Membrane specificity of the human cholesterol transfer protein STARD4.

STARD4 regulates cholesterol homeostasis by transferring cholesterol between the plasma membrane and endoplasmic reticulum. The STARD4 structure features a helix-grip fold surrounding a large hydrophobic cavity holding the sterol. Its access is controlled by a gate formed by the Ω1 and Ω4 loops and the C-terminal α-helix. Little is known about the mechanisms by which STARD4 binds to membranes and extracts/releases cholesterol. All available structures of STARD4 are without a bound sterol and display the same closed conformation of the gate. The cholesterol transfer activity of the mouse STARD4 is enhanced in the presence of anionic lipids, and in particular of phosphatidylinositol biphosphates (PIP2) for which two binding sites were proposed on the mouse STARD4 surface. Yet only one of these sites is conserved in human STARD4. We here report the results of a liposome microarray-based assay and microseconds-long molecular dynamics simulations of human STARD4 with complex lipid bilayers mimicking the composition of the donor and acceptor membranes. We show that the binding of apo form of human STARD4 is sensitive to the presence of PIP2 through two specific binding sites, one of which was not identified on mouse STARD4. We report two novel conformations of the gate in holo-STARD4: a yet-unobserved close conformation and an open conformation of Ω4 shedding light on the opening/closure mechanism needed for cholesterol uptake/release. Overall, the modulation of human STARD4 membrane-binding by lipid composition, and by the presence of the cargo supports the capacity of human STARD4 to achieve directed transfer between specific organelle membranes.

Imaging GPCR Dimerization in Living Cells with Cucurbit[7]uril and Hemicyanine as a "Turn-On" Fluorescence Probe.

Although multiple forms of dimers have been described for GPCR, their dynamics and function are still controversially discussed field. Fluorescence microscopy allows GPCR to be imaged within their native context; however, a key challenge is to site-specifically incorporate reporter moieties that can produce high-quality signals upon formation of GPCR dimers. To this end, we propose a supramolecular sensor approach to detect agonist-induced dimer formation of µ-opioid receptors (µORs) at the surface of intact cells. With the macrocyclic host cucurbit[7]uril and its guest hemicyanine dye tethered to aptamer strands directed against the histidine residues, the sensing module is assembled by host-guest complexation once the histidine-tagged µORs dimerize and bring the discrete supramolecular units into close proximity. With the enhanced sensitivity attributed by the "turn-on" fluorescence emission and high specificity afforded by the intermolecular recognition, in situ visualization of dynamic GPCR dimerization was realized with high precision, thereby validating the supramolecular sensing entity as a sophisticated and versatile strategy to investigate GPCR dimers, which represent an obvious therapeutic target.

Acceptance and Commitment Therapy Among Informal Caregivers of People With Chronic Health Conditions: A Systematic Review and Meta-Analysis.

Importance: Although there is substantial evidence to suggest the health benefits of acceptance and commitment therapy (ACT) among informal caregivers of people with chronic health conditions, the great variation in intervention designs among published studies limits its application. Objectives: To identify intervention characteristics of ACT that are associated with improved psychological health and to assess the acceptability of ACT among informal caregivers. Data Sources: Seven English- and 3 Chinese-language databases without limits on publication dates, the reference lists of previous reviews, and gray literature were searched up to February 2023. Study Selection: Randomized clinical trials comparing the effect of ACT vs control groups on improving psychological health among informal caregivers. Data Extraction and Synthesis: Two reviewers independently screened searched records and extracted data from eligible studies. Random-effects meta-analysis and mixed-effects metaregression were performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. Main Outcomes and Measures: Psychological health outcomes (eg, depressive symptoms) measured by valid measurements and the acceptability of ACT based on identified parameters. Results: A total of 29 studies with 2010 participants, published between 2015 and 2023, were identified. ACT showed moderate to large effect sizes for improving psychological health at postintervention assessments (Hedges g range, -0.55 [95% CI, -0.98 to -0.12] to -1.14 [95% CI, -1.83 to -0.45]) and at 1-to-3-month and 4-to-6-month follow-ups (Hedges g range, -0.47 [95% CI, -0.69 to -0.25] to -1.29 [95% CI, -2.33 to -0.24]). Multivariable metaregression analysis regarding intervention characteristics found that ACT delivered in a mixed individual- and group-based format, face-to-face, or through more intervention sessions was associated with greater improvements for experiential avoidance (face-to-face: ß = -1.170 [95% CI, -2.020 to -0.319]; number of sessions: ß = -0.242 [95% CI, -0.353 to -0.130]), depressive symptoms (mixed delivery format: ß = -2.583 [95% CI, -4.845 to -0.321]; face-to-face: ß = -1.555 [95% CI, -3.002 to -0.108]), or anxiety symptoms (face-to-face: ß = -1.241 [95% CI, -2.337 to -0.146]). In general, ACT had low attrition rates (11%), and participants' adherence (51%-80%) and satisfactory ratings (72%-95%) lend support to its acceptability. Conclusions and Relevance: This systematic review and meta-analysis found that ACT was consistently associated with improvements in psychological health, supporting its application to improve informal care for chronic disease management. This review provides specific details on the design parameters of ACT for achieving greater efficacy.

Barriers and facilitators to offering post-intensive care follow-up services from the perspective of critical care professionals: A qualitative study.

BACKGROUND: Various programmes and models for post-intensive care unit (ICU) follow-up services have been developed worldwide. In China, post-ICU follow-up remains in the exploratory stage and little is known regarding the appropriate form and challenges of implementation, which need to be further explored. AIM: This study aimed to explore and describe the barriers to and facilitators of post-ICU follow-up services from the perspective of critical care professionals. DESIGN: This was a descriptive qualitative study. Semi-structured interviews were conducted with 21 health care workers whose units had offered ICU survivors different forms of follow-up services; the data were analysed by qualitative content analysis during August 2022 and December 2022. SETTING: The study was conducted at 14 ICUs in 11 tertiary hospitals in Shanghai, China. FINDINGS: Seventeen subthemes were extracted as barriers and facilitators in the follow-up of ICU survivors. In the initiating process, the barriers included the restriction of decision-making rights and scope of practice, indifferent attitude towards survivors and repeated work. The facilitators included admitted significance, the needs of ICU survivors, the conscientiousness of professionals and the pioneers and leadership support. In the implementation process, lack of confidence, lack of cooperation in medical consortium, distrusted relationships, restrictions of medical insurance, ageing problems and insufficient human resources acted as barriers, whereas lessons learned, positive feedback and digital support served as facilitators. Furthermore, recommendations and tips were identified for offering follow-up services. CONCLUSION: Medical personnel can better utilize available resources and develop strategies to overcome constraints by gaining insights into the abovementioned barriers and facilitators. The findings of this study can provide a useful reference for structured and systematic follow-ups to ameliorate post-intensive care syndrome in low- and middle-income countries. RELEVANCE TO CLINICAL PRACTICE: Publicity and educational measures play a crucial role in enhancing the awareness of survivors and the consensus of health care professionals from medical consortium regarding impairments after critical care. Leadership and policy support can address numerous obstacles to guiding follow-up services.

Combined exercise and cognitive interventions for adults with mild cognitive impairment and dementia: A systematic review and network meta-analysis.

BACKGROUND: Exercise and cognitive interventions are beneficial for adults with preclinical and clinical dementia, but it is unclear whether the combination of these two components could generate synergistic benefits and what intervention designs would optimize this effect. OBJECTIVES: This review aims to compare the effects of combined exercise and cognitive interventions on cognitive, psychological, functional outcomes, and health-related quality of life with the corresponding single approach and control groups in adults with mild cognitive impairment and dementia. It also aims to identify the optimal intervention design and factors affecting treatment effects. METHODS: A comprehensive search was conducted in ten databases from inception to 23rd November 2022. The methodological quality of studies was evaluated by the Cochrane risk of bias tool. Pairwise meta-analyses were performed to assess the effects of combined interventions relative to the single type of intervention and control groups, with further subgroup analysis to explore the factors affecting treatment effects. Network meta-analyses were used to identify the optimal intervention components. RESULTS: Twenty-nine randomized controlled trials involving 2910 participants were included. The results of pairwise meta-analyses indicated that combined interventions were superior to exercise in improving response inhibition, working memory, and delayed recall, but were not superior to cognitive interventions in all outcomes. Combined interventions were superior to active/passive controls in improving global cognition, response inhibition, immediate recall, delayed recall, category fluency, processing speed, and visuospatial ability. Influences of the clinical severity of dementia (mild cognitive impairment vs dementia), combination format (sequential vs simultaneous combination), mode of delivery (group-based vs individual-based vs mixed), training duration (short: ≤12 weeks vs medium: 13-24 weeks vs long: >24 weeks), and types of control (active vs passive control) were not detected. The network meta-analysis results indicated that the optimal intervention components varied across different outcomes, with multimodal exercise combining cognitive training demonstrated the greatest effects among all other combined or single component interventions in improving global cognition. CONCLUSIONS: This review suggests the advantage of combined interventions over exercise with comparable effects when compared with cognitive interventions in the population with mild cognitive impairment and dementia. Full scale multi-arm randomized controlled trials to compare the effects of combined interventions with cognitive interventions are warranted.

Serum Proteomic Analysis by Nanoflow LC-MS/MS-Based Proteomics in IgA Chronic Kidney Disease.

BACKGROUND: IgA nephropathy (IgAN) is the most frequently occurring primary glomerulonephritis. A lack of specific biomarkers hinders the early diagnosis and treatment of this disease. This study analyzes and validates potential serum biomarkers using mass spectrometry proteomics. METHODS: Global proteomics profiles of serum from 60 patients with IgAN and 43 healthy control subjects were compared to identify significantly changed proteins. These proteins were validated with targeted proteomics using parallel reaction monitoring (PRM) in an independent validation set consisting of samples from 67 different stage IgAN patients and 60 healthy controls. RESULTS: A total of 37 significantly changed proteins were found in the discovery set, among which 18 proteins were identified as potential biomarkers for IgAN through PRM assays in the validation set. Of these 18 proteins, IgGFc-binding protein, MS-A1 light chain variable region, transthyretin, ficolin-3, and myosin-reactive immunoglobulin light chain variable region were up-regulated in different IgAN stages, B cell receptor heavy chain variable region, rheumatoid factor RF-ET6, heavy chain Fab, cryocrystalglobulin CC1 heavy chain variable region, FLJ94213, lumican, and Q68CN4 (uncharacterized protein) were down-regulated in different IgAN stages. These proteins support previous findings that CKD is accompanied by altered immune response. CONCLUSIONS: This study lays the groundwork for additional research using biomarkers to clinically diagnose IgAN. These proteins are potential molecular markers that could help us understand the potential molecular mechanism of IgAN.

HER2-low status may predict poor neoadjuvant chemotherapy response in HR-negative breast cancer: a real-world multicenter study.

OBJECTIVE: We aimed to investigate the impact of human epidermal growth factor receptor 2 status (human epidermal growth factor receptor 2-low versus human epidermal growth factor receptor 2-zero) on pathological response to neoadjuvant chemotherapy and survival outcomes in early-stage breast cancer. METHODS: Patients with primary invasive breast cancer received neoadjuvant chemotherapy between July 2018 and July 2021 were identified from six hospitals. The primary efficacy end-point was total pathological complete response. The second short-term efficacy end-points include breast pathological complete response, axillary lymph nodes pathological complete response and the score of Miller-Payne grade. Long-term efficacy end-point was disease-free survival. RESULTS: 429 patients with human epidermal growth factor receptor 2 negative invasive tumors were included, 267 (62.24%) had human epidermal growth factor receptor 2-low tumors. Hormone receptor-positive patients had a higher percentage of human epidermal growth factor receptor 2-low tumors compared to hormone receptor-negative patients (71.97% versus 42.14%). The pathological response rate was significantly lower in human epidermal growth factor receptor 2-low tumors than in human epidermal growth factor receptor 2-zero tumors for total patients in univariate analysis, including the rates of total pathological complete response (5.2% versus 14.2%), breast pathological complete response (6.4% versus 17.3%), nodes pathological complete response (26.3% versus 37.7%) and MP4-5 (21.2% versus 33.8%). Subgroup analysis showed that the rates of total pathological complete response, breast pathological complete response and MP4-5 were also significantly lower in human epidermal growth factor receptor 2-low tumors versus human epidermal growth factor receptor 2-zero tumors in both univariate and multivariate analysis in hormone receptor-negative subgroup. With the median follow-up of 24 months, disease-free survival was comparable between these two subgroups (P = 0.816). CONCLUSIONS: Our results demonstrate that human epidermal growth factor receptor 2-low tumors achieved a significantly lower pathological complete response rate with conventional chemotherapy than those with human epidermal growth factor receptor 2-zero tumors, especially for hormone receptor-negative group. Large, randomized, prospective studies are needed to confirm our data and further evaluate the prognostic value of human epidermal growth factor receptor 2-low expression.

Teaching PCR for Simultaneous Sensing of Gene Transcription and Downstream Metabolites by Cucurbit[8]uril-Mediated Intervention of Polymerase Activity.

The target of typical PCR analysis is restricted to nucleic acids. To this end, we report here a novel strategy to simultaneously detect genetic and metabolic markers using commercial PCR kits with cucurbit[8]urils (CB[8]) implemented to manipulate the activity of Taq DNA polymerase. CB[8] binds with the nonionic surfactants and displaces them from the polymerase surface, resulting in decreased enzyme activity. Meanwhile, the inhibited enzyme can be reversibly activated when spermine, the downstream metabolite of ornithine decarboxylase (ODC), is present in the sample, which competitively binds to CB[8] and recovers polymerase activity. CB[8] was implemented in conventional PCR kits not only to reduce false-positive results but also to extend the detection range of PCR technology. With this novel method to detect ODC in cell lysates containing both the nucleotides and intracellular metabolites, positive results were only observed in highly active HEK 293T cells, whereas silent cells treated with ODC inhibitor showed negative readouts, therefore providing a simple but elegant dual-modality PCR method for precision diagnosis.

Identification of novel saltiness-enhancing peptides from yeast extract and their mechanism of action for transmembrane channel-like 4 (TMC4) protein through experimental and integrated computational modeling.

Excessive consumption of sodium salt is one of the important inducers of cardiovascular and cerebrovascular diseases. The reduction of physical labor and attention to health make research on low-sodium salt imminent. Ultrafiltration, gel filtration, preparative high-performance liquid chromatography, and liquid chromatography with tandem mass spectrometry were employed for further purification and identification of the salty enhancing peptides in yeast extracts. Moreover, human transmembrane channel-like 4 (TMC4) was constructed and evaluated by computer-based methods, and salt-enhancing peptides were identified based on its allosteric sites. PN, NSE, NE and SPE were further determined to be salty enhancing peptides through sensory evaluation, and their taste mechanism was investigated. The results presented here suggest that silicon screening focused on TMC4 allosteric sites and sensory evaluation experiments can greatly increase the discoverability and identifiability of salty enhancer peptides, and this strategy is the first to be applied to the development of salty enhancer peptides.

Inhibition of Axl Promotes the Therapeutic Effect of Targeted Inhibition of the PI3K/Akt Pathway in NRAS Mutant Melanoma Cells.

Melanoma is a malignant tumor produced by highly aggressive and metastatic melanocytes. NRAS mutation is a relatively common mutation in melanoma cells. Mitogen-activated protein kinase (MAPK) signaling pathway and the PI3K/Akt pathway in melanoma cells are relatively common signaling pathways. In this study, we investigated the effect of inhibition of Axl expression on the targeted inhibition of the PI3K/Akt pathway in NRAS-mutant melanoma cells. In this study, immunohistochemistry and western blot methods were used to detect the expression of Axl and Akt proteins in melanoma cells. Axl inhibitor was added, and it detected the inhibitory efficiency of Akt inhibitor in melanoma cells. Finally, a melanoma mouse model was established, and it detected the proliferation and apoptosis of mouse tumor cells induced by Axl inhibitor and Akt inhibitor. The results showed that Axl and Akt were highly expressed in NRAS-mutant melanoma cells, and stimulation of Axl expression could reduce the inhibitory effect of Akt inhibitor on melanoma cells. The addition of Axl inhibitor can synergistically promote the effect of Akt inhibitor, slow down the proliferation of tumor cells, and induce cell apoptosis. According to the experiment in this study, Axl inhibitor combined with Akt inhibitor has a stronger therapeutic effect on melanoma than Akt inhibitor alone.

Light-Controlled Friction by Carboxylic Azobenzene Molecular Self-Assembly Layers.

Nowadays, reversible friction regulation has become the focus of scientists in terms of the flexible regulatory structure of photosensitive materials and theories since this facilitates rapid development in this field. Meanwhile, as an external stimulus, light possesses great potential and advantages in spatiotemporal control and remote triggering. In this work, we demonstrated two photo-isomerized organic molecular layers, tetra-carboxylic azobenzene (NN4A) and dicarboxylic azobenzene (NN2A), which were selected to construct template networks on the surface of the highly oriented pyrolytic graphite (HOPG) to study the friction properties, corresponding to the arrangement structure of self-assembled layers under light regulation. First of all, the morphology of the self-assembled layers were characterized by a scanning tunneling microscope (STM), then the nanotribological properties of the template networks were measured by atomic force microscope (AFM). Their friction coefficients are respectively changed by about 0.6 and 2.3 times under light control. The density functional theory (DFT) method was used to calculate the relationship between the force intensity and the friction characteristics of the self-assembled systems under light regulation. Herein, the use of external light stimulus plays a significant role in regulating the friction properties of the interface of the nanometer, hopefully serving as a fundamental basis for further light-controlling research for the future fabrication of advanced on-surface devices.

Similar seed dispersal systems by local frugivorous birds in native and alien plant species in a coastal seawall forest.

Frugivorous birds play an important role in seed dispersal. Alien plant species' seeds are dispersed by local birds in order to establish populations in new habitats. Alien plant species that produce fruits similar to that of native species have the potential to attract local birds, creating new mutualistic systems that are similar to the local ones. In autumn 2018 and 2019, we studied the seed dispersal systems of an alien plant species, Phytolacca americana, and a native species, Cayratia japonica, in a coastal seawall forest. Both plant species' fruit, frugivorous bird foraging behaviors, seed germination rates, and seedling microhabitats were examined to determine whether the alien species had a similar seed dispersal system to that of the native species. Our results showed that P. americana and C. japonica had similar fruit type, color, and ripening period. There was a positive correlation between the percentage rate of fruit ripening and the percentage rate of fruit missing for both plant species, indicating that local frugivorous birds have the potential to sufficiently disperse the alien seeds to enable its spread in the coastal seawall forest (simple linear regression, P. americana: ß = 0.863 ± 0.017, R2 adj = 0.978, P < 0.01; C. japonica: ß = 0.787 ± 0.034, R2 adj = 0.898, P < 0.01). Eleven bird species consumed the fruits of the alien species or native species during the study period. Similar results were shown across alien and native species in bird foraging behavior (feeding frequency, feeding duration and first stop distance) indicating that a similar seed dispersal relationship had been established between local frugivorous and both plant species. The alien plant had a higher number of fruits carried by birds, suggesting that P. americana had a slightly higher fruit consumption than that of C. japonica (t-test, P < 0.01). Alien plant seedlings grow more abundant in forest gap microhabitat (t-test, P < 0.01). Our results confirmed that bird digestion promotes seed germination success in both plant species. Our study suggests that in a narrow coastal seawall forest, alien plant species can successfully establish their populations by relying on similar seed dispersal systems as the local species.

The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-ß Signaling Pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. Herein, we explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC. METHODS: Next-generation sequencing was conducted to compare the expression of different lncRNAs in TNBC tumor and paracancerous tissues, after which ADAMTS9-AS2differential expression in these tumor tissues was evaluated via qPCR. The functional role of this lncRNA was assessed by overexpressing it in vitro and in vivo. FISH and PCR were used to assess the localization of ADAMTS9-AS2within cells. Downstream targets of ADAMTS9-AS2 signaling were identified via RNA pulldown assays and transcriptomic sequencing. RESULTS: The expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size. Overexpressing ADAMTS9-AS2 promoted the apoptotic death and cell cycle arrest of tumor cells in vitro and inhibited tumor growth in vivo. From a mechanistic perspective, ADAMTS9-AS2 was found to control the expression of RPL22 and to thereby modulate TGF-ß signaling to control TNBC progression. CONCLUSION: ADAMTS9-AS2 controls the expression of RPL22 and thereby regulates TNBC malignancy via the TGF-ß signaling pathway.

A host-based two-gene model for the identification of bacterial infection in general clinical settings.

OBJECTIVES: In this study, we aimed to develop a simple gene model to identify bacterial infection, which can be implemented in general clinical settings. METHODS: We used a clinically availablereal-time quantitative polymerase chain reaction platform to conduct focused gene expression assays on clinical blood samples. Samples were collected from 2 tertiary hospitals. RESULTS: We found that the 8 candidate genes for bacterial infection were significantly dysregulated in bacterial infection and displayed good performance in group classification, whereas the 2 genes for viral infection displayed poor performance. A two-gene model (S100A12 and CD177) displayed 93.0% sensitivity and 93.7% specificity in the modeling stage. In the independent validation stage, 87.8% sensitivity and 96.6% specificity were achieved in one set of case-control groups, and 93.6% sensitivity and 97.1% specificity in another set. CONCLUSIONS: We have validated the signature genes for bacterial infection and developed a two-gene model to identify bacterial infection in general clinical settings.

Low Expression of PLAT in Breast Cancer Infers Poor Prognosis and High Immune Infiltrating Level.

PURPOSE: Breast cancer accounts for the highest incidence of tumors in women. Immune infiltrating of the tumor microenvironment positively correlates with the overall survival of breast cancer patients. PLAT can affect the development of many cancers, but its mechanism in breast cancer is unclear. We assessed the correlation between PLAT and immune infiltrating in breast cancer based on the TCGA database. PATIENTS AND METHODS: The expression and DNA methylation of PLAT in breast cancer with different clinical characteristics was tested by Wilcoxon signed rank test and displayed by box plot. Sequentially, Kaplan-Meier plot was employed to compare the difference in overall survival rates between patients with different expressed levels. Univariate and multivariate Cox regression analyses were used to validate whether PLAT is an independent prognostic factor of breast cancer. After that, GO, KEGG, and gene-set enrichment analysis were employed to do functional enrichment analysis. Finally, TIMER, TISIDB database, and ssGSEA algorithm were used to assess the correlation between PLAT expression and various immune characteristics. The correlation between PLAT expression and DNA methylation was examined by Pearson correlation coefficient. RESULTS: PLAT displays differential expression levels in breast cancer patients with various clinical characteristics. As an independent protective factor for breast cancer, PLAT may significantly correlate with the immune status of breast cancer by adjusting many immune molecules and affecting the immune infiltration in the tumor microenvironment. DNA methylation of PLAT downregulates the gene expression and affects the prognosis of breast cancer. CONCLUSION: PLAT can be considered a potential biomarker to predict breast cancer prognosis and might contribute to the development of immunological treatment strategies.

Effects of nurse-led interventions on early detection of cancer: A systematic review and meta-analysis.

BACKGROUND: Early detection of cancer serves an important strategy for cancer control, but its uptake rate remains relatively limited. Nurse-led interventions may have potential benefits for the early detection of cancer, but the evidence remains unclear. OBJECTIVES: Synthesise the evidence on the impact of nurse-led interventions on early cancer detection. The primary outcome was early cancer detection uptake rate. Secondary outcomes were cancer knowledge, early detection beliefs, diagnosed precancerous lesions and early-stage cancers. DESIGN: A systematic review and meta-analysis of randomised controlled trails. DATA SOURCES: Eight English language databases (British Nursing Index, Cochrane Central Register of Controlled Trials, CINAHL Complete, EMBASE, Ovid Emcare, Medline, Scopus, Web of Science Core Collection) and three Chinese language databases (Chinese Biomedical Literature Databases, China Journal Net, and Wanfang Data) were searched from inception date to September 2019. Grey literature and reference lists of included studies were also examined. REVIEW METHODS: Two reviewers independently assessed eligibility, extracted data and evaluated methodological quality using the Cochrane risk of bias (RoB 2.0) tool. Meta-analyses and descriptive analyses were used. Subgroup analyses were conducted for study settings and intervention types. RESULTS: Ten studies examined the effects of nurse-led interventions, including education, patient reminders, counselling, and patient navigation, on early detection of breast or cervical cancer, colorectal cancer, and lung cancer. Nurse-led interventions improved the uptake rates of mammography [risk ratio (RR) = 1.97; 95% confidence interval (CI): 1.17-3.33; p = 0.01], clinical breast examination (RR = 2.16; 95% CI: 1.02-4.59; p = 0.05), regular breast self-examination (RR = 2.01; 95% CI: 1.54-2.63; p < 0.001), and colonoscopy (RR = 1.90; 95% CI: 1.57-2.30; p < 0.001), but not of faecal blood occult tests. Subgroup analyses showed significantly improved mammography and clinical breast examination uptake rates for interventions conducted at health centres, and that patient navigation had better effects on improving colonoscopy uptake rates than did counselling. The intervention also improved cancer knowledge, early detection beliefs, and cases of detected precancerous lesions. CONCLUSIONS: Nurse-led interventions may improve early cancer detection uptake rates, cancer knowledge, early detection beliefs, and cases of detected precancerous lesions. The effects of nurse-led interventions conducted in home settings on improving mammography and clinical breast examination uptake rates may need further exploration. Patient navigation may be superior to counselling in improving colonoscopy uptake rates. Social media may be an option for delivering early cancer detection guidance, but needs to be further explored. Tweetable abstract: Nurse-led interventions have potential effects on promoting early detection of cancer.

Proteome profiling of gestational diabetes mellitus at 16-18 weeks revealed by LC-MS/MS.

BACKGROUND: The practices used to diagnose gestational diabetes mellitus (GDM) could only be carried out around the time of detectable symptoms, and predictive capacity is little. METHODS: LC-MS/MS was conducted to explore overview proteomics for GDM complicated pregnant woman at 16-18 gestation weeks, while normal pregnant for control. Enzyme-linked immunosorbent assay was further applied in an independent cohort of 15 GDM cases and 15 controls for verification. RESULTS: The results indicated that 24 protein expression levels were significantly changed in GDM group samples, and inflammation, oxidative stress, insulin resistance, blood coagulation, and lipid homeostasis were associated with GDM. The abnormal expression of CRP and IGFBP2 was verified in the first-trimester maternal plasma in women who subsequently developed GDM. CONCLUSIONS: This study not only identified 24 potential predictive biomarkers for GDM also provided a global overview of protein rearrangements induced by GDM.

Macroscale Light-Controlled Lubrication Enabled by Introducing Diarylethene Molecules in a Nanoconfinement.

Reversible friction regulation is of long-standing great interest in the fields of both industry and scientific research, so some materials and theories have been developed aiming to solve this problem. Light-sensitive materials are promising because of the easy controllable switching of the properties and structures. Here, a reversible light-controlled macrolubrication was realized by regulating the performance of nanoscale light-sensitive molecules adsorbed on contact surfaces. In this work, symmetric diarylethene and asymmetric diarylethene had been designed and synthesized as functional materials. The friction forces were found to be obviously increased upon exposure to ultraviolet light and decayed to the initial value under visible light. In addition, the friction coefficient changed alternately with ultraviolet and visible illumination. According to the results of experiments and simulation of material properties, the behavior was suggested to be attributed to the difference in shear stiffness of the nanoscale diarylethene molecule adsorption layer triggered by two wavelength lights. This work not only provides a new lubrication regulation technology but also develops intelligent engineering materials.

Role of regulatory T cells and CD8+ T lymphocytes in the dissemination of circulating tumor cells in primary invasive breast cancer.

Circulating tumor cells (CTCs) dissemination is involved in tumor metastasis and is an independent prognostic factor in patients with primary and metastatic breast cancer. Regulatory T cells (Tregs) and cluster of differentiation (CD)8+ T lymphocytes are the main types of immune cells in the tumor microenvironment and exert opposite roles on the progression and outcome of breast cancer. The aim of the present study was to evaluate the associations between CTCs and intratumoral/peritumoral Tregs and CD8+ T lymphocytes in breast cancer. Peripheral CTCs were detected by a multi-marker quantitative polymerase chain reaction platform in 167 patients with invasive breast cancer. Intratumoral/peritumoral Tregs and CD8+ T lymphocytes were assessed by immunohistochemistry in 167 patients with invasive breast cancer to establish an association between these cell types and detection of peripheral CTCs. CTCs were detected in 55% of the patients with breast cancer. The prevalence of CTCs was positively associated with the number of intratumoral (P=0.002) and peritumoral Tregs (P=0.045), and the primary tumor size (P=0.012). This result was verified by analyzing intratumoral Tregs (P=0.044) and primary tumor size (P=0.044) with multivariate analysis, which indicated that the CTC-positive rate increased with an increasing number of intratumoral Tregs and a larger tumor size In the multivariate analysis, other variables including menopause, tumor-node-metastasis stage and peritumoral Tregs were not associated with the prevalence of CTCs. The prevalence of CTCs was inversely and weakly associated with the number of peritumoral CD8+ T lymphocytes using the univariate analysis, however this result was not statistically significant (P=0.470). In conclusion, regulatory T cells and CD8+ T lymphocytes may be involved, at least in part, in the CTCs dissemination of breast cancer, whereby Tregs appear to exert the dominant effect. Furthermore, the role of Tregs in the progression of breast cancer may be mediated by suppressing the dissemination of CTCs, which is primarily determined by intratumoral Tregs.