Radiomics-based machine learning models for differentiating pathological subtypes in cervical cancer: a multicenter study.

Purpose: This study was designed to determine the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics-based machine learning (ML) in the classification of cervical adenocarcinoma (AC) and squamous cell carcinoma (SCC). Methods: Pretreatment 18F-FDG PET/CT data were retrospectively collected from patients who were diagnosed with locally advanced cervical cancer at two centers. Radiomics features were extracted and selected by the Pearson correlation coefficient and least absolute shrinkage and selection operator regression analysis. Six ML algorithms were then applied to establish models, and the best-performing classifier was selected based on accuracy, sensitivity, specificity, and area under the curve (AUC). The performance of different model was assessed and compared using the DeLong test. Results: A total of 227 patients with locally advanced cervical cancer were enrolled in this study (N=136 for the training cohort, N=59 for the internal validation cohort, and N=32 for the external validation cohort). The PET radiomics model constructed based on the lightGBM algorithm had an accuracy of 0.915 and an AUC of 0.851 (95% confidence interval [CI], 0.715-0.986) in the internal validation cohort, which were higher than those of the CT radiomics model (accuracy: 0.661; AUC: 0.513 [95% CI, 0.339-0.688]). The DeLong test revealed no significant difference in AUC between the combined radiomics model and the PET radiomics model in either the training cohort (z=0.940, P=0.347) or the internal validation cohort (z=0.285, P=0.776). In the external validation cohort, the lightGBM-based PET radiomics model achieved good discrimination between SCC and AC (AUC = 0.730). Conclusions: The lightGBM-based PET radiomics model had great potential to predict the fine histological subtypes of locally advanced cervical cancer and might serve as a promising noninvasive approach for the diagnosis and management of locally advanced cervical cancer.

A Novel Integrated Pipeline for Site-Specific Quantification of N-glycosylation.

The site-specific N-glycosylation changes of human plasma immunoglobulin gamma molecules (IgGs) have been shown to modulate the immune response and could serve as potential biomarkers for the accurate diagnosis of various diseases. However, quantifying intact N-glycopeptides accurately in large-scale clinical samples remains a challenge, and the quantitative N-glycosylation of plasma IgGs in patients with chronic kidney diseases (CKDs) has not yet been studied. In this study, we present a novel integrated intact N-glycopeptide quantitative pipeline (termed GlycoQuant), which combines our recently developed mass spectrometry fragmentation method (EThcD-sceHCD) and an intact N-glycopeptide batch quantification software tool (the upgraded PANDA v.1.2.5). We purified and digested human plasma IgGs from 58 healthy controls (HCs), 48 patients with membranous nephropathy (MN), and 35 patients with IgA nephropathy (IgAN) within an hour. Then, we analyzed the digested peptides without enrichment using EThcD-sceHCD-MS/MS, which provided higher spectral quality and greater identified depth. Using upgraded PANDA, we performed site-specific N-glycosylation quantification of IgGs. Several quantified intact N-glycopeptides not only distinguished CKDs from HCs, but also different types of CKD (MN and IgAN) and may serve as accurate diagnostic tools for renal tubular function. In addition, we proved the applicability of this pipeline to complex samples by reanalyzing the intact N-glycopeptides from cell, urine, plasma, and tissue samples that we had previously identified. We believe that this pipeline can be applied to large-scale clinical N-glycoproteomic studies, facilitating the discovery of novel glycosylated biomarkers. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00150-w.

Colloidal Ag2SbBiSe4 nanocrystals as n­type thermoelectric materials.

Materials with low intrinsic thermal conductivity are essential for the development of high-performance thermoelectric devices. At the same time, the solution processing of these materials may enable the cost-effective production of the devices. Herein, we detail a high-yield and scalable colloidal synthesis route to produce Ag2SbBiSe4 nanocrystals (NCs) using amine-thiol-Se chemistry. The quaternary chalcogenide material is consolidated by a rapid hot-press maintaining the cubic crystalline structure. Transport measurements confirm that n-type Ag2SbBiSe4 exhibits an inherently ultralow lattice thermal conductivity of ca. 0.34 W m-1K-1 at 760 K. Moreover, a modulation doping strategy based on the blending of semiconductor Ag2SbBiSe4 and metallic Sn NCs is demonstrated to control the charge carrier concentration in the final composite material. The introduction of Sn nanodomains additionally blocks phonon propagation thus contributing to reducing the thermal conductivity of the final material. Ultimately, a peak thermoelectric figure of merit value of 0.64 at 760 K is achieved for n-type Ag2SbBiSe4-Sn nanocomposites that also demonstrate a notable Vickers hardness of 185 HV.

Wheat Transcription Factor TaMYB60 Modulates Cuticular Wax Biosynthesis by Activating TaFATB and TaCER1 Expression.

Cuticular wax mixtures cover the epidermis of land plants and shield plant tissues from abiotic and biotic stresses. Although cuticular wax-associated traits are employed to improve the production of bread wheat, regulatory mechanisms underlying wheat cuticular wax biosynthesis remain poorly understood. In this research, partially redundant transcription factors TaMYB60-1 and TaMYB60-2 were identified as positive regulators of wheat cuticular wax biosynthesis. Knock-down of wheat TaMYB60-1 and TaMYB60-2 genes by virus-induced gene silencing resulted in attenuated wax accumulation and enhanced cuticle permeability. The roles of wheat fatty acyl-ACP thioesterase genes TaFATB1 and TaFATB2 in cuticular wax biosynthesis were characterized. Silencing wheat TaFATB1 and TaFATB2 genes led to reduced wax accumulation and increased cuticle permeability, suggesting that TaFATB1 and TaFATB2 genes positively contribute to wheat cuticular wax biosynthesis. Importantly, transcription factors TaMYB60-1 and TaMYB60-2 exhibit transcriptional activation ability and could stimulate the expression of wax biosynthesis genes TaFATB1, TaFATB2, and ECERIFERUM 1 (TaCER1). These findings support that transcription factor TaMYB60 positively regulates wheat cuticular wax biosynthesis probably by activating transcription of TaFATB1, TaFATB2, and TaCER1 genes.

Synthesis of kanamycin-azole hybrids and investigation of their antifungal activities.

The World Health Organization (WHO) recognizes Candida albicans and Cryptococcus neoformans as the critical priority fungal pathogens for which therapeutic solutions are needed. Azole-based antifungal agents, including triazoles, diazoles, and thiazoles, are widely used in the treatments for fungal infections. In light of past successes in the transformation of antibacterial kanamycin into antifungal derivatives via chemical modifications, a new library of kanamycin-azole hybrids was synthesized and tested against a panel of azole-resistant and susceptible Candida and Cryptococcus strains. Structure activity relationship (SAR) studies revealed pivotal roles for antifungal activity of the azole ring (imidazole vs triazole) and halogen substituents on the benzene ring (F vs Cl). Most notably, hybrids 13, 14 and 15 were active against resistant C. albicans, C. tropicalis and C. neoformans strains and non-toxic towards mammalian cells. Mode of action investigations using fluorogenic dyes, (SYTOXTM) showed the fungal active compounds could permeabilize fungal membranes even at » MICs. These findings reveal novel azole-based antifungals that could offer new therapeutic options for candidiasis and cryptococcosis.

Synthetic minority oversampling and iterative fluorescence-suppression integrated algorithm for Raman spectrum pesticide detection system.

Raman spectrum preprocessing method for automatic denoising and suppression of the fluorescent background. In this method, noise is reduced using wavelet transform, and a modified polynomial curve fitting method is implemented such that an algorithm can independently identify the optimal curve parameters for fluorescent background suppression. To address the problem of imbalanced datasets, the present study employed a synthetic minority oversampling technique to increase the volume of data in minority classes. This technique enables the prediction of pesticides that are otherwise difficult to detect, and the prediction accuracy is comparable to that of detection with large data volumes. The proposed convolutional neural network model was verified to accurately identify the type of single pesticides and composition of mixed pesticides. The prediction accuracy for mixed pesticides reached 99.1%.

Quantitative Assessment of New Frontiers in Dermatochalasis and Periorbital Hyperpigmentation Treatment: The Role of Cross-Linked Porcine Collagen.

BACKGROUND: Collagen dermal fillers have shown efficacy in addressing age-related changes in facial appearance. However, their potential in rejuvenating the periorbital region remains unexplored. The aim of this study was to evaluate the effectiveness, clinical safety, and patient satisfaction associated with the utilization of collagen dermal fillers in individuals with dermatochalasis and periorbital hyperpigmentation. METHODS: This study was reviewed and approved by the institutional review board of China Medical University Hospital (IRB No. CMUH107-REC2-157). Adults diagnosed with dermatochalasis or periorbital hyperpigmentation received periorbital injections of a sterile cross-linked highly-purified specific antigen free porcine dermal collagen (FACIALGAIN® Collagen Implant with Lidocaine, Sunmax Biotechnology Co. Ltd., Taipei, Taiwan) and were assessed for hydration, elasticity, pigmentation index, redness index, lightness value, and density with the DermaLab® Combo Multiparameter Skin Analysis System (Cortex Technology, Hadsund, Denmark) and Cutometer® Dual MPA 580 (Courage+Khazaka electronic GmbH, Köln, Germany). Data was collected prior to injection and at 1 week, 4 weeks, and 12 weeks after injection. Patient satisfaction on volume augmentation, decrease in hyperpigmentation, persistence, and overall satisfaction were also recorded. RESULTS: A total of 12 samples each were recruited for dermatochalasis and periorbital hyperpigmentation. For dermatochalasis subjects, hydration of the periorbital tissue significantly increased at week 1 and 4 (p = 0.011 and p = 0.015). Elasticity decreased by week 4 and persisted until week 12 (p = 0.001 and 0.014). For periorbital hyperpigmentation patients, lightness value increased significantly starting week 1 (p = 0.016), tapering off at week 12. Elasticity decreased by week 4 and persisted until week 12 (p = 0.002 and p = 0.002). Median overall patient satisfaction was 4 out of 5 for the dermatochalasis group and 4.5 out of 5 for the periorbital hyperpigmentation group, with a mild but insignificant decrease by week 12. CONCLUSIONS: DermaLab® Combo and Cutometer® Dual MPA 580 are considered effective methods for evaluating patients undergoing dermal filler injections. The utilization of cross-linked porcine collagen dermal filler injections can serve as a minimally invasive approach to enhance skin laxity in dermatochalasis and address discoloration in periorbital hyperpigmentation. However, it is important to note that regular treatments may be necessary to sustain the desired outcomes. 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/0026 .

[Prediction of liberation cutting intensity effect on the growth of Korean pine in secondary forest based on double dummy variable model]. / åŸºäºŽåŒå“‘å˜é‡æ¨¡åž‹é¢„æµ‹é€å ‰æŠšè‚²å¼ºåº¦å¯¹æ¬¡ç”Ÿæž—å† çº¢æ¾ç”Ÿé•¿çš„å½±å“.

"Planting conifer and reserving broadleaved tree" is an effective way to restore broad-leaved pine forest of temperate zone in Northeast China. Liberation cutting can promote the growth of Korean pine (Pinus koraiensis) under forest crown and accelerate the succession. However, how liberation cutting intensity affects the growth of Korean pine in secondary forest is still unclear. Taking the "Planting conifer and reserving broadleaved tree" Korean pine forest in Changbai Mountain as the object, we constructed a growth model of diameter at breast height (DBH) and tree height of Korean pine with double dummy variables (liberation cutting intensity and tree classification) to predict the growth of Korean pine plantation under different liberation cutting intensities, i.e. control (no liberation cutting), light-intensity liberation cutting (retaining upper canopy closure 0.6), medium-intensity liberation cutting (0.4), heavy-intensity liberation cutting (0.2) and clear cutting (cutting all upper broadleaf trees) stands. We analyzed the effects of liberation cutting intensities on DBH, tree height, and the ratio of tree height to DBH. The results showed that among six theoretical growth equations, the Gompertz model on the DBH (R2=0.46) and tree height (R2=0.81) was optimal basic model. The R2 of the DBH model was increased to 0.65 and 0.89, respectively, after the single dummy variable and the double dummy variable were introduced into the basic model, while the R2 of the tree height model was increased to 0.84 and 0.94. Therefore, the double dummy variable model was the most suitable for predicting the growth of Korean pine. The growth of DBH of pressed tree increased with the increases of liberation cutting intensity (increase by 145.8%-933.3%) during the whole simulation period (0-80 a). Average and dominant trees showed the same pattern at 42 and 60 a. In the early and middle stages of liberation cutting (20 and 42 a), clear cutting and heavy-intensity liberation cutting had similar effects on the height growth of dominant trees (64.8%-68.5%), average trees (100.0%-144.2%), and pressed trees (138.5%-183.9%). The effects of medium-intensity liberation cutting and light-intensity liberation cutting on the height growth were similar (24.3%-35.1%, 56.0%-92.3%, 84.6%-103.2%). While in the middle and late period (42 and 80 a), height growth of three grade trees increased with the increases of liberation cutting intensity. Under each liberation cutting intensity, the ratio of height to DBH of the dominant, average, and pressed trees increased successively, ranging from 0.50-0.95, 0.64-1.23, and 0.73-4.33, respectively. Only the pressed tree decreased with the increases of liberation cutting intensity at 0-80 a. Therefore, about 40 years after the implementation of liberation cutting, the promoting effect of different liberation cutting intensities on DBH growth was significantly weakened, the promoting effect on tree height growth was significantly enhanced, and the ratio of tree height to diameter began to increase. In order to alleviate forest competition, second liberation cutting should be carried out for light-intensity liberation cutting and medium-intensity liberation cutting stands to further release the growth potential of Korean pine, and thinning management should be carried out in clear cutting and heavy-intensity liberation cutting stands.

Prognostic nomogram combining 18F-FDG PET/CT radiomics and clinical data for stage III NSCLC survival prediction.

The aim of this study was to establish and validate the precision of a novel radiomics approach that integrates 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scan data with clinical information to improve the prognostication of survival rates in patients diagnosed with stage III Non-Small Cell Lung Cancer (NSCLC) who are not candidates for surgery. We evaluated pretreatment 18F-FDG PET-CT scans from 156 individuals diagnosed with stage III inoperable NSCLC at Shandong Cancer Hospital. These individuals were divided into two groups: a training set comprising 110 patients and an internal validation set consisting of 46 patients. By employing random forest classifier and cox proportional hazards model , we identified and utilized relevant features to create predictive models and a nomogram. The effectiveness of these models was assessed through the use of the receiver operating characteristics(ROC) curves, Kaplan-Meier (KM) curves, and the application of the nomogram. Our findings showed that the combined model, which integrates both clinical and radiomic data, outperformed those based solely on clinical or radiomic features in predicting 3-year overall survival(OS). Furthermore, calibration plots revealed a high level of agreement between predicted and actual survival times. The research successfully established a predictive radiomics model that integrates 18F-FDG PET/CT imaging with clinical indicators to enhance survival predictions for patients with stage III inoperable NSCLC.

Variability of morphology in photoplethysmographic waveform quantified with unsupervised wave-shape manifold learning for clinical assessment.

Objective.We investigated fluctuations of the photoplethysmography (PPG) waveform in patients undergoing surgery. There is an association between the morphologic variation extracted from arterial blood pressure (ABP) signals and short-term surgical outcomes. The underlying physiology could be the numerous regulatory mechanisms on the cardiovascular system. We hypothesized that similar information might exist in PPG waveform. However, due to the principles of light absorption, the noninvasive PPG signals are more susceptible to artifacts and necessitate meticulous signal processing.Approach.Employing the unsupervised manifold learning algorithm, dynamic diffusion map, we quantified multivariate waveform morphological variations from the PPG continuous waveform signal. Additionally, we developed several data analysis techniques to mitigate PPG signal artifacts to enhance performance and subsequently validated them using real-life clinical database.Main results.Our findings show similar associations between PPG waveform during surgery and short-term surgical outcomes, consistent with the observations from ABP waveform analysis.Significance.The variation of morphology information in the PPG waveform signal in major surgery provides clinical meanings, which may offer new opportunity of PPG waveform in a wider range of biomedical applications, due to its non-invasive nature.

Epitaxial Growth of Ga2O3: A Review.

Beta-phase gallium oxide (ß-Ga2O3) is a cutting-edge ultrawide bandgap (UWBG) semiconductor, featuring a bandgap energy of around 4.8 eV and a highly critical electric field strength of about 8 MV/cm. These properties make it highly suitable for next-generation power electronics and deep ultraviolet optoelectronics. Key advantages of ß-Ga2O3 include the availability of large-size single-crystal bulk native substrates produced from melt and the precise control of n-type doping during both bulk growth and thin-film epitaxy. A comprehensive understanding of the fundamental growth processes, control parameters, and underlying mechanisms is essential to enable scalable manufacturing of high-performance epitaxial structures. This review highlights recent advancements in the epitaxial growth of ß-Ga2O3 through various techniques, including Molecular Beam Epitaxy (MBE), Metal-Organic Chemical Vapor Deposition (MOCVD), Hydride Vapor Phase Epitaxy (HVPE), Mist Chemical Vapor Deposition (Mist CVD), Pulsed Laser Deposition (PLD), and Low-Pressure Chemical Vapor Deposition (LPCVD). This review concentrates on the progress of Ga2O3 growth in achieving high growth rates, low defect densities, excellent crystalline quality, and high carrier mobilities through different approaches. It aims to advance the development of device-grade epitaxial Ga2O3 thin films and serves as a crucial resource for researchers and engineers focused on UWBG semiconductors and the future of power electronics.

Photobiomodulation associated with alginate-based engineered tissue on promoting chondrocytes-derived biological responses for cartilage regeneration.

Articular cartilage is a connective tissue with limited self-healing potential, frequently affected by trauma and degenerative changes, leading to osteoarthritis. Photobiomodulation paired with engineered tissue can improve cartilage's poor intrinsic healing and overcome its restricted self-regeneration. In this study, alginate-based scaffolds were fabricated with varying concentrations of CaCl2 to achieve optimal mechanical, biocompatible, and biodegradable properties. The fluence-dependence of near-infrared (NIR) laser irradiation (830 nm) on chondrocyte viability and proliferation was investigated in a 2D environment across fluences (2.5-10 J/cm2). Optimal conditions of 3 % w/v CaCl2 and 5 J/cm2 were identified to construct alginate scaffolds and promote chondrocyte growth in 2D and 3D cultures. Single PBM (830 nm, 5 J/cm2) further exhibited a significant relative intensity of collagen type II immunostaining and stimulation of Col2a1 expression in 2D culture. Multiple PBM sessions (830 nm, 5 J/cm2) significantly enhanced chondrocyte proliferation and glycosaminoglycan production in alginate scaffolds, with a protocol of one session every four days being the most effective. Scanning electron microscopy revealed PBM-induced secretory granule formation, corresponding to a significant increase in extracellular vesicle release. Consequently, integrating PBM and alginate-based scaffolds is a promising technique for accelerating and optimizing cartilage regeneration, with potential application in tissue engineering.

Defining the Treatment Window: Early Versus Late Pulsed Dye Laser Therapy for Posttraumatic and Surgical Scars in Asian Patients.

OBJECTIVES: This retrospective study evaluates the effectiveness of pulsed dye laser (PDL) treatment in early versus late treatment groups for traumatic or postoperative scars. The study aims to determine the threshold between early and late treatment. Additionally, it investigates factors that may influence wound healing outcomes. METHODS: The medical records of 147 patients who underwent PDL treatment at our institution between January 2018 and December 2022 were retrospectively reviewed. Inclusion criteria were patients receiving PDL treatment for traumatic or postoperative scars. Out of these patients, we selected those who were willing to receive telephone interviews or re-visit at a scheduled time. Eventually, 52 participants were included in our study. A standardized questionnaire was administered to all participants during telephone interviews, encompassing inquiries regarding their medical history, treatment experiences, and the patient component of the Patient and Observer Scar Assessment Scale. Among the enrolled patients, 38 were contacted and interviewed via telephone, while the remaining 14 patients attended follow-up visits where photographs of their current skin condition were captured. The pretreatment and latest follow-up photographs obtained from the clinical database were independently scored in a blinded manner by two dermatologist reviewers using both the Vancouver Scar Scale and the Manchester Scar Scale. RESULTS: Among the 52 patients, 43 (82.7%) were successfully treated with good response. The correlation coefficients between week-to-treatment initiation and posttreatment MSS and VSS among patients with good response were 0.50 (p < 0.001) and 0.46 (p = 0.002), respectively. Given these findings, we established a treatment initiation threshold of 10 weeks, distinguishing patients into early and late treatment groups. The early treatment group showed borderline significantly lower posttreatment MSS and VSS scores than the late treatment group (MSS: 7.5 ± 2.1 vs. 9.3 ± 2.5, p = 0.011; VSS: 2.8 ± 2.0 vs. 4.5 ± 2.3, p = 0.011). Furthermore, both MSS and VSS of posttreatment showed significantly greater improvement in the early treatment group (4.4 ± 1.6 vs. 3.2 ± 1.9; p = 0.03 and 3.8 ± 1.8 vs. 2.8 ± 1.4; p = 0.04). CONCLUSIONS: Early intervention using a PDL within 10 weeks post-injury achieved better outcomes in treating traumatic and postoperative scars based on both clinical and patient opinions.

The I4790K mutation of the ryanodine receptor is responsible for anthranilic diamide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae).

Insecticide resistance in Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is a major constraint on the global production of cruciferous crops. For effective management of insecticide resistance, it is necessary to develop a molecular detection tool for predicting insecticide resistance levels based on the mutation frequency of target sites. In this study, a susceptible strain (SHggt) of P. xylostella was subjected to chlorantraniliprole and tetraniliprole selection under laboratory conditions to obtain the CHLSel and TETSel strains, respectively, to determine their resistance development, cross-resistance and mutation frequencies of the P. xylostella ryanodine receptor (PxRyR). In addition, the tetraniliprole resistance and the mutation frequencies of the PxRyR from 7 field populations were evaluated. Continuous selection over 30 generations resulted in resistance ratios (RRs) of 7,073.2-fold and 6,971.0-fold for the CHLSel and TETSel strains, respectively, and thousandfold increases in cross-resistance to unexposed diamides, e.g., cyantraniliprole and flubendiamide, were observed. For the field populations, three out of seven populations have developed more than thousandfold resistance to tetraniliprole. Among the three investigated target site mutations in PxRyR, only I4790K was detected in both laboratory-selected strains. However, 2 mutations, I4790K and G4946E, were detected in field populations. A positive correlation between RRs and K allele frequencies was observed in the laboratory-selected/relaxed strains and field populations of P. xylostella. These results suggest a possible link between the development of anthranilic diamide resistance and the frequency of the PxRyR I4790K mutation, which can be used to develop effective strategies for diamide resistance management in P. xylostella.

Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy.

Telethonin/titin-cap (TCAP) encodes a Z-disc protein that plays important roles in sarcomere/T-tubule interactions, stretch-sensing and signaling. Mutations in TCAP are associated with muscular dystrophy and cardiomyopathy; however, the complete etiology and its roles in myocardial infarction and regeneration are not fully understood. Here, we generated tcap gene knockout zebrafish with CRISPR/Cas9 technology and observed muscular dystrophy-like phenotypes and abnormal mitochondria in skeletal muscles. The stretch-sensing ability was inhibited in tcap-/- mutants. Moreover, Tcap deficiency led to alterations in cardiac morphology and function as well as increases in reactive oxygen species (ROS) and mitophagy. In addition, the cardiac regeneration and cardiomyocyte proliferation ability of tcap-/- mutants were impaired, but these impairments could be rescued by supplementation with ROS scavengers or autophagy inhibitors. Overall, our study demonstrates the essential roles of Tcap in striated muscle function and heart regeneration. Additionally, elevations in ROS and autophagy may account for the phenotypes resulting from Tcap deficiency and could serve as novel therapeutic targets for muscular dystrophy and cardiomyopathy.

Discovery of Cell Number-Interstitial Fluid Volume (CIF) Ratio Reveals Secretory Autophagy Pathway to Supply eHsp90α for Wound Healing.

Cell secretion repairs tissue damage and restores homeostasis throughout adult life. The extracellular heat shock protein-90alpha (eHsp90α) has been reported as an exosome cargo and a potential driver of wound healing. However, neither the mechanism of secretion nor the genetic evidence for eHsp90α in wound healing has been substantiated. Herein, we show that tissue injury causes massive deposition of eHsp90α in tissues and secretion of eHsp90α by cells. Sequential centrifugations of conditioned medium from relevant cell lines revealed the relative distributions of eHsp90α in microvesicle, exosome and trypsin-sensitive supernatant fractions to be approximately <2%, <4% and >95%, respectively. Establishing the cell-number-to-interstitial-fluid-volume (CIF) ratio for the microenvironment of human tissues as 1 × 109 cells: 1 mL interstitial fluid enabled us to predict the corresponding tissue concentrations of eHsp90α in these fractions as 3.74 µg/mL, 5.61 µg/mL and 178 µg/mL. Remarkably, the 178 µg/mL eHsp90α matches the previously reported 100-300 µg/mL of recombinant eHsp90α whose topical application promotes maximum wound healing in animal models. More importantly, we demonstrate that two parallel secretory autophagy-regulating gene families, the autophagy-regulating (AR) genes and the Golgi reassembly-stacking protein (GRASP) genes work together to mediate the secretion of the physiological concentration of eHsp90α to promote wound healing. Thus, utilization of the CIF ratio-based extrapolation method may enable investigators to rapidly predict biomarker targets from cell-conditioned-medium data.

Previously unrecognized and potentially consequential challenges facing Hsp90 inhibitors in cancer clinical trials.

Targeting the heat shock protein-90 (Hsp90) chaperone machinery in various cancers with 200 monotherapy or combined-therapy clinical trials since 1999 has not yielded any success of food and drug administration approval. Blames for the failures were unanimously directed at the Hsp90 inhibitors or tumors or both. However, analyses of recent cellular and genetic studies together with the Hsp90 data from the Human Protein Atlas database suggest that the vast variations in Hsp90 expression among different organs in patients might have been the actual cause. It is evident now that Hsp90ß is the root of dose-limiting toxicity (DLT), whereas Hsp90α is a buffer of penetrated Hsp90 inhibitors. The more Hsp90α, the safer Hsp90ß, and the lower DLT are for the host. Unfortunately, the dramatic variations of Hsp90, from total absence in the eye, muscle, pancreas, and heart to abundance in reproduction organs, lung, liver, and gastrointestinal track, would cause the selection of any fair toxicity biomarker and an effective maximum tolerable dose (MTD) of Hsp90 inhibitor extremely challenging. In theory, a safe MTD for the organs with high Hsp90 could harm the organs with low Hsp90. In reverse, a safe MTD for organs with low or undetectable Hsp90 would have little impact on the tumors, whose cells exhibit average 3-7% Hsp90 over the average 2-3% Hsp90 in normal cells. Moreover, not all tumor cell lines tested follow the "inhibitor binding-client protein degradation" paradigm. It is likely why the oral Hsp90 inhibitor TAS-16 (Pimitespib), which bypasses blood circulation and other organs, showed some beneficiary efficacy by conveniently hitting tumors along the gastrointestinal track. The critical question is what the next step will be for the Hsp90 chaperone as a cancer therapeutic target.

Examining drivers of NFT purchase intention: The impact of perceived scarcity and risk.

The emergence of non-fungible tokens (NFTs) has elicited both excitement and apprehension among consumers, who find themselves influenced by the perceived scarcity and the perceived risks surrounding these novel digital assets. This study investigates the factors influencing consumer adoption of NFTs by integrating the concepts of perceived scarcity and perceived risks within the theoretical framework of the Theory of Planned Behavior (TPB). Employing structural equation modeling, the research evaluates the impact of perceived scarcity, perceived ease of use, attitudes, subjective norms, perceived behavioral control, and perceived risk on NFT purchase intentions. The findings reveal that perceived scarcity and perceived ease of use significantly positively affect consumers' intentions to purchase NFTs. Conversely, perceived risk exerts a negative effect on purchase intentions. Additionally, the study demonstrates that attitudes, subjective norms, and perceived behavioral control positively affect NFT purchase intentions. This study provides a behavioral roadmap for navigating the complex love-hate relationship consumers have with NFTs, shedding light on the factors that motivate individuals to embrace or avoid these digital collectibles.

Heart rate variability biofeedback enhances cognitive, motor, psychological, and autonomic functions in post-stroke rehabilitation.

Post-stroke patients often experience psychological distress and autonomic nervous system (ANS) dysregulation, impacting their well-being. This study evaluated the effectiveness of heart rate variability (HRV) biofeedback on cognitive, motor, psychological, and ANS functions in sixty-two ischemic stroke patients (43 males, mean age = 60.1) at a Medical Center in southern Taiwan. To prevent interaction, we allocated patients to the HRV biofeedback or control (usual care) group based on their assigned rehabilitation days, with 31 patients in each group. Assessments conducted at baseline, three, and six months included the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment for Upper Extremities (FMA-UE), Perceived Stress Scale, Hospital Anxiety and Depression Scales (HADS), and HRV indices. Mixed-effect models were used to analyze Group by Time interactions. The results revealed significant interactions across all functions. At 3 months, significant improvements in the HRV biofeedback group were observed only in MoCA, FMA-UE, and HADS-depression scores compared to the control group. By 6 months, all measured outcomes demonstrated significant improvements in the biofeedback group relative to the control group. These results suggest that HRV biofeedback may be an effective complementary intervention in post-stroke rehabilitation, warranting further validation.