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The present study was to evaluate the effects of different levels of soybean meal (SBM) substitute for fish meal (FM) on the growth performance, antioxidant capacities, and intestine health of Asian red-tailed catfish, Hemibagrus wyckioides. Five isonitrogenous and isolipidic diets were prepared: the FM diets contained 50 % fish meal, based on which four SBM diets were formulated as substitutes for 15 %, 30 %, 45 % and 60 % FM in the FM group diets, namely SBM15, SBM30, SBM45, and SBM60. Compared with the FM group, the SBM45 and SBM60 groups exhibited significantly elevated serum glutamate pyruvate transaminase (GPT) levels and showed evidence of liver oxidative stress injury. Concurrently, there were decreases in triglyceride (TG) and total cholesterol (TC) levels (P

Objectives Functional impairment is an early stage of disability, and timely identification and intervention are critical for the health of older adults. However, little is known about the functional impairment of Chinese older adults due to the absence of specialised assessment tools. This study aimed to explore the prevalence and socio-demographic characteristics of functional impairment in Chinese community-dwelling older adults using the Function Impairment Screening Tool (FIST), which was previously developed based on the Delphi method.Design Cross-sectional study.Setting Community-based.Participants The study included 6444 community-dwelling older adults from the China Comprehensive Geriatric Assessment Study.Results The FIST identified functional impairment in 31.3% of Chinese community-dwelling older adults. The prevalence was higher among women and individuals in rural areas and increased with age. Illiteracy, no spouse, living alone, poor self-reported health, low income, limited meat intake, less exercise, chronic diseases and geriatric syndromes were associated with functional impairment. Furthermore, after adjusting for related variables, functional impairment was independently associated with disability (OR=138.5, 95% CI 70.0 to 273.9), frailty (OR=13.7, 95% CI 10.3 to 18.3), immobility (OR=6.9, 95% CI 5.4 to 8.9), fractures (OR=2.2, 95% CI 1.5 to 3.3) and falls (OR=2.6, 95% CI 1.8 to 3.7).Conclusion Approximately one-third of Chinese community-dwelling older adults experienced functional impairment, and its prevalence was associated with socio-psychological characteristics, lifestyle, chronic diseases and geriatric syndromes.

Abstract The olfactory system can generate unique sensory memories of various odorous molecules, guiding emotional and cognitive decisions. However, most existing electronic noses remain constrained to momentary concentration, failing to trigger specific memories for different smells. Here, we report an artificial olfactory memory system utilizing conductive metal-organic frameworks (Ce-HHTP) that integrates sensing and memory and exhibits short- and long-term memory responses to alcohols and aldehydes. Experiments and theoretical calculations show that distinct memories are derived from the specific combinations of Ce-HHTP with O atoms in different guest. An unmanned aircraft equipped with this system realized the sensory memories in established areas. Moreover, the fusion of portable detection boxes and wearable flexible electrodes demonstrated the immense potential in off-site pollution monitoring and health management. This work represents an artificial olfactory memory system with two specific sensory memories under simultaneous conditions, laying the foundation for bionic design with qualities of human olfactory memory.

Abstract Purpose Liver was one of the most common distant metastatic sites in breast cancer. Patients with distant metastasis were identified as American Joint Committee on Cancer (AJCC) stage IV indicating poor prognosis. However, few studies have predicted the survival in females with T1-2N0-1 breast cancer who developed liver metastasis. This study aimed to explore the clinical features of these patients and establish a nomogram to predict their overall survival. Results 1923 patients were randomly divided into training (n = 1154) and validation (n = 769) cohorts. Univariate and multivariate analysis showed that age, marital status, race, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), chemotherapy, surgery and bone metastasis, brain metastasis were considered the independent prognostic indicators. We developed a nomogram according to these ten parameters. The consistency index (c-index) was 0.72 (95% confidence interval CI 0.70–0.74) in the training cohort, 0.72 (95% CI 0.69–0.74) in the validation cohort. Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 1-, 3- and 5-year prognoses. Decision curve analysis curves in both the training and validation cohorts demonstrated that the nomogram showed better prediction than the AJCC TNM (8th) staging system. Kaplan Meier curve based on the risk stratification system showed that the low-risk group had a better prognosis than the high-risk group (P

Fusarium graminearum is the main pathogenic fungus causing wheat head blight. It not only causes severe crop yield reduction, but also produces fungal toxins such as deoxynivalenol (DON) and 15-acetyl deoxynivalenol (15-ADON), which are dangerous food pollutants to people and livestock. For the genetic functional study of Fusarium graminearum, it is often necessary to culture mycelium on LTB medium in the laboratory to investigate its regulatory effect on DON and 15-ADON synthesis. However, the detection of DON and 15-ADON in the mycelium is focused on extracellular, with less focus on the detection of intracellular. Simultaneous detection of intracellular and extracellular DON and 15-ADON can provide more in-depth information of fungal toxin production and secretion functions. In the study, a method based on gas chromatography-mass spectrometry (GC-MS) for simultaneous detection of DON and 15-ADON was developed. The solvents for extracting DON and 15-ADON can be completely separated and the calibration curves of each extract show good linear relationship within a certain range. The mass spectrometric characteristic scan shows high ionization efficiency for both DON and 15-ADON. The retention time of DON and 15-ADON in chromatogram are 6.98 and 7.68 min, respectively. Qualitative analysis of DON was performed using m/z 295, 235, and 193 under single ion monitor (SIM) mode, while m/z 392, 235, and 193 were used for 15-ADON. The highest intensity ion m/z 235 was selected for the quantification of DON, and m/z 193 for the quantification of 15-ADON. This method was used to detect the intracellular and extracellular levels of DON and 15-ADON in wild-type PH-1 and tri5 mutant with DON biosynthesis deficiency. The intracellular DON and 15-ADON levels in PH-1 are determined to be (149.13±9.15) μg/g and (1833.31±185.33) μg/g, extracellular levels are (5910.35±468.23) μg/g and (45222.12±2726.81) μg/g, respectively. The study identified a mutant strain with the deletion of the first enzyme involved in the synthesis pathway of DON and 15-ADON，both DON and 15-ADON are not detected in the extracellular and intracellular of the tri5 mutant. Additionally, this research confirms that after 7 days of cultivation in LTB medium, the wild-type strain exhibits higher levels of 15-ADON in both intracellular and extracellular compared to DON, with extracellular levels of DON and 15-ADON being higher than intracellular levels. This method can provide a methodological reference for the functional study of toxin synthesis in Fusarium graminearum.

Purpose: Function impairment is an early stage of disability in older adults and requires timely intervention. We have previously developed Function Impairment Screening Tool (FIST) based on the Delphi method, which has good reliability and validity, but the predictive effect is unknown. Therefore, we aimed to explore the role of FIST in predicting long-term mortality in community-dwelling older adults. Participants and methods: Data were from the Beijing Longitudinal Study of Aging. A total of 1,833 older adults with 8 years of follow-up were included. Function impairment was assessed using FIST. Cox proportional hazards model was used to calculate the predictive effect of FIST on 8-year all-cause mortality. Results: According to FIST, approximately half of the older adults had function impairment (47.6%). The prevalence of function impairment varied across populations. Logistic regression analysis showed that age, female, rural, poor health satisfaction, not drinking tea, and low Mini-Mental State Examination and intrinsic capacity score were associated with function impairment. Furthermore, function impairment was associated with poor physical function and high mortality. Cox analysis showed that FIST could predict 8-year mortality (hazard ratio [HR] = 3.26, 95% confidence interval [CI] 2.74–3.87), and this relationship persisted after adjusting for age, sex, area, marital status, live alone, educational level, smoking, drinking alcohol, and chronic diseases (HR = 1.79, 95% CI 1.45–2.17). Discussion: FIST can predict 8-year mortality in community-dwelling older adults. More attention should be paid to older adults with function impairment and early intervention should be provided.

Purpose To evaluate the safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer.Materials and methods A total of 27 patients with 40 liver lesions underwent fluorescence-assisted laparoscopic ablation between January 2020 to March 2023. The sensitivity of indocyanine green (ICG)-fluorescence imaging, technique effectiveness rate and complications of fluorescence-assisted laparoscopic thermal ablation were evaluated.Results In total, 33 out of the 40 lesions were identified by ICG-fluorescence imaging technique, with the sensitivity of 82.5%. The sensitivity of ICG-fluorescence imaging of tumor detection in liver surface of parenchyma was significantly higher than that in the deeply located hepatic parenchyma (96.8% vs 33.3%, p = 0.002). ICG-fluorescence imaging procedures detected 4 lesions that cannot be seen on intraoperative ultrasound. It provides clear demarcation lines on the hepatic surface. Technical success is achieved if the necrotic zone had at least a 5 mm ablative margin around the outer edge of the ICG-fluorescence image. Technical success of fluorescence laparoscopic radiofrequency ablation (FLRFA) and fluorescence laparoscopic microwave ablation (FLMWA) was 100% (27/27). Technical effectiveness is defined by the complete necrotic lesions of the local tumor tissue during follow-up. According to the CT/MRI one month after FLRFA or FLMWA, the technical efficacy rate was 92.5% (37/40) and local tumor progression occurred in 7.5% (3/40) of the enrolled lesions. During the follow-up period, no major complications were observed.Conclusion ICG-fluorescence imaging guided laparoscopic thermal ablation was feasible, safe and effective.

Abstract Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.

Nanofibers serve as widely employed tissue engineering scaffolds in diverse biomedical applications. When implanted in vivo, it is crucial for tissue engineering scaffolds to be visualizable, enabling the monitoring of their shape, position, and performance. This capability facilitates the effective assessment of implant deformations, displacements, degradations, and functionalities. However, in many biomedical imaging techniques such as magnetic resonance imaging (MRI), the contrast of tissue engineering scaffolds is often inadequate. MRI is particularly notable for its effectiveness in imaging soft tissues. Previous endeavors to enhance the contrast of tissue engineering scaffolds in MRI have involved the use of negative contrast agents (CAs). Nonetheless, negative CAs can result in artifacts, thus favoring the preference for positive CAs due to their ability to generate clearer boundaries. In this study, we successfully prepared composite polyamide 6 nanofibrous scaffolds with ultrafine dispersion Fe(OH)3 nanoparticles using electrospinning and in-situ growth techniques. The relaxation properties of the magnetic nanofibrous scaffolds confirmed the successful production of scaffolds suitable for positive imaging. In vitro cell seeding experiments demonstrated the efficient proliferation and adhesion of endothelial cells and fibroblasts. In vivo studies further revealed the biocompatibility and functionality of the scaffolds. These findings indicate that the prepared PA6/Fe(OH)3 composite nanofibrous scaffolds can enable straightforward, safe, and efficient in vivo positive contrast MRI monitoring, thereby playing a pivotal role in the integration of diagnosis and treatment within tissue engineering scaffolds.

Purpose: To study the role of mitochondrial metabolism and obtain novel biomarkers in immunotherapy for non-small cell lung cancer (NSCLC). Methods: We collected the 188 genes involved in mitochondrial metabolism(MMGs) from the MSIGDB project and then quantified the activity of mitochondrial metabolism. All the NSCLC patients were divided into C1 and C2 clusters based on the 26 prognosis-related MMGs. The differences in biology, differential immune microenvironment, chronic hypoxia and prognosis between C1 and C2 patients were also analyzed. In addition, we validated the results of bioinformatics analysis in lung cancer tissues and cell lines. Results: Patients in the C2 cluster had a higher level of mitochondrial metabolism. Patients in the C2 cluster responded better to immunotherapy and had a lower level of T-cell exclusion. The markers of T-cell failure were upregulated in the C1 patients. Hypoxia can lead to a high percentage of C1 patients. ADH1C might be involved in mitochondrial metabolism and immunotherapy response, which can be affected by hypoxia, making it an underlying biomarker. The expression levels of ADH1C in BEAS-2B, H1299, A549 and H460 cells were detected, revealing that ADH1C is upregulated in lung cancer cells. We observed that patients with low ADH1C expression had a longer survival time. The enzyme activities of HK, PK, LDH and SDH were significantly reduced in H1299 and H460 cells with ADH1C knockdown, along with more ROS. Furthermore, the expression levels of PD-L1 and HHLA2 in tumor tissues were analyzed, which found that ADH1C was significantly positively correlated with the expression of PD-L1 and HHLA2. Conclusions: In summary, our study comprehensively explored the molecules involved in mitochondrial metabolism and their role in immunotherapy and T lymphocyte failure.

Purpose: To determine whether microRNA could be a therapy target of erectile dysfunction (ED) and the underlying mechanisms. Materials and Methods: Eight-week-old fasting male SD rats were intraperitoneally injected with streptozotocin to construct diabetic rat models. Diabetic ED rats were treated with miRNA-92a inhibitor. The cavernous nerves were electrically stimulated to measure the intracavernous pressure and mean arterial pressure of rats in each group. After the detection, the penile cavernous tissues are properly stored for subsequent experiments. Rat aortic endothelial cells were used in in vitro studies. Results:The expression of miR-92a was significantly increased in the corpus cavernosum of Streptozocin (STZ)-induced diabetic rats and injection of miR-92a antagomir into the corpus cavernosum of diabetic rats significantly increased eNOS/NO/ cGMP signaling pathway activities, cavernous endothelial cell proliferation, endothelial cell-cell junction protein expression and decreased the levels of oxidative stress. These changes restored erectile function in STZ-induced diabetic rats. Moreover, in vitro study demonstrated that the miR-92a expression increased significantly in endothelial cells treated with high glucose, inhibiting AMPK/eNOS and AMPK/Nrf2/HO-1 signaling pathways in rat aortic endothelial cells via targeting Prkaa2, causing endothelial dysfunction and overactive oxidative stress, miR-92a inhibitor can improve the above parameters. Conclusions: miRNA-92a inhibitor could exert an inhibition role on oxidative stress and endothelial dysfunction to improve diabetic ED effectively.

ROS1 rearrangement is found in 0.9%–2.6% of people with non-small-cell lung cancers (NSCLCs). Tyrosine kinase inhibitors (TKIs) target ROS1 and can block tumor growth and provide clinical benefits to patients. This review summarizes the current knowledge on ROS1 rearrangements in NSCLCs, including the mechanisms of ROS1 oncogenicity, epidemiology of ROS1-positive tumors, methods for detecting rearrangements, molecular characteristics, therapeutic agents, and mechanisms of drug resistance.

Large-scale multi-building and multi-floor indoor localization has recently been the focus of intense research in indoor localization based on Wi-Fi fingerprinting. Although significant progress has been made in developing indoor localization algorithms, few studies are dedicated to the critical issues of using existing and constructing new Wi-Fi fingerprint databases, especially for large-scale multi-building and multi-floor indoor localization. In this paper, we first identify the challenges in using and constructing Wi-Fi fingerprint databases for large-scale multi-building and multi-floor indoor localization and then provide our recommendations for those challenges based on a case study of the UJIIndoorLoc database, which is the most popular publicly available Wi-Fi fingerprint multi-building and multi-floor database. Through the case study, we investigate its statistical characteristics with a focus on the three aspects of (1) the properties of detected wireless access points, (2) the number, distribution and quality of labels, and (3) the composition of the database records. We then identify potential issues and ways to address them using the UJIIndoorLoc database. Based on the results from the case study, we not only provide valuable insights on the use of existing databases but also give important directions for the design and construction of new databases for large-scale multi-building and multi-floor indoor localization in the future.

Objective: To investigate the frailty, as estimated by accumulated health deficits, in association with the symptomatic carotid atherosclerosis and in relation to five-year cardiovascular (CVD) outcomes. Methods: This is a five-year prospective cohort study. Secondary analysis of data from the Beijing Longitudinal Study on Aging. Community-dwelling people aged 55+ years (n = 1257) have been followed between 2009 and 2014, and having carotid ultrasonography examinations with no CVD events at baseline. Frailty was quantified using the deficit accumulation-based frailty index (FI), constructed from 37 health deficits assessed at baseline. The association between the degree of frailty and carotid atherosclerosis was examined using odds ratios (OR) with multivariate logistic regression analyses. Effects of frailty on the probability of five-year cardiovascular events and mortality were evaluated using Cox proportional hazard ratios (HR). The analyses were adjusted for demographics, baseline carotid atherosclerosis status, and CVD risk factors. Results: The FI showed characteristic properties and was independently associated with the major carotid atherosclerosis symptoms, including carotid artery intima-media thickening (the most frail vs. the least frail: OR = 4.39: 1.98–7.82), carotid plaque (OR = 3.41: 1.28–6.54), and carotid plaque stability (OR = 1.19, 95 % CI: 1.01–3.59). Compared with the least frail, the most frail individuals were more likely to develop a cardiovascular event in five years, including myocardial infarction (HR = 3.38, 95 % CI = 1.84–6.19), stroke (HR = 1.26, 95 % CI = 1.00–5.87), CVD death (HR = 6.33, 95 % CI = 1.69–11.02), and all-cause death (HR = 5.95, 95 % CI = 2.74–8.95). Conclusion: Deficit accumulation was closely associated with carotid atherosclerosis risks and strongly predicted five-year CVD events. The frailty index can be used to help identify older adults at high risks of CVD for improved preventive healthcare.

Abstract Background Frailty can be operationalized based on the accumulation of deficits using a frailty index (FI) and is associated with an increased risk of adverse health outcomes. Here, we aim to compare validity of a FI from laboratory data with that of the common clinical FI for prediction of mortality in adults aged 55 + years, also examine whether combined FI could improve identification of adults aged 55 + years at increased risk of death. Methods Data for this analysis were obtained from the Beijing Longitudinal Study of Aging that involved 1,257 community-dwelling Chinese people, aged 55 + years at baseline. The main outcome measure was 5-year mortality. An FI-self-report based on 30 self-reported health-related data was constructed. An FI-lab was developed using laboratory data, in addition to pulse, systolic and diastolic blood pressure, pulse pressure, body mass index (BMI) and waist. A combined FI comprised all items from each FI. Kaplan–Meier survival curve and Cox proportional hazards models were performed to evaluate the risk of each FI on death. The area under receiver operating characteristic(ROC) curves were used to compare the discriminative performance of each FI. Results Of 1257 participants, 155 died and 156 lost at the end of the 5-year follow-up. The mean FI-self-report score was 0.11 ± 0.10, the FI-lab score was 0.33 ± 0.14 and FI-combined score was 0.19 ± 0.09. Higher frailty level defined by each FI was associated with higher risk of death. After adjustment for age and sex, Cox proportional hazards models showed that the higher scores of frailty were associated with a higher risk of mortality for each FI, the hazard ratios for the FI-self-report and FI-lab and FI-combined were 1.04 (1.03 to 1.05) and 1.02 (1.01 to 1.03) and 1.05 (1.04 to 1.07), respectively. The areas under the ROC curve were 0.79 (0.77–0.82) for the FI-self-report, 0.77(0.75–0.80) for the FI-lab and 0.81(0.78–0.82) for FI-combined. Conclusions A FI from laboratory data can stratify older adults at increased risk of death alone and in combination with FI based on self-report data. Assessment in clinical settings of creating an FI using routine collected laboratory data needs to be further developed.

Abstract Background Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear. Methods In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray. Results The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression. Conclusion Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.

Abstract The associations of blood pressure components with cardiovascular risks and death remain unclear, and the definition of wide pulse pressure (PP) is still controversial. Using data from 1257 participants without a history of cardiovascular disease, who were followed for 4.84 years, we performed multivariable Cox regression analyses to assess how systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP contribute to risks of cardiovascular events and all‐cause death. Among all participants, SBP and PP were significantly associated with the risks of cardiovascular events and all‐cause death (all p < .05). DBP was not significantly associated with the risk of all‐cause death; rather, it was only associated with a marginally significant 1% increased risk for cardiovascular events (p = 0.051). In participants aged

Location fingerprinting using Received Signal Strength Indicators (RSSIs) has become a popular technique for indoor localization due to its use of existing Wi-Fi infrastructure and Wi-Fi-enabled devices. Artificial intelligence/machine learning techniques such as Deep Neural Networks (DNNs) have been adopted to make location fingerprinting more accurate and reliable for large-scale indoor localization applications. However, the success of DNNs for indoor localization depends on the availability of a large amount of pre-processed and labeled data for training, the collection of which could be time-consuming in large-scale indoor environments and even challenging during a pandemic situation like COVID-19. To address these issues in data collection, we investigate multi-dimensional RSSI data augmentation based on the Multi-Output Gaussian Process (MOGP), which, unlike the Single-Output Gaussian Process (SOGP), can exploit the correlation among the RSSIs from multiple access points in a single floor, neighboring floors, or a single building by collectively processing them. The feasibility of MOGP-based multi-dimensional RSSI data augmentation is demonstrated through experiments using the hierarchical indoor localization model based on a Recurrent Neural Network (RNN)—i.e., one of the state-of-the-art multi-building and multi-floor localization models—and the publicly available UJIIndoorLoc multi-building and multi-floor indoor localization database. The RNN model trained with the UJIIndoorLoc database augmented with the augmentation mode of “by a single building”, where an MOGP model is fitted based on the entire RSSI data of a building, outperforms the other two augmentation modes and results in the three-dimensional localization error of 8.42 m.

Cognitive impairment is a major global disease, manifests as a decline in cognitive functioning and endangers the health of the population worldwide. The incidence of cognitive impairment has increased rapidly with an increasingly aging population. Although the mechanisms of cognitive impairment have partly been elucidated with the development of molecular biological technology, treatment methods are very limited. As a unique form of programmed cell death, pyroptosis is highly pro-inflammatory and is closely associated with the incidence and progression of cognitive impairment. In this review, we discuss the molecular mechanisms of pyroptosis briefly and the research progress on the relationship between pyroptosis and cognitive impairment and its potential therapeutic values, to provide a reference for research in the field of cognitive impairment.

Abstract Background Radial artery (RA) atherosclerosis in acute coronary syndrome (ACS) patients has not been systematically observed in vivo. The study aims to characterize plaque morphology and intimal hyperplasia of the RA in patients with ACS, using optical coherence tomography (OCT). Methods In this retrospective study involving 239 ACS patients underwent RA OCT without guidewire shadow, 3 groups were divided according to the following criteria: radial artery plaque (RAP) group included patients with fibrous, lipid or calcified plaque; patients without RAP were further classified into radial intimal hyperplasia (RIH) group (intima media thickness ratio [IMR] ≥ 1) or normal group (IMR

Abstract Background ApoE gene polymorphism and serum total homocysteine (tHcy) has been reportedly associated with cognition. In this study, we assessed the association of combined ApoE gene polymorphism and tHcy with cognition in Chinese elder adults. Methods A cross- sectional study was carried out by recruiting 1458 community-dwelling people aged 55+ and above in Beijing in 2009. All participants were interviewed using a standard questionnaire and underwent a physical examination. The mini-mental scale examination (MMSE) score was used in assessing cognitive function. Fasting venous blood samples were taken for ApoE rs429358, rs7412 genotyping, tHcy and other serum lipid measurements. Results Participants with high serum tHcy level showed a relatively lower orientation, attention abilities as well as the total MMSE score than the group with normal tHcy after adjusting confounding factors. ApoE rs429358 and rs7412 variants were observed to have the highest serum TC and TG level in the subjects with high serum tHcy level (p

BackgroundLymph node (LN) metastasis is strongly associated with distant metastasis of renal cell carcinoma (RCC) and indicates an adverse prognosis. Accurate LN-status prediction is essential for individualized treatment of patients with RCC and to help physicians make appropriate surgical decisions. Thus, a prediction model to assess the hazard index of LN metastasis in patients with RCC is needed.MethodsPartial data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Data of 492 individuals with RCC, collected from the Southwest Hospital in Chongqing, China, were used for external validation. Eight indicators of risk of LN metastasis were screened out. Six machine learning (ML) classifiers were established and tuned, focused on predicting LN metastasis in patients with RCC. The models were integrated with big data analytics and ML algorithms. Based on the optimal model, we developed an online risk calculator and plotted overall survival using Kaplan–Meier analysis.ResultsThe extreme gradient-boosting (XGB) model was superior to the other models in both internal and external trials. The area under the curve, accuracy, sensitivity, and specificity were 0.930, 0.857, 0.856, and 0.873, respectively, in the internal test and 0.958, 0.935, 0.769, and 0.944, respectively, in the external test. These parameters show that XGB has an excellent ability for clinical application. The survival analysis showed that patients with predicted N1 tumors had significantly shorter survival (p

ABSTRACT: Lung cancer has the highest incidence and mortality rate worldwide. Immunotherapy is a universal treatment for lung cancer, but its overall treatment remains a challenge. Tumor immunoediting is a process in which the immune system restricts or promotes tumor development through elimination, equilibrium, and escape to change tumor immunogenicity and obtain an immunosuppressive mechanism to promote disease progression. An increasing number of immunotherapy drugs, including monoclonal antibody-targeting drugs and chimeric antigen (Ag) receptor-modified T cells (CAR-T cells), have been used in clinical therapy. Additionally, cancer vaccine development and new clustered regularly spaced short palindromes (CRISPR)- based combination therapies against cancer open up new avenues for immunotherapy. However, these immunotherapies cause autoimmune induction and non-specific inflammation, with many limitations. The development and study of nanoparticle systems have shown the possibility of localization, pharmacokinetic programming, and immunomodulator co-delivery. Rapid advances in nanotechnology over the past decade have provided a strategic impetus for cancer immunotherapy improvements. Nanotechnology advancements in various aspects, such as virus-like size, high surface-volume ratio, and surface modifications to precisely target specific cell types, can be investigated through cancer vaccine and immunomodulator delivery system development. This review presents the current immunotherapy approaches for lung cancer and emphasizes the current process and prospects of the fusion of cancer immunotherapy, nanotechnology, bioengineering, and drug delivery.

BackgroundPrimary tracheal or bronchial tumors are relatively uncommon, whether benign or malignant. Sleeve resection is an excellent surgical technique for most primary tracheal or bronchial tumors. However, depending on the size and location of the tumor, thoracoscopic wedge resection of trachea or bronchus can be performed with the assistance of a fiberoptic bronchoscope for some malignant and benign tumors.Case DescriptionWe performed a single incision video-assisted bronchial wedge resection in a patient with a left main bronchial hamartoma with a size of 7 × 5 × 5 mm. The patient was discharged from the hospital six days after the surgery with no postoperative complications. There was no obvious discomfort during the 6-month postoperative follow-up, and the reexamination of fiberoptic bronchoscopy revealed no evident stenosis of the incision.ConclusionsThrough the detailed case study and literature review, we believe that tracheal or bronchial wedge resection is a significantly superior technique under the appropriate conditions. Video-assisted thoracoscopic wedge resection of trachea or bronchus should be a new and excellent development direction of minimally invasive bronchial surgery.

The global burden of cancer is increasing rapidly, and nanomedicine offers promising prospects for enhancing the life expectancy of cancer patients. Janus nanoparticles (JNPs) have garnered considerable attention due to their asymmetric geometry, enabling multifunctionality in drug delivery and theranostics. However, achieving precise control over the self-assembly of JNPs in solution at the nanoscale level poses significant challenges. Herein, a low-temperature reversed-phase microemulsion system was used to obtain homogenous Mn3O4-Ag2S JNPs, which showed significant potential in cancer theranostics. Structural characterization revealed that the Ag2S (5–10 nm) part was uniformly deposited on a specific surface of Mn3O4 to form a Mn3O4-Ag2S Janus morphology. Compared to the single-component Mn3O4 and Ag2S particles, the fabricated Mn3O4-Ag2S JNPs exhibited satisfactory biocompatibility and therapeutic performance. Novel diagnostic and therapeutic nanoplatforms can be guided using the magnetic component in JNPs, which is revealed as an excellent T1 contrast enhancement agent in magnetic resonance imaging (MRI) with multiple functions, such as photo-induced regulation of the tumor microenvironment via producing reactive oxygen species and second near-infrared region (NIR-II) photothermal excitation for in vitro tumor-killing effects. The prime antibacterial and promising theranostics results demonstrate the extensive potential of the designed photo-responsive Mn3O4-Ag2S JNPs for biomedical applications.

Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics. Here, we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles (ICG-Ga NPs) containing clinically approved gallium (III) (Ga3+) and liver targeting indocyanine green (ICG) molecules to eradicate multi-drug resistant (MDR) bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking. The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane, further boost the endocytosis of Ga3+, then replace iron in bacteria cells to disrupt bacterial iron metabolism, and demonstrate the synergetic bacterial killing and biofilm disrupting effects. The ICG-Ga NPs show an excellent therapeutic effect against extended spectrum β-lactamases Escherichia coli (ESBL E. coli) and significantly improve treatment outcomes in infected liver abscess and keratitis. Meanwhile, the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route, guaranteeing the biocompatibility. The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.

Numerous epidemiological and laboratory studies on essential trace elements have reported protective associations in developing various cancer types, including esophagus cancer (EC). However, the results are not always consistent. Some essential trace elements could play a vital role in preventing esophagus cancer. Some showed no association with esophageal cancer risk, while others harmed individuals. This article reviews the association between the intake or supplementation of essential trace elements (especially zinc, copper, iron, and selenium) and the risk of esophageal cancer. Generally, zinc intake may decrease the risk of esophageal cancer (EC), especially in high esophageal squamous cell carcinoma (ESCC) prevalence regions. The association between copper supplementation and EC remains uncertain. Total iron consumption is thought to be associated with lower EC risk, while heme iron intake may be associated with higher EC risk. Selenium intake showed a protective effect against EC, especially for those individuals with a low baseline selenium level. This review also prospects the research direction of the association between EC and essential trace elements.

Abstract Background Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. Methods In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. Results Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels

Lung adenocarcinoma (LUAD) usually contains heterogeneous histological subtypes, among which the micropapillary (MIP) subtype was associated with poor prognosis while the lepidic (LEP) subtype possessed the most favorable outcome. However, the genomic features of the MIP subtype responsible for its malignant behaviors are substantially unknown. In this study, eight FFPE samples from LUAD patients were micro-dissected to isolate MIP and LEP components, then sequenced by whole-exome sequencing. More comprehensive analyses involving our samples and public validation cohorts on the two subtypes were performed to better decipher the key biological and evolutionary mechanisms. As expected, the LEP and MIP subtypes exhibited the largest disease-free survival (DFS) differences in our patients. EGFR was found with the highest mutation frequency. Additionally, shared mutations were observed between paired LEP and MIP components from single patients, and recurrent mutations were verified in the Lung-Broad, Lung-OncoSG, and TCGA-LUAD cohorts. Distinct biological processes or pathways were involved in the evolution of the two components. Besides, analyses of copy number variation (CNV) and intratumor heterogeneity (ITH) further discovered the possible immunosurveillance escape, the discrepancy between mutation and CNV level, ITH, and the pervasive DNA damage response and WNT pathway gene alternations in the MIP component. Phylogenetic analysis of five pairs of LEP and MIP components further confirmed the presence of ancestral EGFR mutations. Through comprehensive analyses combining our samples and public cohorts, PTP4A3, NAPRT, and RECQL4 were identified to be co-amplified. Multi-omics data also demonstrated the immunosuppression prevalence in the MIP component. Our results uncovered the evolutionary pattern of the concomitant LEP and MIP components from the same patient that they were derived from the same initiation cells and the pathway-specific mutations acquired after EGFR clonal mutation could shape the subtype-specificity. We also confirmed the immunosuppression prevalence in the MIP subtype by multi-omics data analyses, which may have resulted in its unfavorable prognosis.

PurposeIn clinical work, accurately measuring the volume and the size of breast cancer is significant to develop a treatment plan. However, it is time-consuming, and inter- and intra-observer variations among radiologists exist. The purpose of this study was to assess the performance of a Res-UNet convolutional neural network based on automatic segmentation for size and volumetric measurement of mass enhancement breast cancer on magnetic resonance imaging (MRI).Materials and methodsA total of 1,000 female breast cancer patients who underwent preoperative 1.5-T dynamic contrast-enhanced MRI prior to treatment were selected from January 2015 to October 2021 and randomly divided into a training cohort (n = 800) and a testing cohort (n = 200). Compared with the masks named ground truth delineated manually by radiologists, the model performance on segmentation was evaluated with dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC). The performance of tumor (T) stage classification was evaluated with accuracy, sensitivity, and specificity.ResultsIn the test cohort, the DSC of automatic segmentation reached 0.89. Excellent concordance (ICC > 0.95) of the maximal and minimal diameter and good concordance (ICC > 0.80) of volumetric measurement were shown between the model and the radiologists. The trained model took approximately 10–15 s to provide automatic segmentation and classified the T stage with an overall accuracy of 0.93, sensitivity of 0.94, 0.94, and 0.75, and specificity of 0.95, 0.92, and 0.99, respectively, in T1, T2, and T3.ConclusionsOur model demonstrated good performance and reliability for automatic segmentation for size and volumetric measurement of breast cancer, which can be time-saving and effective in clinical decision-making.

Purpose: This study aimed to develop a prognostic indicator based on epithelial-mesenchymal transition (EMT)-related long noncoding RNAs (lncRNAs) and explore the function of EMT-related lncRNAs in malignant progression in lung adenocarcinoma (LUAD).Materials and methods: A LUAD dataset was acquired from The Cancer Genome Atlas (TCGA) to identify prognostic EMT-related lncRNAs via differential expression analysis and univariate Cox regression analysis. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was utilized for variable selection and model construction. The EMT-related prognostic index (ERPI) was calculated according to the model and served as a classifier to divide LUAD individuals into high-ERPI and low-ERPI groups. A nomogram incorporating ERPI and clinicopathological variables was constructed. TCGA-LUAD, GSE50081, and GSE31210 were used to test the predictive capacity of the ERPI and nomogram. The characteristics of the tumor microenvironment (TME) were evaluated via the ESTIMATE, TIMER, and ssGSEA algorithms. Gene set variation analysis (GSVA) and ssGSEA were used to annotate the functions of the high-ERPI and low-ERPI groups. CCK8, transwell assay, wound-healing assay, and clone formation assay were conducted to clarify the biological functions of prognostic EMT-related lncRNAs.Results: Ninety-seven differentially expressed EMT-related lncRNAs were identified, 15 of which were related to overall survival (OS). A prognostic signature was constructed based on 14 prognostic EMT-related lncRNAs to calculate the ERPI of each patient, and the predictive ability of ERPI was verified in TCGA, GSE50081, and GSE31210. The low-ERPI group survived longer and had a lower percentage of patients in advanced stage than the high-ERPI group. The nomogram had the highest predictive accuracy, followed by ERPI and stage. Patients with low ERPI had higher infiltration degree of immune cells and stronger immune responses than those with high ERPI. A series of in vitro experiments demonstrated that knockdown of LINC01138 dampened variability, proliferation, and motility of A549 and H460 cells.Conclusion: Our study developed a prognostic classifier with robust prognostic performance and clarified the biological functions of LINC01138 in LUAD, aiding in making individual treatments for patients with LUAD and dissecting the mechanism of oncogenesis.

Objective To explore the association of depression, as well as untreated hypertension or diabetes with all-cause death in community-based postmenopausal women in Beijing. Methods A cohort of 863 community-based postmenopausal women with no history of cardiovascular heart disease (CHD), stroke, cancer, or dementia was investigated on 20 July–28 September 2009 at baseline. Depression was diagnosed using the 30-item Center for Epidemiologic Studies Depression (CES-D) scale with CES-D ≥ 11. Meanwhile, data on health behavior, physical comorbidity, and social support at baseline were collected. These individuals were followed up from 20 July to 30 August 2014. All-cause mortality and cause of death were surveyed. Results After a median follow-up of 4.97 years, 120 subjects died of all-cause. Twenty-four died of stroke, 19 died of myocardial infarction, 21 died of cancer. The others died of aging, infection, and accident. Depression and untreated HP were significantly associated with all-cause mortality in Cox models after full adjustment for all of the potential confounders (Depression HR: 2.16, 95%CI: 1.35–3.46; Untreated hypertension HR: 1.84, 95%CI: 1.12–3.02). However, negative correlation of untreated diabetes on all-cause mortality was observed in this population (HR: 1.36, 95%CI: 0.75–2.49). When depression was co-existing with hypertension/diabetes, the HR for mortality elevated significantly (Depression co-existing with hypertension HR = 3.87, 95% CI: 2.07–7.23; Depression co-existing with diabetes HR = 5.02, 95% CI: 1.5–16.79). Conclusions It is suggested we should take sufficient care of postmenopausal females with depression and control blood pressure and glucose more effectively. Abbreviations: HP: Hypertension; DM: Diabetes; TC: Cholesterol; TG: Triglyceride; BMI: Body-Mass Index; CES-D: Center for Epidemiologic Studies Depression; CDC: Centers for Disease Control and Prevention; HR: Hazard Ratio; CI: Confidence Interval; ADL: Activities of daily living scale

A chitosan/deoxyribonucleic acid (CHI/DNA)5 coating was constructed by layer-by-layer (LbL) assembly dip coating method with Mg(OH)2 coating as an inner protective layer on AZ31 alloy. X-ray diffractometry, X-ray photoelectron spectrometry, Fourier transform infrared spectroscopy and field-emission scanning electron microscopy were utilized to represent the chemical compositions and surface morphologies of the coatings. Electrochemical tests and hydrogen evolution measurements were implemented to confirm the good corrosion resistance of the composite coating in artificial body fluid. Antimicrobial activity of the composite coatings was tested via the plate-counting method, and the cytotoxicity of the samples was appraised by MTT assay and Live/dead staining. A double action was put into effect for the composite coating, which the inner Mg(OH)2 coating plays the part of physical barrier, and the outer (CHI/DNA)5 coating is employed as an inducer to fabricate a biocompatible Ca-P corrosion product coating during immersion, making up for its thin thickness. Otherwise, the composite coating is also beneficial for the growth of bone, resulting from the biomineralization effect of the outer polyelectrolyte multilayer. The good antibacterial property of the (CHI/DNA)5/Mg(OH)2 coating is ascribed to the contact-killing strength of CHI. Thus, the obtained (CHI/DNA)5/Mg(OH)2 coating has a wide application prospect in the field of Mg-based bone implantation.

The mechanisms associated with Caveolin-1 (Cav-1) mediated metabolic changes in prostate cancer are unclear. Here, the authors show that Cav-1 promotes rewiring of cancer cell lipid metabolism towards a program of exogenous lipid scavenging and vesicle biogenesis that intersects with mitochondrial dynamics in prostate tumors.

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.

There has been significant interest in designing heterostructured nanoparticles with excellent synergistic properties and multifunctionality. Herein, this work reports on the design of reactive oxygen species- (ROS-) responsive Ag decorated TiO2 hybrid nanorods (HNRs) with dual functionalities of enhanced photodynamic therapy and antibacterial activity. A de-wetting phenomenon was employed to nucleate and crystallize Ag nanoparticles onto the surface of TiO2 nanorods resulting in Ag-TiO2 hybrid nanocomposites. The use of the Pluronic® F-127 polymer, which is permitted by the Food and Drug Administration (FDA), remarkably improved the biocompatibility of Ag-TiO2 HNRs tested in 4T1 breast cancer cells. Furthermore, Ag-TiO2 HNRs endocytosed by cancer cells produced high intracellular ROS under UV conditions (5.6 mW cm−2), resulting in cancer cell apoptosis. Similarly, the distinctive features of Ag NPs on TiO2 nanorods slow down the recombination rate of electrons–holes, and exhibited 90% killing efficacy against Escherichia coli (gram-negative/rods) and Staphylococcus aureus (gram-positive/cocci). The potential of photo-activated Ag-TiO2 HNRs, as demonstrated in this work, indicates that this heterostructured material is a promising novel dual-therapeutic strategy against cancer cells and microbial agents.

Background Primary dental caries is the most prevalent oral disease among preschool children, which can cause severe damage to teeth and even affect the mental well-being of children. Various studies have demonstrated that the oral microbiome plays a pivotal role in the onset and development of dental caries. However, it remains uncertain about the key microbial markers associated with caries, owing to the limited evidence. Methods Fifteen S-ECC children and fifteen healthy controls were selected from three-year-old children in this study. Their clinical data and oral saliva samples were collected. Shotgun sequencing was conducted to investigate the microbial differences and the relevant functions between the two groups. Results We observed no apparent difference in oral microbial community diversity between the two groups. Still, at the genus/species levels, several characteristic genera/species such as Propionibacterium, Propionibacterium acidifaciens, Prevotella denticola, Streptococcus mutans and Actinomyces sp. oral taxon 448/414 increased significantly in S-ECC children, compared with the oral health group. Furthermore, we found that functional pathways involving glycolysis and acid production, such as starch and sucrose metabolism, fructose and mannose metabolism, glycolysis/gluconeogenesis, were prominently up-regulated in the high-caries group. Conclusions Our study showed that dental caries in children were associated with the alterations in the oral microbiota at the composition and functional levels, which may potentially inspire the exploration of microbial diagnosis or therapeutic treatments.

In view of the elevated labor intensity and low efficiency of ramie fiber decortication, we designed a simple automatic ramie decortication machine in line with the characteristics of the ramie fiber decortication process, design requirements and market demand through an innovative design and theoretical analysis of key components such as the clamping and conveying device and the fiber detecting device, and identified the key factors and parameters affecting the quality of ramie decortication. We develop a mathematical model of the fiber percentage of fresh stalks and the ramie fiber impurity rate by considering decortication clearance, the drum speed, and the conveyance speed as factors, and determine the effect of operating parameters on ramie decortication and the optimal combination of parameters. Finally, a multi-objective optimization test was performed using the Box–Behnken test. In this paper, based on the results of the multi-objective parameter optimization analysis, the optimal parameters for ramie peeling were determined, namely, a decortication clearance of 3.7 mm, and a conveyance speed of 340 rpm. According to the optimized parameters, the ramie peeling process was experimentally validated. Using the optimized parameters, a validation test of the ramie direction in this study was performed. As indicated by the results, the percentage of fiber in the fresh stalk reached 5.05%, and the impurity rate in the ramie fiber was 1.24%. The relative errors of all metrics and model predictions were less than 5%, thus validating the accuracy of the prediction model. The machine achieved a production efficiency of 78.5 kg·h−1, which is in line with the design specifications. The raw fiber had a gum content of 23.45 percent, and the stripped fiber met the national standard for secondary ramekin fiber. This study lays a theoretical basis while providing technical support for fully automatic ramie decorticators.

Abstract Background Previous studies have suggested that the relative heterogeneity of frailty declines with increases in age and the level of the frailty index (FI). In this study, we investigated the sex difference in the relative heterogeneity of frailty and its response to health‐protective factors, in a Chinese community sample. Methods Data used for this secondary analysis were obtained from the Beijing Longitudinal Study of Aging that involved 3257 community‐dwelling Chinese people aged 55 years and older at baseline. An FI was constructed for each indicial using 35 variables assessing health‐related problems. A protection index (PI) consisting of 27 variables assessing lifestyle and social engagement was also built. The relative heterogeneity of frailty, as measured by the coefficient of variation (CV) of the FI, was calculated as the ratio of the standard deviation to the mean FI for different age, FI, and PI groups, and for the five‐year survival status. Results The CV decreased with the increase in age (F = 20.60, P = .006) and the FI (F = 57.59, P = .001), consistent in both sexes. In each age group, the CV was higher in men than in women (t = 3.25, P = .018). A great level of protection was associated with a significantly reduced mortality, and an increased CV (t = 2.91, P = .027). Conclusions Our data demonstrate that a gender difference exists in the relative heterogeneity of frailty, which is negatively related to age and frailty as well as positively associated with health protection and the five‐year survival.

The level of selenocysteine (Sec) in the human body is closely related to a variety of pathophysiological states, so it is important to study its fluorescence sensing mechanism for designing efficient fluorescent probes. Herein, we used time-dependent density functional theory to investigate the fluorescence sensing mechanism of phenanthroimidazole derivates A4 and B4 for the detection of Sec, which are proposed to be designed based on excited state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) mechanisms. The calculation results show that the fluorescence quenching mechanism of A4 and B4 is due to the photo-induced electron transfer (PET) process with the sulfonate group acts as the electron acceptor. Subsequently, A4 and B4 react with Sec, the sulfonate group is substituted by hydroxyl groups, PET is turned off, and significant fluorescence enhancement of the formed A3 and B3 is observed. The theoretical results suggest that the fluorescence enhancement mechanism of B3 is not based on ICT mechanism, and the charge transfer phenomenon was not observed by calculating the frontier molecular orbitals, and proved to be a local excitation mode. The reason for the fluorescence enhancement of A3 based on ESIPT is also explained by the calculated potential energy curves.

Serine/arginine (SR) proteins are essential pre-mRNA splicing factors in eukaryotic organisms. Our previous studies have shownthat the unique SR-specific protein kinase Srk1 is important for RNA splicing and gene transcription in Fusarium graminearum, and interacts with two SR proteins, FgSrp1 and FgSrp2. In this study, we have identified an SR-like protein called Sgh1 in F. graminearum, which is orthologous to budding yeast paralogous Gbp2 and Hrb1. Our data have shownthat the Sgh1 is involved in vegetative growth, conidiation, sexual reproduction, DON synthesis, and plant infection. Moreover, the Sgh1 is mainly localized to the nucleus. RNA-seq analysis has shownthat the expression of over 1100 genes and the splicing efficiency in over 300 introns were affected in the Δsgh1 mutant. Although the RS domain and all three of the RRM domains are important for the Sgh1 functions, only the RS domain is responsible for its nuclear localization. Finally, we verified that the Sgh1 interacts with the unique SR-specific kinase Srk1 in F. graminearum by the yeast-two hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Taken together, our results have revealed that the Sgh1 regulates the fungal development, plant infection, and the pre-mRNA processing, and the RS domain regulates the function of the Sgh1 by modulating its nucleocytoplasmic shuttling.

ObjectivesMacrophage-derived exosomes (Mφ-Exos) are involved in tumor onset, progression, and metastasis, but their regulation in oral squamous cell carcinoma (OSCC) is not fully understood. RBPJ is implicated in macrophage activation and plasticity. In this study, we assessed the role of Mφ-Exos with RBPJ overexpression (RBPJ-OE Mφ-Exos) in OSCC.Materials and MethodsThe long non-coding RNA (lncRNA) profiles in RBPJ-OE Mφ-Exos and THP-1-like macrophages (WT Mφ)-Exos were evaluated using lncRNA microarray. Then the functions of Mφ-Exo-lncRNA in OSCC cells were assessed via CCK-8, EdU, and Transwell invasion assays. Besides, luciferase reporter assay, RNA immunoprecipitation, and Pearson’s correlation analysis were adopted to confirm interactions. Ultimately, a nude mouse model of xenografts was used to further analyze the function of Mφ-Exo-lncRNAs in vivo.ResultsIt was uncovered that lncRNA LBX1-AS1 was upregulated in RBPJ-OE Mφ-Exos relative to that in WT Mφ-Exos. RBPJ-OE Mφ-Exos and LBX1-AS1 overexpression inhibited OSCC cells to proliferate and invade. Meanwhile, LBX1-AS1 knockdown boosted the tumor to grow in vivo. The effects of RBPJ-OE Mφ-Exos on OSCC cells can be reversed by the LBX1-AS1 knockdown. Additionally, mechanistic investigations revealed that LBX1-AS1 acted as a competing endogenous RNA of miR-182-5p to regulate the expression of FOXO3.ConclusionExo-LBX1-AS1 secreted from RBPJ-OE Mφ inhibits tumor progression through the LBX1-AS1/miR-182-5p/FOXO3 pathway, and LBX1-AS1 is probably a diagnostic biomarker and potential target for OSCC therapy.

Hypoxia plays a key role in colorectal cancer (CRC) metastasis, but its underlying mechanism remains largely unknown. Dicer1, an RNase, has been considered as a tumor regulator in many tumors. However, whether Dicer1 affects CRC progression under hypoxia remains uncertain. In this study, we found that Dicer1 expression was induced by hypoxia in CRC cells and it mediates hypoxia-induced CRC cell progression. Furthermore, we found that the expression of tRF-20-MEJB5Y13, a small non-coding RNA derived from tRNA, was increased under hypoxic conditions, and its upregulation by Dicer1 resulted in hypoxia-induced CRC cell invasion and migration. These results advance the current understanding of the role of Dicer1 in regulating hypoxia signals and provide a new pathway for the development of therapeutic interventions for inhibiting cancer progression.

Objectives Intrinsic capacity (IC) was proposed by the WHO as a new concept for capturing an individual’s functional capacities across their lifetime. We aimed to investigate the prevalence and factors associated with IC decline and examine associations between IC and adverse outcomes among community-dwelling older adults in China.Design A cross-sectional study.Setting Community, China.Participants Data were derived from the China Comprehensive Geriatric Assessment Study, a population-based nationally representative sample. IC comprises of five domains: locomotion, cognition, vitality, sensory and psychology. Participants were deemed to have IC decline if they showed a decline in any of the five domains. Sociodemographic characteristics, chronic diseases, geriatric syndromes and adverse outcomes were also examined.Results Of the 5823 community-dwelling participants aged 60–98 years, 2506 had IC decline (weighted 39.9%): 57.7% in western, 38.3% in northern, 33.7% in northwest, 36.1% in middle, 16.9% in eastern and 19.8% in northeast China. The number of participants with decline in the locomotion, cognition, vitality, sensory and psychological domains were 1039 (17.8%), 646 (11.1%), 735 (12.6%), 824 (14.2%) and 713 (12.2%), respectively. Age, northern residence, low education, being unmarried, low income, less exercise, less meat intake, insomnia, memory loss, urinary incontinence, constipation, slowness, chronic obstructive pulmonary disease and osteoarthritis were related to IC decline. After adjusting for age, sex, area, district, marriage, education, waist–hip ratio, smoking, alcohol consumption, exercise, income and chronic diseases, IC decline was independently associated with risk of frailty, disability, falls, fractures and immobility.Conclusion The prevalence of IC decline in China is high. IC decline was significantly associated with adverse outcomes, after adjustment for related variables. Efforts promoting IC to delay functional dependence should focus on modifiable factors, including negative social factors, poor lifestyle, chronic diseases and geriatric syndromes.

lncRNAs are related to the progression of various diseases, including oral squamous cell carcinoma (OSCC), which is a common squamous cell carcinoma of the head and neck. Tumor-associated macrophages and tumor cells are significant components of tumor microenvironment. M2 polarization of tumor-associated macrophages is a crucial actor in tumor malignancy and metastasis. In this study, we studied the molecular mechanism of lncRNA DCST1-AS1 in OSCC. Here, we reported that DCST1-AS1 was significantly increased in OSCC cells. We found that loss of DCST1-AS1 obviously inhibited the proliferation, migration, and invasion of OSCC cells and xenograft tumor growth. Meanwhile, silencing of DCST1-AS1 also repressed the percentage of macrophages expressing M2 markers CD206 and CD11b. DCST1-AS1 shRNA enhanced the percentage of macrophages expressing M1 markers CD80 and CD11c. Then, we observed that loss of DCST1-AS1 suppressed OSCC progression via inactivating NF-κB signaling. As well established, NF-κB signaling exerts critical roles in tumor progression, and our study proved that DCST1-AS1 could regulate NF-κB signaling. We proved that blocking the NF-κB pathway using antagonists greatly downregulated OSCC progression and M2 macrophage polarization induced by the overexpression of DCST1-AS1. To sum up, we reported that DCST1-AS1 plays an important role in modulating OSCC tumorigenicity and M2 macrophage polarization through regulating the NF-κB pathway.

N6-Methyladenosine (m6A) modification is one of the commonest chemical modifications in eukaryotic mRNAs, which has essential effects on mRNA translation, splicing, and stability. Currently, there is a rising concern on the regulatory role of m6A in tumorigenesis. As a known component in the m6A methyltransferase complex, METTL3 (methyltransferase-like 3) plays an essential role in m6A methylation. Till now, the functions of METTL3 in oral squamous cell carcinoma (OSCC) and its relative mechanism remain to be explored. In this research, through the GEPIA database, we found that high METTL3 expression has a correlation with poor prognosis of squamous cell carcinoma of head and neck. qRT-PCR displayed that METTL3 was highly expressed in OSCC cells. Functionally, METTL3 knockdown reduced the invasion, migration, and proliferation competence of OSCC cells and attenuated the activation of CD8+ T cells. In contrast, METTL3 overexpression resulted in opposite results. GEPIA, UALCAN, and SRAMP databases, PCR, western blot, and m6A RNA methylation assay confirmed the m6A modification of PRMT5 and PD-L1 mediated by METTL3. In conclusion, our results displayed that METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and PD-L1, suggesting that METTL3 may be a therapeutic target for OSCC patients.

Background. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. Materials and Methods. Gene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs). Results. In this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration. Conclusion. In summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.

LINC01355 has been demonstrated to be dysregulated in several cancers. However, the exact molecular function of LINC01355 in the pathogenesis of OSCC remains unstudied. Here, we reported the effect of LINC01355 in OSCC and investigated the mechanisms. Firstly, we found that the results indicated LINC01355 was increased in OSCC cells. Knockdown of LINC01355 repressed OSCC cell proliferation, migration, and invasion. Recently, immunotherapy is a significant method for the treatment of cancers, in which CD8+ T cells exhibit a significant role. The influence of LINC01355 on the antitumor activity of CD8+ T cells was also focused in this study. As shown, the silence of LINC01355 could repress OSCC tumor growth via inducing CD8+ T cell immune responses. In addition, we found that downregulation of LINC01355 significantly restrained CD8+ T cell apoptosis, induced CD8+ T cell percentage, and enhanced the cytolysis activity when cocultured with OSCC cells. It has been reported that the Notch pathway represses CD8+ T cell activity in cancer patients. In our present study, we displayed that lack of LINC01355 suppressed OSCC malignant behaviors and enhanced the antitumor activity of CD8+ T cells via inactivating Notch signaling. We showed that decreased LINC01355 significantly restrained the Notch signal via a decrease of Notch-1, JAG-1, and HES-1. Repression of Notch1 reversed the effect of LINC01355 in OSCC cells. In conclusion, it was implied that LINC01355 might induce the development of OSCC via modulating the Notch signal pathway, which could provide a candidate therapeutic target for OSCC.

Objective To compare the short- and long-term outcomes of radiofrequency ablation (RFA) versus liver resection and chemotherapy for liver metastases from gastric cancer. Methods We retrospectively evaluated 50 patients who underwent curative gastrectomy and local treatments for liver metastases (RFA, n = 20; liver resection, n = 20; and chemotherapy, n = 10) from 2008 to 2018. Results The short- and long-term outcomes of each local treatment were evaluated. The median overall survival (OS) after RFA was similar to that after liver resection (20 vs. 20 months, respectively) and longer than that after chemotherapy (20 vs. 10 months, respectively). The 3-year OS and progression-free survival (PFS) rates after RFA were 20% and 10%, respectively, while those in the liver resection group were 23.5% and 23.5%, respectively. The 3-year OS rate after chemotherapy was 10%. The size and number of metastases were prognostic factors for patients with gastric cancer with liver metastasis without statistical significance. Conclusions Among patients with liver metastasis from gastric cancer, OS and PFS were satisfactory and comparable between RFA and liver resection but better than those of chemotherapy. RFA is an appropriate option for patients with gastric cancer who have a solitary liver metastasis measuring ≤3.0 cm.

Abstract Background Physical frailty, characterized by reduced physiologic complexity and ability to cope with stressors, is closely associated with cognitive impairment, which increases the risk of poor clinical outcomes. To better capture the association between frailty and cognitive impairment, a new construct, cognitive frailty, has been proposed. Cognitive frailty is a clinical condition characterized by the simultaneous presence of physical frailty and cognitive impairment. There is little evidence on the relationship between physical frailty and cognition, as well as cognitive frailty, in Chinese older adults. We aimed to elucidate whether physical frailty is associated with cognitive impairment in an older Chinese population. Methods Data were obtained from the China Comprehensive Geriatric Assessment Study. The sample comprised 3202 community-dwelling adults, aged 60 years and older, from seven Chinese cities. Physical frailty was assessed using a modified, four-item version of the Fried criteria, according to frailty phenotype. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Results The prevalence of physical frailty, prefrailty, cognitive impairment, and cognitive frailty was 9.9, 33.9, 7.5, and 2.3%, respectively (weighted: 8.8, 33.8, 6.5, and 2.0%). The prevalence of the combination of prefrail/frail and cognitive impairment was 5.1% (weighted 4.5%). Frail participants performed worse on global cognition and all cognitive domains than robust and prefrail participants. The MMSE total score was positively correlated with walking speed and negatively correlated with age and frailty. A multivariate logistic regression revealed that after adjusting for age, gender, education level, living area, and chronic diseases, frailty, exhaustion, slowness, and inactivity were significantly associated with poor global cognition. Conclusions The standard prevalence of physical frailty, prefrailty, cognitive impairment, and cognitive frailty in community-dwelling older adults in China was 8.8, 33.8, 6.5, and 2.0%, respectively. Frailty, exhaustion, slowness, and inactivity were significantly associated with poor global cognition.