Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.460
Filtrar
1.
Hepatobiliary Surg Nutr ; 12(2): 155-168, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37124678

RESUMO

Background: Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma (HCC), which greatly limits long-term survival. We aimed to identify predictors and long-term prognosis of early and late recurrence after HCC resection. Methods: Multicenter data of patients who underwent HCC resection between 2002 and 2016 were analyzed. Recurrence was divided into early (≤2 years) and late recurrence (>2 years after surgery). Predictors of early and late recurrence, and prognostic factors of post-recurrence survival (PRS) were identified by univariate and multivariate analyses. Results: Among 1,426 patients, 554 (38.8%) and 348 (24.4%) developed early and late recurrence, respectively. Independent predictors associated with early recurrence included preoperative alpha-fetoprotein level >400 µg/L, resection margin <1 cm, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor at the first diagnosis of HCC; independent predictors associated with late recurrence included male, cirrhosis, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor. Patients with early recurrence had a lower likelihood of undergoing potentially curative treatments for recurrence (37.2% vs. 48.0%, P<0.001) and a worse median PRS (13.5 vs. 36.6 months, P<0.001) vs. patients who had late recurrence. Multivariate analysis revealed that early recurrence and irregular postoperative surveillance were independently associated with worse PRS [hazard ratio (HR) =1.250, 95% CI: 1.016-1.538, P=0.035; and HR =1.983, 95% CI: 1.677-2.345, P<0.001]. Conclusions: Predictors associated with early and late recurrence after curative resection for patients with HCC were generally same, although several did differ. Patients with late recurrence had better long-term survival than patients with early recurrence.

2.
Medicine (Baltimore) ; 102(18): e33709, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37144991

RESUMO

RATIONALE: Testicular torsion accounting for 25% of acute scrotal disease, is an acute surgical condition. Atypical presentations of testicular torsion may lead delay diagnosis. PATIENT CONCERNS: A 7-year-old boy was admitted to the pediatric emergency department with continuous and progressive left scrotal pain for 2 days, associated symptoms and signs included left scrotal swelling and erythema. The pain started 4 days ago as left lower abdominal pain which then migrated to the left scrotum. DIAGNOSES: Physical examination showed left scrotum skin redness, swelling, local heat, tenderness, high-riding testis, absence of the left side cremasteric reflex and a negative Prehn's sign. Subsequent point of care ultrasound of scrotum revealed increased volume of the left testicle, inhomogeneous hypo-echoic left testis, and no detectable flow in the left testis. Left testicular torsion was diagnosed. INTERVENTIONS: Surgical examination confirmed testicular torsion showing 720° counterclockwise rotation of the spermatic cord with ischemic changes in the left testis and epididymis. OUTCOMES: The patient was stabilized and discharged after left orchiectomy, right orchiopexy and antibiotic therapy. LESSONS: Symptoms of testicular torsion may be atypical, especially in prepubertal age. Detailed history, physical examination, point of care ultrasound usage and timely urologist consultation and intervention are important for prompt rescue to prevent testicular loss, testicular atrophy, and eventual impairment of fertility.


Assuntos
Doenças dos Genitais Masculinos , Torção do Cordão Espermático , Masculino , Criança , Humanos , Torção do Cordão Espermático/diagnóstico , Torção do Cordão Espermático/cirurgia , Testículo/cirurgia , Orquiectomia , Escroto , Dor Abdominal/cirurgia , Doença Aguda
3.
Nat Commun ; 14(1): 2865, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208348

RESUMO

Three-dimensional (3D) covalent organic frameworks (COFs) possess higher surface areas, more abundant pore channels, and lower density compared to their two-dimensional counterparts which makes the development of 3D COFs interesting from a fundamental and practical point of view. However, the construction of highly crystalline 3D COF remains challenging. At the same time, the choice of topologies in 3D COFs is limited by the crystallization problem, the lack of availability of suitable building blocks with appropriate reactivity and symmetries, and the difficulties in crystalline structure determination. Herein, we report two highly crystalline 3D COFs with pto and mhq-z topologies designed by rationally selecting rectangular-planar and trigonal-planar building blocks with appropriate conformational strains. The pto 3D COFs show a large pore size of 46 Å with an extremely low calculated density. The mhq-z net topology is solely constructed from totally face-enclosed organic polyhedra displaying a precise uniform micropore size of 1.0 nm. The 3D COFs show a high CO2 adsorption capacity at room temperature and can potentially serve as promising carbon capture adsorbents. This work expands the choice of accessible 3D COF topologies, enriching the structural versatility of COFs.

4.
Nano Lett ; 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37212654

RESUMO

To achieve better properties of van der Waals (vdW) devices, vdW heterointerfaces with substrates such as hexagonal boron nitride (h-BN) were introduced to alleviate adverse substrate effects. However, the premature dielectric breakdown and its scale limitation make wider application of h-BN substrates challenging. Here we report a fluoride-based substrate that substantially improves optoelectronic and transport properties of dichalcogenide devices, with enhancement factors comparable to those of h-BN. A model system of wafer-scale fluoride calcium (CaF2) ultrathin films with the preferable growth direction along [111] is prepared by the magnetron sputtering method. Results show that the constructed SnS2/CaF2 and WS2/CaF2 devices exhibit 1 order of magnitude higher than devices based on the SiO2 substrate in electronic mobility and photoresponsivity. Theoretical calculations reveal that devices based on fluoride substrates are immune from the Coulomb impurity scattering by forming quasi-vdW interfaces, exhibiting great potential for high responsivity and mobility of photogenerated carriers in 2D vdW devices.

5.
Opt Lett ; 48(7): 1786-1789, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221766

RESUMO

In parametric conversion, phase-matching techniques such as birefringence and quasi phase-matching (PM) with the designed crystal angle or periodically poled polarities are employed to fulfill the requirement of momentum conservation. However, directly using phase-mismatched interactions in nonlinear media with large quadratic nonlinear coefficient remains unheeded. Here, for the first time to the best of our knowledge, we study the phase-mismatched difference-frequency generation (DFG) in an isotropic cadmium telluride (CdTe) crystal, with the comparison of other DFG processes based on birefringence-PM, quasi-PM, and random-quasi-PM. Long-wavelength mid-infrared (LWMIR) phase-mismatched DFG with an ultra-broadband spectral tuning range of 6-17 µm based on CdTe is demonstrated. Thanks to the giant quadratic nonlinear coefficient (∼109 pm/V) and good figure of merit in the parametric process, the output power up to 100 µW is obtained, which is comparable to or even better than the DFG output from a polycrystalline ZnSe with the same thickness facilitated by random-quasi-PM. A proof-of-concept demonstration in gas sensing of CH4 and SF6 is conducted based on the phase-mismatched DFG as a typical application. Our results demonstrate the feasibility of phase-mismatched parametric conversion in producing useful LWMIR power and ultra-broadband tunability in a simple and convenient way without the necessity of controlling the polarization, phase-matching angle, or pole periods, which could find applications in the fields of spectroscopy and metrology.

6.
Water Res ; 239: 120052, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37178664

RESUMO

Non-point nitrate pollution in groundwater has been accelerated by agricultural development, but sustainable nitrogen removal is a challenge because of its wide distribution and negative side effects. Surface agricultural practices (SAPs), which are demonstrably effective in driving the downward infiltration of dissolved organic carbon (DOC), have not been well explored for their potential to enhance nitrate attenuation in groundwater. Therefore, a combination of soil column and groundwater incubation experiments was performed to investigate the carbon and nitrogen responses to different SAPs (manure fertilization, lucerne planting, and straw return). The soil column experiment showed that SAPs promoted DOC and reduced nitrate leaching into groundwater, and straw treatment witnessed the highest DOC leaching flux (252.71 g m-2 yr-1) and lowest nitrate leaching flux (9.51 g m-2 yr-1). The groundwater incubation experiment showed that leachates from the straw treatment displayed the best denitrification-enhancement performance, with the highest NO3--N reduction efficiency (92.93%) and rate (1.627 mg/day), N2 selectivity (99.78%), and net nitrogen removal (0.09 mg). Furthermore, Fourier transform ion cyclotron resonance mass spectrometry confirmed that CHOS molecules with lower double bond equivalents (0-5) and larger carbon numbers (10-15) were more accessible to denitrifiers. This study provides a new path for the sustainable control of non-point source nitrate pollution.


Assuntos
Água Subterrânea , Poluição Difusa , Poluentes Químicos da Água , Nitratos/análise , Poluição Difusa/análise , Poluentes Químicos da Água/química , Agricultura , Solo , Nitrogênio/análise , Monitoramento Ambiental , Carbono/análise , Matéria Orgânica Dissolvida
7.
Front Endocrinol (Lausanne) ; 14: 1175198, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223016

RESUMO

Aims: Glucokinase activators (GKAs) promote the activity of glucokinase (GK) and is under development for the treatment of diabetes. The efficacy and safety of GKAs require evaluation. Methods: This meta-analysis included randomized controlled trials (RCTs) with a duration of at least 12 weeks conducted in patients with diabetes. The primary objective of this meta-analysis was the difference of hemoglobin A1c (HbA1c) change from baseline to study end between GKA groups and placebo groups. Risk of hypoglycemia and laboratory indicators were also evaluated. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for the continuous outcomes, and odds ratios (ORs) and 95% CI were calculated for the risk of hypoglycemia. Results: Data from 13 RCTs with 2,748 participants treated with GKAs and 2,681 control participants were analyzed. In type 2 diabetes, the level of HbA1c decreased greater in patients with GKA treatment compared with placebo (WMD = -0.339%, 95% CI -0.524 to -0.154%, P < 0.001). The OR comparing GKA versus placebo was 1.448 for risk of hypoglycemia (95% CI 0.808 to 2.596, P = 0.214). The WMD comparing GKA versus placebo was 0.322 mmol/L for triglyceride (TG) levels (95% CI 0.136 to 0.508 mmol/L, P = 0.001). When stratified by drug type, selectivity, and study duration, a significant difference was found between groups. In type 1 diabetes, the result of HbA1c change and lipid indicators showed no significant difference between the TPP399 group and the placebo group. Conclusions: In patients with type 2 diabetes, GKA treatment was associated with a better glycemic control but a significant elevation in TG concentration in general. The efficacy and safety varied with drug type and selectivity. Systematic review registration: International Prospective Register of Systematic Reviews, identifier CRD42022378342.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Glucoquinase , Hemoglobinas Glicadas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente
8.
Entropy (Basel) ; 25(5)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37238513

RESUMO

The Space-Air-Ground Integrated Network (SAGIN) expands cyberspace greatly. Dynamic network architecture, complex communication links, limited resources, and diverse environments make SAGIN's authentication and key distribution much more difficult. Public key cryptography is a better choice for terminals to access SAGIN dynamically, but it is time-consuming. The semiconductor superlattice (SSL) is a strong Physical Unclonable Function (PUF) to be the hardware root of security, and the matched SSL pairs can achieve full entropy key distribution through an insecure public channel. Thus, an access authentication and key distribution scheme is proposed. The inherent security of SSL makes the authentication and key distribution spontaneously achieved without a key management burden and solves the assumption that excellent performance is based on pre-shared symmetric keys. The proposed scheme achieves the intended authentication, confidentiality, integrity, and forward security, which can defend against masquerade attacks, replay attacks, and man-in-the-middle attacks. The formal security analysis substantiates the security goal. The performance evaluation results confirm that the proposed protocols have an obvious advantage over the elliptic curve or bilinear pairings-based protocols. Compared with the protocols based on the pre-distributed symmetric key, our scheme shows unconditional security and dynamic key management with the same level performance.

9.
Bioengineering (Basel) ; 10(5)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37237690

RESUMO

Nickel plating electrolytes prepared by using a simple salt solution can achieve nickel plating on laser-induced graphene (LIG) electrodes, which greatly enhances the electrical conductivity, electrochemical properties, wear resistance, and corrosion resistance of LIG. This makes the LIG-Ni electrodes well suited for electrophysiological, strain, and electrochemical sensing applications. The investigation of the mechanical properties of the LIG-Ni sensor and the monitoring of pulse, respiration, and swallowing confirmed that the sensor can sense insignificant deformations to relatively large conformal strains of skin. Modulation of the nickel-plating process of LIG-Ni, followed by chemical modification, may allow for the introduction of glucose redox catalyst Ni2Fe(CN)6 with interestingly strong catalytic effects, which gives LIG-Ni impressive glucose-sensing properties. Additionally, the chemical modification of LIG-Ni for pH and Na+ monitoring also confirmed its strong electrochemical monitoring potential, which demonstrates application prospects in the development of multiple electrochemical sensors for sweat parameters. A more uniform LIG-Ni multi-physiological sensor preparation process provides a prerequisite for the construction of an integrated multi-physiological sensor system. The sensor was validated to have continuous monitoring performance, and its preparation process is expected to form a system for non-invasive physiological parameter signal monitoring, thus contributing to motion monitoring, disease prevention, and disease diagnosis.

10.
Front Med (Lausanne) ; 10: 1175787, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228403

RESUMO

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare musculoskeletal disease characterized by dermatological and osteoarticular lesions. However, SAPHO syndrome is difficult to be diagnosed due to the rarity and complexity. Additionally, there is no standard treatment for SAPHO syndrome based on limited experience. Percutaneous vertebroplasty (PVP) has rarely been reported to treat SAPHO syndrome. We reported a 52-year-old female patient who had a sex-month history of back pain. Palmoplantar pustulosis appeared on the hands and feet. Vertebral destruction was observed on computed tomography (CT) scanning. Laboratory examination showed that erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated. Finally, the patient was diagnosed with SAPHO syndrome and treated with PVP. After the surgery, the back pain was significantly relieved. In this study, we mainly discussed the treatment methods of SAPHO syndrome, and provided a potential treatment for SAPHO syndrome, especially with vertebral destruction, kyphosis, and even pathological fractures.

11.
Cell Death Discov ; 9(1): 147, 2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37149721

RESUMO

B7-H3 is an attractive target for immunotherapy because of its high expression across multiple solid tumors, including prostate cancer, and restricted expression in normal tissues. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematological tumors. However, the potency of CAR-T cell therapy in solid tumors is still limited. Here, we examined the expression of B7-H3 in prostate cancer tissues and cells and developed a second-generation CAR that specifically targets B7-H3 and CD28 as costimulatory receptor to explore its tumoricidal potential against prostate cancer in vitro and in vivo. The high expression of B7-H3 was detected on both the surface of PC3, DU145 and LNCaP cells and prostate cancer tissues. B7-H3 CAR-T cells efficiently controlled the growth of prostate cancer in an antigen-dependent manner in vitro and in vivo. Moreover, tumor cells could induce the proliferation of CAR-T cells and the release of high levels of cytokines of IFN-γ and TNF-α in vitro. Results demonstrated that B7-H3 is a potential target for prostate cancer therapy that supports the clinical development of B7-H3 specific CAR-T cells for prostate cancer.

12.
Int J Biol Macromol ; 242(Pt 1): 124744, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37148950

RESUMO

Organic fertilizers-derived volatiles attract Holotrichia parallela during oviposition. However, the mechanisms underlying the perception of oviposition cues in H. parallela remain unclear. Here, H. parallela odorant-binding protein 3 (HparOBP3) was identified as a key OBP. Bioinformatics analysis showed that HparOBP3 clustered together with Holotrichia oblita OBP8. HparOBP3 was mainly expressed in the antennae of both sexes. Recombinant HparOBP3 exhibited distinct binding affinities towards 22 compounds released by organic fertilizers. After 48 h of RNA interference (RNAi), the expression of HparOBP3 in male and female antennae was decreased by 90.77 % and 82.30 %, respectively. In addition, silencing of HparOBP3 significantly reduced the electrophysiological responses and tropism of males to cis-3-hexen-1-ol, 1-hexanol, and (Z)-ß-ocimene as well as females to cis-3-hexen-1-ol, 1-hexanol, benzaldehyde, and (Z)-ß-ocimene. Molecular docking indicated that hydrophobic residues Leu-83, Leu-87, Phe-108, and Ile-120 of HparOBP3 were important amino acids for interacting with ligands. Mutation of the key residue, Leu-83, significantly diminished the binding ability of HparOBP3. Furthermore, acrylic plastic arena bioassays showed that the attraction and oviposition indexes of organic fertilizers to H. parallela were reduced by 55.78 % and 60.11 %, respectively, after silencing HparOBP3. These results suggest that HparOBP3 is essential in mediating the oviposition behavior of H. parallela.

13.
Heliyon ; 9(5): e15587, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37090428

RESUMO

The COVID-19 pandemic continues to threaten human health worldwide as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around Y453 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values ranging from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on broadly neutralizing chimeric antibodies to create K-RBD-hAb-60 and -62, which still retain excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.

14.
Chem Commun (Camb) ; 59(37): 5555-5558, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37071468

RESUMO

A comprehensive structure-activity relationship study on antibody Fc-glycosylation has been performed using the chimeric anti-SSEA4 antibody chMC813-70 as a model. The α-2,6 sialylated biantennary complex type glycan was identified as the optimal Fc-glycan with significant enhancement in antibody effector functions, including binding to different Fc receptors and ADCC.


Assuntos
Fragmentos Fc das Imunoglobulinas , Imunoglobulina G , Glicosilação , Relação Estrutura-Atividade , Polissacarídeos/metabolismo
15.
Chemosphere ; 331: 138769, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37100252

RESUMO

Analyzing the levels of anticancer medications in biological samples and body fluids reveals important details on the course and effects of chemotherapy. p (L-Cys)/graphitic-carbon nitride (g-C3N4)/GCE, a modified glassy carbon electrode, was created for the current study's electrochemical detection of methotrexate (MTX), a drug used to treat breast cancer, in pharmaceutical fluid samples. l-Cysteine was electro-polymerized on the surface of the g-C3N4/GCE after the g-C3N4 was first modified to prepare the p (L-Cys)/g-C3N4/GCE. Analyses of morphology and structure showed that well-crystalline p (L-Cys) on g-C3N4/GCE was successfully electropolymerized. Studying the electrochemical characteristics of p (L-Cys)/g-C3N4/GCE using CV and DPV techniques revealed a synergistic impact between g-C3N4 and l-cysteine that improved the stability and selectivity of the electrochemical oxidation of MTX while enhancing the electrochemical signal. Results showed that 7.5-780 µM was the linear range, and that 0.11841 µA/µM and 6 nM, respectively, were the sensitivity and limit of detection. The applicability of the suggested sensors was assessed using real pharmaceutical preparations, and the results showed that p (L-Cys)/g-C3N4/GCE had a high degree of precision. Five breast cancer patients who volunteered and provided prepared blood serum samples between the ages of 35 and 50 were used to examine the validity and accuracy of the proposed sensor in the current work for the determination of MTX. The results showed good recovery values (greater than 97.20%), appropriate accuracy (RSD less than 5.11%), and good agreement between the ELISA and DPV analysis results. These findings showed that p (L-Cys)/g-C3N4/GCE can be applied as a trustworthy MTX sensor for MTX level monitoring in blood samples and pharmaceutical samples.


Assuntos
Neoplasias da Mama , Carbono , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Carbono/química , Metotrexato , Cisteína , Neoplasias da Mama/tratamento farmacológico , Eletrodos , Preparações Farmacêuticas , Técnicas Eletroquímicas/métodos
16.
Nanomaterials (Basel) ; 13(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37110900

RESUMO

Smart responsive materials can react to external stimuli via a reversible mechanism and can be directly combined with a triboelectric nanogenerator (TENG) to deliver various intelligent applications, such as sensors, actuators, robots, artificial muscles, and controlled drug delivery. Not only that, mechanical energy in the reversible response of innovative materials can be scavenged and transformed into decipherable electrical signals. Because of the high dependence of amplitude and frequency on environmental stimuli, self-powered intelligent systems may be thus built and present an immediate response to stress, electrical current, temperature, magnetic field, or even chemical compounds. This review summarizes the recent research progress of smart TENGs based on stimulus-response materials. After briefly introducing the working principle of TENG, we discuss the implementation of smart materials in TENGs with a classification of several sub-groups: shape-memory alloy, piezoelectric materials, magneto-rheological, and electro-rheological materials. While we focus on their design strategy and function collaboration, applications in robots, clinical treatment, and sensors are described in detail to show the versatility and promising future of smart TNEGs. In the end, challenges and outlooks in this field are highlighted, with an aim to promote the integration of varied advanced intelligent technologies into compact, diverse functional packages in a self-powered mode.

17.
Front Biosci (Landmark Ed) ; 28(4): 80, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37114540

RESUMO

BACKGROUND: The purpose of the present study was to investigate the role of the 5-Fluorouracil (5-FU) resistance-related factor dihydropyrimidine dehydrogenase (DPD) in tumor immunity and prognosis and to study the relationship between drug resistance and the immune microenvironment of colon cancer. METHODS: Bioinformatics methods were used to analyze the expression of DPD associated with prognosis, immunity, microsatellite instability, and tumor mutational burden in colon cancer. Immunohistochemistry (IHC) was used to detect DPD, MLH1, MSH2, MSH6, and PMS2 in 219 colon cancer tissue samples. Additional IHC analyses were conducted to detect CD4, CD8, CD20, and CD163 in 30 colon cancer tissue samples with the most extensive immune infiltration. The significance of the correlations and clinical significance of DPD with immune infiltration, immune-related markers, microsatellite instability-related indicators, and prognosis were evaluated. RESULTS: The major findings of the present study are as follows: (1) DPD was expressed in tumor and immune cells and associated with certain immune cell-related markers, particularly M2 macrophages that expressed CD163. (2) DPD expression significantly and positively correlated with immune cell markers and immune checkpoints PD-1 and PD-L1. High expression of DPD in immune cells, but not tumor cells, led to increased immune infiltration. (3) High expression of DPD in immune and tumor cells induced 5-FU resistance and was associated with unfavorable prognosis. (4) DPD expression closely correlated with microsatellite instability and tumor mutational burden and led to resistance to 5-FU in patients with microsatellite instability. (5) Bioinformatics analyses revealed that DPD was enriched in immune-related functions and pathways such as activation of T cells and macrophages. CONCLUSIONS: DPD plays an important role in the immune microenvironment and drug resistance of colon cancers and their functional association.


Assuntos
Neoplasias do Colo , Di-Hidrouracila Desidrogenase (NADP) , Humanos , Di-Hidrouracila Desidrogenase (NADP)/genética , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Instabilidade de Microssatélites , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Biomarcadores Tumorais/metabolismo , Microambiente Tumoral
18.
Artigo em Inglês | MEDLINE | ID: mdl-37073664

RESUMO

INTRODUCTION: Ding-Zhi-Xiao-Wan (DZXW) produces potential antidepressant-like effects. However, its antidepressant mechanisms are still unclear. The studies were searched from public databases to analyze the antidepressant effects of DZXW by Meta-analysis. METHOD: The compounds of DZXW and genes associated with compounds or depression were obtained from databases. The genes overlapping between DZXW compounds and depression were compared by Venn diagram. A network of medicine-ingredients-targets-disease was constructed, visualized, and analyzed. Protein-protein interaction, gene ontology, pathway enrichment, and molecular docking were performed to evaluate the potential mechanisms of DZXW for the treatment of depression. RESULT: Meta-analysis showed that the antidepressant-like effects were produced by DZXW. The network pharmacology analysis showed that a total of 74 compound-related genes and 12607 PTSD-related genes were identified in the databases with 65 overlapping genes. The active ingredients derived from DZXW (i.e Beta-sitosterol, Stigmasterol, Fumarine, Hederagenin) elicited the antidepressant-like effects by targets, such as ACHE, HTR2A, and CHRM1. Moreover, the signaling pathways, like neuroactive ligand-receptor interaction, pathways in cancer, and cholinergic synapse, might play important roles in the treatment of depression by DZXW. CONCLUSION: This study provides studies analysis and molecular evidence with the beneficial effects of DZXW for the treatment of depression.

19.
Nano Lett ; 23(8): 3444-3450, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37014732

RESUMO

Highly doped lanthanide luminescent nanoparticles exhibit unique optical properties, providing exciting opportunities for many ground-breaking applications, such as super-resolution microscopy, deep-tissue bioimaging, confidentiality, and anticounterfeiting. However, the concentration-quenching effect compromises their luminescence efficiency/brightness, hindering their wide range of applications. Herein, we developed a low-temperature suppression cross-relaxation strategy, which drastically enhanced upconversion luminescence (up to 2150-fold of green emission) in Er3+-rich nanosystems. The cryogenic field opens the energy transport channel of Er3+ multiphoton upconversion by further suppressing phonon-assisted cross-relaxation. Our results provide direct evidence for understanding the energy loss mechanism of photon upconversion, deepening a fundamental understanding of the upconversion process in highly doped nanosystems. Furthermore, it also suggests the potential applications of upconversion nanoparticles for extreme ambient-temperature detection and anticounterfeiting.

20.
Toxicol In Vitro ; 90: 105601, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37031912

RESUMO

Humans are continuously exposed to toxic chemicals such as nitro-chlorobenzene (CDNB) through occupation, water, and even the air we breathe. Due to the severe toxicity caused by the high electrophilicity of CDNB, occupational and environmental exposure to CDNB can produce toxic effects that ultimately lead to cell damage. CDNB can be eliminated from organisms by binding to GSH, the catalytic product of glutathione S-transferase P1 (GSTP1). Therefore, GSTP1 plays an important role in the detoxification of CDNB. However, subtle variations in GSTP1 can result in single nucleotide polymorphisms (SNPs). Indeed, the correlation between the clinical outcome of the disease and certain genotypes of GSTP1 has been extensively studied, however, their impact on the metabolic detoxification of toxicants such as CDNB remains to be elucidated. Among the various SNPs of GSTP1, I105V has a significant effect on the catalytic activity of GSTP1. In this paper, a GSTP1 I105V polymorphism model was successfully established, and its effect on CDNB metabolism and toxicity was studied by computer analysis including molecular docking and molecular dynamics simulation. The result demonstrated that the binding capacity of CDNB decreases with the I105V mutation of GSTP1(p < 0.001), indicating the changes in its detoxification efficacy in CDNB-induced cell damage. Organisms expressing GSTP1 V105 are more susceptible to cell damage caused by CDNB than individuals expressing GSTP1 I105 (p < 0.001). In sum, the data in this study provide prospective insights into the mechanism and capacity of CDNB detoxification in the GSTP1 allele, extending the CDNB-mediated toxicological profile. In addition, the heterogeneity of the GSTP1 allele should be included in toxicological studies of individuals exposed to CDNB.


Assuntos
Glutationa S-Transferase pi , Glutationa Transferase , Humanos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Glutationa S-Transferase pi/genética , Simulação de Acoplamento Molecular , Genótipo , Polimorfismo de Nucleotídeo Único
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...