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1.
Front Psychiatry ; 15: 1335554, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957739

RESUMO

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

2.
Cell Death Dis ; 15(7): 474, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38956060

RESUMO

Colorectal cancer (CRC) is one of the most common tumors of the digestive system worldwide. KRAS mutations limit the use of anti-EGFR antibodies in combination with chemotherapy for the treatment of CRC. Therefore, novel targeted therapies are needed to overcome the KRAS-induced oncogenesis. Recent evidence suggests that inhibition of PI3K led to ferroptosis, a nonapoptotic cell death closely related to KRAS-mutant cells. Here, we showed that a selective PI3Kδ inhibitor TYM-3-98 can suppress the AKT/mTOR signaling and activate the ferroptosis pathway in KRAS-mutant CRC cells in a concentration-dependent manner. This was evidenced by the lipid peroxidation, iron accumulation, and depletion of GSH. Moreover, the overexpression of the sterol regulatory element-binding protein 1 (SREBP1), a downstream transcription factor regulating lipid metabolism, conferred CRC cells greater resistance to ferroptosis induced by TYM-3-98. In addition, the effect of TYM-3-98 was confirmed in a xenograft mouse model, which demonstrated significant tumor suppression without obvious hepatoxicity or renal toxicity. Taken together, our work demonstrated that the induction of ferroptosis contributed to the PI3Kδ inhibitor-induced cell death via the suppression of AKT/mTOR/SREBP1-mediated lipogenesis, thus displaying a promising therapeutic effect of TYM-3-98 in CRC treatment.


Assuntos
Neoplasias Colorretais , Ferroptose , Lipogênese , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas p21(ras) , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1 , Serina-Treonina Quinases TOR , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Serina-Treonina Quinases TOR/metabolismo , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Camundongos , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Mutação/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia
3.
Adv Mater ; : e2405906, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38943439

RESUMO

Deep-sea equipment usually operates under dwell-fatigue condition, which means the equipped energy storage devices must survive under the changing pressure. Special mechanical designs should be considered to maintain the electrochemical performance of electrodes under this extreme condition. In this work, an effective assembly strategy is proposed to accommodate the dwell-fatigue loading using Ag decorated reduced graphene oxide (rGO) foam (denoted as AGF) as a superelastic and robust Zn host. The wet-press assembly process enables the formation of highly porous and robust framework. The strong synergetic effect between rGO and Ag further guarantees AGF's superelasticity and ultrahigh mechanical strength. Meanwhile, the homogeneously distributed Ag species on the rGO sheets act as zincophilic sites to effectively facilitate Zn plating. Furthermore, AGF offers enough space to address the expansion during the charge and discharge cycles. As expected, the symmetrical cell using this AGF@Zn host demonstrates a long lifespan over 400 h at a depth-of-discharge of 50%. It is worth mentioning that the superelastic AGF host realizes stable Zn plating/stripping under varying pressures.

4.
J Proteomics ; 304: 105233, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925350

RESUMO

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

5.
Virulence ; 15(1): 2367671, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38910312

RESUMO

Viral diseases are among the main threats to public health. Understanding the factors affecting viral invasion is important for antiviral research. Until now, it was known that most viruses have very low plaque-forming unit (PFU)-to-particle ratios. However, further investigation is required to determine the underlying factors. Here, using quantitative single-particle analysis methods, the invasion of Semliki Forest virus (SFV), Japanese encephalitis virus (JEV), and influenza A virus (IAV) containing attachment to the cell surface, entry into the cell, transport towards the cell interior, and fusion with endosomes to release nucleocapsids were quantitatively analysed in parallel. It was found that for SFV with an PFU-to-particle ratio of approximately 1:2, an entry efficiency of approximately 31% limited infection. For JEV, whose PFU-to-particle ratio was approximately 1:310, an attachment efficiency of approximately 27% and an entry efficiency of 10% were the main factors limiting its infection. Meanwhile, for IAV with PFU-to-particle ratios of 1:8100, 5% attachment efficiency, 9% entry efficiency, and 53% fusion efficiency significantly limited its infection. These results suggest that viruses with different infectivities have different limited steps in the invasion process. Moreover, there are significant differences in attachment efficiencies among viruses, emphasizing the pivotal role of attachment in viral invasion. The influence of the virus purification method on virus invasion was also investigated. This study, for the first time, reports the efficiencies of different stages of virus invasion, leading to a better understanding of virus invasion and providing a protocol to quantitatively analyse the virus invasion efficiency.


Assuntos
Vírus da Influenza A , Vírus da Floresta de Semliki , Internalização do Vírus , Vírus da Influenza A/fisiologia , Animais , Vírus da Floresta de Semliki/fisiologia , Humanos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Linhagem Celular , Ligação Viral , Endossomos/virologia
6.
Am J Health Promot ; : 8901171241258375, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831423

RESUMO

PURPOSE: Presenting a chain mediation model to investigate whether mobile phone dependence results in a reduction in health-related quality of life (HRQoL) among Chinese college students, through the mediating effect of chronotype and sleep quality. DESIGN AND SETTING: A cross-sectional survey was conducted on students from a Chinese university using a validated structured questionnaire. SAMPLE: 2014 freshmen. MEASURES: The study measured the students' level of mobile phone dependence using the Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use. Chronotype and sleep quality were measured by the Chinese version of the Morningness-Eveningness Questionnaire (MEQ) and the Pittsburgh Sleep Quality Index (PSQI), respectively. HRQoL was evaluated using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), including a descriptive system and a visual analog scale (VAS). ANALYSIS: Descriptive statistical analysis, correlation analysis, and mediation analysis. RESULTS: Mobile phone dependence had a significant negative effect on HRQoL as indicated by both the EQ-5D-5L index score and EQ-VAS score (P < .001 for both). Additionally, it was found to significantly predict chronotype (MEQ score) (ß = -.546, P < .001) and sleep quality (PSQI score) (ß = .163, P < .001). Chronotype negatively predict sleep quality (ß = -.058, P < .001), and sleep quality was a significant negative predictor of HRQoL (EQ-5D-5L index score, ß = -.008, P < .001; EQ-VAS score, ß = -1.576, P < .001). CONCLUSION: Mobile phone dependence negatively impacts students' HRQoL through chronotype and sleep quality, and there is a chain mediating effect. Students should consider making lifestyle changes to improve their HRQoL and promote health.

7.
BMC Cancer ; 24(1): 714, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858644

RESUMO

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.


Assuntos
Artrite Reumatoide , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Análise da Randomização Mendeliana , Miosinas/genética , Perfilação da Expressão Gênica , Transcriptoma , Locos de Características Quantitativas , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Multiômica
9.
Arab J Gastroenterol ; 25(2): 194-204, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38705811

RESUMO

BACKGROUND AND STUDY AIMS: Immunotherapy has emerged as a hot topic in cancer treatment in recent years and has also shown potential in the treatment of Helicobacter pylori-associated gastric cancer. However, there is still a need to identify potential immunotherapy targets. MATERIAL AND METHODS: We used the GSE116312 dataset of Helicobacter pylori-associated gastric cancer to identify differentially expressed genes, which were then overlapped with immune genes from the ImmPort database. The identified immune genes were used to classify gastric cancer samples and evaluate the relationship between classification and tumor mutations, as well as immune infiltration. An immune gene-based prognostic model was constructed, and the expression levels of the genes involved in constructing the model were explored in the tumor immune microenvironment. RESULTS: We successfully identified 60 immune genes and classified gastric cancer samples into two subtypes, which showed differences in prognosis, tumor mutations, immune checkpoint expression, and immune cell infiltration. Subsequently, we constructed an immune prognostic model consisting of THBS1 and PDGFD, which showed significant associations with macrophages and fibroblasts. CONCLUSION: We identified abnormal expression of THBS1 and PDGFD in cancer-associated fibroblasts (CAFs) within the tumor immune microenvironment, suggesting their potential as therapeutic targets.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Fator de Crescimento Derivado de Plaquetas , Neoplasias Gástricas , Trombospondina 1 , Microambiente Tumoral , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Helicobacter pylori/imunologia , Helicobacter pylori/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/complicações , Trombospondina 1/genética , Prognóstico , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/metabolismo , Mutação , Linfocinas
10.
Int J Psychophysiol ; 201: 112359, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38714215

RESUMO

Impaired facial expression perception is a core element in depression, but the underlying mechanism remains controversial. This event-related potential study investigated how attention modulates facial expression perception in depression using a nonclinical sample. A group of healthy controls (HC, N = 39) and a group of individuals with subsyndromal depression (SD, N = 39) categorized faces based on either facial expression (happy vs. sad) or gender (male vs. female). Behaviorally, the SD group was less sensitive to the emotional valence of facial expression than the HC group when their attention was directed to facial expression, as revealed by comparable subjective ratings and accuracy rates in response to facial expressions. When attention was directed towards facial gender, the SD group versus the HC group showed a negative bias, as revealed by a faster N170 for sad faces than happy faces. Together, our findings suggest that attention plays a role in understanding the relationship between depression and facial expression perception.


Assuntos
Atenção , Depressão , Eletroencefalografia , Potenciais Evocados , Expressão Facial , Reconhecimento Facial , Humanos , Masculino , Feminino , Reconhecimento Facial/fisiologia , Adulto , Adulto Jovem , Potenciais Evocados/fisiologia , Atenção/fisiologia , Depressão/fisiopatologia , Percepção Social , Emoções/fisiologia
11.
Mol Neurobiol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714582

RESUMO

Neuropathic pain (NP) resulting from a lesion or disease of the somatosensory system can lead to loss of function and reduced life quality. Neuroinflammation plays a vital role in the development and maintenance of NP. Exercise as an economical, effective, and nonpharmacological treatment, recommended by clinical practice guidelines, has been proven to alleviate chronic NP. Previous studies have shown that exercise decreases NP by modifying inflammation; however, the exact mechanisms of exercise-mediated NP are unclear. Therefore, from the perspective of neuroinflammation, this review mainly discussed the effects of exercise on inflammatory cytokines in different parts of NP conduction pathways, such as the brain, spinal cord, dorsal root ganglion, sciatic nerve, and blood in rat/mice models. Results suggested that exercise training could modulate neuroinflammation, inhibit astrocyte glial cell proliferation and microglial activation, alter the macrophage phenotype, reduce the expression of proinflammatory cytokines, increase anti-inflammatory cytokine levels, and positively modulate the state of the immune system, thereby relieving NP.

12.
Nanomaterials (Basel) ; 14(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38727403

RESUMO

With the rapid development of anion exchange membrane technology and the availability of high-performance non-noble metal cathode catalysts in alkaline media, the commercialization of anion exchange membrane fuel cells has become feasible. Currently, anode materials for alkaline anion-exchange membrane fuel cells still rely on platinum-based catalysts, posing a challenge to the development of efficient low-Pt or Pt-free catalysts. Low-cost ruthenium-based anodes are being considered as alternatives to platinum. However, they still suffer from stability issues and strong oxophilicity. Here, we employ a metal-organic framework compound as a template to construct three-dimensional porous ruthenium-tungsten-zinc nanocages via solvothermal and high-temperature pyrolysis methods. The experimental results demonstrate that this porous ruthenium-tungsten-zinc nanocage with an electrochemical surface area of 116 m2 g-1 exhibits excellent catalytic activity for hydrogen oxidation reaction in alkali, with a kinetic density 1.82 times and a mass activity 8.18 times higher than that of commercial Pt/C, and a good catalytic stability, showing no obvious degradation of the current density after continuous operation for 10,000 s. These findings suggest that the developed catalyst holds promise for use in alkaline anion-exchange membrane fuel cells.

13.
J Agric Food Chem ; 72(20): 11351-11359, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38720167

RESUMO

Tobacco mosaic virus (TMV), as one of the most traditional and extensive biological stresses, poses a serious threat to plant growth and development. In this work, a series of 1-phenyl/tertbutyl-5-amino-4-pyrazole oxadiazole and arylhydrazone derivatives was synthesized. Bioassay evaluation demonstrated that the title compounds (P1-P18) without a "thioether bond" lost their anti-TMV activity, while some of the ring-opening arylhydrazone compounds exhibited superior in vivo activity against TMV in tobacco. The EC50 value of title compound T8 for curative activity was 139 µg/mL, similar to that of ningnanmycin (NNM) (EC50 = 152 µg/mL). Safety analysis revealed that compound T8 had no adverse effects on plant growth or seed germination at a concentration of 250 µg/mL. Morphological observation revealed that compound T8 could restore the leaf tissue of a TMV-stressed host and the leaf stomatal aperture to normal. A mechanism study further revealed that compound T8 not only restored the photosynthetic and growth ability of the damaged host to normal levels but also enhanced catalase (CAT) activity and reduced the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the damaged host, thereby reducing the oxidation damage to the host. TMV-green fluorescent protein (GFP) experiments further demonstrated that compound T8 not only slowed the transmission speed of TMV in the host but also inhibited its reproduction. All of the experimental results demonstrated that compound T8 could reduce the oxidative damage caused by TMV stress and regulate the photosynthetic ability of the host, achieving the ability to repair damage, to make the plant grow normally.


Assuntos
Antivirais , Hidrazonas , Nicotiana , Oxidiazóis , Doenças das Plantas , Vírus do Mosaico do Tabaco , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/fisiologia , Oxidiazóis/química , Oxidiazóis/farmacologia , Hidrazonas/farmacologia , Hidrazonas/química , Hidrazonas/síntese química , Nicotiana/virologia , Nicotiana/efeitos dos fármacos , Doenças das Plantas/virologia , Antivirais/farmacologia , Antivirais/síntese química , Antivirais/química , Desenho de Fármacos , Relação Estrutura-Atividade , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Estrutura Molecular
14.
Infect Drug Resist ; 17: 1979-1986, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800580

RESUMO

Purpose: The present study was designed to investigate the resistance determinants and virulence factors of 45 Trueperella pyogenes isolates from clinical bovine mastitis in Hexi Corridor of Gansu, China. Methods: Minimum inhibitory concentrations (MICs) was tested by E-test method. Gene of antimicrobial resistance, virulence integrase and integron gene cassettes were determined by PCR and DNA sequencing. Results: The T. pyogenes isolates exhibited high resistance to streptomycin (88.9%) and tetracycline (64.4%), followed by erythromycin (15.6%) and gentamicin (13.3%). Resistance to streptomycin was most commonly encoded by aadA9 (88.9%); and to tetracycline, by tetW (64.4%). Importantly, all streptomycin-resistant isolates carried aadA9 alone or in combination with aadA1, aadA11 and strA-strB. Similarly, all tetracycline-resistant isolates harbored tetW alone or in combination with tetA33. Meanwhile, ermX was detected in 13.3% isolates, only one erythromycin-resistant isolate was not identified for this gene. Moreover, all T. pyogenes isolates carried class 1 integrons, and 17.8% of them contained gene cassettes, including arrays aadA1-aadB (4.4%), aad A24-dfrA1-ORF1 (2.2%) and aadA1 (2.2%). Furthermore, all tested isolates harbored virulent genes plo and fimA, followed by fimC (88.9%), fimE (86.6%) nanP (75.6%), nanH (40.0%), cbpA (35.6%) and fimG (6.7%). Conclusion: To our knowledge, this is the first report of integron gene cassettes of T. pyogenes isolates from bovine mastitis cases in China. These findings are useful for developing the prevention and the virulence factors of T. pyogenes could be promising candidates for vaccine antigens for bovine mastitis caused by T. pyogenes in China.

15.
Heliyon ; 10(9): e30310, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38742080

RESUMO

Background: Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods: This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results: Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion: The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.

16.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38741268

RESUMO

Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost-benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.


Assuntos
Anedonia , Motivação , Recompensa , Anedonia/fisiologia , Humanos , Masculino , Feminino , Adulto Jovem , Motivação/fisiologia , Eletroencefalografia , Adulto , Potenciais Evocados/fisiologia , Encéfalo/fisiologia , Adolescente
17.
Breast Cancer ; 31(4): 539-551, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38630392

RESUMO

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Feminino , Fosfatidilinositol 3-Quinases/metabolismo , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de MTOR/uso terapêutico , Inibidores de MTOR/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
18.
Life Sci ; 347: 122662, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38670450

RESUMO

AIMS: PI3Kδ is expressed predominately in leukocytes and is commonly found to be aberrantly activated in human B-cell lymphomas. Although PI3Kδ has been intensively targeted for discovering anti-lymphoma drugs, the application of currently approved PI3Kδ inhibitors has been limited due to unwanted systemic toxicities, thus warranting the development of novel PI3Kδ inhibitors with new scaffolds. MAIN METHODS: We designed TYM-3-98, an indazole derivative, and evaluated its selectivity for all four PI3K isoforms, as well as its efficacy against various B-cell lymphomas both in vitro and in vivo. KEY FINDINGS: We identified TYM-3-98 as a highly selective PI3Kδ inhibitor over other PI3K isoforms at both molecular and cellular levels. It showed superior antiproliferative activity in several B-lymphoma cell lines compared with the approved first-generation PI3Kδ inhibitor idelalisib. TYM-3-98 demonstrated a concentration-dependent PI3K/AKT/mTOR signaling blockage followed by apoptosis induction. In vivo, TYM-3-98 showed good pharmaceutical properties and remarkably reduced tumor growth in a human lymphoma xenograft model and a mouse lymphoma model. SIGNIFICANCE: Our findings establish TYM-3-98 as a promising PI3Kδ inhibitor for the treatment of B-cell lymphoma.


Assuntos
Antineoplásicos , Classe I de Fosfatidilinositol 3-Quinases , Linfoma de Células B , Inibidores de Fosfoinositídeo-3 Quinase , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Animais , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Camundongos , Antineoplásicos/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Indazóis/farmacologia , Indazóis/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus
19.
Front Oncol ; 14: 1363812, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601765

RESUMO

Background: Artificial intelligence (AI) models, clinical models (CM), and the integrated model (IM) are utilized to evaluate the response to neoadjuvant chemotherapy (NACT) in patients diagnosed with gastric cancer. Objective: The objective is to identify the diagnostic test of the AI model and to compare the accuracy of AI, CM, and IM through a comprehensive summary of head-to-head comparative studies. Methods: PubMed, Web of Science, Cochrane Library, and Embase were systematically searched until September 5, 2023, to compile English language studies without regional restrictions. The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria. Forest plots were utilized to illustrate the findings of diagnostic accuracy, while Hierarchical Summary Receiver Operating Characteristic curves were generated to estimate sensitivity (SEN) and specificity (SPE). Meta-regression was applied to analyze heterogeneity across the studies. To assess the presence of publication bias, Deeks' funnel plot and an asymmetry test were employed. Results: A total of 9 studies, comprising 3313 patients, were included for the AI model, with 7 head-to-head comparative studies involving 2699 patients. Across the 9 studies, the pooled SEN for the AI model was 0.75 (95% confidence interval (CI): 0.66, 0.82), and SPE was 0.77 (95% CI: 0.69, 0.84). Meta-regression was conducted, revealing that the cut-off value, approach to predicting response, and gold standard might be sources of heterogeneity. In the head-to-head comparative studies, the pooled SEN for AI was 0.77 (95% CI: 0.69, 0.84) with SPE at 0.79 (95% CI: 0.70, 0.85). For CM, the pooled SEN was 0.67 (95% CI: 0.57, 0.77) with SPE at 0.59 (95% CI: 0.54, 0.64), while for IM, the pooled SEN was 0.83 (95% CI: 0.79, 0.86) with SPE at 0.69 (95% CI: 0.56, 0.79). Notably, there was no statistical difference, except that IM exhibited higher SEN than AI, while maintaining a similar level of SPE in pairwise comparisons. In the Receiver Operating Characteristic analysis subgroup, the CT-based Deep Learning (DL) subgroup, and the National Comprehensive Cancer Network (NCCN) guideline subgroup, the AI model exhibited higher SEN but lower SPE compared to the IM. Conversely, in the training cohort subgroup and the internal validation cohort subgroup, the AI model demonstrated lower SEN but higher SPE than the IM. The subgroup analysis underscored that factors such as the number of cohorts, cohort type, cut-off value, approach to predicting response, and choice of gold standard could impact the reliability and robustness of the results. Conclusion: AI has demonstrated its viability as a tool for predicting the response of GC patients to NACT Furthermore, CT-based DL model in AI was sensitive to extract tumor features and predict the response. The results of subgroup analysis also supported the above conclusions. Large-scale rigorously designed diagnostic accuracy studies and head-to-head comparative studies are anticipated. Systematic review registration: PROSPERO, CRD42022377030.

20.
J Affect Disord ; 357: 77-84, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38670464

RESUMO

BACKGROUND: Depression and anxiety co-occur frequently and there is heterogeneity in the co-occurrence of such symptoms; however, few previous studies investigated the heterogeneity based on person-centered perspectives in adolescents. The primary aim of our study was to explore it using latent profile analysis (LPA), a person-centered statistical approach. METHOD: The Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) were used to examine depression and anxiety symptoms in 7422 Chinese adolescents from 23 primary and secondary schools. To investigate latent profiles and assess profile validity, we employed Latent Profile Analysis (LPA), multinomial logistic regression, and analysis of variance. RESULTS: A three-profile model was suggested as the optimum: low (69.9 %), moderate (21.6 %), and high depression/anxiety (8.5 %). Female with higher negative cognitive bias and higher emotional regulation difficulty are more likely to be categorized in the high depression/anxiety group. Internet addiction, academic "Lying flat" and involution are significantly and positively linked with the severity of anxiety and depression. LIMITATIONS: Reliance on self-reported measures may lead to response bias; the cross-sectional design limits our ability to study how symptom profiles and category membership change over time. CONCLUSIONS: Three latent profiles of the co-occurrence of depression and anxiety presented a parallel pattern, which serves as a poignant reminder of the imperative need to identify Chinese adolescents who may be at elevated risk for depression and/or anxiety, and promoting intervention that are meticulously tailored to address the unique symptom presentations of each individual.


Assuntos
Ansiedade , Depressão , Humanos , Adolescente , Feminino , Masculino , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , China/epidemiologia , Comorbidade , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/psicologia , Análise de Classes Latentes , Questionário de Saúde do Paciente , Regulação Emocional , Inquéritos e Questionários
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