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Conductive hydrogels have been widely applied in human-computer interaction, tactile sensing, and sustainable green energy harvesting. Herein, a double cross-linked network composite hydrogel (MWCNTs/CNWs/PAM/SA) by constructing dual enhancers acting together with PAM/SA was constructed. By systematically optimizing the compositions, the hydrogel displayed features advantages of good mechanical adaptability, high conductivity sensitivity (GF = 5.65, 53 ms), low hysteresis (<11 %), and shape memory of water molecules and temperature. The nanocellulose crystals (CNWs) were bent and entangled with the backbone of the polyacrylamide/ sodium alginate (PAM/SA) hydrogel network, which effectively transferred the external mechanical forces to the entire physical and chemical cross-linking domains. Multi-walled carbon nanotubes (MWCNTs) were filled into the cross-linking network of the hydrogel to enhance the conductivity of the hydrogel effectively. Notably, hydrogels are designed as flexible tactile sensors that can accurately recognize and monitor electrical signals from different gesture movements and temperature changes. It was also assembled as a friction nanogenerator (TENG) that continuously generates a stable open circuit voltage (28 V) for self-powered small electronic devices. This research provides a new prospect for designing nanocellulose and MWCNTs reinforced conductive hydrogels via a facile method.
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Structural regulation of Pd-based electrocatalytic hydrodechlorination (EHDC) catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challenging. Herein, a support electron inductive effect of Pd-Mn/Ni foam catalyst was proposed via in-situ Mn doping to optimize the electronic structure of the Ni foam (NF), which can inductive regulation of Pd for improving the EHDC performance. The mass activity and current efficiency of Pd-Mn/NF catalyst are 2.91 and 1.34 times superior to that of Pd/NF with 2,4-dichlorophenol as model compound, respectively. The Mn-doped interlayer optimized the electronic structure of Pd by bringing the d-state closer to the Fermi level than Pd on the NF surface, which optimizied the binding of EHDC intermediates. Additionally, the Mn-doped interlayer acted as a promoter for generating H* and accelerating the EHDC reaction. This work presents a simple and effective regulation strategy for constructing high-efficient cathode catalyst for the EHDC of chlorinated organic compounds.
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Manganês , Níquel , Paládio , Catálise , Paládio/química , Manganês/química , Níquel/química , Técnicas Eletroquímicas/métodos , Eletrodos , Clorofenóis/química , HalogenaçãoRESUMO
Although the nonmonotonic variation in the diffusion coefficients of alcohol and water with changing alcohol concentrations in aqueous solutions has been reported for many years, the underlying physical mechanisms remain unclear. Using molecular dynamics simulations, we investigated the molecular diffusion mechanisms in aqueous methanol solutions. Our findings reveal that the molecular diffusion is co-influenced by hydrogen bonding and the hydrophobic ends of methanol molecules. A stronger hydrogen bond (HB) network and a higher concentration of hydrophobic ends of methanol molecules both enhance molecular correlations, thereby slowing molecular diffusion in the solution. As methanol concentration increases, the HB network weakens, facilitating molecular diffusion. However, the increased concentration of hydrophobic ends counteracts this effect. Consequently, the diffusion coefficients of water and methanol molecules exhibit nonmonotonic changes. Previous studies have only focused on the role of HB networks. For the first time, we have identified the impact of the hydrophobic ends of alcohol on molecular diffusion in aqueous alcohol solutions. Our research contributes to a better understanding and manipulation of the properties of aqueous alcohol solutions and even liquids with complex compositions.
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Muscle stem cells (MuSCs) are effective in treating inflammatory diseases driven by overactive innate immune responses, such as colitis and acute lung injury, due to their immunomodulatory properties. However, their potential in treating diseases driven by adaptive immune responses is still uncertain. When primed with inflammatory cytokines, MuSCs strongly suppressed T cell activation and proliferation in vitro in co-culture with activated splenocytes or peripheral blood mononuclear cells. Systemic administration of MuSCs from both mice and humans alleviated pathologies in mice with concanavalin A-induced acute liver injury, characterized by hyperactivated T lymphocytes. Importantly, MuSCs showed significant species-specific differences in their immunoregulatory functions. In mouse MuSCs (mMuSCs), deletion or inhibition of inducible nitric oxide synthase (iNOS) reduced their immunosuppressive activity, and absence of iNOS negated their therapeutic effects in liver injury. Conversely, in human MuSCs (hMuSCs), knockdown or inhibition of indoleamine 2,3-dioxygenase (IDO) eliminated their immunosuppressive effects, and loss of IDO function rendered hMuSCs ineffective in treating liver injury in mice. These results reveal significant species-specific differences in the mechanisms by which MuSCs mediate T cell immunosuppression. Mouse MuSCs rely on iNOS, while human MuSCs depend on IDO expression. This highlights the need to consider species-specific responses when evaluating MuSCs' therapeutic potential in immune-related disorders.
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Óxido Nítrico Sintase Tipo II , Linfócitos T , Animais , Humanos , Linfócitos T/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Células-Tronco/metabolismo , Células-Tronco/imunologia , Especificidade da Espécie , Ativação Linfocitária/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Camundongos Endogâmicos C57BL , Terapia de Imunossupressão/métodos , Tolerância Imunológica , Proliferação de Células , Concanavalina A/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/imunologiaRESUMO
A novel citric acid (CA) modulation strategy was developed to prepare strong magnetic CoFe-LDH/CoFe2O4-C composites, which were combined with dielectric barrier discharge (DBD) to effectively degrade levofloxacin (LEV) in wastewater. Kelvin probe force microscopy (KPFM) test showed that CA modulation facilitated a more powerful internal electric field to drive rapid charge migration. The addition of CoFe-LDH/CoFe2O4-C increased LEV degradation from 78.2 % to 98.6 % and reduced energy efficiency from 24.77 to 8.93 kWh m-3. Quenching experiments and electron paramagnetic resonance (EPR) spectra showed the CoFe-LDH/CoFe2O4-C could take full advantage of the active substances originating from DBD plasma and highlighted the role of 1O2 and ·O2-. Density functional theory (DFT) calculation revealed that the heterojunction can not only drive faster electron migration but also reduce the energy barrier of O3 decomposition. Possible degradation pathways for LEV were proposed. This study opened up a new avenue for the synthesis of applicable catalysts for plasma systems in water treatment areas.
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Purpose: This study aimed to report a newly developed, high-fidelity synthetic simulator to simulate excision and primary anastomotic (EPA) bulbar urethroplasty and its clinical use for new practitioners in shortening the learning curve. Material and Methods: The bulbar urethral anastomosis simulator consists of several standardized components created according to the actual size of the male patient. Interns, novice residents, and fellows inexperienced with urethral reconstruction (n = 10, 5, 5) from different medical centres were invited to participate in the training programme. Two reconstructive urology experts monitored each practice. Following the training, three kinds of validity testing were used to assess the simulator: face, content, and construct. In the intern group, the task performance in the first five training sessions and the last five training ones were compared using a self-control approach. In the resident and fellow group, the real surgical data, including estimated blood loss, operative duration, and 6-month post-operative success rate of trainees after training, are plotted, which are compared with that of reconstructive urology experts (n = 5) included retrospectively to study the effectiveness of the simulator in shortening the learning curve. Results: The overall mean satisfaction rate for the simulators was inspiring and evaluated by experts. In the intern group, significant improvement can be achieved through 10 training sessions (p < 0.05). In clinical practice, the intraoperative indicators and surgical success rate of both the training groups showed the tendency to close or even better than those in the expert group. In terms of the learning curve, training groups performed better compared with experts in the early stages of their careers. Conclusions: In conclusion, this synthetic training simulator for bulbar urethral anastomosis is novel, effective, and convenient for beginners of different groups. The training course can bridge the gap between preclinical use and actual surgery via this simulator.
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BACKGROUND: Muscle invasive bladder cancer (MIBC) is a life-threatening malignant tumor characterized by high metastasis rates, poor prognosis, and limited treatment options. Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 represent an emerging treatment for MIBC immunotherapy. However, the characteristics of patients likely to benefit from immunotherapy remain unclear. METHODS: We performed single-cell mass cytometry (CyTOF) analysis of 179,483 single cells to characterize potential immunotherapy-related cancer stem cells (CSCs)-like populations in the tumor microenvironment of 38 MIBC tissues. The upregulated expression of IGF2BP3 in CD274 + ALDH + CSC-like cells, which was associated with poor clinical prognosis, was analyzed by bulk RNA-sequencing data from an in-house cohort. The functional role of IGF2BP3 was determined through cell proliferation, colony formation, cell apoptosis and sphere formation assays. The regulation of SPHK1 expression by IGF2BP3 was investigated using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and bulk RNA-sequencing (bulk RNA-seq). We further utilized single-nucleus RNA sequencing (snRNA-seq) data from 67,988 cells of 25 MIBC tissues and single-cell RNA sequencing (scRNA-seq) data from MIBC patient-derived organoids to characterize the molecular features of bladder cancer cells co-expressing IGF2BP3 and SPHK1. Spatial transcriptomics (ST) and co-detection by indexing (CODEX) analysis were used to describe the spatial distribution and interactions of IGF2BP3 + SPHK1 + bladder cancer cells and immune cells. RESULTS: A subset of CD274 + ALDH + CSC-like cells was identified, associating with immunosuppression and low survival rates in MIBC patients. IGF2BP3, an m6A reader gene, was found to be upregulated in the CD274 + ALDH + CSC-like cell population and linked to poor clinical prognosis in MIBC. Knockout of IGF2BP3 dramatically promoted cell apoptosis and reduced cell proliferation in T24 cells. By integrating MeRIP-seq and bulk RNA-seq analyses, we identified SPHK1 served as a substrate for IGF2BP3 in an m6A-dependent manner. Further snRNA-seq, scRNA-seq, ST, and CODEX analysis revealed a closer topographical distance between IGF2BP3 + SPHK1 + bladder cancer cells and exhausted CD8 + T cells, providing one explanation for the superior response to immunotherapy in IGF2BP3 + SPHK1 + bladder cancer cells-enriched patients. Finally, an ICI-associated signature was developed based on the enriched genes of IGF2BP3 + SPHK1 + bladder cancer cells, and its potential ability to predict the response to immunotherapy was validated in two independent immunotherapy cohort. CONCLUSIONS: Our study highlighted the critical involvement of the IGF2BP3/SPHK1 signaling in maintaining the stemness of CSCs and promoting MIBC progression. Additionally, these findings suggested that the IGF2BP3/SPHK1 signaling might serve as a biomarker for prognosis and immunotherapy response in MIBC.
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Imunoterapia , Invasividade Neoplásica , Células-Tronco Neoplásicas , Proteínas de Ligação a RNA , Transdução de Sinais , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/imunologia , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Linhagem Celular Tumoral , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Pessoa de Meia-Idade , Proliferação de Células , Músculos/patologia , Músculos/metabolismo , Idoso , MultiômicaRESUMO
Squid, as a very important economic marine species, accounts for 5â¯% of the total catch of fish and cephalopods. The waste from the processing process of squid can be used for collagen extraction, which has great application value in the field of biomedical materials. Here, we obtained squid cartilage gelatin (SCG) with different molecular weights by adjusti.ng the reaction conditions and used for the treatment of chronic wounds in diabetes. SCG extracted at low temperatures and short heating times demonstrated a more intact structure, higher molecular weight, and superior gel stability. Based on cell study and transcriptome analysis, SCG with high molecular weight significantly promoted cell adhesion, because it provided more contact sites for cells, whereas small molecules of SCG could directly reduce inflammation. Animal studies have demonstrated that SCG significantly promotes diabetic wound healing as evidenced by reducing inflammation, inducing vascular regeneration, promoting tissue growth, re-epithelialization, collagen deposition and remodeling. This study elucidated the immunoregulatory mechanisms of SCG with different molecular weights, and validated its potential application in chronic wound healing in diabetes.
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Introduction: This study aimed to compare the clinical efficacy of sexual stimulation with that of placebo in the treatment of distal ureteral stones. Methods: We searched PubMed, Web of Science, Cochrane Library, and Google Scholar from January 1, 2000 to December 31, 2022 for studies comparing the efficacy of sexual stimulus with that of placebo for the treatment of distal ureteral stones. RevMan 5.3 software was used to pool the data. The study protocol was registered on PROSPERO (Registration Number: CRD42023432408). Results: A total of six randomized controlled trials comprising 535 cases of distal ureteral stones were included in this study. Among these, 273 cases were associated with sexual intercourse or masturbation 3-4 times a week, while 262 cases only received symptomatic treatment. The pooled results showed that the 2-week [risk ratios (RR) = 1.77, 95 % confidence interval (CI): 1.34, 2.33] and 4-week [RR = 1.48, 95 % CI: 1.29, 1.69] ureteral stone expulsion rates of the sexually stimulated group were significantly higher than those of the placebo group (ps < 0.01). Additionally, sexual stimulation was associated with a shorter ureteral stone expulsion time [weighted mean differences (WMD) = -3.74, 95 % CI: -6.27, -1.22, p < 0.01] and a decreased prevalence of renal colic attacks [WMD = -0.61, 95 % CI: -1.01, -0.22, p < 0.01] compared with those of the placebo group. Conclusion: Appropriate sexual stimulation can enhance the spontaneous expulsion of distal ureteral stones in patients presenting with tolerable pain.
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Starch is a fundamental material in the food industry. However, the inherent structural constraints of starch impose limitations on its physicochemical properties, including thermal instability, viscosity, and retrogradation. To address these obstacles, polyphenols are extensively employed for starch modification owing to their distinctive structural characteristics and potent antioxidant capabilities. Interaction between the hydroxyl groups of polyphenols and starch results in the formation of inclusion or non-inclusion complexes, thereby inducing alterations in the multiscale structure of starch. These modifications lead to changes in the physicochemical properties of starch, while simultaneously enhancing its nutritional value. Recent studies have demonstrated that both thermal and non-thermal processing exert a significant influence on the formation of starch-polyphenol complexes. This review meticulously analyzes the techniques facilitating complex formation, elucidating the critical factors that dictate this process. Of noteworthy importance is the observation that thermal processing significantly boosts these interactions, whereas non-thermal processing enables more precise modifications. Thus, a profound comprehension and precise regulation of the production of starch-polyphenol complexes are imperative for optimizing their application in various starch-based food products. This in-depth study is dedicated to providing a valuable pathway for enhancing the quality of starchy foods through the strategic integration of suitable processing technologies.
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Manipulação de Alimentos , Polifenóis , Amido , Amido/química , Amido/metabolismo , Polifenóis/química , Manipulação de Alimentos/métodos , Antioxidantes/química , ViscosidadeRESUMO
Chitosan is a polymeric polysaccharide with widely application. At present, commercialized chitosan obtained by deacetylating chitin with acid-alkali method. The homogeneity of the molecular weight of chitosan is difficult to adjust due to the low homogeneity of chitosan itself and the degradation effect of the extraction process. And the single source of raw material has limited the further development of chitosan. In this study, diatoms were used as the source of chitosan extraction through alkalization freeze-thaw method, and response surface methodology was also used to optimize the best preparation conditions of diatom chitosan. The extracted chitosan from diatom was ß-type chitosan with low molecular weight, great homogeneity. Diatom chitosan was able to reduce blood loss and clotting time >30 % in vivo experiment compared to control. The hemolysis rate of diatom chitosan was lower than 1 %, and the survival rate was higher than 95 % when co-cultured with L929 cells. Diatom chitosan with 0.005 % could inhibit E. coli and S. aureus by >90 %. Considering the large-scale cultivation properties of diatom, the extraction of diatom chitosan based on alkalization freeze-thaw method will provide a viable solution for obtaining ß-chitosan with homogeneity on a large scale.
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Quitosana , Diatomáceas , Quitosana/química , Quitosana/farmacologia , Diatomáceas/química , Animais , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Hemólise/efeitos dos fármacos , Peso Molecular , Linhagem CelularRESUMO
The recruitment of the protein spleen tyrosine kinase (Syk) to membrane-bound immune receptors is an essential step in initiating an immune response mediated through the activated receptors. Syk recognizes intracellular phosphorylated regions of membrane receptors known as immunoreceptor tyrosine-based activation motifs (ITAMs) defined by a sequence with two tyrosine (Y) amino acids separated by a certain spacing of six to eight residues: YXX(I/L)X6-8YXX(I/L). Syk with doubly phosphorylated ITAM is high-affinity and negatively regulated when Syk itself becomes phosphorylated. While the role of Syk in immune signaling is well characterized, recent information affords new functionality to Syk related to cytoplasmic processes, including the clearance of stress granules and P-bodies, both formed by liquid-liquid phase separation. Little to nothing is known about the molecular interactions involving Syk in these cytoplasmic processes. Given the essential role of receptor ITAMs in recruiting and localizing Syk for immune signaling, we explore here the possibility of a similar localization mechanism occurring for cytoplasmic processes by searching sequences of proteins related to Syk cytoplasmic function for regions that resemble receptor ITAMs. Protein sequence databases were generated from a Syk-dependent phosphoproteome and from genes related to P-bodies. A search of these databases for ITAM-like sequences yielded 102 unique hits, and 33 of these were synthesized and tested experimentally for binding to Syk tandem SH2 domains. The equilibrium dissociation constants were 0.1-50 µM for 28 peptides, and binding was negatively regulated by phosphorylation for many peptides. These results identify cytoplasmic proteins with potential for regulating the localization of Syk in a phosphorylation-dependent manner to nonmembrane cellular regions.
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Quinase Syk , Quinase Syk/metabolismo , Quinase Syk/química , Sequência de Aminoácidos , Citosol/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/química , Fosforilação , Motivo de Ativação do Imunorreceptor Baseado em Tirosina , Humanos , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/genéticaRESUMO
Nonlinear-optical (NLO) crystals capable of controlling and manipulating light to generate coherent radiation at challenging wavelengths are of significant interest. However, designing a new UV NLO crystal remains difficult due to the rigid requirements for structure and properties. Herein, we have successfully designed and synthesized a novel noncentrosymmetric (NCS) rare-earth borate UV NLO crystal, K3Y3(BO3)4, through the heterovalence substitution of YAl3(BO3)4. K3Y3(BO3)4 (KYBO) crystallizes in the NCS and polar space group of P63mc, with the structure formed by the interconnectioned BO3 triangles and YO8 polyhedra through corner-sharing and edge-sharing. The property measurements indicate that KYBO is second-harmonic-generation-active with a moderate response, â¼2 × KDP. Meanwhile, KYBO can exhibit a short UV cutoff edge (λcutoff < 190 nm), indicating its potential as a new UV or deep-UV NLO crystal.
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ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. AIM OF STUDY: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. MATERIALS AND METHODS: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. RESULTS: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. CONCLUSION: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.
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BACKGROUND: Skin aging is characterized by an imbalance between the generation and degradation of extracellular matrix molecules (ECM). Matrix metalloproteinases (MMPs) are the primary enzymes responsible for ECM breakdown. Intrinsic and extrinsic stimuli can induce different MMPs. However, there is limited literature especially on the summary of skin MMPs and potential inhibitors. OBJECTIVE: We aim to focus on the upregulation of MMP expression or activity in skin cells following exposure to UV radiation. We also would like to offer valuable insights into potential clinical applications of MMP inhibitors for mitigating skin aging. METHODS: This article presents the summary of prior research, which involved an extensive literature search across diverse academic databases including Web of Science and PubMed. RESULTS: Our findings offer a comprehensive insight into the effects of MMPs on skin aging after UV irradiation, including their substrate preferences and distinct roles in this process. Additionally, a comprehensive list of natural plant and animal extracts, proteins, polypeptides, amino acids, as well as natural and synthetic compounds that serve as inhibitors for MMPs is compiled. CONCLUSION: Skin aging is a complex process influenced by environmental factors and MMPs. Research focuses on UV-induced skin damage and the formation of Advanced Glycosylation End Products (AGEs), leading to wrinkles and impaired functionality. Inhibiting MMPs is crucial for maintaining youthful skin. Natural sources of MMP inhibitor substances, such as extracts from plants and animals, offer a safer approach to obtain inhibitors through dietary supplements. Studying isolated active ingredients can contribute to developing targeted MMP inhibitors.
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In immunology, the role of macrophages extends far beyond their traditional classification as mere phagocytes; they emerge as pivotal architects of the immune response, with their function being significantly influenced by multidimensional environmental stimuli. This review investigates the nuanced mechanisms by which diverse external signals ranging from chemical cues to physical stress orchestrate macrophage polarization, a process that is crucial for the modulation of immune responses. By transitioning between pro-inflammatory (M1) and anti-inflammatory (M2) states, macrophages exhibit remarkable plasticity, enabling them to adapt to and influence their surroundings effectively. The exploration of macrophage polarization provides a compelling narrative on how these cells can be manipulated to foster an immune environment conducive to tissue repair and regeneration. Highlighting cutting-edge research, this review presents innovative strategies that leverage the dynamic interplay between macrophages and their environment, proposing novel therapeutic avenues that harness the potential of macrophages in regenerative medicine. Moreover, this review critically evaluates the current challenges and future prospects of translating macrophage-centered strategies from the laboratory to clinical applications.
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Amides are an important type of synthetic intermediate used in the chemical, agrochemical, pharmaceutical, and nutraceutical industries. The traditional chemical process of converting nitriles into the corresponding amides is feasible but is restricted because of the harsh conditions required. In recent decades, nitrile hydratase (NHase, EC 4.2.1.84) has attracted considerable attention because of its application in nitrile transformation as a prominent biocatalyst. In this review, we provide a comprehensive survey of recent advances in NHase research in terms of natural distribution, enzyme screening, and molecular modification on the basis of its characteristics and catalytic mechanism. Additionally, industrial applications and recent significant biotechnology advances in NHase bioengineering and immobilization techniques are systematically summarized. Moreover, the current challenges and future perspectives for its further development in industrial applications for green chemistry were also discussed. This study contributes to the current state-of-the-art, providing important technical information for new NHase applications in manufacturing industries.
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Rationale: Azoospermia is a significant reproductive challenge. Differentiating between non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) is crucial as each type requires distinct management strategies. Testicular microcirculation plays a profound role in spermatogenic functions. However, current diagnostic methods are limited in their ability to effectively elucidate this crucial connection. Methods: We employed ultrasound localization microscopy (ULM) to visualize testicular microcirculation in NOA and OA patients and quantified the testicular hemodynamic parameters. Pearson correlation analysis was conducted to investigate the inner connection between parameters of testicular microcirculation and clinical spermatogenic functions. We conducted multiple logistic regression analysis to establish a new diagnostic model that integrates follicle-stimulating hormone (FSH) and mean vascular diameter to distinguish NOA from OA. Results: Our findings demonstrated significant differences in vascular parameters between NOA and OA, with NOA characterized by lower mean vascular diameter (p < 0.001), vessel density (p < 0.001), and fractal number (p < 0.001). Testicular volume showed a moderate positive correlation with mean vascular diameter (r = 0.419, p < 0.01) and vessel density (r = 0.415, p < 0.01); Mean vascular diameter exhibited negative correlations with both FSH (r = -0.214, p < 0.05) and age (r = -0.240, p < 0.05); FSH (r = -0.202, p < 0.05) and luteinizing hormone (LH) (r = -0.235, p < 0.05) were negatively correlated with mean blood flow velocity. The diagnostic model demonstrated an area under the curve (AUC) of 0.968. We also reported a method to map the vascular pressure distribution derived from the blood flow velocity generated by ULM. Conclusions: ULM provides a non-invasive and detailed assessment of testicular microvascular dynamics. The ULM-derived vascular parameters are able to connect testicular microcirculation to spermatogenic functions. The combination of FSH and mean vascular diameter enhances diagnostic precision and holds potential for distinguishing NOA from OA.
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Azoospermia , Hormônio Foliculoestimulante , Microcirculação , Espermatogênese , Testículo , Masculino , Humanos , Testículo/irrigação sanguínea , Testículo/diagnóstico por imagem , Azoospermia/diagnóstico por imagem , Azoospermia/fisiopatologia , Adulto , Hormônio Foliculoestimulante/sangue , Ultrassonografia/métodos , Pessoa de Meia-Idade , Microscopia/métodosRESUMO
Facilitating the surface reconstruction of pre-catalysts has been considered an effective strategy for constructing low-cost and highly efficient OER electrocatalysts. Metal doping is a feasible way to activate the surface reconstruction, thus enhancing the OER performance. Herein, we report a facile hydrothermal method to synthesize a series of Zn-doped Ni-MOF on nickel foam (NiZn-MOF/NF) as promising pre-catalysts toward the oxygen evolution reaction (OER). The Zn leaching of NiZn-MOF/NF can promote the surface self-reconstruction of NiZn-MOF/NF into oxygen-vacancy-rich NiOOH after electrochemical activation. Benefiting from the optimized electronic structure, abundant defects, more accessible active sites, and enhanced electrical conductivity, the reconstructed metal oxyhydroxide hybrids exhibit better electrocatalytic activity than the catalysts transformed from Ni-MOF/NF without Zn doping. The optimized NiZn-MOF/NF-OH as an OER catalyst has an overpotential of 336 mV at 100 mA cm-2, and a Tafel slope of 65.9 mV dec-1, as well as stability over 12 h. This work reveals that Zn cation-doping/leaching induces the surface reconstruction of pre-catalysts for enhanced oxygen catalytic activity, which provides a new approach for the development of advanced electrocatalysts.
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BACKGROUND: Previous studies have demonstrated the benefits of ideal cardiovascular health (CVH) in reducing cardiovascular risk. However, its role in subclinical atherosclerosis (SA) progression remains unclear. We aim to examine the association of CVH, estimated by the American Heart Association's new Life's Essential 8 (LE8), with the progression of SA. METHODS: This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for 5.7 years. The LE8 score (range, 0-100) consisted of blood pressure, lipids, glucose, body mass index, smoking status, diet health, physical activity and sleep health was evaluated in 1998 and 2008-2009. Progression of SA was determined by carotid plaque and coronary artery calcification (CAC) in 2008-2009 and 2013-2014. Log-binomial regression model was used to estimate the association of LE8 score with SA progression. RESULTS: Each 10 points increment in LE8 score was associated with 15.2% (RR: 0.848, 95% CI: 0.797-0.902), 17.7% (RR: 0.823, 95% CI: 0.766-0.884) and 12.0% (RR: 0.880, 95% CI: 0.845-0.916) lower risks of carotid plaque, CAC and overall SA progression, respectively. Compared with participants with non-ideal CVH at both visits, the participants with ideal CVH at both visits had 39.1% (RR: 0.609, 95% CI: 0.494-0.752), 41.0% (RR: 0.590, 95% CI: 0.456-0.764) and 29.7% (RR: 0.703, 95% CI: 0.598-0.825) lower risks of carotid plaque, CAC and overall SA progression, respectively. CONCLUSIONS: Higher LE8 scores were associated with lower risks of SA progression. Besides, long-term maintenance of optimal CVH was more beneficial to prevent SA progression.