Prognosis stratification of cancer patients treated with immune checkpoint inhibitors through lung immune prognostic index: a meta-analysis and systematic review.

BACKGROUND: Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), the prognostic value of the LIPI in a pancancer setting remains unclear. METHODS: A comprehensive search was conducted until July 2023 across the PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies evaluating the prognostic value of the LIPI in cancer patients treated with ICIs. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). We described and compared the pooled outcomes by stratifying the patients based on different groupings of LIPI (good vs. intermediate [0 vs. 1], good vs. poor [0 vs. 2], and good vs. intermediate / poor [0 vs. 1 + 2]). RESULTS: A total of 9959 patients in 35 studies were included. A higher score of LIPI was associated with impaired OS. The pooled HRs were 1.69 (95% CI: 1.55-1.85, p < 0.001; 0 vs. 1), 3.03 (95% CI: 2.53-3.63, p < 0.001; 0 vs. 2), and 2.38 (95% CI: 1.97-2.88, p < 0.001; 0 vs. 1 + 2). A higher LIPI score was associated with shorter PFS. The pooled HRs were 1.41 (95% CI: 1.31-1.52, p < 0.001; 0 vs. 1), 2.23 (95% CI: 1.87-2.66, p < 0.001; 0 vs. 2), and 1.65 (95% CI: 1.46-1.86, p < 0.001; 0 vs. 1 + 2). Similarly, a higher LIPI score was associated with a lower ORR. The pooled ORs were 0.63 (95% CI: 0.54-0.75, p < 0.001; 0 vs. 1) and 0.38 (95% CI: 0.29-0.50, p < 0.001; 0 vs. 2). A higher LIPI score was associated with a lower DCR. The pooled ORs were 0.47 (95% CI: 0.35-0.61, p < 0.001; 0 vs. 1) and 0.19 (95% CI: 0.12-0.30, p < 0.001; 0 vs. 2). CONCLUSION: In patients with NSCLC or other solid tumours, the lung immune prognostic index could robustly stratify the clinical outcomes into three groups among the patients who receive ICIs. LIPI is a low-cost, simple, accessible, and accurate prognostic tool in a pancancer setting and it may contribute to the evaluation of risk stratification in patients treated with ICIs.

Effects of low-tube voltage coronary CT angiography on plaque and pericoronary fat assessment: intraindividual comparison.

OBJECTIVES: To investigate the effects of low tube voltage on coronary plaques and pericoronary fat assessment, and to compare their extent among various levels of low voltage. MATERIALS AND METHODS: Patients were recommended for high-pitch low-tube voltage coronary computed tomography angiography (CCTA), and they were included if they had poor image quality and were referred to a conventional CCTA. The patients were classified into a low-voltage group (with 70-kV, 80-kV, and 90-kV subgroups) and a conventional group (100/120 kV). Their total plaque and subcomponent volumes and pericoronary fat attenuation index (FAI) were measured. RESULTS: A total of 1002 image slices (from 65 patients and 74 plaques) were included, including 21, 31, 13, 4, and 61 patients in the 70-kV, 80-kV, 90-kV, 100-kV, and 120-kV groups respectively. The CT values of noncalcified plaques in the conventional and low-voltage groups were 54.6 ± 21.3 HU and 31.5 ± 22.6 HU, respectively (p < 0.05). Compared with the conventional group, the necrotic core and calcification volume were increased, and the fibrolipid volume, periplaque, and right coronary artery FAI were decreased in the low-voltage group and its subgroups (p < 0.001). The magnitude of changes in fibrous and calcification volumes increased in the 70-kV subgroup compared with that in the 90-kV subgroup (p < 0.05). CONCLUSION: Low tube voltages, particularly of 70 kV, have a significant effect on coronary plaque and FAI. The effect of low voltage on plaque composition is characterized by a polarization pattern, i.e., a decrease in fibrolipid (medium density) and an increase in necrotic core (low density) and calcification (high density). CLINICAL RELEVANCE STATEMENT: Our results highlight the comparability and repeatability of plaque and pericoronary fat assessments facilitated by the same or a similar tube voltage. It is necessary to carry out studies on the specificity threshold of low tube voltage at each level. KEY POINTS: • Low tube voltage had a significant effect on coronary plaque and pericoronary fat, particularly 70 kV. • The effect of low tube voltage on plaque composition shows the shift from medium-density mixed components to low- and high-density components. • It is necessary to correct the specificity threshold or attenuation difference for low tube voltage at each level.

Young Chinese female body skin pigmentation map: A pilot study.

BACKGROUND: Most studies have discussed variations in facial skin colour based on age, gender, and anatomical site within a specific ethnic group. However, skin pigmentation on the body is also a concern for many people. AIM: The aim of this study is to gather baseline data for Chinese young females, conduct a comprehensive assessment of body skin pigmentation, and create a body skin pigmentation map. METHOD: Individual type angle (ITA°) was registered by CL 400 and melanin index (MI) was registered by MX 18 in 100 body points of 20 Chinese females. A total of 12,000 measurements were recorded. RESULT: Our results showed significant differences among the symmetrical points on both sides of the body, including the clavicle, inner wrists, groin, inner ankle, elbow, armpit, waist side, the space between the thumb and index finger, instep, back shoulder, and popliteal space. Of all the points tested on the body, the points with the most severe skin pigmentation were the back of the neck, the heel, the elbow, and the popliteal space. CONCLUSION: This is the first comprehensive study of skin pigmentation conducted on the human body. In young Chinese women, the points with the most severe skin pigmentation were the back of the neck, heels, elbows, and the popliteal space.

Development and validation of a prospective questionnaire for assessing oily sensitive skin.

BACKGROUND: Skin type has a strong influence on how sensitive skin develops, with oily skin accounting for a larger proportion of sensitive skin. However, there has not been a scientifically sound questionnaire for determining oily sensitive (OS)-type skin in prior studies. OBJECTIVES: In order to identify OS-type skin in the general population, we therefore intend to create an OS-type skin evaluation questionnaire, develop various thresholds through data analysis and classify skin based on two dimensions of sensitivity and oiliness. METHODS: A questionnaire with questions regarding subjects' basic information, skin oiliness and skin sensitivity was given to each individual who participated in the study (n = 1297). To define the thresholds for OS-type skin, receiver-operating characteristic (ROC) curves were generated. The results of the lactic acid stinging test (LAST) and noninvasive instrument information obtained were compared with the thresholds mentioned above to verify the effectiveness of this tool. RESULTS: According to the ROC curves, questionnaire cut-off values of 11.5, 20.5 and 29.5 can be used to detect mildly, moderately and severely sensitive skin, respectively. In addition, the questionnaire cut-off values of 22.5 and 31.5 can be used to detect moderately and severely oily skin, respectively. According to our study, the four sensitive-skin groups' LAST scores differed significantly from one another, while the skin sebum levels differed significantly between the three oily groups. Additionally, the EI and LAST scores were significantly correlated with skin sensitivity levels, whereas sebum, moisture and EI were positively correlated with skin oiliness levels. CONCLUSIONS: We developed an OS-type skin evaluation questionnaire that has been tested and shown scientifically to be a promising method for evaluating OS-type skin and to completely examine the traits of sensitive and oily skin.

CONTEXTE: Le type de peau a une forte influence sur la sensibilité de la peau, avec une peau grasse représentant une plus grande proportion de peaux sensibles. Cependant, il n'y a pas eu de questionnaire scientifiquement fiable pour déterminer le type de peau sensible grasse (OS) dans les études antérieures. OBJECTIFS: Afin d'identifier la peau grasse et sensible dans la population générale, nous avons donc l'intention de créer un questionnaire d'évaluation de la peau grasse et sensible, d'élaborer différents seuils par l'analyse des données et de catégoriser à partir de deux dimensions de sensibilité et d'état huileux. MÉTHODES: Un questionnaire comprenant des questions sur les informations de base des sujets, la sécrétion de sébum de la peau et la sensibilité cutanée a été distribué à chaque individu ayant participé à l'étude (n = 1297). Pour définir les seuils des peaux grasse et sensible, des courbes sensibilité/spécificité (receiver-operating characteristic, ROC) ont été générées. Les résultats du test de picotement à l'acide lactique (LAST) et les informations obtenues à l'aide d'instruments non invasifs ont été comparés aux seuils mentionnés ci-dessus pour vérifier l'efficacité de cet outil. RÉSULTATS: Selon les courbes ROC, des valeurs limites du questionnaire de 11,5, 20,5 et 29,5 peuvent être utilisées pour détecter une sensibilité cutanée légère, modérée et sévère, respectivement. De plus, les valeurs de seuil du questionnaire de 22,5 et 31,5 peuvent être utilisées pour détecter respectivement une peau modérément et sévèrement grasse. Selon notre étude, les scores LAST des quatre groupes à peau sensible différaient significativement les uns des autres, tandis que les taux de sébum cutané différaient significativement entre les trois groupes à peau grasse. De plus, les scores IE et LAST étaient significativement corrélés avec les taux de sensibilité cutanée, tandis que le sébum, l'humidité et l'IE étaient positivement corrélés avec les taux de graisse cutané. CONCLUSIONS: Nous avons développé un questionnaire d'évaluation de la peau grasse et sensible qui a été testé et qui s'est avéré scientifiquement être une méthode prometteuse pour évaluer la peau grasse et sensible et pour examiner complètement les caractéristiques de la peau sensible et grasse.

"Dramatic Growth" of Microbial Aerosols for Visualization and Accurate Counting of Bioaerosols.

While the global COVID-19 pandemic has subsided, microbial aerosol detection has become of high concern. Timely, accurate, and highly sensitive monitoring of microbial aerosols in indoor air is the basis for effective prevention and control of infectious diseases. At present, no commercial equipment or reliable technology can simultaneously control the detection time and limit at 6 h and 102 CFU/mL, respectively. Based on the "safety size range" of particulate matter in the air, we propose a new method of microbial dilation detection, which enables the pathogen to grow rapidly and dramatically into a polymeric microsphere, larger in size than the coexisting aerosol particles. "Like a crane standing among chickens", the microorganism can be easily visualized and counted. Different from routine chemical and biological sensing technologies, this method can achieve absolute counting of microbial particles, and the simple principles can be developed into devices for different life scenarios.

Ultra-fast Redox Pulse for Stable Electrochemiluminescence on AuNP-Based Biosensors and Mechanism Investigation.

A novel sandwich-type biosensor denoted as "MIP-analyte-Ab" was constructed on a glassy carbon electrode modified with gold nanoparticles (AuNPs@GCE), which is dedicated to explore a general solution for electrochemical tests in a relatively high potential range on Au electrodes. In particular, parasitic reactions of Au oxidation severely hindered the electrochemiluminescence (ECL) reactions of the Ru(bpy)32+/tripropylamine (TPrA) system. In this work, we designed an ultra-fast redox pulse to alleviate reversible oxidation of Au with a potential range of -0.5 to 0.9 V. Stable ECL signals were generated in the last 3 ms of each run (RSD = 5.86%), and interesting mechanisms were revealed. The ultra-high-frequency sampler indicated that free diffusion of TPrA•+ was the rate-determining step at 0.9 V, and it followed a totally different route with ECL at 1.3 V. Furthermore, we proposed a particular ECL reaction route at 0.9 V with C5 desosamine of the analyte, azithromycin, involved for the first time, based on results of radical identification. We believe that our work paved the way for the application of Au-based sandwich-type biosensors in environmental monitoring.

HPV E7-drived ALKBH5 promotes cervical cancer progression by modulating m6A modification of PAK5.

Human papillomavirus (HPV) infection is a causative agent of cervical cancer (CC). N6-methyladenosine (m6A) modification is implicated in carcinogenesis and tumor progression. However, the involvement of m6A modification in HPV-involved CC remains unclear. Here we showed that HPV E6/7 oncoproteins affected the global m6A modification and E7 specifically promoted the expression of ALKBH5. We found that ALKBH5 was significantly upregulated in CC and might serve as a valuable prognostic marker. Forced expression of ALKBH5 enhanced the malignant phenotypes of CC cells. Mechanistically, we discovered that E7 increased ALKBH5 expression through E2F1-mediated activation of the H3K27Ac and H3K4Me3 histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Moreover, ALKBH5 promoted tumorigenesis and metastasis of CC by regulating PAK5. Overall, our findings herein demonstrate a significant role of ALKBH5 in CC progression in HPV-positive cells. Thus, we propose that ALKBH5 may serve as a prognostic biomarker and therapeutic target for CC patients.

Effects of Temperature, Light and Salt on the Production of Fucoxanthin from Conticribra weissflogii.

Fucoxanthin is a natural active substance derived from diatoms that is beneficial to the growth and immunity of humans and aquatic animals. Temperature, light and salinity are important environmental factors affecting the accumulation of diatom actives; however, their effects on the production of fucoxanthin in C. weissflogii are unclear. In this study, single-factor experiments are designed and followed by an orthogonal experiment to determine the optimal combination of fucoxanthin production conditions in C. weissflogii. The results showed that the optimum conditions for fucoxanthin production were a temperature of 30 °C, a light intensity of 30 umol m-2 s-1 and a salinity of 25. Under these conditions, the cell density, biomass, carotenoid content and fucoxanthin content of C. weissflogii reached 1.97 × 106 cell mL-1, 0.76 g L-1, 2.209 mg L-1 and 1.372 mg g-1, respectively, which were increased to 1.53, 1.71, 2.50 and 1.48 times higher than their initial content. The work sought to give useful information that will lead to an improved understanding of the effective method of cultivation of C. weissflogii for natural fucoxanthin production.

Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate.

Trichloroethylene (TCE) triggers a severe hypersensitivity syndrome in the occupational population dependent on dendritic cells (DCs). Chloral hydrate (CH), the major oxidative metabolite of TCE, has been proved to be the culprit causative substance of TCE-induced hypersensitivity by human patch tests. Because redox imbalance is essential for chemical sensitizers-induced maturation of DCs, we predicted that CH would activate DCs by the nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. This study selected THP-1 cells as the in vitro DC model, and we evaluated the cell activation markers, intracellular oxidative stress, and Nrf2 pathway related genes expression in response to CH in THP-1 cells. CH displayed significant stimulation of THP-1 cells activation, including CD54 and CD86 expression, IL-8 release, and cell migration, and damaged the redox balance by triggering ROS generation, GSH consumption, and antioxidase activities modulation. The levels of Nrf2 and its downstream genes (HO-1 and NQO1) in mRNA and protein expressions were upregulated by CH, and CH also promoted the nuclear translocation of Nrf2. Subsequently, we investigated the effects of antioxidant on Nrf2-mediated cell defense in CH treated cells. Pretreatment with curcumin dramatically reduced cell activation and oxidative stress triggered by CH in THP-1 cells. We also confirmed the specific role of Nrf2 in CH-induced cell activation using NRF2-knockout cells. Deficiency of Nrf2 inhibited cell activation and downregulated HO-1 and NQO1 expression in CH-challenged cells. These findings suggest that Nrf2-dependent redox homeostasis plays a pivotal role in CH-induced activation of THP-1 cells, thereby providing new knowledge of the allergen as well as the molecular mechanism involving in TCE-induce hypersensitivity syndrome.

Bifidobacterium infantis strain YLGB-1496 possesses excellent antioxidant and skin barrier-enhancing efficacy in vitro.

Atopic dermatitis (AD) is a recurring allergic skin disease that has a high incidence. Orally applied Bifidobacteria ameliorate signs of irritated skin and enhance the skin barrier. The present study investigated the safety and efficacy of a topically used cell-free culture supernatant (CFS) from a Bifidobacterium infantis strain using in vitro evaluation methods. The results showed that CFS had strong free radical scavenging activity on DPPH, ABTS, ·OH and O2 -radicals. CFS treatment fundamentally reduced the intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) contents and improved the activities of antioxidant enzymes (CAT, SOD and GSH-Px) in H2 O2 -treated HaCaT cells. Notably, the upregulation of skin physical barrier gene (FLG, LOR, IVL, AQP3 and TGM1) expression and skin antimicrobial peptide gene (CAMP, hBD-2 and hBD-3) expression by CFS might contribute to skin barrier resistance. CFS was non-irritating to the skin and eyes. CFS from the Bifidobacterium infantis strain had strong antioxidant properties on the skin and strengthened skin barrier function, and it was safe for topical use.

Influence of food matrix and food processing on the chemical interaction and bioaccessibility of dietary phytochemicals: A review.

Consumption of phytochemicals-rich foods shows the health effect on some chronic diseases. However, the bioaccessibility of these phytochemicals is extremely low, and they are often consumed in the diet along with the food matrix. The food matrix can be described as a complex assembly of various physical and chemical interactions that take place between the compounds present in the food. Some studies indicated that the physiological response and the health benefits of phytochemicals are resultant in these interactions. Some food substrates inhibit the absorption of phytochemicals via this interaction. Moreover, processing technologies have been developed to facilitate the release and/or to increase the accessibility of phytochemicals in plants or breakdown of the food matrix. Food processing processes may disrupt the activity of phytochemicals or reduce bioaccessibility. Enhancement of functional and sensorial attributes of phytochemicals in the daily diet may be achieved by modifying the food matrix and food processing in appropriate ways. Therefore, this review concisely elaborated on the mechanism and the influence of food matrix in different parts of the digestive tract in the human body, the chemical interaction between phytochemicals and other compounds in a food matrix, and the various food processing technologies on the bioaccessibility and chemical interaction of dietary phytochemicals. Moreover, the enhancing of phytochemical bioaccessibility through food matrix design and the positive/negative of food processing for dietary phytochemicals was also discussed in this study.

Quantitative analysis of enhanced CT in differentiating well-differentiated pancreatic neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.

OBJECTIVE: To identify quantitative CT features for distinguishing well-differentiated pancreatic neuroendocrine tumors (PNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PNECs). MATERIALS AND METHODS: Seventeen patients with PNECs and 131 patients with PNETs confirmed by biopsy or surgery were retrospectively included. General demographic (sex, age) and CT quantitative parameters (arterial/portal absolute enhancement, arterial/portal relative enhancement ratio, arterial/portal enhancement ratio) were collected. Univariate and multivariate logistic regression analyses were performed to confirm independent variables for differentiating PNECs from PNETs. Receiver operating characteristic (ROC) curves for each quantitative parameter were generated to determine their diagnostic ability. RESULTS: PNECs had a much lower mean arterial/portal absolute enhancement value (19.5 ± 11.0 vs. 78.8 ± 47.2; 28.1 ± 15.8 vs. 77.0 ± 39.4), arterial/portal relative enhancement ratio (0.57 ± 0.36 vs. 2.03 ± 1.31; 0.80 ± 0.52 vs. 1.99 ± 1.13), and arterial/portal enhancement ratio (0.62 ± 0.27 vs. 1.22 ± 0.49; 0.74 ± 0.19 vs. 1.21 ± 0.36) than PNETs (all p < 0.001). After multivariable analysis, arterial absolute enhancement (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93, 0.99) and portal absolute enhancement (OR: 0.96, 95% CI: 0.92, 0.99) were independent factors for differentiating PNECs from PNETs. For each quantitative parameter, arterial lesion enhancement yielded the highest diagnostic performance, with an area under the curve (AUC) of 0.922 (95% CI: 0.867-0.960), followed by portal absolute enhancement. CONCLUSIONS: Arterial/portal absolute enhancements were independent predictors with good diagnostic accuracy for differentiating between PNETs and PNECs. Quantitative parameters of enhanced CT can distinguish PNECs from PNETs. KEY POINTS: • PNECs were hypovascular and had a much lower enhanced CT attenuation in both arterial and portal phases than well-differentiated PNETs. • Quantitative parameters derived from enhanced CT can be used to distinguish PNECs from PNETs. • Arterial absolute enhancement and portal absolute enhancement were independent predictive factors for differentiating between PNETs and PNECs.

Associations between loneliness and frailty among older adults: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND: Previous studies have demonstrated the associations between loneliness and frailty in late life. However, there is a lack of consensus on the direction of the relationship. The present study aimed to examine the interdependencies between loneliness and frailty over time. METHODS: Data on participants aged 60 years old and above were collected from the 2011, 2013, and 2015 samples of the China Health and Retirement Longitudinal Study (CHARLS). Loneliness was measured by a single question from the Centre for Epidemiological Studies Depression scale, and frailty was assessed by the Physical Frailty Phenotype (PFP) scale. Cross-lagged panel models were utilized to examine the potential bidirectional relationship between loneliness and frailty. RESULTS: Reciprocal associations were found between loneliness and frailty. Furthermore, we found that baseline frailty and early change in frailty had a significant predictive effect on late change in loneliness. Higher baseline loneliness in older adults may create a potentially vicious cycle that influenced early change in frailty and continued to cause late change in loneliness. CONCLUSION: A bidirectional relationship may exist between loneliness and frailty among older Chinese adults over 60 years old. Lonely older adults should be alerted to the potential self-reinforcing cycle of loneliness that affects their health.

A Biomimetic Drug Delivery System by Integrating Grapefruit Extracellular Vesicles and Doxorubicin-Loaded Heparin-Based Nanoparticles for Glioma Therapy.

Existing nanoparticle-mediated drug delivery systems for glioma systemic chemotherapy remain a great challenge due to poor delivery efficiency resulting from the blood brain barrier/blood-(brain tumor) barrier (BBB/BBTB) and insufficient tumor penetration. Here, we demonstrate a distinct design by patching doxorubicin-loaded heparin-based nanoparticles (DNs) onto the surface of natural grapefruit extracellular vesicles (EVs), to fabricate biomimetic EV-DNs, achieving efficient drug delivery and thus significantly enhancing antiglioma efficacy. The patching strategy allows the unprecedented 4-fold drug loading capacity compared to traditional encapsulation for EVs. The biomimetic EV-DNs are enabled to bypass BBB/BBTB and penetrate into glioma tissues by receptor-mediated transcytosis and membrane fusion, greatly promoting cellular internalization and antiproliferation ability as well as extending circulation time. We demonstrate that a high-abundance accumulation of EV-DNs can be detected at glioma tissues, enabling the maximal brain tumor uptake of EV-DNs and great antiglioma efficacy in vivo.

Assessment of the mechanism of drug resistance in Trichophyton mentagrophytes in response to various substances.

BACKGROUND: Trichophyton mentagrophyte (TM), a zoonotic pathogen, has been endangering public health due to emerging drug resistance. Although increased attention is paid to this issue, there is very limited research available on drug resistance in TM. In this study, we studied the gene and proteomic changes, morphological changes, cellular fat localization, fat content changes, and biofilm of TM treated with different substances. RESULTS: The TM growth curve showed a positive correlation with the concentration of Fenarimol (FE), genistein (GE), clotrimazole (KM), and Miconazole nitrate salt (MK). The morphology of TM cells changed in different degrees after treatment with different substances as observed by TEM and SEM. The results showed that under KM and berberine hydrochloride (BB) treatment, a total of 3305 differentially expressed genes were detected, with the highest number in the KM-treated group (578 up-regulated and 615 down-regulated). A total of 847 proteins and 1850 peptides were identified in TM proteomics. Nile red staining showed that the fat content of TM was significantly higher in the BB-, ethidium bromide- (EB), FE-, KM-, Adriamycin hydrochloride- (YA), and MK-treated group compared to the control group. Results of the biofilm thickness showed that it gradually increased under treatment with specific concentrations of KM or BB, which may be related to the up-regulation of ERG25 and CYP related gene proteins. CONCLUSIONS: It is suggested that in order to effectively deal with dermatomycosis caused by TM, it is necessary to inhibit the expression of ERG25 and CYP related genes and fat metabolism, which can result in the inhibition of the production of biofilm by the fungus and solve the problem of fungal drug resistance in clinical settings.

MicroRNA-138-1-3p sensitizes sorafenib to hepatocellular carcinoma by targeting PAK5 mediated ß-catenin/ABCB1 signaling pathway.

BACKGROUND: Sorafenib is a kinase inhibitor that is used as a first-line therapy in advanced hepatocellular carcinoma (HCC) patients. However, the existence of sorafenib resistance has limited its therapeutic effect. Through RNA sequencing, we demonstrated that miR-138-1-3p was downregulated in sorafenib resistant HCC cell lines. This study aimed to investigate the role of miR-138-1-3p in sorafenib resistance of HCC. METHODS: In this study, quantitative real-time PCR (qPCR) and Western Blot were utilized to detect the levels of PAK5 in sorafenib-resistant HCC cells and parental cells. The biological functions of miR-138-1-3p and PAK5 in sorafenib-resistant cells and their parental cells were explored by cell viability assays and flow cytometric analyses. The mechanisms for the involvement of PAK5 were examined via co-immunoprecipitation (co-IP), immunofluorescence, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). The effects of miR-138-1-3p and PAK5 on HCC sorafenib resistant characteristics were investigated by a xenotransplantation model. RESULTS: We detected significant down-regulation of miR-138-1-3p and up-regulation of PAK5 in sorafenib-resistance HCC cell lines. Mechanistic studies revealed that miR-138-1-3p reduced the protein expression of PAK5 by directly targeting the 3'-UTR of PAK5 mRNA. In addition, we verified that PAK5 enhanced the phosphorylation and nuclear translocation of ß-catenin that increased the transcriptional activity of a multidrug resistance protein ABCB1. CONCLUSIONS: PAK5 contributed to the sorafenib resistant characteristics of HCC via ß-catenin/ABCB1 signaling pathway. Our findings identified the correlation between miR-138-1-3p and PAK5 and the molecular mechanisms of PAK5-mediated sorafenib resistance in HCC, which provided a potential therapeutic target in advanced HCC patients.

Life satisfaction of 511 elderly Chinese stroke survivors: moderating roles of social functioning and depression in a quality of life model.

OBJECTIVE: Using a published quality of life model, to investigate the moderating roles played by social functioning and post-stroke depression in buffering the relationship between physical functioning and life satisfaction among elderly Chinese stroke survivors. DESIGN: Cross-sectional survey through face-to-face interviews. SETTING: Fangshan district of the Beijing Municipality in China. PARTICIPANTS: A representative random sample of 511 community-dwelling elderly Chinese stroke survivors aged 60 years or above. In total, 127 participants were categorized as stroke survivors with clinical depression and 384 without. MEASURES: Satisfaction With Life Scale, Center for Epidemiologic Studies Depression Scale, International Residential Assessment Instrument Activities of Daily Living Hierarchy scale, International Residential Assessment Instrument Instrumental Activities of Daily Living Performance scale, De Jong Gierveld Loneliness Scale, and Lubben Social Network Scale. RESULTS: Analyses revealed that the unique variance shown by social functioning (16%) is more important than physical functioning (5%) or depressive symptoms (12%) in promoting life satisfaction among all elderly stroke survivors. The moderation model denotes the interaction effect between depressed mood and physical functioning (ß = .152 to .176, p < .001) for all stroke survivors. For stroke survivors without clinical depression, loneliness (ß = .264 to .287, p < .001) and social support (ß = .115 to .151, p < .05) buffered the relationship between physical functioning and life satisfaction; whereas for those with clinical depression, only loneliness (ß = -.264 to .236, p < .05) moderated the corresponding relationship. CONCLUSIONS: Social functioning and post-stroke depression buffered the relationship between physical dependence and life satisfaction among elderly Chinese stroke survivors.

Grade 3 Pancreatic Neuroendocrine Tumors on MDCT: Establishing a Diagnostic Model and Comparing Survival Against Pancreatic Ductal Adenocarcinoma.

OBJECTIVE. The purpose of this study is to establish a diagnostic model for differentiating grade 3 (G3) pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs) and to analyze survival outcomes. MATERIALS AND METHODS. Twenty patients with G3 PNETs and 58 patients with PDACs confirmed by surgery or biopsy were retrospectively included. Demographic and radiologic information was collected. Univariate analyses and binary logistic regression analyses were performed to identify independent factors and establish a diagnostic model. An ROC curve was created to determine diagnostic ability. Kaplan-Meier survival analysis was performed. RESULTS. Patients with G3 PNETs were more likely to present with normal carbohydrate antigen (CA) 19-9 levels, normal pancreatic ducts, and round tumors with well-defined margins and higher portal enhancement ratios than were patients with PDAC (p < 0.05). After multivariate analysis, a normal CA 19-9 level (odds ratio, 0.0125; 95% CI, 0.0008-0.2036), round tumor shape (odds ratio, 0.0143; 95% CI, 0.0004-0.5461), and pancreatic duct dilation of 4 mm or less (odds ratio, 17.9804; 95% CI, 1.0098-320.1711) were independent predictors of G3 PNETs. The AUC of the ROC curve was 0.916, and sensitivity and specificity were 90.0% and 81.0%, respectively. Furthermore, patients with G3 PNETs had better overall survival than patients with PDACs. Among patients in the G3 PNET subgroup, patients with liver or lymph node metastases had worse overall survival than patients without metastases. CONCLUSION. A diagnostic model was established to differentiate G3 PNETs from PDACs. A normal CA 19-9 level, round tumor shape, and pancreatic duct dilation of 4 mm or less were factors that were strongly predictive of G3 PNET.

Construction of SCO-Active Fe(II) Mononuclear Complexes from the Thio-pybox Ligand.

The development of new spin-crossover complexes provides novel promising switching materials with significant potential at the molecular level. Ter-imine-type molecules represent one of the important classes of ligands in creating SCO-active complexes. Herein we report a family of mononuclear Fe(II) SCO-active compounds constructed from a new type of ter-imine ligand named the thio-pybox ligand (2,6-bis(4,4-dimethyl-4,5-dihydrothiazol-2-yl)pyridine, L1). Through the variation of counteranions, some cases display complete SCO and with T1/2 near ambient temperature. Among them, annealed [FeII(L1)2](ClO4)2 [1(ClO4)] shows T1/2↓ and T1/2↑ as 319 and 349 K, respectively. The wide thermal hysteresis of ΔT = 30 K originated from the weak interaction between complex cations and counteranions in the crystal lattice. Impressively, its high-spin population can be increased considerably by annealing at high temperature. The metastable high-spin phase is stable in the successive magnetic measurements and would gradually relax to its initial state with high population of low-spin configuration at ambient temperature. In acetonitrile-diluted solution, 1(ClO4) still maintains SCO with an estimated T1/2 at 240 K. Differential scanning calorimetry discloses the structural phase at around 355 K in the first heating process and the increase in the high-spin population concomitant with annealing was also corroborated by 57Fe Mössbauer measurements. Additionally, the influences on SCO by counteranion and ligand structure are investigated, which show that the fine tuning of complex structures can affect the behavior of the spin state significantly. Finally, magneto-structural correlation studies were performed on the structures of 1(ClO4) and its oxygen analogue at multiple temperatures. The analyses of some structural parameters, including terminal N···N donor separation, bite angle, patulous angle, and the root mean squared deviation indicate that the replacement of the oxygen atom with a sulfur atom can effectively improve the flexibility and release the steric strain and thus tune the SCO toward ambient temperature. Our research demonstrates the rational design of the ligand can lead to new SCO-active compounds with high performance.

A 5.86 Million Quality Factor Cylindrical Resonator with Improved Structural Design Based on Thermoelastic Dissipation Analysis.

The cylindrical resonator is the core component of cylindrical resonator gyroscopes (CRGs). The quality factor (Q factor) of the resonator is one crucial parameter that determines the performance of the gyroscope. In this paper, the finite element method is used to theoretically investigate the influence of the thermoelastic dissipation (TED) of the cylindrical resonator. The improved structure of a fused silica cylindrical resonator is then demonstrated. Compared with the traditional structure, the thermoelastic Q (QTED) of the resonator is increased by 122%. In addition, the Q factor of the improved cylindrical resonator is measured, and results illustrate that, after annealing and chemical etching, the Q factor of the resonator is significantly higher than that of the cylindrical resonators reported previously. The Q factor of the cylindrical resonator in this paper reaches 5.86 million, which is the highest value for a cylindrical resonator to date.