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1.
J Cell Commun Signal ; 18(2): e12022, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38946719

ABSTRACT

Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients (n = 20) compared to their normal controls (n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1ß treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1ß-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.

2.
Cell ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38964329

ABSTRACT

The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown. Here, we investigated the HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchored states, revealing that sialoglycan binding induces a conformational change of the NTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition, exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1 features an insertion subdomain that recognizes TMPRSS2 through three previously undiscovered interfaces. Furthermore, structural investigation of HCoV-HKU1A in combination with mutagenesis and binding assays confirms a conserved receptor recognition pattern adopted by HCoV-HKU1. These studies advance our understanding of the complex viral-host interactions during entry, laying the groundwork for developing new therapeutics against coronavirus-associated diseases.

3.
Heliyon ; 10(12): e32888, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38994077

ABSTRACT

Selenoneine, an ergothioneine analog, is important for antioxidation and detoxification. SenB and SenA are two crucial enzymes that form carbon-selenium bonds in the selenoneine biosynthetic pathway. To investigate their underlying catalytic mechanisms, we obtained complex structures of SenB with its substrate UDP-N-acetylglucosamine (UDP-GlcNAc) and SenA with N-α-trimethyl histidine (TMH). SenB adopts a type-B glycosyltransferase fold. Structural and functional analysis of the interaction network at the active center provide key information on substrate recognition and suggest a metal-ion-independent, inverting mechanism is utilized for SenB-mediated selenoglycoside formation. Moreover, the complex structure of SenA with TMH and enzymatic activity assays highlight vital residues that control substrate binding and specificity. Based on the conserved structure and substrate-binding pocket of the type I sulfoxide synthase EgtB in the ergothioneine biosynthetic pathway, a similar reaction mechanism was proposed for the formation of C-Se bonds by SenA. The structures provide knowledge on selenoneine synthesis and lay groundwork for further applications of this pathway.

4.
Acta Radiol ; : 2841851241257775, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38870345

ABSTRACT

BACKGROUND: Preoperative effective assessment of cervical lymph node metastasis in thyroid cancer plays an important role in formulating the surgical plan. PURPOSE: To investigate the significance of synthetic magnetic resonance imaging (MRI) for quantitatively analyzing cervical lymph node metastasis in thyroid cancer. MATERIAL AND METHODS: A retrospective analysis was conducted on 30 patients with thyroid cancer, consisting of 19 thyroid cancer nodules, 45 metastatic lymph nodes, and 47 non-metastatic lymph nodes. Regions of interest (ROIs) for each type of nodule were manually delineated using a workstation. Quantitative parameters, such as T1, T2, and proton density (PD) values, were automatically extracted from synthetic MRI scans. Statistical tests and regression analysis were performed to assess differences and correlations among the quantitative parameters. RESULTS: There were no significant differences in the quantitative parameter values between the primary tumor and metastatic lymph node tissues (P > 0.05). However, significant differences were observed in the quantitative parameters between the primary tumor and non-metastatic lymph node tissues and between the metastatic and non-metastatic lymph node tissues (P < 0.05). The diagnostic accuracy for cervical lymph node metastasis in thyroid cancer was 94.4% for the T1 and T2 combined index, 91.9% for T2, 86.8% for T1, and 71.7% for PD values. CONCLUSION: The application of quantitative parameters from synthetic MRI can assist clinicians in accurately planning surgical interventions for thyroid cancer patients before surgery.

5.
Structure ; 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38925121

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly all over the world. The main protease (Mpro) is significant to the replication and transcription of viruses, making it an attractive drug target against coronaviruses. Here, we introduce a series of novel inhibitors which are designed de novo through structure-based drug design approach that have great potential to inhibit SARS-CoV-2 Mproin vitro. High-resolution structures show that these inhibitors form covalent bonds with the catalytic cysteine through the novel dibromomethyl ketone (DBMK) as a reactive warhead. At the same time, the designed phenyl group beside the DBMK warhead inserts into the cleft between H41 and C145 through π-π stacking interaction, splitting the catalytic dyad and disrupting proton transfer. This unique binding model provides novel clues for the cysteine protease inhibitor development of SARS-CoV-2 as well as other pathogens.

6.
Toxics ; 12(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38922090

ABSTRACT

Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology of AD-like lesions triggered by chronic Pb exposure in adult mice. To emulate the chronic effects of Pb, we established a rodent model spanning 10 months of controlled Pb administration, dividing 52 C57BL/6J mice into groups receiving varying concentrations of Pb (1, 2, or 4 g/L) alongside an unexposed control. Blood Pb levels were monitored using serum samples to ensure accurate dosing and to correlate with observed toxicological outcomes. Utilizing the Morris water maze, a robust behavioral assay for assessing cognitive functions, we documented a dose-dependent decline in learning and memory capabilities among the Pb-exposed mice. Histopathological examination of the hippocampal tissue revealed tell-tale signs of AD-like neurodegeneration, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. At the molecular level, a significant upregulation of AD-associated genes, namely amyloid precursor protein (APP), ß-secretase 1 (BACE1), and tau, was observed in the hippocampal tissue of Pb-exposed mice. This was accompanied by a corresponding surge in the protein levels of APP, BACE1, amyloid-ß (Aß), and phosphorylated tau (p-tau), further implicating Pb in the dysregulation of these key AD markers. The expression of CDR1as, a long non-coding RNA implicated in AD pathogenesis, was found to be suppressed in Pb-exposed mice. This observation suggests a potential mechanistic link between Pb-induced neurotoxicity and the dysregulation of the CDR1as/miR-671 axis, which warrants further investigation. Moreover, our study identified a dose-dependent alteration in the intracellular and extracellular levels of the transcription factor nuclear factor-kappa B (NF-κB). This finding implicates Pb in the modulation of NF-κB signaling, a pathway that plays a pivotal role in neuroinflammation and neurodegeneration. In conclusion, our findings underscored the deleterious effects of Pb exposure on the CNS, leading to the development of AD-like pathology. The observed modulation of NF-κB signaling and miR-671/CDR1as regulation provides a plausible mechanistic framework for understanding the neurotoxic effects of Pb and its potential contribution to AD pathogenesis.

7.
Int J Mol Sci ; 25(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38928199

ABSTRACT

Tomato fruit ripening is accompanied by carotenoid accumulation and color changes. To elucidate the regulatory mechanisms underlying carotenoid synthesis during fruit ripening, a combined transcriptomic and metabolomic analysis was conducted on red-fruited tomato (WP190) and orange-fruited tomato (ZH108). A total of twenty-nine (29) different carotenoid compounds were identified in tomato fruits at six different stages. The abundance of the majority of the carotenoids was enhanced significantly with fruit ripening, with higher levels of lycopene; (E/Z)-lycopene; and α-, ß- and γ-carotenoids detected in the fruits of WP190 at 50 and 60 days post anthesis (DPA). Transcriptome analysis revealed that the fruits of two varieties exhibited the highest number of differentially expressed genes (DEGs) at 50 DPA, and a module of co-expressed genes related to the fruit carotenoid content was established by WGCNA. qRT-PCR analysis validated the transcriptome result with a significantly elevated transcript level of lycopene biosynthesis genes (including SlPSY2, SlZCIS, SlPDS, SlZDS and SlCRTSO2) observed in WP190 at 50 DPA in comparison to ZH108. In addition, during the ripening process, the expression of ethylene biosynthesis (SlACSs and SlACOs) and signaling (SlEIN3 and SlERF1) genes was also increased, and these mechanisms may regulate carotenoid accumulation and fruit ripening in tomato. Differential expression of several key genes in the fruit of two tomato varieties at different stages regulates the accumulation of carotenoids and leads to differences in color between the two varieties of tomato. The results of this study provide a comprehensive understanding of carotenoid accumulation and ethylene biosynthesis and signal transduction pathway regulatory mechanisms during tomato fruit development.


Subject(s)
Carotenoids , Fruit , Gene Expression Regulation, Plant , Metabolome , Solanum lycopersicum , Transcriptome , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Solanum lycopersicum/growth & development , Fruit/genetics , Fruit/metabolism , Fruit/growth & development , Carotenoids/metabolism , Gene Expression Profiling/methods , Lycopene/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Pigmentation/genetics , Color
8.
Insights Imaging ; 15(1): 133, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38825662

ABSTRACT

OBJECTIVE: To investigate the anatomic risk factors of knee in patients with acute non-contact anterior cruciate ligament (aACL) ruptures to develop ramp lesions. METHODS: A total of 202 subjects were retrospectively divided into three groups: (1) aACL ruptures combined with ramp lesions group (n = 76); (2) isolated ACL ruptures group (n = 56) and (3) normal controls group (n = 70). Quantitative morphological parameters on MRI were measured including: diameter of medial femoral condyle (MFC), anterior-posterior length and depth of medial tibial plateau (MTP AP length and depth), lateral posterior tibial slope (LPTS) and medial posterior tibial slope (MTPS), asymmetry of LPTS and MPTS (LMPTS), lateral meniscal slope (LMS), and medial meniscal slope (MMS). RESULTS: The MTP AP length, MTP AP length/MFC diameter ratio, MTP depth, LPTS and the asymmetry of LMPTS showed significant differences among the three groups (p < 0.001). The risk factors associated with the ramp lesions including a longer MTP AP length (OR 1.17, 95% CI 1.00-1.44, p = 0.044), increased MTP depth (OR 1.91, 95% CI 1.22-3.00, p = 0.005) and lager ratio (OR 1.11, 95% CI 1.01-1.22, p = 0.036). The highest AUC was the MTP AP length/MFC diameter ratio (0.74; 95% CI, 0.66-0.82). The combination model increased higher accuracy (0.80; 95% CI, 0.72-0.88). CONCLUSION: Several bony anatomic characteristics of the knee, especially the morphology of medial tibia plateau, are additional risk factors for aACL ruptures to develop ramp lesions. CRITICAL RELEVANCE STATEMENT: Predictive anatomic risk factors of the knee for patients with acute non-contact anterior cruciate ligament (aACL) ruptures to develop ramp lesions, especially the morphology of medial tibia plateau, are detectable by MRI. KEY POINTS: Ramp lesion development can complicate aACL ruptures and requires specific treatment. Longer AP length and increased MTP depth are risk factors for concurrent ramp lesions. Identification of ramp lesions allows for the most appropriate treatment.

9.
Fish Physiol Biochem ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38907741

ABSTRACT

Avermectin is a commonly used insect repellent for aquaculture and crops, but it is easy to remain in the aquatic environment, causing organism disorders, inflammation, and even death. This resulted in significant economic losses to the carp aquaculture industry. Silybin has antioxidant, anti-inflammatory, and anti-apoptotic properties. However, it is unclear whether Silybin counteracts gill damage caused by avermectin exposure. Therefore, we modeled avermectin exposure and Silybin intervention by adding 2.404 µg/L avermectin to water and 400 mg/kg of Silybin to feed. Gill tissue was collected and analyzed in depth during a 30-day experimental period. The results showed that avermectin exposure induced structural disorganization of gill filaments and led to increased reactive oxygen species, inhibition of antioxidant functions, induction of inflammatory responses, and endoplasmic reticulum stress in addition to the endogenous apoptotic pathway. In contrast, Silybin effectively alleviated pathological changes and reduced reactive oxygen species levels, thereby attenuating oxidative stress and endogenous apoptosis and inhibiting endoplasmic reticulum stress pathways. In addition, Silybin reduced avermectin-induced gill tissue inflammation in carp, and it is considered that it might modulate the cGAS-STING pathway. In summary, Silybin alleviates avermectin-induced oxidative damage within the carp's respiratory system by modulating the cGAS-STING pathway and endoplasmic reticulum stress. The main goal is to understand how Silybin reduces oxidative damage caused by avermectin in carp gills, offering management strategies. Concurrently, the current study proposes that Silybin can serve as a dietary supplement to reduce the risks brought on by repellent buildup in freshwater aquaculture.

10.
Cell Death Dis ; 15(6): 458, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38937437

ABSTRACT

SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S351, S470-471and S493-494 as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.


Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , COVID-19 , SARS-CoV-2 , Single-Domain Antibodies , Spike Glycoprotein, Coronavirus , SARS-CoV-2/immunology , SARS-CoV-2/drug effects , Single-Domain Antibodies/pharmacology , Single-Domain Antibodies/immunology , Humans , Animals , COVID-19/immunology , COVID-19/virology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Mice , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Neutralizing/pharmacology , COVID-19 Drug Treatment , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , HEK293 Cells , Mice, Inbred BALB C , Protein Binding , Female
11.
Mol Ther ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822525

ABSTRACT

Single monoclonal antibodies (mAbs) can be expressed in vivo through gene delivery of their mRNA formulated with lipid nanoparticles (LNPs). However, delivery of a mAb combination could be challenging due to the risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureus first in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice. Intravenous delivery of each mRNA/LNP or the trio (1 mg/kg each) induced functional antibody expression after 24 h (10-100 µg/mL) with 64%-78% cognate-chain paired IgG expression after 3 days, and an absence of non-cognate chain pairing for scFv-Fc. We did not observe reduced neutralizing activity for each mAb compared with the level of expression of chain-paired mAbs. Delivery of the trio mRNA protected mice in an S. aureus-induced dermonecrosis model. Intravenous administration of the three mRNA in non-human primates achieved peak serum IgG levels ranging between 2.9 and 13.7 µg/mL with a half-life of 11.8-15.4 days. These results suggest nucleic acid delivery of mAb combinations holds promise and may be a viable option to streamline the development of therapeutic antibodies.

12.
Cancer Immunol Immunother ; 73(7): 129, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744688

ABSTRACT

Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.


Subject(s)
Antigens, Neoplasm , Cancer Vaccines , Lung Neoplasms , Vaccines, Subunit , Animals , Antigens, Neoplasm/immunology , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Mice , Cancer Vaccines/immunology , Vaccines, Subunit/immunology , Humans , Mice, Inbred C57BL , Female , Immunotherapy/methods , Cell Line, Tumor , Protein Subunit Vaccines
13.
Environ Sci Pollut Res Int ; 31(25): 37337-37355, 2024 May.
Article in English | MEDLINE | ID: mdl-38771539

ABSTRACT

Groundwater plays a pivotal role in the water resources of Shicheng County; however, the issue of excessive fluoride content in groundwater and its associated health risks often goes unnoticed. Groundwater assumes a crucial role in the hydrological dynamics of Shicheng County; nevertheless, the matter concerning elevated levels of fluoride within groundwater and its accompanying health hazards frequently evades attention. The hydrogeochemical analysis, obscure comprehensive water quality assessment based on cloud model, and probabilistic human health risk assessment using Monte Carlo simulation were conducted on 34 collected water samples. The findings indicate that the predominant groundwater hydrochemical types are SO4·Cl-Na and HCO3-Na. The processes of rock weathering and cation exchange play crucial roles in influencing water chemistry. Groundwater samples generally exhibit elevated concentrations of F-, surpassing the drinking water standard, primarily attributed to mineral dissolution. The concentrations of F- in more than 52.94% and 23.53% of the groundwater samples exceeded the acceptable non-carcinogenic risk limits for children and adults, respectively. Considering the inherent uncertainty in model parameters, it is anticipated that both children and adults will have a probability exceeding 49.36% and 30.50%, respectively, of being exposed to elevated levels of F ions in groundwater. The utilization of stochastic simulations, in contrast to deterministic methods, enables a more precise depiction of health risks. The outcomes derived from this investigation possess the potential to assist policymakers in formulating strategies aimed at ensuring the provision of secure domestic water supplies.


Subject(s)
Environmental Monitoring , Groundwater , Water Pollutants, Chemical , Groundwater/chemistry , Risk Assessment , Humans , Water Pollutants, Chemical/analysis , China , Water Quality , Fluorides/analysis , Drinking Water/chemistry , Monte Carlo Method
14.
Genetica ; 152(2-3): 83-100, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38743131

ABSTRACT

Xylanase inhibitor proteins (XIP) are widely distributed in the plant kingdom, and also exist in rice. However, a systematic bioinformatics analysis of this gene family in rice (OsXIP) has not been conducted to date. In this study, we identified 32 members of the OsXIP gene family and analyzed their physicochemical properties, chromosomal localization, gene structure, protein structure, expression profiles, and interaction networks. Our results indicated that OsXIP genes exhibit an uneven distribution across eight rice chromosomes. These genes generally feature a low number of introns or are intronless, all family members, except for OsXIP20, contain two highly conserved motifs, namely Motif 8 and Motif 9. In addition, it is worth noting that the promoter regions of OsXIP gene family members feature a widespread presence of abscisic acid response elements (ABRE) and gibberellin response elements (GARE-motif and TATC-box). Quantitative Real-time PCR (qRT-PCR) analysis unveiled that the expression of OsXIP genes exhibited higher levels in leaves and roots, with considerable variation in the expression of each gene in these tissues both prior to and following treatments with abscisic acid (ABA) and gibberellin (GA3). Protein interaction studies and microRNA (miRNA) target prediction showed that OsXIP engages with key elements within the hormone-responsive and drought signaling pathways. The qRT-PCR suggested osa-miR2927 as a potential key regulator in the rice responding to drought stress, functioning as tissue-specific and temporally regulation. This study provides a theoretical foundation for further analysis of the functions within the OsXIP gene family.


Subject(s)
Gene Expression Regulation, Plant , Multigene Family , Oryza , Plant Proteins , Oryza/genetics , Oryza/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Promoter Regions, Genetic , Abscisic Acid/pharmacology , Abscisic Acid/metabolism , MicroRNAs/genetics , Phylogeny , Gibberellins/metabolism , Gibberellins/pharmacology , Chromosomes, Plant/genetics
15.
Respir Res ; 25(1): 218, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789950

ABSTRACT

OBJECTIVE: To evaluate the predictive value of PD-1 expression in T lymphocytes for rehospitalization due to acute exacerbations of COPD (AECOPD) in discharged patients. METHODS: 115 participants hospitalized with COPD (average age 71.8 ± 6.0 years) were recruited at Fujian Provincial Hospital. PD1+T lymphocytes proportions (PD1+T%), baseline demographics and clinical data were recorded at hospital discharge. AECOPD re-admission were collected at 1-year follow-up. Kaplan-Meier analysis compared the time to AECOPD readmissions among groups stratified by PD1+T%. Multivariable Cox proportional hazards regression and stratified analysis determined the correlation between PD1+T%, potential confounders, and AECOPD re-admission. ROC and DCA evaluated PD1+T% in enhancing the clinical predictive values of Cox models, BODE and CODEX. RESULTS: 68 participants (59.1%) were AECOPD readmitted, those with AECOPD readmission exhibited significantly elevated baseline PD-1+CD4+T/CD4+T% and PD-1+CD8 + T/CD8 + T% compared to non-readmitted counterparts. PD1+ T lymphocyte levels statistically correlated with BODE and CODEX indices. Kaplan-Meier analysis demonstrated that those in Higher PD1+ T lymphocyte proportions had reduced time to AECOPD readmission (logRank p < 0.05). Cox analysis identified high PD1+CD4+T and PD1+CD8+T ratios as risk factors of AECOPD readmission, with hazard ratios of 1.384(95%CI [1.043-1.725]) and 1.401(95%CI [1.013-1.789]), respectively. Notably, in patients aged < 70 years and with fewer than twice AECOPD episodes in the previous year, high PD1+T lymphocyte counts significantly increased risk for AECOPD readmission(p < 0.05). The AECOPD readmission predictive model, incorporating PD1+T% exhibited superior discrimination to the Cox model, BODE index and CODEX index, AUC of ROC were 0.763(95%CI [0.633-0.893]) and 0.734(95%CI [0.570-0.899]) (DeLong's test p < 0.05).The DCA illustrates that integrating PD1+T% into models significantly enhances the utility in aiding clinical decision-making. CONCLUSION: Evaluation of PD1+ lymphocyte proportions offer a novel perspective for identifying high-risk COPD patients, potentially providing insights for COPD management. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR, URL: www.chictr.org.cn/ ), Registration number: ChiCTR2200055611 Date of Registration: 2022-01-14.


Subject(s)
Programmed Cell Death 1 Receptor , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/immunology , Male , Female , Aged , Programmed Cell Death 1 Receptor/metabolism , Prospective Studies , Middle Aged , Disease Progression , Patient Readmission , Cohort Studies , Hospitalization/statistics & numerical data , Hospitalization/trends , Aged, 80 and over , Follow-Up Studies , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
16.
Med Phys ; 51(7): 4635-4645, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38753987

ABSTRACT

BACKGROUND: Currently, an advanced imaging method may be necessary for magnetic resonance imaging (MRI) to diagnosis and quantify liver fibrosis (LF). PURPOSE: To evaluate the feasibility of the multicompartmental restriction spectrum imaging (RSI) model to characterize LF in a mouse model. METHODS: Thirty mice with carbon tetrachloride (CCl4)-induced LF and eight control mice were investigated using multi-b-value (ranging from 0 to 2000 s/mm2) diffusion-weighted imaging (DWI) on a 3T scanner. DWI data were processed using RSI model (2-5 compartments) with the Bayesian Information Criterion (BIC) determining the optimal model. Conventional ADC value and signal fraction of each compartment in the optimal RSI model were compared across groups. Receiver operating characteristics (ROC) curve analysis was performed to determine the diagnosis performances of different parameters, while Spearman correlation analysis was employed to investigate the correlation between different tissue compartments and the stage of LF. RESULTS: According to BIC results, a 4-compartment RSI model (RSI4) with optimal ADCs of 0.471 × 10-3, 1.653 × 10-3, 9.487 × 10-3, and > 30 × 10-3, was the optimal model to characterize LF. Significant differences in signal contribution fraction of the C1 and C3 compartments were observed between LF and control groups (P = 0.018 and 0.003, respectively). ROC analysis showed that RSI4-C3 was the most effective single diffusion parameter for characterizing LF (AUC = 0.876, P = 0.003). Furthermore, the combination of ADC values and RSI4-C3 value increased the diagnosis performance significantly (AUC = 0.894, P = 0.002). CONCLUSION: The 4-compartment RSI model has the potential to distinguish LF from the control group based on diffusion parameters. RSI4-C3 showed the highest diagnostic performance among all the parameters. The combination of ADC and RSI4-C3 values further improved the discrimination performance.


Subject(s)
Disease Models, Animal , Liver Cirrhosis , Animals , Liver Cirrhosis/diagnostic imaging , Mice , Image Processing, Computer-Assisted/methods , Diffusion Magnetic Resonance Imaging , Mice, Inbred C57BL , Carbon Tetrachloride , Magnetic Resonance Imaging , Male , ROC Curve , Feasibility Studies
17.
Nat Commun ; 15(1): 4106, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750031

ABSTRACT

China's extensive planted forests play a crucial role in carbon storage, vital for climate change mitigation. However, the complex spatiotemporal dynamics of China's planted forest area and its carbon storage remain uncaptured. Here we reveal such changes in China's planted forests from 1990 to 2020 using satellite and field data. Results show a doubling of planted forest area, a trend that intensified post-2000. These changes lead to China's planted forest carbon storage increasing from 675.6 ± 12.5 Tg C in 1990 to 1,873.1 ± 16.2 Tg C in 2020, with an average rate of ~ 40 Tg C yr-1. The area expansion of planted forests contributed ~ 53% (637.2 ± 5.4 Tg C) of the total above increased carbon storage in planted forests compared with planted forest growth. This proactive policy-driven expansion of planted forests has catalyzed a swift increase in carbon storage, aligning with China's Carbon Neutrality Target for 2060.

18.
Arch Toxicol ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806717

ABSTRACT

A mechanism exploration is an important part of toxicological studies. However, traditional cell and animal models can no longer meet the current needs for in-depth studies of toxicological mechanisms. The three-dimensional (3D) organoid derived from human embryonic stem cells (hESC) or induced pluripotent stem cells (hiPSC) is an ideal experimental model for the study of toxicological effects and mechanisms, which further recapitulates the human tissue microenvironment and provides a reliable method for studying complex cell-cell interactions. This article provides a comprehensive overview of the state of the 3D organoid technology in toxicological studies, including a bibliometric analysis of the existing literature and an exploration of the latest advances in toxicological mechanisms. The use of 3D organoids in toxicology research is growing rapidly, with applications in disease modeling, organ-on-chips, and drug toxicity screening being emphasized, but academic communications among countries/regions, institutions, and research scholars need to be further strengthened. Attempts to study the toxicological mechanisms of exogenous chemicals such as heavy metals, nanoparticles, drugs and organic pollutants are also increasing. It can be expected that 3D organoids can be better applied to the safety evaluation of exogenous chemicals by establishing a standardized methodology.

19.
Nano Lett ; 24(22): 6560-6567, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38775289

ABSTRACT

Kagome lattice AV3Sb5 has attracted tremendous interest because it hosts correlated and topological physics. However, an in-depth understanding of the temperature-driven electronic states in AV3Sb5 is elusive. Here we use scanning tunneling microscopy to directly capture the rotational symmetry-breaking effect in KV3Sb5. Through both topography and spectroscopic imaging of defect-free KV3Sb5, we observe a charge density wave (CDW) phase transition from an a0 × a0 atomic lattice to a robust 2a0 × 2a0 superlattice upon cooling the sample to 60 K. An individual Sb-atom vacancy in KV3Sb5 further gives rise to the local Friedel oscillation (FO), visible as periodic charge modulations in spectroscopic maps. The rotational symmetry of the FO tends to break at the temperature lower than 40 K. Moreover, the FO intensity shows an obvious competition against the intensity of the CDW. Our results reveal a tantalizing electronic nematicity in KV3Sb5, highlighting the multiorbital correlation in the kagome lattice framework.

20.
Int J Biol Macromol ; 269(Pt 1): 132005, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38777686

ABSTRACT

To enhance the mechanics performance, sensitivity and response range of multi-responsive photonic films, herein, a facile method for fabricating multi-responsive films is demonstrated using the evaporative self-assembly of a mixture of grape skin red (GSR), cellulose nanocrystal (CNC), polyvinyl alcohol (PVA) and deep eutectic solvent (DES). The prepared materials exhibited excellent thermal stability, strain properties, solvent resistance, ultraviolet (UV) resistance and antioxidant activity. Compared to a pure PVA film, the presence of GSR strengthened the antioxidant property of the film by 240.1 % and provided excellent UV barrier capability. The additional cross-linking of DES and CNC promoted more efficient phase fusion, yielding a film strain of 41.5 %. The addition of hydrophilic compound GSR, wetting and swelling due to the DES and the surface inhomogeneity of the films rendered the multi-responsive films high sensitivity, wide response range and multi-cyclic stability in environments with varying pH and humidity. A sample application showed that a PVA/CNC/DES film has the potential to differentiate between fresh, sub-fresh and fully spoiled shrimps. The above results help in designing intelligent thin film materials that integrate antioxidant properties, which help in monitoring the changes in food freshness and food packaging.


Subject(s)
Antioxidants , Cellulose , Nanoparticles , Polyvinyl Alcohol , Polyvinyl Alcohol/chemistry , Cellulose/chemistry , Nanoparticles/chemistry , Antioxidants/chemistry , Deep Eutectic Solvents/chemistry , Food Packaging/methods , Vitis/chemistry , Food Analysis/methods , Hydrogen-Ion Concentration
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