Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection.

Polyamines are critical metabolites involved in various cellular processes and often dysregulated in cancers. Kaposi's sarcoma-associated Herpesvirus (KSHV), a defined human oncogenic virus, leads to profound alterations of host metabolic landscape to favor development of KSHV-associated malignancies. In our studies, we identified that polyamine biosynthesis and eIF5A hypusination are dynamically regulated by KSHV infection through modulation of key enzymes (ODC1 and DHPS) of these pathways. During KSHV latency, ODC1 and DHPS are upregulated along with increase of hypusinated eIF5A (hyp-eIF5A), while hyp-eIF5A is further induced along with reduction of ODC1 and intracellular polyamines during KSHV lytic reactivation. In return these metabolic pathways are required for both KSHV lytic reactivation and de novo infection. Further analysis unraveled that synthesis of critical KSHV latent and lytic proteins (LANA, RTA) depends on hypusinated-eIF5A. We also demonstrated that KSHV infection can be efficiently and specifically suppressed by inhibitors targeting these pathways. Collectively, our results illustrated that the dynamic and profound interaction of a DNA tumor virus (KSHV) with host polyamine biosynthesis and eIF5A hypusination pathways promote viral propagation, thus defining new therapeutic targets to treat KSHV-associated malignancies.

Effects of initial corncob particle size on the short-term composting for preparation of cultivation substrates for Pleurotus ostreatus.

The short-term composting based on corncob for preparing Pleurotus ostreatus cultivation medium originated from agricultural production practices and so lacked systematic investigation. In this study, the influences of a Dafen (15 mm, DFT) and Xiaofen (5 mm, XFT) initial particle size (IPS) of corncob on the microbial succession and compost quality were examined. Results demonstrated that XFT compost was better suited for mushroom cultivation due to its high biological efficiency of 70 % and the absence of contamination. The composting microbes differed significantly between the DFT and XFT composts. During composting, the genera of Bacillus, Acinetobacter, Lactobacillus, Streptomyces, and Paenibacillus were majorly found in the DFT compost, while Acinetobacter, Lactobacillus, Puccinia, Bacteroides, and Bacillus genera dominated the XFT compost. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that throughout the thermophilic phase, XFT compost had much greater relative abundances of sequences relevant to energy, carbohydrate, and amino acid metabolism than DFT compost. Analysis of network correlations and Mantel tests indicated that IPS reduction could increase microbial interactions. Overall, adjusting the IPS of corncob to 5 mm increased microbial interactions, improved compost quality, and thereby boosted the P. ostreatus yield. These findings will be pertinent in optimizing the composting process of cultivation medium for P. ostreatus.

Microbiological analysis and antibiotic selection strategy in neck abscesses among patients with diabetes mellitus.

PURPOSE: This study aimed to analyze the clinical characteristics, pathogen distribution, drug sensitivity, and antibiotic treatment strategies of patients with neck abscesses with or without diabetes. METHODS: A retrospective analysis was conducted on 2194 patients who underwent neck abscess surgery at our hospital over the past 13 years. Patients were grouped as NAwithDM (neck abscess with diabetes mellitus) or NAwithoutDM (neck abscess without diabetes mellitus). Clinical features, pathogen distribution, and antibiotic sensitivity were compared between the groups. Venn diagrams were used to illustrate the antibiotics effective against all three predominant pathogens. RESULTS: A total of 2194 patients with neck abscesses were included in this study, with 579 patients (26.43%) in the NAwithDM group and 1612 patients (73.51%) in the NAwithoutDM group. There were no significant differences in sex or age distribution between the two groups (all P > 0.05). However, there were significant differences in BMI, length of hospital stays, occurrence of laryngeal obstruction, hypertension, and hypoalbuminemia between the two groups (all P < 0.05). In the NAwithoutDM group, the top three pathogens were Streptococcus constellatus, Klebsiella pneumoniae, and Staphylococcus aureus. The antibiotics that were simultaneously effective against all three pathogens were ceftriaxone, moxifloxacin, and ampicillin/sulbactam. In the NAwithDM group, the top three pathogens were Streptococcus pyogenes, Streptococcus pneumoniae, and Streptococcus constellatus. The antibiotics that were simultaneously effective against all three pathogens were compound sulfamethoxazole, cefuroxime, levofloxacin, ciprofloxacin, vancomycin, and imipenem. CONCLUSION: Neck abscess patients with diabetes have distinct clinical features. Therefore, it is crucial to pay attention to these clinical features and manage them accordingly during the treatment process. Empirical antibiotic treatment should be tailored to individual patient groups. Sulfamethoxazole-methoxazole is recommended for neck abscess patients with diabetes, while ceftriaxone or moxifloxacin is recommended for those without diabetes.

Mapping the risk factors, pathogens, and antibiotic of pharyngocutaneous fistula in patients after neck open surgery.

PURPOSE: Current literature lacks consensus on risk factors for pharyngocutaneous fistula (PCF), and empirical antibiotic guidelines for PCF are limited. The aim of this study was to reduce the incidence of PCF and improve antibiotic treatment efficacy for patients with PCF after open neck surgery by analyzing their clinical characteristics, pathogenic bacteria, and antibiotic susceptibility. METHODS: This study was a 13-year single-center retrospective cohort study, including 699 patients who underwent open neck surgery for laryngeal and hypopharyngeal cancer. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with the occurrence of PCF after surgery. The microbial species causing PCF were analyzed, and the antibiotic sensitivity of the top three pathogens was assessed. Venn diagrams were used to illustrate the antibiotics that exhibited 100% sensitivity against all three identified pathogens. RESULTS: The incidence of PCF after open neck surgery was 8%. Logistic univariate and multivariate analyses revealed that flap reconstruction (OR = 3.62, 95% CI [2.02-6.52]), history of preoperative radiotherapy (OR = 2.01, 95% CI [1.31-2.73]), significant postoperative bleeding (OR = 1.79, 95% CI [1.11-2.69]), and history of diabetes (OR = 1.34, 95% CI [1.29-2.46]) were significantly associated with PCF occurrence. Among the 38 cases of PCF patients, the top three identified pathogens were Pseudomonas aeruginosa, Escherichia coli, and Enterobacter cloacae. The antibiotics cefepime, meropenem, ticarcillin/clavulanic acid, and cefoperazone/sulbactam showed 100% sensitivity against these top three pathogens. CONCLUSION: Special attention should be given to patients undergoing open neck surgery, especially those with intraoperative flap reconstruction, a history of preoperative radiotherapy, postoperative bleeding, or diabetes. Strengthening monitoring and care is crucial in preventing the occurrence of PCF. According to antibiotic usage guidelines and considering the distribution of pathogens in PCF patients, empirical antibiotic treatment with cefoperazone/sulbactam or ticarcillin/clavulanic acid is recommended prior to obtaining susceptibility test results.

One-Pot Three Carbon Dots with Various Lifetimes Rooted in Different Decarboxylation Degrees for Matrix-Free, Anti-Oxygen, and Time-Resolved Information Encryption and Cellular Imaging.

Activating long-lived room temperature phosphorescence (RTP) in the aqueous environment and thus realizing matrix-free, anti-oxygen, and time-resolved information encryption and cellular imaging remain a great challenge. Here, we fabricated three types of carbon dots (C-dots), i.e., fluorescent C-dots (F-C-dots) and two types of phosphorescent C-dots denoted as Pw-C-dots and Py-C-dots by a one-pot strategy. Their formation was attributed to the difference in the decarboxylation degree at high temperatures using trimesic acid (TMA) as a sole precursor. Unexpectedly, the yield reached as high as ∼92%, and the proportions were ∼27% for F-C-dots, ∼17% for Pw-C-dots, and ∼56% for Py-C-dots. These nanomaterials could help implement carbon peaking and carbon neutrality. Both green RTP of the two C-dots resulted from the small energy gap (ΔEST). These two RTP C-dots had a long lifetime of over 270 ms with a relatively high quantum yield (4.5 and 6.2%). They exhibited excellent photostability and anti-photobleaching performances. The dry and wet powders of the RTP C-dots were applied to high-level information encryption. The lifelike patterns were greatly different from those of the original ones and could last for several seconds to the naked eye, demonstrating that the RTP C-dots could be potentially employed as anti-oxygen and time-resolved contrast reagents. Most significantly, the cellular imaging experiments showed that the biofriendly PVP-coated Py-C-dots could localize at lysosomes and sustain hundreds of milliseconds. This approach not only pioneers a time-resolved lysosome localization model but also opens up a promising door for anti-oxygen and time-resolved RTP cytoimaging.

Cochlear Reimplantation Rate and Cause: a 22-Year, Single-Center Experience, and a Meta-Analysis and Systematic Review.

OBJECTIVES: In terms of cochlear reimplantation, there is no consensus on the definition, range, or calculation formulation for the reimplantation rate. This study aims to put forward a relatively standardized and more explicit definition based on a literature review, calculate the rate of cochlear reimplantation, and examine the classification and distribution of the reimplantation causes. DESIGN: A systematic review and retrospective study. A relatively clearer definition was used in this study: cochlear reimplantation is the implantation of new electrodes to reconstruct the auditory path, necessitated by the failure or abandonment of the initial implant. Seven English and Chinese databases were systematically searched for studies published before July 23, 2021 regarding patients who accepted cochlear reimplantation. Two researchers independently applied the inclusion and exclusion criteria to select studies and complete data extraction. As the effect size, the reimplantation rate was extracted and synthesized using a random-effects model, and subgroup and sensitivity analyses were performed to reduce heterogeneity. In addition, a retrospective study analyzed data on cochlear reimplantation in a tertiary hospital from April 1999 to August 2021. Kaplan-Meier survival analysis and the log-rank test were adopted to analyze the survival times of cochlear implants and compare them among different subgroups. RESULTS: A total of 144 articles were included, with 85,851 initial cochlear implantations and 4276 cochlear reimplantations. The pooled rate of cochlear reimplantation was 4.7% [95% CI (4.2% to 5.1%)] in 1989 to 2021, 6.8% [95% CI (4.5% to 9.2%)] before 2000, and 3.2% [95% CI (2.7% to 3.7%)] after 2000 ( P =0.003). Device failures accounted for the largest proportion of reimplantation (67.6% [95% CI (64.0% to 71.3%)], followed by medical reasons (28.9% [95% CI (25.7% to 32.0%)]). From April 1999 to August 2021, 1775 cochlear implants were performed in West China Hospital (1718 initial implantations and 57 reimplantations; reimplantation rate 3.3%). In total, 45 reimplantations (78.9%) were caused by device failure, 10 (17.5%) due to medical reasons, and 2 (3.5%) from unknown reasons. There was no difference in the survival time of implants between adults and children ( P = 0.558), while there existed a significant difference between patients receiving implants from different manufacturers ( P < 0.001). CONCLUSIONS: The cochlear reimplantation rate was relatively high, and more attention should be paid to formulating a standard definition, calculation formula, and effect assessment of cochlear reimplantation. It is necessary to establish a sound mechanism for long-term follow-up and rigorously conduct longitudinal cohort studies.

[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Nucleolar protein NOP2/NSUN1 suppresses HIV-1 transcription and promotes viral latency by competing with Tat for TAR binding and methylation.

Recent efforts have been paid to identify previously unrecognized HIV-1 latency-promoting genes (LPGs) that can potentially be targeted for eradication of HIV-1 latent reservoirs. From our earlier orthologous RNAi screens of host factors regulating HIV-1 replication, we identified that the nucleolar protein NOP2/NSUN1, a m5C RNA methyltransferase (MTase), is an HIV-1 restriction factor. Loss- and gain-of-function analyses confirmed that NOP2 restricts HIV-1 replication. Depletion of NOP2 promotes the reactivation of latently infected HIV-1 proviruses in multiple cell lines as well as primary CD4+ T cells, alone or in combination with latency-reversing agents (LRAs). Mechanistically, NOP2 associates with HIV-1 5' LTR, interacts with HIV-1 TAR RNA by competing with HIV-1 Tat protein, as well as contributes to TAR m5C methylation. RNA MTase catalytic domain (MTD) of NOP2 mediates its competition with Tat and binding with TAR. Overall, these findings verified that NOP2 suppresses HIV-1 transcription and promotes viral latency.

Profiling of immune related genes silenced in EBV-positive gastric carcinoma identified novel restriction factors of human gammaherpesviruses.

EBV-associated gastric cancer (EBVaGC) is characterized by high frequency of DNA methylation. In this study, we investigated how epigenetic alteration of host genome contributes to pathogenesis of EBVaGC through the analysis of transcriptomic and epigenomic datasets from NIH TCGA (The Cancer Genome Atlas) consortium. We identified that immune related genes (IRGs) is a group of host genes preferentially silenced in EBV-positive gastric cancers through DNA hypermethylation. Further functional characterizations of selected IRGs reveal their novel antiviral activity against not only EBV but also KSHV. In particular, we showed that metallothionein-1 (MT1) and homeobox A (HOXA) gene clusters are down-regulated via EBV-driven DNA hypermethylation. Several MT1 isoforms suppress EBV lytic replication and release of progeny virions as well as KSHV lytic reactivation, suggesting functional redundancy of these genes. In addition, single HOXA10 isoform exerts antiviral activity against both EBV and KSHV. We also confirmed the antiviral effect of other dysregulated IRGs, such as IRAK2 and MAL, in scenario of EBV and KSHV lytic reactivation. Collectively, our results demonstrated that epigenetic silencing of IRGs is a viral strategy to escape immune surveillance and promote viral propagation, which is overall beneficial to viral oncogenesis of human gamma-herpesviruses (EBV and KSHV), considering that these IRGs possess antiviral activities against these oncoviruses.

Global cognitive function is associated with sex, educational level, occupation type, and speech recognition rate in older Chinese adults: a single-center, prospective, cross-sectional study.

BACKGROUND: The development of cognitive impairment may be delayed if its risk factors are identified and detected, if its developmental trend can be predicted, and if early intervention can be performed. This study primarily aimed to investigate the association between global cognitive function and hearing loss, educational level, and occupation type and to determine any differences in such associations according to sex among older Chinese adults. METHODS: In this cross-sectional study, we prospectively recruited 219 individuals above 55 years old in an otolaryngology outpatient clinic who could write independently and had no severe vision impairment. Audiometric examinations included otoscopy, acoustic immittance, pure-tone audiometry, and speech audiometry for each ear. Cognitive function was evaluated by using the Chinese version of the Mini-Mental State Examination (MMSE). Multivariable linear regression analyses were performed to evaluate the relationship between variables and MMSE scores after adjusting for independent variables that were statistically significant in the univariable analyses. RESULTS: We enrolled 219 individuals: 98 men (mean ± standard deviation age, 63.08 ± 6.64 years) and 121 women (62.64 ± 7.17 years). The overall MMSE scores of the normal hearing group and the mild, moderate, and severe-to-profound hearing loss groups were 24.00 (5.00), 24.00 (5.00), 23.00 (5.00), and 23.00 (13.00), respectively. MMSE scores were higher among participants with higher educational levels (p < 0.001) and were significantly correlated with occupation type (p < 0.001). MMSE scores were significantly higher in men than in women (p < 0.001). However, after the analysis of the five subdomains, significant differences were only observed for attention and calculation (p < 0.001) and language (p = 0.011). We further compared the distribution of educational levels between men and women by using the chi-square test; there was no significant difference in educational level between the sexes (p = 0.070). CONCLUSIONS: We reported statistically significant relationships between global cognitive function and sex, educational level, and occupation type. Sex-specific strategies may be required to improve healthcare policies.

Prevalence of sleep impairment in patients with tinnitus: a systematic review and single-arm meta-analysis.

PURPOSE: This study aimed to comprehensively review the literature and synthesize relevant data to examine the pooled prevalence of poor sleep quality (sleep impairment) and assess overall sleep quality in patients with tinnitus. METHODS: This meta-analysis systematically searched both English (PubMed, Embase, and Web of Science) and Chinese (Wanfang Data Chinese database, Veep Chinese Database, and Chinese National Knowledge Infrastructure) databases. Data extraction and quality assessment were independently performed by two authors. The pooled prevalence of sleep impairment and poor sleep quality was calculated via a random-effects model. Sub-group and sensitivity analyses were performed to explore the source of heterogeneity. RESULTS: A total of seven studies were included with a total sample of 3041 tinnitus participants. The pooled prevalence of sleep impairment was 53.5% (95% confidence interval: 40.2-66.8%) and the I2 was 97.8% (Q = 7.90, p = 0.000). There were significant differences in the prevalence of poor sleep quality between males and females (39.1% vs. 44.6%, P = 0.034), between different PSQI cut-off values ≥ 7 and > 5 (53.1% vs. 53.8%, P = 0.000), and between sample sizes > 200 and ≤ 200 (54.0% vs. 52.7%, P = 0.000). In non-Asia area, the prevalence (56.6%, 95% CI: 42.6-70.5%) was lower than that in Asia areas (34.5%, 95% CI: 25.7-43.3%). CONCLUSION: Sleep impairment is common among patients with tinnitus. Development of interventions for conditions associated with poor sleep quality should be recommended to offer a safe and efficacious solution for this population.

Risk factors for Meniere disease: a systematic review and meta-analysis.

PURPOSE: To summarized the latest evidence of risk factors for developing MD. METHODS: We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, CBM, VIP, WanFANG, and CNKI, and ClinicalTrials.gov. till June 2021 for cohort and case-control studies investigating risk factors for MD. The exposure group was participants with a clinical diagnosis of MD which was made according to the diagnostic scale of the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), the control group was participants without MD. The outcome was determined by incidence or prognostic of MD. Paired reviewers independently screened citations, assessed bias risk of included studies using the Newcastle-Ottawa Scale. Odds ratios (OR), hazard ratios(HR), relative risk(RR) and 95% confidence interval (CI) were calculated for dichotomous data. The statistical analyses were carried out with the use of Review Manager 5.3. The level of statistical heterogeneity for pooled data were assessed by using I2 statistics and Q-test. RESULTS: 768 abstracts and articles were identified by our search, of which 25 studies (n = 1, 471, 944) were included. There were 18 cohort studies, 7 case-control studies. Three distinct subgroups (age, sex, sleep) were identified. There were a total of two studies involving age, two studies involving gender and two studies involving sleep disorder. High to moderate methodological quality established that age [hazard ratios (HR) 2.21, 95% CI 1.85-2.65, I2 = 0%] and sleep disorder[HR 1.68, 95% CI 1.47-1.93, I2 = 0%] were risk factors for MD. While there was little evidence showing that sex was not a risk factor for MD [HR 1.61, 95% CI 0.91-2.84, I2 = 74%]. CONCLUSION: The current evidence supports the suggestion that age and sleep disorder are risk factors for MD. Sex, gene, and hypothyroidism are tentative risk factors but conflicting/inconclusive results. FUNDING: No external funding. REGISTRATION: CRD42021248199 (Prospero).

A CRISPR/Cas9 screen identifies the histone demethylase MINA53 as a novel HIV-1 latency-promoting gene (LPG).

Although combination antiretroviral therapy is potent to block active replication of HIV-1 in AIDS patients, HIV-1 persists as transcriptionally inactive proviruses in infected cells. These HIV-1 latent reservoirs remain a major obstacle for clearance of HIV-1. Investigation of host factors regulating HIV-1 latency is critical for developing novel antiretroviral reagents to eliminate HIV-1 latent reservoirs. From our recently accomplished CRISPR/Cas9 sgRNA screens, we identified that the histone demethylase, MINA53, is potentially a novel HIV-1 latency-promoting gene (LPG). We next validated MINA53's function in maintenance of HIV-1 latency by depleting MINA53 using the alternative RNAi approach. We further identified that in vitro MINA53 preferentially demethylates the histone substrate, H3K36me3 and that in cells MINA53 depletion by RNAi also increases the local level of H3K36me3 at LTR. The effort to map the downstream effectors unraveled that H3K36me3 has the cross-talk with another epigenetic mark H4K16ac, mediated by KAT8 that recognizes the methylated H3K36 and acetylated H4K16. Removing the MINA53-mediated latency mechanisms could benefit the reversal of post-integrated latent HIV-1 proviruses for purging of reservoir cells. We further demonstrated that a pan jumonji histone demethylase inhibitor, JIB-04, inhibits MINA53-mediated demethylation of H3K36me3, and JIB-04 synergizes with other latency-reversing agents (LRAs) to reactivate latent HIV-1.

Biomarkers of Alzheimer's disease in severe obstructive sleep apnea-hypopnea syndrome in the Chinese population.

PURPOSE: Patients with severe obstructive sleep apnea-hypopnea syndrome are often accompanied by symptoms such as decreased cognitive function and daytime sleepiness, while cognitive function is often associated with biomarkers of Alzheimer's disease. Therefore, this study aims to explore the level of Alzheimer's disease biomarkers in the plasma of obstructive sleep apnea-hypopnea syndrome patients as well as the relationship between cognitive function and daytime sleepiness. METHODS: Between May and July 2019, 35 patients requiring hospitalization for severe obstructive sleep apnea-hypopnea syndrome and 16 normal control patients were selected from West China Hospital. Alzheimer's disease biomarkers (Aß40, Aß42, t-tau, p-tau) in plasma were detected by ELISA in all 51 subjects. The differences in Alzheimer's disease biomarkers between the two groups were compared. In addition, a correlation analysis of disease-related indicators and univariate analysis of the risk factors of obstructive sleep apnea-hypopnea syndrome was conducted using the logistic regression model. RESULTS: The plasma levels of Alzheimer's disease biomarkers (Aß40, t-tau, p-tau) in patients with severe obstructive sleep apnea-hypopnea syndrome were significantly higher than those in the control group (29.24 ± 32.52, 13.18 ± 10.78, p = 0.049; 11.88 ± 7.05, 7.64 ± 4.17, p = 0.037; 26.31 ± 14.41, 17.34 ± 9.12, p = 0.027). Aß42, Aß40, t-tau, and p-tau were significantly negatively correlated with mean oxygen saturation, low oxygen saturation and Mini-Mental State examination scale scores, and positively correlated with oxygen desaturation index and Epworth Sleepiness Scale scores. T-tau and p-tau can be used as new risk factors for obstructive sleep apnea-hypopnea syndrome. CONCLUSION: Alzheimer's disease biomarkers in the plasma of obstructive sleep apnea-hypopnea syndrome patients are higher than those in the control group, and the mechanism of action may be related to sleep disorders and night hypoxia. The Alzheimer's disease biomarkers deposited in plasma may also cause the decline of patients' cognitive function, increased daytime sleepiness and accelerate the progression of obstructive sleep apnea-hypopnea syndrome.

Analysis of main pathogenic bacteria and drug sensitivity in patients with chronic suppurative otitis media and middle ear cholesteatoma in China.

BACKGROUND: Chronic suppurative otitis media (CSOM) and middle ear cholesteatoma (MEC) were classified as different diseases recently. Owing to the difference in pathogeneses, the pathogenic bacteria of the two diseases can be different. However, few studies have compared the two types of pathogenic bacteria. OBJECTIVE: To analyze the main pathogenic bacteria and drug sensitivities in patients of Southwest China with CSOM and MEC and compare the difference of ear dryness rate between empirical and sensitive medication. METHODS: According to the data of culture of ear discharge and postoperative pathological examination, the patients were divided into CSOM and MEC groups. A cohort study was carried out in 1087 hospitalized patients with CSOM and MEC in the Department of Otolaryngology head and neck surgery, West China Hospital from January 2015 to June 2019. RESULTS: Pathogenic bacteria were detected in 467 of 726 cases of CSOM (64.46%) and in 190 of 361 cases of MEC (52.63%). Of the positive cases, 53.96% involved gram-positive (G+) bacteria and 46.04% involved gram-negative (G-) bacteria in the CSOM group; 41.05% involved G+ bacteria and 58.95% involved G- bacteria in the MEC group (P < 0.05). In the CSOM group, the top four pathogens were Staphylococcus aureus (33.62%), Pseudomonas aeruginosa (23.98%), Proteus (16.92%), and Coagulase-negative Staphylococci (10.28%). The top four pathogens in the MEC group were Proteus (22.11%), S. aureus (21.05%), P. aeruginosa (15.26%), and coagulase-negative staphylococci (8.42%). S. aureus was more sensitive to ciprofloxacin and moxifloxacin in the MEC group than in the CSOM group (= 14.286, P < 0.001; = 8.244, P < 0.01). P. aeruginosa was more sensitive to neomycin and tobramycin in the MEC group than in the CSOM group (= 21.285, P < 0.001; = 4.060, P < 0.05). The sensitivity rate of coagulase-negative staphylococci to neomycin in the MEC group was higher than that in the CSOM group (= 5.126, P < 0.05). The sensitivity of Proteus to piperacillin tazobactam in the CSOM group was higher than that in the MEC group (= 8.881, P < 0.05). The dry ear rate of patients with sensitive drug was significantly higher than the patients with empirical drug (= 19.431, P < 0.001). CONCLUSION: The detection rate of G+ bacteria in the CSOM group was higher than that in the MEC group. The detection rate of G- bacteria in the CSOM group was lower than that in the MEC group. The main pathogens in the two groups included S. aureus, P. aeruginosa, Proteus and coagulase negative Staphylococcus. The dry ear rate of patients who used sensitive drugs was significantly higher than the patients who used empirical drugs. Reducing the rate of empirical use of antibiotics as much as possible and selecting antibiotics reasonably were beneficial to the improvement of dry ear rate after surgery.

Circular RNA circ-FOXM1 facilitates cell progression as ceRNA to target PPDPF and MACC1 by sponging miR-1304-5p in non-small cell lung cancer.

Circular RNAs (circRNAs) have recently been considered as key regulators in carcinogenesis. Nevertheless, the study of circRNAs involved in non-small cell lung cancer (NSCLC) remains largely unclear. In this study, we aim to explore the clinical significance, regulatory effect and mechanism of circ-FOXM1 in NSCLC. The results indicated that circ-FOXM1 overexpression was observed in NSCLC tissues and closely associated with lymph node invasion, higher TNM stage, and unfavorable prognosis. Furthermore, knockdown and ectopic expression of circ-FOXM1 significantly inhibited and promoted the growth, migration and invasion of NSCLC cells, respectively. Mechanistically, miR-1304-5p was discovered as a direct target of circ-FOXM1. Circ-FOXM1 upregulated the level of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) and metastasis-associated in colon cancer 1 (MACC1) by sponging miR-1304-5p, thereby increasing the proliferation and invasion of NSCLC cells. Taken together, this work revealed that circ-FOXM1/miR-1304-5p/PPDPF/MACC1 signaling was essential for the development and progression of NSCLC.

Curaxin CBL0137 has the potential to reverse HIV-1 latency.

A cure for human immunodeficiency virus type-1 (HIV-1) has been hampered by the limitation of current combination antiretroviral therapy (cART) to address the latent reservoirs in HIV-1 patients. One strategy proposed to eradicate these reservoirs is the "shock and kill" approach, where latency-reversing agents (LRAs) are used to reactivate and promote viral cell death and/or immune killing of reactivated cells. Here, we report that curaxin CBL0137, an antitumor compound, can potentiate tumor necrosis factor-α-mediated reactivation of latently infected HIV-1cell lines. Additionally, the single use of CBL0137 is sufficient to reactivate HIV-1 latent reservoirs in peripheral mononuclear cells (PBMCs) isolated from HIV-1 positive, cART-treated, aviremic patients. Thus, CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach.

A composite consisting of bromine-doped carbon dots and ferric ions as a fluorescent probe for determination and intracellular imaging of phosphate.

A composite probe has been developed for fluorometric determination and imaging of phosphate in real water samples and in cells. The method is based on the use of weakly blue fluorescent bromine-doped carbon dots (C-dots) containing aromatic carbon-bromine groups and loaded with Fe3+ ions. The carboxy, phenolic hydroxy and aldehyde groups on the surface of the C-dots can coordinate with Fe3+ to form an adsorbed complex that reduces the blue fluorescence through an inner filter effect. If phosphate is added, it will capture Fe3+ on the surface of C-dots and restore fluorescence by ~88% via a displacement approach. The probe, best operated at excitation/emission maxima of 370/418 nm, has a linear response in the 0.4 to 22 µM phosphate concentration range and a 0.25 µM of detection limit. The relative standard deviation (at a phosphate level of 8.0 µM) is 3.6% (for n = 5). The method was applied to confocal imaging of phosphate in HeLa cells. Graphical abstractSchematic representation of the synthesis of bromine-doped carbon dots (C-dots) by a "one-step" approach. They are shown to be capable of (a) detecting phosphate in real water samples through the displacement approach, and (b) of imaging intracellular phosphate.

Zika virus: The transboundary pathogen from mosquito and updates.

Zika virus (ZIKV) is a mosquito-borne flavivirus that was relatively obscure until outbreaks started in 2013. ZIKV is associated with neurological manifestations such as Guillan-Barrè Syndrome in adult and microcephaly in the newborn population. Although the majority of disease mechanisms of ZIKV is unclear, some information was updated with new scientific evidence. Currently, there are no approved drugs or vaccine that can be used for therapy during ZIKV infection. Based on the transmission mechanism of ZIKV, vector control and safe sex seem to be the most effective available preventive measures against ZIKV spread. This study summarized the current ZIKV epidemiology, the status of the existing pathogenic mechanism of ZIKV, the development of potential compounds and vaccines against ZIKV, and the control efforts against ZIKV.

Molecular cloning of porcine 2',5'-oligoadenylate synthetase-like protein and its role in porcine reproductive and respiratory syndrome virus infection.

Porcine 2',5'-oligoadenylate synthetase-like protein is an essential antiviral protein induced by interferons; however, its bioinformatics, genetic characteristics and immunological characteristics related to porcine reproductive and respiratory syndrome virus are still unknown. In this study, porcine 2',5'-oligoadenylate synthetase-like protein was cloned, and various attributes were predicted by bioinformatics analysis. Through RNAi depletion and overexpression methods, it was determined that porcine OASL not only inhibits porcine reproductive and respiratory virus replication but also activates interferon-beta production and the interferon-beta promoter, promoting the expression of interferon-beta mRNA. Through the depletion of different amino acids at the N and C termini, the antiviral activity and promoting the activity of interferon beta were evaluated. The results demonstrated that 31-60 amino acids at the N terminus were critical for virus replication. This study laid a theoretical foundation for exploring the characteristics of the porcine 2',5'-oligoadenylate synthetase-like protein and suggested a new strategy for the prevention and control of porcine reproductive and respiratory syndrome virus and investigation of the therapeutic mechanism of this protein.