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BackgroundThe accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues.ResultsA total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5' untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue-tissue interconnection involved in different traits and construct the first bovine trait similarity network.ConclusionsThese validated results show significant improvement over current bovine genome annotations.

KRAS mutations drive a quarter of cancer mortality, and most are undruggable. Several inhibitors of the MAPK pathway are FDA approved but poorly tolerated at the doses needed to adequately extinguish RAS/RAF/MAPK signaling in the tumor cell. We found that oncogenic KRAS signaling induced ferrous iron (Fe2+) accumulation early in and throughout mutant KRAS-mediated transformation. We converted an FDA-approved MEK inhibitor into a ferrous iron-activatable drug conjugate (FeADC) and achieved potent MAPK blockade in tumor cells while sparing normal tissues. This innovation allowed sustainable, effective treatment of tumor-bearing animals, with tumor-selective drug activation, producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation, and FeADCs hold promise for improving the treatment of KRAS-driven solid tumors.

Objective To investigate the evidence-based Traditional Chinese Medicine(TCM) nursing interventions on myelosuppression after chemotherapy. Methods Through evidence-based nursing strategies, relevant literature on the improvement of myelosuppression after chemotherapy by TCM was searched at home and abroad, clinical evidence was found, and a TCM nursing plan was formulated and implemented in a patient with degree II myelosuppression after chemotherapy and refused to take the medication. Results Through the application of evidence, the myelosuppression was effectively improved, the white blood cells count (WBC) and the absolute number of neutrophils reached normal levels, and the whole cycle of chemotherapy was successfully completed. Conclusion Evidence-based nursing can effectively provide a strong basis for prevention and treatment of myelosuppression after chemotherapy and improve the quality of care. (目的 基于循证实践探讨化疗后骨髓抑制患者的中医护理措施。方法 基于循证护理策略, 检索国内外有关中医疗法改善化疗后骨髓抑制的相关文献, 查找临床证据, 制定中医护理方案, 应用于1例化疗后出现II度骨髓抑制拒绝药物干预的患者。结果 通过循证证据应用, 采用中医外治疗法, 患者骨髓抑制情况得到有效改善, 白细胞(WBC)总数、中性粒细胞(ANC)绝对数达到正常水平, 并成功完成周期化疗。结论 循证护理可有效地为化疗后骨髓抑制干预提供有力依据, 提高护理质量。)

To study disease development, an inventory of an organ's cell types and understanding of physiologic function is paramount. Here, we performed single-cell RNA-sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We describe an epithelial-mesenchymal transitory axis in our three pancreatic duct subpopulations and identify osteopontin as a regulator of this fate decision as well as human duct cell dedifferentiation. Our results further identify functional heterogeneity within pancreatic duct subpopulations by elucidating a role for geminin in accumulation of DNA damage in the setting of chronic pancreatitis. Our findings implicate diverse functional roles for subpopulations of pancreatic duct cells in maintenance of duct cell identity and disease progression and establish a comprehensive road map of murine pancreatic duct cell, pancreatobiliary cell, and intrapancreatic bile duct cell homeostasis.

Desmoplasia describes the deposition of extensive extracellular matrix and defines primary pancreatic ductal adenocarcinoma (PDA). The acellular component of this stroma has been implicated in PDA pathogenesis and is being targeted therapeutically in clinical trials. By analyzing the stromal content of PDA samples from numerous annotated PDA data sets and correlating stromal content with both anatomic site and clinical outcome, we found PDA metastases in the liver, the primary cause of mortality to have less stroma, have higher tumor cellularity than primary tumors. Experimentally manipulating stromal matrix with an anti-lysyl oxidase like-2 (anti-LOXL2) antibody in syngeneic orthotopic PDA mouse models significantly decreased matrix content, led to lower tissue stiffness, lower contrast retention on computed tomography, and accelerated tumor growth, resulting in diminished overall survival. These studies suggest an important protective role of stroma in PDA and urge caution in clinically deploying stromal depletion strategies.

ObjectiveTo explore the changing trend of negative predictive value and number of false negatives in screening tests under the condition of low infection rate of infectious diseases.MethodsAssuming that the population is 20 million， to calculate the negative predictive value， numbers of true negatives and false negatives of the combination of different sensitivity （75.0%， 80.0%， 85.0%， 90.0%， 95.0%， 99.0%） and specificity （90.0%， 95.0%， 99.0%， 99.9%） when the disease infection rate of the population is 0.10%， 1.0% and 5.0% respectively.ResultsWhen the population infection rate is 0.1%， with the screening test sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.98‒19.96 million. When the sensitivity is 75.0%， the negative predictive value is 99.972%‒99.975%， and the number of false negatives is 5 000； When the sensitivity increases to 99.0%， the negative predictive value is 99.999%， and the number of false negatives decreases to 200. When the population infection rate is 1.0%， a screening test with sensitivity ≥75.0% and specificity ≥90.0% can detect about 17.82‒19.78 million true negatives in 20 million population. When the sensitivity is 75.0%， the negative predictive value is 99.720%‒99.748%， and the number of false negatives is 50 000； When the sensitivity increases to 99.0%， the negative predictive value increases to 99.990%， and the number of false negatives decreases to 2 000. When the population infection rate is 5.0%， with sensitivity ≥75.0% and specificity ≥90.0%， the number of true negatives in 20 million people is about 17.10‒18.98 million； when the sensitivity is 75.0%， the negative predictive value is 98.559%‒98.700%， and the number of false negatives can reach 250 000； When the sensitivity is 99.0%， the negative predictive value increases to 99.942%‒99.947%， and the number of false negatives decreases to 10 000. The lower the infection rate of the population， the fewer false negatives will appear in the screening.ConclusionThe number of false negatives in large-scale screenings increases exponentially with the increase of infection rate. Screenings should be carried out as early as possible in a pandemic of infectious diseases， so as to control the spread of the pandemic as soon as possible.

ObjectiveTo explore the positive predictive value （PPV） and false positive （FP） number of screening test in mass testing when the prevalence of infection is low.MethodsAssuming a population of 20 million with the prevalence of disease infection ranging from 0.1% to 5.0%， PPV， true positive （TP） and FP numbers were calculated under different scenarios of combination of sensitivity （99.0%， 99.5%， and 100.0%） with specificity （97.0%， 97.5%， 98.0%， 98.5%， 99.0%， 99.5%， and 99.9%）.ResultsFor low infection prevalence （≤5.0%）， specificity has a greater impact on PPV than sensitivity； with the decrease of infection prevalence， the increase in PPV elevates when the specificity increases. When the infection prevalence is >1.0%， the closer the specificity is to 99.9%， the closer the PPV is to 100.0%. However， when the infection prevalence is

Simple Summary: The rumen is a large organ unique to cattle and other ruminants and is essential for the ingestion, digestion, and absorption of large quantities of plant-based food. Cattle and likely all ruminants, however, are not born with a voluminous, functional rumen. There is remarkable postnatal growth and development in the rumen. This review summarizes the major postnatal changes in the structure and function of the bovine rumen, the major factors causing these changes, and, more importantly, the biological mechanisms underlying these changes. The rumen plays an essential role in the physiology and production of agriculturally important ruminants such as cattle. Functions of the rumen include fermentation, absorption, metabolism, and protection. Cattle are, however, not born with a functional rumen, and the rumen undergoes considerable changes in size, histology, physiology, and transcriptome from birth to adulthood. In this review, we discuss these changes in detail, the factors that affect these changes, and the potential molecular and cellular mechanisms that mediate these changes. The introduction of solid feed to the rumen is essential for rumen growth and functional development in post-weaning calves. Increasing evidence suggests that solid feed stimulates rumen growth and functional development through butyric acid and other volatile fatty acids (VFAs) produced by microbial fermentation of feed in the rumen and that VFAs stimulate rumen growth and functional development through hormones such as insulin and insulin-like growth factor I (IGF-I) or through direct actions on energy production, chromatin modification, and gene expression. Given the role of the rumen in ruminant physiology and performance, it is important to further study the cellular, molecular, genomic, and epigenomic mechanisms that control rumen growth and development in postnatal ruminants. A better understanding of these mechanisms could lead to the development of novel strategies to enhance the growth and development of the rumen and thereby the productivity and health of cattle and other agriculturally important ruminants. [ABSTRACT FROM AUTHOR]

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2–5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine. [ABSTRACT FROM AUTHOR]