Construction of BSA-ZnO&Quercetin based multifunctional bionic self-assembly system and their antibacterial mechanism study.

The misuse of antibiotics has led to the growing problem of multidrug-resistant (MDR) bacteria, and there is still a lack of effective antibacterial agents that can replace antibiotics. Therefore, the design and development of multifunctional nanomaterials with long-term inhibitory effects on drug-resistant bacteria are extremely challenging. In this study, a multifunctional biomimetic self-assembly system, BSA-ZnO&Quercetin, based on bovine serum albumin (BSA), ZnO, and quercetin, was established using a simple and controllable method. The prepared self-assembly system has high stability and biocompatibility, and could fully combine the performance advantages of each component. BSA-ZnO&Quercetin showed excellent broad-spectrum antibacterial activity without inducing bacterial resistance. The related antibacterial mechanism of BSA-ZnO&Quercetin primarily involves biofilm inhibition and destruction, and inducing the production of reactive oxygen species, resulting in the death of the bacteria. The biomimetic self-assembly system BSA-ZnO&Quercetin constructed in this research is expected to replace antibiotics for antibacterial application.

Hydroxamate Siderophores Intensify the Co-Deposition of Cadmium and Silicon as Phytolith-Like Particulates in Rice Stem Nodes: A Natural Strategy to Mitigate Grain Cadmium Accumulation.

Sequestration of cadmium (Cd) in rice phytolith can effectively restrict its migration to the grains, but how hydroxamate siderophore (HDS) affects phytolith formation within rice plants especially the fate of Cd and silicon (Si) remains poorly understood. Here, we found that the addition of HDS increased the content of dissolved Si and Cd in soil pore water as well as its absorption by the rice roots during the reproductive growth stage. HDS effectively trapped orthosilicic acid and Cd ions at the third stem nodes of rice plants via hydrogen bonds and chelation interactions, which then rapidly deposited on the xylem cell wall through hydrophobic interactions. Ultimately, Cd was immobilized as phytolith-like particulates in the form of CdSiO3. Field experiments verified that Cd accumulation was significantly reduced by 46.4% in rice grains but increased by 41.2% in rice stems after HDS addition. Overall, this study advances our understanding of microbial metabolites enhancing the instinctive physiological barriers within rice plants.

Unraveling the secrets: Evolution of resistance mediated by membrane proteins.

Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand, animals, bacteria, fungi, plants, and insects exhibit convergent evolution, leading to the development of similar resistance mechanisms. On the other hand, influenced by diverse environmental pressures and structural differences among organisms, they also demonstrate divergent resistance characteristics. Membrane protein-mediated resistance mechanisms are prevalent across animals, bacteria, fungi, plants, and insects, reflecting their shared survival strategies evolved through convergent evolution to address similar survival challenges. However, variations in ecological environments and biological characteristics result in differing responses to resistance. Therefore, examining these differences not only enhances our understanding of adaptive resistance mechanisms but also provides crucial theoretical support and insights for addressing drug resistance and advancing pharmaceutical development.

DNA-stable isotope probing and metagenomics reveal Fe(II) oxidation by core microflora in microoxic rhizospheric habitats to mitigate the accumulation of cadmium and phenanthrene in rice.

Rice rhizosphere soil-porewater microdomains exist within an iron (Fe)-rich microoxic habitat during paddy soil flooding. However, the response mechanisms of core microflora in this habitat to Fe(II)-oxidation-mediated cadmium (Cd) and phenanthrene (Phen) remain unclear. Using gel-stabilized gradient systems to replicate the microoxic conditions in the rice rhizosphere porewater, we found that microaerophilic rhizobacteria drove Fe(II) oxidation to yield iron oxides, thereby reducing the Cd and Phen contents in the rhizosphere porewater and rice (Cd and Phen decreased by 15.9%-78.0% and 10.1%-37.4%, respectively). However, co-exposure to Cd and Phen resulted in a greater reduction in the Cd uptake and a greater increase in the Phen uptake in rice as compared to those in the Cd or Phen treatments, possibly attributing to the cation-π interactions between Cd and Phen, as well as competition between the adsorption sites on the roots. The elevation of Cd-tolerant genes and Phen-degradation genes in biogenic cell-mineral aggregates unveiled the survival strategies of rhizobacteria with respect to Cd and Phen in the microoxic habitat. Potential Cd-tolerant rhizobacteria (e.g., Pandoraea and Comamonas) and Phen-degradation rhizobacteria (e.g., Pseudoxanthobacter) were identified through the DNA-SIP and 16S rRNA gene amplicon sequencing. Metagenomic analysis further confirmed that these core microbes harbor Cd-tolerant, Phen-degradation, and Fe(II) oxidation genes, supporting their metabolic potential for Cd and/or Phen in the microoxic habitat of the rice rhizosphere. These findings suggest the potential mechanism and ecological significance of core rhizospheric microbial-driven Fe(II) oxidation in mitigating the bioavailability of Cd and Phen in paddy soil during flooding.

Stabilization of dimeric PYR/PYL/RCAR family members relieves abscisic acid-induced inhibition of seed germination.

Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Discovering common pathogenetic processes between periodontitis and Alzheimer's disease by bioinformatics and system biology approach.

BACKGROUND: There is increasing evidence that inflammation plays a key role in the pathophysiology of periodontitis (PT) and Alzheimer's disease (AD), but the roles of inflammation in linking PT and AD are not clear. Our aim is to analyze the potential molecular mechanisms between these two diseases using bioinformatics and systems biology approaches. METHODS: To elucidate the link between PT and AD, we selected shared genes (SGs) with gene-disease-association scores of ≥ 0.1 from the Disease Gene Network (DisGeNET) database, followed by extracting the hub genes. Based on these genes, we constructed gene ontology (GO) enrichment analysis, pathway enrichment analysis, protein-protein interaction (PPI) networks, transcription factors (TFs)-gene networks, microRNAs (miRNAs)-gene regulatory networks, and gene-disease association analyses. Finally, the Drug Signatures database (DSigDB) was utilized to predict candidate molecular drugs related to hub genes. RESULTS: A total of 21 common SGs between PT and AD were obtained. Cell cytokine activity, inflammatory response, and extracellular membrane were the most important enriched items in GO analysis. Interleukin-10 Signaling, LTF Danger Signal Response Pathway, and RAGE Pathway were identified as important shared pathways. IL6, IL10, IL1B, TNF, IFNG, CXCL8, CCL2, MMP9, TLR4 were identified as hub genes. Both shared pathways and hub genes are closely related to endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Importantly, glutathione, simvastatin, and dexamethasone were identified as important candidate drugs for the treatment of PT and AD. CONCLUSIONS: There is a close link between PT and AD pathogenesis, which may involve in the inflammation, ER and mitochondrial function.

Interaction between polycyclic aromatic hydrocarbons and thymine (T)-base induces double-strand DNA distortion in different species.

Polycyclic aromatic hydrocarbons (PAHs) are potent inhibitors of DNA that can induce genetic damage, abnormal gene expression, and metabolic disorders upon interfacing with biological macromolecules. However, the mechanism of their interactions with DNA remains elusive. Therefore, this study selected three representative PAHs, including phenanthrene (Phen), pyrene (Pyre), and benzo[a]pyrene (B[a]P), and explored their binding mechanisms with the double-strand DNA (dsDNA) from different species, including 1J1V (Escherichia coli), 6J5B (Arabidopsis thaliana), and 6Q1V (Homo sapiens). The results revealed that binding between PAHs and dsDNA occurred in the groove via van der Waals forces and π-π stacking, with the carboxyl oxygen atom of the thymine (T)-base within dsDNA being the key binding site. This result was further confirmed by the spectroscopic experiments, where significant changes in the peak of the T-base were observed after PAHs-dsDNA binding. More interestingly, the total binding energies of Pyre with the three dsDNA were -138.800 kJ/mol (Pyre-1J1V), -105.523 kJ/mol (Pyre-6J5B), and -127.567 kJ/mol (Pyre-6Q1V), respectively, all of which were higher than those of Phen and B[a]P. This suggests that that Pyre has the strongest dsDNA binding ability. Additionally, analysis of the thermodynamic parameters indicated that the interactions between the three PAHs and dsDNA were exothermic reactions. In contrast, the Pyre-dsDNA interaction predominantly involved van der Waals forces and hydrogen bonding due to the enthalpy change (∆H) < 0 and entropy change (∆S) < 0, while the Phen-dsDNA and B[a]P-dsDNA interactions predominantly involved hydrophobic forces due to ∆H > 0 and ∆S > 0. Furthermore, Pyre caused local distortion of dsDNA, which was more pronounced under atomic force microscopy (AFM). In summary, this study has unveiled a new phenomenon of binding between PAHs and dsDNA. This sheds light on the carcinogenic potential and environmental impacts of PAHs pollution.

Bibliometric Analysis of Forensic Human Remains Identification Literature from 1991 to 2022.

OBJECTIVES: To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification research. METHODS: The data retrieved and extracted from the Web of Science Core Collection (WoSCC), the core database of the Web of Science information service platform (hereinafter referred to as "WoS"), was used to analyze the trends and topic changes in research on forensic identification of human remains from 1991 to 2022. Network visualisation of publication trends, countries (regions), institutions, authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10. RESULTS: A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained. The journal with the largest number of publications was Forensic Science International (164 articles). The country (region) with the largest number of published papers was China (90 articles). Katholieke Univ Leuven (Netherlands, 21 articles) was the institution with the largest number of publications. Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation, and the most commonly studied remains were teeth. CONCLUSIONS: The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing. However, the scope of both international and domestic collaborations remains limited. Traditionally, human remains identification has primarily relied on key areas such as the pelvis, skull, and teeth. Looking ahead, future research will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.

[Genetic diversity of SP1 population of space mutagenized Pueraria montana].

To explore the mutagenic effect of the space environment on Pueraria montana and select the elite germplasm with good growth conditions and high isoflavone content, this study observed the agronomic traits, determined the flower isoflavone content, and labeled amplified fragment length polymorphism(AFLP) fluorescent molecular markers of 79 P. montana plants exposed to space mutagenesis(SP1 group) and 10 control plants of P. montana(CK group). Excel 2019, SPSS 25.0, NTSYSpc-2.11F, and Popgen 32 were employed to analyze the genetic diversity and perform the cluster analysis. The results showed that the SP1 group presented changed leaf hairy attitude and flower structure and higher CV and H' of quantitative traits than the CK group. The cluster analysis screened out five plants in the SP1 group. Ten P. montana plants in the SP1 group had higher content of 6″-O-xylosyl-tectoridin and tectoridin in the flowers than the control group, with the total content of both exceeding 11%. After clustering, 9 plants in the SP1 group were separated. Nine pairs of polymorphic primers were screened out frrom 64 pairs of primers. A total of 1 620 polymorphic loci were detected, with the average percentage of polymorphic loci(PPL) of 83.33%. The average Nei's gene diversity index(H) and Shannon's information index(I) were 0.192 2 and 0.305 2, respectively. After clustering, 4 plants in the SP1 group were screened out. According to the above results, plants No. 30, No. 66, and No. 89 in the SP1 group were subjected to greater mutagenic effect by the space environment and presented better growth and higher flower isoflavone content. Moreover, plant No. 30 showed the flower structure variation and flower weight two times of that in the CK group. These plants can be used as key materials for the subsequent experiments.

The effects of ACSM-based exercise on breast cancer-related lymphoedema: a systematic review and meta-analysis.

Background: Breast cancer-related lymphedema (BCRL) frequently occurs after axillary lymph node dissection and remains incurable even with lymphaticovenular anastomosis. Exercise interventions have emerged as a potential non-pharmacological management approach. However, standardized exercise recommendations tailored to BCRL patients are lacking. Purpose: This study evaluated the impact of high and low compliance exercise interventions, aligned with ACSM recommendations, on quality of life (QOL), shoulder range of motion (ROM), and arm volume in BCRL patients. It further aimed to determine the optimal exercise dosage, assessed via the FITT (frequency, intensity, time, type) principle, that maximizes health benefits for BCRL patients. Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, we conducted a comprehensive literature search in various databases, including PubMed, Embase, Cochrane Library, and Web of Science, encompassing the period from the inception of these databases to December 2023. We extracted data on exercise form, frequency, intensity, duration, repetitions, and sets from the identified studies. Subsequently, a meta-analysis and review were conducted. The exercise interventions were evaluated based on ACSM recommendations and categorized as either high or low compliance with ACSM standards. Fixed or random effects models were employed to compare outcomes across study subgroups with comparable results. Additionally, funnel plot analyses, sensitivity analyses, and Egger's and Begg's tests were conducted to evaluate the potential for bias. Results: 15 studies encompassing 863 patients with BCRL were analyzed. Eleven studies exhibited high ACSM compliance, while four demonstrated low ACSM compliance. Regarding QOL, the overall standard mean difference (SMD) was 0.13 (95% CI: -1.07, 1.33). Specifically, the SMD for the high-adherence subgroup was 0.91 (95% CI: 0.33, 1.49; p = 0.002). For ROM, the overall SMD was 1.21 (95% CI: -0.19, 2.61). For arm volume, the overall SMD was -0.06 (95% CI: -0.22, 0.10). QOL results differed significantly in the high-adherence subgroup, whereas no significant effect on ROM or arm volume was observed. Conclusion: The study revealed significant QOL improvements in patients with high ACSM compliance, contrasted with those with low compliance. Conversely, no notable changes in ROM or arm volume were observed. Notably, the high adherence group tended to show better ROM during exercise and stable arm volume. Future research is needed to validate these findings.

[Quality evaluation and grading standard discussion on Cinnamomi Ramulus].

This study explored the relationship between the appearance traits and internal components of Cinnamomi Ramulus pieces, so as to provide a reference for the quality evaluation and the formulation of grade standards. This study determined the appearance traits and index component contents of 41 batches of Cinnamomi Ramulus pieces in the core producing areas of Guangxi and Guangdongand established the HPLC characteristic map method. The weight of the pieces, the narrowest diameter, and the widest diameter of the tr ansverse section were used as the indices of appearance traits. The content of index components(cinnamic acid and cinnamalde hyde)was determined by the established content determination method. The chromatographic characteristics were determinedon a Waters XBridge C_(18)(4. 6 mm×250 mm, 5 µm) column with a mobile phase consisting of 0. 1% phosphoric acidacetonitrile and gradient elution at the flow rate of 1 mL ·min~(-1). The column temperature was 30 ℃, and the detection wavelength was 254 nm. Cluster analysis, principal component analysis, and other stoichiometric methods were used to analyze the correlation between theap pearance traits and the index/characteristic components of Cinnamomi Ramulus pieces and compare the qu ality differences of the piecesfrom different batches and plac es. The results showed that the larger weight, the narrowest diameter, andthe widest diameter of the tra nsverse section indicated lowercontent of main indexes/characteristic components, and there was a synergistic decreasing trend amongd ifferent components. The overall quality of Cinnamomi Ramulus pieces in Guangdong Province and Guangxi Province was similar, but there were still differences between different origins and different batches of the same origin. It is scientific and feasible to evaluatethe quality of Cinnamomi Ramulus pieces and establish grading standards based on the appearance traits and index/character istic components. The research provides a more scientific and comprehensive basis for the quality control evaluation and standardformulation of Cinnamomi Ramulus.

Effectiveness of influenza vaccination on hospitalization outcomes among older patients with diabetes.

OBJECTIVE: In older populations admitted for diabetes, limited evidence suggests that influenza vaccination protects against hospitalization outcomes. METHODS: This study pooled 27,620 hospitalizations recorded for elderly diabetes patients from the Beijing Elderly Influenza Vaccination Information Registration Database (2013-2018) and the Beijing Urban Employee Basic Medical Insurance Database (2013-2018). Generalized linear regression and propensity score matching were conducted to estimate the effects of influenza vaccination on hospitalization outcomes (in-hospital all-cause mortality, readmission, length and costs of hospitalization), adjusting for measurable confounding factors. The low influenza period (May-July) was used as a reference period to adjust for unmeasured confounding factors during the peak influenza period (November-January). RESULTS: In propensity score matching, influenza vaccination in peak influenza period could reduce the risk of in-hospital death (OR: 0.47[0.22,0.97]) and readmission (OR: 0.70[0.60,0.81]), length of hospitalization (ß: -1.32[-1.47, -1.17]) and medical costs (GMR: 0.90[0.88,0.92]). After adjusting for unmeasured confounding factors, influenza vaccination was associated with 17% (ratio of ORs: 0.83 [0.69, 1.02]) lower risk of readmission and shorter length of hospitalization (difference in ß: -0.23 [-0.62, 0.16]). The subgroup analyses showed that male patients with older age and poorer health conditions could benefit more after influenza vaccination. CONCLUSION: Influenza vaccination could significantly improve hospitalization outcomes in elderly diabetic patients. This provides evidence supporting free influenza vaccination policies for vulnerable populations in low- and middle-income countries.

Altered Brain Glymphatic Function at Diffusion-Tensor MRI in Pre-cirrhotic Metabolic Dysfunction-Associated Fatty Liver Disease.

RATIONALE AND OBJECTIVES: To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. MATERIALS AND METHODS: A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. RESULTS: MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = -0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = -0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (-23.853 [-45.417, -2.289], P = 0.030) in MAFLD with MetS group. CONCLUSION: MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS.

Immune checkpoint inhibitors-induced diabetes mellitus (review).

Immune checkpoint inhibitors (ICIs) have become extensively utilized in the early-stage treatment of various cancers, offering additional therapeutic possibilities for patients with advanced cancer. However, certain patient populations are susceptible to experiencing toxic adverse effects from ICIs, such as thyrotoxicosis, rashes, among others. Specifically, ICIDM, induced by immune checkpoint inhibitors, exhibits characteristics similar to insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). ICIDM is characterized by a rapid onset and may coincide with severe ketoacidosis. Despite a favorable response to insulin therapy, patients typically require lifelong insulin dependence. After discussing the autoimmune adverse effects and the specifics of ICIs-induced diabetes mellitus (ICIDM), it is important to note that certain patient populations are particularly susceptible to experiencing toxic adverse effects from ICIs. Specifically, ICIDM, which is triggered by immune checkpoint inhibitors, mirrors the characteristics of insulin-dependent diabetes mellitus (Type 1 Diabetes Mellitus, T1DM). This article conducts an in-depth analysis of the literature to explore the pathogenesis, disease progression, and treatment strategies applicable to diabetes induced by immune checkpoint inhibitors (ICIDM).

The biological characteristics and infection dynamics of a novel H3N2 canine influenza virus genotype in beagles.

BACKGROUND: The canine influenza virus (CIV) outbreak has garnered considerable attention as it poses a significant threat to dog health. During the H3N2 CIV evolution in beagles, the virus formed a new clade after 2019 and gradually became more adaptable to other mammals. Therefore, successfully elucidating the biological characteristics and constructing a canine influenza infection model is required for CIV characterization. METHODS: We performed genetic analyses to examine the biological characteristics and infection dynamics of CIV. RESULTS: The genotype of our H3N2 CIV strain (from 2019 in Shanghai) belonged to the 5.1 clade, which is now prevalent in China. Using MDCK cells, we investigated viral cytopathic effects. Virus size and morphology were observed using transmission electron microscopy. Beagles were also infected with 104, 105, and 106 50% egg-infectious doses (EID50). When compared with the other groups, the 106 EID50 group showed the most obvious clinical symptoms, the highest virus titers, and typical lung pathological changes. Our results suggested that the other two treatments caused mild clinical manifestations and pathological changes. Subsequently, CIV distribution in the 106 EID50 group was detected by hematoxylin and eosin (H&E) and immunofluorescence (IF) staining, which indicated that CIV primarily infected the lungs. CONCLUSIONS: The framework established in this study will guide further CIV prevention strategies.

Paeonol and glycyrrhizic acid in combination ameliorate the recurrent nitroglycerin-induced migraine-like phenotype in rats by regulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine. AIM OF THE STUDY: This research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats. MATERIALS AND METHODS: Using a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques. RESULTS: Following treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1ß and TNF-α. CONCLUSIONS: Our findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

Application of capsaicin and calcium phosphate-loaded MOF system for tumor therapy involving calcium overload.

Calcium overload therapy refers to the condition of intracellular Ca2+ overload, which causes mitochondrial damage and leads to the uncontrolled release of apoptotic factors into the cytoplasm through the open mitochondrial permeability pore. Based on this, it is playing an increasingly important role in the field of oncology due to its good efficacy and small side effects. However, the regulation of calcium homeostasis by cancer cells themselves, insufficient calcium ions (Ca2+) in tumor sites and low efficiency of calcium entering tumor have limited its efficacy, resulting in unsatisfactory therapeutic effect. Therefore, a novel CAP/BSA@TCP-ZIF-8 nanoparticle drug carrier system was constructed that can provide Ca2+ from exogenous sources for pH-controlled degradation and drug release at the same time. Both in vivo and in vitro experiments have proved that the nanomaterial can activate TRPV1 channels and provide exogenous Ca2+ to cause Ca2+ overload and apoptosis, thus achieving anti-tumor effects.

New insights into how freeze-drying and cryo-milling affects the fine structure and digestibility of gelatinized starch.

Freeze-drying (FD) and cryo-milling (CM) are common methods for preparing powder gelatinized starch samples. This study investigates the structural characterization of raw/gelatinized maize starches and digestibility after FD/CM processes to elucidate their effect on starch digestibility determination. Results showed that FD slightly increased digestibility, while higher initial glucose content in CM samples, especially for gelatinized samples. Only FD retained the granular morphology and relative crystallinity (RC), while gelatinized-FD decreased RC by 75%. CM decreased RC by 12%, while gelatinized-CM decreased it by 97%. Combined with short-range and chain structural results, FD tended to disrupt internal connected chains through volume stress, while CM cleaved glycosidic bonds in external chain. Stretched chains in gelatinized starch promoted the breakage of chains during shearing and their efficient binding with digestive enzymes. These findings would provide a basis for pre-treatment of powder samples and processes of starch- rich foods.

H3N2 canine influenza virus-like particle vaccine with great protection in beagle dogs.

In 2016, a distinct branch of H3N2 canine influenza virus (CIV) emerged, which has mutations related to mammalian adaptation and has replaced previously prevalent strains. This branch poses a risk of zoonotic infection. To prevent and control H3N2 CIV, an H3N2 virus-like particle (VLP) vaccine based on the insect cell baculovirus expression system has been developed in the study. The H3N2 VLP vaccine induced high titers of hemagglutination inhibition (HI) antibodies in nasal and muscular immunized beagle dogs. Meanwhile, the VLP vaccine provided effective protection against homologous virus challenge comparable to inactivated H3N2 canine influenza virus. In addition, the intranasal H3N2 VLP vaccine induced significantly higher Th1, Th2, and Th17 immune responses, respectively (p,0.05). Importantly, intramuscular injection of VLP and inactivated H3N2 virus has complete protective effects against homologous H3N2 virus attacks. Nasal immunization with H3N2 VLP can partially protect beagles from H3N2 influenza. IMPORTANCE: A new antigenically and genetically distinct canine influenza virus (CIV) H3N2 clade possessing mutations associated with mammalian adaptation emerged in 2016 and substituted previously circulating strains. This clade poses a risk for zoonotic infection. In our study, intramuscular injection of the H3N2 virus-like particle (VLP) vaccine and inactivated H3N2 CIV confer completely sterilizing protection against homologous H3N2 canine influenza virus challenge. Our results provide further support for the possibility of developing VLP vaccines that can reliably induce immunity in animal species.