Exerkines: Benign adaptation for exercise and benefits for non-alcoholic fatty liver disease.

Exercise has multiple beneficial effects on human metabolic health and is regarded as a "polypill" for various diseases. At present, the lack of physical activity usually causes an epidemic of chronic metabolic syndromes, including obesity, cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Remarkably, NAFLD is emerging as a serious public health issue and is associated with the development of cirrhosis and hepatocellular carcinoma. Unfortunately, specific drug therapies for NAFLD and its more severe form, non-alcoholic steatohepatitis (NASH), are currently unavailable. Lifestyle modification is the foundation of treatment recommendations for NAFLD and NASH, especially for exercise. There are under-appreciated organs that crosstalk to the liver during exercise such as muscle-liver crosstalk. Previous studies have reported that certain exerkines, such as FGF21, GDF15, irisin, and adiponectin, are beneficial for liver metabolism and have the potential to be targeted for NAFLD treatment. In addition, some of exerkines can be modified for the new proteins and get enhanced functions, like IL-6/IC7Fc. Another importance of exercise is the physiological adaptation that combats metabolic diseases. Thus, this review aims to summarize the known exerkines and utilize a multi-omics mining tool to identify more exerkines for the future research. Overall, understanding the mechanisms by which exercise-induced exerkines exert their beneficial effects on metabolic health holds promise for the development of novel therapeutic strategies for NAFLD and related diseases.

Dose-response relationship between physical activity and the morbidity and mortality of cardiovascular disease among individuals with diabetes: A meta-analysis of prospective cohort studies.

BACKGROUND: Diabetes, a chronic condition affecting various organs, is frequently associated with abnormal lipid metabolism, notably increased cholesterol and triglyceride levels. These lipid abnormalities are closely linked to the development and advancement of cardiovascular disease (CVD). Although regular physical activity (PA) has consistently shown benefits in reducing CVD risk in the general population, its precise influence on CVD risk among diabetic patients remains uncertain, particularly regarding dose-response relationships. OBJECTIVE: This study aimed to summarize the evidence from prospective studies on the association between PA and CVD morbidity and mortality in individuals with diabetes, and to explore the optimal levels for public health recommendation. METHODS: We systematically reviewed prospective cohort studies in PubMed, EMBASE, and Web of Science up to December 2022, with inclusion criteria specifying the studies published in English and included adult participants diagnosed with diabetes. A random-effects model was used to pool the relative risk (RR) with the corresponding 95% confidence interval (CI) comparing the highest with the lowest PA categories in each study for qualitative evaluation. In addition, linear and spline regression analyses were used to estimate dose-response associations. RESULTS: The meta-analysis included 12 prospective cohort studies, involving a total of 109,820 participants with diabetes. The combined results revealed that higher levels of PA were associated with a reduced risk of CVD. The RR of CVD for the highest compared with the lowest PA category was 0.62 (95% CI, 0.51-0.73). In addition, there were four studies describing leisure-time physical activity (LTPA) and the pooled RR was 0.68 (95% CI, 0.52-0.83) for the highest versus the lowest activity. The linear regression model revealed that each 10 MET-h/week of incrementally higher PA was associated with a 19.0% (95% CI, 11.6%-25.7%) and a 6.9% (95% CI, 4.5%-9.3%) reduction in CVD morbidity and mortality. Additionally, spline regression curves showed nonlinear relationships between PA levels and the risk of CVD and CVD mortality (both P-nonlinearity <0.001), with a limited reduction in CVD risk and some further reduction in CVD mortality above 20 MET-h per week of PA levels. CONCLUSIONS: For patients with diabetes, especially type 2 diabetes, there was a dose-response relationship between increased PA and reduced risk of CVD morbidity and mortality. The observed PA threshold is consistent with the recommended level for the general population. Gradually moving from inactivity to a guideline-recommended PA level could therefore significantly reduce the burden of CVD in patients with diabetes.

Exercise-Mediated Protection against Air Pollution-Induced Immune Damage: Mechanisms, Challenges, and Future Directions.

Air pollution, a serious risk factor for human health, can lead to immune damage and various diseases. Long-term exposure to air pollutants can trigger oxidative stress and inflammatory responses (the main sources of immune impairment) in the body. Exercise has been shown to modulate anti-inflammatory and antioxidant statuses, enhance immune cell activity, as well as protect against immune damage caused by air pollution. However, the underlying mechanisms involved in the protective effects of exercise on pollutant-induced damage and the safe threshold for exercise in polluted environments remain elusive. In contrast to the extensive research on the pathogenesis of air pollution and the preventive role of exercise in enhancing fitness, investigations into exercise resistance to injury caused by air pollution are still in their infancy. In this review, we analyze evidence from humans, animals, and cell experiments on the combined effects of exercise and air pollution on immune health outcomes, with an emphasis on oxidative stress, inflammatory responses, and immune cells. We also propose possible mechanisms and directions for future research on exercise resistance to pollutant-induced damage in the body. Furthermore, we suggest strengthening epidemiological studies at different population levels and investigations on immune cells to guide how to determine the safety thresholds for exercise in polluted environments.

Recombinase polymerase amplification combined with lateral flow dipstick assay for rapid visual detection of A.simplex (s. s.) and A.pegreffii in sea foods.

Anisakiasis is a food-borne parasitic disease mainly caused by the third stage of Anisakis simplex (s. s.) and Anisakis pegreffii. Traditional methods for detecting of Anisakis involve morphology identification such as visual inspection, enzyme digestion, and molecular methods based on PCR, but they have certain limitations. In this study, the internal transcribed spacer 1 (ITS 1) regions of Anisakis were targeted to develop a visual screening method for detecting A. simplex (s. s.) and A. pegreffii in fish meat based on recombinase polymerase amplification (RPA) combined with lateral flow dipstick (LFD). Specific primers and probes were designed and optimized for temperature, reaction time, and detection threshold. LFD produced clear visual results that were easily identifiable after a consistent incubation of 10-20 min at 37 °C. The whole process of DNA amplification by RPA and readout by LFD did not exceed 30 min. In addition, the detection limit is up to 9.5 × 10-4 ng/µL, and the detection of the artificially contaminated samples showed that the developed assay can effectively and specifically detect A. simplex (s. s.) and A. pegreffii, which fully meet the market's requirements for fish food safety supervision.

A taxonomic revision of the Sinopterus complex (Pterosauria, Tapejaridae) from the Early Cretaceous Jehol Biota, with the new genus Huaxiadraco.

Tapejarids are edentulous pterosaurs particularly abundant in the Chinese Jiufotang Formation, counting with over 10 described specimens and dozens of undescribed ones. A total of seven nominal tapejarid species (within two genera) have been proposed, though it is disputed how many of those are valid instead of sexual or ontogenetic morphs of fewer, or a single, species. However, detailed revisions of the matter are still lacking. In the present work, we provide a specimen-level survey of anatomical variation in previously described Jiufotang tapejarid specimens, as well as of six new ones. We present qualitative and morphometric comparisons, aiming to provide a basis for a taxonomic reappraisal of the complex. Our results lead us to interpret two Jiufotang tapejarid species as valid: Sinopterus dongi and Huaxiadraco corollatus (gen. et comb. nov.). Our primary taxonomic decisions did not rely around cranial crest features, which have typically been regarded as diagnostic for most of these proposed species albeit ever-growing evidence that these structures are highly variable in pterosaurs, due to ontogeny and sexual dimorphism. However, a reassessment of premaxillary crest variation in the Sinopterus complex reveals that while much of the observed variation (crest presence and size) can easily be attributed to intraspecific (ontogenetic and sexual) variation, some of it (crest shape) does seem to represent interspecific variation indeed. A phylogenetic analysis including the species regarded as valid was also performed.

A new darwinopteran pterosaur reveals arborealism and an opposed thumb.

Pterosaurs, which lived during the Mesozoic, were the first known vertebrates to evolve powered flight.1,2 Arboreal locomotion has been proposed for some taxa,3,4 and even considered to have played a role in the origin of pterosaur flight.5,6 Even so, there is still need for comprehensive quantitative ecomorphological analyses.3,4 Furthermore, skeletal adaptations correlated to specialized lifestyles are often difficult to recognize and interpret in fossils. Here we report on a new darwinopteran pterosaur that inhabited a unique forest ecosystem from the Jurassic of China. The new species exhibits the oldest record of palmar (or true) opposition of the pollex, which is unprecedented for pterosaurs and represents a sophisticated adaptation related to arboreal locomotion. Principal-coordinate analyses suggest an arboreal lifestyle for the new species but not for other closely related species from the same locality, implying a possible case of ecological niche partitioning. The discovery adds to the known array of pterosaur adaptations and the history of arborealism in vertebrates. It also adds to the impressive early bloom of arboreal communities in the Jurassic of China, shedding light on the history of forest environments.

Dental microwear of a basal ankylosaurine dinosaur, Jinyunpelta and its implication on evolution of chewing mechanism in ankylosaurs.

Jinyunpelta sinensis is a basal ankylosaurine dinosaur excavated from the mid Cretaceous Liangtoutang Formation of Jinyun County, Zhejiang Province, China. In the present study, its dental microwear was observed using a confocal laser microscope. Jinyunpelta had steep wear facets that covered most of buccal surfaces of posterior dentary teeth. Observation of dental microwear on the wear facet revealed that scratch orientation varied according to its location within the wear facet: vertically (i.e. apicobasally) oriented scratches were dominant in the upper half of the wear facet, and horizontally (i.e. mesiolaterally) oriented ones were in the bottom of the facet. These findings indicated that Jinyunpelta adopted precise tooth occlusion and biphasal jaw movement (orthal closure and palinal lower jaw movement). The biphasal jaw movement was widely observed among nodosaurids, among ankylosaurids, it was previously only known from the Late Cretaceous North American taxa, and not known among Asian ankylosaurids. The finding of biphasal jaw movement in Jinyunpelta showed sophisticate feeding adaptations emerged among ankylosaurids much earlier (during Albian or Cenomanian) than previously thought (during Campanian). The Evolution of the biphasal jaw mechanism that contemporaneously occurred among two lineages of ankylosaurs, ankylosaurids and nodosaurids, showed high evolutionary plasticity of ankylosaur jaw mechanics.

New information on the Cretaceous sauropod dinosaurs of Zhejiang Province, China: impact on Laurasian titanosauriform phylogeny and biogeography.

Titanosaurs were a globally distributed clade of Cretaceous sauropods. Historically regarded as a primarily Gondwanan radiation, there is a growing number of Eurasian taxa, with several putative titanosaurs contemporaneous with, or even pre-dating, the oldest known Southern Hemisphere remains. The early Late Cretaceous Jinhua Formation, in Zhejiang Province, China, has yielded two putative titanosaurs, Jiangshanosaurus lixianensis and Dongyangosaurus sinensis. Here, we provide a detailed re-description and diagnosis of Jiangshanosaurus, as well as new anatomical information on Dongyangosaurus. Previously, a 'derived' titanosaurian placement for Jiangshanosaurus was primarily based on the presence of procoelous anterior caudal centra. We show that this taxon had amphicoelous anterior-middle caudal centra. Its only titanosaurian synapomorphy is that the dorsal margins of the scapula and coracoid are approximately level with one another. Dongyangosaurus can clearly be differentiated from Jiangshanosaurus, and displays features that indicate a closer relationship to the titanosaur radiation. Revised scores for both taxa are incorporated into an expanded phylogenetic data matrix, comprising 124 taxa scored for 548 characters. Under equal weights parsimony, Jiangshanosaurus is recovered as a member of the non-titanosaurian East Asian somphospondylan clade Euhelopodidae, and Dongyangosaurus lies just outside of Titanosauria. However, when extended implied weighting is applied, both taxa are placed within Titanosauria. Most other 'middle' Cretaceous East Asian sauropods are probably non-titanosaurian somphospondylans, but at least Xianshanosaurus appears to belong to the titanosaur radiation. Our analyses also recover the Early Cretaceous European sauropod Normanniasaurus genceyi as a 'derived' titanosaur, clustering with Gondwanan taxa. These results provide further support for a widespread diversification of titanosaurs by at least the Early Cretaceous.

The most basal ankylosaurine dinosaur from the Albian-Cenomanian of China, with implications for the evolution of the tail club.

The tail club knob is a highly specialized structure thought to characterize a subgroup of the ankylosaurine ankylosaurians, and the oldest documented tail club knob in the fossil record occurred in the Campanian ankylosaurine Pinacosaurus. Here we report a new ankylosaurid Jinyunpelta sinensis, gen. et sp. nov., from the Albian-Cenomanian Liangtoutang Formation, Jinyun County, Zhejiang, China. This is the first definitive and the best preserved ankylosaurid dinosaur ever found in southern China. Jinyunpelta possesses unique cranial features differs from other ankylosaurs including two paranasal apertures level with and posterior to the external naris, a triangular fossa on the anterodorsal edge of the maxilla, an antorbital fossa in the junction between the maxilla, lacrimal and jugal, and an anterior process of the prearticular that lies ventral to the splenial. Our phylogenetic analysis suggests Jinyunpelta as the most basal ankylosaurine dinosaur. Jinyunpelta has a tail club with interlocking caudal vertebrae and a well-developed tail club knob, it represents the oldest and the most basal ankylosaurian known to have a well-developed tail club knob. The new discovery thus demonstrates that a large and highly modified tail club evolved at the base of the ankylosaurine ankylosaurs at least about 100 million years ago.

A psittacosaurid-like basal neoceratopsian from the Upper Cretaceous of central China and its implications for basal ceratopsian evolution.

Psittacosauridae (parrot-beaked dinosaurs) represents the first major radiation of ceratopsians (horned dinosaurs). However, psittacosaurids are divergent from the general morphology found in other ceratopsians, and this has resulted in their uncertain systematic position among ceratopsians. Here we describe a new basal neoceratopsian dinosaur, Mosaiceratops azumai gen. et sp. nov. based on a partial semi-articulated skeleton recovered from the Upper Cretaceous Xiaguan Formation of Neixiang County, Henan Province, China. Although our phylogenetic analysis supports this taxon as the most basal neoceratopsian, Mosaiceratops exhibits many features previously considered unique to the Psittacosauridae among the basal Ceratopsia. These include a relatively highly positioned external naris, a proportionally large premaxilla, the nasal extending ventral to the external naris, slender postorbital and temporal bars, a large notch between the basal tubera, and the edentulous premaxilla. Thus, the discovery of Mosaiceratops reduces the morphological disparity between the Psittacosauridae and other basal ceratopsians. Character optimization suggests that basal neoceratopsians have re-evolved premaxillary teeth; a major reversal previously unknown in any dinosaur clade. The new specimen also highlights the mosaic nature of evolution among early ceratopsians and supports the phylogenetic hypothesis that the Psittacosauridae is a relatively derived clade, rather than the most basal group of the Ceratopsia.

A new Cretaceous Metatherian mammal from Henan, China.

We report a new deltatheroidan mammal from the Upper Cretaceous of Henna, China. The new taxon, Lotheridium mengi, is based on a nearly complete skull and associated lower jaws with full adult dentition. Deltatheroidans are known mostly from fragmentary specimens from Asia and North America. Previous views on deltatheroidan relationships were diverse, but recent studies favored their metatherian affinity. The new specimen represents the most complete skull known for deltatheroidans and provides additional evidence that deltatheroidans already had the distinctive metatherian dental formula and replacement pattern and several other derived metatherian features, supporting the metatherian status for this clade. The new species also indicates that deltatheroidan mammals were more diverse and had broader geographical distributions than previously thought.

An egg-adult association, gender, and reproduction in pterosaurs.

A sexually mature individual of Darwinopterus preserved together with an egg from the Jurassic of China provides direct evidence of gender in pterosaurs and insights into the reproductive biology of these extinct fliers. This new find and several other examples of Darwinopterus demonstrate that males of this pterosaur had a relatively small pelvis and a large cranial crest, whereas females had a relatively large pelvis and no crest. The ratio of egg mass to adult mass is relatively low, as in extant reptiles, and is comparable to values for squamates. A parchment-like eggshell points to burial and significant uptake of water after oviposition. This evidence for low parental investment contradicts the widespread assumption that reproduction in pterosaurs was like that of birds and shows that it was essentially like that of reptiles.

Evidence for modular evolution in a long-tailed pterosaur with a pterodactyloid skull.

The fossil record is a unique source of evidence for important evolutionary phenomena such as transitions between major clades. Frustratingly, relevant fossils are still comparatively rare, most transitions have yet to be documented in detail and the mechanisms that underpin such events, typified by rapid large scale changes and for which microevolutionary processes seem insufficient, are still unclear. A new pterosaur (Mesozoic flying reptile) from the Middle Jurassic of China, Darwinopterus modularis gen. et sp. nov., provides the first insights into a prominent, but poorly understood transition between basal, predominantly long-tailed pterosaurs and the more derived, exclusively short-tailed pterodactyloids. Darwinopterus exhibits a remarkable 'modular' combination of characters: the skull and neck are typically pterodactyloid, exhibiting numerous derived character states, while the remainder of the skeleton is almost completely plesiomorphic and identical to that of basal pterosaurs. This pattern supports the idea that modules, tightly integrated complexes of characters with discrete, semi-independent and temporally persistent histories, were the principal focus of natural selection and played a leading role in evolutionary transitions.