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1.
Artigo em Inglês | MEDLINE | ID: mdl-38573883

RESUMO

Artificial synaptic devices are emerging as contenders for next-generation computing systems due to their combined advantages of self-adaptive learning mechanisms, high parallel computation capabilities, adjustable memory level, and energy efficiency. Optoelectronic devices are particularly notable for their responsiveness to both voltage inputs and light exposure, making them attractive for dynamic modulation. However, engineering devices with reconfigurable synaptic plasticity and multilevel memory within a singular configuration present a fundamental challenge. Here, we have established an organic transistor-based synaptic device that exhibits both volatile and nonvolatile memory characteristics, modulated through gate voltage together with light stimuli. Our device demonstrates a range of synaptic behaviors, including both short/long-term plasticity (STP and LTP) as well as STP-LTP transitions. Further, as an encoding unit, it delivers exceptional read current levels, achieving a program/erase current ratio exceeding 105, with excellent repeatability. Additionally, a prototype 4 × 4 matrix demonstrates potential in practical neuromorphic systems, showing capabilities in the perception, processing, and memory retention of image inputs.

2.
Gen Psychiatr ; 37(2): e101288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595856

RESUMO

Background: Anxiety disorders are the most common psychiatric problems, affecting approximately 1 in 12 children and 1 in 4 adolescents. Understanding the incidence, burden and correlated risks of anxiety disorders among children and adolescents can help identify areas of success, stagnation and emerging threats, thereby facilitating effective improvement strategies. Aims: To estimate the incidence and burden trends of anxiety disorders in children and adolescents from 1990 to 2019 in 204 countries and compare the incidence and disease burden in different countries. To examine the association between anxiety disorders and social indicators (healthcare access and quality of life). Methods: Data were obtained from the Global Burden of Disease Study 2019. The age-standardised incidence rates (ASIRs) and disability-adjusted life years (DALYs) were reported to assess the burden of anxiety disorders, and the estimated annual percentage change was calculated to quantify the temporal trends. Pearson's correlation was used to investigate country-level risk factors for incidence and DALYs. Results: Globally, there were 932 million incident cases of anxiety disorders in children and adolescents, 739.29 per 100 000 ASIRs and 380.62 million DALYs in 2019. From 1990 to 2019, the estimated annual percentage change of incidence of anxiety disorders decreased by 2.2%. Significant variations were observed in the age-standardised burden rate and the changing trend of anxiety disorders among countries. Portugal reported the highest ASIR of anxiety disorders, while Mexico had the largest increase rate of ASIR. In 2019, Portugal reported the highest number of DALYs (1001.71 million), and India (212.09 million) reported the lowest number of DALYs. The burden of anxiety disorders was positively correlated with the average number of psychiatrists, psychologists and nurses in the mental health sector (per 100 000), and quality of life and the correlation coefficients were 0.58, 0.67, 0.43 and 0.53, respectively. Conclusions: The incidence and global burden of anxiety disorders in adolescents have continued to decrease over the past 30 years. However, the incidence and disease burden in developed countries are still increasing steadily. Policymakers should design and implement mental health strategies for adolescents based on their specific developmental status, as well as the cultural and regional characteristics of each country.

3.
Oncogene ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594504

RESUMO

Ferroptosis has been demonstrated a promising way to counteract chemoresistance of multiple myeloma (MM), however, roles and mechanism of bone marrow stromal cells (BMSCs) in regulating ferroptosis of MM cells remain elusive. Here, we uncovered that MM cells were more susceptible to ferroptotic induction under the interaction of BMSCs using in vitro and in vivo models. Mechanistically, BMSCs elevated the iron level in MM cells, thereby activating the steroid biosynthesis pathway, especially the production of lanosterol, a major source of reactive oxygen species (ROS) in MM cells. We discovered that direct coupling of CD40 ligand and CD40 receptor constituted the key signaling pathway governing lanosterol biosynthesis, and disruption of CD40/CD40L interaction using an anti-CD40 neutralizing antibody or conditional depletion of Cd40l in BMSCs successfully eliminated the iron level and lanosterol production of MM cells localized in the Vk*MYC Vk12653 or NSG mouse models. Our study deciphers the mechanism of BMSCs dictating ferroptosis of MM cells and highlights the therapeutic potential of non-apoptosis strategies for managing refractory or relapsed MM patients.

4.
Cryobiology ; 115: 104892, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38593909

RESUMO

Refreezing the remaining genetic resources after in vitro fertilization (IVF) can conserve genetic materials. However, the precise damage inflicted by repeated freezing and thawing on bovine sperm and its underlying mechanism remain largely unexplored. Thus, this study investigates the impact of repeated freeze-thaw cycles on sperm. Our findings indicate that such cycles significantly reduce sperm viability and motility. Furthermore, the integrity of the sperm plasma membrane and acrosome is compromised during this process, exacerbating the advanced apoptosis triggered by oxidative stress. Additionally, transmission electron microscopy exposed severe damage to the plasma membranes of both the sperm head and tail. Notably, the "9 + 2" structure of the tail was disrupted, along with a significant decrease in the level of the axonemal protein DNAH10, leading to reduced sperm motility. IVF outcomes revealed that repeated freeze-thaw cycles considerably impair sperm fertilization capability, ultimately reducing the blastocyst rate. In summary, our research demonstrates that repeated freeze-thaw cycles lead to a decline in sperm viability and motility, attributed to oxidative stress-induced apoptosis and DNAH10-related dynamic deficiency. As a result, the utility of semen is compromised after repeated freezing.

5.
J Colloid Interface Sci ; 667: 460-469, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38643743

RESUMO

Electrochemical nitrogen reduction (eNRR) is a cost-effective and environmentally sustainable approach for ammonia production. MoS2, as a typical layered transition metal compound, holds significant potential as an electrocatalyst for the eNRR. Nevertheless, it suffers from a limited number of active sites and low electron transfer efficiency. In this study, we constructed a heterostructure by depositing SnO2 (an n-type semiconductor) nanoparticles on MoS2 (a p-type semiconductor). This unique interfacial structure not only generates abundant interfacial contacts but also facilitates the transfer of electrons from SnO2 to MoS2, leading to the formation of an interfacial electric field. Theoretical calculations demonstrate that this electric field increases the number of active electrons, facilitating N2 adsorption and NN bond activation. Moreover, it increases the degree of orbital overlap between N2 and SnO2/MoS2, effectively reducing the energy barrier of the rate-determining step. Benefiting from the interfacial electric field effect, the SnO2/MoS2 catalyst exhibits significant catalytic activity and selectivity towards eNRR, with an ammonia yield of 47.1 µg h-1 mg-1 and a Faraday efficiency of 19.3 %, surpassing those reported for the majority of MoS2- and SnO2-based catalysts.

6.
Plant Cell Environ ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644635

RESUMO

Crown removal revitalises sand-fixing shrubs that show declining vigour with age in drought-prone environments; however, the underlying mechanisms are poorly understood. Here, we addressed this knowledge gap by comparing the growth performance, xylem hydraulics and plant carbon economy across different plant ages (10, 21 and 33 years) and treatments (control and crown removal) using a representative sand-fixing shrub (Caragana microphylla Lam.) in northern China. We found that growth decline with plant age was accompanied by simultaneous decreases in soil moisture, plant hydraulic efficiency and photosynthetic capacity, suggesting that these interconnected changes in plant water relations and carbon economy were responsible for this decline. Following crown removal, quick resprouting, involving remobilisation of root nonstructural carbohydrate reserves, contributed to the reconstruction of an efficient hydraulic system and improved plant carbon status, but this became less effective in older shrubs. These age-dependent effects of carbon economy and hydraulics on plant growth vigour provide a mechanistic explanation for the age-related decline and revitalisation of sand-fixing shrubs. This understanding is crucial for the development of suitable management strategies for shrub plantations constructed with species having the resprouting ability and contributes to the sustainability of ecological restoration projects in water-limited sandy lands.

7.
Inorg Chem ; 63(15): 6948-6956, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38575907

RESUMO

Conductive metal-organic frameworks (cMOFs), which have high porosity and intrinsic electron conductivity, are regarded as ideal candidates for electromagnetic wave (EMW) absorption materials. Controlling the nanostructure of absorbers may be one of the effective strategies to improve the electromagnetic wave (EMW) absorption performance. Herein, a series of conductive Cu-HHTP MOFs (HHTP = 2,3,6,7,10,11-hexahydroxytriphenyl hydrates) with different nanostructures or crystal morphologies were successfully synthesized by using different structural inducers to regulate the changes in the morphology, thereby improving the EMW absorption performance. Specifically, when ammonia was used as an inducer, the obtained A-Cu-HHTP with a nanosheet structure exhibited excellent EMW absorption performance. The minimum reflection loss (RLmin) can reach -51.08 dB at 7.25 GHz with a thickness of 4.4 mm, and the maximum effective absorption bandwidth (EAB) can cover 5.73 GHz at 2.5 mm. The influence of the nanostructures of the cMOFs on the dielectric and EMW absorption performance was clarified. The nanosheet structure of A-Cu-HHTP increases its specific surface area, which expands multiple scattering and reflection paths of incident EMW; Meanwhile, the unique structure facilitates the formation of more heterogeneous interfaces, optimizing impedance matching. The significant improvement in EMW performance is mainly attributed to multiple reflections and scattering as well as impedance matching. This work not only provides a simple and effective strategy for improving electromagnetic wave absorption performance but also offers guidelines for preparing morphology functional cMOF materials.

8.
J Ethnopharmacol ; 329: 118142, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583730

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (Fabaceae) is a traditional medicinal herb used to treat various diseases, including kidney disease, asthma, psoriasis and vitiligo. AIM OF THE STUDY: To explore the antibacterial activity of Psoralea corylifolia L. and its bioactive components against Mycobacterium abscessus (M. abscessus). MATERIALS AND METHODS: Ultra high performance liquid chromatography was utilized to analyze the bioactive fractions and compounds present in 30%, 60%, and 90% ethanol extracts of Psoralea corylifolia L.. The antibacterial effects of Psoralea corylifolia L. and potential active ingredients were determined by minimum inhibitory concentration (MIC). The bactericidal activity of the active ingredient isobavachalcone was evaluated and then scanning electron microscopy was used to explore the bactericidal mechanism of isobavachalcone. RESULTS: The 90% ethanol extracts of Psoralea corylifolia L. showed significant antibacterial activity against M. abscessus, with an MIC of 156 µg/mL. Isobavachalcone was identified as the bioactive ingredient, and testing of 118 clinical isolates of M. abscessus indicated their MICs ranged from 2 to 16 µg/mL, with an average MIC of 8 µg/mL. Furthermore, the minimum bactericidal concentration/MIC ratio and the time-kill test indicated rapid bactericidal activity of isobavachalcone against M. abscessus. Finally, we found that the bactericidal mechanism of isobavachalcone involved damage to the bacterial cell membrane, causing wrinkled and sunken cell surface and a noticeable reduction in bacterial length. CONCLUSION: Psoralea corylifolia L. ethanol extracts as well as its active component isobavachalcone show promising antimicrobial activity against M. abscessus.

9.
Int J Soc Psychiatry ; : 207640241243280, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570908

RESUMO

BACKGROUND: The rising prevalence of depressive symptoms presents a pressing global public health concern, exacerbated by prevailing social inequality. AIM: This study seeks to identify latent profiles of social inequality perception and explore their associations with depressive symptoms. METHODS: Data were obtained from the China Family Panel Studies (CFPS) involving 10,529 residents aged 18 years and above. Latent profile analysis (LPA) was used to identify different patterns of social inequality perception. Multiple linear regression analysis examined the links between these patterns and depressive symptoms. RESULTS: Three distinct patterns of social inequality perception were identified: the disappointed pattern (TDP), the neutral pattern (TNP), and the positive pattern (TPP). Perceived social inequality was significantly associated with short-term and long-term depressive symptoms (ß = .51, 95% CI [0.29, 0.72] vs. ß = .51, 95% CI [0.27, 0.74]). Increases in social inequality perception patterns were also related to more severe depressive symptoms (ß = .55, 95% CI [0.36, 0.74]). CONCLUSIONS: Increasing perceived social inequality is closely linked to elevated depressive symptoms in Chinese adults. This underscores the need for tailored strategies aimed at addressing heightened perceptions of social inequality to reduce the risk of depressive symptoms.

10.
Sci Rep ; 14(1): 8118, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582908

RESUMO

Water pollution deteriorates ecosystems and has a great threaten to the environment. The environmental benefits of wastewater treatment are extremely important to minimize pollutants. Here, the biochar purchased from the related industry was used to treat the wastewater which contained high concentration of vanadium (V). The concentration of vanadium was measured by the IC-OES and the results showed that 96.1% vanadium (V) was reduced at selected reaction conditions: the mass ratio of biochar to vanadium of 5.4, reaction temperature of 90 °C, reaction time at 60 min and concentration of H2SO4 of 10 g/L, respectively. Response surface methodology confirmed that all the experimental parameters had positive effect on the reduction of vanadium (V), which could improve the reduction efficiency of vanadium (V) as increased. The influence of each parameter on the reduction process followed the order: A (Concentration of H2SO4) > C (mass ratio of biochar to vanadium) > B (mass ratio of biochar to vanadium). Especially, the mass ratio of biochar to vanadium and concentration of H2SO4 had the greatest influence on the reduction process. This paper provides a versatile strategy for the treatment of wastewater containing vanadium (V) and shows a bright tomorrow for wastewater treatment.

11.
Medicine (Baltimore) ; 103(14): e37589, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579090

RESUMO

BACKGROUND: Chronic gouty arthritis, a prevalent metabolic disorder, has prompted interest in the role of diet and lifestyle in its management. This study examines alkaline water as a non-pharmacological adjunct to traditional medicine, hypothesizing its positive effects on uric acid levels and gout symptoms. METHODS: In this research, 400 chronic arthritis patients from Guangdong Hydropower Hospital (September 2021-September 2023) were randomly assigned to groups receiving varying concentrations of alkaline water alongside conventional Western medicine, or Western medicine alone. A 1-year follow-up involved assessments using visual analogue scales, joint swelling scores, functional assessment scales, and biochemical markers (serum uric acid, creatinine, urea nitrogen) for comprehensive evaluation. RESULTS: Pain relief: High-concentration alkaline water significantly reduced VAS pain scores posttreatment (P < .05). Joint swelling: Greatest improvement observed in high-concentration group (P < .001). Daily activity capability: Notable enhancements in daily activity scores in experimental groups (P < .05). Range of joint motion: All groups showed significant improvement posttreatment (P < .05). Inflammatory markers: Experimental groups experienced a notable decrease in C-reactive protein, especially in the low concentration group (P < .001). Erythrocyte sedimentation rate decreases were marginal and not statistically significant (P > .05). Interleukin-1ß and tumor necrosis factor-α levels significantly decreased, particularly in the low concentration group. Serum uric acid levels: Significant reduction in serum uric acid observed in all alkaline water groups (P < .05), contrasting with the control group. CONCLUSION: Alkaline water, particularly at high concentrations, effectively alleviated pain, reduced joint swelling, enhanced daily activities, and improved joint motion in chronic gouty arthritis treatment. It significantly reduced key inflammatory markers (C-reactive protein, interleukin-1ß, tumor necrosis factor-α) and serum uric acid levels, suggesting its potential as a valuable adjunct in gout management. The limited impact on erythrocyte sedimentation rate warrants further investigation.


Assuntos
Artrite Gotosa , Gota , Humanos , Artrite Gotosa/tratamento farmacológico , Ácido Úrico , Fator de Necrose Tumoral alfa/metabolismo , Proteína C-Reativa , Interleucina-1beta/metabolismo , Gota/tratamento farmacológico , Dor , Água
12.
Cells ; 13(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38607009

RESUMO

Cold exposure exerts negative effects on hippocampal nerve development in adolescent mice, but the underlying mechanisms are not fully understood. Given that ubiquitination is essential for neurodevelopmental processes, we attempted to investigate the effects of cold exposure on the hippocampus from the perspective of ubiquitination. By conducting a ubiquitinome analysis, we found that cold exposure caused changes in the ubiquitination levels of a variety of synaptic-associated proteins. We validated changes in postsynaptic density-95 (PSD-95) ubiquitination levels by immunoprecipitation, revealing reductions in both the K48 and K63 polyubiquitination levels of PSD-95. Golgi staining further demonstrated that cold exposure decreased the dendritic-spine density in the CA1 and CA3 regions of the hippocampus. Additionally, bioinformatics analysis revealed that differentially ubiquitinated proteins were enriched in the glycolytic, hypoxia-inducible factor-1 (HIF-1), and 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathways. Protein expression analysis confirmed that cold exposure activated the mammalian target of rapamycin (mTOR)/HIF-1α pathway. We also observed suppression of pyruvate kinase M2 (PKM2) protein levels and the pyruvate kinase (PK) activity induced by cold exposure. Regarding oxidative phosphorylation, a dramatic decrease in mitochondrial respiratory-complex I activity was observed, along with reduced gene expression of the key subunits NADH: ubiquinone oxidoreductase core subunit V1 (Ndufv1) and Ndufv2. In summary, cold exposure negatively affects hippocampal neurodevelopment and causes abnormalities in energy homeostasis within the hippocampus.


Assuntos
Hipocampo , Piruvato Quinase , Camundongos , Animais , Piruvato Quinase/metabolismo , Hipocampo/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Mamíferos/metabolismo
13.
Heliyon ; 10(7): e29299, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623252

RESUMO

Early mutation identification guides patients with colorectal cancer (CRC) toward targeted therapies. In the present study, 414 patients with CRC were enrolled, and amplicon-based targeted next-generation sequencing (NGS) was then performed to detect genomic alterations within the 73 cancer-related genes in the OncoAim panel. The overall mutation rate was 91.5 % (379/414). Gene mutations were detected in 38/73 genes tested. The most frequently mutated genes were TP53 (60.9 %), KRAS (46.6 %), APC (30.4 %), PIK3CA (15.9 %), FBXW7 (8.2 %), SMAD4 (6.8 %), BRAF (6.5 %), and NRAS (3.9 %). Compared with the wild type, TP53 mutations were associated with low microsatellite instability/microsatellite stability (MSI-L/MSS) (P = 0.007), tumor location (P = 0.043), and histological grade (P = 0.0009); KRAS mutations were associated with female gender (P = 0.026), distant metastasis (P = 0.023), TNM stage (P = 0.013), and histological grade (P = 0.004); APC mutations were associated with patients <64 years of age at diagnosis (P = 0.04); PIK3CA mutations were associated with tumor location (P = 4.97e-06) and female gender (P = 0.018); SMAD4 mutations were associated with tumor location (P = 0.033); BRAF mutations were associated with high MSI (MSI-H; P = 6.968e-07), tumor location (P = 1.58e-06), and histological grade (P = 0.04). Mutations in 164 individuals were found to be pathogenic or likely pathogenic. A total of 26 patients harbored MSI-H tumors and they all had at least one detected gene mutation. Mutated genes were enriched in signaling pathways associated with CRC. The present findings have important implications for improving the personalized treatment of patients with CRC in China.

14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 223-229, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38595237

RESUMO

OBJECTIVE: To understand the health status, influencing factors and spatial distribution of the Chinese floating population and to evaluate the health equity of the floating population. METHODS: All the data were collected from the 2017 Migrant Population Dynamic Monitoring Survey in China, binary Logistic regression was used to analyze the factors that might affect the health of the floating population, and the concentration index method was used to evaluate the health equity of the floating population. Spatial autocorrelation analyses the spatial aggregation of health status and health equity. RESULTS: The unhealthy rate of the floating population in China was 2.71%. Age and gender show a statistically significant impact on self-rated health; that is, as age increases, the self-rated health of the migrant population gradually deteriorates, and women are more likely to think that they are unhealthy. Fairness analysis shows that the concentration index of the floating population is 0.021 7, the urban household registration floating population is 0.021 6, and the rural household registration floating population is 0.021 9. It is shown that the fairness of the health status of the floating population is biased towards the high-income class, and the rural household registration floating population' s health unfairness is greater than that of the urban household registration migration population. Moreover, Moran' s i=0.211 for self-rated health and Moran' s i=0.291 for the unhealthy rate indicate that self-rated health has a spatial aggregation trend. Moran' s i=0.136 showed the characteristics of spatial clustering, and the two-week prevalence fairness of the floating population was mainly in the northern and southeastern coastal areas. CONCLUSION: In general, the health status of the floating population in China is relatively good. The main influencing factors of health included gender and age. The central tendency of health inequity is reflected in the southeast coastal and northern regions, which are characterized by poverty. Attention to spatial aggregation is not only helpful to analyze the reasons of floating population, but also to study the health differences between different regions and health-related factors, to improve the overall health level of the whole population.


Assuntos
Sistemas de Informação Geográfica , População Rural , Humanos , Feminino , China/epidemiologia , População Urbana , Nível de Saúde
15.
Cell Commun Signal ; 22(1): 235, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643161

RESUMO

BACKGROUND: Antral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined. METHODS: Whole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9Q308X/S415T mouse model was generated based on the variant found in one of the patients. RESULTS: Two probands with bi-allelic GDF9 variants (GDF9His209GlnfsTer6/S428T, GDF9Q321X/S428T) and eight GDF9S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement. CONCLUSIONS: GDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.


Assuntos
Infertilidade Feminina , Camundongos , Animais , Feminino , Humanos , Infertilidade Feminina/metabolismo , Folículo Ovariano/metabolismo , Oócitos/química , Oócitos/metabolismo , Células da Granulosa/metabolismo , Estrogênios/metabolismo , Fator 9 de Diferenciação de Crescimento/genética , Fator 9 de Diferenciação de Crescimento/análise , Fator 9 de Diferenciação de Crescimento/metabolismo
16.
Clin Chim Acta ; 558: 117893, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582244

RESUMO

BACKGROUND: Compare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias. METHODS: Data was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020. RESULTS: 232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia. CONCLUSION: There are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.

17.
J Transl Med ; 22(1): 367, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637885

RESUMO

BACKGROUND: Ovarian cancer (OC) is characterized by its rapid growth and spread which, accompanied by a low 5-year survival rate, necessitates the development of improved treatments. In ovarian cancer, the selective overexpression of Mucin-16 (MUC16, CA125) in tumor cells highlights its potential as a promising target for developing anti-tumor therapies. However, the potential effectiveness of CAR-T cell therapy that targets MUC16 in ovarian cancer cells is unknown. METHODS: The expression of MUC16 in viable OC cells was detected using immunofluorescence and flow cytometry techniques. A MSLN-CAR construct, comprising the MUC16-binding polypeptide region of mesothelin (MSLN), a CD8 hinge spacer and transmembrane domain, 4-1BB, and CD3ζ endo-domains; was synthesized and introduced into T cells using lentiviral particles. The cytotoxicity of the resultant CAR-T cells was evaluated in vitro using luciferase assays. Cytokine release by CAR-T cells was measured using enzyme-linked immunosorbent assays. The anti-tumor efficacy of the CAR-T cells was subsequently assessed in mice through both systemic and local administration protocols. RESULTS: MSLN-CAR T cells exhibited potent cytotoxicity towards OVCAR3 cells and their stem-like cells that express high levels of MUC16. Also, MSLN-CAR T cells were inefficient at killing SKOV3 cells that express low levels of MUC16, but were potently cytotoxic to such cells overexpressing MUC16. Moreover, MSLN-CAR T cells delivered via tail vein or peritoneal injection could shrink OVCAR3 xenograft tumors in vivo, with sustained remission observed following peritoneal delivery of MSLN-CAR T cells. CONCLUSIONS: Collectively, these results suggested that MSLN-CAR T cells could potently eliminate MUC16- positive ovarian cancer tumor cells both in vitro and in vivo, thereby providing a promising therapeutic intervention for MUC16-positive patients.


Assuntos
Mesotelina , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Apoptose , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Methods Mol Biol ; 2787: 3-38, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656479

RESUMO

In this chapter, we explore the application of high-throughput crop phenotyping facilities for phenotype data acquisition and the extraction of significant information from the collected data through image processing and data mining methods. Additionally, the construction and outlook of crop phenotype databases are introduced and the need for global cooperation and data sharing is emphasized. High-throughput crop phenotyping significantly improves accuracy and efficiency compared to traditional measurements, making significant contributions to overcoming bottlenecks in the phenotyping field and advancing crop genetics.


Assuntos
Produtos Agrícolas , Mineração de Dados , Processamento de Imagem Assistida por Computador , Fenótipo , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Mineração de Dados/métodos , Processamento de Imagem Assistida por Computador/métodos , Gerenciamento de Dados/métodos , Ensaios de Triagem em Larga Escala/métodos
19.
Immunol Cell Biol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650445

RESUMO

Unraveling the complexities of T cell aging is essential for developing targeted interventions to enhance immune function in the elderly. This article for the Highlights of 2023 Series integrates recent findings published in 2023, offering a panoramic view of the current understanding of T cell aging and its implications.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38626164

RESUMO

OBJECTIVE: To investigate the clinical features, imaging characteristics and molecular profile of Sellar neurocytoma (SN). METHODS: Clinical, imaging, and pathological features of eleven cases of sellar neurocytoma were retrospectively analyzed. Electron microscopy was performed in five cases. Molecular features were detected in tumor tissue by RNA sequencing, qPCR and IHC. RESULTS: The clinical features of SN patients showed high incidence of hyponatremia (73%,8/11) and the tumors tended to invaded lateral side of saddle area from preoperative imaging analysis. The tumors had positive NeuN, SYN, NF, SSTR2 immunohistochemistry staining. Tumor transcriptomic analysis suggested a new LMCD1-AS1:GRM7-AS1 fusion gene event and increased expression of 10 hypothalamus-secreted hormones in SN. 15 differentially expressed genes were verified for qPCR verification. SSTR2 has been verified by immunohistochemistry. CONCLUSIONS: Hyponatremia is the dominant clinical features of SN. Preoperative imaging suggests that growth toward the dorsal region is the imaging feature of SN. SSTR2 expression and LMCD1-AS1:GRM7-AS1 fusion gene event expected to become a new molecular marker for SN. Somatostatin receptor ligand therapy may be a potential therapy for SN.

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