Efficient and multiplex gene upregulation in plants through CRISPR-Cas-mediated knockin of enhancers.

Gene upregulation through genome editing is important for plant research and breeding. Targeted insertion of short transcriptional enhancers (STEs) into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with transgenesis. Here, we introduce an "in locus activation" technique in rice that leverages well-characterized STEs for refined, heritable, and multiplexed gene upregulation.

Rapid and dynamic detection of endogenous proteins through in locus tagging in rice.

Understanding the behavior of endogenous proteins is crucial for functional genomics, yet their dynamic characterization in plants presents substantial challenges. Whereas mammalian studies have leveraged in locus tagging with the luminescent HiBiT peptide and genome editing for rapid quantification of native proteins, this approach remains unexplored in plants. Here, we introduce the in locus HiBiT tagging of rice proteins and demonstrate its feasibility in plants.

In-locus gene silencing in plants using genome editing.

Gene silencing is crucial in crop breeding for desired trait development. RNA interference (RNAi) has been used widely but is limited by ectopic expression of transgenes and genetic instability. Introducing an upstream start codon (uATG) into the 5'untranslated region (5'UTR) of a target gene may 'silence' the target gene by inhibiting protein translation from the primary start codon (pATG).

Targeted G-to-T base editing for generation of novel herbicide-resistance gene alleles in rice.

A newly developed rice guanine base editor (OsGTBE) achieves targeted and efficient G-to-T editing (C-to-A in the opposite strand) in rice. Using OsGTBE to edit endogenous herbicide-resistant loci generated several novel alleles conferring herbicide resistance, highlighting its utility in creating valuable germplasm and enhancing genetic diversity..

Efficient and heritable A-to-K base editing in rice and tomato.

Cytosine and adenosine base editors (CBE and ABE) have been widely used in plants, greatly accelerating gene function research and crop breeding. Current base editors can achieve efficient A-to-G and C-to-T/G/A editing. However, efficient and heritable A-to-Y (A-to-T/C) editing remains to be developed in plants.

STOP1 and STOP1-like proteins, key transcription factors to cope with acid soil syndrome.

Acid soil syndrome leads to severe yield reductions in various crops worldwide. In addition to low pH and proton stress, this syndrome includes deficiencies of essential salt-based ions, enrichment of toxic metals such as manganese (Mn) and aluminum (Al), and consequent phosphorus (P) fixation. Plants have evolved mechanisms to cope with soil acidity.

Puerarin Attenuates High-Glucose and High-Lipid-Induced Inflammatory Injury in H9c2 Cardiomyocytes via CAV3 Protein Upregulation.

Background: Inflammation plays a crucial role in the development of diabetic cardiomyopathy (DCM), including inflammation caused by high-glucose and high-lipid (HGHL). Targeting inflammation may provide a useful strategy for preventing and treating DCM. Puerarin has been shown to reduce the inflammation, apoptosis and hypertrophy of cardiomyocytes induced by HGHL, in which this study aims to investigate the underlying mechanisms.

Contribution of whole slide imaging-based deep learning in the assessment of intraoperative and postoperative sections in neuropathology.

The pathological diagnosis of intracranial germinoma (IG), oligodendroglioma, and low-grade astrocytoma on intraoperative frozen section (IFS) and hematoxylin-eosin (HE)-staining section directly determines patients' treatment options, but it is a difficult task for pathologists. We aimed to investigate whether whole-slide imaging (WSI)-based deep learning can contribute new precision to the diagnosis of IG, oligodendroglioma, and low-grade astrocytoma. Two types of WSIs (500 IFSs and 832 HE-staining sections) were collected from 379 patients at multiple medical centers.

Targeted insertion of regulatory elements enables translational enhancement in rice.

editing of agronomically-important genes to optimize their spatiotemporal expression is becoming an important breeding approach. Compared to intensive studies on mRNA transcription, manipulating protein translation by genome editing has not been well exploited. Here, we found that precise knock-in of a regulating element into the 5'UTR of a target gene could efficiently increase its protein abundance in rice.

Oncolytic HSV-1 suppresses cell invasion through downregulating Sp1 in experimental glioblastoma.

Gliomas are highly aggressive intracranial tumors that are difficult to resect and have high lethality and recurrence rates. According to WHO grading criteria, glioblastoma with wild-type IDH1 has a poorer prognosis than WHO grade 4 IDH-mutant astrocytomas. To date, no effective therapeutic strategies have been developed to treat glioblastoma.

Cut-dip-budding delivery system enables genetic modifications in plants without tissue culture.

Of the more than 370 000 species of higher plants in nature, fewer than 0.1% can be genetically modified due to limitations of the current gene delivery systems. Even for those that can be genetically modified, the modification involves a tedious and costly tissue culture process.

[Retracted] MicroRNA‑181 serves an oncogenic role in breast cancer via the inhibition of SPRY4.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the Transwell cell migration assay data shown in Figs. 3B and 9B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal.

The function and mechanism of the JARID2/CCND1 axis in modulating glioma cell growth and sensitivity to temozolomide (TMZ).

A maximal surgical resection followed by radiotherapy and chemotherapy with temozolomide (TMZ) as the representative agent is the standard therapy for gliomas. However, tumor cell resistance to radiotherapy and chemotherapy leads to poor prognosis and high mortality in patients with glioma. In the present study, we demonstrated that JARID2 was downregulated and CCND1 was upregulated within glioma tissues of different grades and glioma cells.

Diagnosis and Individualized Treatment of Secondary Central Nervous System Lymphoma: A Case Report.

Non-Hodgkin lymphoma can disseminate to the central nervous system at initiation of treatment for systemic lymphoma or spread during the relapse of systematic lymphoma with CNS involvement, which is defined as secondary central nervous system lymphoma (SCNSL). The incidence of SCNSL depends on the pathological type of lymphoma and is especially high in aggressive lymphoma. SCNSL has a poor prognosis because of the lack of effective treatment regimens.

Long-Term Survival Outcomes and Treatment Experience of 64 Patients With Esthesioneuroblastoma.

Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy, lacking a unified staging system and treatment. Management at a single center was retrospectively evaluated to inform future treatment options and prognostic factors. Clinical data of 64 consecutive ENB patients, including prognostic factors and treatment methods, were reviewed retrospectively.

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells.

Background: Glioblastoma (GBM) is an immunosuppressive, highly vascular and devastating malignant brain tumor. Even with progressive combination treatment that includes surgery, radiotherapy, and chemotherapy, the prognosis for GBM patients is still extremely poor. Oncolytic adenovirus (OAd) can specifically replicate in GBM cells, permitting the rapid copy of the therapeutic genes it carries.

Macrophage polarization contributes to the efficacy of an oncolytic HSV-1 targeting human uveal melanoma in a murine xenograft model.

Uveal melanoma (UM), the most common primary malignant tumor of the eye in adults, is difficult-to-treat. UM has a relatively high mortality secondary to distant metastasis and poor overall survival with existing therapies. The oncolytic virus herpes simplex virus type-1 (HSV-1) has been approved for clinical use in melanoma.

Targeted, efficient sequence insertion and replacement in rice.

CRISPR-Cas9 methods have been applied to generate random insertions and deletions, large deletions, targeted insertions or replacements of short sequences, and precise base changes in plants. However, versatile methods for targeted insertion or replacement of long sequences and genes, which are needed for functional genomics studies and trait improvement in crops, are few and largely depend on the use of selection markers. Building on methods developed in mammalian cells, we used chemically modified donor DNA and CRISPR-Cas9 to insert sequences of up to 2,049 base pairs (bp), including enhancers and promoters, into the rice genome at an efficiency of 25%.