Conversion therapy with immunotherapy plus chemotherapy achieves a pathological complete response in stage IIIC NSCLC

As stage IIIC non-small cell lung cancer (NSCLC) is not recommended for surgical resection, the survival and prognosis for stage IIIC NSCLC remain poor. More powerful and individualized therapies are urgently needed to improve the prognosis of stage IIIC NSCLC. Recently, immunotherapeutics have been increasingly considered in the neoadjuvant therapy of NSCLC. This study presents a patient with stage IIIC NSCLC achieving a pathological complete response (pCR) following conversion therapy with immunotherapy plus chemotherapy. This case also presents a histologic transformation from squamous cell carcinoma to adenocarcinoma after prolonged progression-free survival (PFS) following surgery. Collectively, this case suggests that conversion immunotherapy with chemotherapy and subsequent surgery can be considered and benefits a subset of unresectable stage IIIC NSCLC

Global trends and hotspots of gastrointestinal microbiome and toxicity based on bibliometrics

BackgroundToxicity concerns persist in the fields of public health, environmental science, and pharmacology. The intricate and vital role of the gastrointestinal microbiome in influencing toxicity and overall human health has gained increasing recognition in recent years. This study presents a comprehensive bibliometric analysis to evaluate the global scientific output, emerging trends, and research focal points in the area of gastrointestinal microbiome and toxicity.MethodsThe Web of Science Core Collection database was retrieved for publications on the gastrointestinal microbiome and toxicity from 1980 to 2022. Our analysis included scholarly research papers written in English and excluded duplicate publications. We used Biblioshiny and R to summarize the count and citation metrics of included articles, and visualized research trends and keywords. CiteSpace was used to identify reference literature, keywords, and citation bursts. VOSviewer was used to visualize the network of related countries, institutions, authors, co-cited authors, and keywords.ResultsA total of 2,140 articles were included, allowing us to identify significant countries, institutions, authors, and research focal points. Our results indicate a growing trend in the field, with China and the United States leading the research. The most productive journal in this area is Science of the Total Environment. Key findings revealed that research hotspots have shifted from drugs to environmental pollutants, emphasizing microplastics. Important mechanisms studied include oxidative stress, metabolism, inflammation, and apoptosis, with target organs being the gastrointestinal tract, liver, and brain. Furthermore, we highlight the rising significance of the gut-brain axis and the usage of zebrafish as a model organism.ConclusionDespite certain limitations, such as focusing solely on English-language publications and excluding unpublished literature, our findings provide valuable insights into the current state of research on toxicity and the gastrointestinal microbiome. In the future, modifications to the gastrointestinal microbiome could offer new directions for treating and mitigating toxicity. These discoveries provide a comprehensive perspective on the broader scope of this research field

The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo

AbstractSupranutritional selenite has anti-cancer therapeutic effects in vivo; however, the detailed mechanisms underlying these effects are not clearly understood. Further studies would broaden our understanding of the anti-cancer effects of this compound and provide a theoretical basis for its clinical application. In this study, we primarily found that selenite exposure inhibited phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC) cells. Moreover, the selenite-induced inhibitory effect on PKD1 activation was involved in suppression of the CREB signalling pathway. Additionally, we discovered that selenite treatment can upregulate p38 MAPK phosphorylation, which results in inhibition of the PKD1/CREB/Bcl-2 survival pathway and triggers apoptosis. Finally, we established a colorectal cancer xenograft model and found that selenite treatment markedly inhibits tumour growth through the MAPK/PKD1/CREB/Bcl-2 pathway in vivo. Our results demonstrated that a supranutritional dose of selenite induced CRC cell apoptosis through inhibition of the PKD1/CREB/Bcl-2 axis both in vitro and in vivo

Prognostic role of pre-treatment serum ALB in Patients with oropharyngeal cancer: A retrospective cohort study

BackgroundThe morbidity of oropharyngeal cancer (OPC) is continuing to rise in numerous developed countries. An accurate prognostic assessment is needed to evaluate the malignant degree or risk classification to optimize treatment. Albumin (ALB) as an independent prognostic indicator of cancer survival has been established in previous studies. This study investigated the prognostic value of pre-treatment serum ALB in OPC patients.MethodsThe clinicopathological data of 246 patients diagnosed with OPC from 2010 to 2019 were analyzed retrospectively. Analyze the relationship between ALB and clinicopathological characteristics of patients. The optimal cut-off values for ALB were determined via Cutoff Finder (Method for cutoff determination: Survival: significance (log-rank test)). To determine the independent prognostic factors, the Cox proportional hazards model was used to perform univariate and multivariate analyses of the serum ALB levels related to overall survival (OS) and disease-free survival (DFS).ResultsThe optimal cut-off point for ALB was 39.15 g/L determined via Cutoff Finder. Serum ALB levels were significantly associated with age (P=0.047), Presence of comorbidity (P=0.009), Charlson score index (P=0.007), Hemoglobin (P<0.001), Neutrophil to Lymphocyte Ratio (P=0.002), Albumin-To-Alkaline Phosphatase Ratio (P<0.001), Alkaline phosphatase (P=0.005), T stage (P=0.016), and HPV status (P=0.002). In the univariate and multivariate analyses, ALB was found to be an independent prognostic indicator for DFS (HR =0.39, 95% CI:0.23-0.66, P=0.000) and OS (HR =0.46, 95% CI: 0.25-0.83, P=0.01) in OPC patients.ConclusionsPre-treatment serum ALB could serve as a valuable prognostic biomarker for the prognostic stratification of OPC patients

Study on Flavor Characteristics and Nutritional Evaluation of Free Amino Acids in Walnut Pellicle

In order to explore the composition, taste characteristics and nutritional value of free amino acids in pellicle of different varieties of walnut, the content of free amino acid in the pellicle of 6 walnut varieties was detected, and the taste activity value (TAV) analysis, principal component analysis and comprehensive evaluation were carried out. The results showed that a total of 17 free amino acids could be detected in the pellicle of walnut, with a total content of 2673.86~3490.12 mg/kg. Nine medicinal amino acids accounted for 57.67%~68.23% of the total amino acids, and Leu was the first limiting amino acid in the pellicle. Glu, Asp, Thr, Cys and Arg were the main amino acids of free amino acids in the pellicle, with Glu having the highest content. The TAV value of Glu among the six cultivars was 2.34~3.81, which contributed the most to the umami of the pellicle. The TAV values of Arg in 'Jing 861', 'Bokexiang' and 'Jinboxiang 8' were 1.03~1.26, which contributed to the bitterness of the pellicle. Among the flavor amino acids, the content of umami amino acids was the highest, while aromatic amino acids had the lowest contentm. The ratio of bitter to sweet amino acid content in the 'Nonghe 1', 'Jing 861', 'Bokexiang' and 'Jinboxiang 8' was greater than 1. While the ratio of bitter to sweet amino acid content in the 'Fenhe 2' and ' Fenhe 4' was less than 1. The comprehensive quality of amino acids was also relatively higher. The amino acids in pellicle had high nutritional value and medicinal value, and the taste was bitter, as a food auxiliary material to supplement Thr, Ile and sulfur-containing amino acids, it could increase the overall taste richness of food

Evaluation of the Antidepressant Effect of the Functional Beverage Containing Active Peptides, Menthol and Eleutheroside, and Investigation of Its Mechanism of Action in Mice

Pozadina istraživanja. Depresija je postala globalna prijetnja ljudskom zdravlju. Znanstvenici provode različita ispitivanja uključujući i analizu prehrane kako bi riješili taj problem. Mnogi bioaktivni spojevi iz hrane imaju antidepresivni učinak. No, mali se broj istraživanja bavi razvojem industrijskih prehrambenih proizvoda s antidepresivnim učinkom. Svrha je ovoga rada bila ocijeniti antidepresivni učinak i mehanizme djelovanja funkcionalnog napitka pripremljenog od nekoliko sastojaka s mogućim antidepresivnim svojstvima. Eksperimentalni pristup. Napitak se sastoji od ulja paprene metvice, aktivnih peptida iz kazeina kravljeg mlijeka i ekstrakta sibirskog ginsenga (Acanthopanax senticosus), čiji je aktivni sastojak eleuterozid. Ispitan je dodatak različitih udjela ekstrakta sibirskog ginsenga da bi se utvrdila optimalna koncentracija eleuterozida u ovom funkcionalnom napitku, radi postizanja najboljeg antidepresivnog učinka. Provedena su opsežna ispitivanja ponašanja, uključujući preliminarne testove akutnog stresa te kroničnog nepredvidljivog blagog stresa. Rezultati i zaključci. Rezultati pokazuju da napitak s 15 mg/kg eleuterozida može bitno smanjiti vrijeme mirovanja miša u testovima vješanja za rep i prisilnog plivanja, pozitivno utjecati na preferenciju saharoze i promjene ponašanja u testu otvorenog polja, povećati udjel dopamina, norepinefrina, serotonina i aktivnost superoksid dismutaze, te smanjiti udjel malondialdehida u mozgu miševa. To potvrđuje da su poboljšana neurotransmisija monoamina i antioksidacijski status mogući mehanizmi antidepresivnog učinka. Novina i znanstveni doprinos. U ovom je radu predložen sastav funkcionalnog napitka s antidepresivnim svojstvima za učinkovitu prevenciju i liječenje depresije.Research background. Depression has become a global threat to human health. In order to solve it, researchers have conducted multi-faceted studies including diet. Many food-derived bioactive substances have shown antidepressant effects. However, there are few studies on the design of industrialized food with antidepressant effect. This study aims to evaluate the antidepressant effect of afunctional beverage made from several ingredients with potential antidepressant function and investigate its antidepressant mechanisms. Experimental approach. The beverage consists of peppermint oil, active peptides derived from bovine milk casein and Acanthopanax senticosus extract (ASE) whose active ingredient is eleutheroside. Different amounts of ASE were evaluated to determine the optimal concentration of eleutheroside in this functional beverage to deliver the best antidepressant effect through extensive behavioral testing, including preliminary acute stress experiments and further chronic unpredictable mild stress test. Results and conclusions. The results demonstrated that the beverage with 15 mg/kg of eleutheroside could significantly reduce the mice’s immobility time of tail suspension test and forced swimming test, recover mice’s sucrose preference and behavior changes in the open field test, improve the contents of dopamine, norepinephrine, 5-hydroxytryptamine and the activity of superoxide dismutase and reduce the content of malondialdehyde in mice’s brains, which indicated that the improvement of monoamine neurotransmitter systems and antioxidation was one potential mechanism of antidepressant action. Novelty and scientific contribution. This study provides a design of antidepressant functional beverage and an efficient way for the prevention and treatment of depression

Integrating machine learning algorithms and multiple immunohistochemistry validation to unveil novel diagnostic markers based on costimulatory molecules for predicting immune microenvironment status in triple-negative breast cancer

IntroductionCostimulatory molecules are putative novel targets or potential additions to current available immunotherapy, but their expression patterns and clinical value in triple-negative breast cancer (TNBC) are to be clarified. MethodsThe gene expression profiles datasets of TNBC patients were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Diagnostic biomarkers for stratifying individualized tumor immune microenvironment (TIME) were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Additionally, we explored their associations with response to immunotherapy via the multiplex immunohistochemistry (mIHC). ResultsA total of 60 costimulatory molecule genes (CMGs) were obtained, and we determined two different TIME subclasses (“hot” and “cold”) through the K-means clustering method. The “hot” tumors presented a higher infiltration of activated immune cells, i.e., CD4 memory-activated T cells, resting NK cells, M1 macrophages, and CD8 T cells, thereby enriched in the B cell and T cell receptor signaling pathways. LASSO and SVM-RFE algorithms identified three CMGs (CD86, TNFRSF17 and TNFRSF1B) as diagnostic biomarkers. Following, a novel diagnostic nomogram was constructed for predicting individualized TIME status and was validated with good predictive accuracy in TCGA, GSE76250 and GSE58812 databases. Further mIHC conformed that TNBC patients with high CD86, TNFRSF17 and TNFRSF1B levels tended to respond to immunotherapy. ConclusionThis study supplemented evidence about the value of CMGs in TNBC. In addition, CD86, TNFRSF17 and TNFRSF1B were found as potential biomarkers, significantly promoting TNBC patient selection for immunotherapeutic guidance

A global monthly field of seawater pH over 3 decades: a machine learning approach

The continuous uptake of anthropogenic CO2 by the ocean leads to ocean acidification, which is an ongoing threat to the marine ecosystem. The ocean acidification rate was globally documented in the surface ocean but limited below the surface. Here, we present a monthly four-dimensional 1°×1° gridded product of global seawater pH, derived from a machine learning algorithm trained on pH observations at total scale and in-situ temperature from the Global Ocean Data Analysis Project (GLODAP). The constructed pH product covers the years 1992–2020 and depths from the surface to 2 km on 41 levels. Three types of machine learning algorithms were used in the pH product construction, including self-organizing map neural networks for region dividing, a stepwise algorithm for predictor selection, and feed-forward neural networks (FFNN) for non-linear relationship regression. The performance of the machine learning algorithm was validated using real observations by a cross validation method, where four repeating iterations were carried out with 25 % varied observations for each evaluation and 75 % for training. The constructed pH product is evaluated through comparisons to time series observations and the GLODAP pH climatology. The overall root mean square error between the FFNN constructed pH and the GLODAP measurements is 0.028, ranging from 0.044 in the surface to 0.013 at 2000 m. The pH product is distributed through the data repository of the Marine Science Data Center of the Chinese Academy of Sciences at http://dx.doi.org/10.12157/IOCAS.20230720.001 (Zhong et al., 2023)

Modeling and Experimental Testing of an Unmanned Surface Vehicle with Rudderless Double Thrusters.

Motion control of unmanned surface vehicles (USVs) is a crucial issue in sailing performance and navigation costs. The actuators of USVs currently available are mostly a combination of thrusters and rudders. The modeling for USVs with rudderless double thrusters is rarely studied. In this paper, the three degrees of freedom (DOFs) dynamic model and propeller thrust model of this kind of USV were derived and combined. The unknown parameters of the propeller thrust model were reduced from six to two. In the three-DOF model, the propulsion of the USV was completely provided by the resultant force generated by double thrusters and the rotational moment was related to the differential thrust. It combined the propeller thrust model to represent the thrust in more detail. We performed a series of tests for a 1.5 m long, 50 kg USV, in order to obtain the model parameters through system identification. Then, the accuracy of the modeling and identification results was verified by experimental testing. Finally, based on the established model and the proportional derivative+line of sight (PD+LOS) control algorithm, the path-following control of the USV was achieved through simulations and experiments. All these demonstrated the validity and practical value of the established model

Pattern and Predictive Factors of Metastasis in Lymph Nodes Posterior to the Right Recurrent Laryngeal Nerve in Papillary Thyroid Carcinoma

ObjectiveThe right cervical central lymph nodes include lymph nodes anterior to the right recurrent laryngeal nerve (LN-arRLN) and lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN), and are separated by the right recurrent laryngeal nerve (RLN). LN-prRLN is a common site of nodal recurrence after the resection of papillary thyroid carcinoma (PTC). However, the complexity in anatomical structure brings difficulties in determining the surgical scope, so it is necessary to assess the pattern and predictive factors of right cervical central lymph nodes, especially LN-prRLN metastasis in papillary thyroid carcinoma.MethodsA total of 562 diagnosed PTC patients who underwent right or total thyroidectomy were enrolled in this retrospective study. The clinicopathological features were collected, univariate and multivariate analyses were performed to determine predictive factors of the right central lymph node metastasis.ResultsIn this study, the metastatic rates of the right CLN, the LN-arRLN and the LN-prRLN were 59.6% (335/562), 51.8% (291/562) and 30.4% (171/562), respectively. And 22.6% (127/562) of patients had both LN-arRLN and LN-prRLN metastasis. Among patients without LN-arRLN metastasis, the rate of LN-prRLN metastasis was 16.2% (44/271), accounting for 25.7% of the LN-prRLN metastasis group. Factors associated with an increased risk of LN-arRLN metastasis include male, age below 55 years, tumor size > 1cm, extrathyroidal extension (ETE), clinical lymph nodes metastasis(cN1), lateral lymph node metastasis, and left CLN metastasis. In addition, ETE, lateral lymph node metastasis, and LN-arRLN metastasis were independent factors of LN-prRLN metastasis. The predictive factors of LN-prRLN in cN0 PTC were further explored, revealing that tumor size ≥1.5cm, ETE, and LN-arRLN metastasis were independent predictors of LN-prRLN metastasis in cN0 PTC.ConclusionThe LN-prRLN should not be ignored in surgery because of its high rate of metastasis. Our findings indicate that thorough dissection of central lymph nodes, especially LN-prRLN is crucial in clinical work