Brown adipocyte mineralocorticoid receptor deficiency impairs metabolic regulation in diet-induced obese mice.

Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high-fat diet (HFD) feeding, BAT MR KO (BMRKO) mice manifested significantly increased bodyweight, fat mass, serum fasting glucose, and impaired glucose homeostasis compared with littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production, or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared with LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and proinflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced AKT phosphorylation was substantially blunted in eWAT but not liver or skeletal muscle of BMRKO-HFD mice compared with LC-HFD mice. These data suggest that BAT MR is required to maintain metabolic homeostasis, likely through its regulation of fatty acid metabolism in BAT and impacts on eWAT and liver.

Identification of TCR repertoires in asymptomatic COVID-19 patients by single-cell T-cell receptor sequencing.

The T cell-mediated immune responses associated with asymptomatic infection (AS) of SARS-CoV-2 remain largely unknown. The diversity of T-cell receptor (TCR) repertoire is essential for generating effective immunity against viral infections in T cell response. Here, we performed the single-cell TCR sequencing of the PBMC samples from five AS subjects, 33 symptomatic COVID-19 patients and eleven healthy controls to investigate the size and the diversity of TCR repertoire. We subsequently analyzed the TCR repertoire diversity, the V and J gene segment deference, and the dominant combination of αß VJ gene pairing among these three study groups. Notably, we revealed significant TCR preference in the AS group, including the skewed usage of TRAV1-2-J33-TRBV6-4-J2-2 and TRAV1-2-J33-TRBV6-1-J2-3. Our findings may shed new light on understanding the immunopathogenesis of COVID-19 and help identify optimal TCRs for development of novel therapeutic strategies against SARS-CoV-2 infection.

Effect of artificial liver blood purification treatment on the survival of critical ill COVID-19 patients.

Our aim was to investigate the effect of artificial liver blood purification treatment on the survival of severe/critical patients with coronavirus disease 2019 (COVID-19). A total of 101 severe and critical patients with coronavirus SARS-CoV-2 infection were enrolled in this open, case-control, multicenter, prospective study. According to the patients' and their families' willingness, they were divided into two groups. One was named the treatment group, in which the patients received artificial liver therapy plus comprehensive treatment (n = 50), while the other was named the control group, in which the patients received only comprehensive treatment (n = 51). Clinical data and laboratory examinations, as well as the 28-day mortality rate, were collected and analyzed. Baseline data comparisons on average age, sex, pre-treatment morbidity, initial symptoms, vital signs, pneumonia severity index score, blood routine examination and biochemistry indices etc. showed no difference between the two groups. Cytokine storm was detected, with a significant increase of serum interleukin-6 (IL-6) level. The serum IL-6 level decreased from 119.94 to 20.49 pg/mL in the treatment group and increased from 40.42 to 50.81 pg/mL in the control group (P < .05), indicating that artificial liver therapy significantly decreased serum IL-6. The median duration of viral nucleic acid persistence was 19 days in the treatment group (ranging from 6 to 67 days) and 17 days in the control group (ranging from 3 to 68 days), no significant difference was observed (P = .36). As of 28-day follow-up,17 patients in the treatment group experienced a median weaning time of 24 days, while 11 patients in the control group experienced a median weaning time of 35 days, with no significant difference between the two groups (P = .33). The 28-day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group, with a significant difference (z = 3.70, P < .001). Cytokine storm is a key factor in the intensification of COVID-19 pneumonia. The artificial liver therapy blocks the cytokine storm by clearing inflammatory mediators, thus preventing severe cases from progressing to critically ill stages and markedly reducing short-term mortality.

Clinical characteristics and outcomes of cancer patients with COVID-19.

This retrospective study aimed to analysis clinical characteristics and outcomes of cancer patients with novel coronavirus disease-19 (COVID-19). Medical records, laboratory results and radiologic findings of 52 cancer patients with COVID-19 were collected, clinical characteristics and outcomes were summarized. A total of 52 cancer patients with COVID-19 were included. Median age of 52 cancer patients with COVID-19 was 63 years (34-98). Thirty-three (63.5%) patients were mild and 19 (36.5%) were severe/critical. Lung cancer was the most frequent cancer type (10, 19.2%). The common symptoms were as follows: fever (25%), dry cough (17.3%), chest distress (11.5%), and fatigue (9.6%). There were 33 (63.5%) patients had comorbidities, the most common symptom was hypertension (17, 51.5%). Twenty-six (78.8%) patients developed pneumonia on admission. Lymphocytes (0.6 × 109/L) decreased in both mild and severe/critical patients. Median levels of D-dimer, C-reactive protein, procalcitonin, and lactate dehydrogenase were 2.8 mg/L, 70.5 mg/L, 0.3 ng/mL, and 318 U/L, respectively, which increased significantly in severe/critical patients compared with the mild patients. Interleukin-6 (12.6 pg/mL) increased in both mild and severe/critical patients, there was a significant difference between them. Complications were observed in 29 (55.8%) patients, such as liver injury (19, 36.5%), acute respiratory distress syndrome (9, 17.3%), sepsis (8, 15.4%), myocardial injury (8, 15.4%), renal insufficiency (4, 7.7%), and multiple organ dysfunction syndrome (3, 5.8%). Eleven (21.2%) patients with cancer died. The infection rate of severe acute respiratory syndrome coronavirus 2 in patients with cancer was higher than the general population, cancer patients with COVID-19 showed deteriorating conditions and poor outcomes.

Analysis of 92 deceased patients with COVID-19.

This retrospective study aimed to analyze the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19). We collected the medical records of 92 patients with COVID-19, who died in the time period ranging from 6 January 2020 to 25 February 2020, in Renmin Hospital of Wuhan University and summarized the clinical characteristics of complications. There were 91 death cases in which different complications were developed, including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91), and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. However, one patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID-19. The main complications of deceased patients with COVID-19 were ARDS, myocardial injury, liver injury, renal insufficiency, and MODS.

Siderophores in clinical isolates of Klebsiella pneumoniae promote ciprofloxacin resistance by inhibiting the oxidative stress.

To explore the relevance of and understand the potential mechanisms behind the production of siderophores by clinical isolates of K. pneumoniae and ciprofloxacin (CIP) resistance, we divided the K. pneumoniae isolates into two groups based on bacterial siderophores production: high siderophore-yielding group (39 strains) and low siderophore-yielding group (38 strains). The rate of CIP resistance in K. pneumoniae (27/39 = 69.23%) from the high siderophore-yielding group was significantly higher than that (16/38 = 42.11%) in the low siderophore-yielding group (p < 0.05). Furthermore, we noted that bacterial siderophores production was positively correlating with CIP resistance as indicated by the minimum inhibitory concentration (MIC; p < 0.05). However, siderophore-related antibiotic resistance had no relationship with DNA gyrase GyrA mutation (p > 0.05). Siderophore-related antibiotic resistance was accompanied by efflux pump functions, but was not directly relevant to it. Furthermore, we found that the oxidative stress response was significantly lower in high siderophore-yielding strains compared to those isolates which had a low siderophores yield (12.17 vs. 30.91 of average fluorescence value; p < 0.01). There was a consistent inverse correlation between the production of bacterial siderophores and oxidative stress response (p < 0.05). Although CIP induced oxidative stress in both high and low siderophore-yielding strains (p < 0.01), oxidative stress in high siderophore-yielding strains was significantly lower than in low siderophore-yielding strains (p < 0.01). Our data suggest that siderophores of K. pneumoniae clinical isolates promote CIP resistance through inhibition of the bacterial oxidative stress response, indicating that reduction of bacterial oxidative stress could provide a new avenue for control of bacterial drug resistance.

Synthesis of Aldehydes by Organocatalytic Formylation Reactions of Boronic Acids with Glyoxylic Acid.

Reported herein is a conceptually novel organocatalytic strategy for the formylation of boronic acids. New reactivity is engineered into the α-amino-acid-forming Petasis reaction occurring between aryl boronic acids, amines, and glyoxylic acids to prepare aldehydes. The operational simplicity of the process and its ability to generate structurally diverse and valued aryl, heteroaryl, and α,ß-unsaturated aldehydes containing a wide array of functional groups, demonstrates the practical utility of the new synthetic strategy.

Synergistic effects of baicalein with cefotaxime against Klebsiella pneumoniae through inhibiting CTX-M-1 gene expression.

BACKGROUND: Generation of extended- spectrum ß- lactamases is one of the major mechanisms by which clinical Klebsiella pneumoniae develop resistance to antibiotics. Combined antibiotics prove to be a relatively effective method of controlling such resistant strains. Some of Chinese herbal active ingredients are known to have synergistic antibacterial effects. This study is aimed to investigate synergistic effects of Chinese herbal active ingredients with cefotaxime on the extended- spectrum ß- lactamase positive strains of Klebsiella pneumoniae, and to analyze mechanism of synergistic action, providing experimental evidence for clinical application of antimicrobial drugs. RESULTS: For total sixteen strains including fifteen strains of cefotaxime resistant K. pneumoniae and one extended- spectrum ß- lactamase positive standard strain, the synergy rates of cefotaxime with baicalein, matrine, and clavulanic acid were 56.3 %, 0 %, and 100 %, respectively. The fractional inhibitory concentration index of combined baicalein and cefotaxime was correlated with the percentage decrease of cefotaxime MIC of all the strains (r = -0.78, p <0.01). In the group of synergy baicalein and cefotaxime, the transcribed mRNA level of CTX-M-1 after treatment of baicalein was decreased significantly (p <0.05). Moreover, the CTX-M-1 mRNA expression percentage inhibition (100 %, 5/5) was significantly higher than non- synergy group (25 %, 1/4) (p <0.05). CONCLUSIONS: Our study demonstrated that baicalein exhibited synergistic activity when combined with cefotaxime against some of extended- spectrum ß- lactamases positive K. pneumoniae strains by inhibiting CTX-M-1 mRNA expression. However, no direct bactericidal or bacteriostatic activity was involved in the synergistic action. Baicalein seems to be a promising novel effective synergistic antimicrobial agent.

Facile Installation of 2-Reverse Prenyl Functionality into Indoles by a Tandem N-Alkylation-Aza-Cope Rearrangement Reaction and Its Application in Synthesis.

An unprecedented tandem N-alkylation-ionic aza-Cope (or Claisen) rearrangement-hydrolysis reaction of readily available indolyl bromides with enamines is described. Due to the complicated nature of the two processes, an operationally simple N-alkylation and subsequent microwave-irradiated ionic aza-Cope rearrangement-hydrolysis process has been uncovered. The tandem reaction serves as a powerful approach to the preparation of synthetically and biologically important, but challenging, 2-reverse quaternary-centered prenylated indoles with high efficiency. Notably, unusual nonaromatic 3-methylene-2,3-dihydro-1H-indole architectures, instead of aromatic indoles, are produced. Furthermore, the aza-Cope rearrangement reaction proceeds highly regioselectively to give the quaternary-centered reverse prenyl functionality, which often produces a mixture of two regioisomers by reported methods. The synthetic value of the resulting nonaromatic 3-methylene-2,3-dihydro-1H-indole architectures has been demonstrated as versatile building blocks in the efficient synthesis of structurally diverse 2-reverse prenylated indoles, such as indolines, indole-fused sultams and lactams, and the natural product bruceolline D.

Damage to the Blood-Aqueous Barrier in Ocular Blunt Trauma and Its Association with Intraocular Pressure Elevation.

BACKGROUND: The aim of this study is to provide a quantitative evaluation of the blood-aqueous barrier (BAB) in patients with ocular blunt trauma and evaluate its association with intraocular pressure (IOP) elevation. METHODS: This is a prospective case-control study, and the following 3 groups were included: elevated IOP (45 patients with an elevated IOP secondary to ocular blunt trauma), normal IOP (27 patients with a normal IOP after ocular blunt trauma), and healthy controls. The main outcome measures were IOP and BAB function evaluated using a laser flare-cell meter (LFCM). RESULTS: Patients had significantly higher flare intensities and cell counts than the normal controls (both p < 0.001), and the elevated-IOP group displayed even higher LFCM readings than the normal-IOP group. Aqueous flare and cell readings were positively correlated with IOP (r = 0.529 and 0.590, respectively, p < 0.001). LFCM readings in the elevated-IOP group were still significantly high even on postraumatic day 120 following anti-inflammatory treatment. CONCLUSION: BAB dysfunction occurred following ocular blunt trauma. Eyes with an elevated IOP displayed a more seriously disturbed BAB and a longer recovery course. Examination with a LFCM provides insight into the pathophysiology of IOP elevation and assists in making decisions concerning anti-inflammatory treatment during follow-up.

Construction of chiral bridged tricyclic benzopyrans: enantioselective catalytic Diels-Alder reaction and a one-pot reduction/acid-catalyzed stereoselective cyclization.

An asymmetric two-step approach to chiral bridged tricyclic benzopyrans, core structures featured in various natural products, is described. In the synthesis, an unprecedented enantioselective catalytic decarboxylative Diels-Alder reaction is developed using readily available coumarin-3-carboxylic acids and aldehydes as reactants under mild reaction conditions. Notably, the decarboxylation-assisted release of the catalyst enables the process to proceed efficiently with high enantio- and diastereoselectivity. Furthermore, a one-pot procedure for either a LiAlH4 - or NaBH4 -mediated reduction with subsequent acid-catalyzed intramolecular cyclization of the Diels-Alder adducts was identified for the efficient formation of the chiral bridged tricyclic benzopyrans.

Understanding the Design of Fear Appeals by Applying the Extended Parallel Process Model: A Qualitative Analysis of COVID-19 Public Service Announcements.

PURPOSE: Identify how early COVID-19 public health messages incorporated in the tenets of the extended parallel process model (EPPM). SETTING: YouTube videos developed by governmental departments, medical institutions, news organizations, and non-profit organizations in the United States were aggregated. METHOD: This qualitative study conducted a keyword search to identify public service announcements (PSAs). The sample was further refined after searching PSAs that contained fear appeals. A thematic analysis was performed by using the constant comparative method. SAMPLE: A total of forty-three videos was included in the final analysis. RESULT: Two themes emerged regarding messages aimed at arousing the perceived severity of threat. These themes include emphasizing the consequences of being infected and utilizing personal narratives. Perceived susceptibility of threat was aroused by emphasizing that some groups have higher risks than others. Two themes emerged around arousing perceived response efficacy: (1) the authority of professionals; and (2) altruism and personal responsibility. One way was identified to arouse perceived self-efficacy, which is informing the protective measures. CONCLUSION: Multiple strategies were used in PSAs about COVID-19 to arouse fear during the early stages of the pandemic. The utilization of self-efficacy was oversimplified, by not providing details about the rationale for the recommended behavior.

Comparison of Financial Hardship and Healthcare Utilizations Associated with Cancer in the United States Medicare Programs during the COVID-19 Pandemic.

BACKGROUND: In the United States, Medicare beneficiaries diagnosed with cancer often face significant financial challenges due to the expensive nature of cancer treatments and increased cost-sharing responsibilities. However, there is limited knowledge regarding the financial hardships and healthcare utilizations faced by those enrolled in Medicare Advantage (MA) compared to those in traditional fee-for-service Medicare (TM) during the COVID-19 pandemic. Our study aims to investigate the subjective financial hardships experienced by individuals enrolled in TM and MA and to determine whether these two Medicare programs exhibit differences in healthcare utilization during the pandemic. METHODS: We utilized data from the 2020-2022 National Health Interview Survey (NHIS), focusing on nationally representative samples of cancer survivors aged 65 or older. Financial hardship was categorized into three distinct groups: material (e.g., problems with medical bills), psychological (e.g., worry about paying), and behavioral (e.g., delayed care due to cost). Healthcare utilization included wellness visits (preventive care), emergency care services, hospitalizations, and telehealth. We used survey design-adjusted analysis to compare the study outcomes between MA and TM. RESULTS: Among a weighted sample of 4.4 million Medicare beneficiaries with cancer (mean age: 74.9), 76% were enrolled in MA plans. Cancer survivors with a college degree (59.3% vs. 49.8%) and high family income (38.2% vs. 31.1%) were more likely to enroll in MA plans. There were no significant differences in any material, psychological, or behavioral financial hardship domains between beneficiaries with MA and TM plans except forgone counseling due to cost. For healthcare utilization measures, cancer survivors in MA were more likely than those in TM to have flu vaccination (77.2% vs. 70.1%) and experience lower hospitalizations (16.0% vs. 20.0%). However, there were no differences in other health service utilizations between MA and TM. CONCLUSION: While no significant differences were observed in any materialized, psychological, or behavioral financial hardships, older cancer survivors enrolled in MA plans were more likely to receive vaccinations and lower hospitalization rates during COVID-19. Although other preventive or primary care visits (i.e., wellness visits) were higher, their difference did not reach statistical significance. As MA grows in popularity, it is essential to consistently monitor and evaluate the performance and outcomes of Medicare plans for cancer survivors as we navigate the post-pandemic landscape.

SPG21, a potential oncogene targeted by miR-128-3p, amplifies HBx-induced carcinogenesis and chemoresistance via activation of TRPM7-mediated JNK pathway in hepatocellular carcinoma.

PURPOSE: Chronic hepatitis B virus (HBV) infection is the primary risk factor for the malignant progression of hepatocellular carcinoma (HCC). It has been reported that HBV X protein (HBx) possesses oncogenic properties, promoting hepatocarcinogenesis and chemoresistance. However, the detailed molecular mechanisms are not fully understood. Here, we aim to investigate the effects of miR-128-3p/SPG21 axis on HBx-induced hepatocarcinogenesis and chemoresistance. METHODS: The expression of SPG21 in HCC was determined using bioinformatics analysis, quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC). The roles of SPG21 in HCC were elucidated through a series of in vitro and in vivo experiments, including real-time cellular analysis (RTCA), matrigel invasion assay, and xenograft mouse model. Pharmacologic treatment and flow cytometry were performed to demonstrate the potential mechanism of SPG21 in HCC. RESULTS: SPG21 expression was elevated in HCC tissues compared to adjacent non-tumor tissues (NTs). Moreover, higher SPG21 expression correlated with poor overall survival. Functional assays revealed that SPG21 fostered HCC tumorigenesis and invasion. MiR-128-3p, which targeted SPG21, was downregulated in HCC tissues. Subsequent analyses showed that HBx amplified TRPM7-mediated calcium influx via miR-128-3p/SPG21, thereby activating the c-Jun N-terminal kinase (JNK) pathway. Furthermore, HBx inhibited doxorubicin-induced apoptosis by engaging the JNK pathway through miR-128-3p/SPG21. CONCLUSION: The study suggested that SPG21, targeted by miR-128-3p, might be involved in enhancing HBx-induced carcinogenesis and doxorubicin resistance in HCC via the TRPM7/Ca2+/JNK signaling pathway. This insight suggested that SPG21 could be recognized as a potential oncogene, offering a novel perspective on its role as a prognostic factor and a therapeutic target in the context of HCC.

Variant 1 of KIAA0101, overexpressed in hepatocellular carcinoma, prevents doxorubicin-induced apoptosis by inhibiting p53 activation.

UNLABELLED: KIAA0101 overexpression was detected in numerous malignant solid tumors and involved in tumor progression; however, the correlation between KIAA0101 expression level and human hepatocellular carcinoma (HCC) was controversial. Our data revealed abnormal expression of the KIAA0101 transcript variant 1 (KIAA0101 tv1) at both messenger RNA and protein levels in HCC tissues and cell lines assessed by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), virtual northern blot, western blot, and immunohistochemical analysis, especially in stage 3-4 HCCs. NIH3T3 cells transfected with KIAA0101 tv1 induced colony formation in vitro and tumor xenorafts in vivo, implying the oncogenic potential of KIAA0101 tv1. Semiquantitative RT-PCR, real-time quantitative RT-PCR, and western blot analysis demonstrated that doxorubicin (Adriamycin, ADR) treatment down-regulated expression of the KIAA0101 tv1, whereas it increased the acetylation of the p53 protein. Additionally, KIAA0101 tv1 prevented cells from apoptosis caused by ADR through suppressing the acetylation of p53 at Lys382. Immunoprecipitation analysis and mammalian two-hybrid assay indicated that KIAA0101 tv1 bound to the transactivation region (1-42 amino acids) of p53 and strongly inhibits its transcriptional activity. Taken together, our data suggest that KIAA0101 tv1 played an important role in the late stage of metastatic HCC and prevented apoptosis after chemotherapeutic drug treatment through inhibiting the transcriptional activity of the p53 gene. CONCLUSION: KIAA0101 tv1 may function as a regulator, promoting cell survival in HCC through regulating the function of p53. Suppression of the KIAA0101 tv1 function is likely to be a promising strategy to develop novel cancer therapeutic drugs.

Specific patterns of gyrA mutations determine the resistance difference to ciprofloxacin and levofloxacin in Klebsiella pneumoniae and Escherichia coli.

BACKGROUND: Wide use of ciprofloxacin and levofloxacin has often led to increased resistance. The resistance rate to these two agents varies in different clinical isolates of Enterobacteriaceae. Mutations of GyrA within the quinolone resistance-determining regions have been found to be the main mechanism for quinolone resistance in Enterobacteriaceae. It has been shown that only some of the mutations in the gyrA gene identified from clinical sources were involved in fluoroquinolone resistance. Whether different patterns of gyrA mutation are related to antimicrobial resistance against ciprofloxacin and levofloxacin is unclear. METHODS: The minimum inhibitory concentration (MIC) of ciprofloxacin and levofloxacin were determined by the agar dilution method followed by PCR amplification and sequencing of the quinolone resistance determining region of gyrA to identify all the mutation types. The correlation between fluoroquinolone resistance and the individual mutation type was analyzed. RESULTS: Resistance differences between ciprofloxacin and levofloxacin were found in 327 isolates of K. pneumoniae and E. coli in Harbin, China and in the isolates reported in PubMed publications. GyrA mutations were found in both susceptible and resistant isolates. For the isolates with QRDR mutations, the resistance rates to ciprofloxacin and levofloxacin were also statistically different. Among the 14 patterns of alterations, two single mutations (Ser83Tyr and Ser83Ile), and three double mutations (Ser83Leu+Asp87Asn, Ser83Leu+Asp87Tyr and Ser83Phe+Asp87Asn) were associated with both ciprofloxacin and levofloxacin resistance. Two single mutations (Ser83Phe and Ser83Leu) were related with ciprofloxacin resistance but not to levofloxacin. Resistance difference between ciprofloxacin and levofloxacin in isolates harboring mutation Ser83Leu+Asp87Asn were of statistical significance among all Enterobacteriaceae (P<0.001). CONCLUSIONS: Resistance rate to ciprofloxacin and levofloxacin were statistically different among clinical isolates of Enterobacteriaceae harboring GyrA mutations. Ser83Leu+Asp87Asn may account for the antimicrobial resistance difference between ciprofloxacin and levofloxacin.

Knowledge, attitude and practice of antibiotics: a questionnaire study among 2500 Chinese students.

BACKGROUND: Recently, many scientists including bacteriologists have begun to focus on social aspects of antibiotic management especially the knowledge, attitude and practice (KAP) among the general population regarding antibiotic use. However, relatively few works have published on the relationship between KAP and medical education. In this study, we analyze the present status of Chinese medical (MS)- and non-medical (NS) students' KAP on the use of antibiotics, and examine the influence of Chinese medical curriculum on the appropriate usage of antibiotics among medical students. METHODS: In this study, 2500 students from 3 universities (including one medical university) in Northeastern China participate in the questionnaire survey on students' knowledge, attitude and practice toward antibiotic usage. Wilcoxon rank sum test and Chi square test were used to analyze questionnaire-related discrete and categorical variables respectively, in order to assess the impact of the medical curriculum on students' KAP towards antibiotics. RESULTS: 2088 (83.5%) respondents (MS-1236 and NS-852) were considered valid for analysis. The level of knowledge of MS on the proper use of antibiotics was significantly higher than that of NS (p < 0.0001). However, based on their responses on actual practice, MS were found to rely on antibiotics more than NS (p < 0.0001). Moreover, the knowledge and attitude of MS towards antibiotic use improved with the increase in grade with discriminate use of antibiotics concurrently escalating during the same period. CONCLUSIONS: This study indicates that Chinese medical curriculum significantly improves students' knowledge on antibiotics and raises their attention on antibiotic resistance that may result from indiscriminate use of antibiotics. The study also shows an excessive use of antibiotics especially among the more senior medical students, signifying a deficiency of antibiotics usage instruction in their curriculum. This might explain why there are frequent abuses of antibiotics in both hospital and community settings from a certain angle.

Effect of corneal flap thickness on opaque bubble layer formation in Visumax FS-LASIK using GEE analysis.

Introduction: This study aimed to investigate two types of corneal flap thickness on opaque bubble layer (OBL) formation in Visumax femtosecond laser-assisted stromal for situ keratomileusis (FS-LASIK). Methods: This retrospective study analyzed 203 eyes of 103 patients (32 men and 71 women) who underwent Visumax FS-LASIK between January 2020 and June 2020, and according to corneal flap thickness, they were divided into the 100-µm group (64 eyes) and the 110-µm group (139 eyes). Anterior-segment examination revealed no abnormal findings. Preoperatively, intraocular pressure (IOP), central corneal thickness (CCT), residual stromal thickness (RST), spherical power, cylindrical power, flat keratometry (K1), steep keratometry (K2), and biomechanical parameters including deformation amplitude (DA) ratio, Integrated Radius, stiffness parameter at first applanation (SP-A1), and Ambrosio relational thickness to the horizontal profile (ARTh) were evaluated. Primary outcomes were the incidence of OBL formation in the two groups compared by the Chi-square test and the correlation between the incidence of OBL and the above preoperative data by Spearman's Rho test. Secondary outcomes were the comparisons corrected by the generalized estimating equation (GEE) model. Results: The incidence of OBL formation in the 100-µm group was 59.4 %, which was higher than that in the 110-µm group (23.0 %) with a significant difference (χ2 = 25.635, P < 0.001). The thinner corneal flap thickness (r = -0.355, P < 0.001) and higher spherical power (r = -0.142, P < 0.05) correlated with OBL formation. Higher K1 (r = 0.217, P < 0.01) and K2 (r = 0.198, P < 0.01) also correlated with OBL formation. The results of the GEE correction analysis showed higher rates of OBL formation in the 100-µm group (odds ratio [OR] = 4.704, 95 % CI 1.681-13.161, P < 0.01). Conclusions: OBL was more likely to occur with the 100-µm corneal flap than with the 110-µm corneal flap in Visumax FS-LASIK. The risk of OBL formation in the 100-µm group was 4.704 times higher than that in the 110-µm group.

Developmental and cardiac toxicity assessment of Ethyl 3-(N-butylacetamido) propanoate (EBAAP) in zebrafish embryos.

Ethyl 3-(N-butylacetamido) propanoate (EBAAP) is one of the most widely used mosquito repellents worldwide, and is also commonly used to produce cosmetics. Residues have recently been detected in surface and groundwater in many countries, and their potential to harm the environment is unknown. Therefore, more studies are needed to fully assess the toxicity of EBAAP. This is the first investigation into the developmental toxicity and cardiotoxicity of EBAAP on zebrafish embryos. EBAAP was toxic to zebrafish, with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). EBAAP exposure also reduced body length, slowed the yolk absorption rate, induced spinal curvature and pericardial edema, decreased heart rate, promoted linear lengthening of the heart, and diminished cardiac pumping ability. The expression of heart developmental-related genes (nkx2.5, myh6, tbx5a, vmhc, gata4, tbx2b) was dysregulated, intracellular oxidative stress increased significantly, the activities of catalase (CAT) and superoxide dismutase (SOD) decreased, and malondialdehyde (MDA) content increased significantly. The expression of apoptosis-related genes (bax/bcl2, p53, caspase9, caspase3) was significantly upregulated. In conclusion, EBAAP induced abnormal morphology and heart defects during the early stages of zebrafish embryo development by potentially inducing the generation and accumulation of reactive oxygen species (ROS) in vivo and activating the oxidative stress response. These events dysregulate the expression of several genes and activate endogenous apoptosis pathways, eventually leading to developmental disorders and heart defects.

An organocatalytic cascade approach toward polysubstituted quinolines and chiral 1,4-dihydroquinolines-unanticipated effect of N-protecting groups.

A matter of protection: The outcome of a divergent organocatalytic aza-Michael/aldol cascade process toward quinolines and 1,4-dihydroquinolines depends on the choice of the N-protecting group (see scheme; TEA = triethylamine, TMS = trimethylsilyl). Use of an electron-donating sulfonyl group results in an unanticipated aza-Michael/aldol/aromatization cascade to give polysubstituted quinolines (right). In contrast, chiral 1,4-dihydroquinolines are obtained with an electron-withdrawing sulfonyl group (left).