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. Additionally, we illustrate a mechanism of a complex gene fusion of three gene segments (HSD17B4-DMXL1-TNFAIP8) that we refer to "greedy fusion". Our findings also provided evidence that expressions of GGFs are downregulated during the tumor regressive phase, which is associated with DNA methylation level. This study presents a comprehensive landscape of gene fusions (GFs) in CTVT, which offers a valuable genetic resource for exploring potential genetic mechanisms underlying the development of cancers in both dogs and humans.

Prospective comparison of acupuncture with sham acupuncture to determine impact on sedation and analgesia in mechanically ventilated critically ill patients (PASSION study): protocol for a randomised controlled trial.

INTRODUCTION: Sedation and analgesia are recommended to be employed in the intensive care unit (ICU) to enhance patient comfort and safety, facilitate mechanical ventilation and reduce oxygen demands. However, the increasing evidence demonstrates that excessive sedation and analgesia might prolong mechanical ventilation and increase costs and mortality. Acupuncture is known to be able to attenuate pain, anxiety and agitation symptoms while avoiding excessive sedation and analgesia caused by drugs. Therefore, we present a protocol to investigate whether acupuncture, used for sedation and analgesia, can reduce the duration of mechanical ventilation, save medical resources and reduce the mortality of critically ill patients receiving mechanical ventilation. METHODS AND ANALYSIS: Prospective, randomised controlled trial is conducted on 180 adult medical/surgical ICU patients with mechanical ventilation needing sedation at 3 ICUs between 03 November 2021 and 16 August 2023. Patients will be treated with analgesia and sedation to achieve desired target sedation levels (Richmond Agitation Sedation Score of -2 to 1). Enrolled patients will be randomly assigned in a ratio of 1:1:1 to receive deep needle insertion with combined manual and alternating-mode electrical stimulation on acupoints (AC group), superficial needle insertion without manual stimulation and electrical stimulation on non-acupoints (SAC group), or no acupuncture intervention (NAC group). The primary outcome is the duration of mechanical ventilation from randomisation until patients are free of mechanical ventilation (including non-invasive) without reinstitution for the following 48 hours. Secondary endpoints include the dose of administered sedatives and analgesic at comparable sedation levels throughout the study, ICU length of stay, hospital length of stay. Additional outcomes include the prevalence and days of delirium in ICU, mortality in ICU and within 28 days after randomisation, and the number of ventilator free days in 28 days. ETHICS AND DISSEMINATION: This trial was approved by the ethics committee at Guangdong Provincial Hospital of Chinese Medicine. We will publish the study results. TRIAL REGISTRATION NUMBER: ChiCTR2100052650.

Sclerostin aggravates cardiac remodeling after myocardial infarction by inhibition of Wnt/ß-catenin signaling pathway.

Background: The serum levels of sclerostin (SOST) are significant elevated in patients with pathological cardiac remodeling after myocardial infarction (MI). However, the mechanisms of SOST in cardiac remodeling remain largely uncharacterized. Methods: Collecting patients with MI who presented with or without left ventricular (LV) remodeling, we investigated differences in SOST expression. The influence of overexpression and silenced of SOST on the angiogenesis of cardiac microvascular endothelial cells (CMECs) was explored through in vitro experiments, and the impact of SOST on Wnt signaling marker proteins was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Finally, we observed the effects of SOST on cardiac function and morphology in mice MI model, and verified the role of the Wnt signaling marker proteins in vivo. Results: Serum SOST was significantly increased in patients with cardiac remodeling. Increased SOST expression was also observed in the infarcted hearts of C57BL/6 mice that underwent ligation of the left anterior descending branch of the coronary artery to induce MI. Furthermore, loss and gain of function experiments were conducted to investigate the role of SOST in post-infarct cardiac remodeling in vivo and in vitro. Overexpression of SOST promoted the proliferation and migration of cardiac fibroblasts (CFs), and inhibited angiogenesis of CMECs. In addition, overexpressing SOST in mice significantly deteriorated the post-infarct cardiac remodeling, as shown by the increased LV end systolic and end diastolic dimensions, decreased ejection fraction, and increased myocyte cross-section area and myocardial fibrosis. However, suppressing SOST expression showed the opposite results. The expression of Wnt signaling marker proteins was inhibited after overexpression of SOST, and enhanced after suppression of SOST in vivo and in vitro, suggesting involvement of the Wnt signaling pathway. Conclusions: The present study demonstrated that SOST aggravates post-infarct pathological myocardial remodeling by inhibiting angiogenesis of CMECs while promoting the proliferation of CFs, and this may be mediated by the Wnt signaling pathway. These results suggested that SOST might act as a biomarker to predict detrimental postinfarct cardiac remodeling, and may be a potential therapeutic target for the treatment of MI.

Environmental impacts of reclaimed asphalt pavement on leaching of metals into groundwater.

To investigate the environmental impacts of reclaimed asphalt pavement (RAP) while it was freshly processed (i.e. hot mixed asphalt or HMA) and after being subjected to weathering, three RAP materials, namely north-RAP, central-RAP, south-RAP, from three plants and one fresh HMA loose mix samples (Fresh-HMA) throughout New Jersey, USA underwent four different weathering processes including: UV and precipitation weathering on unbounded RAP, UV and precipitation weathering on compacted RAP, weathering by heat and moisture cycles, and groundwater flow-through leaching. Batch experiments were conducted to mimic releasing of trace elements in weak acidic leachate from landfills. North-RAP and central-RAP released levels of Pb greater than the United States Environmental Protection Agency (USEPA) primary drinking water maximum contaminant level (MCL) of 15 µg/L. Novel two-column experiments (a RAP column followed by a soil column) were conducted to investigate the release of trace elements from RAP and the attenuation effect of soil on potential pollutants. The results of these experiments showed that pollutants released from RAPs such as Mn and Ni were largely attenuated in the soil. The results suggest that RAP can be used as an unbound material in environments except those acidic (i.e., pH < 5 as in mines with sulfur-containing minerals and landfills with acidic environment).

A retrospective study of female reproductive parameters in the Kunming dog.

The Kunming dog is the first and only working dog breed from China to be recognized worldwide. As a domestic working dog, its excellent working performance has been well established; however, its normal reproductive parameters are not well understood. Therefore, this study was conducted to document the main reproductive parameters of this purebred working dog in field breeding conditions. Data on 1004 heats (753 with mating) from 203 bitches between 2008 to 2014, were collected and analyzed. The pregnancy rate and whelping rate was 79.42% and 75.30%, respectively. Finally, for 567 litters (4298 puppies), the mean litter size was 7.19 ± 0.12 puppies (range 1-15). The mean gestation period and birth weight were approximately 61.64 ± 0.10 days and 407.25 ± 1.21 g. The mean sex ratio was 1.03 males to 1.00 female. Estrus occurred throughout the year with no significant differences between seasons and months (P > 0.05), which confirms that Kunming dogs are non-seasonal breeders; births occurred in every month of the year. Pregnant bitches exhibited significantly longer inter-estrus intervals than non-pregnant bitches (220.85 ± 2.05 vs. 180.19 ± 2.94 days, P < 0.05). Bitch parity influenced litter size, and the gestation length and birth weight of the puppies were negatively affected by litter size. This study helps elucidate the reproductive potential of this breed and provides reference values for reproductive performance in the Kunming dog.

Birth of puppies of predetermined sex after artificial insemination with a low number of sex-sorted, frozen-thawed spermatozoa in field conditions.

The aim of this study was to evaluate fertility and sex ratios after artificial insemination in dogs under field conditions. Semen was cryopreserved as unsorted (control) or was separated into X- and Y-chromosome-bearing sperm using a cell sorter. Sixty female dogs were inseminated with frozen-thawed spermatozoa of 100 × 106 unsorted (a dose in practice) and 4 × 106 sorted (X and Y group, respectively). A total of 20 dogs became pregnant and 126 puppies were born from the three groups. The percentage of parturition was similar for the X (5/20; 25.0%) and Y (4/20; 20.0%) group (P > 0.05), but lower than controls (11/20; 55.0%) (P < 0.05). Ultimately 28 out of the 32 puppies produced from X group were female (87.5%) and 19/22 (86.4%) puppies of Y group were male. In contrast, sex ratio (51.4% to 48.6%) in the control was significantly different from the X, Y group (P < 0.05). However, male and female puppies in the control had similar birth weights and weaning weights to those from the X and Y groups. This preliminary information indicated that normal puppies of predicted sex can be produced with low numbers of sorted cryopreserved dog spermatozoa at a farm level, making sperm-sexing technology potentially applicable for elite breeding units.