Beyond flavor: the versatile roles of eugenol in health and disease.

Eugenol, a phenylpropanoid compound, is found in various dietary resources and medicinal plants. From a historical perspective, eugenol is widely employed as a flavoring agent in the food and fragrance industries. Here, this review mainly focuses on recent advances in eugenol with respect to its versatile physiological roles in health and disease and discusses the mechanisms. Emerging evidence has highlighted that eugenol exhibits multiple biological activities in cancer, diabetes, obesity, cardiovascular diseases, and neurodegenerative diseases. It also has analgesic, anti-inflammatory, and antioxidant qualities and has lethal or inhibiting effects on various viruses, bacteria, fungi, and parasites. The manuscript also contains some patents that have been filed thus far regarding the production and application of eugenol. Overall, these benefits make eugenol a promising nutritional supplement which fulfils its historical function as a flavoring agent, opening up new possibilities for the creation of therapeutic agents for the treatment of disease.

Molecular landscape of ERBB2 alterations in 3000 advanced NSCLC patients.

ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 insertion Y772_A775dupYVMA was the most frequent alteration (58% vs 41.6% in the Chinese vs the US), followed by G776delinsVC/LC/VV/IC (10.7% vs 9.7%), and S310X (10.5% vs 15.4%). EGFR ex20 insertions were identified in the A767-V774 region, whereas ERBB2 ex20 insertions were observed in the Y772-P780 region. Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.

Chronic UVB exposure induces hepatic injury in mice: Mechanistic insights from integrated multi-omics.

Chronic UVB exposure poses a significant threat to both skin and visceral health. In recent years, the adverse role of chronic UVB exposure in liver health has been suggested but not fully elucidated. This study aims to comprehensively investigate the effects of chronic UVB exposure on liver health in male SKH-1 hairless mice and clarify potential mechanisms through multi-omics approaches. The findings suggested that 10-week chronic skin exposure to UVB not only triggers hepatic inflammation and oxidative stress but also, more importantly, results in lipid metabolism abnormalities in the liver. Hepatic transcriptomic analysis revealed significant alterations in various signaling pathways and physiological processes associated with inflammation, oxidative stress, and lipid metabolism. Further lipidomic analysis illustrated significant changes in the metabolism of glycerolipids, sphingolipids, and glycerophospholipids in the liver following chronic UVB exposure. The 16S rRNA sequencing analysis indicated that chronic UVB exposure disrupts the structure and function of the microbiota. In search of potential mechanisms used by the microbiome to regulate the hepatic disease morphology, we filtered mouse fecal supernatants and cultured the supernatants with HepG2 cells. Fecal supernatant from UVB-exposed mice induced increased secretion of the inflammatory cytokine IL-8, accumulation of MDA, reduced SOD activity, and decreased lipid content in normal hepatic cells. In summary, skin chronic exposure to UVB induces multiple liver injuries and gut microbiota dysbiosis in mice and gut microbiota metabolites may be one of the contributing factors to hepatic injury caused by chronic UVB exposure. These discoveries deepen the comprehension of the health risks associated with chronic UVB exposure.

Diabetes-induced muscle wasting: molecular mechanisms and promising therapeutic targets.

Diabetes has become a serious public health crisis, presenting significant challenges to individuals worldwide. As the largest organ in the human body, skeletal muscle is a significant target of this chronic disease, yet muscle wasting as a complication of diabetes is still not fully understood and effective treatment methods have yet to be developed. Here, we discuss the targets involved in inducing muscle wasting under diabetic conditions, both validated targets and emerging targets. Diabetes-induced skeletal muscle wasting is known to involve changes in various signaling molecules and pathways, such as protein degradation pathways, protein synthesis pathways, mitochondrial function, and oxidative stress inflammation. Recent studies have shown that some of these present potential as promising therapeutic targets, including the neuregulin 1/epidermal growth factor receptor family, advanced glycation end-products, irisin, ferroptosis, growth differentiation factor 15 and more. This study's investigation and discussion of such pathways and their potential applications provides a theoretical basis for the development of clinical treatments for diabetes-induced muscle wasting and a foundation for continued focus on this disease.

Oleuropein Supplementation Ameliorates Long-Course Diabetic Nephropathy and Diabetic Cardiomyopathy Induced by Advanced Stage of Type 2 Diabetes in db/db Mice.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of diabetic nephropathy and diabetic cardiomyopathy. However, the efficacy of OP on the long-course of these diabetes complications has not been investigated. Therefore, in this study, to investigate the relieving effects of OP intake on these diseases, and to explore the underlying mechanisms, db/db mice (17-week-old) were orally administrated with OP (200 mg/kg bodyweight) for 15 weeks. We found that OP reduced expansion of the glomerular mesangial matrix, renal inflammation, renal fibrosis, and renal apoptosis. Meanwhile, OP treatment exerted cardiac anti-fibrotic, anti-inflammatory, and anti-apoptosis effects. Notably, transcriptomic and bioinformatic analyses indicated 290 and 267 differentially expressed genes in the kidney and heart replying to OP treatment, respectively. For long-course diabetic nephropathy, OP supplementation significantly upregulated the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. For long-course diabetic cardiomyopathy, p53 and cellular senescence signaling pathways were significantly downregulated in response to OP supplementation. Furthermore, OP treatment could significantly upregulate the transcriptional expression of the ATPase Na+/K+ transporting subunit alpha 3, which was enriched in the cGMP-PKG signaling pathway. In contrast, OP treatment could significantly downregulate the transcriptional expressions of cyclin-dependent kinase 1, G two S phase expressed protein 1, and cyclin B2, which were enriched in p53 and cellular senescence signal pathways; these genes were confirmed by qPCR validation. Overall, our findings demonstrate that OP ameliorated long-course diabetic nephropathy and cardiomyopathy in db/db mice and highlight the potential benefits of OP as a functional dietary supplement in diabetes complications treatment.

Enhanced Survival with Lymphadenectomy in Early-Stage Metachronous Second Primary Lung Cancer: A Retrospective Analysis.

INTRODUCTION: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer (MSPLC) remains poorly understood. This retrospective study aimed to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. METHODS: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score-matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score-matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% in the non-lymphadenectomy group (HR: 0.76; 95% confidence interval 0.64-0.90; p = 0.002). CONCLUSION: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggest the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

Revitalizing Photoaging Skin through Eugenol in UVB-Exposed Hairless Mice: Mechanistic Insights from Integrated Multi-Omics.

Chronic ultraviolet (UV) exposure causes photoaging, which is primarily responsible for skin damage. Nutritional intervention is a viable strategy for preventing and treating skin photoaging. Eugenol (EU) presents anti-inflammatory and antioxidant properties, promotes wound healing, and provides contact dermatitis relief. This study explored the ability of EU to mitigate skin photoaging caused by UVB exposure in vitro and in vivo. EU alleviated UVB-induced skin photodamage in skin cells, including oxidative stress damage and extracellular matrix (ECM) decline. Dietary EU alleviated skin photoaging by promoting skin barrier repair, facilitating skin tissue regeneration, and modulating the skin microenvironment in photoaged mice. The transcriptome sequencing results revealed that EU changed the skin gene expression profiles. Subsequent pathway enrichment analyses indicated that EU might reverse the pivotal ECM-receptor interaction and cytokine-cytokine receptor interaction signaling pathways. Furthermore, EU alleviated the intestinal dysbiosis induced by chronic UVB exposure. Spearman analysis results further revealed the close connection between gut microbiota and skin photoaging. Considering the near-inevitable UVB exposure in modern living, the findings showed that the EU effectively reverted skin photoaging, offering a potential strategy for addressing extrinsic skin aging.

Dietary Isoeugenol Supplementation Attenuates Chronic UVB-Induced Skin Photoaging and Modulates Gut Microbiota in Mice.

Photoaging, the primary cause of skin aging damage, results from chronic ultraviolet (UV) exposure, leading to dryness and wrinkle formation. Nutritional intervention has emerged as a practical approach for preventing and addressing the effect of skin photoaging. The primary aromatic compound isolated from clove oil, isoeugenol (IE), has antibacterial, anti-inflammatory, and antioxidant qualities that work to effectively restrict skin cancer cell proliferation. This investigation delved into the advantages of IE in alleviating skin photoaging using UVB-irradiated skin fibroblasts and female SKH-1 hairless mouse models. IE alleviated UVB-induced photodamage in Hs68 dermal fibroblasts by inhibiting matrix metalloproteinase secretion and promoting extracellular matrix synthesis. In photoaged mice, dietary IE reduced wrinkles, relieved skin dryness, inhibited epidermal thickening, and prevented collagen loss. Additionally, the intestinal dysbiosis caused by prolonged UVB exposure was reduced with an IE intervention. The results of Spearman's analysis showed a strong correlation between skin photoaging and gut microbiota. Given the almost unavoidable UVB exposure in contemporary living, this research demonstrated the efficacy of dietary IE in reversing skin photoaging, presenting a promising approach to tackle concerns related to extrinsic skin aging.

Dietary supplementation with α-ionone alleviates chronic UVB exposure-induced skin photoaging in mice.

Photoaging is widely regarded as the most significant contributor to skin aging damage. It is triggered by prolonged exposure to ultraviolet (UV) light and typically manifests as dryness and the formation of wrinkles. Nutritional intervention is a viable strategy for preventing and treating skin photoaging. In previous studies, we demonstrated that α-ionone had ameliorating effects on photoaging in both epidermal keratinocytes and dermal fibroblasts. Here, we investigated the potential anti-photoaging effects of dietary α-ionone using a UVB-irradiated male C57BL/6N mouse model. Our findings provided compelling evidence that dietary α-ionone alleviates wrinkle formation, skin dryness, and epidermal thickening in chronic UVB-exposed mice. α-Ionone accumulated in mouse skin after 14 weeks of dietary intake of α-ionone. α-Ionone increased collagen density and boosted the expression of collagen genes, while attenuating the UVB-induced increase of matrix metalloproteinase genes in the skin tissues. Furthermore, α-ionone suppressed the expression of senescence-associated secretory phenotypes and reduced the expression of the senescence marker p21 and DNA damage marker p53 in the skin of UVB-irradiated mice. Transcriptome sequencing results showed that α-ionone modifies gene expression profiles of skin. Multiple pathway enrichment analyses on both the differential genes and the entire genes revealed that α-ionone significantly affects multiple physiological processes and signaling pathways associated with skin health and diseases, of which the p53 signaling pathway may be the key signaling pathway. Taken together, our findings reveal that dietary α-ionone intervention holds promise in reducing the risks of skin photoaging, offering a potential strategy to address skin aging concerns.

Survival of small-cell lung cancer patients after surgery: A single-center retrospective cohort study.

This study summarized and analyzed the clinical characteristics and prognosis of small-cell lung cancer (SCLC) patients after surgical treatment. The clinical data of 130 patients (99 males and 31 females) with SCLC treated by surgery and confirmed by postoperative pathological examination at Peking Union Medical College Hospital from April 2004 to April 2019 were retrospectively analyzed. Clinical characteristics, surgery, pathological stage, and perioperative treatment were summarized. Kaplan-Meier survival curve and Cox regression analysis were performed. Pathological examination revealed that 36 (27.69%) patients had stage I SCLC, 22 (16.92%) patients had stage II SCLC, 65 (50.00%) patients had stage III SCLC, and 7 (5.39%) patients had stage IV SCLC. The overall median survival time was 50 months (95% confidence interval, 10.8-89.2 months). The median survival time of stage I, II, III and IV SCLC patients was 148, 42, 32, and 10 months, respectively. In patients who underwent surgical treatment, postoperative adjuvant therapy and tumor stage were independent prognostic factors for survival (p < 0.05).Lobectomy and lymph nodes resection combined with adjuvant therapy were cautiously recommended for stage I-IIIa SCLC patients.

Necroptosis-related signatures identify two distinct hepatocellular carcinoma subtypes: Implications for predicting drug sensitivity and prognosis.

Background: Necroptosis is associated with oncogenesis, tumor immunity and progression. This research aims to investigate the association of necroptosis-related genes with drug sensitivity and prognosis in hepatocellular carcinoma (HCC). Methods: Based on necroptosis-related signatures, HCC patients retrieved from the TCGA database were categorized. Survival outcomes, mutation profile, immune microenvironment, and drug sensitivity between HCC subtypes were further compared. Then, LASSO analysis was performed to construct a necroptosis-related prognostic signature, which was further evaluated using another independent cohort. Results: A total of 371 patients with HCC could be categorized into two necroptosis-related subtypes. About 36% of patients were allocated to subtype A, with worse survival, more mutant TP53, and a lower likelihood of immunotherapy response. In contrast, patients in subtype B had a favorable prognosis, with lower expression of immunosuppressive signatures but a lower abundance of B and CD8+ T-cell infiltration. The prognostic risk score calculated using the expression levels of nine genes involved in the necroptosis pathway (MLKL, FADD, XIAP, USP22, UHRF1, CASP8, RIPK3, ZBP1, and FAS) showed a significant association with tumor stage, histologic grade, and Child‒Pugh score. Additionally, the risk score model was proven to be accurate in both the training and independent external validation cohorts and performed better than the TNM staging system and three well-recognized risk score models. Conclusions: Based on necroptosis-related signatures, we identified two HCC subtypes with distinctive immune microenvironments, mutation profiles, drug sensitivities, and survival outcomes. A novel well-performing prognostic model was further constructed.

The prognostic role of WeChat-based instant doctor-patient communication in patients with advanced pancreatic cancer.

BACKGROUND: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) need timely medical assistance since the emergence of complications due to the disease and antitumor treatment. Studies have confirmed that instant messaging can improve the quality of life and compliance of cancer patients. However, the prognostic role of instant doctor-patient communication based on instant messaging applications in PDAC has not been studied. METHODS: Patients with PDAC who received first-line chemotherapy at Peking Union Medical College Hospital between January 2015 and October 2022 were reviewed. We categorized patients into two groups according to whether they received WeChat-based instant doctor-patient communication, and the prognosis and toxicity data between the two groups were compared. RESULTS: A total of 431 PDAC patients were enrolled, of whom 163 had long-term instant communication with their doctors based on WeChat, and 268 did not receive WeChat-based instant communication. There was no significant correlation between WeChat-based communication and first-line chemotherapy overall response rate (14.1% vs. 8.6%, p = 0.074), incidence of grade ≥ 3 adverse events (66.9% vs. 65.7%, p = 0.814) or overall survival (14.7 vs. 13.9 months, p = 0.170) in all enrolled patients. However, patients who received WeChat-based instant communication had a higher completion rate of first-line chemotherapy (42.0% vs. 30.7%, p = 0.023). Consistently, in the patients who developed grade ≥ 3 adverse events (n = 231), those who received WeChat-based instant communication had significantly longer overall survival (17.3 vs. 15.3 months, p = 0.018), even after adjustment for biases. CONCLUSIONS: WeChat-based instant doctor-patient communication demonstrated no superiority in improving the efficacy of chemotherapy or preventing chemotherapy toxicity in PDAC patients, but it may contribute to improving the completion rate of chemotherapy and the prognosis in patients who experienced severe adverse events. IMPLICATIONS FOR CANCER SURVIVORS: Instant doctor‒patient communication may help to timely and appropriately deal with adverse events and prolong the survival time of patients with PDAC, supporting the promotion of mobile technology in clinical practice.

Chronic exposure to UVB induces nephritis and gut microbiota dysbiosis in mice based on the integration of renal transcriptome profiles and 16S rRNA sequencing data.

Ultraviolet (UV) is a common and abundant environmental factor that affects daily life. Although the effects of UV radiation on the skin have been extensively reported, studies on the influence of UV radiation on internal organs are still limited. This study aimed to evaluate the influence of UVB exposure on the kidney of mice and to investigate the possible mechanism. In the present study, histopathology changes, oxidative stress, and inflammatory response were used to evaluate the kidney and colon injury induced by UVB exposure. The results showed that the 14-week chronic skin exposure to UVB triggers a kidney injury response characterized by macrophage infiltration, elevated oxidative stress as well as inflammatory and injury markers. The RNA sequencing demonstrated that chronic UVB exposure could alter the kidney transcriptomic profile distinguished by the regulation of genes involved in the Notch signaling pathway, JAK-STAT signaling pathway, and ECM-receptor interaction. Besides, chronic UVB exposure also resulted in gut dysbiosis, manifested as colon macrophage infiltration, stimulated inflammatory responses, impaired barrier integrity, and microbiota structural and functional disorders. The Spearman analysis results further revealed a strong correlation between gut microbiota and kidney injury. In conclusion, skin chronic exposure to UVB causes nephritis and gut microbiota dysbiosis in mice, and these findings provide new insight into the underlying risks of chronic UVB exposure to human wellness.

Cedrol, a Major Component of Cedarwood Oil, Ameliorates High-Fat Diet-Induced Obesity in Mice.

SCOPE: Excellent health-promoting effects of cedrol (CED), including anti-inflammatory, anti-arthritic, and antinociceptive effects, have been reported. The present study aims to investigate the preventive effects of CED on high-fat diet (HFD)-induced obesity and the related metabolic syndrome, and to delineate the underlying mechanism. METHODS AND RESULTS: Ten-week-old C57BL/6J mice are fed chow, HFD, or HFD supplemented with CED (0.2% w/w) for 19 weeks. Results demonstrate that CED effectively reduces HFD-induced body weight gain, decreases visceral fat pad weight, and significantly prevents adipocyte hypertrophy in mice. HFD-induced hepatic steatosis, glucose intolerance, insulin resistance, and gluconeogenesis are ameliorated by CED supplementation. 16S rRNA analysis reveals that CED does not change gut microbiota composition at the phylum and genus levels, indicating that CED may have limited effects on gut microbiota in HFD-fed mice. Further transcriptome analysis of epididymal white adipose tissue reveals reprogrammed RNA profiles by CED. CONCLUSION: These results demonstrate that incorporating CED in the diet can prevent HFD-induced obesity and related metabolic syndrome, and highlight that CED can be a promising dietary component for obesity therapeutic intervention.

Genomic landscape and efficacy of HER2-targeted therapy in patients with HER2-mutant non-small cell lung cancer.

Background: HER2-targeted therapy provides survival benefits to HER2-mutant non-small cell lung cancer (NSCLC). A better understanding of the clinical and genomic characterization of treatment-naïve HER2-positive NSCLC, as well as the efficacy of and resistance to HER2-targeted therapy in HER2-altered NSCLC, could promote further improvement of HER2 targeted therapy. Methods: HER2-altered NSCLC patients was retrospectively included and their genomic profiles were performed by next-generation sequencing. The clinical outcomes included overall response rate, disease control rate and progression-free survival. Results: Among 176 treatment-naïve patients with HER2 alterations, 64.8% harbored HER2 mutations with/without HER2 amplification, and 35.2% carried HER2 amplification only. Molecular characterization was correlated with tumor stage that late-stage NSCLC with HER2 oncogenic mutations showed a higher prevalence of TP53 mutations and a higher tumor mutation burden. However, this correlation was not found in patients with HER2 amplification only. Twenty-one patients with HER2 alterations treated with pyrotinib or afatinib were retrospectively enrolled. Pyrotinib yielded a longer median progression-free survival than afatinib (5.9 [95% CI, 3.8-13.0] vs. 4.0 months [95% CI, 1.9-6.3], P = 0.06) in these patients. Analysis of the genomic profiles before and after anti-HER2 targeted therapies identified de novo HER2 copy number gain and G518W mutation, as well as mutations involving DNA damage repair signaling, SWI-SNF complex, and epigenetic regulations as potential resistance mechanisms. Conclusion: HER2-mutant NSCLC had different molecular features from HER2-amplified NSCLC, and its genomic profile was dependent of tumor stage. Pyrotinib had superior therapeutic effects than afatinib in HER2-altered NSCLC, although larger cohorts are warranted to validate it. HER2-dependent and -independent resistance mechanisms to afatinib and pyrotinib were unveiled.

α-Ionone protects against UVB-induced photoaging in epidermal keratinocytes.

Objective: To evaluate whether α-ionone, an aromatic compound mainly found in raspberries, carrots, roasted almonds, fruits, and herbs, inhibits UVB-mediated photoaging and barrier dysfunction in a human epidermal keratinocyte cell line (HaCaT cells). Methods: The anti-photoaging effect of α-ionone was evaluated by detecting the expression of barrier-related genes and matrix metalloproteinases (MMPs) in HaCaT cells. The levels of reactive oxygen species, oxidation product, antioxidant enzyme, and inflammatory factors were further analysed to underline the protective effect of α-ionone on epidermal photoaging. Results: It was found that α-ionone attenuated UVB-induced barrier dysfunction by reversing keratin 1 and filaggrin in HaCaT cells. α-Ionone also reduced the protein amount of MMP-1 and mRNA expression of MMP-1 and MMP-3 in UVB-irradiated HaCaT cells, implying protective effects on extracellular matrix. Furthermore, HaCaT cells exposed to α-ionone showed significant decreases in interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α as compared to UVB-irradiated HaCaT cells. α-Ionone treatment significantly inhibited the UVB-induced intracellular reactive oxygen species increase and malondialdehyde accumulation. Therefore, the beneficial effects of α-ionone on inhibiting MMPs secretion and barrier damage may be related to attenuated inflammation and oxidative stress. Conclusion: Our results highlight the protective effects of α-ionone on epidermal photoaging and promote its clinic application as a potential natural anti-photodamage agent in future.

Peripheral CD8+CD28+ T lymphocytes predict the efficacy and safety of PD-1/PD-L1 inhibitors in cancer patients.

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes. Methods: We retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry. Results: Patients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/µL, p < 0.001). Using 190/µL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p < 0.001) and overall survival (OS, not reached versus 16.2 months, p < 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/µL. Conclusions: High circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/µL) may also indicate the emergence of severe irAEs.

The gut odorant receptor and taste receptor make sense of dietary components: A focus on gut hormone secretion.

Odorant receptors (ORs) and taste receptors (TRs) are expressed primarily in the nose and tongue in which they transduce electrical signals to the brain. Advances in deciphering the dietary component-sensing mechanisms in the nose and tongue prompted research on the role of gut chemosensory cells. Acting as the pivotal interface between the body and dietary cues, gut cells "smell" and "taste" dietary components and metabolites by taking advantage of chemoreceptors-ORs and TRs, to maintain physiological homeostasis. Here, we reviewed this novel field, highlighting the latest discoveries pertinent to gut ORs and TRs responding to dietary components, their impacts on gut hormone secretion, and the mechanisms involved. Recent studies indicate that gut cells sense dietary components including fatty acid, carbohydrate, and phytochemical by activating relevant ORs, thereby modulating GLP-1, PYY, CCK, and 5-HT secretion. Similarly, gut sweet, umami, and bitter receptors can regulate the gut hormone secretion and maintain homeostasis in response to dietary components. A deeper understanding of the favorable influence of dietary components on gut hormone secretion via gut ORs and TRs, coupled with the facts that gut hormones are involved in diverse physiological or pathophysiological phenomena, may ultimately lead to a promising treatment for various human diseases.

Patients' Preference for Physician Attire in the Internal Medicine Outpatient Department.

Objective: To investigate patients' preference and the attitude towards physician attire in an internal medicine clinic in China. Methods: This study was conducted from 1 January 2021 to 30 June 2021 in a tertiary care hospital in China. We surveyed 126 patients in the hospital with 6 sets of pictures of commonly worn physician attires in the hospital setting with a two-part questionnaire. The first part listed respondent demographics to collect basic information. The second part of the questionnaire was administered to adult patients who received care in the internal medicine clinics (outpatients). Survey forms collected demographic data (age, gender, patient age, education, marital status, and employment status), asked questions regarding 6 specific attires (scrubs, scrubs and white coat, casual, casual and white coat, business suit, and formal and white coat), and behavioral items (professional, responsible, reliable, knowledgeable, succession rate, and medical safety), finally, to assess the preference of attire on overall perception. Results: Scrubs and white coat scored the highest through 6 domains about physicians' attire (professional, reliable, responsible, knowledgeable, medical safety, and succession rate, p < 0.05 for all comparisons). A casual suit without a white coat was the least preferred across the surveyed attributes. There was a significant preference gap between wearing a white coat and not wearing a white coat (p < 0.001). Physician attire to white coat was considered as more professional, reliable, responsible, knowledgeable, having greater medical safety, and a higher success rate than attires without white coat. Conclusion: Patients felt that the physician wearing a white coat was better than other attires. Scrubs and white coat was the most popular attire. Hospital or related authorities may promote the standardized wearing of white coats, leading in a greater patient-physician relationship.

Ectopic odorant receptors responding to flavor compounds in skin health and disease: Current insights and future perspectives.

Skin, the largest organ of human body, acts as a barrier to protect body from the external environment and is exposed to a myriad of flavor compounds, especially food- and plant essential oil-derived odorant compounds. Skin cells are known to express various chemosensory receptors, such as transient potential receptors, adenosine triphosphate receptors, taste receptors, and odorant receptors (ORs). We aim to provide a review of this rapidly developing field and discuss latest discoveries related to the skin ORs activated by flavor compounds, their impacts on skin health and disease, odorant ligands interacting with ORs exerting specific biological effects, and the mechanisms involved. ORs are recently found to be expressed in skin tissue and cells, such as keratinocytes, melanocytes, and fibroblasts. To date, several ectopic skin ORs responding to flavor compounds, are involved in different skin biological processes, such as wound healing, hair growth, melanin regulation, pressure stress, skin barrier function, atopic dermatitis, and psoriasis. The recognition of physiological role of skin ORs, combined with the fact that ORs belong to a highly druggable protein family (G protein-coupled receptors), underscores the potential of skin ORs responding to flavor compounds as a novel regulating strategy for skin health and disease.