[Research progress in genetics of noise-induced hearing loss].

Noise-induced hearing loss（NIHL） is an acquired sensorineural hearing loss induced by long-term noise exposure. The susceptibility of exposed people may vary even in the same noise environment. With the development of sequencing techniques, genes related to oxidative stress, immunoinflammatory, ion homeostasis, energy metabolism, DNA damage repair and other mechanisms in NIHL have been reported continuously. And some genes may interact with noise exposure indexes. In this article, population studies on NIHL-related gene polymorphisms and gene-environment interactions in the past 20 years are reviewed, aimed to providing evidence for the construction of NIHL-related risk prediction models and the formulation of individualized interventions.

WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

Experimental validation and comprehensive analysis of m6A methylation regulators in intervertebral disc degeneration subpopulation classification.

Intervertebral disc degeneration (IVDD) is one of the most prevalent causes of chronic low back pain. The role of m6A methylation modification in disc degeneration (IVDD) remains unclear. We investigated immune-related m6A methylation regulators as IVDD biomarkers through comprehensive analysis and experimental validation of m6A methylation regulators in disc degeneration. The training dataset was downloaded from the GEO database and analysed for differentially expressed m6A methylation regulators and immunological features, the differentially regulators were subsequently validated by a rat IVDD model and RT-qPCR. Further screening of key m6A methylation regulators based on machine learning and LASSO regression analysis. Thereafter, a predictive model based on key m6A methylation regulators was constructed for training sets, which was validated by validation set. IVDD patients were then clustered based on the expression of key m6A regulators, and the expression of key m6A regulators and immune infiltrates between clusters was investigated to determine immune markers in IVDD. Finally, we investigated the potential role of the immune marker in IVDD through enrichment analysis, protein-to-protein network analysis, and molecular prediction. By analysising of the training set, we revealed significant differences in gene expression of five methylation regulators including RBM15, YTHDC1, YTHDF3, HNRNPA2B1 and ALKBH5, while finding characteristic immune infiltration of differentially expressed genes, the result was validated by PCR. We then screen the differential m6A regulators in the training set and identified RBM15 and YTHDC1 as key m6A regulators. We then used RBM15 and YTHDC1 to construct a predictive model for IVDD and successfully validated it in the training set. Next, we clustered IVDD patients based on the expression of RBM15 and YTHDC1 and explored the immune infiltration characteristics between clusters as well as the expression of RBM15 and YTHDC1 in the clusters. YTHDC1 was finally identified as an immune biomarker for IVDD. We finally found that YTHDC1 may influence the immune microenvironment of IVDD through ABL1 and TXK. In summary, our results suggest that YTHDC1 is a potential biomarker for the development of IVDD and may provide new insights for the precise prevention and treatment of IVDD.

New findings on CD16brightCD62Ldim neutrophil subtypes in sepsis-associated ARDS: an observational clinical study.

Background: The CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS. Methods: We prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients' peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection. Results: Of the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days. Conclusion: We identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.

An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking.

Background: Identifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. Methods: Surface EEG signals and real-time Ca2+ activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. Results: An EEG waveform derivative - a modified theta-to-delta ratio (EEG Ratio) - accurately tracks real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions. Conclusions: The identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.

The global burden of ischemic heart disease attributed to high fasting plasma glucose: Data from 1990 to 2019.

Background: Ischemic heart disease (IHD) is the leading cause of death worldwide. High fasting plasma glucose (FPG) is an increasing risk factor for IHD. We aimed to explore the long-term trends of high FPG-attributed IHD mortality during 1990-2019. Methods: Data were obtained from the Global Burden of Disease Study 2019 database. Deaths, disability-adjusted life-years (DALYs), the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) of IHD attributable to high FPG were estimated by sex, socio-demographic index (SDI), regions and age. Estimated annual percentage changes (EAPCs) were calculated to assess the trends of ASMR and ASDR of IHD attributable to high FPG. Results: IHD attributable to high FPG deaths increased from 1.04 million (0.62-1.63) in 1990 to 2.35 million (1.4-3.7) in 2019, and the corresponding DALYs rose from 19.82 million (12.68-29.4) to 43.3 million (27.8-64.2). In 2019, ASMR and ASDR of IHD burden attributable to high FPG were 30.45 (17.09-49.03) and 534.8 (340.7-792.2), respectively. The highest ASMR and ASDR of IHD attributable to high FPG occurred in low-middle SDI quintiles, with 39.28 (22.40-62.76) and 742.3 (461.5-1117.5), respectively, followed by low SDI quintiles and middle SDI quintiles. Males had higher ASMR and ASDR compared to females across the past 30 years. In addition, ASRs of DALYs and deaths were highest in those over 95 years old. Conclusion: High FPG-attributed IHD mortality and DALYs have increased dramatically and globally, particularly in low, low-middle SDI quintiles and among the elderly. High FPG remains a great concern on the global burden of IHD and effective prevention and interventions are urgently needed to curb the ranking IHD burden, especially in lower SDI regions.

Clinical Significance of HMGB1 and Autophagy-Related Genes in Sinonasal Inverted Papilloma.

OBJECTIVES: Sinonasal inverted papilloma (SNIP) is a noncancerous tumor that develops in the mucous membrane of the nasal sinuses. Many malignancies are tightly linked to autophagy, an intracellular self-degradation mechanism. HMGB1 has demonstrated its ability to modulate autophagy in many pathological conditions. This work investigates how HMGB1 and other genes involved in autophagy contribute to SNIP. MATERIAL AND METHODS: The study included 45 patients with SNIP and a control group consisting of 28 individuals. In each group, qPCR was employed to examine the mRNA expression levels of genes correlated with autophagy and HMGB1. HMGB1 and genes associated with autophagy were examined for protein expression levels via Western Blot and immunohistochemical staining assays. At the same time, the association between HMGB1 and genes involved in autophagy was discovered through correlation analysis. Furthermore, Krouse staging was utilized for investigating the expression levels of HMGB1 and other autophagy-related genes at various stages in clinically staged SNIP patients. RESULTS: LC3B, ATG5, and Beclin1 autophagy-related genes and HMGB1 were substantially expressed in SNIP. Additionally, there was a positive correlation between HMGB1 and these genes. During various phases of SNIP, the levels of HMGB1 expression and autophagy-related genes were notably elevated at stage T4 compared with stage T2. CONCLUSION: Clinical staging in SNIP is correlated with HMGB1 expression in conjunction with autophagy-related genes LC3B, ATG5, and Beclin1, suggesting the possibility of novel prognostic indicators. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Designing a conjugate vaccine targeting Klebsiella pneumoniae ST258 and ST11.

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant. The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

Activation of CaMKII/HDAC4 by SDF1 contributes to pulmonary arterial hypertension via stabilization Runx2.

Stromal derived factor 1 (SDF1) has been shown to be involved in the pathogenesis of pulmonary artery hypertension (PAH). However, the detailed molecular mechanisms remain unclear. To address this, we utilized primary cultured rat pulmonary artery smooth muscle cells (PASMCs) and monocrotaline (MCT)-induced PAH rat models to investigate the mechanisms of SDF1 driving PASMCs proliferation and pulmonary arterial remodeling. SDF1 increased runt-related transcription factor 2 (Runx2) acetylation by Calmodulin (CaM)-dependent protein kinase II (CaMKII)-dependent HDAC4 cytoplasmic translocation, elevation of Runx2 acetylation conferred its resistance to proteasome-mediated degradation. The accumulation of Runx2 further upregulated osteopontin (OPN) expression, finally leading to PASMCs proliferation. Blocking SDF1, suppression of CaMKII, inhibition the nuclear export of HDAC4 or silencing Runx2 attenuated pulmonary arterial remodeling and prevented PAH development in MCT-induced PAH rat models. Our study provides novel sights for SDF1 induction of PASMCs proliferation and suggests that targeting SDF1/CaMKII/HDAC4/Runx2 axis has potential value in the management of PAH.

Low expression of miR-182 caused by DNA hypermethylation accelerates acute lymphocyte leukemia development by targeting PBX3 and BCL2: miR-182 promoter methylation is a predictive marker for hypomethylation agents + BCL2 inhibitor venetoclax.

BACKGROUND: miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. METHODS: To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro. RESULTS: miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation. CONCLUSIONS: Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.

Structural insights into the Clp protein degradation machinery.

The Clp protease system is important for maintaining proteostasis in bacteria. It consists of ClpP serine proteases and an AAA+ Clp-ATPase such as ClpC1. The hexameric ATPase ClpC1 utilizes the energy of ATP binding and hydrolysis to engage, unfold, and translocate substrates into the proteolytic chamber of homo- or hetero-tetradecameric ClpP for degradation. The assembly between the hetero-tetradecameric ClpP1P2 chamber and the Clp-ATPases containing tandem ATPase domains from the same species has not been studied in depth. Here, we present cryo-EM structures of the substrate-bound ClpC1:shClpP1P2 from Streptomyces hawaiiensis, and shClpP1P2 in complex with ADEP1, a natural compound produced by S. hawaiiensis and known to cause over-activation and dysregulation of the ClpP proteolytic core chamber. Our structures provide detailed information on the shClpP1-shClpP2, shClpP2-ClpC1, and ADEP1-shClpP1/P2 interactions, reveal conformational transition of ClpC1 during the substrate translocation, and capture a rotational ATP hydrolysis mechanism likely dominated by the D1 ATPase activity of chaperones.IMPORTANCEThe Clp-dependent proteolysis plays an important role in bacterial homeostasis and pathogenesis. The ClpP protease system is an effective drug target for antibacterial therapy. Streptomyces hawaiiensis can produce a class of potent acyldepsipeptide antibiotics such as ADEP1, which could affect the ClpP protease activity. Although S. hawaiiensis hosts one of the most intricate ClpP systems in nature, very little was known about its Clp protease mechanism and the impact of ADEP molecules on ClpP. The significance of our research is in dissecting the functional mechanism of the assembled Clp degradation machinery, as well as the interaction between ADEP1 and the ClpP proteolytic chamber, by solving high-resolution structures of the substrate-bound Clp system in S. hawaiiensis. The findings shed light on our understanding of the Clp-dependent proteolysis in bacteria, which will enhance the development of antimicrobial drugs targeting the Clp protease system, and help fighting against bacterial multidrug resistance.

Clinical and genetic architecture of a large cohort with auditory neuropathy.

Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.

Intraventricular or intrathecal polymyxin B for treatment of post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria: a 8-year retrospective study.

PURPOSE: Post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a life-threatening complication. This study aimed to assess the current practices and clinical outcomes of intravenous (IV) combined with intraventricular (IVT)/intrathecal (ITH) polymyxin B in treating CRGNB intracranial infection. METHODS: A retrospective study was conducted on patients with post-neurosurgical intracranial infection due to CRGNB from January 2013 to December 2020. Clinical characteristics and treatment outcomes were collected and described. Kaplan-Meier survival and multivariate logistic regression analyses were performed. RESULTS: The study included 114 patients, of which 72 received systemic antimicrobial therapy combined with IVT/ITH polymyxin B, and 42 received IV administration alone. Most infections were caused by carbapenem-resistant Acinetobacter baumannii (CRAB, 63.2%), followed by carbapenem-resistant Klebsiella pneumoniae (CRKP, 31.6%). Compared with the IV group, the IVT/ITH group had a higher cerebrospinal fluid (CSF) sterilization rate in 7 days (p < 0.001) and lower 30-day mortality (p = 0.032). In the IVT/ITH group, patients with CRKP infection had a higher initial fever (p = 0.014), higher incidence of bloodstream infection (p = 0.040), lower CSF sterilization in 7 days (p < 0.001), and higher 30-day mortality (p = 0.005) than those with CRAB infection. Multivariate logistic regression analysis revealed that the duration of IVT/ITH polymyxin B (p = 0.021) was independently associated with 30-day mortality. CONCLUSIONS: Intravenous combined with IVT/ITH polymyxin B increased CSF microbiological eradication and improved clinical outcomes. CRKP intracranial infections may lead to more difficult treatment and thus warrant attention and further optimized treatment.

Validation of a new assessment of hostile attribution bias in romantic relationships: The Hostile Attributions in Romantic Relationships Test.

While hostile attributional bias (a tendency to interpret others' behaviors as intentionally hostile) is associated with negative outcomes in romantic relationships, no measure has been developed specifically for this context. Here, we describe the development and validation of a self-report questionnaire across three studies, named Hostile Attribution in Romantic Relationships Test. Study 1 introduces the development and preliminary validation (N = 152). Study 2 tests the validity and test-retest stability of the modified version revised based on findings in Study 1 (N = 151). Study 3 reports the translation and validation of a Chinese version (N = 630). The final 9-vignette scale is the first to specifically measure hostile attribution bias in romantic relationships, with good internal reliability, test-retest stability, and convergent validity. Factor analysis reveals a three-factor structure reflecting direct hostile attribution, indirect hostile attribution, and benign attribution to partners' behaviors. Implications regarding couple dynamics and clinical therapeutic interventions are discussed.

Phytoplasma: A plant pathogen that cannot be ignored in agricultural production-Research progress and outlook.

Phytoplasmas are phloem-restricted plant-pathogenic bacteria transmitted by insects. They cause diseases in a wide range of host plants, resulting in significant economic and ecological losses worldwide. Research on phytoplasmas has a long history, with significant progress being made in the past 30 years. Notably, with the rapid development of phytoplasma research, scientists have identified the primary agents involved in phytoplasma transmission, established classification and detection systems for phytoplasmas, and 243 genomes have been sequenced and assembled completely or to draft quality. Multiple possible phytoplasma effectors have been investigated, elucidating the molecular mechanisms by which phytoplasmas manipulate their hosts. This review summarizes recent advances in phytoplasma research, including identification techniques, host range studies, whole- or draft-genome sequencing, effector pathogenesis and disease control methods. Additionally, future research directions in the field of phytoplasma research are discussed.

Identification of Pyroptosis-Related Genes Regulating the Progression of Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an immunologic disease, and pyroptosis, an inflammation-based cellular death, strictly modulates CRSwNP pathology, whereas the pyroptosis genes and mechanisms involved in CRSwNP remain unclear. Herein, we explored disease biomarkers and potential therapeutic targets for pyroptosis and immune regulation in CRSwNP using bioinformatics analysis and tissue-based verification. METHODS: We retrieved the transcriptional profiles of the high-throughput dataset GSE136825 from the Gene Expression Omnibus database, as well as 170 pyroptosis-related gene expressions from GeneCards. Using R, we identified differentially expressed pyroptosis-related genes and examined the potential biological functions of the aforementioned genes using Gene Ontology, Kyoto Encyclopedia of the Genome pathway, immune infiltration, and protein-protein interaction (PPI) network analyses, thereby generating a list of hub genes. The hub genes were, in turn, verified using real-time quantitative polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB). Ultimately, using the StarBase and miRTarBase databases, we estimated the targeting microRNAs and long chain non-coding RNAs. RESULTS: We demonstrated that the identified pyroptosis-related genes primarily modulated bacterial defense activities, as well as inflammasome immune response and assembly. Moreover, they were intricately linked to neutrophil and macrophage infiltration. Furthermore, we validated the tissue contents of hub genes AIM2, NLPR6, and CASP5 and examined potential associations with clinical variables. We also developed a competitive endogenous RNA (ceRNA) modulatory axis to examine possible underlying molecular mechanisms. CONCLUSION: We found AIM2, CASP5, and NLRP6, three hub genes for pyroptosis in chronic rhinosinusitis with nasal polyps, by biological analysis, experimental validation, and clinical variable validation.

Reduced Proliferative Capacity and Defense against Staphylococcus aureus in Human Nasal Mucosal Epithelium Lacking ZNF365.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nose characterized by barrier disruption and environmental susceptibility, and the deletion of ZNF365 may be a factor inducing these manifestations. However, there is no study on the mechanism of action between CRSwNP and ZNF365. Therefore, this study focuses on the effect of the zinc finger protein ZNF365 on the proliferation of nasal mucosal epithelial cells and their defense against Staphylococcus aureus (S. aureus). METHODS: Immunohistochemistry and Western blot were applied to verify the changes of ZNF365 expression in nasal polyp tissues and control tissues, as well as in primary epithelial cells. ZNF365 was knocked down in human nasal mucosa epithelial cell line (HNEpc), and the proliferation, migration, and transdifferentiation of epithelium were observed by immunofluorescence, QPCR, CCK8, and cell scratch assay. The changes of mesenchymal markers and TLR4-MAPK-NF-κB pathway were also observed after the addition of S. aureus. RESULTS: ZNF365 expression was reduced in NP tissues and primary nasal mucosal epithelial cells compared to controls. Knockdown of ZNF365 in HNEpc resulted in decreased proliferation and migration ability of epithelial cells and abnormal epithelial differentiation (decreased expression of tight junction proteins). S. aureus stimulation further inhibited epithelial cell proliferation and migration, while elevated markers of epithelial-mesenchymal transition and inflammatory responses occurred. CONCLUSION: ZNF365 is instrumental in maintaining the proliferative capacity of nasal mucosal epithelial cells and defending against the invasion of S. aureus. The findings suggest that ZNF365 may participate in the development of CRSwNP.

Heat Shock Protein 22 Attenuates Nerve Injury-induced Neuropathic Pain Via Improving Mitochondrial Biogenesis and Reducing Oxidative Stress Mediated By Spinal AMPK/PGC-1α Pathway in Male Rats.

Heat shock protein 22 (hsp22) plays a significant role in mitochondrial biogenesis and redox balance. Moreover, it's well accepted that the impairment of mitochondrial biogenesis and redox imbalance contributes to the progress of neuropathic pain. However, there is no available evidence indicating that hsp22 can ameliorate mechanical allodynia and thermal hyperalgesia, sustain mitochondrial biogenesis and redox balance in rats with neuropathic pain. In this study, pain behavioral test, western blotting, immunofluorescence staining, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Dihydroethidium staining are applied to confirm the role of hsp22 in a male rat model of spared nerve injury (SNI). Our results indicate that hsp22 was significantly decreased in spinal neurons post SNI. Moreover, it was found that intrathecal injection (i.t.) with recombinant heat shock protein 22 protein (rhsp22) ameliorated mechanical allodynia and thermal hyperalgesia, facilitated nuclear respiratory factor 1 (NRF1)/ mitochondrial transcription factor A (TFAM)-dependent mitochondrial biogenesis, decreased the level of reactive oxygen species (ROS), and suppressed oxidative stress via activation of spinal adenosine 5'monophosphate-activated protein kinase (AMPK)/ peroxisome proliferative activated receptor γ coactivator 1α (PGC-1α) pathway in male rats with SNI. Furthermore, it was also demonstrated that AMPK antagonist (compound C, CC) or PGC-1α siRNA reversed the improved mechanical allodynia and thermal hyperalgesia, mitochondrial biogenesis, oxidative stress, and the decreased ROS induced by rhsp22 in male rats with SNI. These results revealed that hsp22 alleviated mechanical allodynia and thermal hyperalgesia, improved the impairment of NRF1/TFAM-dependent mitochondrial biogenesis, down-regulated the level of ROS, and mitigated oxidative stress through stimulating the spinal AMPK/PGC-1α pathway in male rats with SNI.

Polysaccharide peptide treatment eliminates strawberry viruses and promotes strawberry plant growth and rooting in tissue culture media.

Based on our previous finding that polysaccharide peptide (PSP) has substantial antiviral activity, we cultured strawberry plants infected with strawberry mild yellow edge virus (SMYEV) or strawberry vein banding virus (SVBV) in Murashige and Skoog (MS) media supplemented with PSP to test its ability to eliminate these viruses. PSP not only improved the elimination of SMYEV and SVBV but also promoted the growth and rooting of strawberry plants in tissue culture. On the 45th day, the average height of the 'Ningyu' strawberry plants in the 1 mg/mL PSP treatment group was 1.91 cm, whereas that of the plants in the control group was 1.51 cm. After the same time point, the number of new leaves on the tissue culture media supplemented with 1 mg/mL and 500 µg/mL PSP and without PSP were 4.92, 4.41, and 3.53, respectively. PSP also promoted strawberry rooting and significantly increased both the length and number of roots. In addition, after treatment with 1 mg/mL PSP treatment in tissue culture for 45 days followed by meristem-shoot-tip culture, the elimination rates of SMYEV and SVBV in regenerated 'Ningyu' strawberry plants ranged from 60% to 100%. This study investigated the use of the antiviral agent PSP for virus elimination. PSP has a low production cost and thus has great application potential for virus elimination in crop plants.