Sesquilignans: Current research and potential prospective.

Lignans are widely distributed in nature, primarily found in the xylem and resins of plants, with the constituent units C6-C3, and their dimers are the most common in plants. In recent years, the trimeric sesquilignans have also received increasing attention from scholars. More than 200 derivatives have been isolated and identified from nearly 50 families, most of which are different types (monoepoxy lignans, bisepoxy lignans, benzofuran lignans) connected with simple phenylpropanoids through ether bonds, C-C bonds, and oxygen-containing rings to constitute sesquilignans. Some of them also possess pharmacological properties, including antioxidants, hepatoprotectives, antitumors, anti-inflammatory properties, and other properties. In addition, the chemical structure of sesquilignans is closely related to the pharmacological activity, and chemical modification of methoxylation enhances the pharmacological activity. In contrast, phenolic hydroxyl and hydroxyl glycosides reduce the pharmacological activity. Therefore, the present review aims to summarize the chemical diversity, bioactivities, and constitutive relationships to provide a theoretical basis for the more profound development and utilization of sesquilignans.

Schisandrol A, the Major Active Constitute in Schisandra chinensis: A Review of Its Preparation, Biological Activities, and Pharmacokinetics Analysis.

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage.

Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Development and external validation of a nomogram for predicting short-term prognosis in patients with acute pulmonary embolism.

BACKGROUND: Accurate assessment and timely intervention play a crucial role in ameliorating poor short-term prognosis of acute pulmonary embolism (APE) patients. The currently employed scoring models exhibit a degree of complexity, and some models may not comprehensively incorporate relevant indicators, thereby imposing limitations on the evaluative efficacy. Our study aimed to construct and externally validate a nomogram that predicts 30-day all-cause mortality risk in APE patients. METHODS: Clinical data from APE patients in Intensive Care-IV database was included as a training cohort. Additionally, we utilized our hospital's APE database as an external validation cohort. The nomogram was developed, and its predictive ability was evaluated using receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis. RESULTS: A collective of 1332 patients and 336 patients were respectively enrolled as the training cohort and the validation cohort in this study. Five variables including age, malignancy, oxygen saturation, blood glucose, and the use of vasopressor, were identified based on the results of the multivariate Cox regression model. The ROC value for the nomogram in the training cohort yielded 0.765, whereas in the validation group, it reached 0.907. Notably, these values surpassed the corresponding ROC values for the Pulmonary Embolism Severity Index, which were 0.713 in the training cohort and 0.754 in the validation cohort. CONCLUSIONS: The nomogram including five indicators had a good performance in predicting short-term prognosis in patients with APE, which was easier to apply and provided better recommendations for clinical decision-making.

Stripping Mechanism of Surfactant System Based on Residual Oil on the Surface of Sand-Conglomerate Rocks with Different Grain Size Mineral Compositions.

During the development of a sand-conglomerate reservoir, there is a huge variation in rock grain size and different åmineral compositions of different-sized sand grains. The mineral composition and microstructure of the rock both have an impact on the characteristics of the remaining oil in the reservoir. The stripping mechanism of a surfactant system on sand-conglomerate surface crude oil with varied grain size minerals was explored in this paper. Sand-conglomerate was classified and analyzed to determine their wettability and stripping oil effects. The optimization of the surfactant solution system and molecular dynamics simulation revealed the surfactant stripping mechanism on crude oil on distinct sandstone minerals. The results of the study showed that montmorillonite minerals are more readily adsorbed by surfactants. The crude oil within them is more likely to compete for adsorption and to be stripped off, and then extracted with the recovery fluid. The surfactant solution system can increase the hydrophilicity of the rock surface, make the crude oil on the rock surface shrink and gather, and enhance the transportation ability of the displacement fluid. And the emulsification seals part of the pore in the reservoir, increases the displacement pressure, and improves the overall wave volume. The results of this paper are of great significance for the efficient development of sand-conglomerate reservoirs.

Adenosinergic Modulation of Layer 6 Microcircuitry in the Medial Prefrontal Cortex Is Specific to Presynaptic Cell Type.

Adenosinergic modulation in the PFC is recognized for its involvement in various behavioral aspects including sleep homoeostasis, decision-making, spatial working memory and anxiety. While the principal cells of layer 6 (L6) exhibit a significant morphological diversity, the detailed cell-specific regulatory mechanisms of adenosine in L6 remain unexplored. Here, we quantitatively analyzed the morphological and electrophysiological parameters of L6 neurons in the rat medial prefrontal cortex (mPFC) using whole-cell recordings combined with morphological reconstructions. We were able to identify two different morphological categories of excitatory neurons in the mPFC of both juvenile and young adult rats with both sexes. These categories were characterized by a leading dendrite that was oriented either upright (toward the pial surface) or inverted (toward the white matter). These two excitatory neuron subtypes exhibited different electrophysiological and synaptic properties. Adenosine at a concentration of 30 µM indiscriminately suppressed connections with either an upright or an inverted presynaptic excitatory neuron. However, using lower concentrations of adenosine (10 µM) revealed that synapses originating from L6 upright neurons have a higher sensitivity to adenosine-induced inhibition of synaptic release. Adenosine receptor activation causes a reduction in the probability of presynaptic neurotransmitter release that could be abolished by specifically blocking A1 adenosine receptors (A1ARs) using 8-cyclopentyltheophylline (CPT). Our results demonstrate a differential expression level of A1ARs at presynaptic sites of two functionally and morphologically distinct subpopulations of L6 principal neurons, suggesting the intricate functional role of adenosine in neuronal signaling in the brain.

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer.

BACKGROUND: The controlling nutritional status (CONUT) score effectively reflects a patient's nutritional status, which is closely related to cancer prognosis. This study investigated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer, and compared the predictive ability of the CONUT score with other indexes. AIM: To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection. METHODS: This retrospective analysis included 217 patients with newly diagnosed colorectal. The CONUT score was calculated based on the serum albumin level, total lymphocyte count, and total cholesterol level. The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve. The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Using the cutoff value of the CONUT score, patients were stratified into CONUT low (n = 189) and CONUT high groups (n = 28). The CONUT high group had worse overall survival (OS) (P = 0.013) and relapse-free survival (RFS) (P = 0.015). The predictive performance of CONUT was superior to the modified Glasgow prognostic score, the prognostic nutritional index, and the neutrophil-to-lymphocyte ratio. Meanwhile, the predictive performances of CONUT + tumor node metastasis (TNM) stage for 3-year OS [area under the receiver operating characteristics curve (AUC) = 0.803] and 3-year RFS (AUC = 0.752) were no less than skeletal muscle mass index (SMI) + TNM stage. The CONUT score was negatively correlated with SMI (P < 0.01). CONCLUSION: As a nutritional indicator, the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer, and its predictive ability was superior to other indexes. The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

Radiofrequency ablation vs. hepatectomy for liver metastases from gastrointestinal stromal tumors.

For patients with gastrointestinal stromal tumors (GISTs) and liver metastases, there is still debate about whether radiofrequency ablation (RFA) or hepatectomy is preferable. The present study aimed to compare the clinical outcomes of RFA with hepatectomy in patients with GISTs and liver metastases. The present retrospective study consisted of a cohort of 43 patients who had been diagnosed with liver metastases from GISTs between January 2010 and December 2022. The study included 18 patients who received RFA combined with tyrosine kinase inhibitor (TKI) therapy (RFA group) and 25 patients who underwent hepatectomy combined with TKI therapy (hepatectomy group). For the patients with liver metastases, the progression-free survival (PFS) rates at 1, 3 and 5 years were 66.5, 38.2 and 33.9%, respectively. Notably, patients in the hepatectomy group exhibited significantly improved PFS times compared with those in the RFA group (median PFS, 42.7 months vs. 14.3 months; P=0.034). Furthermore, the time to imatinib treatment failure (TTF) was notably improved in the hepatectomy group compared with that in the RFA group, and this difference was statistically significant (median TTF, 71.1 vs. 38.0 months; P=0.041). However, the overall survival (OS) times of patients who received RFA and those who had hepatectomy did not differ significantly (median OS, not reached vs. not reached, P=0.120). There was no statistically significant distinction in PFS and TTF between patients who underwent hepatectomy combined with postoperative TKI and those who underwent hepatectomy combined with perioperative TKI (median PFS, 29.5 vs. not reached; P=0.520; median TTF, 66.4 months vs. 71.1 months; P=0.430). The univariate and multivariate analyses consistently identified the sole prognostic factor affecting PFS as hepatectomy combined with TKI therapy (hazard ratio, 0.379; 95% CI, 0.159-0.899; P=0.028). In conclusion, hepatectomy combined with TKI therapy improved prognosis for patients with liver metastases to a greater extent than RFA combined with TKI therapy. For this type of patient, hepatectomy may be a preferable option.

Bilateral chylothorax after left neck lymphadenectomy for thyroid cancer: A case report.

Introduction: Chylothorax is caused by lymphatic chyle fluid leaking back through the thoracic duct and accumulating in the pleural cavity. It is related to a thoracic duct injury or occlusion. It is rare to have bilateral chylothorax after cervical lymph node dissection for thyroid cancer diagnosis. Case report: A 28-year-old woman was admitted to our hospital with bilateral hypoechoic thyroid nodules and cervical lymph node abnormalities. She underwent thyroidectomy and lymphadenectomy but developed chylothorax 3 days after surgery. She was treated with bilateral thoracic drainage, electrolyte supplementation, and somatostatin, and was discharged 17 days post-treatment. Conclusion: Bilateral chylothorax is a rare complication of thyroid cancer surgery. Early diagnosis and treatment, especially the detection of dyspnea, are key. Also, unobstructed bilateral thoracic drainage, improved surgical skills, and reduced thoracic duct injuries can help reduce complications.

Surveillance and Outcomes of Pediatric Hematopoietic Stem Cell Transplantation Recipients During the Recent COVID-19 Outbreak in China.

Background: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT. Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected. Results: The median age of the cohort was 7±3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p<0.05, Fisher's Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72-99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19. Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic's impact on their care.

Ligand-modulated nickel-catalyzed regioselective silylalkylation of alkenes.

Organosilicon compounds have shown tremendous potential in drug discovery and their synthesis stimulates wide interest. Multicomponent cross-coupling of alkenes with silicon reagents is used to yield complex silicon-containing compounds from readily accessible feedstock chemicals but the reaction with simple alkenes remains challenging. Here, we report a regioselective silylalkylation of simple alkenes, which is enabled by using a stable Ni(II) salt and an inexpensive trans-1,2-diaminocyclohexane ligand as a catalyst. Remarkably, this reaction can tolerate a broad range of olefins bearing various functional groups, including alcohol, ester, amides and ethers, thus it allows for the efficient and selective assembly of a diverse range of bifunctional organosilicon building blocks from terminal alkenes, alkyl halides and the Suginome reagent. Moreover, an expedient synthetic route toward alpha-Lipoic acid has been developed by this methodology.

A Comprehensive Review on the Chemical Composition, Pharmacology and Clinical Applications of Ganoderma.

Ganoderma is the dried fruiting bodiy of Ganoderma lucidum (Leyss.ex Fr.) Karst. or Ganoderma sinense Zhao, Xu et Zhang, belonging to the family Polyporaceae, which grows mainly in tropical, subtropical, and temperate regions. As a traditional Chinese medicine, Ganoderma has been used in China for more than 2000 years because of its medicinal properties, such as relieving cough and asthma, providing nourishment, and strengthening. Currently, more than 470 natural compounds have been obtained from the fungus, mainly including terpenoids, steroids, alkaloids, phenols, and other types of compounds. Modern pharmacological studies have shown that Ganoderma has antitumor, anti-inflammatory, hypoglycemic, hypolipidemic, and immunomodulatory effects. It is mainly used in clinical practice for the treatment of Diabetic Nephropathy and malignant tumors, with few side effects and high safety. This paper reviews the progress of research on its chemical composition, pharmacological effects, and clinical applications, with the goal of providing a basis for the better development and utilization of Ganoderma.

Significant influence of water molecules on the SO3 + HCl reaction in the gas phase and at the air-water interface.

The products resulting from the reactions between atmospheric acids and SO3 have a catalytic effect on the formation of new particles in aerosols. However, the SO3 + HCl reaction in the gas-phase and at the air-water interface has not been considered. Herein, this reaction was explored exhaustively by using high-level quantum chemical calculations and Born Oppenheimer molecular dynamics (BOMD) simulations. The quantum calculations show that the gas-phase reaction of SO3 + HCl is highly unlikely to occur under atmospheric conditions with a high energy barrier of 22.6 kcal mol-1. H2O and (H2O)2 play obvious catalytic roles in reducing the energy barrier of the SO3 + HCl reaction by over 18.2 kcal mol-1. The atmospheric lifetimes of SO3 show that the (H2O)2-assisted reaction dominates over the H2O-assisted reaction within the altitude range of 0-5 km, whereas the H2O-assisted reaction is more favorable within an altitude range of 10-50 km. BOMD simulations show that H2O-induced formation of the ClSO3-⋯H3O+ ion pair and HCl-assisted formation of the HSO4-⋯H3O+ ion pair were identified at the air-water interface. These routes followed a stepwise reaction mechanism and proceeded at a picosecond time scale. Interestingly, the formed ClSO3H in the gas phase has a tendency to aggregate with sulfuric acids, ammonias, and water molecules to form stable clusters within 40 ns simulation time, while the interfacial ClSO3- and H3O+ can attract H2SO4, NH3, and HNO3 for particle formation from the gas phase to the water surface. Thus, this work will not only help in understanding the SO3 + HCl reaction driven by water molecules in the gas-phase and at the air-water interface, but it will also provide some potential routes of aerosol formation from the reaction between SO3 and inorganic acids.

TRIM6: An Upregulated Biomarker with Prognostic Significance and Immune Correlations in Gliomas.

This study investigates the expression and prognostic value of TRIM6 in gliomas, the most prevalent primary brain and spinal cord tumors. Our results show that TRIM6 is predominantly overexpressed in glioma tissues and is associated with reduced overall survival, disease-specific survival, and progression-free interval. Furthermore, TRIM6 expression is correlated with WHO grade and primary treatment outcomes. Functional analysis indicates that interactions between cytokines and their receptors play a critical role in the prognosis of glioma patients. A protein-protein interaction network reveals 10 hub genes closely linked to cytokine-cytokine receptor interaction. In vitro experiments demonstrate that silencing TRIM6 impairs the proliferation, invasion, and migration of glioma cells, while overexpressing TRIM6 enhances these abilities. Additionally, TRIM6 expression is positively associated with the abundance of innate immune cells and negatively associated with the abundance of adaptive immune cells. In summary, TRIM6 is significantly upregulated in gliomas and linked to poor prognosis, making it a potential diagnostic and prognostic biomarker. TRIM6 plays a crucial role in promoting cell viability, clonogenic potential, migration, and invasion in glioma cells. It may regulate glioma progression by modulating cytokine-cytokine receptor interaction, leading to an inflammatory response and an imbalance in immunomodulation, thereby representing a potential therapeutic target.

Physical activity and cancer risk: a dose-response analysis for the Global Burden of Disease Study 2019.

OBJECTIVE: Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the dose-response relationships between total physical activity and the risk of breast, colon, lung, gastric, and liver cancers. METHODS: A systematic review and dose-response analysis were conducted using PubMed and Embase from January 1, 1980 to March 20, 2023. Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included. The search was confined to publications in the English language with a specific focus on human studies. Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys (NHANES) and the Global Burden of Disease 2019 database. RESULTS: A total of 98 studies, involving a combined population of 16,418,361 individuals, were included in the analysis. Among the included studies, 57 focused on breast cancer, 17 on lung cancer, 23 on colon cancer, 5 on gastric cancer, and 7 on liver cancer. Overall, elevated levels of physical activity exhibited an inverse correlation with the risk of cancer. The dose-response curve for lung cancer exhibited a non-linear pattern, with the greatest benefit risk reduction observed at 13,200 MET-minutes/week of physical activity, resulting in a 14.7% reduction in risk (relative risk 0.853, uncertainty interval 0.798 to 0.912) compared to the inactive population. In contrast, the dose-response curves for colon, gastric, breast, and liver cancers showed linear associations, indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks. However, the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers. Compared to individuals with insufficient activity (total activity level < 600 MET-minutes/week), individuals with high levels of activity (≥ 8,000 MET-minutes/week) experienced a 10.3% (0.897, 0.860 to 0.934) risk reduction for breast cancer; 5.9% (0.941, 0.884 to 1.001) for lung cancer; 7.1% (0.929, 0.909 to 0.949) for colon cancer; 5.1% (0.949, 0.908 to 0.992) for gastric cancer; 17.1% (0.829, 0.760 to 0.903) for liver cancer. CONCLUSIONS: This study demonstrated a significant inverse relationship between total physical activity and the risk of breast, gastric, liver, colon, and lung cancers.

Simultaneous Determination of 54 Pesticides in Proso Millet Using QuEChERS with Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

To assess the potential risks posed to the environment and human health, analyzing pesticide residues in proso millet is important. This paper aimed to develop a modified QuEChERS method with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the analysis of 54 pesticide residues in proso millet. Parameters including the mobile phase of the instrument, the acidity of the extraction solvent, and the type of absorbents were optimized to provide satisfactory performance. The method was validated concerning linearity, limit of quantification (LOQ), matrix effect, accuracy, and precision. In detail, the linearity of the matrix-matched calibration curve was acceptable with correlation coefficients (R2) higher than 0.99. The mean recovery was in the range of 86% to 114% with relative standard deviations (RSDs) ≤ 20% (n = 5). The LOQ was determined to be 0.25-10 µg/kg. The developed method was feasible for the determination of multiple pesticide residues in proso millet.

Development of a thyroid cancer prognostic model based on the mitophagy-associated differentially expressed genes.

BACKGROUND: The prevalence of thyroid cancer (ThyC), a frequent malignant tumor of the endocrine system, has been rapidly increasing over time. The mitophagy pathway is reported to play a critical role in ThyC onset and progression in many studies. This research aims to create a mitophagy-related survival prediction model for ThyC patients. METHODS: Genes connected to mitophagy were found in the GeneCards database. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided information on the expression patterns of ThyC-related genes. To identify differentially expressed genes (DEGs), R software was employed. The prognostic significance of each DEG was assessed using the prognostic K-M curve. The prognostic model was built using LASSO, ROC, univariate, and multivariate Cox regression analyses. Finally, a nomogram model was developed to predict the survival outcome of ThyC patients in the clinical setting. RESULTS: Through differential analysis, functional enrichment analysis, and protein-protein interaction (PPI) network analysis, we screened 10 key genes related to mitophagy in ThyC. The risk model was eventually developed using LASSO and Cox regression analyses based on the six DEGs related to mitophagy. An altered expression level of a mitophagy-related prognostic gene, GGCT, was found to be the most significant one, according to the KM survival curve analysis. An immunohistochemical (IHC) investigation revealed that ThyC tissues expressed higher levels of GGCT than normal thyroid tissues. The ROC curve verified the satisfactory performance of the model in survival prediction. Multivariate Cox regression analysis showed that the pathological grade, residual tumor volume, and initial tumor lesion type were significantly linked to the prognosis. Finally, we created a nomogram to predict the overall survival rate of ThyC patients at 3-, 5-, and 7- year time points. CONCLUSION: The nomogram risk prediction model was developed to precisely predict the survival rate of ThyC patients. The model was validated based on the most significant DEG GGCT gene expression in ThyC. This model may serve as a guide for the creation of precise treatment plans for ThyC patients.

Global patterns of cancer transitions: A modelling study.

Cancer is a major contributor to global disease burden. Many countries experienced or are experiencing the transition that non-infection-related cancers replace infection-related cancers. We aimed to characterise burden changes for major types of cancers and identify global transition patterns. We focused on 10 most common cancers worldwide and extracted age-standardised incidence and mortality in 204 countries and territories from 1990 to 2019 through the Global Burden of Disease Study. Two-stage modelling design was used. First, we applied growth mixture models (GMMs) to identify distinct trajectories for incidence and mortality of each cancer type. Next, we performed latent class analysis to detect cancer transition patterns based on the categorisation results from GMMs. Kruskal-Wallis H tests were conducted to evaluate associations between transition patterns and socioeconomic indicators. Three distinct patterns were identified as unfavourable, intermediate and favourable stages. Trajectories of lung and breast cancers had the strongest association with transition patterns among men and women. The unfavourable stage was characterised by rapid increases in lung, breast and colorectal cancers alongside stable or decreasing burden of gastric, cervical, oesophageal and liver cancers. In contrast, the favourable stage exhibited rapid declines in most cancers. The unfavourable stage was associated with lower sociodemographic index, health expenditure, gross domestic product per capita and higher maternal mortality ratio (P < .001 for all associations). Our findings suggest that unfavourable, intermediate and favourable transition patterns exist. Countries and territories in the unfavourable stage tend to be socioeconomically disadvantaged, and tailored intervention strategies are needed in these resource-limited settings.

Determination of the influence of water on the SO3 + CH3OH reaction in the gas phase and at the air-water interface.

Liu et al. (Proc. Natl. Acad. Sci. U. S. A, 2019, 116, 24966-24971) showed that at an altitude of 0 km, the reaction of SO3 with CH3OH to form CH3OSO3H reduces the amount of H2SO4 produced by the hydrolysis of SO3 in regions polluted with CH3OH. However, the influence of the water molecule has not been fully considered yet, which will limit the accuracy of calculating the loss of SO3 in regions polluted with CH3OH. Here, the influence of water molecules on the SO3 + CH3OH reaction in the gas phase and at the air-water interface was comprehensively explored by using high-level quantum chemical calculations and Born-Oppenheimer molecular dynamics (BOMD) simulations. Quantum chemical calculations show that both pathways for the formation of CH3OSO3H and H2SO4 with water molecules have greatly lowered energy barriers compared to the naked SO3 + CH3OH reaction. The effective rate coefficients reveal that H2O-catalyzed CH3OSO3H formation (a favorable route for CH3OSO3H formation) can be competitive with H2O-assisted H2SO4 formation (a favorable process for H2SO4 formation) at high altitudes up to 15 km. BOMD simulations found that H2O-induced formation of the CH3OSO3-⋯H3O+ ion pair and CH3OH-assisted formation of HSO4- and H3O+ ions were observed at the droplet surface. These interfacial routes followed a loop-structure or chain reaction mechanism and proceeded on a picosecond time scale. These results will contribute to better understanding of SO3 losses in the polluted areas of CH3OH.