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1.
Neural Regen Res ; 20(3): 858-872, 2025 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38886958

RESUMO

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

2.
J Environ Sci (China) ; 147: 244-258, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003044

RESUMO

4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, ß-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.


Assuntos
Caenorhabditis elegans , Estrogênios , Nitrofenóis , Reprodução , Transdução de Sinais , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Reprodução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Nitrofenóis/toxicidade , Estrogênios/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos
3.
J Environ Sci (China) ; 147: 617-629, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003076

RESUMO

The manganese-cobalt mixed oxide nanorods were fabricated using a hydrothermal method with different metal precursors (KMnO4 and MnSO4·H2O for MnOx and Co(NO3)2⋅6H2O and CoCl2⋅6H2O for Co3O4). Bamboo-like MnO2⋅Co3O4 (B-MnO2⋅Co3O4 (S)) was derived from repeated hydrothermal treatments with Co3O4@MnO2 and MnSO4⋅H2O, whereas Co3O4@MnO2 nanorods were derived from hydrothermal treatment with Co3O4 nanorods and KMnO4. The study shows that manganese oxide was tetragonal, while the cobalt oxide was found to be cubic in the crystalline arrangement. Mn surface ions were present in multiple oxidation states (e.g., Mn4+ and Mn3+) and surface oxygen deficiencies. The content of adsorbed oxygen species and reducibility at low temperature declined in the sequence of B-MnO2⋅Co3O4 (S) > Co3O4@MnO2 > MnO2 > Co3O4, matching the changing trend in activity. Among all the samples, B-MnO2⋅Co3O4 (S) showed the preeminent catalytic performance for the oxidation of toluene (T10% = 187°C, T50% = 276°C, and T90% = 339°C). In addition, the B-MnO2⋅Co3O4 (S) sample also exhibited good H2O-, CO2-, and SO2-resistant performance. The good catalytic performance of B-MnO2⋅Co3O4 (S) is due to the high concentration of adsorbed oxygen species and good reducibility at low temperature. Toluene oxidation over B-MnO2⋅Co3O4 (S) proceeds through the adsorption of O2 and toluene to form O*, OH*, and H2C(C6H5)* species, which then react to produce benzyl alcohol, benzoic acid, and benzaldehyde, ultimately converting to CO2 and H2O. The findings suggest that B-MnO2⋅Co3O4 (S) has promising potential for use as an effective catalyst in practical applications.


Assuntos
Cobalto , Compostos de Manganês , Oxirredução , Óxidos , Tolueno , Óxidos/química , Compostos de Manganês/química , Catálise , Cobalto/química , Tolueno/química , Poluentes Atmosféricos/química
4.
Angew Chem Int Ed Engl ; : e202409931, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38957113

RESUMO

The alkylation of nucleophiles is among the most fundamental and well-developed transformations in chemistry. However, to achieve selective alkylation of complex substrates remains a nontrivial task. We report herein a general and selective alkylation method without using strong acids, bases, or metals. In this method, the readily available phosphinites/phosphites, in combination with ethyl acrylate, function as effective alkylating agents. Various nucleophilic groups, including alcohols, phenols, carboxylic acids, imides, and thiols can be alkylated. This method can be applied in the late-stage alkylation of natural products and pharmaceutical agents, achieving chemo- and site-selective modification of complex substrates. Experimental studies indicate the relative reactivity of a nucleophile depends on its acidity and its steric environment. Mechanistic studies suggest the reaction pathway resembles that of the Arbuzov-Michalis reaction.

5.
Angew Chem Int Ed Engl ; : e202407890, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958602

RESUMO

Developing novel n-type organic semiconductors is an enduring research endeavour, given their pivotal roles in organic electronics and their relative scarcity compared to p-type counterparts. In this study, a new strategy was employed to synthesize n-type organic semiconductors featuring fully-fused conjugated backbone. By attaching two sets of adjacent amino and formyl groups to the indacenodithiophene-based central cores and triggering a tandem reaction of Knoevenagel condensation-intramolecular cyclization, DFA1 and DFA2 were realized. The solution-processed organic field effect transistors based on DFA1 exhibited unipolar n-type transport character with a decent electron mobility of ca. 0.10 cm2 V-1 s-1 (ca. 0.038 cm2 V-1 s-1 for DFA2 based devices). When employing DFA1 as a third component in organic solar cells, a high power conversion efficiency of 19.2% can be achieved in ternary devices fabricated with PM6:L8-BO:DFA1. This work paves a new pathway in the molecular engineering of n-type organic semiconductors, propelling relevant research forward.

6.
Opt Lett ; 49(13): 3737-3740, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950255

RESUMO

An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.

7.
Front Immunol ; 15: 1405146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947338

RESUMO

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Aprendizado de Máquina , Terapia Neoadjuvante , Tomografia Computadorizada por Raios X , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Masculino , Feminino , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Imunoterapia/métodos , Nomogramas , Resultado do Tratamento , Adulto , Radiômica
8.
ACS Omega ; 9(25): 27748-27753, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947823

RESUMO

Superatoms are crucial in the assembly of functional and optoelectronic materials. This study investigates the endohedral metallo-boron nitride [boron nitride (BN)] fullerenes U@B12N12, Cm@B12N12, and U@B16N16 in theory. Our findings confirm that U@B12N12, Cm@B12N12, and U@B16N16 are superatoms and their electronic configurations are 1P61S21D101F142P62S22D102F123P6, 1P61S21D101F141G161H162S22P62D102F12, and 1P61S21D101F142P62S22D102F14, respectively. Notably, the orbital energy levels in these superatoms exhibit a flipping phenomenon, deviating from those of previous superatom studies. Further, the orbital composition analyses reveal that superatomic orbitals 1S, 1P, 1D, and 1F mainly originate from BN cages, whereas the 2S, 2P, 2D, 2F, and 3P superatomic orbitals arise from hybridizations between BN cage orbitals and the 7s, 7p, 6d, and 5f orbitals of actinide atoms. And the energy gap of endohedral metallo-BN fullerene superatoms is reduced by introducing actinide atoms. Additionally, the analyses of ionization potentials and electron affinities show that U@B12N12, Cm@B12N12, and U@B16N16 have lower ionization potentials and higher electron affinities, suggesting decreased stability compared to that of pure BN cages. This instability may be linked to the observed flipping of the superatomic orbital energy levels. These insights introduce new members to the superatom family and offer new building blocks for the design of nanoscale materials with tailored properties.

9.
Front Oncol ; 14: 1412370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957318

RESUMO

Malignant tumors are complex systemic chronic diseases and one of the major causes of human mortality. Targeted therapy, chemotherapy, immunotherapy, and radiotherapy are examples of mainstream allopathic medicine treatments that effective for intermediate and advanced malignant tumors. The ongoing use of conventional allopathic medicine has resulted in adverse responses and drug resistance, which have hampered its efficacy. As an important component of complementary and alternative medicine, Chinese medicine has been found to have antitumor effects and has played an important role in enhancing the therapeutic sensitivity of mainstream allopathic medicine, reducing the incidence of adverse events and improving immune-related functions. The combined application of adjuvant Chinese medicine and mainstream allopathic medicine has begun to gain acceptance and is gradually used in the field of antitumor therapy. Traditional natural medicines and their active ingredients, as well as Chinese patent medicines, have been proven to have excellent therapeutic efficacy and good safety in the treatment of various malignant tumors. This paper focuses on the mechanism of action and research progress of combining the above drugs with mainstream allopathic medicine to increase therapeutic sensitivity, alleviate drug resistance, reduce adverse reactions, and improve the body's immune function. To encourage the clinical development and use of Chinese herb adjuvant therapy as well as to provide ideas and information for creating safer and more effective anticancer medication combinations, the significant functions of Chinese herb therapies as adjuvant therapies for cancer treatment are described in detail.

10.
World Neurosurg ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960308

RESUMO

OBJECTIVE: To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). METHODS: A randomized, single -blind,sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the Day 3 and Day 21 of treatment.The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs,latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score (LESS), spinal cord independence measure (SCIM) score and gait parameters (stride speed, stride frequency, stride length, ground reaction force). RESULTS: On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the lower extremity motor score and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS and SCIM between the two groups (p<0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (p<0.01), and the ground reaction force (GRF) was increased (p<0.05). There was no significant difference in the LESS of the lower limbs between the two groups (p > 0.05). CONCLUSIONS: ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

11.
BMC Public Health ; 24(1): 1763, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956557

RESUMO

OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.


Assuntos
Saúde Global , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/epidemiologia , Masculino , Feminino , Incidência , Saúde Global/estatística & dados numéricos , Mortalidade/tendências , Previsões , Distribuição por Sexo
12.
Int J Gen Med ; 17: 2791-2800, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962174

RESUMO

Purpose: Pain is a common yet undertreated symptom of Parkinson's disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD. Patients and Methods: A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I-III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10). Results: The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred. Conclusion: The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.

13.
Front Oncol ; 14: 1371594, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962262

RESUMO

Objectives: Lung cancer is the leading cause of cancer death, and 80-85% of all lung cancer cases are non-small cell lung cancer (NSCLC). Surgical resection is the standard treatment for early-stage NSCLC. However, lung resection, a surgical procedure, can result in complications and increased mortality. Recent studies have shown a significant correlation between complications after lung resection and right ventricular dysfunction. Methods: Transthoracic echocardiography-derived right ventricular-pulmonary artery coupling (RV-PAC) was utilized to assess right ventricular function in these patients. Multivariate logistic regression analysis was also conducted to assess risk factors independently associated with RV-PA uncoupling. The 3- and 5-year cumulative survival rates were estimated with Kaplan-Meier curves, and differences between groups were analyzed using the Mantel-Cox log-rank test. Results: RV-PA uncoupling was defined as a TAPSE/PASP value < 0.67 mm/mm Hg according to spline analysis. The results of multivariable logistic regression analysis indicated that diabetes is an independent risk factor for right ventricular dysfunction after lung resection in patients with NSCLC. Kaplan-Meier analysis revealed a significant decrease in the survival rate of patients with RV-PA uncoupling at both the 3-year follow-up (73% vs 40%, p < 0.001) and 5-year follow-up (64% vs 37%, p < 0.001). Conclusions: After lung resection for NSCLC, the patient's right ventricular function predicts prognosis. Patients with right ventricular dysfunction, particularly those with diabetes mellitus, have a worse prognosis. It is crucial to actively prevent and correct risk factors to reduce the mortality rate in these patients.

14.
Eur J Med Chem ; 276: 116633, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38968785

RESUMO

Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.

15.
Anal Chim Acta ; 1316: 342852, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38969409

RESUMO

BACKGROUND: With the advent of personalized medical approaches, precise and tailored treatments are expected to become widely accepted for the prevention and treatment of diabetes. Paper-based colorimetric sensors that function in combination with smartphones have been rapidly developed in recent years because it does not require additional equipment and is inexpensive and easy to perform. In this study, we developed a portable, low-cost, and wearable sweat-glucose detection device for in situ detection. RESULTS: The sensor adopted an integrated biomimetic nanoenzyme of glucose oxidase (GOx) encapsulated in copper 1, 4-benzenedicarboxylate (CuBDC) (GOx@CuBDC) through a biomimetic mineralization process. CuBDC exhibited a peroxide-like effect, cascade catalytic effect with the encapsulated GOx, and increased the enzyme stability. GOx@CuBDC and 3,3,5,5-tetramethylbenzidine were combined to form a hybrid membrane that achieved single-step paper-based glucose detection. SIGNIFICANCE AND NOVELTY: This GOx@CuBDC-based colorimetric glucose sensor was used to quantitatively analyze the sweat-glucose concentration with smartphone readings. The sensor exhibited a good linear relationship over the concentration range of 40-900 µM and a limit of detection of 20.7 µM (S/N = 3). Moreover, the sensor performed well in situ monitoring and in evaluating variations based on the consumption of foods with different glycemic indices. Therefore, the fabricated wearable sweat-glucose sensors exhibited optimal practical application performance.


Assuntos
Técnicas Biossensoriais , Colorimetria , Cobre , Glucose Oxidase , Glucose , Smartphone , Suor , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Cobre/química , Suor/química , Humanos , Glucose/análise , Dispositivos Eletrônicos Vestíveis , Limite de Detecção , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo
16.
Exp Gerontol ; 194: 112514, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971132

RESUMO

Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). The transcriptional coactivator PPARγ coactivator 1 (PGC-1a) has been identified as a key regulator of mitochondrial biogenesis and function. However, the precise structure/function relationship between PGC-1a and mitochondrial quality control remains incompletely understood. In this study, we investigated the impact of PGC-1a on AD pathology and its underlying mechanisms with a specific focus on mitochondrial axonal transport. Additionally, we generated two PGC-1α mutants by substituting leucine residues at positions 148 and 149 within the LKKLL motif or at positions 209 and 210 within the LLKYL motif with alanine. Subsequently, we examined the effects of these mutants on mutAPP-induced abnormalities in anterograde and retrograde axonal transport, disrupted mitochondrial distribution, and impaired mitophagy. Mutagenesis studies revealed that the LLKYL motif at amino acid position 209-210 within PGC-1α plays an essential role in its interaction with estrogen-related receptors (ERRα), which is necessary for restoring normal mitochondrial anterograde axonal transport, maintaining proper mitochondrial distribution, and ultimately preventing neuronal apoptosis. Furthermore, it was found that the Leu-rich motif at amino acids 209-210 within PGC-1α is crucial for rescuing mutAPP-induced impairment in mitophagy and loss of membrane potential by restoring normal mitochondrial retrograde axonal transport. Conversely, mutation of residues 148 and 149 in the LKKLL motif does not compromise the effectiveness of PGC-1α. These findings provide valuable insights into the molecular determinants governing specificity of action for PGC-1α involved in regulating mutAPP-induced deficits in mitochondrial axonal trafficking. Moreover, they suggest a potential therapeutic target for addressing Alzheimer's disease.

17.
Mol Cancer Res ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967522

RESUMO

Heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) is considered a cancer-promoting heterogeneous nuclear ribonucleoprotein in many cancers, but its function in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. HnRNPAB was highly expressed in PDAC tissues compared to normal pancreatic tissues, and high expression of hnRNPAB was associated with poor overall survival and recurrence-free survival in PDAC patients. HnRNPAB promotes migration and invasion of PDAC cells in vitro. In xenograft tumor mouse models, hnRNPAB deprivation significantly attenuated liver metastasis. HnRNPAB mRNA and protein levels are positively associated with MYC in PDAC cells. Mechanistically, hnRNPAB bound to MYC mRNA and prolonged its half-life of MYC mRNA. HnRNPAB induced PDAC cells to secret CXCL8 via MYC, which promoted neutrophils recruitment and facilitated tumor cells entrancing into the hepatic parenchyma. These findings point to a novel regulatory mechanism via which hnRNPAB promotes PDAC metastasis. Implications: Hnrnpab participates in the post-transcriptional regulation of the oncogene MYC by binding and stabilizing MYC mRNA, thereby promoting liver metastasis in PDAC.

18.
Afr J Reprod Health ; 28(6): 39-46, 2024 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-38979680

RESUMO

This study was designed to assess the connection between human capital development and the employment of women in China from 1990 to 2020. Data was collected from the World Development Indicators, after which it was subjected to Dynamic Ordinary Least Squares and Granger causality econometric analysis. The results from the study showed that human capital development and women employment had a negative but insignificant relationship. Similarly, a unidirectional relationship existed between female employment and government capital expenditure in China, while a bidirectional association ran between women employment and government expenditure on education in the country. Therefore, it is concluded that human capital development and government expenditure on education are the strong motivating factors that drive GDP growth rate and women employment in China. Consequently, we recommend that policymakers in China should consider massive investment in human capital development in order to enhance women employment in the country. Additionally, policymakers should embark on policies and programmes that foster the expansion of China`s GDP growth rate as a measure to increase employment opportunities for women.


Cette étude a été conçue pour évaluer le lien entre le développement du capital humain et l'emploi des femmes en Chine de 1990 à 2020. Les données ont été collectées à partir des indicateurs de développement mondial, après quoi elles ont été soumises à une analyse économétrique des moindres carrés ordinaires dynamiques et de la causalité de Granger. Les résultats de l'étude ont montré que le développement du capital humain et l'emploi des femmes entretenaient une relation négative mais insignifiante. De même, il existait une relation unidirectionnelle entre l'emploi des femmes et les dépenses publiques en capital en Chine, tandis qu'une association bidirectionnelle existait entre l'emploi des femmes et les dépenses publiques d'éducation dans le pays. Par conséquent, nous concluons que le développement du capital humain et les dépenses publiques consacrées à l'éducation sont les principaux facteurs de motivation qui déterminent le taux de croissance du PIB et l'emploi des femmes en Chine. Par conséquent, nous recommandons aux décideurs politiques chinois d'envisager des investissements massifs dans le développement du capital humain afin d'améliorer l'emploi des femmes dans le pays. En outre, les décideurs politiques devraient se lancer dans des politiques et des programmes qui favorisent l'expansion du taux de croissance du PIB chinois afin d'augmenter les opportunités d'emploi pour les femmes.


Assuntos
Emprego , Humanos , China/epidemiologia , Emprego/estatística & dados numéricos , Feminino , Adulto , Fatores Socioeconômicos , Desenvolvimento Econômico , Mulheres Trabalhadoras/estatística & dados numéricos
19.
Ann Plast Surg ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38980950

RESUMO

BACKGROUND: Breast reduction surgery has witnessed significant advancements in recent years; however, it continues to pose challenges for both surgeons and patients when dealing with cases involving excessive breast volume and severe breast ptosis. This study aimed to assess the aesthetic outcomes and the impact on the quality of life, as measured by the BREAST-Q questionnaire, in patients with gigantomastia and severe breast ptosis who underwent reduction mammaplasty using the superomedial-based pedicle technique. METHODS: We present a retrospective series comprising 84 patients who underwent reduction mammoplasty utilizing the superomedial pedicle technique. The surgical resections exceeded 1 kg per breast, with a mean resection weight of 1506.58 g (right breast) and 1500.32 g (left breast). The preoperative mean suprasternal notch to nipple distance measured 40.50 cm (right breast) and 40.38 cm (left breast). Postoperatively, the patients were followed up for a minimum of 6 months. Both preoperative and postoperative BREAST-Q surveys were administered to the participants, and scores were analyzed using descriptive statistics. RESULTS: Complications were observed in 3 patients (3.57%), characterized by partial loss of the areola, which resolved spontaneously over time. Additionally, 2 cases of hematoma and 2 instances of minor delayed wound healing were reported. All patients expressed satisfaction with their aesthetic outcomes, as they achieved a natural breast shape and minimal scarring, along with symptomatic relief. CONCLUSIONS: The superomedial pedicle reduction mammaplasty technique has demonstrated its ability to produce satisfactory aesthetic outcomes and long-term benefits in patients with excessively large breasts. Careful patient selection and postoperative management are vital for achieving optimal results. Further investigations involving larger sample sizes and longer follow-up periods are warranted to validate our findings. LEVEL OF EVIDENCE: IV.

20.
Front Public Health ; 12: 1434089, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989120

RESUMO

Background: Empathy, as one of the fundamental principles of nursing professionalism, plays a pivotal role in the formation and advancement of the nursing team. Nursing interns, as a reserve force within the nursing team, are of significant importance in terms of their ability to empathize. This quality is not only directly related to the degree of harmony in the nurse-patient relationship and the enhancement of patient satisfaction, but also plays a pivotal role in the promotion of the quality of nursing services to a new level. Aim: The objective of this study was to gain a deeper understanding of the current state of nursing interns' empathic abilities. To this end, we sought to examine empathic performance under different profile models and to identify the key factors influencing these profile models. Methods: The study utilized 444 nursing interns from 11 tertiary general hospitals in Inner Mongolia as research subjects. The study employed a number of research tools, including demographic characteristics, the Jefferson Scale of Empathy, and the Professional Quality of Life Scale. A latent profile model of nursing interns' empathy ability was analyzed using Mplus 8.3. The test of variability of intergroup variables was performed using the chi-square test. Finally, the influencing factors of each profile model were analyzed by unordered multi-categorical logistic regression analysis. Results: The overall level of empathy among nursing interns was found to be low, with 45% belonging to the humanistic care group, 43% exhibiting low empathy, and 12% demonstrating high empathy. The internship duration, empathy satisfaction, secondary traumatic stress, only child, place of birth, and satisfaction with nursing were identified as factors influencing the latent profiles of empathy in nursing interns (p < 0.05). Conclusion: There is considerable heterogeneity in nursing interns' ability to empathize. Consequently, nursing educators and administrators should direct greater attention to interns with lower empathy and develop targeted intervention strategies based on the influences of the different underlying profiles.


Assuntos
Empatia , Humanos , Estudos Transversais , Masculino , Feminino , Adulto , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricos , Relações Enfermeiro-Paciente , Inquéritos e Questionários , China , Competência Clínica
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