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1.
Scand Stat Theory Appl ; 51(2): 672-696, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-39101047

RÉSUMÉ

This article proposes a distance-based framework incentivized by the paradigm shift towards feature aggregation for high-dimensional data, which does not rely on the sparse-feature assumption or the permutation-based inference. Focusing on distance-based outcomes that preserve information without truncating any features, a class of semiparametric regression has been developed, which encapsulates multiple sources of high-dimensional variables using pairwise outcomes of between-subject attributes. Further, we propose a strategy to address the interlocking correlations among pairs via the U-statistics-based estimating equations (UGEE), which correspond to their unique efficient influence function (EIF). Hence, the resulting semiparametric estimators are robust to distributional misspecification while enjoying root-n consistency and asymptotic optimality to facilitate inference. In essence, the proposed approach not only circumvents information loss due to feature selection but also improves the model's interpretability and computational feasibility. Simulation studies and applications to the human microbiome and wearables data are provided, where the feature dimensions are tens of thousands.

2.
Environ Pollut ; : 124673, 2024 Aug 03.
Article de Anglais | MEDLINE | ID: mdl-39103040

RÉSUMÉ

Numerous studies have explored the health impacts of individual metal exposures, yet the effects of metal mixtures on human endogenous metabolism remain largely unexplored. We aimed to assess the serum metabolic signatures of people exposure to metal mixtures. Serum and urine samples were collected from 186 workers at a steel factory in Anhui, China, in September 2019. Inductively coupled plasma mass spectrometry was used to analyze the concentrations of 23 metal elements. Serum metabolome was determined by liquid chromatography-mass spectrometry (LC-MS). A metabolome-wide association study (MWAS) was performed across the metal exposures and metabolism using quantile g-computation modeling. Pathway enrichment analysis was performed using MetaboAnalyst analysis. We identified 226 metabolites associated with metal mixtures, primarily involving lipid metabolism (glycerophospholipids, sphingolipids), amino acid metabolism (arginine and proline, alanine, aspartate and glutamate metabolism) and caffeine metabolic pathways. Exposure to metal mixtures is mainly associated with alterations in lipid metabolism and amino acid metabolism, particularly in the glycerophospholipid and arginine and proline metabolism pathway.

4.
World J Oncol ; 15(4): 675-681, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38993259

RÉSUMÉ

Background: While timely assessment of long-term survival for patients with bone cancer is essential for evaluation on early detection and prognosis level of treatment of bone cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with bone cancer in Eastern China. Methods: Patients diagnosed with bone cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Five-year relative survival (RS) of bone cancer patients was calculated by period analysis for overall and the stratification. We further predicted 5-year RS during upcoming 2019 - 2023 using a model-based period analysis and survival data during 2004 - 2018. Results: Overall, 5-year RS for patients with bone cancer during 2014 - 2018 reached 46.6%, being 40.8% for male and 51.0% for female. Five-year RS declined along with aging, decreasing from 58.9% for age < 45 years to 41.5% for age > 60 years, while 5-year RS for urban area was higher compared to rural area (59.1% vs. 44.3%). The 5-year RS during upcoming 2019 - 2023 reached 48.3%. We found a clear upward trend in 5-year RS during 2004 - 2023 for overall and the stratification by sex, age at diagnosis, and region. Conclusions: We found that, for first time in China using period analysis, most up-to-date 5-year RS for patients with bone cancer reached 46.6% during 2014 - 2018, and is projected to reach 48.3% for the period 2019 - 2023, which has important implications for timely evaluation on early detection and prognosis level of treatment for patients with bone cancer in Eastern China.

5.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3095-3112, 2024 Jun.
Article de Chinois | MEDLINE | ID: mdl-39041169

RÉSUMÉ

According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.


Sujet(s)
Tumeurs , Humains , Tumeurs/génétique , Tumeurs/traitement médicamenteux , Médecine de précision , RNA-Seq , Médecine traditionnelle chinoise , Constitution physique/génétique
6.
ACS Nano ; 18(29): 18963-18979, 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-39004822

RÉSUMÉ

Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.


Sujet(s)
Chitosane , Systèmes de délivrance de médicaments , Hydrogels , Inhibiteurs de points de contrôle immunitaires , Nanocomposites , Tumeurs de l'ovaire , Tumeurs du péritoine , Animaux , Hydrogels/composition chimique , Tumeurs du péritoine/traitement médicamenteux , Tumeurs du péritoine/secondaire , Tumeurs du péritoine/anatomopathologie , Souris , Chitosane/composition chimique , Chitosane/analogues et dérivés , Femelle , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Inhibiteurs de points de contrôle immunitaires/composition chimique , Inhibiteurs de points de contrôle immunitaires/administration et posologie , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/anatomopathologie , Nanocomposites/composition chimique , Humains , Antinéoplasiques/composition chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/administration et posologie , Souris de lignée BALB C , Glycérol/composition chimique , Glycérol/analogues et dérivés , Lignée cellulaire tumorale , Polymères/composition chimique , Polyesters
7.
Nat Commun ; 15(1): 6057, 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39025843

RÉSUMÉ

Although molecular vibronic spectra generation is pivotal for chemical analysis, tackling such exponentially complex tasks on classical computers remains inefficient. Quantum simulation, though theoretically promising, faces technological challenges in experimentally extracting vibronic spectra for molecules with multiple modes. Here, we propose a nontrivial algorithm to generate the vibronic spectra using states with zero displacements (squeezed vacuum states) coupled to a linear optical network, offering ease of experimental implementation. We also fabricate an integrated quantum photonic microprocessor chip as a versatile simulation platform containing 16 modes of single-mode squeezed vacuum states and a fully programmable interferometer network. Molecular vibronic spectra of formic acid and thymine under the Condon approximation are simulated using the quantum microprocessor chip with high reconstructed fidelity ( > 92%). Furthermore, vibronic spectra of naphthalene, phenanthrene, and benzene under the non-Condon approximation are also experimentally simulated. Such demonstrations could pave the way for solving complicated quantum chemistry problems involving vibronic spectra and computational tasks beyond the reach of classical computers.

8.
J Clin Periodontol ; 2024 Jul 14.
Article de Anglais | MEDLINE | ID: mdl-39004511

RÉSUMÉ

AIM: Periodontitis is one of the most common oral diseases and a major cause of tooth loss in adults. Environmental pollution is closely associated with the prevalence of periodontitis. However, few studies have focused on the association between volatile organic compounds (VOCs) and periodontitis. This cross-sectional study aims to examine whether exposure to VOCs is associated with periodontitis, based on data from the National Health and Nutrition Examination Survey (NHANES, 2011-2014). MATERIALS AND METHODS: We analysed data on blood VOC levels, periodontitis and related covariates from 2772 participants of the NHANES. The association between the blood VOCs and periodontitis was analysed using weighted logistic regression analysis, the restricted cubic spline (RCS) model and the weighted quantile sum (WQS) regression model. Interaction tests and mediation analysis were also conducted. RESULTS: After adjusting for covariates, for each natural constant-fold increase in 1,4-dichlorobenzene, the odds of having periodontitis increased by 16% (odds ratio = 1.16; 95% confidence interval: 1.08-1.24, p < .001). WQS regression model indicated that 1,4-dichlorobenzene contributed the most to the association between VOC co-exposure and periodontitis. Mediation analysis further revealed that total bilirubin levels mediated the association between 1,4-dichlorobenzene and the prevalence of periodontitis, accounting for 4.32%. In addition, the positive association between o-xylene and periodontitis was more pronounced in the <65-year-old group. CONCLUSIONS: This study has provided relatively little evidence to demonstrate a specific link between VOCs and periodontitis. Nonetheless, exposure to VOCs remains a non-negligible public health concern, and further research is required to investigate the association and potential mechanisms of action between VOCs and periodontitis.

9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 687-692, 2024 Aug 18.
Article de Chinois | MEDLINE | ID: mdl-39041566

RÉSUMÉ

OBJECTIVE: To evaluate the effects of fine particle matter (PM2.5) and ozone (O3) combined exposure on adenosine triphosphate (ATP) amount and ATPase activities in nasal mucosa of Sprague Dawley (SD) rats. METHODS: Twenty male SD rats were divided into control group (n=10) and exposure group (n=10) by random number table method. The rats were fed in the conventional clean environment and the air pollutant exposure system established by our team, respectively, and exposed for 208 d. During the exposure period, the concentrations of PM2.5 and O3 in the exposure system were monitored, and a comprehensive assessment of PM2.5 and O3 in the exposure system was conducted by combining self-measurement and site data. On the 208 d of exposure, the core, liver, spleen, kidney, testis and other major organs and nasal mucosal tissues of the rats were harvested. Each organ was weighed and the organ coefficient calculated. The total amount of ATP was measured by bioluminescence, and the activities of Na+-K+ -ATPase and Ca2+ -ATPase were detected by spectrophotometry. The t test of two independent samples was used to compare the differences among the indicator groups. RESULTS: From the 3rd week to the end of exposure duration, the body weight of the rats in the exposure group was higher than that in the control group (P < 0.05), and there was no significant difference in organ coefficients between the two groups. The average daily PM2.5 concentration in the exposure group was (30.68±19.23) µg/m3, and the maximum 8 h ozone concentration (O3-8 h) was (82.45±35.81) µg/m3. The chemiluminescence value (792.4±274.1) IU/L of ATP in nasal mucosa of the rats in the exposure group was lower than that in the control group (1 126.8±218.1) IU/L. The Na+-K+-ATPase activity (1.53±0.85) U/mg in nasal mucosa of the rats in the exposure group was lower than that in the control group (4.31±1.60) U/mg (P < 0.05). The protein content of nasal mucosa in the control group and the exposure group were (302.14±52.51) mg/L and (234.58±53.49) mg/L, respectively, and the activity of Ca2+-ATPase was (0.81±0.27) U/mg and (0.99±0.73) U/mg, respectively. There was no significant difference between the groups. CONCLUSION: The ability of power capacity decreased in the rat nasal mucossa under the sub-chronic low-concentration exposure of PM2.5 and O3.


Sujet(s)
Adénosine triphosphate , Polluants atmosphériques , Muqueuse nasale , Ozone , Matière particulaire , Rat Sprague-Dawley , Animaux , Mâle , Rats , Muqueuse nasale/métabolisme , Adénosine triphosphate/métabolisme , Adenosine triphosphatases/métabolisme , Sodium-Potassium-Exchanging ATPase/métabolisme , Exposition environnementale/effets indésirables
10.
J Tissue Viability ; 2024 Jun 28.
Article de Anglais | MEDLINE | ID: mdl-38951048

RÉSUMÉ

BACKGROUND: It is well known that women have been plagued by various skin problems. However, research on the characteristics of women's skin at different ages is still inadequate. In addition, there is a lack of research on the extent of women's skincare habits and skin care awareness. METHODS: A cross-sectional survey on skin was carried out in Shanghai, China, which was conducted by means of a questionnaire. 3678 women, aged 18-59 years, participated in the study. The information collected focused on the importance they place on their skin, the skin problems they have, and their use and perception of skin care products. RESULTS: Before the age of 25, the most common skin problems that women face are dryness and oiliness, while after the age of 30, skin-ageing issues begin to appear and worsen with age. In addition, the higher the level of education, the higher the frequency of and compliance with sunscreen use, and the economy also affects women's use of sunscreen. Importantly, the importance women place on their skin and the level of sunscreen awareness affects women's use of sunscreen. CONCLUSIONS: This study was conducted to understand the skin characteristics of women of different age groups as well as to determine the factors that influence the use of sunscreens, which will not only promote women's skin care practices and product development, but also provide important clues for future activities on sunscreen use and health promotion.

11.
J Hepatol ; 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38992769

RÉSUMÉ

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

12.
Adv Mater ; : e2405840, 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-38994697

RÉSUMÉ

Numerous efforts are devoted to reducing the defects at perovskite surface and/or grain boundary; however, the grown-in defects inside grain is rarely studied. Here, the influence of cooling rate on the point defects concentration in polycrystalline perovskite film during heat treatment processing is investigated. With the combination of theoretical and experimental studies, this work reveals that the supersaturated point defects in perovskite films generate during the cooling process and its concentration improves as the cooling rate increases. The supersaturated point defects can be minimized through slowing the cooling rate. As a result, the optimized FAPbI3 polycrystalline films achieve a superior carrier lifetime of up to 12.6 µs and improved stability. The champion device delivers a 25.47% PCE (certified 24.7%) and retain 90% of their initial value after >1100 h of operation at the maximum power point. These results provide a fundamental understanding of the mechanisms of grown-in defects formation in polycrystalline perovskite film.

13.
J Wildl Dis ; 2024 Jul 17.
Article de Anglais | MEDLINE | ID: mdl-39013547

RÉSUMÉ

Chronic phalaris toxicity (CPT) is a neurological disease caused by animals ingesting toxins produced by early growth stages of Phalaris aquatica, a pasture plant introduced to the southeastern regions of Australia postcolonization. Little is known about the clinical progression of CPT in wildlife, as incidents are sporadic and predominantly reported when animals are in the end stages of disease and in a poor welfare state. We studied a cohort of 35 eastern gray kangaroos (Macropus giganteus) affected by CPT to clarify clinical prognosis and survival rates. Kangaroos were captured in May, June, and July of 2022 at Plenty Gorge Parklands, Victoria, Australia. Each animal was radiotracked for 180 d, clinical progression and disease outcomes monitored twice a week. By the conclusion of the study, 24 animals had died (19 by euthanasia due to deterioration, five found dead). Ten animals survived, with two demonstrating a reduction in clinical signs and eight showing full resolution of clinical signs. One animal was disqualified from the study. The overall survival rate was 29.4% (95% confidence interval 17.5-49.5%). The survival duration of animals that died ranged from 5 to 133 d. There was no difference in survival rate based on sex (P=0.2), age class (P=0.49) or the month of capture (P=0.49). These results suggest that CPT is an important health and welfare concern for at-risk macropod populations, with high case-fatality rates and prolonged clinical durations. Further research to manage the disease via methods such as reducing Phalaris aquatica plant coverage and preventative treatments for animals is warranted to reduce disease incidences and improve disease outcomes in wildlife populations.

14.
J Mater Chem B ; 12(31): 7497-7518, 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39021127

RÉSUMÉ

Dental diseases, such as dental caries and periodontal disorders, constitute a major global health challenge, affecting millions worldwide and often resulting in tooth loss. Traditional dental treatments, though beneficial, typically cannot fully restore the natural functions and structures of teeth. This limitation has prompted growing interest in innovative strategies for tooth regeneration methods. Among these, the use of dental stem cells to generate functional tooth modules represents an emerging and promising approach in dental tissue engineering. These modules aim to closely replicate the intricate morphology and essential physiological functions of dental tissues. Recent advancements in regenerative research have not only enhanced the assembly techniques for these modules but also highlighted their therapeutic potential in addressing various dental diseases. In this review, we discuss the latest progress in the construction of functional tooth modules, especially on regenerating dental pulp, periodontal tissue, and tooth roots.


Sujet(s)
Régénération , Ingénierie tissulaire , Dent , Humains , Animaux , Cellules souches/cytologie , Pulpe dentaire/cytologie , Structures d'échafaudage tissulaires/composition chimique
15.
Toxics ; 12(7)2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-39058137

RÉSUMÉ

Estrogens can affect the immune inflammatory response through estrogen receptor alpha (ERα), but the specific role of estrogen member receptor G-protein coupled receptor 1 (GPER1) in this process remains unclear. In this study, we evaluated the effects of tetrachlorobisphenol A (TCBPA), which has estrogen activity, on immune inflammatory-related indicators of Jurkat cells, as well as investigated the role of GPER1 in these effects. The results showed that TCBPA at lower concentrations significantly promoted the viability of Jurkat cells, whereas higher concentrations decreased cell viability. TCBPA at concentrations ranging from 1 to 25 µM increased the intracellular reactive oxygen species (ROS) levels. Additionally, treatment with 10 µM TCBPA increased the protein expression of ERα and GPER1, elevated the phosphorylation of protein kinase B (p-Akt), and upregulated the mRNA levels of GPER1, Akt, and phosphoinositide 3-kinase (PI3K) genes. Treatment with 10 µM TCBPA also upregulated the protein or gene expression of pro-inflammatory cytokines, such as interleukins (IL1ß, IL2, IL6, IL8, IL12α) and tumor necrosis factor alpha (TNFα) in Jurkat cells. Furthermore, pretreatment with a GPER1 inhibitor G15 significantly reduced the mRNA levels of Akt induced by 10 µM TCBPA. Moreover, the upregulation of mRNA expression of RelA (p65), TNFα, IL6, IL8, and IL12α induced by 10 µM TCBPA was also significantly attenuated after G15 pretreatment. These findings suggest that TCBPA upregulates the expression of genes related to inflammatory responses by activating the GPER1-mediated PI3K/Akt signaling pathway. This study provides new insights into the mechanism of TCBPA-induced inflammatory response.

16.
J Enzyme Inhib Med Chem ; 39(1): 2367129, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-39051546

RÉSUMÉ

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.


Sujet(s)
Arginine , Glutamine , Tumeurs , Proline , Humains , Glutamine/métabolisme , Tumeurs/métabolisme , Tumeurs/traitement médicamenteux , Tumeurs/anatomopathologie , Proline/métabolisme , Proline/composition chimique , Arginine/métabolisme , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/synthèse chimique , Structure moléculaire , Animaux
17.
BMC Infect Dis ; 24(1): 745, 2024 Jul 29.
Article de Anglais | MEDLINE | ID: mdl-39075343

RÉSUMÉ

BACKGROUND: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children. METHOD: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed. RESULTS: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes. CONCLUSIONS: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens.


Sujet(s)
Abcès hépatique à pyogènes , Humains , Abcès hépatique à pyogènes/microbiologie , Abcès hépatique à pyogènes/épidémiologie , Mâle , Femelle , Études rétrospectives , Enfant d'âge préscolaire , Enfant , Nourrisson , Pékin/épidémiologie , Adolescent , Klebsiella pneumoniae/isolement et purification , Antibactériens/usage thérapeutique , Facteurs de risque , Staphylococcus aureus/isolement et purification
18.
Eur J Pharmacol ; 979: 176862, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39068974

RÉSUMÉ

We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.

19.
J Affect Disord ; 363: 239-248, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-39038625

RÉSUMÉ

With increasing prevalence rate of depression by years, more attention has been paid to the influence of environmental pollutants on depression, but relationship between exposure to volatile organic compounds (VOCs) and depression is rarely studied. Therefore, this cross-sectional study use the National Center for Health Statistics (NHANES) database (2013-2016 years) to explore association between exposure to multiple VOCs and depression in general population. Multiple linear and logistic regression models were used to analyze the association between urinary VOC metabolism (mVOCs) and depression. To further analyze effect of multiple mVOCs mixed exposure, Bayesian kernel machine regression (BKMR) models were performed. A total of 3240 participants and 16 mVOCs were included in the analysis. Results showed that 10 mVOCs exposure were positively correlated with depression by multiple linear and logistic regression models, especially CYMA and MHBMA3, which also showed significant positive association with depression in BKMR model. Mixed exposure of multiple mVOCs was significantly positively correlated with depression. Gender differences were existed in effects of some VOCs concentrations on depression. AAMA, CYMA and MA had significant positive correlations with depression by women, and DHBMA had significant positive correlations with depression by men. Hence, this study showed that exposing to VOCs might have negative impacts on depression, and impact of CYMA and MHBMA3 on depression may be more evident, which provide new ideas for prevention and control of depression. But further research and exploration are needed to clarify the mechanism and influence factors of this relationship, to demonstrate the reliability of these relationship.

20.
Light Sci Appl ; 13(1): 167, 2024 Jul 16.
Article de Anglais | MEDLINE | ID: mdl-39013861

RÉSUMÉ

The robust operation of quantum entanglement states is crucial for applications in quantum information, computing, and communications1-3. However, it has always been a great challenge to complete such a task because of decoherence and disorder. Here, we propose theoretically and demonstrate experimentally an effective scheme to realize robust operation of quantum entanglement states by designing quadruple degeneracy exceptional points. By encircling the exceptional points on two overlapping Riemann energy surfaces, we have realized a chiral switch for entangled states with high fidelity. Owing to the topological protection conferred by the Riemann surface structure, this switching of chirality exhibits strong robustness against perturbations in the encircling path. Furthermore, we have experimentally validated such a scheme on a quantum walk platform. Our work opens up a new way for the application of non-Hermitian physics in the field of quantum information.

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