Discovery of Selective PDE1 Inhibitors Alleviating Pulmonary Fibrosis by the Regulation of TGF-β/Smads and MAPK Pathways.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease with limited treatment options. Our preliminary research identified phosphodiesterase 1 (PDE1) as a potential therapeutic target for IPF treatment. However, both the molecular recognition mechanism between PDE1 inhibitors and the protein, as well as the antifibrotic mechanism, remain incompletely understood.

Study on in-situ and ex-situ catalytic pyrolysis of waste tires based on low-cost catalysts.

With the increase in the quantity of waste tires, the proper disposal of waste tires has received increasing attention. Pyrolysis is an environmentally friendly technology that converts waste tires into usable resources. However, the added value of the pyrolysis products is relatively low.

Spatially Resolved Panoramic in vivo CRISPR Screen via Perturb-DBiT.

Spatially resolved in vivo CRISPR screening integrates gene editing with spatial transcriptomics to examine how genetic perturbations alter gene expression within native tissue environments. However, current methods are limited to small perturbation panels and the detection of a narrow subset of protein-coding RNAs. We present Perturb-DBiT, a distinct and versatile approach for the simultaneous co-sequencing of spatial total RNA whole-transcriptome and single-guide RNAs (sgRNAs), base-by-base, on the same tissue section.

Optimization of Mechanical and Dynamic Properties of Tread Rubber Using Fumed Silica and Hydration Processing.

Fumed silica, a nanomaterial with a high specific surface area, excellent chemical stability, and electrical insulation, serves as an effective filler for rubber compounding. Compared to traditional carbon black, silica (SiO), the main component of fumed silica, improves the hardness and tear resistance of tread rubber, making it a viable substitute in some formulations. However, silica-filled compounds generally exhibit lower tensile properties and abrasion resistance than carbon black.

Haploid facultative parthenogenesis in sunflower sexual reproduction.

Flowering plant sexual reproduction requires double fertilization, yielding embryo and endosperm seed compartments: the latter supports embryo growth and seed germination. In an experiment to generate haploid embryos through inhibition of pollen phospholipase activity in sunflower (Helianthus annus), we serendipitously discovered that emasculated sunflowers spontaneously form parthenogenic haploid seed. Exploration of genetic, chemical and environmental factors demonstrated that a specific genotype background enabled high parthenogenesis and that full spectrum high-intensity light supplementation boosted parthenogenesis, yielding hundreds of haploid seeds per head.

Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering.

The pleiotropic effects of human disease and the complex nature of gene-interaction networks require knock-in mice allowing for multiplexed gene perturbations. Here we describe a series of knock-in mice with a C57BL/6 background and with the conditional or constitutive expression of LbCas12a or of high-fidelity enhanced AsCas12a, which were inserted at the Rosa26 locus. The constitutive expression of Cas12a in the mice did not lead to discernible pathology and enabled efficient multiplexed genome engineering.

Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8 T-cell infiltration while reducing neutrophils.

Spatially Resolved CRISPR Screen Sequencing via Perturb-DBiT.

Perturb-seq enabled the profiling of transcriptional effects of genetic perturbations in single cells but lacks the ability to examine the impact on tissue environments. We present Perturb-DBiT for simultaneous co-sequencing of spatial transcriptome and guide RNAs (gRNAs) on the same tissue section for in vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding of how genetic modifications affect cellular behavior and tissue architecture. This platform supports a variety of delivery vectors, gRNA library sizes, and tissue preparations, along with two distinct gRNA capture methods, making it adaptable to a wide range of experimental setups.

Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues.

The capability to spatially explore RNA biology in formalin-fixed paraffin-embedded (FFPE) tissues holds transformative potential for histopathology research. Here, we present pathology-compatible deterministic barcoding in tissue (Patho-DBiT) by combining in situ polyadenylation and computational innovation for spatial whole transcriptome sequencing, tailored to probe the diverse RNA species in clinically archived FFPE samples. It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms, and high-sensitivity transcriptomic mapping of clinical tumor FFPE tissues stored for 5 years.

Central memory CD4+ T cells play a protective role against immune checkpoint inhibitor-associated myocarditis.

Aims: The widespread use of immune checkpoint inhibitors (ICIs) has demonstrated significant survival benefits for cancer patients and also carries the risk of immune-related adverse events. ICI-associated myocarditis is a rare and serious adverse event with a high mortality rate. Here, we explored the mechanism underlying ICI-associated myocarditis.

Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc).

Objectives: In the complex panorama of autoimmune diseases, the characterisation of pivotal contributing autoantibodies that are involved in disease progression remains challenging. This study aimed to employ a global antibody profiling strategy to identify novel antibodies and investigate their association with systemic sclerosis (SSc).

Methods: We implemented this strategy by conducting immunoprecipitation (IP) following on-bead digestion with the sera of patients with SSc or healthy donors, using antigen pools derived from cell lysates.

Spatially Exploring RNA Biology in Archival Formalin-Fixed Paraffin-Embedded Tissues.

Spatial transcriptomics has emerged as a powerful tool for dissecting spatial cellular heterogeneity but as of today is largely limited to gene expression analysis. Yet, the life of RNA molecules is multifaceted and dynamic, requiring spatial profiling of different RNA species throughout the life cycle to delve into the intricate RNA biology in complex tissues. Human disease-relevant tissues are commonly preserved as formalin-fixed and paraffin-embedded (FFPE) blocks, representing an important resource for human tissue specimens.

Circ_0030042 inhibits trophoblast cell growth, invasion and epithelial-mesenchymal transition process in preeclampsia via miR-942-5p/LITAF.

Background: There is increasing evidence that circular RNAs (circRNAs) are involved in the processes of preeclampsia (PE). Circ_0030042 was found to be abnormally expressed in PE patients. However, the role and molecular mechanism of circ_0030042 in PE progression remains unclear.

Study on 2-arylbenzo[]furans from and their fragmentation patterns with Q-Orbitrap mass spectrometry.

One new 2-arylbenzo[]furan named iteafuranal F () as well as two known analogues () were isolated from the 95% EtOH extract of aerial parts of . Their chemical structures were constructed based on extensive analyses of UV, IR, 1D/2D NMR and HRMS spectra. Antioxidant assays revealed significant superoxide anion radical scavenging capacity of with IC value of 0.

Study on synergistic pyrolysis and kinetics of mixed plastics based on spent fluid-catalytic-cracking catalyst.

At present, disposable plastic products such as plastic packaging are very common in our daily life. These products are extremely easy to cause serious damage to the soil and marine environment due to their short design and service life, difficulties in degradation, or long degradation cycles. Thermochemical method (pyrolysis or catalytic pyrolysis) is an efficient and environmentally friendly way to treat plastic waste.

Study on the Mechanism and Experiment of Styrene Butadiene Rubber Reinforcement by Spent Fluid Catalytic Cracking Catalyst.

Spent Fluid Catalytic Cracking (FCC) Catalyst is a major waste in the field of the petroleum processing field, with a large output and serious pollution. The treatment cost of these waste catalysts is high, and how to achieve their efficient reuse has become a key topic of research at home and abroad. To this end, this paper conducted a mechanistic and experimental study on the replacement of some carbon blacks by spent FCC catalysts for the preparation of rubber products and explored the synergistic reinforcing effect of spent catalysts and carbon blacks, in order to extend the reuse methods of spent catalysts and reduce the pollution caused by them to the environment.

Preference Characteristics on Consumers' Online Consumption of Fresh Agricultural Products under the Outbreak of COVID-19: An Analysis of Online Review Data Based on LDA Model.

Since the outbreak of the COVID-19 pandemic in 2020, China has adopted a zero-clearing policy under closed control. It is rather common for residents who are quarantined at home to buy fresh agricultural products online, when COVID-19 spread in big cities. Many e-commerce platforms are trying to develop online shopping channels for fresh agricultural products.

Locked-in syndrome responding to endovascular treatment.

Background: Locked-in syndrome (LiS) is a rare and devastating condition in patients with acute basilar artery occlusion. However, the benefits of endovascular treatment (EVT) for LiS remain unclear.

Objective: To assess the outcomes associated with EVT and identify the factors associated with outcomes of LiS.

Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer.

The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses new challenges in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of an antibody targeting a conserved and universal epitope is urgently needed.

The prominent role of a CDR1 somatic hypermutation for convergent IGHV3-53/3-66 antibodies in binding to SARS-CoV-2.

In the fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), monoclonal antibodies (mAbs) serve as key strategies for the rapid prevention and treatment of COVID-19. However, analysis to fully characterize functional SARS-CoV-2 mAbs is still needed. In this study, by interrogating 1,695 published or patented mAbs of human origin and validated SARS-CoV-2-binding potency, we found a highly preferential usage of IGHV3-53/3-66 germline genes that was then revealed as a distinct selectivity of SARS-CoV-2-induced humoral immunity across other coronaviruses.

Graphene aerogel with excellent property prepared by doping activated carbon and CNF for free-binder supercapacitor.

In this paper, the two-step activation Eucommia wood tar-based activated carbon (ETAC), cellulose nanofibers (CNF) and reduced graphene oxide (rGO) were assembled to form composite aerogel in mild condition. Impressively, the doping of optimizing ETAC greatly improved the overall specific surface area (SSA) of the aerogel, and the CNF extracted from Eucommia ulmoides wood was used to enhance the mechanical properties of graphene aerogel. Besides, the composite aerogels with high content of ETAC (67% of mass ratio) possessed efficient MnOx deposition capability (1540 mg/g), which could assemble an asymmetric free-binder supercapacitor, exhibiting an ultrahigh specific capacitance and prominent cycling stability.