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Abstract Background Tai Chi (TC) holds a unique and valued place in promoting the physical and mental health of college students. Its significance is underscored by its incorporation as a compulsory physical education course in every university in China. TC, with its rich tradition, places a strong emphasis on posture control as a core sports ability. However, the students in Tai Chi Elective Course (TCEC) have very poor posture control ability. This study protocol investigates the potential of Tan Tui (TT) to address these issues, as TT is a fundamental skill for beginners of traditional Chinese martial arts and has a track record of enhancing lower limb strength and balance, making it a promising choice for improving posture control in TCEC. Methods/design To investigate the impact of different intensities of TT exercises on posture control in TCEC students, we have designed a randomized, double-blind, parallel-controlled trial. Seventy-six students in the TCEC will be randomly divided into low-intensity Tan Tui (LTT), medium-intensity Tan Tui (MTT), and high-intensity Tan Tui exercises group (HTT) and control group (CON), each with 19 people. The LTT group, MTT group, and HTT group will be given different intensity of TT exercises, and the CON group will be given regular TCEC. The intervention period will be 6 weeks (2 times a week, 20 min each time). At baseline (before), 4 weeks of intervention (middle), and 6 weeks of intervention (after), the Unipedal Stance Test (UST), the Star Excursion Balance Test (SEBT), 60°/s angular velocity knee joint flexion and extension relative peak torque (RPT), and knee joint position perception (KJPP) will be evaluated. Discussion This is the first randomized controlled trial protocol from the perspective of training intensity to evaluate the effect of different intensity of TT exercises on posture control of students in TCEC. Should our research reveal a significant intervention effect, the results will offer preliminary, higher-quality evidence supporting the positive impact of varying intensities of Tan Tui exercises on posture control in TCEC students. Trial registration Chinese Clinical Trial Registry ChiCTR2000039109. Registered on October 17, 2020.

Hepatocellular carcinoma (HCC) is distinguished by its insidious onset, difficult treatment, and poor prognosis. Ribosomal Protein Lateral Stalk Subunit P0 (RPLP0) is implicated in numerous tumor progression processes. Nevertheless, the regulatory mechanism of RPLP0 in HCC progression remains unclear. Our study suggested that RPLP0 exhibits high expression levels in HCC and possesses promising diagnostic capabilities, as indicated by its area under the curve (AUC) of 0.908. Further analysis showed that RPLP0 was a significant independent prognostic factor, and elevated expression levels of RPLP0 were linked with poorer overall survival (OS) and progression-free interval (PFI) outcomes. Additionally, reducing RPLP0 levels led to a decrease in HCC cell proliferation, clonality, invasion, migration, and xenograft tumor growth, as well as an increase in apoptosis. Furthermore, our findings indicated that microRNA(miR)-450b-5p induced downregulation of RPLP0, leading to the suppression of the JAK/STAT3 pathway and consequently hindering the advancement of HCC. The study indicates that RPLP0 plays a role as a carcinogenic factor in HCC and carries important diagnostic and prognostic implications. Targeting the miR-450b-5p/RPLP0/JAK/STAT3 axis has potential clinical value in treating HCC.

Micro-hole aerostatic bearings are important components in micro-low-gravity simulation of aerospace equipment, and the accuracy of micro-low-gravity simulation tests is affected by them. In order to eliminate the influence of air resistance on the attitude control accuracy of remote sensing satellites and achieve high fidelity of micro-low-gravity simulation tests, in this study, a design and parameter optimization method was proposed for micro-hole aerostatic bearings for a vacuum environment. Firstly, the theoretical analysis was conducted to investigate the impact of various bearing parameters and external conditions on the bearing load capacity and mass flow. Subsequently, a function model describing the variation in bearing load capacity and mass flow with bearing parameters was obtained utilizing a BP neural network. The parameters of aerostatic bearings in a vacuum environment were optimized using the non-dominated sorting genetic algorithm (NSGA-II) with the objectives of maximizing the load capacity and minimizing the mass flow. Subsequently, experimental tests were conducted on the optimized bearings in both atmospheric and vacuum conditions to evaluate their load capacity and mass flow. The results show that in a vacuum environment, the load capacity and mass flow of aerostatic bearings are increased compared to those in standard atmospheric conditions. Furthermore, it has been determined that the optimal solution for the bearing’s load capacity and mass flow occurs when the bearing has an orifice aperture of 0.1 mm, 36 holes, and an orifice distribution diameter of 38.83 mm. The corresponding load capacity and mass flow are 460.644 N and 11.816 L/min, respectively. The experimental and simulated errors are within 10%; thus, the accuracy of the simulation is verified.

Abstract Background Patellofemoral pain syndrome (PFPS) is a chronic disease. Its early symptoms are mild and can be relieved by rest after the pain. If there is no effective rehabilitation, it may develop into patellofemoral arthritis. Physiotherapy and appropriate exercise intervention can improve PFPS and postural control during exercise. Tan Tui (TT) is an effective means to improve postural control. Whether combined kinesio taping (KT) can be used as an effective treatment for PFPS patients’ recovery has not yet been confirmed. Methods/design Seventy-two eligible patients with early-stage PFPS will be recruited and randomized into 4 groups: TT + KT group (n = 18), TT + KTp group (n = 18), KT group (n = 18), and CON group (n = 18). The TT + KT group was treated with TT combined with KT intervention; the TT + KTp group was treated with TT and KT placebo technical intervention; the KT group was treated with KT intervention alone; the CON group was treated with routine activities. All 4 groups received 30 min, three times a week, for a total of 6 weeks of intervention training. Measurements will be performed at baseline, mid-intervention (4 weeks), and post-intervention (6 weeks) with visual analog scale/score, (VAS), Knee joint Lysholm function score (Lysholm), UniPedal Stance Test (UST), Star Excursion Balance Test ( SEBT), Relative Peak Torque, (RPT), and Knee joint Position PercePtion (KJPP), to check the maintenance of the effect of any intervention. Discussion For the first time in this trial, the impact will be evaluated. If the results are the same as expected, they will provide evidence that TT combined with KT sticking intervention can promote the posture control of patients with early PFPS. Trial registration Chinese Clinical Trial Registry ChiCTR2100051166. Registered on 15 September 2021.

The solution of equilibrium positions is a critical component in the calculation of the dynamic characteristic coefficients of aerostatic bearings. The movement of the rotor in one direction leads to bidirectional variations in the air film force, resulting in low efficiency when using conventional calculation methods. It can even lead to iterative divergence if the initial value is improperly selected. This study concentrates on the orifice throttling aerostatic bearings and proposes a novel method called the bivariate interpolation method (BIM) to calculate the equilibrium position. The equilibrium equation for the rotor under the combined influence of air film forces, gravity, and external loads is established. A calculation program based on the finite difference method is developed to determine the equilibrium position. The process of solving the equilibrium position and the convergence is compared with the secant method and the search method. Furthermore, the variation trend of the equilibrium position and stiffness when the external loads changes are studied based on the BIM. Finally, the correctness of the BIM to solve the equilibrium position is proved by comparing it with the experiment results. The calculation results indicate that the BIM successfully resolves the problem of initial value selection and exhibits superior computational efficiency and accuracy. The equilibrium position initially moves away from the direction of the external load as the load increases, and then this gradually approaches the load direction. The main stiffness increases with increases in the external load, while the variation in cross stiffness depends on the direction of the external load.

Abstract Background Functional ankle instability (FAI) of college football players is an important risk factor affecting their training and competition. Physical therapy and appropriate sports intervention can improve the stability of FAI patients. Previous studies have shown that Tai Chi (TC) and Kinesio taping (KT) can improve the posture control ability of FAI patients. However, whether Tai Chi combined with Kinesio taping effect patch can be used as an effective exercise for rehabilitation of college football players with FAI is not yet proven. Methods/design Fifty-three FAI college football players were randomly assigned to 3 groups: TC+KT (n = 20); TC+KTp (placebo Kinesio taping, KTp, placebo) (n = 17), and KT (n = 16). The TC+KT group received TC and KT functional correction technical intervention, the TC+KTp group received TC and placebo KT technical intervention, and the KT group received KT functional correction technical intervention. Each of the three groups received 30 min each time, 3 times a week, for a total of 6 weeks of intervention training. Star Excursion Balance Test (SEBT) and UniPedal Stance Test (UST) at baseline (before), 4 weeks after intervention (middle), and 6 weeks after intervention (after) and Toe Touch Test (TTT) were evaluated. Discussion For the first time in this trial, the impact will be evaluated. If the results are the same as expected, they will provide evidence that Tai Chi combined with Kinesio taping sticking intervention can promote the posture control of college football players with FAI. Trial registration Chinese Clinical Trial Registry ChiCTR1900027253 . Registered on 6 November 2019.

Support-free cross-linked polyethyleneimine sorbent (CPEI) for CO2 capture was evaluated as the regenerable sorbent. The total amines available for the CO2 capture on CPEI were determined by the polyethyleneimine/glutaraldehyde ratio for the synthesis of CPEI. The CO2 capacity of CPEI in the slurry bubble column reactor reached 4.92 mmol/g, which is 1.97 times higher than that obtained under anhydrous conditions. The adsorption kinetics of CPEI in the reactor were investigated in terms of the CPEI amount, the CO2 fraction, the gas flow rate, temperature, and the total amines available. The experimental breakthrough curves for the sorbent were well-fitted with a fractional-order kinetic model. The modeling analysis found the influence of diffusion resistance on the adsorption is more significant than that of the driving force. The CO2 capacity of CPEI remained almost constant during the temperature swing adsorption/desorption cycles.

The knowledge inference techniques for financial health diagnosis of power grid enterprises was studied.Combining experts system with neural network,expert system framework was used,finishing storage and representation of partial knowledge with neural network,thus overcoming the limitations of traditional diagnosismethods,organi cally integrating experts’knowledge in the field with self-learning abilities of neutral network.More accurate real-time status detection and intelligent diagnosis for financial health of power grid enterprise were realized.

In-situ connectability among modules of a space system can provide significantly enhanced flexibility, adaptability, and robustness for space exploration and servicing missions. Connection of modules in extra-terrestrial environment is hence a topic of rising importance in modern orbital or planetary missions. As an example, the increasing number of satellites sent to space have introduced a large set of connections of various type, for transferring mechanical loads, data, electrical power and heat from one module to another. This paper provides a comprehensive review of published work in space robotic connections and presents the different transfer types developed and used to date in robotic applications for orbital and extra-terrestrial planetary missions. The aims of this paper are to present a detailed analysis of the state of the art available technologies, to make an analysis of and comparison among different solutions to common problems, to synthesize and identify future connectability research, and to lay the foundation for future European space robotic connectability effort and work for a complex and growing important future space missions. All types are described in their base characteristics and evaluated for orbital and planetary environments. This analysis shows that despite the large number of connectors developed for each of the four functionalities (mechanical, thermal, data, and electrical power) here considered, the trend is that researchers are integrating more than one functionalizes into a single equipment or device, to reduce costs and improve standardization. The outcomes of this literature review have contributed toward the design of a future multifunctional, standard and scalable interface at the early stage of the Standard Interface for Robotic Manipulation of Payloads in Future Space Missions (SIROM) project, a European Commission funded Horizon 2020 project. SIROM interfaces will be employed by European prime contractors in future extra-terrestrial missions.

Aiming at surrounding rock damage induced by dynamic disturbance from blasting excavation of rock-anchored beam in rock mass at moderate or far distance in underground cavern, numerical model of different linear charging density and crustal stress in underground cavern is established by adopting dynamic finite element software based on borehole layout, charging, and rock parameter of the actual situation of a certain hydropower station. Through comparison in vibration velocity, contour surface of rock mass excavation, and the crushing extent of excavated rock mass between calculation result and field monitoring, optimum linear charging density of blast hole is determined. Studies are also conducted on rock mass vibration in moderate or far distance to blasting source, the damage of surrounding rock in near-field to blasting source, and crushing degree of excavated rock mass under various in situ stress conditions. Results indicate that, within certain range of in situ stress, the blasting vibration is independent of in situ stress, while when in situ stress is increasing above certain value, the blasting vibration velocity will be increasing and the damage of surrounding rock and the crushing degree of excavated rock mass will be decreasing.

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.

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Abstract Liver kinase B1 (LKB1) is a serine/threonine kinase controlling cell homeostasis. Among post-translational modification, Sumoylation is vital for LKB1 activating adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK), the key regulator in energy metabolism. Of note, AMPK-regulated fatty acid metabolism is highly involved in maintaining normal renal function. However, the regulative mechanisms of LKB1 Sumoylation remain elusive. In this study, we demonstrated that β-catenin, a notorious signal in renal fibrosis, inhibited the Sumoylation of LKB1, thereby disrupting fatty acid oxidation in renal tubular cells and triggering renal fibrosis. Mechanically, we found that Sumo3 was the key mediator for LKB1 Sumoylation in renal tubular cells, which was transcriptionally inhibited by β-catenin/Transcription factor 4 (TCF4) signaling. Overexpression of Sumo3, not Sumo1 or Sumo2, restored β-catenin-disrupted fatty acid metabolism, and retarded lipid accumulation and fibrogenesis in the kidney. In vivo, conditional knockout of β-catenin in tubular cells effectively preserved fatty acid oxidation and blocked lipid accumulation by maintaining LKB1 Sumoylation and AMPK activation. Furthermore, ectopic expression of Sumo3 strongly inhibited Wnt1-aggravated lipid accumulation and fibrogenesis in unilateral ischemia-reperfusion mice. In patients with chronic kidney disease, we found a loss of Sumo3 expression, and it was highly related to LKB1 repression. This contributes to fatty acid metabolism disruption and lipid accumulation, resulting in renal fibrosis. Overall, our study revealed a new mechanism in fatty acid metabolism dysfunction and provided a new therapeutic target pathway for regulating Sumo modification in renal fibrosis.

Alcohol abuse is one of the major public health problems in the world and is associated with various health conditions. However, little is known about the effect of alcohol consumption on acute kidney injury (AKI). In this study, we demonstrate that chronic and binge alcohol feeding with a Lieber-DeCarli diet containing 5 % ethanol for 10 days, followed by a single dose of 31.5 % ethanol by gavage, aggravated AKI after ischemia-reperfusion injury (IRI) in female, but not in male, mice. Kidney dysfunction, histopathology and tubular cell apoptosis were more severe in EtOH-fed female mice after IRI, compared to pair-fed controls. RNA sequencing and experimental validation uncovered that activation of integrin β1 and its downstream c-Jun NH2-terminal kinase (JNK) aggravated AKI in EtOH-fed mice. Knockdown of integrin β1 inhibited JNK phosphorylation and alleviated AKI in EtOH-fed mice, whereas activation of integrin β1 by agonist antibody increased JNK phosphorylation, worsened renal histological injury and tubular cell apoptosis, and aggravated kidney dysfunction. In vitro, activation of integrin β1 increased JNK phosphorylation and induced tubular epithelial cell apoptosis. The detrimental effect of EtOH feeding was primarily mediated by acetaldehyde, as its levels were increased in the blood, liver and kidney of female mice fed with ethanol. Acetaldehyde per se activated integrin β1/JNK signaling and induced tubular cell apoptosis in vitro. These findings suggest that alcohol consumption increases vulnerability to AKI in female mice, which is probably mediated by acetaldehyde/integrin β1/JNK signaling cascade.

Energy metabolism disorder, mainly exhibiting the inhibition of fatty acid degradation and lipid accumulation, is highly related with aging acceleration. However, the intervention measures are deficient. Here, we reported Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), especially EPA, exerted beneficial effects on maintaining energy metabolism and lipid homeostasis to slow organ aging. As the endogenous agonist of peroxisome proliferator–activated receptor α (PPARα), Omega-3 PUFAs significantly boosted fatty acid β-oxidation and ATP production in multiple aged organs. Consequently, Omega-3 PUFAs effectively inhibited age-related pathological changes, preserved organ function, and retarded aging process. The beneficial effects of Omega-3 PUFAs were also testified in mfat-1 transgenic mice, which spontaneously generate abundant endogenous Omega-3 PUFAs. In conclusion, our study innovatively demonstrated Omega-3 PUFAs administration in diet slow aging through promoting energy metabolism. The supplement of Omega-3 PUFAs or fat-1 transgene provides a promising therapeutic approach to promote healthy aging in the elderly.

Acute kidney injury (AKI) is in high prevalence worldwide but with no therapeutic strategies. Programmed cell death in tubular epithelial cells has been reported to accelerate a variety of AKI, but the major pathways and underlying mechanisms are not defined. Herein, we identified that pyroptosis was responsible for AKI progression and related to ATP depletion in renal tubular cells. We found that FAM3A, a mitochondrial protein that assists ATP synthesis, was decreased and negatively correlated with tubular cell injury and pyroptosis in both mice and patients with AKI. Knockout of FAM3A worsened kidney function decline, increased macrophage and neutrophil cell infiltration, and facilitated tubular cell pyroptosis in ischemia/reperfusion injury model. Conversely, FAM3A overexpression alleviated tubular cell pyroptosis, and inhibited kidney injury in ischemic AKI. Mechanistically, FAM3A promoted PI3K/AKT/NRF2 signaling, thus blocking mitochondrial reactive oxygen species (mt-ROS) accumulation. NLRP3 inflammasome sensed the overload of mt-ROS and then activated Caspase-1, which cleaved GSDMD, pro-IL-1β, and pro-IL-18 into their mature forms to mediate pyroptosis. Of interest, NRF2 activator alleviated the pro-pyroptotic effects of FAM3A depletion, whereas the deletion of NRF2 blocked the anti-pyroptotic function of FAM3A. Thus, our study provides new mechanisms for AKI progression and demonstrates that FAM3A is a potential therapeutic target for treating AKI.

Abstract Kidney fibrosis, characterized by the activation and expansion of the matrix-producing fibroblasts, is the common outcome of chronic kidney disease (CKD). While fibroblast proliferation is well studied in CKD, little is known about the regulation and mechanism of fibroblast depletion. Here, we show that exosomes derived from stressed/injured tubules play a pivotal role in dictating fibroblast apoptosis and fate. When human kidney tubular cells (HK-2) were stimulated with TGF-β1, they produced and released increased amounts of exosomes (TGFβ-Exo), which prevented renal interstitial fibroblasts from apoptosis. In vivo, injections of TGFβ-Exo promoted renal fibroblast survival, whereas blockade of exosome secretion accelerated fibroblast apoptosis in obstructive nephropathy. Proteomics profiling identified the tumor necrosis factor-α-induced protein 8 (TNFAIP8) as a key component enriched in TGFβ-Exo. TNFAIP8 was induced in renal tubular epithelium and enriched in the exosomes from fibrotic kidneys. Knockdown of TNFAIP8 in tubular cells abolished the ability of TGFβ-Exo to prevent fibroblast apoptosis. In vivo, gain- or loss- of TNFAIP8 prevented or aggravated renal fibroblast apoptosis after obstructive injury. Mechanistically, exosomal-TNFAIP8 promoted p53 ubiquitination leading to its degradation, thereby inhibiting fibroblasts apoptosis and inducing their proliferation. Collectively, these results indicate that tubule-derived exosomes play a critical role in controlling the size of fibroblast population during renal fibrogenesis through shuttling TNFAIP8 to block p53 signaling. Strategies to target exosomes may be effective strategies for the therapy of fibrotic CKD.

Fibrillin-1 (FBN1) is a large, cysteine-rich, calcium binding extracellular matrix glycoprotein encoded by FBN1 gene. It serves as a structural component of microfibrils and provides force-bearing mechanical support in elastic and nonelastic connective tissue. As such, mutations in the FBN1 gene can cause a wide variety of genetic diseases such as Marfan syndrome, an autosomal dominant disorder characterized by ocular, skeletal and cardiovascular abnormalities. FBN1 also interacts with numerous microfibril-associated proteins, growth factors and cell membrane receptors, thereby mediating a wide range of biological processes such as cell survival, proliferation, migration and differentiation. Dysregulation of FBN1 is involved in the pathogenesis of many human diseases, such as cancers, cardiovascular disorders and kidney diseases. Paradoxically, both depletion and overexpression of FBN1 upregulate the bioavailability and signal transduction of TGF-β via distinct mechanisms in different settings. In this review, we summarize the structure and expression of FBN1 and present our current understanding of the functional role of FBN1 in various human diseases. This knowledge will allow to develop better strategies for therapeutic intervention of FBN1 related diseases.

Introduction: The severe cases of COVID-19, a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often present with acute kidney injury (AKI). Although old age and preexisting medical conditions have been identified as principal risk factors for COVID-19-associated AKI, the molecular basis behind such a connection remains unknown. In this study, we investigated the pathogenic role of Klotho deficiency in COVID-19-associated AKI and explored the therapeutic potential of Klotho-derived peptide 1 (KP1).Methods: We assessed the susceptibility of Klotho deficient Kl/Kl mice to developing AKI after expression of SARS-CoV-2 N protein. The role of KP1 in ameliorating tubular injury was investigated by using cultured proximal tubular cells (HK-2) in vitro and mouse model of ischemia-reperfusion injury (IRI) in vivo.Results: Renal Klotho expression was markedly downregulated in various chronic kidney disease (CKD) models and in aged mice. Compared to wild-type counterparts, mutant KL/KL mice were susceptible to overexpression of SARS-CoV-2 N protein and developed kidney lesions resembling AKI. In vitro, expression of N protein alone induced HK-2 cells to express markers of tubular injury, cellular senescence, apoptosis and epithelial-mesenchymal transition, whereas both KP1 and Klotho abolished these lesions. Furthermore, KP1 mitigated kidney dysfunction, alleviated tubular injury and inhibited apoptosis in AKI model induced by IRI and N protein.Conclusion: These findings suggest that Klotho deficiency is a key determinant of developing COVID-19-associated AKI. As such, KP1, a small peptide recapitulating Klotho function, could be an effective therapeutic for alleviating AKI in COVID-19 patients.

Abstract Chronic kidney disease (CKD) and heart failure (HF) are highly prevalent, aggravate each other, and account for substantial mortality. However, the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and their precise central pathway remain limited. Here, we combined virus tracing techniques with optogenetic techniques to map a polysynaptic central pathway linking kidney afferent nerves to subfornical organ (SFO) and thereby to paraventricular nucleus (PVN) and rostral ventrolateral medulla that modulates sympathetic outflow. This kidney-brain neural circuit was overactivated in mouse models of CKD or HF and subsequently enhanced the sympathetic discharge to both the kidney and the heart in each model. Interruption of the pathway by kidney deafferentation, selective deletion of angiotensin II type 1a receptor (AT1a) in SFO, or optogenetic silence of the kidney-SFO or SFO-PVN projection decreased the sympathetic discharge and lessened structural damage and dysfunction of both kidney and heart in models of CKD and HF. Thus, kidney afferent nerves activate a kidney-brain neural circuit in CKD and HF that drives the sympathetic nervous system to accelerate disease progression in both organs. These results demonstrate the crucial role of kidney afferent nerves and their central connections in engaging cardiorenal interactions under both physiological and disease conditions. This suggests novel therapies for CKD or HF targeting this kidney-brain neural circuit.

Abstract Background Intramuscular fat (IMF) content is a critical indicator of pork quality, and abnormal IMF is also relevant to human disease as well as aging. Although N6-methyladenosine (m6A) RNA modification was recently found to regulate adipogenesis in porcine intramuscular fat, however, the underlying molecular mechanisms was still unclear. Results In this work, we collected 20 longissimus dorsi muscle samples with high (average 3.95%) or low IMF content (average 1.22%) from a unique heterogenous swine population for m6A sequencing (m6A-seq). We discovered 70 genes show both differential RNA expression and m6A modification from high and low IMF group, including ADIPOQ and SFRP1, two hub genes inferred through gene co-expression analysis. Particularly, we observed ADIPOQ, which contains three m6A modification sites within 3′ untranslated and protein coding region, could promote porcine intramuscular preadipocyte differentiation in an m6A-dependent manner. Furthermore, we found the YT521‑B homology domain family protein 1 (YTHDF1) could target and promote ADIPOQ mRNA translation. Conclusions Our study provided a comprehensive profiling of m6A methylation in porcine longissimus dorsi muscle and characterized the involvement of m6A epigenetic modification in the regulation of ADIPOQ mRNA on IMF deposition through an m6A-YTHDF1-dependent manner.

Kidney fibrosis is associated with tubular injury, oxidative stress and activation of interstitial fibroblasts. However, whether these events are somehow connected is poorly understood. In this study, we show that glutathione peroxidase-3 (GPX3) depletion in renal tubular epithelium after kidney injury plays a central role in orchestrating an oxidatively stressed extracellular microenvironment, which drives interstitial fibroblast activation and proliferation. Through transcriptional profiling by RNA-sequencing, we found that the expression of GPX3 was down-regulated in various models of chronic kidney disease (CKD), which was correlated with induction of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase-4 (NOX4). By using decellularized extracellular matrix (ECM) scaffold, we demonstrated that GPX3-depleted extracellular microenvironment spontaneously induced NOX4 expression and reactive oxygen species (ROS) production in renal fibroblasts and triggered their activation and proliferation. Activation of NOX4 by advanced oxidation protein products (AOPPs) mimicked the loss of GPX3, increased the production of ROS, stimulated fibroblast activation and proliferation, and activated protein kinase C-α (PKCα)/mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 3 (STAT3) signaling. Silencing NOX4 or inhibition of MAPK with small molecule inhibitors hampered fibroblast activation and proliferation. In mouse model of CKD, knockdown of NOX4 repressed renal fibroblast activation and proliferation and alleviated kidney fibrosis. These results indicate that loss of GPX3 orchestrates an oxidatively stressed extracellular microenvironment, which promotes fibroblast activation and proliferation through a cascade of signal transduction. Our studies underscore the crucial role of extracellular microenvironment in driving fibroblast activation and kidney fibrosis.

G2/M arrest of epithelial cells leads to fibrosis with unclear mechanisms. This study identifies a protein-encoding circRNA, circBNC2, which inhibits epithelial cells G2/M arrest to prevent fibrotic maladaptive repair in damaged kidney and liver, revealing a potential intervention target for fibrosis.

Abstract Acute kidney injury (AKI) is in high prevalence in the world. However, the therapeutic strategies for AKI are still in mystery. Studies have shown to improve autophagy and lysosomal function could inhibit AKI. But their modulators need to be explored in detail. Annexin A2 (ANXA2) is a phospholipid-binding protein involving in organelle membrane integrity function, suggesting its important role in autophagy and lysosome homeostasis. It implicates ANXA2 potentially protects against AKI. However, this has not been elucidated. Herein, we found that ANXA2 is increased in renal tubules in cisplatin-induced AKI mice. Ectopic expression of ANXA2 improved lysosomal functions and enhanced autophagic flux, further protecting against renal tubular cell apoptosis and kidney injury. Conversely, knockdown of ANXA2 inhibited lysosomal function and autophagy, which aggravated the progression of AKI. Transcriptome sequencing revealed β-catenin signaling is highly responsible for this process. In vitro, we found ANXA2 induced β-catenin activation, further triggering T-cell factor-4 (TCF4)-induced transcription factor EB (TFEB). Furthermore, TFEB promoted lysosome biogenesis to enhance autophagic flux, resulting in the alleviation of AKI. Our new findings underline ANXA2 is a new therapeutic potential for AKI through modulating autophagy and lysosomal function. The underlying mechanism is associated with its inductive effects on β-catenin/TFEB pathway.