From Monocyclization to Pentacyclization: A Versatile Plant Cyclase Produces Diverse Sesterterpenes with Anti-Liver Fibrosis Potential.

A prolific multi-product sesterterpene synthase CbTPS1 is characterized from the medicinal Brassicaceae plant Capsella bursa-pastoris. Twenty different sesterterpenes including 16 undescribed compounds, possessing 10 different mono-/di-/tri-/tetra-/penta-carbocyclic skeletons, including the unique 15-membered macrocyclic and 24(15→14)-abeo-capbuane scaffolds, are isolated and structurally elucidated from engineered Escherichia coli strains expressing CbTPS1. Site-directed mutagenesis assisted by molecular dynamics simulations resulted in the variant L354M with up to 13.

Influence of Postmastectomy Radiotherapy on Overall Survival in Patients With Clinical Prognostic Stage I-III Breast Cancer With Positive Responses and Achieving YPN0 Following Neoadjuvant Therapy: A Propensity Score Matching Based on the SEER Database.

Introduction: The role of postmastectomy radiotherapy (PMRT) in clinical prognostic stage I-III breast cancer patients with positive responses and achieving ypN0 after Neoadjuvant therapy (NAT) is controversial.

Methods: 3557 patients with TNM clinical prognostic stage (AJCC 8th Edition) I-III breast cancer with positive responses and achieving ypN0 following neoadjuvant therapy were selected from the Surveillance, Epidemiology, and End Results (SEER) database and followed through the end of 2020. COX proportional hazards models were employed to examine the associations between clinical or pathological parameters and OS.

β-Hydroxybutyrate suppresses M1 macrophage polarization through β-hydroxybutyrylation of the STAT1 protein.

β-Hydroxybutyrate (β-OHB), the primary ketone body, is a bioactive metabolite that acts as both an energy substrate and a signaling molecule. Recent studies found that β-OHB inhibits the production of pro-inflammatory cytokines in macrophages, but its underlying molecular mechanisms have not yet been fully elucidated. Lysine β-hydroxybutyrylation (Kbhb), a post-translational modification mediated by β-OHB, plays a key role in regulating the expression and activity of modified proteins.

Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome secondary to dorsal pontine infarction.

Background: Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is an uncommon ocular motor disorder which is featured by binocular exotropia and bilateral internuclear ophthalmoplegia.

Methods: A 71-year-old man with hypertension presented to the emergency department with sudden-onset diplopia. Neurological examination, neuroimaging, blood and cerebrospinal fluid (CSF) testing were performed.

VDGE: a data repository of variation database for gene-edited animals across multiple species.

Gene-edited animals are crucial for addressing fundamental questions in biology and medicine and hold promise for practical applications. In light of the rapid advancement of gene editing technologies over the past decade, a dramatically increased number of gene-edited animals have been generated. Genome editing at off-target sites can, however, introduce genomic variations, potentially leading to unintended functional consequences in these animals.

Dog10K: an integrated Dog10K database summarizing canine multi-omics.

The diversity observed in canine breed phenotypes, together with their risk for heritabily disorders of relevance to dogs and humans, makes the species an ideal subject for studies aimed at understanding the genetic basis of complex traits and human biomedical models. Dog10K is an ongoing international collaboration that aims to uncover the genetic basis of phenotypic diversity, disease, behavior, and domestication history of dogs. To best present and make the extensive data accessible and user friendly, we have established the Dog10K (http://dog10k.

Historic dog Furs Unravel the Origin and Artificial Selection of Modern Nordic Lapphund and Elkhound dog Breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100 to 200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding.

Transcriptomic and intervention evidence reveals domestic dogs as a promising model for anti-inflammatory investigation.

Domestic dogs have great potential to expand our understanding of the determinants of aging. To understand the aging pattern of domestic dogs and evaluate whether they can be used as an aging model, we performed RNA sequencing on white blood cells from domestic dogs aged 1-9 years and treated aged dogs with classical antiaging approaches. We obtained 30 RNA sequencing libraries and identified 61 age-associated genes with dynamic changes, the majority of which were related to metabolism and immune function, which may be predominant biomarkers for aging in dogs.

Establishment of nonobstructive coronary microcirculatory disorders in rabbits using three established methods and a comparative study.

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared.

Metformin improves nonalcoholic fatty liver disease in db/db mice by inhibiting ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is the primary complication of type 2 diabetes (T2DM)-related liver disease, lacking effective treatment options. Metformin (Met), a widely prescribed anti-hyperglycemic medication, has been found to protect against NAFLD. Ferroptosis, a newly discovered form of cell death, is associated with the development of NAFLD.

Germline gene fusions across species reveal the chromosomal instability regions and cancer susceptibility.

The canine transmissible venereal tumor (CTVT) is a clonal cell-mediated cancer with a long evolutionary history and extensive karyotype rearrangements in its genome. However, little is known about its genetic similarity to human tumors. Here, using multi-omics data we identified 11 germline gene fusions (GGFs) in CTVT, which showed higher genetic susceptibility than others.

Cost-effectiveness of drug treatment for young and middle-aged stage 1 hypertensive patients with high risk.

Background: Drug treatment was recommended for stage 1 hypertensive patients (blood pressure of 130-139 / 80-89 millimetres of mercury (mmHg)) with high cardiovascular disease (CVD) risk in the 2017 Hypertension Clinical Practice Guidelines, 2018 Chinese guidelines and 2021 World Health Organization guidelines, but not in other guidelines. However, evidence on the cost-effectiveness of drug treatment among young and middle-aged patients remains scarce. This study aimed to compare the cost-effectiveness of drug treatment vs.

Association between the Khorana risk score and all-cause mortality in Japanese patients with gastric and colorectal cancer: A retrospective cohort study.

Background: The Khorana risk score (KRS) has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer. Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited.

Aim: To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity.

Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing.

Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans.

Impacts of gait biomechanics of patients with thoracolumbar kyphosis secondary to Scheuermann's disease.

Thoracolumbar kyphosis (TLK) is a common feature in patients with spinal deformities. However, due to limited studies, the impacts of TLK on gait have not been reported. The objective of the study was to quantify and evaluate the impacts of gait biomechanics of patients with TLK secondary to Scheuermann's disease.

Homeostasis of flavonoids and triterpenoids most likely modulates starch metabolism for pollen tube penetration in rice.

In angiosperms, the timely delivery of sperm cell nuclei by pollen tube (PT) to the ovule is vital for double fertilization. Penetration of PT into maternal stigma tissue is a critical step for sperm cell nuclei delivery, yet little is known about the process. Here, a male-specific and sporophytic mutant xt6, where PTs are able to germinate but unable to penetrate the stigma tissue, is reported in Oryza sativa.

Hologenomic insights into mammalian adaptations to myrmecophagy.

Highly specialized myrmecophagy (ant- and termite-eating) has independently evolved multiple times in species of various mammalian orders and represents a textbook example of phenotypic evolutionary convergence. We explored the mechanisms involved in this unique dietary adaptation and convergence through multi-omic analyses, including analyses of host genomes and transcriptomes, as well as gut metagenomes, in combination with validating assays of key enzymes' activities, in the species of three mammalian orders (anteaters, echidnas and pangolins of the orders Xenarthra, Monotremata and Pholidota, respectively) and their relatives. We demonstrate the complex and diverse interactions between hosts and their symbiotic microbiota that have provided adaptive solutions for nutritional and detoxification challenges associated with high levels of protein and lipid metabolisms, trehalose degradation, and toxic substance detoxification.

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study.

Objective: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes.

Patients And Methods: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5.