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Abstract Background Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder, and transposable elements (TEs) have been hypothesized to play a significant role in its development. However, limited research has explored this connection. Our study aimed to examine the relationship between TE expression and SLE pathogenesis. Methods We analyzed whole blood RNA-seq datasets from 198 SLE patients and 84 healthy controls. The REdiscoverTE pipeline was employed to quantify TE and other gene expressions, identifying differentially expressed TEs. A TE score was calculated to measure overall TE expression for each sample. Gene ontology and gene set enrichment analyses were conducted to explore the functional implications of TE upregulation. Independent datasets were utilized to replicate the results and investigate cell type-specific TE expression. Results Our analysis identified two distinct patient groups: one with high TE expression and another with TE expression comparable to controls. Patients with high TE expression exhibited upregulation of pathways involving nucleic acid sensors, and TE expression was strongly correlated with interferon (IFN) signatures. Furthermore, these patients displayed deregulated cell composition, including increased neutrophils and decreased regulatory T cells. Neutrophils were suggested as the primary source of TE expression, contributing to IFN production. Conclusions Our findings suggest that TE expression may serve as a crucial mediator in maintaining the activation of interferon pathways, acting as an endogenous source of nucleic acid stimulators in SLE patients.

Abstract Objectives This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. Methods We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. Results Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. Conclusion Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Superplastic forming is considered a highly efficient technique for shaping intricate components from titanium matrix composites (TMCs). In this work, high-temperature TMCs with 5 vol% (TiBw + TiCp) reinforcements underwent superplastic tensile tests at various temperatures and strain rates. The results demonstrated that at all deformation temperatures (900 °C–1050 °C) and strain rates (5 × 10−3 s−1 to 10−4 s−1), the elongation of composite sheets surpassed 100%. The strain rate of 10−3 s−1 and a temperature of 1000 °C were found to yield the maximum elongation of 328.1%. At 900 °C, the matrix grains maintain a lamellar morphology during the main stage of deformation, and dynamic recovery (DRV) is the primary mechanism of matrix softening. At 1000 °C, wide-range dynamic recrystallization (DRX) takes place, and grain boundary slip coordinated by grain rotation is the main mechanism of deformation. At 1050 °C, the matrix grains undergo DRX and grow rapidly by migration, and the number of grain boundaries decreases dramatically, resulting in poor superplastic qualities. In the early stages of superplastic deformation, micropores sprout at the triple grain boundaries and at the interfaces between the reinforcements and the matrix. As the deformation proceeds, the micropores extend along the tensile direction and connect with each other to form cavity stringers (CS). The distance between the CS rapidly narrows as the stretching process continues, and eventually the CS links horizontally to form cavity coalescence (CC). Micropore dilatation around the reinforcements causes debonding and cavitation, leading to material failure.

In order to study the influence of the heat storage coefficient of the furnace side evaporation section and superheating section on the primary frequency modulation capacity of the thermal power unit under the deep modulation working conditions, a refined simulation model suitable for the thermal power under the deep modulation working condition was built, based on the typical model in the transient stability program PSD-BPA, and the control logic of the thermal power unit under the actual furnace-machine coordination mode. The correctness of the model was verified by the actual primary frequency modulation data of a DC furnace with a rated power Pe of 1 000 MW at 35%Pe working conditions. Through the simulation model, the influence of the heat storage coefficient of the evaporation section and the superheat section of the furnace side on the primary frequency modulation capacity of the unit under the deep modulation condition was explored. It is found that the smaller the heat storage coefficient of the evaporation section on the furnace side, the stronger the primary frequency modulation response ability of the unit. The larger the heat storage coefficient of the superheated section on the furnace side, the more friendly it is to the primary frequency modulation of the unit. The frequency regulation capability of the unit can be improved by increasing or decreasing the heat storage coefficient in the evaporation and overheat sections. In addition, the refined model of primary frequency regulation established can provide analysis of the margin of primary frequency regulation for thermal power units for power production and regulatory authorities, which is beneficial for the safety of new power systems.

In this work, Mg–7Y–5Zn-0.1V alloys were prepared by 1-D forging followed by multi-step rolling. The rolling reduction dependence of the microstructure and tensile properties of the Mg–7Y–5Zn-0.1V alloy was experimentally investigated. The results indicated that the bimodal matrix microstructures are formed, and the fibrous 18R long-period stacking ordered (LPSO) phase and kinked 14H-LPSO phase are observed after 1-D forging. As the rolling deformation increased, the fibrous 18R-LPSO fractured into block and distributed more homogeneous. The lamellar 14H-LPSO fractured more severely, and it re-precipitated within the matrix when the deformation reached 50 %. The average grain size decreased gradually with increasing rolling deformation, and the minimum was 5.07 μm. After rolling, the {0001} and {0001} textures disappeared. The grain refinement of rolling alloy was mainly due to the fact that dynamic recrystallization (DRX) and substructures were generated within some grains, while the forging alloy was mainly due to DRX. The mechanisms of DRX were discontinuous DRX (DDRX) and twin-induced DRX (TDRX) after forging, and continuous DRX (CDRX) and DDRX after rolling. The strength reached its maximum when the rolling deformation amount reached 60 %, with a yield strength (YS) of 350 MPa and an ultimate tensile strength (UTS) of 385 MPa. Compared to the as-cast Mg–7Y–5Zn-0.1V alloy, its strength increased by 56 % and 63 %, respectively. The improvement of mechanical properties was mainly attributed to fine grain strengthening and dislocation strengthening.

Abstract Background Occupational blood and body fluid exposure (OBEs) is a highly concerning global health problem in health facilities. Improper or inadequate post-exposure practices increase the risk of infection with bloodborne pathogens. Understanding risk factors for OBEs and evaluating the post-exposure practices will contribute to healthcare workers’ (HCWs) well-being. Methods This study retrospectively synthesized and reviewed the 10-year data (from 2010 to 2020) on OBEs in a tertiary teaching hospital. Results A total of 519 HCWs have reported OBEs, increasing yearly from 2010 to 2020. Of these, most were nurses (247 [47.2%]), female (390 [75.1%]), at 23–27 years old (207 [39.9%]). The hepatitis B was the primary bloodborne pathogen exposed to HCWs, with 285 (54.9%) cases, internal medicine was the main exposure site (161 [31.0%]), and sharp injury was the main exposure route (439 [84.6%]). Data analysis shows that there are significant differences between exposure route, exposed pathogens, and exposure site among the different occupational categories (X 2 = 14.5, 43.7, 94.3, all P

Epoxide hydrolases (EHs) catalyze the conversion of epoxides into vicinal diols. The epoxide hydrolase gene from P. chrysosporium was previously cloned and subjected to site-directed mutation to study its enzyme activity, but the results were unsatisfactory. This study used error prone PCR and DNA shuffling to construct a PchEHA mutation library. We performed mutation-site combinations on PchEHA based on enzyme activity measurement results combined with directed evolution technology. More than 15,000 mutants were randomly selected for the preliminary screening of PchEHA enzyme activity alongside 38 mutant strains with increased enzyme activity or enantioselectivity. Protein expression and purification were conducted to determine the hydrolytic activity of PchEHA, and three mutants increased their activity by more than 95% compared with that of the wt. After multiple rounds of screening and site-specific mutagenesis, we found that F3 offers the best enzyme activity and enantioselectivity; furthermore, the molecular docking results confirmed this result. Overall, this study uncovered novel mutants with potential value as industrial biocatalysts.

Due to its good corrosion resistance and high rigidity, fluoroplastic steel heat exchangers have become one of the main feasible solutions to the problem of flue gas waste heat recovery. Therefore, a heat transfer performance test of a fluoroplastic steel heat exchanger was carried out, and a new heat transfer correlation (Nu = 0.11Re0.72Pr0.36, 1900 < Re < 4100, Pr ≈ 0.8) of a fluid transverse tube bank suitable for smooth fluoroplastic surfaces was proposed. Comparing the results of the proposed correlation and the Zhukauskas correlation, the calculation discrepancy was decreased when using the proposed correlation, and the average discrepancy dropped from 16.8% to 3.3%. As the thickness of the fluoroplastic film was reduced, the gap between the two correlations widened. Thus, the Zhukauskas correlation was not applicable to fluoroplastic steel heat exchangers with a thin fluoroplastic film. However, the deviation between the two correlations decreased as the condensing heat transfer area increased. For the fluoroplastic steel heat exchanger with a large condensation heat transfer area, the Zhukauskas correlation could still be utilized. It was interesting to observe that the deviation between the two correlations was reduced when only flue gas condensation was present, but it showed an increasing trend with the increase in condensation intensity.

In order to expand the use of bubble green vegetables, bubble green freeze-dried powder was used as raw material to fabricate dried noodles in this study. The effects of adding the bubble green powder on the flour characteristics, dough tensile properties were discussed. The effects of the additions of green powder, water and salt on the cooking loss, texture and edible quality of the dried noodles were studied, and the processing of bubble green dried noodles was optimized. The results showed that, the dough formation time and stability in the flour characteristics decreased after adding bubble green vegetable powder. Meanwhile, the water absorption rate and weakening degree of the dough increased. The tensile energy, tensile resistance, ductility and maximum tensile resistance in the dough tensile characteristics decreased because of the addition of bubble green vegetables powder. Therefore, the bubble green powder was not conducive to the formation of dough gluten network structure. The processing technology of bubble green dried noodles was optimized. The sensory evaluation of bubble green noodles was 90.12 points when the addition of bubble green powder, water, and salt was 1.30%, 36.00%, and 1.90%, respectively. Blocking effect of bubble green powder on the formation of some gluten networks was observed by scanning electron microscopy and laser confocal microscopy, which preliminarily explained the change trend of decreasing hardness, decreasing chewiness and increasing cooking loss in the texture of dried noodles.

Abstract Currently, there are no in-situ methods to quantify drilling-vibration response characteristics of different lithologies. Here, we quantified the vibration responses of four lithologies (limestone, sandstone, coal, and mudstone) using a combination of theoretical deduction and numerical simulation. First, a drilling-vibration model of a particular rock was established, and the differential equations of motion and vibration responses to rock/drill bit interactions with the formation were derived. Next, finite-element simulation was adopted to simulate the rock/drill-bit interactions of the four lithologies. Finally, the Hilbert–Huang transform (HHT) was applied to extract characteristic waveforms, frequency bands, peak frequencies, and marginal spectra of vibration signals. Simulations revealed that the highest and lowest vibration responses were observed in limestone and mudstone, respectively. Vibration acceleration was proportional to the Young's modulus of rocks, whereas vibration displacement and velocity were inversely proportional to Young's modulus, compressive strength, and density. Based on the HHT results, among the four lithologies, vibration responses had the largest characteristic frequency segments and peak frequencies in limestone (28.1–34.6 kHz and 33.4 kHz, respectively), whereas those of mudstone were the smallest (15.6–21.3 kHz and 19.6 kHz, respectively). The results of this study provide a theoretical basis for establishing an identification method and expert knowledge database of lithology based on drilling-vibration responses.

Abstract Background Global transcription machinery engineering (gTME) is an effective approach employed in strain engineering to rewire gene expression and reshape cellular metabolic fluxes at the transcriptional level. Results In this study, we utilized gTME to engineer the positive transcription factor, DegU, in the regulation network of major alkaline protease, AprE, in Bacillus pumilus. To validate its functionality when incorporated into the chromosome, we performed several experiments. First, three negative transcription factors, SinR, Hpr, and AbrB, were deleted to promote AprE synthesis. Second, several hyper-active DegU mutants, designated as DegU(hy), were selected using the fluorescence colorimetric method with the host of the Bacillus subtilis ΔdegSU mutant. Third, we integrated a screened degU(L113F) sequence into the chromosome of the Δhpr mutant of B. pumilus SCU11 to replace the original degU gene using a CRISPR/Cas9 system. Finally, based on transcriptomic and molecular dynamic analysis, we interpreted the possible mechanism of high-yielding and found that the strain produced alkaline proteases 2.7 times higher than that of the control strain (B. pumilus SCU11) in LB medium. Conclusion Our findings serve as a proof-of-concept that tuning the global regulator is feasible and crucial for improving the production performance of B. pumilus. Additionally, our study established a paradigm for gene function research in strains that are difficult to handle.

In coal mine production, advance and precise identification of coal-rock interface can improve recovery and reduce mining risk, which is one of the bottleneck technologies to realize intelligent coal mining. Azimuth electromagnetic wave logging instrument has larger detecting depth and the azimuth resolution ability, which has a certain advantage in coal-rock interface detection, in order to study the oil the applicability of the azimuth electromagnetic wave instrument Periscope in coalfield well logging, coal log level layered formation model was established, using the generalized reflection coefficient method and finite element numerical simulation method, Taking Periscope as an example, the detection characteristics of coal seam boundary are investigated. Application of Periscope instrument transmitting frequency and spacing, set its instrument radius drill pipe radius of the commonly used for coal mine, the simulation results show that the geological response in line with the typical characteristics of signals in the interface, geological signal change with instrument rotation Angle with periodic response, frequency and delineation of distance is not a simple positive correlation, spaced and offset distance have positive correlation, The geological signal amplitude increases with the increase of coal layer thickness, but when the thickness increases to a certain value, the geological signal does not change with the thickness. When the eccentricity is large, the geological signal is affected by the eccentricity, and the azimuth electromagnetic wave measurement response can reflect the resistivity change of the goaf. Results show that the geological signal detection ability of the coal rock boundary by frequency resistivity contrast, layer thickness, spacing, and a variety of factors, such as electromagnetic wave instrument Periscope bearing geological signal has the azimuth resolution, can be used to set of coal rock interface detection model and identification of mined-out area, but in the case of surrounding rock and coal seam resistivity are high, It is necessary to increase the source distance of the instrument or select the appropriate transmission frequency to meet the requirements of the measurement signal intensity.

As a fault occurs in a low-frequency transmission line zone， the modular multilevel matrix converters （M3Cs） at both ends of the line limit the fault current amplitude and phase. Under such a circumstance， the current on both sides displays the characteristics of through current， which in turn leads to poor sensitivity or even failure to operate of the traditional phase-based line differential protection. To solve the above problems， the electrical characteristics of the line after a fault and the adaptability of the phase differential protection are analyzed first based on the architecture of the low-frequency transmission system. Then three logical criteria based on the sampling values are given in combination with the differential principle of sampling values， which together with the steady-state differential threshold current and the low ratio braking equation constitute a differential protection method applicable to low-frequency transmission lines. Finally， a model of the low-frequency transmission system is built in RTDS （real-time digital simulation） system， and the effectiveness of the method used in low-frequency transmission lines is verified through the simulation analysis of different types of faults within and outside the lines， which lays the foundation for subsequent engineering applications.

Objectives: To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB.Methods: Following the PRIMSA guideline, 14 studies reporting HPV infection in RB acquired from six databases were included.Results: The prevalence of HPV from 941 RB samples was 15.6% [95% confidence interval (CI): 7.3–30]. Mexico followed by India and Brazil had the highest HPV prevalence in RB samples, 61.7% (95% CI: 17–93), 22.5% (95% CI: 9–47), and 12.1% (95% CI: 2–52), in order. HPV 16 was the most common genotype presented in RB samples 23% (95% CI: 9–47), followed by HPV 18 10% (95% CI: 3–30) and the combined HPV 16–18 6% (95% CI: 0–50). We did not find a significant association between HPV and RB [odds ratio (OR): 12.2; 95% CI: 0.65–232; p = 0.09]. However, after removing the largest-weighted study, a significant association between HPV and RB was observed (OR: 45.9; 95% CI; 8.6–245; p < 0.001).Conclusion: HPV prevalence in RB samples was 15% and HPV 16 was the most presented genotype in RB samples. There may be an association between HPV and RB that is needed to be confirmed by high quality future studies. Preventive and treatment measures against HPV infection are essential for the prevention of any possible consequences, in particular, RB.

A diet that is high in sugar and fat is a precursor to various chronic diseases, especially hyperlipidemia. Patients with hyperlipidemia have increased levels of plasma free fatty acids and an ectopic accumulation of lipids. The kidney is one of the main organs affected by this disease and, recently, there have been more studies conducted on renal injury caused by hyperlipidemia. The main pathological mechanism is closely related to renal lipotoxicity. However, in different kidney cells, the reaction mechanism varies due to the different affinities of the lipid receptors. At present, it is believed that in addition to lipotoxicity, hyperlipidemia induced-renal injury is also closely related to oxidative stress, endoplasmic reticulum stress, and inflammatory reactions, which are the result of multiple factors. Exercise plays an important role in the prevention of various chronic diseases and recently emerging researches indicated its positive effects to renal injury caused by hyperlipidemia. However, there are few studies summarizing the effects of exercise on this disease and the specific mechanisms need to be further explored. This article summarizes the mechanisms of hyperlipidemia induced-renal injury at the cellular level and discusses the ways in which exercise may regulate it. The results provide theoretical support and novel approaches for identifying the intervention target to treat hyperlipidemia induced-renal injury.

Brown rice, as a kind of whole-grain food, has attracted significant attention due to its health benefits. This paper aimed to investigate the effect of rice bran content and retrograded time on the physicochemical properties and culinary qualities of brown rice noodles (BRNs). The results indicated that the addition of rice bran altered the pasting properties, gel properties, and texture of the brown rice flours (BRFs). The optimal cooking time and water absorption of BRNs were reduced after the incorporation of rice bran to 14.9% and 41.9%, respectively, while the breaking rate increased from 2.2% to 23.3%. The color of BRNs became darker and yellower, and the overall acceptability by the consumer decreased. The addition of rice bran also led to a decrease in hardness, chewiness and crystallinity. The binding water inside the BRNs decreased, while the free water increased, resulting in a looser structure. This study revealed that the retrograded time of the BRNs also affected its quality. When the retrograded time was 7 h, the cooked BRNs had a lower breaking rate, good hardness, cohesiveness, chewiness, and better overall acceptability by consumers. The structure was compact, the internal binding water content of BRN was higher, and the free water content was lower. This study provides insights into developing nutritionally healthy, high-quality novel rice flour products, and offers a theoretical basis for the industrial production of BRNs.

Abstract Mud shale, used in drilling engineering, is prone to hydration and expansion, resulting in creep deformation that leads to wellbore shrinkage and pipe sticking incidents. Studying the creep characteristics of mud shale is significant for designing a reasonable well structure and determining the lower limit of drilling fluid density. The influence of moisture content on rock strength and creep mechanical properties were studied using water absorption, uniaxial compression, and creep tests. Test results show that with an increase in the moisture content, the mud shale was damaged and softened; moreover, the elastic modulus decreased with increase in moisture content. Under the same load level, the instantaneous strain increased with increasing moisture content. Under different loading stresses, the creep of the rock had nonlinear characteristics, which could be divided into three different creep stages: attenuation, second, and accelerated creep. A new improved creep model based on the Nishihara model was established to describe the accelerated creep characteristics of mud shale under different moisture contents. The ageing degradation and water-bearing weakening effects were introduced. The Levenberg–Marquardt nonlinear least-squares method was applied to invert the creep parameters. The results show that the simulated creep curves, generated using the new creep model, conform to the experimental ones. The relationship between the drilling fluid density and wellbore shrinkage ratio can be defined using this model; it provides a reference for reasonably determining the drilling fluid density.

Abstract As an important mechanism to maintain cellular homeostasis, autophagy exerts critical functions via degrading misfolded proteins and damaged organelles. Recent years, alternative autophagy, a new type of autophagy has been revealed, which shares similar morphology with canonical autophagy but is independent of Atg5/Atg7. Investigations on different diseases showed the pivotal role of alternative autophagy during their physio-pathological processes, including heart diseases, neurodegenerative diseases, oncogenesis, inflammatory bowel disease (IBD), and bacterial infection. However, the studies are limited and the precise roles and mechanisms of alternative autophagy are far from clear. It is necessary to review current research on alternative autophagy and get some hint in order to provide new insight for further study. Video Abstract

ObjectiveTo systematically evaluate the attentional bias in patients with depression toward emotional stimuli and to explore eye movement indicators and potential regulatory variables that can distinguish such patients from healthy individuals.MethodsCase–control studies regarding eye-tracking in major depressive disorder published in PubMed, Web of Science, ScienceDirect, The Cochrane Library, EBSCOhost, Embase, China National Knowledge Infrastructure, Wanfang, and VIP databases from database initiation until March 12, 2022 were included in the present meta-analysis. Two researchers independently screened the literature and performed data extraction. The quality of the literature was assessed using the Newcastle–Ottawa quality assessment scale.RevMan 5.4 software was used for Meta-analysis.ResultsOverall, 14 studies were included, including 1,167 participants (Ndepression = 474; Nhealthy = 693). We found that (1) fixation duration was significantly lower for positive emotional stimuli in the depression group than that in the healthy group; however, for negative stimuli, the fixation duration was significantly more in the depression group than in the healthy group. No significant difference was observed in terms of neutral emotional stimuli between groups. (2) Patients with depression exhibited a significantly lower fixation count for positive emotional stimuli than healthy individuals, whereas the fixation count for negative emotional stimuli was significantly higher in the depression group than in the healthy group. No significant difference was found for neutral emotional stimuli between groups. (3) No significant difference was detected in terms of the first fixation duration of the positive, negative, and neutral emotional stimuli between groups. (4) subgroup analysis indicated that age effected fixation duration for positive emotional stimuli. In addition, age and the type of negative emotional picture (sad, dysphoric, threat, anger) effected fixation duration for negative emotional stimuli.ConclusionOur research supports that patients with depression exhibit a negative attention bias toward emotional stimuli, and the fixation duration and fixation counts may be used as auxiliary objective indicators for depression screening.

Although it is important to accurately detect deception, limited research in this area has been undertaken involving Asian people. We aim to address this gap by undertaking research regarding the identification of deception in Asians in realistic environments. In this study, we develop a Chinese Werewolf Deception Database (C2W2D), which consists of 168 video clips (84 deception videos and 84 honest videos). A total of 1,738,760 frames of facial data are recorded. Fifty-eight healthy undergraduates (24 men and 34 women) and 26 drug addicts (26 men) participated in a werewolf game. The development of C2W2D is accomplished based on a “werewolf” deception game paradigm in which the participants spontaneously tell the truth or a lie. Two synced high-speed cameras are used to capture the game process. To explore the differences between lying and truth-telling in the database, descriptive statistics (e.g., duration and quantity) and hypothesis tests are conducted using action units (AUs) of facial expressions (e.g., t-test). The C2W2D contributes to a relatively sizable number of deceptive and honest samples with high ecological validity. These samples can be used to study the individual differences and the underlying mechanisms of lies and truth-telling between drug addicts and healthy people.

In recent years, immune checkpoint inhibitors (ICIs), represented by PD-1/PD-L1 monoclonal antibodies, have become a research hotspot in the field of oncology treatment. Immunotherapy has shown significant survival advantages in a variety of solid tumors. However, the phenomenon of hyperprogressive disease (HPD) in some patients treated with immunotherapy is gradually getting more attention and focus. An early understanding of the characteristics of HPD is crucial to optimize the treatment strategy. We report a patient with unresectable stage III lung adenocarcinoma who developed HPD with metastasis during consolidation therapy with durvalumab after chemoradiation. To further investigate the potential mechanism of HPD after anti-PD-L1 treatment, primary lung baseline tissue, baseline plasma, post-immunotherapy plasma, and liver metastasis samples of the patient were detected via next-generation sequencing (NGS). Then, multiplex immunohistochemistry (mIHC) was performed on primary lung baseline tissue and liver metastasis samples. KRAS and p.G12C were identified as the major driver mutation genes. With a low tumor mutation burden (TMB) value, the patient presented a very high percentage of CD8+PD-L1+ T cells that infiltrated in the baseline tissue, with 95.5% of all CD8+ cells expressing PD-L1 and a low percentage of CD8+ T cells expressing PD-1. After the emergence of HPD from immunotherapy, liver metastases were similarly infiltrated with an extremely high proportion of CD8+PD-L1+ T cells, with 85.6% of all CD8+ cells expressing PD-L1 and almost no CD8+ T cells expressing PD-1. The extreme infiltration of PD-L1+CD8+ T cells in the tumor microenvironment of baseline tissue might be associated with the aggressive tumor growth observed in anti-PD-L1 treatment for related HPD and could be a potential biomarker for HPD development.

Abstract This study presents the distribution rule of in situ stress in the northeast Sichuan basin and its relationship with fracture. Sixty-seven sets of core samples of 21 Wells from the terrigenous clastic rock formation (Shaximiao, Qianfoya, Xujiahe) and marine carbonate formation (Jialingjiang, Leikoupo, Feixianguan) in the northeast Sichuan basin were tested by acoustic emission experiment. The in situ stress variation with the depth was established and the corresponding regression analysis was done. The horizontal principal stress direction of terrigenous clastic rock formation and marine carbonate rock formation was obtained by combining the dual diameter data of 6 wells and the imaging logging data of 3 wells. The results show that the vertical stress in the northeast of Sichuan basin has a linear relationship with the depth, and there is little difference between the vertical stress and the overburden weight of rocks. The maximum and minimum horizontal principal stress and horizontal shear stress increase with the burial depth. The divergence degree of horizontal shear stress with depth greater than 3000 m is greater than that of the stratum smaller than 3000 m. The horizontal stress plays a dominant role in the northeast Sichuan basin. With the increase in depth, the influence of tectonic stress field decreases and the vertical stress increases. Impacted by Dabashan and Qinling plate tectonic movement, the direction of in situ stress in marine carbonate strata is nearly east–west. The direction of maximum horizontal principal stress in terrigenous clastic rock formation is basically northwest–southeast. The imaging logging data show that the fracture direction is consistent with the horizontal principal stress direction, and the present in situ stress direction is favorable to the secondary reconstruction of natural fractures, and the fractures keep good opening. The distribution law of in situ stress in northeast Sichuan basin shows σ H > σ V > σ h , indicating that the fault activity in this area is dominated by strike-slip type, the tectonic stress field is dominated by horizontal tectonic stress, in addition that the stress state is conducive to reverse fault activity.

Abstract Rock typing is an extremely critical step in the estimation of carbonate reservoir quality and reserves in the Middle East. In order to recognize the rock types of carbonate reservoirs in the Mishrif Formation better, classify the reservoirs accurately, and establish the permeability model in line with the study area precisely, it is necessary to study the recognition method conforming to the actual situation of the study area. The practice shows that the current recognition methods based on capillary pressure curve, flow unit and NMR logging data can effectively distinguish rock types, but a large number of accurate experimental data are required, which can only be applied in a few cored well, however, cannot be applied in the whole oil field. In this study, based on core, thin section, logging data, the sedimentary characteristics of carbonate reservoir, logging response of four rock types as well as porosity and permeability characteristics of Mishrif Formation in W are comprehensively studied. Based on Bayesian stepwise discriminant theory in multivariate statistics, the Bayesian discrimination model based on conventional logging data is established. The examining results showed that, compared with the description of logging and coring, the accuracy of Bayesian discriminant model and cross confirmation rate have achieved more than 80% for the original sample. Reliability verification showed that the matching degree of the rock type recognized in the non-cored well with the core and mud logging was as high as 90%, which matched the depositional environment of the entire region. The study results confirm the validity and generalizability of the Bayesian method to identify and predict rock types, which can be applied to the entire Middle East region to solve the problem of the lack of core data to accurately evaluate the quality of non-cored wells and accurately predict production, meeting the needs of actual reservoir evaluation and production development in the Middle East.

Synthetic chemical pesticides are primarily used to manage plant pests and diseases, but their widespread and unregulated use has resulted in major health and environmental hazards. Using biocontrol microbes and their bioactive compounds is a safe and sustainable approach in plant protection. In this study, a furoic acid (FA) compound having strong antibacterial activity against soil-borne phytopathogenic bacterium Ralstonia solanacearum [causal agent of bacterial wilt (BW) disease] was isolated from Aspergillus niger and identified as 5-(hydroxymethyl)-2-furoic acid compound through spectroscopic analyses (liquid chromatography–mass spectrometry (MS), electron ionization MS, and NMR). The SEM study of bacterial cells indicated the severe morphological destructions by the FA compound. The FA was further evaluated to check its potential in enhancing host resistance and managing tomato BW disease in a greenhouse experiment and field tests. The results showed that FA significantly enhanced the expression of resistance-related genes (PAL, LOX, PR1, and PR2) in tomato and caused a significant reduction (11.2 log10 colony-forming units/g) of the R. solanacearum population in soil, resulting in the reduction of bacterial wilt disease severity on tomato plants and increase in plant length (58 ± 2.7 cm), plant biomass (28 ± 1.7 g), and root length (13 ± 1.2 cm). The findings of this study suggested that the fungus-derived FA compound can be a potential natural compound of biological source for the soil-borne BW disease in tomato.

A geometric equation of borehole deformation under stress was deduced based on the basic theory of elasticity. Subsequently, we established the quantitative relationship between the in situ stress and geometrical parameters of borehole deformation. Furthermore, we proposed an in situ stress prediction model based on borehole deformation. Additionally, numerical simulations of borehole morphology in different lithologies under in situ stress were conducted to analyze the deformation effect. Logging parameters that are sensitive to the shear wave time difference, such as longitudinal wave time difference, density, and natural gamma radiation, were selected for training using an artificial neural network (ANN) to predict the shear wave time difference. The results demonstrated that 1) combining the theoretical derivation and numerical simulation, the borehole geometry under stress was quasi-elliptic, and 2) compared with the existing shear wave time difference curve, the predicted geometry by the ANN was consistent with the actual geometry. Consequently, compared with the tested data from acoustic emission, the overall error of the in situ stress predicted using the new method was less than 9.2%. Moreover, the accuracy of the coal seam was the highest, wherein the average errors of the maximum and minimum horizontal principal stresses were 2.01 and 2.56%, respectively, which confirms the feasibility of the proposed method.

Abstract Introduction Spinal cord injury (SCI) is a neurological, medically incurable disorder. Human pluripotent stem cells (hPSCs) have the potential to generate neural stem/progenitor cells (NS/PCs), which hold promise in the treatment of SCI by transplantation. In our study, we aimed to establish a chemically defined culture system using serum-free medium and ascorbic acid (AA) to generate and expand long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) differentiated from hPSCs effectively and stably. Methods We induced human embryonic stem cells (hESCs)/induced PSCs (iPSCs) to neurospheres using a newly established in vitro induction system. Moreover, lt-NES cells were derived from hESC/iPSC-neurospheres using two induction systems, i.e., conventional N2 medium with gelatin-coated plates (coated) and N2+AA medium without pre-coated plates (AA), and were characterized by reverse transcription polymerase chain reaction (RT-PCR) analysis and immunocytochemistry staining. Subsequently, lt-NES cells were induced to neurons. A microelectrode array (MEA) recording system was used to evaluate the functionality of the neurons differentiated from lt-NES cells. Finally, the mechanism underlying the induction of lt-NES cells by AA was explored through RNA-seq and the use of inhibitors. Results HESCs/iPSCs were efficiently induced to neurospheres using a newly established induction system in vitro. lt-NES cells derived from hESC/iPSC-neurospheres using the two induction systems (coated vs. AA) both expressed the neural pluripotency-associated genes PAX6, NESTIN, SOX1, and SOX2. After long-term cultivation, we found that they both exhibited long-term expansion for more than a dozen generations while maintaining neuropluripotency. Moreover, the lt-NES cells retained the ability to differentiate into general functional neurons that express β-tubulin at high levels. We also demonstrated that AA promotes the generation and long-term expansion of lt-NES cells by promoting collagen synthesis via the MEK-ERK1/2 pathway. Conclusions This new chemically defined culture system was stable and effective regarding the generation and culture of lt-NES cells induced from hESCs/iPSCs using serum-free medium combined with AA. The lt-NES cells induced under this culture system maintained their long-term expansion and neural pluripotency, with the potential to differentiate into functional neurons. Graphical abstract

Background: Liquiritin (LQ) is one of the main flavonoids extracted from the roots of Glycyrrhiza spp., which are widely used in traditional Chinese medicine. Studies in both cellular and animal disease models have shown that LQ attenuates or prevents oxidative stress, inflammation, and apoptosis. However, the potential therapeutic effects of LQ on pressure overload-induced cardiac hypertrophy have not been so far explored. Therefore, we investigated the cardioprotective role of LQ and its underlying mechanisms in the aortic banding (AB)-induced cardiac hypertrophy mouse model.Methods and Results: Starting 3 days after AB surgery, LQ (80 mg/kg/day) was administered daily over 4 weeks. Echocardiography and pressure-volume loop analysis indicated that LQ treatment markedly improved hypertrophy-related cardiac dysfunction. Moreover, hematoxylin and eosin, picrosirius red, and TUNEL staining showed that LQ significantly inhibited cardiomyocyte hypertrophy, interstitial fibrosis, and apoptosis. Western blot assays further showed that LQ activated LKB1/AMPKα2/ACC signaling and inhibited mTORC1 phosphorylation in cardiomyocytes. Notably, LQ treatment failed to prevent cardiac dysfunction, hypertrophy, and fibrosis in AMPKα2 knockout (AMPKα2−/−) mice. However, LQ still induced LKB1 phosphorylation in AMPKα2−/− mouse hearts. In vitro experiments further demonstrated that LQ inhibited Ang II-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) by increasing cAMP levels and PKA activity. Supporting the central involvement of the cAMP/PKA/LKB1/AMPKα2 signaling pathway in the cardioprotective effects of LQ, inhibition of Ang II-induced hypertrophy and induction of LKB1 and AMPKα phosphorylation were no longer observed after inhibiting PKA activity.Conclusion: This study revealed that LQ alleviates pressure overload-induced cardiac hypertrophy in vivo and inhibits Ang II-induced cardiomyocyte hypertrophy in vitro via activating cAMP/PKA/LKB1/AMPKα2 signaling. These findings suggest that LQ might be a valuable adjunct to therapeutic approaches for treating pathological cardiac remodeling.

Lung cancer is the most common solid tumor in the worldwide. Targeted therapy and immunotherapy are important treatment options in advanced non-small cell lung cancer (NSCLC). The association of PTEN mutation and tumor immunotherapy is less established for patients with NSCLC. We present the case of an Asian woman diagnosed with stage IV lung adenocarcinoma harboring an ERBB2 mutation. She received Nivolumab treatment when her disease progresses after previous chemotherapy and Afatinib treatment. However, the patient did not response to Nivolumab. PTEN mutation was detected by next-generation sequencing (NGS) after treatment with Nivolumab. PTEN, a secondary mutation, may be served as a biomarker of resistance to anti-PD-1 immunotherapy in lung adenocarcinoma. The relationship between PTEN mutation and immunotherapy is complex and needs further study.

The microstructure and cellular transition characteristics of an intermetallic Ti-42Al-3Nb-1Mo-0.1B (at.%) alloy were investigated. The as-cast microstructure of the alloy is mainly composed of (α2+γ) lamellar structure and (β+γ) mixture structure, which distributes along the boundaries of the lamellar colonies. In order to study the phase transformation of lamellar structure at aging temperature, a two-step heat treatment was carried out. After the first step of annealing treatment at 1,260 °C, the microstructure with relatively finer lamellar space and (γ+β/B2) mixture structure is obtained. Aging treatment, as the second heat treatment step, has significant influence on the microstructure, attributing to a cellular reaction of α2+γ→ γ+β. With the increase of aging temperature, the (α2+γ) lamellar structure continues to dissolve, whereas the contents of both the equiaxed γ and β/B2 grains continuously increase. Besides, the orientation of lamellae α2, equiaxed γ and equiaxed β/B2 in the cellular transition region follows a specific relationship of {0–11}ββ//{0001}α2α2//{1–11}γγ.

The optimum strategy for heart failure (HF) treatment has yet to be elucidated. This study intended to test the benefit of a combination of valsartan (VAL) and perifosine (PER), a specific AKT inhibitor, in protecting against pressure overload induced mouse HF. Mouse were subjected to aortic banding (AB) surgery to establish HF models and then were given vehicle (HF), VAL (50 mg/kg/d), PER (30 mg/kg/d) or combination of VAL and PER for 4 weeks. Mouse with sham surgery treated with VEH were used for control (VEH). VAL or PER treatment could significantly alleviate mouse heart weight, attenuate cardiac fibrosis and improve cardiac function. The combination treatment of VAL and PER presented much better benefit compared with VAL or PER group respectively. PER treatment significantly inhibited AKT/GSK3β/mTORC1 signaling. Besides the classic AT1 inhibition, VAL treatment significantly inhibited MAPK (ERK1/2) signaling. Furthermore, VAL and PER treatment could markedly prevent neonatal rat cardiomyocyte hypertrophy and the activation of neonatal rat cardiac fibroblast. Combination of VAL and PER also presented superior beneficial effects than single treatment of VAL or PER in vitro experiments respectively. This study presented that the combination of valsartan and PER may be a potential treatment for HF prevention.

Abstract Bacillus subtilis S1-4, isolated from chicken feather could efficiently degrade feathers by secreting several extracellular proteases. In order to get insight into the individual protease involved in keratin hydrolysis, a keratinase designed as BsKER71 was cloned and expressed in Bacillus subtilis WB600. In silico analysis revealed that BsKER71 protein contained a mature protein of 36.1 kDa. Further, purified BsKER71 could hydrolyze a variety of natural proteins, such as fibrous protein, collagen protein, casein, keratin and bovine serum albumin. In addition, this keratinase exhibited high enzyme activity in a wide range of pH and optimal pH of 10.0 and 9.0 in the hydrolysis of casein and keratin, respectively. Similarly, the optimal temperature was 55 °C and 50 °C for the hydrolysis of above two substrates, respectively. The hydrolytic activity was significantly inhibited by phenylmethanesulfonyl fluoride (PMSF), indicating the presence of serine residue in the active site. Moreover, ethylenediaminetetraacetic acid (EDTA) and phenanthroline moderately inhibited the hydrolytic activity. The catalytic activity was stimulated by Mg2+ and Ca2+, but greatly inhibited by Cu2+. Furthermore, several chemicals exhibited different effects on the hydrolysis of casein and keratin by BsKER71. These results provided a better understanding of BsKER71 from feather degrading bacterium B. subtilis S1-4.

Objectives: Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2.Methods and results: Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60–70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PSR staining showed that Sesn2 overexpression significantly alleviated cardiac hypertrophy and fibrosis in mice hearts induced by pressure overload. Meanwhile, adenovirus-mediated-Sesn2 overexpression markedly suppressed angiotensin II-induced neonatal rat cardiomyocyte hypertrophy in vitro. Mechanistically, Sesn2 overexpression increased AMPKα2 phosphorylation but inhibited mTORC1 phosphorylation. The cardiac protections of Sesn2 overexpression were also via regulating oxidative stress by enhancing Nrf2/HO-1 signaling, restoring SOD activity, and suppressing NADPH activity. Particularly, we first proved the vital role of AMPKα2 in the regulation of Sesn2 with AMPKα2 knockout (AMPKα2-/-) mice and Sesn2 transgenic mice crossed with AMPKα2-/-, since Sesn2 overexpression failed to improve cardiac function, inhibit cardiac hypertrophy and fibrosis, and attenuate oxidative stress after AMPKα2 knockout.Conclusion: This study uniquely revealed that Sesn2 overexpression showed little genetic toxicity in mice hearts and inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.

Immunofluorescence is a technique to visualize the localization of specific molecule targets within cells using the specificity of antibodies. Here, we describe a protocol to detect two different protein components in a cell simultaneously. Antibody concentrations to be used vary from cell to cell and should be optimized for different cell types. In this protocol, we perform co-immunofluorescence of mitochondrial ribosomal protein L7/L12 (MRPL12) and nuclear factor erythroid 2-related factor 2 (Nrf2), a potential transcription factor of MRPL12, in HK-2 cells, as an example. Taking advantage of the diverse set of antibodies raised in different species, we are able to analyze the colocalization and expression of these proteins.

This study aimed to investigate the role and mechanisms of Receptor interacting protein kinase 2 (RIP2) in pressure overload-induced cardiac remodeling. Human failing or healthy donor hearts were collected for detecting RIP2 expression. RIP2 cardiomyocyte-specific overexpression, RIP2 global knockout, or wild-type mice were subjected to sham or aortic banding (AB) surgery to establish pressure overload-induced cardiac remodeling in vivo. Phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) were used for further investigation in vitro. The expression of RIP2 was significantly upregulated in failing human heart, mouse remodeling heart, and Ang II-treated NRCMs. RIP2 overexpression obviously aggravated pressure overload-induced cardiac remodeling. Mechanistically, RIP2 overexpression significantly increased the phosphorylation of TAK1, P38, and JNK1/2 and enhanced IκBα/p65 signaling pathway. Inhibiting TAK1 activity by specific inhibitor completely prevented cardiac remodeling induced by RIP2 overexpression. This study further confirmed that RIP2 overexpression in NRCM could exacerbate PE-induced NRCM hypertrophy and TAK1 silence by specific siRNA could completely rescue RIP2 overexpression-mediated cardiomyocyte hypertrophy. Moreover, this study showed that RIP2 could bind to TAK1 in HEK293 cells, and PE could promote their interaction in NRCM. Surprisingly, we found that RIP2 overexpression caused spontaneous cardiac remodeling at the age of 12 and 18 months, which confirmed the powerful deterioration of RIP2 overexpression. Finally, we indicated that RIP2 global knockout attenuated pressure overload-induced cardiac remodeling via reducing TAK1/JNK1/2/P38 and IκBα/p65 signaling pathways. Taken together, RIP2-mediated activation of TAK1/P38/JNK1/2 and IκBα/p65 signaling pathways played a pivotal role in pressure overload-induced cardiac remodeling and spontaneous cardiac remodeling induced by RIP2 overexpression, and RIP2 inhibition might be a potential strategy for preventing cardiac remodeling.

BackgroundLung adenocarcinoma (LUAD) is a highly mortal cancer. Tertiary lymphoid structures (TLS) are ectopic lymphoid organs with similar morphological and molecular characters to secondary lymphoid organ. The aim of this study is to investigate the prognostic effect of a gene signature associated with TLSs, including B-cell-specific genes.MethodsClinical data of 515 LUAD patients in the TGCA cohort were used to examine the relationship of TLS signature with immune microenvironment, tumor mutational burden (TMB), and driver gene mutations. Patients were divided into the TLS signature high group and TLS signature low group, and comparative analysis of survival and its influencing factors between the two groups was performed. The resulting data were then validated in the GSE37745 cohort.ResultsTLS signature high group had significantly better overall survival (OS) and progression-free interval (PFI) as well as significantly higher infiltration of immune cell subsets, cancer immune cycle (CIC) signature except for immunogram score2 (IGS2), and expression of major checkpoint genes than the TLS signature low group. Notably, while TLS signature was not markedly associated with TMB and mutation frequencies of driver genes, there were significant differences in overall survival of patients with given mutation status of EGFR, KRAS, BRAF and TP53 genes between the TLS signature high and low groups.ConclusionThis study provided evidence that LUAD patients with high TLS signature had a favorable immune microenvironment and better prognosis, suggesting that TLS signature is an independent positive prognostic factor for LUAD patients.

Abstract Background Bacillus pumilus is a Gram-positive and endospore-forming bacterium broadly existing in a variety of environmental niches. Because it produces and secrets many industrially useful enzymes, a lot of studies have been done to understand the underlying mechanisms. Among them, scoC was originally identified as a pleiotropic transcription factor negatively regulating protease production and sporulation in B. subtilis. Nevertheless, its role in B. pumilus largely remains unknown. Results In this study we successfully disrupted scoC gene in B. pumilus BA06 and found increased total extracellular protease activity in scoC mutant strain. Surprisingly, we also found that scoC disruption reduced cell motility possibly by affecting flagella formation. To better understand the underlying mechanism, we performed transcriptome analysis with RNA sequencing. The result showed that more than one thousand genes were alternated at transcriptional level across multiple growth phases, and among them the largest number of differentially expressed genes (DEGs) were identified at the transition time point (12 h) between the exponential growth and the stationary growth phases. In accordance with the altered phenotype, many protease genes especially the aprE gene encoding alkaline protease were transcriptionally regulated. In contrast to the finding in B. subtilis, the aprN gene encoding neutral protease was transcriptionally downregulated in B. pumilus, implicating that scoC plays strain-specific roles. Conclusions The pleiotropic transcription factor ScoC plays multiple roles in various cellular processes in B. pumilus, some of which were previously reported in B. subtilis. The supervising finding is the identification of ScoC as a positive regulator for flagella formation and bacterial motility. Our transcriptome data may provide hints to understand the underlying mechanism.

Background: Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this study was to investigate the effects of LIQ in LPS-induced SCM model.Methods: Mice were pre-treated with LIQ for 7 days before they were injected with LPS (10 mg/kg) for inducing SCM model. Echocardiographic analysis was used to evaluate cardiac function after 12 h of LPS injection. Thereafter, mice were sacrificed to collect hearts for molecular and histopathologic assays by RT-PCR, western-blots, immunohistochemical and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining analysis respectively. AMPKα2 knockout (AMPKα2−/−) mice were used to elucidate the mechanism of LIQ Neonatal rat cardiomyocytes (NRCMs) treated with or without LPS were used to further investigate the roles and mechanisms of LIQ in vitro experiments.Results: LIQ administration attenuated LPS-induced mouse cardiac dysfunction and reduced mortality, based upon the restoration of EF, FS, LVEDs, heart rate, dp/dt max and dp/dt min deteriorated by LPS treatment. LIQ treatment also reduced mRNA expression of TNFα, IL-6 and IL-1β, inhibited inflammatory cell migration, suppressed cardiac oxidative stress and apoptosis, and improved metabolism. Mechanistically, LIQ enhanced the phosphorylation of AMP-activated protein kinase α2 (AMPKα2) and decreased the phosphorylation of mTORC1, IκBα and NFκB/p65. Importantly, the beneficial roles of LIQ were not observed in AMPKα2 knockout model, nor were they observed in vitro model after inhibiting AMPK activity with an AMPK inhibitor.Conclusion: We have demonstrated that LIQ exerts its protective effects in an SCM model induced by LPS administration. LIQ reduced inflammation, oxidative stress, apoptosis and metabolic alterations via regulating AMPKα2 dependent signaling pathway. Thus, LIQ might be a potential treatment or adjuvant for SCM treatment.

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease but the efficacy of current treatment remains unsatisfactory. The pathogenesis of DKD needs a more in-depth research. Ubiquitin specific proteases 36 (USP36), a member of deubiquitinating enzymes family, has aroused wide concerns for its role in deubiquitinating and stabilizing target proteins. Nevertheless, the role of USP36 in diabetes has never been reported yet. Herein, we identified an increased expression of USP36 both in vitro and in vivo in diabetic renal tubular epithelial cells (TECs), and its overexpression is related to the enhanced epithelial-to-mesenchymal transition (EMT). Further investigation into the mechanisms proved that USP36 could directly bind to and mediate the deubiquitination of dedicator of cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF) that could activate Wnt/β-catenin signaling pathway and induce EMT. Our study revealed a new mechanism that USP36 participates in the pathogenesis of DKD, and provided potential intervening targets accordingly.

SNTA1 encodes α1-syntrophin, a scaffold protein, which is a component of the dystrophin-associated protein complex. Additionally, α1-syntrophin interacts with SCN5A and nNOS–PMCA4b complex in cardiomyocytes. SNTA1 is a susceptibility locus for arrhythmia and cardiomyopathy. We generated a homozygous SNTA1 knockout human embryonic stem cell (H9SNTA1KO) using the CRISPR/Cas9 system. H9SNTA1KO maintained pluripotency and a normal karyotype and differentiated into three germ layers in vivo.

In this study, a method using ultrahigh-performance liquid chromatography with photodiode array (UHPLC-PDA) was established and validated for the simultaneous quantification of 10 active components, including eight macamides and two glucosinolates, in Lepidium meyenii (maca). A gas chromatographic mass spectroscopy (GC-MS) method was used to determine the levels of three benzyl isothiocyanates and two sterols in maca. Liquid chromatographic separation was achieved on a Waters Acquity UHPLC HSS T3 column (2.1 mm × 100 mm, 1.8 μm) with gradient elution over 15 min. The mobile phase was (B) acetonitrile-(A) 10 mM aqueous ammonium phosphate, and the detection wavelength was 210 nm. The gas chromatographic separation was performed on an SH-Rxi-1 MS column, and the ionization mode was electron ionization (EI). Two methods were confirmed to have desirable precision (RSD

Cardiac remodeling is a common pathological process in various heart diseases, such as cardiac hypertrophy, diabetes-associated cardiomyopathy and ischemic heart diseases. The inhibition of cardiac remodeling has been suggested to be a potential strategy for preventing heart failure. However, the mechanisms involved in cardiac remodeling are quite complicated. Recent studies have reported a close correlation between autophagy and energy homeostasis in cardiac remodeling associated with various heart diseases. In this review, we summarize the roles of autophagy and energy homeostasis in cardiac remodeling and discuss the relationship between these two processes in different conditions to identify potential targets and strategies for treating cardiac remodeling by regulating autophagy.