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1.
Front Genet ; 15: 1397390, 2024.
Article in English | MEDLINE | ID: mdl-38962452

ABSTRACT

Objective: Numerous studies have reported that metformin can reduce the risk of tumor development. However, some of the results of these studies are conflicting, necessitating a more reliable evaluation. Methods: We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis. Results: MR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae. Conclusion: Metformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings.

2.
J Anim Sci Biotechnol ; 15(1): 89, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38951898

ABSTRACT

BACKGROUND: Sows commonly experience insulin resistance in late gestation and lactation, causing lower feed intake and milk production, which can lead to higher mortality rates in newborn piglets. The probiotic Lactobacillus rhamnosus GG (LGG) is known to improve insulin resistance. However, whether supplementing LGG can improve insulin sensitivity in sows and enhance lactation performance, particularly the early survival of offspring remains unclear. Hence, we explored the effects and mechanisms of supplementing LGG during late gestation and lactation on sow insulin sensitivity, lactation performance, and offspring survival. In total, 20 sows were randomly allocated to an LGG (n = 10) and control group (n = 10). RESULTS: In sows, LGG supplementation significantly improved insulin sensitivity during late gestation and lactation, increased feed intake, milk production and colostrum lactose levels in early lactation, and enhanced newborn piglet survival. Moreover, LGG treatment significantly reshaped the gut microbiota in sows, notably increasing microbiota diversity and enriching the relative abundance of insulin sensitivity-associated probiotics such as Lactobacillus, Bifidobacterium, and Bacteroides. Serum metabolite and amino acid profiling in late-gestation sows also revealed decreased branched-chain amino acid and kynurenine serum levels following LGG supplementation. Further analyses highlighted a correlation between mitigated insulin resistance in late pregnancy and lactation by LGG and gut microbiota reshaping and changes in serum amino acid metabolism. Furthermore, maternal LGG enhanced immunity in newborn piglets, reduced inflammation, and facilitated the establishment of a gut microbiota. CONCLUSIONS: We provide the first evidence that LGG mitigates insulin resistance in sows and enhances offspring survival by modulating the gut microbiota and amino acid metabolism.

3.
Cell Rep ; 43(7): 114478, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38985668

ABSTRACT

Lyssavirus is a kind of neurotropic pathogen that needs to evade peripheral host immunity to enter the central nervous system to accomplish infection. NLRP3 inflammasome activation is essential for the host to defend against pathogen invasion. This study demonstrates that the matrix protein (M) of lyssavirus can inhibit both the priming step and the activation step of NLRP3 inflammasome activation. Specifically, M of lyssavirus can compete with NEK7 for binding to NLRP3, which restricts downstream apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. The serine amino acid at the 158th site of M among lyssavirus is critical for restricting ASC oligomerization. Moreover, recombinant lab-attenuated lyssavirus rabies (rabies lyssavirus [RABV]) with G158S mutation at M decreases interleukin-1ß (IL-1ß) production in bone-marrow-derived dendritic cells (BMDCs) to facilitate lyssavirus invasion into the brain thereby elevating pathogenicity in mice. Taken together, this study reveals a common mechanism by which lyssavirus inhibits NLRP3 inflammasome activation to evade host defenses.

4.
Front Microbiol ; 15: 1415365, 2024.
Article in English | MEDLINE | ID: mdl-38989030

ABSTRACT

Theiler's murine encephalomyelitis virus (TMEV) infected mice have been often used as an animal model for Multiple sclerosis (MS) due to their similar pathology in the central nervous system (CNS). So far, there has been no effective treatment or medicine to cure MS completely. The drugs used in the clinic can only reduce the symptoms of MS, delay its recurrence, and increase the interval between relapses. MS can be caused by many factors, and clinically MS drugs are used to treat MS regardless of what factors are caused rather than MS caused by a specific factor. This can lead to inappropriate medicine, which may be one of the reasons why MS has not been completely cured. Therefore, this review summarized the drugs investigated in the TMEV-induced disease (TMEV-IDD) model of MS, so as to provide medication guidance and theoretical basis for the treatment of virus-induced MS.

5.
Opt Lett ; 49(12): 3476-3479, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38875649

ABSTRACT

A high average power re-frequency operation Fe:ZnSe laser using laser diode side-pumped free-running Er:YAG lasers as activating sources is presented. Two pieces of subsurface layer doped Fe:ZnSe polycrystal are adoptive in a reflective resonator configuration and face-cooled by liquid nitrogen. A maximal Fe:ZnSe laser power of 105 W at a wavelength of 4.1 µm is achieved upon pumping by ten home-made Er:YAG lasers with fiber coupled output working at a frequency of 250 Hz and a pulse duration of ∼420 µs. Corresponding to the maximum Fe:ZnSe laser power, the optical-optical efficiency and slope efficiency with respect to the absorbed pump power are 43% and 44% respectively. The beam quality factor M2 is measured to be 3.4. To the best of our knowledge, it is the highest output average power of an Fe:ZnSe laser reported.

6.
J Multidiscip Healthc ; 17: 2961-2972, 2024.
Article in English | MEDLINE | ID: mdl-38933695

ABSTRACT

Objective: Postoperative delirium (POD), a common complication affecting short- and long-term prognosis in elderly patients, leads to a heavy burden on social economy and health care. The main purpose of this study is to conduct a bibliometric analysis of the 100 most frequently cited articles on POD. Methods: "Postoperative delirium" and its synonyms were searched in the Web of Science (WoS) core database. The top-100 cited articles were automatically selected by sorting the records in descending order. Key information such as author, journal, article type, publication year, citations, since 2013 usage count, institution, country, and keywords were extracted and analyzed. VOSviewer software was applied to do the visualization analyses of institution co-operation, author interaction, author co-citation, and keywords co-occurrence. The CiteSpace software was used to analyze keywords burst. Results: Most articles were published by authors and institutions in the United States of America (USA). Inouye was the most influential author of this field. The journals that recorded these articles had a high impact factor (IF), with a highest IF of 168.9 and an average IF of 18.04. Cohort studies were the main document type in this field (42 publications), followed by randomized controlled trial (RCT) and systematic reviews or meta-analysis (18 and 14, respectively). The 10 keywords with the highest appearance were "delirium", "risk-factors", "surgery", "confusion assessment method", "elderly patients", "hip fracture", "intensive care unit", "cardiac surgery", "general anesthesia", and "risk". Moreover, "double blind" and "cardiac surgery" were the most recent booming keywords. Conclusion: We indicated the current research status and tendency of POD by analyzing the 100 most influential articles on POD. The USA is the leader in this field. Prospective study is the preference for authors to cite. Cardiac surgery remains the primary research carrier and the hotspots in the near future may be double-blind studies.

7.
Front Neurosci ; 18: 1396345, 2024.
Article in English | MEDLINE | ID: mdl-38933815

ABSTRACT

Background: Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the progression of PD. It was proposed that neuroinflammation leads to neuronal death, making targeting neuroinflammation a promising therapeutic strategy. Our previous studies have demonstrated that rhein protects neurons in vitro by inhibiting neuroinflammation, and it has been found to exhibit neuroprotective effects in Alzheimer's disease and epilepsy, but its neuroprotective mechanisms and effects on PD are still unclear. Methods: PD animal model was induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). ELISA, RT-qPCR, western blot and Immunofluorescence were used to detect the levels of inflammatory cytokines and M1 polarization markers. The protein expression levels of signaling pathways were measured by western blot. Hematoxylin-eosin (HE) staining showed that rhein did not damage the liver and kidney. Two behavioral tests, pole test and rotarod test, were used to evaluate the improvement effect of rhein on movement disorders. The number of neurons in the substantia nigra was evaluated by Nissl staining. Immunohistochemistry and western blot were used to detect tyrosine hydroxylase (TH) and α-synuclein. Results: Rhein inhibited the activation of MAPK/IκB signaling pathway and reduced the levels of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and M1 polarization markers of microglia in vivo. In a mouse model of PD, rhein ameliorated movement disorders, reduced dopaminergic neuron damage and α-synuclein deposition. Conclusion: Rhein inhibits neuroinflammation through MAPK/IκB signaling pathway, thereby reducing neurodegeneration, α-synuclein deposition, and improving movement disorders in Parkinson's disease.

8.
Small Methods ; : e2400707, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38923411

ABSTRACT

For N-type tunnel-oxide-passivated-contact silicon solar cells, optimal Ag/Al-Si contact interface is crucial to improve the efficiency. However, the specific roles of Ag and Al at the interface have not been clearly elucidated. Hence, this work delves into the sintering process of Ag/Al paste and examines the impact of the Ag/Al-Si interface structure on contact quality. By incorporating TeO2 into PbO-based Ag/Al paste, the Ag/Al-Si interface structure can be modulated. It can be found that TeO2 accelerates the sintering of Ag powder and increases Ag colloids within glass layer, while it simultaneously impedes the diffusion of molten Al. It leads to a reduced Al content near the Ag/Al-Si interface and a shorter diffusion distance of Al into Si. Notably, it can be demonstrated that the diffusion of Al in Si layer is more effective to reduce the contact resistance than the precipitation of Ag colloids. Therefore, the PbO-based Ag/Al paste, which favors Al diffusion, leads to solar cells with lower contact resistance and series resistance, higher fill factor, and superior photoelectric conversion efficiency. In brief, this work is significant for optimizing metallization of silicon solar cells and other semiconductor devices.

9.
Biology (Basel) ; 13(6)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38927307

ABSTRACT

Ulcerative colitis (UC) is an inflammatory bowel disease that causes chronic inflammation in the large intestine. The etiology of UC is complex and incompletely understood, with potential contributing factors including genetic susceptibility, environmental influences, immune dysregulation, and gut barrier dysfunction. Despite available therapeutic drugs, the suboptimal cure rate for UC emphasizes the necessity of developing novel therapeutics. Traditional Chinese Medicine (TCM) has attracted great interest in the treatment of such chronic inflammatory diseases due to its advantages, such as multi-targets and low side effects. In this study, a mouse model of Dextran Sulfate Sodium (DSS)-induced acute colitis was established and the efficacy of Zhenqi Granule, a TCM preparation composed of the extractives from Astragali Radix and Fructus Ligustri Lucidi, was evaluated. The results showed that treatment with Zhenqi Granule prior to or post-DSS induction could alleviate the symptoms of colitis, including weight loss, diarrhea, hematochezia, colon length shortening, and pathological damage of colon tissues of the DSS-treated mice. Further, network pharmacology analysis showed that there were 98 common targets between the active components of Zhenqi Granule and the targets of UC, and the common targets were involved in the regulation of inflammatory signaling pathways. Our results showed that Zhenqi Granule had preventive and therapeutic effects on acute colitis in mice, and the mechanism may be that the active components of Zhenqi Granule participated in the regulation of inflammatory response. This study provided data reference for further exploring the mechanism of Zhenqi Granule and also provided potential treatment strategies for UC.

10.
New Phytol ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849320

ABSTRACT

Flowering is a vital agronomic trait that determines the economic value of most ornamental plants. The flowering time of rose (Rosa spp.) is photoperiod insensitive and is thought to be tightly controlled by light intensity, although the detailed molecular mechanism remains unclear. Here, we showed that rose plants flower later under low-light (LL) intensity than under high-light (HL) intensity, which is mainly related to the stability of PHYTOCHROME-INTERACTING FACTORs (RcPIFs) mediated by OPEN STOMATA 1-Like (RcOST1L) under different light intensity regimes. We determined that HL conditions trigger the rapid phosphorylation of RcPIFs before their degradation. A yeast two-hybrid screen identified the kinase RcOST1L as interacting with RcPIF4. Moreover, RcOST1L positively regulated rose flowering and directly phosphorylated RcPIF4 on serine 198 to promote its degradation under HL conditions. Additionally, phytochrome B (RcphyB) enhanced RcOST1L-mediated phosphorylation of RcPIF4 via interacting with the active phyB-binding motif. RcphyB was activated upon HL and recruited RcOST1L to facilitate its nuclear accumulation, in turn leading to decreased stability of RcPIF4 and flowering acceleration. Our findings illustrate how RcPIF abundance safeguards proper rose flowering under different light intensities, thus uncovering the essential role of RcOST1L in the RcphyB-RcPIF4 module in flowering.

11.
Adv Sci (Weinh) ; : e2404049, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38899839

ABSTRACT

The rapid rise of antibiotic resistance and slow discovery of new antibiotics have threatened global health. While novel phage lysins have emerged as potential antibacterial agents, experimental screening methods for novel lysins pose significant challenges due to the enormous workload. Here, the first unified software package, namely DeepLysin, is developed to employ artificial intelligence for mining the vast genome reservoirs ("dark matter") for novel antibacterial phage lysins. Putative lysins are computationally screened from uncharacterized Staphylococcus aureus phages and 17 novel lysins are randomly selected for experimental validation. Seven candidates exhibit excellent in vitro antibacterial activity, with LLysSA9 exceeding that of the best-in-class alternative. The efficacy of LLysSA9 is further demonstrated in mouse bloodstream and wound infection models. Therefore, this study demonstrates the potential of integrating computational and experimental approaches to expedite the discovery of new antibacterial proteins for combating increasing antimicrobial resistance.

12.
Cell Commun Signal ; 22(1): 343, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38907279

ABSTRACT

Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.


Subject(s)
DNA-Directed RNA Polymerases , Human Umbilical Vein Endothelial Cells , Mitochondria , Humans , Animals , Mice , Mitochondria/metabolism , DNA-Directed RNA Polymerases/metabolism , DNA-Directed RNA Polymerases/genetics , Diabetic Retinopathy/pathology , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/genetics , Mice, Inbred C57BL , Cell Proliferation , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Male , Neovascularization, Physiologic/genetics , Cell Movement , Apoptosis , Angiogenesis
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124691, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38909557

ABSTRACT

The allure of substantial profits has perpetuated the illicit trade of counterfeit vintage labels for baijiu. While various approaches have been employed to intelligently ascertain the vintage of baijiu, many of them are both cost-intensive and time-consuming. This work pioneered the use of Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, coupled with chemometric analysis, offering a non-destructive and economically viable method for discriminating sauce-flavor baijiu across different aging periods (1-, 2-, and 3-year). In this research, principal component analysis (PCA) was first conducted to explore clustering trends among distinct vintage groups. Subsequently, the effect of spectral pre-processing on modeling performance was explored. For wavelength selection, four wavelength selection methods (ReliefF, random forest variable importance (RFVI), variable importance in projection (VIP), and Venn) were first used to identify the subset of candidate features that potentially best mapped the vintage labels. Immediately following this, to explore the possibility of further improving the identification capabilities of the model as well as to reduce the redundant data that may still be present, sequential backward selection (SBS) was utilized for secondary feature reduction within the subset of candidates. The amalgamation of these two techniques is termed a "hybrid wavelength selection strategy." Additionally, the dimensionality reduction effects of PCA and kernel principal component analysis (KPCA) were compared to demonstrate the robustness of the proposed method. Finally, classification models such as partial least squares discriminant analysis (PLS-DA), random forest (RF), and grasshopper optimization algorithm-based support vector machine (GOA-SVM) were developed. The results show that the spectral data need not be pre-processed, and the proposed hybrid wavelength selection strategy can further improve the identification ability of the model. Among the many models developed, ReliefF-SBS-GOA-SVM emerged as the most proficient classification model, yielding accuracy, sensitivity, and specificity rates of 94.44%, 95.23%, and 94.44%, respectively. This method not only holds promise for the discrimination of baijiu class attributes such as brand, origin, flavor, and vintage but also exhibits potential applicability in other non-targeted identification studies involving spectroscopy methodologies.

14.
Structure ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38823379

ABSTRACT

Carboxysomes are large self-assembled microcompartments that serve as the central machinery of a CO2-concentrating mechanism (CCM). Biogenesis of carboxysome requires the fine organization of thousands of individual proteins; however, the packaging pattern of internal RuBisCOs remains largely unknown. Here we purified the intact ß-carboxysomes from Synechococcus elongatus PCC 7942 and identified the protein components by mass spectrometry. Cryo-electron tomography combined with subtomogram averaging revealed the general organization pattern of internal RuBisCOs, in which the adjacent RuBisCOs are mainly arranged in three distinct manners: head-to-head, head-to-side, and side-by-side. The RuBisCOs in the outermost layer are regularly aligned along the shell, the majority of which directly interact with the shell. Moreover, statistical analysis enabled us to propose an ideal packaging model of RuBisCOs in the ß-carboxysome. These results provide new insights into the biogenesis of ß-carboxysomes and also advance our understanding of the efficient carbon fixation functionality of carboxysomes.

15.
Ann Lab Med ; 44(5): 385-391, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38835211

ABSTRACT

Patient-based real-time QC (PBRTQC) uses patient-derived data to assess assay performance. PBRTQC algorithms have advanced in parallel with developments in computer science and the increased availability of more powerful computers. The uptake of Artificial Intelligence in PBRTQC has been rapid, with many stated advantages over conventional approaches. However, until this review, there has been no critical comparison of these. The PBRTQC algorithms based on moving averages, regression-adjusted real-time QC, neural networks and anomaly detection are described and contrasted. As Artificial Intelligence tools become more available to laboratories, user-friendly and computationally efficient, the major disadvantages, such as complexity and the need for high computing resources, are reduced and become attractive to implement in PBRTQC applications.


Subject(s)
Algorithms , Quality Control , Humans , Neural Networks, Computer , Artificial Intelligence , Laboratories, Clinical/standards
16.
Science ; 384(6700): 1091-1095, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38843321

ABSTRACT

Successive cleavages of amyloid precursor protein C-terminal fragment with 99 residues (APP-C99) by γ-secretase result in amyloid-ß (Aß) peptides of varying lengths. Most cleavages have a step size of three residues. To elucidate the underlying mechanism, we determined the atomic structures of human γ-secretase bound individually to APP-C99, Aß49, Aß46, and Aß43. In all cases, the substrate displays the same structural features: a transmembrane α-helix, a three-residue linker, and a ß-strand that forms a hybrid ß-sheet with presenilin 1 (PS1). Proteolytic cleavage occurs just ahead of the substrate ß-strand. Each cleavage is followed by unwinding and translocation of the substrate α-helix by one turn and the formation of a new ß-strand. This mechanism is consistent with existing biochemical data and may explain the cleavages of other substrates by γ-secretase.


Subject(s)
Amyloid Precursor Protein Secretases , Amyloid beta-Peptides , Amyloid beta-Protein Precursor , Presenilin-1 , Humans , Amyloid beta-Peptides/chemistry , Amyloid beta-Protein Precursor/chemistry , Amyloid Precursor Protein Secretases/chemistry , Crystallography, X-Ray , Models, Molecular , Peptide Fragments/metabolism , Peptide Fragments/chemistry , Presenilin-1/chemistry , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Proteolysis , Substrate Specificity
17.
Cardiovasc Diabetol ; 23(1): 201, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867282

ABSTRACT

BACKGROUND: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. METHODS: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. RESULTS: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC. CONCLUSION: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Angiopathies , Diet, Mediterranean , Intra-Abdominal Fat , Prediabetic State , Protective Factors , Risk Reduction Behavior , Humans , Prediabetic State/epidemiology , Prediabetic State/diagnosis , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Male , Female , Middle Aged , Intra-Abdominal Fat/physiopathology , Aged , Risk Factors , Risk Assessment , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/prevention & control , Time Factors , Incidence , Adiposity , United Kingdom/epidemiology , Adult , Diet, Healthy , Exercise , Healthy Lifestyle , Obesity, Abdominal/diagnosis , Obesity, Abdominal/epidemiology , Obesity, Abdominal/physiopathology , Prospective Studies
18.
Elife ; 132024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900147

ABSTRACT

Transport and localization of melanosome at the periphery region of melanocyte are depended on myosin-5a (Myo5a), which associates with melanosome by interacting with its adaptor protein melanophilin (Mlph). Mlph contains four functional regions, including Rab27a-binding domain, Myo5a GTD-binding motif (GTBM), Myo5a exon F-binding domain (EFBD), and actin-binding domain (ABD). The association of Myo5a with Mlph is known to be mediated by two specific interactions: the interaction between the exon-F-encoded region of Myo5a and Mlph-EFBD and that between Myo5a-GTD and Mlph-GTBM. Here, we identify a third interaction between Myo5a and Mlph, that is, the interaction between the exon-G-encoded region of Myo5a and Mlph-ABD. The exon-G/ABD interaction is independent from the exon-F/EFBD interaction and is required for the association of Myo5a with melanosome. Moreover, we demonstrate that Mlph-ABD interacts with either the exon-G or actin filament, but cannot interact with both of them simultaneously. Based on above findings, we propose a new model for the Mlph-mediated Myo5a transportation of melanosomes.


Subject(s)
Adaptor Proteins, Signal Transducing , Melanosomes , Myosin Type V , Protein Binding , Melanosomes/metabolism , Myosin Type V/metabolism , Myosin Type V/genetics , Animals , Mice , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Humans , Myosin Heavy Chains/metabolism , Myosin Heavy Chains/genetics , Melanocytes/metabolism
19.
Environ Sci Pollut Res Int ; 31(30): 42792-42809, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38878248

ABSTRACT

In this work, salicylic acid (SA) was used to induce the self-assembly of octadecyl trimethyl ammonium chloride (OTAC), a cationic surfactant, into three-dimensional wormlike micelle aggregates. These aggregates act as a soft template for hierarchical MgAl hydrotalcite (LDH) to create a multi-level pore structure adsorption material. Scanning electron microscopy characterization showed that the surface of the hierarchical hydrotalcite exhibited a dense layered structure, unlike the monolayer structure of ordinary hydrotalcite. Furthermore, the hierarchical MgAl-LDH possesses a significantly larger specific surface area (113.94 m2/g) and wide pore size distribution ranging more extensively from 2 to 80 nm, which significantly has an impressive adsorption effect on sulfonated lignite (SL), with a maximum adsorption capacity of 192.7 mg/g at pH = 7. Extensive research has been conducted on the adsorption mechanism of hierarchical MgAl-LDH, attributing it to surface adsorption due to the unique multi-level structure of the adsorbent. After two cycles of regeneration experiments, the adsorption capacity of the adsorbent remained at a high level of 179.1 mg/g, demonstrating the excellent renewability of hierarchical MgAl-LDH. Moreover, the hierarchical hydrotalcite showed high adsorption capacity in the adsorption of sulfonated lignite, which was attributed to its larger specific surface area and superior pore structure to expose more active sites.


Subject(s)
Aluminum Hydroxide , Magnesium Hydroxide , Aluminum Hydroxide/chemistry , Magnesium Hydroxide/chemistry , Adsorption
20.
Aging (Albany NY) ; 16(11): 10004-10015, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38862259

ABSTRACT

OBJECTIVE: A neurodevelopmental illness termed as the autism spectrum disorder (ASD) is described by social interaction impairments. Previous studies employing resting-state functional imaging (rs-fMRI) identified both hyperconnectivity and hypoconnectivity patterns in ASD people. However, specific patterns of connectivity within and between networks linked to ASD remain largely unexplored. METHODS: We utilized a meticulously selected subset of high-quality data, comprising 45 individuals diagnosed with ASD and 47 HCs, obtained from the ABIDE dataset. The pre-processed rs-fMRI time series signals were partitioned into ninety regions of interest. We focused on eight intrinsic connectivity networks and further performed intra- and inter-network analysis. Finally, support vector machine was used to discriminate ASD from HC. RESULTS: Through different sparsities, ASD exhibited significantly decreased intra-network connectivity within default mode network and dorsal attention network, increased connectivity between limbic network and subcortical network, and decreased connectivity between default mode network and limbic network. Using the classifier trained on altered intra- and inter-network connectivity, multivariate pattern analyses classified the ASD from HC with 71.74% accuracy, 70.21% specificity and 75.56% sensitivity in 10% sparsity of functional connectivity. CONCLUSIONS: ASD showed characteristic reorganization of the brain networks and this provided new insight into the underlying process of the functional connectome dysfunction in ASD.


Subject(s)
Autism Spectrum Disorder , Brain , Magnetic Resonance Imaging , Humans , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/diagnostic imaging , Male , Female , Adult , Brain/diagnostic imaging , Brain/physiopathology , Young Adult , Support Vector Machine , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Connectome , Adolescent
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