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Abstract Background Sulfur microbial diet (SMD) is a dietary pattern closely related to the intestinal load of sulfur-metabolizing microbes in humans. Diet and microbes may play an important role in the carcinogenesis of esophagus. However, epidemiological studies on SMD and esophageal cancer (EC) risk are scarce. Here, we evaluated this association based on a large American cohort. Methods In the cohort of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a SMD score was calculated to evaluate participants’ compliance of SMD pattern, with higher scores presenting greater adherence. Cox hazards regression model was used to explore the association between the SMD score and the incidence of EC, esophageal squamous cell carcinoma (ESCC), and esophageal adenocarcinoma (EA). Subgroup analyses were conducted to figure out potential modifiers interacting with SMD on EC. Sensitivity analyses were used to testify the robustness of our main result. Results Among 101,752 participants, 154 EC cases, consisted of 41 ESCC cases and 97 EA cases, were identified with mean follow-up of 8.9 years. In the fully adjusted model, the highest versus the lowest quartiles of the SMD score were found to be associated with an increased risk of EC and ESCC (EC: HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HRQ4 vs. Q1: 1.41; P = 0.144 for trend). The main result remained through a series of sensitivity analyses. Subgroup analyses showed a stronger association between SMD and EC in participants with no regular consumption of aspirin (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 vs. Q1: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction). Conclusion Adherence to the SMD pattern may be associated with increased risks of EC and ESCC, particularly for EC in individuals who do not regularly consume aspirin.

Abstract Purpose Low-fat dietary (LFD) pattern refers to a dietary structure with reduced fat intake. The aim was to investigate the association between LFD pattern and risk of head and neck cancer (HNC). Methods Data were derived from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. LFD score was used to assess adherence to an LFD pattern, with higher scores indicating greater adherence. Cox regression was used to evaluate the association between LFD score and risk of HNC and its subtypes. To visualize the trend in risk of HNC and its subtypes with changing LFD score, restricted cubic spline plots were utilized. A series of subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results. Results Among 98,459 participants of PLCO trial, 268 cases with HNC were identified during an average of 8.8 years of follow-up. In the fully adjusted model, participants in the highest compared with the lowest quartiles of LFD score had a lower risk of HNC (HR Q4 vs. Q1: 0.60; 95% CI: 0.40–0.90; P for trend = 0.026) and larynx cancer (HRQ4 vs. Q1: 0.46; 95% CI: 0.22–0.96; P for trend = 0.039). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of HNC and its subtypes (all P for nonlinearity > 0.05). The primary association remained robust in the sensitivity analysis. Conclusion Our findings suggest that adherence to an LFD pattern may lower the risk of HNC in the US population.

ObjectivesTo examine the association between the age at onset of diabetes and the risk of all-cause mortality in a population of individuals diagnosed with type 2 diabetes mellitus (T2DM) and to identify risk factors associated with all-cause mortality in young-onset T2DM (YOD) patients in China.MethodsThis study utilized a cohort of 9759 patients who were diagnosed with T2DM and who were registered and enrolled in the National Basic Public Health Service Management Program in Qinghe District (now Qingjiangpu District) and Huai’an District, Huai’an City, Jiangsu Province, China. The patients were observed from November 2013 to July 2014, and all-cause mortality data were obtained by comprehensive matching with the Huai’an City Resident Mortality Database as of December 31, 2019. A Cox proportional hazards model was used to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) for all-cause mortality risk during the follow-up period among patients with varying disease onset ages. Additionally, subgroup analyses were conducted based on sex, age, lifestyle factors, and baseline clinical parameters.ResultsA total of 7572 patients with T2DM, including 2874 men and 4698 women aged 57.9 ± 8.0 years, were ultimately included in the study. 1) At baseline, a greater proportion of YOD patients were engaged in high-intensity activities, had a longer sleep duration, had a longer duration of T2DM, had a family history of T2DM, had microvascular complications (kidney disease, retinopathy, neuropathy, diabetic foot, etc.), and received glucose-lowering treatment. Moreover, patients in the YOD group also had significantly greater baseline HbA1c, FBG, and estimated glomerular filtration rate (eGFR) than did those in the onset at 41-60 years (MD) group and the onset at 61-75 years (SD) group. 2) During the six-year follow-up period, a total of 1057 deaths were documented. After adjusting for confounding factors and utilizing SD as the reference group, the HRs for deaths occurring in the YOD and MD groups were 1.383 (95% CI: 0.717-2.667) and 1.006 (95% CI: 0.763-1.326), respectively. Moreover, the risk of death in the YOD group remained highest in the sensitivity analysis that excluded patients with coronary heart disease at baseline, stroke patients, and patients who died within the first three years of follow-up. 3) Sleep duration was identified as an independent risk factor for mortality in the YOD group, with a notable increase in the risk of all-cause mortality when sleep duration exceeded 9 hours per day.ConclusionThe risk of all-cause mortality in YOD patients was 1.38 times greater than that in MD and SD patients, and the longer the sleep duration was, the greater the risk of death, especially when sleep duration exceeded 9 hours per day.

BackgroundLifelines Diet Score (LLDS) was developed based on the 2015 Dutch Dietary Guidelines and current international scientific evidence. As a dietary quality assessment tool, the LLDS aims to evaluate the association between the Lifeline diet and the risk of chronic diseases. However, the evidence linking LLDS to lung cancer risk is currently limited.ObjectiveOur objective was to explore whether adherence to the LLDS is associated with reduced incidence and mortality of lung cancer, including its major histological subtypes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).MethodsData for this research were sourced from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Trial. The LLDS for each participant was calculated based on responses to the dietary history questionnaire (DHQ), and subsequently analyzed after being categorized into quintiles. The Cox proportional hazards regression model was utilized to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) for both the incidence and mortality of lung cancer, SCLC and NSCLC. Additionally, stratified analyses were conducted to ascertain possible effect modifiers, and several sensitivity analyses were performed to evaluate the robustness of the findings.ResultsDuring the mean follow-up periods of 8.8 years for incidence and 15.1 years for mortality, we identified 1,642 new cases and 1,172 related deaths from lung cancer. Participants in the highest quartiles of LLDS compared to those in the lowest exhibited a reduced incidence (HRQ4:Q1 = 0.80, 95% CI = 0.68–0.94, P for trend = 0.003) and mortality (HRQ4:Q1 = 0.81, 95%CI = 0.67–0.98, P for trend = 0.009) of lung cancer. Furthermore, this negative association remained for SCLC incidence (HRQ4:Q1 = 0.55, 95% CI = 0.35–0.87, P for trend = 0.002) and mortality (HRQ4:Q1 = 0.42, 95% CI = 0.25–0.70, P for trend 0.05). The sensitivity analyses substantiated the robustness of the results.ConclusionIn conclusion, our research indicates that among 98,459 U.S. adults aged 55 and older, adherence to the LLDS is linked to a diminished incidence and mortality of lung cancer.

Abstract Background Carbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear. Methods We followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers. Results During follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67–0.96, P trend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44–0.86, P trend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality. Conclusions Our findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.

Objectives: There is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. Design: A prospective cohort study with a mean follow-up time of 8.8 years. Setting and participants: This study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. Methods: Dietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. Results: During a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66−0.89), NSCLC (HR, 0.79; 95% CI, 0.67−0.93), and SCLC (HR, 0.59; 95% CI, 0.38−0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60−0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10–1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20–3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. Conclusions: Our findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.

Abstract Reactive oxygen species (ROS) act as a group of signaling molecules in rice functioning in regulation of development and stress responses. Respiratory burst oxidase homologues (Rbohs) are key enzymes in generation of ROS. However, the role of the nine Rboh family members was not fully understood in rice multiple disease resistance and yield traits. In this study, we constructed mutants of each Rboh genes and detected their requirement in rice multiple disease resistance and yield traits. Our results revealed that mutations of five Rboh genes (RbohA, RbohB, RbohE, RbohH, and RbohI) lead to compromised rice blast disease resistance in a disease nursery and lab conditions; mutations of five Rbohs (RbohA, RbohB, RbohC, RbohE, and RbohH) result in suppressed rice sheath blight resistance in a disease nursery and lab conditions; mutations of six Rbohs (RbohA, RbohB, RbohC, RbohE, RbohH and RbohI) lead to decreased rice leaf blight resistance in a paddy yard and ROS production induced by PAMPs and pathogen. Moreover, all Rboh genes participate in the regulation of rice yield traits, for all rboh mutants display one or more compromised yield traits, such as panicle number, grain number per panicle, seed setting rate, and grain weight, resulting in reduced yield per plant except rbohb and rbohf. Our results identified the Rboh family members involved in the regulation of rice resistance against multiple pathogens that caused the most serious diseases worldwide and provide theoretical supporting for breeding application of these Rbohs to coordinate rice disease resistance and yield traits.

Abstract Background There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population. Methods A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses. Results Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; P trend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose–response association between renal cancer risk with DRRD score was observed (P nonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (P interaction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all P trend

Abstract Background Despite the possible contribution of dairy products to the development or prevention of cancers, there is a lack of epidemiological evidence linking low‐fat dairy consumption to the risk of developing lung cancer. This research was conducted to fill this knowledge gap. Methods The data for this research were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The Cox proportional risk model was employed to evaluate the link between low‐fat dairy consumption and the risk of developing lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were measured in both unadjusted and adjusted models. A series of predefined subgroup analyses were performed to identify potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. Results The study included data from 98,459 individuals. During a total of 869,807.9 follow‐up person‐years, 1642 cases of lung cancer were observed, with an incidence of 0.189 cases for every 100 person‐years. In the fully adjusted model, participants in the highest quartile of low‐fat dairy consumption had a significantly decreased risk of lung cancer compared to the ones in the lowest quartile (HRquartile 4 vs. 1: 0.769, 95% CI: 0.664, 0.891, ptrend = 0.005). The restricted cubic spline plot revealed an inverse nonlinear dose–response relationship between low‐fat dairy consumption and lung cancer risk (pnonlinearity = 0.008). Subgroup analyses demonstrated that the inverse association was stronger among participants with higher daily caloric intake (pinteraction = 0.031). Various sensitivity analyses produced consistent results. Conclusion Consuming more low‐fat dairy products is significantly linked to a reduced risk of developing lung cancer, indicating that an appropriate increase in the use of low‐fat dairy products may help prevent lung cancer.

Abstract Background The plant-based paleolithic diet (PD) and the paleolithic-like lifestyle (PLL) may reduce the risk of chronic diseases, including colorectal adenomas. These dietary and lifestyle approaches are proposed to exert their effects through mechanisms such as reducing inflammation, oxidative stress, and insulin levels. However, whether PD and PLL is associated with the risk of colorectal cancer (CRC) has not been determined. Methods A cohort of 74,721 individuals who participated in the PLCO study were included in this analysis. Adherence to the PD and PLL was assessed using PD and PLL scores, where higher scores indicated greater adherence. Multivariable Cox models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subsites (proximal colon cancer and distal CRC). Subgroup analyses were conducted to identify potential effect modifiers. Results During a mean follow-up of 9.2 years, a total of 694 CRC cases were identified. Participants in the highest compared with the lowest quartiles of PD score had a lower risk of CRC (Q4 vs Q1: HR 0.76, 95% CI 0.61–0.95, P trend = 0.009) and proximal colon cancer (Q4 vs Q1: HR 0.73, 95% CI 0.55–0.97, P trend = 0.02). A stronger inverse association was observed for PLL score with the risk of CRC (Q4 vs Q1: HR 0.64, 95% CI 0.51–0.81, P trend

BackgroundThe intricate role of oxidative stress (OS) in colorectal cancer (CRC) initiation is underscored by an imbalance between pro-oxidants and antioxidants. Utilizing the Oxidative Balance Score (OBS) as a metric, this study aims to investigate the association between OS exposure and CRC risk, while also examining potential sex-specific differences in a large U.S. cohort.MethodsThe study included 98,395 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. To construct the OBS, 14 dietary and lifestyle factors intricately associated with oxidative stress were quantified. A higher OBS value indicated a more favorable oxidative balance pattern or diminished OS exposure. Due to sex-specific differences in OBS, associations were evaluated separately for men and women based on Cox regression analysis. Subgroup analyses were conducted to elucidate potential modifiers.ResultsDuring 867,963.4 person-years of follow-up, 1,054 CRCs occurred. The mean (SD) age and OBS were 65.52 (5.73) years and 14.09 (3.95) points, respectively. In the fully adjusted Cox model, we observed an inverse association between OBS and CRC incidence in women (HRQ5vsQ1: 0.72; 95% CI: 0.52, 0.99; P for trend = 0.018) but not men. Subgroup analyses revealed the inverse association was more pronounced among women without versus with a family history of CRC (HRQ5vsQ1: 0.66, 95% CI: 0.47–0.93; P for trend = 0.001; P for interaction = 0.001). The results remained robust after several sensitivity analyses.ConclusionHigher OBS was associated with lower CRC risk in women but not men; this inverse association was stronger among women without a family history of CRC. These findings suggest exposure to OS may confer sex-specific CRC risk effects, especially for women without a family history of CRC.

Abstract Background Eutrema salsugineum (2n = 14), a halophyte in the family Brassicaceae, is an attractive model to study abiotic stress tolerance in plants. Two versions of E. salsugineum genomes that previously reported were based on relatively short reads; thus, the repetitive regions were difficult to characterize. Results We report the sequencing and assembly of the E. salsugineum (Shandong accession) genome using long-read sequencing and chromosome conformation capture data. We generated Oxford Nanopore long reads at high depth (> 60X) of genome coverage with additional short reads for error correction. The new assembly has a total size of 295.5 Mb with 52.8% repetitive sequences, and the karyotype of E. salsugineum is consistent with the ancestral translocation Proto-Calepineae Karyotype structure in both order and orientation. Compared with previous assemblies, this assembly has higher contiguity, especially in the centromere region. Based on this new assembly, we predicted 25,399 protein-coding genes and identified the positively selected genes associated with salt and drought stress responses. Conclusion The new genome assembly will provide a valuable resource for future genomic studies and facilitate comparative genomic analysis with other plants.

BackgroundThe EAT-Lancet diet (ELD) is a recommended dietary pattern for achieving simultaneous improvements in both individual health and environmental sustainability. While research on the association between ELD and colorectal cancer (CRC) remains scarce, the potential impact of nutrition on CRC prevention and progression is a topic of growing interest. This study aims to investigate the relationship between adherence to the ELD and the risk of CRC, shedding light on the role of nutrition in CRC prevention.MethodsA total of 98,415 participants were included. A Diet History Questionnaire (DHQ) was used to collect dietary information, and an ELD score was used to assess adherence to ELD. Higher scores indicated greater adherence. Cox hazard regression analyses were conducted to examine whether there were associations between the ELD score and CRC risk. The restricted cubic spline (RCS) model was used to further explore the dose-response association between the ELD score and CRC incidence. Subgroup analyses were conducted to identify potential modifiers that interacted with ELD on CRC incidence, and sensitivity analyses were performed to evaluate the robustness of the established association.ResultsDuring a mean follow-up of 8.82 years, a total of 1,054 CRC cases were documented. We found a statistically significant correlation between the ELD score and CRC risk (Q4 vs. Q1: HR 0.81, 95% CI 0.67–0.98; P for trend = 0.034) after adjusting for potential confounders. No statistically significant associations were discovered between ELD adherence and CRC by anatomical site. Subgroup analyses found no interactional factor, sensitivity analyses, and the RCS model showed a robustness and linearity association (P-linearity >0.05).ConclusionWe concluded that adherence to ELD contributes to the prevention of CRC.

BackgroundAdherence to the diabetes risk reduction diet (DRRD) may potentially reduce the risk of developing head and neck cancer (HNC) as the diet includes fruits and limits red and processed meats, known risk factors for HNC. However, there is currently no epidemiological research to investigate this potential association.MethodsThe present study utilized data on demographics, lifestyles, medications, and diets of participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to explore the potential association between adherence to DRRD and the risk of HNC. We used a DRRD score to evaluate adherence to the dietary pattern and employed Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HNC risk. Several subgroup analyses were carried out to identify potential effect modifiers, and multiple sensitivity analyses were performed to evaluate the stability of the correlation. The nine components of the DRRD was assessed separately for its association with the risk of HNC.ResultsDuring a mean follow up of 8.84 years, 279 cases of HNC were observed. DDRD score was found to be inversely associated with the risk of HNC (HR Q4 vs. Q1: 0.582; 95% CI: 0.396, 0.856; p = 0.005 for trend) in a linear dose–response manner (p = 0.211 for non-linearity). Subgroup analysis indicated this inverse correlation was more pronounced among participants who had never smoked (HRQ4 vs. Q1: 0.193; 95% CI: 0.073, 0.511; p

Heat stress in pear cultivar results in upregulation of long non-coding RNA HILinc1, which binds to and stabilizes PbHILT1 mRNA, which codes for a protein that interacts with heat shock factor A1b, improving thermotolerance.

BackgroundSulfur microbial diet (SMD), related to the enrichment of sulfur-metabolizing gut bacteria, has been confirmed to be linked to an elevated risk of early-onset colorectal adenoma in young females. However, it remains unclear whether SMD is associated with the risk of colorectal adenoma in older people, who are at greater risk for colorectal cancer.MethodsAll data on participants in this study were retrieved from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening test. Participants’ adherence to this dietary pattern was assessed using SMD score. Hazard ratios (HR) and 95% confidence intervals (CI) were adopted in Cox proportional hazards regression models to assess the link between SMD score and the incidence of colorectal adenoma in participants included in the study. Specific stratified analyses were constructed to assess whether this association changed in different conditions, whereas the robustness of the association was examined through sensitivity analyses.ResultsThe mean baseline age of participants was 62.1 (SD 5.2) years (range 54.0–75.0 years). During 19,468,589 person-years of follow-up, 992 colorectal adenoma cases were documented in a total of 17,627 included participants. In a fully adjusted model, an increased risk of colorectal adenoma was determined in participants in the highest quartile of SMD score in comparison with those in the lowest quartile (HRquartile4 vs. HRquartile1 = 1.23; 95% CI: 1.02, 1.47; p = 0.017 for trend). This positive association between SMD score and adenoma risk was more evident in participants who were current or former smokers (p = 0.029 for interaction).ConclusionIn this study, our results support a role for the SMD in the carcinogenicity of colorectal cancer precursors among older adults. Nevertheless, these results require validation through more research.

Abstract Introduction Immunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + . Methods This retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival. Results The statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P

BackgroundDietary approaches to stop hypertension (DASH) eating pattern is linked to anti-inflammatory responses and antioxidation, which overlap with the pathogenesis of lung cancer. However, there is insufficient epidemiological evidence to link this dietary pattern to lung cancer risk conclusively.AimTo determine if adherence to the DASH diet is linked to a lower risk of developing lung cancer in a large prospective study.MethodologyThe data of participants were retrieved from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A DASH score was calculated based on 8 dietary components to reflect adherence to DASH, with greater scores representing higher adherence. Three Cox proportional hazards models were constructed to analyze the association between DASH scores and lung cancer risk, including an unadjusted model and two adjusted models (model 1 for demographics and model 2 for fully confounding factors). A restricted cubic spline plot was utilized to illustrate the likelihood of developing lung cancer across the entire range of DASH scores. The association between each of the 8 DASH components and the risk of lung cancer was assessed separately. Several subgroup analyses were conducted to identify potential modifiers, and several sensitivity analyses were performed to verify the robustness of the findings.ResultsThe study involved 98,459 individuals in total. The mean (standard deviation) DASH score was 24.00 (4.62) points, along with the mean follow-up period of 8.84 (1.94) years. Lung cancer was identified in 1642 cases over 869807.9 person-years of follow-up, and the overall incidence rate was 0.189 cases/100 person-years. Participants in the highest quartile in the fully adjusted model had a relatively decreased risk of developing lung cancer in comparison to those in the lowest quartile (HRquartile 4 versus 1: 0.647; 95% CI: 0.557, 0.752; Ptrend

Vultures are the only obligate scavengers among extant vertebrates. They provide valuable ecological services in ecosystems through removing carcasses, thus preventing the growth of other scavenger populations and the spread of pathogens. Moreover, their specific diets expose them to various deadly pathogens, which makes them potential candidates for studying molecular adaptations required to survive this extremely specialized scavenging habit. In this review, we summarize the morphological characteristics and behavioral habits, origin and phylogeny, and molecular adaptations to scavenging in both Old and New World vultures. The two groups of vultures share a similar appearance, indicative of convergent evolution. Vultures have experienced different degrees of specialization in their sensory organs; Old World vultures depend on sight, while New World ones depend on both smell and sight. Combined fossil records and molecular data suggest that vultures evolved independently, with distinct phylogenetic positions. We also explored their adaptation to scavenging in facial and intestinal microbiomes, gastric acid secretion and immunity. Compared with the facial microbiome, the intestinal microbiome had a lower diversity, dominated by Fusobacteria and Clostridia. The phages and single invertebrate species Adineta vaga, which feeds on dead bacteria and protozoa, present in the gut suggest a possible alternative defense mechanism. Several genes involved in gastric acidic secretion (including ATP4B, SLC26A7 and SST) and immunity (including BCL6, STING, and TLRs) undergoing positive selection likely have essential roles in eliminating invasive pathogens and initiating an innate immune response. Taken together, this review presents the current research status of vultures and highlights the use of vultures as a model for exploring molecular adaptations of dietary specialization in birds. It also provides a theoretical basis for the study of the genetic mechanisms of vultures to scavenging, and contributes to the formulation of vulture conservation strategies.

BackgroundLow-fat diet reduces the risk of chronic metabolic diseases such as obesity and diabetes, which exhibit overlapping mechanisms with liver cancer. However, the association between low-fat diet and liver cancer risk remains unclear.AimTo investigate whether adherence to low-fat diet is associated with a reduced risk of liver cancer in a prospective study.Materials and methodsData of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A low-fat diet score was calculated to reflect adherence to low-fat dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for liver cancer incidence with adjustment for potential covariates. Restricted cubic spline model was used to characterize liver cancer risk across the full range of the low-fat diet score. Prespecified subgroup analyses were used to identify potential impact modifiers. Sensitivity analyses were performed to test the robustness of this association.ResultsA total of 98,455 participants were included in the present analysis. The mean (standard deviation) age, low-fat diet score, and follow-up time were 65.52 (5.73) years, 14.99 (6.27) points, and 8.86 (1.90) years, respectively. During 872639.5 person-years of follow-up, 91 liver cancers occurred, with an overall incidence rate of 0.01 cases per 100 person-years. In the fully adjusted Cox model, the highest versus the lowest quartile of low-fat diet score was found to be associated with a reduced risk of liver cancer (HRQ4 vs. Q1: 0.458; 95% CI: 0.218, 0.964; P = 0.035 for trend), which remained associated through a series of sensitivity analyses. The restricted cubic spline model showed a linear dose–response association between low-fat diet score and liver cancer incidence (p = 0.482 for non-linear). Subgroup analyses did not show significant interaction between low-fat diet score and potential impact modifiers in the incidence of liver cancer.ConclusionIn this study, low-fat diet score is associated with reduced liver cancer risk in the US population, indicating that adherence to low-fat diet may be helpful for liver cancer prevention. Future studies should validate our findings in other populations.

BackgroundColorectal cancer (CRC) is a common cancer and has a poor prognosis. The coagulation system and fibrinolysis system are closely related to the progression of malignant tumors and is also related to the immunotherapy of malignant tumors. Herein, we tried to predict survival and the immunotherapy effect for patients with CRC using a novel potential prognostic model.MethodsThrough online data of TCGA and GEO, we screened significantly differentially expressed genes (DEGs) to construct a prognostic model, followed by obtaining immune-related genes (IRGs) from the ImmPort database and coagulation- and fibrinolysis-related genes (CFRGs) from the GeneCards database. The predictive power of the model is assessed by Kaplan–Meier survival curves as well as the time-dependent ROC curve. Moreover, univariate and multivariate analyses were conducted for OS using Cox regression models, and the nomogram prognostic model was built. In the end, we further studied the possibility that CXCL8 was associated with immunocyte infiltration or immunotherapy effect and identified it by immunohistochemistry and Western blot.ResultsFive DEGs (CXCL8, MMP12, GDF15, SPP1, and NR3C2) were identified as being prognostic for CRC and were selected to establish the prognostic model. Expression of these genes was confirmed in CRC samples using RT-qPCR. Notably, those selected genes, both CFRGs and IRGs, can accurately predict the OS of CRC patients. Furthermore, CXCL8 is highly correlated with the tumor microenvironment and immunotherapy response in CRC.ConclusionOverall, our established IRGPI can very accurately predict the OS of CRC patients. CXCL8 reflects the immune microenvironment and reveals the correlation with immune checkpoints among CRC patients.

In recent years government publicity was extensively used to convey environmental issues; therefore, it is important to explore the role of green government publicity influencing people’s pro-environmental behaviors (PEBs). This study is to uncover the impact of China’s green government publicity on people’s willingness to use green packaging. This research collected data from Guangzhou of China, we used convenient sampling and online questionnaire survey to gather data, and there were 584 effective samples. Using the statistical software Amos17.0, the results reveal that green government publicity has a significant effect on environmental concerns and moral obligation. Environmental concerns and moral obligation both have positive effects on PEBs. In addition, Environmental concerns and moral obligation all have mediating effects in the relationship between green government publicity and people’s PEBs.

Chondroitin sulfate-mediated albumin corona nanoparticles were readily prepared without any chemical reaction, and their active tumor targeting and therapeutic effects were examined. Negatively charged chondroitin sulfate (CS) and positively charged doxorubicin (DOX) self-assembled into nanoparticles (CS-DOX-NPs) via electrostatic interactions. Bovine serum albumin (BSA) was then adsorbed on the surface of CS-DOX-NPs to form albumin corona nanoparticles (BC-DOX-NPs) protected from endogenous proteins. Due to the dual effect of BSA and CS, BC-DOX-NPs interacted with the gp60, SPARC and CD44 receptors on tumor cells, facilitating their rapid and efficient transcytosis and improving their accumulation and uptake within tumor tissues. The simultaneous presence of BSA and CS also allowed BC-DOX-NPs to target CD44 efficiently, leading to greater cellular uptake and cytotoxicity against 4T1 cells than CS-DOX-NPs or free DOX. Intravenous injection of BC-DOX-NPs into orthotopic 4T1 tumor-bearing mice led to greater drug accumulation at the tumor site than with CS-DOX-NPs or free DOX, resulting in significant inhibition of tumor growth and lower exposure of major organs to the drug.

Objectives Poor symptom appraisal (detection, interpretation and response to symptoms) plays a major role in prolonged prediagnosis interval in various health conditions. Theories and models have been proposed to study the symptom appraisal process but how they could be employed to improve symptom appraisal remains unclear. We therefore aimed to review approaches to improving symptom appraisal in the literature and to develop a theoretical framework that could guide the development of approaches to improving symptom appraisal among individuals in the general population.Design Systematic review.Data sources Medline, Web of Science, PsycINFO, Embase, CINAHL and Scopus were searched from inception to 30 March 2021.Eligibility criteria We included original articles in English in which approaches to improve the detection, interpretation or response to symptoms for symptomatic individuals were described. We excluded articles in which approaches were developed to improve symptom appraisal among healthcare professionals.Data extraction and synthesis A predefined data extraction form was used to extract the development, characteristics and evaluation of approaches to improving symptom appraisal. This formed the basis for the narrative synthesis.Results Of 19 046 publications identified from the literature search, 112 were selected for full-text review and 29 approaches comprising provision of knowledge of symptoms/signs and additional components (eg, symptom self-examination and comparison) for symptom appraisal were included in the synthesis. Less than half (41.4%) of these approaches were developed based on theories/models. Interestingly, despite the variety of theories/models adopted in developing these approaches, the components of these approaches were similar.Conclusion Symptom appraisal is an essential process in a patient’s journey that can be targeted to facilitate early diagnosis but is largely unstudied. Building on the literature, we proposed a theoretical framework and approaches to improving symptom appraisal. This could facilitate early identification of a variety of health conditions in the general population.Trial registration number CRD42021279500.

Background Fatty acid-binding protein 4 (FABP4) has been reported to be associated with tumor progress and poor prognosis in various cancers. However, the relationship between FABP4 expression and tumor immunity in colon adenocarcinoma (COAD) is still poorly understood. Methods FABP4 mRNA expression was analyzed using The Cancer Genome Atlas (TCGA)-COAD data. FABP4 protein staining was performed by immunohistochemistry (IHC) staining in our 10 paired COAD samples and corresponding adjacent noncancerous tissues. The association between FABP4 and immune cell infiltration was evaluated by Tumor Immune Estimation Resource (TIMER) database. FABP4 coexpressed genes were identified based on Cancer Cell Line Encyclopedia (CCLE) database, which were employed for further enrichment analysis. FABP4 related immunomodulators was identified by Tumor and Immune System Interaction Database (TISIDB) database, and a prognostic risk signature was constructed based on FABP4-related immunomodulators using stepwise Cox regression analysis. A nomogram consists of FABP4 related immunomodulators signature and clinical parameters was developed to predict the overall survival (OS). Results In TCGA data, we found that the decreased FABP4 mRNA expression in COAD samples compared with normal samples, and low FABP4 mRNA expression was associated with B cells, CD4+ T cells, CD8+ T cells, myeloid dendritic cells, macrophages, and neutrophils. In our 10 paired samples, the protein levels of COAD were lower in all COAD tissues than in their adjacent noncancerous tissues. Functional enrichment analysis revealed that FABP4 coexpressed genes were mostly enriched in immune-related pathways. Based on 54 FABP4-related immunomodulators, a 2-gene FABP4-related prognostic risk signature was developed, and the signature stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The Nomogram consists of the prognostic signature and clinical parameters had a certain predictability for prognosis of COAD patients. Conclusion These findings suggest that FABP4 is associated with 2-gene immune signature which also correlate with the prognosis of COAD patients.

Abstract Objective Patient involvement in treatment decisions is recommended in clinician‐patient encounters. Little is known about how oncologists engage patients in shared decision making in non‐Western countries. We assessed the prevalence of shared decision making among Singaporean oncologists and analysed how they discussed prognosis. Methods We audio‐recorded 100 consultations between advanced cancer patients and their oncologists. We developed a coding system to assess oncologist encouragement of patient participation in decision making and disclosure of an explicit prognosis. We assessed patient and oncologist characteristics that predicted these behaviours. Results Forty‐one consultations involved treatment discussions. Oncologists almost always listed more than one treatment option (90%). They also checked patient understanding (34%), discussed pros and cons (34%) and addressed uncertainty (29%). Oncologists discussed prognosis mostly qualitatively (34%) rather than explicitly (17%). They were more likely to give an explicit prognosis when patients/caregivers asked questions related to prognosis. Conclusion Oncologists in our sample engaged their patients in decision making. They have areas in which they can improve to involve patients at a deeper level to ensure shared decision making. Findings will be used to develop an intervention targeting oncologists and patients to promote patient involvement in decision making.

Abstract Condition monitoring (CM) of wind turbine becomes significantly important part of wind farms in order to cut down operation and maintenance costs. The large amount of CM system vibration data collected from wind turbines are posing challenges to operators in signal processing. It is crucial to design sensitive and reliable condition indicator (CI) in wind turbine CM system. Bearing plays an important role in wind turbine because of its high impact on downtime and component replacement. CIs for wind turbine bearing monitoring are reviewed in the paper, and the advantages and disadvantages of these indicators are discussed in detail. A new engineering CI (ECI), which combined the energy and kurtosis representation of the vibration signal, is proposed to meet the requirement of easy applicability and early detection in wind turbine bearing monitoring. The quantitative threshold setting method of the ECI is provided for wind turbine CM practice. The bearing run‐to‐failure experiment data analysis demonstrates that ECI can evaluate the overall condition and is sensitive to incipient fault of bearing. The effectiveness in engineering of ECI is validated though a certain amount of real‐world wind turbine generator and gearbox bearing vibration data.

Abstract Background The purpose of this research was to assess the feasibility of reconstructing the middle hepatic vein (MHV) with resected left portal vein during left hemihepatectomy. Methods From January 2014 to January 2018, six patients received left hemihepatectomy combined with MHV reconstruction using the resected left portal vein in West China Hospital. We reviewed the clinical data including patient details, surgical technique, graft patency, and operative results. Results All six patients underwent left hemihepatectomy for liver tumors located at left hepatocaval confluence. In these patients, MHV was resected due to tumor invading and reconstructed using the resected left portal vein as graft. The mean operating time was 316 min. Two patients developed complications: one experienced bile leakage and one experienced pleural effusion. No patient developed vascular graft complications. All the grafts remained unobstructed, and no local tumor recurrence occurred during the observation period of 13–41 months. Conclusions Our results indicated that the left portal vein was a safe graft for hepatic vein reconstruction. In addition, left hemihepatectomy combined with middle hepatic vein resection and reconstruction using the left portal vein can be performed safely to treat liver tumors located at hepatocaval confluence.

Abstract Rolling element bearings are key components of mechanical equipment. The bearing fault characteristics are affected by the interaction in the vibration signals. The low harmonics of the bearing characteristic frequencies cannot be usually observed in the Fourier spectrum. The frequency loss in the bearing vibration signal is presented through two independent experiments in this paper. The existence of frequency loss phenomenon in the low frequencies, side band frequencies and resonant frequencies and revealed. It is demonstrated that the lost frequencies are actually suppressed by the internal action in the bearing fault signal rather than the external interference. The amplitude and distribution of the spectrum are changed due to the interaction of the bearing fault signal. The interaction mechanism of bearing fault signal is revealed through theoretical and practical analysis. Based on mathematical morphology, a new method is provided to recover the lost frequencies. The multi-resonant response signal of the defective bearing are decomposed into low frequency and high frequency response, and the lost frequencies are recovered by the combination morphological filter (CMF). The effectiveness of the proposed method is validated on simulated and experimental data.

Recently, perovskites have garnered great attention owing to their outstanding characteristics, such as tunable bandgap, rapid absorption reaction, low cost and solution-based processing, leading to the development of high-quality and low-cost photovoltaic devices. However, the key challenges, such as stability, large-area processing, and toxicity, hinder the commercialization of perovskite solar cells (PSCs). In recent years, several studies have been carried out to overcome these issues and realize the commercialization of PSCs. Herein, the stability and photovoltaic efficiency improvement strategies of perovskite solar cells are briefly summarized from several directions, such as precursor doping, selection of hole/electron transport layer, tandem solar cell structure, and graphene-based PSCs. According to reference and analysis, we present our perspective on the future research directions and challenges of PSCs.

Accurate wind speed prediction can improve the utilization efficiency of wind energy effectively. However, the original time series signals of wind speed present nonlinear or non-stationary characteristics, which make wind speed forecasting very difficult. A new pre-processing method of wind speed signal, named improved empirical wavelet transform (IEWT), is proposed in this paper, which is inspired by the spectrum segmentation theory of EWT. Then, a novel hybrid model combining IEWT and least square support vector machine (LSSVM) is put forward to predict short-term wind speed. In order to achieve better prediction results, the parameters are jointly optimized through bird swarm algorithm (BSA) in this model. The prediction performance of the established hybrid model is tested with practical wind speed signal of four seasons from a wind farm situated in Zhejiang, China. The experimental results indicate that the presented hybrid forecasting model can effectively follow the change of wind speed, which exhibits more superior predicting performance than other popular models.

Distylium chinense is a dominant native evergreen shrub or small tree in the riparian forests in the Three Gorges Reservoir zone in China. The genetic diversity and population structure of D. chinense within and among eight populations was analyzed by ISSR (Inter Simple Sequence Repeat) and SRAP (Sequence-Related Amplified Polymorphism) markers. A high level of genetic diversity was observed at the species level (H = 0.3465, I = 0.5039 in ISSR; H = 0.1924, I = 0.4123 in SRAP) and at the population level (H = 0.3047, I = 0.4471 in ISSR; H = 0.1543, I = 0.3415 in SRAP). The genetic differentiation among population (Gst = 0.1205, Nm = 1.8247 in ISSR and Gst = 0.1976, Nm = 1.015 in SRAP) indicated low levels of genetic variation among populations and high levels of genetic polymorphism within populations. AMOVA (Analyses of molecular variance) also suggested that the main source of variation was within populations (93.9% in ISSR and SRAP in 81.9%). UPGMA (Unweighted Pair Group Method with Arithmetic means) cluster analysis and PCA (Principal Component Analysis) based on ISSR and SRAP amplification showed that populations from the same or adjacent regions were classified together. However, Mantel's test demonstrated that there was no significant correlation between the genetic distance and the geographical distance of each population (P > 0.05). Thus, the declining status of this species is likely due to the destruction of natural habitats, anthropogenic activities and overharvesting, rather than a loss of genetic diversity. Keywords: Distylium chinense, ISSR, SRAP, Genetic structure, Genetic diversity

Wind turbines work in strong background noise, and multiple faults often occur where features are mixed together and are easily misjudged. To extract composite fault of rolling bearings from wind turbines, a new hybrid approach was proposed based on multi-point optimal minimum entropy deconvolution adjusted (MOMEDA) and the 1.5-dimensional Teager kurtosis spectrum. The composite fault signal was deconvoluted using the MOMEDA method. The deconvoluted signal was analyzed by applying the 1.5-dimensional Teager kurtosis spectrum. Finally, the frequency characteristics were extracted for the bearing fault. A bearing composite fault signal with strong background noise was utilized to prove the validity of the method. Two actual cases on bearing fault detection were analyzed with wind turbines. The results show that the method is suitable for the diagnosis of wind turbine compound faults and can be applied to research on the health behavior of wind turbines.

Psychopathy is a personality development disorder increasing the risk of antisocial behavior. Studies on the relationship between psychopathy and decision-making have received limited attention and the result of studies is mixed. A present study examines whether or not the different factors of psychopathy are related to decision-making under risk and ambiguity in offenders and how they are related. Also, the study investigates whether general intelligence is associated with decision-making or moderates the relationship between psychopathy and decision-making. The results showed that only antisocial factor of psychopathy significantly correlates with Game of Dice Task (GDT) risky selections, but there no general relation between psychopathy and Iowa Gambling Task (IGT) performance. Lastly, general intelligence neither is related to decision-making under risk and ambiguity nor moderates the relationship between decision-making and psychopathy. The study results show that antisocial factor of psychopathy was associated with decision-making under risk rather than ambiguity. Our results also suggest that the antisocial factor of psychopathy was more related to executive dysfunction in offenders.

Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes and is one of the main causes of end-stage renal disease (ESRD) in many countries. The pathological features of DKD are the hypertrophy of mesangial cells, apoptosis of podocytes, glomerular basement membrane (GBM) thickening, accumulation of extracellular matrix (ECM), glomerular sclerosis, and tubulointerstitial fibrosis. The etiology of DKD is very complicated and many factors are involved, such as genetic factors, hyperglycemia, hypertension, hyperlipidemia, abnormalities of renal hemodynamics, and metabolism of vasoactive substances. Although some achievements have been made in the exploration of the pathogenesis of DKD, the currently available clinical treatment methods are still not completely effective in preventing the progress of DKD to ESRD. CHM composed of natural products has traditionally been used for symptom relief, which may offer new insights into therapeutic development of DKD. We will summarize the progress of Chinese herbal medicine (CHM) in the treatment of DKD from two aspects. In clinical trials, the Chinese herbal formulas were efficacy and safety confirmed by the randomized controlled trials. In terms of experimental research, studies provided evidence for the efficacy of CHM from the perspectives of balancing metabolic disorders, reducing inflammatory response and oxidative stress, antifibrosis, protecting renal innate cells, and regulating microRNA and metabolism. CHM consisting of different ingredients may play a role in synergistic interactions and multiple target points in the treatment of DKD.

Datura metel L. is a widely used traditional herbal medicine, and withanolides and amides are the two groups of main bioactive constituents in Datura metel seeds. This study aimed to elucidate the metabolism of four representative bioactive compositions containing daturataturin A (1), daturametelin I (2), N-trans-feruloyltyramine (3), and cannabisin F (4) in rats. After separately oral administration of 20 mg/kg withanolides (1, 2) and amides (3, 4) to rats, a total of 12, 24, and 21 metabolites were detected in the plasma, urine, and fecal samples, respectively. Among them, three hydroxylated metabolites, 1-M3, 2-M2, and 3-M5, were detected in plasma and rat liver microsome incubation system in high abundance. Two metabolites of 1 and 2 were unambiguously identified by comparing with reference standards. Particularly, the methylated metabolite 27α-methoxy-(22R)-22,26-epoxy-27-[(β-D-glucopyranosyl)oxy]ergosta-2,4,6,24-tetraene-1,26-dione (daturametelin L) is a new compound. The withanolides could readily get hydroxylation or methylation metabolism. Meanwhile, the phase II metabolism (glucuronidation or sulfation) was the major reaction for the amides. This is the first study on in vivo metabolism of these active compounds in seeds of Datura metel.

BACKGROUND: The alkaloid camptothecin analog SN38 is a potent antineoplastic agent, but cannot be used directly for clinical application due to its poor water solubility. Currently, the prodrug approach on SN38 has resulted in 3 FDA-approved cancer therapeutics, irinotecan, ONIVYDE, and Trodelvy. However, only 2-8% of irinotecan can be transformed enzymatically in vivo into the active metabolite SN38, which severely limits the drugs efficacy. While numerous drug delivery systems have been attempted to achieve effective SN38 delivery, none have produced drug products with antitumor efficacy better than irinotecan in clinical trials. Therefore, novel approaches are urgently needed for effectively delivering SN38 to cancer cells with better efficacy and lower toxicity. METHODS: Based on the unique properties of human serum albumin (HSA), we have developed a novel single protein encapsulation (SPE) technology to formulate cancer therapeutics for improving their pharmacokinetics (PK) and antitumor efficacy and reducing their side effects. Previous application of SPE technology to doxorubicin (DOX) formulation has led to a promising drug candidate SPEDOX-6 (FDA IND #, 152154), which will undergo a human phase I clinical trial. Using the same SPE platform on SN38, we have now produced two SPESN38 complexes, SPESN38-5 and SPESN38-8. We conducted their pharmacological evaluations with respect to maximum tolerated dose, PK, and in vivo efficacy against colorectal cancer (CRC) and soft tissue sarcoma (STS) in mouse models. RESULTS: The lyophilized SPESN38 complexes can dissolve in aqueous media to form clear and stable solutions. Maximum tolerated dose (MTD) of SPESN38-5 is 250 mg/kg by oral route (PO) and 55 mg/kg by intravenous route (IV) in CD-1 mice. SPESN38-8 has the MTD of 45 mg/kg by IV in the same mouse model. PK of SPESN38-5 by PO at 250 mg/kg gave mouse plasma AUC0-∞ of 0.05 and 4.5 nmol × h/mL for SN38 and SN38 glucuronidate (SN38G), respectively, with a surprisingly high molar ratio of SN38G:SN38 = 90:1. However, PK of SPESN38-5 by IV at 55 mg/kg yielded much higher mouse plasma AUC0-∞ of 19 and 28 nmol × h/mL for SN38 and SN38G, producing a much lower molar ratio of SN38G:SN38 = 1.5:1. Antitumor efficacy of SPESN38-5 and irinotecan (control) was evaluated against HCT-116 CRC xenograft tumors. The data indicates that SPESN38-5 by IV at 55 mg/kg is more effective in suppressing HCT-116 tumor growth with lower systemic toxicity compared to irinotecan at 50 mg/kg. Additionally, SPESN38-8 and DOX (control) by IV were evaluated in the SK-LMS-1 STS mouse model. The results show that SPESN38-8 at 33 mg/kg is highly effective for inhibiting SK-LMS-1 tumor growth with low toxicity, in contrast to DOXs insensitivity to SK-LMS-1 with high toxicity. CONCLUSION: SPESN38 complexes provide a water soluble SN38 formulation. SPESN38-5 and SPESN38-8 demonstrate better PK values, lower toxicity, and superior antitumor efficacy in mouse models, compared with irinotecan and DOX.

A prime-target interference task was used to investigate the effects of cognitive aging on reactive and proactive control in which frequency confounds and feature repetitions were eliminated from the cognitive control measures. We used distributional analyses to explore the dynamics of the two control functions by distinguishing the strength of incorrect response capture and the efficiency of suppression control. For reactive control, within-trial conflict control and between-trial conflict adaption were analyzed. The statistical analysis showed that there were no reliable between-trial conflict adaption effects for both young and older adults. For within-trial conflict control, the results revealed that older adults showed larger interference effects on mean RT and mean accuracy. Distributional analyses showed that the decline mainly stemmed from inefficient suppression rather than from stronger incorrect responses. For proactive control, older adults showed comparable proactive conflict resolution than young adults on mean RT and mean accuracy. Distributional analyses showed older adults were as effective as younger adults in adjusting their responses to minimize automatic response capture and actively suppress the direct response activation based on congruency proportion information. The results suggest that older adults were less proficient at suppressing interference after conflict was detected but can anticipate and prevent inference in response to congruency proportion manipulation. The results challenge earlier views that older adults have selective deficits in proactive control but are spared in reactive control.

Torsional vibration responses of a nonlinear shafting system are studied by a modified Riccati torsional transfer matrix combining with the Newmark-β method. Firstly, the system is modeled as a chain consisting of an elastic spring with concentrated mass points, from which a multi-segment lumped mass model is established. Secondly, accumulated errors are eliminated from the eigenfrequencies and responses of the system's torsional vibration by this newly developed procedure. The incremental transfer matrix method, combining the modified Riccati torsional transfer matrix with Newmark-β method, is further applied to solve the dynamical equations for the torsional vibration of the nonlinear shafting system. Lastly, the shafting system of a turbine-generator is employed as an illustrating example, and simulation analysis has been performed on the transient responses of the shaft's torsional vibrations during typical power network disturbances, such as three-phase short circuit, two-phase short circuit and asynchronous juxtaposition. The results validate the present method and are instructive for the design of a turbo-generator shaft.