A 3D-printed multi-channel microfluidic device for precise dissolved oxygen regulation in cancer hypoxia research.

Hypoxia plays a critical role in cancer progression, therapy resistance, and metastasis, yet establishing precise, physiologically relevant dissolved oxygen (DO) gradients for in vitro cell studies remains technically challenging. Here, we developed a novel 3D-printed microfluidic platform that generates eight parallel DO gradients (0-100 % saturation) for multiplexed hypoxia research. The integrated system combines a modular microplate adapter with a precise DO concentration gradient generation chip, creating stable linear oxygen profiles that faithfully mimic different in vivo tumor microenvironments.

Deficient FANCL Predisposes to Endothelial Damage: A New Therapeutic Target for Pulmonary Hypertension.

Clinical observations have suggested an association between alkylating agent-based chemotherapy and pulmonary arterial hypertension (PAH). The Fanconi anemia (FA) pathway, the principal mechanism for resolving alkylating agent-induced DNA damage, has been implicated in this process. To establish the interplay among the FA pathway, DNA damage, and PAH.

UCHL1 regulates adiponectin receptors in Sertoli cells to maintain testicular homeostatic balance.

Disruptions in testicular homeostasis can lead to impaired spermatogenesis and male infertility. Such disturbances may result from various factors, including viral or bacterial infections, toxic injuries, and genetic mutations or deletions. The maintenance of testicular homeostasis is governed by a complex interplay of various cells, hormones, paracrine factors, genes, and enzymes.

Socket shield technique for immediate implant placement after dental trauma: a case report.

Anterior teeth are often extracted due to dental trauma, periodontal disease, and other factors. During the healing period of sockets, the loose bundle bone in the buccal side of the anterior teeth usually produces vertical and horizontal bone absorption. How to remain and reconstruct alveolar crest contour in the esthetic zone is a challenge to dentists.

Comparison of flexible ureteroscopy with flexible and navigable suction ureteral access sheath and mini-percutaneous nephrolithotripsy for the treatment of impacted upper ureteral stones: a retrospective study.

Background And Objective: The treatment of impacted upper ureteral stones remains a significant challenge for urologists. Standard treatment protocols often favor Mini-Percutaneous Nephrolithotripsy (Mini-PCNL). It has been supposed to be associated with a higher stone clearance rate and a lower incidence of ureteral stricture compared to Flexible Ureteroscopy (FURS).

Genome-Wide Identification, Molecular Evolution, and Expression Divergence of , , , and Gene Family in Barley.

Organic and inorganic nutrients, osmotic components, associated protein cofactors, and signaling molecules regulate biotic and abiotic stresses in plants. Earlier reports suggest that plant cells activate anion channels and induce the efflux of anions at the plasma membrane under drought. Herein, (), (), (), and MECHANOSENSITIVE CHANNEL of SMALL CONDUCTANCE-LIKE (, ) gene family were reported in barley.

Design, Synthesis, and Evaluation of Selective PDE4 Inhibitors for the Therapy of Pulmonary Injury.

Pulmonary inflammation is the main cause of lung injury. Phosphodiesterase 4 (PDE4) is a promising anti-inflammatory target for the treatment of respiratory diseases. Herein, we designed and synthesized 43 compounds in two novel series of benzimidazole derivatives as PDE4 inhibitors.

Establishing a Multifaceted Comprehensive Maternity Cohort Facilitates Understanding of How Environmental Exposures Impact Perinatal Health.

China's "three-child policy", implemented in response to population aging, has made the protection of maternal and infant health an urgent priority. In this environmental and medical big-data era, the Zhejiang Environmental and Birth Health Research Alliance (ZEBRA) maternity cohort was established with the aim of identifying risk factors for perinatal morbidity and mortality from the perspectives of both observational epidemiology and experimental etiology. Compared with conventional birth cohorts, the inclusion of a maternity cohort allows greater scope for research and places an emphasis on maternal health.

The HIF2α-dependent upregulation of SETDB1 facilitates hypoxia-induced functional and phenotypical changes of pulmonary microvascular endothelial cells.

Emerging studies have reported the vital role of histone modification in the dysfunction of pulmonary vascular endothelial cells, which acts as the key reason to drive the hypoxia-induced pulmonary vascular remodeling and pulmonary hypertension (PH). This study aims to investigate the role of a histone 3 lysine 9 (H3K9) methyltransferase, SET domain bifurcated 1 (SETDB1), in hypoxia-induced functional and phenotypical changes of pulmonary vascular endothelial cells. Primarily cultured rat pulmonary microvascular endothelial cells (PMVECs) were used as cell model.

Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer: A Nonrandomized Clinical Trial.

Importance: Chimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC).

Objective: To evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC).

Transcriptomic profiling highlights cell proliferation in the progression of experimental pulmonary hypertension in rats.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression.

N6-methyladenosine-driven miR-143/145-KLF4 circuit orchestrates the phenotypic switch of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

Background: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

TAK1 Activation by NLRP3 Deficiency Confers Cardioprotection Against Pressure Overload-Induced Cardiomyocyte Pyroptosis and Hypertrophy.

A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation.

Improved STMask R-CNN-based defect detection model for automatic visual inspection of an optics lens.

A lens defect is a common quality issue that has seriously harmed the scattering characteristics and performance of optical elements, reducing the quality consistency of the finished products. Furthermore, the energy hotspots coming from the high-energy laser through diffraction of optical component defects are amplified step by step in multi-level laser conduction, causing serious damage to the optical system. Traditional manual detection mainly relies on experienced workers under a special light source environment with high labor intensity, low efficiency, and accuracy.

Allene oxide synthase 1 contributes to limiting grain arsenic accumulation and seedling detoxification in rice.

Arsenic (As) is a cancerogenic metalloid ubiquitously distributed in the environment, which can be easily accumulated in food crops like rice. Jasmonic acid (JA) and its derivatives play critical roles in plant growth and stress response. However, the role of endogenous JA in As accumulation and detoxification is still poorly understood.

Proteomic and Phosphoproteomic Analysis of Right Ventricular Hypertrophy in the Pulmonary Hypertension Rat Model.

Pulmonary arterial hypertension (PAH) is a progressive disease that affects both the lungs and heart. Right ventricle (RV) hypertrophy is a primary pathological feature of PAH; however, its underlying molecular mechanisms remain insufficiently studied. In this study, we employed tandem mass tag (TMT)-based quantitative proteomics for the integrative analysis of the proteome and phosphoproteome of the RV derived from monocrotaline-induced PAH model rats.

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures.

UCHL1 maintains microenvironmental homeostasis in goat germline stem cells.

Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C-terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti-inflammatory function of UCHL1 in a poly(I:C)-induced inflammation model to maintain microenvironmental homeostasis.

SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells.

Exposure to the spike protein or receptor-binding domain (S-RBD) of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy. In this study, angiotensin-converting enzyme 2 humanized inbred (hACE2 Tg) mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium. Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration ([Ca]) via acute activation of TRPV4, and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel (SOCC) key component Orai1 in cultured human pulmonary arterial endothelial cells (PAECs).