Extracellular matrix stiffness and tumor-associated macrophage polarization: new fields affecting immune exclusion.

In the malignant progression of tumors, there is deposition and cross-linking of collagen, as well as an increase in hyaluronic acid content, which can lead to an increase in extracellular matrix stiffness. Recent research evidence have shown that the extracellular matrix plays an important role in angiogenesis, cell proliferation, migration, immunosuppression, apoptosis, metabolism, and resistance to chemotherapeutic by the alterations toward both secretion and degradation. The clinical importance of tumor-associated macrophage is increasingly recognized, and macrophage polarization plays a central role in a series of tumor immune processes through internal signal cascade, thus regulating tumor progression. Immunotherapy has gradually become a reliable potential treatment strategy for conventional chemotherapy resistance and advanced cancer patients, but the presence of immune exclusion has become a major obstacle to treatment effectiveness, and the reasons for their resistance to these approaches remain uncertain. Currently, there is a lack of exact mechanism on the regulation of extracellular matrix stiffness and tumor-associated macrophage polarization on immune exclusion. An in-depth understanding of the relationship between extracellular matrix stiffness, tumor-associated macrophage polarization, and immune exclusion will help reveal new therapeutic targets and guide the development of clinical treatment methods for advanced cancer patients. This review summarized the different pathways and potential molecular mechanisms of extracellular matrix stiffness and tumor-associated macrophage polarization involved in immune exclusion and provided available strategies to address immune exclusion.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study.

BACKGROUND: Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS: Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS: Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION: FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.

cis-Regulatory variation affecting gene expression contributes to the improvement of maize kernel size.

cis-Regulatory variations contribute to trait evolution and adaptation during crop domestication and improvement. As the most important harvested organ in maize (Zea mays L.), kernel size has undergone intensive selection for size. However, the associations between maize kernel size and cis-regulatory variations remain unclear. We chose two independent association populations to dissect the genetic architecture of maize kernel size together with transcriptomic and genotypic data. The resulting phenotypes reflected a strong influence of population structure on kernel size. Compared with genome-wide association studies (GWASs), which accounted for population structure and relatedness, GWAS based on a naïve or simple linear model revealed additional associated single-nucleotide polymorphisms significantly involved in the conserved pathways controlling seed size in plants. Regulation analyses through expression quantitative trait locus mapping revealed that cis-regulatory variations likely control kernel size by fine-tuning the expression of proximal genes, among which ZmKL1 (GRMZM2G098305) was transgenically validated. We also proved that the pyramiding of the favorable cis-regulatory variations has contributed to the improvement of maize kernel size. Collectively, our results demonstrate that cis-regulatory variations, together with their regulatory genes, provide excellent targets for future maize improvement.

Strong External Electric Fields Reduce Explosive Sensitivity: A Theoretical Investigation into the Reaction Selectivity in NH2NO2∙∙∙NH3.

Controlling the selectivity of a detonation initiation reaction of explosive is essential to reduce sensitivity, and it seems impossible to reduce it by strengthening the external electric field. To verify this, the effects of external electric fields on the initiation reactions in NH2NO2∙∙∙NH3, a model system of the nitroamine explosive with alkaline additive, were investigated at the MP2/6-311++G(2d,p) and CCSD(T)/6-311++G(2d,p) levels. The concerted effect in the intermolecular hydrogen exchange is characterized by an index of the imaginary vibrations. Due to the weakened concerted effects by the electric field along the -x-direction opposite to the "reaction axis", the dominant reaction changes from the intermolecular hydrogen exchange to 1,3-intramolecular hydrogen transference with the increase in the field strengths. Furthermore, the stronger the field strengths, the higher the barrier heights become, indicating the lower sensitivities. Therefore, by increasing the field strength and adjusting the orientation between the field and "reaction axis", not only can the reaction selectivity be controlled, but the sensitivity can also be reduced, in particular under a super-strong field. Thus, a traditional concept, in which the explosive is dangerous under the super-strong external electric field, is theoretically broken. Compared to the neutral medium, a low sensitivity of the explosive with alkaline can be achieved under the stronger field. Employing atoms in molecules, reduced density gradient, and surface electrostatic potentials, the origin of the reaction selectivity and sensitivity change is revealed. This work provides a new idea for the technical improvement regarding adding the external electric field into the explosive system.

Fine mapping qKRN5.04 provides a functional gene negatively regulating maize kernel row number.

KEY MESSAGE: Zm00001d016075 was identified by fine mapping qKRN5.04. The function of Zm00001d016075, negatively modulating maize (Zea Mays L.) kernel row number (KRN), was verified by CRISPR-Cas9. InDel308 located in the promoter of Zm00001d016075 has potential for use as a molecular marker to identify KRN in maize breeding. Kernel row number (KRN), controlled by multiple quantitative trait loci (QTLs), is one of the most important traits that relate to maize production and domestication. Here, fine mapping was conducted to study a major QTL, qKRN5.04, to a 65-kb genomic region using a progeny test strategy in an advanced backcross population, in which Nong531 (N531) and the inbred line of Silunuo (SLN) were employed as the recurrent and the donor parent, respectively. Within this region, there was only one gene (Zm00001d016075) based on the B73 reference genome. Furthermore, we performed regional association mapping using a panel of 236 diverse inbred lines and observed that all significant SNPs were located within Zm00001d016075. The expression of Zm00001d016075 was significantly higher in N531 and qKRN5.04N531 than qKRN5.04SLN, resulting from the different promoter activity of Zm00001d016075. Sequence analysis revealed that InDel308, located in the promoter of Zm00001d016075, was related to the KRN variation in different maize inbred lines. Using the CRISPR-Cas9 strategy, we determined Zm00001d016075 played a role in negatively regulating KRN and had a moderate effect on 10-kernel width, 100-kernel weight, kernels per ear, and grain yield per ear. These results provide critical insights on the genetic basis and quantitative variation for KRN.

Genome-wide association studies and whole-genome prediction reveal the genetic architecture of KRN in maize.

BACKGROUND: Kernel row number (KRN) is an important trait for the domestication and improvement of maize. Exploring the genetic basis of KRN has great research significance and can provide valuable information for molecular assisted selection. RESULTS: In this study, one single-locus method (MLM) and six multilocus methods (mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB and ISIS EM-BLASSO) of genome-wide association studies (GWASs) were used to identify significant quantitative trait nucleotides (QTNs) for KRN in an association panel including 639 maize inbred lines that were genotyped by the MaizeSNP50 BeadChip. In three phenotyping environments and with best linear unbiased prediction (BLUP) values, the seven GWAS methods revealed different numbers of KRN-associated QTNs, ranging from 11 to 177. Based on these results, seven important regions for KRN located on chromosomes 1, 2, 3, 5, 9, and 10 were identified by at least three methods and in at least two environments. Moreover, 49 genes from the seven regions were expressed in different maize tissues. Among the 49 genes, ARF29 (Zm00001d026540, encoding auxin response factor 29) and CKO4 (Zm00001d043293, encoding cytokinin oxidase protein) were significantly related to KRN, based on expression analysis and candidate gene association mapping. Whole-genome prediction (WGP) of KRN was also performed, and we found that the KRN-associated tagSNPs achieved a high prediction accuracy. The best strategy was to integrate all of the KRN-associated tagSNPs identified by all GWAS models. CONCLUSIONS: These results aid in our understanding of the genetic architecture of KRN and provide useful information for genomic selection for KRN in maize breeding.

The retromer protein ZmVPS29 regulates maize kernel morphology likely through an auxin-dependent process(es).

Kernel size and morphology are two important yield-determining traits in maize, but their molecular and genetic mechanisms are poorly characterized. Here, we identified a major QTL, qKM4.08, which explains approximately 24.20% of the kernel morphology variance in a recombinant population derived from two elite maize inbred lines, Huangzaosi (HZS, round kernel) and LV28 (slender kernel). Positional cloning and transgenic analysis revealed that qKM4.08 encodes ZmVPS29, a retromer complex component. Compared with the ZmVPS29 HZS allele, the ZmVPS29 LV28 allele showed higher expression in developing kernels. Overexpression of ZmVPS29 conferred a slender kernel morphology and increased the yield per plant in different maize genetic backgrounds. Sequence analysis revealed that ZmVPS29 has been under purifying selection during maize domestication. Association analyses identified two significant kernel morphology-associated polymorphic sites in the ZmVPS29 promoter region that were significantly enriched in modern maize breeding lines. Further study showed that ZmVPS29 increased auxin accumulation during early kernel development by enhancing auxin biosynthesis and transport and reducing auxin degradation and thereby improved kernel development. Our results suggest that ZmVPS29 regulates kernel morphology, most likely through an auxin-dependent process(es).

Candidate loci for the kernel row number in maize revealed by a combination of transcriptome analysis and regional association mapping.

BACKGROUND: The kernel row number (KRN) of an ear is an important trait related to yield and domestication in maize. Exploring the underlying genetic mechanisms of KRN has great research significance and application potential. RESULTS: In the present study, N531 with a KRN of 18-22 and SLN with a KRN of 4-6 were used as the recurrent parent and the donor parent, respectively, to develop two introgression lines (ILs), IL_A and IL_B, both of which have common negative-effect alleles from SLN on chromosomes 1, 5 and 10 and significantly reduced inflorescence meristem (IM) diameter and KRN compared with those of N531. We used RNA-Seq to investigate the transcriptome profiles of 5-mm immature ears of N531, IL_A and IL_B. We identified a total of 2872 differentially expressed genes (DEGs) between N531 and IL_A, 2428 DEGs between N531 and IL_B and 1811 DEGs between IL_A and IL_B. A total of 1252 DEGs were detected as overlapping DEGs, and 89 DEGs were located on the common introgression fragments. Furthermore, three DEGs (Zm00001d013277, Zm00001d015310 and Zm00001d015377) containing three SNPs associated with KRN were identified using regional association mapping. CONCLUSIONS: These results will facilitate our understanding of ear development and provide important candidate genes for further study on KRN.

Characterization and fine mapping of qkrnw4, a major QTL controlling kernel row number in maize.

KEY MESSAGE: A major QTL controlling kernel row number, qkrnw4, was identified by combining linkage analysis and association mapping. Within qkrnw4, on the basis of its expression and bioinformatics analysis, Zm00001d052910 was supposed to be the candidate gene for kernel row number. Kernel row number (KRN) is an important yield-related trait that affects kernel number in maize. Understanding the genetic basis of KRN is important for increasing maize yields. In the present study, by the use of a near-isogenic line (NIL) that has a B73 background and that consistently displays a low KRN across environments, qkrnw4, a major quantitative trait locus (QTL) associated with KRN within a yield trait-related QTL hotspot in bin 4.08, was finely mapped to an ~ 33-kb interval. Regional association analysis of a nested association mapping population comprising 5000 recombinant inbred lines revealed Zm00001d052910, which encodes a protein with an unknown function, as the important candidate gene responsible for qkrnw4. Different expression levels of this candidate gene in immature ears were detected between the NIL and its recurrent parent. Moreover, the expression of several auxin-related genes was consistent with that of the candidate gene. Furthermore, the potential associations of this candidate gene with well-known inflorescence-related genes were discussed. The results of this study provide important information for the genetic elucidation of KRN variation in maize.

Genome-wide analysis of the pentatricopeptide repeat gene family in different maize genomes and its important role in kernel development.

BACKGROUND: The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in land plants (450 PPR genes in Arabidopsis, 477 PPR genes in rice and 486 PPR genes in foxtail millet) and is important for plant development and growth. Most PPR genes are encoded by plastid and mitochondrial genomes, and the gene products regulate the expression of the related genes in higher plants. However, the functions remain largely unknown, and systematic analysis and comparison of the PPR gene family in different maize genomes have not been performed. RESULTS: In this study, systematic identification and comparison of PPR genes from two elite maize inbred lines, B73 and PH207, were performed. A total of 491 and 456 PPR genes were identified in the B73 and PH207 genomes, respectively. Basic bioinformatics analyses, including of the classification, gene structure, chromosomal location and conserved motifs, were conducted. Examination of PPR gene duplication showed that 12 and 15 segmental duplication gene pairs exist in the B73 and PH207 genomes, respectively, with eight duplication events being shared between the two genomes. Expression analysis suggested that 53 PPR genes exhibit qualitative variations in the different genetic backgrounds. Based on analysis of the correlation between PPR gene expression in kernels and kernel-related traits, four PPR genes are significantly negatively correlated with hundred kernel weight, 12 are significantly negatively correlated with kernel width, and eight are significantly correlated with kernel number. Eight of the 24 PPR genes are also located in metaQTL regions associated with yield and kernel-related traits in maize. Two important PPR genes (GRMZM2G353195 and GRMZM2G141202) might be regarded as important candidate genes associated with maize kernel-related traits. CONCLUSIONS: Our results provide a more comprehensive understanding of PPR genes in different maize inbred lines and identify important candidate genes related to kernel development for subsequent functional validation in maize.

Characterization and fine mapping of qkc7.03: a major locus for kernel cracking in maize.

KEY MESSAGE: A major locus conferring kernel cracking in maize was characterized and fine mapped to an interval of 416.27 kb. Meanwhile, combining the results of transcriptomic analysis, the candidate gene was inferred. Seed development requires a proper structural and physiological balance between the maternal tissues and the internal structures of the seeds. In maize, kernel cracking is a disorder in this balance that seriously limits quality and yield and is characterized by a cracked pericarp at the kernel top and endosperm everting. This study elucidated the genetic basis and characterization of kernel cracking. Primarily, a near isogenic line (NIL) with a B73 background exhibited steady kernel cracking across environments. Therefore, deprived mapping populations were developed from this NIL and its recurrent parent B73. A major locus on chromosome 7, qkc7.03, was identified to be associated with the cracking performance. According to a progeny test of recombination events, qkc7.03 was fine mapped to a physical interval of 416.27 kb. In addition, obvious differences were observed in embryo development and starch granule arrangement within the endosperm between the NIL and its recurrent parent upon the occurrence of kernel cracking. Moreover, compared to its recurrent parent, the transcriptome of the NIL showed a significantly down-regulated expression of genes related to zeins, carbohydrate synthesis and MADS-domain transcription factors. The transcriptomic analysis revealed ten annotated genes within the target region of qkc7.03, and only GRMZM5G899476 was differently expressed between the NIL and its recurrent parent, indicating that this gene might be a candidate gene for kernel cracking. The results of this study facilitate the understanding of the potential mechanism underlying kernel cracking in maize.

Identification of genetic variants associated with maize flowering time using an extremely large multi-genetic background population.

Flowering time is one of the major adaptive traits in domestication of maize and an important selection criterion in breeding. To detect more maize flowering time variants we evaluated flowering time traits using an extremely large multi- genetic background population that contained more than 8000 lines under multiple Sino-United States environments. The population included two nested association mapping (NAM) panels and a natural association panel. Nearly 1 million single-nucleotide polymorphisms (SNPs) were used in the analyses. Through the parallel linkage analysis of the two NAM panels, both common and unique flowering time regions were detected. Genome wide, a total of 90 flowering time regions were identified. One-third of these regions were connected to traits associated with the environmental sensitivity of maize flowering time. The genome-wide association study of the three panels identified nearly 1000 flowering time-associated SNPs, mainly distributed around 220 candidate genes (within a distance of 1 Mb). Interestingly, two types of regions were significantly enriched for these associated SNPs - one was the candidate gene regions and the other was the approximately 5 kb regions away from the candidate genes. Moreover, the associated SNPs exhibited high accuracy for predicting flowering time.

Fine-mapping of qGW4.05, a major QTL for kernel weight and size in maize.

BACKGROUND: Kernel weight and size are important components of grain yield in cereals. Although some information is available concerning the map positions of quantitative trait loci (QTL) for kernel weight and size in maize, little is known about the molecular mechanisms of these QTLs. qGW4.05 is a major QTL that is associated with kernel weight and size in maize. We combined linkage analysis and association mapping to fine-map and identify candidate gene(s) at qGW4.05. RESULTS: QTL qGW4.05 was fine-mapped to a 279.6-kb interval in a segregating population derived from a cross of Huangzaosi with LV28. By combining the results of regional association mapping and linkage analysis, we identified GRMZM2G039934 as a candidate gene responsible for qGW4.05. Candidate gene-based association mapping was conducted using a panel of 184 inbred lines with variable kernel weights and kernel sizes. Six polymorphic sites in the gene GRMZM2G039934 were significantly associated with kernel weight and kernel size. CONCLUSION: The results of linkage analysis and association mapping revealed that GRMZM2G039934 is the most likely candidate gene for qGW4.05. These results will improve our understanding of the genetic architecture and molecular mechanisms underlying kernel development in maize.

[Expression of ZEB1 in the prepuce of hypospadias children and its implication].

OBJECTIVE: To investigate the expression of zinc finger E-box binding homebox 1 (ZEB1) in the prepuce of hypospadias children and its relationship to the incidence of hypospadias. METHODS: Prepuce tissues were collected from 37 children aged 6-15 months undergoing hypospadias repair and 11 age-matched controls receiving circumcision. Based on the position of the urethral meatus, the hypospadias cases were classified as severe (n = 13) and mild-moderate (n = 24). The mRNA and protein expressions of ZEB1 were determined by immunohistochemistry and RT-PCR. RESULTS: The expression of the ZEB1 protein was remarkably higher in the severe (100% [13/13]) and mild-moderate hypospadias patients (75.0% [18/24]) than in the controls (9.1% [1/11]), with statistically significant differences between any two groups (P < 0.05). RT-PCR showed the integrated density value (IDV) of the ZEB1 mRNA expression to be (0.67 ± 0.21), (0.81 ± 0.24), and (1.55 ± 0.29) in the control, mild-moderate, and severe hypospadias patients, respectively, significantly higher in the severe hypospadias than in the control and mild-moderate hypospadias groups (P < 0.05), but with no significant difference between the latter two (P = 0.64). CONCLUSION: The expression of ZEB1 is significantly increased in hypospadias patients, and its upregulation is positively correlated with the severity of hypospadias, which suggests that the overexpression of ZEB1 may contribute to the development of hypospadias.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Hydrothermally formed functional niobium oxide doped tungsten nanorods.

Nanorod forms of metal oxides are recognized as one of the most remarkable morphologies. Their structure and functionality have driven important advancements in a vast range of electronic devices and applications. In this work, we postulate a novel concept to explain how numerous localized surface states can be engineered into the bandgap of niobium oxide nanorods using tungsten. We discuss their contributions as local state surface charges for the modulation of a Schottky barrier height, the relative dielectric constant and their respective conduction mechanisms. Their effects on hydrogen gas molecule interaction mechanisms are also examined herein. We synthesized niobium tungsten oxide (Nb17W2O25) nanorods via a hydrothermal growth method and evaluated the Schottky barrier height, ideality factor, dielectric constant and trap energy level from the measured I-V versus temperature characteristics in the presence of air and hydrogen to show the validity of our postulations.

[Effects and mechanism of osthole on intestinal ischemia-reperfusion injury in mice].

OBJECTIVE: To explore the protective role of osthole in intestinal ischemia-reperfusion (I/R) injury in mice and examine its underlying mechanism. METHODS: A murine model of intestinal I/R injury was established with clamping of superior mesenteric artery for 120 min and then clamping was relieved for 60 min. Forty-five SD male mice weighing 27-31 g were randomly divided into 3 groups (n = 15 each): sham group (S), I/R injury group (I/R) and I/R plus osthole treatment group (Ost+). Intestinal wet/dry weight ratio, superoxide dismutase (SOD), malondialdehyde (MDA) in serum were examined by colorimetric assay and diamine oxidase (DAO) was examined by automatic biochemical analyzer, the levels of tumor necrosis factor (TNF) -α, interleukin (IL)-1ß and IL-2 were examined by enzyme-linked immunosorbent assay (ELISA). Intestinal barrier permeability was detected by Evans blue (EB) test. One-way ANOVA was used to analyze all experimental data variance. RESULTS: Intestinal tissues wet/dry weight ratios, Evans blue content and Chiu's score of I/R group mice were significantly higher than those of S and Ost+ groups (0.80% ± 0.03% vs 0.77% ± 0.02% & 0.78% ± 0.02%, (0.11 ± 0.04) vs (0.05 ± 0.02) & (0.06 ± 0.02) µg/mg, 3.42 ± 0.73 vs 0.87 ± 0.35 & 2.63 ± 0.58, P < 0.05 or P < 0.01) . Serum level of DAO, MDA, IL-1ß & TNF-α of I/R group mice were significantly higher than those of S and Ost+ groups ( (18.9 ± 4.0) vs (14.5 ± 2.3) & (16.0 ± 2.6) U/L, (8.4 ± 1.2) vs (6.9 ± 1.7) & (6.1 ± 2.4) µmol/L, (93 ± 6) vs (51 ± 4) & (67 ± 5) ng/L, (467 ± 31) vs (235 ± 21) & (323 ± 30) ng/L, P < 0.01 or P < 0.05) . Serum SOD activity and IL-2 level were significantly lower than those of S and Ost+ groups ( (75 ± 7) vs (93 ± 16) & (89 ± 5) U/ml, (95 ± 16) vs (198 ± 14) & (139 ± 11) ng/L, all P < 0.05) . All parameters showed no significant difference between S and Ost+ groups (all P > 0.05). CONCLUSIONS: Treatment of osthole may protect murine intestinal tissue against intestinal I/R injury. And the mechanisms may be due to its actions of preventing oxygen stress and inflammatory responses.

Late Cambrian geomagnetic instability after the onset of inner core nucleation.

The Ediacaran Period marks a pivotal time in geodynamo evolution when the geomagnetic field is thought to approach the weak state where kinetic energy exceeds magnetic energy, as manifested by an extremely high frequency of polarity reversals, high secular variation, and an ultralow dipole field strength. However, how the geodynamo transitioned from this state into one with more stable field behavior is unknown. Here, we address this issue through a high-resolution magnetostratigraphic investigation of the ~494.5 million-year-old Jiangshanian Global Standard Stratotype and Point (GSSP) section in South China. Our paleomagnetic results document zones with rapid reversals, stable polarity and a ~80 thousand-year-long interval without a geocentric axial dipole field. From these changes, we suggest that for most of the Cambrian, the solid inner core had not yet grown to a size sufficiently large to stabilize the geodynamo. This unusual field behavior can explain paleomagnetic data used to define paradoxical true polar wander, supporting instead the rotational stability of the solid Earth during the great radiation of life in the Cambrian.

Prognostic model for the prediction of cancer-specific survival in elderly patients with stage I-III gastric cancer.

Elderly patients with gastric cancer (GC) exhibit unique physiological conditions and population characteristics. However, no efficient predictive tools have been developed for this patient subgroup. We extracted data on elderly patients diagnosed with stage I-III GC between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database, and applied Cox regression analysis to examine factors associated with cancer-specific survival (CSS). A prognostic model was developed and validated to predict CSS. We assessed the performance of the prognostic model and stratified patients based on their prognostic scores. Notably, 11 independent prognostic factors, including age, race, grade, the tumor-node-metastasis (TNM) stage, T-stage, N-stage, operation, tumor size, regional nodes, radiation, and chemotherapy, associated with CSS were identified using multivariate Cox regression. A nomogram was constructed based on these predictors. The C-index score of the nomogram was 0.802 (95% (confidence interval) [CI]: 0.7939-0.8114), which is superior to the American Joint Commission on Cancer (AJCC) TNM staging prediction ability in the training cohort (C-index: 0.589; 95% CI: 0.5780-0.6017). Based on the receiver operating characteristic (ROC) and calibration curve, the predicted value of the nomogram demonstrated a satisfactory accuracy with the actual observation value. Additionally, decision curve analysis (DCA) showed that the nomogram had a more ideal clinical net benefit than TNM staging. Survival analysis of the different risk groups confirmed the noteworthy clinical and statistical utility of the nomogram in prognosis stratification. This retrospective study reports the successful creation and validation of a nomogram for predicting CSS at 1-, 3- and 5-years in elderly patients with stage I-III GC. This nomogram critically guides personalized prognostic assessments and may contribute to clinical decision-making and consultation for postoperative survival.