Stack growth of wafer-scale van der Waals superconductor heterostructures.

Two-dimensional (2D) van der Waals (vdW) heterostructures have attracted considerable attention in recent years1-5. The most widely used method of fabrication is to stack mechanically exfoliated micrometre-sized flakes6-18, but this process is not scalable for practical applications. Despite thousands of 2D materials being created, using various stacking combinations1-3,19-21, hardly any large 2D superconductors can be stacked intact into vdW heterostructures, greatly restricting the applications for such devices. Here we report a high-to-low temperature strategy for controllably growing stacks of multiple-layered vdW superconductor heterostructure (vdWSH) films at a wafer scale. The number of layers of 2D superconductors in the vdWSHs can be precisely controlled, and we have successfully grown 27 double-block, 15 triple-block, 5 four-block and 3 five-block vdWSH films (where one block represents one 2D material). Morphological, spectroscopic and atomic-scale structural analyses reveal the presence of parallel, clean and atomically sharp vdW interfaces on a large scale, with very little contamination between neighbouring layers. The intact vdW interfaces allow us to achieve proximity-induced superconductivity and superconducting Josephson junctions on a centimetre scale. Our process for making multiple-layered vdWSHs can easily be generalized to other situations involving 2D materials, potentially accelerating the design of next-generation functional devices and applications22-24.

Autocrine FGF1 signaling promotes glucose uptake in adipocytes.

Fibroblast growth factor 1 (FGF1) is an autocrine growth factor released from adipose tissue during over-nutrition or fasting to feeding transition. While local actions underlie the majority of FGF1's anti-diabetic functions, the molecular mechanisms downstream of adipose FGF receptor signaling are unclear. We investigated the effects of FGF1 on glucose uptake and its underlying mechanism in murine 3T3-L1 adipocytes and in ex vivo adipose explants from mice. FGF1 increased glucose uptake in 3T3-L1 adipocytes and epididymal WAT (eWAT) and inguinal WAT (iWAT). Conversely, glucose uptake was reduced in eWAT and iWAT of FGF1 knockout mice. We show that FGF1 acutely increased adipocyte glucose uptake via activation of the insulin-sensitive glucose transporter GLUT4, involving dynamic crosstalk between the MEK1/2 and Akt signaling proteins. Prolonged exposure to FGF1 stimulated adipocyte glucose uptake by MEK1/2-dependent transcription of the basal glucose transporter GLUT1. We have thus identified an alternative pathway to stimulate glucose uptake in adipocytes, independent from insulin, which could open new avenues for treating patients with type 2 diabetes.

Pectic oligosaccharides: enzymatic preparation, structure, bioactivities and application.

Pectic oligosaccharides have become novel bioactive components. However, the comprehensive preparation methods, structural features, bioactivities and application of them lack a systematic review. Here, we focused on the enzymatic preparation of pectic oligosaccharides, and attempted to outline relationships among the enzymolysis condition, structure, bioactivities and application of pectic oligosaccharides. Pectic oligosaccharides were characterized by the oligosaccharides with units of →4)-α-GalpA-(1→4)-α-GalpA-(1→ or →4)-α-GalpA-(1→2)-α-Rhap-(1→. Enzymatic method was the most suitable approach for pectic oligosaccharides preparation that was significantly affected by the enzyme's type, time and concentration. Besides, pectic oligosaccharides possessed various bioactivities including prebiotic, anti-glycosylation, antioxidant, anticancer and lipid metabolism-regulation activities, which were closely associated with the molecular weight, the structure of side chain and the monosaccharide composition. Especially, many pectic oligosaccharides with low molecular weight demonstrated high prebiotic activities, and those with arabinogalactan side chains exhibited strong anticancer activities. Moreover, pectic oligosaccharides have been used in food preservatives, dairy product additives and food processing aids. Nevertheless, the industrial application, novel technology exploration, and structure-bioactivity relationship of pectic oligosaccharides remain a demanding and significant task for future work.

Tai Chi-Induced Exosomal LRP1 is Associated With Memory Function and Hippocampus Plasticity in aMCI Patients.

OBJECTIVES: The study was designed to identify the potential peripheral processes of circulating exosome in response to Tai Chi (TC) exercise and the possibility of its loaded cargos in mediating the effects of TC training on cognitive function among older adults with amnestic mild cognitive impairment (aMCI). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter randomized controlled trial. One hundred community-dwelling old adults with aMCI were randomly assigned (1:1) to experimental (n = 50) and control groups (n = 50). INTERVENTION: The experimental group participated in TC exercise 5 times/week, with each session lasting 60 minutes for 12 weeks. Both experimental and control groups received health education every 4 weeks. MEASUREMENTS: The primary outcome was global cognitive function. Neurocognitive assessments, MRI examination, and large-scale proteomics analysis of peripheric exosome were conducted at baseline and after 12-week training. Outcome assessors and statisticians were blinded to group allocation. RESULTS: A total of 96 participants (96%) completed all outcome measurements. TC training improved global cognitive function (adjusted mean difference [MD] = 1.9, 95%CI 0.93-2.87, p <0.001) and memory (adjusted MD = 6.42, 95%CI 2.09-10.74, p = 0.004), increased right hippocampus volume (adjusted MD = 88.52, 95%CI 13.63-163.4, p = 0.021), and enhanced rest state functional connectivity (rsFC) between hippocampus and cuneus, which mediated the group effect on global cognitive function (bootstrapping CIs: [0.0208, 1.2826], [0.0689, 1.2211]) and verbal delay recall (bootstrapping CI: [0.0002, 0.6277]). Simultaneously, 24 differentially expressed exosomal proteins were detected in tandem mass tag-labelling proteomic analysis. Of which, the candidate protein low-density lipoprotein receptor-related protein 1 (LRP1) was further confirmed by parallel reaction monitoring and ELISA. Moreover, the up-regulated LRP1 was both positively associated with verbal delay recall and rsFC (left hippocampus-right cuneus). CONCLUSION: TC promotes LRP1 release via exosome, which was associated with enhanced memory function and hippocampus plasticity in aMCI patients. Our findings provided an insight into potential therapeutic neurobiological targets focusing on peripheric exosome in respond to TC exercise.

Large-scale array for radio astronomy on the farside (LARAF).

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1-50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

Trapping Hydrogen Molecules between Perfect Graphene.

There is a lack of deep understanding of hydrogen intercalation into graphite due to many challenges faced during characterization of the systems. Therefore, a suitable route to trap isolated hydrogen molecules (H2) between the perfect graphite lattices needs to be found. Here we realize the formation of hydrogen bubbles in graphite with controllable density, size, and layer number. We find that the molecular H2 cannot be diffused between nor escape from the defect-free graphene lattices, and it remains stable in the pressurized bubbles up to 400 °C. The internal pressure of H2 inside the bubbles is strongly temperature dependent, and it decreases as the temperature rises. The proton permeation rate can be estimated at a specific plasma power. The producing method of H2 bubbles offers a useful way for storing hydrogen in layered materials, and these materials provide a prospective research platform for studying nontrivial quantum effects in confined H2.

Electroacupuncture improves vascular cognitive impairment no dementia: A Randomized Clinical Trial.

BACKGROUND: Electroacupuncture (EA) could represent a clinically effective treatment strategy for patients with vascular cognitive impairment no dementia (VCIND). This randomized trial aims to explore the underlying mechanism of EA in VCIND patients through cognitive function assessment and neuroimaging assessment. METHODS: 140 eligible patients with VCIND were recruited and randomly divided into EA group (n = 70) and Control group (n = 70). The Montreal Cognitive Assessment (MoCA), and the Auditory Verbal Learning Test (AVLT), the Stroop color-naming task (STROOP), and the resting-state functional magnetic resonance imaging assessment. The EA group received treatment for 30 min/day, 5 times/week, for 8 weeks. RESULTS: EA intervention could increase the MoCA score and improve the neutral and consistency response of the STROOP test in VCIND patients (P < 0.05). fMRI functional connectivity analysis showed that, after EA, the default mode network (DMN) function of the posterior cingulate gyrus, left middle frontal gyrus, left anterior cingulate gyrus, left and right superior temporal gyrus, right insula, left precentral gyrus and other brain regions were significantly higher than that in the control group. The functional connectivity between the posterior cingulate gyrus-left middle frontal gyrus and the posterior cingulate gyrus-right superior temporal gyrus was positively correlated with cognitive function (P < 0.05). Gray Matter Volume increased in VCIND after EA(P < 0.05). CONCLUSIONS: EA can increase the functional connectivity between posterior cingulate gyrus-other gyri in VCIND patients. The functional connectivity is positively correlated with cognitive function.

120-GBaud 16-QAM silicon photonics IQ modulator for data center interconnection.

We demonstrated all-silicon IQ modulators (IQMs) operating at 120-GBaud 16-QAM with suitable bandwidth, and output power. We required optical signal-to-noise-ratio (rOSNR) that have promising potential to be used in 800-Gbps small-form-factor pluggable transceivers for data center interconnection. First, we tested an IQM chip using discrete drivers and achieved a per-polarization TX output power of -18.74 dBm and an rOSNR of 23.51 dB over a 100-km standard SMF. Notably, a low BER of 1.4e-3 was obtained using our SiP IQM chip without employing nonlinear compensation, optical equalization, or an ultra-wide-bandwidth, high-ENOB OMA. Furthermore, we investigated the performance of a 3D packaged transmitter by emulating its frequency response using an IQM chip, discrete drivers, and a programmable optical filter. With a laser power of 17 dBm, we achieved a per-polarization output power of -15.64 dBm and an rOSNR of 23.35 dB.

An evolving view on food viscosity regulating gastric emptying.

Viscosity is a property of most foods. The consumption of the high-viscosity food is associated with a variety of physiological responses, one of which is their ability to regulate gastric emptying and modulate postprandial glycemic response. Gastric emptying has been proven to be a key step affecting the digestion and absorption of food, whereas, the relationship between viscosity and gastric emptying is still far away from being understood. Here, we reviewed the factors that influence food viscosity and food viscosity changes during digestion. Besides, the effect of food viscosity on gastric emptying and food-viscosity-physiological response were highlighted. Finally, "quantitative relationship" of viscosity and gastric emptying was discussed. This review can contribute to the understanding that how food viscosity affects gastric emptying, and help for developing foods that could control satiety and manage body weight for the specific populations.

Advanced review on type II collagen and peptide: preparation, functional activities and food industry application.

Type II collagen is a homologous super-helical structure consisting of three identical α1(II) chains. It is a major component of animal cartilage, and is widely used in the food industry. Type II collagen can be extracted by acids, salts, enzymes, and via auxiliary methods and can be further hydrolyzed chemically and enzymatically to produce collagen peptides. Recent studies have shown that type II collagen and its polypeptides have good self-assembly properties and important biological activities, such as maintaining cartilage tissue integrity, inducing immune tolerance, stimulating chondrocyte growth and redifferentiation, and providing antioxidant benefits. This review focuses specifically on type II collagen and describes its structure, extraction, and purification, as well as the preparation of type II collagen peptides. In particular, the self-assembly properties and functional activities of type II collagen and collagen peptides are reviewed. In addition, recent research advances in the application of type II collagen and collagen peptides in functional foods, food additives, food coating materials, edible films, and carriers for the food industry are presented. This paper provides more detailed and comprehensive information on type II collagen and peptide for their application.

Effects of Exercise Training Under Hypoxia versus Normoxia on Cognitive Function in Clinical and Non-Clinical Populations: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the effects of exercise training under hypoxia versus normoxia on cognitive function in clinical and non-clinical populations. DATA SOURCES: From inception to June 13th, 2022, a systematic search was performed on PubMed, Web of Science, Embase, Scopus, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials comparing the effects of exercise under hypoxic vs normoxic on cognition in clinical and non-clinical populations were included. The systematic search generated 14,894 relevant studies, of which 12 were finally included. DATA EXTRACTION: Two reviewers independently extracted data from included studies. Results were expressed as standardized mean difference (SMD). Each included study was assessed using the Cochrane Risk of Bias 1.0 (RoB1.0) tool. Finally, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to rate the certainty of evidence for each outcome. DATA SYNTHESIS: Overall, 12 studies with a total of 338 participants met the inclusion criteria. The pooled results suggested that hypoxia exercise had a small but not statistically significant positive effect on overall cognitive function (SMD=0.064, 95% confidence interval (CI): -0.156-0.284, P=.567, very low-certainty evidence), when compared with normoxic exercise. Regarding the domain-specific cognitive functions, there was a medium and significant positive effect on memory (SMD=0.594, 95% CI: 0.068 to 1.120, P=.027, very low-certainty evidence), while effects on visuospatial function (SMD=0.490, 95% CI: -0.030 to 1.010, P=.065, very low-certainty evidence), attention (SMD=0.037, 95% CI: -0.340 to 0.414, P=.847, very low-certainty evidence), executive function (SMD=0.096, 95% CI: -0.268 to 0.460, P=.605, very low-certainty evidence), and processing speed (SMD=-0.145, 95% CI: -0.528 to 0.239, P=.459, very low-certainty evidence) were not statistically significant. CONCLUSIONS: The current pooled results revealed that hypoxic exercise was related to improved cognitive performance. Nevertheless, exercise under hypoxia did not have a significant advantage in cognitive promotion when compared with exercise under normoxia.

Effect of Multicomponent Exercise on Cognition, Physical Function and Activities of Daily Life in Older Adults With Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-analysis.

OBJECTIVE: To review the evidence for the effectiveness of multicomponent exercise (an exercise program combining aerobic, endurance, balance, and flexibility exercises) on cognition, physical function, and activities of daily living in people with dementia and mild cognitive impairment (MCI). DATA SOURCES AND STUDY SELECTION: We conducted this study under the guidance of a designated protocol (PROSPERO CRD42022324641). Pertinent randomized controlled trials were selected from PubMed, Embase, Web of Science, and the Cochrane Library by 2 independent authors through May 2022. DATA EXTRACTION: Two authors independently extracted the data and assessed the quality of the included studies following the Cochrane Risk of Bias tool. Outcome data were extracted in a random effects model and estimated as Hedges' g and 95% confidence interval (CI). To validate specific results, the Egger test combined the Duval and Tweedie "trim and fill" method and sensitivity analysis with study removed were performed. DATA SYNTHESIS: A total of 21 publications were eligible for the quantitative analysis. In dementia, estimates of Hedges' g showed effects on global cognition (g=0.403; 95% CI, 0.168-0.638; P<.05), especially executive function (g=0.344; 95% CI, 0.111-0.577; P<.05), flexibility (g=0.671; 95% CI, 0.353-0.989; P<.001), agility and mobility (g=0.402; 95% CI, 0.089-0.714; P<.05), muscle strength (g=1.132; 95% CI, 0.420-1.845; P<.05), and activities of daily living (g=0.402; 95% CI, 0.188-0.615; P<.05). Also, a positive trend was observed in gait speed. Additionally, multicomponent exercise had positive effects on global cognition (g=0.978; 95% CI, 0.298-1.659; P<.05) and executive function (g=0.448; 95% CI, 0.171-0.726; P<.05) in patients with MCI. CONCLUSIONS: Our findings confirm the viability of multicomponent exercise as a management strategy for patients with dementia and MCI.

Electroacupuncture protective effects after cerebral ischemia are mediated through miR-219a inhibition.

BACKGROUND: Electroacupuncture (EA) is a complementary and alternative therapy which has shown protective effects on vascular cognitive impairment (VCI). However, the underlying mechanisms are not entirely understood. METHODS: Rat models of VCI were established with cerebral ischemia using occlusion of the middle cerebral artery or bilateral common carotid artery. The brain structure and function imaging were measured through animal MRI. miRNA expression was detected by chip and qPCR. Synaptic functional plasticity was detected using electrophysiological techniques. RESULTS: This study demonstrated the enhancement of Regional Homogeneity (ReHo) activity of blood oxygen level-dependent (BOLD) signal in the entorhinal cortical (EC) and hippocampus (HIP) in response to EA treatment. miR-219a was selected and confirmed to be elevated in HIP and EC in VCI but decreased after EA. N-methyl-D-aspartic acid receptor1 (NMDAR1) was identified as the target gene of miR-219a. miR-219a regulated NMDAR-mediated autaptic currents, spontaneous excitatory postsynaptic currents (sEPSC), and long-term potentiation (LTP) of the EC-HIP CA1 circuit influencing synaptic plasticity. EA was able to inhibit miR-219a, enhancing synaptic plasticity of the EC-HIP CA1 circuit and increasing expression of NMDAR1 while promoting the phosphorylation of downstream calcium/calmodulin-dependent protein kinase II (CaMKII), improving overall learning and memory in VCI rat models. CONCLUSION: Inhibition of miR-219a ameliorates VCI by regulating NMDAR-mediated synaptic plasticity in animal models of cerebral ischemia.

Electroacupuncture promotes neurogenesis in the dentate gyrus and improves pattern separation in an early Alzheimer's disease mouse model.

BACKGROUND: Impaired pattern separation occurs in the early stage of Alzheimer's disease (AD), and hippocampal dentate gyrus (DG) neurogenesis participates in pattern separation. Here, we investigated whether spatial memory discrimination impairment can be improved by promoting the hippocampal DG granule cell neogenesis-mediated pattern separation in the early stage of AD by electroacupuncture (EA). METHODS: Five familial AD mutations (5 × FAD) mice received EA treatment at Baihui and Shenting points for 4 weeks. During EA, mice were intraperitoneally injected with BrdU (50 mg/kg) twice a day. rAAV containing Wnt5a shRNA was injected into the bilateral DG region, and the viral efficiency was evaluated by detecting Wnt5a mRNA levels. Cognitive behavior tests were conducted to assess the impact of EA treatment on cognitive function. The hippocampal DG area Aß deposition level was detected by immunohistochemistry after the intervention; The number of BrdU+/CaR+ cells and the gene expression level of calretinin (CaR) and prospero homeobox 1(Prox1) in the DG area of the hippocampus was detected to assess neurogenesis by immunofluorescence and western blotting after the intervention; The gene expression levels of FZD2, Wnt5a, DVL2, p-DVL2, CaMKII, and p-CaMKII in the Wnt signaling pathway were detected by Western blotting after the intervention. RESULTS: Cognitive behavioral tests showed that 5 × FAD mice had impaired pattern separation (P < 0.001), which could be improved by EA (P < 0.01). Immunofluorescence and Western blot showed that the expression of Wnt5a in the hippocampus was decreased (P < 0.001), and the neurogenesis in the DG was impaired (P < 0.001) in 5 × FAD mice. EA could increase the expression level of Wnt5a (P < 0.05) and promote the neurogenesis of immature granule cells (P < 0.05) and the development of neuronal dendritic spines (P < 0.05). Interference of Wnt5a expression aggravated the damage of neurogenesis (P < 0.05), weakened the memory discrimination ability (P < 0.05), and inhibited the beneficial effect of EA (P < 0.05) in AD mice. The expression level of Wnt pathway related proteins such as FZD2, DVL2, p-DVL2, CAMKII, p-CAMKII increased after EA, but the effect of EA was inhibited after Wnt5a was knocked down. In addition, EA could reduce the deposition of Aß plaques in the DG without any impact on Wnt5a. CONCLUSION: EA can promote hippocampal DG immature granule cell neogenesis-mediated pattern separation to improve spatial memory discrimination impairment by regulating Wnt5a in 5 × FAD mice.

Efficacy and safety of acupuncture combined with rehabilitation training for poststroke cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Accumulated evidence has proven that both acupuncture and rehabilitation therapy are beneficial for stroke sequelae. However, there is no systematic review to identify the efficacy and safety of acupuncture combined with rehabilitation training for poststroke cognitive impairment (PSCI). Therefore, the aim of this study was to assess the efficacy and safety of acupuncture combined with rehabilitation therapy for patients with PSCI. METHODS: We searched nine databases, including PubMed, Embase, Scopus, Web of Science, EBSCO, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wan Fang, from their inception to September 2022. Randomized controlled trials (RCTs) examining the effect of acupuncture combined with rehabilitation on PSCI were included. The primary outcomes were the Mini-Mental State Examination (MMSE) score, Montreal Cognitive Assessment (MoCA) score, Modified Barthel Index (MBI) score, and Fugl-Meyer Assessment (FMA) score. The quality of the methodology was evaluated by Cochrane's risk of bias tool. Meta-analyses were performed by Revman 5.3 software. RESULTS: A total of 18 RCTs involving 1654 patients were included. The overall methodological quality of the included studies was low. Pooled results demonstrated that acupuncture combined with rehabilitation could significantly improve the clinical efficacy of PSCI (OR=3.23, 95% CI: 2.13 to 4.89), MMSE score (MD= 2.85, 95% CI: 2.56 to 3.15), MoCA score (MD= 2.18, 95% CI: 1.38 to 2.97), MBI score (MD= 9.23, 95% CI: 5.62 to 12.84), and FMA score (MD=5.72, 95% CI: 3.48 to 7.96). CONCLUSIONS: Acupuncture combined with rehabilitation may produce better outcomes than rehabilitation alone in the treatment of PSCI. However, the safety of combined interventions is still unclear. Therefore, research with more rigorous study designs and RCTs with larger sample sizes is still needed.

Schisandrin B Alleviates Renal Tubular Cell Epithelial-Mesenchymal Transition and Mitochondrial Dysfunction by Kielin/Chordin-like Protein Upregulation via Akt Pathway Inactivation and Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase Pathway Activation in Diabetic Kidney Disease.

Diabetic kidney disease is a common complication of diabetes and remains the primary cause of end-stage kidney disease in the general population. Schisandrin B (Sch B) is an active ingredient in Schisandra chinensis. Our study illustrates that Sch B can mitigate renal tubular cell (RTC) epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction in db/db mice, accompanied by the downregulation of TGF-ß1 and the upregulation of PGC-1α. Similarly, Sch B demonstrated a protective effect by reducing the expression of TGF-ß1, α-SMA, fibronectin, and Col I, meanwhile enhancing the expression of E-cadherin in human RTCs (HK2 cells) stimulated with high glucose. Moreover, under high glucose conditions, Sch B effectively increased mitochondrial membrane potential, lowered ROS production, and increased the ATP content in HK2 cells, accompanied by the upregulation of PGC-1α, TFAM, MFN1, and MFN2. Mechanistically, the RNA-seq results showed a significant increase in KCP mRNA levels in HK2 cells treated with Sch B in a high glucose culture. The influence of Sch B on KCP mRNA levels was confirmed by real-time PCR in high glucose-treated HK2 cells. Depletion of the KCP gene reversed the impact of Sch B on TGF-ß1 and PGC-1α in HK2 cells with high glucose level exposure, whereas overexpression of the KCP gene blocked EMT and mitochondrial dysfunction. Furthermore, the PI3K/Akt pathway was inhibited and the AMPK pathway was activated in HK2 cells exposed to a high concentration of glucose after the Sch B treatment. Treatment with the PI3K/Akt pathway agonist insulin and the AMPK pathway antagonist compound C attenuated the Sch B-induced KCP expression in HK2 cells exposed to a high level of glucose. Finally, molecular autodock experiments illustrated that Sch B could bind to Akt and AMPK. In summary, our findings suggested that Sch B could alleviate RTC EMT and mitochondrial dysfunction by upregulating KCP via inhibiting the Akt pathway and activating the AMPK pathway in DKD.

Chlorogenic acid improves intestinal morphology by enhancing intestinal stem-cell activity.

BACKGROUND: Chlorogenic acid (CGA), as one of the most abundant naturally occurring phenolic acids, has been documented to be beneficial for intestinal health. However, the underlying mechanism is still not fully understood. The adult intestinal stem cell is the critical driver of epithelial homeostasis and regeneration. RESULTS: This study hypothesized that CGA exerted intestinal health effects by modulating intestinal stem-cell functions. Lgr5-EGFP mice were treated for 14 days, and intestinal organoids derived from these mice were treated for 3 days, using CGA solution. In comparison with the control group, CGA treatment increased intestinal villous height and crypt depth in mice and augmented the area expansion and the number of budding intestinal organoids. Quantitative polymerase chain reaction (qPCR) analysis revealed that CGA treatment significantly increased the expression of genes coding intestinal stem-cell markers in intestinal tissue and organoids, and upregulated the expression of genes coding secretory cell lineages and enterocytes, although not statistically significantly. Fluorescence-activated cell-sorting analysis further confirmed that CGA augmented the number of stem cells. 5-Ethynyl-2'-deoxyuridine (EdU) incorporation and Ki67 immunostaining results also demonstrated that CGA treatment enhanced intestinal stem-cell proliferation. CONCLUSION: Altogether, our findings indicate that CGA could activate intestinal stem-cell and epithelial regeneration, which could contribute to the improvement of intestinal morphology or organoid growth of mice. This highlights a promising mechanism for CGA as an excellent candidate for the formulation of dietary supplements and functional foods for intestinal protection. © 2023 Society of Chemical Industry.

Specific surface modification of liposomes for gut targeting of food bioactive agents.

Liposomes have become a research hotspot in recent years as food delivery systems with attractive properties, including the bilayer structure assembled like the cell membrane, reducing the side-effect and improving environmental stability of cargos, controlling release, extending duration of functional ingredients, and high biodegradable and biocompatible abilities in the body. However, the conventional liposomes lack stability during storage and are weak in targeted absorption in the gastrointestinal track. At present, surface modification has been approved to be an effective platform to shield these barricades and help liposomes deliver the agents safely and effectively to the ideal site. In this review, the gastrointestinal stability of conventional liposomes, cargo release models from liposomes, and the biological fate of the core materials after release were emphasized. Then, the strategies in both physical and chemical perspectives to improve the stability and utilization of liposomes in the gastrointestinal tract, and the emerging approaches for improving gut targeting by specifically modified liposomes and the intestinal receptors relative to liposomes/cargos absorption were highlighted. Last but not the least, the safety, challenges, and opportunities for the improvement of liposomal bioavailability were also discussed to inspire new applications of liposomes as oral carriers.

A meta-analysis of the effect of endoscopic submucosal dissection compared with gastrectomy on the wound infection in early stomach cancer subjects.

We conducted a meta-analysis to assess the effect of endoscopic submucosal dissection compared with gastrectomy on the wound infection in early stomach cancer subjects. A systematic literature search up to November 2022 was performed and 2765 related studies were evaluated. The chosen studies comprised 7842 early stomach cancer subjects participated in the selected studies' baseline trials; 3308 of them used the endoscopic submucosal dissection, while 4534 used gastrectomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the wound infection in endoscopic submucosal dissection versus gastrectomy for early stomach cancer by the dichotomous methods with a random or fixed effect model. The use of endoscopic submucosal dissection resulted in significantly lower wound infection (OR, 0.45; 95% CI, 0.34-0.60, P < .001) with no heterogeneity (I2  = 8%) compared with the gastrectomy for early stomach cancer. The use of endoscopic submucosal dissection resulted in significantly lower wound infection compared with the gastrectomy for early stomach cancer. The small sample size of some studies in the comparison calls for care when analysing the results.

Neuroprotective effects of alisol A 24-acetate on cerebral ischaemia-reperfusion injury are mediated by regulating the PI3K/AKT pathway.

BACKGROUND: Neuroinflammation and apoptosis are involved in the pathogenesis of ischaemic stroke. Alisol A 24-acetate (24A) exerts a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A on global cerebral ischaemia/reperfusion (GCI/R) injury remains unclear. METHODS: GCI/R mice were used to investigate the neuroprotective effect of 24A. Modified neurological deficit scores, Morris water maze and object recognition tests were used to evaluate behaviours. Metabolism in brain regions was detected using magnetic resonance spectroscopy (MRS), and changes in microglia, astrocytes and neurons were detected. Inflammation and apoptosis were measured. RESULTS: The results showed that 24A suppressed neurological deficits scores and improved GCI/R induced cognitive dysfunction. It was also observed that 24A could alleviate neuroinflammation, which manifested as 24A inhibited microglia and astrocytes proliferation, downregulated the expression of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in the GCI/R mice brain. The apoptosis of neurons reduced, and dendritic spines of hippocampal neurons increased in the presence of 24A. In addition, 24A could up-regulate the expression of phosphorylated phosphoinositide 3-kinases (p-PI3K) and phosphorylated protein kinase B (p-AKT) in GCI/R mice brain, and all the morphological, neurological, and biochemical changes of 24A treatment were abolished by the application of PI3K/AKT pathway inhibitor LY294002. CONCLUSIONS: Taken together, our study indicated that 24A alleviated GCI/R injury by inhibiting neuroinflammation and apoptosis through the regulation of the PI3K/AKT pathway.