VGLL4 has previously been identified as a negative regulator of YAP. Here we show that VGLL4 regulates muscle regeneration in both YAP-dependent and YAP-independent manners at different stages. Knockout of VGLL4 in mice leads to smaller myofiber size and defective muscle contraction force. Furthermore, our studies reveal that knockout of VGLL4 results in increased muscle satellite cells proliferation and impaired myoblast differentiation, which ultimately leads to delayed muscle regeneration. Mechanistically, the results show that VGLL4 works as a conventional repressor of YAP at the proliferation stage of muscle regeneration. At the differentiation stage, VGLL4 acts as a co-activator of TEAD4 to promote MyoG transactivation and facilitate the initiation of differentiation in a YAP-independent manner. Moreover, VGLL4 stabilizes the protein-protein interactions between MyoD and TEAD4 to achieve efficient MyoG transactivation. Our findings define the dual roles of VGLL4 in regulating muscle regeneration at different stages and may open novel therapeutic perspectives for muscle regeneration.

Biomarkers of paleolake deposits from Qarhan Salt Lake in Qaidam Basin, northwest China were systematically analyzed and the A-C series compounds of branched aliphatic alkanes with quaternary substituted carbon atom (BAQCs) were identified. The homologous distinguished three series, A-C, were identified as 5,5-diethylalkanes, 6,6-diethylalkanes and 5-butyl, 5-ethylalkanes series, and their relative abundance was A > B > C. Series A and C were characterized by odd carbon numbers, whereas series B was characterized by even carbon numbers. The high values of series A corresponded with the high values of series B and C. Therefore, it can be concluded that series A, B and C possess a similar biological origin. The abundance of series A was relatively low in the lower part of the section compared with that in the upper part, implying that these series originated from bacteria and/or algae more prevalent in fresh-mesohaline water, and such kinds of bacteria and/or algae are most likely to be thermophilous species. The A25/nC 25 ratio differences in the section show that such branched aliphatic alkanes can be treated as one kind of environmental change proxy for paleolake evolution and may provide important information for the climate reconstruction of the Late Pleistocene.Qaidam Basin, shell bar section, branched aliphatic alkanes, paleoenvironment

Sediments from Xinyun Lake in central Yunnan, southwest China, provide a record of environmental history since the Holocene. With the application of multi-proxy indicators (total organic carbon (TOC), total nitrogen (TN), δ13C and δ15N isotopes, C/N ratio, grain size, magnetic susceptibility (MS) and CaCO3 content), as well as accelerator mass spectrometry (AMS) 14C datings, four major climatic stages during the Holocene have been identified in Xingyun′s catchment. A marked increase in lacustrine palaeoproductivity occurred from 11.06 to 9.98 cal. ka BP, which likely resulted from an enhanced Asian southwest monsoon and warm-humid climate. Between 9.98 and 5.93 cal. ka BP, a gradually increased lake level might have reached the optimum water depth, causing a marked decline in coverage by aquatic plants and lake productivity of the lake. This was caused by strong Asian southwest monsoon, and coincided with the global Holocene Optimum. During the period of 5.60–1.35 cal. ka BP, it resulted in a warm and dry climate at this stage, which is comparable to the aridification of India during the mid- and late Holocene. The intensifying human activity and land-use in the lake catchment since the early Tang Dynasty (∼1.35 cal. ka BP) were associated with the ancient Dian culture within Xingyun’s catchment. The extensive deforestation and development of agriculture in the lake catchment caused heavy soil loss. Our study clearly shows that long-term human activities and land-use change have strongly impacted the evolution of the lake environment and therefore modulated the sediment records of the regional climate in central Yunnan for more than one thousand years.

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