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1.
Anal Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597812

RESUMO

As two mainstream ionic detection techniques, ionic current rectification (ICR) suffers from large fluctuations in trace level detection, while resistive-pulse sensing (RPS) encounters easy clogs in high-concentration detection. By rationally matching the nanopore size with the DNA tetrahedron (TDN), this work bridges the two techniques to achieve reliable detection with wide linearity. As a representative analyte, miRNA-10b could specifically combine with and release TDN from the interior wall, which thus induced the simultaneous generation of distinct ICR and RPS signals. The ICR signals could be attributed to the balance between the effective orifice and surface charge density of the inner wall, while the RPS signals were induced by the complex of miRNA-10b and TDN passing through the nanopore. Such an operation contributed to a wide detection range of 1 fM-1 nM with a good linearity. The feasibility of this method is also validated in single-cell and real plasma detection.

2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 267-272, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38595243

RESUMO

OBJECTIVE: To analyze the clinical characteristics of hemodialysis patients with corona virus disease 2019 (COVID-19) in a single-center from Beijing. METHODS: Patients with COVID-19 who received regular hemodialysis at Peking University Third Hospital from November 30, 2022 to January 4, 2023 were selected as the study objects. Clinical symptoms, severity and duration of symptoms during the period of virus positive were investigated in the form of questionnaires, and the basic information of the patients, as well as the results of blood tests (routine blood and blood biochemistry, etc.) before and after infection, dialysis treatment and the outcome of the disease were collected by consulting medical records. RESULTS: A total of 203 subjects were included in this study, including 148 mild cases (72.91%), 23 medium cases (11.33%), 32 severe and critical cases (15.76%), and 16 (7.88%) deaths occured during the follow-up. Clinical symptoms mainly included respiratory symptoms (among which 81.77% had cough, 68.97% had expectoration), fever (81.28%) and fatigue (65.52%), and fatigue and weakness had the longest duration [9 (5, 15) days] among all symptoms. Twenty-six patients (12.8%) reduced the dialysis sessions [1 (1, 2) times], 25 patients (12.32%) had the behavior of early finishing dialysis (27 times), reducing the dialysis time by 30.0 (20.0, 30.5) minutes. Univa-riate analysis showed that the hemoglobin, creatinine, urea nitrogen and ultrafiltration decreased signi-ficantly after infection (P < 0.05). There were significant differences in age, albumin, hemoglobin, creatinine levels and vascular access types among the patients with different clinical subtypes, and the changes of dialysis sessions, fever, expectoration and fatigue degree were also different among the patients with different clinical subtypes (P < 0.05). Multivariate Logistic regression analysis showed that age (OR=1.051, 95%CI: 1.017-1.086, P=0.003) and albumin levels (OR=0.905, 95%CI: 0.803-1.019, P=0.098) corrected by fever, expectoration and fatigue levels were still associated with the occurrence of pneumonia. CONCLUSION: The morbidity of pneumonia and the proportion of deaths in hemodialysis patients with COVID-19 were higher, and some clinical symptoms lasted for a longer time than the general population. During the infection period, the incidence of dialysis-related complications increased, hemoglobin and nutritional status decreased. Elderly patients and patients with low albumin level had a higher risk of developing pneumonia after infection.


Assuntos
COVID-19 , Humanos , Idoso , COVID-19/epidemiologia , COVID-19/terapia , Creatinina , Diálise Renal , Albuminas , Hemoglobinas
3.
Adv Sci (Weinh) ; : e2307269, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445899

RESUMO

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

4.
Heliyon ; 10(5): e26436, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449626

RESUMO

Effectively utilizing information from multiple sources and fewer labeled operating condition samples from a sucker-rod pumping system for oil production can improve the recognition effects and engineering practicability. Nevertheless, this is a challenging energy environment scientific application research subject, and therefore, this study proposes an operating state recognition scheme that relies on multisource nonlinear kernel learning and p-Laplacian high-order manifold regularization logistic regress. Specifically, three measured features are selected and extracted, i.e., wellhead temperature signal, electrical power signal, and ground dynamometer cards, based on mechanism analysis, expert experience, and prior knowledge. Finally, we establish the operating condition recognition model to recognize by the multisource p-Laplacian regularization kernel logistic regress algorithm. The experimental data are derived from 60 wells of a common high-pressure and low-permeability thin oil reservoir block of an oil field in China. The corresponding trials highlight that our scheme outperforms traditional recognition methods by exploiting single-source and multiple-feature data. In the context of fewer labeled samples, the proposed method has a greater recognition effect, engineering practicability, and better model robustness than the existing schemes based on other high-order manifold learning, verifying our method's effectiveness.

5.
Adv Mater ; : e2311242, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504494

RESUMO

Recent years have witnessed a growing interest in bio-based thermosetting resins in terms of environmental concerns and the desire for sustainable industrial practices. Beyond sustainability, utilizing the structural diversity of renewable feedstock to craft bio-based thermosets with customized functionalities is very worthy of expectation. There exist many bio-based compounds with inherently unique chemical structures and functions, some of which are even difficult to synthesize artificially. Over the past decade, great efforts are devoted to discovering/designing functional properties of bio-based thermosets, and notable progress have been made in antibacterial, antifouling, flame retardancy, serving as carbon precursors, and stimuli responsiveness, among others, largely expanding their application potential and future prospects. In this review, recent advances in the field of functional bio-based thermosets are presented, with a particular focus on molecular structures and design strategies for discovering functional properties. Examples are highlighted wherein functionalities are facilitated by the inherent structures of bio-based feedstock. Perspectives on issues regarding further advances in this field are proposed at the end.

6.
Hum Vaccin Immunother ; 20(1): 2324538, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38509699

RESUMO

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.


Assuntos
Poliomielite , Poliovirus , Vacinas contra Rotavirus , Humanos , Lactente , Anticorpos Neutralizantes , Anticorpos Antivirais , China , Imunogenicidade da Vacina , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral , Vacinas Atenuadas
7.
Nano Lett ; 24(14): 4241-4247, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38546270

RESUMO

Electrochemistry that empowers innovative nanoscopic analysis has long been pursued. Here, the concept of aggregation-enabled electrochemistry (AEE) in a confined nanopore is proposed and devised by reactive oxygen species (ROS)-responsive aggregation of CdS quantum dots (QDs) within a functional nanopipette. Complementary Faradaic and non-Faradaic operations of the CdS QDs aggregate could be conducted to simultaneously induce the signal-on of the photocurrents and the signal-off of the ionic signals. Such a rationale permits the cross-checking of the mutually corroborated signals and thus delivers more reliable results for single-cell ROS analysis. Combined with the rich biomatter-light interplay, the concept of AEE can be extended to other stimuli-responsive aggregations for electrochemical innovations.

8.
Anal Chem ; 96(8): 3679-3685, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38353671

RESUMO

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance (gm) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum gm and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 µM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Peroxidase do Rábano Silvestre/química , Colina , Técnicas Biossensoriais/métodos
9.
Heliyon ; 10(2): e24523, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304801

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multi-system and multi-organ dysfunction, and is easily misdiagnosed early in the disease course. We aimed to accurately predict early SLE nomogram to provide a reference basis for the early clinical diagnosis of SLE. Methods: We retrospectively analyzed 167 patients who were first diagnosed with SLE at Fengxian District Central Hospital, Shanghai, between March 2017 and October 2022. Three groups of 129 physically healthy subjects, 67 patients with rheumatoid arthritis, and 40 patients with rashes were selected as controls during the same period. Patients with SLE and control group were randomly divided into training (n = 217) and validation (n = 141) group. Univariate and multivariate analyses were used to identify independent risk factors for early SLE diagnosis. The independent risk factors for diagnosis were used to construct a nomogram to predict early SLE. Results: Based on the training group, three variables were identified as independently influencing early SLE: platelets (odds ratio OR = 0.993, P = 0.047), albumin (OR = 0.833, P = 0.007), and complement component 1q (OR = 0.956, P = 0.000). The precision of the nomogram was assessed using C-index values and calibration plot diagrams. The C-index values were 0.929 for training group and 0.898 for validation group. Both the training group and validation group calibration curves showed good predicted outcomes. Conclusion: The construction of a nomogram can accurately predict the risk of early SLE. The model showed good discriminatory power and calibration for use in the diagnosis of SLE, providing a visual tool and reference basis for the early diagnosis of SLE.

10.
Nat Commun ; 15(1): 1435, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365915

RESUMO

Multiple structural phases of tellurium (Te) have opened up various opportunities for the development of two-dimensional (2D) electronics and optoelectronics. However, the phase-engineered synthesis of 2D Te at the atomic level remains a substantial challenge. Herein, we design an atomic cluster density and interface-guided multiple control strategy for phase- and thickness-controlled synthesis of α-Te nanosheets and ß-Te nanoribbons (from monolayer to tens of µm) on WS2 substrates. As the thickness decreases, the α-Te nanosheets exhibit a transition from metallic to n-type semiconducting properties. On the other hand, the ß-Te nanoribbons remain p-type semiconductors with an ON-state current density (ION) up to ~ 1527 µA µm-1 and a mobility as high as ~ 690.7 cm2 V-1 s-1 at room temperature. Both Te phases exhibit good air stability after several months. Furthermore, short-channel (down to 46 nm) ß-Te nanoribbon transistors exhibit remarkable electrical properties (ION = ~ 1270 µA µm-1 and ON-state resistance down to 0.63 kΩ µm) at Vds = 1 V.

11.
Nat Commun ; 15(1): 1467, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368411

RESUMO

The noncentrosymmetric ferromagnetic Weyl semimetal CeAlSi with simultaneous space-inversion and time-reversal symmetry breaking provides a unique platform for exploring novel topological states. Here, by employing multiple experimental techniques, we demonstrate that ferromagnetism and pressure can serve as efficient parameters to tune the positions of Weyl nodes in CeAlSi. At ambient pressure, a magnetism-facilitated anomalous Hall/Nernst effect (AHE/ANE) is uncovered. Angle-resolved photoemission spectroscopy (ARPES) measurements demonstrated that the Weyl nodes with opposite chirality are moving away from each other upon entering the ferromagnetic phase. Under pressure, by tracing the pressure evolution of AHE and band structure, we demonstrate that pressure could also serve as a pivotal knob to tune the positions of Weyl nodes. Moreover, multiple pressure-induced phase transitions are also revealed. These findings indicate that CeAlSi provides a unique and tunable platform for exploring exotic topological physics and electron correlations, as well as catering to potential applications, such as spintronics.

12.
Chem Commun (Camb) ; 60(17): 2373-2376, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38318933

RESUMO

This work reports the construction of a miniaturized Ag/AgCl nanoelectrode on a nanopipette, which is capable of dual-functions of single-cell drug infusion and chloride detection and is envisioned to promote the study of chloride-correlated therapeutic effects.


Assuntos
Cloretos , Compostos de Prata , Prata
13.
Atherosclerosis ; 390: 117470, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342025

RESUMO

BACKGROUND AND AIMS: Myotubularin-related protein 7 (MTMR7) suppresses proliferation in various cell types and is associated with cardiovascular and cerebrovascular diseases. However, whether MTMR7 regulates vascular smooth muscle cell (VSMC) and vascular intimal hyperplasia remains unclear. We explored the role of MTMR7 in phenotypic switching of VSMC and vascular intimal hyperplasia after injury. METHODS AND RESULTS: MTMR7 expression was significantly downregulated in injured arteries. Compared to wild type (WT) mice, Mtmr7-transgenic (Mtmr7-Tg) mice showed reduced intima/media ratio, decreased percentage of Ki-67-positive cells within neointima, and increased Calponin expression in injured artery. In vitro, upregulating MTMR7 by Len-Mtmr7 transfection inhibited platelet derived growth factor (PDGF)-BB-induced proliferation, migration of VSMC and reversed PDGF-BB-induced decrease in expression of Calponin and SM-MHC. Microarray, single cell sequence, and other bioinformatics analysis revealed that MTMR7 is highly related to glucose metabolism and mammalian target of rapamycin complex 1 (mTORC1). Further experiments confirmed that MTMR7 markedly repressed glycolysis and mTORC1 activity in PDGF-BB-challenged VSMC in vitro. Restoring mTORC1 activity abolished MTMR7-mediated suppression of glycolysis, phenotypic shift in VSMC in vitro and protection against vascular intimal hyperplasia in vivo. Furthermore, upregulating MTMR7 in vitro led to dephosphorylation and dissociation of p62 from mTORC1 in VSMC. External expression of p62 in vitro also abrogated the inhibitory effects of MTMR7 on glycolysis and phenotypic switching in PDGF-BB-stimulated VSMC. CONCLUSIONS: Our study demonstrates that MTMR7 inhibits injury-induced vascular intimal hyperplasia and phenotypic switching of VSMC. Mechanistically, the beneficial effects of MTMR7 are conducted via suppressing p62/mTORC1-mediated glycolysis.


Assuntos
Músculo Liso Vascular , Neointima , Camundongos , Animais , Becaplermina/farmacologia , Becaplermina/metabolismo , Proliferação de Células , Músculo Liso Vascular/patologia , Hiperplasia/patologia , Neointima/metabolismo , Camundongos Transgênicos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/farmacologia , Glucose/metabolismo , Miócitos de Músculo Liso/patologia , Movimento Celular , Células Cultivadas , Mamíferos
14.
Food Chem X ; 21: 101140, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38322763

RESUMO

The effect of adding bamboo shoots to stewing on the quality and flavor of chicken soup has never been reported. Therefore, this study investigated the effects of 4 kinds of bamboo shoots on the edible quality, volatile and water-soluble flavor components of Chahua chicken soup. The results showed that adding bamboo shoots changed the sensory and nutritional quality of chicken soup. A total of 62 volatile flavor components were identified by HS-SPME-GC-MS, of which 12 were identified as characteristic volatile flavor components, and 9 were the main reasons for the flavor differences between bamboo shoot chicken soup with blank chicken soup. LC-MS found that after adding bamboo shoots, the differential water-soluble components in chicken soup significantly increased, and most of the increased components have been proven to have physiological functional activity. In conclusion, adding bamboo shoots improved the nutritional and sensory quality, and changed the flavor components of chicken soup.

15.
ACS Sens ; 9(2): 988-994, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38258286

RESUMO

Herein, the first iontronic photoelectrochemical (PEC) biorecognition probing is devised by rational engineering of a dual-functional bioconjugate, i.e., a light-sensitive intercalated structural DNA, as a smart gating module confined within a nanotip, which could respond to both the incident light and biotargets of interest. Light stimulation of the bioconjugate could intensify the negative charge at the nano-orifice to sustain enhanced ionic current. The presence of proteins (e.g., acetylcholinesterase, AChE) or nucleic acids (e.g., microRNA (miR)-10b) could lead to bioconjugate release with altered ionic signaling. The practical applicability of the methodology is confirmed by AChE detection in human serum and miR-10b detection in single cells.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Humanos , Acetilcolinesterase/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , DNA
16.
Medicine (Baltimore) ; 103(4): e36653, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277544

RESUMO

BACKGROUND: Previous clinical trials have reported that acupoint catgut embedding (ACE) is a useful modality for weight loss. However, no study has specifically investigated the effectiveness and safety of comparing verum and sham ACE in adults with obesity. Thus, this study aimed to evaluate the effectiveness and safety of comparing verum and sham ACE in obese adults. METHODS: A comprehensive literature search was conducted in the electronic databases of PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and China Biomedical Literature Service System from inception to April 1, 2022. Randomized clinical trials that focused on evaluating the effectiveness of comparing verum and sham ACE in adults with obesity were included. The primary outcomes included reduction in body weight, body mass index, hip circumference, and waist circumference. The secondary outcomes consisted of a decrease in body fat percentage and the occurrence rate of adverse events. The methodological quality of the included randomized clinical trials was evaluated using the Cochrane Risk-of-bias tool. Statistical analysis was performed using RevMan 5.4 software. RESULTS: Six trials involving 679 adults with obesity were included in this study and entered in the data analysis of systematic review and meta-analysis. Results of the meta-analysis revealed significant reduction in body weight (mean difference [MD] = -1.68, 95% confidence intervals (CI) [-2.34, -1.01], I2 = 51%, P < .001), body mass index (MD = -0.51, 95% CI [-0.81, -0.21], I2 = 74%, P < .001), hip circumference (MD = -1.11, 95% CI [-1.67, -0.55], I2 = 0%, P < .001), waist circumference (MD = -2.42, 95% CI [-3.38, -1.45], I2 = 68%, P < .001), and decrease in body fat percentage (MD = -0.83, 95% CI [-1.30, -0.36], I2 = 16%, P < .001) in comparing verum and sham ACE. However, no significant difference was identified in AEs (odds ratio = 1.53, 95% CI [0.80, 2.95], I2 = 0%, P = .20) between the 2 groups. CONCLUSION: ACE is effective in the treatment of obesity in adults with safety profile. Further studies with higher quality and larger sample size are warranted to confirm the current findings.


Assuntos
Pontos de Acupuntura , Categute , Adulto , Humanos , Categute/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade/tratamento farmacológico , Peso Corporal
17.
Anal Chem ; 96(5): 2135-2141, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38252409

RESUMO

A facile route for exponential magnification of transconductance (gm) in an organic photoelectrochemical transistor (OPECT) is still lacking. Herein, photoresponsive hydrogen-bonded organic frameworks (PR-HOFs) have been shown to be efficient for gm magnification in a typical poly(ethylene dioxythiophene):poly(styrenesulfonate) OPECT. Specifically, 450 nm light stimulation of 1,3,6,8-tetrakis (p-benzoic acid) pyrene (H4TBAPy)-based HOF could efficiently modulate the device characteristics, leading to the considerable gm magnification over 78 times from 0.114 to 8.96 mS at zero Vg. In linkage with a DNA nanomachine-assisted steric hindrance amplification strategy, the system was then interfaced with the microRNA-triggered structural DNA evolution toward the sensitive detection of a model target microRNA down to 0.1 fM. This study first reveals HOFs-enabled efficient gm magnification in organic electronics and its application for sensitive biomolecular detection.


Assuntos
Ácido Benzoico , MicroRNAs , Hidrogênio , Polietileno , DNA
18.
Anal Chem ; 96(5): 2094-2099, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38258322

RESUMO

Direct single-cell caspase-3 (Casp-3) analysis has remained challenging. A study of single-cell Casp-3 could contribute to revealing the fundamental pathogenic mechanisms in Casp-3-associated diseases. Here, a biomimetic nanochannel capable of single-cell sampling and ionic detection of intracellular Casp-3 is devised, which is established upon the installment of target-specific organic molecules (luc-DEVD) within the orifice of a glass nanopipette. The specific cleavage of luc-DEVD by Casp-3 could induce changes of inner-surface chemical groups and charge properties, thus altering the ionic response of the biomimetic nanochannel for direct Casp-3 detection. The practical applicability of this biomimetic nanochannel is confirmed by probing intracellular Casp-3 fluctuation upon drug stimulation and quantifying the Casp-3 evolution during induced apoptosis. This work realizes ionic single-cell Casp-3 analysis and provides a different perspective for single-cell protein analysis.


Assuntos
Apoptose , Biomimética , Caspase 3/metabolismo , Apoptose/fisiologia
19.
Small ; : e2307281, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225701

RESUMO

Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti-inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA-DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA-DCF) as the MNs tips and then modifying the surface of MNs tips with a self-adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti-inflammatory cell tests and therapeutic animal experiments, down-regulating the expression levels of pro-inflammatory factors and alleviating articular cartilage destruction.

20.
Technol Cancer Res Treat ; 23: 15330338231198972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38200714

RESUMO

Background: To investigate the expression of high mobility group box B-1 (HMGB-1) in patients with colorectal cancer (CRC) and its association with clinicopathological features and prognosis in colorectal carcinoma by combining bioinformatics and clinical data analysis, and to clarify the role of HMGB-1. To examine whether HMGB-1 expression is related to the damage of the intestinal mucosal barrier, and then explore the potential HMGB-1-dependent mechanisms affecting the progression of CRC. Methods: CRC datasets of GSE12945, GSE17536, and GSE17537 from the public gene chip database were screened and downloaded. Clinical information and CRC tissue samples from patients with stage I-III CRC from the hospital were collected. Serum samples of patients were applied by enzyme-linked immunosorbent assay on HMGB-1, and were divided into high and low HMGB-1 expression, which was examined by 16S rDNA sequencing. Immunohistochemistry was performed to examine the relationship between the expression of HMGB-1 and tight junction protein, occludin, tumor necrosis factor-α, and interferon-γ. Results: Based on the Cutoff value of 10.24 ng/mL, the CRC patients were divided into high and low expression groups. In the HMGB-1H patient group, the TNM staging, overall survival, disease-free survival, recurrence, and metastasis were inferior to the HMGB-1L group. The results of 16S rDNA sequencing demonstrated that the Providencia genus was found to be enriched in the HMGB-1L group. Immunohistochemical results showed that HMGB-1 expression was negatively correlated with the expression of ZO-1 and occludin (R = 0.035, R = 0.003, P < .05), but was positively correlated with the expression of TNF-α and IFN-γ (R = 0.016, R = 0.001, P < .05). Conclusion: The survival of CRC patients with positive HMGB-1 expression was significantly shortened, which may be related to the decrease of Rovitensis content, the decreased expression of ZO-1 and occludin, and the increased levels of TNF-α and IFN-γ, which in turn damage the intestinal mucosal barrier, leading to the development of CRC.


Assuntos
Neoplasias Colorretais , Fator de Necrose Tumoral alfa , Humanos , Neoplasias Colorretais/genética , DNA Ribossômico , Ocludina , Prognóstico
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