Enhanced phosphorus weathering contributed to Late Miocene cooling.

Late Miocene climate evolution provides an opportunity to assess Earth's climate sensitivity to carbon cycle perturbation under warmer-than-modern conditions. Despite its relevance for understanding the climate system, the driving mechanisms underlying profound climate and carbon cycle changes - including the enigmatic Late Miocene cooling from 7 to 5.4 million years ago - remain unclear.

Highly efficient construction of monkey blastoid capsules from aged somatic cells.

Blastoids-blastocyst-like structures created in vitro-emerge as a valuable model for early embryonic development research. Non-human primates stem cell-derived blastoids are an ethically viable alternative to human counterparts, yet the low formation efficiency of monkey blastoid cavities, typically below 30%, has limited their utility. Prior research has predominantly utilized embryonic stem cells.

Enantioselective reductive cross-couplings to forge C(sp)-C(sp) bonds by merging electrochemistry with nickel catalysis.

Motivated by the inherent benefits of synergistically combining electrochemical methodologies with nickel catalysis, we present here a Ni-catalyzed enantioselective electroreductive cross-coupling of benzyl chlorides with aryl halides, yielding chiral 1,1-diaryl compounds with good to excellent enantioselectivity. This catalytic reaction can not only be applied to aryl chlorides/bromides, which are challenging to access by other means, but also to benzyl chlorides containing silicon groups. Additionally, the absence of a sacrificial anode lays a foundation for scalability.

Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells.

Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the major arteries in vivo.

SPHK1 enhances olaparib resistance in ovarian cancer through the NFκB/NRF2/ferroptosis pathway.

PARPis resistance is a challenge in the treatment of ovarian cancer. To investigate the potential mechanism involved in olaparib resistance of ovarian cancer, high-throughput sequencing was performed on olaparib-resistant SKOV3 cell line named SK/Ola. SPHK1 was upregulated in SK/Ola cells and was related to the PFS and OS in ovarian cancer patients.

Thyroid Endocrine Disrupting Potential of Fluoxetine in Zebrafish Larvae.

Fluoxetine (FLX), a typical selective serotonin reuptake inhibitors, has been frequently detected in aquatic environment and wild fish. However, little is known about its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 1, 3, 10, and 30 μg/L of FLX for 6 days.

The prevalence of PD-L1 expression in patients with advanced oesophageal cancer: the EXCEED observational study.

Aims: There are limited data on programmed death ligand 1 (PD-L1) expression in oesophageal cancer (OC) from multicentre studies conducted across China. We aimed to determine the prevalence of high PD-L1 expression in patients with advanced OC.

Methods: The EXCEED study was a multicentre, retrospective analysis of data from six tertiary hospitals that evaluated PD-L1 expression in adults with advanced OC or advanced head and neck squamous cell carcinoma.

Effects of omega-3 polyunsaturated fatty acids on inflammation resolution and angiogenesis in fat grafts in a controlled mouse model.

Background: The upregulation or delay of acute inflammation at any stage limits fat graft survival. Active endogenous inflammation resolution mechanisms and mediators are novel therapeutic tools for inflammation. This study explored the effects of supplementation of omega-3 polyunsaturated fatty acids (PUFAs) deriving specialized proresolving mediators (SPMs) on postoperative inflammation and graft survival in vivo.

Indoxyl sulfate (IS) mediates pro-inflammatory responses in severe pneumonia in patients with rheumatoid arthritis associated interstitial lung disease.

Object: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have a high risk of serious infection, in particular severe pneumonia. This study aimed to investigate the transcriptional landscape, lower respiratory tract (LRT) microbiome and metabolomic profiles in the lung of RA-ILD patients with pneumonia.

Method: A total of 10 RA-ILD with pneumonia were enrolled in this study.

HDAC2 promotes colorectal tumorigenesis by triggering dysregulation of lipid metabolism through YAP1.

Dysfunction of lipid metabolism is important for the development and progression of colorectal cancer, but the underlying mechanisms remain unclear. Here, HDAC2 was identified as highly expressed in both adenoma and colorectal cancer. We aimed to explore the roles and mechanisms of HDAC2 in lipid metabolism in colorectal cancer.

Alternative splicing of vascular calcification: Insights, opportunities, and challenges.

Vascular calcification(VC) significantly increases the risk of cardiovascular events, leading to thickening of the myocardium and arteries, coronary heart disease, heart failure, and potentially triggering myocardial infarction and sudden cardiac death. Although VC is a reversible process, there are currently no methods or medications in clinical practice that can completely reverse or cure it. The current treatment strategies primarily focus on slowing the progression of VC and exploring new diagnostic and therapeutic approaches, making the identification of early diagnostic markers for VC particularly important.

Enthalpy driven temperature-sensitive conformational changes in a metamorphic protein involved in the cyanobacterial circadian clock.

Metamorphic proteins switch reversibly between distinctly different folds often with different functions under physiological conditions. Here, the kinetics and thermodynamics of the fold-switching at different temperatures in a metamorphic protein, KaiB, involved in cyanobacterial circadian clock, reveal that enthalpy-driven the fold-switching to form fold-switched KaiB (fsKaiB) and the fsKaiB and ground-state KaiB (gsKaiB) are more dominantly at lower and higher temperatures, respectively. Thermodynamic analysis indicates that conformational and solvent entropy have opposing effects on KaiB's fold-switching.

Impact of hydrodynamic cavitation-assisted microbubble with N, CO, and air on pasting, morphological, and thermal properties of starches from different botanical origins.

Microbubble-assisted starch modification (MASM) using different gases (N, CO and air) was employed to assess the effects of hydrodynamic cavitation (HC) on various botanical starches, including potato, wheat, corn and rice. SEM showed that N- and CO- microbubbles created more pronounced holes and cracks on the starch surfaces than air-microbubbles. The hydrodynamic cavitation-assisted microbubble (HCAM) treatment significantly reduced the amorphous and crystalline structures in potato and wheat starches, with less impact observed in corn and rice.

Targeted Gut Microbiome Therapy: Applications and Prospects of Probiotics, Fecal Microbiota Transplantation and Natural Products in the Management of Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM.

Transcriptomics-Based Investigation of Resistance Differences to Swine Fever between Large White pigs and Min pigs.

The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the mechanisms of disease resistance in these breeds could lay the groundwork for genetic improvements in pig immunity, potentially augmenting overall pig productivity. In this study, whole blood samples were collected from pre- and post- swine fever vaccinated Min and Large White pigs for transcriptome sequencing.

IRF1-RIG-I signaling defects in the aged alveolar epithelial cells may contribute to decreased pulmonary antiviral immune responses.

Background: Alveolar epithelial cells (AECs) are the primary targets of many pathogens and play an important role in sensing viruses and regulating immunity. Yet, little is known about the antiviral responses in the aged AECs.

Methods: The responses of young or aged AECs after viral infection were analyzed using methods such as flow cytometry, quantitative real-time PCR, Western blot detection, and transwell chemotaxis assay.

Assessing the African burden of breast cancer: A demographic analysis using Global Cancer Observatory 2022.

Background: Breast cancer is a major health issue for women in Africa. This study aims to assess the burden of the disease using the latest estimates from Global Cancer Observatory 2022.

Methods: Data were sourced from the Global Cancer Observatory 2022.

Towards practical and privacy-preserving CNN inference service for cloud-based medical imaging analysis: A homomorphic encryption-based approach.

Background And Objective: Cloud-based Deep Learning as a Service (DLaaS) has transformed biomedicine by enabling healthcare systems to harness the power of deep learning for biomedical data analysis. However, privacy concerns emerge when sensitive user data must be transmitted to untrusted cloud servers. Existing privacy-preserving solutions are hindered by significant latency issues, stemming from the computational complexity of inner product operations in convolutional layers and the high communication costs of evaluating nonlinear activation functions.

Lift-CM: An integrated lift-heater centrifugal microfluidic platform for point-of-care pathogen nucleic acid detection using isothermal amplification and CRISPR/Cas12a.

Pathogen nucleic acid detection technology based on isothermal amplification and CRISPR/Cas12a system offers advantages in terms of high sensitivity, high specificity, and rapidity. However, this method has not been widely applied because of its shortcomings in utilizing conventional instruments, which cannot satisfy the requirements for Point of Care Testing (POCT), such as integration, convenience, and miniaturization. In this study, we developed an integrated lift-heater centrifugal microfluidic platform (Lift-CM) to automate the processes of isothermal amplification and CRISPR/Cas12a detection.

Comprehensive multiomics analysis reveals the effects of French fries and chicken breast meat on the oxidative degradation of lipids in soybean oil during deep-frying.

This study investigated the oxidative degradation of lipids in soybean oil used for frying French fries (SOFFF) and chicken breast meat (SOFCBM) using integrated volatolomics and oxidative lipidomics. Water in the food matrix promotes triglyceride hydrolysis. The rate of lipid hydrolysis was higher in SOFCBM, whereas the rate of lipid oxidation was higher in SOFFF.

A comprehensive review of the impact of anthocyanins from purple/black Rice on starch and protein digestibility, gut microbiota modulation, and their applications in food products.

This review explores the impact of anthocyanins derived from purple and black rice on starch and protein digestibility, gut microbiota modulation, and their applications in food production. Anthocyanins are shown to reduce starch digestibility by forming complexes with starch, thereby inhibiting key digestive enzymes. Additionally, they can influence protein digestion by inducing structural changes that enhance resistance to digestive processes.

Design, Synthesis, and biological evaluation of 7H-Pyrrolo[2,3-d]pyrimidines as potent HPK1 kinase inhibitors.

Hematopoietic progenitor kinase 1 (HPK1) has emerged as a promising target for cancer immunotherapy due to its critical role as a negative regulator of T cell receptor (TCR) signaling. Despite this potential, no HPK1 inhibitors have been approved for cancer treatment, underscoring the need for structurally novel inhibitors. Herein, we describe the design, synthesis and biological evaluation of a series of potent HPK1 inhibitors based on our previously identified hit 9.