Barley yellow dwarf virus-GAV 17K protein disrupts thiamine biosynthesis to facilitate viral infection in plants.

Thiamine functions as a crucial activator modulating plant health and broad-spectrum stress tolerances. However, the role of thiamine in regulating plant virus infection is largely unknown. Here, we report that the multifunctional 17K protein encoded by barley yellow dwarf virus-GAV (BYDV-GAV) interacted with barley pyrimidine synthase (HvTHIC), a key enzyme in thiamine biosynthesis. HvTHIC was found to be localized in chloroplast via an N-terminal 74-amino acid domain. However, the 17K-HvTHIC interaction restricted HvTHIC targeting to chloroplasts and triggered autophagy-mediated HvTHIC degradation. Upon BYDV-GAV infection, the expression of the HvTHIC gene was significantly induced, and this was accompanied by accumulation of thiamine and salicylic acid. Silencing of HvTHIC expression promoted BYDV-GAV accumulation. Transcriptomic analysis of HvTHIC silenced and non-silenced barley plants showed that the differentially expressed genes were mainly involved in plant-pathogen interaction, plant hormone signal induction, phenylpropanoid biosynthesis, starch and sucrose metabolism, photosynthesis-antenna protein, and MAPK signaling pathway. Thiamine treatment enhanced barley resistance to BYDV-GAV. Taken together, our findings reveal a molecular mechanism underlying how BYDV impedes thiamine biosynthesis to uphold viral infection in plants.

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: the role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates procellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Detecting Cellular Microstructural Changes of Liver Fibrosis with Time-Dependent Diffusion MRI.

Background The potential of time-dependent diffusion MRI in imaging the progression from liver fibrosis to cirrhosis has not been established. Purpose To assess the effectiveness of time-dependent diffusion MRI in mapping the microstructure and characterizing cellular attributes during the progression of liver fibrosis to cirrhosis and to investigate its potential in grading liver fibrosis. Materials and Methods This prospective study, performed between December 2022 and October 2023, used 60 rats to establish a liver fibrosis model by means of diethylnitrosamine administration, with five additional rats serving as control animals. Time-dependent diffusion MRI was performed with equivalent diffusion time of 5.4, 10.7, and 69.3 msec on a 3.0-T scanner. Time-dependent diffusion MRI-based microstructural parameters, including cell diameter, intracellular volume fraction (ICVF), cellularity, and extracellular diffusivity, were estimated with use of the imaging microstructural parameters using limited spectrally edited diffusion, or IMPULSED, model. The fitted microstructural parameters were validated with histopathologic measurements. Results All 60 rats developed liver fibrosis, with a noticeable decrease in cell diameter and an increase in ICVF and cellularity observed as liver fibrosis progressed. The diameter measured at pathologic examination ranged from 11.4 µm to 35.4 µm, aligning with the range of 12.4-33.4 µm observed in time-dependent diffusion MRI, which indicated a strong correlation (r = 0.84; P < .001). The quantified ICVF at pathologic examination ranged from 0.28 to 0.89 and varied from 0.23 to 0.85 at time-dependent diffusion MRI, showing a high correlation (r = 0.62; P < .001). The cellularity observed at pathologic examination increased from 0.74 to 5.85, while the cellularity measured at time-dependent diffusion MRI ranged from 0.77 to 3.70, showing a correlation (r = 0.44; P < .001). Conclusion This study revealed the changes in quantitative microstructural mapping across the spectrum from liver fibrosis to cirrhosis. Cell diameter, ICVF, and cellularity are reliable markers for liver fibrosis, with diameter and ICVF presenting good discrimination ability. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Matos and Metens in this issue.

Long-term radiological and pulmonary function abnormalities at 3†years after COVID-19 hospitalisation: a longitudinal cohort study.

BACKGROUND: This study aimed to evaluate the longitudinal progression of residual lung abnormalities (ground-glass opacities, reticulation and fibrotic-like changes) and pulmonary function at 3 years following coronavirus disease 2019 (COVID-19). METHODS: This prospective, longitudinal cohort study enrolled COVID-19 survivors who exhibited residual lung abnormalities upon discharge from two hospitals. Follow-up assessments were conducted at 6 months, 12 months, 2 years and 3 years post-discharge, and included pulmonary function tests, 6-min walk distance (6MWD), chest computed tomography (CT) scans and symptom questionnaires. Non-COVID-19 controls were retrospectively recruited for comparative analysis. RESULTS: 728 COVID-19 survivors and 792 controls were included. From 6 months to 3 years, there was a gradual improvement in reduced diffusing capacity of the lung for carbon monoxide (D LCO <80% predicted: 49% versus 38%; p=0.001), 6MWD (496 versus 510 m; p=0.002) and residual lung abnormalities (46% versus 36%; p<0.001), regardless of disease severity. Patients with residual lung abnormalities at 3 years more commonly had respiratory symptoms (32% versus 16%; p<0.001), lower 6MWD (494 versus 510 m; p=0.003) and abnormal D LCO (57% versus 27%; p<0.001) compared with those with complete resolution. Compared with controls, the proportions of D LCO impairment (38% versus 17%; p<0.001) and respiratory symptoms (23% versus 2.2%; p<0.001) were significantly higher in the matched COVID-19 survivors at the 3-year follow-up. CONCLUSIONS: Most patients exhibited improvement in radiological abnormalities and pulmonary function over time following COVID-19. However, more than a third continued to have persistent lung abnormalities at the 3-year mark, which were associated with respiratory symptoms and reduced diffusion capacity.

Delta-radiomics features for predicting the major pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

OBJECTIVES: To investigate if delta-radiomics features have the potential to predict the major pathological response (MPR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC) patients. METHODS: Two hundred six stage IIA-IIIB NSCLC patients from three institutions (Database1 = 164; Database2 = 21; Database3 = 21) who received neoadjuvant chemoimmunotherapy and surgery were included. Patients in Database1 were randomly assigned to the training dataset and test dataset, with a ratio of 0.7:0.3. Patients in Database2 and Database3 were used as two independent external validation datasets. Contrast-enhanced CT scans were obtained at baseline and before surgery. The delta-radiomics features were defined as the relative net change of radiomics features between baseline and preoperative. The delta-radiomics model and pre-treatment radiomics model were established. The performance of Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) for predicting MPR was also evaluated. RESULTS: Half of the patients (106/206, 51.5%) showed MPR after neoadjuvant chemoimmunotherapy. For predicting MPR, the delta-radiomics model achieved a satisfying area under the curves (AUCs) values of 0.768, 0.732, 0.833, and 0.716 in the training, test, and two external validation databases, respectively, which showed a superior predictive performance than the pre-treatment radiomics model (0.644, 0.616, 0.475, and 0.608). Compared with iRECIST criteria (0.624, 0.572, 0.650, and 0.466), a mixed model that combines delta-radiomics features and iRECIST had higher AUC values for MPR prediction of 0.777, 0.761, 0.850, and 0.670 in four sets. CONCLUSION: The delta-radiomics model demonstrated superior diagnostic performance compared to pre-treatment radiomics model and iRECIST criteria in predicting MPR preoperatively in neoadjuvant chemoimmunotherapy for stage II-III NSCLC. CLINICAL RELEVANCE STATEMENT: Delta-radiomics features based on the relative net change of radiomics features between baseline and preoperative CT scans serve a vital support tool in accurately identifying responses to neoadjuvant chemoimmunotherapy, which can help physicians make more appropriate treatment decisions. KEY POINTS: • The performances of pre-treatment radiomics model and iRECIST model in predicting major pathological response of neoadjuvant chemoimmunotherapy were unsatisfactory. • The delta-radiomics features based on relative net change of radiomics features between baseline and preoperative CT scans may be used as a noninvasive biomarker for predicting major pathological response of neoadjuvant chemoimmunotherapy. • Combining delta-radiomics features and iRECIST can further improve the predictive performance of responses to neoadjuvant chemoimmunotherapy.

Effects of polymerization types on plastics ingestion and biodegradation by Zophobas atratus larvae, and successions of both gut bacterial and fungal microbiomes.

Recent studies demonstrated that plastic degradation in Zophobas atratus superworms is related to the gut microbiota. To determine whether the biodegradation and gut-microbiota were influenced by ingested plastic polymerization types, foams of polypropylene (PP), polyurethane (PU) and ethylene vinyl acetate (EVA) were selected as representatives of polyolefins, polyester and copolymers, and the sole feedstock for superworms for 45 d. Both growth and survival rates of superworms were influenced by the type of plastic diet. Although the total consumptions of EVA- and PP-fed groups were similar at 29.03 ± 0.93 and 28.89 ± 1.14 mg/g-larva, which were both significantly higher than that of PU-fed groups (21.63 ± 2.18 mg/g-larva), the final survival rates of the EVA-fed group of 36.67 ± 10.41% exhibited significantly lower than that of the PP- and PU-fed groups of 76.67 ± 2.89% and 75.00 ± 7.07%, respectively, and even the starvation group of 51.67 ± 10.93%. The Illumina MiSeq results revealed similarities in the dominant gut bacterial communities between PU- and EVA-fed groups, with an increase in relative abundance of Lactococcus, but significant differences from the PP-fed groups, which had two predominant genera of unclassified Enterobacteriaceae and Enterococcus. Compared to bran-fed groups, changes in gut fungal communities were similar across all plastics-fed groups, with an increase in the dominant abundance of Rhodotorula. The abundance of Rhodotorula increased in the order of polyolefin, polyester, and copolymer. In summary, plastic ingestion, larval growth, and changes in gut bacterial and fungal community of superworms were all influenced by foam diets of different polymerization types, and especially influences on the gut microbiomes were different from each other.

Highly efficient recovery of Zn (II) from zinc-containing wastewater by tourmaline tailings geopolymers to in-situ construct nanoscale ZnS for the photodegradation of tetracycline hydrochloride.

While treating zinc-containing wastewater, recovering zinc for reuse as a secondary resource has significant environmental and economic benefits. Herein, based on the alkali-activated tourmaline tailings geopolymers (TTG) after adsorption of zinc ions (Zn (II)), a series of new composites with in-situ construction ZnS nanoparticles on TTG (ZnS/TTG) were synthesized, and used as photocatalysts for the photodegradation of tetracycline hydrochloride (TCH) in solution. Specifically, ZnS nanoparticles were uniformly and stably distributed in the layered structure of TTG, interweaving with each other to generate an interfacial electric field, which could induce more photocarrier generation. Meanwhile, TTG acted as an electron acceptor to accelerate the electron transfer at the interface, thus enhancing the photodegradation activity for TCH. The active radical quenching experiments combined with the ESR indicated that the active species produced during the photocatalytic degradation of TCH by ZnS/TTG composites were •O2- and photogenerated h+. When the initial concentration of Zn (II) was 60 mg/L, the synthesized 60-ZnS/TTG composites (0.5 g/L) reached 91.53% degradation efficiency of TCH (10 mg/L) at pH = 6. Furthermore, the possible pathways and mechanism of 60-ZnS/TTG composites photodegraded TCH were revealed with the aid of degraded intermediates. This report not only proposed valuable references for reusing heavy metal ions and removing TCH from wastewater, but also provided promising ideas for realizing the conversion of used adsorbents into high-efficiency photocatalysts.

Fabrication of nano-hammer shaped CuO@HApNWs for catalytic degradation of tetracycline.

With widespread and excessive use of antibiotics in medicine, poultry farming, and aquaculture, antibiotic residues have become a significant threat to both eco-environment and human health. In this paper, using hydroxyapatite nanowires (HApNWs) as an ecologically compatible carrier, a novel nano-hammer shaped conjunction with HApNW conjugating CuO microspheres (CuO@HApNWs) was successfully synthesized by in-situ agglomeration method. The catalytic degradation performance of the nano-hammer shaped CuO@HApNWs with Fenton-like activation was investigated by using tetracycline (TC) as a representative antibiotic pollutant. Remarkably, it exhibited excellent catalytic activity, which the removal rate of TC got to 92.0% within 40 min, and the pseudo-second-order reaction kinetic constant was 18.33 × 10-3 L mg-1·min-1, which was 26 times and 5 times than that of HApNWs and CuO, respectively. Furthermore, after recycling 6 times, the degradation efficiency of TC still remained above 85 %. Based on radical scavenger tests and electron paramagnetic resonance (EPR) spectroscopy, it demonstrated that the excellent activity of CuO@HApNWs was mainly attributed to the fact that Fenton-like activation promotes the circulation of Cu2+ and Cu+, the generated main active oxygen species (•OH and O2-•) achieve efficient degradation of TC. In summary, the nano-hammer shaped CuO@HApNWs could be in-situ synthesed, and used as an eco-friendly Fenton-like catalyst for effectively catalytic degradation of organic pollutants, which has great potential for wastewater treatment.

Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD.

BACKGROUND: We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/ß-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. METHODS: Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/ß-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/ß-catenin agonist) and XAV939 (Wnt/ß-catenin antagonist) to investigate whether Wnt/ß-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, ß-catenin and PPARγ proteins in the lung tissue. RESULTS: Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased ß-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. CONCLUSIONS: Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/ß-catenin-PPARγ pathway.

Genomic Characteristics of Emerging Intraerythrocytic Anaplasma capra and High Prevalence in Goats, China.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

A cysteine-rich secretory protein involves in phytohormone melatonin mediated plant resistance to CGMMV.

BACKGROUND: Melatonin is considered to be a polyfunctional master regulator in animals and higher plants. Exogenous melatonin inhibits plant infection by multiple diseases; however, the role of melatonin in Cucumber green mottle mosaic virus (CGMMV) infection remains unknown. RESULTS: In this study, we demonstrated that exogenous melatonin treatment can effectively control CGMMV infection. The greatest control effect was achieved by 3 days of root irrigation at a melatonin concentration of 50 µM. Exogenous melatonin showed preventive and therapeutic effects against CGMMV infection at early stage in tobacco and cucumber. We utilized RNA sequencing technology to compare the expression profiles of mock-inoculated, CGMMV-infected, and melatonin+CGMMV-infected tobacco leaves. Defense-related gene CRISP1 was specifically upregulated in response to melatonin, but not to salicylic acid (SA). Silencing CRISP1 enhanced the preventive effects of melatonin on CGMMV infection, but had no effect on CGMMV infection. We also found exogenous melatonin has preventive effects against another Tobamovirus, Pepper mild mottle virus (PMMoV) infection. CONCLUSIONS: Together, these results indicate that exogenous melatonin controls two Tobamovirus infections and inhibition of CRISP1 enhanced melatonin control effects against CGMMV infection, which may lead to the development of a novel melatonin treatment for Tobamovirus control.

Longitudinal Assessment of Chest CT Findings and Pulmonary Function after COVID-19 Infection.

Background Information on pulmonary sequelae and pulmonary function 2 years after recovery from SARS-CoV-2 infection is lacking. Purpose To longitudinally assess changes in chest CT abnormalities and pulmonary function in individuals after SARS-CoV-2 infection. Materials and Methods In this prospective study, participants discharged from the hospital after SARS-CoV-2 infection from January 20 to March 10, 2020, were considered for enrollment. Participants without chest CT scans at admission or with complete resolution of lung abnormalities at discharge were excluded. Serial chest CT scans and pulmonary function test results were obtained 6 months (June 20 to August 31, 2020), 12 months (December 20, 2020, to February 3, 2021), and 2 years (November 16, 2021, to January 10, 2022) after symptom onset. The term interstitial lung abnormality (ILA) and two subcategories, fibrotic ILAs and nonfibrotic ILAs, were used to describe residual CT abnormalities on follow-up CT scans. Differences between groups were compared with the χ2 test, Fisher exact test, or independent samples t test. Results Overall, 144 participants (median age, 60 years [range, 27-80 years]; 79 men) were included. On 2-year follow-up CT scans, 39% of participants (56 of 144) had ILAs, including 23% (33 of 144) with fibrotic ILAs and 16% (23 of 144) with nonfibrotic ILAs. The remaining 88 of 144 participants (61%) showed complete radiologic resolution. Over 2 years, the incidence of ILAs gradually decreased (54%, 42%, and 39% of participants at 6 months, 12 months, and 2 years, respectively; P < .001). Respiratory symptoms (34% vs 15%, P = .007) and abnormal diffusing capacity of lung for carbon monoxide (43% vs 20%, P = .004) occurred more frequently in participants with ILAs than in those with complete radiologic resolution. Conclusion More than one-third of participants had persistent interstitial lung abnormalities 2 years after COVID-19 infection, which were associated with respiratory symptoms and decreased diffusion pulmonary function. Chinese Clinical Trial Registry no. ChiCTR2000038609 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by van Beek in this issue.

Characteristics, Prognosis, and Prediction Model of Heart Failure Patients in Intensive Care Units Based on Preserved, Mildly Reduced, and Reduced Ejection Fraction.

Background: Heart failure (HF) patients in intensive care units (ICUs) are rather poorly studied based on varying left ventricular ejection fraction (LVEF) classification. Characteristics and prognosis of patients in ICUs with HF with mildly reduced ejection fraction (HFmrEF), HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) require further clarification. Methods: Data involving clinical information and 4-year follow-up records of HF patients were extracted and integrated from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Tests were carried out to identity differences among these three HF subtypes. Prognostic analyses were performed using Kaplan-Meier survival analysis and Cox proportional-hazards regression modeling. To develop a novel prediction nomogram, forward selection was used as the best-fit model. Prognostic heterogeneity of the subgroups prespecified by stratification factors in pairwise comparisons was presented using forest plots. Results: A total of 4150 patients were enrolled in this study. HFmrEF had the lowest all-cause mortality rate during the 4-year follow-up, which was significantly different from HFrEF and HFpEF (Log-Rank p < 0.001). The Cox proportional-hazards regression model also showed that a comparison of HFrEF versus HFmrEF indicated a hazard ratio (HR) of 0.76 (95% CI 0.61-0.94, p = 0.011) and HFrEF versus HFpEF indicated a HR 0.93 (95% CI 0.82-1.07, p = 0.307). Following a multivariable analysis, 13 factors were confirmed as independent. A new nomogram was established and quantified with a concordance index (C-index) of 0.70 (95% CI 0.67-0.73), and the internal validation indicated the accuracy of the model. Stratification factors such as a history of coronary artery bypass grafting (CABG) and comorbidity of chronic obstructive pulmonary disease (COPD) induced prognostic heterogeneity among the three subtypes. Conclusions: Clinical characteristics and prognosis significantly varied among the three subtypes of HF patients in ICUs, with HFmrEF patients achieving the best prognosis. The novel prediction model, tailored for this population, showed a satisfying prediction ability.

Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression.

BACKGROUND: Extravillous trophoblast (EVT) cell invasion is a tightly regulated process that requires for a normal pregnancy. The epithelial-mesenchymal transition (EMT) has been implicated in EVT cell invasion. Growth differentiation factor-8 (GDF-8), a member of the transforming growth factor-beta (TGF-ß) superfamily, is expressed in the human placenta and promotes EVT cell invasion by upregulating the expression of matrix metalloproteinase 2 (MMP2). However, the underlying molecular mechanism of GDF-8-induced MMP2 expression remains undetermined. Therefore, the present study aims to examine the role of Snail and Slug, the EMT-related transcriptional regulators, in GDF-8-stimulated MMP2 expression and cell invasion in HTR-8/SVneo human EVT cell line and primary cultures of human EVT cells. METHODS: HTR-8/SVneo and primary cultures of human EVT cells were used to examine the effect of GDF-8 on MMP2 expression and explore the underlying mechanism. For gene silencing and overexpression, the HTR-8/SVneo cell line was used to make the experiments more technically feasible. The cell invasiveness was measured by Matrigel-coated transwell invasion assay. RESULTS: GDF-8 stimulated MMP2 expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effect of GDF-8 on MMP2 expression was blocked by the inhibitor of TGF-ß type-I receptors, SB431542. Treatment with GDF-8 upregulated Snail and Slug expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effects of GDF-8 on Snail and Slug expression were blocked by pretreatment of SB431542 and siRNA-mediated knockdown of SMAD4. Interestingly, using the siRNA knockdown approach, our results showed that Snail but not Slug was required for the GDF-8-induced MMP2 expression and cell invasion in HTR-8/SVneo cells. The reduction of MMP2 expression in the placentas with preeclampsia (PE) was also observed. CONCLUSIONS: These findings discover the physiological function of GDF-8 in the human placenta and provide important insights into the regulation of MMP2 expression in human EVT cells. Video Abstract.

Removal of Aflatoxin B1 and Zearalenone in Mixed Aqueous Solution by Palygorskite-Montmorillonite Materials In Situ Prepared from Palygorskite Mineral.

In view of the animal feeds inevitably contaminated by multiple mycotoxins, eco-friendly and efficient palygorskite-montmorillonite (Pal-Mt) materials were prepared to remove polar aflatoxin B1 (AFB1) and weak polar zearalenone (ZEN) from mixed mycotoxins aqueous solution. The adsorption properties and bonding mechanisms between Pal-Mt materials and mycotoxins (AFB1 and ZEN) were investigated systematically. The as-prepared Pal-Mt showed excellent adsorption capacity for AFB1 and ZEN in single- and binary-mycotoxin systems, indicating the effectiveness of Pal-Mt acting as multiple mycotoxin adsorbents. The kinetics of adsorption for ZEN was fast due to the adsorption on the external surface (film and intraparticle diffusion), while AFB1 molecules permeated into mesopores after the external adsorption for the more planar structure. Adsorption isotherms demonstrated that heterogeneous surface adsorption appeared between Pal-Mt and AFB1, and monolayer adsorption occurred on Pal-Mt and ZEN for different polarities of mycotoxins. Thermodynamic parameters illustrated that the adsorption process of both AFB1 and ZEN onto Pal-Mt was spontaneous and endothermic. The adsorption mechanism studies suggested that hydrogen bonding, electrostatic attraction, calcium bridging linkage, and ion-dipole played fundamental roles in the interaction between Pal-Mt and these two mycotoxins.

Coordination of hydraulic and leaf-level gas exchange traits during water-deficit acclimation in apple rootstocks.

Water deficit episodes impact apple (Malus domestica) productivity through challenging the trees' water status, the influence of extreme high temperature climate has become increasingly prominent in recent years. Rootstocks can bestow specific properties on the fruit trees such as the resistance to drought stress. However, the related hydraulic mechanisms in response to water deficit have not been fully understood. Herein, five rootstocks (SH6, GM256, M9, M26, and MM106) were examined under water limitation. The hydraulic conductance of root (Kroot), shoots (Kshoot), and stems (Kstem-shoot) in the five rootstocks reduced slightly during drought stress. Whereas the leaf water potential and photosynthesis of five rootstocks decreased dramatically when they were exposed to drought stress. Additionally, the Kshoot and Kstem-shoot were strongly correlated with the total plant leaf area. Aquaporins (AQPs) involved in the symplastic water transport pathway, the PIP2:1, TIP1:1, and TIP2:2 mRNA levels of all genotypic rootstocks showed significant regulation under drought stress. We examined the relationships among photosynthesis, apoplastic, and symplastic water movement pathways to achieve a comprehensive understanding of rootstocks' hydraulic strategy for improving drought adaptation. The PIP2:1 and TIP2:1 in leaves were more sensitive to root hydraulic conductance in response to drought stress. Furthermore, the coordinated relationship existed in leaf-specific conductance of shoot (Kl -shoot) and transpiration rate (Tr) under drought stress in the rootstocks. Overall, the drought resistance in the five dwarfing rootstocks is associated with the rapid re-establishment of water-related traits, and the effect of the canopy on the drought resistance in apple rootstocks merits much more attention.

Association of RTN4 indel polymorphisms with the risk of tumorigenesis in the Chinese Han population.

Although studies have reported the association of two insertion/deletion (indel) polymorphisms in the 3'-untranslated region (UTR) of the RTN4 gene with the risk of tumorigenesis, the findings are inconsistent and require further explanation. Comprehensive literature searches were undertaken in Pubmed, Embase, Web of Science, China National Knowledge Infrastructure, and WangFang database. The risk of tumorigenesis was determined using odds ratios (ORs) and 95% confidence intervals (CIs) based on STATA 12.0 software. A total of four case-control studies with 1214 patients and 1850 controls focused on the RTN4 gene TATC/- polymorphism and five case-control studies with 1625 patients and 2321 controls on the RTN4 gene CAA/- polymorphism. Pooled analysis showed that the TATC/- polymorphism was not associated with the risk of tumorigenesis under all genetic models and the CAA/- polymorphism was significantly associated with the risk of tumorigenesis under the homozygote genetic model (Del/Del vs. Ins/Ins: OR=1.32, 95%CI=1.04-1.68, P=0.02). In conclusion, the current findings suggested that the CAA/- polymorphism in the 3'-UTR of the RTN4 gene was significantly associated with the risk of tumorigenesis in the Chinese population and may serve as a valuable marker for predicting tumor risk.

Adsorption and catalytic degradation of bisphenol A and p-chlorophenol by magnetic carbon nanotubes.

Phenolic compounds are common industrial pollutants that seriously endangers water ecology and human health. Therefore, the development of efficient and recyclable adsorbents is of importance for wastewater treatment. In this research, HCNTs/Fe3O4 composites were constructed using co-precipitation way by loading magnetic Fe3O4 particles onto hydroxylated multi-walled carbon nanotubes (MWCNTs), showing excellent adsorption capacity for Bisphenol A (BPA) and p-chlorophenol (p-CP), and excellent catalytic ability of activating potassium persulphate (KPS) for degradation of BPA and p-CP. The adsorption capacity and catalytic degradation potential were evaluated for the removal of BPA and p-CP from solutions. The results showed that the adsorption took only 1 h to reach equilibrium and HCNTs/Fe3O4 had maximum adsorption capacities of 113 mg g-1 for BPA and 41.6 mg g-1 for p-CP at 303 K, respectively. The adsorption of BPA fitted well using the Langmuir, Temkin and Freundlich models while the adsorption of p-CP fitted well using the Freundlich and Temkin models. BPA adsorption on HCNTs/Fe3O4 was dominated by π-π stacking and hydrogen bonding forces. The adsorption included both the mono-molecular layer adsorption on the adsorbent surface and the multi-molecular layer adsorption on the non-uniform surface. The adsorption of p-CP on HCNTs/Fe3O4 was a multi-molecular layer adsorption on a dissimilar surface. The adsorption was controlled by forces such as π-π stacking, hydrogen bonding, partition effect and molecular sieve effect. Moreover, KPS was added to the adsorption system to initiate a heterogeneous Fenton-like catalytic degradation. Over a wide pH range (4-10), 90% of the aqueous BPA solution and 88% of the p-CP solution were degraded in 3 and 2 h, respectively. After three adsorption-regeneration or degradation cycles, the removal of BPA and p-CP remained up to 88% and 66%, indicating that HCNTs/Fe3O4 composite is cost-effective, stable and highly efficient to remove BPA and p-CP from solution.

Tumor microenvironment-responsive DNA-based nanomedicine triggers innate sensing for enhanced immunotherapy.

Lack of proper innate sensing inside the tumor microenvironment could reduce both innate and adaptive immunity, which remains a critical cause of immunotherapy failure in various tumor treatments. Double-stranded DNA (dsDNA) has been evidenced to be a promising immunostimulatory agent to induce type I interferons (IFN-Is) production for innate immunity activation through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, yet the unsatisfactory delivery and susceptibility to nuclease degradation hindered its feasibility for further clinical applications. Herein, we report on the constructed tumor microenvironment-responsive DNA-based nanomedicine loaded by dendritic mesoporous organosilica nanoparticles (DMONs), which provide efficient delivery of dsDNA to induce intratumoral IFN-Is production for triggering innate sensing for enhanced anti-tumor immunotherapy. Extensive in vitro and in vivo evaluations have demonstrated the dramatic IFN-Is production induced by dsDNA@DMONs in both immune cells and tumor cells, which facilitates dendritic cells (DCs) maturation and T cells activation for eliciting the potent innate immune and adaptive immune responses. Desirable biosafety and marked therapeutic efficacy with a tumor growth inhibition (TGI) of 51.0% on the murine B16-F10 melanoma model were achieved by the single agent dsDNA@DMONs. Moreover, dsDNA@DMONs combined with anti-PD-L1 antibody further enhanced the anti-tumor efficacy and led to almost complete tumor regression. Therefore, this work highlighted the immunostimulatory DNA-based nanomedicine as a promising strategy for overcoming the resistance to immunotherapy, by promoting the IFN-Is production for innate immunity activation and remodeling the tumor microenvironment.

A novel radiomics based on multi-parametric magnetic resonance imaging for predicting Ki-67 expression in rectal cancer: a multicenter study.

BACKGROUND: To explore the value of multiparametric MRI markers for preoperative prediction of Ki-67 expression among patients with rectal cancer. METHODS: Data from 259 patients with postoperative pathological confirmation of rectal adenocarcinoma who had received enhanced MRI and Ki-67 detection was divided into 4 cohorts: training (139 cases), internal validation (in-valid, 60 cases), and external validation (ex-valid, 60 cases) cohorts. The patients were divided into low and high Ki-67 expression groups. In the training cohort, DWI, T2WI, and contrast enhancement T1WI (CE-T1) sequence radiomics features were extracted from MRI images. Radiomics marker scores and regression coefficient were then calculated for data fitting to construct a radscore model. Subsequently, clinical features with statistical significance were selected to construct a combined model for preoperative individualized prediction of rectal cancer Ki-67 expression. The models were internally and externally validated, and the AUC of each model was calculated. Calibration and decision curves were used to evaluate the clinical practicality of nomograms. RESULTS: Three models for predicting rectal cancer Ki-67 expression were constructed. The AUC and Delong test results revealed that the combined model had better prediction performance than other models in three chohrts. A decision curve analysis revealed that the nomogram based on the combined model had relatively good clinical performance, which can be an intuitive prediction tool for clinicians. CONCLUSION: The multiparametric MRI radiomics model can provide a noninvasive and accurate auxiliary tool for preoperative evaluation of Ki-67 expression in patients with rectal cancer and can support clinical decision-making.