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Mitochondria and the endoplasmic reticulum (ER) are vital organelles that influence various cellular physiological and pathological processes. Recent evidence shows that about 5%–20% of the mitochondrial outer membrane is capable of forming a highly dynamic physical connection with the ER, maintained at a distance of 10–30 nm. These interconnections, known as MAMs, represent a relatively conserved structure in eukaryotic cells, acting as a critical platform for material exchange between mitochondria and the ER to maintain various aspects of cellular homeostasis. Particularly, ER-mediated Ca 2+ release and recycling are intricately associated with the structure and functionality of MAMs. Thus, MAMs are integral in intracellular Ca 2+ transport and the maintenance of Ca 2+ homeostasis, playing an essential role in various cellular activities including metabolic regulation, signal transduction, autophagy, and apoptosis. The disruption of MAMs observed in certain pathologies such as cardiovascular and neurodegenerative diseases as well as cancers leads to a disturbance in Ca 2+ homeostasis. This imbalance potentially aggravates pathological alterations and disease progression. Consequently, a thorough understanding of the link between MAM-mediated Ca 2+ transport and these diseases could unveil new perspectives and therapeutic strategies. This review focuses on the changes in MAMs function during disease progression and their implications in relation to MAM-associated Ca 2+ transport.

This article presents the high temperature tensile and creep behaviors of a novel high entropy alloy (HEA). The microstructure of this HEA resembles that of advanced superalloys with a high entropy FCC matrix and L1 2 ordered precipitates, so it is also named as “high entropy superalloy (HESA)”. The tensile yield strengths of HESA surpass those of the reported HEAs from room temperature to elevated temperatures; furthermore, its creep resistance at 982 °C can be compared to those of some Ni-based superalloys. Analysis on experimental results indicate that HESA could be strengthened by the low stacking-fault energy of the matrix, high anti-phase boundary energy of the strengthening precipitate, and thermally stable microstructure. Positive misfit between FCC matrix and precipitate has yielded parallel raft microstructure during creep at 982 °C, and the creep curves of HESA were dominated by tertiary creep behavior. To the best of authors’ knowledge, this article is the first to present the elevated temperature tensile creep study on full scale specimens of a high entropy alloy, and the potential of HESA for high temperature structural application is discussed.

A potential link has been reported between skin exposure to aromatic amines, such as ortho-toluidine (OT) and 3,3′-dichloro-4,4′-diaminodiphenylmethane (MOCA), and bladder cancer cases observed in Japanese chemical factories. To evaluate this association, we explored the permeability of OT and MOCA through pig skin and investigated the subsequent changes in plasma and urine concentrations in rats following percutaneous exposure. Employing Yucatan micropig skin, we first executed a permeability test by affixing the skin to a diffusion cell and applying 14 C-labeled OT or MOCA. The receptor fluid’s radioactivity was quantified at intervals of 1, 3, 6, 8, 24, and 48 h after application using a liquid scintillation counter. Next, we applied lint cloths drenched in OT and MOCA solutions to the backs of 7-week-old male F344 rats and monitored plasma and urine concentrations over time. Additionally, we investigated the pharmacokinetics of 14 C-labeled OT or MOCA solutions for 8 h following percutaneous administration. Both OT and MOCA demonstrated high skin penetration; in particular, plasma concentrations significantly rose at 6 h for OT and 8 h for MOCA after exposure. However, OT was rapidly absorbed into the bloodstream and swiftly excreted into the urine, indicating quick absorbability. In contrast, MOCA penetrated the skin quickly but exhibited delayed bloodstream entry and urinary excretion, suggesting slower absorbability. Pharmacokinetic findings revealed the rapid urinary excretion of OT, whereas MOCA was excreted in the urine and potentially in the feces as well via bile. These findings indicate that implementing measures based on chemical absorbability could significantly enhance the management of industrial chemicals where percutaneous absorbability is a concern.

Black net shade treatment attenuates flavonoid biosynthesis in tea plants, while the effect of light quality is still unclear. We investigated the flavonoid and transcriptome profiles of tea leaves under different light conditions, using black nets with different shade percentages, blue, yellow and red nets to alter the light intensity and light spectral composition in the fields. Flavonol glycosides are more sensitive to light intensity than catechins, with a reduction percentage of total flavonol glycosides up to 79.6% compared with 38.7% of total catechins under shade treatment. A total of 29,292 unigenes were identified, and the KEGG result indicated that flavonoid biosynthesis was regulated by both light intensity and light spectral composition while phytohormone signal transduction was modulated under blue net shade treatment. PAL, CHS, and F3H were transcriptionally downregulated with light intensity. Co-expression analysis showed the expressions of key transcription factors MYB12, MYB86, C1, MYB4, KTN80.4, and light signal perception and signaling genes (UVR8, HY5) had correlations with the contents of certain flavonoids (p < 0.05). The level of abscisic acid in tea leaves was elevated under shade treatment, with a negative correlation with TFG content (p < 0.05). This work provides a potential route of changing light intensity and spectral composition in the field to alter the compositions of flavor substances in tea leaves and regulate plant growth, which is instructive to the production of summer/autumn tea and matcha.

Background Numerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear. Methods The miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network. Results In total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 − AS, FOXD2 − AS1, AC105277.1, AC099850.3, STARD4 − AS1, SLC16A1 − AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR − 654, miR − 503, miR − 450a, miR − 379, miR − 369, miR − 190a, miR − 101, and let−7c) were found to be significantly associated with overall survival (log-rank p  < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT. Conclusions In this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.

In this paper, a tunable mid-infrared metasurface based on VO 2 phase change material is proposed for temperature control. The proposed structure consisting of a VO 2 /SiO 2 /VO 2 cavity supports a thermally switchable Fabry-Perot-like resonance mode at the transparency window of the atmosphere. Theoretically, the radiative cooling power density of the proposed metasurface can be switched to four-fold as the device temperature is below/above the phase change temperature of VO 2 . Besides radiative cooling, a passive temperature control application based on this huge cooling power switching ability is theoretically demonstrated. We believe the proposed device can be applied for small radiative cooling and temperature control applications.

TIGAR (TP53-induced glycolysis and apoptosis regulator) is the downstream target gene of p53, contains a functional sequence similar to 6-phosphofructose kinase/fructose-2, 6-bisphosphatase (PFKFB) bisphosphatase domain. TIGAR is mainly located in the cytoplasm; in response to stress, TIGAR is translocated to nucleus and organelles, including mitochondria and endoplasmic reticulum to regulate cell function. P53 family members (p53, p63, and p73), some transcription factors (SP1 and CREB), and noncoding miRNAs (miR-144, miR-885-5p, and miR-101) regulate the transcription of TIGAR. TIGAR mainly functions as fructose-2,6-bisphosphatase to hydrolyze fructose-1,6-diphosphate and fructose-2,6-diphosphate to inhibit glycolysis. TIGAR in turn facilitates pentose phosphate pathway flux to produce nicotinamide adenine dinucleotide phosphate (NADPH) and ribose, thereby promoting DNA repair, and reducing intracellular reactive oxygen species. TIGAR thus maintains energy metabolism balance, regulates autophagy and stem cell differentiation, and promotes cell survival. Meanwhile, TIGAR also has a nonenzymatic function and can interact with retinoblastoma protein, protein kinase B, nuclear factor-kappa B, hexokinase 2, and ATP5A1 to mediate cell cycle arrest, inflammatory response, and mitochondrial protection. TIGAR might be a potential target for the prevention and treatment of cardiovascular and neurological diseases, as well as cancers.

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by pulmonary vascular remodeling leading to increased pulmonary vascular resistance and pulmonary arterial pressure. PAH is a highly morbid cardiopulmonary disease adversely affecting lifespan and quality of life. Despite increased awareness and advances of medical therapies in recent decades, long‐term prognosis and survival remain poor for patients with PAH. Novel therapies that can target the underlying pathobiology of PAH and reverse pulmonary vascular remodeling are clearly needed. In this study, we develop a network module‐based framework to examine potential drug repositioning for PAH. The rationale for this approach is that in order to have therapeutic effects, the targets of potential drugs must be significantly proximate to the disease module of interest in the human protein‐protein interactome. Based on 15 existing drugs for treating PAH, our framework integrates drug‐drug interactions, drug‐drug chemical similarity, drug targets, and PAH disease proteins into the human interactome, and prioritizes candidate drugs for PAH. We identified 53 drugs that could potentially be repurposed for PAH. Many of these candidates have strong literature support. Compared to black‐box‐like machine learning models, network module‐based drug repositioning can provide mechanistic insights into how repositioned drugs can target the underlying pathobiological mechanisms of PAH.

Hypertrophic cardiomyopathy (HCM) is a global and relatively common cause of patient morbidity and mortality and is among the first reported monogenic cardiac diseases. For 30 years, the basic etiology of HCM has been attributed largely to variants in individual genes encoding cardiac sarcomere proteins, with the implication that HCM is fundamentally a genetic disease. However, data from clinical and network medicine analyses, as well as contemporary genetic studies show that single gene variants do not fully explain the broad and diverse HCM clinical spectrum. These transformative advances place a new focus on possible novel interactions between acquired disease determinants and genetic context to produce complex HCM phenotypes, also offering a measure of caution against overemphasizing monogenics as the principal cause of this disease. These new perspectives in which HCM is not a uniformly genetic disease but likely explained by multifactorial etiology will also unavoidably impact how HCM is viewed by patients and families in the clinical practicing community going forward, including relevance to genetic counseling and access to healthcare insurance and psychosocial wellness.

Progress in precision medicine is limited by insufficient knowledge of transcriptomic or proteomic features in involved tissues that define pathobiological differences between patients. Here, myectomy tissue from patients with obstructive hypertrophic cardiomyopathy and heart failure is analyzed using RNA-Seq, and the results are used to develop individualized protein-protein interaction networks. From this approach, hypertrophic cardiomyopathy is distinguished from dilated cardiomyopathy based on the protein-protein interaction network pattern. Within the hypertrophic cardiomyopathy cohort, the patient-specific networks are variable in complexity, and enriched for 30 endophenotypes. The cardiac Janus kinase 2-Signal Transducer and Activator of Transcription 3-collagen 4A2 (JAK2-STAT3-COL4A2) expression profile informed by the networks was able to discriminate two hypertrophic cardiomyopathy patients with extreme fibrosis phenotypes. Patient-specific network features also associate with other important hypertrophic cardiomyopathy clinical phenotypes. These proof-of-concept findings introduce personalized protein-protein interaction networks (reticulotypes) for characterizing patient-specific pathobiology, thereby offering a direct strategy for advancing precision medicine. Understanding patient-specific pathobiological pathways is a critical step for advancing precision medicine. Here the authors show that individualized protein-protein interaction networks provide key insight on patient-level pathobiology and clinically relevant pathophenotypic characteristics in a complex disease.