Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells.

Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Reliability Issues of Mobile Nutrition Apps for Cardiovascular Disease Prevention: Comparative Study.

Background: Controlling saturated fat and cholesterol intake is important for the prevention of cardiovascular diseases. Although the use of mobile diet-tracking apps has been increasing, the reliability of nutrition apps in tracking saturated fats and cholesterol across different nations remains underexplored. Objective: This study aimed to examine the reliability and consistency of nutrition apps focusing on saturated fat and cholesterol intake across different national contexts. The study focused on 3 key concerns: data omission, inconsistency (variability) of saturated fat and cholesterol values within an app, and the reliability of commercial apps across different national contexts. Methods: Nutrient data from 4 consumer-grade apps (COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!) and an academic app (Formosa FoodApp) were compared against 2 national reference databases (US Department of Agriculture [USDA]-Food and Nutrient Database for Dietary Studies [FNDDS] and Taiwan Food Composition Database [FCD]). Percentages of missing nutrients were recorded, and coefficients of variation were used to compute data inconsistencies. One-way ANOVAs were used to examine differences among apps, and paired 2-tailed t tests were used to compare the apps to national reference data. The reliability across different national contexts was investigated by comparing the Chinese and English versions of MyFitnessPal with the USDA-FNDDS and Taiwan FCD. Results: Across the 5 apps, 836 food codes from 42 items were analyzed. Four apps, including COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, significantly underestimated saturated fats, with errors ranging from -13.8% to -40.3% (all P<.05). All apps underestimated cholesterol, with errors ranging from -26.3% to -60.3% (all P<.05). COFIT omitted 47% of saturated fat data, and MyFitnessPal-Chinese missed 62% of cholesterol data. The coefficients of variation of beef, chicken, and seafood ranged from 78% to 145%, from 74% to 112%, and from 97% to 124% across MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, respectively, indicating a high variability in saturated fats across different food groups. Similarly, cholesterol variability was consistently high in dairy (71%-118%) and prepackaged foods (84%-118%) across all selected apps. When examining the reliability of MyFitnessPal across different national contexts, errors in MyFitnessPal were consistent across different national FCDs (USDA-FNDSS and Taiwan FCD). Regardless of the FCDs used as a reference, these errors persisted to be statistically significant, indicating that the app's core database is the source of the problems rather than just mismatches or variances in external FCDs. Conclusions: The findings reveal substantial inaccuracies and inconsistencies in diet-tracking apps' reporting of saturated fats and cholesterol. These issues raise concerns for the effectiveness of using consumer-grade nutrition apps in cardiovascular disease prevention across different national contexts and within the apps themselves.

Ring-Embedded Finger Over Proximal Interphalangeal Joint with Preserved Neurovascularization: A Case Report and Literature Review.

CASE: We present a unique case of a 45-year-old man with his right middle finger embedded with rings. Limited finger flexion was noted because of flexor tendon injury caused by the dorsal migration of the embedded ring through joint. The rings were removed under anesthesia, resulting in the resolution of swelling and recover of osseous structure. Follow-up examinations revealed no residual edema or numbness, indicating preserved neurovascularization, despite the dorsal migration of the ring. CONCLUSION: Our unique case reveals continuous finger ring migration without compromising neurovascular bundles, with review of 30 cases emphasizing the importance of psychiatric consultation. Timely intervention yielded nearly half of patients achieving full recovery.

Acute aerobic exercise modulates cognition and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD) and healthy controls.

Evidence suggests aerobic exercise has beneficial effects on cognitive performance in adults with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms might depend on mechanisms of exercise-mediated brain physiology. The study aims to investigate the effects of acute aerobic exercise on cortical excitability and cognitive performance, and the correlation between these phenomena in adults with ADHD. Twenty-six drug-naïve ADHD adults, and twenty-six age-, and gender-matched healthy controls were assessed with respect to cortical excitability and cognitive performance before and after acute aerobic exercise (a single session for 30 min) or a control intervention. The results show significantly enhanced intracortical facilitation (ICF) and decreased short intracortical inhibition (SICI) after aerobic exercise in healthy subjects. In contrast, SICI was significantly enhanced following acute aerobic exercise in ADHD. In ADHD, furthermore inhibitory control and motor learning were significantly improved after the acute aerobic exercise intervention. Alterations of SICI induced by aerobic exercise, and inhibitory control and motor learning improvement were significantly positively correlated in the ADHD group. Aerobic exercise had partially antagonistic effects in healthy controls, and ADHD patients. Furthermore, aerobic exercise-induced cognition-enhancing effects in ADHD depend on specific alterations of brain physiology, which differ from healthy humans.

3D-printed porous titanium suture anchor: a rabbit lateral femoral condyle model.

BACKGROUND: The inclusion of a connecting path in a porous implant can promote nutrient diffusion to cells and enhance bone ingrowth. Consequently, this study aimed to evaluate the biomechanical, radiographic, and histopathological performance of a novel 3D-printed porous suture anchor in a rabbit femur model. METHODS: Three test groups were formed based on the type of suture anchor (SA): Commercial SA (CSA, Group A, n = 20), custom solid SA (CSSA, Group B, n = 20), and custom porous SA (CPSA, Group C, n = 20). The SAs were implanted in the lateral femoral condyle of the right leg in each rabbit. The rabbits (New Zealand white rabbits, male, mean body weight of 2.8 ± 0.5 kg, age 8 months) underwent identical treatment and were randomized into experimental and control groups via computer-generated randomization. Five rabbits (10 femoral condyles) were euthanized at 0, 4, 8, and 12 weeks post-implantation for micro-CT, histological analysis, and biomechanical testing. RESULTS: At 12 weeks, the CPSA showed a higher BV/TV (median 0.7301, IQR 0.7276-0.7315) than the CSSA and CSA. The histological analysis showed mineralized osteocytes near the SA. At 4 weeks, new bone was observed around the CPSA and had penetrated its porous structure. By 12 weeks, there was no significant difference in ultimate failure load between the CSA and CPSA. CONCLUSIONS: We demonstrated that the innovative 3D-printed porous suture anchor exhibited comparable pullout strength to conventional threaded suture anchors at the 12-week postoperative time-point period. Furthermore, our porous anchor design enhanced new bone formation and facilitated bone growth into the implant structure, resulting in improved biomechanical stability.

Dietary glycemic index and glycemic load predict longitudinal change in glycemic and cardio-metabolic biomarkers among old diabetic adults living in a resource-poor country.

This study aims to investigate longitudinal associations between the dietary glycemic index (GI) and glycemic load (GL) and changes in glycemic and cardio-metabolic outcomes. A 28-month retrospective cohort study included 110 Vietnamese diabetic patients, collecting their dietary GI and GL values along with blood biochemical data from baseline 24-h dietary recall and medical records. Latent class growth modelling identified three distinct HbA1c trajectories during the follow-up period, with 51% of patients achieving good glycemic control. The adjusted linear mixed-effect model showed that 1 unit increase in logarithms in dietary GL was associated with a 0.14% increase in the log-HbA1c. Among poorly controlled diabetic patients, baseline GL values were positively correlated with increases in HbA1c; GI showed effects on changes in fasting plasma glucose and the triglyceride-glucose (TyG) index. No significant association was observed in patients with good glycemic control.

Screening Outcomes of Mammography with AI in Dense Breasts: A Comparative Study with Supplemental Screening US.

Background Comparative performance between artificial intelligence (AI) and breast US for women with dense breasts undergoing screening mammography remains unclear. Purpose To compare the performance of mammography alone, mammography with AI, and mammography plus supplemental US for screening women with dense breasts, and to investigate the characteristics of the detected cancers. Materials and Methods A retrospective database search identified consecutive asymptomatic women (≥40 years of age) with dense breasts who underwent mammography plus supplemental whole-breast handheld US from January 2017 to December 2018 at a primary health care center. Sequential reading for mammography alone and mammography with the aid of an AI system was conducted by five breast radiologists, and their recall decisions were recorded. Results of the combined mammography and US examinations were collected from the database. A dedicated breast radiologist reviewed marks for mammography alone or with AI to confirm lesion identification. The reference standard was histologic examination and 1-year follow-up data. The cancer detection rate (CDR) per 1000 screening examinations, sensitivity, specificity, and abnormal interpretation rate (AIR) of mammography alone, mammography with AI, and mammography plus US were compared. Results Among 5707 asymptomatic women (mean age, 52.4 years ± 7.9 [SD]), 33 (0.6%) had cancer (median lesion size, 0.7 cm). Mammography with AI had a higher specificity (95.3% [95% CI: 94.7, 95.8], P = .003) and lower AIR (5.0% [95% CI: 4.5, 5.6], P = .004) than mammography alone (94.3% [95% CI: 93.6, 94.8] and 6.0% [95% CI: 5.4, 6.7], respectively). Mammography plus US had a higher CDR (5.6 vs 3.5 per 1000 examinations, P = .002) and sensitivity (97.0% vs 60.6%, P = .002) but lower specificity (77.6% vs 95.3%, P < .001) and higher AIR (22.9% vs 5.0%, P < .001) than mammography with AI. Supplemental US alone helped detect 12 cancers, mostly stage 0 and I (92%, 11 of 12). Conclusion Although AI improved the specificity of mammography interpretation, mammography plus supplemental US helped detect more node-negative early breast cancers that were undetected using mammography with AI. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Whitman and Destounis in this issue.

Urinary paraben exposure increases the risk of a low estimated glomerular filtration rate in Taiwanese general population.

BACKGROUND: The inconsistent relationship between chemical exposure and estimated glomerular filtration rate (eGFR) has been examined in only a few studies. We investigated the association between paraben exposure and indicators of renal function in a total of 361 individuals recruiting from a representative study. METHOD: The levels of urinary parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were measured using UPLC-MS/MS. The association between paraben exposure and indices of renal function was assessed using multiple logistic regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: The median levels of urinary parabens in the adult group were significantly higher than those in the minor group, that is, 397 vs. 148 ng/mL for MeP, 38.8 vs. 13.6 ng/mL for EtP, 117 vs. 57.7 ng/mL for PrP, and 6.61 vs. 2.79 ng/mL for BuP (all P < 0.001). In the adult group, multivariate regression models confirmed a positive association between the albumin-to-creatinine ratio and urinary MeP (ß = 0.580) and a positive association of BUN (ß = 0.061) and a negative association of eGFR (ß = -0.051) with urinary EtP (all P < 0.001). In the adult group, compared with the lowest tertile group, the adjusted odds ratio in the third tertile (T3) of urinary EtP levels indicated a 3.08 times increased risk of eGFR abnormalities, followed by the second tertile (T2) with a 2.63 times increased risk. The generalized additive model (GAM) and BKMR models showed a non-linear correlation between urinary EtP levels and early CKD, as well as reduced eGFR. We observed a significant positive cumulative effect of urinary paraben on eGFR, and a significant positive single exposure effect of urinary EtP with eGFR abnormality. CONCLUSION: We found a significant association between exposure to EtP and an increased risk of high BUN levels and decreased eGFR.

Multimodal locomotion ultra-thin soft robots for exploration of narrow spaces.

From power plants on land to bridges over the sea, safety-critical built environments require periodic inspections for detecting issues to avoid functional discontinuities of these installations. However, navigation paths in these environments are usually challenging as they often contain difficult-to-access spaces (near-millimetre and submillimetre-high gaps) and multiple domains (solid, liquid and even aerial). In this paper, we address these challenges by developing a class of Thin Soft Robots (TS-Robot: thickness, 1.7 mm) that can access narrow spaces and perform cross-domain multimodal locomotion. We adopted a dual-actuation sandwich structure with a tuneable Poisson's ratio tensioning mechanism for developing the TS-Robots driven by dielectric elastomers, providing them with two types of gaits (linear and undulating), remarkable output force ( ~ 41 times their weight) and speed (1.16 times Body Length/s and 13.06 times Body Thickness/s). Here, we demonstrated that TS-Robots can crawl, climb, swim and collaborate for transitioning between domains in environments with narrow entries.

Exposure characteristics and cumulative risk assessment of bisphenol A and its substitutes: the Taiwan environmental survey for toxicants 2013.

Introduction: Ever since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute's exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure. Methods: Urine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography-tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated. Results: Our study found that the median level of BPA was significantly higher in adults (9.63 µg/g creatinine) than in minors (6.63 µg/g creatinine) (p < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA. Discussion: Our study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence.

Blocking M2-like macrophage polarization using decoy oligodeoxynucleotide-based gene therapy prevents immune evasion for pancreatic cancer treatment.

M2-like macrophages exhibit immunosuppressive activity and promote pancreatic cancer progression. Reactive oxygen species (ROS) affect macrophage polarization; however, the mechanism remains unclear. This study aimed to elucidate the underlying molecular basis and design a gene therapy to inhibit M2-like polarization. Microarray analysis and IF staining were performed in M1-like and M2-like macrophages to ascertain the expression of CYBB, a major intracellular ROS source. Co-culture assay and syngeneic orthotopic pancreatic cancer mouse models were used to study the mechanism of M2-like skewing. Decoy oligodeoxynucleotides (ODNs) were designed to manipulate CYBB transcription to inhibit M2-like polarization and control tumor growth. Lipopolysaccharide (LPS) treatment polarized U937 cells to M1-like macrophages in which CYBB expression was increased. In contrast, co-culture with PANC-1 cells induced M2-like polarization in U937 cells with CYBB downregulation. High CD204 M2-like expression in combination with low CYBB expression was associated with the worst prognosis in pancreatic cancer patients. STAT6 and HDAC2 in U937 cells were activated by cancer cell-derived IL-4 after coculture and then bound to the CYBB promoter to repress CYBB expression, resulting in M2-like polarization. DPI that inhibits ROS production could block this action. Knockdown of STAT6 and HDAC2 also inhibited M2-like polarization and maintained the M1-like phenotype of U937 cells after coculture. Decoy ODNs interrupting the binding of STAT6 to the CYBB promoter counteracted M2-like polarization and tumor growth and triggered antitumor immunity in vivo. Gene therapy using STAT6-CYBB decoy ODNs can inhibit M2-like polarization, representing a potential therapeutic tool for pancreatic cancer.

Essential trace element and phosphatidylcholine remodeling: Implications for body composition and insulin resistance.

BACKGROUND: Recent studies indicated that bioactive lipids of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) predict unhealthy metabolic phenotypes, but results remain inconsistent. To fill this knowledge gap, we investigated whether essential trace elements affect PC-Lyso PC remodeling pathways and the risk of insulin resistance (IR). METHODS: Anthropometric and blood biochemical data (glucose, insulin, and lipoprotein-associated phospholipase A2 (Lp-PLA2)) were obtained from 99 adults. Blood essential/probably essential trace elements and lipid metabolites were respectively measured by inductively coupled plasma mass spectrometry (ICP-MS), and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULT AND CONCLUSION: Except for LysoPC (O-18:0/0:0), an inverse V shape was observed between body weight and PC and LysoPC species. A Pearson correlation analysis showed that essential/probably-essential metals (Se, Cu, and Ni: r=-0.4∼-0.7) were negatively correlated with PC metabolites but positively correlated with LysoPC (O-18:0/0:0) (Se, Cu, and Ni: r=0.85-0.64). Quantile-g computation showed that one quantile increase in essential metals was associated with a 2.16-fold increase in serum Lp-PLA2 (ß=2.16 (95 % confidence interval (CI): 0.34, 3.98), p=0.023), which are key enzymes involved in PC/Lyso PC metabolism. An interactive analysis showed that compared to those with the lowest levels (reference), individuals with the highest levels of serum PCs (pooled, M2) and the lowest essential/probably essential metals (M1) were associated with a healthier body composition and had a 76 % decreased risk of IR (odds ratio (OR)=0.24 (95 % CI: 0.06, 0.90), p<0.05). In contrast, increased exposure to LysoPC(O-18:0/0:0) (M2) and essential metals (M2) exhibited an 8.22-times highest risk of IR (OR= 8.22 (2.07, 32.57), p<0.05) as well as an altered body composition. In conclusion, overexposure to essential/probably essential trace elements may promote an unhealthy body weight and IR through modulating PC/LysoPC remodeling pathways.

Micronutrient (iron, selenium, vitamin D) supplementation and the gut microbiome.

PURPOSE OF REVIEW: Deficiencies in micronutrients persist as widespread global challenges, where supplementation remains a crucial therapeutic approach. This review aims to elucidate the intricate relationships between micronutrient supplementation - specifically iron, selenium (Se), and vitamin D (Vit D) - and gut microbiota composition, investigating their collective impact on host health and disease susceptibility. RECENT FINDINGS: Maintaining balanced iron levels is essential for gut microbiota equilibrium and host health, as both iron deficiency and excess disrupt gut bacterial balance, affecting colon health. Se supplementation can restore and improve the gut microbial balance, influencing health outcomes not only in the gut but also in areas such as neuroprotection in the brain, testicular health, and metabolic syndrome. Clinical and experimental models demonstrate that Vit D modulates the gut microbiome, enhancing anti-inflammatory effects, supporting metabolic health, and potentially reducing the risk of gut-related behavioral changes and diseases. SUMMARY: Findings of this review emphasize that balanced iron levels are essential for maintaining a healthy gut microbiota composition and underscore the beneficial effects of Se and Vit D in modulating the gut microbiome. The interactions between micronutrients and the gut microbiome are complex but may have a broad spectrum of health outcomes.

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair.

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

The effects of dietary macronutrient composition on resting energy expenditure following active weight loss: A systematic review and meta-analysis.

A systematic review and meta-analysis was conducted to evaluate the relative effectiveness of different dietary macronutrient patterns on changes in resting energy expenditure (REE) in relation to weight loss, categorized as minimal (<5%) and moderate to high (>5%). Changes in REE were assessed using a DerSimonian and Laird random-effects meta-analysis. A diet lower in carbohydrates (CHO) or higher in fat and protein was associated with smaller reductions in REE, with these trends being more pronounced among participants who experienced moderate to high weight loss. Adjusted meta-regression analysis indicated that, within the participants who experienced moderate to high weight loss, each 1% increase in CHO intake was associated with a reduction of 2.30 kcal/day in REE (95% CI: -4.11 to -0.47, p = 0.013). In contrast, a 1% increase in protein and fat intake was correlated with an increase in REE by 3.00 (95% confidence interval [CI] [1.02, 5.07], p = 0.003) and 0.5 (95% CI [-2.43, 3.41], p = 0.740) kcal/day, respectively. No significant associations were found among participants who experienced minimal weight loss. These findings indicate that, under a caloric deficit, the impact of dietary macronutrient composition on REE may vary depending on the degree of weight loss and individual metabolic responses.

An investigation of the acute effects of aerobic exercise on executive function and cortical excitability in adolescents with attention deficit hyperactivity disorder (ADHD).

Previous studies have shown that aerobic exercise has beneficial effects on executive function in adolescents with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms could be partially due to aerobic exercise-induced cortical excitability modulation. The aim of this study was to explore the effects of acute aerobic exercise on executive functions and cortical excitability and the association between these phenomena in adolescents with ADHD. The study was conducted using a complete crossover design. Executive functions (inhibitory control, working memory, and planning) and cortical excitability were assessed in twenty-four drug-naïve adolescents with ADHD before and after acute aerobic exercise or a control intervention. Inhibitory control, working memory, and planning improved after acute aerobic exercise in adolescents with ADHD. Moreover, cortical excitability monitored by transcranial magnetic stimulation (TMS) decreased after intervention in this population. Additionally, improvements in inhibitory control and working memory performance were associated with enhanced cortical inhibition. The findings provide indirect preliminary evidence for the assumption that changes in cortical excitability induced by aerobic exercise partially contribute to improvements in executive function in adolescents with ADHD.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Effect and mechanism of quercetin or quercetin-containing formulas against COVID-19: From bench to bedside.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global coronavirus disease 2019 (COVID-19) pandemic since 2019. Immunopathogenesis and thromboembolic events are central to its pathogenesis. Quercetin exhibits several beneficial activities against COVID-19, including antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antithrombotic effects. Although several reviews have been published, these reviews are incomplete from the viewpoint of translational medicine. The authors comprehensively evaluated the evidence of quercetin against COVID-19, both basically and clinically, to apply quercetin and/or its derivatives in the future. The authors searched the PubMed, Embase, and the Cochrane Library databases without any restrictions. The search terms included COVID-19, SARS-CoV-2, quercetin, antiviral, anti-inflammatory, immunomodulatory, thrombosis, embolism, oxidative, and microbiota. The references of relevant articles were also reviewed. All authors independently screened and reviewed the quality of each included manuscript. The Cochrane Risk of Bias Tool, version 2 (RoB 2) was used to assess the quality of the included randomized controlled trials (RCTs). All selected studies were discussed monthly. The effectiveness of quercetin against COVID-19 is not solid due to methodological flaws in the clinical trials. High-quality studies are also required for quercetin-containing traditional Chinese medicines. The low bioavailability and highly variable pharmacokinetics of quercetin hinder its clinical applications. Its positive impact on immunomodulation through reverting dysbiosis of gut microbiota still lacks robust evidence. Quercetin against COVID-19 does not have tough clinical evidence. Strategies to improve its bioavailability and/or to develop its effective derivatives are needed. Well-designed RCTs are also crucial to confirm their effectiveness in the future.

Removal of heavy metals in water-extracted solution through adsorption by palygorskite and stabilization by comilling.

Removing water-soluble chlorides (WSCs) through water extraction is a common pretreatment technology for recycling municipal solid waste incineration (MSWI) fly ash (FA). However, the extracted solution often contains heavy metals, the concentrations of which exceed standards for effluent. This study aims to investigate the adsorption of heavy metals by palygorskite in water-extracted solution and explore the feasibility of stabilizing heavy metals through comilling palygorskite-adsorbed heavy metals (PAHMs) with water-extracted fly ash (WFA). The experimental parameters include: two-stage water extraction with a liquid-to-solid ratio of 5, adding 0, 0.125, 0.25, 0.5, 1, 2 or 3 g of palygorskite to 100 mL of water-extracted solution, and comilling the mixture of PAHMs and WFA for 0, 0.5, 1, 2, 4, 8, 12, 24 or 96 hours. The experimental results revealed that 3 g of palygorskite in 100 mL of extracted solution could absorb Pb, Cd, Cr, Cu and Zn, meeting the effluent standards. The total amount of Pb, Cd, Cr, Cu and Zn removal rate reached 99.7%. Moreover, 98.44% of the WSCs were not adsorbed, the water extraction process for removing WSCs was not compromised. After the comilling of PAHMs and WFA, the distribution of the heavy metals in the milled blended powder was greater than 99.44%; moreover, toxicity characteristic leaching procedure concentrations were determined to conform to regulatory standards, and the sequential extraction procedure revealed that the heavy metals tended to be in stable fractions. This achieves the goal of preventing secondary pollution from heavy metals during the MSWI FA recycling process.