Prevalence, cognitive characteristics, and influencing factors of amnestic mild cognitive impairment among older adults residing in an urban community in Chengdu, China.

Objective: Dementia is a significant public health concern, and mild cognitive impairment (MCI) serves as a transitional stage between normal aging and dementia. Among the various types of MCI, amnestic MCI (aMCI) has been identified as having a higher likelihood of progressing to Alzheimer's dimension. However, limited research has been conducted on the prevalence of aMCI in China. Therefore, the objective of this study is to investigate the prevalence of aMCI, examine its cognitive characteristics, and identify associated risk factors. Methods: In this cross-sectional study, we investigated a sample of 368 older adults aged 60 years and above in the urban communities of Chengdu, China. The participants underwent a battery of neuropsychological assessments, including the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), Auditory Verbal Learning Test (AVLT), Wechsler's Logical Memory Task (LMT), Boston Naming Test (BNT) and Trail Making Test Part A (TMT-A). Social information was collected by standard questionnaire. Multiple logistic regression analysis was utilized to screen for the risk and protective factors of aMCI. Results: The data analysis included 309 subjects with normal cognitive function and 59 with aMCI, resulting in a prevalence of 16.0% for aMCI. The average age of participants was 69.06 ± 7.30 years, with 56.0% being females. After controlling for age, gender and education, the Spearman partial correlation coefficient between various cognitive assessments and aMCI ranged from -0.52 for the long-term delayed recall scores in AVLT to 0.19 for the time-usage scores in TMT-A. The results indicated that all cognitive domains, except for naming scores (after semantic cue of BNT) and error quantity (in TMT-A), showed statistically significant associations with aMCI. Furthermore, the multiple logistic regression analysis revealed that older age (OR = 1.044, 95%CI: 1.002~1.087), lower educational level, and diabetes (OR = 2.450, 95%CI: 1.246~4.818) were risk factors of aMCI. Conclusion: This study found a high prevalence of aMCI among older adults in Chengdu, China. Individuals with aMCI exhibited lower cognitive function in memory, language, and executive domains, with long-term delayed recall showing the strongest association. Clinicians should prioritize individuals with verbal learning and memory difficulties, especially long-term delayed recall, in clinical practice.

Enhancing Fractionated Cancer Therapy: A Triple-Anthracene Photosensitizer Unleashes Long-Persistent Photodynamic and Luminous Efficacy.

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.

Emerging biomedical imaging-based companion diagnostics for precision medicine.

The tumor heterogeneity, which leads to individual variations in tumor microenvironments, causes poor prognoses and limits therapeutic response. Emerging technology such as companion diagnostics (CDx) detects biomarkers and monitors therapeutic responses, allowing identification of patients who would benefit most from treatment. However, currently, most US Food and Drug Administration-approved CDx tests are designed to detect biomarkers in vitro and ex vivo, making it difficult to dynamically report variations of targets in vivo. Various medical imaging techniques offer dynamic measurement of tumor heterogeneity and treatment response, complementing CDx tests. Imaging-based companion diagnostics allow for patient stratification for targeted medicines and identification of patient populations benefiting from alternative therapeutic methods. This review summarizes recent developments in molecular imaging for predicting and assessing responses to cancer therapies, as well as the various biomarkers used in imaging-based CDx tests. We hope this review provides informative insights into imaging-based companion diagnostics and advances precision medicine.

Smartphone-based versus traditional face-to-face collaborative care for community-dwelling older adults living with dementia in China: protocol for an implementation science-based sequential multiple assignment randomised trial.

INTRODUCTION: The high costs of institutional care and the burdensome demands of home care are challenging for families of adults with dementia. The collaborative care model (CCM) provides a potential solution to these challenges. Leveraging advancements in mobile technologies, smartphone-based management could offer a feasible means of providing collaborative care in a community setting. Therefore, this study aims to establish a CCM for home-cared older adults with dementia to determine the best strategy to deliver collaborative care, including both the channel and frequency of delivery. METHODS AND ANALYSIS: This study will be conducted in the communities of Chengdu city, Sichuan province, China. It is designed under the framework of implementation science. In the first stage, intervention strategies for community-dwelling older adults with dementia and their caregivers will be developed using Delphi methods and focus group interviews. The second stage will involve designing a sequential multiple assignment randomised trial to compare the effectiveness of face-to-face intervention versus a WeChat mini program-based intervention. This comparison will involve 358 pairs of older adults with dementia and their caregivers, with the frequency of intervention also assessed. Follow-up evaluations will be implemented at the 6th, 12th and 18th months post-intervention initiation. Primary outcomes encompass the proportion of patients demonstrating an improvement in quality of life and the proportion of caregivers exhibiting a reduction in caregiver burden. Analysis will be based on the intention-to-treat principle, and the generalised estimating equation approach will be used. Incremental cost-effectiveness ratios will be used to evaluate the cost-effectiveness of different delivery methods and frequencies. ETHICS AND DISSEMINATION: This study has received approval from the Ethics Committee of West China Fourth Hospital/School of Public Health, Sichuan University (Gwll2022004). Informed consent will be obtained for all participants. The findings of the study will be disseminated through peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ChiCTR2200057945.

Organic Afterglow Nanoparticles in Bioapplications.

Organic afterglow nanoparticles are unique optical materials that emit light long after cessation of excitation. Due to their advantages of no need for real-time light excitation, avoiding autofluorescence, low imaging background, high signal-to-background ratio, deep tissue penetration, and high sensitivity, afterglow imaging technology has been widely used in cell tracking, biosensing, cancer diagnosis, and cancer therapy, which provides an effective technical method for the acquisition of molecular information with high sensitivity, specificity and real-time at the cellular and living level. In this review, we summarize and illustrate the recent progress of organic afterglow imaging, focusing on the mechanism of organic afterglow materials and their biological application. Furthermore, we also discuss the potential challenges and the further directions of this field.

Salidroside alleviates dexamethasone-induced inhibition of bone formation via transforming growth factor-beta/Smad2/3 signaling pathway.

Glucocorticoid-induced osteoporosis is the third epidemic osteoporosis following postmenopausal and senileosteoporosis. According to one study, salidroside made ovariectomized rats' bones strong. Salidroside's potential for treating glucocorticoid-induced osteoporosis remains unproven. This study aimed to investigate the protective effect and mechanism of salidroside on dexamethasone-induced osteogenic differentiation and bone formation in MC3T3-E1 cells and zebrafish. The study proved that salindroside had no harmful impact on MC3T3E1 cells. Salidroside significantly relieved dexamethasone-induced inhibition of ALP (alkaline phosphatase) activity and mineralization in MC3T3-E1 cells, and promoted osteogenic differentiation of cells. Salidroside increased the expression of osteopontin (OPN), runt-related transcription factor 2 (Runx2), osterix (Osx), transforming growth factor-beta (TGF-ß) proteins and promoted the phosphorylation of Smad2/3 in MC3T3-E1 cells treated with dexamethasone. In addition, the effect of salidroside in relieving dexamethasone-induced inhibition of osteogenic differentiation in MC3T3-E1 cells can be blocked by TGF-ß receptor type I/II inhibitor (LY2109761). At the same time, we found that salidroside significantly alleviated the inhibition of dexamethasone-induced bone formation in zebrafish and promoted the mineralization of zebrafish skulls. LY2109761 reversed the protective impact of salidroside on dexamethasone-mediated bone impairment in zebrafish. These findings suggested that salidroside alleviated dexamethasone-induced inhibition of osteogenic differentiation and bone formation via TGF-ß/Smad2/3 signaling pathway.

Prediction of suicidal ideation among Chinese college students based on radial basis function neural network.

Background: Suicide is one of the leading causes of death for college students. The predictors of suicidal ideation among college students are inconsistent and few studies have systematically investigated psychological symptoms of college students to predict suicide. Therefore, this study aims to develop a suicidal ideation prediction model and explore important predictors of suicidal ideation among college students in China. Methods: We recruited 1,500 college students of Sichuan University and followed up for 4 years. Demographic information, behavioral and psychological information of the participants were collected using computer-based questionnaires. The Radial Basis Function Neural Network (RBFNN) method was used to develop three suicidal ideation risk prediction models and to identify important predictive factors for suicidal ideation among college students. Results: The incidence of suicidal ideation among college students in the last 12 months ranged from 3.00 to 4.07%. The prediction accuracies of all the three models were over 91.7%. The area under curve scores were up to 0.96. Previous suicidal ideation and poor subjective sleep quality were the most robust predictors. Poor self-rated mental health has also been identified to be an important predictor. Paranoid symptom, internet addiction, poor self-rated physical health, poor self-rated overall health, emotional abuse, low average annual household income per person and heavy study pressure were potential predictors for suicidal ideation. Conclusions: The study suggested that the RBFNN method was accurate in predicting suicidal ideation. And students who have ever had previous suicidal ideation and poor sleep quality should be paid consistent attention to.

Precisely controlling the cellular internalization of DNA-decorated semiconductor polymer nanoparticles for drug delivery.

Nonspecific adhesivity of nanoparticles to cells is regarded as a significant issue of nanomedicine, which brings about many serious drawbacks in applications, including low detection sensitivity, non-targeted biotoxicity and poor diagnostic accuracy. Here, we propose for the first time, DNA-decorated semiconductor polymer nanoparticles (SPN-DNAs), whose adhesivity can be significantly alleviated by controlling the density and thickness of DNA layers. This property is demonstrated to be independent of external conditions such as temperature, concentration, incubation time, ionic strength and cell lines. The mechanism of this phenomenon is also discussed. Finally, based on minimized nonspecific adhesivity to cells, a triggered nanoswitch can be constructed to control cellular internalization and drug delivery.

A novel afterglow nanoreporter for monitoring cancer therapy.

Rationale: Immunogenic cell death (ICD)-associated immunogenicity evoked through reactive oxygen species (ROS) is an efficient way to fight against the immune-dysfunctional microenvironment, so as to provoke potent anti-tumor immunity. However, the unknown ROS dose during cancer therapies may induce adverse immune responses (e.g., insufficient ICD, toxicity toward normal tissues or immune system). Methods: Herein, we developed a pyrido pyrazine - thiophene based semiconducting polymer as novel near-infrared (NIR) organic afterglow nanoparticles for the real-time visualization of self-generated ROS, during photodynamic-mediated immunogenic cell death. Specifically, we introduced the strong "acceptor" (pyrido pyrazine) into thiophene based semiconducting polymer to redshift emission wavelength, and further modulate the "donor" to afford more afterglow reaction sites and reducing ΔEst, so as to enhance luminescence intensity. Results: The semiconducting polymer-based afterglow nanoparticles exhibit strong afterglow emission with longer-wavelength emission (> 800 nm), compared with the reported organic afterglow nanoparticles (e.g., MEHPPV, PFODBT or Chlorin, < 690 nm), which endows this afterglow nanoparticles with a greatly improvement of signal to noise ratio. Moreover, the photodynamic effect of this afterglow nanoparticles can induce immunogenic cell death of cancer cells and further cause immune responses in mice. Conclusions: The NIR afterglow signal presents a good relationship with ROS generation, immunogenic cell death and outcome of treatment. Therefore, it was able to provide a non-invasive tool for predicting the degree of ICD that occurs during ROS-mediated cancer therapy and may contribute to precise immunotherapy.

Novel Sigma-2 receptor ligand A011 overcomes MDR in adriamycin-resistant human breast cancer cells by modulating ABCB1 and ABCG2 transporter function.

Multidrug resistance (MDR) is thought to be one of the main reasons for the failure of chemotherapy in cancers. ATP-binding cassette subfamily B member 1 (ABCB1) or P-glycoprotein (P-gp) and ATP-binding cassette subfamily G member 2 (ABCG2) play indispensable roles in cancer cell MDR. Sigma-2 (σ2) receptor is considered to be a cancer biomarker and a potential therapeutic target due to its high expression in various proliferative tumors. Recently, σ2 receptor ligands have been shown to have promising cytotoxic effects against cancer cells and to modulate the activity of P-glycoprotein (ABCB1) in vitro experiments, but their specific effects and mechanisms remain to be elucidated. We found that A011, a σ2 receptor ligand with the structure of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, showed promising cytotoxicity against breast cancer MCF-7 and adriamycin-resistant MCF-7 (MCF-7/ADR), induced apoptosis, and reversed adriamycin (ADR) and paclitaxel resistance in MCF-7/ADR cells. Furthermore, we demonstrated that A011 increased the accumulation of rhodamine 123 and mitoxantrone in MCF-7/ADR cells. A011 significantly decreased the ATPase activity of the ABCB1 and down-regulated ABCG2 protein expression. In addition, A011, administered alone or in combination with ADR, significantly inhibited tumor growth in the MCF-7/ADR tumor-bearing nude mouse model. A011 may be a potential therapeutic agent for the treatment of tumor resistance.

A011, a novel small-molecule ligand of σ2 receptor, potently suppresses breast cancer progression via endoplasmic reticulum stress and autophagy.

Breast cancer has surpassed lung cancer to become the most commonly diagnosed cancer in women worldwide. Sigma-2 (σ2) receptor is considered to be a potential therapeutic target for breast cancer because of its high expression in breast cancer cells and low expression in normal breast cells. Many σ2 ligands have been reported to have excellent anticancer activity, but their mechanism of action has not been fully elucidated. We discovered that A011 had high affinity and selectivity for σ2 receptor, reduced proliferation in five cancer cell lines, and significantly inhibited the monoclonal formation ability of MCF-7 cells. Furthermore, A011 rapidly increased the levels of intracellular Ca2+ and reactive oxygen species and induced autophagy. Molecular pharmacology studies revealed that A011 induced endoplasmic reticulum stress, activated the PERK-eIF2α-CHOP pathway and inhibited the activation of the PI3K-Akt-mTOR pathway, leading to cell apoptosis. In an in vivo tumor model, A011 showed obvious anti-tumor activity and no significant toxicity. More importantly, our study demonstrated for the first time that endoplasmic reticulum stress is the main mechanism of anti-cancer effects for σ2 ligands, at least for A011. A011 may potentially be useful as a therapeutic agent for treating breast cancer.

[5-Year Readmission Status and Risk Factors for Senile Dementia Patients: A Study Based on Chengdu Municipal Medical Insurance Database].

Objective: To study the status quo of the readmission of senile dementia patients in Chengdu, and to analyze the primary diagnosis, the economic burden and the influencing factors of readmission. Methods: Dementia inpatients aged 60 and above in Chengdu were the subjects of this study. The subjects were diagnosed with dementia between 2013 and 2017. Their heath insurance coverage was either the basic medical insurance for urban employees in Chengdu or the basic medical insurance for urban and rural residents of Chengdu. The rank sum test and the chi-square test were conducted to analyze the differences in readmission rate and the economic burden of hospitalization among subjects with different characteristics. Logistic regression was done to analyze the factors affecting readmission. Results: The total number of dementia inpatients over the 5-year period was 27881 patients (78820 admissions). The 30-day readmission rate was 25.14% (7011/27881) and the 5-year readmission rate was 45.79% (12767/27881). The primary diagnoses of 12767 readmitted patients mainly included dementia (28.57%), circulatory system diseases (24.26%), and respiratory system diseases (23.71%). The economic burden of hospitalization was higher for readmitted patients than that of patients who were not readmitted ( Z=33.777, P<0.001). The occurrence of readmission was correlated to the following factors, advanced age (compared to that of the 60-65 yr. group, the 70-75 yr. group: odds ratio [ OR]=1.123, 95% confidence interval [ CI]: 1.019-1.237, and the 75-80 yr. group: OR=1.123, 95% CI: 1.108-1.218), participation in the basic medical insurance for urban employees ( OR=1.674, 95% CI: 1.578-1.775), types of dementia (compared to unspecified dementia, Alzheimer's dementia group: OR=1.256, 95% CI: 1.163-1.357, Parkinson's disease dementia group: OR=1.774, 95% CI: 1.658-1.898, and mixed-type dementia group: OR=1.750, 95% CI: 1.457-2.103), disease condition (compared with patients with only dementia, those who have other diseases: OR=0.536，95% CI ：0.493-0.583), length of hospital stay ( OR=1.593, 95% CI: 1.552-1.635), and staying at a lower level hospital (compared to that of tertiary hospitals, secondary hospitals: OR=1.319, 95% CI: 1.248-1.395, primary hospitals: OR=1.744, 95% CI: 1.608-1.891, and other hospitals: OR=1.465, 95% CI: 1.311-1.537). Conclusion: Senile dementia patients have a high 30-day readmission rate, and the readmission entails heavy economic burdens on the patients. For the populations covered by medical insurance, the following features are correlated to the occurrence of readmission: advanced age, coverage by the basic medical insurance for urban employees, Alzheimer's dementia, Parkinson's disease dementia, mixed-type dementia, dementia patients without other comorbidities, extended length of stay, and hospitalization at a lower level hospital. However, further research is needed for better understanding of the specific mechanisms so that readmission of senile dementia patients can be reduced and the economic burden of the disease can be minimized.

Generation of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy.

Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL780/FL1113), but a small PA ratio between 755 and 905 nm (PA755/PA905). Oxidation of 1-Br-Et by •OH decreases the FL780/FL1113 while concurrently increasing the PA755/PA905, allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy.

Kaempferol Ameliorates the Inhibitory Activity of Dexamethasone in the Osteogenesis of MC3T3-E1 Cells by JNK and p38-MAPK Pathways.

Kaempferol has been reported to exhibit beneficial effect on the osteogenic differentiation in mesenchymal stem cells (MSC) and osteoblasts. In our previous study, dexamethasone (DEX) demonstrated inhibitory effect on MC3T3-E1 cells differentiation. In this study, we mainly explored the protective effect of kaempferol on the inhibitory activity of DEX in the osteogenesis of MC3T3-E1 cells. We found that kaempferol ameliorated the proliferation inhibition, cell cycle arrest, and cell apoptosis and increased the activity of alkaline phosphatase (ALP) and the mineralization in DEX-treated MC3T3-E1 cells. Kaempferol also significantly enhanced the expression of osterix (Osx) and runt-related transcription factor 2 (Runx2) in MC3T3-E1 cells treated with DEX. In addition, kaempferol attenuated DEX-induced reduction of cyclin D1 and Bcl-2 expression and elevation of p53 and Bax expression. Kaempferol also activated JNK and p38-MAPK pathways in DEX-treated MC3T3-E1 cells. Furthermore, kaempferol improved bone mineralization in DEX-induced bone damage in a zebrafish larvae model. These data suggested that kaempferol ameliorated the inhibitory activity of DEX in the osteogenesis of MC3T3-E1 cells by activating JNK and p38-MAPK signaling pathways. Kaempferol exhibited great potentials in developing new drugs for treating glucocorticoid-induced osteoporosis.

Cyclic Amplification of the Afterglow Luminescent Nanoreporter Enables the Prediction of Anti-cancer Efficiency.

We developed a cyclic amplification method for an organic afterglow nanoreporter for the real-time visualization of self-generated reactive oxygen species (ROS). We promoted semiconducting polymer nanoparticles (PFODBT) as a candidate for emitting near-infrared afterglow luminescence. Introduction of a chemiluminescent substrate (CPPO) into PFODBT (PFODBT@CPPO) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen (1 O2 ). 1 O2 produced by PFODBT@CPPO induced cancer cell necrosis and promoted the release of damage-related molecular patterns, thereby evoking immunogenic cell death (ICD)-associated immune responses through ROS-based oxidative stress. The afterglow luminescent signals of the nanoreporter were well correlated with light-driven 1 O2 generation and anti-cancer efficiency. This imaging strategy provides a non-invasive tool for predicting the therapeutic outcome that occurs during ROS-mediated cancer therapy.

Brief report: A preliminary comparison of self-compassion between adolescents with nonsuicidal self-injury thoughts and actions.

Despite the public health significance of nonsuicidal self-injury (NSSI) among adolescents, little is known about the possible overlaps or differences between individuals with NSSI thoughts and those with NSSI actions. The present study compared between individuals with different NSSI status on self-compassion. With a sample of 606 Chinese adolescents (38.8% females; Mage = 13.58, SD = 1.04), we investigated differences on the six subscales of the Self-Compassion Scale (i.e., self-kindness/self-judgment, common humanity/isolation, and mindfulness/over-identification) across three groups: NSSI-action group (n = 86), NSSI-thought group (n = 98), and no-NSSI group (n = 422). Results revealed that individuals with NSSI thoughts and NSSI actions shared greater self-judgment, isolation, and over-identification than those without NSSI, but differed from each other on self-kindness and common humanity, with individuals with NSSI thoughts reporting more self-kindness and common humanity than those with NSSI actions. Further empirical investigations into the influence of self-compassion on NSSI will benefit the development of interventions for adolescent NSSI.