Human-virus protein-protein interactions maps assist in revealing the pathogenesis of viral infection.

Many significant viral infections have been recorded in human history, which have caused enormous negative impacts worldwide. Human-virus protein-protein interactions (PPIs) mediate viral infection and immune processes in the host. The identification, quantification, localization, and construction of human-virus PPIs maps are critical prerequisites for understanding the biophysical basis of the viral invasion process and characterising the framework for all protein functions. With the technological revolution and the introduction of artificial intelligence, the human-virus PPIs maps have been expanded rapidly in the past decade and shed light on solving complicated biomedical problems. However, there is still a lack of prospective insight into the field. In this work, we comprehensively review and compare the effectiveness, potential, and limitations of diverse approaches for constructing large-scale PPIs maps in human-virus, including experimental methods based on biophysics and biochemistry, databases of human-virus PPIs, computational methods based on artificial intelligence, and tools for visualising PPIs maps. The work aims to provide a toolbox for researchers, hoping to better assist in deciphering the relationship between humans and viruses.

Atomic Evolution Mechanism and Suppression of Edge Threading Dislocations in Nitride Remote Heteroepitaxy.

The majority of dislocations in nitride epilayers are edge threading dislocations (TDs), which diminish the performance of nitride devices. However, it is extremely difficult to reduce the edge TDs due to the lack of available slip systems. Here, we systematically investigate the formation mechanism of edge TDs and find that besides originating at the coalescence boundaries, these dislocations are also closely related to geometrical misfit dislocations at the interface. Based on this understanding, we propose a novel strategy to reduce the edge TD density of the GaN epilayer by nearly 1 order of magnitude via graphene-assisted remote heteroepitaxy. The first-principles calculations confirm that the insertion of graphene dramatically reduces the energy barrier required for interfacial sliding, which promotes a new strain release channel. This work provides a unique approach to directly suppress the formation of edge TDs at the source, thereby facilitating the enhanced performance of photoelectronic and electronic devices.

The dynamic landscape of chromatin accessibility and active regulatory elements in the mediobasal hypothalamus influences the seasonal activation of the reproductive axis in the male quail under long light exposure.

BACKGROUND: In cold and temperate zones, seasonal reproduction plays a crucial role in the survival and reproductive success of species. The photoperiod influences reproductive processes in seasonal breeders through the hypothalamic-pituitary-gonadal (HPG) axis, in which the mediobasal hypothalamus (MBH) serves as the central region responsible for transmitting light information to the endocrine system. However, the cis-regulatory elements and the transcriptional activation mechanisms related to seasonal activation of the reproductive axis in MBH remain largely unclear. In this study, an artificial photoperiod program was used to induce the HPG axis activation in male quails, and we compared changes in chromatin accessibility changes during the seasonal activation of the HPG axis. RESULTS: Alterations in chromatin accessibility occurred in the mediobasal hypothalamus (MBH) and stabilized at LD7 during the activation of the HPG axis. Most open chromatin regions (OCRs) are enriched mainly in introns and distal intergenic regions. The differentially accessible regions (DARs) showed enrichment of binding motifs of the RFX, NKX, and MEF family of transcription factors that gained-loss accessibility under long-day conditions, while the binding motifs of the nuclear receptor (NR) superfamily and BZIP family gained-open accessibility. Retinoic acid signaling and GTPase-mediated signal transduction are involved in adaptation to long days and maintenance of the HPG axis activation. According to our footprint analysis, three clock-output genes (TEF, DBP, and HLF) and the THRA were the first responders to long days in LD3. THRB, NR3C2, AR, and NR3C1 are the key players associated with the initiation and maintenance of the activation of the HPG axis, which appeared at LD7 and tended to be stable under long-day conditions. By integrating chromatin and the transcriptome, three genes (DIO2, SLC16A2, and PDE6H) involved in thyroid hormone signaling showed differential chromatin accessibility and expression levels during the seasonal activation of the HPG axis. TRPA1, a target of THRB identified by DAP-seq, was sensitive to photoactivation and exhibited differential expression levels between short- and long-day conditions. CONCLUSION: Our data suggest that trans effects were the main factors affecting gene expression during the seasonal activation of the HPG axis. This study could lead to further research on the seasonal reproductive behavior of birds, particularly the role of MBH in controlling seasonal reproductive behavior.

Chromatin accessibility and transcriptional landscape in PK-15 cells during early exposure to Aflatoxin B1.

Aflatoxin B1 (AFB1) not only causes significant losses in livestock production but also poses a serious threat to human health. It is the most carcinogenic among known chemicals. Pigs are more susceptible to AFB1 and experience a higher incidence. However, the molecular mechanism of the toxic effect of AFB1 remains unclear. In this study, we used assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq to uncover chromatin accessibility and gene expression dynamics in PK-15 cells during early exposure to AFB1. We observed that the toxic effects of AFB1 involve signaling pathways such as p53, PI3K-AKT, Hippo, MAPK, TLRs, apoptosis, autophagy, and cancer pathways. Basic leucine zipper (bZIP) transcription factors (TFs), including AP-1, Fos, JunB, and Fra2, play a crucial role in regulating the biological processes involved in AFB1 challenge. Several new TFs, such as BORIS, HNF1b, Atf1, and KNRNPH2, represent potential targets for the toxic mechanism of AFB1. In addition, it is crucial to focus on the concentration of intracellular zinc ions. These findings will contribute to a better understanding of the mechanisms underlying AFB1-induced nephrotoxicity and offer new molecular targets.

An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression.

BACKGROUND: Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma. METHODS: Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3. RESULTS: An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4. CONCLUSIONS: Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.

Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum.

BACKGROUND: Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. METHODS: The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC-MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. RESULTS: The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. CONCLUSION: We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

The putative protein kinase Stk36 is essential for ciliogenesis and CSF flow by associating with Ulk4.

Motile cilia lining on the ependymal cells are crucial for cerebrospinal fluid (CSF) flow and its dysfunction is often associated with hydrocephalus. Unc51-like-kinase 4 (Ulk4) was previously linked to CSF flow and motile ciliogenesis in mice, as the hypomorph mutant of Ulk4 (Ulk4tm1a/tm1a ) developed hydrocephalic phenotype resulted from defective ciliogenesis and disturbed ciliary motility, while the underling mechanism is largely obscure. Here, we report that serine/threonine kinase 36 (STK36), a paralog of ULK4, directly interacts with ULK4 and this was demonstrated by yeast two-hybrid (Y2H) in yeast and coimmunoprecipitation (co-IP) assays in HEK293T cells, respectively. The interaction region was confined to their respective N-terminal kinase domain. The hypomorph mutant of Stk36 (Stk36tmE4-/- ) also developed progressive hydrocephalus postnatally and dysfunctional CSF flow, with multiple defects of motile cilia, including reduced ciliary number, disorganized ciliary orientation, defected axonemal structure and inconsistent base body (BB) orientation. Stk36tmE4-/- also disturbed the expression of Foxj1 transcription factor and a range of other ciliogenesis-related genes. All these morphological changes, motile cilia defects and transcriptional dysregulation in the Stk36tmE4-/- are practically copied from that in Ulk4tm1a/tm1a mice. Taken together, we conclude that both Stk36 and Ulk4 are crucial for CSF flow, they cooperate by direct binding with their kinase domain to regulate the Foxj1 transcription factor pathways for ciliogenesis and cilia function, not limited to CSF flow. The underlying molecular mechanism probably conserved in evolution and could be extended to other metazoans.

Clostridium butyricum upregulates GPR109A/AMPK/PGC-1α and ameliorates acute pancreatitis-associated intestinal barrier injury in mice.

Acute pancreatitis frequently causes intestinal barrier damage, which aggravates pancreatitis. Although Clostridium butyricum exerts anti-inflammatory and protective effects on the intestinal barrier during acute pancreatitis, the underlying mechanism is unclear. The G protein-coupled receptors 109 A (GPR109A) and adenosine monophosphate-activated protein kinase (AMPK)/ peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) signaling pathways can potentially influence the integrity of the intestinal barrier. Our study generated acute pancreatitis mouse models via intraperitoneal injection of cerulein and lipopolysaccharides. After intervention with Clostridium butyricum, the model mice showed reduced small intestinal and colonic intestinal barrier damage, dysbiosis amelioration, and increased GPR109A/AMPK/PGC-1α expression. In conclusion, Clostridium butyricum could improve pancreatic and intestinal inflammation and pancreatic injury, and relieve acute pancreatitis-induced intestinal barrier damage in the small intestine and colon, which may be associated with GPR109A/AMPK/PGC-1α.

Bladder neck contracture following transurethral surgery of prostate: a retrospective single-center study.

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.

Lower serum uric acid to serum creatinine ratio as a predictor of poor functional outcome after mechanical thrombectomy in acute ischaemic stroke.

BACKGROUND AND PURPOSE: The ratio of serum uric acid (SUA) to serum creatinine (SCr), representing normalized SUA for renal function, is associated with functional outcome in acute ischaemic stroke (AIS) patients. However, its effect on AIS patients undergoing mechanical thrombectomy (MT) remains unknown. This study aimed to investigate the influence of the SUA/SCr ratio on clinical outcome in MT-treated AIS patients. METHODS: Acute ischaemic stroke patients who underwent MT were continuously enrolled from January 2018 to June 2023. Upon admission, SUA and SCr levels were recorded within the initial 24 h. Stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS) score. Clinical outcome included poor functional outcome (modified Rankin Scale score >2) at 90 days, symptomatic intracranial haemorrhage and death. RESULTS: Amongst 734 patients, 432 (58.8%) exhibited poor functional outcome at 90 days. The SUA/SCr ratio exhibited a negative correlation with NIHSS score (ρ = -0.095, p = 0.010). Univariate analysis revealed a significant association between SUA/SCr ratio and poor functional outcome. After adjusting for confounders, the SUA/SCr ratio remained an independent predictor of functional outcome (adjusted odds ratio 0.348, 95% confidence interval 0.282-0.428, p < 0.001). Receiver operating characteristic curve analysis highlighted the ability of the SUA/SCr ratio to predict functional outcome, with a cutoff value of 3.62 and an area under the curve of 0.757 (95% confidence interval 0.724-0.788, p < 0.001). CONCLUSION: The SUA/SCr ratio is correlated with stroke severity and may serve as a predictor of 90-day functional outcome in AIS patients undergoing MT.

Oxygenation of Phenols with Water as the Oxygen Source and Oxoammonium Salt as the Oxidant.

Aromatic C-H oxygenation is important in both industrial production and organic synthesis. Here we report a metal-free approach for phenol oxygenation with water as the oxygen source using oxoammonium salts as the renewable oxidant. Employing this protocol, various alkyl-substituted phenols were converted into benzoquinones in yields of 59-98%. On the basis of 18O-labeling and kinetic studies, the hydroxy-oxoammonium adduct was proposed to attack the aromatic ring similarly to electrophilic aromatic substitution. We suppose that the findings described here not only provide an efficient and highly selective protocol for aromatic C-H oxygenation but also may encourage further developments of possible transition-metal-free catalytic methods.

Circadian light/dark cycle reversal exacerbates the progression of chronic kidney disease in mice.

Circadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with various metabolic disorders. The influence and mechanism of circadian disruption on renal injury in chronic kidney disease (CKD) remains inadequately understood. Here, we evaluated the impact of environmental light disruption on the progression of chronic renal injury in CKD mice. By using two abnormal light exposure models to induce circadian disruption, we found that circadian disruption induced by weekly light/dark cycle reversal (LDDL) significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy and unilateral ureteral obstruction (UUO). Mechanistically, RNA-seq analysis revealed significant immune and metabolic disorder in the LDDL-conditioned CKD kidneys. Consistently, renal content of ATP was decreased and ROS production was increased in the kidney tissues of the LDDL-challenged CKD mice. Untargeted metabolomics revealed a significant buildup of lipids in the kidney affected by LDDL. Notably, the level of ß-NMN, a crucial intermediate in the NAD+ pathway, was found to be particularly reduced. Moreover, we demonstrated that both ß-NMN and melatonin administration could significantly rescue the light-disruption associated kidney dysfunction. In conclusion, environmental circadian disruption may exacerbate chronic kidney injury by facilitating inflammatory responses and disturbing metabolic homeostasis. ß-NMN and melatonin treatments may hold potential as promising approaches for preventing and treating light-disruption associated CKD.

Pharmacometrics-Enabled DOse OPtimization (PEDOOP) for seamless phase I-II trials in oncology.

We consider a dose-optimization design for a first-in-human oncology trial that aims to identify a suitable dose for late-phase drug development. The proposed approach, called the Pharmacometrics-Enabled DOse OPtimization (PEDOOP) design, incorporates observed patient-level pharmacokinetics (PK) measurements and latent pharmacodynamics (PD) information for trial decision-making and dose optimization. PEDOOP consists of two seamless phases. In phase I, patient-level time-course drug concentrations, derived PD effects, and the toxicity outcomes from patients are integrated into a statistical model to estimate the dose-toxicity response. A simple dose-finding design guides dose escalation in phase I. At the end of the phase I dose finding, a graduation rule is used to assess the safety and efficacy of all the doses and select those with promising efficacy and acceptable safety for a randomized comparison against a control arm in phase II. In phase II, patients are randomized to the selected doses based on a fixed or adaptive randomization ratio. At the end of phase II, an optimal biological dose (OBD) is selected for late-phase development. We conduct simulation studies to assess the PEDOOP design in comparison to an existing seamless design that also combines phases I and II in a single trial.

Exploring the effect of Clostridium butyricum on lung injury associated with acute pancreatitis in mice by combined 16S rRNA and metabolomics analysis.

OBJECTIVES: Acute lung injury is a critical complication of severe acute pancreatitis (SAP). The gut microbiota and its metabolites play an important role in SAP development and may provide new targets for AP-associated lung injury. Based on the ability to reverse AP injury, we proposed that Clostridium butyricum may reduce the potential for AP-associated lung injury by modulating with intestinal microbiota and related metabolic pathways. METHODS: An AP disease model was established in mice and treated with C. butyricum. The structure and composition of the intestinal microbiota in mouse feces were analyzed by 16 S rRNA gene sequencing. Non-targeted metabolite analysis was used to quantify the microbiota derivatives. The histopathology of mouse pancreas and lung tissues was examined using hematoxylin-eosin staining. Pancreatic and lung tissues from mice were stained with immunohistochemistry and protein immunoblotting to detect inflammatory factors IL-6, IL-1ß, and MCP-1. RESULTS: C. butyricum ameliorated the dysregulation of microbiota diversity in a model of AP combined with lung injury and affected fatty acid metabolism by lowering triglyceride levels, which were closely related to the alteration in the relative abundance of Erysipelatoclostridium and Akkermansia. In addition, C. butyricum treatment attenuated pathological damage in the pancreatic and lung tissues and significantly suppressed the expression of inflammatory factors in mice. CONCLUSIONS: C. butyricum may alleviate lung injury associated with AP by interfering with the relevant intestinal microbiota and modulating relevant metabolic pathways.

Tautomeric cinnamoylphloroglucinol-monoterpene adducts from Cleistocalyx operculatus and their antiviral activities.

Guided by 1H NMR spectroscopic experiments using the characteristic enol proton signals as probes, three pairs of new tautomeric cinnamoylphloroglucinol-monoterpene adducts (1-3) were isolated from the buds of Cleistocalyx operculatus. Their structures with absolute configurations were established by spectroscopic analysis, modified Mosher's method, and quantum chemical electronic circular dichroism calculation. Compounds 1-3 represent a novel class of cinnamoylphloroglucinol-monoterpene adducts featuring an unusual C-4-C-1' linkage between 2,2,4-trimethyl-cinnamyl-ß-triketone and modified linear monoterpenoid motifs. Notably, compounds 1-3 exhibited significant in vitro antiviral activity against respiratory syncytial virus (RSV).

Efficacy of mesenchymal stromal cells in the treatment of type 1 diabetes: a systematic review.

To investigate the efficacy of mesenchymal stromal cells in the treatment of type 1 diabetes. Articles about the effects of mesenchymal stromal cells for T1D were retrieved in PubMed, Web of Science, Embase, and the Cochrane Library databases up to July 2023. Additional relevant studies were manually searched through citations. HbA1c, FBG, PBG, insulin requirement and C-peptide were assessed. The risk of bias was evaluated with the ROB 2.0 and ROBINS-I tools. Six RCTs and eight nRCTs were included. Of the 14 studies included, two evaluated BM-MSCs, three evaluated UC-MSCs, five evaluated AHSCT, two evaluated CB-SCs, and two evaluated UC-SCs plus aBM-MNCs. At the end of follow-up, ten studies found that mesenchymal stromal cells improved glycemic outcomes in T1D, while the remaining four studies showed no significant improvement. Findings support the positive impacts observed from utilizing mesenchymal stromal cells in individuals with T1D. However, the overall methodological quality of the identified studies and findings is heterogeneous, limiting the interpretation of the therapeutic benefits of mesenchymal stromal cells in T1D. Methodically rigorous research is needed to further increase credibility.

Surface Plasmon Resonance Enhanced Photoelectrochemical Sensing of Cysteine Based on Au Nanoparticle-Decorated ZnO@graphene Quantum Dots.

In this work, Au nanoparticle-decorated ZnO@graphene core-shell quantum dots (Au-ZnO@graphene QDs) were successfully prepared and firstly used to modify an ITO electrode for the construction of a novel photoelectrochemical biosensor (Au-ZnO@graphene QDs/ITO). Characterization of the prepared nanomaterials was conducted using transmission electron microscopy, steady-state fluorescence spectroscopy and the X-ray diffraction method. The results indicated that the synthesized ternary nanomaterials displayed excellent photoelectrochemical performance, which was much better than that of ZnO@graphene QDs and pristine ZnO quantum dots. The graphene and ZnO quantum dots formed an effective interfacial electric field, enhancing photogenerated electron-hole pairs separation and leading to a remarkable improvement in the photoelectrochemical performance of ZnO@graphene QDs. The strong surface plasmon resonance effect achieved by directly attaching Au nanoparticles to ZnO@graphene QDs led to a notable increase in the photocurrent response through electrochemical field effect amplification. Based on the specifical recognition between cysteine and Au-ZnO@graphene QDs/ITO through the specificity of Au-S bonds, a light-driven photoelectrochemical sensor was fabricated for cysteine detection. The novel photoelectrochemical biosensor exhibited outstanding analytical capabilities in detecting cysteine with an extremely low detection limit of 8.9 nM and excellent selectivity. Hence, the Au-ZnO@graphene QDs is a promising candidate as a novel advanced photosensitive material in the field of photoelectrochemical biosensing.

The combination of allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate mitigates UVB-induced PGE2 synthesis by keratinocytes.

OBJECTIVE: Erythema, characterized by the redness of the skin, is a common skin reaction triggered by various endogenous and exogenous factors. This response is often a result of the activation of underlying inflammatory mechanisms within the skin. The objective of this study is to investigate the potential benefits of applying a combination of skincare ingredients, namely allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate (AB5D), in the modulation of inflammatory factors associated with erythema. Additionally, the study aims to elucidate the mechanisms by which these ingredients exert their combined actions to alleviate erythema-associated inflammation. METHODS: Human epidermal keratinocytes were exposed to UVB and subsequently treated with AB5D. Transcriptomics profiling was performed to analyse the dose-response effect of AB5D treatment on keratinocytes. The quantitation of inflammatory mediators, including PGE2 , IL-1α, IL-6, IL-8, IL-1RA and TNFα, was performed on cultured media. Additionally, the oxygen radical absorbance capacity (ORAC) assay was carried out to evaluate the total antioxidant capacity of both individual ingredients and the AB5D combination. To assess the in-vitro antioxidant effects of AB5D against UVB-induced oxidative stress in hTERT keratinocytes, real-time quantitation of mitochondrial superoxide was measured through live-cell imaging. RESULTS: The application of AB5D to UVB-exposed keratinocytes downregulated gene sets associated with inflammatory responses, highlighting the anti-inflammatory properties of AB5D. Specifically, AB5D effectively reduced the production of PGE2 , leading to the downregulation of inflammatory cytokines. Moreover, our findings indicate that AB5D exhibits antioxidative capabilities, functioning as both an antioxidant agent and a regulator of antioxidant enzyme expression to counteract the detrimental effects of cellular oxidative stress. CONCLUSION: We demonstrated that AB5D can reduce UVB-induced PGE2 , IL-1α, IL-6, IL-8, IL-1RA and TNFα as well as mitochondrial superoxide. These findings suggest that AB5D may alleviate erythema by modulating inflammation via PGE2 and through antioxidation mechanisms.

L'érythème, caractérisé par une rougeur sur la peau, est une réaction cutanée fréquente déclenchée par divers facteurs endogènes et exogènes. Il s'agit d'une réponse qui résulte souvent de l'activation des mécanismes inflammatoires sous-jacents dans la peau. OBJECTIF: cette étude vise à étudier les bénéfices potentiels de l'application d'une association d'ingrédients de soins cutanés, à savoir l'allantoïne, le bisabolol, le D-panthénol et le glycyrrhizinate dipotassique (AB5D) dans la modulation des facteurs inflammatoires associés à l'érythème. En outre, l'étude vise à élucider les mécanismes par lesquels ces ingrédients exercent leurs actions combinées pour soulager l'inflammation associée à l'érythème. MÉTHODES: les kératinocytes épidermiques humains ont été exposés aux UVB et traités par la suite par AB5D. Un profilage transcriptomique a été effectué pour analyser l'effet dose-réponse du traitement par AB5D sur les kératinocytes. La quantification des médiateurs inflammatoires, y compris PGE2, IL-1α, IL-6, IL-8, IL-1RA et TNFα, a été effectuée sur des milieux de culture. En outre, le dosage de la capacité d'absorption des radicaux oxygénés (Oxygen Radical Absorbance Capacity, ORAC) a été effectué pour évaluer la capacité antioxydante totale des deux ingrédients individuels et de l'association AB5D. Pour évaluer les effets antioxydants in vitro de l'AB5D contre le stress oxydatif induit par les UVB dans les kératinocytes hTERT, on a mesuré la quantification en temps réel du superoxyde mitochondrial par des tests d'imagerie des cellules vivantes. RÉSULTATS: l'application de l'AB5D aux ensembles de gènes régulés à la baisse exposés aux kératinocytes UVB associés à des réponses inflammatoires, a mis en évidence les propriétés anti-inflammatoires de l'AB5D. Plus précisément, l'AB5D a efficacement réduit la production de PGE2, entraînant une régulation négative des cytokines inflammatoires. En outre, nos résultats indiquent que l'AB5D présente des capacités antioxydantes. Il fonctionne à la fois comme un agent antioxydant et comme un régulateur de l'expression enzymatique antioxydante pour contrer les effets néfastes du stress oxydatif cellulaire. CONCLUSION: nous avons montré que l'AB5D pouvait réduire la PGE2 induite par les UVB, l'IL-1α, l'IL-6, IL-8, IL-1RA et le TNFα, ainsi que le superoxyde mitochondrial. Ces résultats suggèrent que l'AB5D pourrait soulager l'érythème en modulant l'inflammation via la PGE2 et via des mécanismes d'antioxydation.

The changes and correlation of IL-6 and oxidative stress levels in RAW264.7 macrophage cells induced by PAHs in PM2.5.

The objective of this study was to investigate the effects of anthracene (Ant) with 3 rings, benzo[a]anthracene (BaA) with 4 rings and benzo[b]fluoranthene (BbF) with 5 rings in fine particulate matter (PM2.5) at different exposure times (4 h and 24 h) and low exposure levels (0 pg/mL, 0.1 pg/mL, 1 pg/mL, 100 pg/mL and 10,000 pg/mL) on RAW264.7 cells. The changes of interleukin-6 (IL-6) and oxidative stress levels in RAW264.7 cells were investigated by methyl-thiazolyl-tetrazolium (MTT) and enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to analyze the correlation between variables. Ant, BaA and BbF induced the secretion of IL-6 and the occurrence of oxidative stress in RAW264.7 cells. The inflammatory effect and oxidative damage were exacerbated with prolonged exposure time, increasing exposure concentration and increasing number of PAH rings. At the same time, IL-6 was found to have a certain correlation with the levels of ROS, MDA and SOD. Exposure to atmospheric PAHs at low concentrations can also produce toxic effects on cells, IL-6 and oxidative stress work together in cell damage. The study is expected to provide a theoretical and experimental basis for air pollution control and human health promotion.

Visible-Light-Mediated Activation of Remote C(sp3)-H Bonds by Carbon-Centered Biradical via Intramolecular 1,5- or 1,6-Hydrogen Atom Transfer.

In this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish-Yang reaction. This process is facilitated by excited triplet-state carbon-centered biradicals, enabling the 1,5-HAT reaction by suppressing the critical 1,4-biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6-HAT reactions initiated by excited triplet-state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large-scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern-Volmer experiments, and density functional theory (DFT) calculations.