Association of Well-Being in Middle-Aged and Older Adults With Enhanced Personal Health and Social Support: A Nationally Representative Cohort Study.

OBJECTIVES: This study aimed to explore the relationship between multidimensional factors, such as environment, health status, behavior, social support, and the well-being of middle-aged and older adults. METHODS: This study utilized data from 2 waves of the nationally representative Taiwan Longitudinal Study on Aging Survey Report (TLSA) conducted in 2015 and 2019. The TLSA assesses socioeconomic status, physical and health status, the 5-item World Health Organization Well-Being Index (WHO-5 index), and social support. Data regarding the degree of digital development were obtained from the 2020 Township Digital Development Report. We applied a generalized estimating equation (GEE) to analyze the influencing factors. RESULTS: This study included 4796 participants. Residing in areas with a higher degree of digital development, having a higher socioeconomic status, and experiencing better physical and mental health were significantly associated with well-being. Furthermore, emotional and attentive support mediated the association between physical and mental status and well-being. CONCLUSION: People's awareness of searching for and receiving social support and medical resources is important for enhancing their well-being. It is also crucial to pay attention to the living environment and maintain one's health status to promote well-being.

Physical frailty and oral health as risk factors for low bone density in community-dwelling residents.

This study aimed to explore the association between bone mineral density and physical frailty including nutrition, muscle mass, and oral function. We included participants aged 35-80 years and examined their bone mineral density, serum albumin level, body composition, and variance of hue (VOH) of two-colored gum. We also used the geriatric oral health assessment index (GOHAI). These data were used to calculate the geriatric nutritional risk index (GNRI) and skeletal muscle index (SMI). Multinomial logistic regression was performed to assess the relationship between GNRI, SMI, VOH, GOHAI, and bone mineral density after adjusting for comorbidities, including hypertension, diabetes mellitus, and previous bone fracture. We included 228 participants and classified their bone mineral density as normal, osteopenic, or osteoporotic. Older age (odds ratio (OR) 1.15, 95% confidence interval (CI) [1.08, 1.23]), low GNRI (OR 0.90, 95% CI [0.83, 0.98]), low SMI (OR 0.43, 95% CI [0.27, 0.68]), and high VOH (OR 1.08, 95% CI [1.01, 1.17]) were significantly associated with osteoporosis. Older age (OR 1.08, 95% CI [1.04, 1.11]) and low GNRI (OR 0.93, 95% CI [0.87, 0.99]) were significantly associated with osteopenia. GNRI, SMI, and VOH were significantly associated with osteoporosis among male participants. Although the multinomial logistic regression analysis indicated that GNRI, SMI, VOH, and GOHAI were not significantly associated with osteoporosis or osteopenia among female participants, the demographic distribution showed that older age, low GNRI, and low SMI were significantly associated with bone mineral density decline. Physical frailty, including nutritional decline, muscle mass loss, and poor oral status, is associated with low bone density. This easy-to-use tool can be used to detect osteoporosis early and to prevent osteoporosis and osteoporosis-related fractures.

Transplanting mitochondria from gastric epithelial cells reduces the malignancy of gastric cancer.

Mitochondria are essential for energy supplementation and metabolic homeostasis of cancer cells. Using mitochondria transplantation to reduce the malignancy of gastric cancer (GC) cells is herein proposed. In our study normal human gastric mucous epithelium cell line (GES-1) showed a lower mitochondrial membrane potential (MMP) compared to immortalized human vascular endothelial cell line (EAhy 926) and human gastric adenocarcinoma cell line (AGS). The transplantation of GES-1 mitochondria to AGS were confirmed both by confocal microscopy and flow cytometry. After transplanting GES-1 mitochondria, the AGS showed a reduced cell migration, and invasion without affecting cell viability and apoptosis. Investigating the expression of proteins involved in epithelial-mesenchymal-transition (EMT), transplanted GES-1 mitochondria reduced the expression of mesenchymal markers α-SMA, MMP-9, snail, vimentin and N-cadherin, whereas the epithelial markers E-cadherin and clauding-1 were not changed. The proteins implicated in the cell cycle such as cyclin B1 and D1 were decreased. In mice, inoculation with AGS carrying the transplanted GES-1 mitochondria resulted in smaller sized tumors. Further investigating the mitochondrial balance, the transplanted GES-1 mitochondria were more stably preserved compared to endogenous AGS mitochondria. The MMP, ATP production and mitochondrial mass decreased in GES-1 mitochondria and the mitophagic proteins LC3 II and PINK1 were up-regulated. In conclusion the decreased malignancy of AGS was a result of exogenous GES-1 mitochondria transplantation. This suggests for a therapy with low efficiency mitochondria transplantation in the treatment of cancer cells.

The Clinical Significance and Application of Heart Rate Variability in Dialysis Patients: A Narrative Review.

Autonomic nervous system (ANS) dysfunction is prevalent in end-stage kidney disease (ESKD) patients, carrying significant risks for morbidity and mortality. Heart rate variability (HRV) is a simple and non-invasive method to evaluate ANS functions and predict prognoses in specific patient populations. Since there is a lack of a clear understanding of the clinical significance of HRV in predicting prognoses in ESKD patients, an updated review on this topic is urgently warranted. The clinical significance of HRV in dialysis patients includes its associations with metabolic syndrome, nutritional status, intradialytic hypotension, vascular access failure, major adverse cardiovascular events, and mortality. These findings underscore the essential role of the autonomic reserve, which might denote the elevation of ANS activity as a response to external stimulus. Patients with a higher level of sympathetic activity at the resting stage, but who are unable to adequately elevate their sympathetic activity under stress might be susceptible to a worse outcome in critical circumstances. Further applications of HRV include HRV biofeedback, risk classification, and real-time HRV monitoring. Overall, HRV is an optimal tool for predicting prognoses in dialysis patients. Further study is encouraged in order to gain a clearer understanding of the clinical significance and application of HRV, and thereby enhance the care of ESKD patients.

Mechanical shear flow regulates the malignancy of colorectal cancer cells.

Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor-eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.

Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Dominant dystrophic epidermolysis bullosa is associated with glycolytically active GATA3+ T helper 2 cells which may contribute to pruritus in lesional skin.

BACKGROUND: Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined. OBJECTIVES: To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients. METHODS: Using bulk RNA sequencing, we evaluated affected and unaffected skin biopsy samples from six patients with DDEB (all with the very itchy pruriginosa subtype) and four healthy individuals. Single-cell transcriptomes of affected (n = 2) and unaffected (n = 1) DDEB skin and healthy skin (n = 2) were obtained. Dupilumab treatment was provided for three patients. RESULTS: The skin bulk transcriptome showed significant enrichment of T helper (Th)1/2 and Th17 pathways in affected DDEB skin compared with nonlesional DDEB skin and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3+ Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced visual analogue scale (VAS) itch scores after 12 weeks (mean VAS 3.83) compared with pretreatment (mean VAS 7.83). Bulk RNAseq and quantitative polymerase chain reaction showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin have similar transcriptomic profiles and reduced Th1/Th2 and Th17 pathway enrichment. CONCLUSIONS: Single-cell RNAseq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus.

Dominant dystrophic epidermolysis bullosa (DDEB) is a rare inherited skin disease that causes fragile skin that blisters easily, often triggered by minor injuries. These blisters are accompanied by intense itching, which can be distressing. The underlying cause of DDEB lies in genetic mutations in a gene called COL7A1. This gene encodes 'type VII collagen', a protein crucial for attaching the outer skin layer (epidermis) to the layer beneath (dermis). Although the genetic basis of DDEB is understood, the causes of itch are not known. As well as this, effective treatments for DDEB are lacking, which has driven scientists to explore innovative approaches like repurposing existing drugs. Drug repurposing involves using medications that have already been approved for other health conditions. One such drug is dupilumab, which is used for severe atopic dermatitis (eczema). Dupilumab targets immune cells called Th2 cells, which play a role in inflammation and allergies. While dupilumab has shown promise in relieving DDEB itching, the way it works in this condition is unclear. This study, carried out by a group of researchers in Taiwan, looked at gene expression in DDEB-affected and unaffected skin, and compared it to gene expression in healthy skin samples. We found heightened activity in Th2 immune cells and abnormal gene signals related to itching, similar to atopic dermatitis. These findings support using dupilumab and other anti-inflammatory drugs to alleviate itching in DDEB. Clinical trials will be crucial to evaluate the effectiveness of these drugs for managing DDEB symptoms. This research opens doors for enhanced treatment options and improving the quality of life of people living with DDEB.

SFEMM: A cotton binocular matching method based on YOLOv7x.

The cotton-picking robot needs to locate the target object in space in the process of picking in the field and other outdoor strong light complex environments. The difficulty of this process was binocular matching. Therefore, this paper proposes an accurate and fast binocular matching method. This method used the deep learning model to obtain the position and shape of the target object, and then used the matching equation proposed in this paper to match the target object. Matching precision of this method for cotton matching was much higher than that of similar algorithms. It was 54.11, 45.37, 6.15, and 12.21% higher than block matching (BM), semi global block matching (SGBM), pyramid stereo matching network (PSMNet), and geometry and context for deep stereo regression (GC-net) respectively, and its speed was also the fastest. Using this new matching method, the cotton was matched and located in space. Experimental results show the effectiveness and feasibility of the algorithm.

Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway.

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Recombinant mannan-binding lectin magnetic beads increase pathogen detection in immunocompromised patients.

The microbiological diagnosis of infection for hematological malignancy patients receiving chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients relies primarily on standard microbial culture, especially blood culture, which has many shortcomings, such as having low positive rates, being time-consuming and having a limited pathogenic spectrum. In this prospective observational self-controlled test accuracy study, blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF) samples were collected from chemotherapy or allo-HSCT patients with clinical symptoms of infections who were hospitalized at Peking University First Hospital. Possible pathogens were detected by the method based on recombinant mannan-binding lectin (MBL) magnetic bead enrichment (M1 method) and simultaneously by a standard method. The analytical sensitivity of M1 method was close to that of standard culture method. Besides, the turn-around time of M1-method was significantly shorter than that of standard culture method. Moreover, the M1 method also added diagnostic value through the detection of some clinically relevant microbes missed by the standard method. M1 method could significantly increase the detection efficiency of pathogens (including bacteria and fungi) in immunocompromised patients. KEY POINTS: • The detection results of M1-method had a high coincidence rate with that of standard method • M1 method detected many pathogens which had not been found by standard clinic method.

A novel olfactory biosensor based on ZIF-8@SWCNT integrated with nanosome-AuNPs/Prussian blue for sensitive detection of hexanal.

Hexanal is considered as an important volatile compound indicator for the assessment of freshness and maturity of foods. Therefore, sensitive and stable monitoring of hexanal is highly desired. Herein, an efficient receptor immobilization strategy based on ZIF-8@ Single-walled carbon nanotube (SWCNT) and nanosomes-AuNPs/Prussian blue (PB) was proposed for the development of olfactory biosensors. ZIF-8@SWCNT as dual support materials provided a high density of active sites for nanosomes loading. Moreover, the co-electrodeposition of nanosomes-AuNPs and PB on the sensor interface effectively amplified the electrochemical signal and maintained the activity of the receptor. The combination of ZIF-8@SWCNT with AuNPs/PB imparts excellent sensing performance of the biosensor with a wide detection range of 10-16-10-9 M, a low detection limit of 10-16 M for hexanal, and a long storage stability of 15 days. These results indicate that our biosensor can be a powerful tool for versatile applications in food and other related industries.

Design of fault location algorithm based on online distributed travelling wave for HV power cable.

To tackle the challenge of localization failure due to traveling wave dispersion during a mid-line fault in a long high-voltage cable, this study conducts an in-depth analysis of the refraction characteristics of the cumulative three-phase sheath currents at cross commutation points and direct grounding points, facilitated by detailed theoretical derivation. We introduce the novel concept of a 'first traveling wave attenuation index,' which quantifies the peak of the initial faulted traveling wave. We strategically place distributed traveling wave detection devices solely in the first direct grounding box of each cross-interconnected main section, effectively segmenting the line into five distinct zones. These zones are identified based on the unique transient polarities exhibited by the first traveling wave of fault current at each impedance mismatch point along the cable. To overcome the issue of weak traveling wave signals collected at the first end measurement point, we propose an innovative peak detection method for the first wave. This method harnesses the power of empirical wavelet transform (EWT) and multi-resolution singular value decomposition (MRSVD), providing a significant boost in ranging accuracy compared to traditional wavelet methods. Simulation results validate the efficacy of our proposed fault location method, which accurately pinpoints the fault section by contrasting the polarity of the first wave peak of the sheath current detected at each measurement point. Notably, our method ensures safety and convenience as the equipment does not require direct contact with high voltage.

Clinico-pathological and gene features of 15 nemaline myopathy patients from a single Chinese neuromuscular center.

BACKGROUND: Nemaline myopathy, the most common of the congenital myopathies, is caused by various genetic mutations. In this study, we attempted to investigate the clinical features, muscle pathology and genetic features of 15 patients with nemaline myopathy. RESULTS: Among the 15 patients, there were 9 (60.00%) males and 6 (40.00%) females, and 9 (60.00%) of them came from three families respectively. The age of seeing a doctor ranged from 9 to 52 years old, the age of onset was from 5 to 23 years old, and the duration of disease ranged from 3 to 35 years. Ten out of the 15 patients had high arched palate and elongated face. Only one patient had mild respiratory muscle involvement and none had dysphagia. Muscle biopsies were performed in 9 out of the 15 patients. Pathologically, muscle fibers of different sizes, atrophic muscle fibers and compensatory hypertrophic fibers could be found, and occasionally degenerated and necrotic muscle fibers were observed. Different degrees of nemaline bodies aggregation could be seen in all 9 patients. The distribution of type I and type II muscle fibers were significantly abnormal in patients with nemaline myopathy caused by NEB gene, however, it was basically normal in patients with nemaline myopathy caused by TPM3 gene and ACTA1 gene. Electron microscopic analysis of 6 patients showed that nemaline bodies aggregated between myofibrils were found in 5(83.33%) cases, and most of them were located near the Z band, but no intranuclear rods were found. The gene analysis of 15 NM patients showed that three NM-related genes were harbored, including 11 (73.33%) patients with NEB, 3 (20.00%) patients with TPM3, and 1 (6.67%) patient with ACTA1, respectively. A total of 12 mutation sites were identified and included 10 (83.33%) mutations in exon and 2(16.67%) mutations in intron. CONCLUSIONS: The clinical phenotype of nemaline myopathy is highly heterogeneous. Muscle pathology shows that nemaline bodies aggregation is an important feature for the diagnosis of NM. NEB is the most frequent causative gene in this cohort. The splicing mutation, c.21522 + 3A > G may be the hotspot mutation of the NEB gene in Chinese NM patients.

Evaluating the Effectiveness of School Closure in COVID-19-Related Syndromes From Community-Based Syndromic Surveillance: Longitudinal Observational Study.

BACKGROUND: During the COVID-19 pandemic, a school closure policy was adopted to prevent cluster transmission in schools and subsequent household transmission. However, the effectiveness of school closure is not consistent in studies conducted in different countries. OBJECTIVE: This study aimed to explore the association between school closure and the daily standardized incidence of COVID-19-related syndromes in an outpatient syndromic surveillance system. METHODS: We calculated the incidence of COVID-19-related syndromes derived from a community-based syndromic surveillance system between the first week of January and the second or fourth weeks after school closure in 2021 and 2022 in Taipei City, Taiwan. The effect of school closure on the standardized incidence of COVID-19-related syndromes was evaluated by interrupted time series analysis using an autoregressive integrated moving average with a distributed lag function. The exogenous variables were changes in human mobility measured by Google COVID-19 community mobility reports. Furthermore, the models quantified the influence of different age groups and the hierarchy of medical facilities, such as clinics or community hospitals. RESULTS: School closure was only negatively and significantly associated with the overall standardized incidence of COVID-19-related syndromes in 2021 for 2 weeks after the intervention (coefficient -1.24, 95% CI -2.40 to -0.08). However, in different age groups, school closure had a significantly negative association with the standardized incidence among people aged 13-18 years and ≥65 years for 2 weeks after the intervention in clinics in 2021. In community hospitals, school closure was significantly positively associated with the standardized incidence among people aged 19-24 years in 2021. In 2022, 2 weeks after the intervention, school closure had a significantly negative association with the standardized incidence among people aged 0-6, 7-12, and 19-24 years in community hospitals and aged >45 years in clinics. Furthermore, the standardized incidence was positively associated with movement change toward grocery and pharmacy stores in all age groups in 2022. In addition, movement changes toward residences were significantly positively associated with the standardized incidence among all age groups. CONCLUSIONS: Overall, school closure effectively suppresses COVID-19-related syndromes in students owing to the reduction of physical contact. In addition, school closure has a spillover effect on elderly people who stay at home.

A nigroincertal projection mediates aversion and enhances coping responses to potential threat.

Recent studies have shown that the non-DA neurons in the ventral tegmental area (VTA) and substantia nigra (SN) not only modulate motivational behaviors but also regulate defensive behaviors. While zona incerta (ZI) is a threat-responsive substrate and receives innervations from the ventral midbrain, the function of the ventral midbrain-to-ZI connection remains poorly defined. Here, we demonstrate that the ZI receives heterogenous innervations from the ventral midbrain. By utilizing a retrograde AAV preferentially labeling non-DA neurons in the ventral midbrain, we found that ZI-projecting non-DA cells in the ventral midbrain are activated by restraint stress. We focused on the SN and found that SN-to-ZI GABAergic input is engaged by a predatory odor. Sustained pan-neuronal SN-to-ZI activation results in aversion and enhances defensive behaviors, likely through a disinhibition mechanism to recruit downstream brain regions that regulate defensive behaviors. Collectively, our results reveal a novel role of nigroincertal projection in mediating negative valence and regulating defensive behaviors.

Sensitivity analysis of selection bias: a graphical display by bias-correction index.

Background: In observational studies, how the magnitude of potential selection bias in a sensitivity analysis can be quantified is rarely discussed. The purpose of this study was to develop a sensitivity analysis strategy by using the bias-correction index (BCI) approach for quantifying the influence and direction of selection bias. Methods: We used a BCI, a function of selection probabilities conditional on outcome and covariates, with different selection bias scenarios in a logistic regression setting. A bias-correction sensitivity plot was illustrated to analyze the associations between proctoscopy examination and sociodemographic variables obtained using the data from the Taiwan National Health Interview Survey (NHIS) and of a subset of individuals who consented to having their health insurance data further linked. Results: We included 15,247 people aged ≥20 years, and 87.74% of whom signed the informed consent. When the entire sample was considered, smokers were less likely to undergo proctoscopic examination (odds ratio (OR): 0.69, 95% CI [0.57-0.84]), than nonsmokers were. When the data of only the people who provided consent were considered, the OR was 0.76 (95% CI [0.62-0.94]). The bias-correction sensitivity plot indicated varying ORs under different degrees of selection bias. Conclusions: When data are only available in a subsample of a population, a bias-correction sensitivity plot can be used to easily visualize varying ORs under different selection bias scenarios. The similar strategy can be applied to models other than logistic regression if an appropriate BCI is derived.

Tumor-Derived Membrane Vesicles Restrain Migration in Gliomas By Altering Collective Polarization.

Mechanobiology is a cornerstone in physiology. However, its role in biomedical applications remains considerably undermined. In this study, we employed cell membrane vesicles (CMVs), which are currently being used as nanodrug carriers, as tactile cues for mechano-regulation of collective cell behaviors. Gliomas, which are among the most resilient brain tumors and have a low patient survival rate, were used as the cell model. We observed that mechanical responses due to the application of glioma- or microglia-derived CMVs resulted in the doubling of the traction stress of glioma cell collectives with a 10-fold increase in the CMV concentration. Glioma-CMVs constrained cell protrusions and hindered their collective migration, with the migration speed of such cells declining by almost 40% compared to the untreated cells. We speculated that the alteration of collective polarization leads to migration speed changes, and this phenomenon was elucidated using the cellular Potts model. In addition to intracellular force modulation and cytoskeletal reorganization, glioma-CMVs altered drug diffusion within glioma spheroids by downregulating the mechano-signaling protein YAP-1 while also marginally enhancing the associated apoptotic events. Our results suggest that glioma-CMVs can be applied as an adjuvant to current treatment approaches to restrict tumor invasion and enhance the penetration of reagents within tumors. Considering the broad impact of mechano-transduction on cell functions, the regulation of cell mechanics through CMVs can provide a foundation for alternative therapeutic strategies.

Digital oral health biomarkers for early detection of cognitive decline.

BACKGROUND: Oral health could influence cognitive function by stimulating brain activity and blood flow. The quantified oral status from oral inflammation, frailty and masticatory performance were rarely applied to the cognitive function screening. We aimed to adopt non-invasive digital biomarkers to quantify oral health and employ machine learning algorithms to detect cognitive decline in the community. METHODS: We conducted a prospective case-control study to recruit 196 participants between 50 and 80 years old from Puzi Hospital (Chiayi County, Taiwan) between December 01, 2021, and December 31, 2022, including 163 with normal cognitive function and 33 with cognitive decline. Demographics, daily interactions, electronically stored medical records, masticatory ability, plaque index, oral diadochokinesis (ODK), periodontal status, and digital oral health indicators were collected. Cognitive function was classified, and confirmed mild cognitive impairment diagnoses were used for sensitivity analysis. RESULTS: The cognitive decline group significantly differed in ODK rate (P = 0.003) and acidity from SILL-Ha (P = 0.04). Younger age, increased social interactions, fewer cariogenic bacteria, high leukocytes, and high buffering capacity led to lower risk of cognitive decline. Patients with slow ODK, high plaque index, variance of hue (VOH) from bicolor chewing gum, and acidity had increased risk of cognitive decline. The prediction model area under the curve was 0.86 and was 0.99 for the sensitivity analysis. CONCLUSIONS: A digital oral health biomarker approach is feasible for tracing cognitive function. When maintaining oral hygiene and oral health, cognitive status can be assessed simultaneously and early monitoring of cognitive status can prevent disease burden in the future.