Circular RNA KIAA0564 Serves as a Competitive Endogenous RNA for MicroRNA-424-5p, Mediating the Expression of Lysine Demethylase 4a, Thereby Facilitating Intervertebral Disc Degeneration.

A growing body of research has confirmed the involvement of circular RNAs (circRNAs) in the regulation of intervertebral disc degeneration (IDD) progression. However, the underlying molecular networks remain largely elusive. This study aimed to explore whether a novel circRNA, named circKIAA0564, affects nucleus pulposus (NP) cell injury and to elucidate its molecular mechanism. Both in vivo and in vitro IDD models were established, and the expression patterns of circKIAA0564/miR-424-5p/lysine demethylase 4a (KDM4A) were evaluated through quantitative reverse transcription PCR and Western blot analysis. Actinomycin D, RNase R, and Northern blotting were utilized to assess the circular structure of circKIAA0564. The Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay, commercial assay kits, Western blotting, and reactive oxygen species (ROS) probes were employed to assess the inflammatory and oxidative stress status in NP cells and tissues. Hematoxylin and eosin and TUNEL staining were used to evaluate pathological damage in mouse NP tissues. RNA immunoprecipitation and dual-luciferase reporter assays were conducted to assess the direct targeting relationships among circKIAA0564, miR-424-5p, and KDM4A. CircKIAA0564 was found to be abnormally overexpressed in IDD, functioning as a novel circRNA. Knockdown of circKIAA0564 ameliorated interleukin-1 beta (IL-1ß)-induced inflammation and oxidative stress in NP cells. The therapeutic effect of circKIAA0564 knockdown on NP cells was reversed by the silencing of miR-424-5p. Overexpression of circKIAA0564 exacerbated IL-1ß-induced NP cell injury, a process that was reversed by knockdown of KDM4A. CircKIAA0564 activated the toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) signaling pathway by regulating the miR-424-5p/KDM4A axis. CircKIAA0564 exacerbates IL-1ß-induced inflammation and oxidative stress in NP cells by competitively binding miR-424-5p, thereby mediating KDM4A and activating the TLR4/NF-κB/NLRP3 signaling pathway. These findings provide robust data support for targeted therapy of IDD and the development of future pharmaceuticals.

Aspartate Aminotransferase/Platelet Ratio Index Upon Admission Predicts 24-Week Mortality in Patients With HIV-Associated Talaromyces marneffei.

Background: A high aspartate aminotransferase/platelet ratio index (APRI) predicts mortality in patients with severe infection. This study aims to assess the potential of APRI as a predictor for mortality in patients with HIV-associated Talaromyces marneffei (HTM). Methods: Associations between APRI and CD4 count, white blood cell count, C-reactive protein (CRP) level, procalcitonin (PCT) level, and cytokines were assessed in 119 patients. Univariate and multivariate Cox regression models were used to predict APRI on 24-week mortality. Results: APRI was positively associated with CRP (r = 0.190, P = .039), PCT (r = 0.220, P = .018), interleukin 6 (r = 0.723, P < .001), interleukin 10 (r = 0.416, P = .006), and tumor necrosis factor α (r = 0.575, P < .001) and negatively associated with CD4 count (r = -0.234, P = .011). In total, 20.2% (24/119) of patients died within the 24-week follow-up. The 24-week survival rate was 88.0% for patients with APRI <5.6% and 61.1% for those with APRI ≥5.6 (log-rank P < .001). After adjustment for sex, age, body mass index, and CD4 count, as well as serum levels of hemoglobin, APRI ≥5.6 (adjusted hazard ratio [95% CI]; 3.0 [1.2-7.1], P = .015), PCT ≥1.7 ng/mL (3.7 [1.5-9.6], P = .006), and non-amphotericin B deoxycholate treatment (2.8 [1.2-6.6], P = .018) were independent risk factors for 24-week mortality. Conclusions: For patients with HTM, APRI is associated with severity and is an independent risk factor for 24-week mortality.

The central nervous system is a potential reservoir and possible origin of drug resistance in hepatitis B infection.

Background: The significance of hepatitis B virus (HBV) in cerebrospinal fluid (CSF) is unclear. Methods: Synchronous serum and CSF samples were collected from 13 patients. HBV DNA, full-length genome, quasispecies, phylogenetic tree, compartmentalization and mutation of the reverse transcriptase (RT) region were performed based on PCR and sequencing methods. Results: HBV DNA was detected in the CSF of 3 antiviral-naïve individuals and 1 individual after successful antiviral therapy. Complete full-length HBV genomes were isolated from the CSF of 5 individuals, including 2 with undetectable serum HBV DNA. Ten individuals exhibited distinct CSF-serum quasispecies, 8 harbored independent CSF-serum genetic compartmentalization and phylogenetic trees, and 5 lamivudine/entecavir-associated resistance mutations only in the CSF. The frequencies of rtL180M and rtM204I/V mutations in both serum and CSF were higher in HIV-HBV-coinfected individuals than in the HBV-monoinfected ones (serum: rtL180M: 3.9% vs. 0, P = 0.004; rtM204I/V: 21.3% vs. 0, P < 0.001; CSF: rtL180M: 7.6% vs. 0, P = 0.026; rtM204I/V 7.6% vs. 1.6%, P = 0.097). Conclusion: CSF is a potential HBV reservoir, and HBV in CSF harbors distinct evolution and mutation characteristics from those in serum. HIV infection increases the possibility of HBV rtL180M and rtM204I/V mutations in both serum and CSF.

Clinical Features, Phenotypic Markers and Outcomes of Diffuse Large B-Cell Lymphoma between HIV-Infected and HIV-Uninfected Chinese Patients.

Background: The effect of HIV infection on the clinicopathological characteristics of diffuse large B-cell lymphoma (DLBCL) remains debatable. Methods: Fifty-three HIV-infected and ninety-three HIV-uninfected DLBCL patients were enrolled in the retrospective study by propensity score matching for sex, age, body mass index and international prognostic index (IPI) at a ratio of 1:2. The clinicopathological characteristics were compared between the two groups. Results: HIV-infected DLBCL patients had lower white blood cell counts [×109/L; 4.4 (3.4−5.6) vs. 6.1 (4.2−8.2), p < 0.001], platelet counts (×109/L; 184.7 ± 89.3 vs. 230.0 ± 113.9, p = 0.014) and serum albumin (g/L; 37.3 ± 6.9 vs. 41.3 ± 6.2, p < 0.001) but higher incidences of central nervous system (CNS) involvement (9.4% vs. 1.1%, p = 0.014), bone marrow involvement (24.5% vs. 11.5%, p = 0.044) and Epstein−Barr viremia (61.1% vs. 26.7%, p = 0.002) than HIV-uninfected patients. In terms of histopathology, HIV-infected patients had higher positivity of Epstein−Barr virus-encoded small RNA (EBER) (41.7% vs. 6.7%, p = 0.002), but lower CD20 (90.2% vs. 98.7%, p= 0.029) and CD79a (23.1% vs. 53.7%, p < 0.001) expression. The overall response rate (ORR) at the end of chemotherapy (70.2% vs. 87.8%, p= 0.012) and 1-year overall survival (OS) (61.7% vs. 84.2%, log-rank p = 0.006) in HIV-infected patients were significantly lower than those in HIV-uninfected patients. Multivariate analysis suggested IPI ≤2.0 [adjusted odds ratio (AOR) (95% confidence interval): 5.0 (1.2−21.2), p = 0.030] was associated with ORR, hypoalbuminemia [AOR: 3.3 (1.3−9.1), p = 0.018] and CNS involvement [AOR: 3.3 (1.0−10.5), p = 0.044] were associated with reduced 1-year OS in HIV-infected patients. Conclusion: HIV-infected DLBCL patients have unique blood profiles and phenotypic markers. Low ORR and 1-year OS were observed in HIV-infected DLBCL patients in our study, even in the HAART era.

Less is More: Trace Amount of a Cyclic Sulfate Electrolyte Additive Enable Ultra-Stable Graphite Anode for High-Performance Potassium-Ion Batteries.

Graphite can be successfully used as an anode for potassium-ion batteries (PIBs), while its conversion to KC8 leads to huge volume expansion, destruction of solid electrolyte interphase (SEI), and thus poor cycling stability. Incorporating additives into electrolytes is an economical and effective way to construct robust SEI for high-performance PIBs. Herein, we developed a series of sulfur-containing additives for PIB graphite anodes, and the impacts of their molecular structure and contents on the SEI are also systematically investigated. Compared with butylene sulfites and 1,3-propane sultone, the 1,3,2-dioxathiolane 2,2-dioxide (DTD) additive endows the graphite electrode (GE) with a higher reversible capacity, and better cycling stability in both the dilute potassium bis(fluorosulfonyl)imide (KFSI)- and potassium hexafluorophosphate (KPF6)-based carbonate electrolyte, as a result of a thinner and sulfate-enriched SEI. Moreover, the addition of a trace amount (0.2 wt %) DTD to the electrolyte can effectively protect the GE running over 800 cycles at 1 C. Excessive additives in the electrolyte will induce continuous SEI growth and render a rapid capacity fading of the GE. This strategy using the electrolyte additive paves the way for the design of novel PIB electrolytes and thus provides a great opportunity for commercial PIBs.

Single and Repeated Episodes of Candida Species Isolated From Cerebrospinal Fluid for Diagnosing Probable Candida meningitis.

Background: The clinical relevance of single or repeated episodes of Candida spp. in cerebrospinal fluid (CSF) in adult patients is debatable. Methods: Forty-two patients with positive Candida episodes in CSF were enrolled in this retrospective study. Results: A total of 42.9% (18/42) were determined to have probable Candida meningitis (PCM). Neurosurgery [odds ratio (OR) (95% confidence interval), OR: 14.4 (1.6-126.1), P = 0.004], lumbar drainage [OR: 5.8 (1.5-23.3), P = 0.009], VP shunt [(OR: 5.6 (1.2-25.8), P = 0.020)], external ventricular drainage [OR: 4.7 (1.3-17.7), P = 0.018], CRP ≥ 10.0 mg/L [OR: 4.9 (1.3-18.1), P = 0.034], and postsurgical broad-spectrum antibiotics [OR: 9.5 (1.8-50.5), P = 0.004] were risk factors associated with PCM. A single CSF Candida episode for the diagnosis of PCM had 7.7% (0.4-37.9%) sensitivity and 20.7% (8.7-40.3%) specificity, whereas repeated episodes of Candida had 66.7% (41.2-85.6%) sensitivity and 95.8% (76.9-99.8%) specificity. No significant difference was found in radiological imaging or CSF profiles between PCM and non-PCM patients. A total of 37.5% (9/24) of patients without PCM received empirical antifungal treatment, and 88.9% (16/18) of patients with PCM received preemptive antifungal treatment. PCM patients had hospitalized mortality rates of 50.0% (9/18). The odds ratio of mortality was 23.0 (2.5-208.6) for PCM patients compared with non-PCM patients (P = 0.001). Conclusion: Both single and repeated positive CSF samples have low validity for the diagnosis of PCM, suggesting that novel strategies for diagnosis algorithms of PCM are urgently needed. Empirical antifungal treatment should be started immediately for suspicious patients with risk factors.

Clinical features and Outcomes of Cryptococcemia patients with and without HIV infection.

BACKGROUND: The effects of cryptococcemia on patient outcomes in those with or without HIV remain unclear. METHODS: One hundred and seventy-nine cryptococcemia patients were enrolled in this retrospective study. Demographic characteristics, blood test results and outcome were compared between the two groups. RESULTS: The diagnosis time of Cryptococcus infection was 2.0(0-6.0) days for HIV-infected patients, 5.0 (1.5-8.0) days for HIV-uninfected patients (p = .008), 2.0 (1.0-6.0) days for cryptococcal meningitis (CM) patients and 6.0 (5.0-8.0) days for non-CM patients (p < .001). HIV infection [adjusted odds ratio (AOR) (95% confidence interval): 6.0(2.3-15.9)], CRP < 15 mg/L [AOR:3.7(1.7-8.1)) and haemoglobin > 110 g/L [AOR:2.5(1.2-5.4)] were risk factors for CM development. Forty-six (25.7%) patients died within 90 days. ICU stay [AOR:2.8(1.1-7.1)], hypoalbuminemia [AOR:2.7(1.4-5.3)], no anti-cryptococcal treatment [AOR:4.7(1.9-11.7)] and altered consciousness [AOR:2.4(1.0-5.5)] were independent risk factors for 90-day mortality in all patients. HIV infection did not increase the 90-day mortality of cryptococcemia patients when anti-Cryptococcus treatment was available. Non-Amphotericin B treatment [AOR:3.4(1.0-11.2)] was associated with 90-day mortality in HIV-infected patients, but age ≥ 50.0 years old [AOR:2.7(1.0-2.9)], predisposing disease [AOR:4.1(1.2-14.2)] and altered consciousness [AOR:3.7(1.1-12.9)] were associated with 90-day mortality in HIV-uninfected patients who accepted anti-Cryptococcus treatment. CONCLUSION: HIV infection increased the incidence of CM rather than mortality in cryptococcemia patients. The predictive model was completely divergent in HIV-infected and HIV-uninfected patients, suggesting that novel strategies for diagnosis and treatment algorithms are urgently needed.

A novel salt inducible WRKY transcription factor gene, AhWRKY75, confers salt tolerance in transgenic peanut.

Peanut is an important oilseed crop whose production is threatened by various abiotic and biotic stresses. Study of the molecular mechanism of salt tolerance could provide important information for the salt tolerance of this crop. WRKY transcription factors (TFs) are one of the largest TF families in plants and are involved in growth and development, defense regulation and the stress response. Here, we cloned a novel WRKY transcription factor gene belonging to the WRKY IIc subfamily, AhWRKY75, from the salt-tolerant mutant M34. The expression of AhWRKY75 was induced by NaCl stress treatment. After salt treatment, AhWRKY75-overexpressing peanuts grew better than wild-type plants. Furthermore, several genes related to the reactive oxygen species (ROS) scavenging system were up-regulated; the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were significantly higher in transgenic lines than in non-transgenic control plants; and the malondialdehyde (MDA) and superoxide anion contents were significantly lower in transgenic lines than in control plants. The net photosynthetic rate (Pn), stomatal conductance (GS) and transpiration rate (Tr) of transgenic lines were significantly higher in transgenic plants than in control plants, and the intercellular CO2 concentration (Ci) was significantly lower in transgenic plants than in control plants. These results demonstrated that the AhWRKY75 gene conferred salt tolerance in transgenic peanut lines by improving the efficiency of the ROS scavenging system and photosynthesis under stress treatment. This study identifies a novel WRKY gene for enhancing the tolerance of peanut and other plants to salt stress.

Ultra-broadband 1.0 µm band emission spectroscopy in Pr3+/Nd3+/Yb3+ tri-doped tellurite glass.

Tellurite glasses doped with trivalent Pr3+, Nd3+ and Yb3+ ions were prepared using conventional high-temperature melt-quenching technique and their optical absorption, near-infrared emission, X-ray diffraction (XRD), Raman spectrum, and differential scanning calorimeter (DSC) curve were measured. Upon excitation at 488 nm, an ultra-broadband near-infrared emission extending from 800 to 1120 nm was found to appear owing to the overlapping of the emission bands centered at 900 and 1035 nm of Pr3+, 880 and 1060 nm of Nd3+ as well as 978 nm of Yb3+, respectively. The energy transfer mechanism among Pr3+, Nd3+ and Yb3+ ions which was responsible for the observed ultra-broadband near-infrared emission was investigated to understand the luminescent phenomena. In addition, Judd-Ofelt theory was applied to predict the radiative properties of doped rare-earth ions, and some important radiative parameters such as radiative transition probability, branching ratio and radiative lifetime were derived. Meanwhile, the structural information of amorphous nature and vibrational units was revealed by the XRD pattern and Raman spectrum. Also, the DSC curve displayed the good thermal stability to resist thermal damage for studied tellurite glass with high glass transition temperature. The results indicate that Pr3+/Nd3+/Yb3+ tri-doped tellurite glass is a promising material for ultra-broadband fiber lasers operating around 1.0 µm near-infrared band.