MicroRNA-939 amplifies Staphylococcus aureus-induced matrix metalloproteinase expression in atopic dermatitis.

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. Staphylococcus aureus (S. aureus) colonization on the skin plays an important role in the pathogenesis of AD; however, the mechanism of how it modulates skin immunity to exacerbate AD remains unclear. MicroRNAs are short non-coding RNAs that act as post-transcriptional regulators of genes. They are involved in the pathogenesis of various inflammatory skin diseases. Methods: In this study, we established miRNA expression profiles for keratinocytes stimulated with heat-killed S. aureus (HKSA). The expression of miR-939 in atopic dermatitis patients was analyzed by fluorescence in situ hybridization (FISH). miR-939 mimic was transfected to human primary keratinocyte to investigate its impact on the expression of matrix metalloproteinase genes (MMPs) in vitro. Subsequently, miR-939, along with Polyplus transfection reagent, was administered to MC903-induced atopic dermatitis skin to assess its function in vivo. Results: MiR-939 was highly upregulated in HKSA-stimulated keratinocytes and AD lesions. In vitro studies revealed that miR-939 increased the expression of matrix metalloproteinase genes, including MMP1, MMP3, and MMP9, as well as the cell adhesion molecule ICAM1 in human primary keratinocytes. In vivo studies indicated that miR-939 increased the expression of matrix metalloproteinases to promote the colonization of S. aureus and exacerbated S. aureus-induced AD-like skin inflammation. Conclusions: Our work reveals miR-939 is an important regulator of skin inflammation in AD that could be used as a potential therapeutic target for AD.

Numerical study of the future PM2.5 concentration under climate change and Best-Health-Effect (BHE) scenario.

The Beijing-Tianjin-Hebei (BTH) is one of the key areas with PM2.5 air pollution in China. Driven by the PM2.5 target accessibility of the Interim Target-1 (IT-1) by World Health Organization (WHO) and China's carbon neutrality, this study explored and quantified the contribution of climate change and anthropogenic emission to future PM2.5 in the region. The experiments considered future climate change scenarios RCP8.5, RCP4.5, and RCP2.6 with the baseline (Base) and reduced emission (EIT1) inventories in 2030, and RCP4.5 climate scenario with 3 emission inventories in 2050, the additional strong control emission scenario called Best-Health-Effect (BHE). Under various climate scenarios, the future air quality research modelling system projected annual PM2.5 concentrations nearing 35 µg/m3 in 2030. However, considering only the effect of emission reduction, the annual PM2.5 concentrations under EIT1 emission scenario is about 35% less than under Base scenario in different key years. The future PM2.5 concentrations are highly related to anthropogenic emission from human activities, while climate change by 2030 or 2050 has little impact on future air quality over the BTH region. The BHE emission reduction is significantly required for China to meet the new PM2.5 guideline value of WHO in the future.

Feasibility of an exercise-nutrition-psychology integrated rehabilitation model based on mobile health and virtual reality for cancer patients: a single-center, single-arm, prospective phase II study.

OBJECTIVE: Explore the feasibility of a mobile health(mHealth) and virtual reality (VR) based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. METHODS: We recruited cancer patients in the Oncology department of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from October 2022 to April 2023. The rehabilitation program was provided by a team of medical oncologists, dietitians, psychotherapists, and oncology specialist nurses. Participants received standard anti-cancer therapy and integrated intervention including hospitalized group-based exercise classes, at-home physical activity prescription, behavior change education, oral nutrition supplements, and psychological counseling. An effective intervention course includes two consecutive hospitalization and two periods of home-based rehabilitation (8 weeks). Access the feasibility as well as changes in aspects of physical, nutritional, and psychological status. RESULTS: At the cutoff date of April 2023, the recruitment rate was 75% (123/165). 11.4%patients were lost to follow-up, and 3.25% withdrew halfway. Respectively, the completion rate of nutrition, exercise, and psychology were 85%,55%, and 63%. Nutrition interventions show the highest compliance. The parameters in nutrition, psychology, muscle mass, and quality of life after the rehabilitation showed significant improvements (P < .05). There was no significant statistical difference (P > .05) in handgrip strength and 6-minute walking speed. CONCLUSION: It is feasible to conduct mHealth and VR-based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. A larger multi-center trial is warranted in the future. TRIAL REGISTRATION: ChiCTR2200065748 Registered 14 November 2022.

Clinical characteristics and genetic analysis of children with Omicron BF.7.14 type novel coronavirus-related acute necrotizing encephalopathy.

Background: To explore the clinical characteristics, etiological factors, and clinical-related genetic variant of children with acute necrotizing encephalopathy (ANE) related to the Omicron BF.7.14 novel coronavirus. Methods: Genomic variations were detected through whole exome sequencing. Additionally, we summarized the clinical data to explore the inheritance patterns associated with novel coronavirus-related ANE. Results: This study included four patients (2 males and 2 females) with an average age of 2.78 ± 1.93 years. All the patients had prodromal symptoms of Omicron BF.7.14 virus infection, and exhibited symptoms such as altered consciousness, seizures and cognitive/language disturbances. Cranial MRI scans revealed damage to the thalamus, basal ganglia and brainstem. The cerebrospinal fluid (CSF) cell counts were nearly normal, but protein level in CSF increased significantly. Genetic analysis revealed a novel truncated variant of CRMP2 gene in one patient who suffered more severe coma score and prognosis and dead in the later stages. All children exhibited a decrease in the absolute count of T lymphocytes, helper T cells, suppressor T cells, and NK cells to varying degrees. Furthermore, levels of cytokines, including IL-1 ß, IL-5, IL-6 and IL-8 were significantly elevated in the CSF, especially in patient with truncated variant of CRMP2 gene. Conclusion: The Omicron BF.7.14 type novel coronavirus can lead to ANE, characterized by T cell immunosuppression and a significant increase in cytokine levels in the CSF. The truncated variation of CRMP2 gene may affect the prognosis of ANE by affecting the migration of cerebral T cells.

SERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-type Palmoplantar Keratoderma.

Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive genodermatosis caused by loss-of-function variants in SERPINB7 and is the most prevalent form of inherited palmoplantar keratodermas among Asians. However, there is currently no effective therapy for NPPK because its pathogenesis remains unclear. In this study, Serpinb7-/- mice were generated and spontaneously developed a disrupted skin barrier, which was further exacerbated by acetone-ether-water treatment. The skin of these Serpinb7-/- mice showed weakened cytoskeletal proteins. Additionally, SERPINB7 deficiency consistently led to decreased epidermal differentiation in a three-dimensional human epidermal model. We also demonstrated that SERPINB7 was an inhibitory serpin that mainly inhibited the protease legumain. SERPINB7 bound directly with legumain and inhibited legumain activity both in vitro and in vivo. Furthermore, we found that SERPINB7 inhibited legumain in a 'protease-substrate' manner and identified the cleavage sites of SERPINB7 as Asn71 and Asn343. Overall, we found that SERPINB7 showed the nature of a cysteine protease inhibitor, and identified legumain as a key target protease of SERPINB7. Loss of SERPINB7 function led to overactivation of legumain, which might disrupt cytoskeletal proteins, contributing to the impaired skin barrier in NPPK. These findings may lead to the development of therapeutic strategies for NPPK.

KMT2A Mutations and High Prevalence of dMMR-associated Mutational Signatures as Prognostic Indicators in Metastatic Colorectal Cancer.

The conventional treatment strategies for patients with metastatic colorectal cancer (mCRC) are predominantly guided by the status of RAS and BRAF mutations. Although patients may exhibit analogous pathological characteristics and undergo similar treatment regimens, notable disparities in their prognostic outcomes can be observed. Therefore, tissue and plasma samples from 40 mCRC patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Genomic variations and canonical oncogenic pathways were investigated for their prognostic effects in association with progression-free survival (PFS) of these patients. We found that patients with BRCA2 and KMT2A mutations exhibited worse prognostic outcomes after chemotherapy-based treatment (univariate, P < 0.01). Further pathway analysis indicated that alterations in the homologous recombination pathway and in the KMT2A signaling network were also significantly associated with shortened PFS (univariate, P < 0.01). Additionally, mutation signature analysis showed that patients with higher proportions of defective mismatch repair (dMMR)-related mutational signatures. Had a worse prognosis (univariate, P = 0.02). KMT2A mutations (hazard ratio [HR], 4.47; 95% confidence interval [CI], 1-19.93; P =0.050) and dMMR signature proportions (HR, 3.57; 95% CI, 1.42-8.96; P = 0.007) remained independently associated with PFS after multivariate analysis and the results were further externally validated. These findings may enhance our understanding of this disease and may potentially facilitate the optimization of its treatment approaches.

Single-cell profiling and functional screening reveal crucial roles for lncRNAs in the epidermal re-epithelialization of human acute wounds.

Objectives: Re-epithelialization is an important physiological process for repairing skin barrier function during wound healing. It is primarily mediated by coordinated migration, proliferation, and differentiation of keratinocytes. Long noncoding RNAs (lncRNAs) are essential components of the noncoding genome and participate in various biological processes; however, their expression profiles and function in re-epithelialization during wound healing have not been established. Methods: We investigated the distribution of lncRNAs during wound re-epithelialization by comparing the genomic profiles of uninjured skin and acute wound (AW) from healthy donors. We performed functional screening of differentially expressed lncRNAs to identify the important lncRNAs for re-epithelialization. Results: The expression of multiple lncRNAs is changed during human wound re-epithelialization process. We identified VIM-AS1, SMAD5-AS1, and LINC02581 as critical regulators involved in keratinocyte migration, proliferation, and differentiation, respectively. Conclusion: LncRNAs play crucial regulatory roles in wound re-epithelialization. We established lncRNA expression profile in human acute wounds compared with intact skin, offering valuable insights into the physiological mechanisms underlying wound healing and potential therapeutic targets.

Identification of marine microplastics based on laser-induced fluorescence and principal component analysis.

Although the laser-induced fluorescence method shows great potential for microplastic particle detection, overlapping fluorescence signals make accurate type and proportion identification difficult. This paper presents the identification of marine microplastics based on laser-induced fluorescence and principal component analysis. This method works by measuring the fluorescence spectra of water-containing microplastic samples irradiated with a 405-nm laser, which are then analyzed using the principal component analysis (PCA) method. The nine types of microplastics were differentiated based on their positions in the PCA score plot. The mixed sample was positioned between the pure microplastic samples. The component ratio determines its position relative to that of the pure microplastic samples. The first two principal components of the mixed microplastics were linearly dependent. Natural seawater had less influence on the detection, and a mass concentration as low as 0.03% was detected.

Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer.

Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly cisplatin. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that exhibit marked resistance to cisplatin with association with glycolysis metabolism. Notably, we observed that H3 lysine 18 lactylation (H3K18la) plays a crucial role in activating the transcription of target genes by enriching in their promoter regions. Targeted inhibition of H3K18la effectively restored cisplatin sensitivity in these cisplatin-resistant epithelial cells. Furthermore, H3K18la-driven key transcription factors YBX1 and YY1 promote cisplatin resistance in BCa. These findings enhance our understanding of the mechanisms underlying cisplatin resistance, offering valuable insights for identifying novel intervention targets to overcome drug resistance in Bca.

Surface charging and electrophoretic behavior of conductive polymer micro-droplets in conductive polymer liquid solutions.

This study investigates the surface charging and electrophoretic motion of polyethylene glycol-rich (PEG-rich) micro-droplets in dextran-rich solutions or dextran-rich micro-droplets in PEG-rich solutions. The electrophoretic velocities of the droplets were measured in a centimeter-sized chamber under an optical microscope. It was found that the direction of electrophoretic motion of both the PEG-rich droplets and dextran-rich droplets is opposite to the applied electric field, meaning that both the PEG-rich droplets and dextran-rich droplets are negatively charged. The electrophoretic velocity is independent of droplet size but proportional to the electric field strength. Increasing the NaCl concentration reduces the electrophoretic velocity of PEG-rich droplets and increases it for dextran-rich droplets, suggesting different surface charge changes due to ion affinity. The charge densities and velocities are affected by the PEG and dextran mass fractions. Physical models for droplet surface charging under different conditions were proposed to explain the experimental results.

YTHDC1-Modified m6A Methylation of Hsa_circ_0102678 Promotes Keratinocyte Inflammation Induced by Cutibacterium acnes Biofilm through Regulating miR-146a/TRAF6 and IRAK1 Axis.

INTRODUCTION: CircRNAs are closely related to many human diseases; however, their role in acne remains unclear. This study aimed to determine the role of hsa_circ_0102678 in regulating inflammation of acne. METHODS: First, microarray analysis was performed to study the expression of circRNAs in acne. Subsequently, RNase R digestion assay and fluorescence in situ hybridization assay were utilized to confirm the characteristics of hsa_circ_0102678. Finally, qRT-PCR, Western blotting analysis, immunoprecipitation, luciferase reporter assay, circRNA probe pull-down assay, biotin-labeled miRNA pull-down assay, RNA immunoprecipitation assay, and m6A dot blot assay were utilized to reveal the functional roles of hsa_circ_0102678 on inflammation induced by C. acnes biofilm in human primary keratinocytes. RESULTS: Our investigations showed that the expression of hsa_circ_0102678 was significantly decreased in acne tissues, and hsa_circ_0102678 was a type of circRNAs, which was mainly localized in the cytoplasm of primary human keratinocytes. Moreover, hsa_circ_0102678 remarkably affected the expression of IL-8, IL-6, and TNF-α, which induced by C. acnes biofilm. Importantly, mechanistic studies indicated that the YTHDC1 could bind directly to hsa_circ_0102678 and promote the export of N6-methyladenosine-modified hsa_circ_0102678 to the cytoplasm. Besides, hsa_circ_0102678 could bind to miR-146a and sponge miR-146a to promote the expression of IRAK1 and TRAF6. CONCLUSION: Our findings revealed a previously unknown process by which hsa_circ_0102678 promoted keratinocyte inflammation induced by C. acnes biofilm via regulating miR-146a/TRAF6 and IRAK1 axis.

The co-regulation of the gut microbiome and host genes might play essential roles in metformin gastrointestinal intolerance.

Metformin is commonly used, but approximately 20% of patients experience gastrointestinal intolerance, leading to medication discontinuation for unclear reasons and a lack of effective management strategies. In this study, the 18 fecal and blood samples were analyzed using 16S rRNA and mRNA transcriptome, respectively. These samples included 3 fecal and 4 blood from metformin-tolerant T2D patients before and after metformin treatment (T and Ta), 3 fecal and 5 blood from metformin-intolerant T2D patients before and after treatment (TS and TSa), and 6 fecal samples from healthy controls. The results showed that certain anti-inflammatory gut bacteria and gene, such as Barnesiella (p = 0.046), Parabacteroides goldsteinii (p = 0.016), and the gene JUND (p = 0.0002), exhibited higher levels in metformin-intolerant patients, and which decreased after metformin treatment (p < 0.05). This potentially invalidates patients' anti-inflammatory effect and intestinal mucus barrier protection, which may lead to alterations in intestinal permeability, decreased gut barrier function, and gastrointestinal symptoms, including diarrhea, bloating, and nausea. After metformin treatment, primary bile acids (PBAs) production species: Weissella confusa, Weissella paramesenteroides, Lactobacillus brevis, and Lactobacillus plantarum increased (p < 0.05). The species converting PBAs to secondary bile acids (SBAs): Parabacteroides distasonis decreased (p < 0.05). This might result in accumulation of PBAs, which also may lead to anti-inflammatory gene JUND and SQSTM1 downregulated. In conclusion, this study suggests that metformin intolerance may be attributed to a decrease in anti-inflammatory-related flora and genes, and also alterations in PBAs accumulation-related flora. These findings open up possibilities for future research targeting gut flora and host genes to prevent metformin intolerance.

Lnc-PKNOX1-1 inhibits tumor progression in cutaneous malignant melanoma by regulating NF-κB/IL-8 axis.

Cutaneous malignant melanoma is one of the most lethal cutaneous malignancies. Accumulating evidence has demonstrated the potential influence of long non-coding RNAs (lncRNAs) in biological behaviors of melanoma. Herein, we reported a novel lncRNA, lnc-PKNOX1-1 and systematically studied its functions and possible molecular mechanisms in melanoma. Reverse transcription-quantitative PCR assay showed that lnc-PKNOX1-1 was significantly decreased in melanoma cells and tissues. Low lnc-PKNOX1-1 expression was significantly correlated with invasive pathological type and Breslow thickness of melanoma. In vitro and in vivo experiments showed lnc-PKNOX1-1 dramatically inhibited melanoma cell proliferation, migration and invasion. Mechanically, protein microarray analysis suggested that interleukin-8 (IL-8) was negatively regulated by lnc-PKNOX1-1 in melanoma, which was confirmed by western blot and ELISA. Western blot analysis also showed that lnc-PKNOX1-1 could promote p65 phosphorylation at Ser536 in melanoma. Subsequent rescue assays proved IL-8 overexpression could partly reverse the tumor-suppressing function of lnc-PKNOX1-1 overexpression in melanoma cells, indicating that lnc-PKNOX1-1 suppressed the development of melanoma by regulating IL-8. Taken together, our study demonstrated the tumor-suppressing ability of lnc-PKNOX1-1 in melanoma, suggesting its potential as a novel diagnostic biomarker and therapeutic target for melanoma.

The Communication from Immune Cells to the Fibroblasts in Keloids: Implications for Immunotherapy.

Keloids are a type of fibrotic disease characterized by excessive collagen production and extracellular matrix (ECM) deposition. The symptoms of pain and itching and frequent recurrence after treatment significantly impact the quality of life and mental health of patients. A deeper understanding of the pathogenesis of keloids is crucial for the development of an effective therapeutic approach. Fibroblasts play a central role in the pathogenesis of keloids by producing large amounts of collagen fibers. Recent evidence indicates that keloids exhibit high immune cell infiltration, and these cells secrete cytokines or growth factors to support keloid fibroblast proliferation. This article provides an update on the knowledge regarding the keloid microenvironment based on recent single-cell sequencing literature. Many inflammatory cells gathered in keloid lesions, such as macrophages, mast cells, and T lymphocytes, indicate that keloids may be an inflammatory skin disease. In this review, we focus on the communication from immune cells to the fibroblasts and the potential of immunotherapy for keloids. We hope that this review will trigger interest in investigating keloids as an inflammatory disease, which may open up new avenues for drug development by targeting immune mediators.

Progress in construction and release of natural polysaccharide-platinum nanomedicines: A review.

Natural polysaccharides are natural biomaterials that have become candidate materials for nano-drug delivery systems due to their excellent biodegradability and biocompatibility. Platinum (Pt) drugs have been widely used in the clinical therapy for various solid tumors. However, their extensive systemic toxicity and the drug resistance acquired by cancer cells limit the applications of platinum drugs. Modern nanobiotechnology provides the possibility for targeted delivery of platinum drugs to the tumor site, thereby minimizing toxicity and optimizing the efficacies of the drugs. In recent years, numerous natural polysaccharide-platinum nanomedicine delivery carriers have been developed, such as nanomicelles, nanospheres, nanogels, etc. Herein, we provide an overview on the construction and drug release of natural polysaccharide-Pt nanomedicines in recent years. Current challenges and future prospectives in this field are also put forward. In general, combining with irradiation and tumor microenvironment provides a significant research direction for the construction of natural polysaccharide-platinum nanomedicines and the release of responsive drugs in the future.

TIAM1 acts as an actin organization regulator to control adipose tissue-derived pericyte cell fate.

Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue- and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue-derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.

Synergistic ferroptosis-starvation therapy for bladder cancer based on hyaluronic acid modified metal-organic frameworks.

Bladder cancer (BCa) is one of the most common malignancies of the urinary tract. Metastasis and recurrence of BCa are the leading causes of poor prognosis, and only a few patients can benefit from current first-line treatments such as chemotherapy and immunotherapy. It is urgent to develop more effective therapeutic method with low side effects. Here, a cascade nanoreactor, ZIF-8/PdCuAu/GOx@HA (ZPG@H), is proposed for starvation therapy and ferroptosis of BCa. The ZPG@H nanoreactor was constructed by co-encapsulation of PdCuAu nanoparticles and glucose oxidase into zeolitic imidazolate framework-8 (ZIF-8) modified by hyaluronic acid. The vitro results indicated that ZPG@H enhanced intracellular reactive oxygen species levels and reduced mitochondrial depolarization in the tumor microenvironment. Therefore, the integrated advantages of starvation therapy and chemodynamic therapy endow ZPG@H with a perfect ferroptosis inducing ability. This effectiveness, combined with its excellent biocompatibility and biosafety, means that ZPG@H could make a critical contribution to the development of novel BCa treatments.

High-Performance Integrated Iontronic Circuits Based on Single Nano/Microchannels.

Recently, artificial channel-based ionic diodes and transistors are extensively studied to mimic biological systems. Most of them are constructed vertically and are challenging to be further integrated. Several examples of ionic circuits with horizontal ionic diodes are reported. However, they generally require nanoscale channel sizes to meet the demand for ion-selectivity, resulting in low current output and restricting potential applications. In this paper, a novel ionic diode is developed based on multiple-layer polyelectrolyte nanochannel network membranes. Both bipolar and unipolar ionic diodes can be achieved by simply switching the modification solution. Ionic diodes with a high rectification ratio of ≈226 are achieved in single channels with the largest channel size of 2.5 µm. This design can significantly reduce the channel size requirement and improve the output current level of ionic devices. The high-performance ionic diode with a horizontal structure enables the integration of advanced iontronic circuits. Ionic transistors, logic gates, and rectifiers are fabricated on a single chip and demonstrated for current rectification. Furthermore, the excellent current rectification ratio and the high output current of the on-chip ionic devices highlight the promise of the ionic diode as a component of complex iontronic systems for practical applications.

Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport.

After a skin injury, keratinocytes switch from a state of homeostasis to one of regeneration leading to the reconstruction of the epidermal barrier. The regulatory mechanism of gene expression underpinning this key switch during human skin wound healing is enigmatic. Long noncoding RNAs (lncRNAs) constitute a new horizon in the understanding of the regulatory programs encoded in the mammalian genome. By comparing the transcriptome of an acute human wound and skin from the same donor as well as keratinocytes isolated from these paired tissue samples, we generated a list of lncRNAs showing changed expression in keratinocytes during wound repair. Our study focused on HOXC13-AS, a recently evolved human lncRNA specifically expressed in epidermal keratinocytes, and we found that its expression was temporally downregulated during wound healing. In line with its enrichment in suprabasal keratinocytes, HOXC13-AS was found to be increasingly expressed during keratinocyte differentiation, but its expression was reduced by EGFR signaling. After HOXC13-AS knockdown or overexpression in human primary keratinocytes undergoing differentiation induced by cell suspension or calcium treatment and in organotypic epidermis, we found that HOXC13-AS promoted keratinocyte differentiation. Moreover, RNA pull-down assays followed by mass spectrometry and RNA immunoprecipitation analysis revealed that mechanistically HOXC13-AS sequestered the coat complex subunit alpha (COPA) protein and interfered with Golgi-to-endoplasmic reticulum (ER) molecular transport, resulting in ER stress and enhanced keratinocyte differentiation. In summary, we identified HOXC13-AS as a crucial regulator of human epidermal differentiation.

Dyadic effects of work overcommitment on depression in dual-earner couples: based on the actor-partner interdependence model.

In this study, we aimed to examine the actor and partner effects of overcommitment on depression in dual-earner couples and the potential mediating role of emotional exhaustion at the actor and partner levels. With a cross-sectional design, 172 dual-earner couples in Chongqing, China, completed the measures of overcommitment, emotional exhaustion, and depression. The results showed that (a) overcommitment has a significant actor effect on depression for the husband and wife, and there were gender differences in the partner effects; that is, a wife's overcommitment has a significant partner effect on the husband's depression, while a husband's partner effect was not significant; (b) emotional exhaustion mediated the effects of overcommitment on depression for both husbands and wives at the actor level, while at the partner level, only a wife's exhaustion mediated the partner effect of a wife's overcommitment on a husband's depression. Focusing on couples' interdependence, these results enriched the understanding of the relationship between overcommitment and depression within dual-earner couples.