Electronic Health Literacy Scale-Web3.0 for Older Adults with Noncommunicable Diseases: Validation Study.

BACKGROUND: In the current digital era, eHealth literacy plays an indispensable role in health care and self-management among older adults with noncommunicable diseases (NCDs). Measuring eHealth literacy appropriately and accurately ensures the successful implementation and evaluation of pertinent research and interventions. However, existing eHealth literacy measures focus mainly on individuals' abilities of accessing and comprehending eHealth information (Web1.0), whereas the capabilities for web-based interaction (Web2.0) and using eHealth information (Web3.0) have not been adequately evaluated. OBJECTIVE: This study aimed to examine the reliability, validity, and measurement invariance of the eHealth Literacy Scale-Web3.0 (eHLS-Web3.0) among older adults with NCDs. METHODS: A total of 642 Chinese older adults with NCDs (mean age 65.78, SD 3.91 years; 55.8% female) were recruited in the baseline assessment, of whom 134 (mean age 65.63, SD 3.99 years; 58.2% female) completed the 1-month follow-up assessment. Baseline measures included the Chinese version of the 24-item 3D eHLS-Web3.0, the Chinese version of the 8-item unidimensional eHealth Literacy Scale (eHEALS), and demographic information. Follow-up measures included the 24-item eHLS-Web3.0 and accelerometer-measured physical activity and sedentary behavior. A series of statistical analyses, for example, Cronbach α, composite reliability coefficient (CR), confirmatory factor analysis (CFA), and multigroup CFA, were performed to examine the internal consistency and test-retest reliabilities, as well as the construct, concurrent, convergent, discriminant, and predictive validities, and the measurement invariance of the eHLS-Web3.0 across gender, education level, and residence. RESULTS: Cronbach α and CR were within acceptable ranges of 0.89-0.94 and 0.90-0.97, respectively, indicating adequate internal consistency of the eHLS-Web3.0 and its subscales. The eHLS-Web3.0 also demonstrated cross-time stability, with baseline and follow-up measures showing a significant intraclass correlation of 0.81-0.91. The construct validity of the 3D structure model of the eHLS-Web3.0 was supported by confirmatory factor analyses. The eHLS-Web3.0 exhibited convergent validity with an average variance extracted value of 0.58 and a CR value of 0.97. Discriminant validity was supported by CFA results for a proposed 4-factor model integrating the 3 eHLS-Web3.0 subscales and eHEALS. The predictive validity of the eHLS-Web3.0 for health behaviors was supported by significant associations of the eHLS-Web3.0 with light physical activity (ß=.36, P=.004), moderate to vigorous physical activity (ß=.49, P<.001), and sedentary behavior (ß=-.26, P=.002). Finally, the measurement invariance of the eHLS-Web3.0 across gender, education level, and residence was supported by the establishment of configural, metric, strong, and strict invariances. CONCLUSIONS: The present study provides timely empirical evidence on the reliability, validity, and measurement invariance of the eHLS-Web3.0, suggesting that the 24-item 3D eHLS-Web3.0 is an appropriate and valid tool for measuring eHealth literacy among older adults with NCDs within the Web3.0 sphere.

Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis.

Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, no studies have assessed their roles in mammalian meiosis of females, whose abnormality accounts for over 80% of the cases of gamete-originated human reproductive disease. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of KL2 significantly reduced chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. Importantly, we demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, eliminated KL2 from chromosomes completely. KL2 also interacted with phosphorylated eukaryotic elongation factor-2 kinase; they competed for chromosome binding. We also observed that the phosphorylated KL2 was localized at spindle poles, and that KL2 phosphorylation was regulated by extracellular signal-regulated kinase 1/2. In summary, our study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.

NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

A blended face-to-face and eHealth lifestyle intervention on physical activity, diet, and health outcomes in Hong Kong community-dwelling older adults: a study protocol for a randomized controlled trial.

Background: Aging individuals are vulnerable to various Noncommunicable Diseases (NCDs). Different behaviors are closely related to a decreased risk of suffering from NCDs: sufficient Physical Activity (PA) (e.g., at least 150 mins Moderate-to-vigorous Physical Activity (MVPA) per week) and a healthy daily diet (e.g., at least five portions of Fruit and Vegetable Intake (FVI), 5-6 taels (189.0-226.8 g) Meat, Fish, Egg and Alternatives (MFEA)). Traditional face-to-face interventions were effective in behavior change. However, it was revealed to be resource-intensive and limited transfer due to poor self-regulation skills outside of face-to-face sessions. Thus, eHealth could be a supplement for older adults outside traditional face-to-face settings. The blended approach combining these two interventions might optimize the intervention effects on lifestyle behavior initiation and maintenance, but little research can be found among Hong Kong older adults. Therefore, the study aims to test a blended intervention to promote PA, diet, and health outcomes among Hong Kong community-dwelling older adults. Methods: This study will adopt a 10-week three-arm randomized controlled trial. The blended group will receive weekly (1) two 60-min face-to-face sessions with one for PA and one for diet, and (2) two web-based sessions with one for PA and one for diet. The face-to-face group will receive the same intervention content as the face-to-face sessions in the blended group. The control condition will receive a biweekly telephone call. The outcomes will include MVPA (minutes/week), FVI (portions/day), MFEA consumption (taels/day), social-cognitive factors (self-efficacy, planning, social support, action control), physical health outcomes (clinical indicators, senior physical fitness), mental health outcomes (depression, loneliness) and health-related quality of life. Data collection will be implemented at the pre-test, post-test, and 3-month follow-up test. Discussion: This is the first study evaluating a blended intervention promoting multiple health behaviors among Hong Kong community-dwelling older adults. If the effect of the blended intervention is superior to the traditional face-to-face group and the control group, it will enrich lifestyle intervention approaches and can be applied to older adults, helping them obtain health benefits. Furthermore, a better understanding of mechanisms will also have implications for theory-building. Clinical trial registration: https://www.isrctn.com/ISRCTN32329348, ISRCTN32329348.

Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST.

Although effective initially, prolonged androgen deprivation therapy (ADT) promotes neuroendocrine differentiation (NED) and prostate cancer (PCa) progression. It is incompletely understood how ADT transcriptionally induces NE genes in PCa cells. CREB1 and REST are known to positively and negatively regulate neuronal gene expression in the brain, respectively. No direct link between these two master neuronal regulators has been elucidated in the NED of PCa. We show that REST mRNA is downregulated in NEPC cell and mouse models, as well as in patient samples. Phenotypically, REST overexpression increases ADT sensitivity, represses NE genes, inhibits colony formation in culture, and xenograft tumor growth of PCa cells. As expected, ADT downregulates REST in PCa cells in culture and in mouse xenografts. Interestingly, CREB1 signaling represses REST expression. In studying the largely unclear mechanism underlying transcriptional repression of REST by ADT, we found that REST is a direct target of EZH2 epigenetic repression. Finally, genetic rescue experiments demonstrated that ADT induces NED through EZH2's repression of REST, which is enhanced by ADT-activated CREB1 signaling. In summary, our study has revealed a key pathway underlying NE gene upregulation by ADT, as well as established novel relationships between CREB1 and REST, and between EZH2 and REST, which may also have implications in other cancer types and in neurobiology.

Bootstrapping Deconfined Quantum Tricriticality.

The paradigmatic example of deconfined quantum criticality is the Neel to valence bond solid phase transition. The continuum description of this transition is the N=2 case of the CP^{N-1} model, which is a field theory of N complex scalars in 3D coupled to an Abelian gauge field with SU(N)×U(1) global symmetry. Lattice studies and duality arguments suggest the global symmetry of the CP^{1} model is enhanced to SO(5). We perform a conformal bootstrap study of SO(5) invariant fixed points with one relevant SO(5) singlet operator, which would correspond to two relevant SU(2)×U(1) singlets, i.e., a tricritical point. We find that the bootstrap bounds are saturated by four different predictions from the large N computation of monopole operator scaling dimensions, which were recently shown to be very accurate even for small N. This suggests that the Neel to valence bond solid phase transition is described by this bootstrap bound, which predicts that the second relevant singlet has dimension ≈2.36.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

Ben-JNK signaling is required for host mortality during Periplaneta fuliginosa densovirus infection.

BACKGROUND: Cockroaches are widely acknowledged as significant vectors of pathogenic microorganisms. The Periplaneta fuliginosa densovirus (PfDNV) infects the smoky-brown cockroach P. fuliginosa and causes host mortality, which identifies the PfDNV as a species-specific and environmentally friendly biopesticide. However, although the biochemical characterization of PfDNV has been extensively studied, the immune response against PfDNV remains largely unclear. RESULTS: Here, we investigated the replication of PfDNV and its associated pathological phenotype in the foregut and hindgut. Consequently, we dissected and performed transcriptome sequencing on the foregut, midgut, and hindgut separately. We revealed the up-regulation of immune response signaling pathway c-Jun N-terminal kinase (JNK) and apoptosis in response to viral infection. Furthermore, knockdown of the JNK upstream gene Ben resulted in a decrease in virus titer and delayed host mortality. CONCLUSION: Taken together, our findings provide evidence that the Ben-JNK signaling plays a crucial role in PfDNV infection, leading to excessive apoptosis in intestinal tissues and ultimately resulting in the death of the host. Our results indicated that the host response to PfDNV fosters viral infection, thereby increasing host lethality. This underscores the potential of PfDNV as a viable, environmentally friendly biopesticide. © 2024 Society of Chemical Industry.

YME1L-mediated mitophagy protects renal tubular cells against cellular senescence under diabetic conditions.

BACKGROUND: The senescence of renal tubular epithelial cells (RTECs) is crucial in the progression of diabetic kidney disease (DKD). Accumulating evidence suggests a close association between insufficient mitophagy and RTEC senescence. Yeast mitochondrial escape 1-like 1 (YME1L), an inner mitochondrial membrane metalloprotease, maintains mitochondrial integrity. Its functions in DKD remain unclear. Here, we investigated whether YME1L can prevent the progression of DKD by regulating mitophagy and cellular senescence. METHODS: We analyzed YME1L expression in renal tubules of DKD patients and mice, explored transcriptomic changes associated with YME1L overexpression in RTECs, and assessed its impact on RTEC senescence and renal dysfunction using an HFD/STZ-induced DKD mouse model. Tubule-specific overexpression of YME1L was achieved through the use of recombinant adeno-associated virus 2/9 (rAAV 2/9). We conducted both in vivo and in vitro experiments to evaluate the effects of YME1L overexpression on mitophagy and mitochondrial function. Furthermore, we performed LC-MS/MS analysis to identify potential protein interactions involving YME1L and elucidate the underlying mechanisms. RESULTS: Our findings revealed a significant decrease in YME1L expression in the renal tubules of DKD patients and mice. However, tubule-specific overexpression of YME1L significantly alleviated RTEC senescence and renal dysfunction in the HFD/STZ-induced DKD mouse model. Moreover, YME1L overexpression exhibited positive effects on enhancing mitophagy and improving mitochondrial function both in vivo and in vitro. Mechanistically, our LC-MS/MS analysis uncovered a crucial mitophagy receptor, BCL2-like 13 (BCL2L13), as an interacting partner of YME1L. Furthermore, YME1L was found to promote the phosphorylation of BCL2L13, highlighting its role in regulating mitophagy. CONCLUSIONS: This study provides compelling evidence that YME1L plays a critical role in protecting RTECs from cellular senescence and impeding the progression of DKD. Overexpression of YME1L demonstrated significant therapeutic potential by ameliorating both RTEC senescence and renal dysfunction in the DKD mice. Moreover, our findings indicate that YME1L enhances mitophagy and improves mitochondrial function, potentially through its interaction with BCL2L13 and subsequent phosphorylation. These novel insights into the protective mechanisms of YME1L offer a promising strategy for developing therapies targeting DKD.

Spatial epidemiological analysis of the burden of liver cancer in China.

Background: Liver cancer is one of the most common cancers in the world, with unique regional variations in disability-adjusted life years (DALY) rate, nearly 50% of liver cancer cases occur in China. Therefore, understanding the epidemiological characteristics of liver cancer is of utmost importance. In this study, to analyze the spatial distribution characteristics and clustering of the DALY rate of liver cancer in 1990 and 2017 in China based on provincial administrative divisions, and to explore its possible influencing factor. Methods: The DALY rate data of liver cancer at the provincial level in China were collected, the global autocorrelation of the DALY rate was analyzed by Moran's I, the local autocorrelation of the DALY rate was analyzed by Getis-Ord-Gi*, and the influencing factors related to the DALY rate were analyzed by the least squares regression model. Results: The DALY rate of liver cancer in China generally showed an increasing trend. The DALY rate increased in 22 provinces and decreased in nine provinces. In 2017, the distribution of DALY rate in all provinces showed heterogeneity, with the highest DALY rate in Guangxi (1,363.37/100,000) and the lowest in Beijing (315.78/100,000). In 2017, the low and low clustering were mainly concentrated in Inner Mongolia, Ningxia, Shanxi, Hebei, and Tianjin. The low and high clustering in Yunnan, Guizhou, and Guangdong, were surrounded by the high clustering in neighboring provinces, high and high concentration is mainly concentrated in Hunan and neighboring provinces. The results of the least square regression model showed that the per capita years of education, hepatitis B incidence and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer (P<0.05). Conclusions: The DALY rate of liver cancer in China showed an overall increasing trend. In 2017, the DALY rate of liver cancer in China had a spatial aggregation in the whole country, and the per capita years of education, the incidence of hepatitis B and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer in space.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

Two Birds with One Stone: Polymerized Thermally Activated Delayed Fluorescence Small Molecules.

Thermally activated delayed fluorescence (TADF) polymers show a great potential in low-cost, large-area and flexible full-color flat-panel displays. One of the most promising design rules is based on TADF+Linker, where a small molecular TADF unit is bonded to each other by a simple linker. Unlike the expensive vacuum deposition for small molecules, these polymerized TADF small molecules (Poly-TADF-SMs) are capable of cost-effective solution processing. Meanwhile, the good luminescent property of small molecular TADF emitters can be well inherited by Poly-TADF-SMs so as to bridge the efficiency gap between small molecules and polymers. Herein, we will highlight the recent progress of Poly-TADF-SMs, together with emphasis on their molecular design, photophysical and electroluminescence properties.

Recognition of Aedes aegypti Mosquito Saliva Protein LTRIN by the Human Receptor LTßR for Controlling the Immune Response.

Salivary proteins from mosquitoes have received significant attention lately due to their potential to develop therapeutic treatments or vaccines for mosquito-borne diseases. Here, we report the characterization of LTRIN (lymphotoxin beta receptor inhibitor), a salivary protein known to enhance the pathogenicity of ZIKV by interrupting the LTßR-initiated NF-κB signaling pathway and, therefore, diminish the immune responses. We demonstrated that the truncated C-terminal LTRIN (ΔLTRIN) is a dimeric protein with a stable alpha helix-dominant secondary structure, which possibly aids in withstanding the temperature fluctuations during blood-feeding events. ΔLTRIN possesses two Ca2+ binding EF-hand domains, with the second EF-hand motif playing a more significant role in interacting with LTßR. Additionally, we mapped the primary binding regions of ΔLTRIN on LTßR using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and identified that 91QEKAHIAEHMDVPIDTSKMSEQELQFHY118 from the N-terminal of ΔLTRIN is the major interacting region. Together, our studies provide insight into the recognition of LTRIN by LTßR. This finding may aid in a future therapeutic and transmission-blocking vaccine development against ZIKV.

Associations between Informant-Reported Cognitive Complaint and Longitudinal Cognitive Decline in Subjective Cognitive Decline A 7-Year Longitudinal Study.

OBJECTIVE: This study aimed to determine the predictive values of informant-reported memory decline (IMD) among subjective cognitive decline (SCD) older adults from a 7-year community-based cohort study. METHOD: Ninety SCD participants were included. Demographic data and neuropsychological test scores at both baseline and 7-year follow-up were collected. Differences between SCD with IMD (+IMD) and SCD without IMD (-IMD) were compared. Logistic regression models were used to determine whether baseline IMD could predict diagnostic outcomes at 7-year follow-up. RESULTS: Forty-one percent of SCD adults had IMD. At baseline, the +IMD group showed more depressive symptoms (p = 0.016) than the -IMD group. Furthermore, the Beijing-version Montreal Cognitive Assessment (MoCA), Digit Span Test-Forward, Visual Matching and Reasoning, and Wechsler Adult Intelligence Scale-RC Picture Completion (WAIS-PC) scores in the +IMD group were significantly lower than those in the -IMD group. Fifty-four percent of +IMD participants converted to mild cognitive impairment (MCI) or dementia at follow-up, and 22.6% of the -IMD participants converted to MCI. Follow-up Mini-Mental State Examination, MoCA, and Verbal Fluency Test scores of the +IMD group were significantly lower than those in the -IMD group. The +IMD group was more likely to progress to cognitive impairment at 7-year follow-up (OR = 3.361, p = 0.028). CONCLUSIONS: SCD participants with +IMD may have poorer cognition and are more likely to convert to cognitive impairment over time. Our long-term follow-up study confirmed the importance of informants' perceptions of SCD, which can help clinicians identify individuals at risk of cognitive decline.

Immunomagnetic capture and traceless release of native tumor-derived exosomes from human plasma for exploring interaction with recipient cells by aptamer-functionalized nanoflowers.

BACKGROUND: Tumor-derived exosomes (TEXs) play an important role in the development process of cancer, which can transport a large number of carcinogenic molecules to normal cells, and subsequently promote tumor metastasis. However, TEXs that were utilized in most of previous researches were obtained from the cell medium of tumor cell lines, which cannot reflect the physiological state of primary cells in vivo. Isolation of native TEXs from human plasma with intact function is contributed to exploring the interaction between TEXs and recipient cells for understanding their true biological functions. RESULTS: We developed a strategy that involves both capture and release processes to obtain native TEXs from plasma of cancer patients. An MoS2-based immunomagnetic probe (Fe3O4@MoS2-Au-Aptamer, named as FMAA) with the advantages of high surface area, magnetic response and abundant affinity sites was designed and synthesized to capture TEXs through recognizing high-expression tumor-associated antigens of EpCAM. With the assistance of complementary sequences of EpCAM, TEXs were released with non-destruction and no residual labels. According to NTA analysis, 107-108 TEXs were recovered from per mL plasma of breast cancer patients. The interaction between native TEXs and normal epithelial cells confirms TEXs could induce significant activation of autophagy of recipient cells with co-culture for 12 h. Proteomics analysis demonstrated a total of 637 proteins inside epithelial cells had dynamic expression with the stimulation of TEXs and 5 proteins in the pathway of autophagy had elevated expression level. SIGNIFICANCE: This work not only obtains native TEXs from human plasma with non-destruction and no residual labels, but also explores the interaction between TEXs and recipient cells for understanding their true biological functions, which will accelerate the application of TEXs in the field of biomarkers and therapeutic drugs.

Association between systemic immune inflammation Index and all-cause mortality in incident peritoneal dialysis-treated CKD patients: a multi-center retrospective cohort study.

BACKGROUND: Chronic inflammatory disorders in peritoneal dialysis (PD) contribute to the adverse clinical outcome. Systemic immune inflammation index (SII) is the novel and convenient measurement that is positively associated with various diseases. However, scarce is known regarding the association between SII with all-cause mortality among PD patients. METHODS: In this multi-center retrospective cohort study, 1,677 incident patients with PD were enrolled. Eligible patients were stratified into groups based on SII level: tertile 1(< 456.76), tertile 2(456.76 to 819.03), and tertile 3(> 819.03). The primary endpoint was the all-cause mortality. Both Cox regression analysis and competing risk models were used to examine the association between SII and all-cause mortality. Subgroup analysis was performed to assess the influence of the SII tertiles on all-cause mortality in different subgroups. RESULTS: During the follow-up period of 30.5 ± 20.0 months, 26.0% (437/1,677) patients died, of whom the SII tertile 3 group accounted for 39.1% (171/437) of the deaths. Patients in the SII tertile 3 group had a higher all-cause mortality rate than patients in the SII tertile 1 and 2 groups (log-rank = 13.037, P < 0.001). The SII tertile 3 group was significantly associated with 80% greater risk (95% confidence interval:1.13 to 2.85; P = 0.013) compared with the SII tertile 1 group in multivariable Cox regression analysis. The competing risk model also indicated that the relationship between SII tertiles and all-cause mortality remains (subdistribution hazard ratio: 1.86; 95% confidence interval: 1.15 to 2.02, P = 0.011). Furthermore, the relationship between the log-transformed SII and all-cause mortality in patients with PD was nearly linear (P = 0.124). CONCLUSION: A close relationship was observed between the SII and all-cause mortality in patients undergoing PD, suggesting that more attention should be paid to the SII, which is a convenient and effective measurement in clinical practice.

Outcome of chairside CAD/CAM ceramic restorations on endodontically treated posterior teeth: a prospective study.

OBJECTIVE: The aim of this study was to evaluate the outcome and risk factors for chairside CAD/CAM full cusp coverage restorations on endodontically treated posterior teeth after 3 years of follow-up. METHODS: A total of 245 endodontically treated posterior teeth of 224 patients were included and restored with CAD/CAM full cusp coverage all-ceramic restorations according to a standardized protocol. Patients were recalled after treatments 1 to 3 years and underwent clinical and radiological examinations. At recall, modified FDI criteria were used to determine treatment outcomes by 2 evaluators. Success was determined when FDI scores were 1-2, and failure was indicated when FDI scores were 5. Logistic regression analysis was performed to evaluate potential risk factors. RESULTS: A total of 183 patients presented at recall, and the clinical outcomes of 201 teeth were analyzed with a recall rate of 82.0% for teeth and 81.7% for patients after 1-3 years of follow-up.185 of 201 teeth were found to have FDI scores of 1-2, and the success rate was 92%. No teeth were extracted during the follow-up period. Fourteen failed cases with an FDI score of 5 presented restoration dislocation, fracture of restoration or/and tooth. Logistic regression analysis revealed that oral parafunction (OR 2.281, 95% CI 2.2 ~ 47.5, P value 0.01) was a risk factor for success rate. CONCLUSION: Chairside CAD/CAM all-ceramic full cusp coverage restoration was (could be) a promising alternative for restoring endodontically treated posterior teeth.

Association of albumin to non-high-density lipoprotein cholesterol ratio with mortality in peritoneal dialysis patients.

OBJECTIVE: Malnutrition and inflammation are associated with mortality in peritoneal dialysis (PD) patients. Serum albumin and non-high-density lipoprotein cholesterol (non-HDL-C) are independently associated with mortality in PD patients. Combining albumin and non-HDL-C with mortality may be more plausible in clinical practice. METHODS: This retrospective cohort study included 1954 Chinese PD patients from 1 January 2009 to 31 December 2016. Kaplan-Meier curve was used to determine the relationship between albumin to non-HDL-C ratio and all-cause mortality. Cox regression analysis was applied to assess the independent predictive value while adjusting for confounding factors. Competitive risk analysis was used to examine the effects of other outcomes on all-cause mortality prognosis. RESULTS: In the 33-month follow-up period, there were 538 all-cause deaths. Kaplan-Meier analysis presented significant differences in all-cause mortality. Multivariate Cox regression showed that the risk of all-cause mortality was lower in the moderate group (9.36-12.79) (HR, 0.731; 95% CI, 0.593-0.902, p = 0.004) and the highest group (>12.79) (HR, 0.705; 95% CI, 0.565-0.879, p = 0.002) compared to the lowest group (≤9.36). Competitive risk analysis revealed significant differences for all-cause mortality (p < 0.001), while there was no statistical significance for other competing events. CONCLUSIONS: Low albumin to non-HDL-C ratio was associated with a high risk of all-cause mortality in PD patients. It may serve as a potential prognostic biomarker in PD patients.