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1.
Stem Cell Res ; 81: 103570, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39368271

ABSTRACT

We obtained Peripheral blood mononuclear cells (PBMCs) from a peripheral blood sample of a 19-year-old male schizophrenia patient and successfully established induced pluripotent stem cell (iPSC) line using non-integrated reprogramming technology. This cell line possesses the correct karyotype, shape of an embryonic stem cell, the ability to express particular pluripotency markers, and the capacity to differentiate into three germ layers in vitro. This cell line will serve as an in vitro model for upcoming studies on the etiology of schizophrenia and the creation of novel treatment.

2.
Age Ageing ; 53(10)2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39373574

ABSTRACT

BACKGROUND: Continuity of care is essential to older patients' health outcomes, especially for those with complex needs. It is a key function of primary healthcare. Despite China's policy efforts to promote continuity of care and an integrated healthcare system, primary healthcare centres (PHCs) are generally very underused. OBJECTIVES: To explore the experience and perception of continuity of care in older cancer patients, and to examine how PHCs play a role in the continuity of care within the healthcare system in China. METHODS: A qualitative study using semi-structured interviews was conducted in two tertiary hospitals in Nantong city, Jiangsu province, China. A combination of deductive and inductive analysis was conducted thematically. RESULTS: Interviews with 29 patients highlighted three key themes: no guidance for patients in connecting with different levels of doctors, unmet patients' needs under specialist-led follow-up care, and poor coordination and communication across healthcare levels. This study clearly illustrated patients' lack of personal awareness and experience of care continuity, a key issue despite China's drive for an integrated healthcare system. CONCLUSION: The need for continuity of care at each stage of cancer care is largely unmeasured in the current healthcare system for older patients. PHCs offer benefits which include convenience, less burdened doctors with more time, and lower out-of-pocket payment compared to tertiary hospitals, especially for patients with long-term healthcare needs. However, addressing barriers such as the absence of integrated medical records and unclear roles of PHCs are needed to improve the crucial role of PHCs in continuity of care.


Subject(s)
Continuity of Patient Care , Delivery of Health Care, Integrated , Health Care Reform , Neoplasms , Qualitative Research , Humans , Continuity of Patient Care/organization & administration , China , Male , Aged , Female , Neoplasms/therapy , Delivery of Health Care, Integrated/organization & administration , Aged, 80 and over , Primary Health Care/organization & administration , Interviews as Topic , Middle Aged , Age Factors , Health Knowledge, Attitudes, Practice
3.
NPJ Precis Oncol ; 8(1): 226, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39369126

ABSTRACT

The pathophysiology of immune checkpoint inhibitor-related pneumonitis remains incompletely understood. We conducted single-cell and T-cell receptor transcriptomic sequencing on the bronchoalveolar lavage fluid from five patients with grade ≥2 immune checkpoint inhibitor-related pneumonitis. Our analyses revealed a prominent enrichment of T cells in the bronchoalveolar lavage fluid of patients with immune checkpoint inhibitor-related pneumonitis. Within the CD4 + T cell subset, Tfh-like T cells were highly enriched and exhibited signatures associated with inflammation and clonal expansion. Regulatory T cells were also enriched and displayed enhanced inhibitory functions. Within the CD8 + T-cell subset, effector memory/tissue-resident memory T cells with an elevated cytotoxic phenotype were highly infiltrated. Among myeloid cells, alveolar macrophages were depleted, while pro-inflammatory intermediate monocytes were elevated. Dendritic cells demonstrated enhanced antigen presentation capabilities. Cytokines CXCR4, CXCL13, TNF-α, IFN-α, IFN-γ, and TWEAK were elevated. Through a comprehensive single-cell analysis, we depicted the landscape of immune checkpoint inhibitor-related pneumonitis.

4.
Brain Imaging Behav ; 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39373958

ABSTRACT

Changes in cortical excitability after stroke are closely associated with motor function recovery. This study aimed to clarify the motor network reorganization mechanisms corresponding to the different clinical outcomes of upper limb motor impairment in patients with subacute stroke. Motor function was assessed before rehabilitation (pre), after rehabilitation (post), and at the 1-year follow-up (follow-up) using the Fugl-Meyer assessment upper extremity scale. Further, resting-state functional magnetic resonance imaging (fMRI) data were collected in both pre- and post-conditions. Twenty patients with stroke were categorized into good and poor outcome groups based on motor impairments at the 1-year follow-up. Functional connections between motor-related regions of interest and the rest of the brain were subsequently calculated. Finally, the correlation between motor network reorganization and behavioral improvement at the 1-year follow-up was analyzed. The good outcome group exhibited a positive precondition motor function and continuous improvement, whereas the poor outcome group showed a weak precondition motor function and insignificant improvement. Contralesional hemisphere-related connections were found to be higher in the good outcome group pre-conditioning, with both groups showing minimal change post-conditioning, while no relationship with motor impairment was found. Long interhemispheric connections were decreased and increased in the good and poor outcome groups respectively, and were negatively correlated with motor impairment. Different motor network reorganizations during the subacute phase can influence the varying motor outcomes in the affected upper limb after stroke. These findings may serve as the theoretical basis for future neuromodulatory research.

6.
Front Psychol ; 15: 1381009, 2024.
Article in English | MEDLINE | ID: mdl-39309146

ABSTRACT

Introduction: Tai Chi Chuan (TCC) is a traditional Chinese mind-body exercise widely adopted in Chinese communities and colleges. However, the mindful essence of TCC is rarely emphasized during popularization. This makes it difficult for beginners to benefit from it. The present study aimed to examine the effects of a Mindfulness-enhanced Tai Chi Chuan (MTCC) intervention, which enhances mindfulness components embedded within TCC, on mental and physical health among beginners. Methods: A randomized controlled trial was conducted with 119 healthy college students new to Tai Chi Chuan training. Participants were assigned to either the MTCC group or the TCC group. Both interventions consisted of 10 weekly 90-min training sessions, with the MTCC group emphasizing and enhancing mindfulness components. Outcome measures included mindfulness, depression, anxiety, stress, and physical fitness, assessed at baseline and post-intervention. Results: The results showed that the MTCC group had significantly greater improvements than the TCC group in mindfulness, anxiety, stress, and health-and skill-related physical fitness. There were no significant differences between the two groups in depression. Conclusion: The findings suggest that compared to TCC, MTCC can effectively promote individuals' physical fitness and provide additional benefits to mental well-being. MTCC can be recommended as an accessible and beneficial intervention for beginners to improve mental health and strengthen their bodies. Clinical review registration: https://www.chictr.org.cn/, identifier ChiCTR2200058175.

7.
Colloids Surf B Biointerfaces ; 244: 114179, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39217727

ABSTRACT

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and aggressive, but therapies based on single-targeted nanoparticles frequently address these tumors as a single illness. To achieve more efficient drug transport, it is crucial to develop nanodrug-carrying systems that simultaneously target two or more cancer biomarkers. In addition, combining chemotherapy with near-infrared (NIR) light-mediated thermotherapy allows the thermal ablation of local malignancies via photothermal therapy (PTT), and triggers drug release to improve chemosensitivity. Thus, a novel dual-targeted nano-loading system, DOX@GO-HA-HN-1 (GHHD), was created for synergistic chemotherapy and PTT by the co-modification of carboxylated graphene oxide (GO) with hyaluronic acid (HA) and HN-1 peptide and loading with the anticancer drug doxorubicin (DOX). Targeted delivery using GHHD was shown to be superior to single-targeted nanoparticle delivery. NIR radiation will encourage the absorption of GHHD by tumor cells and cause the site-specific release of DOX in conjunction with the acidic microenvironment of the tumor. In addition, chemo-photothermal combination therapy for cancer treatment was realized by causing cell apoptosis under the irradiation of 808-nm laser. In summary, the application of GHHD to chemotherapy combined with photothermal therapy for OSCC is shown to have important potential as a means of combatting the low accumulation of single chemotherapeutic agents in tumors and drug resistance generated by single therapeutic means, enhancing therapeutic efficacy.


Subject(s)
Carcinoma, Squamous Cell , Doxorubicin , Drug Delivery Systems , Graphite , Infrared Rays , Mouth Neoplasms , Doxorubicin/pharmacology , Doxorubicin/chemistry , Humans , Mouth Neoplasms/drug therapy , Mouth Neoplasms/pathology , Mouth Neoplasms/therapy , Graphite/chemistry , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Hydrogen-Ion Concentration , Drug Carriers/chemistry , Nanoparticles/chemistry , Drug Liberation , Animals , Apoptosis/drug effects , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/administration & dosage , Cell Proliferation/drug effects , Photothermal Therapy , Cell Line, Tumor , Drug Screening Assays, Antitumor , Hyaluronic Acid/chemistry , Cell Survival/drug effects , Mice , Particle Size , Surface Properties
8.
Signal Transduct Target Ther ; 9(1): 256, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39343927

ABSTRACT

Regular physical activity is widely recognized for reducing the risk of various disorders, with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues. However, many individuals, particularly the elderly and those with clinical conditions, are unable to engage in physical exercise, necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules. Histone acetylation and deacetylation significantly influence exercise-induced gene expression, suggesting that targeting histone deacetylases (HDACs) could mimic some exercise responses. In this study, we explored the effects of the HDAC inhibitor Trichostatin A (TSA) on human skeletal muscle myoblasts (HSMMs). Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles (EVs) enriched with miR-873-3p. These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs) by targeting H2 calponin (CNN2). In vivo, systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass. Moreover, TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs, suggesting that HDAC inhibition can replicate exercise-induced bone health benefits. These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis, particularly for individuals unable to exercise. Given the FDA-approved status of various HDAC inhibitors, this approach holds significant promise for rapid clinical translation in osteoporosis treatment.


Subject(s)
Extracellular Vesicles , Histone Deacetylase Inhibitors , Hydroxamic Acids , MicroRNAs , Osteogenesis , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism , Histone Deacetylase Inhibitors/pharmacology , Mice , MicroRNAs/genetics , Humans , Animals , Osteogenesis/drug effects , Osteogenesis/genetics , Hydroxamic Acids/pharmacology , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Cell Differentiation/drug effects , Cell Differentiation/genetics , Osteoporosis/genetics , Osteoporosis/pathology , Osteoporosis/drug therapy , Osteoporosis/metabolism
9.
Cell Rep Med ; 5(9): 101709, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39226895

ABSTRACT

Cryptorchidism, commonly known as undescended testis, affects 1%-9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor ß1 (TGF-ß1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism.


Subject(s)
Cryptorchidism , Gene Expression Profiling , Single-Cell Analysis , Spermatogenesis , Transcriptome , Cryptorchidism/genetics , Cryptorchidism/pathology , Cryptorchidism/metabolism , Male , Humans , Single-Cell Analysis/methods , Spermatogenesis/genetics , Transcriptome/genetics , Testis/metabolism , Testis/pathology , Mast Cells/metabolism , Mast Cells/pathology , Adult , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Infertility, Male/genetics , Infertility, Male/pathology , Fibrosis , Spermatogonia/metabolism , Spermatogonia/pathology
10.
Sci Prog ; 107(3): 368504241280872, 2024.
Article in English | MEDLINE | ID: mdl-39328082

ABSTRACT

Accurately measuring the mechanical properties of high-strength stainless steels is of great significance for ensuring structural safety, predicting long-term performance and optimizing design. However, the standardized tensile test specimens used to obtain strength properties must be fabricated from bulk materials from an in-service structure or component, result in the loss of structural integrity or a reduction in remaining service life. Small punch tests require only miniscule material samples and are widely used to estimate in-service component material characteristics. This study performed small punch tests on three high-strength stainless steels-X17CrNi15-2, 15-5PH, and PH13-8Mo-to obtain the correlations between the small punch tests and the uniaxial tensile test results for each material. The estimated yield stresses obtained from the small punch tests were distributed within a factor of 1.5 on both sides of the unity line when compared with those obtained from the uniaxial tensile tests; the ultimate strength values estimated from the small punch tests correlated quite well with those obtained from the uniaxial tensile tests. An iterative finite element analysis was subsequently established to simulate the small punch tests and thereby obtain the coefficients for a Ludwik power law correlation representing the true stress-strain properties. The finite element predicted force-deflection curves agreed well with the small punch test results, which were also compared with the predictions obtained from empirical equations proposed in previous studies. Finally, the fracture mechanisms of the small punch test specimens were characterized through scanning electron microscopy, indicating that the dimple fracture mechanism dominated the failure mode. The results of this study are expected to inform the application of small punch test to evaluate in-service high-strength stainless steel materials.

11.
Endocrine ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39317856

ABSTRACT

PURPOSE: To explore the clinical characteristics, treatment, and prognosis of growth hormone-secreting pituitary adenoma (GHPA) patients with pediatric-onset, so as to facilitate clinical management. METHODS: A retrospective cohort study was carried out between 102 pediatric-onset GHPA patients admitted to our hospital from January 2013 to June 2022 and 204 adult-onset GHPA patients who were randomly matched. RESULTS: GHPA with pediatric-onset was predominantly male, associated with higher proportion of genetic syndromes, longer course, and delayed diagnosis. Clinical symptoms of visual field defects and menstrual abnormality were more common. The pediatric-onset group exhibited higher growth hormone (GH) nadir during oral glucose tolerance test (OGTT), higher rates of hyperprolactinemia, larger maximum diameter of adenoma, and higher rates of optic chiasm compression, suprasellar invasion, and pituitary apoplexy. Hypertension, diabetes, and obstructive sleep apnea-hypopnea syndrome (OSAHS) were more common in the adult-onset group. Echocardiography results were similar between the two groups. The pediatric-onset group owned significantly higher treatment scores and proportions of multimodal therapy modality, more surgical complications, and a higher proportion of ki67 ≥ 3%. There was no significant difference in the final cure rate, but male patients with adult-onset had a worse prognosis. The recurrence rate was also similar between two groups. Hypopituitarism was more prevalent in the pediatric-onset group, while the adult-onset group had a higher incidence of other tumors. CONCLUSION: Pediatric-onset GHPA patients exhibit distinct clinical characteristics compared to adult-onset patients. Multimodal therapy modalities could help to achieve a cure rate comparable to that of adult-onset patients.

12.
J Ethnobiol Ethnomed ; 20(1): 92, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39334188

ABSTRACT

BACKGROUND: The famous Tang Dynasty monk Yi Jing travelled to ancient India in 671 AD, visited more than 30 regions and returned to China in 695 AD. He wrote Nanhai Jigui Neifa Zhuan, which he completed in 691 AD. It describes the basic rules, namely 'Inner Dharma' (Neifa,) that Buddhist sites and monks should follow in their daily lives. Additionally, the author provided an overview of ancient Indian Buddhist medicine, covering aetiology, diagnosis, medication, acupuncture, health preservation and other aspects, which exhibited distinct characteristics. METHODS: This article first delves into the original text of Nanhai Jigui Neifa Zhuan by reading it thoroughly and extracts core chapters related to hygiene, medicine and health care. Later, the extracted information is meticulously classified and organised. Lastly, through a systematic literature review, keywords search, data screening and comparative analysis, an in-depth and comprehensive exploration and analysis of Nanhai Jigui Neifa Zhuan is conducted within the domains of hygiene, medicine and health care. RESULTS: Nanhai Jigui Neifa Zhuan emphasizes the importance of personal hygiene for ancient Indian monks and introduces the basic theories of ancient Indian medicine. It compares ancient Indian and Chinese medicinal materials, highlighting their respective roles in treating different diseases. Furthermore, it briefly discusses the storage and processing of ancient Indian medicinal materials, poisoning and toxicology, and ancient Indian health preservation ideologies. CONCLUSION: A comprehensive and in-depth study of traditional ancient Indian medicine, including Buddhist medicine and Ayurveda, and its application in the religious environment and communities of the Tang Dynasty (618-907 AD) aids in understanding the treatment methods and health practices of ancient Indian medicine. Additionally, it facilitates a deeper understanding of the similarities, differences and exchange between Chinese and Indian medicine, thereby opening up new horizons for future research.


Subject(s)
Hygiene , India , Humans , History, Ancient , Hygiene/history , Buddhism/history , Medicine, Ayurvedic/history , Delivery of Health Care/history , Knowledge , China
13.
Nutr J ; 23(1): 112, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39342289

ABSTRACT

BACKGROUND: Healthy dietary patterns have been negatively associated with methylation-based measures of biological age, yet previous investigations have been unable to establish the relationship between them and biological aging assessed through blood chemistry-based clinical biomarkers. We sought to assess the associations of 4 dietary metrics with 4 measures of biological age. METHODS: Among 16,666 participants in NHANES 1999-2018, 4 dietary metrics [Dietary inflammatory index (DII), Dietary approaches to stop hypertension index (DASH), Alternate mediterranean diet score (aMED), and Healthy eating index-2015 (HEI-2015)] were calculated through the 'dietaryindex' R package. Twelve blood chemistry parameters were utilized to compute 4 indicators of biological age [homeostatic dysregulation (HD), allostatic load (AL), Klemera-Doubal method (KDM), and phenotypic age (PA)]. Binomial logistic regression models and restricted cubic spline (RCS) regression were employed to evaluate the associations. RESULTS: All 4 dietary metrics were significantly associated with biological age acceleration or deceleration. In comparison to the lowest DII, the odds ratios (ORs) for accelerated HD, AL, KDM, and PA were 1.25 (1.08,1.45), 1.29 (1.11,1.50), 1.34 (1.08,1.65), and 1.61 (1.39,1.87) for the highest. The multivariable-adjusted ORs of the highest quartile of DASH, aMED, and HEI-2015 were 0.85 (0.73,0.97), 0.88 (0.74,1.04), and 0.84 (0.74,0.96) for HD, 0.64 (0.54,0.75), 0.61 (0.52,0.72), and 0.70 (0.59,0.82) for AL, 0.68 (0.54,0.85), 0.62 (0.50,0.76), and 0.71 (0.58,0.87) for KDM, and 0.50 (0.42,0.59), 0.64 (0.54,0.76), and 0.51 (0.44,0.58) for PA when compared with the lowest level. The findings were validated by the best-fitting dose-response curves for the associations. Among participants consuming dietary supplements (Pinteraction < 0.05), the positive effects of a healthy dietary pattern on biological aging were more pronounced. Systemic immune inflammation index (SII) and atherogenic index of plasma (AIP) were identified as being involved in and mediating the associations. CONCLUSIONS: Biological aging assessed through blood chemistry-based clinical biomarkers is negatively associated with diet quality. The anti-aging benefits of improving the diet may be due to its ability to reduce inflammation and lower blood lipids.


Subject(s)
Aging , Diet, Healthy , Nutrition Surveys , Humans , Male , Female , Diet, Healthy/methods , Diet, Healthy/statistics & numerical data , Nutrition Surveys/methods , Nutrition Surveys/statistics & numerical data , Aging/physiology , Middle Aged , Adult , Aged , Biomarkers/blood , Dietary Approaches To Stop Hypertension/methods , Dietary Approaches To Stop Hypertension/statistics & numerical data , United States
14.
Adv Sci (Weinh) ; : e2403222, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316383

ABSTRACT

Fine particulate matter (PM2.5) is suggested to pose a severe risk to the kidneys by inducing functional degradation and chronic kidney diseases (CKD). This study aims to explore the nephrotoxicity of PM2.5 exposure and the underlying mechanism. Herein, based on the UK Biobank, it is found that per interquartile range (IQR) increase in PM2.5 is associated with a 6% (95% CI: 1%-11%), 7% (95% CI: 3%-11%), 9% (95% CI: 4%-13%), 11% (95% CI: 9%-13%), and 10% (95% CI: 8%-12%) increase in the risk of nephritis, hydronephrosis, kidney stone, acute renal failure, and CKD, respectively. In experimental study, noticeable kidney injury, which is the initiation of kidney diseases, is observed with PM2.5 exposure in C57BL/6N mice (n = 8), accompanied with oxidative stress, autophagy and pyroptosis. In vitro, HK-2 cells with PM2.5-stimulation exhibit tubulopathy, increased reactive oxygen species (ROS) generation and activated pyroptosis and autophagy. All changes are abolished by ROS scavenger of N-acetyl-L-cysteine (NAC) both in vivo and in vitro. In conclusion, the study provides evidence showing that PM2.5 exposure is associated with 5 kinds of kidney diseases by directly inducing nephrotoxicity, in which ROS may be the potential target by triggering autophagy and pyroptosis.

15.
Biomed Pharmacother ; 180: 117494, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39321509

ABSTRACT

Cardiovascular disease (CVD) remains the leading cause of death worldwide, with myocardial infarction (MI) being the primary contributor to mortality and disability associated with CVD. Reperfusion therapies are widely recognized as effective strategies for treating MI. However, while intended to restore blood flow, the reperfusion processes paradoxically initiate a series of pathophysiological events that worsen myocardial injury, resulting in ischemia-reperfusion (I/R) injury. Therefore, there is a pressing need for new treatment strategies to reduce the size of MI and enhance cardiac function post-infarction. Macrophages are crucial for maintaining homeostasis and mitigating undesirable remodeling following MI. Extensive research has established a strong link between cellular metabolism and macrophage function. In the context of MI, macrophages undergo adaptive metabolic reprogramming to mount an immune response. Moreover, mitochondrial metabolism in macrophages is evident, leading to significant changes in their metabolism. Therefore, we need to delve deeper into summarizing and understanding the relationship and role between mitochondrial metabolism and macrophage phenotype, and summarize existing treatment methods. In this review, we explore the role of mitochondria in shaping the macrophage phenotype and function. Additionally, we summarize current therapeutic strategies aimed at modulating mitochondrial metabolism of macrophages, which may offer new insights treating of MI.

16.
Nature ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39322678

ABSTRACT

L-lactate modifies proteins through lactylation1, but how this process occurs is unclear. Here we identify the alanyl-tRNA synthetases AARS1 and AARS2 (AARS1/2) as intracellular L-lactate sensors required for L-lactate to stimulate the lysine lactylome in cells. AARS1/2 and the evolutionarily conserved Escherichia coli orthologue AlaRS bind to L-lactate with micromolar affinity and they directly catalyse L-lactate for ATP-dependent lactylation on the lysine acceptor end. In response to L-lactate, AARS2 associates with cyclic GMP-AMP synthase (cGAS) and mediates its lactylation and inactivation in cells and in mice. By establishing a genetic code expansion orthogonal system for lactyl-lysine incorporation, we demonstrate that the presence of a lactyl moiety at a specific cGAS amino-terminal site abolishes cGAS liquid-like phase separation and DNA sensing in vitro and in vivo. A lactyl mimetic knock-in inhibits cGAS, whereas a lactyl-resistant knock-in protects mice against innate immune evasion induced through high levels of L-lactate. MCT1 blockade inhibits cGAS lactylation in stressed mice and restores innate immune surveillance, which in turn antagonizes viral replication. Thus, AARS1/2 are conserved intracellular L-lactate sensors and have an essential role as lactyltransferases. Moreover, a chemical reaction process of lactylation targets and inactivates cGAS.

17.
J Exp Bot ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39324623

ABSTRACT

Heat stress (HS) adversely impacts plant growth, development and grain yield. Heat shock factors (Hsf), especially HsfA2 subclass, play a pivotal role in the transcriptional regulation of genes in response to HS. In this study, the coding sequence of maize ZmHsf17 was cloned. ZmHsf17 contains conserved domains: DNA binding, oligomerization and transcriptional activation. The protein was nuclear localized and had transcription activation activity. Yeast two hybrid and split luciferase complementary assays confirmed the interaction of ZmHsf17 with members of the maize HsfA2 subclass. Overexpression of ZmHsf17 in maize significantly increased chlorophyll content and net photosynthesis rate of maize leaves, and enhanced the stability of cellular membranes. Through integrative analysis of ChIP-seq and RNA-seq datasets, ZmPAH1, encoding phosphatidic acid phosphohydrolase of lipid metabolic pathways, was identified as a target gene of ZmHsf17. The promoter fragment of ZmPAH1 was bound by ZmHsf17 in protein-DNA interaction experiments in vivo and in vitro. Lipidomic data also indicates that the overexpression of ZmHsf17 increased levels of some critical membrane lipid components of maize leaves under HS. This research provides new insights into the role of the ZmHsf17-ZmPAH1 module in regulating thermotolerance in maize.

18.
Nanoscale ; 16(37): 17276-17299, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39240060

ABSTRACT

Tin-lead mixed perovskite solar cells (TLMPSCs), with the advantage of approaching the Shockley-Queisser (S-Q) limit for photovoltaic applications, have been rapidly developed and achieved a power conversion efficiency (PCE) of 23.7%. Although the low toxicity of TLMPSCs is conducive to sustainable development, the oxidation of Sn2+ could destroy the perovskite structure easily. Thus, most researchers are devoted to improving the photoelectric performance and stability through additive engineering, interface engineering, device structure optimization, solvent engineering, etc. However, TLMPs with different A-sites and X-sites in the ABX3 model and an optimal ratio of Sn : Pb still need to be investigated; this is the basis of mechanistic analysis. In this paper, we introduce TLMPSCs with different A-sites, X-sites, and Sn-Pb ratios. The mechanism and properties of the cations are analyzed based on the performance of TLMPSCs. Finally, a series of prospects for optimizing ABX3 are put forward, with the hope of attracting the attention and interest of researchers.

20.
J Environ Manage ; 370: 122425, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39244936

ABSTRACT

Municipal solid waste (MSW) is a major anthropogenic contributor to climate change due to the substantial quantities of greenhouse gas (GHG) emitted by landfills and incineration. Circular waste management has shown promise in reducing GHG emissions; however, it is still in its early stages and requires further optimization. In this study, support vector machine models were developed to determine the compositional dynamics of MSW, which were then integrated to examine the interactions among composition, disposal routes, and GHG emissions. The results from analyzing large-scale transitions from traditional to circular waste management practices showed that GHG mitigation potential will be significantly enhanced as the coverage of circular waste management increases from 35% in 2025 to 100% in 2035 in China. However, these reductions will eventually decrease as waste quantities decline in response to population shrinkage. The results reveal both the GHG mitigation potential and limitations of the circular waste management mode, assisting policymakers and researchers in maximizing its mitigation potential.

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