Catalytic-independent functions of the Integrator-PP2A complex (INTAC) confer sensitivity to BET inhibition.

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.

Decreased lncRNA HNF4A-AS1 facilitates resistance to sorafenib-induced ferroptosis of hepatocellular carcinoma by reprogramming lipid metabolism.

Resistance to sorafenib remains a major challenge in the systemic therapy of liver cancer. However, the involvement of lipid metabolism-related lncRNAs in this process remains unclear. Different expression levels of lipid metabolism-related lncRNAs in HCC were compared by analysis of Gene Expression Omnibus and The Cancer Genome Atlas databases.

OsSRF8 interacts with OsINP1 and OsDAF1 to regulate pollen aperture formation in rice.

In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum.

KLF4 Inhibits the Activation of Human Hepatic Stellate Cell In Vitro.

Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis. Early-stage liver fibrosis is reversible and intimately associated with the state of HSCs. Kruppel-like factor 4 (KLF4) plays a pivotal role in a wide array of physiological and pathological processes.

R-loop-dependent promoter-proximal termination ensures genome stability.

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS) and the transcription regulator Integrator-PP2A (INTAC). Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability.

The Quantification of Bacterial Cell Size: Discrepancies Arise from Varied Quantification Methods.

The robust regulation of the cell cycle is critical for the survival and proliferation of bacteria. To gain a comprehensive understanding of the mechanisms regulating the bacterial cell cycle, it is essential to accurately quantify cell-cycle-related parameters and to uncover quantitative relationships. In this paper, we demonstrate that the quantification of cell size parameters using microscopic images can be influenced by software and by the parameter settings used.

The angiotensin receptor neprilysin inhibitor LCZ696 attenuates renal fibrosis via ASK1/JNK/p38 MAPK-mediated apoptosis in unilateral ureteral obstruction.

The angiotensin receptor neprilysin inhibitor LCZ696 affords superior cardioprotection and renoprotection compared with renin-angiotensin blockade monotherapy, but the underlying mechanisms remain elusive. Herein, we evaluated whether LCZ696 attenuates renal fibrosis by inhibiting ASK1/JNK/p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Rats with UUO were treated daily for 7 days with LCZ696, valsartan, or the selective ATP competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1), GS-444217.

Management of traumatic peripheral artery pseudoaneurysm: A 10-year experience at a single center.

Purpose: This study aimed to report our 10-year experience with the management of iatrogenic (penetrating trauma) and traumatic (blunt or penetrating trauma) peripheral artery pseudoaneurysms, based on data from a tertiary referral center.

Methods: From January 2012 to December 2021, the medical records of consecutive patients with iatrogenic and traumatic peripheral artery pseudoaneurysms were retrospectively reviewed. Patient demographics, clinical features, imaging data, treatment details, and follow-up results were analyzed.

SiC Nanoparticles Strengthened Alumina Ceramics Prepared by Extrusion Printing.

Extrusion-free-form printing of alumina ceramics has the advantages of low cost, short cycle time, and high customization. However, some problems exist, such as the low solid content of ceramic paste and the unsatisfactory mechanical properties of pure alumina ceramics. In this study, SiC nanoparticles were used as a reinforcement phase added to the alumina ceramic matrix.

GC-MS and UHPLC-QTOFMS-assisted identification of the differential metabolites and metabolic pathways in key tissues of .

is an important aromatic medicinal herb widely used in the pharmaceutical and perfume industries. However, our understanding of the phytochemical compounds and metabolites within remains limited. To our knowledge, no integrated studies have hitherto been conducted on the metabolites of the aerial parts of .

Isolation and Characterization of Encoding a Porphobilinogen Deaminase in Rice.

The formation and development of chloroplasts play a vital role in the breeding of high-yield rice ( L.). Porphobilinogen deaminases (PBGDs) act in the early stage of chlorophyll and heme biosynthesis.

Inhibition of RIP1-RIP3-mediated necroptosis attenuates renal fibrosis via Wnt3α/β-catenin/GSK-3β signaling in unilateral ureteral obstruction.

Renal fibrosis represents the final common outcome of chronic kidney disease of virtually any etiology. However, the mechanism underlying the evolution of renal fibrosis remains to be addressed. This study sought to clarify whether RIP1-RIP3-mediated necroptosis is involved in renal fibrosis via Wnt3α/β-catenin/GSK-3β signaling in vitro and in a rat model of unilateral ureteral obstruction (UUO).

OsPHS1 is required for both male and female gamete development in rice.

Meiosis plays an essential role in the production of male and female gametes. Extensive studies have elucidated that homologous chromosome association and pairing are essential for crossing-over and recombination of chromosomal segments. However, the molecular mechanism of chromosome recognition and pairing remains elusive.

Functional analysis of farnesyl pyrophosphate synthase gene and its binding transcription factor PcWRKY44 in regulating biosynthesis of patchouli alcohol.

Farnesyl pyrophosphate synthase (FPPS) plays an important role in the synthesis of plant secondary metabolites, but its function and molecular regulation mechanism remain unclear in . In this study, the full-length cDNA of the FPP synthase gene from () was cloned and characterized. The expressions of are different among different tissues (highly in flowers).

Auxin regulates source-sink carbohydrate partitioning and reproductive organ development in rice.

Carbohydrate partitioning between the source and sink tissues plays an important role in regulating plant growth and development. However, the molecular mechanisms regulating this process remain poorly understood. In this study, we show that elevated auxin levels in the rice mutant cause increased accumulation of sucrose in the photosynthetic leaves but reduced sucrose content in the reproductive organs (particularly in the lodicules, anthers, and ovaries), leading to closed spikelets, indehiscent anthers, and parthenocarpic seeds.

One-step laparoscopic pancreatic necrosectomy verse surgical step-up approach for infected pancreatic necrosis: a case-control study.

Background: The surgical step-up approach often requires multiple debridements and might not be suitable for infected pancreatic necrosis (IPN) patients with various abscesses or no safe route for percutaneous catheter drainage (PCD). This case-control study aimed to investigate the safety and effectiveness of one-step laparoscopic pancreatic necrosectomy (LPN) in treating IPN.

Methods: This case-control study included IPN patients undergoing one-step LPN or surgical step-up in our center from January 2015 to December 2020.

Coenzyme Q10 attenuates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in unilateral ureteral obstruction.

Objective: Coenzyme Q10 (CoQ10) protects against various types of injury, but its role in preventing renal scarring in chronic kidney disease remains an open question. Herein, we evaluated whether CoQ10 attenuates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro.

Methods: Rats with UUO were treated daily with CoQ10 or an RIP inhibitor (necrostatin-1 or GSK872) for 7 days.

Strengthening Effect of Short Carbon Fiber Content and Length on Mechanical Properties of Extrusion-Based Printed Alumina Ceramics.

Extrusion-based ceramic printing is fast and convenient, but the green body strength is too low, and the application prospect is not high. An extrusion-based printing method of alumina ceramics toughened by short carbon fiber is reported in this paper. The bending strength and fracture toughness of 3D-printed alumina ceramics were improved by adding short carbon fiber.

Coordinated regulation of RNA polymerase II pausing and elongation progression by PAF1.

Pleiotropic transcription regulator RNA polymerase II (Pol II)-associated factor 1 (PAF1) governs multiple transcriptional steps and the deposition of several epigenetic marks. However, it remains unclear how ultimate transcriptional outcome is determined by PAF1 and whether it relates to PAF1-controlled epigenetic marks. We use rapid degradation systems and reveal direct PAF1 functions in governing pausing partially by recruiting Integrator-PP2A (INTAC), in addition to ensuring elongation.

Dapagliflozin Alleviates Renal Fibrosis by Inhibiting RIP1-RIP3-MLKL-Mediated Necroinflammation in Unilateral Ureteral Obstruction.

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, offers renoprotection in diabetes. However, potential for use in nondiabetic kidney disease remains unknown. Herein, we assessed whether dapagliflozin alleviates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and .