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Arbutin, a typical optical isomer, has garnered widespread acclaim in the whitening cosmetics for its favorable efficacy and safety. However, the molecular mechanisms underlying α-arbutin and β-arbutin permeating across the skin have not elucidated clearly yet. Herein we aimed to unveil how α-arbutin and β-arbutin interacted with keratin or SC lipids, further demonstrating their relationship with their drug permeability. We found that α-arbutin displayed significantly higher drug accumulation into the porcine skin than β-arbutin within 24 h through in vitro permeation test. Moreover, α-arbutin predominantly induced the alternations of secondary structure of amide II during the drug permeation, which was favorable for α-arbutin permeation. On the contrary, β-arbutin exhibited an observable effect on the stretching vibration of SC lipids, possessing a significantly stronger mixing energy, binding energy and compatibility with ceramide (Cer) than that of α-arbutin, which ultimately restricted its permeation. Interestingly, free fatty acids and ceramides of the SC lipids specifically utilized its oxygen atom of carboxyl group to dock the arbutin molecules, enhancing their affinity with β-arbutin, as confirmed by molecular simulation and 13 Carbon Nuclear Magnetic Resonance. Nevertheless, a favorable compatibility between α-arbutin and keratin was observed. It was emphasized that the distinct spatial configuration and opposite optical rotation of arbutin was the leading factor impacting the intermolecular force between arbutin and the SC, and resulted in a diverse drug permeation. In cellular and in vivo skin pharmacokinetic studies, α-arbutin also possessed a higher cellular uptake and topical bioavailability than β-arbutin. This study revealed the transdermal permeation mechanisms of optical isomer arbutin at the molecular levels, providing methodological reference for the investigations of permeation behaviors of other isomers with similar spatial configuration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Retinol is widely used to treat skin ageing because of its effect on cell differentiation, proliferation and apoptosis. However, its potential benefits appear to be limited by its skin permeability. Herein, we investigated the transcutaneous behavior of retinol in semisolid cosmetics, in both in vitro and in vivo experiments. In vitro experiments used the modified Franz diffusion cell combined with Raman spectroscopy. In in vivo experiments, the content of retinol in rat skin and plasma was detected with HPLC. Retinol in semisolid cosmetics was mainly concentrated in the stratum corneum in the skin of the three animal models tested, and in any case did not cross the skin barrier after a 24 h dermatologic topical treatment in Franz diffusion cells tests. Similar results were obtained in live mice and rats, where retinol did not cross the skin barrier and did not enter the blood circulation. Raman spectroscopy was used to test the penetration depth of retinol in skin, which reached 16 μm out of 34 μm in pig skin, whereas the skin of mouse and rat showed too strong bakground interference. To explore epidermal transport mechanism and intradermal residence, skin transcriptomics was performed in rats, which identified 126 genes upregulated related to retinol transport and metabolism, relevant to the search terms "retinoid metabolic process" and "transporter activity". The identity of these upregulated genes suggests that the mechanism of retinol action is linked to epidermis, skin, tissue and epithelium development., (© 2024. The Author(s).)

High expression of truncated O-glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N-acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues. The current study aimed to determine the role of GALNT6 in ccRCC, and whether GALNT6-mediated O-glycosylation aggravates malignant behaviors. Gain- and loss-of-function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC-derived xenograft tumor growth and lung metastasis. In line with this, silencing of GALNT6 yielded the opposite results. Mechanically, high expression of GALNT6 led to the accumulation of Tn antigen in ccRCC cells. By undertaking immunoprecipitation coupled with liquid chromatography/mass spectrometry, vicia villosa agglutinin blot, and site-directed mutagenesis assays, we found that O-glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6-induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium-derived growth factor (LEDGF) as a key regulator of GALNT6 transcriptional induction in ccRCC growth and an upstream contributor to ccRCC aggressive behavior. Collectively, our findings indicate that GALNT6-mediated abnormal O-glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Retinoids, defined as synthetic or natural derivatives of vitamin A, have been extensively studied as anti-aging molecules that are widely applied in cosmetics. However, due to their physicochemical property, retinoids are highly unstable and extremely sensitive to light, oxygen, and temperature. Moreover, topical application of retinoids often leads to cutaneous irritation. These instabilities and irritant properties of retinoids limit their application in cosmetic and pharmaceutical products., Aim: Our study aimed to provide a systematic review to summarize the mechanisms underlying the instability and irritant properties of retinoids, as well as recent developments in addressing these challenges., Methods: A comprehensive PubMed search was conducted using the following keywords: retinoids, chemical instability, skin irritation, retinoid derivatives, nano lipid-based carriers, liposomes, penetration-enhancer vesicles, ethosomes, niosomes, nanoemulsions, solid lipid nanoparticles, vitamins, soothing and hydrating agents, antioxidants and metal chelator and retinol combinations. Relevant researches published between 1968 and 2023 and studies related to these reports were reviewed., Results: The development of new retinoid derivatives, the utilization of new delivery systems like nano lipid-based carriers and the combination with other compounds like vitamins, soothing agents, antioxidants and metal chelator have been explored to improve the stability, bioavailability, and toxicity of the retinoid family., Conclusions: Through advancements in formulation techniques, structure modification of retinoid derivatives and development of novel nano lipid-based carriers, the chemical instability and skin irritation of retinoids has been mitigated, ensuring their efficacy and potency over extended periods., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Long-term exposure to ultraviolet radiation may cause photoaging of skin tissues. Coreopsis tinctoria Nutt. riches a variety of flavonoids with strong antioxidant activities. In the present study, the main antioxidant flavonoid was isolated from C. tinctoria and identified as okanin by Mass spectrum and Nuclear Magnetic Resonance Spectroscopy. Okanin was found to effectively reduce the malondialdehyde content, increase various intracellular antioxidant enzyme activities, relieve epidermal hyperplasia and dermal damage caused by UVB irradiation, and increase the collagen fibers' content in the dorsal skin tissue of mice. Immunohistochemical analysis showed that okanin effectively counteracted the photoaging effect of UVB-induced by down-regulating IL-1, IL-6, TNF-α, and COX-2, and up-regulating COL-1, COL-3, and HYP expression. In addition, okanin can inhibit skin photoaging by regulating TNF-β/Smad2-3, MAPK, P13K/AKT, and NF-κB signaling pathways. In particular, the three key markers of photoaging, MMP (MMP-1/-3/-9), were down-regulated and five collagen synthesis genes (COL1A1, COL3A1, COL5A2, COL6A1, and COL7A1) were up-regulated, underlines the direct anti-photoaging mechanism of okanin in preventing collagen degradation and promoting collagen synthesis. The current investigation provides new insights into the great potential of okanin in alleviating skin photoaging and lays theoretical references for the development ofanti-photoaging products., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [MJL and PS are from the Shenzhen Hujia Technology Co. but there is no conflict of interest.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives To identify the 5' untranslated region of Zika virus (ZIKV5'UTR) RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site (IRES) located in ZIKV5'UTR and virus production. Methods Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining. Subsequently, liquid chromatography-tandem mass spectrometry (LC-MS/MS), bioinformatics analysis, and western blot were used to identify the candidate proteins binding to ZIKV5'UTR. Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production. Results tRSA RNA pull-down assay, LC-MS/MS, and western blot analysis showed that polypyrimidine tract-binding protein (PTB) bound to the ZIKV 5'UTR Furthermore, dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV (t = 10.220, P < 0.001), while PTB knockdown had the opposite effect (t = 4.897, P < 0.01). Additionally, virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer (t = 6.400, P < 0.01), whereas reducing PTB expression level weakened virus infectivity (t = 5.055, P < 0.01). Conclusion PTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.

Owing to its tyrosinase inhibitory activity, α-arbutin has been added to several skin care products as a skin-lightening agent. However, the protective effect of α-arbutin against ultraviolet A (UVA)-induced photoaging has not been well investigated. The present study was designed to investigate the photoprotective effect and mechanism of α-arbutin against UVA-induced photoaging. In vitro experiments, HaCaT cells were treated with UVA at a dose of 3 J/cm 2 to evaluate the anti-photoaging effect of α-arbutin. α-Arbutin was found to exhibit a strong antioxidant effect by increasing glutathione (GSH) level and inhibiting reactive oxygen species (ROS) production. Meanwhile, α-arbutin markedly improved the expression of sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) proteins, initiating downstream signaling to increase mitochondrial membrane potential and mediate mitochondrial biogenesis, and improve mitochondrial structure significantly. In vivo analysis, the mice with shaved back hair were irradiated with a cumulative UVA dose of 10 J/cm 2 and a cumulative ultraviolet B (UVB) dose of 0.63 J/cm 2 . The animal experiments demonstrated that α-arbutin increased the expression of SIRT3 and PGC-1α proteins in the back skin of mice, thereby reducing UV-induced skin damage. In conclusion, α-arbutin protects HaCaT cells and mice from UVA damage by regulating SIRT3/PGC-1α signaling pathway., Competing Interests: Authors QZ and PS were employed by Shenzhen Hujia Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Zhou, Liang, Liang, Yu, Li, Zhang, Lu, Zheng, Hao, Shu and Liu.)

Objective: To evaluate the effect of multiple single cannulation technique on the complications of arteriovenous fistula., Methods: A comprehensive literature search was conducted to investigate the impact of multiple single cannulation technique on the complications of arteriovenous fistula. The search was performed in both Chinese and English databases including Wanfang Medicine, China National Knowledge Infrastructure, Vip, Pubmed, Embase, and The Cochrane Library, with a search period up to December 20, 2023. Following literature screening and data extraction, the quality of the included studies was assessed using the Cochrane Bias Assessment Tool for Randomized Controlled Trials. Statistical analysis was performed using Review Manager version 5.3., Results: Thirteen papers, totaling 1299 patients, were included in the analysis. The experimental group consisted of 646 patients, while the control group had 595 patients. The meta-analysis revealed that the multiple single cannulation technique was more effective than rope ladder cannulation and buttonhole cannulation in reducing the incidence of angiomas (odds ratio [OR] = 0.19; 95% confidence interval [CI] = 0.10-0.35), stenosis (OR = 0.22; 95% CI 0.13-0.39), thrombosis (OR = 0.17; 95% CI = 0.07-0.39), and blood seepage (OR = 0.13; 95% CI = 0.08-0.21) of arteriovenous fistulas (P < .05). Additionally, it was found to increase the success rate of nurses' single cannulation (OR = 4.20; 95% CI = 1.78-9.95) of arteriovenous fistulas (P < .05)., Conclusion: Multiple single cannulation technique could effectively reduce the incidence of complications of arteriovenous fistula, improve the success rate of cannulation, prolong the life span of arteriovenous fistula, and prolong the survival cycle of hemodialysis patients., Competing Interests: All authors of this article declare no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The vegetable leafminer (Liriomyza sativae) is a devastating invasive pest of many vegetable crops and horticultural plants worldwide, causing serious economic loss. Conventional control strategy against this pest mainly relies on the synthetic chemical pesticides, but widespread use of insecticides easily causes insecticide resistance development and is harmful to beneficial organisms and environment. In this context, a more environmentally friendly pest management strategy based on RNA interference (RNAi) has emerged as a powerful tool to control of insect pests. Here we report a successful oral RNAi in L. sativae after feeding on pak choi (Brassica rapa ssp. chinensis) that transiently express hairpin RNAs targeting vital genes in this pest. First, potentially lethal genes are identified by searching an L. sativae transcriptome for orthologs of the widely used V-ATPase A and actin genes, then expression levels are assessed during different life stages and in different adult tissues. Interestingly, the highest expression levels for V-ATPase A are observed in the adult heads (males and females) and for actin in the abdomens of adult females. We also assessed expression patterns of the target hairpin RNAs in pak choi leaves and found that they reach peak levels 72 h post agroinfiltration. RNAi-mediated knockdown of each target was then assessed by letting adult L. sativae feed on agroinfiltrated pak choi leaves. Relative transcript levels of each target gene exhibit significant reductions over the feeding time, and adversely affect survival of adult L. sativae at 24 h post infestation in genetically unmodified pak choi plants. These results demonstrate that the agroinfiltration-mediated RNAi system has potential for advancing innovative environmentally safe pest management strategies for the control of leaf-mining species., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Kiwifruit ripening is a complex and highly coordinated process that occurs in conjunction with the formation of fruit edible quality. The significance of epigenetic changes, particularly the impact of N6-methyladenosine (m6A) RNA modification on fruit ripening and quality formation, has been largely overlooked. We monitored m6A levels and gene expression changes in kiwifruit at four different stages using LC-MS/MS, MeRIP, RNA-seq, and validated the function of AcALKBH10 through heterologous transgenic expression in tomato. Notable m6A modifications occurred predominantly at the stop codons and the 3' UTRs and exhibited a gradual reduction in m6A levels during the fruit ripening process. Moreover, these m6A modifications in the aforementioned sites demonstrated a discernible inverse relationship with the levels of mRNA abundance throughout the ripening process, suggesting a repression effect of m6A modification in the modulation of kiwifruit ripening. We further demonstrated that AcALKBH10 rather than AcECT9 predominantly regulates m6A levels in ripening-related genes, thereby exerting the regulatory control over the ripening process and the accumulation of soluble sugars and organic acids, ultimately influencing fruit ripening and quality formation. In conclusion, our findings illuminate the epi-regulatory mechanism involving m6A in kiwifruit ripening, offering a fresh perspective for cultivating high-quality kiwifruit with enhanced nutritional attributes., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Coreopsis tinctoria Nutt. is an important medicinal plant in traditional Uyghur medicine. The skin-lightening potential of the flower has been recognized recently; however, the active compounds responsible for that are not clear. In this work, tyrosinase, a target protein for regulating melanin synthesis, was immobilized on the Whatman paper for the first time to screen skin-lightening compounds present in the flower. Quercetagetin-7- O -glucoside ( 1 ), marein ( 2 ), and okanin ( 3 ) were found to be the enzyme inhibitors. The IC 50 values of quercetagetin-7- O -glucoside ( 1 ) and okanin ( 3 ) were 79.06 ± 1.08 μM and 30.25 ± 1.11 μM, respectively, which is smaller than 100.21 ± 0.11 μM of the positive control kojic acid. Enzyme kinetic analysis and molecular docking were carried out to investigate their inhibition mechanism. Although marein ( 2 ) showed a weak inhibition effect in vitro, it inhibited the intracellular tyrosinase activity and diminished melanin production in melanoma B16 cells as did the other two inhibitors. The paper-based ligand fishing method developed in this work makes it effective to quickly screen tyrosinase inhibitors from natural products. This is the first report on the tyrosinase inhibitory effect of those three compounds, showing the promising potential of Coreopsis tinctoria for the development of herbal skin-lightening products.

A photocatalyst-free and EDA complex-enabled radical cascade cyclization reaction of inactive alkenes with bromodifluoroacetamides was reported for the divergent synthesis of fluorine-containing tetralones and quinazolinones. In this transformation, persulfates as electron donors and difluoro bromamide as electron acceptors generate the EDA complex. This is a promising photochemical method with advantages such as mild reaction conditions, simple operation, being metal-free, and excellent functional group tolerance.

Objective: This study aimed to assess the effectiveness of an electronic cannulation atlas in preventing and treating complications of arteriovenous fistula., Methods: The observation group, consisting of 92 dialysis patients from July to December 2021, was managed with an electronic cannulation atlas. After 6 months, the incidence of complications such as stenosis, hematoma, thrombus, aneurysm, and cannulation failure was compared between the groups. Nurse satisfaction with the electronic cannulation atlas system was also assessed through a questionnaire., Results: The observation group had lower incidence rates of arteriovenous fistula stenosis, thrombus, aneurysm, and failure rate of cannulation compared to the control group, with statistically significant differences (p<0.05). The incidence rates of hematoa were similar in both groups, showing no significant difference (p>0.05). After 3 months of management, the incidence of arteriovenous fistula complications in the observation group was significantly lower than in the control group (p<0.05). Additionally, utilizing the electronic cannulation atlas system was found to increase nurses' job satisfaction., Conclusion: The use of electronic cannulation atlas for the treatment of patients' arteriovenous fistula could effectively reduce the incidence of complications of patients' arteriovenous fistula, reduce the failure rate of cannulation, reduce the workload of nurses, and improve the job satisfaction of nurses., Competing Interests: Xu Fang reports a licensed patent for an electronic cannulation mapping device. All authors declare that there is no other conflict of interest in this work., (© 2024 Xu et al.)

We describe small heterojunction polymer dots (Pdots) with deep-red light catalyzed H 2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo-Pdots nanoreactors, which selectively scavenge ⋅OH radicals in live cells and tissues under 650 nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10 times higher than that of the single-component Pdots described previously. Under a total light dose of 360 J/cm 2 , the Lipo-Pdots nanoreactors effectively scavenged ⋅OH radicals and suppressed the expression of pro-inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers., (© 2024 Wiley-VCH GmbH.)

Background: Infant formulas, and pediatric and adult nutritional products, are being fortified with bovine lactoferrin (bLF) due to its beneficial impacts on immune development and gut health. Lactoferrin supplementation into these products requires an analytical method to accurately quantify the concentrations of bLF to meet global regulatory and quality standards., Objective: To develop and validate a lactoferrin method capable of meeting the AOAC INTERNATIONAL Standard Method Performance Requirements (SMPR®) 2020.005., Methods: Powder formula samples are extracted using warm dibasic phosphate buffer, pH 8, then centrifuged at 4°C to remove insoluble proteins, fat, and other solids. The soluble fraction is further purified on a HiTrap heparin solid-phase extraction (SPE) column to isolate bLF from interferences. Samples are filtered, then analyzed by LC-UV using a protein BEH C4 analytical column and quantitated using an external calibrant., Results: The LOQ (2 mg/100 g), repeatability (RSD: 2.0-4.8%), recovery (92.1-97.7%), and analytical range (4-193 mg/100 g) all meet the method requirements as stated in SMPR 2020.005 for lactoferrin., Conclusion: The reported single-laboratory validation (SLV) results demonstrate the ability of this lactoferrin method to meet or exceed the method performance requirements to measure soluble, intact, non-denatured bLF in infant and adult nutritional powder formulas., Highlights: The use of a heparin affinity column to isolate lactoferrin from bovine milk products combined with a selective analytical chromatographic column provides suitable analyte specificity without requiring proprietary equipment or reagents., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL.)

Background and Aim: This study aims to analyze the worldwide prevalence, mortality rates, and disability-adjusted life years (DALYs) attributed to breast cancer in women between 1990 and 2019. Additionally, it seeks to forecast the future trends of these indicators related to the burden of breast cancer in women from 2020 to 2030., Methods: Data from the Global Burden of Disease Study (GBD) 2019 was analyzed to determine the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of DALYs due to breast cancer in women across 204 countries and territories from 1990 to 2019. Socio-economic development levels of countries and regions were assessed using Socio-demographic Indexes, and trends in the burden of breast cancer in women worldwide from 2020 to 2030 were projected using generalized additive models (GAMs)., Results: The estimated annual percentage change (EAPC) in the ASIR breast cancer in women globally was 0.36 from 1990 to 2019 and is expected to increase to 0.44 from 2020 to 2030. In 2019, the ASIR of breast cancer in women worldwide was 45.86 and is projected to reach 48.09 by 2030. The burden of breast cancer in women generally rises with age, with the highest burden expected in the 45-49 age group from 2020 to 2030. The fastest increase in burden is anticipated in Central sub-Saharan Africa (EAPC in the age-standardized death rate: 1.62, EAPC in the age-standardized DALY rate: 1.52), with the Solomon Islands (EAPC in the ASIR: 7.25) and China (EAPC in the ASIR: 2.83) projected to experience significant increases. Furthermore, a strong positive correlation was found between the ASIR breast cancer in women globally in 1990 and the projected rates for 2030 (r = 0.62)., Conclusion: The anticipated increase in the ASIR of breast cancer in women globally by 2030 highlights the importance of focusing on women aged 45-49 in Central sub-Saharan Africa, Oceania, the Solomon Islands, and China. Initiatives such as breast cancer information registries, raising awareness of risk factors and incidence, and implementing universal screening programs and diagnostic tests are essential in reducing the burden of breast cancer and its associated morbidity and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Jin, Bao and Shu.)

Objective: This study assesses the worldwide impact of ischemic stroke caused by ambient particulate matter pollution between 1990 and 2019, utilizing data from the Global Burden of Disease (GBD) 2019., Methods: An analysis was conducted across various subgroups, including region, Socio-demographic Index (SDI) level, country, age, and gender. The study primarily examined metrics such as death cases, death rate, Disability-Adjusted Life Years (DALYs), DALY rate, and age-standardized indicators. The Estimated Annual Percentage Change (EAPC) was calculated to assess trends over time., Results: The study found a moderate increase in the global burden of ischemic stroke attributed to ambient particulate matter, with the age-standardized DALY rate showing an EAPC of 0.41. Subgroup analyses indicated the most substantial increases in Western Sub-Saharan Africa (EAPC 2.64), East Asia (EAPC 2.77), and Eastern Sub-Saharan Africa (EAPC 3.80). Low and middle SDI countries displayed the most notable upward trends, with EAPC values of 3.36 and 3.58 for age-standardized death rate (ASDR) and DALY rate, respectively. Specifically, countries like Equatorial Guinea, Timor-Leste, and Yemen experienced the largest increases in ASDR and age-standardized DALY rate. Furthermore, both death and DALY rates from ischemic stroke due to particulate matter showed significant increases with age across all regions., Conclusion: The study highlights the increasing worldwide health consequences of ischemic stroke linked to particulate matter pollution, particularly in Asia and Africa. This emphasizes the critical necessity for tailored public health interventions in these regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xie, Shu, Li, Chen, Yu and Hu.)

This study delves into the potential therapeutic benefits of Fufang Sanling Granules for kidney cancer, focusing on their active components and the underlying mechanisms of their interaction with cancer-related targets. By constructing a drug-active component-target network based on eight herbs, key active compounds such as kaempferol, quercetin, and linolenic acid were identified, suggesting their pivotal roles in modulating immune responses and cellular signaling pathways relevant to cancer progression. The research further identified 51 central drug-disease genes through comprehensive bioinformatics analyses, implicating their involvement in crucial biological processes and pathways. A novel risk score model, encompassing six genes with significant prognostic value for renal cancer, was established and validated, showcasing its effectiveness in predicting patient outcomes through mutation analysis and survival studies. The model's predictive power was further confirmed by its ability to stratify patients into distinct risk groups with significant survival differences, highlighting its potential as a prognostic tool. Additionally, the study explored the relationship between gene expression within the identified black module and the risk score, uncovering significant associations with the extracellular matrix and immune infiltration patterns. This reveals the complex interplay between the tumor microenvironment and cancer progression. The integration of the risk score with clinical parameters through a nomogram significantly improved the model's predictive accuracy, offering a more comprehensive tool for predicting kidney cancer prognosis. In summary, by combining detailed molecular analyses with clinical insights, this study presents a robust framework for understanding the therapeutic potential of Fufang Sanling Granules in kidney cancer. It not only sheds light on the active components and their interactions with cancer-related genes but also introduces a reliable risk score model, paving the way for personalized treatment strategies and improved patient management in the future., (© 2024 Wiley Periodicals LLC.)

Surfactant-free microemulsions (SFMEs) exhibited remarkable advantages and potential, attributed to their similarity to traditional surfactant-based microemulsions and the absence of surfactants. Herein, a novel SFME was developed utilizing cosmetically approved materials, such as short-chain alcohol as an amphi-solvent, triethyl citrate (TEC) as the nonpolar phase, and water as the polar phase. 1,2-Pentanediol (PtDO)/TEC/water combination can form the largest monophasic zone, accounting for ∼74% of the total phase diagram area, due to an optimal hydrophilic (water)-lipophilic (TEC) balance. Comparable to surfactant-based microemulsion, PtDO/TEC/water SFME can also be categorized into three types: water-in-oil, discontinuous, and oil-in-water. As TEC or water is increased, or PtDO is decreased, the nanoaggregates in PtDO/TEC/water SFME grow from <5 nm to tens of nanometers. The addition of α-arbutin (ABN) does not disrupt PtDO/TEC/water SFME, but rather enhances its formation, resulting in a larger monophasic area and consistent size (2.8-3.8 nm) through participating in interface assembly. Furthermore, ABN-loaded PtDO/TEC/water SFME exhibits remarkable resistance to dilution, exceptional stability, and minimal irritation. Notably, PtDO/TEC/water SFME significantly boosts ABN's solubility in water by 2 times, its percutaneous penetration rate by 3-4 times, and enables a slow-release DPPH • radical scavenging effect. This SFME serves as a safe and cosmetically suitable nanoplatform for the delivery of bioactive substances.

We aimed to unveil the underlying pathogenic mechanisms of skin cancer in relation to metabolic factors and pathway mechanisms. This study utilized the TwoSample Mendelian randomization (MR) method to investigate the causal relationship between 1400 plasma metabolites and skin cancer. The primary method employed was the inverse variance weighting (IVW). Through IVW analysis, we found 105 plasma metabolites associated with Basal Cell Carcinoma (BCC), with the highest association observed for Prolylglycine levels (OR [95% CI]: 1.1902 [1.0274, 1.3788]). For Malignant Melanoma of Skin (MSS), 68 plasma metabolites were linked, with the highest causal relationship seen for 3-Hydroxybutyrate levels (OR [95% CI]: 1.0030 [1.0013, 1.0048]). Regarding actinic keratosis (AK), and the highest association observed for Hexadecadienoate (16:2n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.7125]). Glycerol to palmitoylcarnitine (16: n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.125]) were found to be significant for BCC and AK. Palmitoylcarnitine (C16) had the most positive causal effect for BCC (OR [95% CI]: 1.1777 [1.0493, 1.3218]), while 5-hydroxy-2-methylpyridine sulfate levels had the highest effect for AK (OR [95% CI]: 1.1788 [1.0295, 1.3498]). And 4-guanidinobutanoate levels had the largest positive causal effect (OR [95% CI]: 1.0857 [1.0417, 1.1317]) for BCC, and X-11880 levels for MSS (OR [95% CI]: 1.0013 [1.0000, 1.0025]). The study revealed a positive association between hereditary Glycerol to palmitoylcarnitine (C16) and 5-hydroxy-2-methylpyridine sulfate levels with the risk of developing BCC and AK. Additionally, 4-guanidinobutanoate levels and X 11880 levels were found to be positively associated with the risk of BCC and MMS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The plant cell wall is a dynamic structure that plays an essential role in development, but the mechanism regulating cell wall formation remains poorly understood. We demonstrate that two transcription factors, SlERF.H5 and SlERF.H7, control cell wall formation and tomato fruit firmness in an additive manner. Knockout of SlERF.H5, SlERF.H7, or both genes decreased cell wall thickness, firmness, and cellulose contents in fruits during early development, especially in double-knockout lines. Overexpressing either gene resulted in thicker cell walls and greater fruit firmness with elevated cellulose levels in fruits but severely dwarf plants with lower gibberellin contents. We further identified that SlERF.H5 and SlERF.H7 activate the cellulose biosynthesis gene SlCESA3 but repress the gibberellin biosynthesis gene GA20ox1. Moreover, we identified a conserved LPL motif in these ERFs responsible for their activities as transcriptional activators and repressors, providing insight into how bifunctional transcription factors modulate distinct developmental processes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Over the past decades, increasing evidences have demonstrated that five retinoids, including retinol (ROL), retinol acetate (RAc), retinol propionate (RP), retinol palmitate (RPalm), and hydroxypinacolone retinoate (HPR), can be potential therapeutic agents for skin photoaging. However, therapeutic efficacies and biosafety have never been compared to these compounds. This study aimed to determine the optimal retinoid type(s) for anti-photoaging therapy both in vitro and in vivo. Our data demonstrated that four retinoids (RPalm, RP, HPR and ROL) but not RAc were effective for anti-photoaging treatment at 5 μg/mL in vitro, with action mechanisms associated with antioxidative, anti-inflammatory and anti-skin ECM degradation activities. Notably, both RPalm and RP appeared superior to HPR and ROL for those activities. Importantly, both RPalm and RP were shown to be optimal for anti-photoaging therapy when topically applied at 5 mg/kg in a UVB-induced mice model of photoaging, which is consistent with their high anti-photoaging activities in vitro. Additionally, topical application of these five retinoids showed satisfactory biosafety without causing significant apoptosis in animal organs, although RP application led to a slight decline in animal body weights. Collectively, these data have laid a good foundation for the next development of the clinical application of these retinoids for skin healthcare., (© 2023 American Society for Photobiology.)

Introduction: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT., Methods: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia., Results: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia., Conclusions: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: SGI-1027 is a recognized inhibitor of DNA methyltransferase 1 (DNMT1), and earlier investigations have indicated an inverse correlation between dysregulated DNMT1 expression in gastric cancer (GC) and retinoblastoma 1 ( RB1 ) gene expression. Despite this knowledge, the precise mechanisms underlying the action of SGI-1027 in GC cells remain inadequately comprehended. The primary objective of this study is to elucidate the impact of SGI-1027 on the behavior of GC cells, encompassing aspects such as growth and metastatic potential, by intervening in DNMT1, thereby influencing the regulation of RB1 gene expression., Method: The acquisition of the normal gastric mucosal cell line GES-1 and the human gastric cancer cell line MKN45 was followed by employing Western blot (WB) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) techniques to evaluate the expression levels of RB1 and DNMT1 in these two cell lines. Subsequently, the MKN45 cell line was cultured in medium containing varying concentrations of SGI-1027, and the impact of SGI-1027 on the regulation of RB1 and DNMT1 in GC cells was reassessed using WB and qRT-PCR techniques. To scrutinize the effect of SGI-1027 on GC cells, we utilized the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay to determine cell proliferation and performed Transwell experiments to assess cell migration and invasion capabilities. Throughout this process, we also employed WB to assess the levels of cell cycle-associated proteins (Cyclin D1, Cyclin E1, and Cyclin B1) and proteins related to apoptosis (BCL-2 associated protein X apoptosis regulator (BAX) and B-cell lymphoma 2 apoptosis regulator (BCL-2)). Furthermore, we injected the MKN45 cell line and MKN45 cell line cultured with the optimal concentration of SGI-1027 for 5 days and 10 days into mice subcutaneously and through the tail vein, dividing them into the Model group, Model+SGI-1027 5d group, and Model+SGI-1027 10d group. We monitored changes in tumor size and volume in mice, and tumor tissues as well as lung tissues were collected for hematoxylin and eosin (HE) staining. Finally, DNMT1 expression levels in GC tissues were detected using both WB and immunohistochemistry (IHC) techniques. Additionally, RB1 expression levels in GC tissues were assessed using WB., Result: In contrast to GES-1 cells, MKN45 cells displayed a distinctive profile characterized by increased DNMT1 expression and decreased RB1 expression ( p < 0.05). However, upon the introduction of SGI-1027, a notable decrease in DNMT1 levels within GC cells was observed, concomitant with an elevation in RB1 gene expression, with 25 μmol/L SGI-1027 identified as the optimal concentration ( p < 0.05). Functional assays demonstrated that SGI-1027-treated GC cells exhibited pronounced features of inhibited proliferation, migration, and invasion when compared to untreated MKN45 cells ( p < 0.05). Moreover, in SGI-1027-treated GC cells, the levels of Cyclin D1, Cyclin E1, Cyclin B1, and BCL-2 were significantly reduced, while the expression level of BAX increased ( p < 0.05). Notably, the most pronounced impact was observed at 25 μmol/L SGI-1027, further underscoring its regulatory effects on tumor cell behavior ( p < 0.05). In animal experiments, the Model group exhibited a substantial increase in tumor volume, with HE staining results indicating extensive necrosis in most gastric tissues and noticeable signs of lung metastasis, accompanied by increased DNMT1 expression and decreased RB1 gene expression. In contrast, the SGI-1027 group displayed a reduction in gastric tumor volume, decreased necrosis, and reduced lung tumor metastasis ( p < 0.05). Additionally, the expression of DNMT1 was significantly reduced in SGI-1027-treated GC cells, while RB1 expression increased ( p < 0.05), further confirming the inhibitory effects of SGI-1027 on tumor growth and metastasis., Conclusions: SGI-1027 effectively hinders the proliferation and dissemination of GC cells by downregulating DNMT1 and promoting the expression of RB1 .

Photoperiod is a crucial environmental cue for phenological responses, including growth cessation and winter dormancy in perennial woody plants. Two regulatory modules within the photoperiod pathway explain bud dormancy induction in poplar (Populus spp.): the circadian oscillator LATE ELONGATED HYPOCOTYL 2 (LHY2) and GIGANTEA-like genes (GIs) both regulate the key target for winter dormancy induction FLOWERING LOCUS T2 (FT2). However, modification of LHY2 and GIs cannot completely prevent growth cessation and bud set under short-day (SD) conditions, indicating that additional regulatory modules are likely involved. We identified PtoHY5a, an orthologs of the photomorphogenesis regulatory factor ELONGATED HYPOCOTYL 5 (HY5) in poplar (Populus tomentosa), that directly activates PtoFT2 expression and represses the circadian oscillation of LHY2, indirectly activating PtoFT2 expression. Thus, PtoHY5a suppresses SD-induced growth cessation and bud set. Accordingly, PtoHY5a knockout facilitates dormancy induction. PtoHY5a also inhibits bud-break in poplar by controlling gibberellic acid (GA) levels in apical buds. Additionally, PtoHY5a regulates the photoperiodic control of seasonal growth downstream of phytochrome PHYB2. Thus, PtoHY5a modulates seasonal growth in poplar by regulating the PtoPHYB2-PtoHY5a-PtoFT2 module to determine the onset of winter dormancy, and by fine-tuning GA levels to control bud-break., Competing Interests: Conflict of interest statement. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Antiangiogenic therapy is an effective way to disrupt nutrient supply and starve tumors, but it is restricted by poor efficacy and negative feedback-induced tumor relapse. In this study, a neuropilin-1 (NRP-1)-targeted nanomedicine (designated as FPPT@Axi) is reported for spatiotemporal tumor suppression by combining photodynamic therapy (PDT) with antiangiogenesis. In brief, FPPT@Axi is prepared by utilizing an NRP-1-targeting chimeric peptide (Fmoc-K(PpIX)-PEG 8 -TKPRR) to encapsulate the antiangiogenic drug Axitinib (Axi). Importantly, the NRP-1-mediated targeting property enables FPPT@Axi to selectively concentrate at vascular endothelial and breast cancer cells, facilitating the production of reactive oxygen species (ROS) in situ for specific vascular disruption and enhanced cell apoptosis under light stimulation. Moreover, the codelivered Axi can further inhibit vascular endothelial growth factor receptor (VEGFR) to impair the negative feedback of PDT-induced tumor neovascularization. Consequently, FPPT@Axi spatiotemporally restrains the tumor growth through blocking angiogenesis, destroying tumor vessels, and inducing tumor apoptosis. Such an NRP-1-mediated targeting codelivery system sheds light on constructing an appealing candidate with translational potential by using clinically approved PDT and chemotherapy.

Background: S100A8/S100A9 belong to the S100 calcium-binding protein family and play an essential role in the progression of chronic inflammation in diseases. It also regulates various biological processes such as tumor cell survival, apoptosis, and invasive metastasis. The extracellular form of S100A8/S100A9 functions by modulating cellular oxidative metabolism and facilitating inflammation-to-cancer progression. This modulation occurs through specific binding to receptors like RAGE and TLR4 and activation of signaling pathways including STAT3 and NF-κB. In tumor cells, S100A8 and S100A9 induce phenotypic changes by influencing calcium ion concentrations and other pathways. However, the precise function of high S100A8/S100A9 expression in colorectal cancer cells remains unclear. Methods: To explore the role of S100A8/S100A9 in colorectal cancer, we used immunohistochemistry and data from GEO and TCGA databases to analyze its expression in colorectal cancer cells, normal intestinal mucosa, and adjacent tissues. Functional models of high S100A8/S100A9 expression in colorectal cancer cells were established through transfection with overexpression plasmids. Protein microarrays, enzyme-linked immunosorbent assays (ELISAs), and real-time PCR were employed to assess the expression and secretion of 40 cytokines. MTT and Transwell invasion assays were conducted to evaluate changes in cell proliferation, invasion, and chemotaxis. Finally, tail vein and subcutaneous tumorigenesis assays assessed cell proliferation and migration in vivo. Results: We observed significantly higher expression of S100A8/S100A9 in colorectal cancer epithelial cells compared to normal intestinal mucosa and adjacent tissues. Overexpression of S100A8/S100A9 in mouse colon cancer cells CT26.WT led to differential increases in the secretion levels of various cytokines (CXCL5, CXCL11, GM-CSF, G-CSF, IL1a, IL1b, sTNF RI, and CCL3). Additionally, this overexpression activated signaling pathways such as STAT3, NF-κB, and ERK-MAPK. The synthesis and secretion of inflammatory factors could be inhibited by using NF-κB and ERK-MAPK pathway inhibitors. Moreover, S100A8 promotes the proliferation and invasion of colon cancer cells. Notably, the CXCR2 inhibitor (SB265610) effectively reversed the phenotypic changes induced by the CXCL5/CXCR2 biological axis. Conclusions: Our findings indicate that increased expression of S100A8 and S100A9 in colon cancer epithelial cells enhances the secretion of inflammatory factors by activating NF-κB, ERK-MAPK, and other signaling pathways. S100A8 facilitates colon cancer cell proliferation, invasion, and metastasis through the CXCL5/CXCR2 biological axis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ultraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1β, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound.

Application of retinol (Vitamin A, VA) in skincare is limited for instability, poor water solubility, and skin intolerance that combats skin aging. We employed computer-aided virtual screening and cell experiments with transcriptomics, thereby unveiling the comprehensive gene expression and regulation pathway of photoaging HaCaT cell treated with ferulic acid (FA) in synergizing with VA. Through network pharmacology analysis, the combined use of VA and FA exhibited highly correlated cross-targets with skin aging acting on EGFR, PTPN1, ESR2, GSK3B, BACE1, PYGL, PTGS2 and APP. The indicators of oxidative stress, such as SOD, GSH, MDA, CAT and ROS in HaCaT cells after co-administration, were significantly improved from those in photoaging group ( p <0.0001). 155 differential expressed genes (DEGs) were specific between groups, while reducing the expression of PTGS2 was identified as an important regulatory factor in photoaging HaCaT cells by VA and FA. Those DEGs of co-administration group focused on oxidative-reduction enzyme activity, skin growth, keratinization, and steroid biosynthesis. Apparently, the co-administration of VA and FA effectively mitigated the process of UVB-induced photoaging by reducing oxidative stress injury, inflammation responses, and regulating cell growth. This synergistic approach significantly slowed down the photoaging progression and improved the applied performance of VA in HaCaT cells.

Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE1 76 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the "TFs-Enhancer-Promoter" regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies., (© 2024. The Author(s).)

The plant hormone ethylene plays a critical role in fruit defense against Botrytis cinerea attack, but the underlying mechanisms remain poorly understood. Here, we showed that ethylene response factor SlERF.C1 acts as a key regulator to trigger the ethylene-mediated defense against B. cinerea in tomato fruits without compromising ripening. Knockout of SlERF.C1 increased fruit susceptibility to B. cinerea with no effect on ripening process, while overexpression enhanced resistance. RNA-Seq, transactivation assays, EMSA and ChIP-qPCR results indicated that SlERF.C1 activated the transcription of PR genes by binding to their promoters. Moreover, SlERF.C1 interacted with the mitogen-activated protein kinase SlMPK8 which allowed SlMPK8 to phosphorylate SlERF.C1 at the Ser 174 residue and increases its transcriptional activity. Knocking out of SlMPK8 increased fruit susceptibility to B. cinerea, whereas overexpression enhanced resistance without affecting ripening. Furthermore, genetic crosses between SlMPK8-KO and SlERF.C1-OE lines reduced the resistance to B. cinerea attack in SlERF.C1-OE fruits. In addition, B. cinerea infection induced ethylene production which in turn triggered SlMPK8 transcription and enhanced the phosphorylation of SlERF.C1. Overall, our findings reveal the regulatory mechanism of the 'Ethylene-MPK8-ERF.C1-PR' module in resistance against B. cinerea and provide new insight into the manipulation of gray mold disease in fruits., (© 2024 The Authors New Phytologist © 2024 New Phytologist Foundation.)

GC is a gastrointestinal tumor with high morbidity and mortality. Owing to the high rate of postoperative recurrence associated with GC, the effectiveness of radiotherapy and chemotherapy may be compromised by the occurrence of severe undesirable side effects. In light of these circumstances, KP, a flavonoid abundantly present in diverse herbal and fruit sources, emerges as a promising therapeutic agent with inherent anti-tumor properties. This study endeavors to demonstrate the therapeutic potential of KP in the context of GC while unraveling the intricate underlying mechanisms. Notably, our investigations unveil that KP stimulation effectively promotes the activation of NLRP3 inflammatory vesicles within AGS cells by engaging the NF-κB signaling pathway. Consequently, the signal cascade triggers the cleavage of Caspase-1, culminating in the liberation of IL-18. Furthermore, we ascertain that KP facilitate AGS cell pyroptosis by inducing mitochondrial damage. Collectively, our findings showcase KP as a compelling candidate for the treatment of GC-related diseases, heralding new possibilities for future therapeutic interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. However, the mechanisms underlying ESCC tumorigenesis have not been fully elucidated. Thus, we aimed to determine the key genes involved in ESCC tumorigenesis. The following bioinformatics analyses were performed: identification of differentially expressed genes (DEGs); gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis; integrated analysis of the protein-protein interaction network and Gene Expression Profiling Interactive Analysis database for validation of hub genes. Finally, western blotting and qPCR were used to explore the expression of cell division cycle 6 (CDC6) in ESCC cell lines. Immunohistochemistry analysis of ESCC samples from patients and matched clinical characteristics was used to determine the effects of CDC6. A total of 494 DEGs were identified, and functional enrichment was mainly focused on cell cycle and DNA replication. Biological pathway analysis of the hub genes was closely related to the cell cycle. We found that CDC6 was upregulated in ESCC cell lines and patient tissues and was related to the clinicopathological characteristics of ESCC. In conclusion, this study identified hub genes and crucial biological pathways related to ESCC tumorigenesis and integrated analyses indicated that CDC6 may be a novel diagnostic and therapeutic target for ESCC., (© 2024. The Author(s).)

Background: Anti-IL-5 monoclonal antibodies (mAbs) targeting IL-5 or IL-5 R α (including mepolizumab, benralizumab, and reslizumab) are widely used for inflammatory diseases such as asthma, eosinophilia, and polyangiitis. However, real-world data regarding its safety in a large sample population are incomplete. So, we evaluated the safety of anti-IL-5 mAbs by pharmacovigilance analyzes based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS)., Methods: In disproportionality analysis, four algorithms were employed to detect the signals of anti-IL-5 mAbs from the FAERS between 2016 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the signals of anti-IL-5 mAbs systematically., Results: There are 9,476,351 reports collected from the FAERS database, of which 22,174 reports listed anti-IL-5 mAbs as the 'primary suspected (PS)' drug. A total of 59 (20 new signals, mepolizumab) and 62 (19 new signals, benralizumab) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained synchronously. Finally, we detected that the anti-IL-5 mAbs-induced AEs occurred in 31 organ systems (mepolizumab) and 30 organ systems (benralizumab). For mepolizumab and reslizumab, unexpected and new significant PTs of AEs were found, such as asthmatic crisis, chronic obstructive pulmonary disease (COPD), pneumonia, COVID-19, pneumothorax, adrenal insufficiency and so on. Notably, the risk signal of asthmatic crisis for mepolizumab was stronger than benralizumab (ROR 108.04 [95%CI, 96.09-121.47] vs 26.83 [95%CI, 18.91-38.06]). Comparing with mepolizumab and benralizumab, we found the proportion of serious adverse events in mepolizumab was both greater than benralizumab in each age group (≤20, 20-65, and ≥ 65). The median onset time of mepolizumab was 280 days (interquartile range [IQR] 1-367 days)., Conclusion: Analysis of FAERS data identified anti-IL-5 mAbs-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of anti-IL-5 mAbs. In addition, clinicians may be more aware of the limitations of use in package inserts of anti-IL-5 mAbs: Not for relief of acute bronchospasm or status asthmaticus. Because of some limitations in the FAERS such as self-reports from patients and other confounding factors, the safety of anti-IL-5 mAbs needed more studies in different dimensions, especially the risk of cancer.

As non-point source pollution has emerged as a significant global and regional concern, climate change (CC), land use/cover transformation (LUCT), and management practices (MP) play vital roles in addressing nutrient pollution. However, current studies lack comprehensive quantification and consistent conclusions on the response to these factors, especially for management practices. To quantify and elucidate the impact of representative environmental factors on rapidly urbanizing regions, this study focused on the Shenzhen River, which serves as the most typical urbanizing watershed. Using a process-based distributed hydrological model with a factor-controlled simulation method, we identified significant differences in nutrient concentrations and the impacts of climate variability, land use/cover changes, and anthropogenic interventions from 2003 to 2020. Moreover, effective measures greatly improved water quality in the Shenzhen River during study period, as evident from trend and cluster analysis. However, ecological water supplements implemented since 2016 have led to a slight reduction in simulated runoff performance, and CC may amplify the synergistic effects of precipitation and temperature on the river system. While the implemented practices have been effective in reducing total nitrogen (TN) and total phosphorus (TP) loads, strong TN pollution control is still needed in rapidly urbanizing areas due to the results of land use/cover type changes. Our findings emphasize the intricate interplay among CC, LUCT, and MP in shaping water quality and hydrological processes in rapidly urbanizing watersheds, and clarify the independent effects of these factors on nutrients. This study contributes to a better understanding of the complex interactions between multiple factors in watersheds and provides guidance for sustainable watershed management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Glioma is one of the most common intracranial tumors, characterized by invasive growth and poor prognosis. Actin cytoskeletal rearrangement is an essential event of tumor cell migration. The actin dynamics-related protein scinderin (SCIN) has been reported to be closely related to tumor cell migration and invasion in several cancers., Aim: To investigate the role and mechanism of SCIN in glioma., Methods: The expression and clinical significance of SCIN in glioma were analyzed based on public databases. SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting. Gene silencing was performed using short hairpin RNA transfection. Cell viability, migration, and invasion were assessed using cell counting kit 8 assay, wound healing, and Matrigel invasion assays, respectively. F-actin cytoskeleton organization was assessed using F-actin staining., Results: SCIN expression was significantly elevated in glioma, and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase. Furthermore, SCIN-deficient cells exhibited decreased proliferation, migration, and invasion in U87 and U251 cells. Moreover, knockdown of SCIN inhibited the RhoA/focal adhesion kinase (FAK) signaling to promote F-actin depolymerization in U87 and U251 cells., Conclusion: SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling, thereby promoting the migration and invasion of glioma cells. This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma., Competing Interests: Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Resistance to chemotherapy in gastric cancer (GC) is a ubiquitous challenge for its treatment. Yi-qi-hua-yu-jie-du decoction (YJD), an empirical formula in Traditional Chinese Medicine (TCM), demonstrated survival-prolonging functions in patients with GC. Previous research has shown that YJD could also inhibit drug resistance in GC. However, the precise mechanisms for how YJD accomplishes this remain incompletely explained., Purpose: The research aimed to identify differential metabolic characteristics in cisplatin-resistant GC and investigate whether YJD can target these differences to suppress GC drug resistance., Methods: Metabolomic analysis was conducted to identify metabolic disparities between cisplatin-resistant and parental GC cells, as well as metabolic modifications resulting from YJD intervention in cisplatin-resistant GC cells. The effect of YJD on ferroptosis stimulation was assessed by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), iron ions, the reduced glutathione (GSH) to oxidised glutathione (GSSG) ratio, and alterations in mitochondrial morphology. Western blotting and quantitative real-time polymerase chain reaction (Q-PCR) were employed to verity the mechanisms of YJD-triggered ferroptosis through GPX4 and NRF2 overexpression models, alongside the AKT activator SC79. In vivo validation was conducted using nude mouse xenograft models., Results: Cisplatin-resistant GC exhibited altered GSH/GPX4 metabolism, and ferroptosis was a significantly enriched cell death pattern with YJD treatment in cisplatin-resistant GC cells. Ferroptosis biomarkers, including ROS, MDA, iron ions, the GSH/GSSG ratio, and mitochondrial morphology, were remarkably changed with the YJD intervention. Mechanistic experiments demonstrated that YJD inhibited the phosphorylation cascade activity of the AKT/GSK3β pathway, thereby reducing NRF2 expression. The level of GPX4, a crucial enzyme involved in glutathione metabolism, was attenuated, facilitating ferroptosis induction in cisplatin-resistant GC., Conclusion: The research reveals, for the first time, changes in GSH/GPX4 metabolism in cisplatin-resistant GC cells based on metabolomic analysis. YJD induced ferroptosis in cisplatin-resistant GC by inhibiting GPX4 through the AKT/GSK3β/NRF2 pathway, thus attenuating the cisplatin drug resistance in GC. Our findings identify metabolic changes in cisplatin-resistant GC and establish a theoretical framework for YJD on tackling drug resistance in GC through ferroptosis., Competing Interests: Declaration of Competing Interest There is no financial and personal relationships with other people or organizations that can inappropriately influence the professional judgement of our research., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Pyroptosis, a highly regulated form of cell death, could hold the key to revolutionizing cancer treatment. With cancer posing a significant global health challenge due to its high morbidity and mortality rates, exploring unconventional therapeutic approaches becomes imperative. Chinese medicine, renowned for its holistic principles, presents intriguing possibilities for treating gastric cancer (GC). Notably, baicalin, a prominent component found in the traditional Chinese herb Scutellaria baicalensis Georgi, has shown promising clinical potential in gastric cancer treatment.To shed light on this intriguing phenomenon, a multidisciplinary approach was undertaken, combining systems biology, bioinformatics, and in vitro studies. The primary objective was to unravel the intricate workings underlying baicalein's ability to promote gastric cancer cell pyroptosis.The findings from this comprehensive study unveiled an essential signaling axis involving NF-κB-NLRP3, which plays a pivotal role in the process of baicalein-induced pyroptosis in gastric cancer cells. As the investigation progressed, it became evident that baicalein exhibited a remarkable capability to reverse the effects of the NLRP3 inhibitor, MCC950 Sodium. Excitingly, the efficacy of cell pyroptosis induction by baicalein demonstrated a discernible dose-dependent relationship, showcasing its potential as a valuable therapeutic agent.The complex nature of these findings underscores the intricate interplay between baicalein, NF-κB-NLRP3 signaling, and gastric cancer cell pyroptosis. As the scientific community delves deeper into the world of Pyroptosis and its therapeutic implications, baicalein's potential as a game-changer in the fight against gastric cancer becomes increasingly evident., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

Background: Circular RNAs (circRNAs) are a class of noncoding RNAs that are involved in the progression of many human cancers. The precise gene locus and the roles of circular RNA from Fibronectin type III domain containing 3B (FNDC3B) in OS and its mechanisms of action have not been fully explored., Materials and Methods: qRT-qPCR assay was used to determine gene expressions. CCK8 Assay, EdU assay, wound-healing assay, transwell invasion assay and in vivo xenograft assay were used to perform functional investigations. RNA-FISH, immunofluorescence, RIP assay, RNA stability analysis were applied in mechanistic studies., Results: We found that circFNDC3B downregulated and FNDC3B mRNA upregulated in OS, and might be potential biomarkers for indicating disease progression and prognosis of OS patients. CircFNDC3B acted as a tumor suppressor gene to restrain OS progression and FNDC3B functioned as an oncogene to promote OS progression in vitro and in vivo. RNA binding protein RNA binding motif protein 47 (RBM47) could bind to the flanking introns of circFNDC3B to facilitate the generation of circFNDC3B, resulting in the reduction of FNDC3B mRNA and the circFNDC3B-FNDC3B mRNA imbalance. CircFNDC3B also inhibited FNDC3B mRNA expression by reducing its stability via competitively binding to Insulin-like growth-factor-2 mRNA binding protein (IGF2BP1)., Conclusion: This study demonstrated that RBM47 and IGF2BP1 mediated circular FNDC3B/FNDC3B mRNA imbalance was involved in the malignant processes of OS., (© 2023. The Author(s).)

To explore the influences of chemical oxidation on the physiological and ecological functions of indigenous microorganisms during contaminated soil remediation, three oxidants, including KMnO 4 , Na 2 S 2 O 8 , and O 3 , were selected to investigate their remediation effects on PAHs and the responses to indigenous microorganisms under different liquid-solid ratios, in this study. The results showed that:when the ΣPAHs concentration was 679.1 mg·kg -1 and the dosage of KMnO 4 and Na 2 S 2 O 8 was 1%, the removal efficiency of ΣPAHs reached up to 96.9% and 95.7% under the liquid-solid ratio of 6:1; for the O 3 treatment, the removal efficiency of ΣPAHs was the highest(82.3%) at the O 3 dosage and the liquid-solid ratio of 72 mg·min -1 and 8:1, respectively. The removal efficiency of low ring(3-4 rings) PAHs was higher than that of high ring(5-6 rings) PAHs under different liquid-solid ratios. The highest removal efficiencies were observed for phenanthrene and acenaphthene, whereas for benzo[a]pyrene, only the KMnO 4 treatment provided an effective performance, showing the highest removal efficiency of 97.4%. The microbial quantity analysis indicated that the quantity of soil microorganisms in the soil dropped sharply after being treated with KMnO 4 , decreasing from 10 8 copies·g -1 to 10 5 copies·g -1 , whereas it changed only slightly after being treated with Na 2 S 2 O 8 and O 3 . The community structure analysis showed that Proteobacteria were predominant in the contaminated soil, with the relative abundance of 99.5%. The addition of KMnO 4 and Na 2 S 2 O 8 significantly increased the microbial diversity; in particular, the relative abundance of a variety of microorganisms(such as Ralstonia and Acinetobacter ) that can degrade PAHs was remarkably increased. The analysis of microbial metabolic function pathways revealed that chemical oxidation could simultaneously increase the relative abundance of PAHs-degrading bacteria and improve the ability of organic metabolism. Overall, the KMnO 4 treatment greatly altered the quantity of microorganisms and the structure of the microbial community and the relative abundance of PAHs-degrading microorganisms at the liquid-solid ratio of 6:1.

Background: Assessment of the patient's respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (P aw )-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation., Methods: In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH 2 O to 2 cmH 2 O at a 2 cmH 2 O interval. By performing an end-expiratory airway occlusion maneuver, the negative P aw generated during the first 100 ms (P 0.1 ) and the maximal negative swing of P aw (∆P occ ) were measured. After an end-inspiratory airway occlusion, P aw reached a plateau, and the magnitude of change in plateau from peak P aw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (P mus ) and P mus -time product per minute (PTP mus /min) were used as the reference standard for the patient's effort. High and low effort was defined as P mus  > 10 and < 5 cmH 2 O, or PTP mus /min > 200 and < 50 cmH 2 O s min -1 , respectively., Results: A total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective P mus and PTP mus /min criterion. The receiver operating characteristic area of the three P aw -based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83-0.96), specificity (0.74-0.88), and positive (0.80-0.91) and negative predictive values (0.78-0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using P mus and PTP mus /min criterion, respectively. High receiver operating characteristic areas of the three P aw -based indices by the two criteria were found (0.93-0.95). A high sensitivity (0.80-1.00) and negative predictive value (0.97-1.00) were found with a low positive predictive value (0.23-0.64)., Conclusions: By performing simple airway occlusion maneuvers, the P aw -based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort., (© 2023. The Author(s).)

Background: Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present., Methods: In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs., Results: From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC 025 (information component). The potential strong signals (IC 025  > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy., Conclusion: Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases., (© 2023. The Author(s).)

Introduction: The estimation of global burden of neck pain is lacking. To estimate the trends and burden of neck pain by sex, age, region, and sociodemographic index (SDI)., Material and Methods: The incidence and disability-adjusted life years (DALY) data for neck pain were extracted from the Global Burden of Disease 2019 database. The estimated annual percent change (EAPC) and 95% confidence intervals (CIs) were used to assess the trends in age-standardized incidence and DALY rates from 1990 to 2019., Results: From 1990 to 2019, the global age-standardized incidence rate and age-standardized DALY rate indicated downward trends, with EAPCs of -0.06 and -0.09, respectively. The EAPCs of the age-standardized incidence rate and age-standardized DALY rate were negatively correlated with the SDI in 2019, respectively. The age-standardized incidence rates and age-standardized DALY rates in regions with a high SDI indicated a downward trend, including in high-income North America, Australia, and New Zealand. In 2019, the Philippines and high-income North America had the highest age-standardized incidence and age-standardized DALY rates. From 1990 to 2019, the areas which increased most rapidly in the age-standardized incidence rate and age-standardized DALY rate were in tropical Latin America (EAPCs of 0.53 and 0.60, respectively). Brazil had the most rapid increase in the age-standardized incidence rate and age-standardized DALY rate (EAPCs of 0.55 and 0.61, respectively)., Conclusions: The age-standardized incidence rate and age-standardized DALY rate of neck pain decreased globally from 1990 to 2019. However, there were significant differences concerning sex, age, and regional distributions. Therefore, targeted prevention interventions and risk factor control measures should be reasonably allocated., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia & Banach.)

The emergence of artificial general intelligence (AGI) is transforming radiation oncology. As prominent vanguards of AGI, large language models (LLMs) such as GPT-4 and PaLM 2 can process extensive texts and large vision models (LVMs) such as the Segment Anything Model (SAM) can process extensive imaging data to enhance the efficiency and precision of radiation therapy. This paper explores full-spectrum applications of AGI across radiation oncology including initial consultation, simulation, treatment planning, treatment delivery, treatment verification, and patient follow-up. The fusion of vision data with LLMs also creates powerful multimodal models that elucidate nuanced clinical patterns. Together, AGI promises to catalyze a shift towards data-driven, personalized radiation therapy. However, these models should complement human expertise and care. This paper provides an overview of how AGI can transform radiation oncology to elevate the standard of patient care in radiation oncology, with the key insight being AGI's ability to exploit multimodal clinical data at scale., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The Author Tianming Liu is the Editor in Chief of the journal, the authors Wei Li, Xiang Li, Dajiang Zhu and Dinggang Shen are the Editorial Board Members of the journal, but were not involved in the peer review procedure. This paper was handled by another Editor Board member.

The aryl hydrocarbon receptor (AhR) is widely expressed in the skin. It controls immune-mediated skin responses to various external environmental signals, promote terminal differentiation of epidermal keratinocytes and participates the maintenance of the skin barrier function. As a therapeutic target, AhR activation modulates many diseases progression driven by immune/inflammatory processes such as atopic dermatitis (AD) and psoriasis. In this study, we revealed that GDU-952 is a novel AhR agonist, which is able to decreases IgE serum levels, to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α and to induce immunoregulatory effects through restoring Th1/Th2 immune balance and promoting CD4 + FOXP3 + regulatory T (Treg) populations in AD skin lesions. Furthermore, GDU-952 can strengthen the skin barrier function through upregulating epidermal differentiation-related and tight junction proteins. This may alleviate AD symptoms, such as dermatitis scores, epidermal hyperplasia and mast cell infiltration. These results offer a rationale for further preclinical/clinical studies to evaluate the possible use of GDU-952 in the management of AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Retinyl palmitate (RP) is a vitamin A derivative that has been widely used in anti-aging and skin treatment. The aim of this study is to investigate the effect of RP on UVB (Ultraviolet radiation B) induced photoaging and its potential mechanism. Immunofluorescence assay demonstrates that RP can reduce collagen degradation in skin cells by UVB radiation and reduce apoptosis of skin cells. Cell migration assay reveals that RP can increase cell migration rate, helping to repair skin damage and restore cell viability. Immunohistochemical assays indicate that RP can significantly reduce the expression of IL-6, IL-1β, TNF-α induced by UVB radiation. Moreover, metabolomics and transcriptomics results suggest that RP regulates several metabolic pathways and gene expression, particularly in inflammatory signaling pathways, collagen synthesis and apoptosis, exhibiting significant regulatory effects. Furthermore, network pharmacological analysis predicts that RP may affect UVB-induced photoaging by regulating multiple key proteins and signaling pathways. Overall, this study demonstrates that RP has significant anti-photoaging ability, acting through several pathways including inhibition of inflammatory response, promotion of collagen synthesis and inhibition of apoptosis. These results provide a scientific basis for the application of RP in skin anti-photoaging and therapy, enabling the potential usage of RP to skin care products., Competing Interests: Authors PS, ML, NZ, and YW were employed by the company Shenzhen Hujia Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shu, Li, Zhao, Wang, Zhang and Du.)