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The most striking structural features in the interior of the Shan Plateau, southeast of the eastern Himalayan syntaxis, are a series of NE-trending faults that exhibit sinistral movement and an arcuate geometry. Their origin and tectonic evolution remain poorly understood. Furthermore, a switch in slip sense is recorded along many of these faults, but the timing of kinematic reversal is still unclear, hindering an understanding of the causal geodynamic mechanisms. We conducted an integrative study of apatite and zircon (U-Th)/He thermochronology, 40Ar/39Ar geochronology, and structural and geomorphic analysis to decipher the evolution of two major NE-trending faults: the Nantinghe and Dayingjiang faults. At least three deformation stages are identified within the Nantinghe fault zone, including top-to-the-SE/ESE thrusting, dextral ductile strike-slip shearing, and sinistral movement. Zircon and apatite (U-Th)/He data, collected from the northeastern terminus of the Nantinghe fault, reveal rapid cooling in the early Miocene. Combined with the 40Ar/39Ar data from sinistrally sheared mylonite, left-lateral movement on the Nantinghe fault is inferred to have initiated as early as ca. 20 Ma. The Dayingjiang fault reactivated as a sinistral brittle fault along the dextral Yingjiang shear zone. A two-stage thermal history is identified along the shear zone, with prominent cooling during dextral ductile shearing in the early- to mid-Miocene followed by a lower-magnitude cooling episode at ca. 11 Ma caused by sinistral transtension along the Dayingjiang fault. The evolution of the Nantinghe and Dayingjiang faults suggests that the NE-trending fault system in the Shan Plateau may have developed along preexisting structures and underwent diachronous slip-sense inversion in the late Cenozoic. The northward advance of the eastern Himalayan syntaxis caused a major change in both the regional stress field and fault geometries in the eastern India-Eurasia oblique convergence zone, contributing to the inversion of fault kinematics. [ABSTRACT FROM AUTHOR]

an important role in thermogenesis and energy metabolism. However, the regulatory factors that inhibit BAT activity remain largely unknown. Here, cardiotrophin-like cytokine factor 1 (CLCF1) is identified as a negative regulator of thermogenesis in BAT. Adenovirus-mediated overexpression of CLCF1 in BAT greatly impairs the thermogenic capacity of BAT and reduces the metabolic rate. Consistently, BAT-specific ablation of CLCF1 enhances the BAT function and energy expenditure under both thermoneutral and cold conditions. Mechanistically, adenylate cyclase 3 (ADCY3) is identified as a downstream target of CLCF1 to mediate its role in regulating thermogenesis. Furthermore, CLCF1 is identified to negatively regulate the PERK-ATF4 signaling axis to modulate the transcriptional activity of ADCY3, which activates the PKA substrate phosphorylation. Moreover, CLCF1 deletion in BAT protects the mice against diet-induced obesity by promoting BAT activation and further attenuating impaired glucose and lipid metabolism. Therefore, our results reveal the essential role of CLCF1 in regulating BAT thermogenesis and suggest that inhibiting CLCF1 signaling might be a potential therapeutic strategy for improving obesity-related metabolic disorders. [ABSTRACT FROM AUTHOR]

Headward erosion breaching a formerly closed paleolake has been interpreted as an integration process between individual drainage networks. However, the rarity of well-documented cases of this process makes it difficult to explore the fluvial response or its mechanism. Fortunately, dated deposits from a former paleolake in the Fenwei Basin, coupled with fluvial terraces along the Sanmen Gorge of the Yellow River, provide ample opportunities to replicate the upstream integration process and associated landform response. Herein, we applied terrace correlation and age constraints to construct dated longitudinal profiles throughout the Fenwei Basin and the downstream Sanmen Gorge. We identified two age models in longitudinal profiles: (1) relatively high diachronous terraces (Terrace series A) aged headward from ca. 621 ka to 336 ka, localized in the Sanmen Gorge; and (2) relatively low isochronous terraces (Terrace series B) capped by S2 paleosol (ca. 245-190 ka) developed throughout the basin and the gorge. This study hypothesized these two terrace series to have emerged as a mid-Pleistocene bottom-up integration event. In this event, headward incision initiated at least at ca. 621 ka, progressed upstream at a rate of 79.8 mm/a, and breached the Fenwei Basin at ca. 245 ka. This event is likely ascribed to tectonic subsidence of the North China Plain, and may be the latest integration process between the middle and lower reach of the Yellow River. We synthesize comprehensive models to describe terrace genesis and responses in tectonic, climatic, and bottom-up integration processes, which could widen our understanding of long-term large river behaviors. [ABSTRACT FROM AUTHOR]

The Cenozoic Asian climate system experienced a transformation from a zonal pattern to a monsoon-dominant pattern around the Paleogene-Neogene boundary. A series of dynamic mechanisms, such as uplift of the Tibetan Plateau, retreat of the Paratethys Sea, expansion of the South China Sea, and decreasing atmospheric CO2 content, has been suggested to be responsible for the transformation of the Asian climate pattern. However, the role of topographic growth in eastern China has been rarely considered. As the natural divides of geography, climate, and biology, the two most distinct sets of topographic relief in eastern China, the Qinling and Taihang Mountains, play an important role in shaping the Asian climate pattern. We report low-temperature thermochronology data from the Qinling and Taihang Mountains and use age-elevation relationships and thermal history modeling to show that both mountain ranges experienced a phase of rapid exhumation during the late Oligocene and early Miocene. The building of the Qinling and Taihang Mountains around the Oligocene-Miocene boundary temporally and spatially coincided with the reorganization of the Cenozoic Asian climate regime, suggesting that the mountain building in eastern China acted as a possible driving mechanism for the alleged reorganization of the Cenozoic Asian climate regime. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. However, the molecular mechanisms that promote dysregulation of hepatic triglyceride metabolism and lead to NAFLD are poorly understood, and effective treatments are limited. Leukemia inhibitory factor (LIF) is a member of the interleukin-6 cytokine family and has been shown to regulate a variety of physiological processes, although its role in hepatic triglyceride metabolism remains unknown. In the present study, we measured circulating LIF levels by ELISA in 214 patients with biopsy-diagnosed NAFLD as well as 314 normal control patients. We further investigated the potential role and mechanism of LIF on hepatic lipid metabolism in obese mice. We found that circulating LIF levels correlated with the severity of liver steatosis. Patients with ballooning, fibrosis, lobular inflammation, and abnormally elevated liver injury markers alanine transaminase and aspartate aminotransferase also had higher levels of serum LIF than control patients. Furthermore, animal studies showed that white adipose tissue– derived LIF could ameliorate liver steatosis through activation of hepatic LIF receptor signaling pathways. Together, our results suggested that targeting LIF-LIF receptor signaling might be a promising strategy for treating NAFLD. [ABSTRACT FROM AUTHOR]

Background: The long-term efficacy and safety of time-restricted eating for weight loss are not clear.Methods: We randomly assigned 139 patients with obesity to time-restricted eating (eating only between 8:00 a.m. and 4:00 p.m.) with calorie restriction or daily calorie restriction alone. For 12 months, all the participants were instructed to follow a calorie-restricted diet that consisted of 1500 to 1800 kcal per day for men and 1200 to 1500 kcal per day for women. The primary outcome was the difference between the two groups in the change from baseline in body weight; secondary outcomes included changes in waist circumference, body-mass index (BMI), amount of body fat, and measures of metabolic risk factors.Results: Of the total 139 participants who underwent randomization, 118 (84.9%) completed the 12-month follow-up visit. The mean weight loss from baseline at 12 months was -8.0 kg (95% confidence interval [CI], -9.6 to -6.4) in the time-restriction group and -6.3 kg (95% CI, -7.8 to -4.7) in the daily-calorie-restriction group. Changes in weight were not significantly different in the two groups at the 12-month assessment (net difference, -1.8 kg; 95% CI, -4.0 to 0.4; P = 0.11). Results of analyses of waist circumferences, BMI, body fat, body lean mass, blood pressure, and metabolic risk factors were consistent with the results of the primary outcome. In addition, there were no substantial differences between the groups in the numbers of adverse events.Conclusions: Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction. (Funded by the National Key Research and Development Project [No. 2018YFA0800404] and others; ClinicalTrials.gov number, NCT03745612.). [ABSTRACT FROM AUTHOR]

New apatite (U-Th)/He from the northeastern margin of the Tibetan Plateau (north Qilian Shan) indicate rapid cooling began at ~10 Ma, which is attributed to the onset of faulting and topographic growth. Preservation of the paleo-PRZ in the hanging wall and growth strata in the footwall allow us to calculate vertical and horizontal fault slip rates averaged over the last 10 Myr of ~0.5 mm/yr and ~1 mm/yr respectively, which are within a factor of two consistent with Holocene slip rates and geodetic data. Low fault slip rates since the initiation of the northern Qilian Shan fault suggest that total horizontal offset did not exceed 10 km. Further, emergence of the northern Qilian Shan occurs during a period of increased aridity in northern Tibet but is associated with only a minor expansion of the northern plateau perimeter, which is well established near collision time. Outgrowth of the northern Qilian Shan at ~10 Ma could be simple propagation of the larger Qilian Shan system, occurring in response to decreased slip rates on the Altyn Tagh fault or as a result of the change in GPE of the central plateau. [ABSTRACT FROM AUTHOR]

High-resolution topographic or imagery data effectively reveal geomorphic offsets along faults that can be used to deduce slip-per-event of recurrent rupture events. Documentation of patterns of geomorphic offsets is scarce on faults that undergo both creep and coseismic rupture. In this paper, we used newly acquired high-resolution light detection and ranging (LiDAR) data to compile geomorphic offsets along the Laohu Shan section of the Haiyuan fault, in the northern Tibetan Plateau, where interferometric synthetic aperture radar (InSAR) data suggest creep presently occurs over a 35-km-long stretch at a rate comparable to the long-term geological slip rate, despite evidence for past coseismic fault rupture. Numerous offset gullies identified using the LiDAR data yield a range of offsets from less than 2 m up to 50 m. These offsets have well-separated probability density peaks at 2-3 m, ~7 m, and ~14 m, with increments of 2-3 m, 4-6 m, and 5-7 m. The sequence of paleoseismic events along the Laohu Shan section indicates that the gullies with offsets of 2-3 m are likely related to surface rupture of the historical 1888 Jingtai earthquake, plus subsequent creep. Offset increments of 4-6 m and 5-7 m may represent coseismic slip in past paleoseismic events plus creep during the interseismic period. The creeping Laohu Shan section preserves numerous discrete cumulative offsets, with an offset clustering pattern indistinguishable from that on a locked fault with recurrent earthquake ruptures. Association of offset increments with known paleoseismic events yields a slip rate of 3-5 mm/yr during the past 200 years, roughly similar to the ~5 mm/yr creep rate. If the ratio of surface creep rate to the total fault slip rate has been continuous, then seismic moment release by brittle ruptures, and thus seismic hazard, would be much reduced on the Laohu Shan section of the Haiyuan fault. Alternatively, the current high creep rate may be a transient phenomenon, perhaps after slip following the 2000 Jingtai Mw 5.6 earthquake or in response to the adjacent 1920 M ***8 Haiyuan earthquake rupture that terminated immediately to the east. [ABSTRACT FROM AUTHOR]

China’s historiographical traditions tell of the successful control of a Great Flood leading to the establishment of the Xia dynasty and the beginning of civilization. However, the historicity of the flood and Xia remain controversial. Here, we reconstruct an earthquakeinduced landslide dam outburst flood on the Yellow River about 1920 BCE that ranks as one of the largest freshwater floods of the Holocene and could account for the Great Flood. This would place the beginning of Xia at ~1900 BCE, several centuries later than traditionally thought. This date coincides with the major transition from the Neolithic to Bronze Age in the Yellow River valley and supports hypotheses that the primary state-level society of the Erlitou culture is an archaeological manifestation of the Xia dynasty. [ABSTRACT FROM AUTHOR]

We used airborne light detection and ranging (LiDAR) data to reevaluate the singleevent offsets of the 1920 Haiyuan Ms 8.5 earthquake and the cumulative offsets along the western and middle segments of the coseismic surface rupture zone. Our LiDAR data indicate that the offset observations along both the western and middle segments fall into groups. The group with the minimum slip amount is associated with the 1920 Haiyuan Ms 8.5 earthquake, which ruptured both the western and middle segments. Our research highlights two new interpretations: First, the previously reported maximum displacement of the 1920 earthquake was likely due to at least two earthquakes; second, our results reveal that the cumulative offset probability density (COPD) peaks of the same offset amounts on the western and middle segments do not correspond to one another one-to-one. We suggest that any discussion of the rupture pattern of a certain fault based on the offset data should also consider fault segmentation and paleoseismological data. Therefore, the COPD peaks should be computed and analyzed on fault subsections and not entire fault zones to study the number of paleoearthquakes and their rupture patterns. [ABSTRACT FROM AUTHOR]