Increased resting heart rate indicates high-workload hearts with augmented aortic hydraulic power in hypertensive pigs.

Clarifying the inceptive pathophysiology of hypertensive heart disease helps to impede the disease progression. Through coarctation of the infrarenal abdominal aorta (AA), we induced hypertension in minipigs and evaluated physiological reactions and morpho-functional changes of the heart. Moderate aortic coarctation was achieved with approximately 30 mmHg systolic pressure gradient in minipigs.

Outcomes of upfront primary tumor resection in patients with synchronous wild-type metastatic colorectal cancer.

This multicenter study explored the survival benefits of upfront primary tumor resection (PTR) followed by first-line cetuximab plus chemotherapy in real-world patients with wild-type metastatic colorectal cancer (mCRC). Treatment options for mCRC include chemotherapy, targeted therapy, immunotherapy, and surgery. The efficacy of upfront PTR in managing mCRC remains unclear.

Hypo-osmolarity promotes naive pluripotency by reshaping cytoskeleton and increasing chromatin accessibility.

Introduction: Cell fate determination and transition are of paramount importance in biology and medicine. Naive pluripotency could be achieved by reprogramming differentiated cells. However, the mechanism is less clear.

Tillandsia-Inspired Ultra-Efficient Thermo-Responsive Hygroscopic Nanofibers for Solar-Driven Atmospheric Water Harvesting.

Sorption-based atmospheric water harvesting (SAWH) is a promising approach for supplying water in off-grid arid regions. However, it is difficult to improve the SAWH efficiency because water undergoes multiple phase transformations, such as water vapor-water (desorption and condensation) in the desorption phase. To address this issue, an ultrahygroscopic temperature-responsive hydrogel nanofiber inspired by Tillandsia is developed, comprising poly N-isopropylacrylamide, poly N-dimethylacetamide, and carbon nanotubes and impregnated with lithium chloride (PCP@LiCl).

Overexpression of NUDT16L1 sustains proper function of mitochondria and leads to ferroptosis insensitivity in colorectal cancer.

Cancer research is continuously exploring new avenues to improve treatments, and ferroptosis induction has emerged as a promising approach. However, the lack of comprehensive analysis of the ferroptosis sensitivity in different cancer types has limited its clinical application. Moreover, identifying the key regulator that influences the ferroptosis sensitivity during cancer progression remains a major challenge.

A new paradigm for generating high-quality cardiac pacemaker cells from mouse pluripotent stem cells.

Cardiac biological pacing (BP) is one of the future directions for bradyarrhythmias intervention. Currently, cardiac pacemaker cells (PCs) used for cardiac BP are mainly derived from pluripotent stem cells (PSCs). However, the production of high-quality cardiac PCs from PSCs remains a challenge.

TEAM: Triangular-mEsh Adaptive and Multiscale proton spot generation method.

Background: Proton therapy is preferred for its dose conformality to spare normal tissues and organs-at-risk (OAR) via Bragg peaks with negligible exit dose. However, proton dose conformality can be further optimized: (1) the spot placement is based on the structured (e.g.

Cardinality-constrained plan-quality and delivery-time optimization method for proton therapy.

Background: While minimizing plan delivery time is beneficial for proton therapy in terms of motion management, patient comfort, and treatment throughput, it often poses a tradeoff with optimizing plan quality. A key component of plan delivery time is the energy switching time, which is approximately proportional to the number of energy layers, that is, the cardinality.

Purpose: This work aims to develop a novel optimization method that can efficiently compute the pareto surface between plan quality and energy layer cardinality, for the planner to navigate through this quality-and-efficiency tradeoff and select the appropriate plan of a balanced tradeoff.

CDC-like kinase 3 deficiency aggravates hypoxia-induced cardiomyocyte apoptosis through AKT signaling pathway.

Hypoxia-induced cardiomyocyte apoptosis is one major pathological change of acute myocardial infarction (AMI), but the underlying mechanism remains unexplored. CDC-like kinase 3 (CLK3) plays crucial roles in cell proliferation, migration and invasion, and nucleotide metabolism, however, the role of CLK3 in AMI, especially hypoxia-induced apoptosis, is largely unknown. The expression of CLK3 was elevated in mouse myocardial infarction (MI) models and neonatal rat ventricular myocytes (NRVMs) under hypoxia.

Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity.

Cancer cells can evade immune elimination by activating immunosuppressive signaling pathways in the tumor microenvironment (TME). Targeting immunosuppressive signaling pathways to promote antitumor immunity has become an attractive strategy for cancer therapy. Aurora-A is a well-known oncoprotein that plays a critical role in tumor progression, and its inhibition is considered a promising strategy for treating cancers.

Oleic acid-induced metastasis of KRAS/p53-mutant colorectal cancer relies on concurrent KRAS activation and IL-8 expression bypassing EGFR activation.

Multigene mutations in colorectal cancer (CRC), including KRAS, BRAF, and p53, afford high metastatic ability and resistance to EGFR-targeting therapy. Understanding the molecular mechanisms regulating anti-EGFR-resistant CRC metastasis can improve CRC therapy. This study aimed to investigate the effects of IL-8 and the activation of KRAS on reactive oxygen species (ROS) production and metastasis of hyperlipidemia-associated CRC harboring mutations of KRAS and p53.

Prognostic role of tissue plasminogen activator in coronary artery disease with or without aortic valve sclerosis.

Aims: We sought to investigate the relationship between circulating tissue plasminogen activator (t-PA) level and long-term outcomes in stable coronary artery disease patients with or without aortic valve sclerosis (AVSc).

Methods And Results: Serum levels of t-PA were determined in 347 consecutive stable angina patients with (n = 183) or without (n = 164) AVSc. Outcomes were prospectively recorded as planned clinic evaluations every 6 months up to 7 years.

Y-box binding protein 1 promotes chromatin accessibility to aggravate liver fibrosis.

Y-box binding protein 1 (YBX1) has been reported to be involved in the transcriptional regulation of various pathophysiological processes, such as inflammation, oxidative stress, and epithelial-mesenchymal transformation. However, its precise role and mechanism in regulating hepatic fibrosis remain unclear. In this study, we aimed to investigate the effects of YBX1 on liver fibrosis and its potential mechanism.

Dual role of sprouty2 as an inhibitor of RAS/ERK-driven proliferation and a promoter of cancer invasion in KRAS wild-type colorectal cancer.

Sprouty2 (SPRY2) is known to inhibit the RAS/MAPK/ERK pathway, and is a potential study target for cancer. The effect of SPRY2 in colorectal cancer (CRC) and whether it is influenced by KRAS mutation are not known. We manipulated SPRY2 gene expression and used an activating KRAS-mutant plasmid to determine its effect on CRC cell function in vitro and/or in vivo.

Prospective, open-label, and observational study of cetuximab for metastatic colorectal carcinoma: The OPTIM1SE study.

Aim: The OPTIM1SE study observed long-term real-world outcomes of cetuximab-based infusional 5-fluorouracil (5-FU) regimens for first-line treatment of metastatic colorectal cancer (mCRC) across Asia-Pacific and Middle East regions, aiming to characterize their use, effectiveness, and safety in routine practice.

Methods: OPTIM1SE was a prospective, open-label, observational study. Patients with untreated KRAS wild-type mCRC and distant metastases were treated per locally approved labels and monitored for 3 years via electronic medical records.

The effect of femoral component valgus/varus angle on the mid-term efficacy of unicondylar knee arthroplasty.

Objective: To investigate the effect of femoral component valgus/varus angle (FCVA) on the mid-term outcome after unicondylar knee arthroplasty.

Methods: Patients who underwent unicompartmental knee replacement in the Department of Bone and Joint Surgery, were retrospectively analyzed. According to the postoperative femoral prosthesis internal and external rotation angle, patients were divided into six groups the postoperative femoral prosthesis internal and external rotation angle: standard group, mildly abnormal group.

Histone modification landscape and the key significance of H3K27me3 in myocardial ischaemia/reperfusion injury.

Histone modifications play crucial roles in the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury. However, a genome-wide map of histone modifications and the underlying epigenetic signatures in myocardial I/R injury have not been established. Here, we integrated transcriptome and epigenome of histone modifications to characterize epigenetic signatures after I/R injury.