Mitochondria-targeting Cu2-xSe-TPP with dual enzyme activity alleviates Alzheimer's disease by modulating oxidative stress.

Mitochondrial dysfunction in microglia has been implicated as a key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). Abnormal production of reactive oxygen species (ROS) and neuroinflammation caused by mitochondrial oxidative stress are important factors leading to neuronal death in AD. Herein, a "dual brake" strategy to synergistically halt mitochondrial dysfunction and neuroinflammation targeting mitochondria in microglia is proposed. To achieve this goal, (3-carboxypropyl) triphenyl-phosphonium bromide (TPP)-modified Cu2-xSe nanozymes (Cu2-xSe-TPP NPs) with dual enzyme-like activities was designed. Cu2-xSe-TPP NPs with superoxide dismutase-mimetic (SOD) and catalase-mimetic (CAT) activities can effectively scavenge ROS in the mitochondria of microglia and relieve mitochondrial oxidative stress. In vivo studies demonstrated that Cu2-xSe-TPP NPs can alleviate oxidative stress and promote neuroprotection in the hippocampus of AD model mice. In addition, Cu2-xSe-TPP NPs can regulate the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, promote Aß phagocytosis and reshape the AD inflammatory microenvironment, thus effectively attenuating AD neuropathology and rescuing cognitive deficits in AD model mice. Taken together, this strategy preventing mitochondrial damage and remodeling the inflammatory microenvironment will provide a new perspective for AD therapy.

FengycinA-M3 Inhibits Listeria monocytogenes by Binding to Penicillin-Binding Protein 2B Targets to Disrupt Cell Structure.

The contamination of food with Listeria monocytogenes threatens food safety and human health, and developing a novel, green, and safe antimicrobial substance will offer a new food preservation strategy. FengycinA-M3 is a novel lipid peptide with low cytotoxicity and resistance and has effective antibacterial activity against L. monocytogenes with a minimum inhibitory concentration (MIC) of 4 µg/mL. Further combined transcriptomics and proteomics analysis yielded 20 differentially expressed genes (DEGs). The MICs of the combined use of FengycinA-M3 and Cefalexin on L. monocytogenes were further determined as FengycinA-M3 (2 µg/mL) and Cefalexin (8 µg/mL) using the checkerboard method. In addition, FengycinA-M3 was found to play a role in delaying pork deterioration. This study explored the inhibitory effect of FengycinA-M3 on L. monocytogenes and its mechanism of action. FengycinA-M3 interacted with penicillin-binding protein 2B on the cell membrane of L. monocytogenes, destroying the permeability of the membrane, causing cell membrane rupture, thereby inhibiting the growth of L. monocytogenes. Overall, FengycinA-M3 is a promising candidate for preventing the emergence and spread of L. monocytogenes with potential applications in food processing.

Screening immunomodulatory Q-markers in Astragali Radix based on UHPLC-QTOF-MS analysis and spectrum-effect relationship.

Astragali Radix (AR) is one of the famous traditional Chinese medicines (TCMs) for boosting immunity, whereas the quality markers (Q-markers) of AR have not been clearly researched. The immunomodulatory activities of the bioactive extractions and components were evaluated by NO inhibition rate; phagocytic index; IL-10, TNF-α, IL-1ß, and IL-6 cytokines in RAW264.7 cells; and the relative proliferation rate of spleen cells. The total saponins (TS) and the grade 2 (Xiaoxuan, XX) of AR showed the strongest immunomodulatory activities. At the concentration of 40 µg/mL, the TS increased spleen cells proliferation by 48.0% and upregulated the level of IL-1ß and IL-6. Cytokines in the XX-treated group were at least 1.6 times higher than the control group. A total of 190 common peaks were detected in AR by ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS). The multivariate statistical analyses revealed that 41 compounds were positively correlated with immune responses, and bioactive compounds were verified by using RAW264.7 cell assay. Subsequently, the contents of six compounds in different commercial grades were determined, and the results showed the same trend in contents and activities. Finally, calycosin-7-O-ß-D-glucoside, astragaloside IV, astragaloside II, astragaloside I, isomucronulatol-7-O-glucoside, and 9,10-dimethoxypterocarpan-3-O-glucoside were screened out as immunomodulatory Q-markers of AR.

HPV16 E6-induced M2 macrophage polarization in the cervical microenvironment via exosomal miR-204-5p.

The persistent infection of high-risk human papillomavirus (HPV) and the progression of cervical cancer necessitate the involvement of microenvironmental immunity. As cervical lesions advance, there is an observed increase in the infiltration of type 2 (M2) macrophages. However, the precise mechanism driving this increased infiltration of M2 macrophages remains unclear. In this study, we investigated the role of exosomes in polarising M2 macrophages in cervical lesions associated with HPV E6. Through the analysis of bioinformatics data and clinical specimens, we discovered a positive correlation between HPV E6/E7 mRNA copy number and the level of M2 macrophage infiltration. Exosomes derived from HPV E6 overexpressed (HPV E6+) cervical squamous cell carcinoma (CESC) cells were found to induce the polarisation of macrophages towards M2 type. Specifically, miR-204-5p, enriched in HPV E6 + CESC exosomes, was transported into macrophages and triggered M2 macrophage polarisation by inhibiting JAK2. The clinical relevance of exosomal miR-204-5p in the progression of cervical lesions was validated through serum samples from 35 cases. Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.

Progress in the study of the correlation between sepsis and intestinal microecology.

Sepsis, a disease with high incidence, mortality, and treatment costs, has a complex interaction with the gut microbiota. With advances in high-throughput sequencing technology, the relationship between sepsis and intestinal dysbiosis has become a new research focus. However, owing to the intricate interplay between critical illness and clinical interventions, it is challenging to establish a causal relationship between sepsis and intestinal microbiota imbalance. In this review, the correlation between intestinal microecology and sepsis was summarized, and new therapies for sepsis intervention based on microecological target therapy were proposed, and the shortcomings of bacterial selection and application timing in clinical practice were addressed. In conclusion, current studies on metabolomics, genomics and other aspects aimed at continuously discovering potential probiotics are all providing theoretical basis for restoring intestinal flora homeostasis for subsequent treatment of sepsis.

Enhancing refrigerated chicken breasts preservation: Novel composite hydrogels incorporated with antimicrobial peptides, bacterial cellulose, and polyvinyl alcohol.

Microbial contamination annually leads to substantial food resource loss. Effective food packaging can mitigate food contamination and waste, yet conventional materials such as plastics often lack bacteriostatic activity. This study aimed to synthesise FengycinA-M3@bacterial cellulose@polyvinyl alcohol composite hydrogels via dual cross-linking with hydrogen and borate bonding, with the goal of enhancing antibacterial properties and prolonging the preservation period of refrigerated chicken breast. The composite hydrogel was subjected to comprehensive characterisation for structural, mechanical, water absorption, slow peptide release, antimicrobial capacity, biocompatibility, and chicken breast freshness preservation. The results showed that the composite hydrogel had a porous network structure and excellent gel elasticity and biocompatibility. It was effective in inhibiting Staphylococcus aureus and Escherichia coli, and prolonged the storage time of frozen chicken breast for up to 12 days. These findings emphasise the potential of hydrogel food packaging to prolong storage periods and its suitability for food industry applications due to ease of manufacture.

[Design and application of a specialized protective skirt for patients undergoing extracorporeal membrane oxygenation].

Extracorporeal membrane oxygenation (ECMO) provides continuous extracorporeal respiratory and circulatory support for patients with severe heart and lung failure, in order to maintain their lives. Currently, ECMO is an advanced organ support technology and its application in the clinical field of critical care is becoming increasingly common. When ECMO is implemented via percutaneous cannulation at the bilateral femoral artery and vein, the traditional patient pants cannot be used, which leads to exposure of privacy, easy catching of cold, and easy contamination of bed sheets and covers during defecation, making the patient uncomfortable and increasing the risk of infection. Changing bed sheets and covers not only increases the workload of nurses, but also easily causes pipeline displacement or slipping. It is inconvenient to observe the patient's bleeding, displacement, or dislodgement of the pipeline at any time when wearing patient pants. To solve the problems, nursing staff in the emergency intensive care unit of Henan Provincial People's Hospital have designed a protective skirt specifically designed for patients undergoing ECMO, which has obtained a National Utility Model Patent of China (patent number: ZL 2020 2 08120022.9). The special protective skirt for patients with ECMO mainly consists of a skirt body, a transparent observation window, a hip support part, and a fecal collection part. The transparent observation window is convenient for the puncture site and pipeline observation. After the hip support part is inflated, the patient can separate the perianal skin and urine and feces to avoid the occurrence of incontinence dermatitis. The fecal collection part can collect urine and feces to keep the bed unit clean. The protective skirt has a simple structure and is easy to wear and take off. While protecting patient privacy and ensuring patient comfort, it can also observe the condition of the pipeline at any time. It is suitable for patients with lower limb catheterization or urinary and fecal incontinence, and has certain clinical application and promotion value.

Experimental viral spillover across 25 million year gap in Rodentia reveals limited viral transmission and purifying selection of a picornavirus.

When a virus crosses from one host species to another, the consequences can be devastating. However, animal models to empirically evaluate cross-species transmission can fail to recapitulate natural transmission routes, physiologically relevant doses of pathogens, and population structures of naturally circulating viruses. Here, we present a new model of cross-species transmission where deer mice (Peromyscus maniculatus) are exposed to the natural virome of pet store mice (Mus musculus). Using RNA sequencing, we tracked viral transmission via fecal-oral routes and found the evidence of transmission of murine astroviruses, coronaviruses, and picornaviruses. Deep sequencing of murine kobuvirus revealed tight bottlenecks during transmission and purifying selection that leaves limited diversity present after transmission from Mus to Peromyscus. This work provides a structure for studying viral bottlenecks across species while keeping natural variation of viral populations intact and a high resolution look at within-host dynamics that occur during the initial stages of cross-species viral transmission.IMPORTANCEViral spillover events can have devastating public health consequences. Tracking cross-species transmission in real-time and evaluating viral evolution during the initial spillover event are useful for understanding how viruses adapt to new hosts. Using our new animal model and next generation sequencing, we develop a framework for understanding intrahost viral evolution and bottleneck events, which are very difficult to study in natural transmission settings.

Hepatic protein phosphatase 1 regulatory subunit 3G alleviates obesity and liver steatosis by regulating the gut microbiota and bile acid metabolism.

Intestinal dysbiosis and disrupted bile acid (BA) homeostasis are associated with obesity, but the precise mechanisms remain insufficiently explored. Hepatic protein phosphatase 1 regulatory subunit 3G (PPP1R3G) plays a pivotal role in regulating glycolipid metabolism; nevertheless, its obesity-combatting potency remains unclear. In this study, a substantial reduction was observed in serum PPP1R3G levels in high-body mass index (BMI) and high-fat diet (HFD)-exposed mice, establishing a positive correlation between PPP1R3G and non-12α-hydroxylated (non-12-OH) BA content. Additionally, hepatocyte-specific overexpression of Ppp1r3g (PPP1R3G HOE) mitigated HFD-induced obesity as evidenced by reduced weight, fat mass, and an improved serum lipid profile; hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology. PPP1R3G HOE considerably impacted systemic BA homeostasis, which notably increased the non-12-OH BAs ratio, particularly lithocholic acid (LCA). 16S ribosomal DNA (16S rDNA) sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population, and elevating the relative abundance of Blautia, which exhibited a positive correlation with serum LCA levels. A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent. Mechanistically, PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase (CYP7A1) and sterol-12α-hydroxylase (CYP8B1), and concurrently upregulated oxysterol 7-α hydroxylase and G protein-coupled BA receptor 5 (TGR5) expression under HFD conditions. Furthermore, LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels. These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis, which may serve as potential therapeutic targets for obesity-related disorders.

Effects of the teach-back method on the health status of patients with chronic obstructive pulmonary disease: a real-world community-based cluster-randomized controlled trial.

Background: The teach-back method (TBM), also known as the "show-me" method, is a technique for verifying patients' understanding of health-related information that has been recommended for improving health literacy. However, the research on TBM effect on the outcomes of chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, the aim of this study was to examine the effect of a TBM intervention on the health status of COPD patients. Methods: This real-world community-based cluster-randomized controlled trial enrolled 1,688 patients with COPD from 18 communities in China. Participants received either TBM plus usual care (UC) or UC only. General practitioners were trained in TBM before the intervention. The primary outcomes were depression and anxiety symptoms, as measured by the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes were health-related quality of life and dyspnea, as measured by the COPD Assessment Test (CAT). Dyspnea was assessed using the modified Medical Research Council (mMRC) dyspnea scale. Data on acute exacerbations and deaths were extracted from medical records. Lung function was expressed as the forced expiratory volume in 1 second as a percentage of the predicted value [FEV1 (% pred)]. Results: In total, 336 of the 853 COPD patients in the intervention group (TBM plus UC) had comorbid depression, compared with 329 of the 835 in the control group (UC only). The TBM group showed a significantly greater improvement in HADS depression and anxiety subscale scores (HADS-D and HADS-A, respectively) than the UC group at12 months (t =8.34, P<0.001; t=12.18, P<0.001). The CAT and mMRC scores were significantly lower in the TBM than UC group at 12 months (t=8.43, P<0.001; t=7.23, P<0.001). The numbers of acute exacerbations and deaths were significantly lower in the TBM than UC group at 12 months (mean MCF values were 0.35 and 0.56, respectively [difference of 0.22; 95% confidence interval (CI): -0.41, -0.02; χ2=9.63, P<0.001]. The FEV1 (% pred) was significantly higher in the TBM than UC group at 12 months (t=7.45, P<0.001). Conclusions: General practitioners can use TBM interventions to effectively reduce anxiety, depression, and dyspnea symptoms, decrease the frequency of exacerbations and likelihood of death, and improve health-related quality of life and pulmonary function in patients with COPD. Trial Registration: The trial was registered on the Chinese Clinical Trials Registry (reference: ChiCTR-TRC-12001958).

2-Ethylhexyl Diphenyl Phosphate Induces Autism Spectrum Disorder-Like Behaviors in Offspring Mice by Disrupting Postsynaptic Development.

As organophosphorus flame retardants (OPFRs) are constantly detected in human samples, the neurotoxicity of OPFRs is of concern. In this study, pregnant ICR mice were exposed to 2-ethylhexyl diphenyl phosphate (EHDPP) in drinking water from gestation to lactation to investigate its effects on autism spectrum disorder-like (ASD-like) behaviors in offspring. Serum EHDPP concentrations in dams in the 0.4, 2, and 10 mg/kg groups were 0.282 ± 0.051, 0.713 ± 0.115, and 0.974 ± 0.048 ng/mL, respectively, within the concentration range in humans. At the highest dose, EHDPP exposure induced ASD-like behaviors in both female and male offspring. Significant reductions in mature dendritic spines and structural damage to the postsynaptic density zone were noted in all but the lowest exposure groups, indicating postsynaptic membrane impairment. Mechanistically, EHDPP significantly downregulated disc large MAGUK scaffold protein 4 expression by inhibiting protein kinase B and type 1 insulin-like growth factor receptor phosphorylation. In the heterologous synapse formation assay in vivo, EHDPP significantly reduced the levels of postsynaptic density protein 95 expression in neurons at 1 µM. Overall, the study utilized in vitro and in vivo experiments to confirm that EHDPP damaged postsynaptic membrane formation and might increase the incidence of ASD in offspring.

The effect of polylactic acid ordering on the long-term corrosion protection capacity of biodegradable magnesium alloys.

The polylactic acid (PLA) coatings of different crystallinity were prepared on biodegradable Mg-2.2Zn-0.3Ca alloy wires to improve the long-term anti-corrosion properties. The composition characteristics and microstructure of the samples were investigated by differential scanning calorimetry (DSC), Fourier transform infrared spectroscope (FTIR), wide angle X-ray diffraction (WAXD) and scanning electron microscope (SEM). The corrosion resistance of all samples was investigated by immersion tests and electrochemical techniques in vitro simulated body fluid (SBF). The results indicated heat treatment improved the crystallinity of PLA coating and heated-coating performed protective behaviors in the short and long-term immersion. The corrosion rate of heated samples was lower than that of unheated samples and exhibited superior long term protective effect for Mg alloy wires. The lifetime of heated sample (H2) increased significantly from 33 to 55 days. The initial electrochemical performance of unheated coating was better than heated coating, but it declined more rapidly during the long-term immersion. These results indicated that PLA coating could not ignore the effect of its crystallinity to anti-corrosion ability, and only the suit heat treatment makes PLA coating more ordering and achieves higher corrosion resistance in vitro immersion. Therefore, it has promising potential by controlling effectively the PLA ordering for surgical implant applications.

Shell Distribution of Vitamin K3 within Reinforced Electrospun Nanofibers for Improved Photo-Antibacterial Performance.

Personal protective equipment (PPE) has attracted more attention since the outbreak of the epidemic in 2019. Advanced nano techniques, such as electrospinning, can provide new routes for developing novel PPE. However, electrospun antibacterial PPE is not easily obtained. Fibers loaded with photosensitizers prepared using single-fluid electrospinning have a relatively low utilization rate due to the influence of embedding and their inadequate mechanical properties. For this study, monolithic nanofibers and core-shell nanofibers were prepared and compared. Monolithic F1 fibers comprising polyethylene oxide (PEO), poly(vinyl alcohol-co-ethylene) (PVA-co-PE), and the photo-antibacterial agent vitamin K3 (VK3) were created using a single-fluid blending process. Core-shell F2 nanofibers were prepared using coaxial electrospinning, in which the extensible material PEO was set as the core section, and a composite consisting of PEO, PVA-co-PE, and VK3 was set as the shell section. Both F1 and F2 fibers with the designed structural properties had an average diameter of approximately 1.0 µm, as determined using scanning electron microscopy and transmission electron microscopy. VK3 was amorphously dispersed within the polymeric matrices of F1 and F2 fibers in a compatible manner, as revealed using X-ray diffraction and Fourier transform infrared spectroscopy. Monolithic F1 fibers had a higher tensile strength of 2.917 ± 0.091 MPa, whereas the core-shell F2 fibers had a longer elongation with a break rate of 194.567 ± 0.091%. Photoreaction tests showed that, with their adjustment, core-shell F2 nanofibers could produce 0.222 µmol/L ·OH upon illumination. F2 fibers had slightly better antibacterial performance than F1 fibers, with inhibition zones of 1.361 ± 0.012 cm and 1.296 ± 0.022 cm for E. coli and S. aureus, respectively, but with less VK3. The intentional tailoring of the components and compositions of the core-shell nanostructures can improve the process-structure-performance relationship of electrospun nanofibers for potential sunlight-activated antibacterial PPE.

Structural basis for the type I-F Cas8-HNH system.

The Cas3 nuclease is utilized by canonical type I CRISPR-Cas systems for processive target DNA degradation, while a newly identified type I-F CRISPR variant employs an HNH nuclease domain from the natural fusion Cas8-HNH protein for precise target cleavage both in vitro and in human cells. Here, we report multiple cryo-electron microscopy structures of the type I-F Cas8-HNH system at different functional states. The Cas8-HNH Cascade complex adopts an overall G-shaped architecture, with the HNH domain occupying the C-terminal helical bundle domain (HB) of the Cas8 protein in canonical type I systems. The Linker region connecting Cas8-NTD and HNH domains adopts a rigid conformation and interacts with the Cas7.6 subunit, enabling the HNH domain to be in a functional position. The full R-loop formation displaces the HNH domain away from the Cas6 subunit, thus activating the target DNA cleavage. Importantly, our results demonstrate that precise target cleavage is dictated by a C-terminal helix of the HNH domain. Together, our work not only delineates the structural basis for target recognition and activation of the type I-F Cas8-HNH system, but also guides further developments leveraging this system for precise DNA editing.

Picolinic acid-mediated Mn(II) activated periodate for ultrafast and selective degradation of emerging contaminants: Key role of high-valent Mn-oxo species.

The utilization of periodate (PI, IO4-) in metal-based advanced oxidation processes (AOPs) for the elimination of emerging contaminants (ECs) have garnered significant attention. However, the commonly used homogeneous metal catalyst Mn(II) performs inadequately in activating PI. Herein, we exploited a novel AOP technology by employing the complex of Mn(II) with the biodegradable picolinic acid (PICA) to activate PI for the degradation of electron-rich pollutants. The performance of the Mn(II)-PICA complex surpassed that of ligand-free Mn(II) and other Mn(II) complexes with common aminopolycarboxylate ligands. Through scavenger, sulfoxide-probe transformation, and 18O isotope-labeling experiments, we confirmed that the dominant reactive oxidant generated in the Mn(II)-PICA/PI system was high-valent manganese-oxo species (Mn(V)=O). Due to its reliance on Mn(V)=O, the Mn(II)-PICA/PI process exhibited remarkable selectivity and strong anti-interference during EC oxidation in complex water matrices. Nine structurally diverse pollutants were selected for evaluation, and their lnkobs values in the Mn(II)-PICA/PI system correlated well with their electrophilic/nucleophilic indexes, EHOMO, and vertical IP (R2 = 0.79-0.94). Additionally, IO4- was converted into non-toxic iodate (IO3-) without producing undesired iodine species such as HOI, I2, and I3-. This study provides a novel protocol for metal-based AOPs using PI in combination with chelating agents and high-valent metal-oxo species formation during water purification.

Characterization of sequence variations in the extended flanking regions using massively parallel sequencing in 21 A-STRs and 21 Y-STRs.

In forensic genetics, utilizing massively parallel sequencing (MPS) to analyze short tandem repeats (STRs) has demonstrated several advantages compared to conventional capillary electrophoresis (CE). Due to the current technical limitations, although flanking region polymorphisms had been mentioned in several previous studies, most studies focused on the core repeat regions of STRs or the variations in the adjacent flanking regions. In this study, we developed an MPS system consisting of two sets of multiplex PCR systems to detect not only the STR core repeat regions but also to observe variants located at relatively distant positions in the flanking regions. The system contained 42 commonly used forensic STRs, including 21 autosomal STRs (A-STRs) and 21 Y-chromosomal STRs (Y-STRs), and a total of 350 male individuals from a Chinese Han population were genotyped. The length and sequence variants per locus were tallied and categorized based on length (length-based, LB), sequence without flanking region (core repeat regions sequence-based, RSB), and sequence with flanking region (core repeat and flanking regions sequence-based, FSB), respectively. Allele frequencies, Y-haplotype frequencies, and forensic parameters were calculated based on LB, RSB, and FSB, respectively, to evaluate the improvement in discrimination power, heterozygosity, and effectiveness of forensic systems. The results suggested the sequence variations have more influence on A-STRs and could improve the identification ability of MPS-STR genotyping. Concordance between MPS and CE methods was confirmed by using commercial CE-based STR kits. The impact of flanking region variations on STR genotype analysis and potential factors contributing to discordances were discussed. A total of 58 variations in the flanking regions (53 SNPs/SNVs and 5 InDels) were observed and most variations (48/58) were distributed in A-STRs. In summary, this study delved deeper into the genetic information of forensic commonly used STR and advanced the application of massively parallel sequencing in forensic genetics.

Comparative Analysis of Phytohormone Biosynthesis Genes Responses to Long-Term High Light in Tolerant and Sensitive Wheat Cultivars.

Phytohormones are vital for developmental processes, from organ initiation to senescence, and are key regulators of growth, development, and photosynthesis. In natural environments, plants often experience high light (HL) intensities coupled with elevated temperatures, which pose significant threats to agricultural production. However, the response of phytohormone-related genes to long-term HL exposure remains unclear. Here, we examined the expression levels of genes involved in the biosynthesis of ten phytohormones, including gibberellins, cytokinins, salicylic acid, jasmonic acid, abscisic acid, brassinosteroids, indole-3-acetic acid, strigolactones, nitric oxide, and ethylene, in two winter wheat cultivars, Xiaoyan 54 (XY54, HL tolerant) and Jing 411 (J411, HL sensitive), when transferred from low light to HL for 2-8 days. Under HL, most genes were markedly inhibited, while a few, such as TaGA2ox, TaAAO3, TaLOG1, and TaPAL2, were induced in both varieties. Interestingly, TaGA2ox2 and TaAAO3 expression positively correlated with sugar content but negatively with chlorophyll content and TaAGP expression. In addition, we observed that both varieties experienced a sharp decline in chlorophyll content and photosynthesis performance after prolonged HL exposure, with J411 showing significantly more sensitivity than XY54. Hierarchical clustering analysis classified the phytohormone genes into the following three groups: Group 1 included six genes highly expressed in J411; Group 2 contained 25 genes drastically suppressed by HL in both varieties; and Group 3 contained three genes highly expressed in XY54. Notably, abscisic acid (ABA), and jasmonic acid (JA) biosynthesis genes and their content were significantly higher, while gibberellins (GA) content was lower in XY54 than J411. Together, these results suggest that the differential expression and content of GA, ABA, and JA play crucial roles in the contrasting responses of tolerant and sensitive wheat cultivars to leaf senescence induced by long-term HL. This study enhances our understanding of the mechanisms underlying HL tolerance in wheat and can guide the development of more resilient wheat varieties.

Comprehensive Investigation of Homology and Heterogeneity Between Aurantii Fructus and Aurantii Fructus Immaturus Using Chemometrics Combined with Network Pharmacology.

Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) are distinct herbs outlined by the Chinese Pharmacopoeia. They are sourced from the same plant but harvested at different times, resulting in differences in efficacy. It is important to avoid mixing them clinically and to distinguish between the two. Furthermore, dissimilar cultivation conditions may cause variability in the quality of herbs, so it is vital to differentiate drugs from dissimilar origins. In this study, two plants, AF and AFI from different provinces, were comparatively analyzed based on High Performance Liquid Chromatography (HPLC) fingerprints and classified using chemometric methods. The results indicate that the two medicines can be clearly distinguished. Also, AF and AFI grown in different locations can be distinguished. Ten chemical markers were screened, and their variations were determined, including eriocitrin, narirutin, naringin, meranzin hydrate, naringenin, hesperidin, nobiletin, tangeretin, neohesperidin, and poncirin. Subsequent network pharmacology correlated the screened chemical components with the biological network of the organism. The material basis of the difference in efficacy of the two homologous herbs was explored from the perspective of changes in chemical composition. This study provides a reference for formulating quality evaluation standards for AF and AFI and lays a foundation for the efficacy-related quality research of the two.

Synthesis and Characterization of a Novel Chitosan-Based Nanoparticle-Hydrogel Composite System Promising for Skin Wound Drug Delivery.

As a natural preservative, nisin is widely used in the food industry, while its application in biomedicine is limited due to its susceptibility to interference from external conditions. In this study, a nanoparticle-hydrogel composite system was designed to encapsulate and release nisin. Nisin nanoparticles were identified with a smooth, spherical visual morphology, particle size of 122.72 ± 4.88 nm, polydispersity coefficient of 0.473 ± 0.063, and zeta potential of 23.89 ± 0.37 mV. Based on the sample state and critical properties, three temperature-sensitive hydrogels based on chitosan were ultimately chosen with a rapid gelation time of 112 s, outstanding reticular structure, and optimal swelling ratio of 239.05 ± 7.15%. The composite system exhibited the same antibacterial properties as nisin, demonstrated by the composite system's inhibition zone diameter of 17.06 ± 0.83 mm, compared to 20.20 ± 0.58 mm for nisin, which was attributed to the prolonged release effect of the hydrogel at the appropriate temperature. The composite system also demonstrated good biocompatibility and safety, making it suitable for application as short-term wound dressings in biomedicine due to its low hemolysis rate of less than 2%. In summary, our nanoparticle-based hydrogel composite system offers a novel application form of nisin while ensuring its stability, thereby deepening and broadening the employment of nisin.

The feasibility of establishing a hamster model for HBV infection: in vitro evidence.

Chronic hepatitis B virus (HBV) infection remains a significant public health burden with no cure currently available. The research to cure HBV has long been hampered by the lack of immunocompetent small animal models capable of supporting HBV infection. Here, we set out to explore the feasibility of the golden Syrian hamster as an immunocompetent small rodent model for HBV infection. We first started with in vitro assessments of the HBV replication cycle in primary hamster hepatocytes (PHaHs) by adenoviral HBV (Ad-HBV) transduction. Our results demonstrated that PHaHs support HBV reverse transcription and subsequent cccDNA formation via the intracellular recycling pathway. Next, with luciferase reporter assays, we confirmed that PHaHs support the activities of all HBV major promoters. Then, we transduced PHaHs with an adenoviral vector expressing HBV receptor human Na+/taurocholate cotransporting polypeptide NTCP (Ad-huNTCP), followed by HBV inoculation. While the untransduced PHaHs did not support HBV infection, Ad-huNTCP-transduced PHaHs supported de novo cccDNA formation, viral mRNA transcription, and expression of viral antigens. We then humanized the amino acid (aa) residues of hamster NTCP (haNTCP) critical for HBV entry, aa84-87 and aa157-165, and transfected HepG2 cells with constructs expressing wild-type haNTCP and humanized-haNTCP, H84R/P87N and H84R/P87N/G157K/M160V/M165L, respectively, followed by HBV inoculation. The results showed that the humanization of H84R/P87N alone was sufficient to support HBV infection at a level comparable to that supported by huNTCP. Taken together, the above in vitro evidence supports the future direction of humanizing haNTCP for HBV infection in vivo.IMPORTANCEOne of the biggest challenges in developing an HBV cure is the lack of immunocompetent animal models susceptible to HBV infection. Developing such models in mice has been unsuccessful due to the absence of a functional HBV receptor, human NTCP (huNTCP), and the defect in supporting viral cccDNA formation. In search of alternative models, we report herein multiple lines of in vitro evidence for developing a golden Syrian hamster model for HBV infection. We demonstrate that the primary hamster hepatocytes (PHaHs) support HBV replication, transcription, and cccDNA formation, and PHaHs are susceptible to de novo HBV infection in the presence of huNTCP. Furthermore, expressing hamster NTCP with two humanized residues critical for HBV entry renders HepG2 cells permissive to HBV infection. Thus, our work lays a solid foundation for establishing a gene-edited hamster model that expresses humanized NTCP for HBV infection in vivo.