Translation and adaptation of Shared Care Instrument-Revised for the older adults and their caregivers in Taiwan.

BACKGROUND: The aging population in Taiwan has resulted in an increase in the dependent population and the care load on caregivers. Shared care is an interpersonal process in which support is "traded" to "handle" chronic illnesses by home-care patients and family caregivers. The scale of shared care has received little attention in the Taiwanese cultural context. Thus, this study examined the reliability and validity of the Taiwanese versions of Shared Care Instrument-Revised (SCI-R). METHODS: The content validity, construct validity, and discriminant validity were used to test the validity of the translated questionnaires. The Cronbach's α was used to examine reliability. A total of 500 older adults and their caregivers were recruited from three counties in Taiwan. RESULTS: The reliability and validity of the Chinese version of the scale were within the acceptable range. The Cronbach's α was between 0.838 and 0.95. However, the scale's reliability was higher than that of the original version. This might be because of the inclusion of participants with less severe diseases than the participants in the original study, high social expectations in the Chinese traditional culture, and a large number of similar items. Future research should simplify the items and consider adopting diverse participant selection criteria. CONCLUSIONS: The results of this study can be used to understand shared care in Taiwan.

Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Penicilloneines A and B, Quinolone-Citrinin Hybrids from a Starfish-Derived Penicillium sp.

Penicilloneines A (1) and B (2) are the first reported quinolone-citrinin hybrids. They were isolated from the starfish-derived fungus Penicillium sp. GGF16-1-2, and their structures were elucidated using spectroscopic, chemical, computational, and single-crystal X-ray diffraction methods. Penicilloneines A (1) and B (2) share a common 4-hydroxy-1-methyl-2(1H)-quinolone unit; however, they differ in terms of citrinin moieties, and these two units are linked via a methylene bridge. Penicilloneines A (1) and B (2) exhibited antifungal activities against Colletotrichum gloeosporioides, with lethal concentration 50 values of 0.02 and 1.51 µg/mL, respectively. A mechanistic study revealed that 1 could inhibit cell growth and promote cell vacuolization and consequent disruption of the fungal cell walls via upregulating nutrient-related hydrolase genes, including putative hydrolase, acetylcholinesterase, glycosyl hydrolase, leucine aminopeptidase, lipase, and beta-galactosidase, and downregulating their synthase genes 3-carboxymuconate cyclase, pyruvate decarboxylase, phosphoketolase, and oxalate decarboxylase.

Noninvasive Assessment of hiPSC Differentiation toward Cardiomyocytes Using Pretrained Convolutional Neural Networks and the Channel Pruning Algorithm.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) offer versatile applications in tissue engineering and drug screening. To facilitate the monitoring of hiPSC cardiac differentiation, a noninvasive approach using convolutional neural networks (CNNs) was explored. HiPSCs were differentiated into cardiomyocytes and analyzed using the quantitative real-time polymerase chain reaction (qRT-PCR). The bright-field images of the cells at different time points were captured to create the dataset. Six pretrained models (AlexNet, GoogleNet, ResNet 18, ResNet 50, DenseNet 121, VGG 19-BN) were employed to identify different stages in differentiation. VGG 19-BN outperformed the other five CNNs and exhibited remarkable performance with 99.2% accuracy, recall, precision, and F1 score and 99.8% specificity. The pruning process was then applied to the optimal model, resulting in a significant reduction of model parameters while maintaining high accuracy. Finally, an automation application using the pruned VGG 19-BN model was developed, facilitating users in assessing the cell status during the myocardial differentiation of hiPSCs.

A novel signature integrated endoplasmic reticulum stress and apoptosis related genes to predict prognosis for breast cancer.

Background: Breast cancer (BC) is the primary cause of cancer mortality. Herein, we aimed to establish and verify a prognostic model consisting of endoplasmic reticulum stress and apoptosis related genes (ERAGs) to predict patient survival. Methods: The Cancer Genome Atlas (TCGA) database was used to download gene expression and clinical data to identify the differentially expressed genes (DEGs). Using univariate Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis, the prognostic ERAGs were screened. The predictive performance was evaluated using Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analysis. Furthermore, a nomogram model incorporating clinical parameters and risk scores was constructed and subsequently evaluated using ROC and KM analysis. The correlation analysis, mutation analysis, functional enrichment analysis, and immune infiltration analysis were employed to investigate the specific mechanism of ERAGs. We also used Quantitative Real-Time PCR (RT-qPCR) to verify the differential expression of DE-ERAGs between the breast cancer cell line and mammary epithelial cell line. Results: We constructed a prognostic signature comprising 16 ERAGs. ROC, KM analysis and the nomogram model demonstrated high effectiveness in accurately predicting the overall survival (OS) of BRCA patients. The results of these analysis could provide reference for further mechanism exploration. Conclusion: We developed and assessed a novel molecular predictive model for breast cancer that focuses on endoplasmic reticulum stress and apoptosis in this study. It is a valuable complement to the existing prognostic prediction models for breast cancer.

A novel fluorescence-electrochemiluminescence dual-mode sensing platform for high-precision BRAF gene detection.

In this study, we innovatively synthesized bipyridine ruthenium cluster nanosheets (RuMOFNCs), a novel metal-organic framework material that exhibits both fluorescence and electrochemiluminescence. Gold nanoparticles (AuNPs) were anchored onto RuMOFNCs via bipyridine chelation, enhancing optical signals and creating sites for attaching biologically functional probes. We employed tetraferrocene-modified DNA probes, linked via gold-sulfur (Au-S) bonds, to construct a dual-mode fluorescence-electrochemiluminescence biosensor. This sensor, exploiting exonuclease III (Exo III)-mediated cyclic amplification, inhibits the electron transfer from RuMOFNC to tetraferrocene, resulting in amplified fluorescence and electrochemiluminescence signals. The sensor demonstrates exceptional sensitivity for detecting the BRAF gene, with fluorescence and electrochemiluminescence detection limits of 10.3 aM (range: 0.1 fM to 1 nM) and 3.1 aM (range: 1 aM to 10 pM), respectively. These capabilities are attributed to RuMOFNCs' luminescence properties, tetraferrocene's quenching effect, and the specificity of base pairing. This study's findings hold substantial promise for biomedical research and clinical diagnostics, particularly in precision medicine and early disease detection.

Probe Substrate Dependencies in CYP3A4 Allosteric Inhibition: A Novel Molecular Mechanism Involving F-F' Loop Perturbations.

The biochemical basis for substrate dependences in apparent inhibition constant values (Ki) remains unknown. Our study aims to elucidate plausible structural determinants underpinning these observations. In vitro steady-state inhibition assays conducted using human recombinant CYP3A4 enzyme and testosterone substrate revealed that fibroblast growth factor receptor (FGFR) inhibitors erdafitinib and pemigatinib noncompetitively inhibited CYP3A4 with apparent Ki values of 10.2 ± 1.1 and 3.3 ± 0.9 µM, respectively. However, when rivaroxaban was adopted as the probe substrate, there were 2.0- and 3.2-fold decreases in its apparent Ki values. To glean mechanistic insights into this phenomenon, erdafitinib and pemigatinib were docked to allosteric sites in CYP3A4. Subsequently, molecular dynamics (MD) simulations of apo- and holo-CYP3A4 were conducted to investigate the structural changes induced. Comparative structural analyses of representative MD frames extracted by hierarchical clustering revealed that the allosteric inhibition of CYP3A4 by erdafitinib and pemigatinib did not substantially modulate its active site characteristics. In contrast, we discovered that allosteric binding of the FGFR inhibitors reduces the structural flexibility of the F-F' loop region, an important gating mechanism to regulate access of the substrate to the catalytic heme. We surmised that the increased rigidity of the F-F' loop engenders a more constrained entrance to the CYP3A4 active site, which in turn impedes access to the larger rivaroxaban molecule to a greater extent than testosterone and culminates in more potent inhibition of its CYP3A4-mediated metabolism. Our findings suggest a potential mechanism to rationalize probe substrate dependencies in Ki arising from the allosteric noncompetitive inhibition of CYP3A4.

Observational evidence and mechanisms of aerosol effects on precipitation.

Aerosols greatly influence precipitation characteristics, thereby impacting the regional climate and human life. As an indispensable factor for cloud formation and a critical radiation budget regulator, aerosols can affect precipitation intensity, frequency, geographical distribution, area, and time. However, discrepancies exist among current studies due to aerosol properties, precipitation types, the vertical location of aerosols and meteorological conditions. The development of technology has driven advances in current research, but understanding the aerosol effects on precipitation remain complex and challenging. This paper revolves around the following topics from the two perspectives of Aerosol-Radiation Interaction (ARI) and Aerosol-Cloud Interaction (ACI): (1) the influence of different vertical locations of absorbing/scattering aerosols on the atmospheric thermal structure; (2) the fundamental theories of ARI reducing surface wind speed, redistributing water vapour and energy, and then modulating precipitation intensity; (3) different aerosol types (absorbing versus scattering) and aerosol concentrations causing different precipitation diurnal and weekly variations; (4) microphysical processes (cloud water competition, invigoration effect, and evaporation cooling) and observational evidence of different effects of aerosols on precipitation intensity, including enhancing, inhibiting, and transitional effects from enhancement to suppression; and (5) how meteorology, water vapor and dynamics influencing the effect of ACI and ARI on precipitation. In addition, this review lists the existing issues and future research directions for attaining a more comprehensive understanding of aerosol effects on precipitation. Overall, this review advances our understanding of aerosol effects on precipitation and could guide the improvement of weather and climate models to predict complex aerosol-precipitation interactions more accurately.

[Spatial and temporal distribution characteristics of extreme wind and its effect on wind erosion in Northeast China]. / ä¸œåŒ—åœ°åŒºæžç«¯å¤§é£Žæ—¶ç©ºåˆ†å¸ƒç‰¹å¾åŠå ¶å¯¹é£Žèš€é‡çš„å½±å“.

Under the background of climate change, extreme wind events occur frequently in Northeast China, and the soil erosion caused by these extreme wind events has attracted progressively more attention from scholars. We used the methods of linear analysis, Sen+Mann-Kendal trend analysis, and Kriging interpolation to analyze the spatial and temporal characteristics of extreme wind in Northeast China from 2005 to 2020, and used the RWEQ wind erosion estimation model to calculate the annual soil wind erosion of typical wind erosion sites and wind erosion under extreme wind conditions. The results showed that the extreme wind frequency in Northeast China presented a significant upward trend from 2005 to 2020, with an increase of 2.9 times·a-1. The annual average extreme wind frequency in Northeast China ranged from 1 to 49 times·a-1, and the high frequency areas were distributed in the northwest of Xilin Gol, the west of the Hulunbuir Plateau, and the northeast of Changbai Mountain. The average contribution rate of extreme wind to soil wind erosion in four typical sites (Xilinhot, New Barhu Right Banner, Nenjiang, and Tongyu) was 31%.

In-situ construction of cation vacancies in amphoteric-metallic element-doped NiFe-LDH as ultrastable and efficient alkaline hydrogen evolution electrocatalysts at 1000 mA cm-2.

Developing efficient and stable electrocatalysts at affordable costs is very important for large-scale production of green hydrogen. In this study, unique amphoteric metallic element-doped NiFe-LDH nanosheet arrays (NiFeCd-LDH, NiFeZn-LDH and NiFeAl-LDH) using as high-performance bifunctional electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) were reported, by tuning electronic structure and vacancy engineering. It was found that NiFeCd-LDH possesses the lowest overpotentials of 85 mV and 240 mV (at 10 mA cm-2) for HER and OER, respectively. Density functional theory (DFT) calculations reveal the synergistic effect of Cd vacancies and Cd doping on improving alkaline HER performance, which promote the achievement of excellent catalytic activity and ultrastable hydrogen production at a large current density of 1000 mA cm-2 within 250 h. Besides, the overall water splitting performance of the as-prepared NiFeCd-LDH requires only 1.580 V to achieve a current density of 10 mA cm-2 in alkaline seawater media, underscoring the importance of modifying the electronic properties of LDH for efficient overall water splitting in both alkaline water/seawater environments.

The accessible chromatin landscape of lipopolysaccharide-induced systemic inflammatory response identifying epigenome signatures and transcription regulatory networks in chickens.

Lipopolysaccharide (LPS) can induce systemic inflammatory response (SIR) in animals. Understanding the regulatory mechanism of SIR and therapies to ensure healthy growth is urgently needed. Chromatin remodeling plays a crucial role in the expression of genes involved in immune diseases. In the present study, the ATAC-seq analysis revealed 3491 differential open chromatin sites in the spleen of chicks with SIR induced by LPS challenge, and we presented the motifs on these sites and the associated transcription factors. The regulatory network was presented by combining the differential open chromatin data with the mRNAs and exploded cytokines. Interestingly, the LPS challenge could regulate the mRNA expression of 202 genes through chromatin reprogramming, including critical genes such as TLE1 and JUN, which regulate signaling pathways such as I-κB kinase/NF-κB, Toll-like receptor, and downstream cytokine genes. Furthermore, dietary daidzein could inhibit DNA topoisomerase II, which reprograms the spatial conformation of chromatin in the inflammatory response and attenuates SIR. In conclusion, we successfully identified key genes directly regulated by chromatin reprogramming in SIR and demonstrated the chromatin epigenome signatures and transcriptional regulatory network, which provides an important reference for further research on avian epigenetics. There is great potential for alleviating SIR using dietary daidzein.

Fat intake modifies association between cigarette smoking and lung cancer in a prospective cohort study: A potential explanation for the lung cancer paradox.

BACKGROUND & AIMS: It remains unclear why the association between cigarette smoking and lung cancer was substantially stronger in Western countries than in Asian countries. As experimental studies have revealed that fat intake modulates tobacco carcinogen metabolism and the growth of transplanted or carcinogen-induced lung tumors in mice, the present study sought to investigate whether the association between cigarette smoking and lung cancer was modified by intake of total fat and types of fat (saturated, monounsaturated, and polyunsaturated fats) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. METHODS: During a median follow-up of 8.9 years, 1,425 cases of lung cancer were documented from 100,864 participants eligible for the present analysis. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: After adjustment for established or suspected confounders, the strength of the association between cigarette smoking and lung cancer was remarkably larger among individuals with high fat intake. HRs (95% CIs) comparing current with never smokers were 23.0 (13.4, 39.6), 32.7 (20.3, 52.8), and 59.8 (30.2, 118.2) for the tertile 1 (≤13.48 g/day), tertile 2 (13.49-21.89 g/day), and tertile 3 (≥21.90 g/day) of saturate fat intake, respectively. A similar pattern of the non-significant interaction was observed when the accumulated amount of cigarette smoking (1-19, 20-39, and ≥40 vs. 0 pack-years) was entered into the regression models. CONCLUSIONS: The present study showed that lung cancer risk associated with both the status and accumulated amount of cigarette smoking was remarkably stronger in individuals with high intakes of fat, particularly saturated fat. However, this interaction was not statistically significant and thus warrants further investigations in other studies.

TRIM56: a promising prognostic immune biomarker for glioma revealed by pan-cancer and single-cell analysis.

Tripartite-motif 56 (TRIM56) is a member of the TRIM family, and was shown to be an interferon-inducible E3 ubiquitin ligase that can be overexpressed upon stimulation with double-stranded DNA to regulate stimulator of interferon genes (STING) to produce type I interferon and thus mediate innate immune responses. Its role in tumors remains unclear. In this study, we investigated the relationship between the expression of the TRIM56 gene and its prognostic value in pan-cancer, identifying TRIM56 expression as an adverse prognostic factor in glioma patients. Therefore, glioma was selected as the primary focus of our investigation. We explored the differential expression of TRIM56 in various glioma subtypes and verified its role as an independent prognostic factor in gliomas. Our research revealed that TRIM56 is associated with malignant biological behaviors in gliomas, such as proliferation, migration, and invasion. Additionally, it can mediate M2 polarization of macrophages in gliomas. The results were validated in vitro and in vivo. Furthermore, we utilized single-cell analysis to investigate the impact of TRIM56 expression on cell communication between glioma cells and non-tumor cells. We constructed a multi-gene signature based on cell markers of tumor cells with high TRIM56 expression to enhance the prediction of cancer patient prognosis. In conclusion, our study demonstrates that TRIM56 serves as a reliable immune-related prognostic biomarker in glioma.

The effects of various auditory takeover requests: A simulated driving study considering the modality of non-driving-related tasks.

With the era of automated driving approaching, designing an effective auditory takeover request (TOR) is critical to ensure automated driving safety. The present study investigated the effects of speech-based (speech and spearcon) and non-speech-based (earcon and auditory icon) TORs on takeover performance and subjective preferences. The potential impact of the non-driving-related task (NDRT) modality on auditory TORs was considered. Thirty-two participants were recruited in the present study and assigned to two groups, with one group performing the visual N-back task and another performing the auditory N-back task during automated driving. They were required to complete four simulated driving blocks corresponding to four auditory TOR types. The earcon TOR was found to be the most suitable for alerting drivers to return to the control loop because of its advantageous takeover time, lane change time, and minimum time to collision. Although participants preferred the speech TOR, it led to relatively poor takeover performance. In addition, the auditory NDRT was found to have a detrimental impact on auditory TORs. When drivers were engaged in the auditory NDRT, the takeover time and lane change time advantages of earcon TORs no longer existed. These findings highlight the importance of considering the influence of auditory NDRTs when designing an auditory takeover interface. The present study also has some practical implications for researchers and designers when designing an auditory takeover system in automated vehicles.

Comparison of clinical efficacy of 3D-printed artificial vertebral body and conventional titanium mesh cage in spinal reconstruction after total en bloc spondylectomy for spinal tumors: a systematic review and meta-analysis.

Propose: This meta-analysis aimed to determine whether 3D-printed artificial vertebral bodies (AVBs) have superior clinical efficacy compared to conventional titanium mesh cages (TMCs) for spinal reconstruction after total en bloc spondylectomy (TES) for spinal tumors. Methods: Electronic databases, including PubMed, OVID, ScienceDirect, Embase, CINAHL, Web of Science, Cochrane Library, WANFANG, and CNKI, were searched to identify clinical trials investigating 3D-printed AVB versus conventional TMC from inception to August 2023. Data on the operation time, intraoperative blood loss, preoperative and postoperative visual analogue scale (VAS) scores, preoperative and postoperative Frankel classification of spinal cord injury, vertebral body subsidence, and early complications were collected from eligible studies for a meta-analysis. Data were analyzed using Review Manager 5.4 and Stata 14.0. Results: Nine studies assessing 374 patients were included. The results revealed significant differences between the 3D-printed AVB and conventional TMC groups with regard to operation time (P = 0.04), intraoperative blood loss (P = 0.004), postoperative VAS score (P = 0.02), vertebral body subsidence (P < 0.0001), and early complications (P = 0.02). Conversely, the remaining preoperative VAS score and Frankel classifications (pre-and postoperative) did not differ significantly between the groups. Conclusion: The 3D-printed AVB in spinal reconstruction after TES for spinal tumors has the advantages of a short operative time, little intraoperative blood loss, weak postoperative pain, low occurrence of vertebral body subsidence and early complications, and a significant curative effect. This could provide a strong basis for physicians to make clinical decisions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441521, identifier CRD42023441521.

Effect of Er:YAG Laser Irradiation on Preventing Enamel Caries: A Systematic Review and Meta-Analysis.

Caries is a global health problem, and its prevention has become a main goal of modern dentistry. Laser irradiation is believed to have potential in preventing dental caries. The purpose of this systematic review and meta-analysis was to evaluate whether Er:YAG laser irradiation has the potential to prevent enamel caries. Based on inclusion and exclusion criteria, PubMed, Web of Science, and EMBASE databases were searched; 2 reviewers independently used these search strategies to review titles and abstracts, with no language or date restrictions, up to June 2023. For the quantitative analysis, continuous variables were analysed by standard mean difference (SMD) with a 95% confidence interval (CI). The statistical analyses were conducted using Review Manager and Cochrane Collaboration (2020). A total of 51 potentially eligible studies were identified, of which 16 in vitro studies were eventually included in the quantitative meta-analysis. Three studies showed a low risk of bias, and 13 studies a medium risk of bias. In general, there was no significant difference between the calcium ions released under acidic conditions after laser irradiation. The final results indicated that after Er:YAG laser irradiation, enamel could maintain higher surface microhardness in acidic environments, as well as smaller lesion depth and less mineral loss, revealing its potential in preventing enamel caries. However, the effect of laser irradiation on the release of calcium ions in acidic solutions and the surface microhardness of demineralised enamel was not significant. Therefore, more in vitro and clinical trials are needed in to evaluate whether Er:YAG laser irradiation can effectively prevent enamel caries in clinical settings.

Discovery of a quinoline-containing compound JT21-25 as a potent and selective inhibitor of apoptosis signal-regulating kinase 1 (ASK1).

ASK1 kinase inhibition has become a promising strategy for treating inflammatory diseases, such as non-alcoholic steatohepatitis and multiple sclerosis. Here, we reported the discovery of a promising compound 9h (JT21-25) containing quinoline structures as a potent small molecule inhibitor of ASK1. The compound JT21-25 was selective against MAP3K kinases TAK1 (>1960.8-fold), and much higher than the selectivity of GS-4997 for TAK1 (312.3-fold). In addition, different concentrations of JT21-25 did not show significant toxicity in normal LO2 liver cells, and the cell survival rate was greater than 80 %. The Oil Red O staining experiment showed that at the 4 µM and 8 µM concentrations of JT21-25, only slight cytoplasmic fat droplets were observed in LO2 cells, and there was no significant fusion between fat droplets. In the biochemical analysis experiment, JT21-25 significantly reduced the content of CHOL, LDL, TG, ALT, and AST. In summary, these findings suggested that compound JT21-25 might be valuable for further investigation as a potential candidate in the treatment of associated diseases.

Gradient Pores Enhance Charge Storage Density of Carbonaceous Cathodes for Zn-Ion Capacitor.

Engineering carbonaceous cathode materials with adequately accessible active sites is crucial for unleashing their charge storage potential. Herein, activated meso-microporous shell carbon (MMSC-A) nanofibers are constructed to enhance the zinc ion storage density by forming a gradient-pore structure. A dominating pore size of 0.86 nm is tailored to cater for the solvated [Zn(H2 O)6 ]2+ . Moreover, these gradient porous nanofibers feature rapid ion/electron dual conduction pathways and offer abundant active surfaces with high affinity to electrolyte. When employed in Zn-ion capacitors (ZICs), the electrode delivers significantly enhanced capacity (257 mAh g-1 ), energy density (200 Wh kg-1 at 78 W kg-1 ), and cyclic stability (95% retention after 10 000 cycles) compared to nonactivated carbon nanofibers electrode. A series of in situ characterization techniques unveil that the improved Zn2+ storage capability stems from size compatibility between the pores and [Zn(H2 O)6 ]2+ , the co-adsorption of Zn2+ , H+ , and SO4 2- , as well as reversible surface chemical interaction. This work presents an effective method to engineering meso-microporous carbon materials toward high energy-density storage, and also offers insights into the Zn2+ storage mechanism in such gradient-pore structures.

EGF-driven EGFR/miR-27b-3p/FOXO1 promotes rat FSH synthesis and secretion.

The adenopituitary secretes follicle-stimulating hormone (FSH), which plays a crucial role in regulating the growth, development, and reproductive functions of organisms. Investigating the process of FSH synthesis and secretion can offer valuable insights into potential areas of focus for reproductive research. Epidermal growth factor (EGF) is a significant paracrine/autocrine factor within the body, and studies have demonstrated its ability to stimulate FSH secretion in animals. However, the precise mechanisms that regulate this action are still poorly understood. In this research, in vivo and in vitro experiments showed that the activation of epidermal growth factor receptor (EGFR) by EGF induces the upregulation of miR-27b-3p and that miR-27b-3p targets and inhibits Foxo1 mRNA expression, resulting in increased FSH synthesis and secretion. In summary, this study elucidates the precise molecular mechanism through which EGF governs the synthesis and secretion of FSH via the EGFR/miR-27b-3p/FOXO1 pathway.

NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth.

Calcium homeostasis is critical for cell proliferation, and emerging evidence shows that cancer cells exhibit altered calcium signals to fulfill their need for proliferation. However, it remains unclear whether there are oncogene-specific calcium homeostasis regulations that can expose novel therapeutic targets. Here, from RNAi screen, we report that adenosylhomocysteinase like protein 1 (AHCYL1), a suppressor of the endoplasmic reticulum (ER) calcium channel protein inositol trisphosphate receptor (IP3R), is selectively upregulated and critical for cell proliferation and tumor growth potential of human NRAS-mutated melanoma, but not for melanoma expressing BRAF V600E. Mechanistically, AHCYL1 deficiency results in decreased ER calcium levels, activates the unfolded protein response (UPR), and triggers downstream apoptosis. In addition, we show that AHCYL1 transcription is regulated by activating transcription factor 2 (ATF2) in NRAS-mutated melanoma. Our work provides evidence for oncogene-specific calcium regulations and suggests AHCYL1 as a novel therapeutic target for RAS mutant-expressing human cancers, including melanoma. IMPLICATIONS: Our findings suggest that targeting the AHCYL1-IP3R axis presents a novel therapeutic approach for NRAS-mutated melanomas, with potential applicability to all cancers harboring RAS mutations, such as KRAS-mutated human colorectal cancers.