Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

In vitro induction of tetraploids and their phenotypic and transcriptome analysis in Glehnia littoralis.

BACKGROUND: Glehnia littoralis is a medicinal and edible plant species having commercial value and has several hundred years of cultivation history. Polyploid breeding is one of the most important and fastest ways to generate novel varieties. To obtain tetraploids of G. littoralis in vitro, colchicine treatment was given to the seeds and then were screened based on morphology, flow cytometry, and root tip pressing assays. Furthermore, transcriptome analysis was performed to identity the differentially expressed genes associated with phenotypic changes in tetraploid G. littoralis. RESULTS: The results showed that 0.05% (w/v) colchicine treatment for 48 h was effective in inducing tetraploids in G. littoralis. The tetraploid G. littoralis (2n = 4x = 44) was superior in leaf area, leaf thickness, petiole diameter, SPAD value (Chl SPAD), stomatal size, epidermal tissues thickness, palisade tissues thickness, and spongy tissues thickness to the diploid ones, while the stomatal density of tetraploids was significantly lower. Transcriptome sequencing revealed, a total of 1336 differentially expressed genes (DEGs) between tetraploids and diploids. Chromosome doubling may lead to DNA content change and gene dosage effect, which directly affects changes in quantitative traits, with changes such as increased chlorophyll content, larger stomata and thicker tissue of leaves. Several up-regulated DEGs were found related to growth and development in tetraploid G. littoralis such as CKI, PPDK, hisD and MDP1. KEGG pathway enrichment analyses showed that most of DEGs were enriched in metabolic pathways. CONCLUSIONS: This is the first report of the successful induction of tetraploids in G. littoralis. The information presented in this study facilitate breeding programs and molecular breeding of G. littoralis varieties.

Amorphous Engineering of Scalable Metal-Organic Framework-Derived Electrocatalyst for Highly Efficient Oxygen Evolution Reaction.

The engineering of amorphous metal-organic frameworks (MOFs) offers potential opportunities for the construction of electrocatalysts for efficient oxygen evolution reaction (OER). Herein, highly efficient OER performance and durability in alkaline electrolyte are discovered for MOF-derived amorphous and porous electrocatalysts, which are synthesized in a brief procedure and can be facilely produced in scalable quantities. The structural inheritance of MOF amorphous catalysts is significant for the retention of catalytic sites and the diffusion of electrolytes, and the presence of Fe sites can change the electronic structure and effectively control the adsorption behavior of important intermediates, accelerating reaction kinetics. The obtained amorphous A-FeNi can be transformed from FeNi-MOF effortlessly and instantly, and it only needs low overpotentials of 152 and 232 mV at 10 and 100 mA cm-2 with a Tafel slope of 17 mV dec-1 in 1 m KOH for OER. Moreover, A-FeNi possesses high corrosion resistance and durability, therefore A-FeNi can work continually for at least 400 h at 100 mA cm-2. This work may pave a new avenue for the design of MOFs-related amorphous electrocatalyst.

Constructing Nitrogen-Doped Carbon Hierarchy Structure Derived from Metal-Organic Framework as High-Performance ORR Cathode Material for Zn-Air Battery.

The development of efficient and low-cost catalysts for cathodic oxygen reduction reaction (ORR) in Zn-air battery (ZAB) is a key factor in reducing costs and achieving industrialization. Here, a novel segregated CoNiPt alloy embedded in N-doped porous carbon with a nanoflowers (NFs)-like hierarchy structure is synthesized through pyrolyzing Hofmann-type metal-organic frameworks (MOFs). The unique hierarchical NFs structure exposes more active sites and facilitates the transportation of reaction intermediates, thus accelerating the reaction kinetics. Impressively, the resulting 15% CoNiPt@C NFs catalyst exhibits outstanding alkaline ORR activity with a half-wave potential of 0.93 V, and its mass activity is 7.5 times higher than that of commercial Pt/C catalyst, surpassing state-of-the-art noble metal-based catalysts. Furthermore, the assembled CoNiPt@C+RuO2 ZAB demonstrates a maximum power density of 172 mW cm-2 , which is superior to that of commercial Pt/C+RuO2 ZAB. Experimental results reveal that the intrinsic ORR mass activity is attributed to the synergistic interaction between oxygen defects and pyrrolic/graphitic N species, which optimizes the adsorption energy of the intermediate species in the ORR process and greatly enhances catalytic activity. This work provides a practical and feasible strategy for synthesizing cost-effective alkaline ORR catalysts by optimizing the electronic structure of MOF-derived catalysts.

Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

Association between triglyceride-glucose related indices and mortality among individuals with non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4). RESULTS: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.

Phase separation is required for PML nuclear body biogenesis and function.

PML nuclear body (NB) malfunction often leads to acute leukemia outbreaks and other severe diseases. PML NB rescue is the molecular basis of arsenic success in acute promyelocytic leukemia (APL) treatment. However, it is unclear how PML NBs are assembled. Here, we observed the presence of liquid-liquid phase separation (LLPS) in NB formation by fluorescence recovery after photobleaching (FRAP) experiment. Compared with the wild-type (WT) NBs, PML A216V derived from arsenic-resistant leukemia patients markedly crippled LLPS, but not altered the overall structure and PML RBCC oligomerization. In parallel, we also reported several Leu to Pro mutations that were critical to PML coiled-coil domain. FRAP characterization and comparison between L268P and A216V revealed markedly different LLPS activities in these mutant NBs. Transmission electron microscopy (TEM) inspections of LLPS-crippled and uncrippled NBs showed aggregation- and ring-like PML packing in A216V and WT/L268P NBs, respectively. More importantly, the correct LLPS-driven NB formation was the prerequisite for partner recruitment, post-translational modifications (PTMs), and PML-driven cellular regulations, such as ROS stress control, mitochondria production, and PML-p53-mediated senescence and apoptosis. Altogether, our results helped to define a critical LLPS step in PML NB biogenesis.

Severe pneumonia with co-infection of H5N1 and SARS-CoV-2: a case report.

BACKGROUND: The H5N1 influenza virus is a cause of severe pneumonia. Co-infection of influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to poor prognosis of patients during the COVID-19 epidemic. However, reports on patients co-infected with avian influenza virus and SARS-CoV-2 are scarce. CASE PRESENTATION: A 52-year-old woman presented with a fever, which has persisted for the past eight days, along with worsening shortness of breath and decreased blood pressure. Computed tomography (CT) revealed an air bronchogram, lung consolidation, and bilateral pleural effusion. The subsequent polymerase chain reaction (PCR) of the bronchoalveolar lavage fluid (BALF) revealed positivity for H5N1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSION: The H5N1 influenza virus is a cause of severe pneumonia. The clinical presentation of the patient had a predomination of H5N1 influenza rather than COVID-19. A PCR analysis for the identification of the virus is necessary to reveal the pathogen causing the severe pneumonia. The patient exhibited an excellent prognosis upon the use of the appropriate antiviral medicine.

Integrated ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry-based components analysis and network pharmacology strategy of Gancao Xiexin Decoction in treating gastric ulcer.

Gancao Xiexin Decoction (GCXXD) is a traditional Chinese decoction that is often used in treating gastric ulcers. However, the substance basis and mechanism of action remain unclear. In this study, in vivo and in vitro components of GCXXD were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry. The compound Discover platform was used to ultimately enable rapid identification of compounds. Acquire X intelligent data acquisition technology software was innovatively adopted. In the process of collecting drug-containing plasma, all components detected in blank plasma samples were excluded to eliminate the interference and influence of endogenous components in plasma, making the analysis results more accurate and reliable. At the same time, the possibility of selecting precursor parent ions with low concentration levels within the chromatographic peak can be increased, improving the coverage and integrality of the detection of components in vivo. Also, the targeted network pharmacology strategy combined with molecular docking was established to explore the mechanism of GCXXD in treating gastric ulcers. As a result, 113 components were identified, 41 of which could enter the bloodstream and exert therapeutic effects in vivo. The main effective components are glycyrrhizic acid, 6-gingerol, jatrorrhizine, wogonin, palmatine, and liquiritigenin, main targets in vivo were related to ALB, IL6, and VEGF, which play an important role in anti-inflammatory and promoting angiogenesis. In summary, this study adopted a comprehensive analysis strategy to reveal the pharmacodynamic material basis and mechanism of GCXXD against gastric ulcers, providing a scientific basis for its clinical application.

No causal association between atopic dermatitis and COVID-19 outcomes: A Mendelian randomization study.

BACKGROUND: Frequent hand washing and disinfection during the corona virus disease (COVID-19) pandemic may lead to skin-related disability. The causal relationship between atopic dermatitis (AD), the most common chronic, noninfectious, inflammatory skin disease, and COVID-19 remains unclear. We used Mendelian randomization (MR) to explore the causal inference of atopic dermatitis with COVID-19 outcomes. METHODS: Genome-wide association study (GWAS) data for AD, consisting of 8383 cases and 236,162 controls of European ethnicity, were provided by the FinnGen database. The GWAS outcome data were derived from the COVID-19 Host Genetics Initiative and consisted of COVID-19 susceptibility (122,616 cases and 2,475,240 controls), hospitalization (32,519 cases and 2,062,805 controls), and very severe respiratory disease (13,769 cases and 1,072,442 controls). The inverse variance weighted with a fixed effects model (IVW (fe)) was used as the main statistical approach to assess the causality between AD and COVID-19 in this study. Several other analytical methods have also been used to complement or identify pleiotropy and heterogeneity. RESULTS: MR analysis showed no causality between AD and COVID-19 outcomes. The odds ratios (OR) were 1.00 (95% confidence interval (CI), 0.99-1.02) for susceptibility, 1.00 (95% CI, 0.96-1.04) for hospitalization, 0.97 (95% CI, 0.92-1.03) for very severe respiratory disease by the method of IVW (fe). CONCLUSION: In conclusion, we found no causal relationship between AD and COVID-19 outcomes. This study provides additional ideas for the exploration of the risk factors for COVID-19.

Modulating the m6A Modified Transcription Factor GATA6 Impacts Epithelial Cytokines in Acute Lung Injury.

The methylation of m6A (N6-position of adenosine) has been found to be associated with inflammatory response. We hypothesize that m6A modification plays a role in the inflammation of airway epithelial cells during lung inflammation. However, the precise changes and functions of m6A modification in airway epithelial cells in acute lung injury (ALI) are not well understood. Here we report that METTL3 (methyltransferase-like 3)-mediated m6A of GATA6 (GATA-binding factor 6) mRNA inhibits ALI and the secretion of proinflammatory cytokines in airway epithelial cells. The expression of METTL3 and m6A levels decrease in lung tissues of mice with ALI. In cocultures, peripheral blood monocytes secreted TNF-α, which reduces METTL3 and m6A levels in the human bronchial epithelial cell line BEAS-2B. Knockdown of METTL3 promotes IL-6 and TNF-α release in BEAS-2B cells. Conversely, overexpression of METTL3 increases total RNA m6A level and reduces the levels of proinflammatory cytokines TNF-α, transforming growth factor-ß, and thymic stromal lymphopoietin. Increasing METTL3 in mouse lungs prevented LPS-induced ALI and reduced the synthesis of proinflammatory cytokines. Mechanistically, sequencing and functional analysis show that METTL3 catalyzes m6A in the 3' untranslated region of GATA6 read by YTH N6-Methyladenosine RNA Binding Protein 2 and triggers mRNA degradation. GATA6 knockdown rescues TNF-α-induced inflammatory cytokine secretion of epithelial cells, indicating that GATA6 is a main substrate of METTL3 in airway epithelial cells. Overall, this study provides evidence of a novel role for METTL3 in the inflammatory cytokine release of epithelial cells and provides an innovative therapeutic target for ALI.

Converting Acellular Dermal Matrix into On-Demand Versatile Skin Scaffolds by a Balanceable Crosslinking Approach for Integrated Infected Wounds Therapy.

Ideal tissue-engineered skin scaffolds should possess integrated therapeutic effects and multifunctionality, such as broad-spectrum antibacterial properties, adjustable mechanical properties, and bionic structure. Acellular dermal matrix (ADM) has been broadly used in many surgical applications as an alternative treatment to the "gold standard" tissue transplantation. However, insufficient broad-spectrum antibacterial and mechanical properties for therapeutic efficacy limit the practical clinical applications of ADM. Herein, a balanceable crosslinking approach based on oxidized 2-hydroxypropyltrimethyl ammonium chloride chitosan (OHTCC) was developed for converting ADM into on-demand versatile skin scaffolds for integrated infected wounds therapy. Comprehensive experiments show that different oxidation degrees of OHTCC have significative influences on the specific origins of OHTCC-crosslinked ADM scaffolds (OHTCC-ADM). OHTCC with an oxidation degree of about 13% could prosperously balance the physiochemical properties, antibacterial functionality, and cytocompatibility of the OHTCC-ADM scaffolds. Owing to the natural features and comprehensive crosslinking effects, the proposed OHTCC-ADM scaffolds possessed the desirable multifunctional properties, including adjustable mechanical, degradable characteristics, and thermal stability. In vitro/in vivo biostudies indicated that OHTCC-ADM scaffolds own well-pleasing broad-spectrum antibacterial performances and play effectively therapeutic roles in treating infection, inhibiting inflammation, promoting angiogenesis, and promoting collagen deposition to enhance the infected wound healing. This study proposes a facile balanceable crosslinking approach for the design of ADM-based versatile skin scaffolds for integrated infected wounds therapy.

Two-Layered Biomimetic Flexible Self-Powered Electrical Stimulator for Promoting Wound Healing.

The repair of wound damage has been a common problem in clinic for a long time. Inspired by the electroactive nature of tissues and the electrical stimulation of wounds in clinical practice, the next generation of wound therapy with self-powered electrical stimulator is expected to achieve the desired therapeutic effect. In this work, a two-layered self-powered electrical-stimulator-based wound dressing (SEWD) was designed through the on-demand integration of the bionic tree-like piezoelectric nanofiber and the adhesive hydrogel with biomimetic electrical activity. SEWD has good mechanical properties, adhesion properties, self-powered properties, high sensitivity, and biocompatibility. The interface between the two layers was well integrated and relatively independent. Herein, the piezoelectric nanofibers were prepared by P(VDF-TrFE) electrospinning, and the morphology of the nanofibers was controlled by adjusting the electrical conductivity of the electrospinning solution. Benefiting from its bionic dendritic structure, the prepared piezoelectric nanofibers had better mechanical properties and piezoelectric sensitivity than native P(VDF-TrFE) nanofibers, which can convert tiny forces into electrical signals as a power source for tissue repair. At the same time, the designed conductive adhesive hydrogel was inspired by the adhesive properties of natural mussels and the redox electron pairs formed by catechol and metal ions. It has bionic electrical activity matching with the tissue and can conduct the electrical signal generated by the piezoelectric effect to the wound site so as to facilitate the electrical stimulation treatment of tissue repair. In addition, in vitro and in vivo experiments demonstrated that SEWD converts mechanical energy into electricity to stimulate cell proliferation and wound healing. The proposed healing strategy for the effective treatment of skin injury was provided by developing self-powered wound dressing, which is of great significance to the rapid, safe, and effective promotion of wound healing.

Clinical significance of dynamic variation of low cholesterol and its prognostic value in patients with pyogenic liver abscesses: a retrospective study.

BACKGROUND: Serum lipids variations are closely related to the sepsis progression; however, their value for patients with pyogenic liver abscesses (PLA) has rarely been studied. We investigated the serum lipid level variations in patients with PLA and its predictive value to the disease. METHODS: The study included 328 patients with PLA hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021; 35 (10.67%) in the severe group (SG) and 293 (89.33%) in the non-severe group (nSG). Their clinical records were analyzed retrospectively, and dynamic curves were drawn to clarify the changes in different indicators during the course of the disease. RESULTS: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) (Lp(a)) in the SG were significantly lower than those in nSG (P < 0.001). Total cholesterol (TC) at baseline (OR = 0.184, P < 0.001) was an independent risk factor for severe patients and had the highest predictive value, with an area under the curve of 0.859 and a cut-off value of 2.70 mmol/L (sensitivity = 94.3%, specificity = 63.5%). For patients who met the criteria for drainage surgery, TC, HDL-C and LDL-C levels continued to decrease with antibiotic therapy alone before drainage and began to increase after the surgery. CONCLUSIONS: Low TC level on admission is an independent risk factor for the progression of severe illness in PLA patients, with the highest predictive value surpassing other routine clinical indices. Abscess drainage should be performed as soon as possible for patients whose TC continues to decline after medical treatment.

PRMT1 Modulates Processing of Asthma-Related Primary MicroRNAs (Pri-miRNAs) into Mature miRNAs in Lung Epithelial Cells.

Protein arginine methyltransferase-1 (PRMT1) is an important epigenetic regulator of cell function and contributes to inflammation and remodeling in asthma in a cell type-specific manner. Disease-specific expression patterns of microRNAs (miRNA) are associated with chronic inflammatory lung diseases, including asthma. The de novo synthesis of miRNA depends on the transcription of primary miRNA (pri-miRNA) transcript. This study assessed the role of PRMT1 on pri-miRNA to mature miRNA process in lung epithelial cells. Human airway epithelial cells, BEAS-2B, were transfected with the PRMT1 expression plasmid pcDNA3.1-PRMT1 for 48 h. Expression profiles of miRNA were determined by small RNA deep sequencing. Comparing these miRNAs with datasets of microarrays from five asthma patients (Gene Expression Omnibus dataset), 12 miRNAs were identified that related to PRMT1 overexpression and to asthma. The overexpression or knockdown of PRMT1 modulated the expression of the asthma-related miRNAs and their pri-miRNAs. Coimmunoprecipitation showed that PRMT1 formed a complex with STAT1 or RUNX1 and thus acted as a coactivator, stimulating the transcription of pri-miRNAs. Stimulation with TGF-ß1 promoted the interaction of PRMT1 with STAT1 or RUNX1, thereby upregulating the transcription of two miRNAs: let-7i and miR-423. Subsequent chromatin immunoprecipitation assays revealed that the binding of the PRMT1/STAT1 or PRMT1/RUNX1 coactivators to primary let-7i (pri-let-7i) and primary miR (pri-miR) 423 promoter was critical for pri-let-7i and pri-miR-423 transcription. This study describes a novel role of PRMT1 as a coactivator for STAT1 or RUNX1, which is essential for the transcription of pri-let-7i and pri-miR-423 in epithelial cells and might be relevant to epithelium dysfunction in asthma.

An integrated approach based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, network pharmacology, and molecular docking to study the key effective compounds and mechanism of action of Platycodi Radix in the treatment of chronic obstructive pulmonary disease.

Platycodi Radix (PR) is a valuable herb that is widely used in the treatment of chronic obstructive pulmonary disease in clinics. However, the mechanism of action for the treatment of chronic obstructive pulmonary disease remains unclear due to the lack of in vivo studies. Our study established a novel integrated strategy based on ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry, network pharmacology, and molecular docking to systematically analyze the tissue distribution and active compounds of PR in vivo and the therapeutic mechanism of chronic obstructive pulmonary disease. First, tissue distribution studies have shown that the lung is the organ with the highest distribution of PR compounds. Subsequently, network pharmacology results showed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and mitogen-activated protein kinase signaling pathway were the critical mechanisms of PR against chronic obstructive pulmonary disease. Ultimately, molecular docking results showed that the key targets were stably bound to the corresponding active compounds of PR. Our study is of great significance for the screening of the key effective compounds and the study of the mechanism of action in traditional Chinese medicine and provides data to support the further development and utilization of PR.

The Spliceosome Factor EFTUD2 Promotes IFN Anti-HBV Effect through mRNA Splicing.

Methods: Using a CRISPR/Cas9 gene-editing system, EFTUD2 single allele knockout HepG2.2.15 cells were constructed. Subsequently, the HBV biomarkers in EFTUD2+/- HepG2.2.15 cells and wild-type (WT) cells with or without IFN-α treatment were detected. And the EFTUD2-regulated genes were then identified using mRNA sequence. Selected gene mRNA variants and their proteins were examined by qRT-PCR and Western blotting. To confirm the effects of EFTUD2 on HBV replication and IFN-stimulated gene (ISG) expression, a rescue experiment in EFTUD2+/- HepG2.2.15 cells was performed by EFTUD2 overexpression. Results: IFN-induced anti-HBV activity was found to be restricted in EFTUD2+/- HepG2.2.15 cells. The mRNA sequence showed that EFTUD2 could regulate classical IFN and virus response genes. Mechanistically, EFTUD2 single allele knockout decreased the expression of ISG-encoded proteins, comprising Mx1, OAS1, and PKR (EIF2AK2), through mediated gene splicing. However, EFTUD2 did not affect the expression of Jak-STAT pathway genes. Furthermore, EFTUD2 overexpression could restore the attenuation of IFN anti-HBV activity and the reduction of ISG resulting from EFTUD2 single allele knockout. Conclusion: EFTUD2, the spliceosome factor, is not IFN-inducible but is an IFN effector gene. EFTUD2 mediates IFN anti-HBV effect through regulation of gene splicing for certain ISGs, including Mx1, OAS1, and PKR. EFTUD2 does not affect IFN receptors or canonical signal transduction components. Therefore, it can be concluded that EFTUD2 regulates ISGs using a novel, nonclassical mechanism.

Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development.

Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14-SMXL7 and AtD14-MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants.

Microfluidic Dielectrophoretic Method Enables On-Demand Spatial Arrangement of Bacteria-Encapsulated Agarose Gel Microparticles.

Microbial interactions within a natural or engineered consortium of microbes play an important role in the functions of the consortium. Better understanding these interactions is also important for engineering microbial consortia for specific applications. As such, tools that can enable investigating microbial interactions are highly valuable. One aspect of microbial interactions that impacts community formation is how the spatial organization of individual microbes impacts interactions leading to community formation. Here, we report the development of a tool that can manipulate the spatial organization of microorganisms to investigate the role of these interactions in community formation. Our developed microfluidic platform utilizes dielectrophoretic (DEP) force to perform on-demand spatial arrangement of microorganism-encapsulated agarose gel microparticles. To demonstrate this concept, three gel microparticle manipulators composed of three independently controllable DEP electrodes were utilized for the on-demand spatial arrangement of a specific combination of microparticles, each containing Escherichia coli cells expressing red fluorescence protein, green fluorescent protein, or blank content. The spatially arranged microparticles suspended in carrier oil were first trapped in a downstream particle trapping structure to form a defined microparticle array, followed by the application of an electric field to disrupt the carrier oil barrier so that all gel microparticles were within the same aqueous solution while the individual gel microparticles remain intact, thereby maintaining their spatial arrangements. We demonstrated that this method can be utilized to generate various arrays with differing number of "spacer microparticles", which were blank microparticles, between the two different E. coli-containing microparticles, enabling precise control over spatial distances between the two different cell populations. This method paves the way for more easily investigating bacterial interactions, especially those that depend on their spatial arrangement such as where cell-cell communication plays a major role.

Abundant Dislocation Layered Double Hydroxides Synthesis by Molten Salt with Bound Water Boosting Oxygen Evolution.

Optimizing the adsorption free energy and promoting the active phase transition to further enhance the oxygen evolution reaction (OER) activity remain significant challenges. The adsorption free energy can be optimized by modulating the electronic structure and adjusting the crystal configuration. Meanwhile, the transformation of the active phase can be promoted by introducing strain energy. The theoretical calculations are conducted to verify the rational envisage. However, it is still a great obstacle to introducing strain into the electrocatalysts and avoiding destruction. The stress field caused by dislocation can realize both of the above. Hence, the molten salt with the bound water method is proposed and the abundant dislocation layered double hydroxides (D-NiFe LDH) are constructed. The in situ characterizations further verify the dislocations significantly affect the generation of the active phase and the state of electronic structure. Consequently, the D-NiFe LDH exhibits outstanding OER activity and obtains 10 mA cm-2 , only requiring 199 mV overpotential with fabulous stability (100 mA cm-2 more than 24 h). The work paves a new avenue for the rational introduction dislocations to optimize the crystal configuration and boost the active phase formation, significantly enhancing the OER performance.