Chemical composition,energy and amino acid digestibility in double-low rapeseed meal fed to growing pigs

Background： The nutritional value of rapeseed meal may be variable due to the variation of its chemical composition. And a precise understandin9 of the nutritional value of an ingredient is beneficial for the accurate diet formulation and reduction of feed costs. This study was conducted to determine the chemical composition, dicjestible energy （DE） and metabolizable enercjy （ME） content, and apparent ileal digestibility （AID） and standardized ileal dicjestibility （SID） of amino acids （AA） for growincj pigs. Thirteen solvent-extracted double-low rapeseed meal （DLIRSM） samples were obtained from the main double-low rapeseed producing areas in China. Methods： The DE and ME contents of the 13 DLRSM samples were measured in cjrowin9 pigs （six pigs per DLRSM sample, average initial body weicjht （BW） =48.3 kg）. The AID and SID of AA of 10 DLRSM samples were determined in 12 crossbred barrows （average initial BW = 35.3 kcj） by using two 6 x 6 Latin square designs. Each Latin square comprised one N-flee diet and 5 DLRSM test diets. Results： The chemical composition of DLRSM varied among samples, and the coefficient of variation was greater than ]0 % for ether extract （EE）, neutral detergent fiber （NDF）, acid detergent fiber （ADF）, calcium （Ca）, and total 91ucosinolates. The AA content of DLRSM varied among samples especially for lysine （Lys） and methionine （Met）. On a dry matter （DM） basis, the apparent total tract digestibility （ATFD） of gross energy （GE）, the DE and ME and the ME：DE ratio of DLRSM averaged 62.39 %, 2862 kcal/k9 and 2723 kcal/kcj, and 94.95 %, respectively. The mean value of S1D of Lys was 70.52 % which varied from 66.54-76.54 %. The SID of crude protein （CP）, Met, and threonine （Thr） averaged 72.81%, 82.41%, and 69.76 %, respectively. Conclusions： There was great variability in chemical composition especially in the concentration of EE, NDF and ADF, but no significant differences in energy content of the DLIRSM samples were observed. In addition, the AID and SID of all AA were relatively similar amoncj DLRSM samples except for that of Lys.

Targeting histone deacetylases for cancer therapy: Trends and challenges

Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors(HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

SERBP1 Promotes Stress Granule Clearance by Regulating 26S Proteasome Activity and G3BP1 Ubiquitination and Protects Male Germ Cells from Thermostimuli Damage

Stress granules(SGs)are membraneless cytoplasmic condensates that dynamically assemble in response to various stressors and reversibly disassemble after stimulus removal;however,the mechanisms underlying SG dynamics and their physiological roles in germ cell development are elusive.Here,we show that SERBP1(SERPINE1 mRNA binding protein 1)is a universal SG component and conserved regulator of SG clearance in somatic and male germ cells.SERBP1 interacts with the SG core component G3BP1 and 26S proteasome proteins PSMD10 and PSMA3 and recruits them to SGs.In the absence of SERBP1,reduced 20S proteasome activity,mislocalized valosin containing protein(VCP)and Fas associated factor family member 2(FAF2),and diminished K63-linked polyubiquitination of G3BP1 during the SG recovery period were observed.Interestingly,the depletion of SERBP1 in testicular cells in vivo causes increased germ cell apoptosis upon scrotal heat stress.Accordingly,we propose that a SERBP1-mediated mechanism regulates 26S proteasome activity and G3BP1 ubiquitination to facilitate SG clearance in both somatic and germ cell lines.

Pathological and molecular examinations of postmortem testis biopsies reveal SARS-CoV-2 infection in the testis and spermatogenesis damage in COVID-19 patients

In late December 2019,the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which causes coronavirus disease 2019(COVID-19),was identified in Wuhan,China,and the ensuing pandemic has led to more than 50 million infected individuals and more than one million deaths by November 10,2020(https://covid19.who.int/).Pathologic investigations of autopsy tissue have focused primarily on the lung,heart,and kidney,whereas morphologic data on testis injury and the effects of SARS-CoV-2 infection on spermatogenesis are limited.Although two groups did not detect SARS-CoV-2 in the semen or testes of recovered COVID-19 patients,1,2 another group confirmed SARS-CoV-2 in the semen of patients.3 Therefore,it is currently unknown whether SARS-CoV-2 infection impacts spermatogenesis and male fertility.In the present study,we evaluated the effects of SARS-CoV-2 infection on spermatogenesis by examining the pathophysiology and molecular features of testes obtained from five male COVID-19 patients at autopsy.

The role of PARP1 in the DNA damage response and its application in tumor therapy

Single-strand break repair protein poly(ADP-ribose)polymerase 1(PARP1)catalyzes the poly(ADPribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways,rendering it a promising target in cancer therapy.The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies.However,recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected.The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy.The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair.These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

Miro2 supplies a platform for Parkin translocation to damaged mitochondria

PINK1/Parkin-mediated mitophagy is an important process in selective removal of damaged mitochondria, in which translocation of Parkin to damaged mitochondria is recognized as an initiation step. At present, how the damaged mitochondria are selectively recognized and targeted by Parkin is not fully understood. Here we show that Miro2, an outer mitochondrial membrane protein, undergoes demultimerization from a tetramer to a monomer and alteration in mitochondrial localization upon CCCP treatment, suggesting a CCCP-induced realignment of Miro2. The realignment of Miro2 is tightly regulated by PINK1-mediated phosphorylation at Ser325/Ser430 and by Ca^2+binding to EF2 domain, which are both essential for the subsequent Parkin translocation. Interestingly, ablation of Miro2 in mouse causes delayed reticulocyte maturation, lactic acidosis and cardiac disorders. Furthermore, several Miro2 mutations found in the congenital lactic acidosis patients also disable its realignment and Parkin translocation. These findings reveal an important role of Miro2 to mediate Parkin translocation by sensing both depolarization and Ca^2+release from damaged mitochondria to ensure the accuracy of mitophagy.

Modelling and analysis of hybrid stochastic timed Petri net

In this paper,an interesting Hybrid Stochastic Timed Petri Net(HSTPN)is proposed for a class of hybrid systems.The proposed HSTPN can be adopted to represent hybrid systems with discrete,continuous,conflicting,time-delay and stochastic characteristics simultaneously.The proposed HSTPN outperforms conventional hybrid Petri net models in terms of describing the scalability and immediacy of hybrid systems.Advantages of the HSTPN on describing hybrid system are verified by establishing some equivalent models of HPN and its derived models.