Drought is one of the most severe abiotic stresses, the damage due to which, various plant species mitigate by activating mechanisms that are not yet well understood. Caragana korshinskii is a ...xerophytic shrub found in the semi-arid regions of northwest China with high tolerance to several abiotic stresses, including drought. Based on the de novo transcriptome data from C. korshinskii leaflets collected along a precipitation gradient on the Loess Plateau (China), most of the differentially expressed genes were explored using trend analysis along the precipitation gradient. Gene ontological analysis showed that "phenylpropanoid biosynthesis process → secondary metabolite biosynthetic process" terms were the most significant gene ontologies, whereas Kyoto Encyclopedia of Genes and Genomes-based analysis indicated that the biosynthesis of secondary metabolites was a significant metabolic pathway. Real-time polymerase chain reaction and enzyme activity analyses confirmed the increased transcription of the phenylalanine ammonialyase (PAL) gene in C. korshinskii under drought stress in field and laboratory conditions. These results suggested that C. korshinskii adjusts its secondary metabolism to water-deficit environments and activates PAL by drought stress. Therefore, further studies on the obtained data can expand the current understanding of the molecular and genetic mechanisms responsible for the drought endurance in C. korshinskii.
Tumor‐associated chronic inflammation severely restricts the efficacy of immunotherapy in cold tumors. Here, a programmable release hydrogel‐based engineering scaffold with multi‐stimulation and ...reactive oxygen species (ROS)‐response (PHOENIX) is demonstrated to break the chronic inflammatory balance in cold tumors to induce potent immunity. PHOENIX can undergo programmable release of resiquimod and anti‐OX40 under ROS. Resiquimod is first released, leading to antigen‐presenting cell maturation and the transformation of myeloid‐derived suppressor cells and M2 macrophages into an antitumor immune phenotype. Subsequently, anti‐OX40 is transported into the tumor microenvironment, leading to effector T‐cell activation and inhibition of Treg function. PHOENIX consequently breaks the chronic inflammation in the tumor microenvironment and leads to a potent immune response. In mice bearing subcutaneous triple‐negative breast cancer and metastasis models, PHOENIX effectively inhibited 80% and 60% of tumor growth, respectively. Moreover, PHOENIX protected 100% of the mice against TNBC tumor rechallenge by electing a robust long‐term antigen‐specific immune response. An excellent inhibition and prolonged survival in PHOENIX‐treated mice with colorectal cancer and melanoma is also observed. This work presents a potent therapeutic scaffold to improve immunotherapy efficiency, representing a generalizable and facile regimen for cold tumors.
The delicate and ever‐changing nature of tumor‐associated chronic inflammation adversely affects anticancer immunity efficiency. Herein, a programmable release hydrogel‐based engineering scaffold with multi‐stimulation and reactive oxygen species (ROS)‐response (PHOENIX) is designed to break the chronic inflammatory balance in cold tumors, resulting in enhanced immunotherapy efficiency and represent a generalizable and facile regimen for cold tumor treatment.
Genetic characterization of the Arabidopsis lesion simulating disease 1 (lsd1) mutant, a lesion mimic mutant (LMM), has revealed the essential role of AtLSD1 in the negative regulation of cell death ...and disease resistance. The three zinc-finger motifs found in AtLSD1 revealed a novel plant-specific gene family, whose members are significantly related to programmed cell death (PCD). In this study, we characterized a functional homologue to AtLSD1, TaLSD1, in the wheat-stripe rust fungus pathosystem. The expression of TaLSD1 was differentially induced during incompatible and compatible interactions between wheat and Puccinia striiformis f. sp. tritici (Pst) and was up-regulated by oxidative stress generated by methyl viologen (MV). TaLSD1 was found to be predominately localized in the nucleus of onion epidermal cell. Transient overexpression assays in Nicotiana benthamiana demonstrated that TaLSD1 partially inhibited programmed cell death triggered by a mouse Bax protein, whereas expression of TaLSD1 alone had no influence on the phenotype of tobacco. Knocking down the expression of TaLSD1 through virus-induced gene silencing (VIGS) increased wheat resistance against Pst accompanied by an enhanced hypersensitive response (HR), an increase in PR1 gene expression and a reduction in Pst hyphal growth. Our results suggest that TaLSD1 functions negatively in regulating the plant hypersensitive cell death and is involved in disease resistance of wheat against the stripe rust pathogen.
•We characterized a functional homologue to AtLSD1, TaLSD1 from wheat.•TaLSD1 is induced by Pst infection and oxidative stress.•TaLSD1–GFP fusion protein is predominantly localized within the nucleus.•TaLSD1 partially suppresses Bax-triggered PCD.•Knocking down TaLSD1 expression increases wheat disease resistance against Pst.
As the most common and abundant RNA modification in eukaryotic cells, N6-methyladenosine (m6A) modification plays an important role in different stages of tumor. m6A can participate in the regulation ...of tumor immune escape, so as to enhance the monitoring of tumor by the immune system and reduce tumorgenesis. m6A can also affect the tumor progression by regulating the immune cell responses to tumor in tumor microenvironment. In addition, immunotherapy has become the most popular method for the treatment of cancer, in which targets such as immune checkpoints are also closely associated with m6A. This review discusses the roles of N6-methyladenosine modification in tumor immune regulation, their regulatory mechanism, and the prospect of immunotherapy.
To analyze the clinical phenotype and genetic etiology of three cases of glutaric aciduria type 1 (GA1) in Chinese children.
We performed genetic and metabolic testing using tandem mass spectrometry ...(MS/MS) and gas chromatography–mass spectrometry (GC/MS), followed by trio whole-exome sequencing (trio-WES) and Sanger sequencing. A literature review on glutaric aciduria type 1 (GA1) in Chinese patients was also conducted.
Sequencing results showed each case had compound heterozygous variants in GCDH(NM_000159.4): c.214C > G (p.Arg72Gly) and c.411C > G (p.Tyr137Term) (Case 1), c.214C > G (p.Arg72Gly) and c.1204C > T (p.Arg402Trp) (Case 2), and c.1228G > T (p.Val410Leu) and c.395G > A (p.Arg132Gln) (Case 3). These variants were inherited from their respective parents. Notably, the c.214C > G variant found in two children was a novel variant not previously reported. A review of the literature revealed that, clinically, the majority of patients experienced onset in infancy and early childhood (82%). Additionally, 38.36% were diagnosed through newborn screening, with the primary reasons for the initial visit being delayed development (32.43%) and infections (21.61%). The most common clinical manifestations included increased head circumference (77.19%) and motor developmental delay (65.15%). Biochemically, patients exhibited significant elevations in C5DC (98.51%) and C5DC/C8 (94.87%) in blood, as well as GA (94.37%) and 3OHGA (69.39%) in urine. Radiographically, patients showed a high prevalence of abnormalities in cranial MRI (86.15%) and EEG (73.33%). Genetically, 67 distinct GCDH gene variants were identified among 73 patients, with missense variants being the most prevalent type (73.97%). The most frequent variant was c.1244-2 A > C, observed in 17.12% of cases. Additionally, the majority of variant sites were located in exons 11 (25.37%) and 6 (22.39%).
GCDH variants were identified as the causative factors in the three children. The discovery of the novel variant (c.214C > G) expands the spectrum of pathogenic GCDH variants. These findings facilitate the diagnosis and treatment of affected children and provide a basis for genetic counseling and prenatal diagnosis for their families.
In this paper, a supercell modeling of secondary orientation was established using 90 cubic mosaic units made up of γ’ phase embedded in γ matrix, in accordance with an actual structure of Ni-based ...single crystal superalloys (NSCS). The effects of secondary orientation on the deformation behavior and microstructure evolution of NSCS under uniaxial tensile were studied by a three-dimensional molecular dynamics (MD) simulation. Simulation results showed that secondary orientation had a significant effect on mechanical properties of NSCS, that is, a big fluctuation was found in tensile strength which dropped down almost 50% from a peak (corresponding to the secondary orientations of 18° and 45°) to a trough (those of 34° and 63°). Mechanisms of secondary orientation affecting the deformation behavior were further discussed systematically. The deformation of NSCS under uniaxial tensile was a process tending towards amorphization of microstructure, together with the dislocation formation, merging and break-up. On a micro viewpoint, this work for us will be useful to apprehend the tensile deformation conduct of NSCS.
Molecular self-assembly presents a 'bottom-up' approach to the fabrication of objects specified with nanometre precision. DNA molecular structures and intermolecular interactions are particularly ...amenable to the design and synthesis of complex molecular objects. We report the design and observation of two-dimensional crystalline forms of DNA that self-assemble from synthetic DNA double-crossover molecules. Intermolecular interactions between the structural units are programmed by the design of 'sticky ends' that associate according to Watson-Crick complementarity, enabling us to create specific periodic patterns on the nanometre scale. The patterned crystals have been visualized by atomic force microscopy.
Coevolution of tumor cells and surrounding stroma results in protective protumoral environment, in which abundant vessel, stiff structure and immunosuppression promote each other, cooperatively ...incurring deterioration and treatment compromise. Reversing suchenvironment may transform tumors from treatment‐resistant to treatment‐vulnerable. However, effective reversion requires synergistic comprehensive regression of such environment under precise control. Here, the first attempt to collaboratively retrograde coevolutionary tumor environment to pre‐oncogenesis status, defined as tumor environment regression therapy, is made for vigorous immune response eruption by a switchable prune‐to‐essence nanoplatform (Pres) with simplified composition and fabrication process. Through magnetic targeting and multimodal imaging of Pres, tumor environment regression therapy is guided, optimized and accomplished in a trinity way: Antiangiogenesis is executed to rarefy vessels to impede tumor progression. By seizing the time, cancer associated fibroblasts are eliminated to diminish collagen and loosen the stiff structure for deep penetration of Pres, which alternately functioned in deeper tumors, forming a positive feedback loop. Through this loop, immune cell infiltration, immunosuppression mitigation and immunogenic cells death induction are all fulfilled and further escalated in the regressed environment. These transformations consequently unleashed systemic immune responses and generated immune memory against carcinoma. This study provides new insights intotreatment of solid tumors.
A strategy named tumor environment regression therapy is proposed to regress the coevolutionary tumor environment into the status before tumorigenesis coevolution for antitumor immunity enhancement by switchable Pres, which turns tumor environment from “indestructible fortress” into “vulnerable village” and unleashes vigorous systemic immune responses against TNBC. This strategy consequently accomplishes long‐term and effective inhibition of TNBC.
A novel dinuclear Ru(II) complex, (bpy)(2)Ru(ebipcH(2))Ru(bpy)(2)(ClO(4))(4), where bpy = 2,2'-bipyridine and ebipcH(2) = N-ethyl-4,7-bis(1,10-phenanthroline5,6-fimidazol-2-yl)carbazole, has been ...newly synthesized. The pH effects on UV-vis absorption and emission spectra of the complex are studied, and ground- and excited-state ionization constants of the complex are derived. The binding of the complex to calf thymus (ct) DNA is investigated with absorption and luminescence titrations, steady-state emission quenching, and viscosity measurements. The complex acts as a pH-induced "on-off" emission switch between pH 8.0 and pH 10.0 with a maximum on-off ratio of approximately 100 which is favorably compared with the other imidazole-containing Ru(II) complex congeners, and a strong ct-DNA intercalator with an intrinsic binding constant of 1.31(+/-0.08) x 10(6) M(-)(1) in buffered 50 mM NaCl.
Carbon monoxide (CO) poisoning, the most frequent type of poisoning, alters hemodynamics and creates tissue hypoxia that ultimately leads to thromboembolism. We herein describe a previously healthy ...17-year-old male patient who developed acute CO poisoning while bathing in the same room as a gas heater. He was first treated with urokinase thrombolytic therapy at a local hospital, which proved ineffective. The patient was admitted to our hospital with unstable circulation and was diagnosed with massive pulmonary embolism combined with multiple organ dysfunction syndrome. His Acute Physiology and Chronic Health Evaluation II score was 22, and his Sequential Organ Failure Assessment score was 15. We faced a difficult decision regarding whether to perform surgical embolectomy or to repeat the thrombolysis. We opted to repeat the thrombolysis with successful results. Our experience may help clinicians manage similar cases in the future.
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