Dye-sensitized rare-earth-doped nanoprobe for simultaneously enhanced NIR-II imaging and precise treatment of bacterial infection.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for causing life-threatening infections that result in high morbidity and mortality rates. The development of advanced imaging and therapeutic methods for in vivo diagnosis and treatment of MRSA infections remains challenging. Here, we develop a hybrid nanoplatform based on rare-earth-doped nanoparticles (RENPs) sensitized by a moiety-engineered near-infrared (NIR) TPEO-820 dye and with a ZIF-8 layer that incorporates CysNO, a photochemically triggered nitric oxide donor. We then use the hybrid for both NIR-II bioimaging and photoactivatable treatment of MRSA-infected wounds. We show that the NIR dye sensitization leads to an 8.5-fold enhancement of the downshifting emission and facilitates deep-tissue NIR-II imaging of bacterial infections. Moreover, the sensitization strategy enhances the UV emission of RENPs by two orders of magnitude, leading to the efficiently controllable release of nitric oxide for effective disinfection of MRSA in vitro and in vivo. The hybrid nanoplatform thus offers promising opportunities for simultaneous localization and controllable treatment of MRSA. STATEMENT OF SIGNIFICANCE: Early detection and treatment of MRSA infections are crucial for reducing public health risks. It is a significant challenge that develops sensitive in vivo diagnosis and complete elimination of drug-resistant bacterial infections. Herein, a nanoplatform has been developed for photoactivatable therapy of MRSA infections and deep tissue NIR-II imaging. This platform utilizes lanthanide-doped rare earth nanoparticles (RENPs) that are sensitized by a moiety-engineered near-infrared (NIR) dye TPEO-820. The TPEO-820 sensitized RENPs exhibit 5 times increase in the release of NO concentration for MRSA treatment compared to unsensitized RENPs, enabling precise therapy of MRSA infection both in vitro and in vivo. Moreover, the platform demonstrates NIR-II luminescence in vivo, allowing for sensitive imaging in deep tissue for MRSA infection.

[FARSB stratifies prognosis and cold tumor microenvironment across different cancer types: an integrated single cell and bulk RNA sequencing analysis].

OBJECTIVE: Immunotherapy has brought significant clinical benefits to a subset of patients, but has thus far been disappointing in the treatment of immunologically "cold" tumors. Existing biomarkers that can precisely identify these populations are insufficient. In this context, a potential cold tumor microenvironment (TME) marker FARSB was investigated to reveal its impact on TME and patients' response to immunotherapy across pan-cancer. METHODS: The expression levels and mutational landscape of FARSB in pan-cancer were investigated. Kaplan-Meier and univariate Cox regression analyses were applied to analyze the prognostic significance of FARSB. Pathways affected by FARSB were investigated by gene set enrichment and variation analysis. The relationship between FARSB expression and immune infiltration was examined using the TIMER2 and R packages. Single-cell RNA sequencing (scRNA-seq) data of several cancer types from GSE72056, GSE131907, GSE132465, GSE125449 and PMID32561858 were analyzed to validate the impact of FARSB on the TME. The predictive effect of FARSB on immunotherapy efficacy was explored in 3 immune checkpoint inhibitors (ICIs)- treated cohorts (PMID32472114, GSE176307, and Riaz2017). RESULTS: FARSB expression was significantly higher in 25 tumor tissues than in normal tissues and was associated with poor prognosis in almost all tumor types. FARSB expression exhibited a strong association with several DNA damage repair pathways and was significantly associated with TP53 mutation in lung adenocarcinoma (P < 0.0001, OR=2.25). FARSB characterized a typical immune desert TME and correlated with impaired expression of chemokines and chemokines receptors. Large-scale scRNA-seq analysis confirmed the immunosuppressive role of FARSB and revealed that FARSB potentially shapes the cold TME by impeding intercellular interactions. In 3 ICI-treated cohorts, FARSB demonstrated predictive value for immunotherapy. CONCLUSION: This study provides a pan-cancer landscape of the FARSB gene by integrated single-cell and bulk DNA sequencing analysis and elucidates its biological function to promote DNA damage repair and construct the immune desert TME, suggesting the potential value of FARSB as a novel marker for stratifying patients with poor immunotherapeutic benefits and "cold" TME.

Physiological effects of different stubble height and freeze-thaw stress on Secale cereale L. seedlings.

BACKGROUND: As a biennial plant, Secale cereale L is usually harvested in the autumn in the northern part of China where the temperature difference between day and night is of great disparity Through the pot experiment, the seedlings were cut to 2, 6 and 10 cm stubble height, and the simulated freeze-thaw (FT) stress (10/- 5 °C) was carried out after 6 days regrowth. The physiological effects of FT with different stubble height were revealed by analyzing the relative water content (RWC), osmotic adjustment substance concentration (soluble sugar and protein), membrane peroxidation (MDA) and catalase (CAT) activity. RESULTS: The results demonstrated that under freeze stress (- 5 °C), the content of soluble protein and MDA decreased and the seedlings of 2 cm treatment kept higher level of soluble protein and MDA, while the seedlings of 6 and 10 cm treatments kept higher level of the RWC, soluble sugar content, and CAT activity. After FT stress, the content of soluble sugar and protein, RWC in the 6 cm treatment were higher than those in 2 cm and 10 cm treatments, and the CAT activity in 10 cm treatment was the highest while the MDA content is lower. CONCLUSION: These data suggest that keeping high stubble height is more adaptive for short-term FT stress.

Nanobody-based chimeric antigen receptor T cells designed by CRISPR/Cas9 technology for solid tumor immunotherapy.

Chimeric antigen receptor-based T-cell immunotherapy is a promising strategy for treatment of hematological malignant tumors; however, its efficacy towards solid cancer remains challenging. We therefore focused on developing nanobody-based CAR-T cells that treat the solid tumor. CD105 expression is upregulated on neoangiogenic endothelial and cancer cells. CD105 has been developed as a drug target. Here we show the generation of a CD105-specific nanobody, an anti-human CD105 CAR-T cells, by inserting the sequences for anti-CD105 nanobody-linked standard cassette genes into AAVS1 site using CRISPR/Cas9 technology. Co-culture with CD105+ target cells led to the activation of anti-CD105 CAR-T cells that displayed the typically activated cytotoxic T-cell characters, ability to proliferate, the production of pro-inflammatory cytokines, and the specific killing efficacy against CD105+ target cells in vitro. The in vivo treatment with anti-CD105 CAR-T cells significantly inhibited the growth of implanted CD105+ tumors, reduced tumor weight, and prolonged the survival time of tumor-bearing NOD/SCID mice. Nanobody-based CAR-T cells can therefore function as an antitumor agent in human tumor xenograft models. Our findings determined that the strategy of nanobody-based CAR-T cells engineered by CRISPR/Cas9 system has a certain potential to treat solid tumor through targeting CD105 antigen.

Nondestructive Damage Testing of Beam Structure Based on Vibration Response Signal Analysis.

Nondestructive damage-testing technology based on vibration signal analysis makes full use of the response characteristics of wave and energy. With the advantages of wide bandwidths of response frequency and high sensitivity, the nondestructive testing technology based on vibration signal analysis has a superiority in the application for the detection and characterization of structural defects, and has become one of the important methods for the nondestructive testing of structural material defects and damage. This paper presents a novel method of detection localization and quantitative analysis for local damage in beam structures, based on the response analysis of vibration signals. A damage-detection and -identification algorithm based on a unscented Kalman filter (UKF) was designed, which greatly reduces the computational workload in the process of damage identification over that in conventional methods. The method presented in this paper has significances to widen the application scope of the nondestructive testing method, and increase the recognition efficiency and effectiveness of this kind of method in engineering.

Chemiluminescence-Induced Free Radical-Promoted Cationic Polymerization.

Chemiluminescence (CL) has recently been featured as a new external light source for various photoinduced reactions with attractive features such as eliminating continuous energy supply and advanced light source setups. In the present study, the free-radical-promoted cationic polymerization of cyclohexene oxide, n-butyl vinyl ether, and N-vinyl carbazole under CL irradiation is described. The method is based on the visible-light-induced generation of electron donor radicals from bis-(4-methoxybenzoyl)diethyl germane (BAG), bis(2,4,6-trimethylbenzoyl) phenyl phosphinate, and camphorquinone by CL illumination followed by electron transfer to diphenyl iodonium hexafluorophosphate (Ph2 I+ PF6 - ) to form corresponding cations capable of initiating cationic polymerization. The applicability of the process to network formation is also demonstrated by using a bifunctional monomer, tri(ethylene glycol) divinyl ether.

A Review on Linking the Medicinal Functions of Mushroom Prebiotics with Gut Microbiota.

In recent years, gut microbiota have been linked to prevention and treatment of human diseases. Mushrooms are a source of potentially useful prebiotics because they contain polysaccharides, terpenoids, and other bioactive compounds. In the present review, we have summarized the prebiotic effects of mushrooms on gut microbiota in the context of immunological, metabolic, neurological, and cancer-related diseases in the last five years. We propose that mushrooms can not only change the composition of gut microbiota, but also promote secretion of beneficial metabolites. In addition, we point to the effects of host mRNA expression in gut microbiota as a direction of further study. Overall, these provide a background for further studies on the mechanisms of regulation of gut microbiota by mushrooms.

Gender differences in the association between body mass index and health-related quality of life among adults:a cross-sectional study in Shandong, China.

BACKGROUND: This study aims to assess the association between body mass index (BMI) and health-related quality of life (HRQOL), and to further explore gender differences in BMI-HRQOL association among adults. METHODS: We used data from the fifth Health Service Survey of Shandong Province, which was part of China's National Health Service Survey (NHSS), a total of 27,257 adults aged 18 and over were interviewed. The HRQOL was measured using the EuroQOL-5 Dimensions (EQ-5D) instrument. One-way ANOVA and Post hoc tests were used to compare EQ-5D utility values and visual analogue scale (VAS) scores between BMI categories. Tobit regression models were used to identify the association between BMI and HRQOL for male and female separately after controlling for influential confounders, and to assess gender differences on the relationship between BMI and HRQOL. RESULTS: The prevalence of underweight in men and women were 3.2 and 5.3%, respectively, while the prevalence of overweight/obesity in men and women were 35.7 and 34.6%, respectively. Men had higher EQ-5D utility values and VAS scores than women. The mean EQ-5D utility value and VAS score was highest in obese men and normal-weight women, respectively. After controlling potential confounders, being underweight was significantly and negatively associated with lower HRQOL among adults. The relationship between obesity and gender was that in women obesity was negatively and significantly associated with HRQOL, whereas in men this association was positive but not statistically significant. Results of gender by BMI interaction in regression model showed that this difference between men and women in this respect was significant. CONCLUSIONS: The association between BMI and HRQOL differed by gender and the so-called "obesity-HRQOL paradox" phenomenon was verified in male adults. Gender difference should be considered when implementing targeted weight control programs and appropriate interventions to improve HRQOL.

Association between interpersonal trust and suicidal ideation in older adults: a cross-sectional analysis of 7070 subjects in Shandong, China.

BACKGROUNDS: Suicidal ideation is an important public health issue due to devastating mortality. In the meantime, interpersonal trust was found to be negatively associated with mental disorder and physical health. Although there is increasing evidence that interpersonal trust is a significant predictor of suicidal ideation, evidence of this association is still lacking in the developing world. The aim of this study was to test the association between interpersonal trust and suicidal ideation among older adults in China. METHODS: Using a multi-stage stratified sampling strategy, 7070 older adults aged 60 and above from Shandong Province, China were recruited in this study. Socio-demographic characteristics, health status, family relationship, psychological distress, interpersonal trust and suicidal ideation in the last 12 months were obtained through face to face interviews. The association between interpersonal trust and suicidal ideation was assessed using multiple logistic regression models adjusting for socio-demographic characteristics, health status, family relationship and psychological distress. RESULTS: 7.1% of participants reported suicidal ideation in the past 12 months, which was related to gender, resident area, marital status, educational level, self-rated economic, chronic disease, self-rated health status and family relationship within 1 month, psychological distress and interpersonal trust. After adjusting for sociodemographic factors, health status, family relationship and psychological distress, interpersonal mistrust was associated with two times odds of suicidal ideation when compared to interpersonal trust CONCLUSIONS: The interpersonal trust was associated with suicidal ideation among elderly in Shandong, China. Intervention approaches regarding inducing and promoting interpersonal trust should be developed to prevent suicide.

Rural-urban difference in blood pressure measurement frequency among elderly with hypertension: a cross-sectional study in Shandong, China.

BACKGROUND: Blood pressure measurement is the first step in preventing and controlling hypertension. The objective of this study is to examine the rural-urban difference towards blood pressure measurement among elderly with hypertension. METHODS: A total of 2007 elderly (65+) were selected from the fifth Health Service Survey of Shandong Province in 2013. A standardized questionnaire was used to investigate the demographic characters, socioeconomic status, self-rated health, and blood pressure related index. Three logistic regression models were used to examine the difference in blood pressure measurement between rural and urban elderly. Unadjusted and adjusted logistic regression models were used to explore the associated factors of blood pressure measurement in both rural areas and urban areas. RESULTS: The prevalence of weekly blood pressure measurement in urban elderly was higher than that in rural elderly (63.9% vs 34.3%). The rural elderly had an odds ratio (OR) for weekly blood pressure measurement of 0.467 (95%CI = 0.380-0.575) compared with urban elderly. Binary logistic regression analysis showed that medication frequency and accepting health care professionals' guidance were common associated factors of blood pressure measurement among both rural and urban elderly; personal income was unique associated factor of blood pressure measurement among rural elderly; marital status, education level, self-rated health, and blood pressure level currently were unique associated factors of blood pressure measurement among urban elderly. CONCLUSIONS: There is a big difference in blood pressure measurement between rural and urban elderly. Interventions targeting identified at-risk subgroups, especially for those rural elderly, should be made to reduce such a gap.

Chronic Disease, Disability, Psychological Distress and Suicide Ideation among Rural Elderly: Results from a Population Survey in Shandong.

Objective: Suicide is a major public health and social problem in contemporary societies. Previous studies showed that the older the seniors were, the more likely it was that they would experience disability, chronic disease, or both. The objective of this study was to examine the joint effects of chronic disease and physical disability on suicide ideation while controlling for psychological distress among the rural elderly living in Shandong Province, China. Method: A total of 5514 rural elderly individuals (60+) living in Shandong Province, China were included in this study. Suicidal ideation was assessed by using questions from the National Comorbidity Survey (NCS). Multiple logistic analyses were performed to examine the factors associated with suicide ideation. A path analysis was conducted to test the direct and indirect effects of chronic disease and of activity of daily living (ADL) limitation on suicide ideation while controlling for psychological distress. Results: The prevalence of suicide ideation among the rural elderly in Shandong, China was 11.0%. Psychological distress had the strongest direct (ß = 0.392) and total effect (ß = 0.392), chronic disease (ß = -0.034; ß = -0.063) had both direct and indirect impacts, and ADL (ß = 0.091) had indirect impacts on suicide ideation. Psychological distress was a mediator between chronic disease, ADL limitation, and suicide ideation. Conclusions: Psychological distress was the greatest influencing factor of suicide ideation among the rural elderly, followed by chronic disease and disability. Effective intervention measures should be taken to facilitate the early detection of psychological distress in clinical practice among the rural elderly.

Loneliness and Health Service Utilization among the Rural Elderly in Shandong, China: A Cross-Sectional Study.

OBJECTIVES: To examine the prevalence of loneliness and to explore the association between loneliness and health service utilization among the rural elderly in Shandong Province, China. METHODS: A total of 5514 rural people aged 60 and above from Shandong Province, China, were enrolled in this study. Loneliness was used as a binary variable based on a single-item question. Health service utilization was measured by recent two-week physician visits and annual hospitalizations rates. Multiple logistic regression analysis was performed to examine the association between loneliness and health service utilization. RESULTS: The prevalence of loneliness among the rural elderly in Shandong, China, was 25.0%. Loneliness was associated with higher rates of recent two-week physician visits (OR = 1.260, p < 0.01) and annual hospitalizations (OR = 1.183, p < 0.05). The regression results also showed that self-rated health status and chronic conditions were significant and positively associated with both physician visits and hospitalizations rates. CONCLUSIONS: Loneliness had a significant association with higher odds of health service utilization among the elderly. The independent contribution of loneliness on health service utilization was smaller than self-rated health status and chronic conditions. Thus, healthcare policies need to shift from an emphasis on controlling health utilization and cost to a greater focus on enabling lonely older people to get more social support.

Association of Anthropometric Indices of Obesity with Hypertension in Chinese Elderly: An Analysis of Age and Gender Differences.

This study aims to explore the association of anthropometric indices of obesity with hypertension in Chinese elderly and its possible gender and age differences. A total of 7070 adults age 60 or older were interviewed in a cross-sectional study conducted in 2017. Anthropometric indices for each participant were measured by using standard methods of trained doctoral/master students. We performed two binary logistic regression models to examine the association of the nine different anthropometric indices and hypertension by gender. Lastly, analyses were performed in two steps stratified for age. Comparing individuals with and without hypertension, there were statistically significant differences in anthropometric indices except height, a body shape index (ABSI), and hip index (HI) in males; and except height in females. There were gender differences in the relationship between anthropometric indices and the prevalence of hypertension in Chinese older adults. After stratification by age, the associations of all anthropometric indices became weaker, disappeared, or even went in the opposite direction. Furthermore, body mass index (BMI) in men (except individuals older than 80) and hip circumference (HC) in women showed a significant impact on the risk of hypertension. The association of anthropometric indices of obesity with hypertension in Chinese elderly differ by gender and age. These findings indicate a need to develop gender-specific strategies for the male and female elderly in the primary and secondary prevention of hypertension.