The nuclear pore Y-complex functions as a platform for transcriptional regulation of FLOWERING LOCUS C in Arabidopsis.

The nuclear pore complex (NPC) has multiple functions beyond the nucleo-cytoplasmic transport of large molecules. Subnuclear compartmentalization of chromatin is critical for gene expression in animals and yeast. However, the mechanism by which the NPC regulates gene expression is poorly understood in plants. Here we report that the Y-complex (Nup107-160 complex, a subcomplex of the NPC) self-maintains its nucleoporin homeostasis and modulates FLOWERING LOCUS C (FLC) transcription via changing histone modifications at this locus. We show that Y-complex nucleoporins are intimately associated with FLC chromatin through their interactions with histone H2A at the nuclear membrane. Fluorescence in situ hybridization assays revealed that Nup96, a Y-complex nucleoporin, enhances FLC positioning at the nuclear periphery. Nup96 interacted with HISTONE DEACETYLASE 6 (HDA6), a key repressor of FLC expression via histone modification, at the nuclear membrane to attenuate HDA6-catalyzed deposition at the FLC locus and change histone modifications. Moreover, we demonstrate that Y-complex nucleoporins interact with RNA polymerase II to increase its occupancy at the FLC locus, facilitating transcription. Collectively, our findings identify an attractive mechanism for the Y-complex in regulating FLC expression via tethering the locus at the nuclear periphery and altering its histone modification.

Liquid biopsy of oesophageal squamous cell carcinoma: implications in diagnosis, prognosis, and treatment monitoring.

Oesophageal squamous cell carcinoma (ESCC) is a common malignant tumour of the gastrointestinal tract. Early detection and access to appropriate treatment are crucial for the long-term survival of patients. However, limited diagnostic and monitoring methods are available for identifying early stage ESCC. Endoscopic screening and surgical resection are commonly used to diagnose and treat early ESCC. However, these methods have disadvantages, such as high recurrence, lethality, and mortality rates. Therefore, methods to improve early diagnosis of ESCC and reduce its mortality rate are urgently required. In 1961, Gary et al. proposed a novel liquid biopsy approach for clinical diagnosis. This involved examining exosomes, circulating tumour cells, circulating free DNA, and circulating free RNA in body fluids. The ability of liquid biopsy to obtain samples repeatedly, wide detection range, and fast detection speed make it a feasible option for non-invasive tumour detection. In clinical practice, liquid biopsy technology has gained popularity for early screening, diagnosis, treatment efficacy monitoring, and prognosis assessment. Thus, this is a highly promising examination method. However, there have been no comprehensive reviews on the four factors of liquid biopsy in the context of ESCC. This review aimed to analyse the progress of liquid biopsy research for ESCC, including its classification, components, and potential future applications.

Olympic gels formed through catenation of dsDNA rings regulated by topoisomerase II: A coarse-grained model.

Topological regulation of DNA by topoisomerases in cells is very crucial for life. We propose a coarse-grained model to study the catenation process of double-stranded DNA (dsDNA) rings regulated by topoisomerase II (TOP2) and provide a computational method to characterize the topological structures of the Olympic gels obtained. The function of TOP2 in the catenation of dsDNA rings is implicitly fulfilled by operating the length of a stretchable catch bond in the dsDNA ring. After the catenation reaction of initially noncatenated dsDNA rings in the solution, the Olympic gel is obtained and the interlocked topology of the dsDNA rings can be characterized by a computational method derived from the HOMFLY polynomial, based on which the catenation degree and the complexity of catenation are quantified. Detailed dependence of the catenation degree and the complexity of the catenated topology on key parameters, including the size of the transient broken gap and the duration time of the break on the dsDNA ring during operation by TOP2, the initial molar ratio of TOP2 to the dsDNA rings, and the reaction temperature, has been investigated.

Structural heterogeneity in tetra-armed gels revealed by computer simulation: Evidence from a graph theory assisted characterization.

Designing homogeneous networks is considered one typical strategy for solving the problem of strength and toughness conflict of polymer network materials. Experimentalists have proposed the hypothesis of obtaining a structurally homogeneous hydrogel by crosslinking tetra-armed polymers, whose homogeneity was claimed to be verified by scattering characterization and other methods. Nevertheless, it is highly desirable to further evaluate this issue from other perspectives. In this study, a coarse-grained molecular dynamics simulation coupled with a stochastic reaction model is applied to reveal the topological structure of a polymer network synthesized by tetra-armed monomers as precursors. Two different scenarios, distinguished by whether internal cross-linking is allowed, are considered. We introduce the Dijkstra algorithm from graph theory to precisely characterize the network structure. The microscopic features of the network structure, e.g., loop size, dispersity, and size distribution, are obtained via the Dijkstra algorithm. By comparing the two reaction scenarios, Scenario II exhibits an overall more idealized structure. Our results demonstrate the feasibility of the Dijkstra algorithm for precisely characterizing the polymer network structure. We expect this work will provide a new insight for the evaluation and description of gel networks and further help to reveal the dynamic process of network formation.

DeepDetect: Deep Learning of Peptide Detectability Enhanced by Peptide Digestibility and Its Application to DIA Library Reduction.

In tandem mass spectrometry-based proteomics, proteins are digested into peptides by specific protease(s), but generally only a fraction of peptides can be detected. To characterize detectable proteotypic peptides, we have developed a series of methods to predict peptide digestibility and detectability. Here, we propose a bidirectional long short-term memory (BiLSTM)-based algorithm, named DeepDetect, for the prediction of peptide detectability enhanced by peptide digestibility. Compared with existing algorithms, DeepDetect is featured by its improved prediction accuracy for a wide range of commonly used proteases, covering trypsin, ArgC, chymotrypsin, GluC, LysC, AspN, LysN, and LysargiNase. On 11 test data sets from E. coli, yeast, mouse, and human samples, DeepDetect achieved higher prediction accuracies than PepFormer, a state-of-the-art deep-learning-based peptide detectability prediction algorithm. The results further demonstrated that peptide digestibility can substantially enhance the performance of peptide detectability predictors. As an application, DeepDetect was used to reduce the in silico predicted spectral libraries in data-independent acquisition mass spectrometry data analysis. Experiments using DIA-NN software showed that DeepDetect can significantly accelerate the library search without loss of peptide and protein identification sensitivity.

Nup96 and HOS1 Are Mutually Stabilized and Gate CONSTANS Protein Level, Conferring Long-Day Photoperiodic Flowering Regulation in Arabidopsis.

The nuclear pore complex profoundly affects the timing of flowering; however, the underlying mechanisms are poorly understood. Here, we report that Nucleoporin96 (Nup96) acts as a negative regulator of long-day photoperiodic flowering in Arabidopsis (Arabidopsis thaliana). Through multiple approaches, we identified the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (HOS1) and demonstrated its interaction in vivo with Nup96. Nup96 and HOS1 mainly localize and interact on the nuclear membrane. Loss of function of Nup96 leads to destruction of HOS1 proteins without a change in their mRNA abundance, which results in overaccumulation of the key activator of long-day photoperiodic flowering, CONSTANS (CO) proteins, as previously reported in hos1 mutants. Unexpectedly, mutation of HOS1 strikingly diminishes Nup96 protein level, suggesting that Nup96 and HOS1 are mutually stabilized and thus form a novel repressive module that regulates CO protein turnover. Therefore, the nup96 and hos1 single and nup96 hos1 double mutants have highly similar early-flowering phenotypes and overlapping transcriptome changes. Together, this study reveals a repression mechanism in which the Nup96-HOS1 repressive module gates the level of CO proteins and thereby prevents precocious flowering in long-day conditions.

Long-term exposure to air pollution and incident non-alcoholic fatty liver disease and cirrhosis: A cohort study.

BACKGROUND AND AIMS: Epidemiological evidence regarding the association of air pollution with the risk of non-alcoholic fatty liver disease (NAFLD) is limited. This study was to examine the associations of long-term exposure to various air pollutants and overall air pollution with risk of incident NAFLD as well as cirrhosis, a major liver-related morbidity for NAFLD. METHODS: Included were 456 687 UK residents. Air pollution data included PM2.5 , PM2.5-10 , PM10 , NO2 and NOx . A weighted air pollution score was also generated from PM10 and NOx . Cox proportional hazard models were employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 4978 cases of NAFLD and 1575 cases of incident cirrhosis, over a median follow-up of 11.9 years. PM2.5 , PM10 , NO2 and NOx exposures contributed to the excess risk of NAFLD associated with air pollution score; and the corresponding adjusted HRs (95% CI) were 1.10 (1.05, 1.14), 1.14 (1.09, 1.20), 1.19 (1.13, 1.24) and 1.11 (1.07, 1.15), respectively, for each interquartile range increase in the above specific air pollutants. Similar patterns were also indicated for cirrhosis risk. Alcohol consumption was an effect modifier for the association between air pollution score and NAFLD risk, whereas body mass index modified the association for cirrhosis risk. CONCLUSION: Long-term exposure to air pollution was associated with risks of NAFLD and cirrhosis among the UK population.

Predictive value of serum apolipoprotein A-I in the organ failure of acute pancreatitis: a retrospective cohort study.

BACKGROUND: Organ failure (OF) largely governs the outcomes and mortality in patients with acute pancreatitis (AP), but there is a lack of optimal prognostic biomarker for OF. This study is designed to investigate whether the serum apolipoprotein A-I (Apo A-I) level can predict OF in patients with AP. METHODS: A total of 424 patients with AP were reviewed in the study, and we finally got 228 patients eligible for analysis. Patients were divided into two groups based on serum Apo A-I level. Demographic information and clinical materials were retrospectively collected. The primary outcome was the occurrence of OF. Univariate and multivariate binary logistic regression were conducted to analyze the relationship between Apo A-I and OF. Additionally, we used receiver operating characteristic analysis to clarify the predictive value of serum Apo A-I level for OF and mortality. RESULTS: Ninety-two patients and 136 patients were included in Apo A-I low and non-low groups, respectively. The occurrence of OF was significantly different in the two groups (35.9 vs. 9.6%, p < 0.001). Moreover, serum Apo A-I level markedly decreased across disease severity based on the 2012 Revised Atlanta Classification of AP. The decrease of serum apolipoprotein A-I was an independent risk factor for organ failure (OR: 6.216, 95% CI: 2.610, 14.806, p < 0.001). The area under the curve of serum Apo A-I was 0.828 and 0.889 for OF and mortality of AP, respectively. CONCLUSIONS: Serum Apo A-I level in the early stage of the disease has a high predictive value for OF of AP.

Mediating effect of metabolic diseases on the relationship between hyperuricemia and coronary heart disease.

BACKGROUND AND AIMS: Studies have shown that elevated serum uric acid (SUA) may increase the risk of coronary heart disease (CHD). However, it is still disputable how mediate effects between metabolic diseases and hyperuricemia affect the incidence of CHD. This study aimed to explore whether metabolic diseases may mediate the connection from hyperuricemia at baseline to the elevated incidence risk of CHD during follow-ups. METHODS AND RESULTS: Based on the Jinchang cohort, 48 001 subjects were followed for 9 years between June 2011 and December 2019. Multivariate-adjusted Cox regression models were applied to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). Significantly increased risks of CHD were observed in hyperuricemia (HR:1.46, 95%CI:1.28, 1.67) when compared with normouricemia population. The mediating effect model further demonstrated that metabolic diseases could mediate the association between hyperuricemia and CHD pathogenesis, partially for the combined metabolic diseases with mediation effects of 45.12%, 25.24% for hypertension, 28.58% for overweight or obese status, 29.05% for hypertriglyceridemia, 6.70% for hypercholesterolemia, 3.52% for low high density lipoprotein cholesterol (HDL-C), and 6.51% for high low density lipoprotein cholesterol (LDL-C), respectively. CONCLUSIONS: Hyperuricemia significantly increased the risk of incident CHD, and this association was partly mediated by metabolic diseases.

Long-Term Stability and Optoelectronic Performance Enhancement of InAsP Nanowires with an Ultrathin InP Passivation Layer.

The influence of nanowire (NW) surface states increases rapidly with the reduction of diameter and hence severely degrades the optoelectronic performance of narrow-diameter NWs. Surface passivation is therefore critical, but it is challenging to achieve long-term effective passivation without significantly affecting other qualities. Here, we demonstrate that an ultrathin InP passivation layer of 2-3 nm can effectively solve these challenges. For InAsP nanowires with small diameters of 30-40 nm, the ultrathin passivation layer reduces the surface recombination velocity by at least 70% and increases the charge carrier lifetime by a factor of 3. These improvements are maintained even after storing the samples in ambient atmosphere for over 3 years. This passivation also greatly improves the performance thermal tolerance of these thin NWs and extends their operating temperature from <150 K to room temperature. This study provides a new route toward high-performance room-temperature narrow-diameter NW devices with long-term stability.

Sex-specific and dose-response relationships of urinary cobalt and molybdenum levels with glucose levels and insulin resistance in U.S. adults.

Growing studies have linked metal exposure to diabetes risk. However, these studies had inconsistent results. We used a multiple linear regression model to investigate the sex-specific and dose-response associations between urinary metals (cobalt (Co) and molybdenum (Mo)) and diabetes-related indicators (fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and insulin) in a cross-sectional study based on the United States National Health and Nutrition Examination Survey. The urinary metal concentrations of 1423 eligible individuals were stratified on the basis of the quartile distribution. Our results showed that the urinary Co level in males at the fourth quartile (Q4) was strongly correlated with increased FPG (ß = 0.61, 95% CI: 0.17-1.04), HbA1c (ß = 0.31, 95% CI: 0.09-0.54), insulin (ß = 8.18, 95% CI: 2.84-13.52), and HOMA-IR (ß = 3.42, 95% CI: 1.40-5.44) when compared with first quartile (Q1). High urinary Mo levels (Q4 vs. Q1) were associated with elevated FPG (ß = 0.46, 95% CI: 0.17-0.75) and HbA1c (ß = 0.27, 95% CI: 0.11-0.42) in the overall population. Positive linear dose-response associations were observed between urinary Co and insulin (Pnonlinear = 0.513) and HOMA-IR (Pnonlinear = 0.736) in males, as well as a positive linear dose-response relationship between urinary Mo and FPG (Pnonlinear = 0.826) and HbA1c (Pnonlinear = 0.376) in the overall population. Significant sex-specific and dose-response relationships were observed between urinary metals (Co and Mo) and diabetes-related indicators, and the potential mechanisms should be further investigated.

The long-term efficacy of transoral incisionless fundoplication with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease.

BACKGROUND: To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD). METHODS: A total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital （Shanghai, China）from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects. RESULTS: Follow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference. CONCLUSION: TIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn. TRIAL REGISTRATION: ChiCTR2000034350.

Demographic, physiological and genetic factors linked to the poleward range expansion of the snail Nerita yoldii along the shoreline of China.

Species range shift is one of the most significant consequences of climate change in the Anthropocene. A comprehensive study, including demographic, physiological and genetic factors linked to poleward range expansion, is crucial for understanding how the expanding population occupies the new habitat. In the present study, we investigated the demographic, physiological and genetic features of the intertidal gastropod Nerita yoldii, which has extended its northern limit by ~200 km over the former biogeographical break of the Yangtze River Estuary in recent decades. Data from neutral single nucleotide polymorphisms (SNPs) showed that the new marginal populations formed a distinct cluster established by a few founders. Demographic modelling analysis revealed that the new marginal populations experienced a strong genetic bottleneck followed by recent demographic expansion. Successful expansion that overcame the founder effect might be attributed to its high capacity for rapid population growth and multiple introductions. According to the non-neutral SNPs under diversifying selection, there were high levels of heterozygosity in the new marginal populations, which might be beneficial for adapting to the novel thermal conditions. The common garden experiment showed that the new marginal populations have evolved divergent transcriptomic and physiological responses to heat stress, allowing them to occupy and survive in the novel environment. Lower transcriptional plasticity was observed in the new marginal populations. These results suggest a new biogeographical pattern of N. yoldii has formed with the occurrence of demographic, physiological and genetic changes, and emphasize the roles of adaptation of marginal populations during range expansion.

Serum Uric Acid Levels and Their Changes and Risk of Stroke: A 7-Year Prospective Cohort Study in Northwest China.

INTRODUCTION: It is not clear whether serum uric acid (SUA) levels and their changes over time are associated with the risk of stroke. A 7-year prospective cohort study in northwest China was conducted to analyze effects of SUA and their changes on the risk of stroke. METHODS: A total of 23,262 individuals without cardiovascular disease in the Jinchang cohort were followed up for an average of 5.26 years. The Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence interval (95% CI) of stroke incidence to SUA and relative changes in SUA. Sensitivity analysis was performed after controlling the effect of renal insufficiency. RESULTS: Baseline SUA and relative changes in SUA were positively correlated with the incidence of stroke in both males and females (p for overall association <0.0001). Stroke risk increased by 4.6% per 10% increase in the relative change of SUA (HR = 1.046, 95% CI, 1.007-1.086). The fully adjusted regression analysis demonstrated that only the large gain (>30%) in SUA was associated with an increased risk of stroke by 36.5% (95% CI, 1.8-83.0%), compared with the reference group (participants within ±10% changes in SUA). The same trend was observed in people with normal baseline SUA. In the unadjusted model, the risk of stroke associated with elevated SUA was significantly higher in the hyperuricemia group than in the normal SUA group. CONCLUSION: High initial SUA concentration and an increase in SUA concentration over time would increase the risk of stroke, and this means that there is no safe increase in SUA.

Ambient Air Pollutants and Incident Microvascular Disease: A Cohort Study.

Little is known about the links between long-term exposure to air pollution and risk of incident microvascular disease (retinopathy, peripheral neuropathy, and chronic kidney disease). This study included 396 014 UK residents free of microvascular disease and macrovascular disease at baseline. Annual means of PM2.5, PM2.5-10, PM10, NO2, and NOx were assessed by land use regression models for each participant. A weighted air pollution score was generated from PM10 and NOx. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 11.7 years, 14 327 composite microvascular disease occurred. While none of the air pollutants showed any statistically significant association with the risk of retinopathy, all the air pollutants were linked to the risk of peripheral neuropathy and chronic kidney disease. The adjusted-HRs (95% CIs) for each interquartile range increase in air pollution score were 1.07 (1.05, 1.09), 1.01 (0.94, 1.07), 1.13 (1.08, 1.19), and 1.07 (1.05, 1.10) for overall microvascular disease, retinopathy, peripheral neuropathy, and chronic kidney disease, respectively. In conclusion, long-term exposure to overall air pollution was associated with higher risks of peripheral neuropathy and chronic kidney disease among the general UK population.

Cohort Profile Update: the China Metal-Exposed workers Cohort Study (Jinchang Cohort).

The Jinchang Cohort was an ongoing 20-year ambispective cohort with unique metal exposures to an occupational population. From January 2014 to December 2019, the Jinchang Cohort has completed three phases of follow-up. The baseline cohort was completed from June 2011 to December 2013, and a total of 48 001 people were included. Three phases of follow-ups included 46 713, 41 888, and 40 530 participants, respectively. The death data were collected from 2001 to 2020. The epidemiological, physical examination, physiological, and biochemical data of the cohort were collected at baseline and during follow-up. Biological specimens were collected on the baseline to establish a biological specimen bank. The concentrations of metals in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The new areas of research aim to study the all-cases mortality, the burden of diseases, heavy metals and diseases, and the course of the chain from disease to high-risk outcomes using a combination of macro and micro means, which provided a scientific basis to explore the pathogenesis of multi-etiology and multi-disease and to evaluate the effects of the intervention measures in the population.

Elevated serum bilirubin may significantly reduce coronary heart disease risk in females: A prospective cohort study.

BACKGROUND AND AIMS: There is still inconsistent evidence over the protective effect of total bilirubin on the development of coronary heart disease (CHD). Therefore, we aimed to investigate the association between bilirubin in population subtypes and the risks of CHD between different gender and menstruation subgroups. METHODS AND RESULTS: In this prospective cohort study, 29,750 participants free of CHD with an average age of 47 ± 14 years were recruited at baseline; of these, 720 CHD first-attack cases were collected after 7-years of follow up. The covariate-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). The serum bilirubin concentration was quarterly stratified based on the distribution of healthy population without CHD onset. The HRs of incident CHD decreased with elevated bilirubin in females (ρ trend<0.05), but not males. In postmenopausal females, compared with the lowest quartile of total bilirubin, the adjusted HRs for the third and fourth quartiles were 0.64 (95% CI: 0.45, 0.93) and 0.59 (95% CI: 0.42, 0.86), the adjusted HRs in the third and fourth quartiles of direct bilirubin were 0.56 (0.39, 0.82) and 0.56 (0.38, 0.81), and for indirect bilirubin, corresponding HR in the highest quartile was 0.56 (0.38, 0.83). CONCLUSION: Elevated serum bilirubin was inversely associated with adjusted HRs of CHD in females, especially postmenopausal females. The relationship between elevated direct bilirubin and reduced HRs of CHD may be closer than indirect bilirubin in postmenopausal females.

Placing a New Filter before Removing Embolized Nonconical Filter: A Report of 13 Cases.

OBJECTIVES: Permanent filter placement may result in numerous complications. Filter removal is recommended if there are no risks of pulmonary embolism. This study aimed to explore the feasibility of placing a new filter when the embolized nonconical filter is removed. METHODS: This study included patients who had received a new filter between 2018 and 2019 before the nonconical filters were removed. Patient characteristics, new filter types, thrombus interception rate, filter removal rate, feasibility, and safety were analyzed retrospectively. Feasibility was defined as the successful placement of new filters and the removal of the nonconical filters. Safety was defined as the absence of symptomatic pulmonary embolism and inferior vena cava hemorrhage after removing the nonconical filters, as well as the successful removal of new filters without symptomatic pulmonary embolism. RESULTS: The average indwelling period of the nonconical filters was 29 (range, 17-30) days among the 13 patients. The removal rate of the nonconical filters was 100%. Five patients (38.5%) received new Denali filters, one (7.7%) received a new Celect filter, and 7 (53.8%) received new temporary filters. Thrombi were intercepted in 10 of the patients (76.9%). The removal rate of the replaced new filters was 100%. No rupture or shifting of the new filters occurred. No symptomatic pulmonary embolism was found after the removal of both the nonconical filters and the new filters. The patients were followed up for 3 months after the surgeries, and the inferior vena cavae of 12 (92.3%) patients were patent, and no new embolic events were found. CONCLUSIONS: Placing a new replacement filter before removal of the embolized nonconical filter may be a feasible approach to prevent pulmonary embolism. Both the nonconical filter and the new filter could be removed subsequently after the thrombi were treated.

Prognosis of lung cancer with simple brain metastasis patients and establishment of survival prediction models: a study based on real events.

OBJECTIVES: The aim of this study was to explore risk factors for the prognosis of lung cancer with simple brain metastasis (LCSBM) patients and to establish a prognostic predictive nomogram for LCSBM patients. MATERIALS AND METHODS: Three thousand eight hundred and six cases of LCSBM were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 using SEER Stat 8.3.5. Lung cancer patients only had brain metastasis with no other organ metastasis were defined as LCSBM patients. Prognostic factors of LCSBM were analyzed with log-rank method and Cox proportional hazards model. Independent risk and protective prognostic factors were used to construct nomogram with accelerated failure time model. C-index was used to evaluate the prediction effect of nomogram. RESULTS AND CONCLUSION: The younger patients (18-65 years old) accounted for 54.41%, while patients aged over 65 accounted for 45.59%.The ratio of male: female was 1:1. Lung cancer in the main bronchus, upper lobe, middle lobe and lower lobe were accounted for 4.91%, 62.80%, 4.47% and 27.82% respectively; and adenocarcinoma accounted for 57.83% of all lung cancer types. The overall median survival time was 12.2 months. Survival rates for 1-, 3- and 5-years were 28.2%, 8.7% and 4.7% respectively. We found female (HR = 0.81, 95% CI 0.75-0.87), the married (HR = 0.80; 95% CI 0.75-0.86), the White (HR = 0.90, 95% CI 0.84-0.95) and primary site (HR = 0.45, 95% CI 0.39-0.52) were independent protective factors while higher age (HR = 1.51, 95% CI 1.40-1.62), advanced grade (HR = 1.19, 95% CI 1.12-1.25) and advanced T stage (HR = 1.09, 95% CI 1.05-1.13) were independent risk prognostic factors affecting the survival of LCSBM patients. We constructed the nomogram with above independent factors, and the C-index value was 0.634 (95% CI 0.622-0.646). We developed a nomogram with seven significant LCSBM independent prognostic factors to provide prognosis prediction.

An Efficient Agrobacterium rhizogenes-Mediated Hairy Root Transformation Method in a Soybean Root Biology Study.

The stable genetic transformation of soybean is time-consuming and inefficient. As a simple and practical alternative method, hairy root transformation mediated by Agrobacterium rhizogenes is widely applied in studying root-specific processes, nodulation, biochemical and molecular functions of genes of interest, gene editing efficiency of CRISPR/Cas9, and biological reactors and producers. Therefore, many laboratories have developed unique protocols to obtain hairy roots in composite plants composed of transgenic roots and wild-type shoots. However, these protocols still suffer from the shortcomings of low efficiency and time, space, and cost consumption. To address this issue, we developed a new protocol efficient regeneration and transformation of hairy roots (eR&T) in soybean, by integrating and optimizing the main current methods to achieve high efficiency in both hairy root regeneration and transformation within a shorter period and using less space. By this eR&T method, we obtained 100% regeneration of hairy roots for all explants, with an average 63.7% of transformation frequency, which promoted the simultaneous and comparative analysis of the function of several genes. The eR&T was experimentally verified Promoter:GUS reporters, protein subcellular localization, and CRISPR/Cas9 gene editing experiments. Employing this approach, we identified several novel potential regulators of nodulation, and nucleoporins of the Nup107-160 sub-complex, which showed development-dependent and tissue-dependent expression patterns, indicating their important roles in nodulation in soybean. Thus, the new eR&T method is an efficient and economical approach for investigating not only root and nodule biology, but also gene function.