TPP1 is associated with risk of advanced precursors and cervical cancer survival.

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.

Comparative genomic analyses provide insight into the pathogenicity of three Pseudomonas syringae pv. actinidiae strains from Anhui Province, China.

BACKGROUND: Pseudomonas syringae pv. actinidiae (Psa) is an important bacterial plant pathogen that causes severe damage to the kiwifruit industry worldwide. Three Psa strains were recently obtained from different kiwifruit orchards in Anhui Province, China. The present study mainly focused on the variations in virulence and genome characteristics of these strains based on the pathogenicity assays and comparative genomic analyses. RESULTS: Three strains were identified as biovar 3 (Psa3), along with strain QSY6 showing higher virulence than JZY2 and YXH1 in pathogenicity assays. The whole genome assembly revealed that each of the three strains had a circular chromosome and a complete plasmid. The chromosome sizes ranged from 6.5 to 6.6 Mb with a GC content of approximately 58.39 to 58.46%, and a predicted number of protein-coding sequences ranging from 5,884 to 6,019. The three strains clustered tightly with 8 Psa3 reference strains in terms of average nucleotide identity (ANI), whole-genome-based phylogenetic analysis, and pangenome analysis, while they were evolutionarily distinct from other biovars (Psa1 and Psa5). Variations were observed in the repertoire of effectors of the type III secretion system among all 15 strains. Moreover, synteny analysis of the three sequenced strains revealed eight genomic regions containing 308 genes exclusively present in the highly virulent strain QSY6. Further investigation of these genes showed that 16 virulence-related genes highlight several key factors, such as effector delivery systems (type III secretion systems) and adherence (type IV pilus), which might be crucial for the virulence of QSY6. CONCLUSION: Three Psa strains were identified and showed variant virulence in kiwifruit plant. Complete genome sequences and comparative genomic analyses further provided a theoretical basis for the potential pathogenic factors responsible for kiwifruit bacterial canker.

Extracellular vesicles containing circMYBL1 induce CD44 in adenoid cystic carcinoma cells and pulmonary endothelial cells to promote lung metastasis.

Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. Here, we identified a circRNA derived from MYBL1 pre-mRNA that accompanied overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased lung metastasis and poor overall survival in ACC patients. Ectopic circMYBL1 overexpression promoted malignant phenotypes and lung metastasis of ACC cells. Mechanistically, circMYBL1 formed a circRNA-protein complex with CCAAT enhancer binding protein beta (CEBPB), which inhibited ubiquitin-mediated degradation and promoted nuclear translocation of CEBPB. In the nucleus, circMYBL1 increased the binding of CEBPB to the CD44 promoter region and enhanced its transcription. In addition, circMYBL1 was enriched in small extracellular vesicles (sEVs) isolated from the plasma of ACC patients. Treatment with sEVs containing circMYBL1 in sEVs enhanced pro-metastatic phenotypes of ACC cells, elevated the expression of CD44 in human pulmonary microvascular endothelial cells (HPMECs), and enhanced the adhesion between HPMECs and ACC cells. Moreover, circMYBL1 encapsulated in sEVs increased the arrest of circulating ACC cells in the lung and enhanced the lung metastatic burden. This data suggests that circMYBL1 is a tumor-promoting circRNA that could serve as a potential biomarker and therapeutic target in ACC.

M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.

M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by ß-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of ß-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9.

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

The consistent anti-cancer effect of a simple exercise (Ou MC decrescendo phenomenon exercise) may hold promise for low-cost cancer prevention.

The causal relationship between physical activity and anti-cancer effect are not proved by the current studies. However, Ou MC decrescendo phenomenon treatment (OuDPt), a simple exercise treatment, has shown consistent anti-cancer effects, which evinces the consequent anti-cancer effect by physical activity. The anti-cancer effects through OuDPt in the context of physical activity and human body anatomical axes showed to induce apoptosis, restore apical-basal polarity of cancer cells and mitigate epithelial-mesenchymal transition (EMT) with concomitant clinical regression of uterine endometrial cancer, suppression of ovarian and pancreatic cancer growth, regression of early suspicious pancreatic cancer, enhancement of chemotherapy effect of pancreatic cancer and cessation of cancer-related bleeding, which underlines the most important anti-cancer mechanisms. Although such anti-cancer effects by OuDPt show insufficient efficacy for advanced cancer in long-term treatment, OuDPt may be availed as an Ou MC decrescendo phenomenon exercise for cancer prevention. Further study is warranted.

Inkjet printing of heavy-metal-free quantum dots-based devices: a review.

Inkjet printing (IJP) has become a versatile, cost-effective technology for fabricating organic and hybrid electronic devices. Heavy-metal-based quantum dots (HM QDs) play a significant role in these inkjet-printed devices due to their excellent optoelectrical properties. Despite their utility, the intrinsic toxicity of HM QDs limits their applications in commercial products. To address this limitation, developing alternative HM-free quantum dots (HMF QDs) that have equivalent optoelectronic properties to HM QD is a promising approach to reduce toxicity and environmental impact. This article comprehensively reviews HMF QD-based devices fabricated using IJP methods. The discussion includes the basics of IJP technology, the formulation of printable HMF QD inks, and solutions to the coffee ring effect. Additionally, this review briefly explores the performance of typical state-of-the-art HMF QDs and cutting-edge characterization techniques for QD inks and printed QD films. The performance of printed devices based on HMF QDs is discussed and compared with those fabricated by other techniques. In the conclusion, the persisting challenges are identified, and perspectives on potential avenues for further progress in this rapidly developing research field are provided.

Small molecules targeting canonical transient receptor potential channels: an update.

Transient receptor potential canonical (TRPC) channels belong to an important class of non-selective cation channels. This channel family consists of multiple members that widely participate in various physiological and pathological processes. Previous studies have uncovered the intricate regulation of these channels, as well as the spatial arrangement of TRPCs and the binding sites for various small molecule compounds. Multiple small molecules have been identified as selective agonists or inhibitors targeting different subtypes of TRPC, including potential preclinical drug candidates. This review covers recent advancements in the understanding of TRPC regulation and structure and the discovery of TRPC small molecules over the past few years, with the aim of facilitating research on TRPCs and small-molecule drug discovery.

Analysis of Dietary and Nutritional Status of Tuberculosis Patients in Hulunbuir Region.

Objective: Tuberculosis (TB) is a major public health problem that affects millions of people worldwide. Malnutrition is a common complication of TB and can worsen the disease outcome. The purpose of this study was to investigate the dietary and nutritional status, as well as the dietary structure, of TB patients in Hulunbuir City, Inner Mongolia, China. Additionally, the study aimed to analyze the factors that influence the nutritional status in order to provide a theoretical foundation for the prevention and treatment of TB and related issues. Methods: A cross-sectional study was conducted on 334 randomly selected TB patients from Hulunbuir City Second Hospital. A questionnaire survey was administered to collect information on demographic characteristics, dietary habits, and food intake. Nutritional status was assessed by body mass index (BMI). Dietary diversity score (DDS) was calculated based on the number of food groups consumed in the previous 24 hours. Statistical analysis was performed using SPSS 20.0 software. Descriptive statistics employed rates and composition ratios, and categorical data was represented using frequencies and percentages. The chi-square test was used to analyze the association between nutritional status and other variables, with a significance level set at α=0.05. Multivariable ordinal logistic regression analysis was performed to identify the independent factors affecting the nutritional status of TB patients. Results: The univariate analysis revealed statistically significant differences (P < 0.05) in the nutritional status (as measured by BMI) among tuberculosis patients, considering ethnicity, educational level, smoking, meat-based diet, vegetable consumption, and DDS grading. No statistically significant differences were found regarding gender, age, marital status, occupation, sleep duration, alcohol consumption, and consumption of rice and flour dishes. Statistically significant variables from the univariate analysis were included in a multivariable ordinal logistic regression analysis model. The findings highlighted that educational level (high school or below), smoking, meat-based diet, DDS scores of 1-3, and a primarily vegetable-based diet had independent effects on the nutritional status of tuberculosis patients (all P < 0.05). No significant difference was found in nutritional status between the Han ethnic group and other ethnicities. Conclusion: The study revealed that the dietary and nutritional status of TB patients in Hulunbuir City was suboptimal and influenced by several factors. Smoking, meat-based diet, and low dietary diversity score were the primary risk factors for malnutrition among TB patients. The study suggests that nutritional education and intervention programs should be implemented for TB patients to improve their dietary quality and nutritional status.

Intermittent fasting shifts the diurnal transcriptome atlas of transcription factors.

Intermittent fasting remains a safe and effective strategy to ameliorate various age-related diseases, but its specific mechanisms are not fully understood. Considering that transcription factors (TFs) determine the response to environmental signals, here, we profiled the diurnal expression of 600 samples across four metabolic tissues sampled every 4 over 24 h from mice placed on five different feeding regimens to provide an atlas of TFs in biological space, time, and feeding regimen. Results showed that 1218 TFs exhibited tissue-specific and temporal expression profiles in ad libitum mice, of which 974 displayed significant oscillations at least in one tissue. Intermittent fasting triggered more than 90% (1161 in 1234) of TFs to oscillate somewhere in the body and repartitioned their tissue-specific expression. A single round of fasting generally promoted TF expression, especially in skeletal muscle and adipose tissues, while intermittent fasting mainly suppressed TF expression. Intermittent fasting down-regulated aging pathway and upregulated the pathway responsible for the inhibition of mammalian target of rapamycin (mTOR). Intermittent fasting shifts the diurnal transcriptome atlas of TFs, and mTOR inhibition may orchestrate intermittent fasting-induced health improvements. This atlas offers a reference and resource to understand how TFs and intermittent fasting may contribute to diurnal rhythm oscillation and bring about specific health benefits.

ALMS1-IT1: A Key Player in the Novel Disulfidptosis-Related LncRNA Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

Disulfidptosis is a newly discovered form of programmed cell death that is induced by disulfide stress. It is closely associated with various cancers, including head and neck squamous cell carcinoma (HNSCC). However, the factors involved in the modulation of disulfidptosis-related genes (DRGs) still remain unknown. In this study, we established and validated a novel risk score model composed of 11 disulfidptosis-related lncRNAs (DRLs) based on 24 DRGs in HNSCC. The results revealed strong correlations between the 11-DRL prognostic signature and clinicopathological features, immune cell infiltration, immune-related functions, and disulfidptosis-associated pathways, including NADPH and disulfide oxidoreductase activities. Furthermore, we studied and verified the involvement of ALMS1-IT1, one of the 11 model DRLs, in the disulfidptosis of HNSCC cell lines. A series of assays demonstrated that ALMS1-IT1 modulated cell death under starvation conditions in a pentose phosphate pathway (PPP)-dependent manner. Knockdown of ALMS1-IT1 inhibited the PPP, contributing to a decline in NADPH levels, which resulted in the formation of multiple intermolecular disulfide bonds between actin cytoskeleton proteins and the collapse of F-actin in the cytoplasm. Therefore, ALMS1-IT1, which is highly expressed in SLC7A11high cells, can be considered a promising therapeutic target for disulfidptosis-focused treatment strategies for cancer and other diseases.

Circ1811 suppresses gastric cancer progression by regulating the miR-632/DAPK1 axis.

Compelling evidence has identified circRNAs as crucial regulators in initiation and progression of various cancers, including gastric cancer (GC). However, the function and regulatory mechanisms of circRNAs in GC remain largely unknown. In this study, attention is paid to a novel circular RNA circ1811, which exerts significant downregulated expression in GC tissues compared with adjacent non-cancerous tissues. The expression of circ1811 in GC tumor tissues is negatively correlated with the extent of lymphatic metastasis in GC patients. Overexpression of circ1811 inhibited GC cell proliferation, migration and invasion while promoting apoptosis, whereas knockdown of circ1811 led to the opposite effects. AGO2 RIP and dual luciferase reporter assays indicated that circ1811 directly sponges miR-632 to upregulate the expression of DAPK1. Collectively, circ1811 acts as a tumor-suppressor for GC progression by regulating the miR-632/DAPK1 axis. Our findings suggest the potential of circ1811 as ideal biomarker and therapeutic target for GC.

Circular RNAs as biomarkers and therapeutic targets for gastrointestinal cancers.

Circular RNAs are a class of noncoding RNAs with covalently linked 5' and 3' ends that arise from backsplicing events. The absence of a 5' cap and a 3' poly(A) tail makes circular RNAs relatively more stable than their linear counterparts. They are evolutionary conserved and tissue-specific, and some show disease-specific expression patterns. Although their biological functions remain largely unknown, circular RNAs have been shown to play regulatory roles by acting as microRNA sponges, regulators of RNA-binding proteins, alternative splicing, and parental gene expression, and they could even encode proteins. Over the past few decades, circular RNAs have attracted wide attention in oncology owing to their implications in various tumors. Many circular RNAs have been characterized as key players in gastrointestinal cancers and influence cancer growth, progression, metastasis, and therapeutic resistance. Accumulating evidence reveals that their unique characteristics, coupled with their critical roles in tumorigenesis, make circular RNAs promising non-invasive clinical biomarkers for gastrointestinal cancers. In the present review, we summarized the biological roles of the emerging circular RNAs and their potential as biomarkers and therapeutic targets, which may help better understand their clinical significance in the management of gastrointestinal cancers.

Biomimetic Mineralization Synthesis of Flower-Like Cobalt Selenide/Reduced Graphene Oxide for Improved Electrochemical Deionization.

Rationally and precisely tuning the composition and structure of materials is a viable strategy to improve electrochemical deionization (EDI) performances, which yet faces enormous challenges. Herein, an eco-friendly biomimetic mineralization synthetic strategy is developed to synthesize the flower-like cobalt selenide/reduced graphene oxide (Bio-CoSe2 /rGO) composites and used as advanced sodium ion adsorption electrodes. Benefiting from the slow and controllable reaction kinetics provided by the biomimetic mineralization process, the flower-like CoSe2 is uniformly constructed in the rGO, which is endowed with robust architecture, substantial adsorption sites and rapid charge/ion transport. The Bio-CoSe2 /rGO electrode yields the maximum salt adsorption capacity and salt adsorption rate of 56.3 mg g-1 and 5.6 mg g-1 min-1 respectively, and 92.5% capacity retention after 60 cycles. These results overmatch the pristine CoSe2 and irregular granular CoSe2 /rGO synthesized by a hydrothermal method, proving the structural superiority of the Bio-CoSe2 /rGO composites. Furthermore, the in-depth adsorption kinetics study indicates the chemisorption nature of sodium ion adsorption. The structures of the Bio-CoSe2 /rGO composites after long term EDI cycles are intensively studied to unveil the mechanism behind such superior EDI performances. This study offers one effective method for constructing advanced EDI electrodes, and enriches the application of the biomimetic mineralization synthetic strategy.

Longitudinal Assessment of Quality of Life in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Proton Therapy and Volumetric Modulated Arc Therapy at Different Time Points.

PURPOSE: This retrospective cohort study aims to compare the quality of life (QoL) in patients with nasopharyngeal cancer (NPC) treated with intensity-modulated proton therapy (IMPT) versus volumetric modulated arc therapy (VMAT) at different time points. MATERIALS AND METHODS: We conducted a longitudinal assessment of QoL on 287 newly diagnosed NPC patients (IMPT: 41 and VMAT: 246). We collected outcomes of global QoL, functional QoL, C30 symptoms, and HN35 symptoms from EORTC QLQ-C30 and QLQ-HN35 questionnaires at pre-radiotherapy, during radiotherapy (around 40 Gy), 3 months post radiotherapy, and 12-months post radiotherapy (RT). The generalized estimating equation was utilized to interpret the group effect, originating from inherent group differences; time effect, attributed to RT effects over time; and interaction of the group and time effect. RESULTS: IMPT demonstrated superior mean dose reductions in 12 of the 16 organs at risk compared to VMAT, including a significant (>50%) reduction in the oral cavity and larynx. Both groups exhibited improved scores of global QoL, functional QoL, and C30 symptoms at 12 months post RT compared to the pre-RT status. Regarding global QoL and C30 symptoms, there was no interaction effect of group over time. In contrast, significant interaction effects were observed on functional QoL (p = 0.040) and HN35 symptoms (p = 0.004) during RT, where IMPT created an average of 7.5 points higher functional QoL and 10.7 points lower HN35 symptoms than VMAT. CONCLUSIONS: Compared to VMAT, dose reduction attributed to IMPT could translate into better functional QoL and HN35 symptoms, but the effect is time dependent and exclusively observed during the RT phase.

Free-standing and flexible polyvinyl alcohol-sodium alginate-polypyrrole electrodes based on interpenetrating network hydrogels.

Flexible supercapacitors (FSCs) have attracted much attention due to their strong mechanical flexibility, wearability and portability, which greatly rely on the employed flexible electrodes. The conductive polymer hydrogels with excellent flexibility, processability and capacitive performance are one of the most promising candidates, which are still limited by their poor mechanical properties. Constructing robust interpenetrating polymer networks (IPN) is an effective approach to promote their mechanical properties. Herein, interpenetrating polyvinyl alcohol (PVA)-sodium alginate (SA)-polypyrrole (PPy) hydrogels are prepared by the freeze-thaw and in-situ polymerization method. The IPN structure composed of PVA and SA not only enhances the mechanical properties of hydrogels, but also provides substantial active sites for electrochemical reactions. Moreover, the hydrogen-bonding interaction between different components in the PVA-SA-PPy hydrogel boosts the charge/ion transfer. The optimal PVA-SA-PPy hydrogels show an elongation at break of 380 %, a tensile strength of 1.5 MPa, and a specific capacitance of 2646 mF cm-2 at 2 mA cm-2. The symmetric PVA-SA-PPy FSCs show an energy density of 96.7 µWh cm-2 at a power density of 999.9 µW cm-2, and the capacitance retention is 66.3 % after 10,000 cycles. These exceptional mechanical and electrochemical properties make the PVA-SA-PPy hydrogels a promising candidate for FSCs.