Acetylation stabilizes the signaling protein WISP2 by preventing its degradation to suppress the progression of acute myeloid leukemia.

Acute myeloid leukemia (AML) is challenging to treat due to its heterogeneity, prompting a deep understanding of its pathogenesis mechanisms, diagnosis, and treatment. Here, we found reduced expression and acetylation levels of WISP2 in bone marrow mononuclear cells from AML patients and that AML patients with lower WISP2 expression tended to have reduced survival. At the functional level, overexpression of WISP2 in leukemia cells (HL-60 and Kasumi-1) suppressed cell proliferation, induced cell apoptosis, and exerted antileukemic effects in an in vivo model of AML. Our mechanistic investigation demonstrated that WISP2 deacetylation was regulated by the deacetylase histone deacetylase (HDAC)3. In addition, we determined that crosstalk between acetylation and ubiquitination was involved in the modulation of WISP2 expression in AML. Deacetylation of WISP2 decreased the stability of the WISP2 protein by boosting its ubiquitination mediated by NEDD4 and proteasomal degradation. Moreover, pan-HDAC inhibitors (valproic acid and trichostatin A) and an HDAC3-specific inhibitor (RGFP966) induced WISP2 acetylation at lysine K6 and prevented WISP2 degradation. This regulation led to inhibition of proliferation and induction of apoptosis in AML cells. In summary, our study revealed that WISP2 contributes to tumor suppression in AML, which provided an experimental framework for WISP2 as a candidate for gene therapy of AML.

Key transition technology of ski jumping based on inertial motion unit, kinematics and dynamics.

BACKGROUND: The development and innovation of biomechanical measurement methods provide a solution to the problems in ski jumping research. At present, research on ski jumping mostly focuses on the local technical characteristics of different phases, but studies on the technology transition process are less. OBJECTIVES: This study aims to evaluate a measurement system (i.e. the merging of 2D video recording, inertial measurement unit and wireless pressure insole) that can capture a wide range of sport performance and focus on the key transition technical characteristics. METHODS: The application validity of the Xsens motion capture system in ski jumping was verified under field conditions by comparing the lower limb joint angles of eight professional ski jumpers during the takeoff phase collected by different motion capture systems (Xsens and Simi high-speed camera). Subsequently, the key transition technical characteristics of eight ski jumpers were captured on the basis of the aforementioned measurement system. RESULTS: Validation results indicated that the joint angle point-by-point curve during the takeoff phase was highly correlated and had excellent agreement (0.966 ≤ r ≤ 0.998, P < 0.001). Joint root-mean-square error (RMSE) differences between model calculations were 5.967° for hip, 6.856° for knee and 4.009° for ankle. CONCLUSIONS: Compared with 2D video recording, the Xsens system shows excellent agreement to ski jumping. Furthermore, the established measurement system can effectively capture the key transition technical characteristics of athletes, particularly in the dynamic changes of straight turn into arc in inrun, the adjustment of body posture and ski movement during early flight and landing preparation.

Effects of Exogenous Melatonin on Root Physiology, Transcriptome and Metabolome of Cotton Seedlings under Salt Stress.

Root systems are the key organs through which plants absorb water and nutrients and perceive the soil environment and thus are easily damaged by salt stress. Melatonin can alleviate stress-induced damage to roots. The present study investigated the effects of exogenous melatonin on the root physiology, transcriptome and metabolome of cotton seedlings under salt stress. Salt stress was observed to damage the cell structure and disorder the physiological system of cotton seedling roots. After subjecting melatonin-soaked seeds to salt stress, the activities of SOD, CAT and POD in cotton seedling roots increased by 10-25%, 50-60% and 50-60%, respectively. The accumulation of H2O2 and MDA were significantly decreased by 30-60% and 30-50%, respectively. The contents of soluble sugar, soluble protein and K+ increased by 15-30%, 15-30% and 20-50%, respectively, while the Na+ content was significantly reduced. Melatonin also increased auxin (by 20-40%), brassinosteroids (by 5-40%) and gibberellin (by 5-35%) and promoted melatonin content and root activity. Exogenous melatonin maintained the integrity of root cells and increased the number of organelles. Transcriptomic and metabolomic results showed that exogenous melatonin could mitigate the salt-stress-induced inhibition of plant root development by regulating the reactive oxygen species scavenging system; ABC transporter synthesis; plant hormone signal transduction, endogenous melatonin gene expression; and the expression of the transcription factors MYB, TGA and WRKY33. These results provide a new direction and empirical basis for improving crop salt tolerance with melatonin.

[Preliminary Study on Association Between Intestine Microbiota and Blood Glucose,Blood Lipid Metabolism in Middle-aged and Elderly People in Chengdu].

OBJECTIVE: To investigate the possible relationship between the gut microbiota and hyperlipidemia,hyperglycemia in middle-aged and elderly people in Chengdu. METHODS: 51 of middle-aged and elderly people participated in this study. The concentration of blood glucose and lipid,and the other physiological parameters of the subjects were analyzed,and their fecal microbiota was also profiled by Illumina high-throughput sequencing technique. RESULTS: The fecal microbiota in the middle-aged and elderly were mainly Firmicutes,Bacteroidetes,Proteobacteria,Fusobacteria,Actinobacteria,Verrucomicrobia. The diversity offecalmicrobiota was significantly lower in the subjects with higher blood glucose (P<0.05),while it did not exhibited relationship with changes in blood lipids. At the bacterial phyla: Proteobacteria and Bacteroidetes were respectively significantly higher in middle-aged and elderly women with higher blood glucose (P<0.05). At the bacterial genus: Faecalibacterium was significantly lower in the hyperglycemic subjects (P<0.05),its abundance and blood glucose levels were negatively correlated (r=⁻0.278,P=0.048); Prevotella and Paraprevotella were significantly lower in the high blood lipids group (P<0.05),and both of them were negatively correlated with blood lipid levels (r=⁻0.357,P=0.10; r=⁻0.365,P=0.008). CONCLUSION: The fecal microbiota in the tested middle-aged and elderly subjects varied with blood glucose and blood lipid concentration. Intestinal microbes might posses close relationship with blood glucose and lipid metabolism in middle-aged and elderly people.

Highly Sensitive Electrochemical Determination of Butylated Hydroxyanisole in Food Samples Using Electrochemical-Pretreated Three-Dimensional Graphene Electrode Modified with Silica Nanochannel Film.

The sensitive detection of antioxidants in food is essential for the rational control of their usage and reducing potential health risks. A simple three-dimensional (3D) electrode integrated with an anti-fouling/anti-interference layer possesses great potential for the direct and sensitive electrochemical detection of antioxidants in food samples. In this work, a 3D electrochemical sensor was developed by integrating a 3D graphene electrode (3DG) with vertically ordered mesoporous silica film (VMSF), enabling highly sensitive detection of the common antioxidant, butylated hydroxyanisole (BHA), in food samples. A simple electrochemical polarization was employed to pre-activate the 3DG electrode (p3DG), enhancing its hydrophilicity. Using the p3DG as the supporting electrode, stable modification of VMSF was achieved using the electrochemical assisted self-assembly (EASA) method, without the need for any adhesive agents (VMSF/p3DG). Taking BHA in food as a model analyte, the VMSF/p3DG sensor demonstrated high sensitivity, due to the enrichment by nanochannels, towards BHA. Electrochemical detection of BHA was achieved with a linear range of 0.1 µM to 5 µM and from 5 µM to 150 µM with a low limit of detection (12 nM). Owing to the fouling resistance and anti-interference capabilities of VMSF, the constructed 3D electrochemical sensor can be directly applied for the electrochemical detection of BHA in complex food samples.

Analysis of the impact of traditional ethnic villages in Hani area on sustainable development.

Rapid economic development and accelerated urbanization have seriously affected the development of traditional ethnic villages in China. We used the minimum cumulative resistance (MCR) model based on land use, landscape pattern, and ecosystem service value (ESV) to evaluate the spatio-temporal dynamics of sustainable development in Hani traditional ethnic villages from 1995 to 2020. By analyzing changes in sustainability indicators in the Hani area and different buffer zones, this paper aims to assess the impact of ethnic villages in the Hani Area on sustainable development and provide recommendations for the sustainable development of traditional ethnic Hani villages. The results indicated that: (1) The area of construction land and landscape fragmentation in the Hani area significantly increased and the value of ecosystem services and levels of sustainable development decreased each year during the study period; (2) The area of cropland in the 2 km buffer zone of the traditional ethnic villages increased, the degree of landscape fragmentation, the value of ecosystem services, and the level of sustainable development were lower than in the 4 km buffer zone during the study period. This is due to population increases in traditional ethnic Hani villages, as well as the intensive reclamation of cropland, increased construction land, and landscape fragmentation. We suggest that the Hani should implement scientific land planning and management policies to protect the local ecosystem and realize the sustainable development of traditional ethnic Hani villages.

Optimisation of stable flight posture of ski jumping based on computational fluid dynamics simulation technology.

The stable flight posture that affects sports performance during flight is usually formed by the multiple angles of the athlete-ski posture. At present, research on the flight phase is mainly based on the single-factor impact analysis based on computational fluid dynamics simulation technology, but studies on the multi-factor coupling relationship of two or more factors is less. This study aims to determine the best optimal-level combination based on the simulation model of this work through comprehensive evaluation from the optimisation perspective of multi-factor coupling. Here, a refined model of the athlete-ski system with the characteristics of ski jumping was established. Reynolds time-averaged method was used for the simulation. A three-factor and five-level simulation test was conducted on the relative inclination between skis, the angle between the body and the ski and the ski V-angle through orthogonal experiment design. Our results show that the optimal-level combination of the relative inclination between skis of 120°, the angle between the body and the ski of 20°, and the ski V-angle of 30° is relatively best in terms of aerodynamic characteristics. Simulation results were similar to the results of the winter field data from video analysis, and the results were effective.

Correction: Synergetic osteogenesis of extracellular vesicles and loading RGD colonized on 3D-printed titanium implants.

Correction for 'Synergetic osteogenesis of extracellular vesicles and loading RGD colonized on 3D-printed titanium implants' by Shiqing Ma et al., Biomater. Sci., 2022, 10, 4773-4784, https://doi.org/10.1039/D2BM00725H.

Apicidin confers promising therapeutic effect on acute myeloid leukemia cells via increasing QPCT expression.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by abnormal cell proliferation, apoptosis repression and myeloid differentiation blockade of hematopoietic stem/progenitor cells. Developing and identifying novel therapeutic agents to reverse the pathological processes of AML are of great significance. Here in this study, we found that a fungus-derived histone deacetylase inhibitor, Apicidin, presents promising therapeutic effect on AML by inhibiting cell proliferation, facilitating apoptosis and inducing myeloid differentiation of AML cells. Mechanistic investigation revealed that QPCT is identified as a potential downstream target of Apicidin, which exhibits significantly decreased expression in AML samples compared with the normal controls and is remarkably up-regulated in AML cells upon Apicidin management. Functional study and rescue assay demonstrated that QPCT depletion further promotes cell proliferation, inhibits apoptosis and impairs myeloid differentiation of AML cells, alleviating the anti-leukemic effect of Apicidin on AML. Our findings not only provide novel therapeutic target for AML, but also lay theoretical and experimental foundation for the clinical application of Apicidin in AML patients.

Functional extracellular matrix hydrogel modified with MSC-derived small extracellular vesicles for chronic wound healing.

OBJECTIVES: Diabetic wound healing remains a global challenge in the clinic and in research. However, the current medical dressings are difficult to meet the demands. The primary goal of this study was to fabricate a functional hydrogel wound dressing that can provide an appropriate microenvironment and supplementation with growth factors to promote skin regeneration and functional restoration in diabetic wounds. MATERIALS AND METHODS: Small extracellular vesicles (sEVs) were bound to the porcine small intestinal submucosa-based hydrogel material through peptides (SC-Ps-sEVs) to increase the content and achieve a sustained release. NIH3T3 cell was used to evaluate the biocompatibility and the promoting proliferation, migration and adhesion abilities of the SC-Ps-sEVs. EA.hy926 cell was used to evaluate the stimulating angiogenesis of SC-Ps-sEVs. The diabetic wound model was used to investigate the function/role of SC-Ps-sEVs hydrogel in promoting wound healing. RESULTS: A functional hydrogel wound dressing with good mechanical properties, excellent biocompatibility and superior stimulating angiogenesis capacity was designed and facilely fabricated, which could effectively enable full-thickness skin wounds healing in diabetic rat model. CONCLUSIONS: This work led to the development of SIS, which shows an unprecedented combination of mechanical, biological and wound healing properties. This functional hydrogel wound dressing may find broad utility in the field of regenerative medicine and may be similarly useful in the treatment of wounds in epithelial tissues, such as the intestine, lung and liver.

Synergetic osteogenesis of extracellular vesicles and loading RGD colonized on 3D-printed titanium implants.

Titanium (Ti) and its alloys have been universally used as surgical implants, and the clinical need for modifying titanium surfaces to accelerate early stage osseointegration and prevent implant loosening is in huge demand. 3D printing technology is an accurate and controllable method to create titanium implants with complex nanostructures, which provide enough space to react and fit in the microenvironment of cells. Recently, extracellular vesicles (EVs) have attracted attention in promoting osteogenesis. The vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) have been proved to pack osteogenic-relative RNAs thereby regulating the osteogenic differentiation and mineralization of the target BMSCs. Arg-Gly-Asp (RGD)-derived peptides are typical peptides used to improve cell attachment and proliferation in bone tissue engineering. A novel strategy is proposed to load RGD-derived peptides on EVs with a fusion peptide (EVsRGD) and colonize EVsRGD on the titanium surface via a specific bonding peptide. In this study, we verify that the presence of EVsRGD enables the realization of the synergetic effect of EVs and RGD, enhancing the osteogenic differentiation and mineralization of BMSCs in vitro, resulting in satisfactory osseointegration around implants in vivo.

A drug delivery system constructed by a fusion peptide capturing exosomes targets to titanium implants accurately resulting the enhancement of osseointegration peri-implant.

BACKGROUND: Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs, but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient's body and expected to find a method to treat implant with BMSC-exos in vivo directly. METHODS: A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface. RESULTS: Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy. CONCLUSION: This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.

Molecular characterization of tomato leaf curl China virus, infecting tomato plants in China, and functional analyses of its associated betasatellite.

A novel tomato-infecting begomovirus from Guangxi province, China, was identified and characterized, for which the name Tomato leaf curl China virus (ToLCCNV) was proposed. Phylogenetic and recombination analyses of the virus genomic sequences suggested that ToLCCNV may have arisen by recombination among Tomato leaf curl Vietnam virus (ToLCVV), Tomato leaf curl Gujarat virus (ToLCGV), and an unknown virus. A betasatellite molecule was found to be associated with ToLCCNV (ToLCCNB), and its complete nucleotide sequences were determined. Infectious clones of ToLCCNV and ToLCCNB were constructed and then used for agro-inoculation of plants; ToLCCNV alone infected Nicotiana benthamiana, Nicotiana glutinosa, Petunia hybrida, and Solanum lycopersicum plants, but no symptoms were induced. ToLCCNB was required for induction of leaf curl disease in these hosts. The ßC1 protein of ToLCCNB was identified as a suppressor of RNA silencing and accumulated primarily in the nucleus. Deletion mutagenesis of ßC1 showed that the central part of ßC1 (amino acids 44 to 74) was responsible for both the suppressor activity and nuclear localization.

Feroxichthys panzhouensis sp. nov., a hump-backed colobodontid (Neopterygii, Actinopterygii) from the early Middle Triassic of Panzhou, Guizhou, China.

Neopterygii is a taxonomically diverse clade of ray-finned fishes, including Teleostei, Holostei and closely related fossil taxa. The Colobodontidae is a stem group of large-sized neopterygians with a durophagous feeding adaption from the Middle to Late Triassic marine ecosystems in Europe and South China. Here, we report the discovery of a new colobodontid, Feroxichthys panzhouensis sp. nov., based on a well-preserved specimen from the early Middle Triassic (Anisian) of Panzhou (formerly known as Panxian), Guizhou, China. The discovery extends the geographical distribution of Feroxichthys from eastern Yunnan into western Guizhou, and demonstrates a more rapid diversification of early colobodontids than previously thought. The new species possesses diagnostic features of Feroxichthys (e.g., a fused lacrimal-maxilla), but it is easily distinguished from the type species Feroxichthys yunnanensis and other colobodontids by some derived features on the skull and, especially, the relatively short and deep body with a prominent postcranial hump. This body form, previously unknown in colobodontids, implicates a morphological adaptation to structurally complex habitats in light of ecological studies of modern ray-finned fishes with a similar body form. In addition, the feeding apparatus suggests a more obligate durophagous diet for F. panzhouensis sp. nov. than other colobodontids. Results of a cladistic analysis recover the new species as a sister taxon of F. yunnanensis within the Colobodontidae, and suggest that a hump-backed body form has independently evolved multiple times in Triassic neopterygians. As such, the new finding provides an important addition for our understanding of the morphological and ecological diversity of neopterygian fishes from the Triassic marine ecosystems in South China.

Chimeric Peptides Quickly Modify the Surface of Personalized 3D Printing Titanium Implants to Promote Osseointegration.

Titanium (Ti) and titanium alloys have been widely used in the field of biomedicine. However, the unmatched biomechanics and poor bioactivities of conventional Ti implants usually lead to insufficient osseointegration. To tackle these challenges, it is critical to develop a novel Ti implant that meets the bioadaptive requirements for load-bearing critical bone defects. Notably, three-dimensional (3D)-printed Ti implants mimic the microstructure and mechanical properties of natural bones. Additionally, eco-friendly techniques based on inorganic-binding peptides have been applied to modify Ti surfaces. Herein, in our study, Ti surfaces were modified to reinforce osseointegration using chimeric peptides constructed by connecting W9, RP1P, and minTBP-1 directly or via (GP)4, respectively. PR1P is derived from the extracellular VEGF-binding domain of prominin-1, which increases the expression of VEGF and promotes the binding of VEGF to endothelial cells, thereby accelerating angiogenesis. W9 induces osteoblast differentiation in bone marrow mesenchymal stem cells and human mesenchymal stem cells to promote bone formation. Overall, chimeric peptides promote osseointegration by promoting angiogenesis and osteogenesis. Additionally, chimeric peptides with P3&4 were more effective than those with P1&2 in improving osseointegration, which might be ascribed to the capacity of P3&4 to provide a greater range for chimeric peptides to express their activity. This work successfully used chimeric peptides to modify 3D-Ti implant surfaces to improve osseointegration on the implant-bone surface.

A novel sensitive electrochemical method for the detection of ractopamine in meat food via polycitrulline-modified electrode.

In this paper we report the modification with citrulline of the surface of a glassy carbon electrode (GCE) through cyclic voltammetry to prepare a polycitrulline-modified electrode (PCit/GCE). The electrochemical behaviour of ractopamine on this PCit/GCE was then investigated by cyclic voltammetry, to establish a novel electrochemical method for the detection of ractopamine residues in animal tissue. The optimum preparation conditions for the modified electrode were found to include a polymerisation solution pH of 6.8. The cyclic voltammetry required 12 scan cycles at a scan rate of 40 mV/s with a potential range of -1.6 to 2.3 V. The optimum conditions to determine ractopamine were in a solution of pH 6.0 with cyclic voltammetry performed at a scan rate of 60 mV/s and a potential range of 0.4 to 1.0 V. To analyse meat, the tissue sample was extracted with ethanol, filtered, evaporated to dryness and diluted with phosphate buffered saline at pH of 6.0 before being analysed in the electrochemical cell. The limit of detection of the new method for ractopamine was 1.0 ng/g and the correlation coefficient (R) was 0.9991 in the concentration range of 140-5410 ng/g. Ractopamine residue levels in spiked beef and mutton samples were detected by the modified electrode and the recovery was in the range of 96%-101%, giving results consistent with a validated HPLC method. This study provides a new method for detection and quantification of ractopamine residues in animal tissue.

[Intervention with thumbtack needling on spinal low back pain in Air Force crew: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect on spinal low back pain (SLBP) in Air Force crew treated with novel thumbtack needling therapy and to analyze the relevant factors of the therapeutic effect. METHODS: A total of 120 Air Force crew with SLBP were randomized into a thumbtack needling group (40 cases), an external treatment group (40 cases, 1 case dropped off ) and a combined treatment group (40 cases, 1 case dropped off ). In the thumbtack needling group, the thumbtack needling therapy was adopted. The novel thumbtack needles were inserted at the lower No.6 region of the wrist-ankle acupuncture, Yaotongdian (EX-UE 7), Yaoyangguan (GV 3), etc. Each point was pressed and kneaded for 1 min each time, 3 or 4 times a day. The treatment for 3 days was taken as one course. At the interval of 2 days, 3 courses were required totally. In the external treatment group, shangshi zhitong plaster was compressed on the center of the tender site in the lumbar region, once daily, consecutively for 6 days as one course. At an interval of 1 day, 2 courses were required totally. In the combined treatment group, the treatments in the thumbtack needling group and the external treatment group were used in combination. Before and after treatment, McGill score and the score of Oswestry dysfunction index (ODI) were compared in the patients among the three groups. The average EMG (AEMG) and the mean power frequency (MPF) were analyzed by using JE-TB0810 electromyography (EMG) acquisition system to evaluate the erector spinae tension in the patients before and after treatment. The clinical effect was observed in the patient of each group and the safety was evaluated. Logistic analysis was performed on the relevant factors of therapeutic effect in the patients. RESULTS: Compared with the values before treatment, McGill scores and ODI scores were reduced (P<0.05), and AEMG and MPF increased in the patients of each group after treatment (P<0.05). After treatment, McGill scores and ODI scores in the thumbtack needling group and the combined treatment group were lower than those in the external treatment group (P<0.05), and AEMG and MPF were higher than the external treatment group (P<0.05). The total effective rates were 87.5% (35/40) and 87.2% (34/39) in the thumbtack needling group and the combined treatment group respectively and were higher than 64.1% (25/39) in the external treatment group (P<0.05). The incidence of the adverse reaction in the combined treatment group was higher than the other two groups (P<0.05). The weekly exercise frequency was the independent factor of the therapeutic effect (OR =12.166, P<0.001). CONCLUSION: The thumbtack needling therapy is significantly effective on spinal low back pain in Air Force crew and is of the safety. Hence, this therapy is applicable to be promoted in the primary care army hospital.

Bifidobacterium bifidum TMC3115 Can Characteristically Influence Glucose and Lipid Profile and Intestinal Microbiota in the Middle-Aged and Elderly.

Bifidobacterium bifidum TMC3115 strain (TMC3115) was orally administrated to 47 subjects with mild hyperglycaemia and dyslipidaemia aged 45 to 75 years for 3 weeks. Blood samples were collected before and after intervention for profiling plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol and triglyceride concentrations, as well as fasting blood glucose. Before and 3 and 4 weeks after intervention, the faecal samples were collected to analyse faecal microbiota using the sequencing of 16S rRNA genes with a next-generation sequencer. TMC3115 significantly decreased plasma TC and LDL-C levels of the tested subjects after intervention (P < 0.05). The frequencies of defaecation and faecal odour after the intervention and 1 week later were significantly better than at pre-intervention, respectively. TMC3115 administration increased Firmicutes, Bacteroides and Actinobacteria and decreases in Proteobacteria and Fusobacteria. There were significant increases in the proportions of Dorea and Lachnospira after the intervention (P < 0.05). TMC3115 also increased the level of Firmicutes and decreased that of Bacteroidetes 1 week after the intervention (P < 0.05). Serum triglycerides correlated negatively with the proportions of Bacteroidetes (R = - 0.21, P = 0.047) and Bacteroides (R = - 0.23, P = 0.029), while the relative abundance of Dialister of Firmicutes correlated negatively and significantly with the serum LDL-C (R = - 0.24, P = 0.022) and TC levels (R = - 0.22, P = 0.030). These results indicate that TMC3115 might exhibit beneficial effects on the serum cholesterol metabolism of subjects with dyslipidaemia through modulation of their intestinal microbiota. Trial registration: ChiCTR-OOC-16010271.

Fuyuanichthys wangi gen. et sp. nov. from the Middle Triassic (Ladinian) of China highlights the early diversification of ginglymodian fishes.

A series of well-preserved fossil assemblages from the Middle Triassic marine rock succession in Southwest China provide unique evidences for studying the early evolution of holostean fishes, including Halecomorphi (e.g., bownfin) and Ginglymodi (e.g., gars). Ginglymodi have the earliest record in the early Middle Triassic (Anisian, ∼244 Ma) of China, represented by Kyphosichthys and Sangiorgioichthys sui from Yunnan and S. yangjuanensis from Guizhou. Here, we report the discovery of a new ginglymodian, Fuyuanichthys wangi gen. et sp. nov., based on 22 well-preserved specimens from the lower part of the Zhuganpo member of the Falang Formation in eastern Yunnan and western Guizhou, which documents the first discovery of convincing ginglymodians from the late Middle Triassic (Ladinian, ∼240 Ma) Xingyi biota in China. Fuyuanichthys possesses a unique combination of features that easily distinguishes it from other ginglymodians, such as presence of a median gular and short and edentulous maxillae, and absence of a supramaxilla and supraorbitals. As one of the smallest known ginglymodians with a maximum standard length of ∼75 mm, the new finding further supports that the Middle Triassic Ginglymodi have a relatively small range of body sizes compared with the Halecomorphi from the same ecosystems in China. Results of a phylogenetic analysis recover Fuyuanichthys as a sister taxon to Kyphosichthys at the ginglymodian stem, and provide new insights into the early evolution of this clade.