Anti-inflammatory diet reduces risk of metabolic dysfunction-associated fatty liver disease among US adults: a nationwide survey.

BACKGROUND: While dietary intervention was an important public health strategy for the prevention and intervention of metabolic dysfunction-associated fatty liver disease (MAFLD), the effect of diet-induced inflammation on MAFLD has not been studied in detail. Therefore, we aimed to analyze the relationship between dietary inflammatory index (DII) and MAFLD. METHODS: This study included data from the National Health and Nutrition Examination Survey 2017-2018. MAFLD was diagnosed based on the presence of hepatic steatosis, as determined by transient elastography, along with evidence of either overweight/obesity, type 2 diabetes mellitus, or metabolic dysfunction. DII was calculated using 27 dietary components collected through 24-hour dietary recall questionnaire. Weighted logistic regression was used to analyze the relationship between DII and MAFLD and its main components in three different models. Subgroup analyses were performed by age, sex, and alcohol use. RESULTS: A total of 1991 participants were included, and the MAFLD group had higher DII scores. After adjusting for age, sex, race, physical activity, smoking status, and alcohol use, the highest quartile of DII was associated with increased risk of MAFLD (OR:2.90, 95% CIs: 1.46, 5.75). Overweight/obesity, central obesity, low high density lipoprotein cholesterol (HDL-C) and high C-reactive protein (CRP) also shared the same characteristics in the main components of MAFLD. Results were consistent across subgroups (age, sex, and alcohol use). CONCLUSIONS: A higher DII diet was positively associated with the risk of MAFLD in American adults, particularly as related to overweight/obesity, central obesity, high CRP level, and low HDL-C level.

CucumberAI: Cucumber Fruit Morphology Identification System Based on Artificial Intelligence.

Cucumber is an important vegetable crop that has high nutritional and economic value and is thus favored by consumers worldwide. Exploring an accurate and fast technique for measuring the morphological traits of cucumber fruit could be helpful for improving its breeding efficiency and further refining the development models for pepo fruits. At present, several sets of measurement schemes and standards have been proposed and applied for the characterization of cucumber fruits; however, these manual methods are time-consuming and inefficient. Therefore, in this paper, we propose a cucumber fruit morphological trait identification framework and software called CucumberAI, which combines image processing techniques with deep learning models to efficiently identify up to 51 cucumber features, including 32 newly defined parameters. The proposed tool introduces an algorithm for performing cucumber contour extraction and fruit segmentation based on image processing techniques. The identification framework comprises 6 deep learning models that combine fruit feature recognition rules with MobileNetV2 to construct a decision tree for fruit shape recognition. Additionally, the framework employs U-Net segmentation models for fruit stripe and endocarp segmentation, a MobileNetV2 model for carpel classification, a ResNet50 model for stripe classification and a YOLOv5 model for tumor identification. The relationships between the image-based manual and algorithmic traits are highly correlated, and validation tests were conducted to perform correlation analyses of fruit surface smoothness and roughness, and a fruit appearance cluster analysis was also performed. In brief, CucumberAI offers an efficient approach for extracting and analyzing cucumber phenotypes and provides valuable information for future cucumber genetic improvements.

Molecular dynamics-guided optimization of BGM0504 enhances dual-target agonism for combating diabetes and obesity.

The dual activation of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) has emerged as a promising therapeutic strategy for managing type 2 diabetes and obesity. Tirzepatide, a dual agonist peptide, has exhibited superior clinical efficacy in glycemic and weight control compared to selective GLP-1R agonists. Nevertheless, the structural basis of Tirzepatide's extended half-life, attributed to an acylation side chain on the parent peptide, raises questions regarding its partial agonistic activity. Employing molecular dynamics simulations, we explored the dynamic processes of peptide-receptor interactions. We uncovered a crucial salt bridge between parent peptide and GLP-1R/GIPR at K20, a feature not discernible in cryo-electron microscopy structures. Building upon these insights, we developed an optimization strategy based on the parent peptide which involved repositioning the acylation side chain. The results of both in vitro and in vivo experiments demonstrated that the optimized peptide has twofold to threefold increase in agonistic activity compared to Tirzepatide while maintaining its extended half-life in plasma. This led to the design of BGM0504, which proved to be more effective than its predecessor, Tirzepatide, in both laboratory and animal studies.

Effects of Different Surface Functionalizations of Silica Nanoparticles on Mesenchymal Stem Cells.

Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.

Highly efficient field-free switching of perpendicular yttrium iron garnet with collinear spin current.

Yttrium iron garnet, a material possessing ultralow magnetic damping and extraordinarily long magnon diffusion length, is the most widely studied magnetic insulator in spintronics and magnonics. Field-free electrical control of perpendicular yttrium iron garnet magnetization with considerable efficiency is highly desired for excellent device performance. Here, we demonstrate such an accomplishment with a collinear spin current, whose spin polarization and propagation direction are both perpendicular to the interface. Remarkably, the field-free magnetization switching is achieved not only with a heavy-metal-free material, Permalloy, but also with a higher efficiency as compared with a typical heavy metal, Pt. Combined with the direct and inverse effect measurements, we ascribe the collinear spin current to the anomalous spin Hall effect in Permalloy. Our findings provide a new insight into spin current generation in Permalloy and open an avenue in spintronic devices.

The Pharyngeal Packs for Dental and Otolaryngological Surgery: A Meta-Analysis of High-Quality Randomized Controlled Trials.

Background: Pharyngeal packs are employed to mitigate postoperative nausea and vomiting (PONV) and have become prevalent in dental and otolaryngological surgeries. However, their clinical efficacy continues to be a topic of debate. The objective of the present study was to conduct a quantitative assessment of the impact of pharyngeal packing in dental and otolaryngological surgeries through meta-analysis. Methods: We identified relevant randomized controlled trials (RCTs) through systematic searches of online databases, including PubMed, Embase, and Cochrane Central. Potential eligible studies were evaluated using the Jadad scoring system (range 0-5 points), with only high-quality RCTs (3 points or more) being included. The incidence of PONV, morbidity, and the level of throat pain were aggregated and estimated. Publication bias was evaluated using funnel plot symmetry and the Egger test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to rate the evidence. Results: Ten high-quality RCTs comprising 1026 participants were ultimately included. Subsequent quantitative pooled estimation unveiled that the utilization of pharyngeal packing did not lead to a significant reduction in the incidence of nausea (P = .272), vomiting (P = .775), overall PONV (P = .118), or throat pain (P = .149). By contrast, the application of pharyngeal packs was found to significantly increase the level of throat pain (P = .003). No obvious publication bias was detected, and the majority of evidence was rated high or moderate. Conclusion: Based on the existing evidence, we conclude that pharyngeal packing lacks clinical benefit and is not advised for dental and otolaryngological surgeries.

The Effect of Surgery on the Prognosis of Gastric Lymphoma: A Meta-analysis.

OBJECTIVE: Surgery is an effective clinical approach that has been used for the treatment of gastric lymphoma. However, its specific effect on the prognosis of patients with gastric lymphoma remains largely unknown. The current meta-analysis aimed to identify the effect of surgery on the prognosis of gastric lymphoma. METHODS: We searched the MEDLINE, Embase, and Cochrane Central databases to obtain relevant studies investigating the influence of surgery on overall survival (OS) and relapse-free survival (RFS). We extracted the hazard ratios (HRs) and associated 95% confidence intervals (CIs) of each included report for pooled analysis. We assessed heterogeneity (I2 statistic) and funnel plots to select the data models and evaluate publication bias. RESULTS: Ultimately, we included 12 studies containing 26 comparisons in the current quantitative meta-analysis. The analysis revealed that surgery had no significant effect on OS (HR .83, P = .13) or RFS (HR .78, P = .08). However, subgroup analysis revealed that the effect of surgery on OS differed significantly between the surgery plus conservative therapy subgroup and the conservative therapy alone groups, with HR = .69 (P = .01). No significant publication bias was detected regarding the main outcomes. CONCLUSION: Surgery had a limited effect on the prognosis of patients with gastric lymphoma. However, the use of surgery as an additional therapy may confer potential benefits. This was an interesting research direction, and additional high-quality, large-scale randomized controlled trials should be conducted.

Moringa oleifera leaf extracts protect BMSC osteogenic induction following peroxidative damage by activating the PI3K/Akt/Foxo1 pathway.

OBJECTIVE: We aimed to investigate the therapeutic effects of Moringa oleifera leaf extracts on osteogenic induction of rat bone marrow mesenchymal stem cells (BMSCs) following peroxidative damage and to explore the underlying mechanisms. METHODS: Conditioned medium was used to induce osteogenic differentiation of BMSCs, which were treated with H2O2, Moringa oleifera leaf extracts-containing serum, or the phosphatidyl inositol-3 kinase (PI3K) inhibitor wortmannin, alone or in combination. Cell viability was measured using the MTT assay. Cell cycle was assayed using flow cytometry. Expression levels of Akt, phosphorylated (p)Akt, Foxo1, and cleaved caspase-3 were analyzed using western blot analysis. The mRNA levels of osteogenesis-associated genes, including alkaline phosphatase (ALP), collagen І, osteopontin (OPN), and Runx2, were detected using qRT-PCR. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and ALP activity were detected using commercially available kits. Osteogenic differentiation capability was determined using alizarin red staining. RESULTS: During osteogenic induction of rat BMSCs, H2O2 reduced cell viability and proliferation, inhibited osteogenesis, increased ROS and MDA levels, and decreased SOD and GSH-PX activity. H2O2 significantly reduced pAkt and Foxo1 expression, and increased cleaved caspase-3 levels in BMSCs. Additional treatments with Moringa oleifera leaf extracts partially reversed the H2O2-induced changes. Wortmannin partially attenuated the effects of Moringa oleifera leaf extracts on protein expression of Foxo1, pAkt, and cleaved caspase-3, as well as mRNA levels of osteogenesis-associated genes. CONCLUSION: Moringa oleifera leaf extracts ameliorate peroxidative damage and enhance osteogenic induction of rat BMSCs by activating the PI3K/Akt/Foxo1 pathway.

Ghost spintronic THz-emitter-array microscope.

Terahertz (THz) waves show great potential in nondestructive testing, biodetection and cancer imaging. Despite recent progress in THz wave near-field probes/apertures enabling raster scanning of an object's surface, an efficient, nonscanning, noninvasive, deep subdiffraction imaging technique remains challenging. Here, we demonstrate THz near-field microscopy using a reconfigurable spintronic THz emitter array (STEA) based on the computational ghost imaging principle. By illuminating an object with the reconfigurable STEA followed by computing the correlation, we can reconstruct an image of the object with deep subdiffraction resolution. By applying an external magnetic field, in-line polarization rotation of the THz wave is realized, making the fused image contrast polarization-free. Time-of-flight (TOF) measurements of coherent THz pulses further enable objects at different distances or depths to be resolved. The demonstrated ghost spintronic THz-emitter-array microscope (GHOSTEAM) is a radically novel imaging tool for THz near-field imaging, opening paradigm-shifting opportunities for nonintrusive label-free bioimaging in a broadband frequency range from 0.1 to 30 THz (namely, 3.3-1000 cm-1).

Thioredoxin mitigates H2 O2 -induced inhibition of myogenic differentiation of rat bone marrow mesenchymal stem cells by enhancing AKT activation.

Thioredoxin (Trx) is a hydrogen acceptor of ribonucleotide reductase and a regulator of some enzymes and receptors. It has been previously shown that significantly elevated levels of Trx expression are associated with the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but it is not clear how Trx regulates the effects of hydrogen peroxide (H2 O2 ) on myogenic differentiation of BMSCs. Here, we report that rat BMSCs treated with a high dose (150 µm) of H2 O2 exhibited a significant reduction in viability, cell cycling, and superoxide dismutase and glutathione peroxidase levels, and an increase in reactive oxygen species and malondialdehyde levels, which was accompanied by reductions in protein kinase B activation and forkhead Box O1, myogenic differentiation 1 and myogenin expression during myogenic differentiation. Furthermore, treatment with recombinant human Trx significantly mitigated the effects of H2 O2 on the myogenic differentiation of BMSCs, and this was abrogated by cotreatment with wortmannin [a specific phosphatidylinositol 3-kinase inhibitor]. In summary, our results suggest that treatment with recombinant human Trx mitigates H2 O2 -induced oxidative stress and may promote myogenic differentiation of rat BMSCs by enhancing phosphatidylinositol 3-kinase/protein kinase B/forkhead Box O1 signaling.

Design, synthesis and antitumor activity of a novel PEG-A6-conjugated irinotecan derivative.

A novel PEG-A6-conjugated irinotecan derivative 8 was designed and synthesized as antitumor agent by the PEGylation and A6-peptide modification of irinotecan. In vivo antitumor activity screening assay revealed that 8 exhibited better in vivo antiproliferation activity than irinotecan and its previous PEG-cRGD-conjugated derivative BGC0222 in MIA PaCa-2, NCI-H446, MDA-MB-231, HT-29 and NCI-N87 xenograft models, while the tumor of one in six mice in NCI-H446 assay and the tumors of two in six mice in MIA PaCa-2 assay completely subsided and disappeared within the 21-day period of 8-treatment, indicating that 8 should be a potential antitumor agent.

Design, synthesis and pharmacological evaluation of a novel PEG-cRGD-conjugated irinotecan derivative as potential antitumor agent.

A novel PEG-cRGD-conjugated irinotecan derivative BGC0222 was designed and synthesized as antitumor agent. Antitumor activity screening assay indicated that BGC0222 exhibited better in vitro antiproliferation activity than irinotecan and NKTR-102 against HT29, MIA PaCa-2 and MCF-7 tumor cell lines, with IC50 of 1.83 ±â€¯0.09 µM, 3.95 ±â€¯0.16 µM and 0.68 ±â€¯0.04 µM, respectively, while it displayed better in vivo antiproliferation activity than irinotecan and NKTR-102 in HT-29, MIA PaCa-2, NCI-H446, U-87 MG and MDA-MB-231 xenograft models. The action mechanism of BGC0222 was then investigated by integrin-binding competition (IBC) and chick chorioallantoic membrane (CAM) angiogenesis assays, which indicated that BGC0222 may exert antitumor activity by binding to αvß3 target and consequently inducing neovascularization effect. Pharmacokinetic analysis showed that BGC0222 could slowly and steadily release irinotecan, which was subsequently metabolized into 7-ethyl-10-hydroxycamptothecin (SN-38) in the whole blood.

Home-based HIV testing for men who have sex with men in China: a novel community-based partnership to complement government programs.

BACKGROUND: The coverage of HIV testing among Chinese men who have sex with men (MSM) remains low after the scale-up of free HIV testing at government-sponsored testing sites. We evaluated the feasibility of home-based HIV self-testing and the willingness to be HIV tested at community-based organizations (CBO). METHODS: We recruited MSM via on-line advertisement, where they completed an on-line informed consent and subsequent questionnaire survey. Eligible MSM received HIV rapid testing kits by mail, performed the test themselves and reported the result remotely. RESULTS: Of the 220 men taking a home-based HIV self-testing, 33 MSM (15%) were seropositive. Nearly 65% of the men reported that they were willing to take HIV testing at CBO, while 28% preferred receiving free HIV testing in the government programs at local Centers for Disease Control and Prevention (CDC). Older and lower-income MSM, those who self-reported homosexual orientation, men with no history of sexually transmitted diseases and a lower number of sexual partners in the past six months were associated with preference for taking HIV testing at CBOs. The top three self-reported existing barriers for HIV testing were: no perception of HIV risk (56%), fear of an HIV positive result being reported to the government (41%), and fear of a positive HIV test result (36%). CONCLUSION: Home-based HIV self-testing is an alternative approach for increasing the coverage of HIV testing among Chinese MSM. CBO-based HIV testing is a potential alternative, but further studies are needed to evaluate its feasibility.

The Raf-1 inhibitor GW5074 and the ERK1/2 pathway inhibitor U0126 ameliorate PC12 cells apoptosis induced by 6-hydroxydopamine.

6-Hydroxydopamine (6-OHDA) is a widely used dopaminergic neurotoxin that leads to cell apoptosis in vivo and in vitro, and is a widely accepted experimental model of neurodegeneration in Parkinson's disease. However, the molecular mechanisms responsible for 6-OHDA-induced cell apoptosis are unclear. We found that the treatment of PC12 cells with 6-OHDA resulted in a significant decrease in cell viability and elevated apoptosis as detected by MTT assay, Hoechst 33258 staining, and flow cytometry. In addition, 6-OHDA induced a time-dependent phosphorylation of ERK1/2 at Thr-202/Tyr-204 and of Raf-1 at Ser-338, but a decreased level of Raf-1 phosphorylation at Ser-259. Phosphorylation of ERK1/2 at Thr-202/Tyr-204 and Raf-1 at Ser-338 were inhibited by the Raf-1 inhibitor GW5074, while the ERK1/2 pathway inhibitor U0126 decreased phosphorylation of ERK1/2. Furthermore, 6-OHDA-induced PC12 cells apoptosis was suppressed by GW5074 and U0126. Our results suggest that GW5074 and U0126 act as neuroprotants against 6-OHDA toxicity in PC12 cells by modulating Raf-1/ERK1/2 signaling systems.

[Combination application of radiofrequency ablation in nasal operation].

OBJECTIVE: To investigate the clinical efficacy of radiofrequency ablation in treating the inferior turbinates hypertrophic and allergic rhinitis after septoplasty or nasal polypectomy. METHOD: Ninety-one patients with nasal septum deviation or nasal polyp with inferior turbinates hypertrophic and(or) allergic rhinitis were underwent septoplasty or nasal polypectomy. Sixty-two cases of 91 patients with inferior turbinates hypertrophic or allergic rhinitis underwent radiofrequency ablation, 29 cases did not. The preoperative and postoperative nasal obstructions were investigated by visual analogue scale (VAS). Allergic rhinitis symptoms were assessed by 1997s Haikou standard. RESULT: The nasal obstruction and allergic symptom of 62 patients who underwent radiofrequency ablation were improved in 3 months postoperatively. VAS improved from (89.5+/-8.7) % to (26.2+/-8.7) % (left side) and (90.3+/-10.5) % to (32.1+/-10.3) % (right side) (P < 0.01). In control group: VAS improved from (90.5+/-8.0) % to (39.2+/-8.9) % (left side) and (89.9+/-11.5) % to (48.1+/-8.1) % (right side) (P <0.01). However, the mean of postoperative nasal obstruction VAS in radiofrequency ablation group is significantly higher than that in control group (P <0.01). CONCLUSION: Combination application of radiofrequency ablation in nasal operation to cure the inferior turbinates hypertrophic and allergic rhinitis is a safe, effective and less traumatic method.