Establishment of Cephalic Index by Computed Tomography in Sampled Chinese Children.

OBJECTIVE: Cephalic Index (CI), the ratio of head width to length, is one of the indexes reflecting cranial morphological characteristics. Current norms were established by European and American countries. The purpose of the study was to study anthropometry of cranial parameters using computed tomography scans to establish the CI of the sampled Chinese Children. METHODS: The cross-sectional study was carried out on patients of age younger than 14 years old at Shanghai Children's Medical Center. The measurement of maximum cranial breadth and maximum cranial length were taken on a computed tomography scan machine and recorded for analysis. Cephalic Index was calculated for each age and sex group and compared with previously established norms. RESULTS: Five hundred eighteen patients met the inclusion criteria, including 301 males and 217 females. The means for boys and girls were 87.1 (SD: 4.3) and 85.8 (SD: 4.3), respectively. There was a significant difference between boys and girls (P < 0.01). Cephalic Index in different ages and on applying the 1-way analysis of variance association was statistically insignificant (P = 0.19). CONCLUSIONS: Chinese head shape was brachycephalic. A statistically significant correlation was seen between the CI and sex, while not age.

Glucose and HODEs regulate Aspergillus ochraceus quorum sensing through the GprC-AcyA pathway.

Aspergillus ochraceus is the traditional ochratoxin A (OTA)-producing fungus with density-dependent behaviors, which is known as quorum sensing (QS) that is mediated by signaling molecules. Individual cells trend to adapt environmental changes in a "whole" flora through communications, allowing fungus to occupy an important ecological niche. Signals perception, transmission, and feedback are all rely on a signal network that constituted by membrane receptors and intracellular effectors. However, the interference of density information in signal transduction, which regulates most life activities of Aspergillus, have yet to be elucidated. Here we show that the G protein-coupled receptor (GPCR) to cAMP pathway is responsible for transmitting density information, and regulates the key point in life cycle of A. ochraceus. Firstly, the quorum sensing phenomenon of A. ochraceus is confirmed, and identified the density threshold is 103 spores/mL, which represents the low density that produces the most OTA in a series quorum density. Moreover, the GprC that classified as sugar sensor, and intracellular adenylate cyclase (AcyA)-cAMP-PKA pathway that in response to ligands glucose and HODEs are verified. Furthermore, GprC and AcyA regulate the primary metabolism as well as secondary metabolism, and further affects the growth of A. ochraceus during the entire life cycle. These studies highlight a crucial G protein signaling pathway for cell communication that is mediated by carbohydrate and oxylipins, and clarified a comprehensive effect of fungal development, which include the direct gene regulation and indirect substrate or energy supply. Our work revealed more signal molecules that mediated density information and connected effects on important adaptive behaviors of Aspergillus ochraceus, hoping to achieve comprehensive prevention and control of mycotoxin pollution from interrupting cell communication.

Insights into Molecular Dynamics and Oil Extraction Behavior of the Polymeric Surfactant in a Multilayered Heterogeneous Reservoir.

Interlayer heterogeneity, an inevitable and complex challenge during water flooding, seriously constrains the spread of the sweep region and oil recovery enhancement in multilayered heterogeneous reservoirs. To overcome this challenge, a novel polymeric surfactant, having an excellent performance in the reduction of interfacial tension (IFT) and the increase of viscosity of displacing fluid, is applied for enlarging the sweep resonance and increasing the oil washing efficiency. Through the molecular dynamics (MD) simulation, the molecular distributing mechanisms of the polymeric surfactant at the oil-water interface are analyzed to provide the theoretical basis for explaining the microscopic mechanism of oil extraction. To directly reflect the microscopic behavior of oil extraction, multiple transparent sand-packed models are designed to investigate the flowing behavior of different fluids and the extracted mechanisms of the remaining oil in both pore and macroscales. The multilayered heterogeneous reservoirs consisting of high-, moderate-, and low-permeability layers are fabricated to represent a heterogeneous characteristic. The recognition from the visual experiment and MD simulation can study the performance control, the extracting performance of the remaining oil, and the expression of the displacing front from different perspectives. The results from MD simulation demonstrate that the polymeric surfactant can promote the disintegration of the remaining oil and enhance its mobility. The experimental results indicate that the sweep efficiency is restricted by viscous fingering and tongue advance. Through the analysis of mathematical models, the rising mobility ratio and the location of the displacing front have a strong positive relationship with viscous fingering and tongue advance, which can reasonably explain the plugging performance of the polymeric surfactant, greatly improving the sweeping effect of the whole reservoir. Moreover, the Marangoni effect generated by the IFT gradient can induce the transformation of interfacial energy to displacement kinetic energy by the emulsification of the oil-water interface so that the remaining oil in the blind-end pore can be effectively extracted. However, by comparing data from image quantification techniques and production dynamic performance, the sweep efficiency (484%) was significantly greater than that of oil recovery (300%), demonstrating that the expanded sweep effect still plays a dominant role in the extraction of remaining oil after polymeric surfactant flooding. This study provides a novel plugging and effective washing agent that is expected to be an excellent and comprehensive method for solving the problem of low oil recovery in multilayered heterogeneous reservoirs.

Inflammatory cytokines and stroke and its subtypes: a genetic correlation and two-sample Mendelian randomization study.

Introduction: The causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR). Methods: We performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses. Results: The study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99, p = 0.014), higher interleukin (IL)-1ß, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI: 1.01-1.18, p = 0.027; OR = 1.08, 95% CI: 1.02-1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI: 0.87-0.98, p = 0.006; OR = 0.95, 95% CI: 0.91-1.00, p = 0.031), higher levels of IL-1ß, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI: 1.00-1.19, p = 0.042; OR = 1.07, 95% CI: 1.01-1.15, p = 0.035; OR = 1.06, 95% CI: 1.00-1.12, p = 0.034). Our findings suggest that decreased IL-17 levels could potentially be linked to a higher likelihood of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI: 0.28-0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors. Conclusion: In summary, our research validated that inflammatory markers have a pivotal impact on the development of stroke and could potentially offer a fresh approach to treating this condition.

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models.

T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of phosphatidylserine (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion in vitro and in vivo. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3. ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, which is consistent with the fact that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to the Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wild-type and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.

Evolution Law of Dominant Flow Channel and Enhanced Oil Recovery Measures for Water Flooding in Reservoirs with Partially Sealed Faults.

The presence of strongly sealed faults can divide a reservoir into complex fault blocks, while partially sealed faults can be created by farewell faults within each block, leading to more intricate fluid migration and residual oil distribution. However, oilfields often overlook these partially sealed faults, focusing instead on the entire fault block, which can impact the efficiency of the production system. In addition, the current technology struggles to quantitatively describe the evolution of the dominant flow channel (DFC) during the water-flooding process, especially in reservoirs with partially sealed faults. This limits the ability to formulate effective enhanced oil recovery measures during the high water cut stage. To address these challenges, a large-scale sand model of a reservoir with a partially sealed fault was designed, and water flooding experiments were conducted. Based on the results of these experiments, a numerical inversion model was established. By combining percolation theory and the physical concept of DFC, a new method was proposed to quantitatively characterize DFC using a standardized flow quantity parameter. The evolution law of DFC was then studied, considering the variations of volume and oil saturation of DFC, and the water control effect of different measures was evaluated. The results revealed that, during the early stage of water flooding, a vertical uniform dominant seepage zone formed near the injector. As the water was injected, DFCs from the top of the injector to the bottom of the producers gradually formed in the unoccluded area. However, DFC was only formed at the bottom in the occluded area. During water flooding, the volume of DFC in each area gradually increased and then tended to stabilize. The development of the DFC in the occluded area lagged behind due to gravity and fault occlusion, leading to the formation of an unswept area near the fault in the unoccluded area. The volume of the DFC in the occluded area was the slowest, and the volume was the smallest after stabilization. Although the volume of the DFC near the fault in the unoccluded area grew the fastest, the volume was only higher than that in the occluded area after stabilization. During the high water cut period, the remaining oil was mainly distributed in the upper part of the occluded area, the area near the unoccluded fault, and the top of the reservoir in other areas. The plugging of the lower part of the producers can increase the volume of DFC in the occluded area, and the DFC moves up throughout the entire reservoir. This improves the utilization degree of the remaining oil at the top of the entire reservoir, but the remaining oil near the fault in the unoccluded area remains inaccessible. The combination of producer conversion, drilling infill wells, and producer plugging can alter the injection-production relationship and weaken the occlusion effect of the fault. The occluded area forms a new DFC, leading to a significant increase in the recovery degree. The deployment of infill wells near the fault in the unoccluded area can effectively control the area and improve the utilization of the remaining oil.

Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL-102): A phase 1 study.

Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL-102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18 years of age with histologically confirmed and documented CD20-positive FL, and R/R to previous rituximab-containing treatment regimens. Part one (safety run-in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open-label, single-group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty-six patients were enrolled in CITADEL-102 and all patients received parsaclisib 20 mg once daily for 8 weeks, followed by 20 mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run-in experienced a dose-limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment-emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty-three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens.

Anti-inflammatory Therapy Progress in Major Adverse Cardiac Events after PCI: Chinese and Western Medicine.

Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment.

Corrigendum: Blinatumomab for treating pediatric B-lineage acute lymphoblastic leukemia: A retrospective real-world study.

[This corrects the article DOI: 10.3389/fped.2022.1034373.].

Differential expression of C5aR1 and C5aR2 in innate and adaptive immune cells located in early skin lesions of bullous pemphigoid patients.

Bullous pemphigoid (BP), the by far most frequent autoimmune subepidermal blistering disorder (AIBD), is characterized by the deposition of autoantibodies against BP180 (type XVII collagen; Col17) and BP230 as well as complement components at the dermal-epidermal junction (DEJ). The mechanisms of complement activation in BP patients, including the generation of C5a and regulation of its two cognate C5aRs, i.e., C5aR1 and C5aR2, are incompletely understood. In this study, transcriptome analysis of perilesional and non-lesional skin biopsies of BP patients compared to site-, age-, and sex-matched controls showed an upregulated expression of C5AR1, C5AR2, CR1, and C3AR1 and other complement-associated genes in perilesional BP skin. Of note, increased expressions of C5AR2 and C3AR1 were also observed in non-lesional BP skin. Subsequently, double immunofluorescence (IF) staining revealed T cells and macrophages as the dominant cellular sources of C5aR1 in early lesions of BP patients, while C5aR2 mainly expressed on mast cells and eosinophils. In addition, systemic levels of various complement factors and associated molecules were measured in BP patients and controls. Significantly higher plasma levels of C3a, CD55, and mannose-binding lectin-pathway activity were found in BP patients compared to controls. Finally, the functional relevance of C5aR1 and C5aR2 in BP was explored by two in vitro assays. Specific inhibition of C5aR1, resulted in significantly reduced migration of human neutrophils toward the chemoattractant C5a, whereas stimulation of C5aR2 showed no effect. In contrast, the selective targeting of C5aR1 and/or C5aR2 had no effect on the release of reactive oxygen species (ROS) from Col17-anti-Col17 IgG immune complex-stimulated human leukocytes. Collectively, this study delineates a complex landscape of activated complement receptors, complement factors, and related molecules in early BP skin lesions. Our results corroborate findings in mouse models of pemphigoid diseases that the C5a/C5aR1 axis is pivotal for attracting inflammatory cells to the skin and substantiate our understanding of the C5a/C5aR1 axis in human BP. The broad expression of C5aRs on multiple cell types critical for BP pathogenesis call for clinical studies targeting this axis in BP and other complement-mediated AIBDs.

Endocannabinoid signaling regulates post-operative delirium through glutamatergic mediodorsal thalamus-prelimbic prefrontal cortical projection.

Background: Post-operative delirium (POD), a common post-operative complication that affects up to 73. 5% of surgical patients, could prolong hospital stays, triple mortality rates, cause long-term cognitive decline and dementia, and boost medical expenses. However, the underlying mechanisms, especially the circuit mechanisms of POD remain largely unclear. Previous studies demonstrated that cannabis use might cause delirium-like behavior through the endocannabinoid system (eCBs), a widely distributed retrograde presynaptic neuromodulator system. We also found that the prelimbic (PrL) and intralimbic (IL) prefrontal cortex, a crucial hub for cognition and emotion, was involved in the eCBs-associated general anesthesia recovery. Objectives: The present study aimed to investigate the role of eCBs in POD development, and further clarify its neuronal specificity and circuit specificity attributed to POD. Methods: According to a previous study, 2 h of 1.4% isoflurane anesthesia and simple laparotomy were conducted to establish the POD model in C57/BL6 mice aged 8-12 weeks. A battery of behavioral tests, including the buried food, open field, and Y maze tests, were performed at 24 h before anesthesia and surgery (AS) and 6 and 9 h after AS. The behavioral results were calculated as a composite Z score for the POD assessment. To explore the dynamics of eCBs and their effect on POD regulation, an endocannabinoid (eCB) sensor was microinjected into the PrL, and the antagonists (AM281 and hemopressin) and agonist (nabilone) of type 1 cannabinoid receptor (CB1R), were administered systemically or locally (into PrL). Chemogenetics, combined Cre-loxP and Flp-FRT system, were employed in mutant mice for neuronal specificity and circuit specificity observation. Results: After AS, the composite Z score significantly increased at 6 and 9 but not at 24 h, whereas blockade of CB1R systemically and intra-PrL could specifically decrease the composite Z score at 6 and 9 h after AS. Results of fiber photometry further confirmed that the activity of eCB in the PrL was enhanced by AS, especially in the Y maze test at 6 h post-operatively. Moreover, the activation of glutamatergic neurons in the PrL could reduce the composite Z score, which could be significantly reversed by exogenous cannabinoid (nabilone) at 6 and 9 h post-operatively. However, activation of GABAergic neurons only decreased composite Z score at 9 h post-operatively, with no response to nabilone application. Further study revealed the glutamatergic projection from mediodorsal thalamus (MD) to PrL glutamatergic neurons, but not hippocampus (HIP)-PrL circuit, was in charge of the effect of eCBs on POD. Conclusion: Our study firstly demonstrated the involvement of eCBs in the POD pathogenesis and further revealed that the eCBs may regulate POD through the specific MDglu-PrLglu circuit. These findings not only partly revealed the molecular and circuit mechanisms of POD, but also provided an applicable candidate for the clinical prevention and treatment of POD.

Blinatumomab for treating pediatric B-lineage acute lymphoblastic leukemia: A retrospective real-world study.

Objectives: Blinatumomab was shown to be safe and effective for consolidation therapy in B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to investigate the effectiveness and safety of blinatumomab in pediatric B-ALL patients in a real-world setting. Methods: This was a retrospective, observational study that included patients who initiated blinatumomab treatment between October 1, 2020 and June 20, 2022. Patients with B-ALL diagnosis, age below 18 years, and at least one blinatumomab treatment cycle were included. Treatment-related toxicities were assessed. Result: Totally 23 pediatric patients were included in this study, with a median age of 6 years (range, 2 to 11 years). Blinatumomab therapy was applied for MRD-positive (disease ≥0.01%, n = 3) or chemotherapy-ineligible (n = 20) B-ALL cases. The median follow-up time was 9 months, and all evaluable patients achieved complete molecular remission with undetectable MRD. Four relapsed B-ALL cases proceeded to hematopoietic stem cell transplantation (HSCT) without further bridging therapy, while the others underwent maintenance chemotherapy after blinatumomab treatment. Grade ≥3 febrile neutropenia, white blood cell decrease and seizure were observed in 57%, 48% and 4.3% of patients, respectively. One case discontinued therapy due to neurologic toxicities. Elevated cytokine levels were observed in 4 patients. In all 23 patients, increased T-cell and low B-cell counts (<10/µl) were detected during blinatumomab therapy. Conclusion: These encouraging results suggest blinatumomab in pediatric B-ALL patients with MRD+ or chemotherapy-related toxicities is effective and safe in the short run, although long-term follow-up is still needed.

An unexpected dual-emissive luminogen with tunable aggregation-induced emission and enhanced chiroptical property.

In the literature, organic materials with both aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) effects that can emit with multiple bands both in the solution and aggregated state are rarely reported. Herein we report a novel chiral dual-emissive bismacrocycle with tunable aggregation-induced emission colors. A facile four-step synthesis strategy is developed to construct this rigid bismacrocycle, (1,4)[8]cycloparaphenylenophane (SCPP[8]), which possesses a 1,2,4,5-tetraphenylbenzene core locked by two intersecting polyphenylene-based macrocycles. The luminescent behavior of SCPP[8] shows the unique characteristics of both ACQ effect and AIE effect, inducing remarkable redshift emission with near white-light emission. SCPP[8] is configurationally stable and possesses a novel shape-persistent bismacrocycle scaffold with a high strain energy. In addition, SCPP[8] displays enhanced circularly polarized luminescence properties due to AIE effect.

Blended learning model via small private online course improves active learning and academic performance of embryology.

While blended learning has been growing in popularity in recent years, the effectiveness of this procedure remains controversial. In this report, we assess the effectiveness of blended learning of embryology within international medical students. The participants were international medical students taking embryology in the Bachelor of Medicine and Bachelor of Surgery program. The blended learning group (BLG) consisted of students (n = 43) in the 2018-2019 academic year, taught with blended learning model via a customized small private online course (SPOC). The control traditional teaching group (TTG) consisted students (n = 48) in the 2017-2018 academic year, taught with traditional teaching model. Academic performance, including mean scores and passing ratios on the final exam of two groups were compared and analyzed with a t-test. In addition, a questionnaire directed toward evaluating student's perceptions with the blended learning was administered to students in BLG. The majority of students in BLG actively participated in online self-study activities and discussion in face-to-face class sessions. The mean score and passing ratio were significantly greater than those of students in TTG (p < 0.01). Results from the questionnaire revealed that the majority of BLG students felt that this method was beneficial for their learning of human embryology. The blended learning model, that integrates SPOC with face-to-face class lectures proved a more effective means for the teaching of embryology than the traditional lecture-based teaching model. This blended learning method may serve as a feasible model that can be readily applied for use in other medical courses.

USP5 attenuates NLRP3 inflammasome activation by promoting autophagic degradation of NLRP3.

ABBREVIATIONS: 3-MA: 3-methyladenine; AIM2: absent in melanoma 2; ATG5: autophagy related 5; BafA1: bafilomycin A1; CASP1: caspase 1; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CQ: chloroquine; DUBs: deubiquitinases; IL1B/IL-1ß: interleukin 1 beta; LAMP1: lysosomal associated membrane protein 1; LPS: lipopolysaccharide; MARCHF7/MARCH7: membrane associated RING-CH-type finger 7; NFKB/NF-κB: nuclear factor kappa B; Nig.: nigericin; NLRC4: NLR family CARD domain containing 4; NLRP3: NLR family pyrin domain containing 3; PECs: peritoneal exudate cells; PMN: polymorphonuclear; PMs: peritoneal macrophages; PYCARD/ASC: PYD and CARD domain containing; TLRs: toll like receptors; TNF/TNF-α: tumor necrosis factor; Ub: ubiquitin; USP5: ubiquitin specific peptidase 5; WT: wild type.

Resveratrol Improves Follicular Development of PCOS Rats by Regulating the Glycolytic Pathway.

SCOPE: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility; however, the underlying mechanisms remain ill-defined, and there are no available drugs or strategies for the treatment of PCOS. This study examined the therapeutic effect of resveratrol in a rat model of PCOS. METHODS AND RESULTS: PCOS is induced in rats by administration of letrozole and a high fat diet to determine whether resveratrol has a protective effect. Oral administration of resveratrol significantly decreased body weight, as well as the serum levels of testosterone and follicle stimulating hormone. Resveratrol improved the estrous cycle by restoring the thickness and number of granular cells. Resveratrol increased the levels of lactate and ATP, decreased pyruvate levels, and restored the glycolytic process, upregulating LDHA, HK2, and PKM2. Resveratrol also upregulated SIRT2, thereby modulating the expression of rate-limiting enzymes of glycolysis. CONCLUSION: Resveratrol suppressed damage to the ovaries in PCOS rats by restoring glycolytic activity, providing potential targets for the treatment of PCOS.

Visual Filling Model Experiment Study on the Enhanced Oil Recovery Mechanism of Novel Polymer Viscosity Reducer Flooding in Heavy Oil Reservoirs.

Chemical flooding is an effective method to enhance heavy oil recovery, and the viscosity reducer is often injected into the formation as the main reagent of chemical flooding. In the paper, a novel polymer viscosity reducer (FMP) was used to inject into a visual filling model, which can simulate the reservoir. The mechanism of enhancing heavy oil recovery by FMP is studied by macroscopic and microscopic analysis methods. The model can obtain macroscopic images and production data, including pressure, water cut, and oil recovery. The model can observe some microscopic processes, which can analyze the mechanism of enhanced oil recovery. Five processes of emulsifying viscosity reduction are summarized by using microscopic images: membrane oil removal, gradual emulsification, flocculation into droplet groups, active dispersion, and agglomeration into droplets. The FMP molecules can affect the interfacial properties of oil, water, and rock to enhance the wishing oil efficiency. Moreover, the decrease in the stability of the oil-water interface leads to flocculation into droplet groups and agglomeration into droplets occurring at the throat of the strong seepage zone, which increases the sweep coefficient from 0.56 to 0.90. The oil recovery has increased from 18 to 34%, which indicates that the FMP flooding obviously enhances the effect of heavy oil reservoir development.

Alisol A Inhibited the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells by Inhibiting the Hippo Signaling Pathway.

PURPOSE: Alisol A is a bioactive triterpenoid isolated from the Rhizoma Alismatis. Previous studies have shown that alisol A has anticancer potential. In this study, we explored the effect of alisol A on the growth of nasopharyngeal carcinoma (NPC) cells. MATERIALS AND METHODS: MTT assay, colony formation assay, flow cytometry, transwell assay, wound healing assay, and western blotting were used to assess cell viability, proliferation, cell cycle, migration, invasion, and protein expression, respectively, in vitro. AutoDock Vina and Discovery Studio software were used for molecular docking. RESULTS: Alisol A inhibited the viability, proliferation, migration, and invasion of NPC cells. The molecular docking simulation assay confirmed that alisol A bound to YAP protein. In addition, alisol A promoted the phosphorylation of YAP and suppressed the expression of YAP in NPC cells. CONCLUSION: Alisol A inhibited the proliferation, migration, and invasion of NPC cells by inhibiting the Hippo signaling pathway. Alisol A may be a candidate drug for NPC.

G-protein-coupled receptor GPR17 inhibits glioma development by increasing polycomb repressive complex 1-mediated ROS production.

Glioma is the most common primary tumor in the central nervous system. However, the development of glioma and effective therapeutic strategies remain elusive. Here, we identify GPR17 as a potential target to treat glioma. Data mining with human LGG and GBM samples reveals that GPR17 is negatively correlated with glioma development. Overexpressing GPR17 inhibits glioma cell proliferation and induces apoptosis by raising ROS levels. GPR17-overexpressing glioma cells are less tumorigenic in the brain than in control cells. Mechanistically, GPR17 inhibits the transcription of RNF2, a key component in the PRC1 complex, through cAMP/PKA/NF-κB signaling, leading to reduced histone H2A monoubiquitination. ChIP-Seq and RNA-Seq analyses reveal KLF9 as a direct target of RNF2. KLF9 mediates the functions of GPR17 and RNF2 in glioma cells. Furthermore, activation of GPR17 by its agonist inhibits glioma formation. Our findings have thus identified GPR17 as a key regulator of glioma development and a potential therapeutic target for gliomas.