Many-body effects in the X-ray absorption spectra of liquid water.

SignificanceIn X-ray absorption spectroscopy, an electron-hole excitation probes the local atomic environment. The interpretation of the spectra requires challenging theoretical calculations, particularly in a system like liquid water, where quantum many-body effects and molecular disorder play an important role. Recent advances in theory and simulation make possible new calculations that are in good agreement with experiment, without recourse to commonly adopted approximations. Based on these calculations, the three features observed in the experimental spectra are unambiguously attributed to excitonic effects with different characteristic correlation lengths, which are distinctively affected by perturbations of the underlying H-bond structure induced by temperature changes and/or by isotopic substitution. The emerging picture of the water structure is fully consistent with the conventional tetrahedral model.

FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response.

Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy.

The 5-formyl-tetrahydrofolate proteome links folates with C/N metabolism and reveals feedback regulation of folate biosynthesis.

Folates are indispensable for plant development, but their molecular mode of action remains elusive. We synthesized a probe, "5-F-THF-Dayne," comprising 5-formyl-tetrahydrofolate (THF) coupled to a photoaffinity tag. Exploiting this probe in an affinity proteomics study in Arabidopsis thaliana, we retrieved 51 hits. Thirty interactions were independently validated with in vitro expressed proteins to bind 5-F-THF with high or low affinity. Interestingly, the interactors reveal associations beyond one-carbon metabolism, covering also connections to nitrogen (N) metabolism, carbohydrate metabolism/photosynthesis, and proteostasis. Two of the interactions, one with the folate biosynthetic enzyme DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE 1 (AtDHFR-TS1) and another with N metabolism-associated glutamine synthetase 1;4 (AtGLN1;4), were further characterized. In silico and experimental analyses revealed G35/K36 and E330 as key residues for the binding of 5-F-THF in AtDHFR-TS1 and AtGLN1;4, respectively. Site-directed mutagenesis of AtGLN1;4 E330, which co-localizes with the ATP-binding pocket, abolished 5-F-THF binding as well as AtGLN1;4 activity. Furthermore, 5-F-THF was noted to competitively inhibit the activities of AtDHFR-TS1 and AtGLN1;4. In summary, we demonstrated a regulatory role for 5-F-THF in N metabolism, revealed 5-F-THF-mediated feedback regulation of folate biosynthesis, and identified a total of 14 previously unknown high-affinity binding cellular targets of 5-F-THF. Together, this sets a landmark toward understanding the role of folates in plant development.

Association between n-3 PUFA and lung function: results from the NHANES 2007-2012 and Mendelian randomisation study.

This study aimed to investigate the association between n-3 PUFA and lung function. First, a cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES) 2007-2012 data. n-3 PUFA intake was obtained from 24-h dietary recalls. A multivariable linear regression model was used to assess the observational associations of n-3 PUFA intake with lung function. Subsequently, a two-sample Mendelian randomisation (MR) was performed to estimate the potential causal effect of n-3 PUFA on lung function. Genetic instrumental variables were extracted from published genome-wide association studies. Summary statistics about n-3 PUFA was from UK Biobank. Inverse variance weighted was the primary analysis approach. The observational study did not demonstrate a significant association between n-3 PUFA intake and most lung function measures; however, a notable exception was observed with significant findings in the highest quartile for forced vital capacity (FVC) and % predicted FVC. The MR results also showed no causal effect of circulating n-3 PUFA concentration on lung function (forced expiratory volume in one second (FEV1), ß = 0·01301, se = 0·01932, P = 0·5006; FVC, ß = -0·001894, se = 0·01704, P = 0·9115; FEV1:FVC, ß = 0·03118, se = 0·01743, P = 0·07359). These findings indicate the need for further investigation into the impact of higher n-3 PUFA consumption on lung health.

Clinical features of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with macrophage activation syndrome.

OBJECTIVES: This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) who had macrophage activation syndrome (MAS). METHODS: We retrospectively examined 44 patients with anti-MDA5-positive DM and compared the clinical features between patients with MAS (n = 11) and those without (n=33). Patients without MAS were selected randomly in the same year as those with MAS at a ratio of 3:1. Among patients with MAS, we compared the features between non-survivors and survivors. We used Fisher's exact test, Student's t test, the Mann-Whitney U test and the log-rank test for statistical analysis. RESULTS: Patients complicated with MAS had a significantly higher incidence of infection, heliotrope sign, Gottron's papule, V-neck sign, and higher serum levels of ferritin, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) than those without MAS (p<0.05). Among the 11 patients with MAS, 4 (36.4%) died after intensive treatment. Deceased patients were older, given more combination therapy with tofacitinib (TOF) and had a higher incidence of rapid progressive interstitial lung disease, infection, heart failure and renal impairment than those who survived (p<0.05). CONCLUSIONS: Among anti-MDA5-positive DM, Infection, DM typical rashes, and higher serum levels of ferritin, AST, LDH, and CK were more common in patients complicated with MAS. The mortality of patients with MAS was high, particularly among patients who were older, given more combination therapy with TOF, and had RP-ILD, infection, heart failure and renal impairment.

Causal associations between gut microbiota, metabolites and asthma: a two-sample Mendelian randomization study.

BACKGROUND: While several traditional observational studies have suggested associations between gut microbiota and asthma, these studies are limited by factors such as participant selection bias, confounders, and reverse causality. Therefore, the causal relationship between gut microbiota and asthma remains uncertain. METHODS: We performed two-sample bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationships between gut microbiota and asthma as well as its phenotypes. We also conducted MR analysis to evaluate the causal effect of gut metabolites on asthma. Genetic variants for gut microbiota were obtained from the MiBioGen consortium, GWAS summary statistics for metabolites from the TwinsUK study and KORA study, and GWAS summary statistics for asthma from the FinnGen consortium. The causal associations between gut microbiota, gut metabolites and asthma were examined using inverse variance weighted, maximum likelihood, MR-Egger, weighted median, and weighted model and further validated by MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis. RESULTS: We identified nine gut microbes whose genetically predicted relative abundance causally impacted asthma risk. After FDR correction, significant causal relationships were observed for two of these microbes, namely the class Bacilli (OR = 0.84, 95%CI = 0.76-0.94, p = 1.98 × 10-3) and the order Lactobacillales (OR = 0.83, 95%CI = 0.74-0.94, p = 1.92 × 10-3). Additionally, in a reverse MR analysis, we observed a causal effect of genetically predicted asthma risk on the abundance of nine gut microbes, but these associations were no longer significant after FDR correction. No significant causal effect of gut metabolites was found on asthma. CONCLUSIONS: Our study provides insights into the development mechanism of microbiota-mediated asthma, as well as into the prevention and treatment of asthma through targeting specific gut microbiota.

Pentatricopeptide repeat protein CNS1 regulates maize mitochondrial complex III assembly and seed development.

Mitochondrial function relies on the assembly of electron transport chain complexes, which requires coordination between proteins encoded by the mitochondrion and those of the nucleus. Here, we cloned a maize (Zea mays) cytochrome c maturation FN stabilizer1 (CNS1) and found it encodes a pentatricopeptide repeat (PPR) protein. Members of the PPR family are widely distributed in plants and are associated with RNA metabolism in organelles. P-type PPR proteins play essential roles in stabilizing the 3'-end of RNA in mitochondria; whether a similar process exists for stabilizing the 5'-terminus of mitochondrial RNA remains unclear. The kernels of cns1 exhibited arrested embryo and endosperm development, whereas neither conventional splicing deficiency nor RNA editing difference in mitochondrial genes was observed. Instead, most of the ccmFN transcripts isolated from cns1 mutant plants were 5'-truncated and therefore lacked the start codon. Biochemical and molecular data demonstrated that CNS1 is a P-type PPR protein encoded by nuclear DNA and that it localizes to the mitochondrion. Also, one binding site of CNS1 located upstream of the start codon in the ccmFN transcript. Moreover, abnormal mitochondrial morphology and dramatic upregulation of alternative oxidase genes were observed in the mutant. Together, these results indicate that CNS1 is essential for reaching a suitable level of intact ccmFN transcripts through binding to the 5'-UTR of the RNAs and maintaining 5'-integrity, which is crucial for sustaining mitochondrial complex III function to ensure mitochondrial biogenesis and seed development in maize.

Why Dissolving Salt in Water Decreases Its Dielectric Permittivity.

The dielectric permittivity of salt water decreases on dissolving more salt. For nearly a century, this phenomenon has been explained by invoking saturation in the dielectric response of the solvent water molecules. Herein, we employ an advanced deep neural network (DNN), built using data from density functional theory, to study the dielectric permittivity of sodium chloride solutions. Notably, the decrease in the dielectric permittivity as a function of concentration, computed using the DNN approach, agrees well with experiments. Detailed analysis of the computations reveals that the dominant effect, caused by the intrusion of ionic hydration shells into the solvent hydrogen-bond network, is the disruption of dipolar correlations among water molecules. Accordingly, the observed decrease in the dielectric permittivity is mostly due to increasing suppression of the collective response of solvent waters.

DNA Logic Circuits for Cancer Theranostics.

Cancer diagnosis and therapeutics (theranostics) based on the tumor microenvironment (TME) and biomarkers has been an emerging approach for precision medicine. DNA nanotechnology dynamically controls the self-assembly of DNA molecules at the nanometer scale to construct intelligent DNA chemical reaction systems. The DNA logic circuit is a particularly emerging approach for computing within the DNA chemical systems. DNA logic circuits can sensitively respond to tumor-specific markers and the TME through logic operations and signal amplification, to generate detectable signals or to release anti-cancer agents. In this review, the fundamental concepts of DNA logic circuits are clarified, the basic modules in the circuit are summarized, and how this advanced nano-assembly circuit responds to tumor-related molecules, how to perform logic operations, to realize signal amplification, and selectively release drugs through discussing over 30 application examples, are demonstrated. This review shows that DNA logic circuits have powerful logic judgment and signal amplification functions in improving the specificity and sensitivity of cancer diagnosis and making cancer treatment controllable. In the future, researchers are expected to overcome the existing shortcomings of DNA logic circuits and design smarter DNA devices with better biocompatibility and stability, which will further promote the development of cancer theranostics.

A spatiotemporal transcriptomic network dynamically modulates stalk development in maize.

Maize (Zea mays) is an important cereal crop with suitable stalk formation which is beneficial for acquiring an ideal agronomic trait to resist lodging and higher planting density. The elongation pattern of stalks arises from the variable growth of individual internodes driven by cell division and cell expansion comprising the maize stalk. However, the spatiotemporal dynamics and regulatory network of the maize stalk development and differentiation process remain unclear. Here, we report spatiotemporally resolved transcriptomes using all internodes of the whole stalks from developing maize at the elongation and maturation stages. We identified four distinct groups corresponding to four developmental zones and nine specific clusters with diverse spatiotemporal expression patterns among individual internodes of the stalk. Through weighted gene coexpression network analysis, we constructed transcriptional regulatory networks at a fine spatiotemporal resolution and uncovered key modules and candidate genes involved in internode maintenance, elongation, and division that determine stalk length and thickness in maize. Further CRISPR/Cas9-mediated knockout validated the function of a cytochrome P450 gene, ZmD1, in the regulation of stalk length and thickness as predicted by the WGCN. Collectively, these results provide insights into the high genetic complexity of stalk development and the potentially valuable resources with ideal stalk lengths and widths for genetic improvements in maize.

A Subsidiary Cell-Localized Glucose Transporter Promotes Stomatal Conductance and Photosynthesis.

It has long been recognized that stomatal movement modulates CO2 availability and as a consequence the photosynthetic rate of plants, and that this process is feedback-regulated by photoassimilates. However, the genetic components and mechanisms underlying this regulatory loop remain poorly understood, especially in monocot crop species. Here, we report the cloning and functional characterization of a maize (Zea mays) mutant named closed stomata1 (cst1). Map-based cloning of cst1 followed by confirmation with the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 system identified the causal mutation in a Clade I Sugars Will Eventually be Exported Transporters (SWEET) family gene, which leads to the E81K mutation in the CST1 protein. CST1 encodes a functional glucose transporter expressed in subsidiary cells, and the E81K mutation strongly impairs the oligomerization and glucose transporter activity of CST1. Mutation of CST1 results in reduced stomatal opening, carbon starvation, and early senescence in leaves, suggesting that CST1 functions as a positive regulator of stomatal opening. Moreover, CST1 expression is induced by carbon starvation and suppressed by photoassimilate accumulation. Our study thus defines CST1 as a missing link in the feedback-regulation of stomatal movement and photosynthesis by photoassimilates in maize.

DeePKS + ABACUS as a Bridge between Expensive Quantum Mechanical Models and Machine Learning Potentials.

Recently, the development of machine learning (ML) potentials has made it possible to perform large-scale and long-time molecular simulations with the accuracy of quantum mechanical (QM) models. However, for different levels of QM methods, such as density functional theory (DFT) at the meta-GGA level and/or with exact exchange, quantum Monte Carlo, etc., generating a sufficient amount of data for training an ML potential has remained computationally challenging due to their high cost. In this work, we demonstrate that this issue can be largely alleviated with Deep Kohn-Sham (DeePKS), an ML-based DFT model. DeePKS employs a computationally efficient neural network-based functional model to construct a correction term added upon a cheap DFT model. Upon training, DeePKS offers closely matched energies and forces compared with high-level QM method, but the number of training data required is orders of magnitude less than that required for training a reliable ML potential. As such, DeePKS can serve as a bridge between expensive QM models and ML potentials: one can generate a decent amount of high-accuracy QM data to train a DeePKS model and then use the DeePKS model to label a much larger amount of configurations to train an ML potential. This scheme for periodic systems is implemented in a DFT package ABACUS, which is open source and ready for use in various applications.

Structural and dynamic properties of solvated hydroxide and hydronium ions in water from ab initio modeling.

Predicting the asymmetric structure and dynamics of solvated hydroxide and hydronium in water from ab initio molecular dynamics (AIMD) has been a challenging task. The difficulty mainly comes from a lack of accurate and efficient exchange-correlation functional in elucidating the amphiphilic nature and the ubiquitous proton transfer behaviors of the two ions. By adopting the strongly constrained and appropriately normed (SCAN) meta-generalized gradient approximation functional in AIMD simulations, we systematically examine the amphiphilic properties, the solvation structures, the electronic structures, and the dynamic properties of the two water ions. In particular, we compare these results to those predicted by the PBE0-TS functional, which is an accurate yet computationally more expensive exchange-correlation functional. We demonstrate that the general-purpose SCAN functional provides a reliable choice for describing the two water ions. Specifically, in the SCAN picture of water ions, the appearance of the fourth and fifth hydrogen bonds near hydroxide stabilizes the pot-like shape solvation structure and suppresses the structural diffusion, while the hydronium stably donates three hydrogen bonds to its neighbors. We apply a detailed analysis of the proton transfer mechanism of the two ions and find the two ions exhibit substantially different proton transfer patterns. Our AIMD simulations indicate that hydroxide diffuses more slowly than hydronium in water, which is consistent with the experimental results.

Prognostic significance of tumor-infiltrating lymphocytes and macrophages in nasopharyngeal carcinoma: a systematic review and meta-analysis.

PURPOSE: Many studies have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating macrophages (TIMs) in patients with nasopharyngeal carcinoma (NPC), but the results remain controversial. Here, we performed a meta-analysis to evaluate the prognostic significance of TILs/TIMs in patients with NPC METHODS: The study was registered with PROSPERO (CRD42021234078). PubMed, Embase, and Web of Science databases were searched up to Dec 30, 2020. We reviewed studies that evaluated the relationship between TILs/TIMs and overall survival (OS), disease-free survival (DFS), or progression-free survival (PFS) in NPC. For TILs, CD3, CD4, CD8, and FOXP3 were searched as T-cell markers, CD19 and CD20 as B-cell markers, and CD56 as a natural killer cell marker. For TIMs, CD68 and CD163 were searched as total and M2 macrophage markers, respectively. RESULTS: In total, 19 studies with 3708 NPC were included in this meta-analysis. We found that high total numbers of TILs were significantly associated with favorable OS [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.38-0.57 and PFS (HR 0.48, 95% CI 0.38-0.62)]. In contrast, tumor infiltration by CD3+ T cells (HR 0.55, 95% CI 0.39-0.76), CD4+ T cells (HR 0.40, 95% CI 0.18-0.85), and CD8+ T cells (HR 0.56, 95% CI 0.34-0.93) correlated positively with OS. No significant relationship was found between survival and tumor infiltration by FOXP3+ T cells, CD68+ macrophages, or CD163+ macrophages. CONCLUSION: Our findings revealed that tumor infiltration by CD3+ , CD4+ , and CD8+ T cells could be prognostic biomarkers in NPC.

Comparative Transcriptome Analysis Reveals Mechanisms of Folate Accumulation in Maize Grains.

Previously, the complexity of folate accumulation in the early stages of maize kernel development has been reported, but the mechanisms of folate accumulation are unclear. Two maize inbred lines, DAN3130 and JI63, with different patterns of folate accumulation and different total folate contents in mature kernels were used to investigate the transcriptional regulation of folate metabolism during late stages of kernel formation by comparative transcriptome analysis. The folate accumulation during DAP 24 to mature kernels could be controlled by circumjacent pathways of folate biosynthesis, such as pyruvate metabolism, glutamate metabolism, and serine/glycine metabolism. In addition, the folate variation between these two inbred lines was related to those genes among folate metabolism, such as genes in the pteridine branch, para-aminobenzoate branch, serine/tetrahydrofolate (THF)/5-methyltetrahydrofolate cycle, and the conversion of THF monoglutamate to THF polyglutamate. The findings provided insight into folate accumulation mechanisms during maize kernel formation to promote folate biofortification.

Effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of GDM.

To investigate the effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of gestational diabetes mellitus. 3966 pregnant women were enrolled in this study. Multivariate logistic regression analysis was conducted to estimate the relative risk between pre-pregnancy BMI, gestational weight gain, and adverse pregnancy outcome. Pre-pregnancy BMI was found to be a risk factor for preeclampsia (OR = 1.159), gestational diabetes mellitus (OR = 1.191), gestational hypertension (OR = 1.221), and macrosomia (OR = 1.165). Gestational weight gain was a risk factor for preeclampsia (OR = 1.783), placental abruption (OR = 2.209), and macrosomia (OR = 1.506). Total weight gain during pregnancy cannot be used as a predictor of GDM. Pre-pregnancy BMI is a risk factor for gestational diabetes mellitus complicated with preeclampsia, preterm delivery, gestational hypertension, and macrosomia. Impact statementWhat is already known on this subject? Obesity during pregnancy includes pre-pregnancy obesity and excessive weight gain during pregnancy. Obese pregnant women have a higher risk of pregnancy complications.What do the results of this study add? We focus on the effects of pre-pregnancy BMI on pregnancy outcomes, classified by Asian criteria. Our findings suggest for the first time that excessive weight gain during pregnancy is a risk factor for placental abruption and we specifically point out that total weight gain during pregnancy cannot be used as a predictor of GDM.What are the implications of these findings for clinical practice and/or further research? This study is helpful to monitor the risk of adverse pregnancy outcomes in the Asian population and suggest the risk of pregnancy complications, such as gestational diabetes mellitus and placental abruption.

Single-course antenatal corticosteroids is related to faster growth in very-low-birth-weight infant.

BACKGROUND: Antenatal corticosteroids (ACS) treatment is critical to support survival and lung maturation in preterm infants, however, its effect on feeding and growth is unclear. Prior preterm delivery, it remains uncertain whether ACS treatment should be continued if possible (repeated course ACS), until a certain gestational age is reached. We hypothesized that the association of single-course ACS with feeding competence and postnatal growth outcomes might be different from that of repeated course ACS in very-low-birth-weight preterm infants. METHODS: A multicenter retrospective cohort study was conducted in very-low-birth-weight preterm infants born at 23-37 weeks' gestation in South China from 2011 to 2014. Data on growth, nutritional and clinical outcomes were collected. Repeated course ACS was defined in this study as two or more courses ACS (more than single-course). Infants were stratified by gestational age (GA), including GA < 28 weeks, 28 weeks ≤ GA < 32 weeks and 32 weeks ≤ GA < 37 weeks. Multiple linear regression and multilevel model were applied to analyze the association of ACS with feeding and growth outcomes. RESULTS: A total of 841 infants were recruited. The results, just in very-low-birth-weight preterm infants born at 28-32 weeks' gestation, showed both single and repeated course of ACS regimens had shorter intubated ventilation time compared to non-ACS regimen. Single-course ACS promoted the earlier application of amino acid and enteral nutrition, and higher rate of weight increase (15.71; 95%CI 5.54-25.88) than non-ACS after adjusting for potential confounding factors. No associations of repeated course ACS with feeding, mean weight and weight increase rate were observed. CONCLUSIONS: Single-course ACS was positively related to feeding and growth outcomes in very-low-birth-weight preterm infants born at 28-32 weeks' gestation. However, the similar phenomenon was not observed in the repeated course of ACS regimen.

Plasma Heat Shock Protein 90 Alpha: A Valuable Predictor of Early Chemotherapy Effectiveness in Advanced Non-Small-Cell Lung Cancer.

BACKGROUND Heat shock protein-90 alpha (HSP90a) is more abundant in non-small-cell lung cancer (NSCLC) patients than in control individuals. However, whether it can reflect chemotherapy efficacy remains unknown. This study aimed to investigate the association of HSP90a with chemotherapy in advanced NSCLC. MATERIAL AND METHODS We retrospectively evaluated data from patients admitted to the Department of Respiratory Medicine, Shaoxing People's Hospital, from September 2016 to September 2018 with stage IIIB or IV NSCLC and administered 4 cycles of third-generation platinum-based combination chemotherapy (2 drugs simultaneously). Based on the RECIST1.1 criteria, complete remission (CR), partial response (PR), and stable disease (SD) in 60 cases were determined before and after chemotherapy. Before chemotherapy and after 1, 2, and 4 cycles of chemotherapy, plasma HSP90alpha levels were quantitated by ELISA. Chest CT was performed before and after 2 and 4 cycles of chemotherapy. RESULTS After 1-4 cycles of chemotherapy, plasma HSP90alpha levels were significantly lower than pre-chemotherapy levels (P<0.05). The sums of the longest tumor diameters after 2 and 4 cycles of chemotherapy were decreased compared with pre-chemotherapy values (P<0.05). Plasma HSP90alpha levels and tumor size showed no significant correlation before and after chemotherapy (r=0.244, P=0.06). CONCLUSIONS Plasma HSP90alpha can be considered a valuable predictor of early chemotherapy effectiveness in advanced NSCLC, and is positively correlated with tumor remission after chemotherapy. However, plasma HSP90alpha level is not correlated with tumor diameter and pathological type.

Behcet's disease with peripheral nervous system involvement successfully treated with golimumab: a case report and review of the literature.

Nervous system involvement is a rare and serious complication of Behcet's disease (BD), and the peripheral type is rarer. This article aimed to describe a case of BD with the peripheral nervous system (PNS) involvement and present a comprehensive literature review. One case of BD with PNS involvement was reported and related literature was retrospectively reviewed via PubMed/MEDLINE and Scopus database. The patient was resistant to traditional treatments, such as glucocorticoids and immunosuppressants, but had rapid quiescence after using golimumab. Our literature review suggests that the involved peripheral nerves in BD were diverse, the most common were the tibial nerves and peroneal nerves, vasculitis might be the main cause, and prednisone was still the cornerstone of treatment. TNF-α inhibitors have been increasingly used for refractory BD in recent years. This well-illustrated case demonstrates the potential benefit of golimumab to the patient with PNS involvement. Given the diversity and complexity of PNS involvement, we recommend golimumab as a new trial treatment in clinical practice.

Transcriptome Analysis of Tolerant and Susceptible Maize Genotypes Reveals Novel Insights about the Molecular Mechanisms Underlying Drought Responses in Leaves.

Maize (Zea mays L.) is the most essential food crop in the world. However, maize is highly susceptible to drought stress, especially at the seedling stage, and the molecular mechanisms underlying drought tolerance remain elusive. In this study, we conducted comparative transcriptome and physiological analyses of drought-tolerant (CML69) and susceptible (LX9801) inbred lines subjected to drought treatment at the seedling stage for three and five days. The tolerant line had significantly higher relative water content in the leaves, as well as lower electrolyte leakage and malondialdehyde levels, than the susceptible line. Using an RNA-seq-based approach, we identified 10,084 differentially expressed genes (DEGs) with 6906 and 3178 DEGs been annotated and unannotated, respectively. Two critical sets of drought-responsive DEGs, including 4687 genotype-specific and 2219 common drought-responsive genes, were mined out of the annotated DEGs. The tolerant-line DEGs were predominantly associated with the cytoskeleton, cell wall modification, glycolysis/gluconeogenesis, transport, osmotic regulation, drought avoidance, ROS scavengers, defense, and transcriptional factors. For the susceptible line, the DEGs were highly enriched in the photosynthesis, histone, and carbon fixation pathways. The unannotated DEGs were implicated in lncRNAs, including 428 previously reported and 22% putative TE-lncRNAs. There was consensus on both the physiological response and RNA-seq outcomes. Collectively, our findings will provide a comprehensive basis of the molecular networks mediating drought stress tolerance of maize at the seedling stage.