Transcriptome-wide profiling of A-to-I RNA editing by Slic-seq.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome and is responsible for various biological processes. In this context, we developed a new method based on the highly selective cleavage activity of Endonuclease V against Inosine and the universal activity of sodium periodate against all RNAs to enrich the inosine-containing RNA and accurately identify the editing sites. We validated the reliability of our method in human brain in both Alu and non-Alu elements. The conserved sites of A-to-I editing in human cells (HEK293T, HeLa, HepG2, K562 and MCF-7) primarily occurs in the 3'UTR of the RNA, which are highly correlated with RNA binding and protein binding. Analysis of the editing sites between the human brain and mouse brain revealed that the editing of exons is more conserved than that in other regions. This method was applied to three neurological diseases (Alzheimer's, epilepsy and ageing) of mouse brain, reflecting that A-to-I editing sites significantly decreased in neuronal activity genes.

Delta-SVV as a Predictor for Circulating Blood Volume Evaluation during Intraoperative Period: A Prospective Cohort Study.

Background: Precise fluid therapy is extremely important during surgeries, as enough circulating blood volume ensures tissue perfusion and cell oxygenation. Yet, extra fluid volume could cause other adverse events, such as heart failure, intestinal swelling, etc. Thus, precise evaluation of the circulating blood volume is essential for maintaining sufficient circulating blood volume and avoiding excessive fluid infusion. Objective: This study aimed to evaluate the relationship between SVV and circulating blood volume during intraoperative fluid therapy. Methods: SVV was measured by FloTrac/Vigileo in the study. A prospective cohort study was conducted. 103 patients aged from 20 to 60 years old with an ASA Grade I-II and a diagnosis of meningioma less than 3 centimeters planning for selective neurosurgery were randomly divided into the Crystalloid Group and the Colloid Group. After induction, each Patient received 15 ml/kg of Plasma-Lyte-A or 6% hydroxyethyl starch in 30 min followed by continuous infusion at the speed of 0.1 ml/kg during the next 60 min. Hb concentration, Hct, Delta-BV/kg, and Delta-SVV were recorded every 5 minutes. Results: The delta-SVV and Delta-bv/kg were significantly higher in the Crystalloid Group than that of the Colloid Group. There was a strong linear correlation between Delta-SVV and Delta-bv/kg in both Crystalloid Group (Delta-bv / kg = 1.108 Delta-SVV + 0.0712, P < .001) and Colloid Group (Delta-bv / kg = 1.047 Delta-SVV + 0.4153, P < .001). An equation between Delta-bv/kg and Delta-SVV was established (Delta-bv / kg = 1.099 Delta-SVV + 0.1139, P < .001). Conclusion: In conclusion, SVV measured by FloTrac / Vigileo could guile fluid therapy precisely by predicting the blood volume of patients during the intraoperative period, as it has a strong linear correlation with the blood volume of patients who underwent general anesthesia, meaning anesthesiologist could calculate the exact fluid volume for patients' infusion. Further studies with large cohorts and centers would be needed to validate its efficiency.

Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

Mitophagy suppression by miquelianin-rich lotus leaf extract induces 'beiging' of white fat via AMPK/DRP1-PINK1/PARKIN signaling axis.

BACKGROUND: Lotus (Nelumbo nucifera) leaf has been described to have anti-obesity activity, but the role of white fat 'browning' or 'beiging' in its beneficial metabolic actions remains unclear. Here, 3T3-L1 cells and high-fat-diet (HFD)-fed mice were used to evaluate the effects of miquelianin-rich lotus leaf extract (LLE) on white-to-beige fat conversion and its regulatory mechanisms. RESULTS: Treatment with LLE increased mitochondrial abundance, mitochondrial membrane potential and NAD+ /NADH ratio in 3T3-L1 cells, suggesting its potential in promoting mitochondrial activity. qPCR and/or western blotting analysis confirmed that LLE induced the expression of beige fat-enriched gene signatures (e.g. Sirt1, Cidea, Dio2, Prdm16, Ucp1, Cd40, Cd137, Cited1) and mitochondrial biogenesis-related markers (e.g. Nrf1, Cox2, Cox7a, Tfam) in 3T3-L1 cells and inguinal white adipose tissue of HFD-fed mice. Furthermore, we found that LLE treatment inhibited mitochondrial fission protein DRP1 and blocked mitophagy markers such as PINK1, PARKIN, BECLIN1 and LC-3B. Chemical inhibition experiments revealed that AMPK/DRP1 signaling was required for LLE-induced beige fat formation via suppressing PINK1/PARKIN/mitophagy. CONCLUSION: Our data reveal a novel mechanism underlying the anti-obesity effect of LLE, namely the induction of white fat beiging via AMPK/DRP1/mitophagy signaling. © 2023 Society of Chemical Industry.

Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication?

Diabetes mellitus is a metabolic syndrome which cannot be cured. Recently, considerable interest has been focused on food ingredients to prevent and intervene in complications of diabetes. Polyphenolic compounds are one of the bioactive phytochemical constituents with various biological activities, which have drawn increasing interest in human health. Fruits are part of the polyphenol sources in daily food consumption. Fruit-derived polyphenols possess the anti-diabetic activity that has already been proved either from in vitro studies or in vivo studies. The mechanisms of fruit polyphenols in treating diabetes and related complications are under discussion. This is a comprehensive review on polyphenols from the edible parts of fruits, including those from citrus, berries, apples, cherries, mangoes, mangosteens, pomegranates, and other fruits regarding their potential benefits in preventing and treating diabetes mellitus. The signal pathways of characteristic polyphenols derived from fruits in reducing high blood glucose and intervening hyperglycemia-induced diabetic complications were summarized.

Food phenolics stimulate adipocyte browning via regulating gut microecology.

Fat browning has piqued the interest of researchers as a potential target for treating obesity and related metabolic disorders. Recruitment of brown adipocytes leads to enhanced energy dissipation and reduced adiposity, thus facilitating the maintenance of metabolic homeostasis. Evidence is increasing to support the crucial roles of polyphenols and gut microecology in turning fat "brown". However, it is not clear whether the intestinal microecology is involved in polyphenol-mediated regulation of adipose browning, so this concept is worthy of exploration. In this review, we summarize the current knowledge, mostly from studies with murine models, supporting the concept that the effects of food phenolics on brown fat activation and white fat browning can be attributed to their regulatory actions on gut microecology, including microbial community profile, gut metabolites, and gut-derived hormones. Furthermore, the potential underlying pathways involved are also discussed. Basically, understanding gut microecology paves the way to determine the underlying roles and mechanisms of food phenolics in adipose browning.

Alkaloids from lotus (Nelumbo nucifera): recent advances in biosynthesis, pharmacokinetics, bioactivity, safety, and industrial applications.

Different parts of lotus (Nelumbo nucifera Gaertn.) including the seeds, rhizomes, leaves, and flowers, are used for medicinal purposes with health promoting and illness preventing benefits. The presence of active chemicals such as alkaloids, phenolic acids, flavonoids, and terpenoids (particularly alkaloids) may account for this plant's pharmacological effects. In this review, we provide a comprehensive overview and summarize up-to-date research on the biosynthesis, pharmacokinetics, and bioactivity of lotus alkaloids as well as their safety. Moreover, the potential uses of lotus alkaloids in the food, pharmaceutical, and cosmetic sectors are explored. Current evidence shows that alkaloids, mainly consisting of aporphines, 1-benzylisoquinolines, and bisbenzylisoquinolines, are present in different parts of lotus. The bioavailability of these alkaloids is relatively low in vivo but can be enhanced by technological modification using nanoliposomes, liposomes, microcapsules, and emulsions. Available data highlights their therapeutic and preventive effects on obesity, diabetes, neurodegeneration, cancer, cardiovascular disease, etc. Additionally, industrial applications of lotus alkaloids include their use as food, medical, and cosmetic ingredients in tea, other beverages, and healthcare products; as lipid-lowering, anticancer, and antipsychotic drugs; and in facial masks, toothpastes, and shower gels. However, their clinical efficacy and safety remains unclear; hence, larger and longer human trials are needed to achieve their safe and effective use with minimal side effects.

Intraoperative use of tranexamic acid to reduce blood loss during cytoreductive surgery for advanced ovarian cancer: A randomized controlled clinical trial.

INTRODUCTION: Tranexamic acid reduces blood loss and allogeneic transfusion requirements in various surgical procedures. The role of tranexamic acid during cytoreductive procedures in advanced ovarian cancer is not clear. MATERIAL AND METHODS: This was a single center randomized, controlled, three-armed clinical trial. A total of 150 ovarian cancer patients undergoing cytoreductive surgery were recruited and assigned to three groups (n = 50/group): the control group (normal saline), low-dose group (10 mg/kg bolus + 1 mg/kg continuous infusion of tranexamic acid), and high-dose group (20 mg/kg bolus + 5 mg/kg continuous infusion of tranexamic acid). The primary endpoint was intraoperative blood loss volume and total blood loss volume, and secondary endpoints included intraoperative blood transfusion volumes, vasoactive agent consumption, admission into the intensive care unit, and incidence of postoperative complications within postoperative 30 days. The study was registered at ClinicalTrials.gov ID: NCT04360629. RESULTS: The patients in the high-dose group had less intraoperative (median [IQR]: 625.3 mL [343.5-1210.5]) and total blood loss volume (748.9 mL [292.2-1650.2]) than those in the control group (1015.5 mL [679.4-1015.5], p = 0.012; and 1700.7 mL [458.7-2419.8], p = 0.004, respectively). In contrast, the intraoperative (992.5 mL [539.0-1404.0], p = 0.874) and total blood loss volume (1025.0 mL [381.8-1819.9], p = 0.113) was not significantly reduced in the low-dose group when compared with the control group. Correspondingly, the relative risk of blood transfusion (RR [95% CI], 0.405 [0.180-0.909], p = 0.028) was reduced in the high-dose group and required less intraoperative noradrenaline (881.0 ± 438.3 mg) to maintain stable hemodynamics than the control group (1548.0 ± 349.8 mg, p = 0.001). Furthermore, compared with the control group, the two tranexamic acid groups had decreased intensive care unit admission rates (p = 0.016) without increasing the incidence of postoperative seizure, acute kidney injury, and thromboembolism. CONCLUSIONS: High-dose tranexamic acid is more effective in reducing blood loss and blood transfusion without increasing the risk of postoperative complications. The high-dose regime tended to have a better risk-benefit profile.

Effect of Protein-Glutaminase on Calcium Sulphate-Induced Gels of SPI with Different Thermal Treatments.

The effects of protein-glutaminase (PG) on calcium sulphate (CaSO4)-induced gels of soy protein isolate (SPI) with different heat treatment levels were investigated. The time-dependent degree of deamidation showed that the mild denaturation of the protein favored the deamidation. The particle size distribution showed that the heat treatment increased the SPI particle size, and the particle size distribution of the SPI shifted to the right or increased the proportion of the large particle size component as the degree of deamidation increased for each sample. Rheological analysis showed that the deamidation substantially pushed up the gel temperature and decreased the value of G'. The gel strength and water-holding capacity showed that the higher the amount of enzyme added, the more significant the decrease in gel strength, while the gel water-holding capacity increased. In summary, the deamidation of PG and heat treatment can affect the gel properties of SPI synergistically.

Radio-frequency treatment of medium-gluten wheat: effects of tempering moisture and treatment time on wheat quality.

BACKGROUND: Wheat and wheat flour are important raw materials of staple foods. Medium-gluten wheat is now the dominant wheat in China. In order to expand the application of medium-gluten wheat, radio-frequency (RF) technology was used to improve its quality. Effects of tempering moisture content (TMC) of wheat and RF treatment time on wheat quality were investigated. RESULTS: No evident change in protein content after RF treatment, but a reduction in wet gluten content of the sample with 10-18% TMC and RF treatment for 5 min, was observed. By contrast, protein content increased to 31.0% after RF treatment for 9 min in 14% TMC wheat, achieving the requirement of high-gluten wheat (≥30.0%). Thermodynamic and pasting properties indicated that RF treatment (14% TMC, 5 min) can alter the double-helical structure and pasting viscosities of flour. In addition, the results of textural analysis and sensory evaluation for Chinese steamed bread showed that RF treatment for 5 min with different TMC (10-18%) wheat could deteriorate wheat quality, while the wheat (14% TMC) treated with RF for 9 min had the best quality. CONCLUSION: RF treatment for 9 min can improve wheat quality when the TMC was 14%. The results are beneficial to the application of RF technology in wheat processing and improvement of wheat flour quality. © 2023 Society of Chemical Industry.

Effects of different food ingredients and additives on the digestibility of extruded and roller-dried maize starch and its application in low glycemic index nutritional formula powder.

BACKGROUND: Complex interactions that occur among starch, protein, and fat during food processing affect the taste, texture, and digestibility of starch-based food. The physicochemical properties of starch, in particular its slow digestibility, are greatly influenced by processing techniques such as extrusion and roller-drying. This study investigated the effects of various food ingredients and additives on the digestion properties of maize starch treated with extrusion and roller drying. It designed a nutritional formula to develop low glycemic index products. RESULTS: The extruded group containing raw maize starch, soybean protein isolate, soybean oil, lecithin and microcrystalline cellulose in the ratio of 580:250:58:20:3 had the best slow digestion properties. Nutritional formulas were designed at the above ratio, with supplements including calcium casein peptide, multi-vitamins, sodium ascorbate, fructooligosaccharides, xylitol, and peanut meal. The sample containing 10% peanut meal and a 1:3 ratio of fructooligosaccharides and xylitol additions obtained the highest sensory evaluation scores. An obvious slow digestion effect was observed in samples produced from the optimal formula. CONCLUSION: The results of the present study could contribute to the development and production of a low glycemic index, nutritional powder. © 2023 Society of Chemical Industry.

Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC. METHODS: The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m2 of body-surface area, on days 1-3 of each cycle) with either adebrelimab (20 mg/kg, day 1 of each cycle) or matching placebo, followed by maintenance therapy with adebrelimab or placebo. All treatments were given intravenously in 21-day cycles. Randomisation was done using a centralised interactive web response system with a block size of four, stratified by liver metastases, brain metastases, and lactate dehydrogenase concentration. The primary endpoint was overall survival in patients who received at least one dose of study medication. Safety was analysed in the as-treated population. This study is complete and registered with ClinicalTrials.gov, NCT03711305. FINDINGS: Between Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death). INTERPRETATION: Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population. FUNDING: Jiangsu Hengrui Pharmaceuticals.

Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder with abnormal lipid metabolism. The present study was to identify regulatory genes related to lipid droplets (LDs) abnormal accumulation in NAFLD. METHODS: transcriptomic analysis and bioinformatics analysis (GEO database) were used to identify potential genes in abnormal lipid metabolism of NAFLD. A candidate gene MAP3K4 expression were detected by immunohistochemistry staining in NAFLD and controls. RNA interference and immunoblotting were used to verify the roles of MAP3K4 in the formation of hepatic LDs. RESULTS: A total of 134 candidate genes were screened, including 44 up-regulated genes and 90 down-regulated genes. 29 genes in the protein-protein interaction (PPI) were selected as hub genes, including MAP3K4. The expression levels of MAP3K4 were positively correlated with NAFLD activity score (r = 0.702, p = 0.002). Furthermore, we found a positive correlation of MAP3K4 expression with serum total cholesterol (r = 0.564, p = 0.023), uric acid levels (r = 0.520, p = 0.039), and body mass index (r = 0.574, p = 0.020). Downregulation of MAP3K4 decreased LDs accumulation in HepG2 cells and reduced the expression of CGI-58 and Plin-2 by imbibition of JNK and group IVA cytosolic phospholipase A2 (cPLA2) activation. CONCLUSION: The study revealed a number of regulatory genes related to hepatic lipid metabolism of NAFLD, and demonstrated that MAP3K4 played a pivotal role in the hepatic lipogenesis of NAFLD.

6-Iodopurine as a Versatile Building Block for RNA Purine Architecture Modifications.

Natural modified bases in RNA were found to be indispensable for basic biological processes. In addition, artificial RNA modifications have been a versatile toolbox for the study of RNA interference, structure, and dynamics. Here, we present a chemical method for the facile synthesis of RNA containing C6-modified purine. 6-Iodopurine, as a postsynthetic building block with high reactivity, was used for metal-free construction of C-N, C-O, and C-S bonds under mild conditions and C-C bond formation by Suzuki-Miyaura cross-coupling. Our strategy provides a convenient approach for the synthesis of various RNA modifications, especially for oligonucleotides containing specific structures.

Orthologs of Saccharomyces cerevisiae SFH2, genes encoding Sec14 family proteins, implicated in utilization of n-alkanes and filamentous growth in response to n-alkanes in Yarrowia lipolytica.

The dimorphic yeast Yarrowia lipolytica has an ability to assimilate n-alkanes as carbon and energy sources. In this study, the roles of orthologs of Saccharomyces cerevisiae SEC14 family gene SFH2, which we named SFH21, SFH22, SFH23 and SFH24, of Y. lipolytica were investigated. The transcript levels of SFH21, SFH22 and SFH23, determined by RNA-seq analysis, qRT-PCR analysis and northern blot analysis, were found to increase in the presence of n-alkanes. The deletion mutant of SFH21, but not that of SFH22, SFH23 or SFH24, showed defects in growth in the media containing n-alkanes and in filamentous growth on the solid media containing n-alkanes. Additional deletions of SFH22 and SFH23 significantly exaggerated the defect in filamentous growth of the deletion mutant of SFH21, and expression of SFH22 or SFH24 using the SFH21 promoter partially suppressed the growth defect of the deletion mutant of SFH21 on n-alkanes. These results suggest that SFH2 orthologs are involved in the utilization of n-alkanes and filamentous growth in response to n-alkanes in Y. lipolytica.

Can habitual tea drinking be an effective approach against age-related neurodegenerative cognitive disorders: A systematic review and meta-analysis of epidemiological evidence.

Our present knowledge about the efficacy of tea consumption in improving age-related cognitive disorders is incomplete since previous epidemiological studies provide inconsistent evidence. This unified systematic review and meta-analysis based on updated epidemiological cohort studies and randomized controlled trials (RCTs) evidence aimed to overcome the limitations of previous reviews by examining the efficacy of distinct types of tea consumption. PubMed, Embase, and MEDLINE were searched up to May 20, 2022, and 23 cohorts and 12 cross-sectional studies were included. Random-effects meta-analyses were conducted to obtain pooled RRs or mean differences with 95% CIs. The pooled RRs of the highest versus lowest tea consumption categories were 0.81 (95% CIs: 0.75-0.88) and 0.69 (95% CIs: 0.61-0.77), respectively. The pooled mean difference of four included RCTs revealed a beneficial effect of tea on cognitive dysfunction (MMSE ES: 1.03; 95% CI, 0.14-1.92). Subgroup analyses further demonstrated that green and black tea intake was associated with a lower risk of cognitive disorders in eastern countries, especially in women. The evidence quality was generally low to moderate. The present review provides insight into whether habitual tea consumption can be an effective approach against age-related neurodegenerative cognitive disorders and summarizes potential mechanisms based on currently published literature.

Processed potatoes intake and risk of type 2 diabetes: a systematic review and meta-analysis of nine prospective cohort studies.

The current cohort study shows the inconsistent association between potato consumption and the risk of type 2 diabetes mellitus (T2DM). Therefore, we conducted a systematic review and dose-response meta-analysis of published prospective cohort studies to quantitatively estimate this association. We searched PubMed, Embase, MEDLINE, Web of Knowledge, and the Cochrane Library up to September 2019 for all published articles. Seven of the articles reported nine cohort studies with 383,211 participants, with 23,189 T2DM cases that met the inclusion criteria and were included for our analysis. The results of random effects model pooled relative risk (RR) showed an association between potato intake and the risk of T2DM (pooled RR = 1.13, 95% CI: 1.02-1.26, p > 0.01). In the subgroup analysis, French fries, long-term follow-up, large sample size, and high-quality studies were associated with an increased T2DM risk. Further, a linear dose-response analysis indicated that 100 g/day increment of total potato (RR = 1.05, 95% CI: 1.02-1.08) and French fries (RR = 1.10, 95% CI: 1.07-1.14) consumption may increase the risk of T2DM by 5% and 10%, respectively. Our meta-analysis showed that potato consumption, especially French fries consumption, was associated with increased T2DM risk.

Effect of Ionic Strength on Heat-Induced Gelation Behavior of Soy Protein Isolates with Ultrasound Treatment.

This study investigated the effect of ultrasound on gel properties of soy protein isolates (SPIs) at different salt concentrations. The results showed that ultrasound could significantly improve the gel hardness and the water holding capacity (WHC) of the salt-containing gel (p < 0.05). The gel presents a uniform and compact three-dimensional network structure. The combination of 200 mM NaCl with 20 min of ultrasound could significantly increase the gel hardness (four times) and the WHC (p < 0.05) compared with the SPI gel without treatment. With the increase in NaCl concentration, the ζ potential and surface hydrophobicity increased, and the solubility decreased. Ultrasound could improve the protein solubility, compensate for the loss of solubility caused by the addition of NaCl, and further increase the surface hydrophobicity. Ultrasound combined with NaCl allowed proteins to form aggregates of different sizes. In addition, the combined treatment increased the hydrophobic interactions and disulfide bond interactions in the gel. Overall, ultrasound could improve the thermal gel properties of SPI gels with salt addition.

Synthesis of 2-Oxoquinoline Derivatives as Dual Pim and mTORC Protein Kinase Inhibitors.

Compound VBT-5445 was identified as an inhibitor to block the association of Pim and the protein Enhancer of Decapping 3 (EDC3), a Pim substrate, which normally functions to enhance the decapping of messenger RNA (mRNA). It was also shown to inhibit both the Pim and mTORC protein kinases. The activity of this compound class can be fine-tuned by structural modification. A series of VBT analogs were designed, synthesized, and evaluated. These compounds decrease the growth of multiple cancer types, including pancreas, prostate, breast, lung, and leukemia. Notably, 6-methyl (GRG-1-31, 6d), 4-Bromo (GRG-1-34, 6e), 4-Chloro (GRG-1-35, 6f), and phenylthio substituted (GRG-1-104, 6n) derivatives are highly potent at inhibiting tumor growth. The ability of these compounds to block cancer growth in vitro is highly correlated with their activity as mTORC inhibitors. The toxicity of GRG 1-34 is low in mice treated with twice-daily gavage for 30 days and did not induce weight loss. Pharmacokinetics of a single oral dose demonstrated a peak concentration at 0.5 hours after gavage. In summary, further development of this compound class has the potential to inhibit important signaling pathways and impact cancer treatment.

Clinical results of arthroscopic tight fibrous band release for adult moderate-to-severe gluteal fibrosis using anterior and posterior portals: a retrospective analysis of 118 consecutive cases.

BACKGROUND: To evaluate the clinical outcomes of arthroscopic tight fibrous band release in the treatment of adult moderate-to-severe gluteal fibrosis using anterior and posterior portals during mid-term follow-up. METHODS: The data of 138 patients (58 males, 80 females) aged between 18 and 42 years (mean, 28.6 years), presenting with bilateral moderate-to-severe gluteal fibrosis (GF) from October 2013 to August 2019, was retrospectively analyzed. All patients underwent arthroscopic tight fibrous band release using anterior and posterior portals with radiofrequency energy. Under arthroscopic guidance through the posterior portal, we debrided the fatty tissue overlying the contracted band of the gluteal muscle and excised the contracted bands using a radiofrequency device introduced through the anterior portal. The pre- and post-operative gluteal muscle contracture disability (GD) scale and the patient satisfaction rate were compared to evaluate the curative effect of the operation. RESULTS: The average operation time was 18 min (range, 10-30 min) and the average blood loss was 4 ml (range, 2-10 ml) for unilateral arthroscopic release. Two cases of post-operative minimal hematomas, 2 cases of bruising and 2 cases of local subcutaneous edema were observed as early complications and were cured by conservative treatment. After surgery, all incisions healed in stage I, and no other complications such as wound infection, nerve and blood vessel injury were detected. One hundred eighteen patients were followed up for 6 to 72 months (mean, 36 months). No lateral instability of the hip was observed and all patients returned to normal gait. The degree of adduction of the hip joint in all these 118 patients was significantly improved relative to their pre-operative conditions. One hundred fifteen patients (97.5%) were able to crouch with knees close to each other after surgery. One hundred fourteen patients (96.6%) were able to cross the affected leg completely without any support. The GD scale was improved from 55.5 ± 10.6 before operation to 90.1 ± 5.2 at the last follow-up (p < 0.05). The patient satisfaction rate was 95.8%. CONCLUSION: Arthroscopic tight fibrous band release using anterior and posterior portals is minimally invasive for adult moderate-to-severe gluteal fibrosis, with a high success rate, quick recovery after surgery and reliable medium-term effect.