REGγ Mediated Regulation of p21^Waf/Cip1, p16^INK4aand p14^ARF/p19^ARF<i>in Vivo</i>

p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-degradation of p21Waf/Cip1, p16INK4a and p14ARF remain unclear. In this study, we showed enhanced expression of p21Waf/Cip1, p16INK4a and p19ARF in multiple tissues from REGg–/– mice compared to REGg+/+ mice. Furthermore, we examined the expression of p21Waf/Cip1, p16INK4a and p14ARF in different cancer tissues and observed that the REGγ protein levels were highly expressed in different human cancers while the level of p21Waf/Cip1, p16INK4a and p14ARF appears to be inversely correlated. These results demonstrate that REGγ may exert its function in physiological and pathological conditions through degradation of p21Waf/Cip1, p16INK4a and p14ARF in vivo.

Hepatic TRPC3 loss contributes to chronic alcohol consumption-induced hepatic steatosis and liver injury in mice

Emerging evidence discloses the involvement of calcium channel protein in the pathological process of liver diseases.Transient receptor potential cation channel subfamily C member 3(TRPC3),a ubiquitously expressed non-selective cation channel protein,controls proliferation,inflammation,and immune response via operating calcium influx in various organs.However,our understanding on the biofunction of hepatic TRPC3 is still limited.The present study aims to clarify the role and potential mechanism(s)of TRPC3 in alcohol-associated liver disease(ALD).We recently found that TRPC3 expression plays an important role in the disease process of ALD.Alcohol exposure led to a significant reduction of hepatic TRPC3 in patients with alcohol-related hepatitis(AH)and ALD models.Antioxidants(N-acetylcysteine and mitoquinone)intervention improved alcohol-induced suppression of TRPC3 via a miR-339-5p-involved mechanism.TRPC3 loss robustly aggravated the alcohol-induced hepatic steatosis and liver injury in mouse liver;this was associated with the suppression of Ca^(2+)/calmodulin-dependent protein kinase kinase 2(CAMKK2)/AMP-activated protein kinase(AMPK)and dysregulation of genes related to lipid metabolism.TRPC3 loss also enhanced hepatic inflammation and early fibrosis-like change in mice.Replenishing hepatic TRPC3 effectively reversed chronic alcohol-induced detrimental alterations in ALD mice.Briefly,chronic alcohol exposure-induced TRPC3 reduction contributes to the pathological development of ALD via suppression of the CAMKK2/AMPK pathway.Oxidative stress-stimulated miR-339-5p upregulation contributes to alcohol-reduced TRPC3.TRPC3 is the requisite and a potential target to defend alcohol consumption-caused ALD.

Bi-directional Selection in Upland Rice Leads to Its Adaptive Differentiation from Lowland Rice in Drought Resistance and Productivity

Drought resistance is required in rice breeding to address the challenge of frequent droughts . However, the evolutionary mechanism of rice drought resistance is not fully understood. We investigated the genetic differentiation between upland and lowland rice domesticated in agro-ecosystems with contrasting water-soil conditions using genome-wide SNPs. We estimated morphological differences among upland and lowland rice in drought resistance and productivity through common garden experiments. Upland rice had better drought resistance but poorer productivity. The negative correlations between traits of drought resistance and productivity are attributed to the underlying genetic trade-offs through tight linkages (e.g., DCA1 and OsCesA7) or pleiotropic effects (e.g., LAX1). The genetic trade-offs are comm on and greatly shape the evolutio n of drought resista nee in upland rice . In genomic regions associated with both productivity and drought resistance, signs of balancing selection were detected in upland rice, while signs of directional selection were detected in lowland rice, potentially contributing to their adaptive differentiation. Signs of balancing selection in upland rice resulted from bi-directional selection during its domestication in drought-prone upland agro-ecosystems.Using genome-wide association analysis, we ide ntified several valuable quantitative trait loci associated with drought resista nee, for which highly differentiated genes should be considered candidates. Bi-directional selection breaking tight linkages by accumulating recombination events would be applicable in breeding water-saving and droughtresistance rice.

Blue revolution for food security under carbon neutrality: A case from the water-saving and drought-resistance rice

The increasing concentration of greenhouse gases(GHGs)in Earth's atmosphere leads to global warming,which further causes a series of climate changes and does great harm to both human society and natural ecosystems.Agricultural GHG emissions,mainly in theform of methane(CH4)and nitrous oxide(N2O),areasignificantsourceofGHGs,accountingfor~14%total global GHGs(Zhang et al.,2022).One major source of agricultural GHGs is CH4 emissions from rice paddies,which is responsiblefor~10%-12%ofhuman-inducedCH4emissions(van Groenigen et al.,2013)and contributes~2.40%to the enhanced global warming effect(Zhang et al.,2022).The global warming potential of GHGs emissions from rice systems is roughly four times higher than either wheat or maize(Linquist et al.,2012).