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1.
Cardiovasc Diabetol ; 23(1): 231, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965592

ABSTRACT

BACKGROUND: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. METHODS: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. RESULTS: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. CONCLUSIONS: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.


Subject(s)
Body Mass Index , Cardiovascular Diseases , Cause of Death , Genetic Predisposition to Disease , Multifactorial Inheritance , Obesity , Humans , Male , Middle Aged , Female , Cardiovascular Diseases/mortality , Cardiovascular Diseases/genetics , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Risk Assessment , Prospective Studies , Aged , Obesity/genetics , Obesity/diagnosis , Obesity/mortality , Obesity/epidemiology , United Kingdom/epidemiology , Phenotype , Time Factors , Prognosis , Adult , Obesity, Metabolically Benign/diagnosis , Obesity, Metabolically Benign/mortality , Obesity, Metabolically Benign/genetics , Obesity, Metabolically Benign/epidemiology , Cardiometabolic Risk Factors , Risk Factors , Genetic Risk Score
2.
Opt Lett ; 49(13): 3709-3712, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950248

ABSTRACT

In the past few years, annular structured beams have been extensively studied due to their unique "doughnut" structure and characteristics such as phase and polarization vortices. Especially in the 2 µm wavelength range, they have shown promising applications in fields such as novel laser communication, optical processing, and quantum information processing. In this Letter, we observed basis vector patterns with orthogonality and completeness by finely cavity-mode tailoring with end-mirror space position in a Tm:CaYAlO4 laser. Multiple annular structured beams including azimuthally, linearly, and radially polarized beams (APB, LPB, and RPB) operated at a Q-switched mode-locking (QML) state with a typical output power of ∼18 mW around 1962 nm. Further numerical simulation proved that the multiple annular structured beams are the coherent superposition of different Hermitian Gaussian modes. Using a self-made M-Z interferometer, we have demonstrated that the obtained multiple annular beams have a vortex phase with orbital angular momentum (OAM) of l = ±1. To the best of our knowledge, this is the first observation of vector and scalar annular vortex beams in the 2 µm solid-state laser.

3.
Nature ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961301

ABSTRACT

Pericentric heterochromatin is a critical component of chromosomes marked by histone H3 K9 (H3K9) methylation1-3. However, what recruits H3K9-specific histone methyltransferases to pericentric regions in vertebrates remains unclear4, as does why pericentric regions in different species share the same H3K9 methylation mark despite lacking highly conserved DNA sequences2,5. Here we show that zinc-finger proteins ZNF512 and ZNF512B specifically localize at pericentric regions through direct DNA binding. Notably, both ZNF512 and ZNF512B are sufficient to initiate de novo heterochromatin formation at ectopically targeted repetitive regions and pericentric regions, as they directly recruit SUV39H1 and SUV39H2 (SUV39H) to catalyse H3K9 methylation. SUV39H2 makes a greater contribution to H3K9 trimethylation, whereas SUV39H1 seems to contribute more to silencing, probably owing to its preferential association with HP1 proteins. ZNF512 and ZNF512B from different species can specifically target pericentric regions of other vertebrates, because the atypical long linker residues between the zinc-fingers of ZNF512 and ZNF512B offer flexibility in recognition of non-consecutively organized three-nucleotide triplets targeted by each zinc-finger. This study addresses two long-standing questions: how constitutive heterochromatin is initiated and how seemingly variable pericentric sequences are targeted by the same set of conserved machinery in vertebrates.

4.
J Cereb Blood Flow Metab ; : 271678X241261949, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886876

ABSTRACT

Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery. Numerous evidence suggest that dysregulation of lipid metabolism is associated with cognitive impairment; however, its precise role in the development of POCD is still obscure. In this study, we established a cardiopulmonary bypass (CPB) model in rats and employed the Barnes maze to assess cognitive function, selecting POCD rats for subsequent experimentation. Utilizing mass spectrometry imaging, we detected plenty of lipids accumulates within the hippocampal CA1in the POCD group. Immunofluorescence staining revealed a significant reduction in the fluorescence intensity of calcium-independent phospholipases A2 (iPLA2) in the POCD group compared to the control, while serine palmitoyl transferase (SPT) was markedly increased in the POCD group. Transmission electron microscopy revealed that the number of synapses in hippocampal CA1decreased significantly and postsynaptic density became thinner in POCD group. Furthermore, after reversing the metabolic disorders of iPLA2 and SPT in the rat brain with docosahexaenoic acid and myriocin, the incidence of POCD after CPB was significantly reduced and the disrupted lipid metabolism in the hippocampus was also normalized. These findings may offer a novel perspective for exploring the etiology and prevention strategies of POCD after CPB.

5.
Angew Chem Int Ed Engl ; : e202403671, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38887161

ABSTRACT

Electrochemical carbon dioxide (CO2) reduction reaction (CO2RR) to valuable liquid fuels, such as formic acid/formate (HCOOH/HCOO-) is a promising strategy for carbon neutrality. Enhancing CO-2RR activity while retaining high selectivity is critical for commercialization. To address this, we developed metal-doped bismuth (Bi) nanosheets via a facile hydrolysis method. These doped nanosheets efficiently generated high-purity HCOOH using a porous solid electrolyte (PSE) layer. Among the evaluated metal-doped Bi catalysts, Co-doped Bi demonstrated improved CO2RR performance compared to pristine Bi, achieving ~90% HCOO- selectivity and boosted activity with a low overpotential of ~1.0 V at a current density of 200 mA cm-2. In a solid electrolyte reactor, Co-doped Bi maintained HCOOH Faradaic efficiency of ~72% after a 100-hour operation under a current density of 100 mA cm-2, generating 0.1 M HCOOH at 3.2 V. Density functional theory (DFT) results revealed that Co-doped Bi required a lower applied potential for HCOOH generation from CO2, due to stronger binding energy to the key intermediates OCHO* compared to pure Bi. This study shows that metal doping in Bi nanosheets modifies the chemical composition, element distribution, and morphology, improving CO2RR catalytic activity performance by tuning surface adsorption affinity and reactivity.

6.
Animals (Basel) ; 14(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38929332

ABSTRACT

The intestinal microbiome changes with age, influencing the host's health and immune status. Saccharomyces cerevisiae (S. cerevisiae) positively affects intestinal function in humans and animals, but its effects on gut health and the microbiota profile in aged dogs have not been thoroughly investigated. Twenty aged Labrador Retrievers were divided into two groups: a control group (CON) and a S. cerevisiae group (SC). The experiment lasted for 42 days, with assessments of their intestinal barrier function, inflammatory factors, antioxidant markers, and fecal microbiome composition. The results showed that dietary S. cerevisiae reduced the levels of TNF-α, IL-6, and IL-1ß in the serum (p < 0.05). In the SC group, plasma superoxide dismutase and glutathione peroxidase activities increased, while the level of malondialdehyde significantly decreased (p < 0.05). Additionally, dietary S. cerevisiae lowered the serum zonulin and lipopolysaccharide (LPS) levels (p < 0.05) and inhibited fecal ammonia production (p < 0.05). Furthermore, the microbiota profile showed that dietary S. cerevisiae decreased the abundance of Firmicutes but increased the Chao index, the abundance of Bacteroidetes, and the proportion of Bacteroidetes to Firmicutes (p < 0.05). To conclude, dietary S. cerevisiae can regulate the gut's microbial structure and gut health, which may contribute to the overall health of companion animals as they age.

7.
Int J Mol Sci ; 25(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38928043

ABSTRACT

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189-0.969) and GP17 (OR = 0.709, 95%CI = 0.504-0.995) with growth/differentiation factor 15 (GDF15), GP19 with an advanced glycosylation end-product-specific receptor (RAGE) (OR = 2.142, 95% CI = 1.384-3.316), and GP15 with matrix metalloproteinase 2 (MMP2) (OR = 1.136, 95% CI =1.008-1.282). The reverse MR indicated that genetic liability to RAGE was associated with increased levels of GP17 (OR = 1.125, 95% CI = 1.003-1.261) and GP24 (OR = 1.222, 95% CI = 1.046-1.428), while pulmonary and activation-regulated chemokines (PARC) exhibited causal associations with GP10 (OR = 1.269, 95% CI = 1.048-1.537) and GP15 (OR = 1.297, 95% CI = 1.072-1.570). The findings provided suggested evidence on the bidirectional causality between IgG N-glycans and SASP, which might reveal potential regulatory mechanisms.


Subject(s)
Immunoglobulin G , Mendelian Randomization Analysis , Phenotype , Humans , Glycosylation , Immunoglobulin G/genetics , Immunoglobulin G/metabolism , Polysaccharides/metabolism , Aging/genetics , Aging/metabolism , Polymorphism, Single Nucleotide , Glycoproteins
8.
Chaos ; 34(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38722729

ABSTRACT

This paper investigates dynamical behaviors and controllability of some nonautonomous localized waves based on the Gross-Pitaevskii equation with attractive interatomic interactions. Our approach is a relation constructed between the Gross-Pitaevskii equation and the standard nonlinear Schrödinger equation through a new self-similarity transformation which is to convert the exact solutions of the latter to the former's. Subsequently, one can obtain the nonautonomous breather solutions and higher-order rogue wave solutions of the Gross-Pitaevskii equation. It has been shown that the nonautonomous localized waves can be controlled by the parameters within the self-similarity transformation, rather than relying solely on the nonlinear intensity, spectral parameters, and external potential. The control mechanism can induce an unusual number of loosely bound higher-order rogue waves. The asymptotic analysis of unusual loosely bound rogue waves shows that their essence is energy transfer among rogue waves. Numerical simulations test the dynamical stability of obtained localized wave solutions, which indicate that modifying the parameters in the self-similarity transformation can improve the stability of unstable localized waves and prolong their lifespan. We numerically confirm that the rogue wave controlled by the self-similarity transformation can be reproduced from a chaotic initial background field, hence anticipating the feasibility of its experimental observation, and propose an experimental method for observing these phenomena in Bose-Einstein condensates. The method presented in this paper can help to induce and observe new stable localized waves in some physical systems.

9.
Phytomedicine ; 130: 155693, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38763006

ABSTRACT

BACKGROUND: Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. PURPOSE: We aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). METHODS: Autodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. RESULTS: BA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro. CONCLUSION: BA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.


Subject(s)
Inflammasomes , Liver Diseases, Alcoholic , Mice, Inbred C57BL , Receptors, Cytoplasmic and Nuclear , Animals , Receptors, Cytoplasmic and Nuclear/metabolism , Liver Diseases, Alcoholic/drug therapy , Inflammasomes/metabolism , Inflammasomes/drug effects , Male , Mice , Disease Models, Animal , Liver/drug effects , Liver/pathology , Liver/metabolism , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Ethanol
10.
Orthop Surg ; 16(6): 1407-1417, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38715422

ABSTRACT

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.


Subject(s)
Cervical Vertebrae , Decompression, Surgical , Kyphosis , Spinal Fusion , Humans , Spinal Fusion/methods , Female , Male , Decompression, Surgical/methods , Middle Aged , Kyphosis/surgery , Cervical Vertebrae/surgery , Aged , Retrospective Studies , Spondylosis/surgery , Prognosis
11.
Heliyon ; 10(10): e30977, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813213

ABSTRACT

The trajectory of China's PPP market since 2014, characterized by rapid expansion and a high failure rate, now plunges into a state of limbo and uncertainty. Through a quantitative analysis of failed PPP projects in China from 2014 to 2020, this study investigates the impact of local government institutional quality, private capital business environment, local economic development, and local fiscal affordability on the development and implementation of PPP projects. The findings reveal that larger government size is associated with a higher likelihood of PPP project failure, while a favorable private capital business environment can mitigate the failure rate of local PPP projects. Furthermore, empirical results demonstrate a positive relationship between local fiscal affordability and the success rate of PPP projects. The analysis underscores the significant influence of the institutional environment on the effectiveness of PPP projects and provides policy recommendations for local governments to enhance the business environment and other key factors contributing to the resilience of PPP projects.

12.
Cancer Med ; 13(10): e7284, 2024 May.
Article in English | MEDLINE | ID: mdl-38752442

ABSTRACT

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.


Subject(s)
Hepatitis B virus , Hepatitis B , Humans , Retrospective Studies , Male , Female , Middle Aged , Hepatitis B/complications , Hepatitis B/virology , Hepatitis B/epidemiology , Adult , Aged , Hepatitis B virus/isolation & purification , Young Adult , Prevalence , Lymphoma, Non-Hodgkin/virology , Lymphoma, Non-Hodgkin/epidemiology , Adolescent , Aged, 80 and over , Lymphoma, B-Cell/virology , Lymphoma, B-Cell/epidemiology , Lymphoma, B-Cell/pathology , Lymphoma, B-Cell/mortality , Progression-Free Survival
13.
Environ Sci Technol ; 58(15): 6814-6824, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38581381

ABSTRACT

Identifying persistent, mobile, and toxic (PMT) substances from synthetic chemicals is critical for chemical management and ecological risk assessment. Inspired by the triazine analogues (e.g., atrazine and melamine) in the original European Union's list of PMT substances, the occurrence and compositions of alkylamine triazines (AATs) in the estuarine sediments of main rivers along the eastern coast of China were comprehensively explored by an integrated strategy of target, suspect, and nontarget screening analysis. A total of 44 AATs were identified, of which 23 were confirmed by comparison with authentic standards. Among the remaining tentatively identified analogues, 18 were emerging pollutants not previously reported in the environment. Tri- and di-AATs were the dominant analogues, and varied geographic distributions of AATs were apparent in the investigated regions. Toxic unit calculations indicated that there were acute and chronic risks to algae from AATs on a large geographical scale, with the antifouling biocide cybutryne as a key driver. The assessment of physicochemical properties further revealed that more than half of the AATs could be categorized as potential PMT and very persistent and very mobile substances at the screening level. These results highlight that AATs are a class of PMT substances posing high ecological impacts on the aquatic environment and therefore require more attention.


Subject(s)
Atrazine , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Rivers/chemistry , Triazines/analysis , Atrazine/analysis , China , Environmental Monitoring
14.
J Orthop Translat ; 45: 256-265, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38601199

ABSTRACT

Background: From 1990 to 2019, low back pain (LBP) was the leading cause of years lived with disability (YLDs) in China. However, the change patterns of LBP and its risk factors in China remain unclear. Methods: Data from the Global Burden of Disease Study 2019 were used. We used the join-point regression model and age-period-cohort analysis to evaluate the time trends of attributable risk factors on the burden of LBP. Results: In 2019, the risk factors included in this analysis accounted for 4.36 million YLDs of LBP, representing 42.2% of all YLDs of LBP in China, with 2.86 million due to occupational ergonomic factors, 1.74 million due to smoking, and 0.46 million due to high body mass index (BMI). The age-standardized YLD rates of LBP showed downward trends during 1990-2019, while there was a faster decline between 1990 and 1994. The curves of local drifts, which reflected the average annual percentage change across age groups, showed an increasing trend with age for high BMI and smoking, and a downward trend for occupational ergonomic factors. The YLD rates for LBP increased dramatically with age for high BMI, while it reached a peak at 40-60 years old for occupational ergonomic factors, and 65-80 years old for smoking. The period and cohort rate ratios of LBP YLD decreased in the past 3 decades for occupational ergonomic factors and smoking, while increased for high BMI. Conclusions: Our results provided strong evidence that there were diverse changing patterns for different risk factors, highlighting the need for risk-specific strategies. The translational potential of this article: China has the largest senior population and the fastest aging population in the world. Given that LBP typically occurs in the senior population, there would be an increasing LBP burden on China's health system. This suggests that effective strategies for LBP prevention should be strictly implemented in China, particularly in the senior population, which is of crucial translational potential.

15.
Aging Cell ; : e14163, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566438

ABSTRACT

The transition from ordered to noisy is a significant epigenetic signature of aging and age-related disease. As a paradigm of healthy human aging and longevity, long-lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high-resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs. Importantly, we identified 38,923 genomic regions with LLI-specific lower ME (LLI-specific lower entropy regions, for short, LLI-specific LERs). These regions were overrepresented in promoters, which likely function in transcriptional noise suppression. Genes associated with LLI-specific LERs have a considerable impact on SNP-based heritability of some aging-related disorders (e.g., asthma and stroke). Furthermore, neutrophil was identified as the primary cell type sustaining LLI-specific LERs. Our results highlight the stability of epigenetic order in promoters of genes involved with aging and age-related disorders within LLI epigenomes. This unique epigenetic feature reveals a previously unknown role of epigenetic order maintenance in specific genomic regions of LLIs, which helps open a new avenue on the epigenetic regulation mechanism in human healthy aging and longevity.

16.
Angew Chem Int Ed Engl ; 63(25): e202402546, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38616162

ABSTRACT

Phenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6'-OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one-pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6-fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5-100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof-of-concept for cell-free enzymatic construction of diverse natural products.


Subject(s)
Glycosides , Glycosyltransferases , Protein Engineering , Glycosides/chemistry , Glycosides/biosynthesis , Glycosides/metabolism , Glycosyltransferases/metabolism , Glycosyltransferases/chemistry , Catechol Oxidase/metabolism , Catechol Oxidase/chemistry
17.
Sci Total Environ ; 924: 171700, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38490408

ABSTRACT

The speciation, bioaccumulation, and toxicity of the newly deposited atmospheric heavy metals in the soil-earthworm (Eisenia fetida) system were investigated by a fully factorial atmospheric exposure experiment using soils exposed to 0.8-year and 1.8-year atmospheric depositions. The results shown that the newly deposited metals (Cu, Cd, and Pb) primarily accumulated in the topsoil (0-6 cm) and were present as the highly bioavailable speciation. They can migrate further to increase the concentrations of Cu, Cd, and Pb in soil solution of the deeper layer (at 10 cm) by 12 %-436 %. Earthworms tended to preferentially accumulate the newly deposited metals, which contributed 10 %-61 % of Cu, Cd, and Pb in earthworms. Further, for the unpolluted and moderately polluted soils, the newly deposited metals induced the significant oxidative stress in earthworms, resulting in significant increases in antioxidant enzyme activities (SOD, CAT, and GSH-Px). No significant differences were observed in the levels of heavy metals in soil solutions, bioaccumulation, and enzyme activities in earthworms exposed to 0.8-year and 1.8-year depositions, indicating the bioavailability of atmospheric metals deposited into soils was rapidly decreased with time. This study highlights the high bioaccumulation and toxicity of heavy metals to earthworm from the new atmospheric deposition during the earthworm growing period.


Subject(s)
Metals, Heavy , Oligochaeta , Soil Pollutants , Animals , Copper/toxicity , Copper/analysis , Cadmium , Soil , Bioaccumulation , Lead , Soil Pollutants/toxicity , Soil Pollutants/analysis , Metals, Heavy/toxicity , Metals, Heavy/analysis
18.
RSC Adv ; 14(11): 7564-7570, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38440269

ABSTRACT

The controllable preparation of spherical micro/nano particles of various materials has been achieved via the technology of the laser synthesis and processing of colloids (LSPC) recently. However, there is limited in situ research on the evolution processes of nanoparticles in photothermal transient environments, such as solid-state crystal transformations and changes of state, which limits the understanding and application of LSPC. Photoacoustic (PA) signals are sensitive to the optical, thermal and elastic properties of the medium, and can be used to measure the thermal and spectroscopic properties of matter. In this paper, the PA signals generated by the interaction of the laser with the surrounding liquid medium (ethanol, water, glycerin, etc.) and nanoparticles (Ag, TiO2, CeO2, ZrO2, etc.) are studied when the tunable LSPC technique provides different photothermal conditions (such as thermal expansion, solid crystal transformation and evaporation). It is found that semiconductors with different bandgaps, as light absorbers, have the ability to selectively absorb laser beams of different wavelengths. By changing the wavelength, the PA intensity can be adjusted accordingly. In addition, based on the fast laser heating and tunable fluence characteristics of non-focused laser beams in LSPC technology, transient processes such as material phase transitions and changes of state can be excited separately by adjusting the laser fluence. Taking titanium dioxide as an example, the PA signals generated by laser selective excitation of A-R (anatase into rutile) phase transitions and rutile vaporization can be detected.

19.
Front Plant Sci ; 15: 1305358, 2024.
Article in English | MEDLINE | ID: mdl-38529067

ABSTRACT

Introduction: Early detection of leaf diseases is necessary to control the spread of plant diseases, and one of the important steps is the segmentation of leaf and disease images. The uneven light and leaf overlap in complex situations make segmentation of leaves and diseases quite difficult. Moreover, the significant differences in ratios of leaf and disease pixels results in a challenge in identifying diseases. Methods: To solve the above issues, the residual attention mechanism combined with atrous spatial pyramid pooling and weight compression loss of UNet is proposed, which is named RAAWC-UNet. Firstly, weights compression loss is a method that introduces a modulation factor in front of the cross-entropy loss, aiming at solving the problem of the imbalance between foreground and background pixels. Secondly, the residual network and the convolutional block attention module are combined to form Res_CBAM. It can accurately localize pixels at the edge of the disease and alleviate the vanishing of gradient and semantic information from downsampling. Finally, in the last layer of downsampling, the atrous spatial pyramid pooling is used instead of two convolutions to solve the problem of insufficient spatial context information. Results: The experimental results show that the proposed RAAWC-UNet increases the intersection over union in leaf and disease segmentation by 1.91% and 5.61%, and the pixel accuracy of disease by 4.65% compared with UNet. Discussion: The effectiveness of the proposed method was further verified by the better results in comparison with deep learning methods with similar network architectures.

20.
Molecules ; 29(6)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38542917

ABSTRACT

BACKGROUND: Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis. METHODS: We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors. RESULTS: Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (ß 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (ß -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (ß -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (ß 0.140, 95% CI 0.020 to 0.260, p = 0.023). CONCLUSIONS: In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Glycosylation , Immunoglobulin G/genetics , Aging/genetics
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