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1.
ACS Nano ; 18(32): 21198-21210, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39099110

RESUMEN

The real-time monitoring of low-concentration cytokines such as TNF-α in sweat can aid clinical physicians in assessing the severity of inflammation. The challenges associated with the collection and the presence of impurities can significantly impede the detection of proteins in sweat. This issue is addressed by incorporating a nanosphere array designed for automatic sweat transportation, coupled with a reusable sensor that employs a Nafion/aptamer-modified MoS2 field-effect transistor. The nanosphere array with stepwise wettability enables automatic collection of sweat and blocks impurities from contaminating the detection zone. This device enables direct detection of TNF-α proteins in undiluted sweat, within a detection range of 10 fM to 1 nM. The use of an ultrathin, ultraflexible substrate ensures stable electrical performance, even after up to 30 extreme deformations. The findings indicate that in clinical scenarios, this device could potentially provide real-time evaluation and management of patients' immune status via sweat testing.


Asunto(s)
Biomarcadores , Técnicas Biosensibles , Sudor , Sudor/química , Humanos , Biomarcadores/análisis , Técnicas Biosensibles/instrumentación , Nanotecnología/instrumentación , Factor de Necrosis Tumoral alfa/análisis , Citocinas/análisis , Automatización , Disulfuros , Molibdeno
2.
Digit Health ; 10: 20552076241272589, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39148809

RESUMEN

Background: Children and adolescents who are overweight and obese represent a growing public health issue. The use of step-monitoring devices as an intervention tool may be a simple, cost-effective, and easily replicable solution for addressing obesity in children and adolescents. No prior systematic reviews have evaluated the effectiveness of utilizing step-monitoring devices as an intervention method for obesity in children and adolescents. Methods: Previous studies on using step-monitoring devices to prevent and treat obesity in children and adolescents were identified in the following databases: Web of Science, EMBASE, PubMed, Cochrane Library, SPORTDiscus, and SCOPUS. The search period for each database ranged from the year of their inception to 8 March 2023 (updated in June 2024). Meta-analyses were performed for mean differences (MDs) in body mass index (BMI), BMI z-score (BMI-Z), body fat, waist circumference, and body weight. Results: From 12,907 relevant records, 23 studies were included in this meta-analysis. The included studies were mainly at low risk of bias, except for blinding. Step-monitoring device-based interventions had significant effects in reducing BMI-Z (MD -0.06; 95% CI -0.10 to -0.02), body fat (MD -0.95%; 95% CI -1.35 to -0.54), and body weight (MD -1.23 kg; 95% CI -2.36 to -0.10). However, there was no significant effect on BMI (MD -0.16 kg/m2; 95% CI -0.55 to 0.22) and waist circumference (MD -0.33 cm; 95% CI -1.23 to 0.58). Subgroup analyses indicated that participants who were overweight or obese showed greater intervention effects on BMI and BMI-Z compared to participants with normal weight. The programs with an intervention duration of ≤6 months presented a greater intervention effect on BMI-Z than those with an intervention duration of more than 6 months. The programs that established goals had a greater intervention effect on body fat than those that did not. Conclusions: Step-monitoring devices may be an effective and generalizable intervention tool for the prevention and treatment of obesity in children and adolescents. Future studies should further explore how to set step goals and the duration of interventions to achieve better intervention effects.

3.
Heliyon ; 10(14): e34582, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39149078

RESUMEN

Objective: This study aimed to assess the efficacy of three different fixation methods in treating femoral neck fractures in young patients. Methods: A retrospective analysis was conducted on 35 young patients with femoral neck fractures who underwent surgical treatment. Among them, 16, 12, and 7 patients underwent fixation with three cannulated compression screws (3CS), the femoral neck system (FNS), and the compound compression system (CCS), respectively. Data, including fracture classification, injury-to-surgery time, surgery duration, intraoperative blood loss, fluoroscopy instances, fracture healing time, complications, and Harris score at the final follow-up, were collected and analyzed to compare clinical outcomes among the three fixation methods. Results: All patients were followed for at least 6 months, exhibiting no significant differences in age, gender, injury side, fracture type, or injury-to-operation time among the three groups (P > 0.05). The FNS and CCS groups exhibited shorter operation durations and fewer intraoperative fluoroscopy instances compared to the 3CS group (P < 0.01). Despite the minimally invasive nature of 3CS, the FNS and CCS groups experienced higher intraoperative blood loss (P < 0.01). During follow-up, only one patient with 3CS fixation developed nonunion. Additionally, patients treated with 3CS demonstrated a higher incidence of femoral head necrosis and severe femoral neck shortening than the FNS and CCS groups. Excluding patients with combined nonunion, no significant difference in mean fracture healing time was observed among the three groups (P > 0.05). At the last follow-up, the FNS and CCS groups showed higher Harris scores (P < 0.05). Conclusions: Both FNS and CCS are effective internal fixation systems for the treatment of femoral neck fractures in young patients, yielding more satisfactory clinical functional outcomes than 3CS. Comparatively, the CCS system presents a higher risk of iatrogenic rotation of the proximal fracture segment. Therefore, we advocate the insertion of two to three 2.5 mm Kirschner wires from the upper edge of the femoral neck along the axial direction before CCS lag screw insertion to resist iatrogenic rotational stress.

4.
Angew Chem Int Ed Engl ; : e202411427, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090767

RESUMEN

Regulating the electrical double layer (EDL) structure can enhance the cycling stability of Zn metal anodes, however, the effectiveness of this strategy is significantly limited by individual additives. Inspired by the high-entropy (HE) concept, we developed a multicomponent (MC) EDL structure composed of La3+, Cl-, and BBI anions by adding dibenzenesulfonimide (BBI) and LaCl3 additives into ZnSO4 electrolytes (BBI/LaCl3/ZnSO4). Specifically, La3+ ions accumulate within EDL to shield the net charges on the Zn surface, allowing more BBI anions and Cl- ions to enter this region. Consequently, this unique MC EDL enables Zn anodes to simultaneously achieve uniform electric field, robust SEI layer, and balanced reaction kinetics. Moreover, the synergistic parameter-a novel descriptor for quantifying collaborative improvement-was first proposed to demonstrates the synergistic effect between BBI and LaCl3 additives. Benefitting from these advantages, Zn metal anodes achieved a high reversibility of 99.5% at a depth of discharge (DoD) of 51.3%, and Zn|MnO2 pouch cells exhibited a stable cycle life of 100 cycles at a low N/P ratio of 2.9.

5.
J Colloid Interface Sci ; 675: 630-638, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38991277

RESUMEN

Aqueous Zn-S batteries (AZSBs) have garnered increasing attention in the energy storage field owing to their high capacity, energy density, and cost effectiveness. Nevertheless, sulfur (S) cathodes face challenges, primarily stemming from sluggish reaction kinetics and the formation of an irreversible byproduct (SO42-) during the charge, hindering the progress of AZSBs. Herein, Te-S bonds within S-based cathodes were introduced to enhance electron and ion transport and facilitate the conversion reaction from zinc sulfide (ZnS) to S. This was achieved by constructing heteroatomic TeS-x@Ketjen black composite cathodes (HM-TeS-x@KB, where x  = 36, 9, and 4). The HM-TeS-9@KB electrode exhibits long-term cycling stability, maintaining a capacity decay rate of 0.1 % per cycle over 450 cycles at a current density of 10 A g-1. Crucially, through a combination of experimental data analysis and theoretical calculations, the impact mechanism of Te on the charge and discharge of S active materials within the HM-TeS-9@KB cathode in AZSBs was investigated. The presence of Te-S bonds boost the intrinsic conductivity and wettability of the HM-TeS-9@KB cathode. Furthermore, during the charge, the interaction of preferentially oxidized Te with S atoms within ZnS promotes the oxidation reaction from ZnS to S and suppresses the irreversible side reaction between ZnS and H2O. These findings indicate that the heteroatomization of chalcogen S molecules represents a promising approach for enhancing the electrochemical performance of S cathodes in AZSBs.

6.
Medicine (Baltimore) ; 103(30): e38980, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058856

RESUMEN

Liver cancer with portal vein tumor thrombus (PVTT) is a frequent finding and is related to poor prognosis. Surgical resection provides a more promising prognosis in selected patients. The purpose of this study was to explore the application of 3D (3-dimensional) visualization and image fusion technology in liver cancer with PVTT surgery. 12 patients were treated with surgery between March 2019 and August 2022. The preoperative standard liver volume (SLV), estimated future liver remnant (FLR), FLR/SLV, 3D visualization models, PVTT classification, operation programs, surgical results, and prognosis were collected and analyzed. Twelve patients who had complete data of 3D visualization and underwent hemihepatectomy combined with portal vein tumor thrombectomy. The operation plan was formulated by 3D visualization and was highly consistent with the actual surgery. The SLV was 1208.33 ±â€…63.22 mL, FLR was 734.00 mL and FLR/SLV was 61.62 ±â€…19.38%. The accuracy of classification of PVTT by 3D visualization was 100%, Cheng type Ⅱa (4 cases), Ⅱb (2 cases), Ⅲa (4 cases), and Ⅲb (2 cases). The 3D visualization model was a perfect fusion with the intraoperative live scene and precise guidance for hepatectomy. No patient was suffering from postoperative liver failure and without procedure­associated death. 6 patients died of tumor recurrence, and 2 patients died of other reasons. The 12-month cumulative survival rate was 25.9%. 3D visualization and image fusion technology could be used for precise assessment of FLR, classification of PVTT, surgery navigation, and which was helpful in improving the safety of hepatectomy.


Asunto(s)
Hepatectomía , Imagenología Tridimensional , Neoplasias Hepáticas , Vena Porta , Trombectomía , Humanos , Vena Porta/cirugía , Vena Porta/patología , Vena Porta/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Imagenología Tridimensional/métodos , Hepatectomía/métodos , Trombectomía/métodos , Anciano , Adulto , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/cirugía , Trombosis de la Vena/etiología , Pronóstico , Tomografía Computarizada por Rayos X/métodos
7.
Life (Basel) ; 14(7)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39063624

RESUMEN

The tomato leafminer, Tuta absoluta (Lepidoptera: Gelechiidae), is a highly destructive invasive pest targeting Solanaceae crops. Its olfactory system plays a crucial role in host location, mate finding, and other behavioral activities. However, there is a notable gap in the literature regarding the characterization of its chemosensory genes. In this study, we conducted a genome-wide identification of 58 odorant receptors (ORs) of T. absoluta. The identified ORs exhibit coding sequence (CDS) lengths ranging from 1062 bp to 1419 bp, encoding proteins of 354 to 473 amino acids. Gene structure analysis showed that the majority of these ORs consist of five, seven, eight, or nine exons, collectively representing 67% of the total ORs identified. Through chromosomal mapping, we identified several tandemly duplicate genes, including TabsOR12a, TabsOR12b, TabsOR12c, TabsOR21a, TabsOR21b, TabsOR34a, TabsOR34b, TabsOR34c, TabsOR62a, and TabsOR62b. The phylogenetic analysis indicated that six TabsORs were clustered within the lepidopteran sex pheromone receptor clade, while an expansion clade containing ten TabsORs resulted from tandem duplication events. Additionally, five TabsORs were classified into a specific OR clade in T. absoluta. Furthermore, through RNA-Seq and RT-qPCR analyses, we identified five TabsORs (TabsOR21a, TabsOR26a, TabsOR34a, TabsOR34c, and TabsOR36) exhibiting female-antennae-biased expression. Our study provides a valuable foundation to further investigations into the molecular and ecological functions of TabsORs, particularly in relation to oviposition behavior. These findings provide foundational data for the future exploration of the functions of female-biased expression OR genes in T. absoluta, thereby facilitating the further development of eco-friendly attract-and-kill techniques for the prevention and control of T. absoluta.

8.
Int Immunopharmacol ; 138: 112599, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38959543

RESUMEN

BACKGROUND: Prostate cancer remains a prominent challenge in oncology, with advanced stages showing poor prognosis. The tumor microenvironment (TME), and particularly tumor-associated macrophages (TAMs), plays a crucial role in disease progression. This study explores the single-cell transcriptomics of prostate cancer, determines macrophage heterogeneity, identifies prognostic gene markers, and assesses the role of PPIF in TAMs. METHODS: Single-cell RNA sequencing data from the GEO database (GSE176031) and transcriptome data from the TCGA were processed to characterize cell populations and identify prognostic genes in prostate cancer. Macrophage subpopulations were examined through clustering, followed by gene set scoring based on migration, activation, and proliferation. PPIF expression in macrophages was investigated using multiplex immunofluorescence staining on matched prostate cancer and adjacent non-tumoral tissues. RESULTS: The single-cell analysis identified 9,178 cells, categorized into 10 principal cell types, with macrophages constituting a significant part of the immune microenvironment. Four macrophage subgroups demonstrated distinct functional pathways: phagocytic, immune-regulatory, and proliferative. A total of 39 genes correlated with prostate cancer prognosis were identified, of which 10 carried the most significant prognostic information. Peptidylprolyl Isomerase F (PPIF) expression was significantly higher in TAMs from tumor tissue than normal tissue, indicating its potential regulatory role in the immune microenvironment. CONCLUSION: The intricate cellular architecture of the prostate cancer TME has been elucidated, with a focus on macrophage heterogeneity and functional specialization. Prognostic genes, including PPIF, were associated with survival outcomes, providing potential therapeutic targets. PPIF's prominent expression in TAMs may serve as a lever in cancer progression, warranting further investigation as a biomarker and a molecule of interest for therapeutic targeting within the prostate cancer milieu.


Asunto(s)
Peptidil-Prolil Isomerasa F , Neoplasias de la Próstata , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Análisis de la Célula Individual , Transcriptoma , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Peptidil-Prolil Isomerasa F/genética , Peptidil-Prolil Isomerasa F/metabolismo
9.
Gigascience ; 132024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-39028585

RESUMEN

Sex role differentiation is a widespread phenomenon. Sex pheromones are often associated with sex roles and convey sex-specific information. In Lepidoptera, females release sex pheromones to attract males, which evolve sophisticated olfactory structures to relay pheromone signals. However, in some primitive moths, sex role differentiation becomes diverged. Here, we introduce the chromosome-level genome assembly from ancestral Himalaya ghost moths, revealing a unique olfactory evolution pattern and sex role parity among Lepidoptera. These olfactory structures of the ghost moths are characterized by a dense population of trichoid sensilla, both larger male and female antennal entry parts of brains, compared to the evolutionary later Lepidoptera. Furthermore, a unique tandem of 34 odorant receptor 19 homologs in Thitarodes xiaojinensis (TxiaOr19) has been identified, which presents overlapped motifs with pheromone receptors (PRs). Interestingly, the expanded TxiaOr19 was predicted to have unconventional tuning patterns compared to canonical PRs, with nonsexual dimorphic olfactory neuropils discovered, which contributes to the observed equal sex roles in Thitarodes adults. Additionally, transposable element activity bursts have provided traceable loci landscapes where parallel diversifications occurred between TxiaOr19 and PRs, indicating that the Or19 homolog expansions were diversified to PRs during evolution and thus established the classic sex roles in higher moths. This study elucidates an olfactory prototype of intermediate sex communication from Himalaya ghost moths.


Asunto(s)
Mariposas Nocturnas , Animales , Mariposas Nocturnas/genética , Mariposas Nocturnas/fisiología , Masculino , Femenino , Atractivos Sexuales/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores de Feromonas/genética , Receptores de Feromonas/metabolismo , Filogenia , Conducta Sexual Animal
10.
J Ethnopharmacol ; 334: 118593, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39032663

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Treatment options for hepatic fibrosis, a prevalent liver condition closely linked to cirrhosis, are currently limited. While Guizhi Fuling Wan (GFW), a pill derived from traditional Chinese herbs, has been reported to possess hepatoprotective properties, its therapeutic effect and mechanism in hepatic fibrosis remain elusive. AIM OF THE STUDY: This study aimed to evaluate the anti-fibrotic impact of GFW and its underlying mechanisms in both in vivo and in vitro settings. MATERIALS AND METHODS: Tetrachloromethane (CCl4) was used to induce hepatic fibrosis in male rats. In vitro, activation of hepatic stellate cells (HSCs) was triggered by platelet-derived growth factor-BB (PDGF-BB). In vivo, liver function, pathological alterations, and HSC activation were evaluated. Additionally, the impact of GFW on the activated phenotypes of Lieming Xu-2 (LX-2) cells was examined in vitro. Network pharmacology was employed to identify the potential targets of GFW in hepatic fibrosis. Lastly, the impact of GFW on the PTEN/AKT/mTOR pathway and PTEN ubiquitination in HSCs was investigated. RESULTS: GFW alleviated CCl4-induced liver damage and scarring in rats in a dose-dependent manner and suppressed HSC activation in vivo. Moreover, GFW inhibited the proliferation, migration, differentiation, and extracellular matrix (ECM) production of activated HSCs in vitro. GFW also promoted autophagy and apoptosis of HSCs. Meanwhile, network pharmacology and in vitro studies suggested that GFW inhibits the AKT/mTOR pathway by preventing PTEN degradation by suppressing ubiquitination. CONCLUSION: GFW attenuates Ccl4-induced hepatic fibrosis in male rats by regulating the PTEN/AKT/mTOR signaling pathway, positioning it as a potential candidate for the treatment of hepatic fibrosis.


Asunto(s)
Medicamentos Herbarios Chinos , Células Estrelladas Hepáticas , Cirrosis Hepática , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Humanos , Masculino , Ratas , Tetracloruro de Carbono , Línea Celular , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo
11.
Dig Dis Sci ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987443

RESUMEN

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

12.
Radiology ; 312(1): e240751, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38980180
13.
RSC Adv ; 14(32): 23011-23022, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39040693

RESUMEN

The photo-reduction of bromate (BrO3 -) has attracted much attention due to the carcinogenesis and genotoxicity of BrO3 - in drinking water. In this study, a heterojunction photocatalyst was developed by depositing Au nanoparticles (NPs) onto P25 TiO2 NPs through a one-pot, solvent-thermal process. Due to the unique properties of Au, the Au NPs deposited on the TiO2 surface created a Schottky barrier between the metal and the semiconductor, leading to an effective separation of photo-generated charge carriers as the Au nanoparticles served as electron sinks. The Au/TiO2 photocatalyst demonstrated efficient reduction of BrO3 - under UV light illumination without the need for sacrificial agents. The effect of different Au loading of Au/TiO2 was systematically investigated for its influence on the generation of electrons and the reduction ability of BrO3 -. The results indicate that the 1% Au/TiO2 catalyst exhibited a higher concentration of localized electrons, rendering it more effective in BrO3 - removal. The photocatalytic efficiency for BrO3 - reduction decreased upon the addition of K2S2O8 as an electron quencher, suggesting that the primary factor in this photo-reduction process was the availability of electrons. These findings hold promise for the potential application of the Au/TiO2 catalyst in the removal of BrO3 - from drinking water through photo-reduction.

14.
iScience ; 27(7): 110357, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39055909

RESUMEN

Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.

15.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3125-3131, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39041072

RESUMEN

Traditional Chinese medicine with rich resources in China and definite therapeutic effects on complex diseases demonstrates great development potential. However, the complex composition, the unclear pharmacodynamic substances and mechanisms of action, and the lack of reasonable methods for evaluating clinical safety and efficacy have limited the research and development of innovative drugs based on traditional Chinese medicine. The progress in cutting-edge disciplines such as artificial intelligence and biomimetics, especially the emergence of cell painting and organ-on-a-chip, helps to identify and characterize the active ingredients in traditional Chinese medicine based on the changes in model characteristics, thus providing more accurate guidance for the development and application of traditional Chinese medicine. The application of phenotypic drug discovery in the research and development of innovative drugs based on traditional Chinese medicine is gaining increasing attention. In recent years, the technology for phenotypic drug discovery keeps advancing, which improves the early discovery rate of new drugs and the success rate of drug research and development. Accordingly, phenotypic drug discovery gradually becomes a key tool for the research on new drugs. This paper discusses the enormous potential of traditional Chinese medicine in the discovery and development of innovative drugs and illustrates how the application of phenotypic drug discovery, supported by cutting-edge technologies such as cell painting, deep learning, and organ-on-a-chip, propels traditional Chinese medicine into a new stage of development.


Asunto(s)
Descubrimiento de Drogas , Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Fenotipo , Animales , Desarrollo de Medicamentos
16.
Int J Colorectal Dis ; 39(1): 99, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926205

RESUMEN

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Microambiente Tumoral , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Quimioradioterapia , Resultado del Tratamiento , Estudios Retrospectivos
17.
Imeta ; 3(2): e166, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38882497

RESUMEN

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

18.
Anal Chim Acta ; 1314: 342801, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38876517

RESUMEN

BACKGROUND: Most of the investigations on distinct crystal structures of catalysts are individually focused on the difference of surface functional groups or adsorption properties, but rarely explore the changes of active sites to affect the electrocatalytic performance. Catalysts with diverse crystal structures had been applied to modified electrodes in different electrocatalytic reactions. However, there is currently a lack of an essential understanding for the role of real active sites in catalysts with crystalline structures in electroanalysis, which is crucial for designing highly sensitive sensing interfaces. RESULTS: Herein, cobalt molybdate with divergent crystal structures (α-CoMoO4 and ß-CoMoO4) were synthesized by adjusting the calcination temperature, indicating that α-CoMoO4 (800 °C) (60.00 µA µM-1) had the highest catalytic ability than ß-CoMoO4 (700 °C) (38.68 µA µM-1) and α-CoMoO4 (900 °C) (29.55 µA µM-1) for the catalysis of Pb(II). It was proved that the proportion of Co(II) and Mo(IV) as electron-rich sites in α-CoMoO4 (800 °C) were higher than ß-CoMoO4 (700 °C) and α-CoMoO4 (900 °C), possessing more electrons to participate in the valence cycles of Co(II)/Co(III) and Mo(IV)/Mo(VI) to boost the catalytic reduction of Pb(II). Specifically, Co(II) transferred a part of electrons to Mo(VI), promoting the formation of Mo(IV). Co(II) and Mo(IV), as the electron-rich sites, providing electrons to Pb(II), further accelerating the conversion of Pb(II) into Pb(0). SIGNIFICANCE: In the process of detecting Pb(II), the CoMoO4 structures under different temperatures have distinct content of electron-rich sites Co(II) and Mo(IV). α-CoMoO4 (800 °C), with the highest content are benefited to detect Pb(II). This work is conducive to understanding the effect of the changes of active sites resulting from crystal transformation on the electrocatalytic performance, and provides a way to construct sensitive electrochemical interfaces of distinct active sites.

19.
J Environ Manage ; 364: 121448, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38870797

RESUMEN

Submerged zone in bioretention facilities for stormwater treatment has been approved to be an effective structure amendment to improve denitrification capability. However, the role and influence of water quality changes in the submerged zone under natural continuous random rainfall patterns are still not clear, especially when the rainfall is less than the pore water in the submerged zone. In this study, continuous rainfall events with different rainfall volume (light rain-light rain-heavy rain) were designed in a lab-scale woodchip mulched pyrite bioretention facility to test the effects of rainfall pattern. The results exhibited that light rain events significantly affected the pollutant removal performance of bioretention for the next rainfall. Different effects were observed during the long-term operation. In the 5th month, light rain reduced the ammonia removal efficiency of subsequent rainstorm events by 8.70%, while in the 12th month, when nitrate leakage occurred, light rain led to a 40.24% reduction in the next heavy rain event's nitrate removal efficiency. Additionally, light rain would also affect the concentration of by-products in the next rainfall. Following a light rain, the concentration of sulfate in the subsequent light rainfall can increase by 24.4 mg/L, and by 11.92 mg/L in a heavy rain. The water quality in the submerged zone and media characteristics analysis suggested that nitrogen conversion capacity of the substrate and microbes, such as Nitrospira (2.86%) and Thiobacillus (35.71%), as well as the in-situ accumulation of pollutants under light rain played important roles. This study clarifies the relationship between successive rainfall events and provides a more comprehensive understanding of bioretention facilities. This is beneficial for field study of bioretention facilities in the face of complex rainfall events.


Asunto(s)
Lluvia , Nitratos/análisis , Desnitrificación , Nitrógeno/análisis , Amoníaco/análisis , Contaminantes Químicos del Agua/análisis , Calidad del Agua
20.
Ageing Res Rev ; 98: 102316, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38703951

RESUMEN

The fundamental role of the gut microbiota through the gut-muscle axis in skeletal muscle ageing is increasingly recognised. Metabolites derived from the intestinal microbiota are essential in maintaining skeletal muscle function and metabolism. The energy produced by mitochondria and moderate levels of reactive oxygen species can contribute to this process. Metabolites can effectively target the mitochondria, slowing the progression of muscle ageing and potentially representing a marker of ageing-related skeletal muscle loss. Moreover, mitochondria can contribute to the immune response, gut microbiota biodiversity, and maintenance of the intestinal barrier function. However, the causal relationship between mitochondrial function and gut microbiota crosstalk remains poorly understood. In addition to elucidating the regulatory pathways of the gut-muscle axis during the ageing process, we focused on the potential role of the "exercise-gut-muscle axis", which represents a pathway under stimulation from different exercise modes to induce mitochondrial adaptations, skeletal muscle metabolism and maintain intestinal barrier function and biodiversity stability. Meanwhile, different exercise modes can induce mitochondrial adaptations and skeletal muscle metabolism and maintain intestinal barrier function and biodiversity. Resistance exercise may promote mitochondrial adaptation, increase the cross-sectional area of skeletal muscle and muscle hypertrophy, and promote muscle fibre and motor unit recruitment. Whereas endurance exercise promotes mitochondrial biogenesis, aerobic capacity, and energy utilisation, activating oxidative metabolism-related pathways to improve skeletal muscle metabolism and function. This review describes the effects of different exercise modes through the gut-muscle axis and how they act through mitochondria in ageing to define the current state of the field and issues requiring resolution.


Asunto(s)
Envejecimiento , Ejercicio Físico , Microbioma Gastrointestinal , Músculo Esquelético , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Microbioma Gastrointestinal/fisiología , Ejercicio Físico/fisiología , Envejecimiento/fisiología , Envejecimiento/metabolismo , Mitocondrias/metabolismo , Animales , Mitocondrias Musculares/metabolismo , Mitocondrias Musculares/fisiología
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