Brain-Imaging Mechanisms on Female Abdominal Obesity Treated by "Shu-Mu" Acupoint Catgut Embedding and Compatibility Relation: Study Protocol for a 12-Week Randomized Controlled Trial.

Background: Acupoint catgut embedding (ACE) has been proven to be effective and safe in the treatment of obesity, but few studies have been conducted involving its central mechanisms. Our previous study has demonstrated the effectiveness of Shu-Mu ACE in the treatment of abdominal obesity (AO). However, the neurological mechanism of Shu-Mu ACE for weight loss has not yet been elucidated. The mechanism of the combination of the Shu and Mu acupoints may be related to the central integrative effects of the brain. This paper aims to explore the potential neural mechanisms of Shu-Mu ACE in female patients with AO. Methods and Analysis: A total of 100 eligible female AO patients and 20 healthy female subjects will be recruited for this study. 100 AO patients will be randomly allocated to five groups: Shu-Mu ACE (Group A), Shu ACE (Group B), Mu ACE (Group C), sham ACE (Group D), and waiting-list (Group E). Treatment will be administrated once every two weeks for 12 weeks. The body mass index (BMI), waist circumference (WC), Visual Analog Scales (VAS) of appetite, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) will be utilized to evaluate the clinical efficacy. Outcomes will be assessed at baseline and at each time point of treatment. Multimodal MRI will be performed at baseline and after 12-week treatment and the results will be used to investigate the neural mechanisms of ACE for obesity. Neurological changes and clinical data will be analysed for correlation. Discussions: This study hypothesized that Shu-Mu ACE therapy has a synergistic effect and may treat AO by modulating the neuropathological alterations in the brain. Our findings will demonstrate the neurological mechanism of AO treated by "Shu-Mu" Acupoint Catgut Embedding and compatibility relation. Trial Registration: This trial is registered at the Chinese Clinical Trial Registration Center (No. ChiCTR2100048920).

Acid-sensing ion channel 3 is required for agmatine-induced histamine-independent itch in mice.

Introduction: Itch is a common symptom of many skin and systemic diseases. Identifying novel endogenous itch mediators and the downstream signaling pathways involved will contribute to the development of new strategies for the treatment of chronic itch. In the present study, we adopted behavioral testing, patch clamp recording and metabonomics analysis to investigate the role of agmatine in itch and the underlying mechanism. Methods: Behavioral analysis was used to evaluate the establishing of acute and chronic itch mice model, and to test the effects of different drugs or agents on mice itch behavior. Western blotting analysis was used to test the effect of agmatine on phosphorylation of ERK (p-ERK) expression in the spinal cord. Patch clamp recording was used to determine the effect agmatine on the excitability of DRG neurons and the role of ASIC3. Finally, the metabonomics analysis was performed to detect the concentration of agmatine in the affected skin under atopic dermatitis or psoriasis conditions. Results: We fused a mouse model and found that an intradermal injection of agmatine (an endogenous polyamine) into the nape of the neck or cheek induced histamine-independent scratching behavior in a dose-dependent manner. In addition, the ablation of nociceptive C-fibers by resiniferatoxin (RTX) abolished agmatine-induced scratching behavior. However, agmatine-induced itch was not affected by the pharmacological inhibition of either transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1); similar results were obtained from TRPV1-/- or TRPA1-/- mice. Furthermore, agmatine-induced itch was significantly suppressed by the administration of acid-sensing ion channel 3 (ASIC3) inhibitors, APETx2 or amiloride. Agmatine also induced the upregulation of p-ERK in the spinal cord; this effect was inhibited by amiloride. Current clamp recording showed that the acute perfusion of agmatine reduced the rheobase and increased the number of evoked action potentials in acute dissociated dorsal root ganglion (DRG) neurons while amiloride reversed agmatine-induced neuronal hyperexcitability. Finally, we identified significantly higher levels of agmatine in the affected skin of a mouse model of atopic dermatitis (AD) when compared to controls, and the scratching behavior of AD mice was significantly attenuated by blocking ASIC3. Discussion: Collectively, these results provide evidence that agmatine is a novel mediator of itch and induces itch via the activation of ASIC3. Targeting neuronal ASIC3 signaling may represent a novel strategy for the treatment of itch.

Micronutrients and risks of three main urologic cancers: A mendelian randomization study.

Background: The effect of micronutrients on urologic cancers has been explored in observational studies. We conducted the two-sample mendelian randomization (TSMR) study to investigate whether micronutrients could causally influence the risk of urologic cancers. Methods: Summary statistics for four micronutrients and three main urologic cancers outcomes were obtained from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between them. Sensitivity analyses using multiple methods were also conducted. Results: Genetically predicted one SD increase in serum copper and iron concentrations was causally associated with increased risks of renal cell carcinoma (RCC) (OR = 3.021, 95%CI = 2.204-4.687, P < 0.001, male; OR = 2.231, 95%CI = 1.524-3.953, P < 0.001, female; OR = 1.595, 95%CI = 1.310-1.758, P = 0.0238, male; OR = 1.484, 95%CI = 1.197-2.337, P = 0.0210, female, respectively) and per SD increase in serum zinc levels was related to decreased risks of RCC (OR = 0.131, 95%CI = 0.0159-0.208, P < 0.001, male; OR = 0.124, 95%CI = 0.0434-0.356, P < 0.001, female). No significant results were observed between micronutrients and the risk of bladder cancer after Bonferroni correction. Additionally, per SD increase in serum zinc level was associated with a 5.8% higher risk of prostate cancer (PCa) [OR = 1.058, 95%CI = 1.002-1.116, P = 0.0403, inverse-variance weight (IVW)]. Conclusions: Micronutrients play a vital role in the development of urological tumors. Future studies are required to replicate the findings, explore the underlying mechanisms, and examine the preventive or therapeutic role of micronutrients in clinical settings.

Visual Perception of Breast Free Flap Size is Influenced by Radiation Changes of Surrounding Tissue.

INTRODUCTION: Microsurgical reconstruction for bilateral mastectomy defects after unilateral radiation often results in asymmetry, despite both flap tissues never being radiated. METHODS: Photos of 16 patients who received prior radiation to one breast and underwent bilateral abdominal free flap reconstruction were taken postoperatively. Layperson and expert assessment of were attained via online crowdsourcing and a panel of attending surgeons and senior residents. Stratified by inter-flap weight differences was done for sub-analysis. RESULTS: A totally of 399 laypersons responded with the majority (57.3%) reporting that the radiated breast appeared smaller than the non-radiated breast. When the photos were stratified by inter-flap weight differences, the photos with the radiated side flap weight over 3% more than nonradiated side were significantly more likely to be perceived by laypersons as the same size (OR=2.7, p < 0.001) and of similar aesthetic (OR = 1.9, p < 0.001) when compared with photos with same-sized flaps. Of the expert responses (n=16), the radiated side was perceived as smaller 72.3% of the time and the nonradiated side appeared more aesthetic 52.7% of the time. Contrary to layperson responses, the experts tend to report the radiated side as smaller despite varying flap weight. Interestingly, expert raters were significantly more likely to rate the flaps of equal aesthetics when the radiated side has a flap larger by 3% or more (OR=3.6, p<0.001). CONCLUSION: Higher aesthetic scores were noted when larger flaps were inset to the radiated envelope by both laypersons and experts, suggesting potential technical refinement in reconstructive outcomes.

Engineering an Oxygen-Binding Protein for Photocatalytic CO2 Reductions in Water.

While native CO2-reducing enzymes display remarkable catalytic efficiency and product selectivity, few artificial biocatalysts have been engineered to allow understanding how the native enzymes work. To address this issue, we report cobalt porphyrin substituted myoglobin (CoMb) as a homogeneous catalyst for photo-driven CO2-to-CO conversion in water. The activity and product selectivity were optimized by varying pH and concentrations of the enzyme and the photosensitizer. Up to 2000 TON(CO) was attained at low enzyme concentrations with low product selectivity (15%), while a product selectivity of 74% was reached by increasing the enzyme loading but with a compromised TON(CO). The efficiency of CO generation and overall TON(CO) were further improved by introducing positively charged residues (Lys or Arg) near the active stie of CoMb, which demonstrates the value of tuning the enzyme secondary coordination sphere to enhance the CO2 reducing performance of a protein-based photocatalytic system.

ZnO Nanoparticles Modified by Carbon Quantum Dots for the Photocatalytic Removal of Synthetic Pigment Pollutants.

Synthetic pigment pollutants caused by the rapid development of the modern food industry have become a serious threat to people's health and quality of life. Environmentally friendly ZnO-based photocatalytic degradation exhibits satisfactory efficiency, but some shortcomings of large band gap and rapid charge recombination reduce the removal of synthetic pigment pollutants. Here, carbon quantum dots (CQDs) with unique up-conversion luminescence were applied to decorate ZnO nanoparticles to effectively construct the CQDs/ZnO composites via a facile and efficient route. The ZnO nanoparticles with a spherical-like shape obtained from a zinc-based metal organic framework (zeolitic imidazolate framework-8, ZIF-8) were coated by uniformly dispersive quantum dots. Compared with single ZnO particles, the obtained CQDs/ZnO composites exhibit enhanced light absorption capacity, decreased photoluminescence (PL) intensity, and improved visible-light degradation for rhodamine B (RhB) with the large apparent rate constant (k app). The largest k app value in the CQDs/ZnO composite obtained from 75 mg of ZnO nanoparticles and 12.5 mL of the CQDs solution (∼1 mg·mL-1) was 2.6 times that in ZnO nanoparticles. This phenomenon may be attributed to the introduction of CQDs, leading to the narrowed band gap, an extended lifetime, and the charge separation. This work provides an economical and clean strategy to design visible-light-responsive ZnO-based photocatalysts, which is expected to be used for the removal of synthetic pigment pollutants in food industry.

Comparison of suture-bridge and independent double-row techniques for medium to massive posterosuperior cuff tears: a two-year retrospective study.

BACKGROUND: Transosseous-equivalent suture-bridge (TOE-SB) and independent double-row (IDR) repair techniques were developed to treat rotator cuff tears. The study was designed to prove that both TOE-SB and IDR techniques provided comparable clinical results and retear rate for medium to massive posterosuperior rotator cuff tears, while the surgical time and number of suture anchor used were less in the IDR group. STUDY DESIGN: Level of evidence: level III, Retrospective comparative study. METHODS: Patients with medium to massive posterosuperior rotator cuff tears receiving arthroscopic TOE-SB and IDR between November 2016 to October 2019 were retrospectively enrolled. All patients were confirmed to have grade ≤ 2 fatty infiltration in the muscles of the torn tendons. Revision, concomitant subscapularis tear, acromiohumeral distance < 7 mm, glenohumeral osteoarthritis, partial repair, incomplete repair, partial thickness, or irreparable posterosuperior cuff tear were excluded. Surgical time, number of suture anchor used for the surgery, pre-operative, and post-operative clinical scores such as Constant-Murley score, subjective shoulder value (SSV), and visual analog scale (VAS) were compared. The retear rates between groups were evaluated by ultrasound. RESULTS: Thirty-five IDR and thirty-five TOE-SB repairs were enrolled. The IDR technique required much fewer anchors than TOE-SB did to complete the cuff repair. The mean operation time in IDR and TOE-SB group were 86(18.23), and 114(18.7) (min), respectively (P <  0.01). The mean number of anchors used to complete the cuff repair was 2(0.17) in IDR and 3(0.61) in TOE-SB (P <  0.01). The Constant-Murley score improved from 34.9 ± 6.6 to 80.6 ± 9.4 in the IDR group, and 37.4 ± 6 to 81.9 ± 4.6 in the TOE-SB group (both P <  0.001). SSV improved from 24.6 ± 9.6 to 79.3 ± 10.6 in the IDR, and 27.9 ± 9 to 82.9 ± 6.9 in the TOE-SB group (both P <  0.001). VAS improved from 7.9 ± 0.6 to 1.5 ± 0.7 in the IDR, and 8 ± 0.5 to 1.3 ± 0.6 in the TOE-SB group (both P <  0.001) at final follow-up. No significant difference was found between the retear rates (14.3% in the IDR vs. 17.1% in the TOE-SB, respectively) in the 2-year follow-up. CONCLUSIONS: Both IDR and TOE-SB group provided comparable clinical results and retear rates for medium to massive posterosuperior rotator cuff tears. The surgical time and number of anchors used were less in the IDR group than in the TOE-SB group.

Investigating genetic overlap between antidepressant and lithium response and treatment resistance in major depressive disorder.

Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) within ~ 4 500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores of antidepressant and lithium response for individuals with MDD, and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1 778 ECT-treated MDD cases, nearly all (94%) used antidepressants before first ECT, and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We found that TRD cases tend to have lower genetic load of antidepressant response than non-TRD, although the difference was not significant; furthermore, TRD cases had significantly higher genetic load of lithium response (OR = 1.10-1.12 under different definitions). The results support evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway.

BACKGROUND: Acute liver failure (ALF) is an unpredictable and life-threatening critical illness. The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure. METHODS: Animals were divided into 3 groups, normal, thioacetamide (TAA, ALF model) and TAA + AGK2. Cultured L02 cells were divided into 5 groups, normal, TAA, TAA + mitofusin 2 (MFN2)-siRNA, TAA + AGK2, and TAA + AGK2 + MFN2-siRNA groups. The liver histology was evaluated with hematoxylin and eosin staining, inositol-requiring enzyme 1 (IRE1), activating transcription factor 6ß (ATF6ß), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylated-PERK (p-PERK). C/EBP homologous protein (CHOP), reactive oxygen species (ROS), MFN2 and glutathione peroxidase 4 (GPX4) were measured with Western blotting, and cell viability and liver chemistry were also measured. Mitochondria-associated endoplasmic reticulum membranes (MAMs) were measured by immunofluorescence. RESULTS: The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis, which were reduced by AGK2 pre-treatment. In comparison to the normal group, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ in the TAA-induced ALF model group were significantly increased, which were decreased by AGK2 pre-treatment. The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group, which were enhanced by AGK2 pre-treatment. Compared with the TAA-induced L02 cell, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group. AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell. Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells. CONCLUSIONS: The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Long-term outcomes of shoulder hemiarthroplasty for acute proximal humeral fractures.

PURPOSE: Shoulder hemiarthroplasty (HA) is now rarely indicated for complex proximal humeral fractures due to its unpredictable characteristic of the greater tuberosity (GT) healing. Despite the increasing popularity of reverse shoulder arthroplasty (RSA) in fracture treatment, there are still concerns about failure revision and its application in young populations. The complete negation of HA for fracture treatment is still under debate. METHODS: Eighty-seven out of 135 patients with acute proximal humeral fractures treated with HA were enrolled. Clinical and radiographic evaluations were performed. RESULTS: With a mean follow-up time of 14.7 years, the 10-year prosthetic survival rate was 96.6%. The mean ASES score and Constant score were 79.3 and 81.3, respectively, the mean VAS was 1.1, the average forward flexion was 125.9°, external rotation was 37.2°, and internal rotation was at the L4 level. Nineteen patients (21.8%) displayed GT complications and showed significantly worse outcomes. Glenoid erosion was observed in 64.9% of the patients and resulted in inferior outcomes. The patients who showed good postoperative two year functional outcomes and good acromiohumeral distances usually maintained their results without deterioration over time. CONCLUSIONS: With strict patient selection, a proper surgical technique and closely supervised postoperative rehabilitation, HA could achieve a 96.6% ten year survival rate and good pain relief at an average follow-up of 15 years. Although rarely indicated, HA should have a role in the treatment of acute complex proximal humeral fractures in relatively young and active patients with good GT bone and intact cuff.

The role of bone marrow stimulation in rotator cuff repair: a systematic review and meta-analysis.

PURPOSE: The objective of this study was to investigate whether RCR (rotator cuff repair) with BMS (bone marrow stimulation) can provide a lower retear rate and better shoulder function than arthroscopic RCR alone in rotator cuff tear (RCT) patients. METHOD: The PubMed, Cochrane Library, EMBASE and Web of Science databases were searched until Feb 2022. Risk of bias for randomized controlled trials was evaluated by two independent reviewers with Cochrane collaboration risk bias of tool, and that for cohort studies was evaluated with the Newcastle-Ottawa Scale (NOS). The primary outcome was the retear rate. Secondary outcomes included the American Shoulder and Elbow Surgeons (ASES) score, University of California, Los Angeles Shoulder Scale (UCLA) score, Constant-Murley score (CMS) and visual analogue scale (VAS) score. Subgroup analysis was performed to explore the effect of suture method and tear size on BMS procedure. RESULT: Five randomized controlled trials and four cohort studies with a total of 827 patients were included. The pooled retear rate between the RCR with BMS group and the RCR alone group was significantly different (17.5% vs. 28.9%; P < 0.0001). There were no differences in the ASES score, UCLA score and VAS score. The CMS was significantly higher in RCR with BMS group than the RCR alone groups (P = 0.02), while the difference was well below the MCID. RCR with BMS resulted in a significantly lower retear rate than RCR alone for large and massive RCTs (19.7% vs. 32.5%; P = 0.01). CONCLUSION: Compared with RCR alone, RCR with BMS can significantly reduce the retear rate in arthroscopic RCT patients while not clinically relevant differences were found. BMS may further reduce the retear rate of large and massive RCTs. LEVEL OF EVIDENCE: Level III; Systematic Review and Meta-analysis.

Translation of ionic liquids to be enteric nanoparticles for facilitating oral absorption of cyclosporine A.

Ionic liquids (ILs) attract more and more interests in improving drug transport across membrane, including transdermal, nasal, and oral delivery. However, some drawbacks of ILs impede the application in oral drug delivery, such as rapid precipitation of poorly soluble drugs in stomach. This study aimed to employ enteric mesoporous silica nanoparticles (MSNs) to load ILs to overcome the shortcomings faced in oral administration. The choline sorbate ILs (SCILs) were synthesized by choline bicarbonate and sorbic acid and then adsorbed in mesopores of MSNs after dissolving cyclosporin A (CyA). MSNs loading SCILs and CyA were coated by Eudragit® L100 to form enteric nanoparticles. The in vitro release study showed that the CyA and SCILs released only 10% for 2 h in simulated gastric fluids but more than 90% in simulated intestinal fluid. In addition, SCILs and CyA were able to release from MSNs synchronously. After oral administration, enteric MSNs loading SCILs were capable of improving oral absorption of CyA significantly and the oral bioavailability of CyA was similar with that of oral Neoral®. In addition, the oral absorption of enteric MSNs was higher than that of nonenteric MSNs, which showed that enteric coating was necessary to ILs in oral delivery. These findings revealed great potential of translation of ILs to be enteric nanoparticles for facilitating oral absorption of CyA. It is predictable this delivery system is promising to be a platform for delivering poorly water-soluble drugs and even biologics orally.

Comparison of 3D printing model to 3D virtual reconstruction and 2D imaging for the clinical education of interns in hepatocellular carcinoma: a randomized controlled study.

Background: The clinical education of interns on hepatocellular carcinoma (HCC) is both crucial and difficult in China, even if the education reform has advanced constantly over the years. The value of specific 3D printing model (3DPM) in clinical education of HCC is uncertain, and relevant literatures are very few. This study aimed to explore the effects of a patient-specific 3D printing liver model on the clinical education of HCC. Methods: Three laparoscopic hepatectomies were collected. For each case, a 3D virtual reconstruction (3DVR) and 3DPM were created using multi-detector computed tomography (MDCT) data, respectively. A total of 62 interns were randomly assigned to each group (3DPM, 3DVR, and MDCT groups) through a table of random numbers for random grouping. Following lecture-based HCC education, interns in each group selected a corresponding model of HCC. All interns were tested on the hepatic tumor locations, the vessels adjacent to them, surgical planning, and test time using the centesimal system score within 90 min. A questionnaire investigation on the degree of satisfaction, interest, and helpfulness for improving the comprehension ability of liver anatomy and 3D spatial structures was also recorded. The 3DPM group were compared with both 3DVR and MDCT group by theoretical examination scores and questionnaire survey satisfaction to evaluate the effects of 3DPM on the interns' clinical education in HCC. Results: All the interns completed the test and questionnaire. The 3DPM group gained significantly higher scores on the following test contents: indicating the correct tumor location (3DPM vs. 3DVR, MDCT: 36.7±4.8 vs. 33.2±5.8, 26.8±10.0, P=0.03, P<0.01, respectively), accurately identifying the relationship between the tumor and vessels (3DPM vs. 3DVR, MDCT: 37.1±4.6 vs. 31.6±3.7, 30.0±5.8, P<0.01, P<0.01, respectively), and designing appropriate surgical plans (3DPM vs. 3DVR, MDCT: 8±2.7 vs. 4.9±2.7, 5.9±3.8, P<0.01, P=0.04, respectively). The 3DPM group showed a higher degree of satisfaction (86.2%), interest (92.1%), and helpfulness (80.5%) for improving the comprehension ability of liver anatomy and 3D spatial structures. Conclusions: The clinical teaching by utilizing 3DPM can significantly improve the professional theoretical level, strengthen clinical thinking and comprehensive ability, and improve the teaching effects of HCC for medical interns.

Glycolysis, a new mechanism of oleuropein against liver tumor.

BACKGROUND: Benign and malignant liver tumors are prevalent worldwide. However, there is no effective and comprehensive treatment option for many patients with malignant tumors. Thus, it is critical to prevent benign tumors from worsening, increasing the number of treatment options and effective medications against malignant liver tumors. Oleuropein is a natural and non-toxic product and inhibits tumor growth in various ways. METHODS: We employed bioinformatics analysis and molecular docking to identify potential targets of oleuropein. Surface plasmon resonance (SPR) was used to determine the direct binding strength of the target and compounds. Essential functionalities of the targets were analyzed using gene interference approaches. Transcriptomic studies were performed to observe the global genomic alterations occurring inside cells. Changes in glycolytic metabolites and gene and protein expressions were also detected. The anti-tumor benefits of oleuropein in vivo were determined using a tumor-bearing mouse model. RESULTS: Glucose-6-phosphate isomerase (GPI) was found to be a direct target of oleuropein. GPI discontinuation in liver tumor cells altered the expression of many genes, causing glycogenolysis. GPI interference was associated with PYGM and PFKFB4 inhibitors to inhibit glycolysis in liver tumors. Oleuropein inhibited glycolysis and showed good anti-tumor activity in vivo without adverse side effects. CONCLUSIONS: GPI is a crucial enzyme in glycolysis and the immediate target of oleuropein. GPI expression inside tumor cells affects different physiological functions and signal transduction. Oleuropein has depicted anti-tumor action in vivo without harmful side effects. Moreover, it can control tumor glycolysis through GPI.

Production performance, egg quality, and uterine gene expression for layers as affected by N-Carbamylglutamate supplementation.

Introduction: Supplementation of exogenous additives is a strategy to improve laying performance of layers by regulating uterine function. N-Carbamylglutamate (NCG) as an activator for endogenous arginine synthesis has the potential to regulate the laying performance of layers, but its effects have not been fully understood. Methods: This study investigated the effects of dietary supplementation of NCG on production performance, egg quality, and uterine gene expression in layers. A total of 360 45-week-old layers with a genetic line of Jinghong No. 1 were used in this study. The experimental period was 14 weeks. All birds were divided into 4 treatments with 6 replicates per treatment and 15 birds per replicate. Dietary treatments were based on a basal diet and supplemented with 0, 0.08, 0.12, or 0.16% NCG to form C, N1, N2, and N3 groups. Results and discussion: We found that layers in group N1 had higher egg production rate than those in group C. Egg weight was significantly reduced, while eggshell thickness was significantly improved, by treatment. However, the albumen height and Haugh unit were the lowest in group N3. Based on the above results, groups C and N1 were selected for further transcriptomics analysis of uterine tissue by RNA-seq. More than 7.4 Gb clean reads and 19,882 tentative genes were obtained using the Gallus gallus genome as a reference. Transcriptomics analysis in uterus tissue revealed that 95 differentially expressed genes (DEGs) were upregulated and 127 DEGs were downregulated. Functional annotation and pathway enrichment analysis showed that DEGs in uterine tissue were mainly enriched in glutathione metabolism, cholesterol metabolism, and glycerolipid metabolism, etc. Vitamin A metabolism-related gene, RBP1, nutrient transport-related gene, ALB, protein synthesis-related gene, METTL21C, and calcium transport-related gene, RYR2, CACNB2, RAMP3, and STAC, were significantly regulated by 0.08% NCG supplementation. Therefore, we concluded that NCG supplementation at a dose of 0.08% improved production performance and egg quality of layers by regulating uterus function.

Complementary Operando Electrochemical Quartz Crystal Microbalance and Ultraviolet-visible Spectroscopic Studies: Acetate Effects on Zinc-Manganese Batteries.

Zinc-ion batteries, in which zinc ions and protons do intercalation and de-intercalation during battery cycling with various proposed mechanisms under debate, have been studied. Recently, electrolytic zinc-manganese batteries, exhibiting the pure dissolution-deposition behavior with a large charge capacity, have been accomplished through using electrolytes with Lewis acid. However, the complicated chemical environment and mixed products hinder the investigation though it is crucial to understand the detailed mechanism. Here, cyclic voltammetry coupled electrochemical quartz crystal microbalance (EQCM) and ultraviolet-visible spectrophotometry (UV-Vis) are respectively, at the very first time, used to study the transition from zinc-ion batteries to zinc electrolytic batteries by the continuous addition of acetate ions. These complementary techniques operando trace the mass and the composition evolution. The observed formation and dissolution of zinc hydroxide sulfate (ZHS) and manganese oxides evince the effect of acetate ions on zinc-manganese batteries from an alternative perspective. Both the amount of acetate and the pH value have large impacts on the capacity and Coulombic efficiency of the MnO2 electrode, and thus they should be optimized when constructing a full zinc-manganese battery with high rate capability and reversibility.

RB1-deficient prostate tumor growth and metastasis are vulnerable to ferroptosis induction via the E2F/ACSL4 axis.

Inactivation of the RB1 tumor suppressor gene is common in several types of therapy-resistant cancers, including metastatic castration-resistant prostate cancer, and predicts poor clinical outcomes. Effective therapeutic strategies against RB1-deficient cancers, however, remain elusive. Here we showed that RB1-loss/E2F activation sensitized cancer cells to ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, by upregulating expression of ACSL4 and enriching ACSL4-dependent arachidonic acid-containing phospholipids, which are key components of ferroptosis execution. ACSL4 appeared to be a direct E2F target gene and was critical to RB1 loss-induced sensitization to ferroptosis. Importantly, using cell line-derived xenografts and genetically engineered tumor models, we demonstrated that induction of ferroptosis in vivo by JKE-1674, a highly selective and stable GPX4 inhibitor, blocked RB1-deficient prostate tumor growth and metastasis and led to improved survival of the mice. Thus, our findings uncover an RB/E2F/ACSL4 molecular axis that governs ferroptosis, and also suggest a promising approach for the treatment of RB1-deficient malignancies.

Non-ceruloplasmin-bound copper and copper speciation in serum with extraction using functionalized dendritic silica spheres followed by ICP-MS detection.

The quantification of non-ceruloplasmin-bound copper (NCBC) and total copper in biological fluids is highly required for understanding the correlation of copper with various physiological processes and diseases. In the present work, we developed dendritic spherical silica particles functionalized with EDTA, shortly as DMSPs-EDTA, from the hydrolysis of tetraethyl orthosilicate with the aid of structure-directing agents and subsequent modification of EDTA. DMSPs-EDTA serves as adsorbent with abundant binding sites to facilitate efficient extraction of NCBC. The retained NCBC on DMSPs-EDTA may be readily recovered by stripping with HNO3 (2 mol L-1). By hyphenating with ICP-MS detection, it provides a limit of detection of 1.3 pmol for NCBC. The degradation of ceruloplasmin with 200 mmol L-1 H2O2 releases the bound copper as NCBC to distribute among other ligands, which may be efficiently retained by the adsorbent and facilitate the detection of total copper. The linear ranges of 0.21-10 µmol L-1 and 0.42-30 µmol L-1 were derived for the detection of NCBC and total copper. The recovery rates for spiked NCBC or total copper in serum were derived to be 97-108% and 94-102%, respectively. The analysis of serum for a healthy subject resulted in 1.8 µmol L-1 NCBC and 9.5 µmol L-1 total copper. In addition, the proportions of 8.5-12% for NCBC were derived from the serum of healthy adults, while those for the patients with lung, hepatocellular and esophageal carcinoma were found to be 10-12%, illustrating no obvious difference against the normal group.

Long-term progression pattern of myopic tractional maculopathy: outcomes and risk factors.

PURPOSE: To evaluate the long-term progression pattern of myopic tractional maculopathy (MTM) and the risk factors. METHODS: The prevalence and grade of MTM were assessed with OCT at enrollment and at 2-year follow up. The severity of posterior staphyloma (PS) and presence of dome-shaped macula (DSM) was also evaluated. RESULTS: Totally 610 highly myopic eyes of 610 patients were analyzed. The prevalence of epiretinal membrane (ERM), myopic retinoschisis (MS) and macular hole (MH) increased from 26.7%, 12.1% and 4.4% at enrollment to 41.1%, 18.2% and 9.5% at 2-year follow up, respectively. ERM progressed in 21.8% of eyes, but visual acuity (VA) did not decline significantly in these eyes. MS progressed in 6.8% of eyes, and MH progressed in 14.8% of eyes. Significantly greater BCVA reduction was detected in the eyes with MS or MH progression than the rest (p<0.05). Multivariate analysis showed longer axial length (AL), more-severe PS and absence of DSM were associated with MTM progression. CONCLUSION: In highly myopic eyes, long-term VA was relatively stable in those with ERM, but was significantly affected by MS or MH progression. Longer AL, more-severe PS and absence of DSM were risk factors for MTM progression.