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1.
Photodiagnosis Photodyn Ther ; : 104267, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39009205

RESUMO

OBJECTIVE: To evaluate the effectiveness of low-level red light (LRL) in controlling the progression of myopia in children and adolescents. METHODS: A randomized controlled trial was conducted from March 2022 to June 2022 at the Xuzhou First People's Hospital. A total of 73 children and adolescents with myopia, between the ages of 6 and 14, and meeting the inclusion criteria, were randomly divided into two groups. The experimental group wore single vision spectacles with LRL intervention, while the control group wore single vision spectacles alone. Spherical equivalent refraction (SER), axial length (AL), subfoveal choroidal thickness (SFCT), and best-corrected visual acuity (BCVA) were measured for the participants. Data analysis was performed using chi-square test, independent samples t-test, and Mann-Whitney U test. To compare the changes in SER and AL between groups, we utilized the Generalized Estimating Equations (GEE) model. RESULTS: The experimental group was composed of 36 individuals, while the control group had 37. The mean age of the participants was 8.9 ± 2.0 years. No statistically significant distinctions in SER, AL and SFCT were observed between the two groups at baseline (P > 0.05). After 6 months of intervention, the experimental group's increase in SER (-0.01D; 95% CI: -0.09, 0.06) was higher than that of the control group (-0.41D; 95% CI: -0.51, -0.32), with a significance level of P < 0.001. Furthermore, the changes over time revealed significant differences between the two groups (Wald χ2group×time: 31.576, P < 0.001). The experimental group's AL increase (-0.02mm; 95% CI: -0.07, 0.03) was less than the control group's (0.22mm; 95% CI: 0.19, 0.25) (P < 0.001), with a significant difference over time between them (wald χ2group×time: 62.305, P < 0.001). SFCT change after 6 months in the experimental group was significantly greater (29.19µm; 95% CI: 18.48, 39.91) compared to that of the control group (-6.59µm; 95% CI: -14.28, 1.09) (P < 0.001). No adverse events were observed, and there was no evidence of fundus structural damage on OCT imaging. CONCLUSIONS: The findings suggest that low-level red light can effectively control myopia progression in children and adolescents within 6 months. No adverse reactions were observed.

2.
PLoS One ; 19(7): e0301811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39024248

RESUMO

BACKGROUND: Recent studies have demonstrated the relevance of circulating factors in the occurrence and development of colorectal cancer (CRC); however, the causal relationship remains unclear. METHODS: Summary-level data for CRC were obtained from the UK Biobank (5,657 cases and 372,016 controls), FinnGen cohort (3,022 cases and 215,770 controls), and BioBank Japan Project (BBJ, 7,062 cases and 195,745 controls). Thirty-two peripheral markers with consistent definitions were collected from the three biobanks. Mendelian randomization (MR) was used to evaluate the causal effect of circulating factors on CRC. The effects from the three consortiums were combined using trans-ancestry meta-analysis methods. RESULTS: Our analysis provided compelling evidence for the causal association of higher genetically predicted eosinophil cell count (EOS, odds ratio [OR], 0.8639; 95% confidence interval [CI] 0.7922-0.9421) and red cell distribution width (RDW, OR, 0.9981; 95% CI, 0.9972-0.9989) levels with a decreased risk of CRC. Additionally, we found suggestive evidence indicating that higher levels of total cholesterol (TC, OR, 1.0022; 95% CI, 1.0002-1.0042) may increase the risk of CRC. Conversely, higher levels of platelet count (PLT, OR, 0.9984; 95% CI, 0.9972-0.9996), total protein (TP, OR, 0.9445; 95% CI, 0.9037-0.9872), and C-reactive protein (CRP, OR, 0.9991; 95% CI, 0.9983-0.9999) may confer a protective effect against CRC. Moreover, we identified six ancestry-specific causal factors, indicating the necessity of considering patients' ancestry backgrounds before formulating prevention strategies. CONCLUSIONS: MR findings support the independent causal roles of circulating factors in CRC, which might provide a deeper insight into early detection of CRC and supply potential preventative strategies.


Assuntos
Neoplasias Colorretais , Análise da Randomização Mendeliana , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Masculino , Feminino , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Japão/epidemiologia , Fatores de Risco
3.
Nucleic Acids Res ; 52(W1): W248-W255, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38738636

RESUMO

Knowledge of protein function is essential for elucidating disease mechanisms and discovering new drug targets. However, there is a widening gap between the exponential growth of protein sequences and their limited function annotations. In our prior studies, we have developed a series of methods including GraphPPIS, GraphSite, LMetalSite and SPROF-GO for protein function annotations at residue or protein level. To further enhance their applicability and performance, we now present GPSFun, a versatile web server for Geometry-aware Protein Sequence Function annotations, which equips our previous tools with language models and geometric deep learning. Specifically, GPSFun employs large language models to efficiently predict 3D conformations of the input protein sequences and extract informative sequence embeddings. Subsequently, geometric graph neural networks are utilized to capture the sequence and structure patterns in the protein graphs, facilitating various downstream predictions including protein-ligand binding sites, gene ontologies, subcellular locations and protein solubility. Notably, GPSFun achieves superior performance to state-of-the-art methods across diverse tasks without requiring multiple sequence alignments or experimental protein structures. GPSFun is freely available to all users at https://bio-web1.nscc-gz.cn/app/GPSFun with user-friendly interfaces and rich visualizations.


Assuntos
Proteínas , Software , Proteínas/química , Proteínas/metabolismo , Conformação Proteica , Análise de Sequência de Proteína , Aprendizado Profundo , Sítios de Ligação , Anotação de Sequência Molecular , Redes Neurais de Computação , Sequência de Aminoácidos , Humanos , Internet
4.
Cell Rep Med ; 5(6): 101580, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38776913

RESUMO

Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Imunoterapia Adotiva , Células Matadoras Naturais , Leucemia Mieloide Aguda , Sulfonamidas , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Humanos , Sulfonamidas/farmacologia , Animais , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Camundongos , Imunoterapia Adotiva/métodos , Linhagem Celular Tumoral , NF-kappa B/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos Endogâmicos NOD
5.
Mol Carcinog ; 63(8): 1611-1620, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38780147

RESUMO

Sulforaphane (SFN) exerts anticancer effect on various cancers including gastric cancer. However, the regulatory effect of SFN on programmed death-ligand 1 (PD-L1) and checkpoint blockade therapy in gastric cancer have not been elucidated. Here we demonstrated that SFN suppressed gastric cancer cell growth both in vitro and in vivo study. SFN upregulated PD-L1 expression through activating ΔNP63α in gastric cancer cells. Further, we found that SFN impaired the anticancer effect of anti-PD-L1 monoclonal antibody (α-PD-L1 mab) on gastric cancer cells. These results uncover a novel PD-L1 regulatory mechanism and the double-edged role of SFN in gastric cancer intervention.


Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Isotiocianatos , Neoplasias Gástricas , Sulfóxidos , Fatores de Transcrição , Isotiocianatos/farmacologia , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Antígeno B7-H1/metabolismo , Sulfóxidos/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Animais , Camundongos , Linhagem Celular Tumoral , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus
6.
Food Chem X ; 22: 101341, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38586222

RESUMO

In this study, the improvement mechanism of low-frequency alternating magnetic field (LF-AMF, 5 mT, 3 h) combined with calcium chloride (CaCl2, 0-100 mM) on the gel characteristics of low-salt myofibrillar protein (MP) was investigated. LF-AMF combined with 80 mM CaCl2 treatment increased solubility (32.71%), surface hydrophobicity (40.86 µg), active sulfhydryl content (22.57%), water-holding capacity (7.15%). Besides, the combined treatment decreased turbidity, particle size and intrinsic fluorescence strength of MP. Fourier transform infrared spectroscopy (FT-IR) results indicated that the combined treatment altered the secondary structure of MP by increasing ß-sheet and ß-turn, and reducing α-helix and random coil. The combined treatment also induced a high G' value and shortened T2 relaxation time for forming a homogeneous and compact gel structure. These results revealed that LF-AMF combined CaCl2 treatment could as a potential approach for modifying the gel characteristics of low-salt MP.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38607219

RESUMO

Background: Ropivacaine (Ropi) is a widely utilized anesthetic in cesarean sections (CS), however its optimal dosage remains controversial. Objective: To assess the efficacy and safety of varying doses (10mg, 5mg, 4mg, and 3mg) of Ropi in subarachnoid block (SA) for CS. Methods: A prospective cohort study was conducted, and a total of 74 pregnant women undergoing CS at Nantong Maternal and Child Health Care Hospital between January and June 2023 were selected as the study population. Participants were stratified into groups based on Ropivacaine dosage: Group A (10 mg, n=18), Group B (5 mg, n=26), Group C (4 mg, n=15), and Group D (3 mg, n=15). The total Ropivacaine dosage administered via SA was consistently 10 mg across all groups. We measured anesthetic efficacy, safety profiles, abdominal wall muscle relaxation, pre- and post-anesthesia stress and inflammatory responses before and after anesthesia and compared among the four groups. Results: Group A exhibited the shortest onset time for block initiation and longest recovery duration (P < .05). Group D displayed the highest incidence of patients requiring additional anesthetics and experiencing adverse reactions, whereas the utilization rate of vasopressors was most pronounced in Group A (P < .05). Notably, Group D reported the lowest satisfaction rate regarding abdominal wall muscle relaxation (P < .05). Stress responses were significantly lower in Groups A, B, and C compared to Group D, while the levels of inflammatory factors in Groups B and C were higher than those in Group A but lower than those in Group D (P < .05). Conclusions: Administration of 4 mg hyperbaric Ropi in SA can achieve an optimal anesthesia effect in CS with a high level of safety, along with inducing mild abdominal wall muscle relaxation and attenuating stress and inflammatory responses pre- and post-anesthesia. Thus, it is recommended for clinical application.

8.
J Cell Mol Med ; 28(8): e18256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38527290

RESUMO

Acute myeloid leukaemia (AML) is a prevalent haematological malignancy in which various immune and stromal cells in the bone marrow microenvironment have instrumental roles and substantially influence its progression. KIR2DL is a member of the immunoglobulin-like receptor family and a natural killer (NK) cell surface-specific receptor. However, its impact on immune infiltration regarding AML has not been addressed. We aimed to explore molecular markers associated with the immune microenvironment and prognosis of AML with a particular focus on KIR2DL family members. Analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases revealed that KIR2DL1, KIR2DL3 and KIR2DL4 expression were significantly upregulated in AML and associated with decreased overall survival (OS). Moreover, univariate Cox analysis implicated KIR2DL genes as independent prognostic markers of OS. Functional enrichment analysis revealed that KIR2DL genes were associated with immune cells, the immune microenvironment and NK cell-mediated cytotoxicity. Additionally, immune infiltration analyses revealed that KIR2DL upregulation was associated with stronger immune infiltration. Finally, we performed drug sensitivity profiling of KIR2DL genes using the Cellminer database. Collectively, our findings suggest that KIR2DL1, KIR2DL3 and KIR2DL4 have critical roles in AML and may represent novel biomarker genes for disease prognosis and immune infiltration.


Assuntos
Leucemia Mieloide Aguda , Humanos , Prognóstico , Leucemia Mieloide Aguda/patologia , Medula Óssea/patologia , Microambiente Tumoral/genética
9.
Sci Total Environ ; 927: 172002, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547986

RESUMO

The Yellow River, renowned as the most sediment-laden river globally, grapples with sediment deposition issues compromising reservoir functionality and elevating downstream riverbeds, posing threats to human life and property safety. In response, the Water-Sediment Regulation Scheme (WSRS) has been innovatively implemented to address these challenges. While effectively mitigating sediment deposition, WSRS has concurrently disrupted the equilibrium of the estuarine ecosystem. This paper addresses the understudied but crucial topic of the interannual impact of WSRS on the estuarine ecosystem. Drawing upon physical, chemical, and biological data gathered through field surveys conducted before, during, and after WSRS from 2011 to 2022, the analysis delves into the interannual changes in the estuarine environment, fish eggs and larvae abundance, and species diversity under the influence of WSRS. The findings reveal an interannual decreasing trend in terrestrial material input due to WSRS, juxtaposed with an interannual increasing trend in fish eggs and larvae around the estuary, as well as the species diversity index. Notably, these trends became more pronounced post-2014. Compared to pre-2014, nutrient concentrations experienced a ~20 % decrease, chlorophyll-a concentration increased by 44 %, fish eggs proliferated approximately 1 time, and the species diversity index transitioned from a declining trend to an ascending trajectory. After 12 years of continuous WSRS implementation, the impact on the estuarine ecosystem has demonstrably diminished. This research aims to furnish reference experience and scientific basis for water and sediment regulation in major rivers around the world in terms of estuarine ecology.


Assuntos
Ecossistema , Monitoramento Ambiental , Estuários , Sedimentos Geológicos , Rios , Rios/química , Sedimentos Geológicos/química , Animais , Peixes , China , Biodiversidade
10.
Acta Biomater ; 177: 37-49, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364928

RESUMO

Inflammatory bowel disease (IBD) is a gastrointestinal immune disease that requires clear diagnosis, timely treatment, and lifelong monitoring. The diagnosis and monitoring methods of IBD mainly include endoscopy, imaging examination, and laboratory examination, which are constantly developed to achieve early definite diagnosis and accurate monitoring. In recent years, with the development of nanotechnology, the diagnosis and monitoring methods of IBD have been remarkably enriched. Nanomaterials, characterized by their minuscule dimensions that can be tailored, along with their distinctive optical, magnetic, and biodistribution properties, have emerged as valuable contrast agents for imaging and targeted agents for endoscopy. Through both active and passive targeting mechanisms, nanoparticles accumulate at the site of inflammation, thereby enhancing IBD detection. This review comprehensively outlines the existing IBD detection techniques, expounds upon the utilization of nanoparticles in IBD detection and diagnosis, and offers insights into the future potential of in vitro diagnostics. STATEMENT OF SIGNIFICANCE: Due to their small size and unique physical and chemical properties, nanomaterials are widely used in the biological and medical fields. In the area of oncology and inflammatory disease, an increasing number of nanomaterials are being developed for diagnostics and drug delivery. Here, we focus on inflammatory bowel disease, an autoimmune inflammatory disease that requires early diagnosis and lifelong monitoring. Nanomaterials can be used as contrast agents to visualize areas of inflammation by actively or passively targeting them through the intestinal mucosal epithelium where gaps exist due to inflammation stimulation. In this article, we summarize the utilization of nanoparticles in inflammatory bowel disease detection and diagnosis, and offers insights into the future potential of in vitro diagnostics.


Assuntos
Meios de Contraste , Doenças Inflamatórias Intestinais , Humanos , Distribuição Tecidual , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal , Inflamação
11.
Chem Biodivers ; 21(3): e202400017, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321767

RESUMO

Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1 µM, AChE activity with IC50 value of 6.9 µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6 µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.


Assuntos
Alcaloides , Fritillaria , Fritillaria/química , Alcaloides/farmacologia , Alcaloides/química
12.
J Proteomics ; 296: 105107, 2024 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-38325729

RESUMO

To explore the effect of feeding fermented distiller's grains (FDG) diets on spleen and mesenteric lymph nodes (MLN) immune status and metabolomics in finishing cattle, eighteen Guanling crossbred cattle (18 months old, 250.0 ± 25 kg) were randomly divided into 3 groups: a basal diet (Control) group, an FDG-15% group, and an FDG-30% group (containing 0%, 15% and 30% FDG to partially replace the concentrates, respectively). After 75 days, the spleens and MLN were collected for detection of relative spleen weight, immune parameters, and metabolomic analysis. Compared with the Control group, FDG-30% group significantly increased (P<0.05) the relative spleen weight. In addition, the level of IL-17A in the spleen of the FDG-30% group was significantly higher than that of the FDG-15% group. Metabolomic analysis showed that differential metabolites (VIP>1, P<0.05) of spleen and MLN in FDG-15% and FDG-30% groups are mostly lipids and lipid molecules. KEGG analysis illustrated that choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance were metabolic pathways in spleen shared by FDG-15% group vs.Control group and FDG-30% group vs.Control group, and choline metabolism in cancer was a metabolic pathway in MLN shared by FDG-15% group vs.Control group and FDG-30% group vs.Control group. These results suggest that feeding FDG may promote spleen development by regulating choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance. Additionally, it may affect MLN development by regulating choline metabolism in cancer. SIGNIFICANCE: Fermented distiller's grains (FDG) is a high quality alternative to feed because it is rich in beneficial microorganisms and nutrients. The spleen and mesenteric lymph nodes (MLN) are important peripheral immune organs in animals, whose status reflects the health of the animal. However, there are few reports on the effect of feeding FDG diets on spleen and MLN immune status and metabolomics in domestic animals. In this study, we found that feeding FDG may promote spleen development by regulating choline metabolism in cancer, glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and insulin resistance metabolic pathways, and may affect MLN development by regulating choline metabolism in cancer. This study extends our understanding of the metabolomics of the spleen and MLN in FDG and helps to further understand of the immunomodulatory effects of the FDG diet.


Assuntos
Resistência à Insulina , Neoplasias , Bovinos , Animais , Baço , Fluordesoxiglucose F18 , Ração Animal/análise , Dieta/veterinária , Ácidos Graxos Insaturados , Linfonodos , Glicerofosfolipídeos , Colina
13.
Sensors (Basel) ; 24(4)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38400355

RESUMO

The frequent occurrence of extreme climate events has a significant impact on people's lives. Heavy rainfall can lead to an increase of regional Terrestrial Water Storage (TWS), which will cause land subsidence due to the influence of hydrological load. At present, regional TWS is mostly obtained from Gravity Recovery and Climate Experiment (GRACE) data, but the method has limitations for small areas. This paper used water level and flow data as hydrological signals to study the land subsidence caused by heavy rainfall in the Chaohu Lake area of East China (June 2016-August 2016). Pearson's correlation coefficient was used to study the interconnection between water resource changes and Global Navigation Satellites System (GNSS) vertical displacement. Meanwhile, to address the reliability of the research results, combined with the Coefficient of determination method, the research findings were validated by using different institutional models. The results showed that: (1) During heavy rainfall, the vertical displacement caused by atmospheric load was larger than non-tidal oceanic load, and the influence trends of the two were opposite. (2) The rapidly increasing hydrologic load in the Chaohu Lake area resulted in greater subsidence displacement at the closer CORS station (CHCH station) than the more distant CORS station (LALA station). The Pearson correlation coefficients between the vertical displacement and water level were as high as -0.80 and -0.64, respectively. The phenomenon confirmed the elastic deformation principle of disc load. (3) Although there was a systematic bias between the different environmental load deformation models, the deformation trends were generally consistent with the GNSS monitoring results. The average Coefficients of determination between the different models and the GNSS results were 0.63 and 0.77, respectively. The results demonstrated the effectiveness of GNSS in monitoring short-term hydrological load. This study reveals the spatial-temporal evolution of land deformation during heavy rainfall around Chaohu Lake, which is of reference significance for water resource management and infrastructure maintenance in this area.

14.
BMC Med Genomics ; 17(1): 34, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267993

RESUMO

INTRODUCTION: Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians. METHODS: A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis. RESULTS: No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features. CONCLUSION: This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.


Assuntos
Doença de Dent , Adulto , Feminino , Humanos , Gravidez , Aberrações Cromossômicas , Cromossomos Humanos X , Testes Genéticos , Diagnóstico Pré-Natal
15.
Environ Sci Pollut Res Int ; 31(6): 8677-8688, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38180659

RESUMO

Transboundary water pollution induced by inter-regional trade is a complex and challenging issue due to the multiple jurisdictions involved. This study combined water pollution discharge inventory, multi-regional input-output analysis, discharge responsibility-sharing, and ecological compensation model to advance the collaborative control of water pollution embodied in China's inter-provincial trade. Over a fifth of China's water pollution discharges in 2017, equivalent to 1376 Kt, were a result of inter-provincial trade, which primarily flowed from wealthier coastal provinces to less developed ones. Moreover, the analysis demonstrates a mismatch between economic gains and environmental costs. In particular, Jiangxi and Guangxi bear the greatest environmental impact (64 and 58 Kt, respectively) while only receiving meager economic returns (131 and 80 billion Yuan). The economic benefit shared responsibility results for the great majority of provinces fell between production- and consumption-based discharges, and this compromise-based allocation of responsibility is more likely to gain acceptance across various regions. Provinces such as Shanghai, Jiangsu, and Beijing necessitate the highest compensation volumes to others, with 31 Kt, 25 Kt, and 20 Kt, respectively, while provinces including Guangxi, Jiangxi, and Ningxia require the largest inflows of compensation, totaling 26 Kt, 23 Kt, and 18 Kt, respectively. The compensation outcomes ensure that less developed regions, bearing a greater pollution burden, receive compensation from more developed regions with lower pollution burdens. The compensation values aligned with compensation volumes, with a few exceptions driven by variations in shadow prices of water pollution. Our study sheds light on the inter-provincial water pollution burdens and benefits and provides a quantitative basis for optimizing the responsibility-sharing and compensation strategies in China, thereby promoting regional cooperation on water pollution control.


Assuntos
Conservação dos Recursos Naturais , Poluição da Água , China , Pequim , Modelos Teóricos
16.
Oncogene ; 43(9): 682-692, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216672

RESUMO

Hepatocellular carcinoma (HCC) stands as the fifth most prevalent malignant tumor on a global scale and presents as the second leading cause of cancer-related mortality. DNA damage-based radiotherapy (RT) plays a pivotal role in the treatment of HCC. Nevertheless, radioresistance remains a primary factor contributing to the failure of radiation therapy in HCC patients. In this study, we investigated the functional role of transketolase (TKT) in the repair of DNA double-strand breaks (DSBs) in HCC. Our research unveiled that TKT is involved in DSB repair, and its depletion significantly reduces both non-homologous end joining (NHEJ) and homologous recombination (HR)-mediated DSB repair. Mechanistically, TKT interacts with PARP1 in a DNA damage-dependent manner. Furthermore, TKT undergoes PARylation by PARP1, resulting in the inhibition of its enzymatic activity, and TKT can enhance the auto-PARylation of PARP1 in response to DSBs in HCC. The depletion of TKT effectively mitigates the radioresistance of HCC, both in vitro and in mouse xenograft models. Moreover, high TKT expression confers resistance of RT in clinical HCC patients, establishing TKT as a marker for assessing the response of HCC patients who received cancer RT. In summary, our findings reveal a novel mechanism by which TKT contributes to the radioresistance of HCC. Overall, we identify the TKT-PARP1 axis as a promising potential therapeutic target for improving RT outcomes in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Quebras de DNA de Cadeia Dupla , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Transcetolase/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Reparo do DNA , DNA , Reparo do DNA por Junção de Extremidades , Reparo de DNA por Recombinação , Poli(ADP-Ribose) Polimerase-1/genética
17.
Microbiol Resour Announc ; 13(1): e0044923, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38095439

RESUMO

This study reports the complete genome sequence of Heyndrickxia (Bacillus) coagulans BC99, a promising human probiotic strain isolated from the fecal sample of a healthy infant in Hailaer Inner Mongolia. The genome sequence of BC99 contains a 3,655,496-bp circular chromosome with a GC content of 46.23%. Genome annotation predicted 3,273 protein-coding genes.

18.
Animals (Basel) ; 13(24)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38136811

RESUMO

A total of 30 Simmental crossbred cattle (6.50 months old, 265.0 ± 22.48 kg) were randomly divided into three groups, with 10 heads per group, and fed for 45 days. The diet treatments consisted of the Control group without PFDG supplementation, the PFDG-15% group with 15% PFDG substituting for 15% concentrate, and PFDG-30% group with 30% PFDG substituting for 30% concentrate. The results showed that compared with the Control group, the average daily gain (ADG) of the cattle in the PFDG-30% group decreased significantly (0.890 vs. 0.768 kg/d, p = 0.005). The serum malondialdehyde content of cattle in the PFDG-15% and PFDG-30% groups decreased significantly (p = 0.047) compared to that of the Control group. However, the serum superoxide dismutase activity of cattle in the PFDG-30% group was significantly higher than that of the Control group (p = 0.047). Meanwhile, both the PFDG-15% and PFDG-30% groups (1758.47 vs. 2061.30 µg/mL) showed higher serum levels of immunoglobulin G, while the interleukin-10 concentration was lower in the PFDG-30% group (p = 0.027). In addition, the PFDG-15% and PFDG-30% groups shifted the rumen microbiota by improving the abundances of F082 (related to propionic acid production) and fiber-degrading bacteria (Lachnospiraceae_UGG-009 and Prevotellaceae_UCG-001) and reducing the abundance of the disease-associated bacteria Selenomonas. A Kyoto encyclopedia of genes and genomes (KEGG) analysis illustrated that three key metabolic pathways, including phenylalanine metabolism, pyrimidine metabolism, and tryptophan metabolism, were enriched in the PFDG-15% group, but eight key metabolic pathways, including arachidonic acid metabolism, were enriched in the PFDG-30% group. Importantly, both the PFDG-15% and PFDG-30% groups increased (p < 0.01) the activities of cellulase, lipase, and protease in the rumen. Finally, the different bacterial abundance in the rumen was associated with changes in the ADG, serum antioxidant capacity, immune status, rumen enzyme activity, and metabolites. These results suggest that PFDG alters rumen microbiome abundance, metabolome, and enzyme activity for enhancing serum antioxidant capacity and the immune status, but when the supplemental level reaches 30%, it has a negative effect on ADG and the anti-inflammatory factors in finishing cattle.

19.
Front Vet Sci ; 10: 1238064, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929280

RESUMO

Fermented distiller's grains (FDG)-based diets are nutritious and can improve the growth and intestinal immunity in livestock. However, there is limited research examining the effect of feeding FDG-based diets on changes in intestinal metabolites and related pathways in livestock. In this study, nine Guanling crossbred cattle (Guizhou Guanling Yellow cattle × Simmental cattle) were selected and randomly divided into a basal diet (BD) group and two experimental groups fed with FDG replacing 15% and 30% of the daily ration concentrates (FDG-Case A and FDG-Case B), respectively, with three cattle in each group. Fresh jejunum (J) and cecum (C) tissues were collected for metabolomic analysis. Differential metabolites and metabolic pathways were explored by means of univariate and multivariate statistical analysis. Compared with the J-BD group, 30 and 100 differential metabolites (VIP > 1, p < 0.05) were obtained in the J-FDG-Case A group and J-FDG-Case B group, respectively, and the J-FDG-Case B vs. J-FDG-Case A comparison revealed 63 significantly differential metabolites, which were mainly divided into superclasses including lipids and lipid-like molecules, organoheterocyclic compounds, and organic acids and derivatives. Compared with the C-BD, 3 and 26 differential metabolites (VIP > 1, p < 0.05) were found in the C-FDG-Case A group and C-FDG-Case B group, respectively, and the C-FDG-Case B vs. C-FDG-Case A comparison revealed 21 significantly different metabolites, which were also mainly divided into superclasses including lipids and lipid-like molecules, organoheterocyclic compounds, and organic acids and derivatives. A total of 40 metabolic pathways were identified, with a significance threshold set at p < 0.05. Among them, 2, 14, and 18 metabolic pathways were significantly enriched in the J-FDG-Case A vs. J-BD, J-FDG-Case B vs. J-BD, and J-FDG-Case B vs. J-FDG-Case A comparisons, respectively. Meanwhile, 1, 2, and 3 metabolic pathways were obtained in the C-FDG-Case A vs. C-BD, C-FDG-Case B vs. C-BD, and C-FDG-Case B vs. C-FDG-Case A comparisons, respectively. Furthermore, four significant metabolic pathways, namely insulin resistance, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and primary bile acid biosynthesis, were significantly enriched in Guanling crossbred cattle fed FDG diets. These results suggest that feeding FDG diets may promote the growth and intestinal immunity of Guanling crossbred cattle by regulating metabolic patterns of lipid compounds and related metabolic pathways. This study sheds light on the potential metabolic regulatory mechanisms of FDG diets and offers some references for their use in livestock feed.

20.
Animals (Basel) ; 13(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38003055

RESUMO

Fermented distillers' grains (FDG) are commonly used to enhance the health and metabolic processes of livestock and poultry by regulating the composition and activity of the intestinal microbiota. Nevertheless, there is a scarcity of research on the effects of the FDG diet on the gastrointestinal microbiota and its metabolites in cattle. This study examines the impact of FDG dietary supplements on the gastrointestinal flora and metabolic profile of Guanling cattle. Eighteen cattle were randomly assigned to three treatment groups with six replicates per group. The treatments included a basal diet (BD), a 15% concentrate replaced by FDG (15% FDG) in the basal diet, and a 30% concentrate replaced by FDG (30% FDG) in the basal diet. Each group was fed for a duration of 60 days. At the conclusion of the experimental period, three cattle were randomly chosen from each group for slaughter and the microbial community structure and metabolic mapping of their abomasal and cecal contents were analyzed, utilizing 16S rDNA sequencing and LC-MS technology, respectively. At the phylum level, there was a significant increase in Bacteroidetes in both the abomasum and cecum for the 30%FDG group (p < 0.05). Additionally, there was a significant reduction in potential pathogenic bacteria such as Spirochetes and Proteobacteria for both the 15%FDG and 30%FDG groups (p < 0.05). At the genus level, there was a significant increase (p < 0.05) in Ruminococcaceae_UCG-010, Prevotellaceae_UCG-001, and Ruminococcaceae_UCG-005 fiber degradation bacteria. Non-target metabolomics analysis indicated that the FDG diet significantly impacted primary bile acid biosynthesis, bile secretion, choline metabolism in cancer, and other metabolic pathways (p < 0.05). There is a noteworthy correlation between the diverse bacterial genera and metabolites found in the abomasal and cecal contents of Guanling cattle, as demonstrated by correlation analysis. In conclusion, our findings suggest that partially substituting FDG for conventional feed leads to beneficial effects on both the structure of the gastrointestinal microbial community and the metabolism of its contents in Guanling cattle. These findings offer a scientific point of reference for the further use of FDG as a cattle feed resource.

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