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1.
Neurol Sci ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39271636

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the degeneration of motor neurons and progressive muscle weakness. Heredity plays an important part in the pathogenesis of ALS. Recently, with the emergence of the oligogenic pathogenic mechanism in ALS and the ongoing discovery of new mutated genes and genomic variants, there is an emerging need for larger-scale and more comprehensive genetic screenings in higher resolution. In this study, we performed whole-genome sequencing (WGS) on 34 familial ALS probands lacking the most common disease-causing mutations to explore the genetic landscape of Chinese ALS patients further. Among them, we identified a novel ARPP21 c.1231G > A (p.Glu411Lys) variant and two copy number variations (CNVs) affecting the PFN1 and RBCK1 genes in a patient with ALS-frontotemporal dementia (FTD). This marks the first report of an ARPP21 variant in Chinese ALS-FTD patients, providing fresh evidence for the association between ARPP21 and ALS. Our findings also underscore the potential role of CNVs in ALS-FTD, suggesting that the cumulative effect of multiple rare variants may contribute to disease onset. Furthermore, compared to the averages in our cohort and the reported Chinese ALS population, this patient displayed a shorter survival time and more rapid disease progression, suggesting the possibility of an oligogenic mechanism in disease pathogenesis. Further research will contribute to a deeper understanding of the rare mutations and their interactions, thus advancing our understanding of the genetic mechanisms underlying ALS and ALS-FTD.

2.
Water Res X ; 24: 100246, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39220625

RESUMO

Aquaculture, producing half of global fish production, offers a high-quality protein source for humans. Improving nitrogen use efficiency (NUE) through microbial protein recovery is crucial for increasing fish production and reducing environmental footprint. However, the poor palatability and high moisture content of microbial protein make its utilization challenging. Here, a biofloc-worm reactor was integrated into a recirculating aquaculture system (BW_RAS) for the first time to convert microbial protein into Tubificidae (Oligochaeta) biomass, which was used as direct feed for culturing fish. Batch experiments indicated that an aeration rate of 0.132 m3 L -1 h -1 and a worm density of 0.3 g cm-2 on the carrier were optimal for microbial biomass growth and worm predation, respectively. Compared to the biofloc reactor-based recirculating aquaculture system (B_RAS), the BW_RAS improved water quality, NUE, and fish production by 17.1 % during a 120-day aquaculture period. The abundance of heterotrophic aerobic denitrifier Deinococcus in BW_RAS was one order of magnitude higher than in B_RAS, while heterotrophic bacteria Mycobacterium was more abundant in B_RAS. Denitrifiers cooperated with organic matter degraders and nitrogen assimilation bacteria for protein recovery and gaseous nitrogen loss while competing with predatory bacteria. Function prediction and qPCR indicated greater aerobic respiration, nitrate assimilation, nitrification (AOB-amoA), and denitrification (napA, nirK, nirS, nosZI), but lower fermentation in BWR compared to BR. This study demonstrated that BW_RAS increased microbial protein production and aerobic nitrogen cycling through ongoing worm predation, further enhancing fish production to a commercially viable level.

3.
J Natl Cancer Cent ; 4(3): 249-259, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39281722

RESUMO

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639-0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882-0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60-80%, >40-60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51-0.97) to 0.48 (95% CI, 0.36-0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

4.
BMC Surg ; 24(1): 255, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261821

RESUMO

With the continuous advancements in precision medicine and the relentless pursuit of minimally invasive techniques, Natural Orifice Specimen Extraction Surgery (NOSES) has emerged. Compared to traditional surgical methods, NOSES better embodies the principles of minimally invasive surgery, making scar-free operations possible. In recent years, with the progress of science and technology, Robot-Assisted Laparoscopic Surgery has been widely applied in the treatment of colorectal cancer. Robotic surgical systems, with their clear surgical view and high operational precision, have shown significant advantages in the treatment process. To further improve the therapeutic outcomes for colorectal cancer patients, some scholars have attempted to combine robotic technology with NOSES. However, like traditional open surgery or laparoscopic surgery, the use of the robotic platform presents both advantages and limitations. Therefore, this study reviews the current research status, progress, and controversies regarding Robot-Assisted Laparoscopic Natural Orifice Specimen Extraction Surgery for colorectal cancer, aiming to provide clinicians with more options in the diagnosis and treatment of colorectal cancer.


Assuntos
Neoplasias Colorretais , Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Laparoscopia/métodos , Previsões , Manejo de Espécimes/métodos
5.
J Environ Manage ; 369: 122412, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39236608

RESUMO

Perfluorooctanoic acid (PFOA) as emerging pollutants was largely produced and stable in nature environment. Its fate and effect to the wasted sludge digestion process and corresponding microbial mechanism was rarely reported. This study investigated the different dose of PFOA to the wasted sludge digestion process, where the methane yield and microbial mechanism was illustrated. The PFOA added before digestion were 0-10000 µg/L, no significant variation in daily and accumulated methane production between each group. The 9th day methane yield was significantly higher than other days (p < 0.05). The soluble protein was significantly decreased after 76 days digestion (p < 0.001). The total PFOA in sludge (R2 = 0.8817) and liquid (R2 = 0.9083) phase after digestion was exponentially correlated with PFOA dosed. The PFOA in liquid phase was occupied 54.10 ± 18.38% of the total PFOA in all reactors. The dewatering rate was keep decreasing with the increase of PFOA added (R2 = 0.7748, p < 0.001). The mcrA abundance was significantly correlated with the pH value and organic matter concentration in the reactors. Chloroflexi was the predominant phyla, Aminicenantales, Bellilinea and Candidatus_Cloacimonas were predominant genera in all reactors. Candidatus_Methanofastidiosum and Methanolinea were predominant archaea in all reactors. The function prediction by FAPROTAX and Tax4fun implied that various PFOA dosage resulted in significant function variation. The fermentation and anaerobic chemoheterotrophy function were improved with the PFOA dose. Co-occurrence network implied the potent cooperation among the organic matter degradation and methanogenic microbe in the digestion system. PFOA has little impact to the methane generation while affect the microbe function significantly, its remaining in the digested sludge should be concerned to reduce its potential environmental risks.


Assuntos
Caprilatos , Fluorocarbonos , Metano , Esgotos , Metano/metabolismo , Fluorocarbonos/metabolismo , Anaerobiose , Esgotos/microbiologia , Caprilatos/metabolismo , Reatores Biológicos
6.
Talanta ; 279: 126635, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39089082

RESUMO

Heightened oxidative stress is the principal driver behind the altered metabolism of neurotransmitters within the brains of Parkinson's disease (PD). Hypochlorous acid (HClO), a variant of reactive oxygen species (ROS), plays a crucial role in several lysosomal activities. An irregular concentration of HClO may result in significant molecular damage and contribute to the onset of neurodegenerative disorders. Despite this, the precise role of lysosomal HClO in PD remains unclear, due to its fast reactivity and low levels. This is further complicated by the lack of effective in situ imaging techniques for accurately tracking its dynamics. Therefore, it is of great significance to use effective tools to map the lysosomal HClO during the pathological process of PD. In this study, we propose a fluorogenic probe named Lys-PTZ-HClO for the specific and sensitive detection of HClO. Lys-PTZ-HClO exhibits features like a fast response time (10 s) and a low detection limit (0.72 µM). Benefiting from its superior properties, the probe was used to visualize the basal HClO levels, and the variation of HClO levels in lysosomal of living cells. More importantly, this probe was successfully applied for the first time to reveal increased lysosomal HClO in a cellular model of PD.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Lisossomos , Doença de Parkinson , Ácido Hipocloroso/análise , Ácido Hipocloroso/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Lisossomos/química , Lisossomos/metabolismo , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Imagem Óptica
8.
Curr Protoc ; 4(8): e1122, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39166828

RESUMO

Breast cancer is a prevalent malignancy affecting women worldwide. Currently, there are no precise molecular biomarkers with immense potential for accurately predicting breast cancer development, which limits clinical management options. Recent evidence has highlighted the importance of metastatic and tumor-infiltrating immune cells in modulating the antitumor therapy response. However, the prognostic value of using these features in combination, and their potential for guiding individualized treatment for breast cancer, remains vague. To address this challenge, we recently developed the metastatic and immunogenomic risk score (MIRS), a comprehensive and user-friendly scoring system that leverages advanced bioinformatics methods to facilitate transcriptomics data analysis. To help users become familiar with the MIRS tool and apply it effectively in analyzing new breast cancer datasets, we describe detailed protocols that require no advanced programming skills. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Calculating a MIRS score from transcriptomics data Basic Protocol 2: Predicting clinical outcomes from MIRS scores Basic Protocol 3: Evaluating treatment responses and guiding therapeutic strategies in breast cancer patients Basic Protocol 4: Guidelines for utilizing the MIRS webtool.


Assuntos
Neoplasias da Mama , Redes Neurais de Computação , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Feminino , Prognóstico , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Biologia Computacional/métodos
9.
Int J Surg ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39166963

RESUMO

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has shown satisfactory therapeutic efficacy in unresectable hepatocellular carcinoma (HCC) and is regarded as an important conversion treatment. However, limited information is available regarding the optimal timing of HAIC-based conversion hepatectomy. This study aims to determine the optimal timing for HAIC-based conversion surgery in patients with HCC. METHODS: Data from a retrospective cohort of patients who underwent HAIC-based conversion hepatectomy were reviewed. Oncological outcomes, surgical information, and risk factors were comparatively analyzed. RESULTS: In total, 424 patients with HCC who underwent HAIC-based conversion hepatectomy were included and were divided into responder (n=312) and nonresponder (n=112) groups. The overall survival (OS) and recurrence-free survival (RFS) rates of both the whole responder cohort and patients who achieved a response after 4-6 cycles of HAIC were significantly better than those of the nonresponder cohort. Higher OS and RFS were observed in responders than in nonresponders with advanced-stage HCC. Patients in the responder group had a shorter occlusion duration and less intraoperative blood loss than those in the nonresponder group. There were no significant differences in other surgical information or postoperative complications between the two groups. Tumor response, differentiation, postoperative alpha-fetoprotein level, postoperative protein induced by vitamin K absence or antagonist-II level, age, microvascular invasion, pre-HAIC neutrophil-to-lymphocyte ratio, and preoperative systemic inflammatory response index were independent risk factors for poor long-term survival. CONCLUSIONS: Conversion surgery should be considered when tumor response is achieved. Our findings may be useful in guiding surgeons and patients in decision-making regarding HAIC-based conversion hepatectomy.

10.
Acc Chem Res ; 57(16): 2234-2244, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39115809

RESUMO

ConspectusThe origin of the single chirality of the chemical building blocks of life remains an intriguing topic of research, even after decades of experimental and theoretical work proposing processes that may break symmetry and induce chiral amplification, a term that may be defined as the enhancement of enantiomeric excess starting from prochiral substrates or from a racemic mixture or a small imbalance between enantiomers. Studies aimed at understanding prebiotically plausible pathways to these molecules have often neglected the issue of chirality, with a focus on the stereochemical direction of these reactions generally being pursued after reaction discovery. Our work has explored how the stereochemical outcome for the synthesis of amino acids and sugars might be guided to rationalize the origin of biological homochirality. The mechanistic interconnection between enantioenrichment in these two groups of molecules provides insights concerning the handedness extant in modern biology. In five separate examples involving the synthesis of life's building blocks, including sugars, RNA precursors, amino acids, and peptides, kinetic resolution emerges as a key protocol for enantioenrichment from racemic molecules directed by chiral source molecules. Several of these examples involve means not only for chiral amplification but also symmetry breaking and chirality transfer across a range of racemic monomer molecules. Several important implications emerge from these studies: one, kinetic resolution of the primordial chiral sugar, glyceraldehyde, plays a key role in a number of different prebiotically plausible reactions; two, the emergence of homochirality in sugars and amino acids is inherently intertwined, with clear synergy between the biological hand of each molecule class; three, the origin story for the homochirality of enzymes and modern metabolism points toward kinetic resolution of racemic amino acids in networks that later evolved to include sophisticated and complete catalytic and co-catalytic cycles; four, a preference for heterochiral ligation forming product molecules that cannot lead to biologically competent polymers can in fact be a driving force for a route to homochiral polymer chains; and five, enantioenrichment in complex mixtures need not be addressed one compound at a time, because kinetic resolution induces symmetry breaking and chirality transfer that may lead to general protocols rather than specific cases tailored to each individual molecule. Such chirality transfer mechanisms perhaps presage strategies utilized in modern biology.Our latest work extends the study of monomer enantioenrichment to the ligation of these molecules into the extended homochiral chains leading to the complex polymers of modern biology. A central theme in all of these reactions is the key role that kinetic resolution of a racemic mixture of amino acids or sugars plays in enabling enantioenrichment under prebiotically plausible conditions. This work has uncovered important trends in symmetry breaking, chirality transfer, and chiral amplification. Kinetic resolution of racemic mixtures emerges as a general solution for chiral amplification in prebiotic chemistry, leading to the single chirality of complex biological molecules and genetic polymers.


Assuntos
Aminoácidos , Estereoisomerismo , Cinética , Aminoácidos/química , Peptídeos/química , Peptídeos/síntese química , Prebióticos , Origem da Vida , Açúcares/química , RNA/química
11.
Cell Commun Signal ; 22(1): 400, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143467

RESUMO

A comprehensive understanding of the intricate cellular and molecular changes governing the complex interactions between cells within acne lesions is currently lacking. Herein, we analyzed early papules from six subjects with active acne vulgaris, utilizing single-cell and high-resolution spatial RNA sequencing. We observed significant changes in signaling pathways across seven different cell types when comparing lesional skin samples (LSS) to healthy skin samples (HSS). Using CellChat, we constructed an atlas of signaling pathways for the HSS, identifying key signal distributions and cell-specific genes within individual clusters. Further, our comparative analysis revealed changes in 49 signaling pathways across all cell clusters in the LSS- 4 exhibited decreased activity, whereas 45 were upregulated, suggesting that acne significantly alters cellular dynamics. We identified ten molecules, including GRN, IL-13RA1 and SDC1 that were consistently altered in all donors. Subsequently, we focused on the function of GRN and IL-13RA1 in TREM2 macrophages and keratinocytes as these cells participate in inflammation and hyperkeratinization in the early stages of acne development. We evaluated their function in TREM2 macrophages and the HaCaT cell line. We found that GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5, and CXCL2 in TREM2 macrophages. Additionally, the activation of IL-13RA1 by IL-13 in HaCaT cells promoted the dysregulation of genes associated with hyperkeratinization, including KRT17, KRT16, and FLG. These findings suggest that modulating the GRN-SORT1 and IL-13-IL-13RA1 signaling pathways could be a promising approach for developing new acne treatments.


Assuntos
Acne Vulgar , Pele , Humanos , Acne Vulgar/genética , Acne Vulgar/patologia , Acne Vulgar/metabolismo , Pele/patologia , Pele/metabolismo , Transdução de Sinais/genética , Masculino , Macrófagos/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Subunidade alfa1 de Receptor de Interleucina-13/genética , Subunidade alfa1 de Receptor de Interleucina-13/metabolismo , Feminino
12.
ACS Appl Mater Interfaces ; 16(34): 44927-44937, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39152899

RESUMO

Carbon molecular sieve (CMS) membranes have emerged as attractive gas membranes due to their tunable pore structure and consequently high gas separation performances. In particular, polyimides (PIs) have been considered as promising CMS precursors because of their tunable structure, superior gas separation performance, and excellent thermal and mechanical strength. In the present work, polyphosphoric acid (PPA) was employed as both cross-linker and porogen, it created pores within the PI polymeric matrix, while it also effectively acting as a cross-linker to regulate the ultramicropores of the CMS membranes, thus simultaneously improving both permeability and selectivity of the CMS membranes. By employing PI/PPA hybrid with PPA content of 5 wt % as a precursor, the obtained CMS membrane exhibited a CO2 and He permeability of 1378.3 Barrer and 1431.4 Barrer, respectively, which was an approximately 10-fold increase compared to the precursor membrane. Under optimized conditions, the CO2/CH4 and He/CH4 selectivity of the obtained CMS membrane reached 81.5 and 89.9, respectively, which was 278% and 307% higher than that of the pristine PI membrane. In addition, the membrane exhibited good long-term stability during a one-week continuous test. This study clearly denoted PPA can be used for precisely tailoring the ultramicroporosity of CMS membranes.

13.
J Invest Dermatol ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39182560

RESUMO

A precise regulation of gene expression depends on the accuracy of the 3-dimensional (3D) structure of chromatin; however, the effects of the 3D genome on gene expression in psoriasis remain unknown. In this study, we conducted Hi-C and RNA sequencing on CD4+ T cells collected from 5 patients with psoriasis and 3 healthy controls and constructed a comprehensive 3D chromatin interaction map to delineate the genomic hierarchies, including A/B compartments, topologically associated domains, and chromatin loops. Then, the specific superenhancers related to psoriasis were identified by Hi-C and H3K27ac chromatin immunoprecipitation sequencing data. Subsequently, comprehensive analyses were carried out on the differentially expressed genes that are associated with altered topologically associated domains, loops, and superenhancers in psoriasis. Finally, we screened the candidate target genes and examined the potential functional SNP in psoriasis affected by disruptions of the spatial organization. This study provides a comprehensive reference for examining the 3D genome interactions in psoriasis and elucidating the interplay between spatial organization disruption and gene regulation. We hope that our findings can help clarify the mechanisms underlying the pathogenesis of psoriasis and shed light on the role of 3D genomic structure, therefore informing potential therapeutic approaches.

14.
J Hazard Mater ; 479: 135602, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39191010

RESUMO

Freshwater rivers are hotspots of N2O greenhouse gas emissions. Dissolved organic carbon (DOC) is the dominant electron donor for microbial N2O reduction, which can reduce N2O emission through enriching high N2O affinity denitrifiers or enriching non-denitrifying N2O-reducing bacteria (N2ORB), but the primary regulatory pathway remains unclear. Here, field study indicated that high DOC concentration in rivers enhanced denitrification rate but reduced N2O flux by improving nosZ gene abundance. Then, four N2O-fed membrane aeration biofilm reactors inoculated with river sediments from river channel, estuary, adjacent lake, and a mixture were continuously performed for 360 days, including low, high, and mixed DOC stages. During enrichment stages, the (nirS+nirK)/nosZ ratio showed no significant difference, but the community structure of denitrifiers and N2ORB changed significantly (p < 0.05). In addition, N2ORB strains isolated from different enrichment stages positioned in different branches of the phylogenetic tree. N2ORB strains isolated during high DOC stage showed significant higher maximum N2O-reducing capability (Vmax: 0.6 ± 0.4 ×10-4 pmol h-1 cell-1) and N2O affinity (a0: 7.8 ± 7.7 ×10-12 L cell-1 h-1) than strains isolated during low (Vmax: 0.1 ± 0.1 ×10-4 pmol h-1 cell-1, a0: 0.7 ± 0.4 ×10-12 L cell-1 h-1) and mixed DOC stages (Vmax: 0.1 ± 0.1 ×10-4 pmol h-1 cell-1, a0: 0.9 ± 0.9 ×10-12 L cell-1 h-1) (p < 0.05). Hence, under high DOC concentration conditions, the primary factor in reducing N2O emissions in rivers is the enrichment of complete denitrifiers with high N2O affinity, rather than non-denitrifying N2ORB.


Assuntos
Bactérias , Desnitrificação , Óxido Nitroso , Rios , Óxido Nitroso/metabolismo , Óxido Nitroso/análise , Rios/microbiologia , Rios/química , Bactérias/metabolismo , Bactérias/genética , Sedimentos Geológicos/microbiologia , Reatores Biológicos/microbiologia , Filogenia , Biofilmes , Carbono/metabolismo , Carbono/química , Oxirredução
15.
Talanta ; 278: 126506, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38968659

RESUMO

Diabetes, as a metabolic disorder, has been implicated in organ dysfunction, often correlated with aberrant changes in viscosity. Lysosomal viscosity serves as an indicator of the lysosome's condition and activity, as it always varies synchronously with the change of lysosome's positioning, structure, and internal constituents. Diabetes, a condition within the metabolic disease category, has the potential to disrupt organ function due to irregular changes in viscosity. Therefore, early and precise diagnosis of diabetes is crucial for the prevention and management of diabetic conditions. Understanding the correlation between viscosity variations and lysosomal changes in vivo is vitally important for researching associated diseases. In this study, we developed Lyso-V, a near-infrared (NIR) fluorescent probe targeting lysosomes, with ultrasensitivity to viscosity changes. This probe, designed with a donor-π-bridge-acceptor (D-π-A) structure, exhibits a significant increase in NIR fluorescence intensity (approximately 690 times) when responding to viscosity, due to a twisted intramolecular charge transfer (TICT) mechanism. Furthermore, the probe designed specifically for lysosomes, enables the detection of changes in lysosomal viscosity as well as autophagy processes. Notably, through the application of this probe, we have detected an increased viscosity within the pathological model of the diabetic mouse. Moreover, Lyso-V was employed to measure the viscosity in diabetic mice. Owing to the multifaceted nature of the Lyso-V probe, it is anticipated to act as a practical and potent resource for deepening our understanding of the pathophysiological aspects of diabetes and aiding in its early detection.


Assuntos
Diabetes Mellitus Experimental , Corantes Fluorescentes , Lisossomos , Lisossomos/química , Lisossomos/metabolismo , Animais , Corantes Fluorescentes/química , Viscosidade , Camundongos , Humanos , Masculino , Raios Infravermelhos , Imagem Óptica
16.
Virology ; 597: 110142, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38959723

RESUMO

OBJECTIVES: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. METHODS: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. RESULTS: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. CONCLUSIONS: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.


Assuntos
Anticorpos Antivirais , COVID-19 , Imunoglobulina G , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Reinfecção , SARS-CoV-2 , Humanos , Masculino , Feminino , Anticorpos Antivirais/sangue , COVID-19/imunologia , COVID-19/virologia , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/genética , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Fatores de Risco , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/virologia , Reinfecção/imunologia , Reinfecção/virologia , Adulto , Imunoglobulina G/sangue , Idoso , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunidade Humoral , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem
17.
Sci China Life Sci ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38987431

RESUMO

Winter plants rely on vernalization, a crucial process for adapting to cold conditions and ensuring successful reproduction. However, understanding the role of histone modifications in guiding the vernalization process in winter wheat remains limited. In this study, we investigated the transcriptome and chromatin dynamics in the shoot apex throughout the life cycle of winter wheat in the field. Two core histone modifications, H3K27me3 and H3K36me3, exhibited opposite patterns on the key vernalization gene VERNALIZATION1 (VRN1), correlating with its induction during cold exposure. Moreover, the H3K36me3 level remained high at VRN1 after cold exposure, which may maintain its active state. Mutations in FERTILIZATION-INDEPENDENT ENDOSPERM (TaFIE) and SET DOMAIN GROUP 8/EARLY FLOWERING IN SHORT DAYS (TaSDG8/TaEFS), components of the writer complex for H3K27me3 and H3K36me3, respectively, affected flowering time. Intriguingly, VRN1 lost its high expression after the cold exposure memory in the absence of H3K36me3. During embryo development, VRN1 was silenced with the removal of active histone modifications in both winter and spring wheat, with selective restoration of H3K27me3 in winter wheat. The mutant of Tafie-cr-87, a component of H3K27me3 "writer" complex, did not influence the silence of VRN1 during embryo development, but rather attenuated the cold exposure requirement of winter wheat. Integrating gene expression with H3K27me3 and H3K36me3 patterns identified potential regulators of flowering. This study unveils distinct roles of H3K27me3 and H3K36me3 in controlling vernalization response, maintenance, and resetting in winter wheat.

19.
Materials (Basel) ; 17(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998223

RESUMO

In the laboratory study of alkali-silica reaction (ASR), models attempt to predict the service life of concrete due to ASR by correlating the performance of concrete at high and low temperatures. However, the consequences of elevating temperature are not so encouraging. In this paper, the influence of temperature on the expansion of 2-graded concrete and 3-graded concrete caused by ASR was investigated by curing the concrete under different temperatures ranging from 40 °C to 80 °C. Increased temperature resulted in rapid expansion at the early stages, but the expansion rate of concrete prisms cured at the higher temperatures (70 °C and 80 °C) was slowed down at the later stages, and concrete prisms cured at 50 °C or 60 °C showed the highest expansions during the experimental period. The chemical analysis results of the pore solution expressed from the concrete show that the ASR expansion is significantly influenced by the [OH-]: the decrease in [OH-] leads to the retardation of the ASR expansion. The decrease in [OH-] is attributed to the consumption of OH- ions for the alkali-silica reaction and the decrease in activity of NaOH(aq) influenced by the temperature. For large cross-section specimens, the OH- within the concrete for alkali-silica reactions cannot be effectively compensated by the external alkali solution. In the accelerated test to evaluate ASR for large cross-section specimens, a curing temperature of less than 60 °C is suggested. This study provides critical insights into the temperature dependency of ASR expansion of concrete, offering a curing temperature range for developing predictive models of ASR expansion under varied environmental conditions.

20.
Materials (Basel) ; 17(14)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39063708

RESUMO

In this paper, the effect of waste rock-wool dosage on the workability, mechanical strength, abrasion resistance, toughness and hydration products of PVA and steel fiber-reinforced mortars was investigated. The results showed that the fluidity of the mortar gradually decreased with the increase in the dosage of waste rock wool, with a maximum reduction of 10% at a dosage of 20%. The higher the dosage of waste rock wool, the greater the reduction in compressive strength. The effect of waste rock wool on strength reduction decreases with increasing age. When the dosage of waste rock wool was 10%, the 28 days of flexural and compressive strengths were reduced by 4.73% and 10.59%, respectively. As the dosage of waste rock wool increased, the flexural-to-compressive ratio increased, and at 20%, the maximum value of 28 days of flexural-to-compressive ratio was 0.210, which was increased by 28.05%. At a 5% dosage, the abraded volume was reduced from 500 mm3 to 376 mm3-a reduction of 24.8%. Waste rock wool only affects the hydration process and does not cause a change in the type of hydration products. It promotes the hydration of the cementitious material system at low dosages and exhibits an inhibitory effect at high dosages.

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