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1.
Cell Regen ; 13(1): 9, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630195

RESUMO

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

2.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38581217

RESUMO

Pelleted total mixed ration (P-TMR) feeding, which has become a common practice in providing nutrition for fattening sheep, requires careful consideration of the balance between forage neutral detergent fiber (FNDF) and rumen degradable starch (RDS) to maintain proper rumen functions. The present study aimed to investigate the effects of the dietary FNDF/RDS ratio (FRR) on chewing activity, ruminal fermentation, ruminal microbes, and nutrient digestibility in Hu sheep fed a P-TMR diet. This study utilized eight ruminally cannulated male Hu sheep, following a 4 × 4 Latin square design with 31 d each period. Diets consisted of four FRR levels: 1.0 (high FNDF/RDS ratio, HFRR), 0.8 (middle high FNDF/RDS ratio, MHFRR), 0.6 (middle low FNDF/RDS ratio, MLFRR), and 0.4 (low FNDF/RDS ratio, LFRR). Reducing the dietary FRR levels resulted in a linear decrease in ruminal minimum pH and mean pH, while linearly increasing the duration and area of pH below 5.8 and 5.6, as well as the acidosis index. Sheep in the HFRR and MHFRR groups did not experience subacute ruminal acidosis (SARA), whereas sheep in another two groups did. The concentration of total volatile fatty acid and the molar ratios of propionate and valerate, as well as the concentrate of lactate in the rumen linearly increased with reducing dietary FRR, while the molar ratio of acetate and acetate to propionate ratio linearly decreased. The degradability of NDF and ADF for alfalfa hay has a quadratic response with reducing the dietary FRR. The apparent digestibility of dry matter, organic matter, neutral detergent fiber, and acid detergent fiber linearly decreased when the dietary FRR was reduced. In addition, reducing the dietary FRR caused a linear decrease in OTUs, Chao1, and Ace index of ruminal microflora. Reducing FRR in the diet increased the percentage of reads assigned as Firmicutes, but it decreased the percentage of reads assigned as Bacteroidetes in the rumen. At genus level, the percentage of reads assigned as Prevotella, Ruminococcus, Succinivibrio, and Butyrivibrio linearly decreased when the dietary FRR was reduced. The results of this study demonstrate that the dietary FRR of 0.8 is crucial in preventing the onset of SARA and promotes an enhanced richness of ruminal microbes and also improves fiber digestibility, which is a recommended dietary FRR reference when formulating P-TMR diets for sheep.


Forage neutral detergent fiber (FNDF) and rumen degradable starch (RDS) are key components of carbohydrates in the diet for ruminants, which would reflect saliva secretion and the acid production potential of feed. However, appropriate FNDF to RDS ratios (FRR) applicable to ruminants under the condition of pelleted total mixed ration (P-TMR) feeding have not been reported. In this study, we investigated the effects of the dietary FRR on chewing activity, ruminal fermentation, ruminal microbial communities, and nutrient digestibility of Hu sheep under P-TMR feeding. The results indicate that reducing dietary FRR levels would induce acidosis in sheep, which negatively affected fiber utilization and ruminal bacterial communities. The FRR of 0.8 was a recommended dietary FRR when formulating a P-TMR diet for fattening sheep, as indicated by decreased ruminal acidosis risk and increased richness of ruminal microbes in the rumen as well as nutrient digestibility.


Assuntos
Acidose , Doenças dos Ovinos , Masculino , Feminino , Animais , Ovinos , Leite/metabolismo , Mastigação/fisiologia , Amido/metabolismo , Lactação/fisiologia , Detergentes/metabolismo , Silagem/análise , Propionatos/metabolismo , Fermentação , Rúmen/metabolismo , Fibras na Dieta/metabolismo , Carboidratos da Dieta/metabolismo , Dieta/veterinária , Nutrientes , Acetatos/metabolismo , Acidose/veterinária , Digestão/fisiologia
3.
J Econ Entomol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625052

RESUMO

In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age-stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.

4.
Polymers (Basel) ; 16(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38611239

RESUMO

The current work introduces the synthesis of inorganic salt nano/micro-crystals during the reduction of hydrogen tetrachloroaurate(III) by Pluronic triblock copolymers (P123, PEO20-PPO70-PEO20). The morphologies and component were confirmed using an electron microscope with an electronic differential system (EDS), and the crystal structures were determined with X-ray diffraction (XRD). The morphologies highly depend on the concentrations of Pluronic and pH values. The mean size of the nanocrystal and hollow micro-crystal were controlled typically in the range of 32-150 nm (side length) and 1.4 µm, respectively. Different from the electrospray-ionization (EI) method, a model in which KCl forms a supersaturated solution in the micellar core of Pluronic is used to explain the formation process. This work provides the new insight that inorganic salt nanocrystals could be synthesized with the template of micelles in pure aqueous solutions.

5.
J Zhejiang Univ Sci B ; 25(4): 271-279, 2024 Apr 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38584090

RESUMO

Pancreatic exocrine insufficiency (PEI) can be induced by various kinds of diseases, including chronic pancreatitis, acute pancreatitis, and post-pancreatectomy. The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis, disorder of pancreatic fluid flow, and imbalance of secretion feedback. Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis, with the abundance of Lactobacillus and Bifidobacterium increasing the most, which could be partially reversed by pancreatic enzyme replacement therapy. Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota. Pancreatic exocrine secretions and changes in duodenal pH as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota. In turn, the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk. Going forward, more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.


Assuntos
Insuficiência Pancreática Exócrina , Microbioma Gastrointestinal , Pancreatite , Humanos , Doença Aguda , Disbiose , Insuficiência Pancreática Exócrina/tratamento farmacológico
6.
Appl Radiat Isot ; 208: 111311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593592

RESUMO

Waste liquid stored in the containment sumps of nuclear power plants may contain a variety of radionuclides. Real-time monitoring of containment sump waste liquid can ensure that accidents, such as leakage of cooling water, can be avoided. This paper presents the design of a radioactive monitoring system for waste liquid in a containment sump. The detector and the lead-shield in the measurement unit are optimized through Monte Carlo simulations. Experimental verification showed that the background count rate of the measurement chamber in the system was 418.3 cps, and the detection limit of the detection system was 3.01 Bq/L. Distinct gamma-ray characteristic peaks were also observable, demonstrating the system's ability to identify radioactive nuclides in the waste.

7.
Nat Commun ; 15(1): 3267, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627361

RESUMO

In vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality. This study presents the design of an ATP-free ivSEB for one-pot PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate. Stoichiometric analysis indicates this ivSEB can self-maintain NADP+/NADPH balance and achieve a theoretical molar yield of 133.3%. Leveraging simple one-pot reactions, our ivSEBs achieved a near-theoretical molar yield of 125.5%, the highest PHB titer (208.3 mM, approximately 17.9 g/L) and the fastest PHB production rate (9.4 mM/h, approximately 0.8 g/L/h) among all the reported ivSEBs to date, and demonstrated easy scalability. This study unveils the promising potential of ivBT for the industrial-scale production of PHB and other acetyl-CoA-derived chemicals from starch.


Assuntos
Hidroxibutiratos , Poli-Hidroxibutiratos , Polissacarídeos , Amido , Acetilcoenzima A/metabolismo , Amido/metabolismo , Hidroxibutiratos/metabolismo , Poliésteres/metabolismo , NADP/metabolismo , Biotransformação
8.
J Cardiothorac Surg ; 19(1): 232, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627783

RESUMO

BACKGROUND: The gastric conduit is the most commonly used replacement organ for reconstruction after minimally invasive McKeown esophagectomy. Although the optimal route of gastric conduit remains controversial, the posterior mediastinal route is physiologically preferable but is not without disadvantages. Here, we report the safety and efficacy of a method of gastric conduit reconstruction via the anterior of the pulmonary hilum route. METHODS: We have used the anterior of the pulmonary hilum route since 2021. This procedure involves pulling the gastric conduit up through a substernal tunnel between the right thoracic cavity and the abdominal cavity and passing it into the neck via the anterior of the pulmonary hilum route. In this retrospective study, we compared the clinical outcomes between 20 patients who underwent this procedure and 20 patients who underwent the posterior mediastinal route from 2021 to 2022. RESULTS: No mortality was reported in either group. No significant differences were observed between the two groups in duration of surgery, blood loss, incidence of postoperative complications, and postoperative hospital stay. As a result of the anterior of the pulmonary hilum route, the primary tumor bed and lymph node drainage area were effectively bypassed, which facilitates postoperative adjuvant radiotherapy or chemoradiotherapy. The distance of the gastric conduit accompanying the airway was significantly shorter in the anterior of the pulmonary hilum route group. CONCLUSIONS: Our method is considered to be a safe and useful technique for the reconstruction of gastric conduit.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Humanos , Esofagectomia/métodos , Estudos Retrospectivos , Estômago/cirurgia , Complicações Pós-Operatórias/etiologia , Mediastino/cirurgia , Neoplasias Esofágicas/cirurgia
9.
J Hematol Oncol ; 17(1): 17, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589926

RESUMO

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361).


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Oxaliplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Terapia Neoadjuvante
10.
Neuroreport ; 35(7): 447-456, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38597325

RESUMO

Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Camundongos , Animais , Metaloproteinase 9 da Matriz/metabolismo , Doenças Neuroinflamatórias , AVC Isquêmico/complicações , Infarto da Artéria Cerebral Média/complicações , Lesões Encefálicas/complicações , Inflamação/complicações , Isquemia Encefálica/complicações , Proteína ADAMTS13
11.
Talanta ; 274: 126063, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38599124

RESUMO

Hypochlorite (ClO-), as one of reactive oxygen species (ROS), is closely linked to various illnesses and is essential for the proper functioning of immune system. Hence, monitoring and assessing ClO- levels in organisms are extremely important for the clinical diagnosis of ClO--related disorders. In this study, a novel ClO--selective fluorescent probe, DCP-ClO, was synthesized with dicyanoisophorone-xanthene unit as parent fluorophore, which displayed excellent selectivity towards ClO-, near-infrared emission (755 nm), large Stokes shift (100 nm), real-time response to ClO-, high sensitivity (LOD = 3.95 × 10-8 M), and low cytotoxicity. The recognition mechanism of DCP-ClO towards ClO- was confirmed to be a typical ICT process by HPLC-MS, HR-MS, 1H NMR and theoretical calculations. Meanwhile, DCP-ClO demonstrated remarkable efficacy in monitoring ClO- levels in water samples and eye-catching ability in imaging endogenous/exogenous ClO- in living organisms, which verified its potential as a powerful tool for the recognition of ClO- in complex biological systems.

12.
Br J Ophthalmol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594062

RESUMO

AIMS: To compare the diagnostic performance of 360° anterior segment optical coherence tomography assessment by applying normative percentile cut-offs versus iris trabecular contact (ITC) for detecting gonioscopic angle closure. METHODS: In this multicentre study, 394 healthy individuals were included in the normative dataset to derive the age-specific and angle location-specific normative percentiles of angle open distance (AOD500) and trabecular iris space area (TISA500) which were measured every 10° for 360°. 119 healthy participants and 170 patients with angle closure by gonioscopy were included in the test dataset to investigate the diagnostic performance of three sets of criteria for detection of gonioscopic angle closure: (1) the 10th and (2) the 5th percentiles of AOD500/TISA500, and (3) ITC (ie, AOD500/TISA500=0 mm/mm2). The number of angle locations with angle closure defined by each set of the criteria for each eye was used to generate the receiver operating characteristic (ROC) curve for the discrimination between gonioscopic angle closure and open angle. RESULTS: Of the three sets of diagnostic criteria examined, the area under the ROC curve was greatest for the 10th percentile of AOD500 (0.933), whereas the ITC criterion AOD500=0 mm showed the smallest area under the ROC (0.852) and the difference was statistically significant with or without adjusting for age and axial length (p<0.001). The criterion ≥90° of AOD500 below the 10th percentile attained the best sensitivity 87.6% and specificity 84.9% combination for detecting gonioscopic angle closure. CONCLUSIONS: Applying the normative percentiles of angle measurements yielded a higher diagnostic performance than ITC for detecting angle closure on gonioscopy.

13.
14.
Nat Prod Res ; : 1-6, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587144

RESUMO

Fungi have different genetic expression abilities and biosynthetic pathways under different cultivation conditions, which can produce various secondary metabolites. The "one strain many compounds" strategy is used to activate silent biosynthetic genes of fungi to produce various compounds, which is an effective method. In order to discover various new compounds in the edible fungus Pholiota nameko, a fermentation strategy involving precursor feeding and enzyme inhibitor addition has been employed. A new illudane sesquiterpene (1), along with one known indole diterpenoid alkaloid, cladosporine A (2) were isolated from the extracts of liquid culture of P. nameko. The new compound was identified by combination of 1D and 2D NMR, MS, optical rotation, and ECD calculations. We conducted experiments on the cytotoxicity of all isolated compounds on three cancer cell lines, but we did not observe any significant cytotoxicity (IC50 > 40 µM).

15.
Ann Hematol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605231

RESUMO

BACKGROUND: Real-world data on outcomes of upfront allogeneic hematopoietic stem cell transplantation (allo-HCT) for adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) patients in first complete remission (CR1) is still lacking. METHODS: A single center retrospective study was conducted from 94 consecutive patients received their first allo-HCT between 2010 and 2021, which include 76 patients received upfront allo-HCT and 18 patients received allo-HCT in non-upfront settings. RESULTS: There were no significant differences in most variables. In the upfront allo-HCT group, 52 (68%) patients achieved CR1 with one cycle of induction regimen. 24 (32%) patients achieved CR1 with more than one cycle. In the non-upfront group, there were 14 patients with active disease and 4 patients in second CR before transplant. The majority of patients received antithymocyte globulin-based graft-versus-host disease prophylaxis. Median follow-up time was 51 months for both groups. 5-year overall survival (OS) was 54% in the upfront allo-HCT group. While, in the non-upfront group, 5-year OS were 19% (P = 0.013). 5-year progression free survival in the upfront group was higher than that in the non-upfront group (50% versus 20%, P = 0.02). 5-year cumulative incidence relapse rate was significantly higher in non-upfront group (64% vs. 32%, P = 0.006). While, there was no difference in the 5-year non-relapse mortality (NRM) rate (19% versus 16%, P = 0.56). The most common cause of death was disease progression. In multivariable analysis, non-upfront allo-HCT (hazard ratios (HR) 2.14, P = 0.03) and HCT-CI (≥ 2) (HR 6.07, P = 0.002) were identified to be associated with worse OS. Non-upfront allo-HCT and HCT-CI (≥ 2) were also found to be independent risk factors for higher relapse rate. While, haploidentical-HCT was found to be associated with increased NRM. CONCLUSIONS: Our study indicated that allo-HCT remains an important curative treatment for adult patients with T-ALL, especially when it was performed in the upfront setting.

16.
Plant Commun ; : 100891, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561965

RESUMO

Plants grown under extreme environments represent unique sources for stress-resistant genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic legume shrub with evergreen broadleaves native to the semi-arid and desert regions, however, its drought tolerance mechanisms have not been well understood. Here, we report the assembly of a reference-grade genome, its evolutionary history within the legume family, and examination to its drought tolerance mechanisms. The assembled genome size was 843.07 Mb and 98.7% of the assembly was successfully anchored to the nine chromosomes of the plant. 47,611 genes were predicted to be protein-coding and 70.71% of the genome is composed of repetitive sequences dominated by transposable elements, particularly long-terminal-repeat retrotransposons (LTR-RTs). Evolutionary analyses revealed two whole-genome duplication (WGD) events shared by the genus Ammopiptanthus and other legumes at 130 and 58 million years ago (Mya), whereas no species-specific WGD was found within this genus. Further ancestral genome reconstruction indicated that the A. mongolicus genome had fewer rearrangements within the legume family, confirming it is a "relict plant". Transcriptomic analyses revealed that cuticular wax biosynthesis and transport genes were highly expressed under both normal and polyethylene glycol (PEG)-induced dehydration conditions, and significant induction of ethylene biosynthesis and signaling related genes was also observed in leaves experiencing the dehydration stress, indicating that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Consistently, ectopic expression of AmERF2, an ethylene response factor unique for A. mongolicus, resulted in marked increase of drought tolerance in transgenic Arabidopsis thaliana plants, demonstrating the application potential of A. mongolicus genes in crop improvement.

17.
Nature ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600383

RESUMO

Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens1-7. However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.3 million cells from 17 tissues in Mus musculus and explored the effects of sex and androgens on the molecular programs and cellular populations. In particular, we found that sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were modulated by androgens. Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases. This study lays the groundwork for understanding the sex differences orchestrated by androgens and provides important evidence for targeting the androgen pathway as a broad therapeutic strategy for sex-biased diseases.

18.
Cancer Pathog Ther ; 2(2): 112-120, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38601484

RESUMO

Background: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations. However, the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined. Therefore, this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML. Methods: This study analyzed the clinical data and genetic mutations based on next-generation sequencing (NGS) in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army (PLA) General Hospital from January 2008 to August 2020. Factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in patients newly diagnosed with AML were analyzed. Results: The most adverse prognosis of DCAG-treated patients was observed in those with FLT3-ITD, KIT, PTPN11, GATA2, or IDH1 mutations during univariable analysis, whereas PTPN11 mutation was solely significant in multivariable analysis, with an increased likelihood of CIR (P = 0.001) and reduced LFS duration (P = 0.077). Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk (P = 0.044) and decreased LFS duration (P = 0.042) in multivariable analysis. In this study, we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range. Conclusion: NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.

19.
Int J Gen Med ; 17: 1263-1272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577398

RESUMO

Purpose: To investigate the quantitative assessment of carotid plaque by each parameter of dual-layer detector spectral CT and its diagnostic value in patients with acute cerebral infarction. Patients and Methods: Eighty-three patients with carotid atherosclerotic plaques who underwent spectral CT scanning were retrospectively included. Forty-two patients with acute ischaemic stroke (AIS) were included in the study group, and 41 patients without AIS were included in the control group. We compared the detection of carotid plaques in the two groups and the differences in the spectral quantitative parameters of the plaques in the two groups, and their diagnostic efficacy was obtained. Results: The detection rate of carotid plaques in the AIS group was higher than that in the non-AIS group (p<0.05); the carotid plaques in the AIS group mainly consisted of non-calcified plaques, while those in the non-AIS group mainly consisted of calcified plaques. The effective atomic number (Zeff), slope of the energy spectrum curve (λH), electron density (ED), and iodine-no-water value of the carotid plaques in the AIS group were lower than those in the non-AIS (p<0.05). For the differentiation of the carotid plaques in the AIS group from those in the non-AIS group, the area under the curve (AUC) of Zeff amounted to 0.637 (cut-off value: 11.865; sensitivity: 72.5%; specificity: 56.2%), the AUC of λH amounted to 0.628 (cut-off value: 19.56; sensitivity: 76.3%; specificity: 51.6%), and that for ED amounted to 0.624 (cut-off value: 110.45; sensitivity: 60.0%; specificity: 64.1%), AUC of iodine-no-water value amounted to 0.645 (cut-off value: 9.125; sensitivity: 61.3%; specificity: 65.6%). Conclusion: In summary, the quantitative parameters of dual-layer detector spectral CT can be used to assess plaque stability and have certain value in the diagnosis of AIS. The quantitative parameters can effectively differentiate carotid plaques in AIS and non-AIS patients.

20.
Phytochem Anal ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38487966

RESUMO

INTRODUCTION: Fructus Tribuli, the dried ripe fruit of Tribulus terrestris L., has various beneficial effects, including liver-calming and depression-relieving effects. Raw Fructus Tribuli (RFT) and stir-fried Fructus Tribuli (SFT) are included in the Chinese Pharmacopoeia 2020 edition (Ch. P 2020). However, owing to the lack of specific regulations on SFT-processing parameters in Ch. P 2020, it is difficult to ensure the quality of commercially available SFT. OBJECTIVE: The present study aimed to screen the quality markers (Q-markers) of RFT and SFT and optimize the processing technology of SFT based on the identified Q-markers. METHODS: First, the ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) technology as well as multiple statistical analysis along with network pharmacology was used to comprehensively identify the Q-markers of RFT and SFT. Then, based on single-factor experiments, the Box-Behnken design (BBD) response surface methodology (RSM) was used to optimize the processing technology of SFT and perform process validation. RESULTS: A total of 63 components were identified in RFT and SFT extracts. Terrestrosin D and Terrestrosin K were initially considered the Q-markers of RFT and SFT, respectively. The optimum processing technology conditions were 208°C, 14 min, and 60 r·min-1 . Three batches of process validation were performed, and the mean composite score was 56.87, with a relative standard deviation (RSD) value of 1.13%. CONCLUSION: The content of steroidal saponin components in RFT was significantly different before and after stir-frying. Terrestrosin D and Terrestrosin K were validated as the Q-markers of RFT and SFT, respectively. The identification of Q-markers for RFT and SFT offered a clear index for optimizing the SFT-processing technology and provided a basis for the quality control of RFT and SFT decoction pieces.

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