Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers. METHODS: In this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments. RESULTS: Utilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model. CONCLUSION: The expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.

The fungal quorum-sensing molecule, farnesol, regulates the immune response of vaginal epithelial cells against Candida albicans.

BACKGROUND: Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections-candidiasis, especially vulvovaginal candidiasis (VVC). METHODS: The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes. RESULTS: Only low concentrations (≤ 50 µmol/L) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05). CONCLUSIONS: Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.

Physical-cyber-human framework-based resilience evaluation toward urban power system: Case study from China.

Because the increased frequency, intensity, and duration of extreme weather events have significantly challenged power systems, there has been an increased interest in resilient power systems. This article establishes a multicriteria resilience evaluation framework for urban power systems from a physical-cyber-human system perspective, in which the two principal elements responsible for power system function degradation are described, the three major domains comprising urban power systems are explained, four core capacities that positively contribute to power system resilience are proposed, and 15 (11 objective and four subjective) power system resilience evaluation indicators are identified. Fuzzy hesitant judgment and a Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) aggregation method are employed to minimize the expert divergence and maximize the group consensus. A validation method is designed and a comparison with commonly applied performance-based and attributes-based evaluation methods is conducted. The applicability of the evaluation framework is verified using data from four Chinese municipalities: Shanghai, Beijing, Chongqing, and Tianjin. It was found that Shanghai's resilience was the best, and Chongqing's physical resistance disadvantages would result in the greatest difficulties in coping with extreme event disturbances. Physical, cyber, and human domain resilience enhancement strategies are given for different cities separately. This study provides a practical tool to evaluate, compare, and enhance power system resilience for governments and public utilities.

Cause of death and influencing factors of chronic renal failure on maintenance hemodialysis.

Objective: To investigate the causes of death in patients with chronic renal failure (CRF) on maintenance hemodialysis and its influencing factors. Methods: This is a retrospective study. A total of 300 patients with chronic renal failure undergoing maintenance hemodialysis who were admitted to the Affiliated Hospital of Hebei University from March 2020 to October 2022 were selected as subjects. Various information of patients were collected. In addition, 80 dead patients in this group were investigated for the cause of death, including cardiovascular and cerebrovascular diseases, infections, multi organ failure, and other causes, and the death-related conditions of cardiovascular and cerebrovascular diseases, such as triglyceridr,,total cholesterol, and in blood lipid levels were analyzed. Results: Among the 80 dead patients, cardiovascular and cerebrovascular diseases accounted for a higher proportion of death (66%). Univariate Logistic regression analysis showed that advanced age, plasma homocysteine, blood parathyroid hormone, hyperphosphatemia, hypertension, high volume load and left ventricular hypertrophy were risk factors for death in patients with chronic renal failure on maintenance hemodialysis. Multivariate Logistic regression analysis showed that high volume load, left ventricular hypertrophy and anemia were risk factors for death on maintenance hemodialysis. The levels of hemoglobin (HGB) and high-density lipoprotein (HDL) in patients who died of cardiovascular and cerebrovascular diseases were significantly lower than those in the non-cardio-cerebrovascular death group (P=0.00), and the levels of serum phosphorus, TG and TC were significantly higher than those in the non-cardio-cerebrovascular death group (P, P=0.00; TG, P=0.02; TC, P=0.01). Conclusion: Cardiovascular and cerebrovascular diseases are the leading cause of death in patients with chronic renal failure on maintenance hemodialysis. Adequate dialysis and normal hemoglobin levels are favorable protective factors.

Cognitive processing features of elementary school children with mathematical anxiety: Attentional control theory-based explanation.

A growing body of research suggests that mathematical anxiety (MA) seriously affects an individual's math achievement. However, few studies have focused on the cognitive mechanisms of MA in elementary school children. Based on attention control theory (ACT), this research aimed to explore the cognitive mechanism of MA in elementary school children using two studies. In Study 1, the dual-task paradigm of number memory and computation span was used to investigate the difference in processing efficiency between the high-mathematical anxiety (HMA) group and the low-mathematical anxiety (LMA) group. In total, 59 students with HMA and 54 students with LMA participated in Study 1. The results showed that students with HMA had lower processing efficiency in dealing with high-load math tasks. To further investigate the underlying mechanism of low processing efficiency for students with HMA, Study 2 explored the attention bias toward math-related stimuli of students with HMA using the Posner paradigm. In total, 48 students with HMA and 49 students with LMA participated in Study 2. The results showed that math trials put children with HMA in a state of heightened vigilance in general, which might be related to the low processing efficiency in dealing with high-load math tasks. These findings support the ACT and further reveal the mechanism of MA in elementary school children from a cognitive perspective.

Knockdown of circ_0007290 alleviates oxygen-glucose deprivation-induced neuronal injury by regulating miR-496/PDCD4 axis.

Circular RNAs (circRNAs) are highly enriched in the brain and involved in many types of central nervous system pathologies. Herein, this study aimed to investigate the role and mechanism of circ_0007290 in ischemic stroke. The oxygen-glucose deprivation (OGD) model was established with the HCN-2 cells in vitro. Levels of genes and proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In vitro experiments were conducted using cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry and ELISA, respectively. The levels of lactate dehydrogenase (LDH) were measured using the commercial kit. RNA pull-down and dual-luciferase reporter assay were used to identify the target relationship between miR-496 and circ_0007290 or PDCD4 (programmed cell death protein 4). Circ_0007290 expression was elevated in acute ischemic stroke (AIS) patients and OGD-induced cell injury model. OGD stimulation induced neuronal apoptosis, promoted LDH release, and enhanced inflammation in HCN-2 cells, which all were reversed by the knockdown of circ_0007290. Mechanistically, circ_0007290 served as a sponge for miR-496 to relieve the repression of miR-496 on the expression of its target PDCD4. Moreover, miR-496 inhibition or PDCD4 overexpression abolished the inhibitory effects of circ_0007290 knockdown OGD-evoked neuronal injury. Knockdown of circ_0007290 alleviated OGD-induced neuronal injury by regulating miR-496/PDCD4 axis, providing a novel insight into the pathology of ischemic stroke.

The Open Brain Consent: Informing research participants and obtaining consent to share brain imaging data.

Having the means to share research data openly is essential to modern science. For human research, a key aspect in this endeavor is obtaining consent from participants, not just to take part in a study, which is a basic ethical principle, but also to share their data with the scientific community. To ensure that the participants' privacy is respected, national and/or supranational regulations and laws are in place. It is, however, not always clear to researchers what the implications of those are, nor how to comply with them. The Open Brain Consent (https://open-brain-consent.readthedocs.io) is an international initiative that aims to provide researchers in the brain imaging community with information about data sharing options and tools. We present here a short history of this project and its latest developments, and share pointers to consent forms, including a template consent form that is compliant with the EU general data protection regulation. We also share pointers to an associated data user agreement that is not only useful in the EU context, but also for any researchers dealing with personal (clinical) data elsewhere.

Comparative analysis of the vaginal microbiome of Chinese women with Trichomonas vaginalis and mixed infection.

The high prevalence and serious long-term sequelae of Trichomonas vaginalis (TV) infection worldwide is of a particular concern; however, data regarding the differences in the composition of the vaginal microbiome in cases of single TV infection or mixed infections (i.e., presence of TV and bacterial vaginosis) are scarce. We employed metagenomic sequencing analyses to study gene expression in the vaginal microbiota of women with single TV infection and mixed infection. Women infected with only TV had significantly higher abundance of Mycoplasma, Prevotella, and Streptococcus compared to women without vaginal infection (control). Women infected with mixed infections had a significantly higher abundance of Mycoplasma, Prevotella, Streptococcus, Anaerococcus, Dialister, Peptostreptococcus, Peptoniphilus and a significantly lower abundance of Lactobacillus than TV alone. Mixed infections had a significantly higher abundance of Prevotella, Anaerococcus and Dialister. Our findings suggest that the bacterial community composition varies among healthy women, women with TV alone, and those with mixed infection, and we hypothesize that these bacterial vaginosis (BV)-associated bacterium may play a role in the pathogenesis and recurrence of TV. Probiotic pessaries may necessarily be the answer because shifting the vaginal microbiome and host responses is probably a complex undertaking.

Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/ß-Catenin/CaMKIV pathway.

OBJECTIVE: To investigate the effect of sevoflurane on inflammation of microglia in hippocampus of neonatal rats, and to investigate whether the related mechanism is related to Wnt/ß-Catenin/CaMKIV pathway. METHODS: Neonatal rats were anesthetized with 2% or 3% sevoflurane for 4 h a day for 3 consecutive days. Water maze test was used to detect the effect of sevoflurane anesthesia on memory function of neonatal rats. H&E and Nissl staining were used to observe the pathological damage of hippocampal area of neonatal rats induced by sevoflurane anesthesia. The expression of microglial marker Iba-1 was detected by Immunofluorescence. Immunofluorescence and WB were used to detect the expression CD32b, CD86, TNF-α, IL-6, Wnt3a, ß-Catenin and CaMKIV in hippocampus. To further explore the related mechanism, Wnt-3α inhibitor and activator was treated to study the effect of sevoflurane on microglial inflammation in hippocampus of neonatal rats. RESULTS: Sevoflurane anesthesia significantly increased escape latency time, reduced platform crossing times, and damaged the learning and memory ability of neonatal rats. H&E and Nissl staining results showed that sevoflurane anesthesia caused obvious damage to the hippocampus of neonatal rats. Sevoflurane anesthesia promoted the expression of Iba-1 and activated microglia. Sevoflurane anesthesia not only significantly increased the positive expression of CD32b, CD86, TNF-α and IL-6, but also decreased the expression of Wnt3a, ß-Catenin and CaMKIV. These results suggested that sevoflurane inhibited Wnt/ß-Catenin/CaMKIV pathway. CONCLUSION: Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/ß-Catenin/CaMKIV pathway.

Lysosomal membrane permeabilization and cell death.

Lysosomes are membrane-enclosed organelles that mediate the intracellular degradation of macromolecules. They play an essential role in calcium regulation and have emerged as key signaling hubs in controlling the nutrient response. Maintaining lysosomal integrity and function is therefore crucial for cellular homeostasis. Different forms of stress can induce lysosomal membrane permeabilization (LMP), resulting in the translocation to the cytoplasm of intralysosomal components, such as cathepsins, inducing lysosomal-dependent cell death (LDCD). Here, we review recent advances that have furthered our understanding of the molecular mechanisms of LMP and the methods used to detect it. We discuss several endolysosomal damage-response mechanisms that mediate the repair or elimination of compromised lysosomes and summarize the role of LMP and cathepsins in LDCD and other cell death pathways. Finally, with the emergence of lysosomes as promising therapeutic targets for several human diseases, we review a variety of therapeutic strategies that seek to either destabilize lysosomes or to maintain, enhance or restore lysosomal function.

Involvement of homodomain interacting protein kinase 2-c-Jun N-terminal kinase/c-Jun cascade in the long-term synaptic toxicity and cognition impairment induced by neonatal Sevoflurane exposure.

Sevoflurane is one of the most widely used anesthetics with recent concerns rising about its pediatric application. The synaptic toxicity and mechanisms underlying its long-term cognition impairment remain unclear. In this study, we investigated the expression and roles of homeodomain interacting protein kinase 2 (HIPK2), a stress activating kinase involved in neuronal survival and synaptic plasticity, and its downstream c-Jun N-terminal kinase (JNK)/c-Jun signaling in the long-term toxicity of neonatal Sevoflurane exposure. Our data showed that neonatal Sevoflurane exposure results in impairment of memory, enhancement of anxiety, less number of excitatory synapses and lower levels of synaptic proteins in the hippocampus of adult rats without significant changes of hippocampal neuron numbers. Up-regulation of HIPK2 and JNK/c-Jun was observed in hippocampal granular neurons shortly after Sevoflurane exposure and persisted to adult. 5-((6-Oxo-5-(6-(piperazin-1-yl)pyridin-3-yl)-1,6-dihydropyridin-3-yl)methylene)thiazolidine-2,4-dione trifluoroacetate, antagonist of HIPK2, could significantly rescue the cognition impairment, decrease in long-term potentiation, reduction in spine density and activation of JNK/c-Jun induced by Sevoflurane. JNK antagonist SP600125 partially restored synapse development and cognitive function without affecting the expression of HIPK2. These data, in together, revealed a novel role of HIPK2-JNK/c-Jun signaling in the long-term synaptic toxicity and cognition impairment of neonatal Sevoflurane exposure, indicating HIPK2-JNK/c-Jun cascade as a potential target for reducing the synaptic toxicity of Sevoflurane. Cover Image for this issue: doi: 10.1111/jnc.14757.

Bias twisting in side-tapered PMF Sagnac loop interferometer for simultaneous measurement of directional torsion and temperature.

The polarization-maintaining fiber-based Sagnac loop interferometer (PSLI) is frequently applied in directional torsion measurement, but may suffer from a large temperature cross talk. In this study, a novel method was proposed for fabrication of side-tapered PSLI by a two-step arc-discharge technique at the splicing point. The energy distribution of the taper region was characterized, and comprehensive tests were performed in terms of torsion and temperature. The experimental results showed that, through bias twisting, the measuring areas were effectively gapped and highly sensitive torsion and temperature responses were gained simultaneously. With a small wavelength shift, the torsion sensitivity reached 13.54 dB/rad in the range from -30 to 30 rad/m. Moreover, the temperature sensitivity was found to be -1.579nm/∘C, with a near-zero intensity fluctuation. Therefore, the sensor fabricated herein successfully achieves simultaneous measurement of directional torsion and temperature with high sensitivity and ultralow cross talk. The proposed scheme has the merits of practicality, low cost, and ease of operation, and is very promising for multiparameter engineering monitoring.

miR-146a promotes proliferation, invasion, and epithelial-to-mesenchymal transition in oral squamous carcinoma cells.

Epithelial-to-mesenchymal transition (EMT) is key to invasion and metastasis by oral squamous carcinoma (OSCC) cells. MicroRNAs (miRNAs) such as miRNA-146a are known to be upregulated in OSCC. However, it is unclear whether they are involved in driving EMT. Here, we investigated the effect of miR-146a overexpression on proliferation, migration, and EMT in OSCC cells. OSCC cells were transfected with a plasmid expressing miR-146a precursor. Cell lines that stably overexpressed miRNA-146a were assessed for proliferation, colony formation, and invasiveness in vitro. Expression of markers and regulators of EMT, cell motility, and invasion were measured by qRT-PCR and western blot. Potential miRNA-146a binding sites in the 3'UTR of ST8SIA4 were identified by bioinformatic analysis. To confirm that miRNA-146a binds to and regulates ST8SIA4, we transfected OSCC cell lines with miRNA-146a mimics and a luciferase reporter construct containing either the wild type or mutant 3'UTR of ST8SIA4. OSCC cell lines that overexpressed miR-146a displayed higher proliferation, colony formation, invasion, and MMP-2 activity than cells transfected with a control vector. Overexpression of miR-146a also decreased expression of the epithelial cell marker E-cadherin and increased expression of Twist1, a transcription factor that promotes EMT, as well as markers associated with mesenchymal cells (vimentin and N-cadherin) and tumor invasion (p-paxillin and p-cortactin). Luciferase expression was lower in OSCC cells transfected with miRNA-146a mimics or with luciferase constructs carrying the wild type, but not mutant, 3'UTR of ST8SIA4. Overexpression of miR-146a promotes EMT phenotypes and may drive tumorigenesis and progression in OSCC, making it a useful target for future OSCC treatments.

Antimicrobial Susceptibility Testing of Metronidazole and Clindamycin against Gardnerella vaginalis in Planktonic and Biofilm Formation.

BACKGROUND: Bacterial vaginosis (BV), one of the most common vaginal ecosystem-related microbiologic syndromes, is the most common disorder in women of reproductive age. Gardnerella (G.) vaginalis is the predominant species causing this infection. Our aim was to compare the antimicrobial susceptibilities of metronidazole and clindamycin against G. vaginalis at planktonic and biofilm levels. METHODS: From September 2019 to October 2019, we recruited a total of 10 patients with BV who underwent gynecological examinations at Beijing Obstetrics and Gynecology Hospital. G. vaginalis isolates were obtained from the vagina and identified using their characteristic colony morphology. Sequence data of clinical G. vaginalis isolates were confirmed by comparing 16S rDNA sequences. Subsequently, clinical isolates were evaluated for antimicrobial susceptibilities in vitro to metronidazole and clindamycin at planktonic and biofilm levels. The minimum inhibitory concentration (MIC) for metronidazole and clindamycin was evaluated by antimicrobial susceptibility testing. The minimum biofilm eradication concentration (MBEC) was evaluated by the biofilm inhibition assay. RESULTS: Planktonic clinical isolates showed a significantly higher susceptibility rate (76.67%) and lower resistance rate (23.33%) to clindamycin than to metronidazole (susceptibility rate: 38.24%; resistance rate: 58.82%; P < 0.05 for both). Furthermore, in comparison to planktonic isolates, the minimum inhibitory concentration (MIC) of metronidazole was significantly higher for biofilm-forming isolates (7.3 ± 2.6 µg/mL vs. 72.4 ± 18.3 µg/mL; P=0.005); the resistance rate was 27.3%, and the minimum biofilm eradication concentration (MBEC) was >128 µg/mL. Moreover, the MIC of clindamycin was higher too for biofilm-forming isolates (0.099 ± 0.041 µg/mL vs. 23.7 ± 9.49 µg/mL; P=0.034); the resistance rate was 27.3%, and the MBEC of clindamycin was 28.4 ± 6.50 µg/mL. CONCLUSION: Our results indicate that in comparison to metronidazole, clindamycin seems to be a better choice to tackle G. vaginalis as it exhibits a relatively higher susceptibility rate and lower resistance rate.

Fiber Ring Laser Directional Torsion Sensor with Ultra-Wide Linear Response.

In this paper, a comprehensive passive torsion measurement is performed firstly in a 40-cm-long polarization maintaining fiber-based Sagnac interferometer (PMF-SI), and the non-linear torsion response is found and investigated. Then, a fiber laser torsion sensor (FLTS) with a dual-ring-cavity structure is proposed and experimentally demonstrated, in which the PMF-SI is utilized as the optical filter as well as the sensing unit. In particular, the highly sensitive linear range is adjusted through fine phase modulation, and owing to the flat-top feature of fringes, an ~83.6% sensitivity difference is effectively compressed by the generated lasing. The experimental results show that, without any pre-twisting, the ultra-wide linear response from -175 to 175 rad/m is gained, and the torsion sensitivities are 2.46 and 1.55 nm/rad with high linearity (>0.99) in the clockwise and anti-clockwise directions, respectively. Additionally, a high extinction ratio (>42 dB) and small line-width (~0.14 nm) are obtained in the proposed FLTS, and the corresponding detection limit reaches 0.015 rad/m.

Autophagy: A new concept in autoimmunity regulation and a novel therapeutic option.

Nowadays, pharmacologic treatments of autoinflammatory diseases are largely palliative rather than curative. Most of them result in non-specific immunosuppression, which can be associated with broad disruption of natural and induced immunity with significant and sometimes serious unwanted injuries. Among the novel strategies that are under development, tools that modulate the immune system to restore normal tolerance mechanisms are central. In these approaches, peptide therapeutics constitute a class of agents that display many physicochemical advantages. Within this class of potent drugs, the phosphopeptide P140 is very promising for treating patients with lupus, and likely also patients with other chronic inflammatory diseases. We discovered that P140 targets autophagy, a finely orchestrated catabolic process, involved in the regulation of inflammation and in the biology of immune cells. In vitro, P140 acts directly on a particular form of autophagy called chaperone-mediated autophagy, which seems to be hyperactivated in certain subsets of lymphocytes in lupus and in other autoinflammatory settings. In lupus, the "correcting" effect of P140 on autophagy results in a weaker signaling of autoreactive T cells, leading to a significant improvement of pathophysiological status of treated mice. These findings also demonstrated ex vivo in human cells, open novel avenues of therapeutic intervention in pathological conditions, in which specific and not general targeting is highly pursued in the context of the new action plans for personalized medicines.

Rescue of autophagy and lysosome defects in salivary glands of MRL/lpr mice by a therapeutic phosphopeptide.

Sjögren's syndrome is a multifactorial systemic autoimmune disorder characterized by lymphocytic infiltrates in exocrine organs. Patients present with sicca symptoms, such as extensive dry eyes and dry mouth, and parotid enlargement. Other serious complications include profound fatigue, chronic pain, major organ involvement, neuropathies and lymphomas. Current treatments only focus on relieving symptoms and do not target the origin of the disease, which is largely unknown. The question we addressed here was whether some defects exist in autophagy processes in Sjögren's syndrome and if they can be corrected or minimized using an appropriate mechanism-driven treatment targeting this central survival pathway. Using a recognized murine model of secondary Sjögren's syndrome, we identified molecular alterations of autophagy occurring in the salivary glands of MRL/lpr mice, and discovered that opposite (up- or down-regulated) autophagy events can arise in distinct organs of the same mouse strain, here in lymphoid organs and salivary glands. We showed further that the therapeutic P140 peptide, known to directly act on chaperone-mediated autophagy, rescued MRL/lpr mice from cellular infiltration and autophagy defects occurring in salivary glands. Our findings provide a proof-of-concept that targeting autophagy might represent a promising therapeutic strategy for treating patients with Sjögren's syndrome.

Prognostic significance of IKZF1 deletion in adult B cell acute lymphoblastic leukemia: a meta-analysis.

The IKAROS family zinc finger 1 (IKZF1) gene is frequently altered in adults with B cell acute lymphoblastic leukemia (ALL). Although many studies have indicated that IKZF1 alterations might be associated with poor outcomes in adults with ALL, the results remain controversial. A previous meta-analysis demonstrated the negative prognostic significance of IKZF1 deletion in ALL. However, most of the included studies (14 out of 15) were conducted in pediatric patients with ALL, and age was identified as a significant source of heterogeneity. Thus, performing the present meta-analysis provides valuable information to further elucidate the prognostic value of IKZF1 deletion in adults with ALL. Eight studies were identified that had been published prior to August 1, 2016. The studies included a total of 1008 patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/progression-free survival (PFS)/event-free survival (EFS) were pooled to estimate the prognostic power of IKZF1 deletion. Pooled HRs suggested that IKZF1 deletion had a negative impact on both OS (HR = 1.40, 95% CI 1.13-1.73) and DFS/RFS/PFS/EFS (HR = 1.67, 95% CI 1.28-2.17) in the overall population. Subgroup analyses indicated that IKZF1 deletion could independently predict unfavorable OS (HR = 1.60, 95% CI 1.25-2.06) and DFS/RFS/PFS/EFS (HR = 1.67, 95% CI 1.28-2.17) in BCR-ABL1-negative but not in BCR-ABL1-positive B cell ALL patients. Our meta-analysis suggests that IKZF1 deletion is a poor prognostic factor for adults with B cell ALL and may be more valuable in BCR-ABL1-negative B cell ALL patients.

Functional identification of glutamate cysteine ligase and glutathione synthetase in the marine yeast Rhodosporidium diobovatum.

Glutathione (GSH) fulfills a variety of metabolic functions, participates in oxidative stress response, and defends against toxic actions of heavy metals and xenobiotics. In this study, GSH was detected in Rhodosporidium diobovatum by high-performance liquid chromatography (HPLC). Then, two novel enzymes from R. diobovatum were characterized that convert glutamate, cysteine, and glycine into GSH. Based on reverse transcription PCR, we obtained the glutathione synthetase gene (GSH2), 1866 bp, coding for a 56.6-kDa protein, and the glutamate cysteine ligase gene (GSH1), 2469 bp, coding for a 90.5-kDa protein. The role of GSH1 and GSH2 for the biosynthesis of GSH in the marine yeast R. diobovatum was determined by deletions using the CRISPR-Cas9 nuclease system and enzymatic activity. These results also showed that GSH1 and GSH2 were involved in the production of GSH and are thus being potentially useful to engineer GSH pathways. Alternatively, pET-GSH constructed using vitro recombination could be used to detect the function of genes related to GSH biosynthesis. Finally, the fermentation parameters determined in the present study provide a reference for industrial GSH production in R. diobovatum.

Epidemiologic characterization of 30 confirmed cases of human infection with avian influenza A(H7N9) virus in Hangzhou, China.

BACKGROUND: We examined the clinical and epidemiological characteristics of 30 cases of human infection with avian influenza A(H7N9) virus in Hangzhou and investigated their external environments to provide evidence for contact tracing and disease prevention and control. METHODS: The cases confirmed from April 1 through May 1, 2013 were studied. Field epidemiologic surveys were conducted to collect the clinical and epidemiologic data. Case-related and environmental specimens were collected for etiologic detection. RESULTS: Thirty cases of human infection with avian influenza A(H7N9) virus were confirmed in Hangzhou from April 1 through May 1, 2013, including one pregnant woman and three deaths. The median age of the patients was 62 years (range: 38-86 years). Twenty-three of the patients were men (76.67%). The median duration between disease onset and occurrence of respiratory failure and confirmed diagnosis was 5 and 6 days, respectively. Maximum medical observation of 666 close contacts of the patients revealed no irregularity. Of 314 external environmental specimens, the overall positive detection rate of H7N9 nucleic acid was 28.98%. Eight districts of Hangzhou city had positive detections in the external environments, the highest rate being in Yuhang District (78.13%). Statistical analysis of the specimen collection locations indicates a significant difference between the case-linked locations and the non-case locations (χ2 = 16.563, p < 0.05) in terms of H7N9 viral nucleic acid detection rate. No epidemiologic link has been found among the 30 cases. CONCLUSIONS: Most of the infected were retired individuals aged 60 years or older. Men made the majority. The cases are sporadic at present, with no evidence of human-to-human transmission. Exposures to poultry and live poultry markets may be important sources of infection.