Integrated Transcriptomics and Metabolomics Analyses Provide Insights into Qingke in Response to Cold Stress.

The survival and productivity of qingke in high altitude (>4300 m, average yearly temperature <0 °C) of the Tibetan Plateau are significantly impacted by low-temperature stress. Uncovering the mechanisms underlying low-temperature stress response in cold-tolerant qingke varieties is crucial for qingke breeding. Herein, we conducted a comprehensive transcriptomic and metabolomic analysis on cold-sensitive (ZQ) and cold-tolerant (XL) qingke varieties under chilling and freezing treatments and identified lipid metabolism pathways as enriched in response to freezing treatment. Additionally, a significant positive correlation was observed between the expression of C-repeat (CRT) binding factor 10A (HvCBF10A) and Gly-Asp-Ser-Leu-motif lipase (HvGDSL) and the accumulation of multiple lipids. Functional analysis confirmed that HvCBF10A directly binds to HvGDSL, and silencing HvCBF10A resulted in a significant decrease in both HvGDSL and lipid levels, consequently impairing the cold tolerance. Overall, HvCBF10A and HvGDSL are functional units in actively regulating lipid metabolism to enhance freezing stress tolerance in qingke.

Vancomycin-loaded silk fibroin microspheres in an injectable hydrogel for chronic osteomyelitis therapy.

Introduction: Chronic osteomyelitis remains a clinical challenge in orthopedics. Methods: In this study, silk fibroin microspheres (SFMPs) loaded with vancomycin are entrapped in an injectable silk hydrogel to form a vancomycin delivery system for treatment of chronic osteomyelitis. Results and Discussion: Vancomycin showed continuous release from the hydrogel for up to 25 days. The hydrogel shows strong antibacterial activity against both Escherichia coli and Staphylococcus aureus and a long antibacterial duration of 10 days without a decrease in the antibacterial effect. The injection of vancomycin-loaded silk fibroin microspheres entrapped in the hydrogel into the infected site of rat tibia reduced bone infection and improved bone regeneration compared with other treatment groups. Conclusion: Thus, the composite SF hydrogel features a sustained-release profile and good biocompatibility, making it promising for application in osteomyelitis treatment.

Genome-Wide Splicing Quantitative Expression Locus Analysis Identifies Causal Risk Variants for Non-Small Cell Lung Cancer.

Alternative RNA splicing is an essential mechanism linking genetic variation to human diseases. While the signals from genome-wide association studies (GWAS) have been linked to expression quantitative trait loci (eQTL) in previous studies, further work is needed to better elucidate the relationship to other genetic regulatory mechanisms, such as splicing QTLs (sQTL). Here, we performed a genome-wide sQTL analysis to identify variants that might affect RNA splicing in 1,010 non-small cell lung cancer (NSCLC) samples from The Cancer Genome Atlas. The identified sQTLs were largely independent of eQTLs and were predominantly enriched in exonic regions, genetic regulatory elements, RNA-binding protein (RBP) binding sites, and known NSCLC risk loci. In addition, target genes affected by sQTLs (sGenes) were involved in multiple processes in cancer, including cell growth, apoptosis, metabolism, immune infiltration, and drug responses, and sGenes were frequently altered genetically in NSCLC. Systematic screening of sQTLs associated with NSCLC risk using GWAS data from 15,474 cases and 12,375 controls identified an sQTL variant rs156697-G allele that was significantly associated with an increased risk of NSCLC. The association between the rs156697-G variant and NSCLC risk was further validated in two additional large population cohorts. The risk variant promoted inclusion of GSTO2 alternative exon 5 and led to higher expression of the GSTO2 full-length isoform (GSTO2-V1) and lower expression of the truncated GSTO2 isoform (GSTO2-V2), which was induced by RBP quaking (QKI). Mechanistically, compared with GSTO2-V1, GSTO2-V2 inhibited NSCLC cells proliferation by increasing S-glutathionylation of AKT1 and thereby functionally blocking AKT1 phosphorylation and activation. Overall, this study provides a comprehensive view of splicing variants linked to NSCLC risk and provides a set of genetic targets with therapeutic potential. SIGNIFICANCE: Analysis of sQTL reveals the role of genetically driven mRNA splicing alterations in NSCLC risk and elucidates that rs156697 variant impacts risk by altering GSTO2 splicing.

Integrative metabolomic and transcriptomic analyses reveal the mechanisms of Tibetan hulless barley grain coloration.

Cereal grains accumulate anthocyanin during developmental process. The anthocyanin content increases at grain filling stages to develop grain coloration in cereals. However, anthocyanin biosynthesis responsible for grain coloring and its regulatory mechanisms controlled by structural and functional genes remain unclear. Therefore, this study aimed to explore the global map of metabolic changes linked to grain coloration of Tibetan hulless barley (qingke) using an integrative metabolome and transcriptome approach. Grains from three colored qingke cultivars at different developmental stages were considered for molecular and metabolic investigations. A total of 120 differentially accumulated metabolites (DAMs) and 8,327 differentially expressed genes (DEGs) were filtered. DEGs were mainly enriched in the phenylpropanoid and flavonoid pathways. The transcript levels of anthocyanin biosynthesis genes (PAL, C4H, 4CL, CHS, FLS, F3H, F3'H, DFR, ANS, GT, OMT, and MAT) significantly upregulate in colored qingke compared to the non-colored variety. During grain development and maturation, the strong correlation of HvMYC2 expression with anthocyanin contents and anthocyanin biosynthesis genes suggested it as a critical gene in anthocyanin accumulation. Further results confirmed that HvMYC2 could be activated by HvMYB and be a positive regulator of UV-B and cold tolerance in qingke. In addition, verification based on enzymatic assays indicated that six key modifier enzymes could catalyze glycosylation, malonylation, and methylation of anthocyanins, thereby dissecting the major anthocyanin modification pathway in colored qingke. Overall, our study provides global insight into anthocyanin accumulation and the mechanism underlying grain coloration in qingke.

Ultrasound-guided microwave ablation as a palliative treatment for mycosis fungoides eyelid involvement: A case report.

BACKGROUND: Mycosis fungoides (MF) is a form of lymphoma derived from heterogeneous T cells, and eyelid involvement is extremely rare. The common methods to treat eyelid involvement are radiotherapy and chemotherapy, but their efficacies are limited. Herein, we report a case of advanced-stage MF eyelid involvement, propose ultrasound (US)-guided microwave ablation (MWA) therapy and present a literature review. CASE SUMMARY: A male patient was admitted to our hospital in June 2018 and diagnosed with MF via radiological and histopathological examinations. The patient's condition was not well controlled by various conventional chemotherapies. US-guided MWA was performed to relieve the patient's symptoms and improve his quality of life, showing satisfactory efficacy. CONCLUSION: Eyelid involvement is one of the most troublesome clinical problems for advanced-stage MF patients. This is the first report on the use of US-guided MWA as a palliative therapy for MF eyelid involvement; the treatment successfully relieved the patient's clinical symptoms and reduced his anxiety behaviours. Our study sheds new light on methods for improving the clinical management of eyelid involvement in MF.

A "bottle-around-ship" method to encapsulated carbon nitride and CdTe quantum dots in ZIF-8 as the dual emission fluorescent probe for detection of mercury (II) ion.

A facile and efficient "bottle-around-ship" approach for preparing the ratiometric fluorescent probe has been developed by encapsulating the red-colored fluorescence CdTe quantum dots (QDs) and blue-colored fluorescence graphitic carbon nitride quantum dots (g-CNQDs) into the zeolitic imidazolate metal-organic frameworks (ZIF-8) in one step. At a single excitation of 360 nm, the obtained probe ZIF-8@g-CNQD/CdTe shows the dual-emission peaked at 450 and 633 nm, respectively. The red emission of CdTe QDs is selectively quenched by the Hg2+, whereas the blue fluorescence of g-CNQDs as an internal reference is insensitive, resulting in an apparent color transformation from pink to blue for special recognition of Hg2+. By this approach, the relative fluorescence intensity ratio (F633/F450) decreased linearly with increasing Hg2+ concentration in the 0.2-3.5 µM range with a low limit of detection (LOD) of ~ 46 nM. Therefore, we demonstrate that this "bottle-around-ship" process provides a new strategy for the construction of ratiometric fluorescent Hg2+ probes with good simplicity, high efficiency, and excellent stabilities. Moreover, the obtained Hg2+ fluorescent probe shows good results in the detection of actual samples.

Combined noradrenergic plus antimuscarinic agents for obstructive sleep apnea - A systematic review and meta-analysis of randomized controlled trials.

Currently, no pharmacotherapy is routinely used for obstructive sleep apnea (OSA). Recently, combined noradrenergic plus antimuscarinic agents have been evaluated for the treatment of OSA in several trials. This systematic review and meta-analysis following PRISMA guidelines investigated the efficacy and safety of this combination drug regimen for the treatment of OSA. Seven databases were systematically screened for randomized controlled trials (RCTs) studying combined noradrenergic plus antimuscarinic agents for OSA to April 2022. Nine RCTs were identified for systematic review and five for meta-analysis. There were significant differences between OSA patients taking noradrenergic plus antimuscarinic agents and placebo with respect to sleep apnea-hypopnea index [mean difference (MD) -11.27 events/h, 95%CI (-21.69, -0.84) events/h; P = 0.03]; nadir oxygen saturation [MD 5.06%, 95% CI (2.57, 7.55)%; P < 0.0001], and arousal index [MD -8.17 events/h, 95% CI (-15.01, -1.33) events/h; P = 0.02] but not sleep efficiency. Our systematic review revealed that drug therapy modestly improved loop gain and upper airway collapsibility but decreased arousal threshold. A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on one night significantly reduced OSA severity and improved OSA upper airway function. The long-term efficacy and safety of drug combinations in OSA patients now require further study.

blaKPC-24-Harboring Aeromonas veronii from the Hospital Sewage Samples in China.

KPC-24, different from KPC-2 by a single amino acid alteration at codon 6 (R6P), was initially discovered in Klebsiella pneumoniae in Chile. Here, we reported KPC-24-producing Aeromonas veronii isolates from hospital sewage in China. The blaKPC-24 was cloned and the MICs were tested against ß-lactams antimicrobial agents. KPC-24 exhibited a ß-lactam susceptibility profile similar to that of KPC-2. Whole-genome sequencing and analysis revealed that blaKPC-24 was located within a Tn6296-related region on an IncP-6 plasmid. IMPORTANCE Our study described a variant of K. pneumoniae carbapenemase (KPC), KPC-24, from two A. veronii strains isolated from hospital sewage, in which antibiotics, biocides, pharmaceuticals, and heavy metals may supply an appropriate condition for the evolution of carbapenemases. Some variants exhibited stronger hydrolysis activity to antibiotics and gave rise to a major public health concern. More seriously, Aeromonas species are prevalent in aquatic environments and, thus, may act as a suitable vector for antibiotics-resistance genes and foster the transmission of resistance. We should attach importance to surveying the evolution and transmission of antibiotics-resistance genes.

Lianhuaqingwen alleviates p53-mediated apoptosis in alveolar epithelial cells to prevent LPS-induced ALI.

BACKGROUND: Our previous study found that Lianhuaqingwen reduces lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by suppressing p53-mediated apoptosis. To identify the type of lung cells affected by Lianhuaqingwen, we conducted a cell experiment. METHODS: C57/B6 mice and A549 cells were administered Lianhuaqingwen and LPS. A549 cells were transfected with p53 siRNA to inhibit p53. The degree of ALI in mice was validated by haematoxylin and eosin staining as well as measurement of IL-1ß and MCP-1 levels. In A549 cells, Cell Counting Kit-8 (CCK-8), DHE and TUNEL assays were used to assess cell viability, reactive oxygen species (ROS) production and apoptosis, respectively. Western blot analysis was used to evaluate the protein expression of p53, Bcl-2, Bax, caspase-9 and caspase-3. Co-immunofluorescence was used to detect cytochrome C distribution. KEY FINDINGS: Lianhuaqingwen alleviated LPS-induced ALI in vivo. Lianhuaqingwen at 300 µg/ml increased cell viability, lowered ROS production and reduced apoptotic cells in vitro. Lianhuaqingwen enhanced Bcl-2 expression and reduced Bax, caspase-9 and caspase-3 expression as well as blocked cytochrome C release under LPS stimulation. Treatment with a combination of Lianhuaqingwen and p53 siRNA was more effective than treatment with Lianhuaqingwen alone. CONCLUSION: Lianhuaqingwen inhibits p53-mediated apoptosis in alveolar epithelial cells, thereby preventing LPS-induced ALI.

Development and Validation of a Prognostic Nomogram in Lung Cancer With Obstructive Sleep Apnea Syndrome.

To analyze the prognostic factors and survival rate of lung cancer patients with obstructive sleep apnea (OSA) by nomogram. The nomogram was established by a development cohort (n = 90), and the validation cohort included 38 patients. Factors in the nomogram were identified by Cox hazard analysis. We tested the accuracy of the nomograms by discrimination and calibration, and plotted decision curves to assess the benefits of nomogram-assisted decisions. There were significant difference in sex, apnea hypopnea index (AHI), Tumor Node Metastasis (TNM), coronary heart disease, lowest arterial oxygen saturation [LSpO2 (%)], oxygen below 90% of the time [T90% (min)], the percentage of the total recorded time spend below 90% oxygen saturation (TS90%) and oxygen desaturation index (ODI4) between lung cancer subgroup and lung cancer with OSA subgroup (P < 0.05). Lung cancer patients with OSA age, AHI, TNM, cancer types, BMI and ODI4 were independent prognostic factor. Based on these six factors, a nomogram model was established. The c-index of internal verification was 0.802 (95% CI 0.767-0.885). The ROC curve analysis for the nomogram show 1-year survival (AUC = 0.827), 3-year survival (AUC = 0.867), 5-year survival (AUC = 0.801) in the development cohort were good accuracy. The calibration curve shows that this prediction model is in good agreement. Decision curve analysis (DCA) suggests that the net benefit of decision-making with this nomogram is higher, especially in the probability interval of <20% threshold. The nomogram can predict the prognosis of patients and guide individualized treatment.

Rapamycin ameliorates chronic intermittent hypoxia and sleep deprivation-induced renal damage via the mammalian target of rapamycin (mTOR)/NOD-like receptor protein 3 (NLRP3) signaling pathway.

Rapamycin inhibits the activation of NOD-like receptor protein 3 (NLRP3) by regulating the mammalian target of rapamycin (mTOR) to treat obstructive sleep apnea-related renal injury. Sleep deprivation (SD) and chronic intermittent hypoxia (CIH) mouse models were used to assess the effects of autophagy in vivo. Compared with the control, SD, and CIH groups, the SD+CIH group had lower body weight and higher levels of blood urea nitrogen (BUN), creatinine, and urinary albumin (U-Alb) (P < 0.05); renal injury and oxidative damage occurred in the SD+CIH group, the kidney cell nucleus ruptured, and morphological structure of the cells was unclear in the SD+CIH group. The SD+CIH group demonstrated increased apoptosis compared with the control, SD, and CIH groups using Western blot analysis. Compared to the control, SD, and CIH groups, the SD+CIH group showed a higher degree of microtubule-associated protein light chain 3\ staining. Compared to the SD+CIH group, BUN, creatinine, and U-Alb levels decreased, and apoptosis increased in the SD+CIH+rapamycin group, and the structure of the kidney after rapamycin treatment was well preserved. The mTOR expression was increased in the kidneys of the SD+CIH group. The NLRP3, Gasdermin D (GMDSD), interleukin (IL)-18, IL-1ß, and cleaved-caspase-1 protein levels were higher in the SD+CIH group than the SD+CIH+rapamycin group, and the NLRP3, GMDSD, IL-18, IL-1ß, and cleaved-caspase-1 mRNA levels were higher in the SD+CIH group than the SD+CIH+rapamycin group. Following rapamycin treatment, pyroptosis was suppressed. Rapamycin ameliorates renal damage by inhibiting the mTOR/NLRP3 signaling pathway.

Machine learning-aided risk prediction for metabolic syndrome based on 3 years study.

Metabolic syndrome (MetS) is a group of physiological states of metabolic disorders, which may increase the risk of diabetes, cardiovascular and other diseases. Therefore, it is of great significance to predict the onset of MetS and the corresponding risk factors. In this study, we investigate the risk prediction for MetS using a data set of 67,730 samples with physical examination records of three consecutive years provided by the Department of Health Management, Nanfang Hospital, Southern Medical University, P.R. China. Specifically, the prediction for MetS takes the numerical features of examination records as well as the differential features by using the examination records over the past two consecutive years, namely, the differential numerical feature (DNF) and the differential state feature (DSF), and the risk factors of the above features w.r.t different ages and genders are statistically analyzed. From numerical results, it is shown that the proposed DSF in addition to the numerical feature of examination records, significantly contributes to the risk prediction of MetS. Additionally, the proposed scheme, by using the proposed features, yields a superior performance to the state-of-the-art MetS prediction model, which provides the potential of effective prescreening the occurrence of MetS.

Obstructive Sleep Apnea is Associated with an Increased Prevalence of Polycythemia in Patients with Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with polycythemia. However, there still remain unanswered questions about the relationship between overlap syndrome (OVS), where OSA and COPD coexist, and polycythemia. Here, we aimed to establish the prevalence of polycythemia in OVS patients and to explore the impact of OSA on polycythemia. PATIENTS AND METHODS: Patients with COPD underwent overnight polysomnography (PSG), pulmonary function tests, echocardiography, and complete blood counts. All patients were ethnic Han Chinese and free of prolonged oral corticosteroid use, hematological system disease, severe systemic disease, and other sleep-disordered breathing. OVS was defined as COPD patients with an apnea-hypopnea index ≥15 events/h, and polycythemia was defined as an Hb >165 g/L in men and >160 g/L in women. RESULTS: Eight-hundred and eighty-six patients with COPD were included in the analysis. The prevalence of polycythemia was significantly higher in OVS patients than COPD-alone patients (6.4% vs 2.9%, p < 0.05). The prevalence of polycythemia increased with OSA severity (χ 2 = 7.885, p = 0.007), but not in GOLD grade 3-4 COPD patients (χ 2 = 0.190, p = 0.663). After adjusting for confounders, percentage of total sleep time with SaO2 <90% (TS90) remained independently associated with an increased odds of polycythemia (OR 1.030, 95% CI 1.015-1.046) and, with an increase in TS90, the hemoglobin increased, especially in GOLD grade 1-2 patients (p < 0.05). CONCLUSION: Patients with OVS have a higher prevalence of polycythemia than those with COPD alone, and TS90 is an independent factor for polycythemia, especially in GOLD1-2 COPD patients.

One-year follow-up of 18 women who infected COVID-19 while pregnant.

Data about the sequelae of women who infected COVID-19 while pregnant are scarce. We aimed to describe the prevalence of symptoms, pulmonary functions, and radiological changes at a follow-up of 12 months in 18 pregnant women who developed COVID-19 at different gestational ages. Our results showed that most women who infected COVID-19 while pregnant experienced a progressive improvement of their symptoms within 12 months, however, some still had little COVID-related symptoms but without a reduced quality of life. All their 18 newborns were growing up healthy.

The influence of acute morphine use on obstructive sleep apnea: A systematic review and meta-analysis.

The present study was conducted to systematically evaluate the acute effect of morphine on obstructive sleep apnea (OSA). The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure (CNKI), and Wan-Fang databases were searched for randomised controlled trials studying the influence of morphine on OSA published up to May 24, 2021. The Cochrane risk of bias tool was used to assess study quality and meta-analysis was performed on the included clinical trial results to quantify the impact of morphine on various sleep and respiratory parameters. Three studies (n = 132 patients) were ultimately examined. There were no significant differences between patients with OSA taking morphine and placebo/non-opioids with respect to the sleep Apnea-Hypopnea Index (mean difference [MD] 1.78, 95% confidence interval [CI] -2.41, 5.98; p > 0.05); Oxygen Desaturation Index (MD 1.49, 95% CI -3.21, 6.19; p > 0.05); Obstructive Sleep Apnea Index (MD 0.83, 95% CI -2.08, 3.75; p > 0.05); Hypopnea Index (MD -0.01, 95% CI -2.64, 2.63; p > 0.05); lowest oxygen saturation (MD 0.68, 95% CI -4.50, 5.86; p > 0.05); or sleep oxygen saturation >90% (MD 0.10, 95% CI -1.14, 1.34; p > 0.05). In conclusion, a single dose of 30 or 40 mg morphine does not have a significant effect on sleep or respiratory outcomes compared to placebo in patients with OSA, challenging the orthodoxy that opioids worsen OSA.

Mechanisms Underlying the Effects of Lianhua Qingwen on Sepsis-Induced Acute Lung Injury: A Network Pharmacology Approach.

Background and Purpose: Sepsis is a life-threatening condition associated with secondary multiple organ injury. Acute lung injury (ALI) caused by sepsis has high morbidity and mortality in critical care units. Lianhua Qingwen (LHQW) is a traditional Chinese medicine composing of 11 herbs and 2 medicinal minerals. LHQW exhibits anti-inflammatory activity and is effective in treating pneumonia. Our study aimed to evaluate the effect of LHQW on sepsis-induced ALI and its underlying mechanism. Materials and Methods: A network pharmacology approach was used to predict the bioactive components and effective targets of LHQW in treating ALI. We established ALI model C57/BL6 mice via an intraperitoneal injection of LPS and inhibited p53 expression by pifithrin-α, in order to validate the mechanism by which LHQW exerted protective role in ALI. Hematoxylin-eosin staining was conducted to assess the severity of lung injury. The severity of inflammation was evaluated based on MPO (myeloperoxidase) activity. TUNEL assay was employed to detect apoptotic cells. The levels of p53 and caspase-3 were tested by immunohistochemical staining and Western blotting. The expression levels of Bcl-2, Bax, cytochrome C and caspase-9 were detected by Western blotting. Results: A total of 80 genes were associated with LHQW in the treatment of ALI. After PPI network construction, four active components (quercetin, luteolin, kaempferol and wogonin) and 10 target genes (AKT1, TP53, IL6, VEGFA, TNF, JUN, STAT3, MAPK8, MAPK1, and EGF) were found to be essential for ALI treatment. GO and KEGG analyses indicated that apoptosis pathway was mainly involved in the LHQW-ALI network. Animal experiments showed that LHQW was able to attenuate LPS-induced ALI, and medium-dose LHQW exhibited the most prominent effect. LHQW could inhibit the overexpression of p53 induced by LPS and suppress p53-mediated intrinsic apoptotic pathways by decreasing the levels of Bax, caspase-3 and caspase-9, increasing the expression of Bcl-2, and attenuating the release of cytochrome C in ALI mice. Conclusion: This study reveals that LHQW may alleviate LPS-induced ALI via inhibiting p53-mediated intrinsic apoptosis pathways.

Ablating Aspiration Needle Tract Prior to Microwave Ablation Can Improve Therapeutic Outcomes for Predominantly Cystic Thyroid Nodules.

Purpose: To investigate whether ablating the aspiration needle tract could improve the safety and efficacy of ultrasound-guided microwave ablation (MWA) for predominantly cystic thyroid nodules. Materials and Methods: This retrospective study evaluated 41 predominantly cystic thyroid nodules that underwent MWA between June 2017 and August 2019. The nodules were stratified by different procedures into two groups: the aspiration needle tract was ablated before cyst fluid aspiration and MWA when treating 26 nodules in Group A, while the other 15 nodules in Group B underwent MWA directly after cyst fluid aspiration. Baseline characteristics, intervention time, hospital stays, nodules with intraoperative intracystic hemorrhage, and postoperative complications were compared between the two groups. Volume, volume reduction rate (VRR), compressive score (CS), and aesthetic score (AS) were evaluated during follow-up. Results: Both groups achieved decreases in volume, CS, and AS, as well as an increase in VRR. The volumes and VRRs in Group A at 1, 3, 6, and 12 months were significantly smaller and greater than those in Group B (p < 0.001). The incidence of intraoperative intracystic hemorrhage in Group A was significantly lower than that in Group B (p=0.035). Compared to Group B, hospital stays were much shorter in Group A (p=0.040). There were no significant differences in intervention time, cystic fluid volume or postoperative complications. Conclusion: Aspiration needle tract ablation dramatically reduces the incidence of intraoperative intracystic hemorrhage and markedly improves the efficacy of MWA for predominantly cystic thyroid nodules.

Intermittent hypoxia increases ROS/HIF-1α 'related oxidative stress and inflammation and worsens bleomycin-induced pulmonary fibrosis in adult male C57BL/6J mice.

Obstructive sleep apnea (OSA) has been increasingly recognized as a risk factor for idiopathic pulmonary fibrosis (IPF). The intermittent hypoxia (IH) and re-oxygenation of OSA contribute to poor outcomes of IPF, however, the potential mechanism remains unknown. Here, C57BL/6J mice were administered intratracheal injection of Bleomycin (BLM) or saline and then exposed to IH (alternating cycles of FiO2 21% for 60S and FiO2 10% for 30 s, 40 cycles/hour, 8 h/day) to mimic OSA or intermittent air (IA) for 4 days, 8 days or 21 days. This study found that pulmonary fibrosis in BLM + IH treated mice was more severe than that in BLM + IA group at day 8 and 21, but not observed at day 4. Besides, the expression of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α),which are related to hypoxia reduced oxidative stress and inflammation, were higher in BLM + IH treated mice than BLM + IA mice, and IH increased these indexes in BLM treated mice from day 4 to day 21. Interestingly, a positive linear correlation between the HIF-1α expression and hydroxyproline (HYP) content was observed. We further found some inflammatory cells in bronchoalveolar lavage fluid were increased significantly from day 4 to 21, and there was a positive correlation between inflammation and ROS expression. Our results demonstrated that IH aggravated BLM-induced pulmonary fibrosis, and ROS/HIF-1α related oxidative stress and inflammation involved. The increase of ROS/HIF-1α related oxidative stress and inflammation may be a potential mechanism of moderate-to-severe OSA in potentiating pulmonary fibrosis of IPF, which warrants further study.

Prognostic and Immunological Role of Gasdermin E in Pan-Cancer Analysis.

Despite accumulating cell- or animal-based experiments providing the relationship between Gasdermin E (GSDME) and human diseases, especially in malignant cancers, no pan-cancer analysis about the function of GSMDE in cancer management can be available up to date. Our research, for the first time, explored the potential carcinogenic role of GSDME across 33 tumors from the public platform of TCGA (The cancer genome atlas) database. GSDME is highly expressed in most malignant cancers, and obvious relationship exists between GSDME level and survival prognosis of cancer patients. The expression of GSDME was statically associated with the cancer-associated fibroblast infiltration in diverse cancer types, such as BLCA, CHOL, GBM, KIRC, LIHC, MESO, STAD, and UCEC. Furthermore, pyroptosis, sensory perception of sound, and defense response to bacterium were involved in the functional mechanisms of GSDME expression from GO analysis. Last but not the least, in vitro experiments were also performed to identify GSDME-induced pyroptosis. Our first pan-cancer analysis of GSDME not only broadens the understanding of the carcinogenic roles of GSDME but also provides a promising therapeutic strategy for benefiting an increasing number of cancerous patients based on GSDME-induced pyroptosis.

Identification of biomarkers associated with cervical lymph node metastasis in papillary thyroid carcinoma: Evidence from an integrated bioinformatic analysis.

Integrated analysis of accumulated data is an effective way to obtain reliable potential diagnostic molecular of cervical lymph node metastases (LNM) in papillary thyroid carcinoma (PTC). The benefits of prophylactic lymph node dissection (PLND) for these clinically node-negative (cN0) patients remained considerable controversies. Hence, elucidation of the mechanisms of LNM and exploration of potential biomarkers and prognostic indicators are essential for accurate diagnosis of LNM in PTC patients. Up to date, advanced microarray and bioinformatics analysis have advanced an understanding of the molecular mechanisms of disease occurrence and development, which are necessary to explore genetic changes and identify potential diagnostic biomarkers. In present study, we performed a comprehensive analysis of the differential expression, biological functions, and interactions of LNM-related genes. Two publicly available microarray datasets GSE60542 and GSE129562 were available from Gene Expression Omnibus (GEO) database. Differentially expressed genes between clinically node-positive (cN1) and cN0 PTC samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Our results identified 48 differentially expressed genes (DEGs) genetically associated with LNM in PTC patients. Gene ontology (GO) analyses revealed the changes in the modules were mostly enriched in the regulation of MHC class II receptor activity, the immune receptor activity, and the peptide antigen binding. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs displayed the intestinal immune network for IgA production, staphylococcus aureus infection, and cell adhesion molecules (CAMs). To screen core genes related to LNM of PTC from the protein-protein interaction network, top 10 hub genes were identified with highest scores. Our results help us understand the exact mechanisms underlying the metastasis of cervical LNM in PTC tissues and pave an avenue for the progress of precise medicine for individual patients.