Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-ß.

Purpose: The typical characteristic of COPD is airway remodeling, affected by environmental and genetic factors. However, genetic studies on COPD have been limited. Currently, the Abhd2 gene is found to play a critical role in maintaining alveolar architecture and stability. The research aims to investigate the predictive value of Abhd2 for airway remodeling in COPD and its effect on TGF-ß regulation. Methods: In humans, Abhd2 protein was obtained from peripheral blood monocytes. Peripheral blood TGF-ß, pulmonary surfactant proteins (SPs), metalloproteinases, inflammatory indicators (WBC, NEU, NLR, EOS, CRP, PCT, D-Dimer), chest CT (airway diameter and airway wall thickness), pulmonary function, and blood gas analysis were used to assess airway remodeling. In animals, Abhd2 deficient mice (Abhd2Gt/Gt) using gene trapping and C57BL6 mice were injected intraperitoneally with CSE to construct COPD models. HE staining, Masson staining and immunohistochemistry were used to observe the pathological changes of airway in mice, and RT-PCR, WB, ELISA and immunofluorescence were used to detect the expression of secreted proteins and EMT markers. Results: COPD patients with worse pulmonary function and higher airway remodeling-related inflammatory factors had lower Abhd2 protein expression. Moreover, indicators followed the same trend for COPD patients grouped by prognosis (Group A vs Group B). Serum TGF-ß was negatively correlated with Abhd2 protein expression, FEV1/FVC, FEV1, and FEV1% PRED. In mice, Abhd2 depletion promoted deposition of TGF-ß, leading to more pronounced emphysema, airway thickening, increased alveolar macrophage infiltration, decreased AECII number and SPs, and EMT phenomenon. Conclusion: Downregulation of Abhd2 can promote airway remodeling in COPD by modulating repair after injury and EMT via TGF-ß. This study suggests that Abhd2 may serve as a biomarker for assessing airway remodeling and guiding prognosis in COPD.

Extending Cycling Life Beyond 300 000 Cycles in Aqueous Zinc Ion Capacitors Through Additive Interface Engineering.

Developing low-cost and long-cycling-life aqueous zinc (Zn) ion capacitors (AZICs) for large-scale electrochemical energy storage still faces the challenges of dendritic Zn deposition and interfacial side reactions. Here, an interface engineering strategy utilizing a dibenzenesulfonimide (BBI) additive is employed to enhance the stability of the Zn metal anode/electrolyte interface. The first-principles calculation results demonstrate that BBI anions can be chemically adsorbed on Zn metal. Meanwhile, the experimental results confirm that the BBI-Zn interfacial layer converts the original water-richelectric double layer (EDL) into a water-poor EDL, effectively inhibiting the water related parasitic reaction at the electrode/electrolyte interface. In addition, the BBI-Zn interfacial layer introduces an additional Zn ions (Zn2+ ) migration energy barrier, increasing the Zn2+ de-solvation activation energy, consequently raising the Zn2+ nucleation overpotential, and thus achieving the compact and uniform Zn deposition behavior. Furthermore, the solid electrolyte interphase (SEI) layer derived from the BBI-Zn interfacial layer during cycling can further maintain the interfacial stability of the Zn anode. Owing to the above favorable features, the assembled AZIC exhibits an ultra-long cycling life of over 300 000 cycles based on the additive engineering strategy, which shows application prospects in high-performance AZICs.

Bioinformatics approach to identify the hub gene associated with COVID-19 and idiopathic pulmonary fibrosis.

The coronavirus disease 2019 (COVID-19) has developed into a global health crisis. Pulmonary fibrosis, as one of the complications of SARS-CoV-2 infection, deserves attention. As COVID-19 is a new clinical entity that is constantly evolving, and many aspects of disease are remain unknown. The datasets of COVID-19 and idiopathic pulmonary fibrosis were obtained from the Gene Expression Omnibus. The hub genes were screened out using the Random Forest (RF) algorithm depending on the severity of patients with COVID-19. A risk prediction model was developed to assess the prognosis of patients infected with SARS-CoV-2, which was evaluated by another dataset. Six genes (named NELL2, GPR183, S100A8, ALPL, CD177, and IL1R2) may be associated with the development of PF in patients with severe SARS-CoV-2 infection. S100A8 is thought to be an important target gene that is closely associated with COVID-19 and pulmonary fibrosis. Construction of a neural network model was successfully predicted the prognosis of patients with COVID-19. With the increasing availability of COVID-19 datasets, bioinformatic methods can provide possible predictive targets for the diagnosis, treatment, and prognosis of the disease and show intervention directions for the development of clinical drugs and vaccines.

Saline-Alkaline Stress Resistance of Cabernet Sauvignon Grapes Grafted on Different Rootstocks and Rootstock Combinations.

Grafting the wine grape variety Cabernet Sauvignon onto salinity-tolerant rootstocks can improve salinity tolerance and grape yields in regions with high salinity soils. In this experiment, the effects of different rootstocks and rootstock combinations on the saline-alkaline stress (modified Hoagland nutrient solution + 50 mmol L-1 (NaCl + NaHCO3)) of Cabernet Sauvignon were studied. Correlation and principal component analyses were conducted on several physiological indicators of saline-alkaline stress. Salinity limited biomass accumulation, induced damage to the plant membrane, reduced the chlorophyll content and photosynthetic capacity of plants, and increased the content of malondialdehyde, sodium (Na+)/potassium (K+) ratio, and antioxidant enzyme activities (superoxide dismutase, peroxidase, and catalase). Significant differences in several indicators were observed among the experimental groups. The results indicate that the saline-alkaline tolerance of Cabernet Sauvignon after grafting was the same as that of the rootstock, indicating that the increased resistance of Cabernet Sauvignon grapes to saline-alkaline stress stems from the transferability of the saline-alkaline stress resistance of the rootstock to the scion.

Atomistic Insight into Grain Boundary Deformation Induced Strengthening in Layer-Grained Nanocrystalline Al.

The brittle nature of nanocrystalline metals presents a significant challenge to their widespread application. Extensive efforts have been undertaken to develop materials with high strength and good ductility. In this study, we have discovered a new type of nanocrystalline metal, namely, layer-grained Al, which exhibits both high strength and good ductility owing to its enhanced strain hardening ability as revealed by molecular dynamics simulation. Notably, the layer-grained model displays strain hardening instead of the equiaxed model. The observed strain hardening is attributed to grain boundary deformation, which has previously been associated with strain softening. The simulation findings offer novel insights into the synthesis of nanocrystalline materials possessing high strength and good ductility, thus expanding the potential applications of these materials.

Influence of rootstock on endogenous hormones and color change in Cabernet Sauvignon grapes.

Different rootstocks for grapes can significantly affect fruit color and quality, possibly by affecting hormone contents, related genetic pathways, and fruit coloring mechanisms in skin. 'Cabernet Sauvignon' was grafted to '5BB', 'SO4', '140R', 'CS', '3309M' and 'Vitis riparia' rootstocks, with self-rooting seedlings as the control (CS/CS), and sampled from the early stage of veraison to the ripening stage. The effects of rootstock on the contents of gibberellin (GA3), auxin (IAA), and abscisic acid (ABA) in grape skin were determined alongside the expression levels of eight anthocyanin synthesis related genes using real-time fluorescence quantitative PCR methods. The rootstock cultivars exhibited accelerated fruit color change, and the CS/140R combination resulted in grapes with more color than the control group in the same period. With the development of fruit, the IAA and GA3 contents in the skin of different rootstock combinations showed trends of increasing initially, then decreasing, while the ABA content decreased initially and then increased. During the verasion (28 July), the various 'Cabernet Sauvignon' rootstock combinations exhibited varying degrees of increases in GA3, ABA, and IAA contents; correlation analysis showed that, at the start of veraison, the expression levels of the anthocyanin synthesis-related genes VvCHS, VvDFR, and VvUFGT had strong positive correlations with hormone contents, which indicated they are key genes involved in the endogenous hormone responsive anthocyanin biosynthesis pathway. The results of this study showed that rootstock regulates the fruit coloring process by influencing the metabolism level of peel hormones in the 'Cabernet Sauvignon' grape.

Spatiotemporal dynamics of fluopyram trunk-injection in Pinus massoniana and its efficacy against pine wilt disease.

BACKGROUND: Pine wilt disease (PWD) is a destructive disease of pine trees caused by the pinewood nematode, Bursaphelenchus xylophilus. Fluopyram, a novel nematicide compound with systemic activity, is a prospective trunk-injection agent against pinewood nematodes. The disadvantage of current trunk-injection agents is that they were not evenly distributed in tree tissues and were poor in the persistence of effect and efficiency. Therefore, we investigated the spatiotemporal transport pattern and residue behavior of fluopyram following its injection into the trunk of Pinus massoniana. RESULTS: Fluopyram transport in the trunk occurred through radial diffusion and vertical uptake within 1 week of the injection, reaching all tissues of P. massoniana, including apical branches and needles. Three years after the field test, the infection of PWD declined substantially with treatment using the fluopyram trunk-injection agent, which demonstrated 100% efficacy in both the mild and moderate occurrence areas, and 71.1% efficacy in the severe occurrence area. Fluopyram as trunk-injection agent exerted substantial control over PWD, with its efficacy being influenced by the infection time of PWD. The half-life of 10% fluopyram in treated pine trees was 346.6 days with 3-year persistence. CONCLUSION: The advantages of overall distribution and long persistence of fluopyram in the tree after injection help explain its evident efficacy against PWN. Overall, fluopyram trunk-injection has potential to prevent PWD. © 2023 Society of Chemical Industry.

An abscopal effect in a gastric cancer patient treated with combined chemoimmunotherapy and palliative radiotherapy.

The prognosis of advanced gastric cancer remains poor. Palliative radiotherapy has been utilized to palliate bleeding in unresectable gastric cancer. Recent studies have described that a systemic immune response may be induced by local radiotherapy to the primary tumor lesion. Here we report a rare case of an abscopal effect in a patient with inoperable gastric cancer combined with tumor hemorrhage. A short course of radiotherapy was performed to palliate bleeding; additionally, the patient was treated with chemotherapy and immunotherapy. Complete response was achieved in the lung metastasis lesion. The observed abscopal effect suggests that there may be a synergistic effect between immunotherapy and radiotherapy. This case report supports the combination of immunotherapy and radiotherapy in patients with advanced gastric cancer.

Our case report suggests the potential benefits of immunotherapy combined with palliative radiotherapy in advanced gastric cancer. Metastatic lesions of cancer patients could obtain a treatment response by local radiotherapy to the primary tumor and systemic immunotherapy. The results indicate a synergistic effect of immunotherapy and radiotherapy in activating an antitumor immune response.

The miR-532-E2F1 feedback loop contributes to gastric cancer progression.

Gastric cancer (GC) ranks fourth in incidence and mortality worldwide, ascertaining the pathogenesis of GC is crucial for its treatment. E2F1, which regulates the transcription of genes encoding proteins involved in DNA repair, DNA replication, mitosis and survival of cancer patients, functions as a key regulator in GC progression. However, the underneath mechanism of these processes is not fully elucidated. Here, TCGA database analysis, microarray immunohistochemical technique and western blot showed that E2F1 was highly upregulated in clinical GC tissues and correlated with tumor malignancy. In vitro and in vivo assays confirmed the oncogenic function of E2F1. MiR-532 was decreased and negatively correlated with E2F1 in GC tissues. MiR-532 directly targeted and inhibited E2F1 expression, leading to the decrease of ASK1 and elevation of TXNIP, and affected proliferation, cell cycle, apoptosis and DNA damage in vitro and tumor growth in vivo. Moreover, E2F1 serves as a transcriptional repressor to suppress miR-532 expression and a double-negative feedback loop was formed between them. This study demonstrates the significant roles of the E2F1-miR-532 double-negative feedback loop in GC progression and may represent a potential target for GC therapy.

A novel role of miR-326 in colorectal carcinoma by regulating E2F1 expression.

PURPOSE: Colorectal carcinoma (CRC) ranks third in incidence but second in mortality worldwide, ascertaining the pathogenesis of CRC is crucial for its treatment. Accumulating studies have shown that E2F1 is a key regulator in CRC progression, which regulates the transcription of genes engaged in DNA replication, mitosis and survival of cancer patients, however, the mechanism of these processes is not fully elucidated. METHODS: Here, we determined E2F1 expression in clinical CRC specimens by TCGA database analysis, Microarray immunohistochemical technique and Western blot, respectively. The expression of E2F1 was elevated in CRC tumor tissues, and the patients' total survival time was associated with the level of E2F1. Then the prediction software and meta-analysis were used to predict the miRNAs targeting E2F1. RT-qPCR, TCGA analysis and in situ hybridization experiments were utilized to determine the decreased miR-326 expression in CRC tumor tissues. Luciferase and Western blot assays determined that miR-326 directly targeted E2F1 in CRC cells. Next, CCK8, flow cytometry, Transwell and wound healing assays were used to determine the biological function of miR-326-E2F1 axis in vitro. RESULTS: miR-326 overexpression significantly inhibited the viability, invasion and migration and promoted the apoptosis of CRC cells, but overexpression of both E2F1 and miR-326 in turn increased cell viability, invasion and migration and decreased cell apoptosis. CONCLUSIONS: This study demonstrates the significant roles of miR-326-E2F1 in CRC progression and may represent a potential target for CRC therapy.

A single-cell-resolution fate map of endoderm reveals demarcation of pancreatic progenitors by cell cycle.

A progenitor cell could generate a certain type or multiple types of descendant cells during embryonic development. To make all the descendant cell types and developmental trajectories of every single progenitor cell clear remains an ultimate goal in developmental biology. Characterizations of descendant cells produced by each uncommitted progenitor for a full germ layer represent a big step toward the goal. Here, we focus on early foregut endoderm, which generates foregut digestive organs, including the pancreas, liver, foregut, and ductal system, through distinct lineages. Using unbiased single-cell labeling techniques, we label every individual zebrafish foregut endodermal progenitor cell out of 216 cells to visibly trace the distribution and number of their descendant cells. Hence, single-cell-resolution fate and proliferation maps of early foregut endoderm are established, in which progenitor regions of each foregut digestive organ are precisely demarcated. The maps indicate that the pancreatic endocrine progenitors are featured by a cell cycle state with a long G1 phase. Manipulating durations of the G1 phase modulates pancreatic progenitor populations. This study illustrates foregut endodermal progenitor cell fate at single-cell resolution, precisely demarcates different progenitor populations, and sheds light on mechanistic insights into pancreatic fate determination.

Key Developmental Regulators Suggest Multiple Origins of Pancreatic Beta Cell Regeneration.

Extensive efforts have been done to try to restore the lost ß cell mass for the cure of diabetes. Animal models have been established to provide evidences of cellular origins and contextual regulators of ß cell regeneration. Here, we used a zebrafish ß cell ablation and regeneration model to investigate ß cell neogenesis in the first few days after a near-total ß cell loss. Regeneration of ß cells first occurred within 7 h post-treatment. Developmental regulators such as neurod, pdx1, mnx1, and nkx2.2a were active in the regenerating ß cells, while at the same time suggesting different subpopulations of regenerative cellular origins. Using Cre/loxP-based lineage tracing, we showed that intrapancreatic ductal cells resisted to give rise to regenerating ß cells. Given that transdifferentiation of α cell and δ cell can regenerate ß cell, here we have provided further molecular evidence highly suggesting that the regenerating ß cells originate from multiple cellular origins.

Rational Design of Ion Transport Paths at the Interface of Metal-Organic Framework Modified Solid Electrolyte.

Solid-state lithium batteries have attracted great attention owing to their potential advantages in safety and energy density. Among various solid electrolytes, solid polymer electrolyte is promising due to its good viscoelasticity, lightweight, and low-cost processing. However, key issues of solid polymer electrolyte include poor ionic conductivity and low Li+ transference number, which limit its practical application. Herein, a new-type of ultraviolet cross-linked composite solid electrolyte (C-CSE), composed of ZIF-based ionic conductor (named ZIL) and polymer, is designed with enhanced ion transport. The ZIL is composed of ZIF-8 and ionic liquid, which can provide C-CSE with fast ion transport paths. Moreover, the proper pore size of ZIF-8 can restrict the migration of embedded ionic liquid and thus construct a solid-liquid transport interface between polymer chains and ZIF-8, which could achieve fast ion transport. In addition, ultraviolet irradiation can decrease the crystallization of C-CSE and thus increase the amorphous region. Consequently, the C-CSE show excellent electrochemical performance including high ionic conductivity of 0.426 mS cm-1 at 30 °C, high Li+ transference number of 0.67, and good Li|Li compatibility cycle over 1040 h. Experimental and computational results indicate that diffusion energy barrier of Li+ through ZIF-8 is smaller than that of polymer chains, which reveals a new Li+ transport mechanism between polymer chains and ZIL, from "chain-chain-chain" to "chain-ZIL-chain". This work demonstrates rational design of ion transport paths at the interface of solid electrolyte could facilitate the development of solid-state lithium batteries as a promising novel strategy.

Ternary TiO2/SiOx@C nanocomposite derived from a novel titanium-silicon MOF for high-capacity and stable lithium storage.

A novel titanium-silicon MOF precursor was first designed and constructed via a facile solvothermal process. After subsequent pyrolysis, the derived ternary TiO2/SiOx@C nanocomposite exhibited superior lithium storage performances, which was attributed to their all-in-one architecture of synergistic components, including stable-cycling nanostructured TiO2, high-capacity SiOx and high-conductivity carbon matrix.

Facile formation of tetragonal-Nb2O5 microspheres for high-rate and stable lithium storage with high areal capacity.

Niobium pentoxide (Nb2O5) has attracted great attention as an anode for lithium-ion battery, which is attributed to the high-rate and good stability performances. In this work, TT-, T-, M-, and H-Nb2O5 microspheres were synthesized by a facile one-step thermal oxidation method. Ion and electron transport properties of Nb2O5 with different phases were investigated by both electrochemical analyses and density functional theoretical calculations. Without nanostructuring and carbon modification, the tetragonal Nb2O5 (M-Nb2O5) displays preferable rate capability (121 mAh g-1 at 5 A g-1), enhanced reversible capacity (163 mAh g-1 at 0.2 A g-1) and better cycling stability (82.3% capacity retention after 1000 cycles) when compared with TT-, T-, and H-Nb2O5. Electrochemical analyses further reveal the diffusion-controlled Li+ intercalation kinetics and in-situ X-ray diffraction analysis indicates superior structural stability upon Li+ intercalation/deintercalation. Benefiting from the intrinsic fast ion/electron transport, a high areal capacity of 2.24 mAh cm-2 is obtained even at an ultrahigh mass loading of 22.51 mg cm-2. This work can promote the development of Nb2O5 materials for high areal capacity and stable lithium storage towards practical applications.

The Critical Role of the miR-21-MEG2 Axis in Colorectal Cancer.

Protein tyrosine phosphatase MEG2 (MEG2/PTPN9), a classic tyrosine-specific protein tyrosine phosphatase (PTP), is involved in the progression of liver, breast, and gastric cancers. However, the function and regulation of MEG2 in colorectal cancer (CRC) still remain unclear. In this study, we investigated the expression of MEG2 in CRC and found that MEG2 was downregulated in human CRC tissues compared to normal corresponding tissues. Moreover, in vivo and in vitro assays revealed that MEG2 plays a vital role in CRC cell proliferation, invasion, and apoptosis. In addition, mechanism analysis validated miR-21 as a direct regulator of MEG2, and miR-21 plays a critical role in promoting proliferation, invasion, and suppression of apoptosis in CRC by targeting MEG2. Taken together, this study demonstrates the significant role for miR-21 in regulating MEG2 in CRC and may represent a potential target for CRC therapy.

Using zebrafish as the model organism to understand organ regeneration.

The limited regenerative capacity of several organs, such as central nervous system (CNS), heart and limb in mammals makes related major diseases quite difficult to recover. Therefore, dissection of the cellular and molecular mechanisms underlying organ regeneration is of great scientific and clinical interests. Tremendous progression has already been made after extensive investigations using several model organisms for decades. Unfortunately, distance to the final achievement of the goal still remains. Recently, zebrafish became a popular model organism for the deep understanding of regeneration based on its powerful regenerative capacity, in particular the organs that are limitedly regenerated in mammals. Additionally, zebrafish are endowed with other advantages good for the study of organ regeneration. This review summarizes the recent progress in the study of zebrafish organ regeneration, in particular regeneration of fin, heart, CNS, and liver as the representatives. We also discuss reasons of the reduced regenerative capacity in higher vertebrate, the roles of inflammation during regeneration, and the difference between organogenesis and regeneration.

EpCAM is an endoderm-specific Wnt derepressor that licenses hepatic development.

Mechanisms underlying cell-type-specific response to morphogens or signaling molecules during embryonic development are poorly understood. To learn how response to the liver-inductive Wnt2bb signal is achieved, we identify an endoderm-enriched, single transmembrane protein, epithelial-cell-adhesion-molecule (EpCAM), as an endoderm-specific Wnt derepressor in zebrafish. hi2151/epcam mutants exhibit defective liver development similar to prt/wnt2bb mutants. EpCAM directly binds to Kremen1 and disrupts the Kremen1-Dickkopf2 (Dkk2) interaction, which prevents Kremen1-Dkk2-mediated removal of Lipoprotein-receptor-related protein 6 (Lrp6) from the cell surface. These data lead to a model in which EpCAM derepresses Lrp6 and cooperates with Wnt ligand to activate Wnt signaling through stabilizing membrane Lrp6 and allowing Lrp6 clustering into active signalosomes. Thus, EpCAM cell autonomously licenses and cooperatively activates Wnt2bb signaling in endodermal cells. Our results identify EpCAM as the key molecule and its functional mechanism to confer endodermal cells the competence to respond to the liver-inductive Wnt2bb signal.