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1.
Artículo en Inglés | MEDLINE | ID: mdl-38703990

RESUMEN

Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.

2.
RSC Adv ; 14(21): 14716-14721, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38716097

RESUMEN

Halide solid-state electrolytes (SSEs) are considered promising candidates for practical applications in all-solid-state batteries (ASSBs), due to their outstanding high voltage stability and compatibility with electrode materials. However, Na+ halide SSEs suffer from low ionic conductivity and high activation energy, which limit their applications in sodium all-solid-state batteries. Here, sodium yttrium bromide solid-state electrolytes (Na3YBr6) with a low activation energy of 0.15 eV is prepared via solid state reaction. Structure characterization using X-ray diffraction reveals a monoclinic structure (P21/c) of Na3YBr6. First principle calculations reveal that the low migration activation energy comes from the larger size and vibration of Br- anions, both of which expand the Na+ ion migration channel and reduce its activation energy. The electrochemical window of Na3YBr6 is determined to be 1.43 to 3.35 V vs. Na/Na+, which is slightly narrower than chlorides. This work indicates bromides are a good catholyte candidate for sodium all solid-state batteries, due to their low ion migration activation energy and relatively high oxidation stability.

3.
Chem Commun (Camb) ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716634

RESUMEN

Rh-catalyzed three-component C(sp3)/C(sp2)-H activation has been achieved through a two-directing group strategy. This protocol provides a convenient and efficient pathway for the construction of diverse 8-alkyl quinoline derivatives in one-pot. Furthermore, mechanistic studies revealed that the first C-H amidation was significantly faster than the sequential C-H alkylation.

4.
Sci Total Environ ; : 173172, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740210

RESUMEN

Chronic hypoxia can affect the growth and metabolism of fish and potentially impact gonadal development through epigenetic regulation. Trachinotus blochii (Golden pompano) is widely cultured near the coast and is sensitive to low oxygen conditions. We found that hypoxia and reoxygenation processes acted on multiple targets on the HPG axis, leading to endocrine disorders. Changes in the expression of key genes in the brain (gnrh), pituitary (fsh and lh), ovaries (cyp19a1a, foxl2, and er), and testes (dmrt1, ar, sox9, and gsdf) were associated with significant decreases in estrogen and testosterone levels. Hypoxia and reoxygenation lead to changes in DNA methylation levels in the gonads. Hypoxia upregulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in females and dnmt3a and dnmt3b in males, while reoxygenation down-regulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in males. Whole genome methylation sequencing showed that the number of differentially methylated regions was highest on chromosome 10 (5192) and lowest on chromosome 24 (275). Differentially methylated genes in females and males, as well as between males and females, were enriched in the oxytocin signaling pathway, fatty acid metabolism pathway, and HIF-1a pathway. In summary, hypoxia and reoxygenation can induce endocrine disorders, affect the expression of HPG axis genes, change the methylation pattern and modification pattern of gonad DNA, and then have potential effects on gonad development.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124334, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38678837

RESUMEN

Alkaline phosphatase is an important biomarker for medical diagnosis. An enzymatic fluorescence supramolecular hydrogel with AIE properties was developed and used for sensing alkaline phosphatase in vitro and in living cells. In the presence of ALP, K(TPE)EFYp was partially converted to the hydrogelator K(TPE)EFY and self-assembled into nanofibers to form Hydrogel. With the sol-gel transition and the AIE effect, the fluorescence emission was turned on. The linear concentration range of ALP activity in vitro quantified by this method was determined as 0-3 U/L with aLODat 0.02 U/L. In addition, cell imaging and serum experiment showed that K(TPE)EFYp could also be used to detect ALP activity in living cells and biological samples.


Asunto(s)
Fosfatasa Alcalina , Hidrogeles , Espectrometría de Fluorescencia , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/análisis , Humanos , Hidrogeles/química , Colorantes Fluorescentes/química
6.
JBMR Plus ; 8(5): ziae031, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38606146

RESUMEN

Nonunion resulting from early bone resorption is common after bone transplantation surgery. In these patients, instability or osteoporosis causes hyperactive catabolism relative to anabolism, leading to graft resorption instead of fusion. Systemic zoledronate administration inhibits osteoclastogenesis and is widely used to prevent osteoporosis; however, evidence on local zoledronate application is controversial due to osteoblast cytotoxicity, uncontrolled dosing regimens, and local release methods. We investigated the effects of zolendronate on osteoclastogenesis and osteogenesis and explored the corresponding signaling pathways. In vitro cytotoxicity and differentiation of MC3T3E1 cells, rat bone marrow stromal cells (BMSCs) and preosteoclasts (RAW264.7 cells) were evaluated with different zolendronate concentrations. In vivo bone regeneration ability was tested by transplanting different concentrations of zolendronate with ß-tricalcium phosphate (TCP) bone substitute into rat femoral critical-sized bone defects. In vitro, zolendronate concentrations below 2.5 × 10-7 M did not compromise viability in the three cell lines and did not promote osteogenic differentiation in MC3T3E1 cells and BMSCs. In RAW264.7 cells, zoledronate inhibited extracellular regulated protein kinases and c-Jun n-terminal kinase signaling, downregulating c-Fos and NFATc1 expression, with reduced expression of fusion-related dendritic cell­specific transmembrane protein and osteoclast-specific Ctsk and tartrate-resistant acid phosphatase (. In vivo, histological staining revealed increased osteoid formation and neovascularization and reduced fibrotic tissue with 500 µM and 2000 µM zolendronate. More osteoclasts were found in the normal saline group after 6 weeks, and sequential osteoclast formation occurred after zoledronate treatment, indicating inhibition of bone resorption during early callus formation without inhibition of late-stage bone remodeling. In vivo, soaking ß-TCP artificial bone with 500 µM or 2000 µM zoledronate is a promising approach for bone regeneration, with potential applications in bone transplantation.

7.
Int J Biol Sci ; 20(6): 2219-2235, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617542

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Metabolismo de los Lípidos/genética , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Receptores de Quimiocina , Inflamación
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 505-511, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38660859

RESUMEN

OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. CONCLUSION: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.


Asunto(s)
Mieloma Múltiple , Trasplante de Células Madre de Sangre Periférica , Proteínas Recombinantes , Trombopoyetina , Trasplante Autólogo , Humanos , Mieloma Múltiple/terapia , Proteínas Recombinantes/administración & dosificación , Plaquetas , Recuento de Plaquetas , Masculino , Femenino
9.
Huan Jing Ke Xue ; 45(5): 2962-2970, 2024 May 08.
Artículo en Chino | MEDLINE | ID: mdl-38629557

RESUMEN

The sediment and soil in the Juma River channel pose a risk of pollution to the downstream ecological environment of Beijing and Xiong'an New Area. To address this issue, sediments and soil samples were collected along the river from the source to the Zhangfang outlet. The samples were further divided into three types:main stream sediment (29 samples), riverbank soil (27 samples), and farmland soil (26 samples). Enrichment factor analysis and the potential ecological risk index were employed to investigate the ecological risk. The results showed that the average concentrations of Cd, Hg, Pb, Zn, and Cu in the river sediment and soil in the study area were higher than those in the Baiyangdian Lake sediment and the surface soil of Hebei Province, whereas the concentrations of As, Cr, and Ni were relatively lower. The ranking of heavy metal pollution levels from high to low were Cd > Hg > Pb > Zn > Cu > Cr > Ni > As. The comprehensive ecological risk index showed that farmland soil and riverbank soil were mainly at a slight risk, followed by a moderate risk. The potential ecological risk of the main stream sediment was mainly moderate, severe, and extremely severe, accounting for 35.5%, 24.1%, and 24.1%, respectively, and the main contributing factors of the risk were Cd and Hg. The results of multivariate statistical analysis indicated that the main pollution sources of Cd, Pb, Zn, and Cu were industrial and mining activities. Cr, Ni, and As were mainly controlled by the weathering of the parent rock, and As was also influenced by agricultural activities. Hg was controlled by composite pollution sources such as industrial and mining activities, parent rock weathering, and atmospheric dust fall. Overall, the risk of heavy metal in the soil of the research area was generally at a slight level. However, there was a significant enrichment of Cd and other heavy metal in the sediment of the Taiyu-Sigezhuang-Pengtou River. This river section should be the focus of environmental monitoring, river dredging, and governance.

10.
Cell Commun Signal ; 22(1): 222, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594767

RESUMEN

Csn5 is subunit 5 of the COP9 signalosome (CSN), but the mechanism by which it strictly controls the pathogenicity of pathogenic fungi through autophagy remains unclear. Here, we found that Csn5 deficiency attenuated pathogenicity and enhanced autophagy in Magnaporthe oryzae. MoCSN5 knockout led to overubiquitination and overdegradation of MoTor (the core protein of the TORC1 complex [target of rapamycin]) thereby promoted autophagy. In addition, we identified MoCsn5 as a new interactor of MoAtg6. Atg6 was found to be ubiquitinated through linkage with lysine 48 (K48) in cells, which is necessary for infection-associated autophagy in pathogenic fungi. K48-ubiquitination of Atg6 enhanced its degradation and thereby inhibited autophagic activity. Our experimental results indicated that MoCsn5 promoted K48-ubiquitination of MoAtg6, which reduced the MoAtg6 protein content and thus inhibited autophagy. Aberrant ubiquitination and autophagy in ΔMocsn5 led to pleiotropic defects in the growth, development, stress resistance, and pathogenicity of M. oryzae. In summary, our study revealed a novel mechanism by which Csn5 regulates autophagy and pathogenicity in rice blast fungus through ubiquitination.


Asunto(s)
Ascomicetos , Virulencia , Proteínas , Ubiquitinación , Autofagia
11.
J Ethnopharmacol ; 330: 118217, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38641072

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive. AIM OF THE STUDY: The objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel. METHODS: The therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches. RESULTS: The administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca2+ influx through the channel opening and ultimately relieving pain. CONCLUSIONS: Lig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region.


Asunto(s)
4-Butirolactona , Analgésicos , Ratas Sprague-Dawley , Canal Catiónico TRPA1 , Animales , Canal Catiónico TRPA1/metabolismo , Analgésicos/farmacología , Analgésicos/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , 4-Butirolactona/química , Ratas , Humanos , Dolor/tratamiento farmacológico , Cisteína/farmacología , Cisteína/química , Masculino , Simulación del Acoplamiento Molecular , Células HEK293 , Sitios de Unión , Femenino
12.
Front Microbiol ; 15: 1353710, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38511011

RESUMEN

Introduction: Cordyceps cicadae is a traditional Chinese medicinal fungus known for its rich production of bioactive substances, particularly cyanidin, an anthocyanin commonly found in plants with notable anti-inflammatory, anti-tumor, antiviral, and antibacterial properties. This study revealed two key genes, CcDFR and CcOMT9, affecting cyanidin biosynthesis in C. cicadae. Methods: The roles of these genes in cyanidin production, growth, and development were elucidated through the gene knockout method, phenotypic analysis, transcriptomics, and metabolomics. Results: CcDFR deletion led to reduced cyanidin-3-O-glucoside (C3G), suppressed expression of cyanidin biosynthesis genes, impaired synnemata formation, decreased polysaccharide and adenosine content, and diminished chitinase activity. Meanwhile, the ΔCcOMT9 mutant exhibited an increase in C3G production, promoted expression of cyanidin biosynthesis genes and rising bioactive compounds, suppressed RNA methylation, and led to phenylalanine accumulation with no effect on fruiting body formation. Discussion: We revealed a distinct anthocyanin biosynthesis pathway in C. cicadae and identified two genes with opposite functions, laying the foundation for future genetic modification of cyanidin-producing strains using modern biological techniques. This will shorten the production period of this valuable compound, facilitating the industrial-scale production of cyanidin.

13.
Spine J ; 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38499068

RESUMEN

BACKGROUND CONTEXT: Long-segment pedicle screw instrumentation is widely used to treat complex spinal disorders. Rods are routinely precontoured to maximize assistance on the correcting side of the deformity, but there often exists a residual gap discrepancy between the precontoured rods and screw tulips. No previous research has investigated the diminished pullout strength of the most proximal or distal pedicle screw resulting from a mismatched rod in long-segment pedicle screw instrumentation. PURPOSE: The present study aimed to investigate the decreased pullout force of pedicle screws affected by the gap discrepancy when forcefully engaging a mismatched rod into a tulip in a normal-density porcine spine. STUDY DESIGN: The pedicle screw fixation strength under axial pullout force was compared among three different gap discrepancies between rods and tulips using long porcine spine segments. METHODS: Twelve porcine lumbar vertebrae (L3-L6) were implanted with pedicle screws and rods. Screws on one side had no gap between the tulip and rod (0-mm group), while the most proximal screw on the other side had an intentional gap of 3 mm (3-mm group) or 6 mm (6-mm group). Three hours after forcefully engaging the rod into the tulips at room temperature, the set screws in all specimens were loosened, and each specimen was dissected into individual vertebrae for subsequent pullout testing. RESULTS: The control group exhibited significantly greater pullout strength (1987.68 ± 126.80 N) than the groups from different rod-tulip configurations (p<.05), with significantly greater strength in the 3-mm group (945.62 ± 97.43 N) than the 6-mm group (655.30 ± 194.49 N) (p<.05). Only 47.6% and 33.0% of the pullout strength was retained in the 3-mm and 6-mm groups, respectively, compared to the control group. CONCLUSIONS: Gap discrepancies between rods and tulips can significantly reduce pedicle screw pullout strength, with a correlation between decreased strength and increased gaps. Surgeons should avoid forcefully engaging mismatched rods and consider well-fitted contoured rods in spinal surgery to minimize the risk of screw loosening. CLINICAL SIGNIFICANCE: The gap discrepancy between rod and tulip significantly affected pullout strength, with greater gaps leading to reduced strength. Forcefully engaging mismatched rods into tulips in degenerative spinal surgery should be avoided to minimize the risk of early screw pullout.

14.
Int J Mol Sci ; 25(6)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38542408

RESUMEN

Septins play a key regulatory role in cell division, cytokinesis, and cell polar growth of the rice blast fungus (Magnaporthe oryzae). We found that the organization of the septin ring, which is essential for appressorium-mediated infection in M. oryzae, requires long-chain fatty acids (LCFAs), which act as mediators of septin organization at membrane interfaces. However, it is unclear how septin ring formation and LCFAs regulate the pathogenicity of the rice blast fungus. In this study, a novel protein was named MoLfa1 because of its role in LCFAs utilization. MoLfa1 affects the utilization of LCFAs, lipid metabolism, and the formation of the septin ring by binding with phosphatidylinositol phosphates (PIPs), thereby participating in the construction of penetration pegs of M. oryzae. In addition, MoLfa1 is localized in the endoplasmic reticulum (ER) and interacts with the ER-related protein MoMip11 to affect the phosphorylation level of Mps1. (Mps1 is the core protein in the MPS1-MAPK pathway.) In conclusion, MoLfa1 affects conidia morphology, appressorium formation, lipid metabolism, LCFAs utilization, septin ring formation, and the Mps1-MAPK pathway of M. oryzae, influencing pathogenicity.


Asunto(s)
Ascomicetos , Magnaporthe , Oryza , Septinas/metabolismo , Proteínas Fúngicas/metabolismo , Magnaporthe/fisiología , Citoesqueleto/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas/microbiología , Esporas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica
15.
Comput Biol Med ; 171: 108230, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38442554

RESUMEN

Interpreting single-cell chromatin accessibility data is crucial for understanding intercellular heterogeneity regulation. Despite the progress in computational methods for analyzing this data, there is still a lack of a comprehensive analytical framework and a user-friendly online analysis tool. To fill this gap, we developed a pre-trained deep learning-based framework, single-cell auto-correlation transformers (scAuto), to overcome the challenge. Following DNABERT's methodology of pre-training and fine-tuning, scAuto learns a general understanding of DNA sequence's grammar by being pre-trained on unlabeled human genome via self-supervision; it is then transferred to the single-cell chromatin accessibility analysis task of scATAC-seq data for supervised fine-tuning. We extensively validated scAuto on the Buenrostro2018 dataset, demonstrating its superior performance on chromatin accessibility prediction, single-cell clustering, and data denoising. Based on scAuto, we further developed an interactive web server for single-cell chromatin accessibility data analysis. It integrates tutorial-style interfaces for those with limited programming skills. The platform is accessible at http://zhanglab.icaup.cn. To our knowledge, this work is expected to help analyze single-cell chromatin accessibility data and facilitate the development of precision medicine.


Asunto(s)
Cromatina , ADN , Humanos , Análisis de Secuencia de ADN , Genoma Humano , Análisis de Datos
16.
Mol Cell Oncol ; 11(1): 2309715, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38343433

RESUMEN

Breast cancer was considered as a kind of prone breast tumors with the complicated pathological mechanisms and diverse clinical classifications. In the clinical treatments of HER2-positive tumor patients, HER2 monoclonal antibodies, such as Herceptin, have shown well-defined therapeutic effects. Nevertheless, due to the heterogeneity of breast cancers, drug resistance inevitably appeared during the application of Herceptin. In order to fully understand the immune tolerance status of the tumor microenvironment in the population of sensitive and insensitive patients, this study carried out a series of studies through Luminex cytokines assay, clinicopathological analysis, immunofluorescence, and PCR. The results confirmed that in clinical samples sensitive to Herceptin, there were a large number of macrophages, and the protein expression levels and in situ expression of macrophage-related chemokines and inflammatory mediators are significantly higher than drug-resistant tumor samples. Further studies found that T cell function has a low correlation with tumor growth, and there are obvious obstacles in the process of peripheral blood immune cells entering the tumor microenvironment. In summary, this study provided clues for understanding the clinical drug resistance of HER2 monoclonal antibody and the clinical rational use of drugs and combination drugs.

18.
Anal Sci ; 40(3): 489-499, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38165524

RESUMEN

In our study, we present an innovative method for the analysis and real-time monitoring of peracetic acid (PAA) formation within the near-UV/Vis (visible) wavelength region. PAA's absorption spectrum, influenced by its presence in a complex quaternary equilibrium mixture with hydrogen peroxide (H2O2), acetic acid, and water, lacks discernible peaks. This inherent complexity challenges conventional analytical techniques like Beer's law, which rely on absorption intensity as a foundation. To address this challenge, we introduce a novel approach that centers on the analysis of blue shifts in absorption wavelengths, particularly at an absorbance of 0.8 a.u. This method significantly enhances the precision of calibration curves for both diluted PAA and H2O2, unveiling an exponential correlation between wavelength and the logarithm of concentration for both components. Significantly, our approach allows for real-time and accurate measurements, especially during the dynamic PAA formation reaction. Our results exhibit excellent agreement with data obtained from Fourier-transform infrared (FT-IR) spectroscopy, validating the reliability of our method. It's noteworthy that under stable PAA concentration conditions (after 12 h of solution interaction), both traditional absorption method and our approach closely align with the FT-IR method. However, in dynamic scenarios (0-12 h), the absorption method exhibits higher error rates compared to our approach. Additionally, the increased concentration of a catalyst, sulfuric acid (H2SO4), significantly reduces the errors in both methods, a finding that warrants further exploration. In summary, our study not only advances our understanding of PAA and its spectral behavior but also introduces innovative and precise methods for determining PAA concentration in complex solutions. These advancements hold the potential to revolutionize the field of chemical analysis and spectroscopy.

19.
Cell Commun Signal ; 22(1): 19, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38195499

RESUMEN

The cell cycle is pivotal to cellular differentiation in plant pathogenic fungi. Cell wall integrity (CWI) signaling plays an essential role in coping with cell wall stress. Autophagy is a degradation process in which cells decompose their components to recover macromolecules and provide energy under stress conditions. However, the specific association between cell cycle, autophagy and CWI pathway remains unclear in model pathogenic fungi Magnaporthe oryzae. Here, we have identified MoSwe1 as the conserved component of the cell cycle in the rice blast fungus. We have found that MoSwe1 targets MoMps1, a conserved critical MAP kinase of the CWI pathway, through protein phosphorylation that positively regulates CWI signaling. The CWI pathway is abnormal in the ΔMoswe1 mutant with cell cycle arrest. In addition, we provided evidence that MoSwe1 positively regulates autophagy by interacting with MoAtg17 and MoAtg18, the core autophagy proteins. Moreover, the S phase initiation was earlier, the morphology of conidia and appressoria was abnormal, and septum formation and glycogen degradation were impaired in the ΔMoswe1 mutant. Our research defines that MoSWE1 regulation of G1/S transition, CWI pathway, and autophagy supports its specific requirement for appressorium development and virulence in plant pathogenic fungi. Video Abstract.


Asunto(s)
Ascomicetos , Ciclo Celular , Autofagia , Pared Celular
20.
Conserv Physiol ; 12(1): coad105, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38293637

RESUMEN

Fishing causes direct removal of individuals from wild populations but can also cause a physiological disturbance in fish that are released or discarded after capture. While sublethal physiological effects of fish capture have been well studied in commercial and recreational fisheries, this issue has been overlooked for the ornamental fish trade, where it is common to capture fish from the wild and discard non-target species. We examined metabolic responses to capture and discard procedures in the three-striped dwarf cichlid Apistogramma trifasciata, a popular Amazonian aquarium species that nonetheless may be discarded when not a target species. Individuals (n = 34) were tagged and exposed to each of four treatments designed to simulate procedures during the capture and discard process: 1) a non-handling control; 2) netting; 3) netting +30 seconds of air exposure; and 4) netting +60 seconds of air exposure. Metabolic rates were estimated using intermittent-flow respirometry, immediately following each treatment then throughout recovery overnight. Increasing amounts of netting and air exposure caused an acute increase in oxygen uptake and decrease in available aerobic scope. In general, recovery occurred quickly, with rapid decreases in oxygen uptake within the first 30 minutes post-handling. Notably, however, male fish exposed to netting +60 seconds of air exposure showed a delayed response whereby available aerobic scope was constrained <75% of maximum until ~4-6 hours post-stress. Larger fish showed a greater initial increase in oxygen uptake post-stress and slower rates of recovery. The results suggest that in the period following discard, this species may experience a reduced aerobic capacity for additional behavioural/physiological responses including feeding, territory defence and predator avoidance. These results are among the first to examine impacts of discard practises in the ornamental fishery and suggest ecophysiological research can provide valuable insight towards increasing sustainable practises in this global trade.

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