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1.
Blood ; 143(19): 1965-1979, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38271660

RESUMO

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is often dysregulated in AML. We found that although PI3Kγ is highly enriched in LSCs and critical for self-renewal, it was dispensable for normal hematopoietic stem cells. Mechanistically, PI3Kγ-AKT signaling promotes nuclear factor erythroid 2-related factor 2 (NRF2) nuclear accumulation, which induces 6-phosphogluconate dehydrogenase (PGD) and the pentose phosphate pathway, thereby maintaining LSC stemness. Importantly, genetic or pharmacological inhibition of PI3Kγ impaired expansion and stemness of murine and human AML cells in vitro and in vivo. Together, our findings reveal a key role for PI3Kγ in selectively maintaining LSC function by regulating AKT-NRF2-PGD metabolic pathway. Targeting the PI3Kγ pathway may, therefore, eliminate LSCs without damaging normal hematopoiesis, providing a promising therapeutic strategy for AML.


Assuntos
Classe Ib de Fosfatidilinositol 3-Quinase , Leucemia Mieloide Aguda , Células-Tronco Neoplásicas , Via de Pentose Fosfato , Animais , Humanos , Camundongos , Autorrenovação Celular , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Classe Ib de Fosfatidilinositol 3-Quinase/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Via de Pentose Fosfato/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais
2.
Genomics ; 116(2): 110814, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38432499

RESUMO

Lactate is a glycolysis end product, and its levels are markedly associated with disease severity, morbidity, and mortality in sepsis. It modulates key functions of immune cells, including macrophages. In this investigation, transcriptomic analysis was performed using lactic acid, sodium lactate, and hydrochloric acid-stimulated mouse bone marrow-derived macrophages (iBMDM), respectively, to identify lactate-associated signaling pathways. After 24 h of stimulation, 896 differentially expressed genes (DEG) indicated were up-regulation, whereas 792 were down-regulated in the lactic acid group, in the sodium lactate group, 128 DEG were up-regulated, and 41 were down-regulated, and in the hydrochloric acid group, 499 DEG were up-regulated, and 285 were down-regulated. Subsequently, clinical samples were used to further verify the eight genes with significant differences, among which Tssk6, Ypel4, Elovl3, Trp53inp1, and Cfp were differentially expressed in patients with high lactic acid, indicating their possible involvement in lactic acid-induced inflammation and various physiological diseases caused by sepsis. However, elongation of very long chain fatty acids protein 3 (Elovl3) was negatively correlated with lactic acid content in patients. The results of this study provide a necessary reference for better understanding the transcriptomic changes caused by lactic acid and explain the potential role of high lactic acid in the regulation of macrophages in sepsis.


Assuntos
Ácido Láctico , Sepse , Animais , Camundongos , Humanos , Ácido Láctico/metabolismo , Ácido Láctico/farmacologia , Lactato de Sódio , RNA Mensageiro , Ácido Clorídrico , Sepse/genética , Sepse/metabolismo , Macrófagos/metabolismo
3.
Nano Lett ; 24(8): 2503-2510, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38258747

RESUMO

X-ray scintillators have utility in radiation detection, therapy, and imaging. Various materials, such as halide perovskites, organic illuminators, and metal clusters, have been developed to replace conventional scintillators due to their ease of fabrication, improved performance, and adaptability. However, they suffer from self-absorption, chemical instability, and weak X-ray stopping power. Addressing these limitations, we employ alkali metal doping to turn nonemissive CsPb2Br5 into scintillators. Introducing alkali metal dopants causes lattice distortion and enhances electron-phonon coupling, which creates transient potential energy wells capable of trapping photogenerated or X-ray-generated electrons and holes to form self-trapped excitons. These self-trapped excitons undergo radiative recombination, resulting in a photoluminescence quantum yield of 55.92%. The CsPb2Br5-based X-ray scintillator offers strong X-ray stopping power, high resistance to self-absorption, and enhanced stability when exposed to the atmosphere, chemical solvents, and intense irradiation. It exhibits a detection limit of 162.3 nGyair s-1 and an imaging resolution of 21 lp mm-1.

4.
Hum Genet ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252283

RESUMO

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants-namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)-in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients.

5.
Cell Commun Signal ; 22(1): 379, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068453

RESUMO

Copper is an important metal micronutrient, required for the balanced growth and normal physiological functions of human organism. Copper-related toxicity and dysbalanced metabolism were associated with the disruption of intracellular respiration and the development of various diseases, including cancer. Notably, copper-induced cell death was defined as cuproptosis which was also observed in malignant cells, representing an attractive anti-cancer instrument. Excess of intracellular copper leads to the aggregation of lipoylation proteins and toxic stress, ultimately resulting in the activation of cell death. Differential expression of cuproptosis-related genes was detected in normal and malignant tissues. Cuproptosis-related genes were also linked to the regulation of oxidative stress, immune cell responses, and composition of tumor microenvironment. Activation of cuproptosis was associated with increased expression of redox-metabolism-regulating genes, such as ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS), lipoyltransferase 1 (LIPT1), dihydrolipoamide dehydrogenase (DLD), drolipoamide S-acetyltransferase (DLAT), pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), and pyruvate dehydrogenase E1 subunit beta (PDHB)). Accordingly, copper-activated network was suggested as an attractive target in cancer therapy. Mechanisms of cuproptosis and regulation of cuproptosis-related genes in different cancers and tumor microenvironment are discussed in this study. The analysis of current findings indicates that therapeutic regulation of copper signaling, and activation of cuproptosis-related targets may provide an effective tool for the improvement of immunotherapy regimens.


Assuntos
Morte Celular , Cobre , Imunoterapia , Oxirredução , Humanos , Cobre/metabolismo , Neoplasias Torácicas/patologia , Neoplasias Torácicas/genética , Animais
6.
Langmuir ; 40(23): 12107-12116, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38820070

RESUMO

The dynamic behavior of a viscous droplet impacting a flexible mesh surface with a fixed end is studied by high-speed photography in this work. Our experimental results reveal that surface vibration occurs when the viscous droplet impacts the flexible mesh surface. Simultaneously, the droplet spreads on the upper surface and penetrates into the mesh surface, resulting in a decrease in the spreading diameter on the upper surface. On the lower surface, the droplet elongates and forms multiple ligaments. Notably, different dynamic behaviors are observed when the droplet impacts surfaces with varying Weber (We) numbers due to viscous dissipation and surface vibration. However, as the impact position deviates from the fixed end, the surface vibrational amplitude increases, leading to a decreased diffusion range of the droplet on the lower surface. In addition, the vibration amplitude significantly enhances with increase of the We number. The vibration induces stretching and eventual rupture of the cardinal ligament under specific conditions. The first breaking time of the cardinal ligament delays with the decrease of the We number. As the impact position moves away from the fixed end, this situation is enhanced. Especially, when the stretching direction of the ligament is inconsistent with the vibration direction of the surface, the vibration has a great influence on the stretching behavior of the cardinal ligament.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38530339

RESUMO

The baijiu fermentation environment hosts a variety of micro-organisms, some of which still remain uncultured and uncharacterized. In this study, the isolation, cultivation and characterization of three novel aerobic bacterial strains are described. The cells of strain REN20T were Gram-negative, strictly aerobic, motile and grew at 26-37 °C, at pH 6.0-9.0 and in the presence of 0-5.0   % (w/v) NaCl. The cells of strain REN29T were Gram-negative, strictly aerobic, motile and grew at 15-30 °C, at pH 6.0-9.0 and in the presence of 0-10.0   % (w/v) NaCl. The cells of strain REN33T were Gram-positive, strictly aerobic, motile and grew at 15-37 °C, at pH 5.0-10.0 and in the presence of 0-7.0   % (w/v) NaCl. The digital DNA-DNA hybridization and average nucleotide identity by orthology values between type strains in related genera and REN20T (20.3-36.8 % and 79.8-89.9  %), REN29T (20.3-36.8  % and 74.5-88.5  %) and REN33T (22.6-48.6  % and 75.8-84.2  %) were below the standard cut-off criteria for the delineation of bacterial species, respectively. Based on polyphasic taxonomy analysis, we propose three new species, Bosea beijingensis sp. nov. (=REN20T=GDMCC 1.2894T=JCM 35118T), Telluria beijingensis sp. nov. (=REN29T=GDMCC 1.2896T=JCM 35119T) and Agrococcus beijingensis sp. nov. (=REN33T=GDMCC 1.2898T=JCM 35164T), which were recovered during cultivation and isolation from baijiu mash.


Assuntos
Actinomycetales , Bradyrhizobiaceae , Oxalobacteraceae , Cloreto de Sódio , Filogenia , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Ácidos Graxos/química , Bactérias Aeróbias
8.
Hereditas ; 161(1): 24, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080810

RESUMO

SOLAMEN syndrome is a rare, recently recognized congenital syndrome that is characterized by progressive and hypertrophic diseases involving multiple systems, including segmental overgrowth, lipomatosis, arteriovenous malformation (AVM) and epidermal nevus. According to literatures, SOLAMEN syndrome is caused by heterozygous PTEN mutation. Phenotypic overlap complicates the clinical identification of diseases associated with PTEN heterozygous mutations, making the diagnosis of SOLAMEN more challenging. In addition, SOLAMEN often presents with segmental tissue overgrowth and vascular malformations, increasing the possibility of misdiagnosis as klipple-trenaunay syndrome or Parks-Weber syndrome. Here, we present a case of a child presenting with macrocephaly, patchy lymphatic malformation on the right chest, marked subcutaneous varicosities and capillaries involving the whole body, overgrowth of the left lower limb, a liner epidermal nevus on the middle of the right lower limb, and a large AVM on the right cranial thoracic entrance. Based on the typical phenotypes, the child was diagnosed as SOLAMEN syndrome. detailed clinical, imaging and genetic diagnoses of SOLAMEN syndrome was rendered. Next-generation sequencing (NGS) data revealed that except for a germline PTEN mutation, a PDGFRB variant was also identified. A subsequent echocardiographic examination detected potential cardiac defects. We suggested that given the progressive nature of AVM and the potential severity of cardiac damage, regular echocardiographic evaluation, imaging follow-up and appropriate interventional therapy for AVM are recommended.


Assuntos
PTEN Fosfo-Hidrolase , Criança , Humanos , Masculino , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/diagnóstico , Lipoma , Lipomatose/genética , Lipomatose/diagnóstico , Anormalidades Musculoesqueléticas , Mutação , Nevo/genética , Nevo/diagnóstico , Fenótipo , PTEN Fosfo-Hidrolase/genética , Malformações Vasculares
9.
World J Surg Oncol ; 22(1): 73, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38439060

RESUMO

OBJECTIVE: To investigate the clinical efficacy and prognostic implication of hand-sewn anastomosis in laparoscopic total gastrectomy (LTG). METHODS: Retrospective analysis is adopted to the clinicopathologic data of 112 patients with gastric cancer (GC) who went through LTG in the Department of General Surgery, the Second Affiliated Hospital of Anhui Medical University between October 2020 and October 2022. Among them, 60 individuals receiving medical care were split into the hand-sewn anastomosis group (Group H, N = 60); while, 52 individuals were split into the circular stapler anastomosis group (Group C, N = 52) The clinical efficacy and prognostic conditions of hand-sewn anastomosis are compared with those of circular stapler anastomosis in the application of LTG. RESULTS: The analysis results indicated that no notable difference was observed in intraoperative bleeding volume, time to first flatus (TFF), postoperative hospitalization duration and postoperative complications among the two groups (P > 0.05). Group H had shorter esophagojejunal anastomosis duration (20.0 min vs. 35.0 min) and surgery duration (252.6 ± 19.4 min vs. 265.9 ± 19.8 min), smaller incisions (5.0 cm vs. 10.5 cm), and lower hospitalization costs (58415.0 CNY vs. 63382.5 CNY) compared to Group C (P < 0.05). CONCLUSION: The clinical efficacy and the postoperative complications of hand-sewn esophagojejunostomy are basically equivalent in comparison to the circular stapler anastomosis in the application of LTG. Its advantage lies in shorter esophagojejunal anastomosis duration, shorter surgery duration, smaller incisions, lower hospitalization costs and wider adaptability of the location of the tumor.


Assuntos
Gastrectomia , Laparoscopia , Humanos , Estudos Retrospectivos , Gastrectomia/efeitos adversos , Anastomose Cirúrgica , Complicações Pós-Operatórias/etiologia
10.
Ecotoxicol Environ Saf ; 282: 116758, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39029226

RESUMO

Heavy metal residues in natural ecosystems have emerged as a significant global environmental problem requiring urgent resolution. Because these elements are non-biodegradable, organisms can accumulate excessive levels of heavy metal elements into their tissues. Previous studies suggest that prolonged exposure to heavy metal enrichment poses comprehensive toxicity to various organs in vertebrates. However, few studies have focused on elucidating the molecular mechanism underlying the hepatotoxic effects of heavy metal enrichment in Chiroptera. In this study, 10 Hipposideros armiger individuals were dissected from Yingde City (YD, relatively pollution-free) and Chunwan City (CW, excessive heavy metals emission). Environmental samples were also obtained. To investigate the mechanism of heavy metal toxicity in bat livers, we employed a combination of multi-omics, pathology, and molecular biology methods. Our results revealed significant enrichment of Cd and Pb in the bat livers and food sources in the CW group (P<0.05). Furthermore, prolonged accumulation of heavy metals disrupted hepatic transcription profiles associated with the solute carriers family, the ribosome pathway, ATP usage, and heat shock proteins. Excessive heavy metal enrichment also altered the relative abundance of typical gut microbe taxa significantly (P<0.05), inhibiting tight-junction protein expression. We observed a significant decrease in the levels of superoxide dismutase, glutathione peroxidase, and glutathione (P<0.05), along with elevated reactive oxygen species (ROS) density and malondialdehyde content following excessive heavy metal enrichment. Additionally, hepatic fat accumulation and inflammation injuries were present under conditions of excessive heavy metal enrichment, while the contents of metabolism biomarkers significantly decreased (P<0.05). Consequently, prolonged heavy metal enrichment can induce hepatotoxicity by disturbing the microbes-gut-liver axis and hepatic transcription modes, leading to a decrease in overall metabolic activity in bats. Our study offers strategies for biodiversity conservation and highlights the importance of addressing environmental pollution to raise public awareness.


Assuntos
Quirópteros , Microbioma Gastrointestinal , Fígado , Metais Pesados , Animais , Metais Pesados/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Monitoramento Ambiental/métodos , Estresse Oxidativo/efeitos dos fármacos
11.
J Assist Reprod Genet ; 41(5): 1233-1243, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38536595

RESUMO

AIM: Abnormalities in oocyte maturation, fertilization, and early embryonic development are major causes of primary infertility in women who are undergoing IVF/ICSI attempts. Although many genetic factors responsible for these abnormal phenotypes have been identified, there are more additional pathogenic genes and variants yet to be discovered. Previous studies confirmed that bi-allelic PATL2 deficiency is an important factor for female infertility. In this study, 935 infertile patients with IVF/ICSI failure were selected for whole-exome sequencing, and 18 probands carrying PATL2 variants with a recessive inheritance pattern were identified. METHODS: We estimated that the prevalence contributed by PATL2 was 1.93% (18/935) in our study cohort. RESULTS: 15 novel variants were found in those families, including c.1093C > T, c.1609dupA, c.1204C > T, c.643dupG, c.877-2A > G, c.1228C > G, c.925G > A, c.958G > A, c.4A > G, c.1258T > C, c.1337G > A, c.1264dupA, c.88G > T, c.1065-2A > G, and c.1271T > C. The amino acids altered by the corresponding variants were highly conserved in mammals, and in silico analysis and 3D molecular modeling suggested that the PATL2 mutants impaired the physiologic function of the resulting proteins. Diverse clinical phenotypes, including oocyte maturation defect, fertilization failure, and early embryonic arrest might result from different variants of PATL2. CONCLUSIONS: These results expand the spectrum of PATL2 variants and provide an important reference for genetic counseling for female infertility, and they increase our understanding of the mechanisms of oocyte maturation arrest caused by PATL2 deficiency.


Assuntos
Sequenciamento do Exoma , Fertilização in vitro , Infertilidade Feminina , Mutação , Fenótipo , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Infertilidade Feminina/genética , Infertilidade Feminina/patologia , Adulto , Mutação/genética , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , Gravidez , Linhagem
12.
Sensors (Basel) ; 24(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38793958

RESUMO

Ion mobility spectrometry (IMS) has been widely studied and applied as an effective analytical technology for the on-site detection of volatile organic compounds (VOCs). Despite its superior selectivity compared with most gas sensors, its limited dynamic range is regarded as a major drawback, limiting its further application in quantitative measurements. In this work, we proposed a novel sample introduction method based on pulsed membrane adsorption, which effectively enhanced IMS's ability to measure analytes at higher concentrations. Taking N-methyl-2-pyrrolidone (NMP) as an example, this new sampling method expanded the dynamic range from 1 ppm to 200 ppm. The working principle and measurement strategy of this sampling method were also discussed, providing new insights for the design and application of IMS-based instruments.

13.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38612384

RESUMO

3-methyl-4-nitrophenol (PNMC), a well-known constituent of diesel exhaust particles and degradation products of insecticide fenitrothion, is a widely distributed environmental contaminant. PNMC is toxic to the female reproductive system; however, how it affects meiosis progression in oocytes is unknown. In this study, in vitro maturation of mouse oocytes was applied to investigate the deleterious effects of PNMC. We found that exposure to PNMC significantly compromised oocyte maturation. PNMC disturbed the spindle stability; specifically, it decreased the spindle density and increased the spindle length. The weakened spindle pole location of microtubule-severing enzyme Fignl1 may result in a defective spindle apparatus in PNMC-exposed oocytes. PNMC exposure induced significant mitochondrial dysfunction, including mitochondria distribution, ATP production, mitochondrial membrane potential, and ROS accumulation. The mRNA levels of the mitochondria-related genes were also significantly impaired. Finally, the above-mentioned alterations triggered early apoptosis in the oocytes. In conclusion, PNMC exposure affected oocyte maturation and quality through the regulation of spindle stability and mitochondrial function.


Assuntos
Doenças Mitocondriais , Oócitos , Feminino , Animais , Camundongos , Cresóis , DNA Mitocondrial , Meiose
14.
Sheng Li Xue Bao ; 76(2): 266-288, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658376

RESUMO

Irisin, a peptide produced during exercise, is believed to play a role in regulating energy levels within the body. Moreover, Irisin has the ability to traverse the blood-brain barrier and engage in various pathophysiological processes within the central nervous system. An increasing body of research identifies Irisin as a significant therapeutic target for neurodegenerative diseases, indicating a strong link between Irisin and the development of cognitive impairments. In this paper, we present a concise review of effects of different types of exercise on Irisin production, and the mechanisms underlying the Irisin's intervention in various diseases including metabolic diseases, kidney injury and depression. Following this, we delve into an in-depth exploration of its role in modulating cognitive dysfunction among patients with Alzheimer's disease (AD), focusing on recent advancements in three critical areas: neuroinflammation, mitochondrial dysfunction, and protein misfolding. Finally, we put forth 3 hypotheses: (1) exercise-induced fibronectin type III domain containing protein 5 (FNDC5) stimulation and subsequent Irisin cleavage may be associated with the stress response in energy metabolism; (2) Irisin, as a myokine, likely plays a role in mitochondrial repair mechanisms to ameliorate cognitive impairment in AD patients; (3) Irisin is a homeostatic factor that maintains energy homeostasis and is closely related to the dynamic stability of the body's internal environment.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Exercício Físico , Fibronectinas , Humanos , Doença de Alzheimer/metabolismo , Fibronectinas/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Exercício Físico/fisiologia , Animais , Mitocôndrias/metabolismo
15.
Angew Chem Int Ed Engl ; : e202410457, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004608

RESUMO

Single-atom catalysts have garnered significant attention due to their exceptional atom utilization and unique properties. However, the practical application of these catalysts is often impeded by challenges such as sintering-induced instability and poisoning of isolated atoms due to strong gas adsorption. In this study, we employed the mechanochemical method to insert single Cu atoms into the subsurface of Fe2O3 support. By manipulating the location of single atoms at the surface or subsurface, catalysts with distinct adsorption properties and reaction mechanisms can be achieved. It was observed that the subsurface Cu single atoms in Fe2O3 remained isolated under both oxidation and reduction environments, whereas surface Cu single atoms on Fe2O3 experienced sintering under reduction conditions. The unique properties of these subsurface single-atom catalysts call for innovations and new understandings in catalyst design.

16.
Cell Rep ; 43(5): 114198, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38691451

RESUMO

Hao Gu spoke with Cell Reports about his scientific journey, inspirations to become a scientist, and his work on molecular mechanisms driving the progression of tumors of the digestive system; in particular, he discussed his lab's recent work regarding the role of circDNA2v in colorectal cancer.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , História do Século XXI
17.
J Chromatogr A ; 1731: 465167, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39033707

RESUMO

A mathematical description and experimental outputs exhibited that an ion chronogram from an in-tube solid-phase microextraction (SPME) device linked with mass spectrometry (in-tube-SPME-MS) generally appears as a right-skew unimodal signal with a heavy right tail. Analogous to liquid chromatography coupled with mass spectrometry (LC-MS), in-tube-SPME-MS can utilize the area under its produced ion chronogram for regression analysis and has been shown to be a potential approach for fast quantification of analyte. Different level of unimodity of signal in the ion chronogram could positively or negatively affect the choice of the area used for quantification and finally impact on analysis sensitivity and time efficiency of in-tube-SPME-MS. In the paper, we showed that different in-tube SPME design choices and elution experimental setups produce ion chronograms with controllable varying unimodal peak shape patterns. An improved mathematical model was built based on the plate theory of chromatography and the Van Deemter equation to quantitatively describe the elution process from in-tube-SPME device. A computer simulation was implemented to predict ion chronograms and the results were compared with experimental ion chronograms to show the effectiveness of the model. An optimization framework was further presented based on the model to identify optimal device designs (length and diameter of device) and experimental parameters (flow rate) to track targeted ion chronograms with "desired" peak shape patterns. Empirical elution experiments with the in-tube SPME devices adopting optimized geometric parameters and optimal experimental setups confirmed the consistency between the experimental ion chronograms and the numerical simulations to a certain level.


Assuntos
Modelos Teóricos , Extração em Fase Sólida , Extração em Fase Sólida/instrumentação , Extração em Fase Sólida/métodos , Íons/química , Espectrometria de Massas/instrumentação , Espectrometria de Massas/métodos , Modelos Lineares
18.
Talanta ; 271: 125651, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262130

RESUMO

Modern solid phase microextraction (SPME) device linked with mass spectrometry (SPME-MS) has evolved from producing ion chronogram as flat noisy signal to as unimodal-like signal. We designed a SPME device, which is closer in morphology to LC column, linked it with a miniature mass spectrometer (SPME-Mini MS), and proposed a mathematical model that elution of compound from the SPME device is equivalent to overlay of elution of the compound from the infinite LC columns with the lengths between 0 and the length of the device and it can generate an ion chronogram as right-skew unimodal signal. Rhodamine B as analyte was used for experimental verification and its unimodal signal was used to fit the parameters of a computer simulation program based on the model. The experimental results and simulations empirically cross-confirmed that SPME-Mini MS can generate ion chronogram as clean right-skew unimodal signal. Furthermore, the SPME-Mini MS system was used for quantitative analysis of psychotropic drugs (i.e. risperidone and aripiprazole) in artificial urine. The results preliminarily demonstrated that the system can utilize area under unimodal signal for quantitative analysis and has potential to be applied for on-site, fast and accurate quantification of drugs and other compounds.

19.
Animals (Basel) ; 14(14)2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39061590

RESUMO

The cultivation of the Chinese mitten crab (Eriocheir sinensis) is an important component of China's aquaculture industry and also a field of concern worldwide. It focuses on the selection of high-quality, disease-free juvenile crabs. However, the early maturity rate of more than 18.2% and the mortality rate of more than 60% make it difficult to select suitable juveniles for adult culture. The juveniles exhibit subtle distinguishing features, and the methods for differentiating between sexes vary significantly; without training from professional breeders, it is challenging for laypersons to identify and select the appropriate juveniles. Therefore, we propose a task-aligned detection algorithm for identifying one-year-old precocious Chinese mitten crabs, named R-TNET. Initially, the required images were obtained by capturing key frames, and then they were annotated and preprocessed by professionals to build a training dataset. Subsequently, the ResNeXt network was selected as the backbone feature extraction network, with Convolutional Block Attention Modules (CBAMs) and a Deformable Convolution Network (DCN) embedded in its residual blocks to enhance its capability to extract complex features. Adaptive spatial feature fusion (ASFF) was then integrated into the feature fusion network to preserve the detailed features of small targets such as one-year-old precocious Chinese mitten crab juveniles. Finally, based on the detection head proposed by task-aligned one-stage object detection, the parameters of its anchor alignment metric were adjusted to detect, locate, and classify the crab juveniles. The experimental results showed that this method achieves a mean average precision (mAP) of 88.78% and an F1-score of 97.89%. This exceeded the best-performing mainstream object detection algorithm, YOLOv7, by 4.17% in mAP and 1.77% in the F1-score. Ultimately, in practical application scenarios, the algorithm effectively identified one-year-old precocious Chinese mitten crabs, providing technical support for the automated selection of high-quality crab juveniles in the cultivation process, thereby promoting the rapid development of aquaculture and agricultural intelligence in China.

20.
Sci Rep ; 14(1): 7111, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531907

RESUMO

This study aims to measure anatomical data of the capitate bone, develop an external fixator for treating late-stage osteonecrosis of lunate through Ilizarov technique, and evaluate its biomechanical performance. We selected eight wrist joint specimens to measure various parameters of the capitate bone, including its length, the distance from the junction of capitate head and body to the proximal end, as well as the width of its proximal head and distal body. Additionally, we measured these same indicators in 107 patients who had undergone wrist X-ray examination. Based on our measurements, we categorized the capitate bone into two groups and designed two types of capitate bone Ilizarov external fixator (CIEF) for it. Then, we compared it with the orthofix external fixator (OEF) through dynamic fatigue biomechanical experiments and pull-out resistance experiments. The results of the measurement revealed two categories of general patterns in the capitate bone. The first type maintains a consistent longitudinal axis between the proximal and distal ends. The second type is characterized by its proximal end being close to the radial side and its distal end being close to the ulnar side. In the dynamic tensile fatigue test, CIEF-A and CIEF-B had smaller maximum displacement values compared to the OEF (P < 0.05). In the anti-pull-out experiment, both CIEF-A and CIEF-B exhibited higher maximum pull-out force than the OEF (P < 0.05). CIFE is a treatment for advanced osteonecrosis of the lunate bone. It is specifically designed to align with the anatomical characteristics of the capitate bone, providing excellent biomechanical properties and a simple clinical procedure. However, additional clinical experiments are needed to confirm its effectiveness in the future.


Assuntos
Capitato , Osso Semilunar , Osteonecrose , Humanos , Osteonecrose/cirurgia , Articulação do Punho/cirurgia , Rádio (Anatomia)
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