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1.
PeerJ ; 12: e16952, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38563008

RESUMEN

Background: The aim of this study is to design a deep learning (DL) model to preoperatively predict the occurrence of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: This research collected preoperative ultrasound (US) images and clinical factors of 611 PTMC patients. The clinical factors were analyzed using multivariate regression. Then, a DL model based on US images and clinical factors was developed to preoperatively predict CLNM. The model's efficacy was evaluated using the receiver operating characteristic (ROC) curve, along with accuracy, sensitivity, specificity, and the F1 score. Results: The multivariate analysis indicated an independent correlation factors including age ≥55 (OR = 0.309, p < 0.001), tumor diameter (OR = 2.551, p = 0.010), macrocalcifications (OR = 1.832, p = 0.002), and capsular invasion (OR = 1.977, p = 0.005). The suggested DL model utilized US images achieved an average area under the curve (AUC) of 0.65, slightly outperforming the model that employed traditional clinical factors (AUC = 0.64). Nevertheless, the model that incorporated both of them did not enhance prediction accuracy (AUC = 0.63). Conclusions: The suggested approach offers a reference for the treatment and supervision of PTMC. Among three models used in this study, the deep model relied generally more on image modalities than the data modality of clinic records when making the predictions.


Asunto(s)
Carcinoma Papilar , Aprendizaje Profundo , Neoplasias de la Tiroides , Humanos , Metástasis Linfática/diagnóstico por imagen , Factores de Riesgo , Neoplasias de la Tiroides/diagnóstico por imagen
2.
ACS Appl Bio Mater ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38556979

RESUMEN

Recent advances have been made in second near-infrared (NIR-II) fluorescence bioimaging and many related applications because of its advantages of deep penetration, high resolution, minimal invasiveness, and good dynamic visualization. To achieve high-performance NIR-II fluorescence bioimaging, various materials and probes with bright NIR-II emission have been extensively explored in the past few years. Among these NIR-II emissive materials, conjugated polymers and conjugated small molecules have attracted wide interest due to their native biosafety and tunable optical performance. This review summarizes the brightness strategies available for NIR-II emissive conjugated materials and highlights the recent developments in NIR-II fluorescence bioimaging. A concise, detailed overview of the molecular design and regulatory approaches is provided in terms of their high brightness, long wavelengths, and superior imaging performance. Then, various typical cases in which bright conjugated materials are used as NIR-II probes are introduced by providing step-by-step examples. Finally, the current problems and challenges associated with accessing NIR-II emissive conjugated materials for bright NIR-II fluorescence bioimaging are briefly discussed, and the significance and future prospects of these materials are proposed to offer helpful guidance for the development of NIR-II emissive materials.

3.
Prostate ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38558009

RESUMEN

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition, yet it is challenging for the average BPH patient to find credible and accurate information about BPH. Our goal is to evaluate and compare the accuracy and reproducibility of large language models (LLMs), including ChatGPT-3.5, ChatGPT-4, and the New Bing Chat in responding to a BPH frequently asked questions (FAQs) questionnaire. METHODS: A total of 45 questions related to BPH were categorized into basic and professional knowledge. Three LLM-ChatGPT-3.5, ChatGPT-4, and New Bing Chat-were utilized to generate responses to these questions. Responses were graded as comprehensive, correct but inadequate, mixed with incorrect/outdated data, or completely incorrect. Reproducibility was assessed by generating two responses for each question. All responses were reviewed and judged by experienced urologists. RESULTS: All three LLMs exhibited high accuracy in generating responses to questions, with accuracy rates ranging from 86.7% to 100%. However, there was no statistically significant difference in response accuracy among the three (p > 0.017 for all comparisons). Additionally, the accuracy of the LLMs' responses to the basic knowledge questions was roughly equivalent to that of the specialized knowledge questions, showing a difference of less than 3.5% (GPT-3.5: 90% vs. 86.7%; GPT-4: 96.7% vs. 95.6%; New Bing: 96.7% vs. 93.3%). Furthermore, all three LLMs demonstrated high reproducibility, with rates ranging from 93.3% to 97.8%. CONCLUSIONS: ChatGPT-3.5, ChatGPT-4, and New Bing Chat offer accurate and reproducible responses to BPH-related questions, establishing them as valuable resources for enhancing health literacy and supporting BPH patients in conjunction with healthcare professionals.

4.
Thorac Cancer ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38576119

RESUMEN

INTRODUCTION: Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high-quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non-small cell lung cancer (NSCLC) protocols in China, on the risk-benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. METHODS: To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross-dimensional real-world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit-risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. DISCUSSION: This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.

6.
Small ; : e2400978, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38593307

RESUMEN

Lead (Pb) poisoning and CO2-induced global warming represent two exemplary environmental and energy issues threatening humanity. Various biomass-derived materials are reported to take up Pb and convert CO2 electrochemically into low-valent carbon species, but these works address the problems separately rather than settle the issues simultaneously. In this work, cheap, natural ellagic acid (EA) extracted from common plants is adopted to assemble a stable metal-organic framework (MOF), EA-Pb, by effective capture of Pb2+ ions in an aqueous medium (removal rate close to 99%). EA-Pb represents the first structurally well-defined Pb-based MOF showing selective electrocatalytic CO2-to-HCOO- conversion with Faradaic efficiency (FE) of 95.37% at -1.08 V versus RHE. The catalytic mechanism is studied by 13CO2 labeling, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and theoretical calculation. The use of EA-Pb as an electrocatalyst for CO2 reduction represents a 2-in-1 solution of converting detrimental wastes (Pb2+) as well as natural resources (EA) into wealth (electrocatalytic EA-Pb) for addressing the global warming issue.

7.
Plant Physiol Biochem ; 210: 108589, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38593485

RESUMEN

Carotenoids are important pigmented nutrients synthesized by tomato fruits during ripening. To reveal the molecular mechanism underlying carotenoid synthesis during tomato fruit ripening, we analyzed carotenoid metabolites and transcriptomes in six development stages of tomato fruits. A total of thirty different carotenoids were detected and quantified in tomato fruits from 10 to 60 DPA. Based on differential gene expression profiles and WGCNA, we explored several genes that were highly significant and negatively correlated with lycopene, all of which encode fasciclin-like arabinogalactan proteins (FLAs). The FLAs are involved in plant signal transduction, however the functional role of these proteins has not been studied in tomato. Genome-wide analysis revealed that cultivated and wild tomato species contained 18 to 22 FLA family members, clustered into four groups, and mainly evolved by means of segmental duplication. The functional characterization of FLAs showed that silencing of SlFLA1, 5, and 13 were found to contribute to the early coloration of tomato fruits, and the expression of carotenoid synthesis-related genes was up-regulated in fruits that changed phenotypically, especially in SlFLA13-silenced plants. Furthermore, the content of multiple carotenoids (including (E/Z)-phytoene, lycopene, γ-carotene, and α-carotene) was significantly increased in SlFLA13-silenced fruits, suggesting that SlFLA13 has a potential inhibitory function in regulating carotenoid synthesis in tomato fruits. The results of the present study broaden the idea of analyzing the biological functions of tomato FLAs and preliminary evidence for the inhibitory role of SlFLA13 in carotenoid synthesis in fruit, providing the theoretical basis and a candidate for improving tomato fruit quality.

8.
Br J Pharmacol ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589338

RESUMEN

BACKGROUND AND PURPOSE: It is well acknowledged that tobacco-derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco-derived carcinogen nicotine-derived nitrosamine ketone (NNK)-treated A/J mice. EXPERIMENTAL APPROACH: RNA sequencing was used to detect the level of long non-coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR-328-3p in vitro, and NNK-treated A/J mice were used to test their function in vivo. In vivo levels of miR-328-3p and lncRNA XIST were analysed, using in situ hybridization. miR-328-3p agomir and lncRNA XIST-specific siRNA were used to manipulate in vivo levels of miR-328-3p and lncRNA XIST in A/J mice. KEY RESULTS: LncRNA XIST was up-regulated in NNK-induced lung injury and dominated the NNK-induced ectopic miRNA expression in NNK-induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR-328-3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down-regulated miR-328-3p levels as a miRNA sponge, and miR-328-3p targeted the 3'-UTR of FZD7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR-328 overexpression could rescue NNK-induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK-treated A/J mice. CONCLUSIONS AND IMPLICATIONS: Our results highlight the promotive effect of lncRNA XIST in NNK-induced lung injury and elucidate its post-transcriptional mechanisms, indicating that targeting lncRNA XIST/miR-328-3p could be a potential therapeutic strategy to prevent tobacco carcinogen-induced lung injury in vivo.

9.
Front Microbiol ; 15: 1327464, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585690

RESUMEN

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

11.
bioRxiv ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38645161

RESUMEN

Adult tissues with high cellular turnover require a balance between stem cell renewal and differentiation, yet the mechanisms underlying this equilibrium are unclear. The cornea exhibits a polarized lateral flow of progenitors from the peripheral stem cell niche to the center; attributed to differences in cellular fate. To identify genes that are critical for regulating the asymmetric fates of limbal stem cells and their transient amplified progeny in the central cornea, we utilized an in vivo cell cycle reporter to isolate proliferating basal cells across the anterior ocular surface epithelium and perform single-cell transcriptional analysis. This strategy greatly increased the resolution and revealed distinct basal cell identities with unique expression profiles of structural genes and transcription factors. We focused on Sox9; a transcription factor implicated in stem cell regulation across various organs. Sox9 was found to be differentially expressed between limbal stem cells and their progeny in the central corneal. Lineage tracing analysis confirmed that Sox9 marks long-lived limbal stem cells and conditional deletion led to abnormal differentiation and squamous metaplasia in the central cornea. These data suggest a requirement for Sox9 to brake cell division symmetry as transient cells exit the limbal niche. By inhibiting terminal differentiation of corneal progenitors, forcing them into perpetual symmetric divisions, we replicated the Sox9 loss-of-function phenotype. Our findings reveal an essential role for Sox9 for the spatial regulation of asymmetric fate in the corneal epithelium that is required to sustain tissue homeostasis.

12.
ChemSusChem ; : e202400091, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38623692

RESUMEN

Transition metal oxides (TMOs) are highly dense in energy and considered as promising anode materials for a new generation of alkaline ion batteries. However, their electrode structure is disrupted due to significant volume changes during charging and discharging, resulting in the short cycle life of batteries. In this paper, the hierarchical Ni3V2O8@N-doped carbon (Ni3V2O8@NC) hollow double-shell microspheres were prepared and used as electrode materials for lithium-ion batteries (LIBs). The utilization efficiency and ion transfer rate of Ni3V2O8 were improved by the hollow microsphere structure formed through nanoparticle self-assembly. Furthermore, the uniform N-doped carbon layer not only enhanced the structural stability of Ni3V2O8, but also improved the overall electrical conductivity of the composite. The Ni3V2O8@NC electrode has an initial discharge capacity of up to 1167.3 mAh g-1 at a current density of 0.3 A g-1, a reversible capacity of up to 726.5 mAh g-1 after 200 cycles, and still has a capacity of 567.6 mAh g-1 after 500 cycles at a current density of 1 A g-1, indicating that the material has good cycle stability and high-rate capability. This work presents new findings on the design and fabrication of complex porous double-shell nanostructures.

13.
Mol Cell Biochem ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38625515

RESUMEN

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology. At present, emerging evidences suggest that metabolism alteration is closely associated with α-synuclein aggregation and PD progression, and improvement of key molecules in metabolism might be potentially beneficial in PD treatment. In this review, we highlight the tripartite relationship among metabolic changes, α-synuclein aggregation, and oxidative stress in PD, and offer updated insights into the treatments of PD, aiming to deepen our understanding of PD pathogenesis and explore new therapeutic strategies for the disease.

14.
J Ovarian Res ; 17(1): 70, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561819

RESUMEN

OBJECTIVES: This retrospective study aims to evaluating the subsequent management and outcomes after first-line PARPi progression in Chinese ovarian cancer population. METHODS: Clinical and pathologic variables, treatment modalities, and outcomes were assessed. We investigated the subsequent management and outcomes after first-line PARPi progression. The objective response rate (ORR) and disease control rate (DCR) parameters were evaluated to determine the response to subsequent chemotherapy. For the survival analyses, progression-free survival 1 (PFS1), PFS2, overall survival (OS) and PFS2 - PFS1 were analysed. RESULTS: A total of 124 patients received PARPi maintenance treatment after first-line chemotherapy during the study period in our center. 44 of them (35.5%) experienced a recurrence. The median duration of PARPi in these patients was 11.1 months (range: 1.2-75.1 months). A total of 40 patients (40/44, 90.9%) received subsequent chemotherapy with 35 (35/44, 79.5%) and 5 (5/44, 11.4%) patients received platinum-based and non-platinum-based chemotherapy in our center. 2 patients (4.5%) received target therapy and other 2 patients (4.5%) received best supportive care. 27.3% (12/44) patients received secondary cytoreduction surgery (SCS). After subsequent chemotherapy, 14 patients received PARPi retreatment as maintenance therapy. In patients who received platinum-based regimens (n = 35), 23 of 35 patients (65.7%) had complete/partial response (CR/PR), 8 of 35 (22.9%) had stable disease (SD), and 4 of 35 (12.1%) had progressive disease (PD). The ORR and DCR of patients who received subsequent chemotherapy was 65.7% and 88.6%, respectively. 15 patients (57.7%, 15/26) were reported to be platinum resistant with a platinum-free interval (PFI) of < 6 months in patients whose platinum sensitivity of the second line platinum-based regimens was evaluable. Patients who received SCS after PARPi resistant associated with a borderline better PFS2 (median PFS2: 41.9 vs. 29.2 months, P = 0.051) and a non-significantly increased PFS2-PFS1 (median PFS2-PFS1: 12.2 vs. 9.8 months, P = 0.551). Patients with a PFI ≥ 12 months had a significantly better PFS2 (median PFS2: 37.0 vs. 25.3 months, P < 0.001) and a tendency towards a better PFS2-PFS1 than those with a PFI < 12 months (median PFS2-PFS1: 11.2 vs. 8.5 months, P = 0.334). A better PFS2 was observed in patients who received second PARPi maintenance therapy (median PFS2 of 35.4 vs. 28.8 months); however, the difference was not statistically significant (P = 0.200). A better PFS2-PFS1 was observed in patients who received second PARPi maintenance therapy (median PFS2-PFS1: 13.6 vs. 8.9 months, P = 0.002) than those without. CONCLUSIONS: In summary, some degree of resistance to standard subsequent platinum and non-platinum chemotherapy is noted in the entire cohort. A trend towards higher benefit from subsequent chemotherapy after first-line PARP inhibitors progression was observed in the PFI ≥ 12 months subgroup than those with PFI < 12 months. PARPi retreatment as maintenance therapy and SCS can be offered to some patients with PARPi resistance.


Asunto(s)
Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Estudios Retrospectivos , Neoplasias Ováricas/patología , Supervivencia sin Progresión , Análisis de Supervivencia , Platino (Metal)/farmacología , Platino (Metal)/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico
15.
Biomaterials ; 308: 122544, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38579591

RESUMEN

Exosomes, as nanoscale extracellular vesicles (EVs), are secreted by all types of cells to facilitate intercellular communication in living organisms. After being taken up by neighboring or distant cells, exosomes can alter the expression levels of target genes in recipient cells and thereby affect their pathophysiological outcomes depending on payloads encapsulated therein. The functions and mechanisms of exosomes in cardiovascular diseases have attracted much attention in recent years and are thought to have cardioprotective and regenerative potential. This review summarizes the biogenesis and molecular contents of exosomes and details the roles played by exosomes released from various cells in the progression and recovery of cardiovascular disease. The review also discusses the current status of traditional exosomes in cardiovascular tissue engineering and regenerative medicine, pointing out several limitations in their application. It emphasizes that some of the existing emerging industrial or bioengineering technologies are promising to compensate for these shortcomings, and the combined application of exosomes and biomaterials provides an opportunity for mutual enhancement of their performance. The integration of exosome-based cell-free diagnostic and therapeutic options will contribute to the further development of cardiovascular regenerative medicine.

16.
Med ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38582088

RESUMEN

Over the past decades, nanomedicine researchers have dedicated their efforts to developing nanoscale platforms capable of more precisely delivering drug payloads to attack tumors. Cancer nanovaccines are exhibiting a distinctive capability in inducing tumor-specific antitumor responses. Nevertheless, there remain numerous challenges that must be addressed for cancer nanovaccines to evoke sufficient therapeutic effects. Cell membrane-derived nanovaccines are an emerging class of cancer vaccines that comprise a synthetic nanoscale core camouflaged by naturally derived cell membranes. The specific cell membrane has a biomimetic nanoformulation with several distinctive abilities, such as immune evasion, enhanced biocompatibility, and tumor targeting, typically associated with a source cell. Here, we discuss the advancements of cell membrane-derived nanovaccines and how these vaccines are used for cancer therapeutics. Translational endeavors are currently in progress, and additional research is also necessary to effectively address crucial areas of demand, thereby facilitating the future successful translation of these emerging vaccine platforms.

17.
Acad Radiol ; 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38582684

RESUMEN

RATIONALE AND OBJECTIVES: To explore and validate the clinical value of ultrasound (US) viscosity imaging in differentiating breast lesions by combining with BI-RADS, and then comparing the diagnostic performances with BI-RADS alone. MATERIALS AND METHODS: This multicenter, prospective study enrolled participants with breast lesions from June 2021 to November 2022. A development cohort (DC) and validation cohort (VC) were established. Using histological results as reference standard, the viscosity-related parameter with the highest area under the receiver operating curve (AUC) was selected as the optimal one. Then the original BI-RADS would upgrade or not based on the value of this parameter. Finally, the results were validated in the VC and total cohorts. In the DC, VC and total cohorts, all breast lesions were divided into the large lesion, small lesion and overall groups respectively. RESULTS: A total of 639 participants (mean age, 46 years ± 14) with 639 breast lesions (372 benign and 267 malignant lesions) were finally enrolled in this study including 392 participants in the DC and 247 in the VC. In the DC, the optimal viscosity-related parameter in differentiating breast lesions was calculated to be A'-S2-Vmax, with the AUC of 0.88 (95% CI: 0.84, 0.91). Using > 9.97 Pa.s as the cutoff value, the BI-RADS was then modified. The AUC of modified BI-RADS significantly increased from 0.85 (95% CI: 0.81, 0.88) to 0.91 (95% CI: 0.87, 0.93), 0.85 (95% CI: 0.80, 0.89) to 0.90 (95% CI: 0.85, 0.93) and 0.85 (95% CI: 0.82, 0.87) to 0.90 (95% CI: 0.88, 0.92) in the DC, VC and total cohorts respectively (P < .05 for all). CONCLUSION: The quantitative viscous parameters evaluated by US viscosity imaging contribute to breast cancer diagnosis when combined with BI-RADS.

18.
FEBS J ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38652546

RESUMEN

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils. Knockout of tdh causes a decrease in neutrophil number and slightly suppresses their acute injury-induced migration, but, unlike the mESCs, the level of H3K4me3 is not evidently reduced in neutrophils sorted from the kidney marrow of adult tdh-null zebrafish. These phenotypes are dependent on the enzymatic activity of Tdh. Importantly, a soluble supplement of nutrients that are able to fuel the acetyl-CoA pool, such as pyruvate, glucose and branched-chain amino acids, is sufficient to rescue the reduction in neutrophils caused by tdh deletion. In summary, our study presents evidence for the functional requirement of Tdh-mediated threonine metabolism in a developmental process in vivo. It also provides an animal model for investigating the nutritional regulation of myelopoiesis and immune response, as well as a useful tool for high-throughput drug/nutrition screening.

19.
BMC Biol ; 22(1): 81, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609978

RESUMEN

BACKGROUND: Response to oxidative stress is universal in almost all organisms and the mitochondrial membrane protein, BbOhmm, negatively affects oxidative stress responses and virulence in the insect fungal pathogen, Beauveria bassiana. Nothing further, however, is known concerning how BbOhmm and this phenomenon is regulated. RESULTS: Three oxidative stress response regulating Zn2Cys6 transcription factors (BbOsrR1, 2, and 3) were identified and verified via chromatin immunoprecipitation (ChIP)-qPCR analysis as binding to the BbOhmm promoter region, with BbOsrR2 showing the strongest binding. Targeted gene knockout of BbOsrR1 or BbOsrR3 led to decreased BbOhmm expression and consequently increased tolerances to free radical generating compounds (H2O2 and menadione), whereas the ΔBbOsrR2 strain showed increased BbOhmm expression with concomitant decreased tolerances to these compounds. RNA and ChIP sequencing analysis revealed that BbOsrR1 directly regulated a wide range of antioxidation and transcription-associated genes, negatively affecting the expression of the BbClp1 cyclin and BbOsrR2. BbClp1 was shown to localize to the cell nucleus and negatively mediate oxidative stress responses. BbOsrR2 and BbOsrR3 were shown to feed into the Fus3-MAPK pathway in addition to regulating antioxidation and detoxification genes. Binding motifs for the three transcription factors were found to partially overlap in the promoter region of BbOhmm and other target genes. Whereas BbOsrR1 appeared to function independently, co-immunoprecipitation revealed complex formation between BbClp1, BbOsrR2, and BbOsrR3, with BbClp1 partially regulating BbOsrR2 phosphorylation. CONCLUSIONS: These findings reveal a regulatory network mediated by BbOsrR1 and the formation of a BbClp1-BbOsrR2-BbOsrR3 complex that orchestrates fungal oxidative stress responses.


Asunto(s)
Ciclinas , Factores de Transcripción , Factores de Transcripción/genética , Peróxido de Hidrógeno , Ciclo Celular , Estrés Oxidativo , Antioxidantes
20.
Nanoscale ; 16(16): 8151-8161, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38572680

RESUMEN

The rational design of the dimension and geometry of a plasmonic semiconductor cocatalyst is vitally important for efficient utilization of near-infrared (NIR) light and superior photocatalytic hydrogen generation. Herein, hollow cubic CuSe@CdS composites with different sizes and strong localized surface plasmon resonance (LSPR) were prepared by selenizing size-tunable Cu2O templates and loading CdS nanoparticles. The size of hollow cubic CuSe can affect the surface area and the conduction band potential through the size effect, regulating the carrier behavior of the CuSe@CdS heterojunction. The CuSe@CdS composites show enhanced and wide absorption in the full spectrum due to the LSPR effect of CuSe. Meanwhile, the composites show excellent photocatalytic hydrogen capacity in the full spectrum in a 0.35 M Na2S/0.25 M Na2SO3 sacrificial reagent solution. The best hydrogen production rate of CSCE2 is 1.518 mmol g-1 h-1 (5.54 times higher than that of CdS) under Vis light (780 > λ > 420 nm) irradiation and 0.28 mmol g-1 h-1 under NIR light (λ > 780 nm) illumination. Interestingly, the photocatalytic activity for H2 under Vis-NIR light (λ > 420 nm) is about 3 times (up to 4.45 mmol g-1 h-1) higher than that without NIR light assistance, due to the photothermal effect. Various analyses and DFT calculations demonstrate that the p-n heterojunction formed in the composites consists of p-type CuSe and n-type CdS, which achieves efficient carrier transfer and separation under the synergistic effect of the size effect and the photothermal effect. In addition, the expansion of the photocatalytic performance to the NIR range is mainly due to the "hot-electron" injection mechanism induced by the LSPR effect of CuSe. The reasonable design coupled with the plasmonic materials offers a new path to achieving the highly efficient conversion of solar energy to hydrogen energy.

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