3°-NEUTMA0°. More than 70% of patients had different FMA and TMA phenotypes. There were 92.9% of CPAK distributed in types I to IV, with type I accounting for 53.9%. The FMA phenotypes were less changed if the aMA and rKA were chosen, and the TMA phenotypes were less changed if the AA and rKA were chosen. CONCLUSION: Compared with the CPAK, the functional knee phenotypes were more suitable for the Chinese OA population with a wide distribution and a varus tendency, and it seemed more appropriate to choose aMA and rKA as TKA alignment targets for resection. LEVEL OF EVIDENCE: Level Ⅲ.

Construction of scalable multi-channel DNA nanoplatform for the combined detection of ctDNA biomarkers of ovarian cancer.

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNA determination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers.

Early ontogenesis from embryo to juvenile in Senegalese sole Solea senegalensis under laboratory conditions.

Senegalese sole, Solea senegalensis, is a flatfish of high commercial value in the world. It has been identified as an interesting and promising species for marine commercial aquaculture diversification in Europe for at least four decades and was introduced to China in 2003. Early ontogenesis from embryo to juvenile stages in S. senegalensis was analysed under controlled laboratory conditions to provide morphological information for aquaculture. From 0 to 59 days post hatching (dph), 10-20 larvae were sampled and measured each day (0-17 dph) or every 2-6 days (17-59 dph). Morphological characteristics from the egg to the juvenile stage were described. The eggs were separate and spherical with multiple oil globules. After 3 dph, the yolk sac was completely absorbed, mouth and anus were open, a swim bladder appeared, and larvae began feeding on rotifers (Brachionus plicatilis). The larvae began metamorphosis as the notochord flexed upward and the left eye migrated upward after 10 dph. The left eye migrated to the dorsal midline at 15 dph. At 19 dph, the left eye was translocated to the right-ocular side, and the juveniles adopted a benthic lifestyle. The swim bladder degenerated, and the juveniles completed metamorphosis at 23 dph. The growth patterns of some parameters (TL, SL, BH, BW) during larval and juvenile development stages were identified. The inflection points, which are slopes of growth changes, were calculated in growth curves. Three inflection points occurring in the growth curves of larvae and juveniles were found to be associated with metamorphosis, weaning, and transitions in feeding habits. The basic information of embryo development and ontogenesis in this study represents a valuable contribution to the S. senegalensis industry, especially in artificial breeding and rearing techniques.

Recent advances and new insights on the construction of photocatalytic systems for environmental disinfection.

Photocatalysis, as a sustainable and environmentally friendly green technology, has garnered widespread recognition and application across various fields. Especially its potential in environmental disinfection has been highly valued by researchers. This study commences with foundational research on photocatalytic disinfection technology and provides a comprehensive overview of its current developmental status. It elucidates the complexity of the interface reaction mechanism between photocatalysts and microorganisms, providing valuable insights from the perspectives of materials and microorganisms. This study reviews the latest design and modification strategies (Build heterojunction, defect engineering, and heteroatom doping) for photocatalysts in environmental disinfection. Moreover, this study investigates the research focuses and links in constructing photocatalytic disinfection systems, including photochemical reactors, light sources, and material immobilization technologies. It studies the complex challenges and influencing factors generated by different environmental media during the disinfection process. Simultaneously, a comprehensive review extensively covers the research status of photocatalytic disinfection concerning bacteria, fungi, and viruses. It reveals the observable efficiency differences caused by the microstructure of microorganisms during photocatalytic reactions. Based on these influencing factors, the economy and effectiveness of photocatalytic disinfection systems are analyzed and discussed. Finally, this study summarizes the current application status of photocatalytic disinfection products. The challenges faced by the synthesis and application of future photocatalysts are proposed, and the future development in this field is discussed. The potential for research and innovation has been further emphasized, with the core on improving efficiency, reducing costs, and strengthening the practical application of photocatalysis in environmental disinfection.

Deep eutectic solvents pretreatment enhances methane production from anaerobic digestion of waste activated sludge: Effectiveness evaluation and mechanism elucidation.

Anaerobic digestion (AD) is a prevalent waste activated sludge (WAS) treatment, and optimizing methane production is a core focus of AD. Two DESs were developed in this study and significantly increased methane production, including choline chloride-urea (ChCl-Urea) 390% and chloride-ethylene glycol (ChCl-EG) 540%. Results showed that ChCl-Urea mainly disrupted extracellular polymeric substances (EPS) structures, aiding in initial sludge solubilization during pretreatment. ChCl-EG, instead, induced sludge self-driven organic solubilization and enhanced hydrolysis and acidification processes during AD process. Based on the extent to which the two DESs promoted AD for methane production, the AD process can be divided into stage Ⅰ and stage Ⅱ. In stage Ⅰ, ChCl-EG promoted methanogenesis more significantly, microbiological analysis showed both DESs enriched aceticlastic methanogens-Methanosarcina. Notably, ChCl-Urea particularly influenced polysaccharide-related metabolism, whereas ChCl-EG targeted protein-related metabolism. In stage Ⅱ, ChCl-Urea was more dominant than ChCl-EG, ChCl-Urea bolstered metabolism and ChCl-EG promoted genetic information processing in this stage. In essence, this study investigated the microbial mechanism of DES-enhanced sludge methanogenesis and provided a reference for future research.

Rational Design of the Spatial Effect in a Fe(II)/α-Ketoglutarate-Dependent Dioxygenase Reverses the Regioselectivity of C(sp3)-H Bond Hydroxylation in Aliphatic Amino Acids.

The hydroxylation of remote C(sp3)-H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high-value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)-H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α-ketoglutarate-dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Crystal structure analysis, molecular dynamics simulations, and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on these results, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L-Homoleucine (5 a) was reversed from the γ site (1 : 12) to the δ site (>99 : 1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)-H bonds, but also provides a theoretical guidance for the precision-driven modification of similarly remote C(sp3)-H bonds in complex molecules.

Comprehensively analysis of splicing factors to construct prognosis prediction classifier in prostate cancer.

Splicing factors (SFs) are proteins that control the alternative splicing (AS) of RNAs, which have been recognized as new cancer hallmarks. Their dysregulation has been found to be involved in many biological processes of cancer, such as carcinogenesis, proliferation, metastasis and senescence. Dysregulation of SFs has been demonstrated to contribute to the progression of prostate cancer (PCa). However, a comprehensive analysis of the prognosis value of SFs in PCa is limited. In this work, we systematically analysed 393 SFs to deeply characterize the expression patterns, clinical relevance and biological functions of SFs in PCa. We identified 53 survival-related SFs that can stratify PCa into two de nove molecular subtypes with distinct mRNA expression and AS-event expression patterns and displayed significant differences in pathway activity and clinical outcomes. An SF-based classifier was established using LASSO-COX regression with six key SFs (BCAS1, LSM3, DHX16, NOVA2, RBM47 and SNRPN), which showed promising prognosis-prediction performance with a receiver operating characteristic (ROC) >0.700 in both the training and testing datasets, as well as in three external PCa cohorts (DKFZ, GSE70769 and GSE21035). CRISPR/CAS9 screening data and cell-level functional analysis suggested that LSM3 and DHX16 are essential factors for the proliferation and cell cycle progression in PCa cells. This study proposes that SFs and AS events are potential multidimensional biomarkers for the diagnosis, prognosis and treatment of PCa.