Correlation of negative emotion, fatigue level and internet addiction in college students: implication for coping strategies.

BACKGROUND: Internet addiction has an important influence on the development of physical and mental health of college students. The purpose of this study is to evaluate the current status and the correlation between college students' negative emotion, fatigue level and Internet addiction disorder, and to provide reference for the care and management of college students. METHODS: We conducted a questionnaire survey on a cluster sample of college students from October to November 15, 2022. Internet addiction scale, fatigue assessment scale and positive and negative emotion scale were used for survey. Pearson correlation analysis and mediating effect test were performed to analyze the correlation and effects. RESULTS: A total of 1546 valid questionnaires were collected. The incidence of internet addiction in college student was 20.38%. The total score of internet addiction was 52.94 ± 12.47, the total fatigue score was 69.27 ± 3.19, the score of positive emotion of college students was 31. 41 ± 5.09, and the negative emotion score was 18.54 ± 5.68. The total score of internet addiction were positively correlated with score of negative emotion (all P < 0. 05). The total score of internet addiction scale of college students were positively correlated and each factor score of with the score of fatigue severity (all P < 0. 05). Fatigue played an intermediary role in the prediction of negative emotion and internet addiction of college students, with an intermediary role of-0.433, accounting for 76.35% of the total effect. CONCLUSION: The college students' positive emotion may be strengthened to reduce their fatigue level and negative emotion so as to reduce internet addiction.

Integrated metabolic and epigenetic mechanisms in cardiomyocyte proliferation.

Heart disease continues to be the leading cause of mortality worldwide, primarily attributed to the restricted regenerative potential of the adult human heart following injury. In contrast to their adult counterparts, many neonatal mammals can spontaneously regenerate their myocardium in the first few days of life via extensive proliferation of the pre-existing cardiomyocytes. Reasons for the decline in regenerative capacity during postnatal development, and how to control it, remain largely unexplored. Accumulated evidence suggests that the preservation of regenerative potential depends on a conducive metabolic state in the embryonic and neonatal heart. Along with the postnatal increase in oxygenation and workload, the mammalian heart undergoes a metabolic transition, shifting its primary metabolic substrate from glucose to fatty acids shortly after birth for energy advantage. This metabolic switch causes cardiomyocyte cell-cycle arrest, which is widely regarded as a key mechanism for the loss of regenerative capacity. Beyond energy provision, emerging studies have suggested a link between this intracellular metabolism dynamics and postnatal epigenetic remodeling of the mammalian heart that reshapes the expression of many genes important for cardiomyocyte proliferation and cardiac regeneration, since many epigenetic enzymes utilize kinds of metabolites as obligate cofactors or substrates. This review summarizes the current state of knowledge of metabolism and metabolite-mediated epigenetic modifications in cardiomyocyte proliferation, with a particular focus on highlighting the potential therapeutic targets that hold promise to treat human heart failure via metabolic and epigenetic regulations.

Mechanistically derived patient-level framework for precision medicine identifies a personalized immune prognostic signature in high-grade serous ovarian cancer.

An accurate prognosis assessment for cancer patients could aid in guiding clinical decision-making. Reliance on traditional clinical features alone in a complex clinical environment is challenging and unsatisfactory in the era of precision medicine; thus, reliable prognostic biomarkers are urgently required to improve a patient staging system. In this study, we proposed a patient-level computational framework from mechanistic and translational perspectives to establish a personalized prognostic signature (named PLPPS) in high-grade serous ovarian carcinoma (HGSOC). The PLPPS composed of 68 immune genes achieved accurate prognostic risk stratification for 1190 patients in the meta-training cohort and was rigorously validated in multiple cross-platform independent cohorts comprising 792 HGSOC patients. Furthermore, the PLPPS was shown to be the better prognostic factor compared with clinical parameters in the univariate analysis and retained a significant independent association with prognosis after adjusting for clinical parameters in the multivariate analysis. In benchmark comparisons, the performance of PLPPS (hazard ratio (HR), 1.371; concordance index (C-index), 0.604 and area under the curve (AUC), 0.637) is comparable to or better than other published gene signatures (HR, 0.972 to 1.340; C-index, 0.495 to 0.592 and AUC, 0.48-0.624). With further validation in prospective clinical trials, we hope that the PLPPS might become a promising genomic tool to guide personalized management and decision-making of HGSOC in clinical practice.

What information can we gain from the quality appraisal of guidelines with physical activity recommendations for cancer patients?A systematic review using the AGREE II and AGREE-REX tools.

PURPOSE: There has been growing amount of evidence supporting the benefits of physical activity (PA) on oncological patients' cancer-related health outcomes. Although guidelines on cancer rehabilitation are widely available, the varying quality and practical applicability limited the clinical application of PA recommendations. To assist the future development of guidelines, in this systematic review, we evaluated the quality and applicability of current cancer rehabilitation guidelines with PA recommendations and synthesized PA recommendations for the oncological population. METHODS: A systematic search was conducted in PubMed, CINAHL, PEDro, EMBASE, and guideline repositories to identify guidelines with PA recommendations for cancer patients from 1 May 2016 to 1 June 2022. The quality of included guidelines was appraised using the tools "Appraisal of Guidelines for Research and Evaluation II" (AGREE II) and AGREE-REX (Recommendation Excellence). PA recommendations were synthesized from the guidelines. RESULTS: Sixteen guidelines were extracted. The AGREE II domain "clarity of presentation" obtained the highest score, while "applicability" received the lowest, ranging from 33.33% to 98.58%. The AGREE-REX domains "values and preferences" and "implementability" generally scored lower and ranged from 45.83% to 74.17% and 55% to 88.33%, respectively. Eight high-quality guidelines were identified, and the included PA recommendations were extracted. CONCLUSION: There were some disparities in the quality of the included guidelines. Methodological weaknesses were commonly observed in domains "applicability," "values and preferences," and "implementability"; particular attention should be given to these domains when developing future guidelines. Furthermore, this analysis indicated that more rigorous, high-quality studies are needed to generate evidence for supporting PA recommendations and provide guidance on research gaps in the field of cancer rehabilitation.

Is physical activity effective against cancer-related fatigue in lung cancer patients? An umbrella review of systematic reviews and meta-analyses.

OBJECTIVES: To discuss the effects of physical activity on cancer-related fatigue (CRF) in lung cancer patients, summarize the types of physical activity in the published reviews, assess the quality of the evidence, and provide suggestions for the clinical selection of exercise intervention. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews were searched through 8 November 2021 to identify relevant systematic reviews and meta-analyses. We also performed a manual search of the reference lists of included articles as supplements. Two researchers independently performed literature screening, data extraction, and quality assessment. The umbrella review has been registered in the International Prospective Register of Systematic Review (PROSPERO) registry (CRD42021292548). RESULTS: From the 13 systematic reviews or meta-analyses identified, 10 physical activity interventions were included. The most mentioned intervention was aerobic combined with resistance exercise; however, no reduction of the symptoms of CRF was observed in lung cancer patients by this exercise intervention. Most of the patients who performed aerobic exercises alone showed improvement in CRF after the intervention. In addition, Tai Chi and breathing exercises have been shown to improve fatigue, but more high-quality research is still needed to support its effectiveness. CONCLUSIONS: Aerobic exercise, respiratory muscle training, aerobic combined with balance training, and other exercise interventions have been shown to improve CRF in lung cancer patients. But it should be noted that according to the different treatment methods and disease stages of patients, individualized rehabilitation programs should be developed for patients. Due to the low methodological quality and evidence quality of some systematic reviews and meta-analyses included in this study, more high-quality clinical studies and systematic reviews are still needed for validation in the future. This umbrella review helps to identify effective ways of exercise to improve fatigue in lung cancer patients before dedicated evidence-based medical guidelines are established.

Focus on the impact of social factors and lifestyle on the disease burden of low back pain: findings from the global burden of disease study 2019.

BACKGROUND: Low back pain (LBP) is one of the leading causes of disability worldwide. Differences in social backgrounds and lifestyles in various regions and countries may contribute to the discrepancies in the disease burden of LBP. METHODS: Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of LBP disability-adjusted life years (DALYs). Temporal trends in ASR were also analyzed using estimated annual percentage change (EAPC). The Age-period-cohort (APC) model was used to estimate age, period and cohort trends in DALYs of LBP. An autoregressive integrated moving average (ARIMA) model was used to forecast DALYs of LBP trends from 2020 to 2035. RESULTS: The DALYs due to LBP increased from 1990 to 2019. The APC model showed that the risk of DALYs for global LBP increased with age and year and that the risk of DALYs was lower in the later-born cohort than in the earlier-born cohort. The main risk factors which GBD estimates were available for DALYs of LBP include smoking, occupational ergonomic factors and high BMI. It is expected that DALYs of LBP will continue to rise until 2035. CONCLUSION: From 1990 to 2019, the global disease burden of LBP remained high. It is necessary to pay attention to the influence of social factors and lifestyle on LBP. Focusing on the impact of social factors as well as lifestyle on the prognosis of LBP and targeting interventions may further reduce the disease burden of LBP.

Evidence Mapping Based on Systematic Reviews of Cognitive Behavioral Therapy for Neuropathic Pain.

Objective: This evidence mapping is aimed at identifying, summarizing, and analyzing the available evidence on cognitive behavioral therapy (CBT) for neuropathic pain (NP). Methods: This study was conducted following the methodology of Global Evidence Mapping (GEM). Searches were conducted in PubMed, Embase, the Cochrane Library, and PsycINFO to identify systematic reviews (SRs) with or without meta-analysis published before February 15, 2022. The authors independently assessed eligibility, extracted data, and evaluated the methodological quality of the included SRs using AMSTAR-2. The results were presented in the tables and a bubble plot based on the identified population-intervention-comparison-outcome (PICO) questions. Results: A total of 34 SRs met the eligibility criteria. According to the AMSTAR-2, 2 SRs were rated "high," 2 SRs were rated "moderate," 6 SRs were rated "low," and 24 SRs were rated "critically low." The most common study design utilized to evaluate the efficacy of CBT for NP was the randomized controlled trial. In total, 24 PICOs were identified. Migraine was the most studied population. CBT for NP usually reaches the "potentially better" result at follow-up. Conclusions: Evidence mapping is a useful way to present existing evidence. Currently, the existing evidence on CBT for NP is limited. Overall, the methodological quality of the included SRs was low. Further improvements in the methodological quality of SRs and more research on the most efficient CBT formats for NP are recommended in the future.

A 5'-tiRNA fragment that inhibits proliferation and migration of laryngeal squamous cell carcinoma by targeting PIK3CD.

tRNA-derived small RNAs (tsRNAs) participate in several biological processes, including carcinogenesis. The correlations between tsRNAs and human cancers are attracting substantial attention. Nevertheless, the involvement of tsRNAs in laryngeal squamous cell carcinoma (LSCC) progression remains unclear. We constructed tsRNAs expression profiles in LSCC and adjacent normal tissues by next-generation sequencing. Interestingly, we identified a specific 5'-tiRNA fragment (tRF-33-Q1Q89P9L842205) that was significantly downregulated and was closely associated with lymph node metastasis and advanced stages of LSCC. Importantly, we found that tRF-33-Q1Q89P9L842205 suppressed cell growth, proliferation, migration, invasion and induced apoptosis in LSCC by directly silencing phosphoinositide 3-kinase catalytic subunit (PIK3CD). We speculated that tRF-33-Q1Q89P9L842205 is a potential diagnostic biomarker for LSCC and acts as a tumor suppressor by directly targeting PIK3CD.

Downregulation of LAPTM4B Contributes to the Impairment of the Autophagic Flux via Unopposed Activation of mTORC1 Signaling During Myocardial Ischemia/Reperfusion Injury.

RATIONALE: Impaired autophagic flux contributes to ischemia/reperfusion (I/R)-induced cardiomyocyte death, but the underlying molecular mechanisms remain largely unexplored. OBJECTIVE: To determine the role of LAPTM4B (lysosomal-associated transmembrane protein 4B) in the regulation of autophagic flux and myocardial I/R injury. METHODS AND RESULTS: LAPTM4B was expressed in murine hearts but downregulated in hearts with I/R (30 minutes/2 hours) injury and neonatal rat cardiomyocytes with hypoxia/reoxygenation (6 hours/2 hours) injury. During myocardial reperfusion, LAPTM4B-knockout (LAPTM4B-/-) mice had a significantly increased infarct size and lactate dehydrogenase release, whereas adenovirus-mediated LAPTM4B-overexpression was cardioprotective. Concomitantly, LAPTM4B-/- mice showed higher accumulation of the autophagy markers LC3-II (microtubule-associated protein 1A/1B-light chain 3), but not P62, in the I/R heart, whereas they did not alter chloroquine-induced further increases of LC3-II and P62 in both sham and I/R hearts. Conversely, LAPTM4B-overexpression had opposite effects. The hypoxia/reoxygenation-reduced viability of neonatal rat cardiomyocytes, ratio of autolysosomes/autophagosomes, and function of lysosomes were further decreased by LAPTM4B-knockdown but reversed by LAPTM4B-overexpression. Moreover, the LAPTM4B-overexpression-mediated benefits were abolished by knockdown of lysosome-associated membrane protein-2 (an autophagosome-lysosome fusion protein) in vivo and by the autophagy inhibitor bafilomycin A1 in vivo. In contrast, rapamycin (Rapa) successfully restored the impaired autophagic flux in LAPTM4B-/- mice and the subsequent myocardial I/R injury. Mechanistically, LAPTM4B regulated the activity of mTORC1 (mammalian target of rapamycin complex 1) via interacting with mTOR through its EC3 (extracelluar) domain. Thus, mTORC1 was overactivated in LAPTM4B-/- mice, leading to the repression of TFEB (transcription factor EB), a master regulator of lysosomal and autophagic genes, during myocardial I/R. The mTORC1 inhibition or TFEB-overexpression rescued the LAPTM4B-/--induced impairment in autophagic flux and I/R injury, whereas TFEB-knockdown abolished the LAPTM4B-overexpression-mediated recovery of autophagic flux and cardioprotection. CONCLUSIONS: The downregulation of LAPTM4B contributes to myocardial I/R-induced impairment of autophagic flux via modulation of the mTORC1/TFEB pathway. Graphic Abstract: A graphic abstract is available for this article.

Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma.

BACKGROUND: Pyroptosis plays an essential role in tumor immune responses and inflammation related to chemotherapy. Herein, we studied the characteristic patterns of pyroptosis in head and neck squamous cell carcinoma (HNSCC) to determine their prognostic and therapeutic effects. METHODS: Consensus clustering analysis was performed to classify patients into pyroptosis or gene clusters. A novel pyroptosis score was constructed by principal component analysis. Kaplan-Meier survival curves were used to show the prognostic value. We also assessed the functional enrichment, tumor mutation burden, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between high and low pyroptosis score group. RESULTS: Two distinct pyroptosis clusters were defined based on the mRNA expression profiles of PRGs, which were related to immune activation in HNSCC. Notably, a pyroptosis score was constructed according to different expression gene signatures, and then, each HNSCC patient was classified into a low or high pyroptosis score group. Patients with low pyroptosis scores had better immunotherapeutic responses and higher sensitivities to chemotherapeutic agents (paclitaxel, docetaxel, and gemcitabine). Kaplan-Meier survival curves showed that the pyroptosis patterns were independent prognostic indicators regardless of the level of tumor mutation burden. CONCLUSIONS: Pyroptosis plays an essential role in immune infiltration in HNSCC. Quantifying the pyroptosis score of individual patients might suggest prognostic, immunotherapeutic, and chemotherapeutic strategies for HNSCC.

Expression profile and prognostic value of CXCR family members in head and neck squamous cell carcinoma.

BACKGROUND: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). METHODS: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features, and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). RESULTS: CXCRs were differentially expressed in HNSCC. As shown by Kaplan-Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. CONCLUSIONS: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

Ferroptosis as a target for protection against cardiomyopathy.

Heart disease is the leading cause of death worldwide. A key pathogenic factor in the development of lethal heart failure is loss of terminally differentiated cardiomyocytes. However, mechanisms of cardiomyocyte death remain unclear. Here, we discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy. In canonical apoptosis and/or necroptosis-defective Ripk3-/-, Mlkl-/-, or Fadd-/-Mlkl-/- mice, DOX-treated cardiomyocytes showed features of typical ferroptotic cell death. Consistently, compared with dexrazoxane, the only FDA-approved drug for treating DOX-induced cardiotoxicity, inhibition of ferroptosis by ferrostatin-1 significantly reduced DOX cardiomyopathy. RNA-sequencing results revealed that heme oxygenase-1 (Hmox1) was significantly up-regulated in DOX-treated murine hearts. Administering DOX to mice induced cardiomyopathy with a rapid, systemic accumulation of nonheme iron via heme degradation by Nrf2-mediated up-regulation of Hmox1, which effect was abolished in Nrf2-deficent mice. Conversely, zinc protoporphyrin IX, an Hmox1 antagonist, protected the DOX-treated mice, suggesting free iron released on heme degradation is necessary and sufficient to induce cardiac injury. Given that ferroptosis is driven by damage to lipid membranes, we further investigated and found that excess free iron accumulated in mitochondria and caused lipid peroxidation on its membrane. Mitochondria-targeted antioxidant MitoTEMPO significantly rescued DOX cardiomyopathy, supporting oxidative damage of mitochondria as a major mechanism in ferroptosis-induced heart damage. Importantly, ferrostatin-1 and iron chelation also ameliorated heart failure induced by both acute and chronic I/R in mice. These findings highlight that targeting ferroptosis serves as a cardioprotective strategy for cardiomyopathy prevention.

[Automatic Post-operative Cervical Cancer Target Area and Organ at Risk Outlining Based on Fusion Convolutional Neural Network].

CT image based organ segmentation is essential for radiotherapy treatment planning, and it is laborious and time consuming to outline the endangered organs and target areas before making radiation treatment plans. This study proposes a fully automated segmentation method based on fusion convolutional neural network to improve the efficiency of physicians in outlining the endangered organs and target areas. The CT images of 170 postoperative cervical cancer stage IB and IIA patients were selected for network training and automatic outlining of bladder, rectum, femoral head and CTV, and the neural network was used to localize easily distinguishable vessels around the target area to achieve more accurate outlining of CTV.

Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients. METHODS: Our study recruited 53 pediatric MG patients and 46 age- and gender-matched healthy controls (HC). We sequenced the fecal samples of recruited individuals using whole-genome shotgun sequencing and analyzed the data with in-house bioinformatics pipeline. RESULTS: We built an MG disease classifier based on the abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale. The classifier obtained 94% area under the curve (AUC) in cross-validation and 84% AUC in the independent validation cohort. Gut microbiome analysis revealed the presence of human adenovirus F/D in 10 MG patients. Significantly different pathways and gene families between MG patients and HC belonged to P. copri, Clostridium bartlettii, and Bacteroides massiliensis. Based on functional annotation, we found that the gut microbiome affects the production of short-chain fatty acids (SCFAs), and we confirmed the decrease in SCFA levels in pediatric MG patients via serum tests. CONCLUSIONS: The study indicated that altered fecal microbiota might play vital roles in pediatric MG's pathogenesis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric MG.

CT based automatic clinical target volume delineation using a dense-fully connected convolution network for cervical Cancer radiation therapy.

BACKGROUND: It is very important to accurately delineate the CTV on the patient's three-dimensional CT image in the radiotherapy process. Limited to the scarcity of clinical samples and the difficulty of automatic delineation, the research of automatic delineation of cervical cancer CTV based on CT images for new patients is slow. This study aimed to assess the value of Dense-Fully Connected Convolution Network (Dense V-Net) in predicting Clinical Target Volume (CTV) pre-delineation in cervical cancer patients for radiotherapy. METHODS: In this study, we used Dense V-Net, a dense and fully connected convolutional network with suitable feature learning in small samples to automatically pre-delineate the CTV of cervical cancer patients based on computed tomography (CT) images and then we assessed the outcome. The CT data of 133 patients with stage IB and IIA postoperative cervical cancer with a comparable delineation scope was enrolled in this study. One hundred and thirteen patients were randomly designated as the training set to adjust the model parameters. Twenty cases were used as the test set to assess the network performance. The 8 most representative parameters were also used to assess the pre-sketching accuracy from 3 aspects: sketching similarity, sketching offset, and sketching volume difference. RESULTS: The results presented that the DSC, DC/mm, HD/cm, MAD/mm, ∆V, SI, IncI and JD of CTV were 0.82 ± 0.03, 4.28 ± 2.35, 1.86 ± 0.48, 2.52 ± 0.40, 0.09 ± 0.05, 0.84 ± 0.04, 0.80 ± 0.05, and 0.30 ± 0.04, respectively, and the results were greater than those with a single network. CONCLUSIONS: Dense V-Net can correctly predict CTV pre-delineation of cervical cancer patients and can be applied in clinical practice after completing simple modifications.

tRNAIni CAT inhibits proliferation and promotes apoptosis of laryngeal squamous cell carcinoma cells.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) brings a heavy blow to the patient's voice. Transfer RNA (tRNA) is a common RNA, the roles of tRNAs in LSCC are largely unknown. METHODS: The tRNA expression profile in LSCC tissues and adjacent normal tissues was measured by a tRNA qRT-PCR array. The expression level of tRNAIni CAT in LSCC tissues and plasmas was detected by qRT-PCR. The receiver operating characteristic (ROC) curve was established. tRNAIni CAT was upregulated by a lentivirus vector in the LSCC cell line. Moreover, tRNAIni CAT was upregulated in LSCC xenograft nude mouse model and the xenografts were used for pathological analysis and transmission electron microscope (TEM) observation. RESULTS: The top 10 upregulated tRNAs were tRNALys CTT -1, tRNALeu TAA , tRNAPhe GAA , tRNALeu CAG , tRNATyr ATA , tRNAMet CAT , tRNATyr GTA -1, tRNAThr CGT , tRNATyr GTA -2, tRNAAla AGC ; and the top 10 downregulated tRNAs were tRNAIni CAT , mt-tRNAGlu TTC , tRNAVal CAC -3, mt-tRNATrp TCA , mt-tRNATyr GTA , mt-tRNALys TTT , mt-tRNAThr TGT , mt-tRNAAsp GTC , mt-tRNAAsn GTT , mt-tRNAPro TGG . tRNAIni CAT was downregulated in LSCC tissues and plasma. The area under the ROC curve (AUC) in LSCC tissues and the plasma of patients with LSCC was 0.717 and 0.808, respectively. tRNAIni CAT inhibited LSCC cell proliferation and promoted apoptosis. The in vivo results showed that tRNAIni CAT inhibited the growth of the xenografts and promoted apoptosis. CONCLUSIONS: This is the first study to provide tRNA expression profiles for LSCC tissues. tRNAIni CAT may be used as a new biomarker for the early diagnosis of LSCC. tRNAIni CAT inhibits cell proliferation and promotes apoptosis in vitro and in vivo.

Automatic segmentation of pelvic organs-at-risk using a fusion network model based on limited training samples.

Background: Efficient and accurate methods are needed to automatically segmenting organs-at-risk (OAR) to accelerate the radiotherapy workflow and decrease the treatment wait time. We developed and evaluated the use of a fused model Dense V-Network for its ability to accurately segment pelvic OAR.Material and methods: We combined two network models, Dense Net and V-Net, to establish the Dense V-Network algorithm. For the training model, we adopted 100 kV computed tomography (CT) images of patients with cervical cancer, including 80 randomly selected as training sets, by which to adjust parameters of the automatic segmentation model, and the remaining 20 as test sets to evaluate the performance of the convolutional neural network model. Three representative parameters were used to evaluate the segmentation results quantitatively.Results: Clinical results revealed that Dice similarity coefficient values of the bladder, small intestine, rectum, femoral head and spinal cord were all above 0.87 mm; and Jaccard distance was within 2.3 mm. Except for the small intestine, the Hausdorff distance of other organs was less than 9.0 mm. Comparison of our approaches with those of the Atlas and other studies demonstrated that the Dense V-Network had more accurate and efficient performance and faster speed.Conclusions: The Dense V-Network algorithm can be used to automatically segment pelvic OARs accurately and efficiently, while shortening patients' waiting time and accelerating radiotherapy workflow.

PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery.

Proteolysis-targeting chimeric molecules (PROTACs) represent an emerging technique that is receiving much attention for therapeutic intervention. The mechanism is based on the inhibition of protein function by hijacking a ubiquitin E3 ligase for protein degradation. The hetero-bifunctional PROTACs contain a ligand for recruiting an E3 ligase, a linker, and another ligand to bind with the protein targeted for degradation. Thus, PROTACs have profound potential to eliminate "undruggable" protein targets, such as transcription factors and non-enzymatic proteins, which are not limited to physiological substrates of the ubiquitin-proteasome system. These findings indicate great prospects for PROTACs in the development of therapeutics. However, there are several limitations related to poor stability, biodistribution, and penetrability in vivo. This review provides an overview of the main PROTAC-based approaches that have been developed and discusses the promising opportunities and considerations for the application of this technology in therapies and drug discovery.

Autophagy regulates apoptosis by targeting NOXA for degradation.

Apoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce apoptosis and promote autophagy. Here, we report that autophagy regulates apoptosis by targeting NOXA for degradation. Inhibiting autophagy increases NOXA protein levels by extending the protein half-life. NOXA accumulation effectively suppresses tumor cell growth by inducing apoptosis, which is further enhanced when p53 is present. Mechanistically, NOXA is hijacked by p62 as autophagic cargo, and its three lysine residues at the C-terminus are necessary for NOXA degradation in lysosomes. Taken together, our study demonstrates that NOXA serves as a bridge in the crosstalk between autophagy and apoptosis and implies that autophagy inhibitors could be an effective therapy for cancer, especially wild-type p53-containing cancer.

[A fusion network model based on limited training samples for the automatic segmentation of pelvic endangered organs].

When applying deep learning to the automatic segmentation of organs at risk in medical images, we combine two network models of Dense Net and V-Net to develop a Dense V-network for automatic segmentation of three-dimensional computed tomography (CT) images, in order to solve the problems of degradation and gradient disappearance of three-dimensional convolutional neural networks optimization as training samples are insufficient. This algorithm is applied to the delineation of pelvic endangered organs and we take three representative evaluation parameters to quantitatively evaluate the segmentation effect. The clinical result showed that the Dice similarity coefficient values of the bladder, small intestine, rectum, femoral head and spinal cord were all above 0.87 (average was 0.9); Jaccard distance of these were within 2.3 (average was 0.18). Except for the small intestine, the Hausdorff distance of other organs were less than 0.9 cm (average was 0.62 cm). The Dense V-Network has been proven to achieve the accurate segmentation of pelvic endangered organs.