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Deep learning on graphs has recently achieved remarkable success on a variety of tasks, while such success relies heavily on the massive and carefully labeled data. However, precise annotations are generally very expensive and time-consuming. To address this problem, self-supervised learning (SSL) is emerging as a new paradigm for extracting informative knowledge through well-designed pretext tasks without relying on manual labels. In this survey, we extend the concept of SSL, which first emerged in the fields of computer vision and natural language processing, to present a timely and comprehensive review of existing SSL techniques for graph data. Specifically, we divide existing graph SSL methods into three categories: contrastive, generative, and predictive. More importantly, unlike other surveys that only provide a high-level description of published research, we present an additional mathematical summary of existing works in a unified framework. Furthermore, to facilitate methodological development and empirical comparisons, we also summarize the commonly used datasets, evaluation metrics, downstream tasks, open-source implementations, and experimental study of various algorithms. Finally, we discuss the technical challenges and potential future directions for improving graph self-supervised learning. Latest advances in graph SSL are summarized in a GitHub repository https://github.com/LirongWu/awesome-graph-self-supervised-learning.

Background The effects of pelvic organ prolapse (POP) and stress urinary incontinence (SUI) on sexual activity and female sexual dysfunction (FSD) remain unknown. How female sexual function is affected by surgery to treat SUI and/or POP remains controversial. Aim The objectives of this study were to identify the prevalence of FSD and potential risk factors in women with POP and/or SUI and to assess whether pelvic floor surgery leads to alterations in female sexual function. Methods This investigation was prospective and observational. Informed consent was obtained from women who were scheduled to undergo pelvic floor surgery to manage POP and/or SUI at Peking University People’s Hospital, which is an urban medical center. Sexual function was assessed by an investigator preoperatively and 12 months postoperatively. Outcomes Sexual activity and sexual function before and after surgery were investigated with potential risk factors. Sexual function was measured by 2 validated questionnaires: the Female Sexual Function Index and the PISQ-12 (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form). Results A total of 233 women were recruited, and all were ethnically Chinese. The average age was 63 years (range, 31-83), and 47.2% were sexually active. The lack of sexual activity before surgery was associated with increasing age (mean ± SD, 56.3 ± 9.5 vs 68.4 ± 8.1 years; P < .001) and postmenopausal status (70.0% vs 97.6%, P < .001). Among the sexually active women, 62.7% were diagnosed with FSD. Increasing age (58.6 ± 9.6 vs 52.3 ± 7.8 years, P < .001) and postmenopausal status (82.6% vs 48.8%, P < .001) were associated with the presence of FSD. Overall there was no significant difference between the PISQ-12 score before and 12 months after surgery (34.7 ± 6.7 vs 33.9 ± 6.6, P = .14). Lubrication of the vagina (P = .044) was an independent factor associated with the improvement in quality of sexual life after surgery. Menopause negatively affected the improvement in quality of sexual life after surgery (P = .024). Clinical Implications Menopause and lubrication of the vagina might affect the improvement in sexual function after surgery. Strengths and Limitations Strengths include the prospective design, validated questionnaires, and adequate follow-up time. As a limitation, this study is a single-center study that included only Chinese patients with advanced POP/SUI, so it may not be generalizable to other populations. Conclusion Nearly half of women with symptomatic POP and/or SUI are still sexually active. Increasing age and menopause are associated with a lack of sexual activity. Premenopausal status and better lubrication of the vagina before surgery might lead to an improvement in sexual function after pelvic floor surgery.

Adding CrIII or AlIII salts into the water suspension of platinum group metal (PGM) catalysts accelerated oxyanion pollutant reduction by up to 600%. Our initial attempts of adding K2CrVIO4, K2CrVI2O7, or KCrIII(SO4)2 into Pd/C enhanced BrO3- reduction with 1 atm H2 by 6-fold. Instrument characterizations and kinetic explorations collectively confirmed the immobilization of reduced CrVI as CrIII(OH)3 on the catalyst surface. This process altered the ζ-potentials from negative to positive, thus substantially enhancing the Langmuir-Hinshelwood adsorption equilibrium constant for BrO3- onto Pd/C by 37-fold. Adding AlIII(OH)3 from alum at pH 7 achieved similar enhancements. The Cr-Pd/C and Al-Pd/C showed top-tier efficiency of catalytic performance (normalized with Pd dosage) among all the reported Pd catalysts on conventional and nanostructured support materials. The strategy of adding inert metal hydroxides works for diverse PGMs (palladium and rhodium), substrates (BrO3- and ClO3-), and support materials (carbon, alumina, and silica). This work shows a simple, inexpensive, and effective example of enhancing catalyst activity and saving PGMs for environmental applications.

Although vaping has recently increased as a mode of inhaling marijuana and has been associated with numerous and sometimes fatal cases of acute severe lung injury, smoking remains the most common method of inhaling marijuana and has been studied more extensively. Smoking marijuana has been shown to produce modest but significant short-term bronchodilation both in healthy subjects and in those with asthma. Long-term effects of habitual marijuana smoking include the following: (1) symptoms of chronic bronchitis (increased cough, sputum production, and wheezing); (2) modest effects on lung function in cross-sectional studies (no significant decrease in FEV

Chemotherapy is the first choice in the treatment of cancer and is always preferred to other approaches such as radiation and surgery, but it has never met the need of patients for a safe and effective drug. Therefore, new advances in cancer treatment are now needed to reduce the side effects and burdens associated with chemotherapy for cancer patients. Targeted treatment using nanotechnology are now being actively explored as they could effectively deliver therapeutic agents to tumor cells without affecting normal cells. Dendrimers are promising nanocarriers with distinct physiochemical properties that have received considerable attention in cancer therapy studies, which is partly due to the numerous functional groups on their surface. In this review, we discuss the progress of different types of dendrimers as delivery systems in cancer therapy, focusing on the challenges, opportunities, and functionalities of the polymeric molecules. The paper also reviews the various role of dendrimers in their entry into cells via endocytosis, as well as the molecular and inflammatory pathways in cancer. In addition, various dendrimers-based drug delivery (e.g., pH-responsive, enzyme-responsive, redox-responsive, thermo-responsive, etc.) and lipid-, amino acid-, polymer- and nanoparticle-based modifications for gene delivery, as well as co-delivery of drugs and genes in cancer therapy with dendrimers, are presented. Finally, biosafety concerns and issues hindering the transition of dendrimers from research to the clinic are discussed to shed light on their clinical applications.

Lymph node metastasis can independently predict oral squamous cell carcinoma patients' survival. This study would investigate the genetic and cellular differences between oral squamous cell carcinoma with positive and negative lymph node metastases.We gathered single-cell RNA sequencing and bulk gene expression data from the Cancer Genome Atlas and Gene Expression Omnibus databases. Sixty lymph node-metastasis-related genes were discovered with refined single-cell RNA sequencing data analysis, and consensus clustering provided three molecular subtypes of oral squamous cell carcinoma. Least absolute shrinkage and selection operator analyses were then utilized to establish a five-gene risk model. CIBERSORT analysis revealed the immune infiltration profile of different risk subgroups.Oral squamous cell carcinoma patients were classified into three subtypes based on the 60 lymph node-metastasis-related key genes identified by single-cell RNA sequencing data. Patients in Subtype 3 showed a tendency for lymph node metastasis and poorer prognosis. Moreover, five biomarkers were selected from the 60 genes to construct a five-gene risk model evaluating the risk of lymph node metastasis. A lower probability of lymph node metastasis and a better prognosis was observed in the low-risk group. The immune infiltration of three different risk groups was explored with CIBERSORT. Besides, further analysis implied different sensitivities of anticancer drugs, including immunotherapy drugs and targeted compounds, in the three risk groups.In view of intratumoral heterogeneity, we found 60 genes associated with lymph node metastasis of oral squamous cell carcinoma. Subsequently, we constructed a five-gene signature that could improve the prediction of lymph node metastasis, clinical outcome, and promote individualized treatment strategies for oral squamous cell carcinoma.

Endoscopic ultrasonography (EUS) and magnifying endoscopy (ME) reliably determine indications for endoscopic resection in patients with superficial esophageal squamous cell carcinoma (SESCC). ME is widely accepted for predicting the invasion depth of superficial esophageal cancer with satisfying accuracy. However, the addition of EUS is controversial.To evaluate the diagnostic efficiency of MEWe retrospectively analyzed patients with suspected SESCC who completed both ME and EUS and then underwent endoscopic or surgical resection at Sun Yat-Sen University Cancer Center between January 2018 and December 2021. We evaluated and compared the diagnostic efficiency of EUS and ME according to histological results, and investigated the influencing factors.We included 152 lesions from 144 patients in this study. The diagnostic accuracies of ME and EUS in differentiating invasion depth were not significantly different (73.0% and 66.4%,Preoperative diagnosis of SESCC should be conducted endoscopically using white light and magnification. In China, EUS can be added after obtaining patient consent. Use of a high-frequency miniature probe or miniature probe combined with conventional EUS is preferable.

The phase separation model for transcription suggests that transcription factors (TFs), coactivators, and RNA polymerases form biomolecular condensates around active gene loci and regulate transcription. However, the structural details of condensates remain elusive. In this study, for Nanog, a master TF in mammalian embryonic stem cells known to form protein condensatesin vitro, we examined protein structures in the condensates using residue-level coarse-grained molecular simulations. Human Nanog formed micelle-like clusters in the condensate. In the micelle-like cluster, the C-terminal disordered domains, including the tryptophan repeat (WR) regions, interacted with each other near the cluster center primarily via hydrophobic interaction. In contrast, hydrophilic disordered N-terminal and DNA-binding domains were exposed on the surface of the clusters. Electrostatic attractions of these surface residues were responsible for bridging multiple micelle-like structures in the condensate. The micelle-like structure and condensate were dynamic and liquid-like. Mutation of tryptophan residues in the WR region which was implicated to be important for a Nanog function resulted in dissolution of the Nanog condensate. Finally, to examine the impact of Nanog cluster to DNA, we added DNA fragments to the Nanog condensate. Nanog DNA-binding domains exposed to the surface of the micelle-like cluster could recruit more than one DNA fragments, making DNA-DNA distance shorter.Author summaryIn eukaryotic transcription regulation, enhancer elements far from the promoter are known to modulate transcriptional activity, but the molecular mechanism remains elusive. One of these models, the phase separation model, suggests that transcription factors (TFs), coactivators, and transcription machinery form biomolecular condensates that include enhancer and promoter elements, making enhancer-promoter communication possible via the protein network in the condensate. Nanog, one of the core TFs involved in mammalian embryonic stem cells, has been reported to have the ability to form condensates. In this study, we addressed the structural details of Nanog condensates by performing residue-level coarse-grained molecular simulations. We found that Nanog formed micelle-like clusters via primarily hydrophobic interactions between tryptophan repeat regions in the C-terminal disordered domains within the condensate. On the other hand, highly charged N-terminal and DNA-binding domains were exposed to the surface of the micelle and were responsible for bridging many micelles into a condensate. The micelle-like clusters and condensate were dynamic and liquid-like. In addition, Nanog condensates could induce DNA-DNA attraction mediated by micelle-like structures.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states can drive fibrosis, inflammation, and tissue destruction. In the joint synovium, fibroblasts provide homeostatic maintenance and lubrication. Little is known about what regulates the homeostatic functions of fibroblasts in healthy conditions. We performed RNA sequencing of healthy human synovial tissue and identified a fibroblast gene expression program characterized by enhanced fatty acid metabolism and lipid transport. We found that fat-conditioned media reproduces key aspects of the lipid-related gene signature in cultured fibroblasts. Fractionation and mass spectrometry identified cortisol in driving the healthy fibroblast phenotype, confirmed using glucocorticoid receptor gene ( NR3C1 ) deleted cells. Depletion of synovial adipocytes in mice resulted in loss of the healthy fibroblast phenotype and revealed adipocytes as a major contributor to active cortisol generation via Hsd11 β 1 expression. Cortisol signaling in fibroblasts mitigated matrix remodeling induced by TNFα- and TGFβ, while stimulation with these cytokines repressed cortisol signaling and adipogenesis. Together, these findings demonstrate the importance of adipocytes and cortisol signaling in driving the healthy synovial fibroblast state that is lost in disease.

AimsWe conducted bibliometric and visualization analyses to evaluate the current research status, hotspots, and trends related to the human microbiota markers in colorectal cancer screening.MethodsThe related studies were acquired from the Web of Science Core Collection (WoSCC) database on 5 January 2023. Analyses of the co-occurrence and cooperation relationships between the cited authors, institutions, countries/regions, cited journals, cited articles, and keywords in the studies were carried out using CiteSpace 5.8.R3 software and the Online Analysis platform of Literature Metrology. Additionally, relevant knowledge graphs were drawn to perform visualization analyses; a keywords cluster analysis and a burst analysis were also conducted.ResultsAfter analyzing 700 relevant articles, this bibliometric analysis found that the annual publications showed an increasing trend from 1992 to 2022. Yu Jun from the Chinese University of Hong Kong had the highest cumulative number of publications, whereas Shanghai Jiao Tong University was the most productive institution. China and the USA have contributed the largest number of studies. The keywords frequency analysis demonstrated that “colorectal cancer,” “gut microbiota,” “Fusobacterium nucleatum,” “risk,” and “microbiota” were the most frequent keywords, and the keywords cluster analysis found that the current hotspots were as follows: (a) the precancerous lesions of colorectal cancer (CRC) that need to be screened, such as inflammatory bowel disease (IBD) and advanced adenoma, (b) the gut-derived microbiome for CRC screening, and (c) the early detection of CRC. The burst analysis further showed that the combination of microbiomics with metabolomics might be the future research trend in the field of CRC screening.ConclusionThe findings of the current bibliometric analysis firstly provide an insight into the current research status, hotspots, and future trends in the field of CRC screening based on the microbiome; the research in this field is becoming more in-depth and diversified. Some human microbiota markers, especially “Fusobacterium nucleatum,” are promising biomarkers in CRC screening, and a future hotspot might be the combined analysis of microbiomics and metabolomics for CRC risk screening.

Stroke is a cerebrovascular disease, contributing to major morbidity and mortality worldwide, with significant clinical and socioeconomic burdens [1]. In Malaysia, stroke is ranked as the third leading cause of death after ischemic heart disease and pneumonia with an alarming rising trend [2]. There are two major types of strokes, namely ischemic stroke (IS) and haemorrhagic stroke. IS caused by thromboembolic occlusion of cerebral artery is the main type of stroke in Malaysia, in which it is comprised up to two-third of total reported stroke cases, as compared to the haemorrhagic stroke [3]. Main pathological events of brain ischemia include a series of biological reactions such as oxidative stress, inflammatory cytokine release, and ischemic-reperfusion injury, leading to cell apoptosis and irreversible neurological damage [4]. Up to date, recombinant tissue plasminogen activator (rt-PA) is still the gold standard drug approved by Food and Drug Administration (FDA) for the clinical treatment of IS [5]. However, due to its narrow therapeutic window (

PurposeUnderpinned by Social Cognitive Theory (SCT), this study aimed to examine the mediating role of employees' adaptability in the relationship between the five managerial climate factors (i.e., trust, supportiveness, openness, clarity of goals and participative) and change readiness in public sector organisations.Design/methodology/approachAdopting the quantitative approach, data were collected from 379 administrative and diplomatic officers. Analysis was done using partial least squares structural equation modelling (PLS-SEM).FindingsThe results showed that trust and clarity of goals are significant motivational factors that accelerate employees' adaptability. Adaptability, in turn, was found to mediate the effect of trust and clarity of goals on employees' change readiness.Originality/valueThis study contributes to theory and practice by examining employees' adaptability as an intervening variable in the relationship between managerial climate factors and change readiness with specific reference to the public administration context.

In this article, we propose a learning approach to analyze dynamic systems with an asymmetric information structure. Instead of adopting a game-theoretic setting, we investigate an online quadratic optimization problem driven by system noises with unknown statistics. Due to information asymmetry, it is infeasible to use the classic Kalman filter nor optimal control strategies for such systems. It is necessary and beneficial to develop an admissible approach that learns the probability statistics as time goes forward. Motivated by the online convex optimization (OCO) theory, we introduce the notion of regret, which is defined as the cumulative performance loss difference between the optimal offline-known statistics cost and the optimal online-unknown statistics cost. By utilizing dynamic programming and linear minimum mean square biased estimate (LMMSUE), we propose a new type of online state-feedback control policy and characterize the behavior of regret in a finite-time regime. The regret is shown to be sublinear and bounded by O(lnT) . Moreover, we address an online optimization problem with output-feedback control policy and propose a heuristic online control policy.

Background: Migraine pain location and trigeminocervical convergence have limited diagnostic value and have usually been assessed using non-standard verbal descriptors in a small number of centers. Objective: To use non-verbal descriptors of migraine pain location to determine the prevalence of trigeminocervical convergence mechanisms in patients with episodic and chronic migraine. In addition, we explored the factors associated with the presence of convergence. Methods: A multicenter study was carried out. The explicit pain location was explored by asking subjects to indicate, on an electronic form, three points on the anterolateral side and three points on the posterolateral side of the head and neck that represented the common locations of their migraine pain. We evaluated associations of the pain pattern with demographic and psychological features, comorbidities, lifestyle and other headache characteristics. Results: 97 episodic and 113 chronic migraine patients were included. Convergence was present in 116 migraineurs (55%) who indicated dominance of pain in the posterior cervical region. This site was more often involved in the chronic migraine group (21 vs. 33%; p=0.034). The number of migrainous/altered sensitivity symptoms (OR=1.39; 95%CI 1.14–1.71) was associated with convergence independently of the chronification status. In this symptom group, there were statistical associations between convergence and vomiting (p=0.045), tactile allodynia (p

Background Physical activity (PA), sedentary behaviors (SB), and sleep are interrelated behavior components of a 24-hour day. Research interests continue to increase in examining the inter-relationship of three behaviors and their combined effects on health. The purpose of this study was to develop a comprehensive instrument to measure 24-hour movement behaviors for Chinese college students. Methods The 24-hour movement behaviors questionnaire (24HMBQ) was developed based on a literature review and expert review. The target population (Chinese college students) and an expert panel assessed the face and content validity. After the final revision of the questionnaire, the participants (n = 229) were asked to complete the 24HMBQ twice to examine test-retest reliability. Convergent validity was evaluated using Spearman’s rho, by comparing the 24HMBQ estimates of sleep, SB, and PA with results derived from the Pittsburgh Sleep Quality Index (PSQI), the Adult Sedentary Behaviors Questionnaire in China (ASBQC), and the International Physical Activity Questionnaire - Short Form (IPAQ-SF). Results The 24HMBQ exhibited good face validity and high acceptability to respondents. Regarding content validity, the S-CVI/UA and S-CVI/Ave were 0.88 and 0.97, respectively. As indicated by ICC, the test-retest reliability was considered moderate to excellent, ranging from 0.68 to 0.97 (P Conclusion The 24HMBQ is a feasible questionnaire with suitable validity and moderate to excellent test-retest reliability of all items. It is a promising tool to investigate 24-hour movement behaviors of Chinese college students. The 24HMBQ can be administrated in epidemiological studies.

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial–mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC. Graphical Abstract

PDF file - 2.9MB, In-vitro kinase assay, Histology, Cell proliferation, MANOVA analysis for genomic correlates of drug sensitivity

Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR (IC50 = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC50: PI3Kα = 16 nmol/L; PI3Kβ = 68 nmol/L; PI3Kγ = 25 nmol/L; PI3Kδ = 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials. Mol Cancer Ther; 12(2); 151–61. ©2012 AACR.

PDF file - 663K, Ambit kinome tree, Cell proliferation data, Pharmacokinetics, Body weight changes in PC3 efficacy study, Active vessel stain in COLO-205 efficacy study, MV4-11 efficacy model, Drug sensitivity profiling and correlation to mutation status

XLS file - 167K, Table 1: Cell line drug sensitivity data for SB2343 and mutations in cancer genes. Table 2: Results from MANOVA analysis of cancer genes as modifiers of drug sensitivity

Background: The mTOR pathway is crucial in controlling the growth, differentiation, and survival of neurons, and its pharmacological targeting has promising potential as a treatment for Parkinson’s disease. However, the function of mTORC1 downstream proteins, such as RPS6K, EIF4EBP, EIF-4E, EIF-4G, and EIF4A, in PD development remains unclear. Methods: We performed a Mendelian randomization study to evaluate the causal relationship between mTORC1 downstream proteins and Parkinson’s disease. We utilized various MR methods, including inverse-variance-weighted, weighted median, MR–Egger, MR-PRESSO, and MR-RAPS, and conducted sensitivity analyses to identify potential pleiotropy and heterogeneity. Results: The genetic proxy EIF4EBP was found to be inversely related to PD risk (OR = 0.79, 95% CI = 0.67–0.92, p = 0.003), with the results from WM, MR-PRESSO, and MR-RAPS being consistent. The plasma protein levels of EIF4G were also observed to show a suggestive protective effect on PD (OR = 0.85, 95% CI = 0.75–0.97, p = 0.014). No clear causal effect was found for the genetically predicted RP-S6K, EIF-4E, and EIF-4A on PD risk. Sensitivity analyses showed no significant imbalanced pleiotropy or heterogeneity, indicating that the MR estimates were robust and independent. Conclusion: Our unbiased MR study highlights the protective role of serum EIF4EBP levels in PD, suggesting that the pharmacological activation of EIF4EBP activity could be a promising treatment option for PD.

Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Graphical abstract

Objective The purpose of the study was to examine the associations between mobile phone dependency and sleep quality among college students during COVID-19 outbreak. The potential mediation roles of bedtime procrastination and fear of missing out (FoMO) were investigated. Methods A total of 881 college students completed an online survey in May 2022 in Shanghai, China. Mobile Phone Involvement Questionnaire, Bedtime Procrastination Scale, Bedtime Procrastination Scale and Pittsburgh Sleep Quality Index were used to assess mobile phone dependency, bedtime procrastination, fear of missing out, and sleep quality, respectively. Multiple linear regression and mediation analysis were conducted. Results The correlation analyses indicated mobile phone dependency was positively associated with fear of missing out, bedtime procrastination, and sleep quality among college students. The structural equation modeling analyses revealed that mobile phone dependency had significant indirect effects on sleep quality through bedtime procrastination (indirect effect: 0.030, 95%CI: 0.022–0.041) and fear of missing out (indirect effect: 0.013, 95%CI: 0.003–0.023). Conclusion The findings indicated that bedtime procrastination and fear of missing out partially mediated on the association between mobile phone dependency and sleep quality. Bedtime procrastination and fear of missing out should be considered as potential intervention targets for reducing mobile phone dependency and improving sleep quality in college students.

Background Various atopic dermatitis (AD) phenotypes showed an enormously heterogenic risk for subsequent asthma development. Objective We aimed to investigate the association between AD phenotypes and the risk for progression to asthma. Methods We searched PubMed, Embase, and Web of Science databases for relevant publications. Pooled relative risks (RR) with 95% CI were calculated using the CMA-3.0 software. This study has been registered with PROSPERO (CRD42019129273). Results We analyzed 39 publications with 458,810 participants. The RR for asthma in AD was 2.16 (95% CI, 1.88-2.48). The risk in persistent AD (RR, 3.36; 95% CI, 2.83-3.99) was higher than in transient AD (RR, 1.52; 95% CI, 1.34-1.73), and the risk in severe AD (RR, 2.40; 95% CI, 1.96-2.94) was higher than in mild AD (RR, 1.82; 95% CI, 1.03-3.23) or moderate AD (RR, 1.51; 95% CI, 1.30-1.75). The risk for asthma in early-onset AD was slightly higher than in late-onset AD and higher in boys than in girls. Limitations The AD and asthma definitions differed across the included studies. Conclusion Patients with persistent or severe AD were at a higher risk for developing asthma. These findings further elucidate the atopic march and identify target populations for asthma prevention.

High operation and maintenance costs, and ‘last-mile’ issues for populations not connected to municipal water infrastructure, have limited the utility of centralized reverse osmosis (RO) systems to alleviate water availability issues for rural communities. To address these challenges, a decentralized RO module which employs tubular RO membranes was designed and investigated. The system represents an appropriate technology because it requires minimal pretreatment and it fits in self-contained, low-profile suitcase. This compact desgin also incorporated innovative 3D printed static mixers to minimize salt concentration polarization and to improve performance. Since grid electricity may also be discontinuous in the target use cases, the system was tested with two direct current (DC) power solutions: a photovoltaics-battery configuration and an alternator-battery. The final prototype weighs less than 15 kg and was found to have a production capacity of ∼8 L/h, consuming ∼100 W of pumping power. Experiments of the prototype module revealed a 96% rejection rate of salt from a 1000–2000 ppm synthetic groundwater solution and a >99% rejection coefficient for bovine serum albumin protein and humic acid. From these performance metrics, it was estimated that 36 sets of this decentralized system (with a total CapEx of US$23,400) could provide drinking water for ∼600 rural households at a unit cost of water of 1 LKR/L (0.005 USD/L) in Sri Lanka. Overall, this study demonstrates how computational modeling and 3D printing can be leveraged to develop a compact and cost-effective decentralized RO package that could be rapidly deployed to water-stressed rural areas and in disaster relief applications.