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1.
Int Immunopharmacol ; 132: 112027, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38603860

RESUMO

BACKGROUND AND PURPOSE: Osteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice. METHODS: We predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces. RESULTS: Network pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs. CONCLUSIONS: Our data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.

2.
Am J Case Rep ; 25: e942527, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38519985

RESUMO

BACKGROUND Diffuse intestinal lipomatosis is a rare condition that infiltrates mature fatty tissue into the intestinal submucosa and subserosa of the small or large intestine and can present with intestinal obstruction or torsion. This report is of the case of a 58-year-old woman who had acute torsion of the small bowel due to diffuse small intestinal lipomatosis. CASE REPORT A 58-year-old woman, who was otherwise in good health, arrived at our Emergency Department experiencing sudden, intense pain in the lower abdomen. She also reported abdominal swelling, feelings of nausea, vomiting, and reduced ability to defecate for at least 2 days. The next morning, contrast-enhanced abdominal computed tomography (CT) scan was performed, showing diffuse thickening of the small intestinal wall with hypodensity, fatty density, lumen narrowing, and wall thinning. The small intestine demonstrated a whirlpool-like distribution in the lower right abdomen and localized thickening of the small intestinal wall, suggesting acute intestinal torsion. An hour later, an emergency operation was performed to remove part of the small intestine. Three days later, pathological results showed a thin intestinal wall, expansion of the mucosal layer and submucosa, and hyperplasia of adipose tissue. CONCLUSIONS This report presents a rare case of torsion and small bowel obstruction caused by diffuse intestinal lipomatosis and focuses on the abdominal enhanced CT scan, which showed diffuse thickening of the small intestine, with multiple areas of fat density and torsion of the small intestine in the right lower abdomen. Histopathology is also presented, with the result showing intestinal lipomatosis.


Assuntos
Obstrução Intestinal , Lipomatose , Feminino , Humanos , Pessoa de Meia-Idade , Intestino Delgado/cirurgia , Intestino Delgado/patologia , Abdome , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Tomografia Computadorizada por Raios X , Lipomatose/diagnóstico , Lipomatose/diagnóstico por imagem
3.
Sci Rep ; 14(1): 4333, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383745

RESUMO

In the realm of robotics and automation, robot teleoperation, which facilitates human-machine interaction in distant or hazardous settings, has surged in significance. A persistent issue in this domain is the delays between command issuance and action execution, causing negative repercussions on operator situational awareness, performance, and cognitive load. These delays, particularly in long-distance operations, are difficult to mitigate even with the most advanced computing advancements. Current solutions mainly revolve around machine-based adjustments to combat these delays. However, a notable lacuna remains in harnessing human perceptions for an enhanced subjective teleoperation experience. This paper introduces a novel approach of sensory manipulation for induced human adaptation in delayed teleoperation. Drawing from motor learning and rehabilitation principles, it is posited that strategic sensory manipulation, via altered sensory stimuli, can mitigate the subjective feeling of these delays. The focus is not on introducing new skills or adapting to novel conditions; rather, it leverages prior motor coordination experience in the context of delays. The objective is to reduce the need for extensive training or sophisticated automation designs. A human-centered experiment involving 41 participants was conducted to examine the effects of modified haptic cues in teleoperations with delays. These cues were generated from high-fidelity physics engines using parameters from robot-end sensors or physics engine simulations. The results underscored several benefits, notably the considerable reduction in task time and enhanced user perceptions about visual delays. Real-time haptic feedback, or the anchoring method, emerged as a significant contributor to these benefits, showcasing reduced cognitive load, bolstered self-confidence, and minimized frustration. Beyond the prevalent methods of automation design and training, this research underscores induced human adaptation as a pivotal avenue in robot teleoperation. It seeks to enhance teleoperation efficacy through rapid human adaptation, offering insights beyond just optimizing robotic systems for delay compensations.


Assuntos
Medicina , Robótica , Humanos , Robótica/métodos , Interface Usuário-Computador , Desenho de Equipamento , Automação
4.
JMIR Mhealth Uhealth ; 12: e53262, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300700

RESUMO

BACKGROUND: With the rapid development of mobile health (mHealth) technology, many health apps have been introduced to the commercial market for people with back pain conditions. However, little is known about their content, quality, approaches to care for low back pain (LBP), and associated risks of use. OBJECTIVE: The aims of this research were to (1) identify apps for the self-management of LBP currently on the market and (2) assess their quality, intervention content, theoretical approaches, and risk-related approaches. METHODS: The UK iTunes and Google Play stores were initially searched for apps related to the self-management of LBP in May 2022. A repeat search in June 2023 was conducted to ensure that any relevant new apps developed in the last year were incorporated into the review. A total of 3 keywords recommended by the Cochrane Back and Neck Group were used to search apps "low back pain," "back pain," and "lumbago." The quality of the apps was assessed by using the 5-point Mobile App Rating Scale (MARS). RESULTS: A total of 69 apps (25 iOS and 44 Android) met the inclusion criteria. These LBP self-management apps mainly provide recommendations on muscle stretching (n=51, 73.9%), muscle strengthening (n=42, 60.9%), core stability exercises (n=32, 46.4%), yoga (n=19, 27.5%), and information about LBP mechanisms (n=17, 24.6%). Most interventions (n=14, 78%) are consistent with the recommendations in the National Institute for Health and Care Excellence (NICE) guidelines. The mean (SD) MARS overall score of included apps was 2.4 (0.44) out of a possible 5 points. The functionality dimension was associated with the highest score (3.0), whereas the engagement and information dimension resulted in the lowest score (2.1). Regarding theoretical and risk-related approaches, 18 (26.1%) of the 69 apps reported the rate of intervention progression, 11 (15.9%) reported safety checks, only 1 (1.4%) reported personalization of care, and none reported the theoretical care model or the age group targeted. CONCLUSIONS: mHealth apps are potentially promising alternatives to help people manage their LBP; however, most of the LBP self-management apps were of poor quality and did not report the theoretical approaches to care and their associated risks. Although nearly all apps reviewed included a component of care listed in the NICE guidelines, the model of care delivery or embracement of care principles such as the application of a biopsychosocial model was unclear.


Assuntos
Dor Lombar , Aplicativos Móveis , Autogestão , Telemedicina , Humanos , Dor Lombar/terapia , Tecnologia Biomédica
5.
ACS Appl Mater Interfaces ; 16(5): 5554-5567, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38278767

RESUMO

This research aimed to engineer magnetic hydroxyapatite-coated iron-chromium (HAp-FeCr) microspheres to enhance dental surface polishing and plaque elimination. Utilizing a tailored sol-gel approach, the HAp-FeCr microspheres were synthesized and exhaustively characterized via scanning electron microscopy, energy-dispersive X-ray spectroscopy, ζ-potential, X-ray diffractometry, and X-ray photoelectron spectroscopy methodologies. Key findings showcased that these microspheres retained their magnetic properties post-HAp coating, as evidenced by the magnetization curves. An innovative magnetic polishing system was developed, incorporating these microspheres and a 2000 rpm magnet. Comparative evaluations between traditional air-powder polishing and the proposed magnetic technique demonstrated the latter's superiority. Notably, the magnetic polishing led to a substantial reduction in dental plaque on the tooth surface, decreasing bacterial adhesion and early biofilm formation by Streptococcus gordonii and Lactobacillus acidophilus, where the most pronounced effects were observed in samples with elevated HAp content. A significant 60% reduction in dental plaque was achieved with the magnetic method relative to air-powder polishing. Furthermore, the HAp-FeCr microspheres' biocompatibility was verified through cytotoxicity tests and animal studies. In essence, the magnetic HAp-FeCr microspheres present a novel and efficient strategy for dental treatments, holding immense potential for improving oral health.


Assuntos
Placa Dentária , Durapatita , Animais , Durapatita/química , Ferro , Microesferas , Pós , Fenômenos Magnéticos , Propriedades de Superfície
6.
Inorg Chem ; 63(4): 2060-2071, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38232754

RESUMO

The synthesis of two versatile fluorescent metal-organic frameworks (MOFs), [Eu(4-NCP)(1,4-bdc)]n·0.5H2O (1) and [Eu(4-NCP)(4,4'-bpdc)]n·0.75H2O (2) (HNCP = 2-(4-carboxyphenyl)imidazo(4,5-f)-(1,10)phenanthroline, 1,4-H2bdc = benzene-1,4-dicarboxylic acid, 4,4'-H2bpdc = 4,4'-biphenyldicarboxylic acid), was carried out using a hydrothermal method. These MOFs were characterized through various advanced technologies to determine their structural information. The results indicate that both MOFs exhibited 3D network structures with specific topologies. Furthermore, these MOFs demonstrated exceptional thermal stabilities and adsorption capabilities. Additionally, complex 2 was utilized for studying the fluorescence sensing properties of various micronutrients including metal ions, nitro aromatic compounds, and biological small molecules. Notably, complex 2 showed promising potential as a multifunctional sensor for selectively detecting Fe3+, nitrobenzene, and ascorbic acid in aqueous solutions through fluorescence quenching with low limits of detection (LODs ∼ 10-7 M) and high quenching constants (Ksv ∼ 103 M-1). Moreover, the detection mechanism of complex 2 was further investigated by using experimental methods and DFT calculations.

7.
Microb Cell Fact ; 23(1): 3, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172890

RESUMO

BACKGROUND: Antibiotics biosynthesis is usually regulated by the cluster-situated regulatory gene(s) (CSRG(s)), which directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). Previously, we have demonstrated that LmbU functions as a cluster-situated regulator (CSR) of lincomycin. And it has been found that LmbU regulates twenty non-lmb genes through comparative transcriptomic analysis. However, the regulatory mode of CSRs' targets outside the BGC remains unknown. RESULTS: We screened the targets of LmbU in the whole genome of Streptomyces lincolnensis and found fourteen candidate targets, among which, eight targets can bind to LmbU by electrophoretic mobility shift assays (EMSA). Reporter assays in vivo revealed that LmbU repressed the transcription of SLINC_0469 and SLINC_1037 while activating the transcription of SLINC_8097. In addition, disruptions of SLINC_0469, SLINC_1037, and SLINC_8097 promoted the production of lincomycin, and qRT-PCR showed that SLINC_0469, SLINC_1037, and SLINC_8097 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis. CONCLUSIONS: LmbU can directly regulate genes outside the lmb cluster, and these genes can affect both lincomycin biosynthesis and the transcription of lmb genes. Our results first erected the cascade regulatory circuit of LmbU and regulators outside lmb cluster, which provides the theoretical basis for the functional research of LmbU family proteins.


Assuntos
Proteínas de Bactérias , Streptomyces , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Lincomicina , Streptomyces/genética , Streptomyces/metabolismo , Transcriptoma , Regulação Bacteriana da Expressão Gênica , Antibacterianos/farmacologia , Antibacterianos/metabolismo
8.
Sci Total Environ ; 912: 168770, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38007131

RESUMO

Recent studies indicate that the Asian Water Tower (AWT) is at risk due to climate change, which can negatively impact water and food security in Asia. However, there is a lack of comprehensive information on lakes' spatial and temporal changes in this region. This information is crucial for understanding the risk magnitude and designing strategies. To fill this research gap, we analyzed 89,480 Landsat images from 1977 ± 2 to 2020 ± 2 to investigate the changes in the size of lakes recharged by the AWT. Our findings showed that out of the 209 lakes larger than 50 km2, 176 (84 %) grew during the wet season and 167 (81 %) during the dry season. 74 % of expanded lakes are located in the Inner Tibetan Plateau (TP) and Tarim basins. The lakes that shrank are found mainly in the Helmand, Indus, and Yangtze basins. Over the entire period, the area of shrinkage (55,077.028 km2 in wet season, 53,986.796 km2 in dry) markedly exceeded expansion (13,000.267 km2 in wet, 11,038.805 km2 in dry), with the drastic decline of the Aral Sea being a major contributor to shrinkage, accounting for 90 % of the total loss. From 1990 ± 2 to 2020 ± 2, alpine lakes mostly expanded, plain lakes mostly shrank, with the opposite trend from 1977 ± 2 to 1990 ± 2. Glacial loss and permafrost thawing under global warming in the Inner TP, Tarim Interior, Syr Darya, and Mekong basins were strongly correlated with lake expansion. However, permafrost discontinuities may prevent significant growth of lakes in the Indus and Ganges basins despite increased recharge. Our findings point to the prominence of the risk the lakes recharged by AWT face. Taking immediate action to manage these risks and adaptation is crucial as the AWT retreats and lake recharges are slowed.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38081109

RESUMO

Hypothalamic-Pituitary-Somatotropic (HPS) axis is the essential endocrine system playing important roles in animal growth. Here, the HPS axis were characterized in golden pompano (Trachinotus ovatus) and humpback grouper (Cromileptes altivelis), two marine cultured tropical teleosts representing fast and slow growth patterns, respectively. Through genomic and transcriptomic survey, 32 and 35 HPS genes were characterized in T. ovatus and C. altivelis. Functional domain and phylogeny revealed their conserved function among teleost lineages, with more ssts and igfbps identified and actively expressed in C. altivelis than in T. ovatus. The regulation of HPS genes responding to external stimuli revealed that T. ovatus HPS genes, including gh, igf1/2, igfbp1a/b, igfbp2b and igfbp5b, were differentially expressed under temperature or starvation challenges, while C. altivelis HPS genes were sensitive to salinity change with sst1.2, ghrhrb, igf1, igf2r, igfbp1a and igfbp5a regulated in brains. Strong interactive connectivity of igfbps was found in both T. ovatus and C. altivelis. Moreover, HPS genes evolved differently between T. ovatus and C. altivelis, and positively selected sites were detected in more C. altivelis HPS genes, like in functional domains of igf1ra and igf1rb. The igf1ra evolved faster than igf1rb in teleosts, which may contribute to their functional divergence. In conclusion, this study represented different regulatory and evolutionary patterns of HPS axis between T. ovatus and C. altivelis, which are vital in regulating their growth and will provide comprehensive insights into the cultivation of T. ovatus and C. altivelis in aquaculture.


Assuntos
Bass , Animais , Bass/genética , Peixes/genética , Filogenia , Proteínas de Peixes/genética
10.
Small ; : e2308851, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38112252

RESUMO

Vanadium oxides have aroused attention as cathode materials in aqueous zinc-ion batteries (AZIBs) due to their low cost and high safety. However, low ion diffusion and vanadium dissolution often lead to capacity decay and deteriorating stability during cycling. Herein, vanadium dioxides (VO2 ) nanobelts are coated with a single-atom cobalt dispersed N-doped carbon (Co-N-C) layer via a facile calcination strategy to form Co-N-C layer coated VO2 nanobelts (VO2 @Co-N-C NBs) for cathodes in AZIBs. Various in-/ex situ characterizations demonstrate the interfaces between VO2 layers and Co-N-C layers can protect the VO2 NBs from collapsing, increase ion diffusion, and enhance the Zn2+ storage performance. Additional density functional theory (DFT) simulations demonstrate that Co─O─V bonds between VO2 and Co-N-C layers can enhance interfacial Zn2+ storage. Moreover, the VO2 @Co-N-C NBs provided an ultrahigh capacity (418.7 mAh g-1 at 1 A g-1 ), outstanding long-term stability (over 8000 cycles at 20 A g-1 ), and superior rate performance.

11.
Nat Commun ; 14(1): 8399, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110425

RESUMO

Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.


Assuntos
Ascomicetos , Magnaporthe , Oryza , Oryza/genética , Magnaporthe/genética , Ascomicetos/metabolismo , Transporte Biológico , Doenças das Plantas/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
12.
Orthop Traumatol Surg Res ; : 103769, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37979678

RESUMO

INTRODUCTION: The kinematically alignment (KA) technique for TKA aims to reproduce the pre-arthritic knee anatomy, including both the femoro-tibial and femoro-patellar joints. An in silico study was conducted to compare 3 different femoral component sizing techniques to identify the anatomical landmark which allows closest restoration of the native trochlear anatomy. Our study's question was: what was the best method for sizing the femoral component when performing KA-TKA? It was hypothesized that sizing the femoral component by aiming to restore the groove height would be the best method to restore the native trochlear anatomy. METHODS: GMK sphere® (Medacta) femoral component 3D models were virtually kinematically aligned on 30 tri-dimensional (3D) bony osteoarthritis knee models. The femoral component was mediolaterally positioned to match distal native and prosthetic grooves. Three methods were used to size the femoral component: a conventional method with the anterior femoral cut flush to the femoral cortex (C-KATKA) and two alternative personalized methods aiming to recreate either the medial facet's height (ATM-KATKA) or the groove's height (ATG-KATKA). In-house analysis software was used to compare native and prosthetic trochlear articular surfaces and mediolateral implant overhangs. RESULTS: Compared with the C-KATKA, ATG-KATKA and ATM-KATKA techniques increased the component size by a mean of 0.90 (SD 0.31, min 0.5 to max 1.5) (p<0.001) and 1.02 (SD 0.31, min 0.5 to max 1.5) (p<0.001), respectively. C-KATKA technique substantially proximally understuffed the trochleae with maximum values of 7.11mm (SD 1.39, min 3.93mm to max 10.57mm) in the medial facet, 4.72mm (SD 1.27, min 1.46mm to max 6.86mm) in the lateral facet and 4.51mm (SD 1.40, min 1.92mm to max 7.30mm) in the groove, respectively. Alternative techniques understuffed medial facet with maximum values of 5.07mm (SD 1.29, min 2.83mm to max 8.34mm) and 4.70mm (SD 1.52, min 0.83mm to max 8.04mm) for ATG-KATKA and ATM-KATKA techniques, respectively. There was no significant understuffing of the groove or lateral facet for alternative techniques (ATM and ATG). The ATM-KATKA and ATG-KATKA techniques generated mediolateral implant overhang, mainly postero-lateral, with a rate of 90.0% and 86.7%, respectively. In this study, no mediolateral implant overhang was found for C-KATKA. DISCUSSION/CONCLUSION: The C-KATKA technique substantially understuffs the native trochlear articular surfaces in medial, lateral and groove parts. Alternative techniques (ATM-KATKA and ATG-KATKA) for sizing the femoral component better restore the native trochlear anatomy but also generate a high rate of postero-lateral implant overhangs. Would this postero-lateral implant overhang be clinically deleterious remains unknown? The aspect ratio of contemporary femoral TKA implants can probably be optimized to allow a better anatomical restoration of the anterior femoral compartment. LEVEL OF EVIDENCE: II, in silico study.

13.
Front Endocrinol (Lausanne) ; 14: 1257298, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027135

RESUMO

Objective: Eleutheroside E (EE) is an anti-inflammatory natural compound derived from the edible medicinal herb Acanthopanax senticosus. This study aims to investigate the underlying mechanism of the anti-osteoporosis action of EE through network pharmacology, molecular docking and gut microbiota. Materials and methods: Network pharmacology was used to explore the potential core targets and main pathways mediated by EE in osteoporosis (OP) treatment. Molecular docking was exploited to investigate the interactions between the active anti-OP compounds in EE and the potential downstream targets. Following the multi-approach bioinformatics analysis, ovariectomy (OVX) model was also established to investigate the in vivo anti-OP effects of EE. Results: The top 10 core targets in PPI network were TP53, AKT1, JUN, CTNNB1, STAT3, HIF1A, EP300, CREB1, IL1B and ESR1. Molecular docking results that the binding energy of target proteins and the active compounds was approximately between -5.0 and -7.0 kcal/mol, which EE has the lowest docking binding energy with HIF1A. Enrichment analysis of GO and KEGG pathways of target proteins indicated that EE treatment could potentially alter numerous biological processes and cellular pathways. In vivo experiments demonstrated the protective effect of EE treatment against accelerated bone loss, where reduced serum levels of TRAP, CTX, TNF-α, LPS, and IL-6 and increased bone volume and serum levels of P1NP were observed in EE-treated mice. In addition, changes in gut microbiota were spotted by 16S rRNA gene sequencing, showing that EE treatment increased the relative abundance of Lactobacillus and decreased the relative abundance of Clostridiaceae. Conclusion: In summary, these findings suggested that the characteristics of multi-target and multi-pathway of EE against OP. In vivo, EE prevents the onset of OP by regulating gut microbiota and inflammatory response and is therefore a potential OP drug.


Assuntos
Microbioma Gastrointestinal , Osteoporose , Feminino , Animais , Camundongos , Simulação de Acoplamento Molecular , Osteoclastos , RNA Ribossômico 16S , Osteoporose/tratamento farmacológico , Osteoporose/genética
14.
Cell Death Discov ; 9(1): 429, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030614

RESUMO

Macrophage polarization plays an important role in asthma. Nuclear receptor corepressor 1 (NCOR1) plays an important role in metabolic and cardiovascular diseases by regulating the function of macrophages. The aim of this research was to examine the role and mechanism of macrophage NCOR1 in the development of asthma. We used ovalbumin (OVA) to induce macrophage NCOR1-deficient mice for asthma formation. Our results revealed that macrophage NCOR1 deficiency markedly enhanced allergic airway inflammation. In addition, NCOR1 deficiency in macrophages was found to enhance M2 polarization. Mechanistic studies suggested that NCOR1 promoted macrophage polarization by interacting with PPARγ, contributing to the pathogenesis of asthma. In conclusion, macrophage NCOR1 deficiency promoted the regulation of M2 programming by enhancing PPARγ expression to exacerbate asthma. Macrophage NCOR1 might be a potential target for the treatment of asthma.

15.
Bioorg Chem ; 141: 106842, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37769523

RESUMO

Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development, invasion, metastasis and immune reprogramming, which has been proposed as a potential therapeutic target for cancer. Herein, we employed a structure-based discovery and biological evaluation and discovered that Rottlerin (IC50 = 2.53 µM) and Morusin (IC50 = 8.29 µM) and as selective and potent USP22 inhibitors. Treatment of HCT116 cells and A375 cells with each of the two compounds resulted in increased monoubiquitination of histones H2A and H2B, as well as reduced protein expression levels of Sirt1 and PD-L1, all of which are known as USP22 substrates. Additionally, our study demonstrated that the administration of Rottlerin or Morusin resulted in an increase H2Bub levels, while simultaneously reducing the expression of Sirt1 and PD-L1 in a manner dependent on USP22. Furthermore, Rottlerin and Morusin were found to enhance the degradation of PD-L1 and Sirt1, as well as increase the polyubiquitination of endogenous PD-L1 and Sirt1 in HCT116 cells. Moreover, in an in vivo syngeneic tumor model, Rottlerin and Morusin exhibited potent antitumor activity, which was accompanied by an enhanced infiltration of T cells into the tumor tissues. Using in-depth molecular dynamics (MD) and binding free energy calculation, conserved residue Leu475 and non-conserved residue Arg419 were proven to be crucial for the binding affinity and inhibitory function of USP22 inhibitors. In summary, our study established a highly efficient approach for USP22-specific inhibitor discovery, which lead to identification of two selective and potent USP22 inhibitors as potential drugs in anticancer therapy.


Assuntos
Antígeno B7-H1 , Sirtuína 1 , Humanos , Sirtuína 1/metabolismo , Benzopiranos , Bioensaio
16.
Sci Rep ; 13(1): 13313, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587234

RESUMO

Urban forest is an integral part of the complex urban ecosystem, and tree canopy plays a key role in improving urban climatic environment. Urban Tree Canopy (UTC) is strongly linked to urban thermal environment and living quality of residents. In this study, Luoping County, a mountainous county in southwest China, was selected as the study area to uncover the inner connections between tree canopy and thermal environment, and provide relevant scientific references for the construction of livable forest cities in similar areas. Through eCongnition Developer, ENVI and ArcGIS software, the distribution of Land Surface Temperature (LST) and land cover types in the study area was extracted, 63 patches with super-large and extra-large tree canopy coverage selected, to explore the regulatory effect of UTC patches on urban thermal environment based on SPSS software. Results showed that the highest LST in the research area was 37.63 â„ƒ, the lowest 24.73 â„ƒ, and the average 30.83 â„ƒ. Among the land cover types, the area of buildings and impervious surfaces was 1615.71 hm2, accounting for 55.76% of the total study area, which was the largest proportion and with widespread distribution; the area of grassland and water body was 57.48 hm2 and 12.35 hm2, respectively, taking up 1.98% and 0.43%, with a smaller proportion. Mean LST: impervious surface > bare land > grassland > tree canopy > water body. By increasing the area and perimeter of the patch covered by tree canopy, the cooling rate of the patch can be increased while the temperature inside the patch can be reduced. The relationship between the area and cooling rate is closer than that between perimeter and cooling rate. The increase of perimeter has a stronger alleviation effect on the internal temperature of the patch, whereas, the increase of area has a weaker effect in this respect.

17.
Eur Spine J ; 32(12): 4377-4389, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37640886

RESUMO

BACKGROUND: Chronic low back pain (CLBP) is a highly prevalent musculoskeletal condition affecting 60-80% of the general population within their lifetime. Given the large numbers of people affected, self-management approaches have been introduced as a way to manage this condition with endorsement by the national institute for health and care excellence. Interventions are often termed self-management without defining either content or goals. Our study sought to determine the content, characteristics, and evidence for self-management of CLBP. METHODS: This narrative review was conducted using a systematic approach to search journal articles in English that focused on CLBP self-management. MEDLINE, EMBASE, CINAHL, and PsycINFO databases were used to identify publications with terms relating to back pain and self-management from January 2016 until January 2022. RESULTS: In total, 15 studies were found suitable for inclusion in the review. Core components of self-management strategies include exercise, education, and psychological interventions, but there was a lack of consistency with respect to content. Intervention characteristics were either under-reported or varied. Furthermore, outcome measures used to assess these self-management programmes were diverse, mainly focusing on functional disability and pain intensity. CONCLUSIONS: Inconsistencies in the content of self-management interventions, intervention characteristics, and outcome measures used for assessing self-management programmes were found across the literature. Current self-management approaches do not consider the complex biopsychosocial nature of CLBP. A consensus on the key components of self-management interventions, and how they should be evaluated, will pave the way for research to determine whether self-management can effectively manage CLBP.


Assuntos
Dor Crônica , Dor Lombar , Autogestão , Humanos , Autogestão/métodos , Dor Lombar/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Dor Crônica/terapia , Dor Crônica/psicologia
18.
Atherosclerosis ; 377: 34-42, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37392542

RESUMO

BACKGROUND AND AIMS: We investigated the causal relevance of alcohol intake with measures of carotid artery thickness and atherosclerosis in Chinese adults. METHODS: The study included 22,384 adults from the China Kadoorie Biobank, with self-reported alcohol use at baseline and resurvey, carotid artery ultrasound measurements, and genotyping data for ALDH2-rs671 and ADH1B-rs1229984. Associations of carotid intima media thickness (cIMT), any carotid plaque, and total plaque burden (derived from plaque number and size) with self-reported (conventional analyses) and genotype-predicted mean alcohol intake (Mendelian randomization) were assessed using linear and logistic regression models. RESULTS: Overall 34.2% men and 2.1% women drank alcohol regularly at baseline. Mean cIMT was 0.70 mm in men and 0.64 mm in women, with 39.1% and 26.5% having carotid plaque, respectively. Among men, cIMT was not associated with self-reported or genotype-predicted mean alcohol intake. The risk of plaque increased significantly with self-reported intake among current drinkers (odds ratio 1.42 [95% CI 1.14-1.76] per 280 g/week), with directionally consistent findings with genotype-predicted mean intake (1.21 [0.99-1.49]). Higher alcohol intake was significantly associated with higher carotid plaque burden in both conventional (0.19 [0.10-0.28] mm higher per 280 g/week) and genetic analyses (0.09 [0.02-0.17]). Genetic findings in women suggested the association of genotype-predicted alcohol with carotid plaque burden in men was likely to due to alcohol itself, rather than pleiotropic genotypic effects. CONCLUSIONS: Higher alcohol intake was associated with a higher carotid plaque burden, but not with cIMT, providing support for a potential causal association of alcohol intake with carotid atherosclerosis.


Assuntos
Consumo de Bebidas Alcoólicas , Doenças das Artérias Carótidas , Espessura Intima-Media Carotídea , Placa Aterosclerótica , Adulto , Feminino , Humanos , Masculino , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/genética , População do Leste Asiático , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/genética , Fatores de Risco
19.
Sci Rep ; 13(1): 11307, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438450

RESUMO

The hydrological processes play an important role in stimulating fish spawning behavior. Changes in the natural hydrological processes will alter the populations and distribution of fish, which may have a negative impact on the native aquatic organisms. The aim of this study is to identify the alteration of the water rising process during the fish spawning period and to construct an ecological flow optimization model to restore the water rising conditions for fish reproduction. The Mann-Kendall test and the sliding t-test were used to detect the mutation year of the mean daily flow data sets in the fish spawning period in each monitoring year. Then the data sets can be divided into pre-altered and post-altered periods. The water rising process was characterized by the water rising processes count, the duration, the daily flow increase rate, the date of the water rising process, and the initial water rising flow. The changes in hydrological processes in the middle reaches of the Yangtze River were investigated by comparing the post-altered and pre-altered characteristic parameters. Furthermore, we integrated the statistical values of the five characteristic parameters in pre-altered into an ecological flow optimization model to simulate the natural water rising processes for the spawning of the Four Major Chinese Carps (FMCC) and Chinese Sturgeon (CS). The analysis showed that after the hydrological mutation year, the duration and the initial water rising flow in the FMCC spawning season were increased, with hydrological alteration degrees of 63.10% and 70.16%, respectively; however, the daily flow increase rate was significantly decreased, with hydrological alteration of 86.50%. During the CS spawning season, the water rising processes count and the initial water rising flow were dramatically altered parameters, with hydrological alteration degrees of 50.86% and 83.27%, respectively. The former parameter increased, but the latter decreased significantly in the post-altered period. To induce the spawning activity of FMCC and CS, appropriate ecological flows and hydrological parameters were proposed. These results showed that during the spawning seasons of FMCC and CS, the hydrological processes of the middle reaches of the Yangtze River changed significantly. Therefore, ecological flow must be ensured through ecological operation of upstream reservoirs to provide suitable spawning conditions in target fish spawning grounds.


Assuntos
Carpas , Movimentos da Água , Animais , Hidrologia , Comportamento Sexual Animal
20.
Environ Sci Pollut Res Int ; 30(36): 85184-85197, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37380860

RESUMO

In recent years, . the rapid development of the Yangtze River Delta in China has led to increasingly serious regional eco-environmental problems. Therefore, it is of great significance for the construction of ecological civilization to study the ecosystem health in the Yangtze River Delta. In this paper, the assessment framework of "Vigor-Organization-Resilience" was used to assess the ecosystem health index (EHI) of the Yangtze River Delta from 2000 to 2020, and then the spatial autocorrelation method was used to analyze the agglomeration of EHI in 314 counties in this region. Finally, the eXtreme Gradient Boosting (XGBoost) model and the SHapley Additive exPlanation (SHAP) model were combined to explore the synergistic impact of EHI driving factors. The results show that (1) from 2000 to 2020, the EHI in the Yangtze River Delta is at the level of ordinary health, and gradually decreased; (2) the EHI has significant spatial positive correlation and aggregation; (3) the driving factors in descending order of importance are urbanization level (UL), precipitation (PRE), PM2.5 (PM), normalized difference vegetation index (NDVI), and temperature (TEMP); and (4) the relationship between UL and EHI is logarithmic; PRE and EHI are quartic polynomial; PM, NDVI, TEMP, and EHI are quadratic polynomial. The results of this paper are of great significance to the management and restoration of the ecosystem in this region.


Assuntos
Ecossistema , Rios , Urbanização , Temperatura , China , Cidades
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