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Abstract Background The prognosis of non-small cell lung cancer (NSCLC) is substantially affected by lymph node metastasis (LNM), but there are no noninvasive, inexpensive methods of relatively high accuracy available to predict LNM in NSCLC patients. Methods Clinical data on NSCLC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for LNM were recognized LASSO and multivariate logistic regression. Six predictive models were constructed with machine learning based on risk factors. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the model. Subgroup analysis with different T-stages was performed on an optimal model. A webpage LNM risk calculator for optimal model was built using the Shinyapps.io platform. Results We enrolled 64,012 NSCLC patients, of whom 26,611 (41.57%) had LNM. Using multivariate logistic regression, we finally identified 10 independent risk factors for LNM: age, sex, race, histology, primary site, grade, T stage, M stage, tumor size, and bone metastases. GLM is the optimal model among all six machine learning models in both the training and validation cohorts. Subgroup analyses revealed that GLM has good predictability for populations with different T staging. A webpage LNM risk calculator based on GLM was posted on the shinyapps.io platform ( https://wubopredict.shinyapps.io/dynnomapp/ ). Conclusion The predictive model based on GLM can be used to precisely predict the probability of LNM in NSCLC patients, which was proven effective in all subgroup analyses according to T staging.

With increasing local conflicts worldwide, studying the impact response of body armor is crucial for enhancing soldier survival rates. However, there is still insufficient understanding of the back bulge expansion patterns, the impact waves transmission features, and blunt injury assessing method of body armor. To investigate these problems deeply, the three-dimensional digital image correlation method and numerical models were employed to reveal the ballistic response mechanism of ceramic/ultra-high-molecular-weight polyethylene (UHMWPE) composite body armor impacted by 7.62 mm rifle bullet. This study built theoretical function for the bulge expansion, revealed the wave transmission mechanism and fractures in both materials and their interaction. Firstly, the experiment revealed that the back-face bulge transverse expansion velocity exhibits a double exponential decrease. Secondly, the contour of back-face bulges consistently demonstrated excellent hyperbolic characteristics at various moments. Thirdly, the average Viscous Criterion (VC) and Blunt Criterion (BC) values were 5.37 and 0.95, corresponding to Abbreviated Injury Scale (AIS) values of 6 and 4. Fourthly, the simulation revealed that the ceramics transverse and radial cracks seems primarily induced by shear stress xy; ceramics conical cracks occurring at the boundaries of equivalent stress seems primarily induced by stress in x and y directions. Fifthly, numerical results revealed that the velocity of compression waves within the laminate increases over time in the impact direction and consistent with ceramic velocity impacted on the laminate. These findings lead to experimental and theoretical advances in the impact response mechanism of composite body armor and provide index for improving the protective performance.

Amid escalating localized conflicts worldwide, the elucidation of the mechanisms and quantification blunt trauma the emergency services and military personnel confronted becomes imperatively. However, the understanding of bullet-induced bulge formation on the laminate's back face, impact wave propagation, and consequent trauma assessment methods remains incomplete. This study applies 3-dimension digital image correlation (3D-DIC) method to reveals these phenomena by utilizing a lead-core bullet traveling at 334.93 m/s to impact an ultra-high molecular weight polyethylene (UHMWPE) laminate. The results show that the initial transverse propagation velocity of bulge profile is 24.79% smaller than the theoretical calculation, which indicates the reduction caused by cohesive matrix. The transverse wave demonstrates a double exponential attenuation pattern, which could be decomposed into two single exponential attenuation curves. The bulge profile shows hyperbolic pattern, which reveals the stability of the bulge shape and the temporal evolution pattern. Increasing the laminate-body gap leads to a decline in Blunt Criterion (BC) and the Abbreviated Injury Scale (AIS) values reduce from 2 to 0 correspondingly. The numerical model confirms the compression wave velocity as 1447.77 ± 123.10 m/s in the thickness direction and 9542.86 ± 3087.75 m/s in the fiber direction. These findings reveals and quantified the propagation patterns of back bulge and compressive wave, and thus could provide data-driven insights to improve body armor performance and blunt trauma assessment for individual soldiers.

Composite body armor made of brittle ceramic and tough laminate can protect human body from penetration while reducing weight. However, there is a lack of a simple and comprehensive method for assessing ballistic impact response and blunt injury. In this study, the three-dimensional Digital Image Correlation technique was used to investigate the back-face response of ceramic/ultra-high-molecular-weight-polyethylene laminate composite body armor impacted by a 7.62 mm rifle bullet. Blunt injury assessment was conducted by Bullet Coefficient (BC) and Abbreviated Injury Scale (AIS) criteria. Firstly, the ceramic tile exhibited transverse and radial cracks; the laminate showed thin layers separation, bullet holes and pits, kink, sheared, and torn morphology. Secondly, the bulge button face showed a transition from circular to rectangular shape, and the shear strain distribution exhibited an L-shaped pattern. Thirdly, at the moment of maximum bulge kinetic energy, approximately 8.73 % of bullet kinetic energy converted into total bulge kinetic energy, in which the x- and y-directional kinetic energy accounted for 29.66 %. Fourthly, the BC values decreased as the gap between armor and the human body increased, and the corresponding AIS decreased from 4 to 0. Finally, a Smooth Particle Hydrodynamics and Finite Element Method (SPH-FEM) coupled numerical model was applied to simulate the occurrence of ceramic cracks and laminate damage. This study proposed a quantitative evaluation of ballistic performance and blunt injury of body armor based on the back-face morphology. The results provide quantitative evidence to research the impact mechanism and offer methods for assessing human blunt injury behind the armor.

A meta-analysis of pre-pregnancy maternal body mass index (ppBMI) and placental DNA methylation from 2631 mother-child pairs identifies 27 CpG sites associated with ppBMI, providing insight into how maternal obesity could be associated with metabolic health outcomes in offspring.

Nanotechnology has become the most promising domain to boost the efficiency of enzymes. Enzymes are vital as a green catalyst in many industries, food, pharmaceutical and biomedical, etc. The immobilization process of the enzyme increases its catalytic properties. In this research, a novel method is presented to describe the effect of nano-calcium carbonate on the characteristics of immobilized β-glucosidase, which was extracted from the Agrocybe aegirit. The nano-CaCO3 was produced using the eco-friendly natural deep eutectic solvent. The pure nano -CaCO3 was observed as vaterite, with a size of about 300 nm. The nano-calcium carbonate was coated by a natural polymer sodium alginate compound and then adsorbed chitosan. Further, this obtained composite is cross-linked by the bioactive genipin to immobilize the β-glucosidase. The enzyme/protein loading ratio to the supports was 1:4, respectively. The recovery efficiency of immobilized β-glucosidase was 89.3%, and immobilization yield was 96.452%. Chitosan-coated nano-CaCO3 was used as a carrier for immobilization of β-glucosidase to improve its stability and reusability. In addition to stability and reusability, pH tolerance, temperature tolerance, and enzyme kinetics are the significant parameters that illustrate the proficiency of an immobilized enzyme. The measured optimal enzymatic reaction conditions for the immobilized β-glucosidase were 50 °C and pH 6. Furthermore, it has shown noticeable improvements in thermo-stability and pH tolerance. Temperature tolerance was observed 50% to the initial activity of the immobilized enzyme even after the 3 h of incubation at 50 °C, while pH tolerance was noticed more than 50% and 40% at pH 7 and 8, respectively. The Km and Vmax values of free and immobilized β-glucosidase to 4-nitrophenyl β-D-glucopyranoside were 1.549 μmol/L/min, 0.346 mmol/L and 0.532 μmol/L/min, 0.080 mmol/L, respectively. The immobilized β-glucosidase retains its storability 80% even after 30 days of storage at 4 °C and maintains 93.1% of its residual activity by reusing up to 10 cycles.

Abstract Background Prenatal vitamin use is recommended before and during pregnancies for normal fetal development. Prenatal vitamins do not have a standard formulation, but many contain calcium, folic acid, iodine, iron, omega-3 fatty acids, zinc, and vitamins A, B6, B12, and D, and usually they contain higher concentrations of folic acid and iron than regular multivitamins in the US Nutrient levels can impact epigenetic factors such as DNA methylation, but relationships between maternal prenatal vitamin use and DNA methylation have been relatively understudied. We examined use of prenatal vitamins in the first month of pregnancy in relation to cord blood and placenta DNA methylation in two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk Learning Early Signs (MARBLES) studies. Results In placenta, prenatal vitamin intake was marginally associated with −0.52% (95% CI −1.04, 0.01) lower mean array-wide DNA methylation in EARLI, and associated with −0.60% (−1.08, −0.13) lower mean array-wide DNA methylation in MARBLES. There was little consistency in the associations between prenatal vitamin intake and single DNA methylation site effect estimates across cohorts and tissues, with only a few overlapping sites with correlated effect estimates. However, the single DNA methylation sites with p-value

In greenhouse vegetable production, reductive soil disinfestation (RSD) effectively mitigates soil-borne diseases, yet its impact on the dynamics of soil organic carbon (SOC) has not been adequately examined. This study investigated the distribution of soil aggregates and the organic carbon retention mechanism following intensive RSD treatment. Greenhouse experiments, including control (CK), wheat straw (RSD), and wheat straw with chemical fertilizer (RSD + NP) treatments, indicated augmentation in the formation of macro-aggregates (>2 mm and 0.25–2 mm) under RSD, particularly in the RSD + NP treatment. Silty clay particles transform into macro- and micro-aggregates. Fourier infrared spectroscopy highlighted the augmentation of carbon-containing functional groups in SOC, with aliphatic carbon accumulating in macro-aggregates and aromatic carbon in silt clay. Laboratory culture experiments employing different C/N ratios (RSD1 with wheat straw, RSD2 with kiwifruit branches) underscored the beneficial impact of low C/N ratio organic matter on coarse and fine macro-aggregate content, mean weight diameter, geometric mean diameter, and reduced silt clay. Low C/N ratios enhance SOC retention in large aggregates, while high ratios stabilise micro-aggregate carbon. This research underscores the severe degradation in continuous greenhouse cropping systems and emphasises RSD’s dual benefits—disease prevention and improved SOC retention. Implementing RSD requires careful consideration of organic material choices, specifically their C/N ratios, as a pivotal factor influencing SOC dynamics.

Abstract Background Autism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. Results We use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence. Conclusions Together, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.

Medicine food homology (MFH) substances not only provide essential nutrients as food but also have corresponding factors that can prevent and help treat nutritional imbalances, chronic disease, and other related issues. Endophytic fungi associated with plants have potential for use in drug discovery and food therapy. However, the endophytic fungal metabolites from MFH plants and their effects have been overlooked. Therefore, this review focuses on the various biological activities of 108 new metabolites isolated from 53 MFH-derived endophytic fungi. The paper explores the potential nutritional and medicinal value of metabolites of MFH-derived endophytic fungi for food and medical applications. This research is important for the future development of effective, safe, and nontoxic therapeutic nutraceuticals for the prevention and treatment of human diseases.

Abstract Exosomes are carriers of intercellular information that regulate the tumor microenvironment, and they have an essential role in drug resistance through various mechanisms such as transporting RNA molecules and proteins. Nevertheless, their effects on gemcitabine resistance in triple-negative breast cancer (TNBC) are unclear. In the present study, we examined the effects of exosomes on TNBC cell viability, colony formation, apoptosis, and annexin A6 (ANXA6)/EGFR expression. We addressed their roles in gemcitabine resistance and the underlying mechanism. Our results revealed that exosomes derived from resistant cancer cells improved cell viability and colony formation and inhibited apoptosis in sensitive cancer cells. The underlying mechanism included the transfer of exosomal ANXA6 from resistant cancer cells to sensitive cancer cells. Isobaric peptide labeling–liquid chromatography–tandem mass spectrometry and western blotting revealed that ANXA6 was upregulated in resistant cancer cells and their derived exosomes. Sensitive cancer cells exhibited resistance with increased viability and colony formation and decreased apoptosis when ANXA6 was stably overexpressed. On the contrary, knockdown ANXA6 restored the sensitivity of cells to gemcitabine. Co-immunoprecipitation expression and GST pulldown assay demonstrated that exosomal ANXA6 and EGFR could interact with each other and exosomal ANXA6 was associated with the suppression of EGFR ubiquitination and downregulation. While adding lapatinib reversed gemcitabine resistance induced by exosomal ANXA6. Moreover, ANXA6 and EGFR protein expression was correlated in TNBC tissues, and exosomal ANXA6 levels at baseline were lower in patients with highly sensitive TNBC than those with resistant TNBC when treated with first-line gemcitabine-based chemotherapy. In conclusion, resistant cancer cell-derived exosomes induced gemcitabine resistance via exosomal ANXA6, which was associated with the inhibition of EGFR ubiquitination and degradation. Exosomal ANXA6 levels in the serum of patients with TNBC might be predictive of the response to gemcitabine-based chemotherapy.

Background: Early integration of palliative care (PC) for patients with advanced cancer has been recommended to improve quality of care. This study aims to describe prevalence, temporal trend and predictors of PC use in metastatic breast cancer (mBCa) patients receiving critical care therapies (CCT; included invasive mechanic ventilation, percutaneous endoscopic gastrostomy tube, total parenteral nutrition, tracheostomy and dialysis). Methods: The National Inpatient Sample was queried for mBCa patients receiving CCT between 2005 and 2014. Annual percent changes (APC) were calculated for PC prevalence in the overall cohort and subgroups. Multivariable logistic analysis was used to explore predictors of PC use. Results: Of 5833 mBCa patients receiving CCT, 880 (15.09%) received PC. Rate of PC use increased significantly from 2.53% in 2005 to 25.96% in 2014 (APC: 35.75%; p

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development and influence future health outcomes. Methods We performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth. Samples were split into discovery and replication sets and stratified by sex, and their DNA methylation profiles were tested for differentially methylated regions (DMRs) between ASD and typically developing control cord blood samples. DMRs were mapped to genes and assessed for enrichment in gene function, tissue expression, chromosome location, and overlap with prior ASD studies. DMR coordinates were tested for enrichment in chromatin states and transcription factor binding motifs. Results were compared between discovery and replication sets and between males and females. Results We identified DMRs stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development. Conclusions At birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD and provides novel insights for early diagnosis and therapy.

Abstract Background Insomnia is a global disease with a high incidence and acupuncture therapy is a well appropriate method to treat insomnia. Shenmen (HT 7) and Sanyinjiao (SP 6) are the acupoints most commonly used to treat insomnia. Although they can obviously relieve the clinical symptoms of insomnia, it is unclear whether they must be used together, whether the combination of two acupoints may have a synergistic or antagonistic effect, and whether there is a primary or secondary relationship between the two points in the treatment of insomnia. Further studies are needed. Therefore, in this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia. Methods/design This will be a parallel group randomized controlled trial. The study will recruit 120 patients with insomnia randomly assigned to a control group, an electroacupuncture on HT 7 group, an electroacupuncture on SP 6 group, and an electroacupuncture on HT 7 and SP 6 group. The allocation ratio is 1:1:1:1, with 30 subjects in each group. Meanwhile, ten healthy subjects who meet the study criteria will be recruited as the healthy control group. Patients in the intervention groups will be given ten rounds of electroacupuncture stimulation on the corresponding acupoints for 2 weeks, five times per week, with 2 days of rest between the two treatment courses. Patients in the control group will also receive the same two courses of ten rounds of compensatory acupuncture therapy after a 2-week waiting period for treatment. The major outcome measures of this study include the Sleep Dysfunction Rating Scale, the Insomnia Severity Index, Epworth Sleepiness Scale, the Zung Self-Rating Anxiety Scale, and the Zung Self-Rating Depression Scale, combined with the Measure Your Medical Outcome Profile, to evaluate insomnia and the emotional state of patients with insomnia. The secondary outcome measures include sleep composition monitored by polysomnography and measurements of acetylcholine, serotonin, dopamine, norepinephrine, melatonin, gamma-aminobutyric acid, and metabolic biomarkers in serum. Discussion In this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia, which may provide evidence for the clinical application of acupuncture and acupoint selection in the treatment of insomnia. Trial registration Chinese Clinical Trial Registry, Chi-CTR-1800017483 . Registered on 1 August 2018.

Melts of 3-dimensional dendritic beads-springs, namely coarse-grained soft-clusters, are studied by molecular dynamics simulations. The goal is to elucidate the unique dynamics of giant molecules, and generally speaking, 3-dimensional architectured polymers. When constituted by more than the critical number around 200 beads, soft-clusters cannot diffuse or relax far above their glass transition temperature, although relaxation can happen on the level of beads. Each soft-cluster can only rotate in the cage formed by neighboring soft-clusters. Such a non-diffusing state would transform to the liquid state at exceptionally high temperature, e.g. 10 times the glass transition temperature. Agreeing with experiments, 3D hierarchies lead to unique dynamics, especially their divergent relaxation times with the number of beads. These unique dynamics are in sharp contrast with 1-dimensional chain-like polymers. We name such a special state as ‘cooperative glass’, because of the ‘cooperation’ of the 3D-connected beads. The design of soft-clusters may also resemble cooperative rearranging regions where cooperativeness is contributed by the low temperature, thus offer further insights into the glass problem.

In the field of intelligent driving of freight trains, determining the track line ahead of the train is an important function in the autopilot technology of such trains. Combining the characteristics of freight railway tracks, we conduct an in-depth analysis of the shortcomings of object detection technology in extracting track lines and propose an improved Zhang–Suen (ZS) thinning theory for a railway track line recognition algorithm. Through image preprocessing and single pixel thinning steps, a continuous track line is obtained and then processed by a denoising algorithm to obtain a complete track line. Experimental results show that the track extracted by our method has good continuity and less noise. It can simultaneously perform track detection on straight roads, curves and turnouts, and is suitable for changing weather conditions such as sunny daytime, mild rainy daytime, cloudy daytime, night with lamp lighting and night without lamp lighting conditions.

Radix Rehmanniae and Cornus Officinalis (RR-CO) have been widely used as “nourishing Yin and tonifying kidney” herb pairs for the treatment of diabetes mellitus (DM) and its complications in traditional Chinese medicine (TCM). Based on the theory of “kidney governing reproduction” in TCM, the aim of this study was to investigate the therapeutic effects of RR-CO on DM-induced reproduction damage through regulating testicular glycolysis. Moreover, the regulation of AGEs/RAGE/HIF-1α axis on the testicular glycolysis process has also been studied. Spontaneous DM model KK-Ay mice were used to investigate the protective effect of RR, CO, RR-CO on DM-induced reproductive disturbances. RR, CO, RR-CO improved DM-induced renal and testicular morphology damages. Moreover, the impaired spermatogenesis, germ cell apoptosis and motility in testis induced upon DM were also attenuated by RR, CO or RR-CO, accompanied by an increased level of glycolysis metabolomics such as l-lactate, d-Fructose 1,6-bisphosphate, etc. Meanwhile, glucose membrane transporters (GLUT1, GLUT3), monocarboxylate transporter 4 (MCT4) expression, lactate dehydrogenase (LDH) activity, HIF-1α were upregulated by RR, CO and RR-CO treatment compared with the model group, whereas AGE level and RAGE expression were decreased with the drug administration. The RR-CO group was associated with superior protective effects in comparison to RR, CO use only. Aminoguanidine (Ami) and FPS-ZM1, the AGEs and RAGE inhibitors, were used as a tool drug to study the mechanism, showing different degrees of protection against DM-induced reproductive damage. This work preliminarily sheds light on the herb pair RR-CO exhibited favorable effects against DM-induced reproductive disturbances through enhancing testicular glycolysis, which might be mediated by AGEs/RAGE/HIF-1α axis.

Abstract Background Wilson disease (WD) is an autosomal recessive disease caused by mutations in ATP7B encoding a copper transporter. Consequent copper accumulation results in a variable WD clinical phenotype involving hepatic, neurologic, and psychiatric symptoms, without clear genotype–phenotype correlations. The goal of this study was to analyze alterations in DNA methylation at the whole-genome level in liver and blood from patients with WD to investigate epigenomic alterations associated with WD diagnosis and phenotype. We used whole-genome bisulfite sequencing (WGBS) to examine distinct cohorts of WD subjects to determine whether DNA methylation could differentiate patients from healthy subjects and subjects with other liver diseases and distinguish between different WD phenotypes. Results WGBS analyses in liver identified 969 hypermethylated and 871 hypomethylated differentially methylated regions (DMRs) specifically identifying patients with WD, including 18 regions with genome-wide significance. WD-specific liver DMRs were associated with genes enriched for functions in folate and lipid metabolism and acute inflammatory response and could differentiate early from advanced fibrosis in WD patients. Functional annotation revealed that WD-hypermethylated liver DMRs were enriched in liver-specific enhancers, flanking active liver promoters, and binding sites of liver developmental transcription factors, including Hepatocyte Nuclear Factor 4 alpha (HNF4A), Retinoid X Receptor alpha (RXRA), Forkhead Box A1 (FOXA1), and FOXA2. DMRs associated with WD progression were also identified, including 15 with genome-wide significance. However, WD DMRs in liver were not related to large-scale changes in proportions of liver cell types. DMRs detected in blood differentiated WD patients from healthy and disease control subjects, and distinguished between patients with hepatic and neurologic WD manifestations. WD phenotype DMRs corresponded to genes enriched for functions in mental deterioration, abnormal B cell physiology, and as members of the polycomb repressive complex 1 (PRC1). 44 DMRs associated with WD phenotype tested in a small validation cohort had a predictive value of 0.9. Conclusions We identified a disease-mechanism relevant epigenomic signature of WD that reveals new insights into potential biomarkers and treatments for this complex monogenic disease.

Many genes have oscillating gene expression pattern in circadian centers of the brain. This study shows cortical diurnal DNA methylation oscillation in a mouse model of Prader-Willi syndrome, and describes corresponding changes in gene expression and chromatin compaction.

Harmful algal blooms (HABs) have occurred frequently in coastal waters of China, imposing negative effects on the marine ecological environment. A dataset of HABs and terrestrial runoff was collected and analyzed in this study, and factors responsible for HABs were further explored. Frequency and expansion of HABs peaked between 2001 and 2007, and although they have declined slightly since then, they have remained quite high. Frequency and accumulative area of HABs peaked in 2004–2005, and most occurred from April to August during these years. HABs occurred frequently in the Changjiang (Yangtze River) estuary, and Prorocentrum donghaiense, Noctiluca scientillans, Karenia mikimotoi, and Skeletonema costatum were the main algal species. The increases of eutrophication, the abnormal sea surface temperature caused by climate and ocean currents, and the species invasion caused by the discharge of ballast water may be important factors for the long-term outbreak of HABs in the Chinese coastal waters. These findings provide a better understanding of HABs in China, which will be helpful to further prevention and control.

Ultra-high-molecular-weight polyethylene (UHMWPE) fiber laminate is currently widely used in ballistic protection for its exceptional physical and mechanical properties. However, the dynamic compressive mechanism of UHMWPE laminate remains poorly understood. Therefore, the stress−strain relationship, the influence of different thickness, area, and shape, and the maximum stress and fracture stress are studied in both out-of-plane and in-plane directions under quasi-static and dynamic loading using a universal test machine, Split Hopkinson pressure bar (SHPB), and high-speed camera. Furthermore, numerical models with cohesive elements are developed. The results indicate a dependency on strain rate and loading direction. Firstly, the stress−strain curve of dynamic testing can be divided into different zones according to different loading directions and strain rates. Secondly, with the increase of the strain rate in the dynamic testing, the maximum stress and fracture stress increase as well; relatively speaking, the fracture stress in the out-of-plane direction is greater than the fracture stress in the in-plane direction. Thirdly, both experiment and simulation indicate that the thickness does not influence the modulus clearly the in out-of-plane direction but influences the modulus in the in-plane direction. Fourthly, the fracture stress of dynamic testing is higher than the fracture stress of quasi-static testing in both directions. Finally, the numerical results show good agreement with the experiment in terms of the maximum stress and failure form.

Intracranial hemorrhage remains the most feared complication in tissue plasminogen activator (tPA) thrombolysis for ischemic stroke. However, the underlying molecular mechanisms are still poorly elucidated. In this study, we reported an important role of caveolin-1 (Cav-1) s-nitrosylation in matrix metalloproteinase (MMP)-2 and 9 secretion from tPA-treated ischemic endothelial cells. Brain vascular endothelial cells (bEND3) were exposed to oxygen-glucose deprivation (OGD) for 2 h before adding recombinant human tPA for 6 h. This treatment induced a significant increase of MMP2 and 9 in the media of bEND3 cells and a simultaneous degradation of fibronectin and laminin β-1, the two main components of extracellular matrix (ECM). Inhibition of MMP2 and 9 with SB-3CT completely blocked the degradation of fibronectin and laminin β-1. ODG+tPA treatment led to Cav-1 shedding from bEND3 cells into the media. Notably, OGD triggered nitric oxide (NO) production and S-nitrosylationof Cav-1 (SNCav-1). Meanwhile tPA induced activation of ERK signal pathway and stimulates the secretion of SNCav-1. Pretreatment of bEND3 cells with C-PTIO (a NO scavenger) or U0126 (a specific ERK inhibitor) significantly reduced OGD-induced S-nitrosylation of Cav-1 in cells and blocked the secretion of Cav-1 and MMP2 and 9 into the media as well as the degradation of fibronectin and laminin β-1 in OGD and tPA-treated cells. These data indicate that OGD-triggered Cav-1 S-nitrosylation interacts with tPA-induced ERK activation to augment MMP2 and 9 secretion and subsequent ECM degradation, which may account for the exacerbation of ischemic blood brain barrier damage following tPA thrombolysis for ischemic stroke.