Circ_0084188 promotes colorectal cancer progression by sponging miR-654-3p and regulating kruppel-like factor 12.

To investigate the biological role and mechanism of circ_0084188 in colorectal cancer (CRC). Real-time quantitative polymerase chain reaction and western blot assay were used to detect RNA levels and protein levels in CRC cell lines (HCT116 and SW480), respectively. Cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and colony formation assays. Cell apoptosis was determined using flow cytometry. Cell migration and invasion were measured by transwell assay. Sphere formation efficiency was determined by sphere formation assay. The interaction between microRNA-654-3p (miR-654-3p) and circ_0084188 or Kruppel-like factor 12 (KLF12) was confirmed by a dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Xenograft in CRC mice model was utilized for exploring the role of circ_0084188 in vivo.Circ_0084188 was overexpressed in CRC tissues and cells. Circ_0084188 silencing suppressed cell proliferation, migration, invasion, and stemness and induced apoptosis in CRC cells. Circ_0084188 acted as a sponge for miR-654-3p, and circ_0084188 regulated CRC cell behaviors via sponging miR-654-3p. Moreover, KLF12 was a target of miR-654-3p, and miR-654-3p overexpression inhibited the malignant behaviors of CRC cells by downregulating KLF12. Mechanically, circ_0084188 sponged miR-654-3p to regulate KLF12 expression in CRC cells. In addition, circ_0084188 downregulation inhibited tumor growth in vivo.Circ_0084188 knockdown might repress CRC progression partially via regulating the miR-654-3p/KLF12 axis, providing a novel insight into the pathogenesis of CRC.

Effectiveness of dexmedetomidine on postoperative cognitive dysfunction in elderly patients with fracture: A systematic review.

BACKGROUND: Previous studies have explored the effectiveness of dexmedetomidine on postoperative cognitive dysfunction (POCD) in elderly patients with fracture. However, no systematic review has addressed this issue. Thus, this systematic review investigated the effectiveness of dexmedetomidine on POCD in elderly patients with fracture. METHODS: In this study, we searched electronic databases of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wang Fang and China Science and Technology Journal Database from their initiation to July 1, 2022. We considered randomized controlled trials of dexmedetomidine on POCD in elderly patients with fracture in this study. Primary outcome was measured by mini-mental state examination. Secondary outcomes were measured by total occurrence rate of postoperative cognitive dysfunction, occurrence rate of delirium, visual analogue scale and occurrence rate of adverse events. RESULTS: A total of 10 studies involving 969 elderly patients with fracture are included in this study. Meta-analysis results showed that there were significant differences on mini-mental state examination at 1-day post-surgery [mean difference (MD) = 2.17; random 95% confidence interval (CI), 1.06, 3.28; P < .001; I²=98%], 3-day post-surgery (MD = 2.70; random 95% CI, 1.51, 3.89; P < .001; I²=98%), and 7-day post-surgery (MD = 1.21; random 95% CI, 0.50, 1.93; P < .001; I²=86%), total occurrence rate of postoperative cognitive dysfunction (odds ratio [OR] = 0.26; fixed 95% CI, 0.11, 0.60; P = .002; I²= 0%), occurrence rate of delirium (OR = 0.29; fixed 95% CI, 0.11, 0.78; P = .01; I²= 0%), visual analogue scale (MD = -1.23; random 95% CI, -1.74, -0.72; P < .001; I²=95%), and occurrence rate of adverse events (OR = 0.32; fixed 95% CI, 0.20, 0.50; P < .001; I²= 0%) between the 2 groups. CONCLUSION: The results of this study showed that dexmedetomidine could effectively manage POCD in elderly patients with fracture. However, the overall quality of included trials is not too high. Thus, the present findings should be cautiously referred.

Macrophages promote anti-androgen resistance in prostate cancer bone disease.

Metastatic castration-resistant prostate cancer (PC) is the final stage of PC that acquires resistance to androgen deprivation therapies (ADT). Despite progresses in understanding of disease mechanisms, the specific contribution of the metastatic microenvironment to ADT resistance remains largely unknown. The current study identified that the macrophage is the major microenvironmental component of bone-metastatic PC in patients. Using a novel in vivo model, we demonstrated that macrophages were critical for enzalutamide resistance through induction of a wound-healing-like response of ECM-receptor gene expression. Mechanistically, macrophages drove resistance through cytokine activin A that induced fibronectin (FN1)-integrin alpha 5 (ITGA5)-tyrosine kinase Src (SRC) signaling cascade in PC cells. This novel mechanism was strongly supported by bioinformatics analysis of patient transcriptomics datasets. Furthermore, macrophage depletion or SRC inhibition using a novel specific inhibitor significantly inhibited resistant growth. Together, our findings elucidated a novel mechanism of macrophage-induced anti-androgen resistance of metastatic PC and a promising therapeutic approach to treat this deadly disease.

Retraction Notice to: miR-363 Alleviates Detrusor Fibrosis via the TGF-ß1/Smad Signaling Pathway by Targeting Col1a2 in Rat Models of STZ-Induced T2DM.

[This retracts the article DOI: 10.1016/j.omtn.2020.07.001.].

Regional block anesthesia for adult patients with inguinal hernia repair: A systematic review.

BACKGROUND: Inguinal hernia repair (IHR) is a common surgical technique performed under regional block anesthesia (RBA). Although previous clinical trials have explored the effectiveness and safety of RBA for IHR, no systematic review has investigated its effectiveness and safety in adult patients with IHR. METHODS: This systematic review searched electronic databases (PubMed, Embase, Cochrane Library, CNKI, Wangfang, and VIP) from their inception to July 1, 2022. We included all potential randomized controlled trials that focused on the effects and safety of RBA in adult patients with IHR. Outcomes included operative time, total rescue analgesics, numerical rating scale at 24 hours, occurrence rate of nausea and vomiting, and occurrence rate of urinary retention (ORUCR). RESULTS: Five randomized controlled trials, involving 347 patients with IHR, were included in this study. Meta-analysis results showed that no significant differences were identified on operative time (MD = -0.20; fixed 95% confidence interval [CI], -3.87, 3.47; P = .92; I² = 0%), total rescue analgesics (MD = -8.90; fixed 95% CI, -20.36, 2.56; P = .13; I²â€…= 28%), and occurrence rate of nausea and vomiting (MD = 0.39; fixed 95% CI, 0.13, 1.16; P = .09; I²â€…= 0%) between 2 types of anesthesias. However, significant differences were detected in the numerical rating scale at 24 hours (MD = -1.53; random 95% CI, -2.35, -0.71; P < .001; I²â€…= 75%) and ORUCR (MD = 0.20; fixed 95% CI, 0.05, 0.80; P = .02; I²â€…= 0%) between the 2 management groups. CONCLUSION: The results of this study demonstrated that IHR patients with RBA benefit more from post-surgery pain relief at 24h and a decrease in the ORUCR than those with CSA.

CycC1;1 negatively modulates ABA signaling by interacting with and inhibiting ABI5 during seed germination.

Regulation of seed germination is important for plant survival and propagation. ABSCISIC ACID (ABA) INSENSITIVE5 (ABI5), the central transcription factor in the ABA signaling pathway, plays a fundamental role in the regulation of ABA-responsive gene expression during seed germination; however, how ABI5 transcriptional activation activity is regulated remains to be elucidated. Here, we report that C-type Cyclin1;1 (CycC1;1) is an ABI5-interacting partner affecting the ABA response and seed germination in Arabidopsis (Arabidopsis thaliana). The CycC1;1 loss-of-function mutant is hypersensitive to ABA, and this phenotype was rescued by mutation of ABI5. Moreover, CycC1;1 suppresses ABI5 transcriptional activation activity for ABI5-targeted genes including ABI5 itself by occupying their promoters and disrupting RNA polymerase II recruitment; thus the cycc1;1 mutant shows increased expression of ABI5 and genes downstream of ABI5. Furthermore, ABA reduces the interaction between CycC1;1 and ABI5, while phospho-mimic but not phospho-dead mutation of serine-42 in ABI5 abolishes CycC1;1 interaction with ABI5 and relieves CycC1;1 inhibition of ABI5-mediated transcriptional activation of downstream target genes. Together, our study illustrates that CycC1;1 negatively modulates the ABA response by interacting with and inhibiting ABI5, while ABA relieves the CycC1;1 interaction with and inhibition of ABI5 to activate ABI5 activity for the ABA response, thereby inhibiting seed germination.

Femtosecond Laser Modification of Silica Optical Waveguides for Potential Bragg Gratings Sensing.

The optimum femtosecond laser direct writing of Bragg gratings on silica optical waveguides has been investigated. The silica waveguide has a 6.5 × 6.5 µm2 cross-sectional profile with a 20-µm-thick silicon dioxide cladding layer. Compared with conventional grating inscribed on fiber platforms, the silica planar waveguide circuit can realize a stable performance as well as a high-efficiency coupling with the fiber. A thin waveguide cladding layer also facilitates laser focusing with an improved spherical aberration. Different from the circular fiber core matching with the Gaussian beam profile, a 1030-nm, 400-fs, and 190-nJ laser is optimized to focus on the top surface of the square silica waveguide, and the 3rd-order Bragg gratings are inscribed successfully. A 1.5-mm long uniform Bragg gratings structure with a reflectivity of 90% at a 1548.36-nm wavelength can be obtained. Cascaded Bragg gratings with different periods are also inscribed in the planar waveguide. Different reflection wavelengths can be realized, which shows great potential for wavelength multiplexing-related applications such as optical communications or sensing.

MYC sensitises cells to apoptosis by driving energetic demand.

The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.

Massoia Lactone Displays Strong Antifungal Property Against Many Crop Pathogens and Its Potential Application.

Massoia lactone could be released from liamocins produced by Aureobasidium melanogenum M39. The obtained Massoia lactone was very stable and highly active against many fungal crop pathogens which cause many plant diseases and food unsafety. Massoia lactone treatment not only could effectively inhibit their hyphal growth and spore germination, but also caused pore formation in cell membrane, reduction of ergosterol content, rise in intracellular ROS levels, and leakage of intracellular components, consequently leading to cellular necrosis and cell death. The direct contact of Massoia lactone with Fusarium graminearum spores could stop the development of Fusarium head blight symptom in the diseased wheats. Therefore, Massoia lactone could be a promising candidate for development as an effective and green bio-fungicide because of its high anti-fungal activity and the multiplicity of mode of its action.

Factors Affecting Artificial Insemination Pregnancy Outcome.

OBJECTIVE: The aim of the present study was to explore related clinical pregnancy outcome factors in intrauterine insemination (IUI). MATERIALS AND METHODS: The clinical data of 3984 IUI cycles in 1862 couples experiencing infertility who attended the Reproductive Center of Binzhou Medical University Hospital between July 2006 and July 2017 were retrospectively analyzed. Female and male patient age, endometrial thickness (EMT), the post-wash total motile sperm count (PTMC), artificial insemination timing, insemination frequency, and ovarian stimulation protocols were compared between the study's pregnant group and non-pregnant group in order to explore any correlation. RESULTS: There were statistically significant differences in female and male age, EMT, artificial insemination timing, insemination frequency, and ovarian stimulation protocols between the two groups (p < 0.05). The clinical pregnancy rate was significantly higher in ovarian stimulation cycles than in natural cycles (21.2% and 11.6%, respectively; p < 0.01), the clinical pregnancy rate was significantly higher in double IUI than in single IUI (17.8% and 12.1%, respectively; p < 0.01), and EMT was significantly greater in the pregnant group than in the control group (p < 0.05). However, the differences in clinical pregnancy rates among the PTMC groups were not statistically significant (14.8%, 14.4%, 17.3%, and 17.3%, respectively; p > 0.05). CONCLUSION: The results of the present study demonstrate that the clinical IUI pregnancy rate is correlated with the factors of female age, male age, EMT, artificial insemination timing, insemination frequency, and ovarian stimulation protocols; the ovarian stimulation protocol can noticeably improve the patient pregnancy outcome. Furthermore, compared with single IUI, double IUI can significantly increase the clinical pregnancy rate.

A Conformation Selective Mode of Inhibiting SRC Improves Drug Efficacy and Tolerability.

Despite the approval of several multikinase inhibitors that target SRC and the overwhelming evidence of the role of SRC in the progression and resistance mechanisms of many solid malignancies, inhibition of its kinase activity has thus far failed to improve patient outcomes. Here we report the small molecule eCF506 locks SRC in its native inactive conformation, thereby inhibiting both enzymatic and scaffolding functions that prevent phosphorylation and complex formation with its partner FAK. This mechanism of action resulted in highly potent and selective pathway inhibition in culture and in vivo. Treatment with eCF506 resulted in increased antitumor efficacy and tolerability in syngeneic murine cancer models, demonstrating significant therapeutic advantages over existing SRC/ABL inhibitors. Therefore, this mode of inhibiting SRC could lead to improved treatment of SRC-associated disorders. SIGNIFICANCE: Small molecule-mediated inhibition of SRC impairing both catalytic and scaffolding functions confers increased anticancer properties and tolerability compared with other SRC/ABL inhibitors.

Factors Associated with Gestational Diabetes Mellitus: A Meta-Analysis.

Gestational diabetes mellitus (GDM) is a major public health issue, and the aim of the present study was to identify the factors associated with GDM. Databases were searched for observational studies until August 20, 2020. Pooled odds ratios (ORs) were calculated using fixed- or random-effects models. 103 studies involving 1,826,454 pregnant women were identified. Results indicated that maternal age ≥ 25 years (OR: 2.466, 95% CI: (2.121, 2.866)), prepregnancy overweight or obese (OR: 2.637, 95% CI: (1.561, 4.453)), family history of diabetes (FHD) (OR: 2.326, 95% CI: (1.904, 2.843)), history of GDM (OR: 21.137, 95% CI: (8.785, 50.858)), macrosomia (OR: 2.539, 95% CI: (1.612, 4.000)), stillbirth (OR: 2.341, 95% CI: (1.435, 3.819)), premature delivery (OR: 3.013, 95% CI: (1.569, 5.787)), and pregestational smoking (OR: 2.322, 95% CI: (1.359, 3.967)) increased the risk of GDM with all P < 0.05, whereas history of congenital anomaly and abortion, and HIV status showed no correlation with GDM (P > 0.05). Being primigravida (OR: 0.752, 95% CI: (0.698, 0.810), P < 0.001) reduced the risk of GDM. The factors influencing GDM included maternal age ≥ 25, prepregnancy overweight or obese, FHD, history of GDM, macrosomia, stillbirth, premature delivery, pregestational smoking, and primigravida.

Solitary bone plasmacytoma of the upper cervical spine: A case report.

BACKGROUND: Solitary bone plasmacytoma (SBP) of the upper cervical spine is a rare diagnosis. The exact role of surgery for SBP remains unclear. CASE SUMMARY: We present the first case of SBP of the C2. A 69-year-old Chinese woman presented with severe neck pain and limitation of rotative activity for 2 mo. She underwent anterior one-stage debridement combined with cement augmentation in the C2 to reconstruct stability of the spine. The patient did not receive postoperative radiotherapy. She now remains disease free with no neck pain or neurological deficit after follow-up of 3 years. CONCLUSION: Anterior one-stage debridement combined with cement augmentation of the upper cervical spine may be an alternative treatment for SBP.

Association between PPAR-γ2 gene polymorphisms and diabetic retinopathy risk: a meta-analysis.

A close association between peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) and the development of diabetic retinopathy (DR) has been previously suggested. Herein, a meta-analysis was conducted to explore the association between PPAR-γ2 polymorphisms and DR risk by performing a systematic search and quantitative analysis. Overall, fourteen articles involving 10,527 subjects were included. The pooled results did not reveal an association between PPAR-γ2 rs1801282 C/G and DR susceptibility in the overall population (e.g., the dominant model: CG+GG vs. CC, OR=0.85, 95% CI=0.69-1.06, P=0.15, I2=62.9%). Furthermore, heterogeneity tests, cumulative analyses, sensitivity analyses, and publication bias analyses were conducted and showed that the results were robust. Similarly, race-based subgroup analyses and other subgroup analyses did not reveal an association between the rs1801282 C/G and DR susceptibility. In addition, no significant association was observed between PPAR-γ2 rs3856806 C/T polymorphism and DR risk (e.g., the dominant model: CT+TT vs. CC, OR=1.12, 95%CI=0.91-1.37, P=0.28, I2=27.0%). Overall, based on the current sample size and the level of evidence presented in the study, the results suggest that PPAR-γ2 gene polymorphisms are not associated with DR risk.

Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells.

The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (Tregs), yet how the microbiota-Treg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E2 (PGE2), a well-known mediator of inflammation, inhibits mucosal Tregs in a manner depending on the gut microbiota. PGE2 through its receptor EP4 diminishes Treg-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE2-EP4 signaling modulates mucosal Treg responses and exacerbates intestinal inflammation. Mechanistically, PGE2-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE2-dependent Treg inhibition. Together, our findings provide emergent evidence that PGE2-mediated disruption of microbiota-Treg communication fosters intestinal inflammation.