Can unstimulated whole salivary flow objectively classify salivary gland secretory function in Sjögren's syndrome?

INTRODUCTION: The aim of this study is to investigate whether the testing time for unstimulated whole salivary flow (UWSF) can be shortened to 5 min in patients with suspected Sjögren's syndrome (SjS); and which SjS patients can use UWSF to evaluate salivary gland (SG) secretory function. METHOD: A diagnostic cohort comprising suspected SjS patients was conducted to investigate the correlation between UWSF measurements taken at 10 min (UWSF_10 min) and those taken at 5 min (UWSF_5 min). A group of SjS patients was enrolled for a comparison between UWSF and stimulated whole salivary flow (SWSF). RESULTS: In 734 suspected SjS patients, there was a remarkably high concordance between UWSF_10 min and UWSF_5 min (ICC 0.970, P < 0.001; r 0.973, P < 0.001). Reducing the testing time for UWSF to 5 min resulted in a high PPV of 83.8% and an exceptionally high NPV of 98.7%. In 408 SjS patients, the cut-off values of UWSF_10 min were investigated to classify SG secretory function. Using a threshold of > 0.2 mL/min (36.8%, 150/408) instead of SWSF > 0.7 mL/min (indicating mild secretory hypofunction), the specificity and PPV were found to be 94.2% and 94.0%, respectively; and using a threshold of < 0.05 mL/min (16.9%, 69/408) instead of SWSF ≤ 0.7 mL/min (indicating moderate to severe secretory hypofunction), the specificity was remarkably high at 97.6%, accompanied by a high PPV of 91.3%. CONCLUSIONS: This study supports the possibility of reducing UWSF testing time to 5 min; and the SWSF test may be skipped for SjS patients with USWF > 0.2 mL/min, indicating mild secretory hypofunction, or < 0.05 mL/min, indicating moderate to severe secretory hypofunction. Key Points •A diagnostic cohort of 734 patients with clinical suspicion of SjS provides compelling evidence for the potential to reduce the testing time for UWSF from 10 to 5 min. •Our finding challenges the 2019 treatment recommendation for SjS, which does not require SWSF measurement in SjS patients with UWSF ≥ 0.1 mL/min. •We propose that it may be feasible to consider utilizing UWSF instead of SWSF test for objective classification of SG secretory function in over half of SjS patients.

Design, Synthesis, and Biological Evaluation of Novel Quinoline Derivatives against Phytopathogenic Bacteria Inspired from Natural Quinine Alkaloids.

A series of 2-(trifluoromethyl)-4-hydroxyquinoline derivatives were designed and synthesized with introduction of the antibacterial fragment amino alcohols, and their antibacterial activity against plant phytopathogenic bacteria was evaluated for the development of quinoline bactericides. It is worth noting that compound Qa5 exhibited excellent antibacterial activity in vitro with a minimum inhibitory concentration (MIC) value of 3.12 µg/mL against Xanthomonas oryzae (Xoo). Furthermore, in vivo assays demonstrated that the protective efficacy of Qa5 against rice bacterial blight at 200 µg/mL (33.0%) was superior to that of the commercial agent bismerthiazol (18.3%), while the curative efficacy (35.0%) was comparable to that of bismerthiazol (35.7%). The antibacterial mechanisms of Qa5 indicated that it affected the activity of bacteria by inducing intracellular oxidative damage in Xoo and disrupting the integrity of the bacterial cell membrane. The above results demonstrated that the novel quinoline derivative Qa5 possessed excellent in vitro and in vivo antibacterial activity, indicating its potential as a novel green agricultural antibacterial agent.

Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Fungi and Bacteria.

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 µg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 µg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

A practical risk stratification system based on ultrasonography and clinical characteristics for predicting the malignancy of soft tissue masses.

OBJECTIVE: To establish a practical risk stratification system (RSS) based on ultrasonography (US) and clinical characteristics for predicting soft tissue masses (STMs) malignancy. METHODS: This retrospective multicenter study included patients with STMs who underwent US and pathological examinations between April 2018 and April 2023. Chi-square tests and multivariable logistic regression analyses were performed to assess the association of US and clinical characteristics with the malignancy of STMs in the training set. The RSS was constructed based on the scores of risk factors and validated externally. RESULTS: The training and validation sets included 1027 STMs (mean age, 50.90 ± 16.64, 442 benign and 585 malignant) and 120 STMs (mean age, 51.93 ± 17.90, 69 benign and 51 malignant), respectively. The RSS was constructed based on three clinical characteristics (age, duration, and history of malignancy) and six US characteristics (size, shape, margin, echogenicity, bone invasion, and vascularity). STMs were assigned to six categories in the RSS, including no abnormal findings, benign, probably benign (fitted probabilities [FP] for malignancy: 0.001-0.008), low suspicion (FP: 0.008-0.365), moderate suspicion (FP: 0.189-0.911), and high suspicion (FP: 0.798-0.999) for malignancy. The RSS displayed good diagnostic performance in the training and validation sets with area under the receiver operating characteristic curve (AUC) values of 0.883 and 0.849, respectively. CONCLUSION: The practical RSS based on US and clinical characteristics could be useful for predicting STM malignancy, thereby providing the benefit of timely treatment strategy management to STM patients. CRITICAL RELEVANCE STATEMENT: With the help of the RSS, better communication between radiologists and clinicians can be realized, thus facilitating tumor management. KEY POINTS: There is no recognized grading system for STM management. A stratification system based on US and clinical features was built. The system realized great communication between radiologists and clinicians in tumor management.

Antisense oligonucleotides enhance SLC20A2 expression and suppress brain calcification in a humanized mouse model.

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency.

Clinical features and genetic analysis of 5 cases of infantile-type glycogen storage disease type II: Case reports.

OBJECTIVE: Clinical and genetic mutation analysis was performed on 5 infantile glycogen storage disease type II children in Chinese mainland. METHODS: Clinical data of 5 children with infantile-type glycogen storage disease type II due to the acidic α-glucosidase (GAA) gene variants diagnosed and treated at Hebei Provincial Children's Hospital from January 2018 to April 2020 were retrospectively analyzed. RESULTS: Among the 5 cases, 1 was female and 4 were male, and the age at first diagnosis was from 2 months to 7 months. The first symptoms of all 5 cases showed progressive muscle weakness, hypotonia, and motor developmental backwardness, and all of them had abnormally elevated creatine kinase, and the echocardiograms suggested different degrees of myocardial hypertrophy, with ejection fractions ranging from 44% to 67%. Analysis of GAA gene variations: all 5 cases were compound heterozygous, and a total of 12 variant loci were detected, of which c.2024_2026delACA, c.2853G > A, c.1124G > T, c.574G > A, c.2509C > T, and c.2013G > A were new mutations that had not been reported. FOLLOWUP: All 5 children died before 1 year of age, and the age of death ranged from 7 months to 11.5 months, with a mean survival time of 9.8 months. CONCLUSION: Peripheral blood GAA gene testing and alpha-glucosidase enzyme activity testing is an effective method for diagnosing this disease.

Design, synthesis and cytotoxic activity of sulfonylated derivatives of camptothecin.

With the intention of advancing our research on diverse C-20 derivatives of camptothecin (CPT), 38 CPT derivatives bearing sulphonamide and sulfonylurea chemical scaffolds and different substituent groups have been designed, synthesised and evaluated in vitro for cytotoxicity against four tumour cell lines, A-549 (lung carcinoma), KB (nasopharyngeal carcinoma), MDA-MB-231 (triple-negative breast cancer) and KBvin (an MDR KB subiline). As a result, all the synthesised compounds showed promising in vitro cytotoxic activity against the four cancer cell lines tested, and were more potent than irinotecan. Importantly, compounds 12b, 12f, 12j and 13 l possessed better antiproliferative activity against all tested tumour cell lines with IC50 values of 0.0118 - 0.5478 µM, and resulted approximately 3 to 4 times more cytotoxic than topotecan against multidrug-resistant KBvin subline. Convincing evidences are achieved that incorporation of sulphonamide and sulfonylurea motifs into position-20 of camptothecin confers markedly enhanced cytotoxic activity against cancer cell lines.

Angong Niuhuang Wan ameliorates LPS-induced cerebrovascular edema by inhibiting blood‒brain barrier leakage and promoting the membrane expression of AQP4.

Introduction: Angong Niuhuang Wan (AGNHW), developed during the Qing dynasty (18th century) for the treatment of consciousness disturbances caused by severe infections, has been used to treat brain edema caused by ischemia‒reperfusion. However, it remains unclear whether AGNHW can ameliorate vascular-origin brain edema caused by lipopolysaccharides (LPS). This study explored the ameliorative effects of AGNHW on LPS-induced cerebrovascular edema in mice, as well as the potential underlying mechanisms. Methods: A cerebrovascular edema model was established in male C57BL/6N mice by two intraperitoneal injections of LPS (15 mg/kg), at 0 and 24 h. AGNHW was administered by gavage at doses of 0.2275 g/kg, 0.455 g/kg, and 0.91 g/kg, 2 h after LPS administration. In control mice, normal saline (NS) or AGNHW (0.455 g/kg) was administered by gavage 2 h after intraperitoneal injection of NS. The survival rate, cerebral water content, cerebral venous FITC-dextran leakage, Evans blue extravasation, and expression of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5, phosphorylated caveolin-1 (CAV-1), and cytomembrane and cytoplasmic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) were evaluated. The cerebral tissue phosphoproteome, blood levels of AGNHW metabolites, and the relationships between these blood metabolites and differentially phosphorylated proteins were analyzed. Results: AGNHW inhibited the LPS-induced decrease in survival rate, increase in cerebral water content, decrease in VE-Cadherin expression and increase in phosphorylated CAV-1 (P-CAV-1). AGNHW treatment increased the expression of AQP4 on astrocyte membrane after LPS injection. AGNHW also inhibited the LPS-induced increases in the phosphorylation of 21 proteins, including protein kinase C-α (PKC-α) and mitogen-activated protein kinase 1 (MAPK1), in the cerebral tissue. Eleven AGNHW metabolites were detected in the blood. These metabolites might exert therapeutic effects by regulating PKC-α and MAPK1. Conclusion: AGNHW can ameliorate cerebrovascular edema caused by LPS. This effect is associated with the inhibition of VE-Cadherin reduction and CAV-1 phosphorylation, as well as the upregulation of AQP4 expression on the astrocyte membrane, following LPS injection.

Design, synthesis and antimicrobial activity of novel berberine derivatives.

BACKGROUND: The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria. RESULTS: Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC50 value against Botrytis cinerea was 1.34 µg mL-1. Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC90 values of 3.12 µg mL-1 and 1.56 µg mL-1. A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight. CONCLUSION: This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry.

Current development and structure-activity relationship study of berberine derivatives.

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.

Prenylated Flavonoids Isolated from the Root of Sophora flavescens as Potent Antifungal Agents against Botrytis cinerea.

Sophora flavescens, a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC50 values ranging from 4.76 to 13.94 µg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with EC50 values of 16.12, 16.55, and 16.99 µg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea. It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea. Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.

Roles of estrogen and its receptors in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by abnormal steroid hormone levels in peripheral blood and poor-quality oocytes. In the ovary, androgen is produced by theca cells, and estrogen is produced by granulosa cells. Androgen is converted to estrogen in granulosa cells, with cytochrome P450 aromatase as the limiting enzyme during this process. Estrogen receptors (ER) include ER alpha, ER beta, and membrane receptor GPR30. Studies have demonstrated that the abnormal functions of estrogen and its receptors and estradiol synthesis-related enzymes are closely related to PCOS. In recent years, some estrogen-related drugs have made significant progress in clinical application for subfertility with PCOS, such as letrozole and clomiphene. This article will elaborate on the recent advances in PCOS caused by abnormal expression of estrogen and its receptors and the application of related targeted small molecule drugs in clinical research and treatment.

SIRT4 Protects Müller Glial Cells Against Apoptosis by Mediating Mitochondrial Dynamics and Oxidative Stress.

SIRT4 is a member of the sirtuin family, which is related to mitochondrial function and possesses antioxidant and regulatory redox effects. Currently, the roles of SIRT4 in retinal Müller glial cells, oxidative stress, and mitochondrial function are still unclear. We confirmed, by immunofluorescence staining, that SIRT4 is located mainly in the mitochondria of retinal Müller glial cells. Using flow cytometry and Western blotting, we analyzed cell apoptosis, intracellular reactive oxygen species (ROS) levels, apoptotic and proapoptotic proteins, mitochondrial dynamics-related proteins, and mitochondrial morphology and number after the overexpression and downregulation of SIRT4 in rMC-1 cells. Neither the upregulation nor the downregulation of SIRT4 alone affected apoptosis. SIRT4 overexpression reduced intracellular ROS, reduced the BAX/BCL2 protein ratio, and increased the L-OPA/S-OPA1 ratio and the levels of the mitochondrial fusion protein MFN2 and the mitochondrial cleavage protein FIS1, increasing mitochondrial fusion. SIRT4 downregulation had the opposite effect. Mitochondria tend to divide after serum starvation for 24 h, and SIRT4 downregulation increases mitochondrial fragmentation and oxidative stress, leading to aggravated cell damage. The mitochondrial division inhibitor Mdivi-1 reduced oxidative stress levels and thus reduced cell damage caused by serum starvation. The overexpression of SIRT4 in rMC-1 cells reduced mitochondrial fragmentation caused by serum starvation, leading to mitochondrial fusion and reduced expression of cleaved caspase-3, thus alleviating the cellular damage caused by oxidative stress. Thus, we speculate that SIRT4 may protect retinal Müller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress.

Small Cell Lung Cancer-An Update on Chemotherapy Resistance.

OPINION STATEMENT: Compared to other types of lung cancer, small cell lung cancer (SCLC) exhibits aggressive characteristics that promote drug resistance. Despite platinum-etoposide chemotherapy combined with immunotherapy being the current standard treatment, the rapid development of drug resistance has led to unsatisfactory clinical outcomes. This review focuses on the mechanisms contributing to the chemotherapy resistance phenotype in SCLC, such as increased intra-tumoral heterogeneity, alterations in the tumor microenvironment, changes in cellular metabolism, and dysregulation of apoptotic pathways. A comprehensive understanding of these drug resistance mechanisms in SCLC is imperative for ushering in a new era in cancer research, which will promise revolutionary advancements in cancer diagnosis and treatment methodologies.

Age at natural menopause and associated factors with early and late menopause among Chinese women in Zhejiang province: A cross-sectional study.

OBJECTIVES: Menopause is a significant life transition for women, impacting their physical and psychological health. The age at natural menopause (ANM) and its associated factors have differed by race and region. This study aimed to investigate ANM and associated factors of early and late menopause among Chinese women in Zhejiang province. METHODS: A cross-sectional study was conducted using a multi-stage stratified cluster sampling method to recruit 8,006 women aged 40-69 years who had resided in Zhejiang province for over 6 months between July 2019 and December 2021. Self-reported ANM and sociodemographics, lifestyle behaviors, reproductive history, and health-related factors were collected using questionnaires in face-to-face surveys. ANM were categorized into three groups: early menopause (<45 years), normal menopause (45-54 years), and late menopause (≥55 years). Kaplan-Meier survival analysis was utilized to calculate the median ANM. Multivariable multinomial logistic regression was employed to explore the associated factors of early menopause and late menopause. RESULTS: A total of 6,047 women aged 40-69 years were included for survival analysis, with 3,176 of them for the regression analysis. The overall median ANM was 51 years (Inter-quartile range [IQR]: 51-52). Women who were smokers (odds ratio [OR]:4.54, 95% confidence interval [CI]:1.6-12.84), had irregular menstrual cycles (OR:1.78, 95% CI:1.12-2.83) and hypertension (OR:1.55, 95% CI:1.09-2.21) had a higher odds ratio of early menopause, while central obesity (OR:1.33, 95% CI:1.03-1.73) and hyperlipidemia (OR:1.51, 95% CI:1.04-2.18) were factors associated with late menopause. CONCLUSIONS: This study revealed the associations between ANM and various factors among Chinese women. These factors included socio-demographic factors such as age; life behavior factors like current or prior smoking status; reproductive history factors such as irregular menstrual cycles, miscarriages, and breastfeeding; and health-related factors like central adiposity, hypertension, and hyperlipidemia. These findings provided a basis for understanding factors associated with ANM.

Epidemiology and genotypic diversity of feline bocavirus identified from cats in Harbin, China.

Feline bocavirus (FBoV) is a globally distributed linear, single-stranded DNA virus infect cats, currently classified into three distinct genotypes. Although FBoV can lead to systemic infections, its complete pathogenic potential remains unclear. In this study, 289 blood samples were collected from healthy cats in Harbin, revealing an overall FBoV prevalence of 12.1%. Notably, genotypes 1 and 3 of FBoV were found co-circulating among the cat population in Harbin. Additionally, recombination events were detected, particularly in the newly discovered NG/104 and DL/102 strains. Furthermore, negative selection sites were predominantly observed across the protein coding genes of FBoV. These findings suggest a co-circulation of genetically diverse FBoV strains among cats in Harbin, indicate that purifying selection is the primary driving force shaping the genomic evolution of FBoV, and also underscore the importance of comprehensive surveillance efforts to enhance our understanding of the epidemiology and evolutionary characteristics of FBoV.

Occupational Category and Professional Title Influencing the Knowledge, Attitudes and Practice (KAP) of Quality Training: A Cross-Sectional Survey From a Tertiary General Hospital.

Quality improvement is an international priority, and quality education and training are important parts of hospital quality management. The aim of this study was to understand the knowledge, attitudes and practices (KAP) and its influencing factors related to quality training in medical staff. A questionnaire survey was conducted by convenience sampling to assess the KAP of quality training in Taizhou Enze Medical Center. Principal component analysis was used to extract factors from the questionnaire. Descriptive statistics (frequency, median, mean), Kendall grade correlation analysis, and Mann-Whitney U tests were used to analyze the data. A total of 205 staff members participated in the questionnaire survey. For the 5 factors of the KAP scale, the highest score was factor F4, recognition and support for quality training (mean = 90.55, median = 100), followed by factor F3, perceived benefits (mean = 84.46, median = 85.65). Relatively lower scores were found for factor F2, quality knowledge learning and mastery (mean = 63.09, median = 63.89), and F5, quality management practices and sharing (mean = 82.07, median = 75.00). There was a correlation between the 5 factors. The scores of F2 (quality knowledge learning and mastery) for staff with senior professional titles were higher than those for staff with intermediate professional titles or below. The score of F3 (perceived benefits of quality training) in medical technicians and nurses was higher than in doctors and administrative personnel. Our findings showed that the respondents' attitude toward quality training was positive, but their knowledge mastery and practice behaviors should be further improved. Occupational category and professional title were the influencing factors of the quality training KAP. Therefore, hospital should conduct quality management training at a wider scope according to the competency requirements of different groups, and further optimize the improvement and innovation system.

Noninvasive Light Flicker Stimulation Promotes Optic Nerve Regeneration by Activating Microglia and Enhancing Neural Plasticity in Zebrafish.

Purpose: Forty-hertz light flicker stimulation has been proven to reduce neurodegeneration, but its effect on optic nerve regeneration is unclear. This study explores the effect of 40-Hz light flicker in promoting optic nerve regeneration in zebrafish and investigates the underlying mechanisms. Methods: Wild-type and mpeg1:EGFP zebrafish were used to establish a model of optic nerve crush. Biocytin tracing and hematoxylin and eosin staining were employed to observe whether 40-Hz light flicker promotes regeneration of retinal ganglion cell axons and dendrites. Optomotor and optokinetic responses were evaluated to assess recovery of visual function. Immunofluorescence staining of mpeg1:EGFP zebrafish was performed to observe changes in microglia. Differentially expressed genes that promote optic nerve regeneration following 40-Hz light flicker stimulation were identified and validated through RNA-sequencing analysis and quantitative real-time PCR (qRT-PCR). Results: Zebrafish exhibited spontaneous optic nerve regeneration after optic nerve injury and restored visual function. We observed that 40-Hz light flicker significantly activated microglia following optic nerve injury and promoted regeneration of retinal ganglion cell axons and dendrites, as well as recovery of visual function. Transcriptomics and qRT-PCR analyses revealed that 40-Hz light flicker increased the expression of genes associated with neuronal plasticity, including bdnf, npas4a, fosab, fosb, egr4, and ier2a. Conclusions: To our knowledge, this study is the first to demonstrate that 40-Hz light flicker stimulation promotes regeneration of retinal ganglion cell axons and dendrites and recovery of visual function in zebrafish, which is associated with microglial activation and enhancement of neural plasticity.

Phase Transition Control in Molecular Solids via Complementarity of Hydrogen-Bond Strength.

Phase transitions in molecular solids involve synergistic changes in chemical and electronic structures, leading to diversification in physical and chemical properties. Despite the pivotal role of hydrogen bonds (H-bonds) in many phase-transition materials, it is rare and challenging to chemically regulate the dynamics and to elucidate the structure-property relationship. Here, four high-spin CoII compounds were isolated and systematically investigated by modifying the ligand terminal groups (X=S, Se) and substituents (Y=Cl, Br). S-Cl and Se-Br undergo a reversible structural phase transition near room temperature, triggering the rotation of 15-crown-5 guests and the swing between syn- and anti-conformation of NCX- ligands, accompanied by switchable magnetism. Conversely, S-Br and Se-Cl retain stability in ordered and disordered phases, respectively. H-bonds geometric analysis and ab initio calculations reveal that the electronegativity of X and Y affects the strength of NY-ap-H⋅⋅⋅X interactions. Entropy-driven structural phase transitions occur when the H-bond strength is appropriate; otherwise, the phase stays unchanged if it is too strong or weak. This work highlights a phase transition driven by H-bond strength complementarity - pairing strong acceptor with weak donor and vice versa, which offers a straightforward and effective approach for designing phase-transition molecular solids from a chemical perspective.