Identification of mitochondrial ATP synthase as the cellular target of Ru-polypyridyl-ß-carboline complexes by affinity-based protein profiling.

Ruthenium polypyridyl complexes are promising anticancer candidates, while their cellular targets have rarely been identified, which limits their clinical application. Herein, we design a series of Ru(II) polypyridyl complexes containing bioactive ß-carboline derivatives as ligands for anticancer evaluation, among which Ru5 shows suitable lipophilicity, high aqueous solubility, relatively high anticancer activity and cancer cell selectivity. The subsequent utilization of a photo-clickable probe, Ru5a, serves to validate the significance of ATP synthase as a crucial target for Ru5 through photoaffinity-based protein profiling. Ru5 accumulates in mitochondria, impairs mitochondrial functions and induces mitophagy and ferroptosis. Combined analysis of mitochondrial proteomics and RNA-sequencing shows that Ru5 significantly downregulates the expression of the chloride channel protein, and influences genes related to ferroptosis and epithelial-to-mesenchymal transition. Finally, we prove that Ru5 exhibits higher anticancer efficacy than cisplatin in vivo. We firstly identify the molecular targets of ruthenium polypyridyl complexes using a photo-click proteomic method coupled with a multiomics approach, which provides an innovative strategy to elucidate the anticancer mechanisms of metallo-anticancer candidates.

Posttraumatic Stress Disorder and Type 2 Diabetes Outcomes in Veterans.

Importance: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown. Objective: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD. Design, Setting, and Participants: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to September 30, 2022) to create a cohort of patients aged 18 to 80 years with comorbid PTSD and T2D. Data analysis was performed from March 1 to June 1, 2024. Exposures: Diagnoses of PTSD and T2D. Main Outcomes and Measures: The main outcomes were insulin initiation, poor glycemic control, any microvascular complication, and all-cause mortality. Improvement of PTSD was defined as no longer meeting PTSD diagnostic criteria, per a PTSD Checklist score of less than 33. Entropy balancing controlled for confounding. Survival and competing risk models estimated the association between meeting PTSD criteria and T2D outcomes. Subgroup analyses examined variation by age, sex, race, PTSD severity, and comorbid depression status. Results: The study cohort included 10 002 veterans. More than half of patients (65.3%) were aged older than 50 years and most (87.2%) were men. Patients identified as Black (31.6%), White (62.7%), or other race (5.7%). Before controlling for confounding with entropy balancing, patients who no longer met PTSD diagnostic criteria had similar incidence rates for starting insulin (22.4 vs 24.4 per 1000 person-years), poor glycemic control (137.1 vs 133.7 per 1000 person-years), any microvascular complication (108.4 vs 104.8 per 1000 person-years), and all-cause mortality (11.2 vs 11.0 per 1000 person-years) compared with patients with persistent PTSD. After controlling for confounding, no longer meeting PTSD criteria was associated with a lower risk of microvascular complications (hazard ratio [HR], 0.92 [95% CI, 0.85-0.99]). Among veterans aged 18 to 49 years, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.69 [95% CI, 0.53-0.88]) and all-cause mortality (HR, 0.39 [95% CI, 0.19-0.83]). Among patients without depression, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.73 [95% CI, 0.55-0.97]). Conclusions and Relevance: The findings of this cohort study of patients with comorbid PTSD and T2D suggest that PTSD is a modifiable risk factor associated with a modest reduction in microvascular complications. Further research is needed to determine whether findings are similar in non-VHA health care settings.

Enhancing Lower Eyelid Suspension Outcomes Through Pre-surgical Facial Nerve Reanimation: A Comparative Study.

BACKGROUND: Lower eyelid suspension, a common therapeutic procedure for facial paralysis-induced eyelid retraction, faces challenges due to high recurrence in patients lacking facial muscle function and impedes wider adoption. This research aims to explore the potential effects of restoring orbicularis oculi muscle tension through facial nerve reanimation prior to lower eyelid suspension and to define the indications for lower eyelid suspension. METHODS: The study encompassed 32 individuals with complete facial paralysis, segmented into group A (reanimation group) and group B (non-reanimation group), based on whether the orbicularis oculi muscle's tension was restored through facial nerve reconstruction prior to lower eyelid suspension. Subjective assessments of eyelid closure (the inter-eyelid gap upon gentle closure) and objective methods measures of scleral show (the distance from the pupil's center to the lower eyelid margin, MRD2) were used to provide a comprehensive analysis of long-term effectiveness. RESULTS: The group A exhibited significantly greater long-term improvement in lagophthalmos and lower eyelid ectropion. The alterations in MRD2 measured 2.66 ± 0.27 mm in the group A versus 2.08 ± 0.53 mm in the group B, denoting a statistically significant variance (p < 0.001). Moreover, while the ratio of MRD2 preoperative 6 months postoperative revealed no significant difference between groups, a significant difference emerged in 12 months postoperative (group A: 1.02 ± 0.21; group B: 1.18 ± 0.24; p < 0.05), with the values in group A closer to 1, indicative of enhanced symmetry. CONCLUSIONS: Restoring the tension in the orbicularis oculi muscle through facial nerve reconstruction prior to palmaris longus tendon sling could effectively sustain long-term outcomes of lower eyelid retraction correction and reduce the recurrence rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Room Temperature Phosphorescent Nanofiber Membranes by Bio-Fermentation.

Stimuli-responsive materials exhibiting exceptional room temperature phosphorescence (RTP) hold promise for emerging technologies. However, constructing such systems in a sustainable, scalable, and processable manner remains challenging. This work reports a bio-inspired strategy to develop RTP nanofiber materials using bacterial cellulose (BC) via bio-fermentation. The green fabrication process, high biocompatibility, non-toxicity, and abundant hydroxyl groups make BC an ideal biopolymer for constructing durable and stimuli-responsive RTP materials. Remarkable RTP performance is observed with long lifetimes of up to 1636.79 ms at room temperature. Moreover, moisture can repeatedly quench and activate phosphorescence in a dynamic and tunable fashion by disrupting cellulose rigidity and permeability. With capabilities for repeatable moisture-sensitive phosphorescence, these materials are highly suitable for applications such as anti-counterfeiting and information encryption. This pioneering bio-derived approach provides a reliable and sustainable blueprint for constructing dynamic, scalable, and processable RTP materials beyond synthetic polymers.

Self-assembly of a ruthenium-based cGAS-STING photoactivator for carrier-free cancer immunotherapy.

The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway promotes antitumor immune responses by sensing cytosolic DNA fragments leaked from nucleus and mitochondria. Herein, we designed a highly charged ruthenium photosensitizer (Ru1) with a ß-carboline alkaloid derivative as the ligand for photo-activating of the cGAS-STING pathway. Due to the formation of multiple non-covalent intermolecular interactions, Ru1 can self-assemble into carrier-free nanoparticles (NPs). By incorporating the triphenylphosphine substituents, Ru1 can target and photo-damage mitochondrial DNA (mtDNA) to cause the cytoplasmic DNA leakage to activate the cGAS-STING pathway. Finally, Ru1 NPs show potent antitumor effects and elicit intense immune responses in vivo. In conclusion, we report the first self-assembling mtDNA-targeted photosensitizer, which can effectively activate the cGAS-STING pathway, thus providing innovations for the design of new photo-immunotherapeutic agents.

Autologous Tissue Repair and Total Face Restoration.

Importance: Total face restoration remains a challenge in modern reconstructive surgery. After 17 years of experiments and preliminary clinical studies, a new concept of face prefabrication was developed for face restoration with autologous tissue. Objective: To evaluate the long-term results of face restoration with autologous tissue and report a finalized and standardized approach of face prefabrication. Design, Setting, and Participants: In this single-center long-term retrospective study, 32 patients who underwent total face restoration between 2005 and 2022 were reviewed. These patients underwent total facial reconstruction, which included flap prefabrication, 3-dimensional printing, tissue expansion, and flap transfer with aid of indocyanine green angiography (IGA). The flap first undergoes prefabrication by transferring vascularized fascia under the skin of the selected chest. A tissue expander is then placed under the fascia to create a large, thin, reliable skin flap after expansion. Once completed, the flap is transferred to the face during the second stage of the reconstruction. Intraoperative IGA is performed to guide the design of subsequent openings for facial fissures. Data were analyzed from July to September 2023. Main Outcomes and Measures: Flap healing, reconstructive outcome, and patient recovery were assessed during follow-up. Three questionnaires, including the 36-Item Short Form Health Survey (SF-36), Aesthetic and Functional Status Score of Facial Soft-Tissue Deformities/Defects, and the EuroQoL Health-Related Quality of Life (EQ-5D-5L), were used to evaluate the quality of life and satisfaction with facial aesthetic and functional status. Results: Of 24 included patients, 14 (58%) were male, and the mean (range) age was 32.9 (8-62) years. The mean (range) follow-up was 5.6 (2-12) years. All patients reported a significant improvement in quality of life (SF-36), especially in mean (SD) social functioning (preoperative score, 53.65 [34.51]; postoperative score, 80.73 [19.10]) and emotional stability (preoperative score, 56.67 [25.55]; postoperative score, 71.17 [18.51]). A total of 22 patients (92%) went back to work. Mean (SD) facial aesthetic status (preoperative score, 4.96 [3.26]; postoperative score, 11.52 [3.49]; P < .001) and functional status (preoperative score, 11.09 [3.51]; postoperative score, 15.78 [3.26]; P < .001) also improved. In addition, there was a significant increase in overall satisfaction and self-reported health status (preoperative score, 8.13 [1.52]; postoperative score, 3.58 [2.31]). Conclusions and Relevance: In this study, 5-year follow-up results suggested that this innovative approach to total face restoration offered a safe and valid option for indicated patients, with acceptable reconstructive and cosmetic outcomes.

Generalized channel separation algorithms for accurate camera-based multi-wavelength PTT and BP estimation.

Single-site multi-wavelength (MW) pulse transit time (PTT) measurement was recently proposed using contact sensors with sequential illumination. It leverages different penetration depths of light to measure the traversal of a cardiac pulse between skin layers. This enabled continuous single-site MW blood pressure (BP) monitoring, but faces challenges like subtle skin compression, which importantly influences the PPG morphology and subsequent PTT. We extended this idea to contact-free camera-based sensing and identified the major challenge of color channel overlap, which causes the signals obtained from a consumer RGB camera to be a mixture of responses in different wavelengths, thus not allowing for meaningful PTT measurement. To address this, we propose novel camera-independent data-driven channel separation algorithms based on constrained genetic algorithms. We systematically validated the algorithms on camera recordings of palms and corresponding ground-truth BP measurements of 13 subjects in two different scenarios, rest and activity. We compared the proposed algorithms against established blind source separation methods and against previous camera-specific physics-based method, showing good performance in both PTT reconstruction and BP estimation using a Random Forest regressor. The best-performing algorithm achieved mean absolute errors (MAEs) of 3.48 and 2.61 mmHg for systolic and diastolic BP in a leave-one-subject-out experiment with personalization, solidifying the proposed algorithms as enablers of novel contact-free MW PTT and BP estimation.

Home Through Their Eyes: A Qualitative Exploration of the Meaning of Home for Persons With Dementia and Impact of Physical Environment During Meaning-Making.

OBJECTIVES: This study aimed to examine the meaning of home for persons with dementia and the role of the physical environment during their meaning-making process. In response to a growing number of persons with dementia, there has been a strong advocacy for prioritizing the development of dementia-friendly environments within design practice and research agendas, for which "home" has become one of the important loci. However, of the limited studies on the meaning of home from the perspective of those individuals who continue to live in their own homes after developing dementia, even fewer addressed this issue within the Chinese context. METHODS: Five dyads, persons with dementia and their family caregivers, participated in the qualitative phenomenology study. Ten home visits-2 visits per dyad-were conducted, during which interview data, photographs, and field notes were collected. Phenomenological analysis was applied within and across the data sets. RESULTS: Three key themes emerged-"Three Dimensions of Home" revealed that "home" goes beyond physical residence and immediate family connections, including meaningful objects and places, enduring relationships, self-identity, and lived experiences.; "The Impact of Physical Environment" and "The Impact of Cognitive Impairment" showed the complex interactions between the environment, cognitive impairment, and meaning-making. DISCUSSION: An exploration of the essence of meaning of home within the Chinese context, in person-environment relationships with dementia progression, and implications for future research and practice on dementia-related environments and care were further discussed. This study contributes insights into enhancing the well-being of persons with dementia and benefiting their caregivers.

PEG-functionalized aliphatic polycarbonate brushes with self-polishing dynamic antifouling properties.

Hydrophilic antifouling polymers provide excellent antifouling effects under usual short-term use conditions, but the long-term accumulation of contaminants causes them to lose their antifouling properties. To overcome this drawback, surface-initiated ring-opening graft polymerization (SI-ROP) was performed on the surface of the material by applying the cyclic carbide monomer 4'-(fluorosulfonyl)benzyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (FMC), which contains a sulfonylfluoride group on the side chain, followed by a "sulfur(IV)-fluorine exchange" (SuFEx) post click modification reaction to link the hydrophilic polyethylene glycol (PEG) to the polyFMC (PFMC) brush, and a novel antifouling strategy for self-polishing dynamic antifouling surfaces was developed. The experimental results showed that the antifouling surface could effectively prevent the adsorption of proteins such as bovine serum albumin (BSA, ∼96.4%), fibrinogen (Fg, ∼87.8%) and lysozyme (Lyz ∼69.4%) as well as the adhesion of microorganisms such as the bacteria Staphylococcus aureus (S. aureus) (∼87.5%) and HeLa cells (∼67.2%). Moreover, the enzymatically self-polished surface still has excellent antifouling properties. Therefore, this modification method has potential applications in the field of biosensors and novel antifouling materials.

Privacy-Protected Contactless Sleep Parameters Measurement Using a Defocused Camera.

Sleep monitoring plays a vital role in various scenarios such as hospitals and living-assisted homes, contributing to the prevention of sleep accidents as well as the assessment of sleep health. Contactless camera-based sleep monitoring is promising due to its user-friendly nature and rich visual semantics. However, the privacy concern of video cameras limits their applications in sleep monitoring. In this paper, we explored the opportunity of using a defocused camera that does not allow identification of the monitored subject when measuring sleep-related parameters, as face detection and recognition are impossible on optically blurred images. We proposed a novel privacy-protected sleep parameters measurement framework, including a physiological measurement branch and a semantic analysis branch based on ResNet-18. Four important sleep parameters are measured: heart rate (HR), respiration rate (RR), sleep posture, and movement. The results of HR, RR, and movement have strong correlations with the reference (HR: R = 0.9076; RR: R = 0.9734; Movement: R = 0.9946). The overall mean absolute errors (MAE) for HR and RR are 5.2 bpm and 1.5 bpm respectively. The measurement of HR and RR achieve reliable estimation coverage of 72.1% and 93.6%, respectively. The sleep posture detection achieves an overall accuracy of 94.5%. Experimental results show that the defocused camera is promising for sleep monitoring as it fundamentally eliminates the privacy issue while still allowing the measurement of multiple parameters that are essential for sleep health informatics.

Fundamental and Practical Feasibility of Electrocardiogram Reconstruction from Photoplethysmogram.

Electrocardiogram (ECG) reconstruction from contact photoplethysmogram (PPG) would be transformative for cardiac monitoring. We investigated the fundamental and practical feasibility of such reconstruction by first replicating pioneering work in the field, with the aim of assessing the methods and evaluation metrics used. We then expanded existing research by investigating different cycle segmentation methods and different evaluation scenarios to robustly verify both fundamental feasibility, as well as practical potential. We found that reconstruction using the discrete cosine transform (DCT) and a linear ridge regression model shows good results when PPG and ECG cycles are semantically aligned-the ECG R peak and PPG systolic peak are aligned-before training the model. Such reconstruction can be useful from a morphological perspective, but loses important physiological information (precise R peak location) due to cycle alignment. We also found better performance when personalization was used in training, while a general model in a leave-one-subject-out evaluation performed poorly, showing that a general mapping between PPG and ECG is difficult to derive. While such reconstruction is valuable, as the ECG contains more fine-grained information about the cardiac activity as well as offers a different modality (electrical signal) compared to the PPG (optical signal), our findings show that the usefulness of such reconstruction depends on the application, with a trade-off between morphological quality of QRS complexes and precise temporal placement of the R peak. Finally, we highlight future directions that may resolve existing problems and allow for reliable and robust cross-modal physiological monitoring using just PPG.

Establishment and validation of a tumor-infiltrating γδT cell related prognostic gene signature in head and neck squamous cell carcinoma.

γδT cells are unconventional T cells only accounting for 1-5 % of circulating T lymphocytes. Their potent anti-tumor capability has been evidenced by accumulating studies. However, the prognostic value of γδT cells remains not well documented in head and neck squamous cell carcinoma (HNSCC). In this study, we utilized the TCGA HNSCC database to evaluate the infiltration of γδT cells and the association between γδT cells and clinicopathological factors by related gene signature, which were then validated by a total of 100 collected tumor samples from HNSCC patient cohort. Heterogeneity and functional characteristics of distinct infiltrating γδT cell profiles in HNSCC were then investigated based on the scRNA-seq data from the GEO database. We found higher γδT cell gene signature score was significantly associated with longer survival. Cox regression models showed that γδT cell gene signature could serve as an independent prognostic indicator for HNSCC patients. A high level of γδT cell-related gene signature was positively correlated with the infiltration of tumor-infiltrating lymphocytes and immune score. Through scRNA-seq analysis, we identified that γδ+ Trm cells and γδ+ CTL cells possessed anti-tumor and immunoregulatory properties. Notably, we found a significant association between the presence of these cells and improved survival outcomes. In our cell-cell communication analyses, we identified that γδT cells have the potential to eliminate tumor cells through the secretion of interferon-gamma and granzyme. Collectively, the infiltration of γδT cells may serve as a promising prognostic tool, prompting the consideration of treatment options for patients with HNSCC.

Mycobacterium tuberculosis Infection in School Contacts of Tuberculosis Cases: A Systematic Review and Meta-Analysis.

Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of tuberculosis outcomes from school contacts is not well characterized. We assessed the prevalence of Mycobacterium tuberculosis infection among close school contacts by performing a systematic review. We searched PubMed, Elsevier, China National Knowledge Infrastructure, and Wanfang databases. Studies reporting the number of children who were tested overall and who tested positive were included. Subgroup analyses were performed by study location, index case bacteriological status, type of school, and other relevant factors. In total, 28 studies including 54,707 school contacts screened for M. tuberculosis infection were eligible and included in the analysis. Overall, the prevalence of M. tuberculosis infection determined by the QuantiFERON Gold in-tube test was 33.2% (95% CI, 0.0-73.0%). The prevalences of M. tuberculosis infection based on the tuberculin skin test (TST) using 5 mm, 10 mm, and 15 mm as cutoffs were 27.2% (95% CI, 15.1-39.3%), 24.3% (95% CI, 15.3-33.4%), and 12.7% (95% CI, 6.3-19.0%), respectively. The pooled prevalence of M. tuberculosis infection (using a TST ≥5-mm cutoff) was lower in studies from China (22.8%; 95% CI, 16.8-28.8%) than other regions (36.7%; 95% CI, 18.1-55.2%). The pooled prevalence of M. tuberculosis infection was higher when the index was bacteriologically positive (43.6% [95% CI, 16.5-70.8%] versus 23.8% [95% CI, 16.2-31.4%]). These results suggest that contact investigation and general surveillance in schools from high-burden settings merit consideration as means to improve early case detection in children.

KLF7 regulates super-enhancer-driven IGF2BP2 overexpression to promote the progression of head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous carcinoma (HNSCC) is known for its high aggressiveness and susceptibility to cervical lymph node metastasis, which greatly contributes to its poor prognosis. During tumorigenesis, many types of cancer cells acquire oncogenic super-enhancers (SEs) that drive the overexpression of oncogenes, thereby maintaining malignant progression. This study aimed to identify and validate the role of oncogenic SE-associated genes in the malignant progression of HNSCC. METHODS: We identified HNSCC cell-specific SE-associated genes through H3K27Ac ChIP-seq and overlapped them with HNSCC-associated genes obtained from The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) datasets using weighted gene coexpression network analysis (WGCNA) to identify hub genes. The expression of IGF2BP2 and KLF7 in HNSCC was detected using clinical samples. To determine the biological role of IGF2BP2, we performed CCK-8, colony formation assay, Transwell migration assay, invasion assay, and orthotopic xenograft model experiments. Furthermore, we utilized a CRISPR/Cas9 gene-editing system, small-molecule inhibitors, ChIP-qPCR, and dual-luciferase reporter assays to investigate the molecular mechanisms of IGF2BP2 and its upstream transcription factors. RESULTS: Our study identified IGF2BP2 as a hub SE-associated gene that exhibited aberrant expression in HNSCC tissues. Increased expression of IGF2BP2 was observed to be linked with malignant progression and unfavorable prognosis in HNSCC patients. Both in vitro and in vivo experiments confirmed that IGF2BP2 promotes the tumorigenicity and metastasis of HNSCC by promoting cell proliferation, migration, and invasion. Mechanistically, the IGF2BP2-SE region displayed enrichment for H3K27Ac, BRD4, and MED1, which led to the inhibition of IGF2BP2 transcription and expression through deactivation of the SE-associated transcriptional program. Additionally, KLF7 was found to induce the transcription of IGF2BP2 and directly bind to its promoter and SE regions. Moreover, the abundance of KLF7 exhibited a positive correlation with the abundance of IGF2BP2 in HNSCC. Patients with high expression of both KLF7 and IGF2BP2 showed poorer prognosis. Lastly, we demonstrated that the small molecule inhibitor JQ1, targeting BRD4, attenuated the proliferation and metastatic abilities of HNSCC cells. CONCLUSIONS: Our study reveals the critical role of IGF2BP2 overexpression mediated by SE and KLF7 in promoting HNSCC progression. Targeting SE-associated transcriptional programs may represent a potential therapeutic strategy in managing HNSCC.

The effect of marathon running on the lower extremity kinematics and muscle activities during walking and running tasks.

Patellofemoral pain syndrome (PFPS) is a common injury among runners, and it is thought that abnormal lower extremity biomechanics contribute to its development. However, the relationship between biomechanical changes after a marathon and PFPS injury remains limited. This study aims to investigate whether differences in knee and hip kinematics and lower extremity muscle activities exist in recreational runners before and after a marathon. Additionally, it aims to explore the relationship between these biomechanical changes and the development of PFPS injury. 12 recreational runners participated in the study. Kinematics and muscle activities of the lower extremity were recorded during walking (5 km/h) and running (10 km/h) tasks within 24 hours before and within 5 hours after a marathon. After the marathon, there was a significant decrease in peak knee flexion (walking: p = 0.006; running: p = 0.006) and an increase in peak hip internal rotation (walking: p = 0.026; running: p = 0.015) during the stance phase of both walking and running compared to before the marathon. The study demonstrates a decrease in knee flexion and an increase in hip internal rotation during the stance phase of gait tasks after completing a marathon, which may increase the risk of developing PFPS injury.

Generalized Camera-Based Infant Sleep-Wake Monitoring in NICUs: A Multi-Center Clinical Trial.

The infant sleep-wake behavior is an essential indicator of physiological and neurological system maturity, the circadian transition of which is important for evaluating the recovery of preterm infants from inadequate physiological function and cognitive disorders. Recently, camera-based infant sleep-wake monitoring has been investigated, but the challenges of generalization caused by variance in infants and clinical environments are not addressed for this application. In this paper, we conducted a multi-center clinical trial at four hospitals to improve the generalization of camera-based infant sleep-wake monitoring. Using the face videos of 64 term and 39 preterm infants recorded in NICUs, we proposed a novel sleep-wake classification strategy, called consistent deep representation constraint (CDRC), that forces the convolutional neural network (CNN) to make consistent predictions for the samples from different conditions but with the same label, to address the variances caused by infants and environments. The clinical validation shows that by using CDRC, all CNN backbones obtain over 85% accuracy, sensitivity, and specificity in both the cross-age and cross-environment experiments, improving the ones without CDRC by almost 15% in all metrics. This demonstrates that by improving the consistency of the deep representation of samples with the same state, we can significantly improve the generalization of infant sleep-wake classification.

Multi-site isomerization of synergistically regulated stimuli-responsive AIE materials toward multi-level decryption.

Stimuli-responsive aggregation-induced emission (AIE) materials are highly sensitive and rapidly responsive to external signals, making them ideal solid materials for anti-counterfeiting encryption. However, the limited conformational and packing variations resulting from regio-isomerization with a single substituent restricts the stimuli-responsive behavior of these materials. In this work, several AIE-active regio-structural isomers based on the salicylaldehyde Schiff base scaffold have been straightforwardly obtained through multiple substitutions with bromide and triphenylamine moieties. Solvent-effect experiments demonstrate their different orders of charge-transfer and excited-state intramolecular proton transfer upon photoexcitation, indicating the regulation of excited-state processes via multi-site isomerization. These isomers also demonstrate mechanochromism and acidichromism, allowing for adjustable stimuli-responsive effects. As a demonstration, p-Br-TPA with both mechanochromism and acidichromism can be synergistically utilized for multi-level decryption. This study successfully regulates the evolution of excited states through multi-site isomerization, offering a general approach for achieving tunable stimuli-responsive properties in AIE-active salicylaldehyde Schiff bases toward multi-level decryption.

Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.

Camera-Based Seismocardiogram for Heart Rate Variability Monitoring.

Heart rate variability (HRV) is a crucial metric that quantifies the variation between consecutive heartbeats, serving as a significant indicator of autonomic nervous system (ANS) activity. It has found widespread applications in clinical diagnosis, treatment, and prevention of cardiovascular diseases. In this study, we proposed an optical model for defocused speckle imaging, to simultaneously incorporate out-of-plane translation and rotation-induced motion for highly-sensitive non-contact seismocardiogram (SCG) measurement. Using electrocardiogram (ECG) signals as the gold standard, we evaluated the performance of photoplethysmogram (PPG) signals and speckle-based SCG signals in assessing HRV. The results indicated that the HRV parameters measured from SCG signals extracted from laser speckle videos showed higher consistency with the results obtained from the ECG signals compared to PPG signals. Additionally, we confirmed that even when clothing obstructed the measurement site, the efficacy of SCG signals extracted from the motion of laser speckle patterns persisted in assessing the HRV levels. This demonstrates the robustness of camera-based non-contact SCG in monitoring HRV, highlighting its potential as a reliable, non-contact alternative to traditional contact-PPG sensors.

High preseason temperature variability drives convergence of xylem phenology in the Northern Hemisphere conifers.

Wood growth is key to understanding the feedback of forest ecosystems to the ongoing climate warming. An increase in spatial synchrony (i.e., coincident changes in distant populations) of spring phenology is one of the most prominent climate responses of forest trees. However, whether temperature variability contributes to an increase in the spatial synchrony of spring phenology and its underlying mechanisms remains largely unknown. Here, we analyzed an extensive dataset of xylem phenology observations of 20 conifer species from 75 sites over the Northern Hemisphere. Along the gradient of increase in temperature variability in the 75 sites, we observed a convergence in the onset of cell enlargement roughly toward the 5th of June, with a convergence in the onset of cell wall thickening toward the summer solstice. The increase in rainfall since the 5th of June is favorable for cell division and expansion, and as the most hours of sunlight are received around the summer solstice, it allows the optimization of carbon assimilation for cell wall thickening. Hence, the convergences can be considered as the result of matching xylem phenological activities to favorable conditions in regions with high temperature variability. Yet, forest trees relying on such consistent seasonal cues for xylem growth could constrain their ability to respond to climate warming, with consequences for the potential growing season length and, ultimately, forest productivity and survival in the future.