Explore the vast range of titles available.

Quercetin (3,3′,4′,5,7-pentahydroxyflavone, Qu) is a promising cancer chemo-preventive agent for various cancers because it inhibits disease progression and promotes apoptotic cell death. In our previous study, we demonstrated that Qu could evoke ER stress to enhance drug cytotoxicity in ovarian cancer (OC). However, Qu-induced ER stress in OC is still poorly understood. Here, we demonstrated that Qu evoked ER stress to involve in mitochondria apoptosis pathway via the p-STAT3/Bcl-2 axis in OC cell lines and in primary OC cells. Unexpectedly, inhibition of ER stress did not reverse Qu-induced cell death. Further functional studies revealed that Qu-induced ER stress could activate protective autophagy concomitantly by activating the p-STAT3/Bcl-2 axis in this process. Moreover, the autophagy scavenger 3-MA was shown to enhance Qu’s anticancer effects in an ovarian cancer mice xenograft model. These findings revealed a novel role of ER stress as a “double edge sword” participating in Qu-induced apoptosis of OC and might provide a new angle to consider in clinical studies of biological modifiers that may circumvent drug resistance in patients by targeting protective autophagy pathways.

Protein-coding genes account for only ~2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs). A growing volume of literature has proposed that lncRNAs are important factors in cancer. Colon cancer-associated transcript-1 (CCAT1), an lncRNA, which was first identified in colon cancer, was previously shown to promote tumor development and be a negative prognostic factor in gastric cancer. However, the mechanism through which CCAT1 exerts its oncogenic activity remains largely unknown. Recently, a novel regulatory mechanism has been proposed in which RNAs can cross-talk with each other via competing shared for microRNAs (miRNAs). The proposed competitive endogenous RNAs could mediate the bioavailability of miRNAs on their targets, thus imposing another level of posttranscriptional regulation. In this study, we demonstrated that CCAT1 was upregulated in gallbladder cancer (GBC) tissues. CCAT1 silencing downregulated, whereas CCAT1 overexpression enhanced the expression of miRNA-218-5p target gene Bmi1 through competitively ‘spongeing’ miRNA-218-5p. Our data revealed that CCAT1 knockdown impaired the proliferation and invasiveness of GBC cells, at least in part through affecting miRNA-218-5p-mediated regulation of Bmi1. Moreover, CCAT1 transcript level was correlated with Bmi1 mRNA level in GBC tissues. Together, these results suggest that CCAT1 is a driver of malignancy, which acts in part through ‘spongeing’ miRNA-218-5p.

Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy. Ectopic expression of HULC elicited the autophagy of HCC cells through stabilizing silent information regulator 1 (Sirt1) protein. The investigation for the corresponding mechanism by which HULC stabilized Sirt1 revealed that HULC upregulated ubiquitin-specific peptidase 22 (USP22), leading to the decrease of ubiquitin-mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1. Moreover, we found that miR-6825-5p, miR-6845-5p and miR-6886-3p could decrease the level of USP22 protein by binding to the 3′-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. In addition, we showed that the level of HULC was positively correlated with that of Sirt1 protein in human HCC tissues. Collectively, our data reveals that the pathway ‘HULC/USP22/Sirt1/ protective autophagy’ attenuates the sensitivity of HCC cells to chemotherapeutic agents, suggesting that this pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.

BackgroundSeroma formation is the most common postoperative complication after laparoscopic inguinal hernia repair. Recurrence and seroma formation may be difficult to distinguish. Many adjunctive techniques with which to reduce the incidence of seroma formation after laparoscopic inguinal repair have been described in the literature; however, the evidence for using intraoperative adjunctive techniques is limited. Therefore, the present systematic review was performed to evaluate the effects and limitations of adjunctive techniques used during laparoscopic inguinal hernia repair.MethodsMajor databases (PubMed, Embase, Springer, and Cochrane Library) were searched using the terms “seroma,” “laparoscopic inguinal hernia”, “TAPP”, “TEP”, “inguinal hernia”, “tack”, “barbed suture”, “drainage”, “Endoloop technique”, and “fibrin sealant”. All studies involving adults undergoing laparoscopic/endoscopic inguinal hernioplasty with at least one intervention designed to reduce seroma formation were included.ResultsOf the 965 studies identified, 8 met the inclusion criteria. Six adjunctive techniques were described in the literature. Transversalis fascia (TF) inversion with tacking: one prospective non-randomized controlled study revealed a lower incidence of postoperative seroma after TF inversion with tacking for direct inguinal hernias (4.17% vs. 14.29%, P < 0.05). Endoloop technique: one prospective study of 76 cases involving this technique revealed a low incidence of seroma formation (3.9% at 2 weeks) in direct hernias. Barbed suture closure of TF: one prospective study of 36 direct hernias reported only one clinical palpable seroma that resolved 1 month later. Surgical drains: three trials reported the results of drains, and the pooling results demonstrated significantly less seroma formation in patients with surgical drains (2.1 vs. 23.8%; odds ratio 0.12; 95% confidence interval 0.08–0.19; P < 0.0001). Fibrin sealant: one prospective clinical study of 40 patients with indirect inguinal hernias reported a lower volume (P < 0.001) and lower incidence (5% vs. 15%) of seroma formation in the fibrin group. Distal sac fixation technique: in one prospective study of six patients with large inguinoscrotal hernias, one patient developed a seroma on postoperative day 8.ConclusionSeroma formation is a natural process that cannot be completely prevented following laparoscopic inguinal hernioplasty, especially in patients with direct and large indirect inguinal hernias. Some intraoperative adjunctive techniques are effective in reducing clinically palpable seroma formation in select patients. More randomized controlled trials are needed for further evaluation.

This study investigated the anisotropy of the tensile properties in a duplex stainless steel of 24Cr-5Ni-0.18N based on in situ neutron diffraction experiments. The 24Cr-5Ni-0.18N steel showed a better balance of tensile strength (TS) and uniform elongation (U.El) compared with 329J4L and 329J1 steels. The Lankford value ( r -value) of the 24Cr-5Ni-0.18N steel was comparable to other duplex stainless steels while showing a larger TS. Regarding the anisotropy of the mechanical properties, the results for a test specimen oriented at 45° showed a low yield strength (YS) and TS, but a better U.El and r -value. The hard phase of ferrite ( α ) played an essential role in the YS and TS. The austenite ( γ ) phase, which exhibited a large difference in the lattice strain related to the work hardening, contributed to the U.El, and its effect was further enhanced by the volume fraction of γ . The r -value increased with an increase in the lattice strain of {200} γ or a decrease in that of {200} α in the transverse direction. The lattice strain in the loading and transverse directions obtained by in situ neutron diffraction experiments also helped clarify the excellent r -values of duplex stainless steels.

Ferulic acid, a phenolic acid derived mainly from a Chinese herb Angelica Sinensis Radix (ASR), was reported to reduce the formation of free radicals. Danggui Buxue Tang (DBT), a herbal decoction composing of Astragali Radix (AR) and ASR, has been utilized for more than 800 years in China having known anti-oxidative property. Ferulic acid is a major active ingredient in DBT; however, the role of ferulic acid within the herbal mixture has not been resolved. In order to elucidate the function of ferulic acid within this herbal decoction, a ferulic acid-depleted herbal decoction was created and named as DBTΔfa. The anti-oxidative properties of chemically modified DBT decoction were systemically compared in cultured H9C2 rat cardiomyoblast cell line. The application of DBT and DBTΔfa into the cultures showed functions in (i) decreasing the reactive oxygen species (ROS) formation, detected by laser confocal; (ii) increasing of the activation of Akt; (iii) increasing the transcriptional activity of anti-oxidant response element (ARE); and (iv) increasing the expressions of anti-oxidant enzymes, i.e. NQO1 and GCLM. In all scenario, the aforementioned anti-oxidative properties of DBTΔfa in H9C2 cells were significantly reduced, as compared to authentic DBT. Thus, ferulic acid could be an indispensable chemical in DBT to orchestrate multi-components of DBT as to achieve maximal anti-oxidative functions.

Adenotonsillectomy has been shown to promote “catch-up growth” in children with obstructive sleep apnea. However, its impact on children with mild sleep-disordered breathing (SDB) (i.e., habitual snoring but not frequent obstructive breathing events) remains unclear. This secondary analysis utilized data from the Pediatric Adenotonsillectomy Trial for Snoring (PATS), a multicenter, randomized, single-blinded interventional study. PATS enrolled 459 children aged 3–12 years with mild SDB, all of whom had an obstructive apnea-hypopnea index (OAHI) no greater than 3. These children were randomized to either adenotonsillectomy or watchful waiting and were followed for 12 months. Growth outcomes included height, weight, and body mass index (BMI) expressed in sex- and age-specific percentiles. Sleep parameters were measured using polysomnography. We used multivariable linear regression to assess the statistical significance of differences in these outcomes at 12 months after adenotonsillectomy or randomization between the surgery and watchful waiting groups. Among the 330 children who consented to share data (median age 6.4 years), 231 had an OAHI below 1. After multivariable adjustment, the adenotonsillectomy group had significantly higher increase in height (mean difference: 2.74, 95% confidence interval [CI] 0.33 to 5.15) and weight (mean difference: 2.79, 95% CI 0.29 to 5.28) percentiles at 12-month follow-up, compared with the watchful waiting group. Significant differences were also observed for sleep parameters, including OAHI (mean difference: -1.36, 95% CI -2.07 to -0.65), respiratory disturbance index (mean difference: -0.47, 95% CI -0.74 to -0.20), and oxygen desaturation index (mean difference: -0.99, 95% CI -1.85 to -0.13). The adenotonsillectomy group further demonstrated better sleep architecture, including decreased Stage 1 sleep (mean difference: -1.00, 95% CI -1.90 to -0.11) and increased Stage 2 sleep (mean difference: 2.06, 95% CI 0.54 to 3.59). Subgroup analysis indicated greater benefit of adenotonsillectomy for children at 3–5 years, boys, children with grade III or IV tonsillar hypertrophy, and non-asthmatic children. In conclusion, adenotonsillectomy improved not only sleep-related outcomes but also growth in children with mild SDB, suggesting that surgical intervention may provide additional health benefits beyond symptom relief, particularly in younger children with tonsillar hypertrophy. Trial registration : ClinicalTrials.gov NCT02562040, registered on September 25, 2015.

AimsPerinatal depression threatens the health of maternal women and their offspring. Although screening programs for perinatal depression exist, non-uptake of referral to further mental health care after screening reduces the utility of these programs. Uptake rates among women with positive screening varied widely across studies and little is known about how to improve the uptake rate. This study aimed to systematically review the available evidence on uptake rates, estimate the pooled rate, identify interventions to improve uptake of referral and explore the effectiveness of those interventions.MethodsThis systematic review has been registered in PROSPERO (registration number: CRD42019138095). We searched Pubmed, Web of Science, Cochrane Library, Ovid, Embase, CNKI, Wanfang Database and VIP Databases from database inception to January 13, 2019 and scanned reference lists of relevant researches for studies published in English or Chinese. Studies providing information on uptake rate and/or effectiveness of interventions on uptake of referral were eligible for inclusion. Studies were excluded if they did not report the details of the referral process or did not provide exact uptake rate. Data provided by observational studies and quasi-experimental studies were used to estimate the pooled uptake rate through meta-analysis. We also performed meta-regression and subgroup analyses to explore the potential source of heterogeneity. To evaluate the effectiveness of interventions, we conducted descriptive analyses instead of meta-analyses since there was only one randomised controlled trial (RCT).ResultsOf 2302 records identified, 41 studies were eligible for inclusion, including 39 observational studies (n = 9337), one quasi-experimental study (n = 43) and one RCT (n = 555). All but two studies were conducted in high-income countries. The uptake rates reported by included studies varied widely and the pooled uptake rate of referral was 43% (95% confidence intervals [CI] 35–50%) by a random-effect model. Meta-regression and subgroup analyses both showed that referral to on-site assessment or treatment (60%, 95% CI 51–69%) had a significantly higher uptake rate than referral to mental health service (32%, 95% CI 23–41%) (odds ratio 1.31, 95% CI 1.13–1.52). The included RCT showed that the referral intervention significantly improved the uptake rate (p ＜ 0.01).ConclusionsAlmost three-fifths of women with positive screening results do not take up the referral offers after perinatal depression screening. Referral to on-site assessment and treatment may improve uptake of referral, but the quality of evidence on interventions to increase uptake was weak. More robust studies are needed, especially in low-and middle-income countries.

Parameter specification usually has significant influence on the performance of land surface models (LSMs). However, estimating the parameters properly is a challenging task due to the following reasons: (1) LSMs usually have too many adjustable parameters (20 to 100 or even more), leading to the curse of dimensionality in the parameter input space; (2) LSMs usually have many output variables involving water/energy/carbon cycles, so that calibrating LSMs is actually a multi-objective optimization problem; (3) Regional LSMs are expensive to run, while conventional multi-objective optimization methods need a large number of model runs (typically ~105–106). It makes parameter optimization computationally prohibitive. An uncertainty quantification framework was developed to meet the aforementioned challenges, which include the following steps: (1) using parameter screening to reduce the number of adjustable parameters, (2) using surrogate models to emulate the responses of dynamic models to the variation of adjustable parameters, (3) using an adaptive strategy to improve the efficiency of surrogate modeling-based optimization; (4) using a weighting function to transfer multi-objective optimization to single-objective optimization. In this study, we demonstrate the uncertainty quantification framework on a single column application of a LSM – the Common Land Model (CoLM), and evaluate the effectiveness and efficiency of the proposed framework. The result indicate that this framework can efficiently achieve optimal parameters in a more effective way. Moreover, this result implies the possibility of calibrating other large complex dynamic models, such as regional-scale LSMs, atmospheric models and climate models.

Heat shock proteins (HSPs) participate in diverse physiological processes in insects, and HSP70 is one of the most highly conserved proteins in the HSP family. In this study, full-length cDNAs of three HSP70 genes ( Lthsc70 , Lthsp701 , and Lthsp702 ) were cloned and characterized from Liriomyza trifolii , an important invasive pest of vegetable crops and horticultural crops worldwide. These three HSP70s exhibited signature sequences and motifs that are typical of the HSP70 family. The expression patterns of the three Lthsp70 s during temperature stress and in different insect development stages were studied by real-time quantitative PCR. Lthsp701 was strongly induced by high- and low-temperature stress, but Lthsc70 and Lthsp702 were not very sensitive to temperature changes. All three Lthsp70 s were expressed during insect development stages, but the expression patterns were quite different. The expression of Lthsc70 and Lthsp702 showed significant differences in expression during leafminer development; Lthsc70 was most highly expressed in female adults, whereas Lthsp702 was abundantly expressed in larvae and prepupae. Lthsp701 expression was not significantly different among leafminer stages. These results suggest that functional differentiation within the Lt HSP70 subfamily has occurred in response to thermal stress and insect development.