Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Design method for eliminating spectral line tilt in a multiple sub-pupil ultra-spectral imager (MSPUI).

A multiple sub-pupil ultra-spectral imaging system designed with a single spectrometer and detector can simultaneously detect multiple-channel spectra with ultra-high spectral resolution. However, due to using a prism in the system's front end, the nonlinear dispersion introduces spectral line tilt in the imaging spectra. This phenomenon can lead to bias in the final spectral data. To eliminate this issue, we propose a new design by introducing a second prism to correct this spectral tilt in the system. The angle of spectral line tilt generated by the nonlinear dispersion of the first prism is derived. It provides the theoretical basis for characterizing the second complementary prism. Finally, a UV multiple sub-pupil ultra-spectral imaging system is designed. The system employs two pupil separation prisms and one flat panel array to segment the pupil in three channels, each operating within spectral ranges of 180∼210 nm, 275∼305 nm, and 370∼400 nm, respectively. The spectral resolutions in all three channels are better than 0.1 nm. The corrected spectral line tilt is less than 1/3 of a pixel in the two channels with pupil separation prisms. At a Nyquist frequency of 30 lp/mm, the modulation transfer functions of all three channels are greater than 0.7, ensuring imaging quality. The design results indicate that the method proposed in this paper, utilizing complementary prisms, can effectively correct the spectral line tilt caused by the nonlinear dispersion of the pupil separation prisms. This design approach can be a reference for developing multiple sub-pupil ultra-spectral imaging systems.

Taste preferences, cardiometabolic diseases and mild cognitive impairment: a prospective cohort analysis of older Chinese adults.

Taste preference is a pivotal predictor of nutrient intake, yet its impact on mild cognitive impairment (MCI) remains poorly understood. We aimed to investigate the association between taste preferences and MCI and the role of cardiometabolic diseases (CMD) in this association. The study included older adults, aged 65-90 years, with normal cognitive function at baseline who were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. MCI was measured by the Mini-Mental State Examination, and multivariable Cox regression models were applied. Among 6423 participants, 2534 (39·45 %) developed MCI with an incidence rate of 63·12 - per 1000 person-years. Compared with individuals with insipid taste, those preferring sweetness or spiciness had a higher MCI risk, while saltiness was associated with a lower risk. This association was independent of objective dietary patterns and was more pronounced among urban residents preferring sweetness and illiterate participants preferring spiciness. Notably, among sweet-liking individuals, those with one CMD experienced a significant detrimental effect, and those with co-occurring CMD had a higher incidence rate of MCI. Additionally, regional variations were observed: sweetness played a significant role in regions known for sweet cuisine, while the significance of spiciness as a risk factor diminishes in regions where it is commonly preferred. Our findings emphasize the role of subjective taste preferences in protecting cognitive function and highlight regional variations. Target strategies should focus on assisting individuals with CMD to reduce excessive sweetness intake and simultaneously receiving treatment for CMD to safeguard cognitive function.

Sequestration of Labile Organic Matter by Secondary Fe Minerals from Chemodenitrification: Insight into Mineral Protection Mechanisms.

Labile organic matter (OM) immobilized by secondary iron (Fe) minerals from chemodenitrification may be an effective way to immobilize organic carbon (OC). However, the underlying mechanisms of coupled chemodenitrification and OC sequestration are poorly understood. Here, OM immobilization by secondary Fe minerals from chemodenitrification was investigated at different C/Fe ratios. Kinetics of Fe(II) oxidation and nitrite reduction rates decreased with increasing C/Fe ratios. Despite efficient sequestration, the immobilization efficiency of OM by secondary minerals varied with the C/Fe ratios. Higher C/Fe ratios were conducive to the formation of ferrihydrite and lepidocrocite, with defects and nanopores. Three contributions, including inner-core Fe-O and edge- and corner-shared Fe-Fe interactions, constituted the local coordination environment of mineral-organic composites. Microscopic analysis at the molecular scale uncovered that labile OM was more likely to combine with secondary minerals with poor crystallinity to enhance its stability, and OM distributed within nanopores and defects had a higher oxidation state. After chemodenitrification, high molecular weight substances and substances high in unsaturation or O/C ratios including phenols, polycyclic aromatics, and carboxylic compounds exhibited a stronger affinity to Fe minerals in the treatments with lower C/Fe ratios. Collectively, labile OM immobilization can occur during chemodenitrification. The findings on OM sequestration coupled with chemodenitrification have significant implications for understanding the long-term cycling of Fe, C, and N, providing a potential strategy for OM immobilization in anoxic soils and sediments.

Heavy atom-induced quenching of fluorescent organosilicon nanoparticles for iodide sensing and total antioxidant capacity assessment.

We present a novel approach for iodide sensing based on the heavy-atom effect to quench the green fluorescent emission of organosilicon nanoparticles (OSiNPs). The fluorescence of OSiNPs was significantly quenched (up to 97.4% quenching efficiency) in the presence of iodide ions (I-) through oxidation by hydrogen peroxide. Therefore, OSiNPs can serve as a fluorescent probe to detect I- with high selectivity and sensitivity. The highly selective response is attributed to the hydrophilic surface enabling good dispersion in aqueous solutions and the lipophilic core allowing the generated liposoluble I2 to approach and quench the fluorescence of OSiNPs. The linear working range for I- was from 0 to 50 µM, with a detection limit of 0.1 µM. We successfully applied this nanosensor to determine iodine content in edible salt. Furthermore, the fluorescent OSiNPs can be utilized for the determination of total antioxidant capacity (TAC). Antioxidants reduce I2 to I-, and the extent of quenching by the remaining I2 on the OSiNPs indicates the TAC level. The responses to ascorbic acid, pyrogallic acid, and glutathione were investigated, and the detection limit for ascorbic acid was as low as 0.03 µM. It was applied to the determination of TAC in ascorbic acid tablets and fruit juices, indicating the potential application of the OSiNP-based I2 sensing technique in the field of food analysis.

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

VPAC2 receptor mediates VIP-potentiated insulin secretion via ion channels in rat pancreatic ß cells.

Vasoactive intestinal peptide (VIP), a small neuropeptide composing of 28 amino acids, functions as a neuromodulator with insulinotropic effect on pancreatic ß cells, in which it is of vital importance in regulating the levels of blood glucose. VIP potently agonizes VPAC2 receptor (VPAC2-R). Agonists of VPAC2-R stimulate glucose-dependent insulin secretion. The purpose of this study was to further investigate the possible ion channel mechanisms in VPAC2-R-mediated VIP-potentiated insulin secretion. The results of insulin secretion experiments showed that VIP augmented insulin secretion in a glucose-dependent manner. The insulinotropic effect was mediated by VPAC2-R rather than VPAC1 receptor (VPAC1-R), through the adenylyl cyclase (AC)/protein kinase A (PKA) signalling pathway. The calcium imaging analysis demonstrated that VIP increased intracellular Ca2+ concentration ([Ca2+]i). In addition, in the whole-cell voltage-clamp mode, we found that VIP blocked the voltage-dependent potassium (Kv) channel currents, while this effect was reversed by inhibiting the VPAC2-R, AC or PKA respectively. Taken together, these findings suggest that VIP stimulates insulin secretion by inhibiting the Kv channels, activating the Ca2+ channels, and increasing [Ca2+]i through the VPAC2-R and AC/PKA signalling pathway. These findings provide theoretical basis for the research of VPAC2-R as a novel therapeutic target.

Comparative Proteome and Cis-Regulatory Element Analysis Reveals Specific Molecular Pathways Conserved in Dog and Human Brains.

Brain development and function are governed by precisely regulated protein expressions in different regions. To date, multiregional brain proteomes have been systematically analyzed only for adult human and mouse brains. To understand the underpinnings of brain development and function, we generated proteomes from six regions of the postnatal brain at three developmental stages of domestic dogs (Canis familiaris), which are special among animals in terms of their remarkable human-like social cognitive abilities. Quantitative analysis of the spatiotemporal proteomes identified region-enriched synapse types at different developmental stages and differential myelination progression in different brain regions. Through integrative analysis of inter-regional expression patterns of orthologous proteins and genome-wide cis-regulatory element frequencies, we found that proteins related with myelination and hippocampus were highly correlated between dog and human but not between mouse and human, although mouse is phylogenetically closer to human. Moreover, the global expression patterns of neurodegenerative disease and autism spectrum disorder-associated proteins in dog brain more resemble human brain than in mouse brain. The high similarity of myelination and hippocampus-related pathways in dog and human at both proteomic and genetic levels may contribute to their shared social cognitive abilities. The inter-regional expression patterns of disease-associated proteins in the brain of different species provide important information to guide mechanistic and translational study using appropriate animal models.

Psychological stressors involved in the pathogenesis of premature ovarian insufficiency and potential intervention measures.

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.

Re-exploration of prognosis in type B thymomas: establishment of a predictive nomogram model.

OBJECTIVE: To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model. METHODS: A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression. RESULTS: A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1-128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively). CONCLUSION: The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.

Cholecystokinin-like peptide mediates satiety by inhibiting sugar attraction.

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.

Comparison of the efficacy of neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal in treatment of hypertensive cerebral hemorrhage.

OBJECTIVE: To compare neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal for treatment of hypertensive cerebral hemorrhage. METHOD: Ninety-one patients with hypertensive cerebral hemorrhage admitted to our neurosurgery department from June 2022 to May 2023 were selected: 47 patients who underwent endoscopic hematoma removal with the aid of neuronavigation in observation Group A and 44 who underwent intracerebral hematoma puncture and drainage in control Group B. The duration of surgery, intraoperative bleeding, hematoma clearance rate, pre- and postoperative GCS score, National Institutes of Health Stroke Scale (NIHSS) score, mRS score and postoperative complications were compared between the two groups. RESULTS: The duration of surgery, intraoperative bleeding and hematoma clearance were significantly lower in Group B than in Group A (p < 0.05). Conversely, no significant differences in the preoperative, 7-day postoperative, 14-day postoperative or 1-month postoperative GCS or NIHSS scores or the posthealing mRS score were observed between Groups A and B. However, the incidence of postoperative complications was significantly greater in Group B than in Group A (p < 0.05), with the most significant difference in incidence of intracranial infection (p < 0.05). CONCLUSION: Both neuronavigation-assisted intracerebral hematoma puncture and drainage and neuroendoscopic hematoma removal are effective at improving the outcome of patients with hypertensive cerebral hemorrhage. The disadvantage of neuronavigation is that the incidence of complications is significantly greater than that of other methods; postoperative care and prevention of complications should be strengthened in clinical practice.

Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis.

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Mitophagy mediated by HIF-1α/FUNDC1 signaling in tubular cells protects against renal ischemia/reperfusion injury.

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.

[Sequential mediating role of digital participation and health lifestyle in the relationship between socioeconomic status and depression of older adults].

OBJECTIVE: To explore the potential mechanisms of the relationship between socioeconomic status (SES) and depression of Chinese older adults through the mediating role of digital participation and health lifestyle. METHODS: Using the nationally representative data from the China Family Panel Studies in 2020, 4 846 participants aged 60 years and older were analyzed in our study. We explored the potential mechanisms of the relationship between SES and depression of Chinese older adults in the digital era through a chain multiple mediating effects model. The KHB (The Karlson, Holm, and Breen) method was used to analyze the mediating role of digital participation and health lifestyle and the proportion of mediating effect between the two was also calculated. A series of robustness tests were further conducted and the fit of the model was checked by structural equation modeling. RESULTS: The mean age of the 4 846 older adults included in this study was (68.20±5.07) years, 48.06% of whom were female and 51.94% were male. The KHB results showed that both digital participation and health lifestyle could mediate the relationship between SES and depression of older adults (P < 0.000 1) and the mediating role of health lifestyle accounted for a greater proportion than digital participation. And our study mainly found three potential pathways of SES and depression of older adults, including: (1) SES → digital participation → health lifestyle → depression, (2) SES → health lifestyle → depression, and (3) SES → depression. Structural equation modeling tests proved the overall fit of the model in this study. CONCLUSION: Our findings showed that in the digital age, in addition to the direct relationship between SES and depression of older adults, and the health lifestyle as a mediator between the relationship, there is also a sequential mediating role of digital participation and health lifestyle to reduce the risk of depression. The findings suggest that we should pay more attention to the probability of the digital divide exacerbating health inequalities and socioeconomic inequalities accumulation in the digital age and promote the co-progress of digital literacy and health literacy among older adults.

Impact of the First-Wave COVID-19 Pandemic on Medical Expenditure for Older Adults in China: Lessons from a Natural Experiment.

Older adults' access to healthcare services may have been affected by the COVID-19 pandemic. This study explored the effect of the first wave pandemic on the medical expenditure of older adults in China. Difference-in-Difference models captured both temporal and geographical variation in COVID-19 exposure to estimate the impacts of the pandemic on medical expenditure through a quasi-natural experiment. Data derived from the China Family Panel Studies. Results indicate that exposure to the pandemic significantly decreased total medical expenditures, hospital expenditures, and non-hospital medical expenditures of Chinese older adults by 15% (95% CI 12%-17%), 5% (95% CI 2%-7%), and 15% (95% CI 13%-16%), respectively, for each standardized severity increment. Females, less well-educated people, and individuals without internet access were most susceptible to experiencing these reductions. This study revealed that COVID-19 exerted a detrimental influence on the medical expenditure of older adults in mainland China. The "hidden epidemic" of non-COVID-19 medical needs of older adults deserves more attention on the part of policymakers.

Whole-genome resequencing reveals genetic differences and the genetic basis of parapodium number in Russian and Chinese Apostichopus japonicus.

BACKGROUND: Apostichopus japonicus is an economically important species in the global aquaculture industry. Russian A. japonicus, mainly harvested in the Vladivostok region, exhibits significant phenotypic differentiation, including in many economically important traits, compared with Chinese A. japonicus owing to differences in their habitat. However, both the genetic basis for the phenotypic divergence and the population genetic structure of Russian and Chinese A. japonicus are unknown. RESULT: In this study, 210 individuals from seven Russian and Chinese A. japonicus populations were sampled for whole-genome resequencing. The genetic structure analysis differentiated the Russian and Chinese A. japonicus into two groups. Population genetic analyses indicated that the Russian population showed a high degree of allelic linkage and had undergone stronger positive selection compared with the Chinese populations. Gene ontology terms enriched among candidate genes with group selection analysis were mainly involved in immunity, such as inflammatory response, antimicrobial peptides, humoral immunity, and apoptosis. Genome-wide association analysis yielded eight single-nucleotide polymorphism loci significantly associated with parapodium number, and these loci are located in regions with a high degree of genomic differentiation between the Chinese and Russia populations. These SNPs were associated with five genes. Gene expression validation revealed that three of these genes were significantly differentially expressed in individuals differing in parapodium number. AJAP08772 and AJAP08773 may directly affect parapodium production by promoting endothelial cell proliferation and metabolism, whereas AJAP07248 indirectly affects parapodium production by participating in immune responses. CONCLUSIONS: This study, we performed population genetic structure and GWAS analysis on Chinese and Russian A. japonicus, and found three candidate genes related to the number of parapodium. The results provide an in-depth understanding of the differences in the genetic structure of A. japonicus populations in China and Russia, and provide important information for subsequent genetic analysis and breeding of this species.

Ultra-processed food consumption and the risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1 :1.49; 95% confidence interval [CI]: 1.07-2.07; Ptrend  = .021) in a linear dose-response manner (Pnonlinearity  = .075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1 :2.17; 95% CI: 1.14-4.15) than in those aged ≥65 years (HRquartile 4 vs 1 :1.32; 95% CI: 0.88-1.94), though the interaction test failed to achieve the statistical significance (Pinteraction  = .061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence.

Therapeutic targets and signaling mechanisms of vitamin C activity against sepsis: a bioinformatics study.

Sepsis is a life-threatening complication of pneumonia, including coronavirus disease-2019 (COVID-19)-induced pneumonia. Evidence of the benefits of vitamin C (VC) for the treatment of sepsis is accumulating. However, data revealing the targets and molecular mechanisms of VC action against sepsis are limited. In this report, a bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets, biological functions, and the signaling pathways of VC action against sepsis. As shown in network assays, 63 primary causal targets for the VC action against sepsis were identified from the data, and four optimal core targets for the VC action against sepsis were identified. These core targets were epidermal growth factor receptor (EGFR), mitogen-activated protein kinase-1 (MAPK1), proto-oncogene c (JUN), and signal transducer and activator of transcription-3 (STAT3). In addition, all biological processes (including a top 20) and signaling pathways (including a top 20) potentially involved in the VC action against sepsis were identified. The hub genes potentially involved in the VC action against sepsis and interlaced networks from the Kyoto Encyclopedia of Genes and Genomes Mapper assays were highlighted. Considering all the bioinformatic findings, we conclude that VC antisepsis effects are mechanistically and pharmacologically implicated with suppression of immune dysfunction-related and inflammation-associated functional processes and other signaling pathways. These primary predictive biotargets may potentially be used to treat sepsis in future clinical practice.

Preliminary analysis of immune-related markers in thymic carcinoid.

The immune-related microenvironment of thymic carcinoid has rarely been reported. We analyzed the expression of PD-L1 and VISTA, and the distribution of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the thymic carcinoid by immunohistochemical staining, and showed the correlation between these markers and clinical survival, indicating the potential therapeutic prospects.