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1.
World J Diabetes ; 15(6): 1353-1366, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38983830

RESUMO

BACKGROUND: Obesity in children and adolescents is a serious problem, and the efficacy of exercise therapy for these patients is controversial. AIM: To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers. METHODS: The PubMed, Web of Science, and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October 2023. The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children. RESULTS: In total, 1010 patients from 28 studies were included. Exercise therapy reduced the levels of fasting blood glucose (FBG) [standardized mean difference (SMD): -0.78; 95% confidence interval (CI): -1.24 to -0.32, P = 0.0008], fasting insulin (FINS) (SMD: -1.55; 95%CI: -2.12 to -0.98, P < 0.00001), homeostatic model assessment for insulin resistance (HOMA-IR) (SMD: -1.58; 95%CI: -2.20 to -0.97, P < 0.00001), interleukin-6 (IL-6) (SMD: -1.31; 95%CI: -2.07 to -0.55, P = 0.0007), C-reactive protein (CRP) (SMD: -0.64; 95%CI: -1.21 to -0.08, P = 0.03), and leptin (SMD: -3.43; 95%CI: -5.82 to -1.05, P = 0.005) in overweight and obese children. Exercise training increased adiponectin levels (SMD: 1.24; 95%CI: 0.30 to 2.18, P = 0.01) but did not improve tumor necrosis factor-alpha (TNF-α) levels (SMD: -0.80; 95%CI: -1.77 to 0.18, P = 0.11). CONCLUSION: In summary, exercise therapy improves glucose metabolism by reducing levels of FBG, FINS, HOMA-IR, as well as improves inflammatory status by reducing levels of IL-6, CRP, leptin, and increasing levels of adiponectin in overweight and obese children. There was no statistically significant effect between exercise training and levels of TNF-α. Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.

2.
Front Immunol ; 15: 1398508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983860

RESUMO

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.


Assuntos
ADP-Ribosil Ciclase 1 , Antígeno CD47 , Neoplasias Hematológicas , Antígeno CD47/imunologia , Antígeno CD47/antagonistas & inibidores , Antígeno CD47/metabolismo , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Humanos , Animais , Camundongos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Linhagem Celular Tumoral , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/antagonistas & inibidores , Citotoxicidade Celular Dependente de Anticorpos , Feminino , Antineoplásicos Imunológicos/farmacologia
3.
Sci Rep ; 14(1): 15481, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969666

RESUMO

In order to improve the ability of intelligent reasoning and prediction of 3DR27 model which presented in our previous work, enhance the usability of this model, and better fulfill the demands of real applications for spatial database, we focused on the problem of reasoning with the inverse of 3D cardinal direction relations between spatial objects. In order to realize automated reasoning, an algorithm for computing the inverse of 3D cardinal direction relations based on matrices is proposed on the basis of the mapping between the 3D rectangular cardinal direction relations and 3D interval relation matrix. This algorithm improves the power of reasoning for this model by means of the excellent properties of matrix operations. Theorems are provided to prove formally that our algorithm is correct and complete. This study realized the automatic inference and calculation of the inverse of the 3D cardinal direction relations based on 3DR27 model and further improved the ability of spatial reasoning and spatial analysis of spatial database.

4.
PLoS Med ; 21(7): e1004424, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976754

RESUMO

BACKGROUND: Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea. METHODS AND FINDINGS: We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy. CONCLUSIONS: Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

5.
Int J Biol Macromol ; 275(Pt 2): 133649, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972649

RESUMO

Target-immobilized magnetic beads-based Systematic Evolution of Ligands by Exponential Enrichment (target-immobilized Mag-SELEX) has emerged as a powerful tool for aptamer selection owing to its convenience, efficiency, and versatility. However, in this study we systematically investigated non-specific adsorption in target-immobilized Mag-SELEX and found that the non-specific adsorption of the oligonucleotides to target-labeled magnetic beads was comparable to that of the screening libraries, indicating a substantial portion of captured sequences likely stem from non-specific adsorption. Longer nucleic acid sequences (80 nt and above, such as polyA80 and yeast tRNA) were found to attenuate this non-specific adsorption, with more complex higher-order structures demonstrating greater efficacy, while dNTP and short sequences such as primer sequences (20 nt), polyT(59), or polyA(59), did not possess this capability. Various evidence suggested that hydrophobic interactions and other weak interactions may be the primary underlying cause of non-specific adsorption. Additionally, surface modification of magnetic beads with polar molecule polyethylene glycol (PEG) also yielded a significant reduction in non-specific adsorption. In conclusion, our research underscores the critical importance of closely monitoring non-specific adsorption in target-immobilized Mag-SELEX.

6.
Sci Rep ; 14(1): 15686, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977736

RESUMO

The problem of coal compression under buildings is common in underground mining of coal mines in China. The selection of traditional mining programme is subjective and lacks scientific rationality. In order to solve this problem, this paper studies the evaluation index system and model applicable to the selection of coal filling mining scheme under buildings. A multi-objective evaluation index system integrating economic, technical and adaptive factors is constructed. And an integrated optimization model is established, which is based on the traditional grey target model, combining the game theory optimal combination of weights with the hierarchical analysis method, entropy weight method, Critic method to determine the weights, and then introducing the TOPSIS model and the Mars distance to establish an improved grey target decision-making model. The validity of the evaluation index system and model is verified by taking the example of coal mining under pressure of buildings in five mining areas of a coal mine, which provides technical support for decision makers. This study helps to scientifically and reasonably carry out the preferred mining scheme of coal filling under building pressure.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38954294

RESUMO

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

8.
Anal Methods ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958106

RESUMO

Esophageal cancer is a common cancer with high morbidity and mortality that severely threatens the safety and quality of human life. The strong metastatic nature of esophageal cancer enables it to metastasize more quickly and covertly, making it difficult for current diagnostic and treatment methods to achieve efficient early screening, as well as timely and effective treatment. As a promising solution, nucleic acid aptamers, a kind of special single-stranded DNA or RNA oligonucleotide selected by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, can specifically bind with different molecular targets. In this paper, random DNA single-stranded oligonucleotides were used as the initial library. Using TE-1 cells and HEEC cells as targets, specific binding sequences were selected by 15 rounds of the cell-SELEX method, and the aptamer sequence that binds to TE-1 cells with the most specificity was obtained and named Te4. The Te4 aptamer was further validated for binding specificity, binding affinity, type of target, in vitro cytotoxicity when conjugated with DOX(Te4-DOX), and in vivo distribution. Results of in vitro validation showed that Te4 has outstanding binding specificity with a Kd value of 51.16 ± 5.52 nM, and the target type of Te4 was preliminarily identified as a membrane protein. Furthermore, the cytotoxicity experiment showed that Te4-DOX has specific cytotoxicity towards cultured TE-1 cells. Finally, the results of the in vivo distribution experiment showed that the Te4 aptamer is able to specifically target tumor regions in nude mice, showing great potential to be applied in future diagnosis and targeted therapy of esophageal cancer.

9.
Clin Transl Med ; 14(7): e1749, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38951127

RESUMO

During myocardial ischaemia‒reperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis-mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low-intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI-induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome-dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F-actin pathway. Meanwhile, F-actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS-induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome-dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non-invasive treatment for MIRI.


Assuntos
Modelos Animais de Doenças , Traumatismo por Reperfusão Miocárdica , Animais , Camundongos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/terapia , Ondas Ultrassônicas , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo
10.
Front Immunol ; 15: 1422113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966643

RESUMO

Recent breakthroughs in discovering novel immune signaling pathways have revolutionized different disease treatments. SERPINB9 (Sb9), also known as Proteinase Inhibitor 9 (PI-9), is a well-known endogenous inhibitor of Granzyme B (GzmB). GzmB is a potent cytotoxic molecule secreted by cytotoxic T lymphocytes and natural killer cells, which plays a crucial role in inducing apoptosis in target cells during immune responses. Sb9 acts as a protective mechanism against the potentially harmful effects of GzmB within the cells of the immune system itself. On the other hand, overexpression of Sb9 is an important mechanism of immune evasion in diseases like cancers and viral infections. The intricate functions of Sb9 in different cell types represent a fine-tuned regulatory mechanism for preventing immunopathology, protection against autoimmune diseases, and the regulation of cell death, all of which are essential for maintaining health and responding effectively to disease challenges. Dysregulation of the Sb9 will disrupt human normal physiological condition, potentially leading to a range of diseases, including cancers, inflammatory conditions, viral infections or other pathological disorders. Deepening our understanding of the role of Sb9 will aid in the discovery of innovative and effective treatments for various medical conditions. Therefore, the objective of this review is to consolidate current knowledge regarding the biological role of Sb9. It aims to offer insights into its discovery, structure, functions, distribution, its association with various diseases, and the potential of nanoparticle-based therapies targeting Sb9.


Assuntos
Serpinas , Humanos , Serpinas/metabolismo , Serpinas/uso terapêutico , Animais , Neoplasias/imunologia , Neoplasias/terapia , Granzimas/metabolismo , Transdução de Sinais
11.
J Dermatol Sci ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38960840

RESUMO

BACKGROUND: Psoriasis is an inflammatory skin disease with unclear pathogenesis and unmet therapeutic needs. OBJECTIVE: To investigate the role of senescent CD4+ T cells in psoriatic lesion formation and explore the application of senolytics in treating psoriasis. METHODS: We explored the expression levels of p16INK4a and p21, classical markers of cellular senescence, in CD4+ T cells from human psoriatic lesions and imiquimod (IMQ)-induced psoriatic lesions. We prepared a senolytic gel using B-cell lymphoma 2 (BCL-2) inhibitor ABT-737 and evaluated its therapeutic efficacy in treating psoriasis. RESULTS: Using multispectrum immunohistochemistry (mIHC) staining, we detected increased expression levels of p16INK4a and p21 in CD4+ T cells from psoriatic lesions. After topical application of ABT-737 gel, significant alleviation of IMQ-induced psoriatic lesions was observed, with milder pathological alterations. Mechanistically, ABT-737 gel significantly decreased the percentage of senescent cells, expression of T cell receptor (TCR) α and ß chains, and expression of Tet methylcytosine dioxygenase 2 (Tet2) in IMQ-induced psoriatic lesions, as determined by mIHC, high-throughput sequencing of the TCR repertoire, and RT-qPCR, respectively. Furthermore, the severity of psoriatic lesions in CD4creTet2f/f mice was milder than that in Tet2f/f mice in the IMQ-induced psoriasis model. CONCLUSION: We revealed the roles of senescent CD4+ T cells in developing psoriasis and highlighted the therapeutic potential of topical ABT-737 gel in treating psoriasis through the elimination of senescent cells, modulation of the TCR αß repertoire, and regulation of the TET2-Th17 cell pathway.

12.
Arch Pharm (Weinheim) ; : e2400137, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963324

RESUMO

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

13.
Medicine (Baltimore) ; 103(27): e38825, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968485

RESUMO

The potential relationship between the gut microbiota and prostate cancer, possibly influenced by immune cells, remains unclear. This study employed the mediation Mendelian randomization (MR) technique to investigate the causal link between the gut microbiota, immune cells, and prostate cancer. Data on immune cell activity were sourced from Valeria Orrù's research, whereas the genome-wide association study outcome dataset was obtained from the Integrative Epidemiology Unit database. The bidirectional MR analysis utilized 5 different methods: inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. In addition, the mediating effect of immune cells on the gut microbiota and prostate cancer was explored using mediation analysis. Eighty-three single nucleotide polymorphisms associated with prostate cancer were screened as instrumental variables. In a positive MR analysis with gut microbiota as the exposure factor, IVW showed an association between 8 gut microbiota and prostate cancer. Additionally, 9 types of immune cells have been found to be associated with prostate cancer using methods such as IVW. MR analysis of the gut microbiota on immune cells (beta1) revealed a negative correlation between Bifidobacterium and CD39+ T regulatory cells (Tregs; odds ratio [OR] = 0.785, 95% confidence interval [CI] = 0.627-0.983, P = .03). Furthermore, MR analysis of immune cells in prostate cancer disease (beta2) showed that CD39+Tregs are a risk factor for prostate cancer (OR = 1.215, 95% CI = 1.027-1.354, P = .04). Moreover, MR analysis of gut microbiota in prostate cancer (total effect) indicated that Bifidobacterium is a protective factor for prostate cancer (OR = 0.905, 95% CI = 0.822-0.977, P = .04). The sensitivity analysis verified the robustness of the above results. Mediation analysis demonstrated that CD39+Tregs partially mediate the causal relationship between Bifidobacterium and prostate cancer. This study demonstrates that Bifidobacterium inhibits prostate cancer progression through CD39+Tregs as mediators, providing new ideas and approaches for the treatment and prevention of prostate cancer.


Assuntos
Progressão da Doença , Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata , Humanos , Masculino , Microbioma Gastrointestinal/imunologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Estudo de Associação Genômica Ampla , Linfócitos T Reguladores/imunologia , Análise de Mediação , Bifidobacterium
14.
Sci Rep ; 14(1): 15214, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956214

RESUMO

The concept of volume fracturing has revolutionized the conventional limits of low permeability, expanded the effective resource space, and significantly enhanced oil well production in tight oil reservoir development. This paper elucidates the mechanism of volume fracturing technology for tight sandstone reservoirs by considering multiple factors such as the initiation range of multi-fractures, influence of far-well horizontal principal stress on fracture initiation and propagation, degree of natural fractures development, and mechanical parameters of reservoir rock. Through simulation based on the mechanical parameters of reservoir rock, a comparative analysis was conducted between the model-calculated rock fracture pressure value and measured data from fracturing construction wells in the study area. The results revealed that there was a discrepancy within 10% between the model calculations and actual data. By simulating the effects of different injection volumes of fracturing fluid, pumping rates, and perforation methods on the fracture geometry, optimal design parameters for volume fracturing technology were obtained. Additionally, we propose optimization ideas and suggestions for construction parameters applicable to field operations. The simulation results indicate that a minimum recommended fluid volume scale exceeding 1800 m3 is advised for the reservoir. Based on frictional calculations, it is recommended to have an on-site construction rate not less than 18.0 m3/min along with 36-48 holes/section for perforation purposes. The numerical simulation research presented in this paper provides a theoretical reference basis and practical guidance for the application of fracturing network technology in tight sandstone reservoirs.

15.
Zookeys ; 1204: 301-312, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882565

RESUMO

Three new species of the genera Thiania C. L. Koch, 1846 and Yaginumaella Prószynski, 1979 are described and named as T.bamian sp. nov. (♂♀), T.flacata sp. nov. (♀) and Y.curvata sp. nov. (♂♀), from Hunan Province, China. Detailed descriptions, photos of somatic features and copulatory organs, as well as a distribution map are provided. Nucleotide data for the barcoding gene, cytochrome c oxidase subunit I (COI) of T.bamian sp. nov. (♂♀) and Y.curvata sp. nov. (♀) are provided.

16.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1301-1311, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38886429

RESUMO

Clarifying current situation of farmers' fertilization and yield in citrus producing areas and the effects of different fertilization measures can provide a scientific basis for improving the yield and quality of citrus in China. We retrieved 92 literatures on citrus fertilization from the CNKI and Web of Science to examine the impacts of nitrogen (N), phosphorus (P or P2O5), and potassium (K or K2O) fertilizer dosage and partial productivity under farmers' conventional fertilization and experts' optimized fertilization, as well as the effects of optimized fertilization measures on citrus yield and quality by using meta-analysis approach. The average conventional application rates of N, P2O5, and K2O were 507.3, 262.2, and 369.3 kg·hm-2 in citrus production in China. Compared with conventional fertilization, optimized fertilization resulted in a reduction of N and P2O5 by 14.7% and 8.3%, an increase in K2O application by 6.6%, which promoted partial productivity of N, P2O5, and K2O fertilizers by 7.8%, 18.4%, and 14.7%, correspondingly. The optimized fertilization resulted in 11.9% and 2.8% increase in fruit yield and single fruit weight, while improved vitamin C content (Vc, 3.1%), total soluble solids (TSS, 5.9%) and total sugar content (TSC, 8.6%). Additionally, it also led to a reduction in titratable acid (TA, -3.4%) and total acid content (TAC, -3.6%), and consequently elevated the TSS/TA (14.0%) and TSC/TAC (9.5%). Among different optimized fertilization methods, the effect of optimized NPK + medium and/or micro element fertilizer on citrus yield and fruit quality was the best, especially NPK decrement ≤25% between optimized NPK measures. The effect of conventional NPK + organic fertilizer was higher than conventional NPK + medium and/or micro element fertilizer. However, different citrus varieties, including mandarins, pomelos, and oranges, showed different responses to optimized fertilization. Optimized fertilization management could synergistically improve citrus yield, fertilizer use efficiency, and fruit quality. Therefore, the strategy of integrated nutrient management1 with reducing NPK fertilizer, balancing medium and/or micro nutrient fertilizer and improving soil fertility by organic fertilizer should be adopted according to local conditions in citrus producing areas of China.


Assuntos
Citrus , Fertilizantes , Frutas , Nitrogênio , Fósforo , Fertilizantes/análise , Citrus/crescimento & desenvolvimento , China , Fósforo/análise , Nitrogênio/análise , Frutas/crescimento & desenvolvimento , Frutas/química , Nutrientes/análise , Agricultura/métodos , Potássio/análise , Biomassa , Produção Agrícola/métodos
17.
MedComm (2020) ; 5(6): e587, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840773

RESUMO

Human enterovirus A71 (EV-A71) is a significant etiological agent responsible for epidemics of hand, foot, and mouth disease (HFMD) in Asia-Pacific regions. There are presently no licensed antivirals against EV-A71, and the druggable target for EV-A71 remains very limited. The phenotypic hit 10,10'-bis(trifluoromethyl) marinopyrrole A derivative, herein termed MPA-CF3, is a novel potent small-molecule inhibitor against EV-A71, but its pharmacological target(s) and antiviral mechanisms are not defined. Here, quantitative chemoproteomics deciphered the antiviral target of MAP-CF3 as host factor coatomer subunit zeta-1 (COPZ1). Mechanistically, MPA-CF3 disrupts the interaction of COPZ1 with the EV-A71 nonstructural protein 2C by destabilizing COPZ1 upon binding. The destruction of this interaction blocks the coatomer-mediated transport of 2C to endoplasmic reticulum, and ultimately inhibits EV-A71 replication. Taken together, our study disclosed that MPA-CF3 can be a structurally novel host-targeting anti-EV-A71 agent, providing a structural basis for developing the COPZ1-targeting broad-spectrum antivirals against enteroviruses. The mechanistic elucidation of MPA-CF3 against EV-A71 may offer an alternative COPZ1-involved therapeutic pathway for enterovirus infection.

18.
Biosensors (Basel) ; 14(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38920569

RESUMO

Traditional single nucleic acid assays can only detect one target while multiple nucleic acid assays can detect multiple targets simultaneously, providing comprehensive and accurate information. Fluorescent microspheres in multiplexed nucleic acid detection offer high sensitivity, specificity, multiplexing, flexibility, and scalability advantages, enabling precise, real-time results and supporting clinical diagnosis and research. However, multiplexed assays face challenges like complexity, costs, and sample handling issues. The review explores the recent advancements and applications of fluorescent microspheres in multiple nucleic acid detection. It discusses the versatility of fluorescent microspheres in various fields, such as disease diagnosis, drug screening, and personalized medicine. The review highlights the possibility of adjusting the performance of fluorescent microspheres by modifying concentrations and carrier forms, allowing for tailored applications. It emphasizes the potential of fluorescent microsphere technology in revolutionizing nucleic acid detection and advancing health, disease treatment, and medical research.


Assuntos
Técnicas Biossensoriais , Microesferas , Ácidos Nucleicos , Ácidos Nucleicos/análise , Humanos , Corantes Fluorescentes
19.
Artigo em Inglês | MEDLINE | ID: mdl-38834162

RESUMO

BACKGROUND: The Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. The objective of our study was to examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices. METHODS: The CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS). RESULTS: Among 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of patients received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p < 0.001) and were less likely to receive HRT (22.4% vs 56.6%, p < 0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p < 0.01), bleeding (52% vs 33%, p < 0.01), and mortality (38% vs 25%; p < 0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.0/5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4). CONCLUSIONS: In this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival. CONDENSED ABSTRACT: High capacity Impella heart pumps are capable of provide up to 5.5 liter/min of flow while upper body surgical placement allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation.

20.
PLoS One ; 19(6): e0303017, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913673

RESUMO

Clanis bilineata Walker (Lepidoptera: Sphingidae), a burgeoning edible insect, is experiencing rising demand in China and other regions. Despite this interest, larval production is currently constrained by the limitations of artificial production technologies, particularly the selection of optimal host plants. This study rigorously evaluated the performance of C. bilineatha larvae on four main host plants: round-leaf soybean, pointed-leaf soybean, black locust, and kudzu. Preference tests demonstrated that the larvae were most attracted to black locust (34.76 ± 4.65%), with subsequent preferences for kudzu (25.00 ± 6.12%), round-leaf soybean (23.17 ± 2.79%), and pointed-leaf soybean (14.02 ± 4.74%). No significant preference differences were noted between round-leaf soybean and either black locust or kudzu. In feeding assays, the larvae exhibited a marked preference for round-leaf soybean (37.36 ± 0.81 g, total feeding amount for larvae), followed by kudzu (37.26 ± 0.82 g), pointed-leaf soybean (35.38 ± 1.31 g), and black locust (28.53 ± 0.81 g). When the larvae were fed on round-leaf soybean, they exhibited significantly higher survival rate (39.33 ± 0.90%), body weight (9.75 ± 0.07 g), total biomass (383.43 ± 7.35 g), pupation rate (87.78 ± 1.73%), and egg production (189.80 ± 1.06 eggs/female) compared to other hosts. These findings uncovered that round-leaf soybean significantly enhances larval performance, suggesting its potential for improving C. bilineata larval production and sustainability in cultivation systems.


Assuntos
Glycine max , Larva , Animais , Larva/fisiologia , Glycine max/parasitologia , Lepidópteros/fisiologia , Feminino
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