Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement.The raw data have been submitted to Gene Expression Omnibus (GEO) under series GSE25406.

BackgroundAs an important factor affecting meat quality, intramuscular fat (IMF) content is a topic of worldwide concern. Emerging evidences indicate that microRNAs play important roles in adipocyte differentiation. However, miRNAome has neither been studied during porcine intramuscular preadipocyte differentiation, nor compared with subcutaneous preadipocytes. The objectives of this study were to identify porcine miRNAs involved in adipogenesis in primary preadipocytes, and to determine whether intramuscular and subcutaneous adipocytes differ in the expression and regulation of miRNAs.ResultsmiRNAomes in primary intramuscular and subcutaneous adipocytes during differentiation were first sequenced using the Solexa deep sequencing method. The sequences and relative expression levels of 224 known (98.2% in miRbase 18.0) and 280 potential porcine miRNAs were identified. Fifty-four of them changed in similar pattern between intramuscular vascular stem cells (IVSC) and subcutaneous vascular stem cells (SVSC) differentiation, such as miR-210, miR-10b and miR-99a. Expression levels of 10 miRNAs were reversely up-or down-regulated between IVSC and SVSC differentiation, 19 were up-or down-regulated only during IVSC differentiation and 55 only during SVSC differentiation. Additionally, 30 miRNAs showed fat-depot specific expression pattern (24 in cells of intramuscular origin and 6 in cells of subcutaneous origin). These adipogenesis-related miRNAs mainly functioned by targeting similar pathways in adipogenesis, obesity and syndrome.ConclusionComparison of miRNAomes in IVSC and SVSC during differentiation revealed that many different miRNAs are involved in adipogenesis, and they regulate SVSC and IVSC differentiation through similar pathways. These miRNAs may serve as biomarkers or targets for enhancing IMF content, and uncovering their function in IMF development will be of great value in the near future.

Indoleamine 2,3-dioxygenase (IDO), an immune checkpoint, is a promising target for cancer immunotherapy. However, current IDO inhibitors are not approved for clinical use yet; therefore, new IDO inhibitors are still demanded. To identify new IDO inhibitors, we have built naive Bayesian (NB) and recursive partitioning (RP) models from a library of known IDO inhibitors derived from recent publications. Thirteen molecular fingerprints were used as descriptors for the models to predict IDO inhibitors. An in-house compound library was virtually screened using the best machine learning model, which resulted in 50 hits for further enzyme-based IDO inhibitory assays. Consequently, we identified three new IDO inhibitors with IC values of 1.30, 4.10, and 4.68 μM. These active compounds also showed IDO inhibitory activities in cell-based assays. The compounds belong to the tanshinone family, a typical scaffold family derived from Danshen (a Chinese herb), the dried root of , which has been widely used in China, Japan, the United States, and other European countries for the treatment of cardiovascular and cerebrovascular diseases. Thus, we discovered a new use for Danshen using machine learning methods. Surface plasmon resonance (SPR) experiments proved that the inhibitors interacted with the IDO target. Molecular dynamic simulations demonstrated the binding modes of the IDO inhibitors.

The photocatalyst-free electron donor–acceptor (EDA) complex photochemistry was deemed to expand the potential of photodriven radical chemistry. Here, we report a cross-coupling reaction of thianthrenium salt functionalized arenes and sodium sulfinates via a photopromoted single electron transfer (SET) process of an EDA complex. A series of biarylsulfones were obtained with high site-selectivity and reactivity. This mild and practical radical reaction could be applied on the bioactive and DNA-encoded molecules.

AimsTo evaluate the effects of couple‐based dyadic interventions on breast cancer patients and their intimate partners and compare the effects between interventions with different durations (<3 months; =3 months; >3 months).DesignA systematic review and meta‐analysis.Data sourcesSix English databases, PubMed, Embase, Web of Science Core Collection, the Cochrane Library, Medline, PsycINFO, and three Chinese databases, China National Knowledge Infrastructure (CNKI), WanFang, and Weipu (VIP), from database inception to 19 February 2022.Review MethodsThe quality of the included RCTs was evaluated using the Cochrane risk‐of‐bias tool and the data analysis was performed by using RevMan 5.4 and Stata 15. The outcomes were categorized into five aspects: dyadic relationship, overall quality of life (QOL), physical health, psychological health and social adjustment.ResultsNineteen RCTs were included. For patients' overall effects, couple‐based dyadic interventions can improve sexual frequency, psychological health (anxiety; depression; well‐being; body image) and social adjustment (family function‐cohesion; social function‐total). In the subgroup analysis, it can adjust patients' relationship satisfaction (>3 months), sexual frequency (>3 months), depression (<3 months and >3 months), well‐being (>3 months), and body image (3 months). For intimate partners, no statistically significant overall effects were found, and all results in the subgroup analyses showed no statistical significance.ConclusionsThe results revealed the different effects of couple‐based dyadic interventions on dyads. It also suggested that tailored intervention duration should be a focus in future studies to obtain the potential actor‐partner benefits.ImpactThis study revealed that the overall effects of the couple‐based dyadic interventions include enhancing patients' sexual frequency, psychological health and social adjustment. Clinical practitioners should consider the intimate partners' outcomes and conduct couple‐based dyadic interventions that contain more tailored elements to achieve better effects.No Patient or Public ContributionRegistration: The systematic review and meta‐analysis of RCTs has been registered in PROSPERO (Number: CRD 42021286679).