Ruthenium Single-Atom Modulated Protonated Iridium Oxide for Acidic Water Oxidation in Proton Exchange Membrane Electrolysers.

Proton exchange membrane water electrolysers promise to usher in a new era of clean energy, but they remain a formidable obstacle in designing active and durable electrocatalysts for the acidic oxygen evolution reaction (OER). In this study, a protonated iridium oxide embedded with single-atom dispersed ruthenium atoms (H3.8Ir1- xRuxO4) that demonstrates exceptional activity and stability in acidic water oxidation is introduced. The single Ru dopants favorably induce localized oxygen vacancies in the Ir─O lattice, synergistically strengthening the adsorption of OOH* intermediates and enhancing the intrinsic OER activity. In addition, the preferential oxidation of Ru and the electronegativity of the oxygen vacancies significantly stabilize the Ir─O active sites, improving the OER stability. Consequently, the H3.8Ir1─ xRuxO4 catalyst shows an overpotential of 255 mV at 10 mA cm-2 and displays exceptional catalytic endurance in acidic electrolytes, surpassing 1100 h, representing a remarkable one-order-of-magnitude increase in stability compared to that of pristine H3.8IrO4. A proton exchange membrane electrolyser utilizing the H3.8Ir1- xRuxO4 catalyst as an anode exhibits stable performance for more than 1280 h under a high current density of 2 A cm-2.

The amino acid transporter SLC16A10 promotes melanogenesis by facilitating the transportation of phenylalanine.

Phenylalanine is a crucial amino acid in the process of melanogenesis. However, the exact mechanism by which it is transported into melanocytes has not been disclosed. The aim of this study was to identify and examine the key transporters that are responsible for phenylalanine transportation and evaluate their significance in melanogenesis. The amino acid transporter SLC16A10 was found to be up-regulated in both melasma (GSE72140) and sun-exposed skin (GSE67098). The protein levels of SLC16A10 were proportional to the melanin content in melanocytic nevi, indicating that SLC16A10 was related to melanogenesis. After SLC16A10 overexpression, melanin increased significantly in MNT1 cells. Meanwhile, the expression of melanogenesis-related proteins such as TYR and TYRP1 increased, while their RNA levels did not change. Transcriptomics data indicated that SLC16A10 can enhance the function of ribosome. Furthermore, targeted metabolomics data and ELISA results demonstrated SLC16A10 mainly affected the transport of phenylalanine into the cells. Then, phenylalanine was added to the cell culture medium after SLC16A10 overexpression, melanin synthesis in cells furtherly increased, which verified that SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine. Finally, we found that SLC16A10 expression increased after UVB irradiation. Knockdown SLC16A10 reduced UVB-induced melanin production and phenylalanine uptake by cells. In summary, SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine, and upregulation SLC16A10 is likely responsible for the UVB-induced hyperpigmentation as well.

Dietary fiber-rich Lentinula edodes stems influence the structure and in vitro digestibility of low-moisture extruded maize starches.

Low-moisture extrusion (LME) can be used to improve the utilization of dietary fiber-rich Lentinula edodes stems (LES). The incorporation of dietary fiber can affect heat-induced interactions of starch molecules, which are critical for modifying starch characteristics via LME. In this work, a blend of LES and maize starch was extruded into a product at low moisture (30 %, w/v). The structure, physicochemical properties, and in vitro digestibility of extruded maize starches were investigated at different LES levels. The results showed that low levels (<7 %) of LES increased the crystallinity of LME-produced starch, while high levels (>7 %) did not. Because of the LES's soluble to insoluble dietary fiber ratios, the increased crystallinity of LES-added starch led to greater molecular ordering and the formation of an elastic gel after LME. At a suitable LES level (~3 %), highly crystallized starches were resistant to enzymolysis and had a high proportion of resistant starch. The obtained findings would contribute to a better understanding of how dietary fiber-rich LES affects starch extrusion and provide an alternative use for boosting the value of LES by-products.

Properties and functions of acylated starch with short-chain fatty acids: a comprehensive review.

Short-chain fatty acids (SCFAs) are the primary energy source of colonic epithelial cells, but oral SCFAs are digested, absorbed, or degraded before reaching the colon. The acylated starch with SCFAs can be fermented and release specific SCFAs under the action of colonic intestinal microbiota. This review first introduces the preparation method, reaction mechanism, and substitution factors. Second, the structure, physical and chemical properties, in vitro function, and mechanism of acylated starch were expounded. Finally, the application of acylated starch in foods is introduced, and its safety is evaluated, providing a basis for the further development of acylated starch-based foods. The acylated starch obtained by different acylation types and preparation methods is different in particle, molecular, and crystal structures, leading to changes in the function and physicochemical properties. Meanwhile, acylated starch has the functional potential of targeted delivery of SCFAs to the colon, which can increase SCFAs in feces and intestine, selectively regulate the intestinal microbiota, and produce a prebiotic effect conducive to host health. The safety of acetylated starch has been supported by relevant studies, which have been widely used in various food fields and have great potential in the food industry.

Effect of lotus seed resistant starch on the bioconversion pathway of taurocholic acid by regulating the intestinal microbiota.

Taurocholic acid (TCA) is abundant in the rat intestine and has multiple health benefits. In the gut, intestinal microbiota can transform TCA into different bile acid (BA) derivatives, with the composition of microbiota playing a crucial role in the transformation process. This study aims to investigate how lotus seed resistant starch (LRS) can regulate microbiota to influence BA transformation. A fecal fermentation study was conducted in vitro, using either LRS, high-amylose maize starch (HAMS), or glucose (GLU) to analyze microbiota composition, BA content, and metabolic enzyme activities over different fermentation times. Bioinformatics analysis found that LRS increased the relative abundance of Enterococcus, Bacillus, and Lactobacillus, and decreased Escherichia-Shigella, compared with HAMS and GLU. LRS also reduced total BA content and accelerated the conversion of TCA to cholic acid, deoxycholic acid, and other derivatives. These results reveal that LRS and GLU tend to mediate the dehydroxy pathway, whereas HAMS tends to secrete metabolic enzymes in the epimerization pathway. Therefore, the evidence that LRS may regulate TCA bioconversion may benefit human colon health research and provide an important theoretical basis, as well as offer new concepts for the development of functional foods.

Butyryl group distribution modulates the structure and properties of butyrylated maize starch focused on amylose contents.

In this study, four types of maize starch with different amylose contents (3 %, 25 %, 40 %, and 70 %) were used to prepare butyrylated starches. Based on amylose contents, the influence of butyryl group distribution on the structure, thermal and digestive properties of butyrylated maize starch was investigated. The butyrylation reaction mainly substituted butyryl groups on amylose, and the butyryl groups were most easily substituted for the hydroxyl group at the C6 position. The degree of substitution of butyrylated starch reached its maximum when the amylose content was 40 %, and the degree of substitution did not correlate linearly with the amylose content. The butyrylation reaction increased the surface roughness, decreased the crystallinity, enthalpy value and molecular weight of native starch granules, resulting in a decrease in the degree of internal order of the starch and inducing the rearrangement of the amylose molecular chains in the amorphous region of the starch. The combination of the amylose content and the substitution of butyryl groups on amylose affected the digestibility of starch and ultimately increased its resistance. The Pearson correlation coefficient further confirmed the correlation between the distribution of butyryl groups and the structure and properties of butyrylated starch.

Quality properties of fish ball with abalone and its relationship with sensory properties.

In this work, whiteness, water-holding capacity, gel strength, textural profile analysis were performed to examine the quality of fish balls with abalone (FBA). In addition, a correlation between quality and sensory properties was established. The addition of abalone significantly increased the water holding capacity, gel strength and textural properties of FBA, and decreased their whiteness, the best overall quality was achieved at 9 % w/w abalone addition. The E-nose and E-tongue results revealed that the addition of abalone changed the flavour of FBA. HS-SPME-GC-MS identified 65 volatile organic compounds (VOCs) and proved to be effective in reducing fishy flavour. E-nose can distinguish between the VOCs in FBA. Moreover, Umami and 1-octen-3-ol can serve as important indicators to observe changes in the quality of FBA, as they were positively connected with WHC, gumminess, chewiness, resilience, a*, hexanal, etc. The results provided a theoretical basis for the development of abalone and surimi products.

Pressure-dominated steam explosion for modifying textured soy proteins: Structure and in vitro digestion kinetics.

Textured Soy Proteins (TSPs) have been employed as building blocks in various food processes, but their availability remains limited. In this research, influence of Steam Explosion (SE) with pressure ranges (0, 0.5, 1.0, 1.5 MPa) on the structure and in vitro digestibility of TSPs was investigated. The results showed that 0.5 and 1.0 MPa significantly increased the relative content of ß-sheets and decreased the relative content of α-helices and ß-turns. Correlation analysis revealed that the structural changes made the TSP brittle, with lower thermal stability and resistance to digestion. Moreover, SE decreased the degree of hydrolysis of TSPs in the gastric stage, with the lowest degree observed for the TSP at 0.5 MPa. However, in the intestinal phase, 1.0 and 1.5 MPa significantly increased the hydrolysis degree. These findings provide a better understanding of the SE pressure-modulated quality characteristics of TSPs and suggest the processing potential of modified TSPs as functional ingredients.

The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.

Endometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive. This study demonstrates that the hot POLE P286R mutation impedes endometrial tumorigenesis by inducing DNA breakage and activating the cGAS-STING signaling pathway. The POLE mutations were found to inhibit the proliferation and stemness of primary human EC cells. Mechanistically, the POLE mutants enhance DNA damage and suppress its repair through the interaction with DNA repair proteins, leading to genomic instability and the upregulation of cytoplasmic DNA. Additionally, the POLE P286R mutant also increases cGAS level, promotes TBK1 phosphorylation, and stimulates inflammatory gene expression and anti-tumor immune response. Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective cancer therapy.

Association of tirofiban treatment with outcomes following endovascular therapy in cardioembolic stroke: insights from the RESCUE BT randomized trial.

BACKGROUND AND PURPOSE: The efficacy and safety of tirofiban in endovascular therapy for cardioembolic ischemic stroke patients remain controversial. This study aimed to evaluate the role of intravenous tirofiban before endovascular therapy in cardioembolic stroke. METHODS: This post hoc analysis utilized data from the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke) trial, which was an investigator-initiated, randomized, double-blind, placebo-controlled trial. Participants were randomized to receive either tirofiban or a placebo in a 1:1 ratio before undergoing endovascular therapy. The study included patients aged 18 years or older, presenting with occlusion of the internal carotid artery or middle cerebral artery (MCA) M1/M2 within 24 h of the last known well time, and with a stroke etiology of cardioembolism. The primary efficacy outcome was global disability at 90 days, assessed using the modified Rankin Scale (mRS). The safety outcome included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days. RESULTS: A total of 406 cardioembolic stroke patients were included in this study, with 212 assigned to the tirofiban group and 194 assigned to the placebo group. Tirofiban treatment did not correlate with a favorable shift towards a lower 90-day mRS score (adjusted common odds ratio [OR], 0.91; 95% CI 0.64-1.3; p = 0.617). However, the tirofiban group had a significantly higher risk of symptomatic intracranial hemorrhage (sICH) within 48 h (adjusted OR, 3.26; 95% CI 1.4-7.57; p = 0.006) compared to the placebo group. The adjusted odds ratio (aOR) for mortality within 90 days was 1.48 (95% CI 0.88-2.52; p = 0.143). CONCLUSIONS: Tirofiban treatment was not associated with a lower level of disability and increased the incidence of sICH after endovascular therapy in cardioembolic stroke patients.

Structural and Physicochemical Properties of a Chinese Yam Starch-Tea Polyphenol Complex Prepared Using Autoclave-Assisted Pullulanase Treatment.

Interactions between food components have a positive impact in the field of food science. In this study, the effects of tea polyphenol on the structural and physicochemical properties of Chinese yam starch using autoclave-assisted pullulanase treatment were investigated. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, rapid visco analysis, differential scanning calorimetry, and the 3,5-dinitrosalicylic acid method were applied in this study. The results showed that the Chinese yam starch-tea polyphenol complex formed a structural domain with higher thermal stability along with lower pasting viscosities than native starch. The in vitro digestibility of Chinese yam starch decreased with the addition of the tea polyphenol, and the amount of resistant starch content in the complex was 56.25 ± 1.37%, significantly higher than that of native starch (p < 0.05). In addition, the complex showed a B+V-type crystalline structure, which confirmed that the interaction modes between the starch and tea polyphenol include hydrogen bonding and hydrophobic interactions. Moreover, the appearance of an irregular sponge network structure of the complex further supported the interactions between the starch and tea polyphenol. This study provides a theoretical basis for the development of functional foods using Chinese yam starch.

Bile acid and its bidirectional interactions with gut microbiota: a review.

Bile acids (BAs) are an important metabolite produced by cholesterol catabolism. It serves important roles in glucose and lipid metabolism and host-microbe interaction. Recent research has shown that different gut-microbiota can secrete different metabolic-enzymes to mediate the deconjugation, dehydroxylation and epimerization of BAs. In addition, microbes mediate BAs transformation and exert physiological functions in metabolic diseases may have a potentially close relationship with diet. Therefore, elaborating the pathways by which gut microbes mediate the transformation of BAs through enzymatic reactions involved are principal to understand the mechanism of effects between dietary patterns, gut microbes and BAs, and to provide theoretical knowledge for the development of functional foods to regulate metabolic diseases. In the present review, we summarized works on the physiological function of BAs, as well as the classification and composition of BAs in different animal models and its organs. In addition, we mainly focus on the bidirectional interactions of gut microbes with BAs transformation, and discuss the effects of diet on microbial transformation of BAs. Finally, we raised the question of further in-depth investigation of the food-gut microbial-BAs relationship, which might contribute to the improvement of metabolic diseases through dietary interventions in the future.

Physiochemical Quality, Microbial Diversity, and Volatile Components of Monascus-Fermented Hairtail Surimi.

In order to study the effects and mechanism of Monascus on the quality of hairtail surimi, high-throughput sequencing technology, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC/MS), and electronic nose techniques were used to investigate the changes in the quality, microbial diversity, and volatile flavor compounds of Monascus-fermented hairtail surimi (MFHS) during fermentation. The results showed that the total volatile basic nitrogen (TVB-N) index of hairtail surimi fermented by Monascus for 0-5 h met the requirements of the national standard. Among them, the 1 h group showed the best gel quality, which detected a total of 138 volatile substances, including 20 alcohols, 7 aldehydes, 12 olefins, 4 phenols, 12 alkanes, 8 ketones, 15 esters, 6 acids, 16 benzenes, 4 ethers, and 8 amines, as well as 26 other compounds. In addition, the dominant fungal microorganisms in the fermentation process of MFHS were identified, and a Spearman correlation analysis showed that 16 fungal microorganisms were significantly correlated with the decrease in fishy odor substances in the fermented fish and that 8 fungal microorganisms were significantly correlated with the increase in aromatic substances after fermentation. In short, Monascus fermentation can eliminate and reduce the fishy odor substances in hairtail fish, increase and improve the aromatic flavor, and improve the quality of hairtail surimi gel. These findings are helpful for revealing the mechanism of the quality formation of fermented surimi and provide guidance for the screening of starter culture in the future.

AHEGC: Adaptive Hindsight Experience Replay With Goal-Amended Curiosity Module for Robot Control.

With shaped reward functions, reinforcement learning (RL) has recently been successfully applied to several robot control tasks. However, designing a task-relevant and well-performing reward function takes time and effort. Still, if RL can train an agent to complete a task in a sparse reward environment, it is an effective way to address the difficulty of reward function design, but it is still a significant challenge. To address this issue, the pioneering hindsight experience replay (HER) method dramatically enhances the probability of acquiring skills in sparse reward environments by transforming unsuccessful experiences into helpful training samples. However, HER still requires a lengthy training period. In this article, we propose a new technique based on HER termed adaptive HER with goal-amended curiosity module (AHEGC) for further enhancing sample and exploration efficiency. Specifically, an adaptive adjustment strategy of hindsight experience (HE) sampling rate and reward weights is developed to enhance sample efficiency. Furthermore, we introduce a curiosity mechanism to encourage more efficient exploration of the environment and propose a goal-amended (GA) curiosity module as a solution to the problem of over-seeking novelty caused by the curiosity introduced. We conducted experiments on six demanding robot control tasks with binary rewards, including Fetch and Hand environments. The results show that the proposed method outperforms existing methods regarding learning ability and convergence speed.

Fraxin inhibits melanogenesis by suppressing the ERK/MAPK pathway and antagonizes oxidative stress by activating the NRF2 pathway.

Hyperpigmentation disorders, such as melasma and freckles, are highly prevalent and draw increasing attention. Patients thus tend to seek effective and safe cosmetic whitening agents. Fraxin, a bioactive substance extracted from Cortex Fraxini, possesses anti-inflammation and antioxidant properties. In this study, we further explored the anti-melanogenic activities of fraxin were explored in vitro and in vivo. We found that pretreatment with fraxin decreased the melanin content of MNT1 cells and zebrafishes. In MNT1 cells, melanogenesis-related proteins, such as MITF, TYR, TYRP1, and DCT were down-regulated and tyrosinase activity was reduced under fraxin treatment. Further exploration of the mechanism revealed that fraxin could inhibit the phosphorylation of ERK, which is closely related to melanogenesis. Besides, fraxin also protected MNT1 cells from H2O2-induced apoptosis via scavenging reactive oxygen species (ROS) in cells. Further experimentation revealed that fraxin could activate NRF2 and upregulate antioxidase CAT and HO-1. In conclusion, fraxin could be an effective agent with anti-melanogenesis and antioxidant properties for hyperpigmentation disorders.

Fuzhuan brick tea ameliorates hepatic steatosis and steatohepatitis through gut microbiota-derived aryl hydrocarbon receptor ligands in high-fat diet-induced obese mice.

High-fat diet (HFD) induced obesity and its associated conditions, such as hepatic steatosis and steatohepatitis, are major health concerns worldwide. Previous studies have reported the excellent efficiency of Fuzhuan brick tea (FBT) in attenuating HFD-induced obesity and metabolic disorders. In this study, we investigated the effects of FBT on hepatic steatosis and simple steatohepatitis in HFD-induced obese mice, as well as the metabolic function of the gut microbiome using metagenomics and metabolomics. The results showed that FBT ameliorated dyslipidemia, hepatic steatosis and steatohepatitis in HFD-induced obese mice by normalizing the gut microbiota structure and tryptophan metabolism. FBT increased the cecal abundance of aryl hydrocarbon receptor (AhR)-ligand producing bacteria such as Lactobacillus_reuteri and Lactobacillus_johnsonii, at the expense of AhR-ligand consuming bacteria, such as Faecalibaculum_rodentium and Escherichia_coli, and elevated the cecal contents of AhR-ligands such as IAA, IPA, and KYNA. Furthermore, FBT regulated the expressions of AhR and its targeted lipometabolic genes such as Pemt, Fasn, and SREBP-1c, as well as other inflammatory genes including TNF-α, IL-6, and IL-1ß in the liver of mice. Overall, these findings highlight the beneficial effects of FBT on obesity-related hepatic steatosis and steatohepatitis via microbiota-derived AhR signaling.

UVB promotes melanogenesis by regulating METTL3.

Ultraviolet (UV) radiation is the primary exogenous inducer of skin pigmentation, although the mechanism has not been fully elucidated. N6-methyladenosine (m6 A) modification is one of the key epigenetic form of gene regulation that affects multiple biological processes. The aim of this study was to explore the role and underlying mechanisms of m6 A modification in UVB-induced melanogenesis. Low-dose UVB increased global m6 A modification in melanocytes (MCs) and MNT1 melanoma cell line. The GEPIA database predicted that methyltransferase METTL3 is positively correlated with the melanogenic transcription factor MITF in the sun-exposed skin tissues. After METTL3 respectively overexpressed and knocked down in the MNT1, the melanin content and melanogenesis-related genes were significantly upregulated after overexpression of METTL3, especially with UVB irradiation, and downregulated after METTL3 knockdown. METTL3 levels were also higher in melanocytic nevi with high melanin content. METTL3 overexpression and knockdown also altered the protein level of YAP1. SRAMP analysis predicted four high-potential m6 A modification sites on YAP1 mRNA, of which three were confirmed by methylated RNA immunoprecipitation. Inhibition of YAP1 expression can partially reverse melanogenesis induced by overexpression of METTL3. In conclusion, UVB irradiation promotes global m6 A modification in MCs and upregulates METTL3, which increases the expression level of YAP1 through m6 A modification, thereby activating the co-transcription factor TEAD1 and promoting melanogenesis.

Ratiometric and discriminative visualization of autophagic processes with a novel dual-responded lysosome-specific fluorescent probe.

BACKGROUND: Autophagy is a critical self-eating pathway involved in numerous physiological and pathological processes. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fluctuations in the lysosomal microenvironment is vital for tracking the dynamic process of autophagy. Although much effort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy. METHODS: Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the performance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury. RESULTS: We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual-wavelength emission, and small background interference. The ratiometric fluorescent signal (R = I 610/I 460) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion effect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starvation or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible effect of hepatoprotective drugs on this event. CONCLUSIONS: In this study, we developed the first ratiometric dual-responsive fluorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety.

Proteomic analysis reveals that Polygonatum cyrtonema Hua polysaccharide ameliorates mice muscle atrophy in chemotherapy-induced cachexia.

Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64 mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.

Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway.

Global warming and rising temperature significantly increase the incidence of heat stress, which is known to affect the process of inflammation and aging. However, the effect of heat stress on skin melanogenesis is not fully known. We found that healthy foreskin tissues underwent significant pigmentation when exposed to 41°C. Furthermore, heat stress promoted melanogenesis in pigment cells by increasing the paracrine effects of keratinocytes. High-throughput RNA sequencing showed that heat stress activates the Hedgehog (Hh) signaling pathway in keratinocytes. The agonists of Hh signaling promote the paracrine effect of keratinocytes on melanogenesis. In addition, transient receptor potential vanilloid (TRPV) 3 agonists activate the Hh signaling in keratinocytes and augment its paracrine effect on melanogenesis. The heat-induced activation of Hh signaling is dependent on TRPV3-mediated Ca2+ influx. Heat exposure promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway. Our findings provide insights into the mechanisms of heat-induced skin pigmentation.