A novel network-based adaptive fault-tolerant control of switched nonlinear systems subject to multiple faults under prescribed performance.

It is the first report about fault-tolerant-based prescribed performance control of switched nonlinear systems under multiple faults. The concerned faults include not only external faults but also actuator faults. In the process of backstepping control design, prescribed performance control is fully considered, and the combination of unknown nonlinear functions is estimated by multi-dimensional Taylor network. Finally, the developed adaptive fault-tolerant control strategy guarantees the boundedness of all controlled signals while prescribed tracking performance is satisfied. In an effort to further manifest the validity of the fault-tolerant controller, a numerical simulation and a practical simulation are introduced.

User Evaluation of a Chat-Based Instant Messaging Support Health Education Program for Patients With Chronic Kidney Disease: Preliminary Findings of a Formative Study.

BACKGROUND: Artificial intelligence-driven chatbots are increasingly being used in health care, but few chat-based instant messaging support health education programs are designed for patients with chronic kidney disease (CKD) to evaluate their effectiveness. In addition, limited research exists on the usage of chat-based programs among patients with CKD, particularly those that integrate a chatbot aimed at enhancing the communication ability and disease-specific knowledge of patients. OBJECTIVE: The objective of this formative study is to gather the data necessary to develop an intervention program of chat-based instant messaging support health education for patients with CKD. Participants' user experiences will form the basis for program design improvements. METHODS: Data were collected from April to November 2020 using a structured questionnaire. A pre-post design was used, and a total of 60 patients consented to join the 3-month program. Among them, 55 successfully completed the study measurements. The System Usability Scale was used for participant evaluations of the usability of the chat-based program. RESULTS: Paired t tests revealed significant differences before and after intervention for communicative literacy (t54=3.99; P<.001) and CKD-specific disease knowledge (t54=7.54; P<.001). Within disease knowledge, significant differences were observed in the aspects of CKD basic knowledge (t54=3.46; P=.001), lifestyle (t54=3.83; P=.001), dietary intake (t54=5.51; P<.001), and medication (t54=4.17; P=.001). However, no significant difference was found in the aspect of disease prevention. Subgroup analysis revealed that while the findings among male participants were similar to those of the main sample, this was not the case among female participants. CONCLUSIONS: The findings reveal that a chat-based instant messaging support health education program may be effective for middle-aged and older patients with CKD. The use of a chat-based program with multiple promoting approaches is promising, and users' evaluation is satisfactory. TRIAL REGISTRATION: ClinicalTrials.gov NCT05665517; https://clinicaltrials.gov/study/NCT05665517.

Perspectives of the Elderly with Mild Cognitive Impairment Living Alone on Participating in a Dementia Prevention Program: A Q Methodology Study.

This study aimed to identify and describe the various patterns of perspectives among older adults with mild cognitive impairment (MCI) living alone on participating in a dementia prevention program. Q methodology was applied to investigate the perspectives of 30 community-dwelling elderly people with MCI living alone from March to August 2018. As Q methodology applies a forced distribution through the Q-sorting technique, it could capture participants' perspective patterns. Thirty-two Q-statements were constructed to explore the participants' attitudes regarding their participation in a dementia prevention program. The participants performed Q-sorting to rank the 32 statements into a Q-sort grid. Principal component analysis was conducted using the PQ Method 2.35 software to identify patterns in participants' perspectives. Four patterns of shared perspectives, accounting for 54.65% of the total variance, were identified: (a) awareness of health benefits and readiness to take preventive actions; (b) emphasis on cost consideration, and not ready to participate; (c) concern about family's attitude and needing family support; (d) emphasis on medical care and needing providers' recommendation. The exploration of clusters of the elderly with MCI could assist health professionals in acknowledging elderly people's attitudes and responses towards participating in a dementia prevention program.

New partnerships among single older adults: a Q methodology study.

BACKGROUND: The social structure is changing with an increase in the ratio of the older population, resulting in a growing number of older people being faced with singlehood. This study identified and described single older adults' differing perspectives on new relationships. METHOD: We used a Q methodology approach for data collection and analysis, following in-depth interviews with 10 participants. Q statements were developed through content analysis of the interview data, which were then subjected to Q sorts performed by 49 older adults. A factor analysis was then completed on the collected data using PQ Method software. RESULTS: Five factors regarding common attitudes toward pursuing a new partner, which accounted for 53% of the total variance, were obtained in the final model: (1) being single, a companion, and already acquainted with the other person/potential partner; (2) high spiritual compatibility and a caring disposition; (3) an emphasis on physical intimacy and companionship; (4) easily influenced by others' comments and highly concerned about being alone; and (5) physical and financial independence. CONCLUSIONS: Clustering older adults according to their attitudes can help in acknowledging their expectations about new relationships in later life. IMPLICATIONS: Practitioners can engage in successful consultations based on the recognition.

Likelihood of a fecal occult blood test uptake among older adults: comparisons between health professionals and healthcare volunteers based on the health belief model.

BACKGROUND: Health professionals and healthcare volunteers play a critical role in promoting uptake of the fecal occult blood test (FOBT), which is an effective screening method for colorectal cancer. However, previous studies paid less attention to investigating both groups regarding their intention to undergo the test. This study used the Health Belief Model (HBM) to explore the likelihood of an FOBT uptake among health professionals and healthcare volunteers aged 50 years or older. METHODS: A cross-sectional survey was conducted at public health centers in a county in northern Taiwan. Health professionals and healthcare volunteers were invited to complete the questionnaires. Overall, 391 valid questionnaires were obtained (response rate = 93.10%). Structural equation modeling was used to examine the associations among the variables based on the HBM. RESULTS: The HBM explained 45, 44, and 50% of the variance in the likelihood of undergoing an FOBT in all participants, health professionals, and healthcare volunteers, respectively. The explained variance in healthcare volunteers outweighed that of professionals by 6%. Perceived benefits and self-efficacy significantly affected the likelihood of undergoing an FOBT. Self-efficacy significantly mediated the effects of perceived severity, benefits, and barriers on the likelihood of an FOBT uptake. A borderline significant difference in structural coefficients was found across groups. CONCLUSIONS: The HBM model was used to examine the likelihood of an FOBT uptake among health professionals and healthcare volunteers, and the results showed that self-efficacy was the optimal predictor of the likelihood of an FOBT uptake, followed by perceived benefits. Future multifactorial interventions to promote FOBT uptake among health professionals and healthcare volunteers aged 50-75 years could include these significant factors.

Patterns of perspectives on fall-prevention beliefs by community-dwelling older adults: a Q method investigation.

BACKGROUND: Falling has high incidence and reoccurrence rates and is an essential factor contributing to accidental injury or death for older adults. Enhancing the participation of community-dwelling older adults in fall-prevention programs is crucial. Understanding fall-prevention beliefs will be beneficial for developing a community-based fall-prevention program. The aim of the present study was to identify the distinct types of subjective views on the fall-prevention beliefs of community-dwelling older adults aged 80 years and older by applying the Q method. METHODS: The Q method was adopted to investigate the pattern of perception on fall-prevention beliefs. Forty-two older adults aged 80 - 92 years from a community care center in Northern Taiwan were recruited and requested to complete a Q-sorting. A series of Q-sorts was performed by the participants to rank 30 statements into a normal distribution Q-sort grid. The Q-sorts were subjected to principal component analysis by using PQMethod software Version 2.35. RESULTS: Four statistically independent perspectives were derived from the analysis and reflected distinct viewpoints on beliefs related to fall prevention. Participants in the Considerate perspective believed that health problems caused by falling were serious and fall prevention could decrease the burden they place on their family. Participants in the Promising perspective believed that existing health problems could cause a fall and that fall prevention contributed to their well-being. Participants in the Adaptable perspective perceived low barriers to execute fall prevention and displayed self-confidence and independence in preventing falls. Participants in the Ignorance perspective believed that they could not prevent falls and perceived barriers to fall prevention. CONCLUSIONS: By combining theoretical constructs and the Q methodology approach, this study identified four distinct perspectives on fall prevention among community-dwelling older adults. Critical reflection on older adult personal perspectives and interpretations of the required responsive approach is a key element for appropriating fall-prevention support.

Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice.

AIM: To investigate the effects of Recql5 deficiency on liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal). METHODS: Liver injury was induced in wild type (WT) or Recql5-deficient mice using LPS/D-Gal, and assessed by histological, serum transaminases, and mortality analyses. Hepatocellular apoptosis was quantified by transferase dUTP nick end labeling assay and Western blot analysis of cleaved caspase-3. Liver inflammatory chemokine and cytochrome P450 expression was analyzed by quantitative reverse transcription-PCR. Neutrophil infiltration was evaluated by myeloperoxidase activity. Expression and phosphorylation of ERK, JNK, p65, and H2A.X was determined by Western blot. Oxidative stress was evaluated by measuring malondialdehyde production and nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity. RESULTS: Following LPS/D-Gal exposure, Recql5-deficient mice exhibited enhanced liver injury, as evidenced by more severe hepatic hemorrhage, higher serum aspartate transaminase and alanine transaminase levels, and lower survival rate. As compared to WT mice, Recql5-deficient mice showed an increased number of apoptotic hepatocytes and higher cleaved caspase-3 levels. Recql5-deficient mice exhibited increased DNA damage, as evidenced by increased γ-H2A.X levels. Inflammatory cytokine levels, neutrophil infiltration, and ERK phosphorylation were also significantly increased in the knockout mice. Additionally, Recql5-deficient mice exhibited increased malondialdehyde production and elevated inducible nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity, indicative of enhanced oxidative stress. Moreover, CYP450 expression was significantly downregulated in Recql5-deficient mice after LPS/D-Gal treatment. CONCLUSION: Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression.

SCP phosphatases suppress renal cell carcinoma by stabilizing PML and inhibiting mTOR/HIF signaling.

The tumor-suppressor protein promyelocytic leukemia (PML) is aberrantly degraded in multiple types of human cancers through mechanisms that are incompletely understood. Here, we show that the phosphatase SCP1 and its isoforms SCP2/3 dephosphorylate PML at S518, thereby blocking PML ubiquitination and degradation mediated by the prolyl isomerase Pin1 and the ubiquitin ligase KLHL20. Clinically, SCP1 and SCP3 are downregulated in clear cell renal cell carcinoma (ccRCC) and these events correlated with PMLS518 phosphorylation, PML turnover, and high-grade tumors. Restoring SCP1-mediated PML stabilization not only inhibited malignant features of ccRCC, including proliferation, migration, invasion, tumor growth, and tumor angiogenesis, but also suppressed the mTOR-HIF pathway. Furthermore, blocking PML degradation in ccRCC by SCP1 overexpression or Pin1 inhibition enhanced the tumor-suppressive effects of the mTOR inhibitor temsirolimus. Taken together, our results define a novel pathway of PML degradation in ccRCC that involves SCP downregulation, revealing contributions of this pathway to ccRCC progression and offering a mechanistic rationale for combination therapies that jointly target PML degradation and mTOR inhibition for ccRCC treatment.

Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells.

AIM: To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency on the cytotoxicity of chemotherapeutic agents toward colorectal cancer cells. METHODS: PTEN-deficient colorectal cancer (CRC) cells were generated by human somatic cell gene targeting using the adeno-associated virus system. The cytotoxic effects of compounds including curcumin, 5-fluorouracil (5-FU), dihydroartemisinin (DHA), irinotecan (CPT-11) and oxaliplatin (OXA) on cancer cells were determined using the MTT assay. Enhanced cytotoxicity of curcumin in PTEN-deficient CRC cells was observed, and this was confirmed using clonogenic assays. Apoptosis and cell cycle progression were analyzed by flow cytometry. Levels of apoptosis and cell cycle-related proteins were examined by Western blotting. RESULTS: We developed an isogenic set of CRC cell lines that differed only in their PTEN status. Using this set of cell lines, we found that disruption of the PTEN gene had no effect on the sensitivity of CRC cells to 5-FU, CPT-11, DHA, or OXA, whereas PTEN disruption increased the sensitivity of CRC cells to curcumin. Loss of PTEN did not alter the curcumin-induced apoptosis in CRC cells. However, PTEN deficiency led to an altered pattern of curcumin-mediated cell cycle arrest. In HCT116 PTEN (+/+) cells, curcumin caused a G2/M phase arrest, whereas it caused a G0/G1 phase arrest in HCT116 PTEN (-/-) cells. Levels of cell cycle-related proteins were consistent with these respective patterns of cell cycle arrest. CONCLUSION: Curcumin shows enhanced cytotoxicity toward PTEN-deficient cancer cells, suggesting that it might be a potential chemotherapeutic agent for cancers harboring PTEN mutations.

A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression.

Tumor hypoxia is associated with disease progression and treatment failure, but the hypoxia signaling mechanism is not fully understood. Here, we show that KLHL20, a Cullin3 (Cul3) substrate adaptor induced by HIF-1, coordinates with the actions of CDK1/2 and Pin1 to mediate hypoxia-induced PML proteasomal degradation. Furthermore, this PML destruction pathway participates in a feedback mechanism to maximize HIF-1α induction, thereby potentiating multiple tumor hypoxia responses, including metabolic reprogramming, epithelial-mesenchymal transition, migration, tumor growth, angiogenesis, and chemoresistance. In human prostate cancer, overexpression of HIF-1α, KLHL20, and Pin1 correlates with PML down-regulation, and hyperactivation of the PML destruction pathway is associated with disease progression. Our study indicates that the KLHL20-mediated PML degradation and HIF-1α autoregulation play key roles in tumor progression.

Transcription phase, protein characteristics of DEV UL45 and prokaryotic expression, antibody preparation of the UL45 des-transmembrane domain.

BACKGROUND: Some UL45 gene function of Herpesvirus was reported. While there was no any report of the duck enteritis virus (DEV) UL45 protein as yet. RESULTS: The UL45 gene and des-transmembrane domain of UL45 (named UL45Δ gene, 295-675bp of UL45) of DEV were amplified by PCR and subcloned into the prokaryotic expression vector pET-32a(+). The constructed recombinant plasmids were transformed into the host strain BL21(DE3) PLysS and induced by IPTG. SDS-PAGE analysis showed the UL45 gene couldn't express while UL45Δ gene was highly expressed. His Purify Kit or salting-out could purify the protein effectively. Using the purified protein to immunize New-Zealand rabbits and produce polyclonal antibody. The agar diffusion reaction showed the titer of antibody was 1:32. Western blot analysis indicated the purified rabbit anti-UL45Δ IgG had a high level of specificity and the UL45 gene was a part of DEV genome. The transcription phase study of UL45 gene showed that expression of UL45 mRNA was at a low level from 0 to 18 h post-infection (pi), then accumulated quickly at 24 h pi and peaked at 42 h pi. It can be detected till 72 h pi. Besides, western blot analysis of purified virion and different viral ingredients showed that the UL45 protein resided in the purified virion and the viral envelope. CONCLUSIONS: The rabbit anti-UL45Δ IgG was produced successfully and it can serve as a good tool for penetrating studies of the function of DEV UL45 protein. The transcription phase and protein characteristics analysis indicated that DEV UL45 gene was a late gene and UL45 protein may be a viral envelope protein.