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Osteoarthritis (OA) is a common clinical chronic degenerative disease characteriszed by articular cartilage degeneration. Mesenchymal stem cells (MSCs) delay OA the development of OA mainly through paracrine effects. The conditioned medium (CM) of MSCs contains all the paracrine components of these cells, and many studies have demonstrated the anti-apoptotic and anti-inflammatory effects of CM in vitro. In this study, we investigated the effect of the CM of infrapatellar fat pad-derived MSCs (IPFSCs) on OA in vitro and in vivo, as well as and the potential underlying mechanisms. The results showed that injection of CM into the knee joint inhibited OA development in a rat model induced by destabilisation of the medial meniscus and anterior cruciate ligament transection. The CM increased the deposition of extracellular matrix-related components (type II collagen and Proteoglycan).In addition, CM inhibited the excessive production of pro-inflammatory mediators in human chondrocytes induced by IL-1 β, including COX2, iNOS, TNF- α and IL-6, and reduced the production of MMP13 and ADAMTS5, thus protecting the degradation of extracellular matrix. The activation of PI3K/AKT/NF- κ B signalling pathway was induced by IL-1β in chondrocytes, which was finally inhibited by CM-IPFSCs treatment. In summary, IPFSC-CM may have therapeutic potential for OA., (S. Karger AG, Basel.)

Objective: Diabetes is considered a significant risk factor for the development of atrial fibrillation/flutter (AF/AFL). However, there is still insufficient evidence to determine the varying effects of different hypoglycemic drugs (HDs) on the incidence of new-onset AF/AFL in diabetic patients. To address this gap, we conducted a network meta-analysis to investigate whether various HDs have different effects on the risk of new-onset AF/AFL compared with insulin., Method: We conducted a comprehensive search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify all clinical trials investigating the association between various HDs or insulin and incident AF/AFL up until April 1, 2024. Bayesian random-effects model was used for network meta-analysis, and the results were expressed as relative risk (RR) and 95% confidence interval (CI)., Result: After searching 2070 articles, a total of 12 studies (2,349,683 patients) were included in the network meta-analysis. The treatment regimen comprised insulin and 8 HDs hypoglycemic drugs, which are sodium-dependent glucose transporters 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), metformin (Met), sulfonylureas (SU), non-sulfonylureas (nSU), thiazolidinedione (TZD) and α-glycosidase inhibitors (AGI). The use of SGLT2i [RR 0.23, 95%CI (0.11, 0.49)], GLP-1RA [RR 0.28, 95%CI (0.13, 0.57)], and DPP4i [RR 0.34, 95%CI (0.17, 0.67)] demonstrated significant efficacy in reducing the incidence of new-onset AF/AFL when compared to insulin. When HDs were compared in pairs, SGLT2i is more effective than Met [RR 0.35, 95% CI (0.19, 0.62)], SU (RR 0.27, 95% CI (0.14, 0.51)], nSU [RR 0.28, 95% CI (0.08, 0.95)], TZD [RR 0.34, 95% CI (0.17, 0.7)], GLP-1RA is more effective Met [RR 0.42, 95% CI (0.25, 0.71)], SU (RR 0.33, 95% CI (0.18, 0.6)], TZD [RR 0.41, 95% CI (0.21, 0.82)], while Met[RR 1.98, 95% CI (1.23, 3.23)], SU [RR 2.54, 95% CI (1.46, 4.43)], TZD [RR 2.01, 95% CI (1.05, 3.79)] was not as effective as DPP4i., Conclusion: SGLT-2i, GLP-1RA, and DPP4i showed a superior efficacy in reducing the risk of new-onset AF/AFL compared to insulin therapy., (© 2024. The Author(s).)

Mesenchymal stem cell (MSC)-based therapy is an effective strategy for regenerative therapy. However, safety and ease of use are still issues to be overcome in clinical applications. Exosomes are naturally derived nanoparticles containing bioactive molecules, which serve as ideal cell-free therapeutic modalities. However, issues such as delivery, long-term preservation and activity maintenance of exosomes are other problems that limit their application. In this study, we proposed the use of rapid freeze-dry-thaw macroporous hydrogels for the encapsulation of HucMSC-derived exosomes (HucMSC-Exos) combined with an antimicrobial peptide coating. This exosome-encapsulated hyaluronic acid macroporous hydrogel HD-DP7/Exo can achieve long-term storage and transport by lyophilization and can be rapidly redissolved for treatment. After comprehensively comparing the therapeutic effects of HucMSC-Exos and HucMSC-loaded hydrogels, we found that HucMSC-Exos could also effectively regulate fibroblasts, vascular endothelial cells, and macrophages and inhibit myofibroblast-mediated fibrosis, thus promoting tissue regeneration and inhibiting scar formation in a mouse model of deep second-degree burn infection healing. These properties of lyophilized storage and whole-process-repair make HD-DP7/Exo have potential application value and application prospects., Competing Interests: Declaration of competing interest The authors declare that they have no competition of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Oxime ethers are attractive compounds in medicinal scaffolds due to the biological and pharmaceutical properties, however, the crucial and widespread step of industrial oxime formation using explosive hydroxylamine (NH 2 OH) is insecure and troublesome. Herein, we present a convenient method of oxime ether synthesis in a one-pot tandem electrochemical system using magnesium based metal-organic framework-derived magnesium oxide anchoring in self-supporting carbon nanofiber membrane catalyst (MgO-SCM), the in situ produced NH 2 OH from nitrogen oxides electrocatalytic reduction coupled with aldehyde to produce 4-cyanobenzaldoxime with a selectivity of 93 % and Faraday efficiency up to 65.1 %, which further reacted with benzyl bromide to directly give oxime ether precipitate with a purity of 97 % by convenient filtering separation. The high efficiency was attributed to the ultrafine MgO nanoparticles in MgO-SCM, effectively inhibiting hydrogen evolution reaction and accelerating the production of NH 2 OH, which rapidly attacked carbonyl of aldehydes to form oximes, but hardly crossed the hydrogenation barrier of forming amines, thus leading to a high yield of oxime ether when coupling benzyl bromide nucleophilic reaction. This work highlights the importance of kinetic control in complex electrosynthetic organonitrogen system and demonstrates a green and safe alternative method for synthesis of organic nitrogen drug molecules., (© 2024 Wiley-VCH GmbH.)

Detecting genes that affect specific traits (such as human diseases and crop yields) is important for treating complex diseases and improving crop quality. A genome-wide association study (GWAS) provides new insights and directions for understanding complex traits by identifying important single nucleotide polymorphisms. Many GWAS summary statistics data related to various complex traits have been gathered recently. Studies have shown that GWAS risk loci and expression quantitative trait loci (eQTLs) often have a lot of overlaps, which makes gene expression gradually become an important intermediary to reveal the regulatory role of GWAS. In this review, we review three types of gene-trait association detection methods of integrating GWAS summary statistics and eQTLs data, namely colocalization methods, transcriptome-wide association study-oriented approaches, and Mendelian randomization-related methods. At the theoretical level, we discussed the differences, relationships, advantages, and disadvantages of various algorithms in the three kinds of gene-trait association detection methods. To further discuss the performance of various methods, we summarize the significant gene sets that influence high-density lipoprotein, low-density lipoprotein, total cholesterol, and triglyceride reported in 16 studies. We discuss the performance of various algorithms using the datasets of the four lipid traits. The advantages and limitations of various algorithms are analyzed based on experimental results, and we suggest directions for follow-up studies on detecting gene-trait associations., (© 2024. Science China Press.)

Objective: The progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT., Method: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of treatment of cIMT with hypoglycemic agents before March 1, 2024. The differences in the changes in cIMT between the treatment group and control group were evaluated., Result: After screening 8395 citations, 25 studies (6675 patients) were included. The results indicated that exenatide had the best efficacy in slowing down cIMT progress, and exenatide [MD=-0.13,95%CI (-0.25, -0.01)], alogliptin [MD=-0.08,95%CI (-0.13, -0.02)] and metformin [MD=-0.05, 95%CI (-0.09, -0.02)] are more effective than placebo., Conclusion: Long-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Yang, Lv, Wu, Hou, Li, Ye, Yang and Wang.)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease characterized by progressive respiratory difficulties. It has a high incidence and disability rate worldwide. However, currently there is still a lack of highly effective treatment methods for COPD, only symptom relief is possible. Therefore, there is an urgent need to explore new treatment options. Almost all cells can secrete extracellular vesicles (EVs), which participate in many physiological activities by transporting cargoes and are associated with the pathogenesis of various diseases. Recently, many scholars have extensively studied the relationship between COPD and EVs, which has strongly demonstrated the significant impact of EVs from different sources on the occurrence and development of COPD. Therefore, EVs are a good starting point and new opportunity for the diagnosis and treatment of COPD. In this review, we mainly describe the current mechanisms of EVs in the pathogenesis of COPD, also the relationship between diagnosis, prognosis, and treatment. At the same time, we also introduce some new methods for COPD therapy based on EVs. It is hoped that this article can provide new ideas for future research and contribute to the development of precision medicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Developing an environmentally friendly soy protein-based film that offers excellent performance has garnered considerable interest while also posing a significant challenge. Herein, we propose the strategy of covalent and noncovalent cross-linking to improve the mechanical properties of the films. First, chemical denaturation was carried out under the combined action of sodium sulfite, sodium dodecyl sulfate, sodium hydroxide, and urea to reshape the structure of the protein to improve the solubility of protein and release active groups. Then, microcrystalline cellulose (MCC) derived from low-cost agro-industrial byproducts (corn husk) was employed to balance the covalent cross-linking reaction between proteins and the noncovalent reaction between MCC and protein. The results indicate that the structure and properties of the soy protein-based films were modified and improved through chemical treatment in conjunction with biomass enhancement. It is concluded that the addition of 1% MCC improves the tensile strength, elastic modulus, water solubility, and water vapor permeability of "MCC-1%" by 64.7, 75.9, 22.7, and 12.9%, respectively. Additionally, the resulting film of "MCC-1%" exhibits better resistance to thermal degradation and improved thermo-stability. However, the elongation at break decreased by increasing the addition of MCC. Thus, this work may provide a simple and affordable approach to preparing a high-performing soy protein-based film., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In recent years, the intensification of global industrialization coupled with the enterprise's production and operating activities have caused pollution, increasing the current environmental pressure. Relevant government departments in China have instituted several stringent measures (environmental protection sensitization and awareness activities, training sessions, and exchange activities targeted towards enterprise managers) to address these rising environmental problems. Though these measures have gained traction over the years, there is a dearth of research on their effectiveness on the green innovation performance of enterprises. To bridge the gap, this research explores the effect of environmental awareness training, knowledge exchange activities, and commitment on green innovation performance with survey data from 285 medical equipment manufacturing companies in China. It further expands the theoretical application of environmental awareness training, commitment, and innovation performance from the lens of the Knowledge-Based View. The findings depict a positive relationship between environmental awareness training and innovation performance. It also finds a mediating influence of environmental commitment in the relationship between environmental awareness training and green innovation performance. Furthermore, environmental knowledge exchange activities positively moderate the relationship between environmental awareness training and environmental commitment. These findings offer valuable insights for the green development of medical equipment manufacturing enterprises and the government to formulate environmental protection policies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: It is advised that patients engage in physical activity to enhance their quality of life and achieve better results. The purpose of the current study was to measure the efficacy of exercise on the physical ability, cardiac function and cardiopulmonary fitness of patients with AF., Method: A comprehensive systematic literature search was performed in PubMed, Embase, and Web of Science from 1991 to 2023 for RCTs comparing physical exercise combined with AF routine treatments to routine treatments alone. The meta-analysis was conducted following PRISMA guidelines. Our main outcomes were physical ability (measured by the 6-min walk test, 6MWT), cardiac function (measured by left ventricular ejection fraction, LVEF) and cardiopulmonary fitness (measured by peak oxygen uptake and resting heart rate). Quality assessments were conducted using the Cochrane Collaboration tool., Results: Thirteen trials involving 672 patients met the criteria for analysis. The results showed that physical exercise increased physical ability by improving the 6MWT (m) performance (MD = 96.99, 95% CI: 25.55-168.43; Z  = 2.66; p  = 0.008); and enhanced peak VO2 (ml/kg per min) (MD = 4.85, 95% CI: 1.55-8.14; Z  = 2.89; p  = 0.004) while reducing resting heart rate (beats per minute, bpm) (MD = -6.14, 95% CI: -11.30 to -0.98; Z  = 2.33; p  = 0.02). However, the results showed that regular exercise could improve LVEF (%) inpatients clinically, which had no statistic difference between experimental and control group (MD = 1.49, 95% CI: -0.25-3.24; Z  = 1.68; p  = 0.09)., Conclusion: Our meta-analysis shows that physical exercise is an effective intervention to improve the exercise ability and cardiopulmonary fitness for AF patients. Meanwhile, we also do not exclude the positive effect of exercise on the improvement of cardiac function (LVEF) in patients with AF. To this end, doctors should consider the positive impact of exercise on patients and give advice on exercise limits in practical clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yang, Wu, Lv, Hou, Ye, Yang, Li, Zuo and Wang.)

Inorganic nitrogen oxide (NO x ) species, such as NO, NO 2 , NO 3 - , NO 2 - generated from the decomposition of organic matters, volcanic eruptions and lightning activated nitrogen, play important roles in the nitrogen cycle system and exploring the origin of life. Meanwhile, excessive emission of NO x gases and residues from industry and transportation causes troubling problems to the environment and human health. How to efficiently handle these wastes is a global problem. In response to the growing demand for sustainability, scientists are actively pursuing sustainable electrochemical technologies powered by renewable energy sources and efficient utilization of hydrogen energy to convert NO x species into high-value organonitrogen chemicals. In this minireview, recent advances of electrocatalytic systems for NO x species valorization in organonitrogen synthesis are classified and described, such as amino acids, amide, urea, oximes, nitrile etc., that have been widely applied in medicine, life science and agriculture. Additionally, the current challenges including multiple side reactions and complicated paths, viable solutions along with future directions ahead in this field are also proposed. The coupling electrocatalytic systems provide a green mode for fixing nitrogen cycle bacteria and bring enlightenment to human sustainable development., (© 2023 Wiley-VCH GmbH.)

Severe burns threaten patient lives due to pain, inflammation, bacterial infection, and scarring. Most burn dressings that are commonly used perform a single function and are not well suited for the management of deep burns. Therefore, a multifunctional antimicrobial peptide- and stem cell-loaded macroporous hydrogel that can fight bacterial infection and regulate wound healing progression by temporally regulating cytokine production by internal stem cells is developed. The macroporous skeletal hydrogel is manufactured via the cryogenic gelation of hyaluronic acid (cryogel). Based on the oxidative polymerization reaction of dopamine, the antimicrobial peptide DP7 is immobilized on the surface of the cryogel (DA7CG). Placental mesenchymal stem cells (PMSCs) are then packaged inside the macroporous hydrogel (DA7CG@C). According to the results of in vitro and in vivo experiments, during the inflammatory phase, DP7 inhibits infection and modulates inflammation; during the proliferative phase, DA7CG@C accelerates the regeneration of skin, blood vessels, and hair follicles via internal stem cells; and during the remodeling phase, DA7CG@C contributes to extracellular matrix remodeling due to the ability of DP7 to regulate the paracrine secretion of PMSCs, synergistically promoting scar-free healing. DA7CG@C can participate in all phases of wound healing; therefore, it is a promising dressing for burn treatment., (© 2023 Wiley-VCH GmbH.)

Terrestrial carbon uptake is critical to the removal of greenhouse gases and mitigation of global warming, which are closely related to land use and cover change (LUCC). However, understanding terrestrial carbon uptake and the LUCC contribution remains unclear because of complex interactions with other drivers (particularly climate change). By proposing an innovative approach of "trajectory analysis", this study aimed to isolate the LUCC contribution to terrestrial carbon uptake over different scales. Methodologically, global land was first divided into sub-regions of land transformations and stable land trajectories. Then, the carbon uptake change in the stable land trajectory was taken as a synthetic influence of climate change, which was used as a reference to isolate the carbon uptake alternation generated from the LUCC contribution in the land transformation trajectories. Finally, future LUCC and the terrestrial carbon uptake response were predicted under different development pathways. The results showed the global mean net ecosystem production (NEP) was 27.44 ± 36.51 g C m -2  yr -1 in the past two decades (2001-2019), generating 3.15 ± 0.88 Pg C yr -1 of the total terrestrial carbon uptake. Both the NEP and total carbon uptake showed significant increasing trends. Specifically, the mean NEP increased from 17.96 g C m -2  yr -1 in 2001 to 37.37 g C m -2  yr -1 in 2019, with the trend written as y = 1.20× + 15.20 (R 2  = 0.62, p < 0.01). Meanwhile, the total carbon uptake increased from 2.35 Pg C yr -1 in 2001 to 4.13 Pg C yr -1 in 2019, which could be written as y = 0.12× + 1.93 (R 2  = 0.56, p < 0.01). Climate change acted as the dominant factor for the trends at the global scale, which contributed 21.26 g C m -2  yr -1 and 1.59 Pg C yr -1 of the mean NEP and total carbon uptake changes in the stable land trajectories (94.30 million km 2 that covered 63.29 % of the global land area), and the historical LUCC contributed -6.30 g C m -2  yr -1 (-40.85 %) and - 0.046 Pg C yr -1 (-57.50 %) of the mean NEP and the total carbon uptake change in the land transformation trajectories (6.64 million km 2 that covered 4.46 % of the global land area), respectively. The maximum LUCC contribution (-61.85 g C m -2  yr -1 ) to the mean NEP occurred in the land transformations from evergreen needleleaf forests to woody savannas, while the maximum contribution (-0.034 Pg C y -1 ) to total carbon uptake was in the deforested regions from evergreen broadleaf forests to woody savannas. Eight SSP-RCP scenarios predictions demonstrated that future terrestrial carbon uptake would increase by an average of 0.015 Pg C yr -1 in 2100 due to global afforestation. SSP4-3.4 and SSP5-3.4 had the greatest potential for increasing carbon uptake, which is expected to reach a maximum increase (0.045 Pg C yr -1 ) in 2100. In contrast, the minimum terrestrial carbon uptake would occur in SSP5-8.5, which had the highest CO 2 emissions. In conclusion, although relatively limited at the global scale, LUCC (particularly forest change) exerted an unneglectable role on terrestrial carbon uptake in land transformation regions. The results of this study will help to clarify terrestrial carbon uptake dynamics and provide a basis for carbon neutral and climatic adaptation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Pyridine oximes produced from aldehyde or ketone with hydroxylamine (NH 2 OH) have been widely applied in pharmaceutics, enzymatic and sterilization. However, the important raw material NH 2 OH exhibits corrosive and unstable properties, leading to substantial energy consumption during storage and transportation. Herein, this work presents a novel method for directly synthesizing highly valuable pyridine oximes using in situ generated NH 2 OH from electrocatalytic NO reduction with well-design nanofiber membranes (Al-NFM) derived from NH 2 -MIL-53(Al). Particularly, 2-pyridinealdoxime, the precursor of antidote pralidoxime (2-PAM) for nerve agents suffering from scarcity and high cost, was achieved with a Faraday efficiency up to 49.8 % and a yield of 92.1 %, attributing to the high selectivity of NH 2 OH production on Al-NFM, further easily reacted with iodomethane to produce 2-PAM. This study proposes a creative approach, having wide universality for synthesizing pyridine and other oximes with a range of functional groups, which not only facilitates the conversion of exhaust gas (NO) and waste water (NO 2 - ) into valuable chemicals especially NH 2 OH production and in situ utilization through electrochemistry, but also holds significant potential for synthesis of neuro detoxifying drugs to humanity security., (© 2023 Wiley-VCH GmbH.)

Osteoarthritis (OA) is a degenerative disease characterized by cartilage wear and degradation. Ginkgolide K (GK) is a natural compound extracted from Ginkgo biloba leaves and possesses anti-inflammatory and anti-apoptotic effects. We found that the biological characteristics of GK were highly consistent with those of OA medications. This study aimed to determine and verify the therapeutic effect of GK on OA and mechanism of its therapeutic effect. For the in vivo experiment, OA rats were regularly injected in the articular cavity with GK, and the curative effects were observed after 4 and 8 weeks. For the in vitro experiment, we treated OA chondrocytes with different concentrations of GK and then detected the related indices of OA. Through the in vivo and in vitro experiments, we found that GK could promote the production of major components of the cartilage extracellular matrix. Transcriptome sequencing revealed that GK may activate hypoxia-inducible factor 1 alpha via the hypoxia signaling pathway, which, in turn, activates yes-associated protein and inhibits apoptosis of OA chondrocytes. GK has a therapeutic effect on OA and, therefore, has the potential to be developed into a new drug for OA treatment., (© 2023 John Wiley & Sons Ltd.)

In today's digital age, the effort of medical enterprises towards green innovation has gained traction in academic and business circles. However, the current research system for medical equipment suppliers lacks a systematic study on how digital transformation can enhance the outcomes of green innovation. This research aims to develop a theoretical framework for digital transformation, environmental resource integration capability, managerial environmental concern and green innovation performance with respect to the resource-based view and conducting empirical analysis using survey data from medical equipment supply enterprises. Our findings reveal that digital transformation has a significant effect on the promotion of green innovation performance through environmental resource integration capability. Moreover, the managerial environmental concern moderates above mediation effect. These findings not only provide compelling insights into the impact of digital transformation on green innovation performance but also have important implications for sustainable development and cleaner production relevant academic research and policy-making., (© 2023. Springer Nature Limited.)

Renal ischemia/reperfusion (I/R) injury, which leads to acute kidney injury (AKI), is a major cause of morbidity and mortality in a variety of clinical situations. This study aimed to investigate the protective role of Mfn2 during renal I/R injury. Overexpression of Mfn2 in NRK-52E rat renal tubular epithelial cells and rats, then we constructed hypoxia reoxygenation (H/R) cells and I/R rat model. Apoptosis, ROS, ATP, Ca 2+ levels in cells and rats, as well as renal tissue and functional injury in rats were detected respectively. Endoplasmic reticulum (ER) stress was further examined in cells and rats. The morphological changes of mitochondria-associated ER membranes (MAMs) were also detected. Mfn2 expression is reduced in H/R-treated NRK-52E cells and renal tissue of I/R rats. At the cellular level, overexpression of Mfn2 promoted cell proliferation, inhibited cell apoptosis, attenuated mitochondrial damage and Ca 2+ overload, and ER stress. In addition, Mfn2 also restored the MAMs structure. In vivo experiments found that overexpression of Mfn2 could improve renal function and alleviate tissue injury. Concomitant with elevated Mfn2 expression in the kidney, reduced renal cell apoptosis, restored mitochondrial function, and reduced calcium overload. Finally, ER stress in rat kidney tissue was alleviated after overexpression of Mfn2. These results reveal that Mfn2 contributes to ER stress, mitochondrial function, and cell death in I/R injury, which provides a novel therapeutic target for AKI., (© 2023. Springer Nature Limited.)

The function of the intestinal tract is critical to human health. Poria cocos is a widely used functional edible fungus in Asia and has been reported to modulate gastrointestinal function. However, the effects of polysaccharides, the main active constituents of Poria cocos, on the intestinal tract remains unclear and is the focus of the study. Poria cocos polysaccharides (PCP) were extracted, characterized, and administered to mice by gavage. The results show that PCP used in this study has a typical polysaccharide peak with a molecular weight of 11.583 kDa and is composed primarily of mannose, D-glucosamine hydrochloride, glucose, galactose, and fucose with a molar ratio of 15.308: 0.967: 28.723: 31.631: 23.371. The methylation results suggest that the PCP backbone may be t-Gal(p), 6-Gal(p) and 2,6-Gal(p). The effects of PCP on the mucosal barrier function of the mouse intestine (duodenum, jejunum, and ileum) were examined in terms of intestinal physiological status, physical barrier, biochemical barrier, immune barrier, and microbial barrier. The results showed that PCP significantly improved the physiological state of mouse intestine. Moreover, PCP strengthened the intestinal physical barrier by upregulating the expression of intestinal Occludin and ZO-1 and downregulating the levels of serum endotoxin, DAO, D-lactate, and intestinal MPO. Regarding biochemical barrier, PCP could upregulate the expression of MUC2, β-defensin, and SIgA in intestinal tissues. In addition, PCP modulated the immune barrier by increasing IL-2, IL-4, IL-6, IL-10, TGF-β, and IFN-γ expression. Besides, PCP increased the level of SCFAs in small intestinal contents. PCP modulates intestinal barrier function by altering the microbial composition of the gut. We also found that PCP could maintain intestinal barrier function by increasing the expression of Wnt/β-Catenin and Lrp5 proteins. Generally, our findings suggested that PCP may be used as a functional food to regulate intestinal mucosal function, thereby enhancing the health of the intestinal and host., Competing Interests: Declaration of competing interest Competing financial interests are non-existent., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Coronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous coronary intervention (PCI) is one of the most effective surgical treatments for CHD with narrowed or blocked blood vessels, which can quickly unblock the blocked vessels and restore coronary blood supply. However, most patients may experience coronary microcirculation disorders (CMDs) and decreased cardiac function after PCI treatment, which directly affects the efficacy of PCI and the prognosis of patients. Preprotein converting enzyme subtilisin/Kexin 9 (PCSK9) inhibitors are novel pleiotropy lipid-lowering drug with dual anti-inflammation and lipid-lowering effects, and represent a new clinical pathway for rapid correction of dyslipidaemia. Therefore, we designed this protocol to systematically evaluate the effects of PCSK9 inhibitors on coronary microcirculation and cardiac function in patients with CHD after PCI, and to provide high-quality evidence-based evidence for the clinical application of PCSK9 inhibitors., Methods and Analysis: This protocol is reported strictly in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Guidelines. We will search PubMed, EMBASE, Web of Science and three Chinese databases (CNKI, Wanfang and VIP database) according to preset search strategies, without language and publication data restrictions. We will work with manual retrieval to screen references that have been included in the literature. Google Scholar will be used to search for grey literature. The final included literature must meet the established inclusion criteria. Titles, abstracts and full text will be extracted independently by two reviewers, and disagreements will be resolved through discussion or the involvement of a third reviewer. Extracted data will be analysed using Review Manager V.5.3. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias. Publication bias will be assessed by funnel plots. Heterogeneity will be assessed by I 2 test and subgroup analyses will be used to further investigate potential sources of heterogeneity. The quality of the literature will be assessed by GRADE score. This protocol will start in January 2026 and end in December 2030., Ethics and Dissemination: This study is a systematic review of published literature data and no special ethical approval was required., Prospero Registration Number: CRD42022346189., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

The conversion of industrial exhaust gases of nitrogen oxides into high-value products is significantly meaningful for global environment and human health. And green synthesis of amino acids is vital for biomedical research and sustainable development of mankind. Herein, we demonstrate an innovative approach for converting nitric oxide (NO) to a series of α-amino acids (over 13 kinds) through electrosynthesis with α-keto acids over self-standing carbon fiber membrane with CoFe alloy. The essential leucine exhibits a high yield of 115.4 μmol h -1 corresponding a Faradaic efficiency of 32.4 %, and gram yield of products can be obtained within 24 hours in lab as well as an ultra-long stability (>240 h) of the membrane catalyst, which could convert NO into NH 2 OH rapidly attacking α-keto acid and subsequent hydrogenation to form amino acid. In addition, this method is also suitable for other nitrogen sources including gaseous NO 2 or liquidus NO 3 - and NO 2 - . Therefore, this work not only presents promising prospects for converting nitrogen oxides from exhaust gas and nitrate-laden waste water into high-value products, but also has significant implications for synthetizing amino acids in biomedical and catalytic science., (© 2023 Wiley-VCH GmbH.)

An unprecedented copper and in situ-generated triflic acid relay-promoted four-component cascade reaction of cyanamides, diaryliodonium triflates, propargylic amines, and H 2 O was established for rapid and concise construction of diverse five-membered cycloguanidines. Copper-catalyzed guanidination/intramolecular hydroamination and in situ-generated HOTf-accelerated hydration proceeded sequentially with high level of chemoselectivity and regioselectivity, and six new bonds were simultaneously built in high yields. Thus, diaryliodonium triflates served not only as an arylation reagent but also as an internal acid promoter, establishing an alternative strategy for highly efficient utilization of diaryliodonium trifates.

How to transfer industrial exhaust gases of nitrogen oxides into high-values product is significantly important and challenging. Herein, we demonstrate an innovative method for artificial synthesis of essential α-amino acids from nitric oxide (NO) by reacting with α-keto acids through electrocatalytic process with atomically dispersed Fe supported on N-doped carbon matrix (AD-Fe/NC) as the catalyst. A yield of valine with 32.1 μmol mg cat -1 is delivered at -0.6 V vs. reversible hydrogen electrode, corresponding a selectivity of 11.3 %. In situ X-ray absorption fine structure and synchrotron radiation infrared spectroscopy analyses show that NO as nitrogen source converted to hydroxylamine that promptly nucleophilic attacked on the electrophilic carbon center of α-keto acid to form oxime and subsequent reductive hydrogenation occurred on the way to amino acid. Over 6 kinds of α-amino acids have been successfully synthesized and gaseous nitrogen source can be also replaced by liquid nitrogen source (NO 3 - ). Our findings not only provide a creative method for converting nitrogen oxides into high-valued products, which is of epoch-making significance towards artificial synthesis of amino acids, but also benefit in deploying near-zero-emission technologies for global environmental and economic development., (© 2023 Wiley-VCH GmbH.)

MicroRNA-146b-5p (miR-146b-5p) is up-regulated during and to suppress the inflammation process, although mechanisms involved in the action of miR-146b-5p have not been fully elucidated. This study examined the anti-inflammation effects of miR-146b-5p in lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs). An increase in human miR-146b-5p (hsa-miR-146b-5p) expression following the mRNA expression of pro-inflammatory cytokines was observed in LPS-stimulated hDPCs. The expression of hsa-miR-146b-5p and pro-inflammatory cytokines was down-regulated by a nuclear factor-kappa B (NF-κB) inhibitor, and the expression of hsa-miR-146b-5p was also decreased by a JAK1/2 inhibitor. Enforced expression of hsa-miR-146b-5p abolished phosphorylation of NF-κB p65 and down-regulated the expression of pro-inflammatory cytokines and NF-κB signaling components, such as interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), and REL-associated protein involved in NF-κB (RELA). Expression of rat miR-146b-5p (rno-miR-146b-5p) and pro-inflammatory cytokine mRNA was also up-regulated in experimentally-induced rat pulpal inflammation in vivo, and rno-miR-146b-5p blocked the mRNA expression of pro-inflammatory mediators and NF-κB signaling components in LPS-stimulated ex vivo cultured rat incisor pulp tissues. These findings suggest that the synthesis of miR-146b-5p is controlled via an NF-κB/IL6/STAT3 signaling cascade, and in turn, miR-146b-5p down-regulates the expression of pro-inflammatory mediators by targeting TRAF6, IRAK1, and RELA in LPS-stimulated hDPCs.

Adaptive array processing technology for a phased array radar is usually based on the assumption of a stationary environment; however, in real-world scenarios, nonstationary interference and noise deteriorate the performance of the traditional gradient descent algorithm, in which the learning rate of the tap weights is fixed, leading to errors in the beam pattern and a reduced output signal-to-noise ratio (SNR). In this paper, we use the incremental delta-bar-delta (IDBD) algorithm, which has been widely used for system identification problems in nonstationary environments, to control the time-varying learning rates of the tap weights. The designed iteration formula for the learning rate ensures that the tap weights adaptively track the Wiener solution. The results of numerical simulations show that in a nonstationary environment, the traditional gradient descent algorithm with a fixed learning rate has a distorted beam pattern and reduced output SNR; however, the IDBD-based beamforming algorithm, in which a secondary control mechanism is used to adaptively update the learning rates, showed a similar beam pattern and output SNR to a traditional beamformer in a Gaussian white noise background; that is, the main beam and null satisfied the pointing constraints, and the optimal output SNR was obtained. Although the proposed algorithm contains a matrix inversion operation, which has considerable computational complexity, this operation could be replaced by the Levinson-Durbin iteration due to the Toeplitz characteristic of the matrix; therefore, the computational complexity could be decreased to O( n ), so additional computing resources are not required. Moreover, according to some intuitive interpretations, the reliability and stability of the algorithm are guaranteed.

Ultrasmall metal nanoparticles (NPs) show high catalytic activity in heterogeneous catalysis but are prone to reunion and loss during the catalytic process, resulting in low chemoselectivity and poor efficiency. Herein, a locking effect strategy is proposed to synthesize high-loading and ultrafine metal NPs in metal-organic frameworks (MOFs) for efficient chemoselective catalysis with high stability. Briefly, the MOF ZIF-90 with aldehyde groups cooperating with diamine chains via aldimine condensation was interlocked, which was employed to confine in situ formation of Au NPs, denoted as Au@L-ZIF-90. The optimized Au@L a -ZIF-90 has highly dispersed Au NPs (2.60 ± 0.81 nm) with a loading amount around 22 wt % and shows a great performance toward 3-aminophenylacetylene (3-APA) from the selective hydrogenation of 3-nitrophenylacetylene (3-NPA) with a high yield (99%) and excellent durability (over 20 cycles), far superior to contrast catalysts without chains locking and other reported catalysts. In addition, experimental characterization and systematic density functional theory calculations further demonstrate that the locked MOF modulates the charge of Au nanoparticles, making them highly specific for nitro group hydrogenation to obtain 3-APA with high selectivity (99%). Furthermore, this locking effect strategy is also applicable to other metal nanoparticles confined in a variety of MOFs, and all of these catalysts locked with chains show great selectivity (≥90%) of 3-APA. The proposed strategy in this work provides a novel and universal method for precise control of the inherent activity of accessible metal nanoparticles with a programmable MOF microenvironment toward highly specific catalysis.

Background: Obesogenic environment is important in driving obesity epidemic. Children spend large amount of their time in schools. School neighborhood environment, as well as its interaction with socioeconomic status (SES) needs to be explored to provide evidence for children obesity prevention policies., Methods: Objective anthropometric measurement, a household structured questionnaire, and school geospatial analyses were carried out on 3670 children (aged 9-12 years) of 26 schools in northeast China. Interaction between SES inter-categorical intersectionality group and school neighborhood environment was tested for the effect on children's body mass index z scores (z-BMI) and waist-hip ratio z scores (z-WHR), following formulation of SES inter-categorical intersectionality group based on household wealth, parental education, and parental occupation., Results: SES groups formed by household wealth, parental education and parental occupation was associated with z-BMI and z-WHR for girls. Those from moderate wealth & self-employed (M&S) families had the highest adjusted z-BMI and z-WHR among all SES groups. School neighborhood environment factors interacted with SES groups in association with WHR for girls. Number of school neighborhood supermarkets and residential sites were negatively associated with z-WHR for girls from M&S families (β= -0.45 (95%CI: -0.76, -0.15) for supermarkets; β= -0.01 (95%CI: -0.03, 0.00) for residential sites). Number of school neighborhood convenience stores and public transport stops were positively associated with z-WHR for girls from M&S families (β = 0.02 (95%CI: 0.00, 0.03) for convenience stores; β = 0.23 (95%CI: 0.15, 0.31) for public transport stops). While non-significant association was found for number of vegetable stores., Conclusion: Girls from moderate wealth & self-employed families may be the group susceptible to school neighborhood environment. Local policies targeted at improving the school neighborhood environment may be one avenue for reducing socioeconomic disparities in obesity especially for girls., (© 2023. The Author(s).)

Introduction: Hypertension (HTN) is the leading cause of disease and death on a global scale. Diet's sodium and potassium levels may synergistically affect blood pressure. Currently, the sodium-to-potassium (Na/K) ratio is becoming a more reliable indicator. There has not been a systematic investigation of the dose-response relationship between dietary sodium, potassium, the Na/K ratio and the incidence of HTN based on the same study criteria. This study will conduct a thorough dose-response meta-analysis of cohort studies to estimate the effects of dietary sodium, potassium, and the Na/K ratio on the incidence of HTN to provide the most accurate reference for sodium and potassium intake., Methods and Analysis: We will identify all relevant prospective and retrospective cohort studies by searching PubMed, Embase and Web of Science (from inception until December 2022). Exposures are 24 hours urinary excretions, and the outcome is the incidence of HTN. Two researchers will perform the literature selection and data extraction separately. The Newcastle-Ottawa Scale will be used to evaluate the quality of the included studies. We will use both linear and non-linear regression models to investigate the dose-response relationship among different levels (≥3) of sodium, potassium, Na/K ratio intake and the incidence of HTN (OR/RR/HR). Subgroup and sensitivity analyses will be applied to assess the potential heterogeneity sources and examine the stability of the results. We will also evaluate heterogeneity across studies and publication bias. Stata V.15.0 and RevMan V.5.0 will be used for statistical analyses., Ethics and Dissemination: According to the Institutional Review Board/Independent Ethics Committee of the Guang'anmen Hospital of the China Academy of Chinese Medical Science, this systematic meta-analysis protocol does not require ethical approval or informed consent. This meta-analysis will be published in a scientific journal with peer reviews., Prospero Registration Number: CRD42022331203., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Lv, Liu, Ye, Cao, Wang, Li, Yang, Li and Wang.)

We aimed to explore the medium- and long-term (≥12 weeks) effects of dapagliflozin on serum uric acid (SUA) level in patients with type 2 diabetes mellitus (T2DM) in the real world study and to explore the influencing factors of dapagliflozin on reducing SUA level. This observational, prospective cohort study was based on the real world. There were 77 patients included in this study. They were divided into two groups. Patients in treatment group (n = 38) were treated as dapagliflozin 10 mg/d combined with therapy of routine glucose-lowering drugs (GLDs), and patients in the control group (n = 39) were treated with their routine GLDs. All measurements of physical examinations, blood, and urine samples, including age, sex, weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and SUA, were collected at baseline for all patients in these two groups and repeated after 12, 24, and 48 weeks of therapy. We compared the changes of metabolic indicators including SUA in these two groups to evaluate the effects of dapagliflozin and analyzed its influencing factors. In the dapagliflozin group, mean SUA levels significantly decreased from 334.2 ± 99.1 μmol/L at baseline to 301.9 ± 73.2 μmol/L after 12 weeks therapy (t = 2.378, p = 0.023). There was no significant statistical difference of SUA levels after 24 weeks treatment of dapagliflozin compared with 12-week and 48-week treatment with dapagliflozin (p > 0.05). We found that baseline SUA had a significant impact on the effect of dapagliflozin on reducing SUA (OR 1.014, 95%CI 1.003−1.025, p = 0.014) by logistic regression analysis. Receiver operating characteristic (ROC) curve showed that T2DM patients with SUA level ≥ 314.5 μmol/L had relative accuracy in recognizing the good effects of dapagliflozin on reducing SUA (sensitivity 76.9%, specificity 76.2%). Combination therapy of dapagliflozin with routine blood-glucose-lowering drugs in T2DM patients showed the significant and sustained stable effect of lowering SUA level in this real-world study.

In this study, 1-methylhydantoin cinnamic imides were synthesized from 1-methylhydantoin and trans -cinnamic acid, and their anti-inflammatory activity was investigated. The anti-inflammatory activity in vitro was evaluated by measuring the contents of NO, TNF-α and IL-1β in the supernatant of RAW264.7 cells stimulated by LPS. The cytotoxicity of 1-methylhydantoin cinnamoyl imides on RAW264.7 cells was detected using the CCK-8 method. The results showed that compounds 2 and 4 can significantly inhibit the release of NO and reduce the secretion of TNF-α and IL-1β. Compound 3 inhibited the production of TNF-α. The inhibition rate of COX was evaluated in vitro. The in vivo anti-inflammatory activities of the five compounds were evaluated by establishing an animal model of xylene ear swelling. The results showed that 1-methylhydantoin cinnamic imides could alleviate xylene-induced ear edema in mice in a dose-dependent manner. Among them, the effect of compound 5 was the most significant. Under the action of high dosage, its ear swelling inhibition rate was as high as 52.08%.

This work was dedicated to evaluating the drying methods (freeze drying, spray drying, and vacuum drying) of food Rana chensinensis ovum protein isolate (RCOPI) based on comparison of the physicochemical and functional properties. The characterization and evaluation were conducted using scanning electron microscopy, surface hydrophobicity, SDS-PAGE, amino acid composition and nutritional parameters, Fourier transform infrared spectroscopy, and autofluorescence spectroscopy. The results showed the protein structure and conformation of RCOPI were greatly affected by drying techniques, leading to different physicochemical and functional properties. RCOPI possessed four main subunit bands distributed around 110, 90, 35 and 32 kDa. Seven essential amino acids were detected, accounting for 43.27-43.65% of total amino acids. Freeze drying RCOPI (FD-RCOPI) showed superior functional features, including solubility, water holding capacity, oil holding capacity, stabilization of Pickering emulsion and antioxidant capacity. FD-RCOPI exhibited applicability for the manufacture of viscous foods, bakery products and Pickering emulsions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to identify the main medicinal active components of Panax ginseng ( P. ginseng ) in the compatibility environment of clinical application. For this purpose, the anti-inflammatory ingredients of P. ginseng were investigated based on its therapeutic effect in Sijunzi Decoction (SJD) which is a widely used traditional Chinese formula., Methods: The fingerprints of 10 batches of SJD consisting of different sources of P. ginseng were established by UPLC technique to investigate the chemical components. At the same time, the anti-inflammatory effects of these components were evaluated by dextran sulfate sodium-induced ulcerative colitis mouse model. Grey relational analysis was applied to explore the correlation degree between fingerprints and anti-inflammatory effects in SJD. Lipopolysaccharide-stimulated RAW264.7 murine macrophages were established to evaluate the anti-inflammatory action of the screened effective substances of P. ginseng ., Results: According to grey relational analysis, notoginsenoside R 1 , ginsenoside Rg 2 and ginsenoside Rb 3 of P. ginseng were the major anti-inflammatory contributions in SJD. They had been proven to be closely associated with the anti-inflammatory process of SJD and displayed a close effect compared with SJD by LPS-stimulated RAW264.7 murine macrophages., Conclusion: Our work provides a general strategy for exploring the pharmacological ingredients of P. ginseng in traditional Chinese formulas which is beneficial for establishing the quality standards of traditional herbs in traditional Chinese medicine prescription based on their clinical therapeutic effect., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Background: Danlou tablet (DLT), the traditional Chinese medicine has been commonly used for dyslipidemia, atherosclerosis, and coronary heart disease. Whether it was effective against vascular injury caused by CIH has remained unknown. The aim of the current study was to observe the effects of DLT on chronic intermittent hypoxia (CIH)-induced vascular injury via regulation of blood lipids and to explore potential mechanisms., Methods: Sixteen 12-week-old male ApoE -/- mice were randomly divided into four groups. The sham group was exposed to normal room air, whereas the other three groups were exposed to CIH. Mice in the CIH + normal saline (NS) group were gavaged with NS. Mice in the CIH + Angptl4-ab group were intraperitoneally injected with Angptl4-antibody. Mice in the CIH + DLT group were gavaged with DLT. After four weeks of intervention, serum lipid concentrations, and serum lipoprotein lipase (LPL) activity were detected. The changes in atherosclerosis in vascular tissue were detected by hematoxylin and eosin (H&E) staining. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were applied to detect the expression levels of hypoxia-induciblefactor-1 (HIF-1), factor-inhibiting HIF-1 (FIH-1), angiopoietin-like 4 (Angptl4), and LPL in different tissues., Results: CIH exposure increases serum lipid levels, decreases serum LPL activity, and exacerbates atherosclerosis. Both Angptl4-ab and DLT treatment reversed the changes in lipid concentration, LPL activity, and atherosclerosis caused by CIH. In the epididymal fat pad, CIH exposure decreased the expression of FIH-1 and increased the expression of HIF-1, whereas DLT treatment increased the expression of FIH-1 and LPL and inhibited the expression of HIF-1 and Angptl4. In heart tissue, the expression levels of LPL and Angptl4 were not affected by modeling or treatment., Conclusions: DLT improved vascular damage by improving the increase in blood lipids induced by CIH, potentially by upregulating FIH-1 and downregulating HIF-1 and Angptl4 in adipose tissue. Therefore, DLT may be a promising agent for the prevention and treatment of CIH-induced vascular injury., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yi Rong et al.)

Rana chensinensis ovum (RCO) is the major waste/by-product of Oviductus Ranae . This study investigated physicochemical characteristics and stability of emulsified Rana chensinensis ovum oil (RCOO) with Rana chensinensis ovum protein isolates (RCOPI) by particle size, zeta potential, scanning electron microscopy (SEM), visual appearance, confocal laser scanning microscopy (CLSM), rheology and antioxidant capacity. The emulsified RCOO demonstrated great stability, antioxidant capacity and rheological properties. The potential application of the emulsified RCOO as a delivery system was studied using quercetin as an example. The stability of encapsulated quercetin was investigated through storage stability, thermal stability and photostability. The bioaccessibility of encapsulated quercetin was explored by in vitro digestion simulation experiments. The results showed the stability and bioaccessibility of quercetin encapsulated in emulsified RCOO was greatly improved. This study showed that the emulsified RCOO is a promising edible delivery system for hydrophobic bio-actives., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: App-based mobile health exercise interventions can motivate individuals to engage in more physical activity (PA). According to the Fogg Behavior Model, it is important that the individual receive prompts at the right time to be successfully persuaded into PA. These are referred to as just-in-time (JIT) interventions. The Playful Active Urban Living (PAUL) app is among the first to include 2 types of JIT prompts: JIT adaptive reminder messages to initiate a run or walk and JIT strength exercise prompts during a walk or run (containing location-based instruction videos). This paper reports on the feasibility of the PAUL app and its JIT prompts., Objective: The main objective of this study was to examine user experience, app engagement, and users' perceptions and opinions regarding the PAUL app and its JIT prompts and to explore changes in the PA behavior, intrinsic motivation, and the perceived capability of the PA behavior of the participants., Methods: In total, 2 versions of the closed-beta version of the PAUL app were evaluated: a basic version (Basic PAUL) and a JIT adaptive version (Smart PAUL). Both apps send JIT exercise prompts, but the versions differ in that the Smart PAUL app sends JIT adaptive reminder messages to initiate running or walking behavior, whereas the Basic PAUL app sends reminder messages at randomized times. A total of 23 participants were randomized into 1 of the 2 intervention arms. PA behavior (accelerometer-measured), intrinsic motivation, and the perceived capability of PA behavior were measured before and after the intervention. After the intervention, participants were also asked to complete a questionnaire on user experience, and they were invited for an exit interview to assess user perceptions and opinions of the app in depth., Results: No differences in PA behavior were observed (Z=-1.433; P=.08), but intrinsic motivation for running and walking and for performing strength exercises significantly increased (Z=-3.342; P<.001 and Z=-1.821; P=.04, respectively). Furthermore, participants increased their perceived capability to perform strength exercises (Z=2.231; P=.01) but not to walk or run (Z=-1.221; P=.12). The interviews indicated that the participants were enthusiastic about the strength exercise prompts. These were perceived as personal, fun, and relevant to their health. The reminders were perceived as important initiators for PA, but participants from both app groups explained that the reminder messages were often not sent at times they could exercise. Although the participants were enthusiastic about the functionalities of the app, technical issues resulted in a low user experience., Conclusions: The preliminary findings suggest that the PAUL apps are promising and innovative interventions for promoting PA. Users perceived the strength exercise prompts as a valuable addition to exercise apps. However, to be a feasible intervention, the app must be more stable., (©Karlijn Sporrel, Shihan Wang, Dick D F Ettema, Nicky Nibbeling, Ben J A Krose, Marije Deutekom, Rémi D D de Boer, Monique Simons. Originally published in JMIR Formative Research (https://formative.jmir.org), 01.08.2022.)

Background: Social distancing has been implemented by many countries to curb the COVID-19 pandemic. Understanding public support for this policy calls for effective and efficient methods of monitoring public opinion on social distancing. Twitter analysis has been suggested as a cheaper and faster-responding alternative to traditional survey methods. The current empirical evidence is mixed in terms of the correspondence between the two methods., Objective: We aim to compare the two methods in the context of monitoring the Dutch public's opinion on social distancing. For this comparison, we quantified the temporal and spatial variations in public opinion and their sensitivities to critical events using data from both Dutch Twitter users and respondents from a longitudinal survey., Methods: A longitudinal survey on a representative Dutch sample ( n = 1,200) was conducted between July and November 2020 to measure opinions on social distancing weekly. From the same period, near 100,000 Dutch tweets were categorized as supporting or rejecting social distancing based on a model trained with annotated data. Average stances for the 12 Dutch provinces and over the 20 weeks were computed from the two data sources and were compared through visualizations and statistical analyses., Results: Both data sources suggested strong support for social distancing, but public opinion was much more varied among tweets than survey responses. Both data sources showed an increase in public support for social distancing over time, and a strong temporal correspondence between them was found for most of the provinces. In addition, the survey but not Twitter data revealed structured differences among the 12 provinces, while the two data sources did not correspond much spatially. Finally, stances estimated from tweets were more sensitive to critical events happened during the study period., Conclusions: Our findings indicate consistencies between Twitter data analysis and survey methods in describing the overall stance on social distancing and temporal trends. The lack of spatial correspondence may imply limitations in the data collections and calls for surveys with larger regional samples. For public health management, Twitter analysis can be used to complement survey methods, especially for capturing public's reactivities to critical events amid the current pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wang, Tjong Kim Sang, Adriaanse, Tummers, Schraagen, Qi, Dastani and Aarts.)

Naturally abundant seawater mineral was employed to engineer banana pseudostem and bamboo biochars through pyrolysis at different low temperatures for improving their adsorption capabilities for methylene blue (MB) and tetracycline (TC). The adsorption capabilities were greatly enhanced as the biochars were pyrolyzed at 300 °C with 50/1 (mL/g) dosage of seawater to biomass. For instance, the engineered banana pseudostem biochar exhibited 8.00 and 6.54 times higher adsorption capabilities than the corresponding pristine biochar for MB (447.79 mg/g vs 55.96 mg/g) and TC (100.59 mg/g vs 16.75 mg/g) at 25 °C, respectively. The characterization results indicated that a large number of carboxylates, lactone acid salts, and alkoxides were generated on the engineered biochar and a high cation exchange capacity was gained. The adsorption of MB was mainly attributed to cation exchange complying with hydrogen bonding and electrostatic interaction, whereas the adsorption of TC was realized by hydrogen bonding and complexation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Traumatic multidrug-resistant (MDR) bacterial infections are deadly threat to the public. To combat MDR bacteria, we developed a dual functional pH-sensitive hydrogel based on peptide DP7 (VQWRIRVAVIRK) and oxidized dextran (DP7-ODEX hydrogel). As an antimicrobial peptide, DP7 can synergize with many antibiotics; thus, we loaded ceftazidime into DP7-ODEX hydrogel, which showed an obvious advantage in MDR P. aeruginosa inhibition. Additionally, due to the interaction between aldehyde groups in oxidized dextran and amine groups from wound tissue, the hydrogel could extend on the irregular surface of skin defects and promote epithelial cells adhesion. DP7 could also be used as a wound-healing peptide and accelerate the healing process. We confirmed that the DP7-ODEX hydrogel exerted formidable therapeutic effects in normal or diabetic wound infection model. According to histomorphology analysis we found that DP7 hydrogel also have a scarless wound healing ability. In summary, we developed a hydrogel fabricated by the dual functional peptide DP7 that can kill multidrug-resistant bacteria colonizing the wound bed and boost scarless wound healing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse., Aims: This study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM)., Methods: A total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity., Results: Age, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 ( p for linear trend <0.05), and the differences between G1 and G2 were also statistically significant ( p < 0.05). Glucose peak of most participants in G1 converged at 5 min, and the curves shape of insulin and C-peptide in G2 were the sharpest among three groups. There was no significant difference in all IVGTT-based indices between G1 and G2, but AUC Ins , AUC Ins /AUC Glu , and △Ins 3 /△Glu 3 in G2 were the highest, and the p- value for linear trend of those indices among three groups were statistically significant ( p < 0.05)., Conclusions: Two patterns of FPIS were in subjects with NGT, while subjects with later time to glucose peak during FPIS might be less likely to develop T2DM in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yuan, Song, Zhao, Duo, Wang, Gao, Liu, Dong, Li, Fu and Zhao.)

Mobile health (mHealth) intervention systems can employ adaptive strategies to interact with users. Instead of designing such complex strategies manually, reinforcement learning (RL) can be used to adaptively optimize intervention strategies concerning the user's context. In this paper, we focus on the issue of overwhelming interactions when learning a good adaptive strategy for the user in RL-based mHealth intervention agents. We present a data-driven approach integrating psychological insights and knowledge of historical data. It allows RL agents to optimize the strategy of delivering context-aware notifications from empirical data when counterfactual information (user responses when receiving notifications) is missing. Our approach also considers a constraint on the frequency of notifications, which reduces the interaction burden for users. We evaluated our approach in several simulation scenarios using real large-scale running data. The results indicate that our RL agent can deliver notifications in a manner that realizes a higher behavioral impact than context-blind strategies., (© 2021. The Author(s).)

Just-in-time adaptive intervention (JITAI) has gained attention recently and previous studies have indicated that it is an effective strategy in the field of mobile healthcare intervention. Identifying the right moment for the intervention is a crucial component. In this paper the reinforcement learning (RL) technique has been used in a smartphone exercise application to promote physical activity. This RL model determines the 'right' time to deliver a restricted number of notifications adaptively, with respect to users' temporary context information (i.e., time and calendar). A four-week trial study was conducted to examine the feasibility of our model with real target users. JITAI reminders were sent by the RL model in the fourth week of the intervention, while the participants could only access the app's other functionalities during the first 3 weeks. Eleven target users registered for this study, and the data from 7 participants using the application for 4 weeks and receiving the intervening reminders were analyzed. Not only were the reaction behaviors of users after receiving the reminders analyzed from the application data, but the user experience with the reminders was also explored in a questionnaire and exit interviews. The results show that 83.3% reminders sent at adaptive moments were able to elicit user reaction within 50 min, and 66.7% of physical activities in the intervention week were performed within 5 h of the delivery of a reminder. Our findings indicated the usability of the RL model, while the timing of the moments to deliver reminders can be further improved based on lessons learned.

As nutrition and a health tonic for both medicine and food, the protein content of Oviductus Ranae is more than 40%, making it an ideal source to produce antioxidant peptides. This work evaluated the effects of six different proteases (pepsin, trypsin, papain, flavourzyme, neutral protease and alcalase) on the antioxidant activity of Oviductus Ranae protein, and analyzed the relationship between the hydrolysis time, the degree of hydrolysis (DH) and the antioxidant activity of the enzymatic hydrolysates. The results showed that the antioxidant activity of Oviductus Ranae protein was significantly improved and the optimal hydrolysis time was maintained between 3-4 h under the action of different proteases. Among them, the protein hydrolysate which was hydrolyzed by pepsin for 180 min had the strongest comprehensive antioxidant activity and was most suitable for the production of antioxidant peptides. At this time, the DH, the DPPH radical scavenging activity, the absorbance value of reducing power determination and the hydroxyl radical scavenging activity corresponding to the enzymatic hydrolysate were 13.32 ± 0.24%, 70.63 ± 1.53%, 0.376 ± 0.009 and 31.96 ± 0.78%, respectively. Correlation analysis showed that there was a significant positive correlation between the hydrolysis time, the DH and the antioxidant activity of the enzymatic hydrolysates, further indicating that the hydrolysates of Oviductus Ranae protein had great antioxidant potential. The traditional anti-aging efficacy of Oviductus Ranae is closely related to the scavenging of reactive oxygen species, and its hydrolysates have better antioxidant capacity, which also provides support for further development of its traditional anti-aging efficacy.

Introduction: Many adults do not reach the recommended physical activity (PA) guidelines, which can lead to serious health problems. A promising method to increase PA is the use of smartphone PA applications. However, despite the development and evaluation of multiple PA apps, it remains unclear how to develop and design engaging and effective PA apps. Furthermore, little is known on ways to harness the potential of artificial intelligence for developing personalized apps. In this paper, we describe the design and development of the Playful data-driven Active Urban Living (PAUL): a personalized PA application. Methods: The two-phased development process of the PAUL apps rests on principles from the behavior change model; the Integrate, Design, Assess, and Share (IDEAS) framework; and the behavioral intervention technology (BIT) model. During the first phase, we explored whether location-specific information on performing PA in the built environment is an enhancement to a PA app. During the second phase, the other modules of the app were developed. To this end, we first build the theoretical foundation for the PAUL intervention by performing a literature study. Next, a focus group study was performed to translate the theoretical foundations and the needs and wishes in a set of user requirements. Since the participants indicated the need for reminders at a for-them-relevant moment, we developed a self-learning module for the timing of the reminders. To initialize this module, a data-mining study was performed with historical running data to determine good situations for running. Results: The results of these studies informed the design of a personalized mobile health (mHealth) application for running, walking, and performing strength exercises. The app is implemented as a set of modules based on the persuasive strategies "monitoring of behavior," "feedback," "goal setting," "reminders," "rewards," and "providing instruction." An architecture was set up consisting of a smartphone app for the user, a back-end server for storage and adaptivity, and a research portal to provide access to the research team. Conclusions: The interdisciplinary research encompassing psychology, human movement sciences, computer science, and artificial intelligence has led to a theoretically and empirically driven leisure time PA application. In the current phase, the feasibility of the PAUL app is being assessed., (Copyright © 2021 Sporrel, De Boer, Wang, Nibbeling, Simons, Deutekom, Ettema, Castro, Dourado and Kröse.)

As one of the featured products in northeast China, Oviductus Ranae has been widely used as a nutritious food, which contains a variety of bioactive unsaturated fatty acids (UFAs). It is necessary to establish a scientific and reliable determination method of UFA contents in Oviductus Ranae . In this work, six principal UFAs in Oviductus Ranae , namely eicosapentaenoic acid (EPA), linolenic acid (ALA), docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid (LA) and oleic acid (OA), were identified using UPLC-MS/MS. The UFAs identified in Oviductus Ranae were further separated based on the optimized RP-HPLC conditions. Quantitative analysis of multi-components by single-marker (QAMS) method was implemented in content determination of EPA, ALA, DHA, ARA and OA, where LA was used as the internal standard. The experiments based on Taguchi design verified the robustness of the QAMS method on different HPLC instruments and chromatographic columns. The QAMS and external standard method (ESM) were used to calculate the UFA content of 15 batches of Oviductus Ranae samples from different regions. The relative error (r < 0.73%) and cosine coefficient showed that the two methods obtained similar contents, and the method validations met the requirements. The results showed that QAMS can comprehensively and effectively control the quality of UFAs in Oviductus Ranae which provides new ideas and solutions for studying the active components in Oviductus Ranae .

Background: It is unclear why some physical activity (PA) mobile health (mHealth) interventions successfully promote PA whereas others do not. One possible explanation is the variety in PA mHealth interventions-not only do interventions differ in the selection of persuasive strategies but also the design and implementation of persuasive strategies can vary. However, limited studies have examined the different designs and technical implementations of strategies or explored if they indeed influenced the effectiveness of the intervention., Objective: This scoping review sets out to explore the different technical implementations and design characteristics of common and likely most effective persuasive strategies, namely, goal setting, monitoring, reminders, rewards, sharing, and social comparison. Furthermore, this review aims to explore whether previous mHealth studies examined the influence of the different design characteristics and technical operationalizations of common persuasive strategies on the effectiveness of the intervention to persuade the user to engage in PA., Methods: An unsystematic snowball and gray literature search was performed to identify the literature that evaluated the persuasive strategies in experimental trials (eg, randomized controlled trial, pre-post test). Studies were included if they targeted adults, if they were (partly) delivered by a mobile system, if they reported PA outcomes, if they used an experimental trial, and when they specifically compared the effect of different designs or implementations of persuasive strategies. The study methods, implementations, and designs of persuasive strategies, and the study results were systematically extracted from the literature by the reviewers., Results: A total of 29 experimental trials were identified. We found a heterogeneity in how the strategies are being implemented and designed. Moreover, the findings indicated that the implementation and design of the strategy has an influence on the effectiveness of the PA intervention. For instance, the effectiveness of rewarding was shown to vary between types of rewards; rewarding goal achievement seems to be more effective than rewarding each step taken. Furthermore, studies comparing different ways of goal setting suggested that assigning a goal to users might appear to be more effective than letting the user set their own goal, similar to using adaptively tailored goals as opposed to static generic goals. This study further demonstrates that only a few studies have examined the influence of different technical implementations on PA behavior., Conclusions: The different implementations and designs of persuasive strategies in mHealth interventions should be critically considered when developing such interventions and before drawing conclusions on the effectiveness of the strategy as a whole. Future efforts are needed to examine which implementations and designs are most effective to improve the translation of theory-based persuasive strategies into practical delivery forms., (©Karlijn Sporrel, Nicky Nibbeling, Shihan Wang, Dick Ettema, Monique Simons. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 18.01.2021.)

Running is a popular form of physical activity. Personal, social, and environmental determinants influence the engagement of the individual. To get insight in the relation between running behavior and external situations for different types of users, we carried out an extensive data mining study on large-scale datasets. We combined 4 years of historical running data (collected by a mobile exercise application from over 10K participants) with weather, topographical and demographical datasets. We introduce weighted frequent item mining for the analysis of the data. In this way, we capture temporal and environmental situations that frequently associate with different running performances. The results show that specific temporal and environmental situations (hour in a day, day in a week, temperature, distance to residential areas, and population density) influence the running performance of users more than other situational features. Hierarchical agglomerative clustering on the running data is used to split runners in two clusters (with sustained and less sustained running behavior). We compared the two groups of runners and found that runners with less sustained behavior are more sensitive to the environmental situations (especially several weather and location related features, such as temperature, weather type, distance to the nearest park) than regular runners. Further analysis focused on the situational features for the less sustained runners. Results show that specific feature values correspond to a better or worse running distance. Not only the influence of individual features was examined but also the interplay between features. Our findings provide important empirical evidence that the role of external situations in the running behavior of individuals can be derived from analysis of the combined historical datasets. This opens up a large potential to take those situations specifically into consideration when supporting individuals which show less sustained behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Scheider, Sporrel, Deutekom, Timmer and Kröse.)

Natural products are precious feedstock in drug discovery and sustainable materials. This work using crystal engineering strategy, visible light, and solvent-free cycloaddition successfully constructed two caffeic acid derivatives, rel -(1 R ,2 R ,3 S ,4 S )-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylate and rel -(1 R ,2 R ,3 S ,4 S )-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylic acid. Because of the multiple stereocenters, it is challenging to prepare those compounds using traditional organic synthesis methods. The crystal engineering Hirshfeld surface analysis and 2D intermolecular interaction fingerprints were applied to synthetic route design. The light resources used in this work was visible LED or free, clean, and renewable sunlight. The evidence suggested that pure stereoisomer was obtained demonstrating the stereospecificity and efficiency of the topochemical cycloaddition reaction. The derivatives exhibited free radical scavenging and antioxidant biological activities, as well as the potential inhibitory activity of fatty acid binding proteins. One of the derivatives is the precursor of the natural product Shimobashiric acid C which paves the way for the total synthesis and further study of Shimobashiric acid C. In addition, the derivatives possess photodegradability at a specific wavelength, which is very attractive for "green" degradable polymeric materials.

Rana chensinensis ovum oil (RCOO) is an emerging source of unsaturated fatty acids (UFAs), but it is lacking in green and efficient extraction methods. In this work, using the response surface strategy, we developed a green and efficient CO 2 supercritical fluid extraction (CO 2 -SFE) technology for RCOO. The response surface methodology (RSM), based on the Box-Behnken Design (BBD), was used to investigate the influence of four independent factors (pressure, flow, temperature, and time) on the yield of RCOO in the CO 2 -SFE process, and UPLC-ESI-Q-TOP-MS and HPLC were used to identify and analyze the principal UFA components of RCOO. According to the BBD response surface model, the optimal CO 2 -SFE condition of RCOO was pressure 29 MPa, flow 82 L/h, temperature 50 °C, and time 132 min, and the corresponding predicted optimal yield was 13.61%. The actual optimal yield obtained from the model verification was 13.29 ± 0.37%, and the average error with the predicted value was 0.38 ± 0.27%. The six principal UFAs identified in RCOO included eicosapentaenoic acid (EPA), α-linolenic acid (ALA), docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid (LA), and oleic acid (OA), which were important biologically active ingredients in RCOO. Pearson correlation analysis showed that the yield of these UFAs was closely related to the yield of RCOO (the correlation coefficients were greater than 0.9). Therefore, under optimal conditions, the yield of RCOO and principal UFAs always reached the optimal value at the same time. Based on the above results, this work realized the optimization of CO 2 -SFE green extraction process and the confirmation of principal bioactive ingredients of the extract, which laid a foundation for the green production of RCOO.