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Abstract Background Renal fibrosis is a prevalent manifestation of chronic kidney disease (CKD), and effective treatments for this disease are currently lacking. Myofibroblasts, which originate from interstitial fibroblasts, aggregate in the renal interstitium, leading to significant accumulation of extracellular matrix and impairment of renal function. The nonreceptor tyrosine kinase c-Abl (encoded by the Abl1 gene) has been implicated in the development of renal fibrosis. However, the precise role of c-Abl in this process and its involvement in fibroblast-myofibroblast transition (FMT) remain poorly understood. Methods To investigate the effect of c-Abl in FMT during renal fibrosis, we investigated the expression of c-Abl in fibrotic renal tissues of patients with CKD and mouse models. We studied the phenotypic changes in fibroblast or myofibroblast-specific c-Abl conditional knockout mice. We explored the potential targets of c-Abl in NRK-49F fibroblasts. Results In this study, fibrotic mouse and cell models demonstrated that c-Abl deficiency in fibroblasts mitigated fibrosis by suppressing fibroblast activation, fibroblast-myofibroblast transition, and extracellular matrix deposition. Mechanistically, c-Abl maintains the stability of the RACK1 protein, which serves as a scaffold for proteins such as c-Abl and focal adhesion kinase at focal adhesions, driving fibroblast activation and differentiation during renal fibrosis. Moreover, specifically targeting c-Abl deletion in renal myofibroblasts could prove beneficial in established kidney fibrosis by reducing RACK1 expression and diminishing the extent of fibrosis. Conclusions Our findings suggest that c-Abl plays a pathogenic role in interstitial fibrosis through the regulation of RACK1 protein stabilization and myofibroblast differentiation, suggesting a promising strategy for the treatment of CKD.

Adipose-derived stromal cells (ADSCs) can be induced to differentiate into neurons, representing the most promising avenue for cell therapy. However, the molecular mechanism and genomic characteristics of the differentiation of ADSCs into neurons remain poorly understood. In this study, cells from the adult ADSCs group, induction 1h, 3h, 5h, 6h, and 8h groups were selected for single-cell RNA sequencing (scRNA-Seq). Samples from these seven-time points were sequenced and analyzed. The expression of neuron marker genes, including NES, MAP2, TMEM59L, PTK2B, CHN1, DNM1, NRSN2, FBLN2, SCAMP1, SLC1A1, DLG4, CDK5, and ENO2, was found to be low in the ADSCs group, but highly expressed in differentiated cell clusters. The expression of stem cell marker genes, including CCND1, IL1B, MMP1, MMP3, MYO10, and BMP2, was the highest in the ADSCs cluster. This expression decreased significantly with the extension of induction time. Gene ontology (GO) enrichment analysis of upregulated genes in the induced samples showed that the biological processes related to neuronal differentiation and development, such as neuronal differentiation, projection, and apoptosis, were significantly upregulated with a longer induction time during cell cluster differentiation. The results of the cell communication analysis demonstrated the gradual formation of complex neural network connections between ADSC-derived neurons through receptor and ligand pairs at 5h after the induction of differentiation.

ObjectiveThis study aims to investigate the influence of the cerebellum on visual selective attention function and its neuromodulatory mechanism in patients with multiple lacunar cerebral infarction (MLCI).MethodsA retrospective analysis was conducted on 210 patients admitted with MLCI from January 2016 to May 2022. Analyzed the electrophysiological characteristics of the P3a and P3b components of vision in both groups, as well as source reconstruction simulations of dipole activation in the brains of the two groups, and analyzed the brain regions with differences in activation strength between the two groups.ResultsThis study found that there was no significant difference in peak amplitude between the two groups, but compared with the control group, the peak latency of the case group was significantly prolonged. Specifically, the P3a peak latency induced by the novel stimulus was longer than that induced by the target stimulus P3b peak latency. Source reconstruction results showed decreased and increased activation in several brain regions in the case group compared to the control group.ConclusionThe study suggests that the impairment of distracted attention capture is more pronounced in patients with MLCI. The cerebellum indirectly influences the ventral and dorsal frontoparietal attention networks by modulating the levels of excitation and inhibition within the cerebral cortex of the attention network. This may represent a potential mechanism through which the cerebellum regulates visual selective attention information in MLCI patients.

Apoptosis is the primary cause of cell death in the differentiation of Adipose-derived stromal cells (ADSCs) into neurons. However, the relationship between endoplasmic reticulum stress (ERS) and death receptor-mediated apoptosis in ADSC-induced neuronal differentiation is not clear. ADSCs were isolated and induced to differentiate into neurons using β-mercaptoethanol. The expression of neuron-specific enolase (NSE), GRP94, CHOP, Fas/FasL, TNFR1/TNF-α, DR5/TRAIL, Caspase8, and Caspase3 in ADSCs was examined using immunocytochemistry and Western blotting before induction, during pre-induction, and after induction. Transmission electron microscopy (TEM) was used to observe changes in the morphology of the endoplasmic reticulum (ER), and the MTT assay was employed to measure cell viability in the uninduced and induced groups. Additionally, the number of apoptotic cells during the induction process was measured using flow cytometry with Annexin V/PI. With increasing induction time, the positive expression rates of CHOP, Fas/FasL, Caspase8, Caspase-3, and NSE gradually increased, while the positive expression rate of GRP94 decreased. TNFR1/TNF-α and DR5/TRAIL peaked at 5 h post-induction and then decreased at 8 h. TEM revealed swelling and expansion of the ER, vacuolar changes, and degranulation in cells. The MTT assay showed a gradual decrease in the absorbance of surviving cells in all groups. Flow cytometry indicated an increasing rate of apoptosis in cells. Therefore, ERS in the normal culture and growth of ADSCs, manifesting as enhanced unfolded protein response (UPR), maintains the normal survival of ADSCs. However, in the process of ADSC-induced differentiation into neurons, ERS and death receptor-mediated apoptosis are significant causes of cell death.

Abstract Purpose Serum neurofilament light chain (sNfL) can reflect nerve damage. Whether migraine can cause neurological damage remain unclear. This study assesses sNfL levels in migraine patients and explores whether there is nerve damage in migraine. Methods A case–control study was conducted in Xiamen, China. A total of 138 migraine patients and 70 healthy controls were recruited. sNfL (pg/mL) was measured on the single-molecule array platform. Univariate, Pearson correlation and linear regression analysis were used to assess the relationship between migraine and sNfL levels, with further subgroup analysis by migraine characteristics. Results Overall, 85.10% of the 208 subjects were female, with a median age of 36 years. sNfL levels were higher in the migraine group than in the control group (4.85 (3.49, 6.62) vs. 4.11 (3.22, 5.59)), but the difference was not significant (P = 0.133). The two groups showed an almost consistent trend in which sNfL levels increased significantly with age. Subgroup analysis showed a significant increase in sNfL levels in patients with a migraine course ≥ 10 years (β = 0.693 (0.168, 1.220), P = 0.010). Regression analysis results show that age and migraine course are independent risk factors for elevated sNfL levels, and there is an interaction between the two factors. Patients aged

With the increase in the number of distributed energy resources (DERs) and electric vehicles (EVs), it is particularly important to solve the problem of EV charging station siting and capacity determination under the distribution network considering a large proportion of DERs. This paper proposes a bi-level planning model for EV charging stations that takes into account the characteristics of the spatial–temporal distribution of charging loads under an uncertain environment. First, the Origin–Destination (OD) matrix analysis method and the real-time Dijkstra dynamic path search algorithm are introduced and combined with the Larin Hypercube Sampling (LHS) method to establish the EV charging load prediction model considering the spatial and temporal distribution characteristics. Second, the upper objective function with the objective of minimizing the cost of EV charging station planning and user charging behavior is constructed, while the lower objective function with the objective of minimizing the cost of distribution network operation and carbon emission cost considering the uncertainty of wind power and photovoltaics is constructed. The constraints of the lower-layer objective function are transformed into the upper-layer objective function through Karush–Kuhn–Tucker (KKT) conditions, the optimal location and capacity of charging stations are finally determined, and the model of EV charging station siting and capacity determination is established. Finally, the validity of the model was verified by planning the coupled IEEE 33-node distribution network with the traffic road map of a city in southeastern South Dakota, USA.

The biological effect of irradiation is not solely determined by the physical dose. Gamma knife radiosurgery may be influenced by dose rate, beam-on-time, numbers of iso-centers, the gap between the individual iso-centers, and the dose‒response of various tissues. The biologically effective dose (BED) for radiosurgery considers these issues. Millions of patients treated with Models B and C provide a vast database to mine BED-related information. This research aims to develop MatBED_B&C, a 3-dimensional (3D) BED analytic approach, to generate a BED for individual voxels in the calculation matrix with related parameters extracted from Gammaplan. This approach calculates the distribution profiles of the BED in radiosurgical targets and organs at risk. A BED calculated on a voxel-by-voxel basis can be used to show the 3D morphology of the iso-BED surface and visualize the BED spatial distribution in the target. A 200 × 200 × 200 matrix can cover a greater range of the organ at risk. The BED calculated by MatBED_B&C can also be used to form BED-volume histograms to generate plan quality metrics, which will be studied in a retrospective study of gamma knife radiosurgery to guide future BED planning. • We develop MatBED_B&C to calculate the 3D BED in radiosurgical targets. • The BED of MatBED_B&C can visualize the BED spatial distribution profiles. • The BED of MatBED_B&C will generate plan quality metrics studied in a retrospective study.

AbstractIntroduction The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients.Methods Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis.Results A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively).Conclusion The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.

Abstract Background Preclinical studies and clinical trials have demonstrated that tumor‐intrinsic activation of the cell cycle program impedes anticancer immunotherapy. Identification of cell cycle‐related biomarkers may provide novel therapeutic targets to augment the efficacy of immunotherapy in hepatocellular carcinoma (HCC). Method and Results Based on the genes related to cell cycle program, two clusters (Cluster 1 and Cluster 2) were detected in HCC patients via non‐negative matrix factorization algorithm. Multivariable‐adjusted Cox regression analysis indicated that the cell cycle gene‐based classification was a significant prognostic factor for predicting the clinical outcome of HCC patients. Cluster 1 showed shorter overall survival time and progression‐free interval time was associated with activated cell cycle program, higher infiltration of myeloid‐derived suppressor cells (MDSCs) and less sensitivity to immunotherapy. A three‐gene prognostic model, including BIRC5, C8G, and SPP1, was constructed to characterize the cell cycle‐based classification of HCC, which had strong robustness and a stable predictive performance. Notably, Birc5 was positively correlated with CD11b expression (a MDSC marker) in HCC tissue. Concordant high expression of Birc5 and intratumor infiltration level of MDSCs were correlated with worse prognosis of HCC patients. In vitro, hepatocellular Birc5 overexpression promoted immunosuppressive CD11b+CD33+HLA‐DR−MDSC expansion from human peripheral blood mononuclear cells. Genetically modified animal model of liver cancer revealed that Birc5 depletion upregulated the genes related to lymphocyte‐mediated immunity, natural killer cell‐mediated immunity, interferon‐gamma production, T‐cell activation, and T‐cell‐mediated cytotoxicity. These results suggest an immunosuppressive function of Birc5 in HCC. Conclusion Birc5 was a potential biomarker and inducer of intratumor infiltration of MDSCs, which led to T cell exclusion or dysfunction in tumor immune microenvironment, consequently resulting in reduced response to ICIs in HCC.

Abstract Myocardial infarction that causes damage to heart muscle can lead to heart failure. The identification of molecular mechanisms promoting myocardial regeneration represents a promising strategy to improve cardiac function. Here we show that IGF2BP3 plays an important role in regulating adult cardiomyocyte proliferation and regeneration in a mouse model of myocardial infarction. IGF2BP3 expression progressively decreases during postnatal development and becomes undetectable in the adult heart. However, it becomes upregulated after cardiac injury. Both gain- and loss-of-function analyses indicate that IGF2BP3 regulates cardiomyocyte proliferation in vitro and in vivo. In particular, IGF2BP3 promotes cardiac regeneration and improves cardiac function after myocardial infarction. Mechanistically, we demonstrate that IGF2BP3 binds to and stabilizes MMP3 mRNA through interaction with N6-methyladenosine modification. The expression of MMP3 protein is also progressively downregulated during postnatal development. Functional analyses indicate that MMP3 acts downstream of IGF2BP3 to regulate cardiomyocyte proliferation. These results suggest that IGF2BP3-mediated post-transcriptional regulation of extracellular matrix and tissue remodeling contributes to cardiomyocyte regeneration. They should help to define therapeutic strategy for ameliorating myocardial infarction by inducing cell proliferation and heart repair.

Abstract Background Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still unclear. Methods The correlation between Notch signaling pathway and macrophage infiltration was investigated in TCGA database and verified in clinical samples of patients with CRC using immunohistochemistry. Gene Set Enrichment Analysis was used to find out genes related to Notch3 expression. Colony formation assay, and flow cytometry were utilized to test tumor growth and immune cell infiltration in vitro and in vivo. Results Using bioinformatics analysis and clinical sample validation, we found that Notch3 was highly expressed in colon tumor tissues compared to adjacent normal tissues, and it participated in regulating the recruitment of macrophages to the tumor microenvironment. Furthermore, we found that the Notch3 expression was positively correlated with the expression of macrophage recruitment-related cytokines in colon tumor tissues. Finally, we demonstrated that depletion of Notch3 had no significant effect on the growth of colon tumor cells in vitro, while, attenuated the growth of colon cancer tumors in vivo. Simultaneous, immunosuppressive cells, macrophages and myeloid-derived suppressor cell (MDSC) infiltration were dramatically reduced in the tumor microenvironment. Conclusion Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC.

Cognitive function represents a complex neurophysiological capacity of the human brain, encompassing a higher level of neural processing and integration. It is widely acknowledged that the cerebrum plays a commanding role in the regulation of cognitive functions. However, the specific role of the cerebellum in cognitive processes has become a subject of considerable scholarly intrigue. In 1998, Schmahmann first proposed the concept of “cognitive affective syndrome (CCAS),” linking cerebellar damage to cognitive and emotional impairments. Since then, a substantial body of literature has emerged, exploring the role of the cerebellum in cognitive neurological function. The cerebellum’s adjacency to the cerebral cortex, brainstem, and spinal cord suggests that the cerebral-cerebellar network loops play a crucial role in the cerebellum’s participation in cognitive neurological functions. In this review, we comprehensively examine the recent literature on the involvement of the cerebellum in cognitive functions from three perspectives: the cytological basis of the cerebellum and its anatomical functions, the cerebellum and cognitive functions, and Crossed cerebellar diaschisis. Our aim is to shed light on the role and mechanisms of the cerebellum in cognitive neurobrain networks.

To date, it is controversial which metallic impurities play crucial role in the laser induced degradation and damage of fused silica at 355 nm. In this work, a First -principles study for the influences of impurities in fused silica are presented, which are usually contaminated during manufacture and post-processing processes. Our results show that Ca, K, Fe and Ce can lead to obvious optical absorption near 355 nm. Moreover, we find that, for K and Ca, the absorption intensity near 355 nm is highly sensitive to the concentration. Our results indicate that K and Ca can easily induce degradation and damage of fused silica at 355 nm. These two impurities should be concerned during manufacture and post-processing processes. The detailed theoretical study reveal that Ca and K can induce obvious impurity states in band gap and the optical absorption near 355 nm is originated from the transition between impurity states to conduction band. Our results also reveal that, for fused silica with Ca impurity, the exciton effect plays an important role for the optical absorptions near 355 nm, while it is not significant for K. Our work helps to explore laser damage mechanism and improve manufacture and post-processing techniques of fused silica.

A two-step physical-chemical etching method, namely large incident angle ion beam etching followed by HF etching, is proposed to remove the damage precursors in fused silica surface to achieve good surface quality and significantly improve the laser damage resistance of fused silica. Ion beam etching with large incident angle is utilized to remove the metal impurities and most subsurface defects in fused silica surface, which can reduce the removal amount of subsequent HF etching of fused silica, thus suppressing the replication and expansion of the subsurface defects, deposition of reaction products and deterioration of surface shape during the HF etching process. After that, HF etching is used to remove the atomic-scale damaged layer and reduce the P–V value of the reflection surface shape induced by ion beam etching. Therefore, a better laser damage performance of fused silica can be obtained by the two-step etching method compared with single ion beam etching and single HF etching. The results show that the two-step physical-chemical etching can be developed to fabricate high-quality and high damage-resistant fused silica optical components with small etching amount and good surface quality for high-power laser application.

An energy storage station (ESS) usually includes multiple battery systems under parallel operation. In each battery system, a power conversion system (PCS) is used to connect the power system with the battery pack. When allocating the ESS power to multi-parallel PCSs in situations with fluctuating operation, the existing power control methods for parallel PCSs have difficulty in achieving the optimal efficiency during a long-term time period. In addition, existing Q-learning algorithms for adaptive power allocation suffer from the curse of dimensionality. To overcome these challenges, an adaptive power control method based on the double-layer Q-learning algorithm for $n$ parallel PCSs of the ESS is proposed in this paper. First, a selection method for the power allocation coefficient is developed to avoid repeated actions. Then, the outer action space is divided into $n$+1 power allocation modes according to the power allocation characteristics of the optimal operation efficiency. The inner layer uses an actor neural network to determine the optimal action strategy of power allocations in the non-steady state. Compared with existing power control methods, the proposed method achieves better performance for both static and dynamic operation efficiency optimization. The proposed method optimizes the overall operation efficiency of PCSs effectively under the fluctuating power outputs of the ESS.

Objective: Current evidence on the immunogenicity of influenza vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To address this need for additional knowledge, we conducted a study on the immunogenicity of trivalent seasonal influenza vaccine (TIV) in COPD patients. Methods: We recruited patients from respiratory outpatient clinics of three hospitals in Tangshan, Hebei province who had stable confirmed COPD, were less than 80 y old, and reported not having had influenza or receiving TIV during the study season prior to enrollment. Patients who had a history of allergy to any TIV component or were classified as having very severe COPD were excluded from the study. Eligible and consenting participants were given one dose of TIV after obtaining a baseline blood sample. A second blood sample was obtained 5 weeks later. We used hemagglutination inhibition (HI) assays to measure antibody responses. We considered seropositive to be an HI titer ≥1:10. We considered seroprotection to be an HI titer ≥1:40 and seroconversion to be either a change from seronegative to a post-vaccination titer of ≥1:40 or a fourfold rise in antibody titer among baseline seropositive subjects. Each subject was followed for 1 month to assess the frequency and type of adverse events. Results: Eighty-eight subjects completed our study; the median age was 64 y; most (62.5%) had moderately severe COPD; 48.9% of the subjects had comorbid conditions in addition to COPD. Post–vaccination seropositive rates for influenza H1N1, H3N2, and B were all 100%; corresponding seroprotection rates were 96.6%, 93.2%, and 98.9%; seroconversion rates were 81.8%, 87.5%, and 75.0%. There were no statistical differences in seroconversion (P = .10) and seroprotection (P = .30) among the three types of influenza virus. Geometric mean titers (1:) of HI antibodies to H1N1, H3N2, and B were 18.8 (95% CI: 14.0–25.1), 12.2 (95% CI: 9.6–15.4), and 31.8 (95% CI: 26.1–38.8) at baseline, and 267.0 (95% CI: 213.8–333.4), 190.3 (95% CI: 151.7–238.6), and 201.1 (95% CI: 166.5-242.8) after vaccination. Conclusion: The immunogenicity of one dose of influenza vaccine was excellent in COPD patients. Our study supports recommending influenza vaccination for COPD patients to provide protection from influenza and its complications.

Abstract Background Studies have suggested that glycoprotein IIb/IIIa antagonists such as tirofiban are beneficial for patients with acute coronary syndromes. However, it is still uncertain about the efficacy and safety of tirofiban in patients with acute ischemic stroke (AIS). Methods In this prospective non-randomized study, 255 AIS patients were recruited from 4 comprehensive stroke centers in China between January, 2017 and May, 2018. Among them,169 patients were treated with aspirin plus clopidogrel and 86 patients were treated with tirofiban. The primary functional outcome was the distribution of the 90 days’ modified Rankin Scale (mRS). The safety outcomes included the incidence of intracranial hemorrhage (ICH) at discharge and mortality at 3 months. Results In the propensity score matched cohort, tirofiban alone was noninferior to the dual antiplatelet with regard to the primary outcome (adjusted common odds ratio, 0.97; 95% confidence interval, 0.46 to 2.04; P = 0.93). Mortality at 90 days was 10% in the dual antiplatelet group and 8% in the tirofiban group (adjusted odds ratio 0.75; 95% CI 0.08 to 7.40, p = 0.81). There was no difference of the ICH rate between two groups (adjusted odds ratio 0.44; 95% CI 0.13 to 1.48, p = 0.18). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar differences were found for functional and safety outcomes. Conclusions Our study suggested that tirofiban use appears to be safe as monotherapy in AIS treatment compared with common dual antiplatelet therapy, however, no improvement in functional outcomes was found. Trial registration Chinese clinical trial registry, ChiCTR2000034443 , 05/07/2020. Retrospectively registered.

The influence of residual heat on the fictive temperature modification zone of fused silica for different CO2 laser scanning time intervals was investigated to precisely control the profiles of hydrofluoric (HF) acid-etched fused silica surface, which were formed by the increasing HF acid-etching rate for fused silica with increasing fictive temperature induced by CO2 laser scanning. The surface profiles of HF acid-etched fused silica treated by different scanning time intervals of CO2 laser were measured by a stylus profilometry, and experimental results indicate that the CO2 laser scanning time intervals intensively influence the HF acid-etched surface profiles of fused silica. The increasing depth of surface profiles treated by shorter scanning time intervals shows that the fictive temperature modification zone significantly expands. Numerical simulations of the fictive temperature modification zone induced by different scanning time intervals indicate that the residual heat of CO2 laser scanning with shorter time intervals leads to a dramatical increase in the fictive temperature modification zone. By adjusting the residual heat of CO2 laser scanning intervals, various surface profiles of fused silica can be obtained by HF acid-etching of fused silica.

BackgroundT-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) expresses on leukemic stem and progenitor populations of non-M3 acute myeloid leukemia (AML) as well as T lymphocytes. TIM-3 is thought to be involved in the self-renewal of leukemic stem cells and the immune escape of AML cells, however its correlation with AML prognosis is still controversial and worthy of further investigation.Methodswe simultaneously assessed TIM-3 expression levels of leukemic blasts and T lymphocytes in the bone marrow of de novo AML patients using flow cytometry. The correlations of TIM-3 expression between leukemic blasts and T lymphocytes and the correlations of TIM-3 expression with various patient parameters were analyzed. In addition, the Cancer Genome Atlas (TCGA) data of AML patients were acquired and analyzed to verify the results.ResultsTIM-3 expression of CD34+ leukemic blasts (R2 = 0.95, p

This paper systematically discusses the multiple source characteristics and formation mechanisms of carbonate-rich fine-grained sedimentary rocks through the analysis of material source and rock formation. The hydrocarbon accumulation characteristics of carbonate-rich fine-grained sedimentary rocks are also summarized. The results show that the main reason for the enrichment of fine-grained carbonate materials in rift lake basins was the supply of multiple material sources, including terrestrial material input, formation of intrabasinal authigenic carbonate, volcanic-hydrothermal material feeding and mixed source. The development of carbonate bedrock in the provenance area controlled the filling scale of carbonate materials in rift lake basins. The volcanic-hydrothermal activity might provide an alkaline fluid to the lake basins to strengthen the material supply for the formation of carbonate crystals. Authigenic carbonate crystals induced by biological processes were the main source of long-term accumulation of fine-grained carbonate materials in the lake basins. Carbonate-rich fine-grained sedimentary rocks with multiple features were formed through the interaction of physical, biochemical and chemical processes during the deposition and post-deposition stages. The source and sedimentary origin of the fine-grained carbonate rock controlled the hydrocarbon accumulation in it. In the multi-source system, the types of “sweet spots” of continental shale oil and gas include endogenous type, terrigenous type, volcanic-hydrothermal type and mixed source type.

A kind of graphene-based perfect absorber which can generate low-threshold and high-extinction-ratio optical bistability in the near-IR band is proposed and simulated with numerical methods. The interaction between input light and monolayer graphene in the absorber can be greatly enhanced due to the perfect absorption. The large nonlinear coefficient of graphene and the strong light-graphene interaction contribute to the nonlinear response of the structure, leading to relatively low switching thresholds of less than 2.5 MW/cm2 for an absorber with a Q factor lower than 1000. Meanwhile, the extinction ratio of bistable states in the absorber reaches an ultrahigh value of 47.3 dB at 1545.3 nm. Moreover, the influence of changing the structural parameters on the bistable behaviors is discussed in detail, showing that the structure can tolerate structural parametric deviation to some extent. The proposed bistable structure with ultra-compact size, low thresholds, high extinction ratio, and ultrafast response time could be of great applications for fabricating high-performance all-optical-communication devices.

Exosomes derived from mesenchymal stem cell (MSC) alleviate kidney damage through autophagy. This study determined whether MSCs relieve renal fibrosis and inhibit autophagy by exosome transfer of miRNA-122a. The gene expression involved in the mTOR signaling pathway and autophagy was assessed in TGF-β1-treated human renal tubular epithelial cells (HK-2) and unilateral ureteral obstruction (UUO) mice before and after MSC-derived exosomes and miRNA-122a mimic treatment. Small RNA (sRNA) next-generation sequencing was also performed on TGF-β1-treated HK-2 cells. MSC-derived exosomes relieve fibrosis caused by TGFβ in HK-2 via regulation of the mTOR signaling pathway and downstream autophagy. Furthermore, we found that MSC-derived exosomes mediate miRNA-122a to relieve renal fibrosis in HK-2 cells in response to TGF-β1 through the regulation of mTOR signaling and autophagy. In the UUO mouse model, miRNA-122a mimic-transfected MSC treatment and its combination with 3-MA both recapitulated the same results as the in vitro experiments, along with reduced expansion of renal tubule, interstitial expansion, and preservation of kidney architecture. The antifibrotic activity of MSC-derived exosomes after renal fibrosis occurs partially by autophagy suppression via excreted exosomes containing mainly miRNA-122a. These findings indicate that the export of miRNA-122a via MSC-derived exosomes represents a novel strategy to alleviate renal fibrosis.

Background: Lifestyles generally change across the life course yet no prospective study has examined direct associations between healthy lifestyle trajectories and subsequent cardiovascular disease (CVD) or all-cause mortality risk.Methods: Healthy lifestyle score trajectories during 2006–2007, 2008–2009, and 2010–2011 were collated through latent mixture modeling. An age-scale based Cox proportional hazard regression model was implemented to calculate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for developing CVD or all-cause mortality across healthy lifestyle trajectories.Results: 52,248 participants were included with four distinct trajectories identified according to healthy lifestyle scores over 6 years i.e., low-stable (n = 11,248), high-decreasing (n = 7,374), low-increasing (n = 7,828), and high-stable (n = 25,799). Compared with the low-stable trajectory, the high-stable trajectory negatively correlated with lower subsequent risk of developing CVD (HR, 0.73; 95% CI, 0.65–0.81), especially stroke (HR, 0.70; 95% CI, 0.62–0.79), and all-cause mortality (HR, 0.89; 95% CI, 0.80–0.99) under a multivariable-adjusted model. A protective effect for CVD events was observed only in men and in those without diabetes, while a reduced risk of all-cause mortality was observed only in those older than 60 years, though interactions were not statistically significant. Marginally significant interactions were observed between the changing body mass index (BMI) group, healthy lifestyle score trajectories and stratified analysis. This highlighted an inverse correlation between the high-stable trajectory and CVD in BMI decreased and stable participants as well as all-cause mortality in the stable BMI group. The low-increasing trajectory also had reduced risk of CVD only when BMI decreased and in all-cause mortality only when BMI was stable.Conclusions: Maintaining a healthy lifestyle over 6 years corresponds with a 27% lower risk of CVD and an 11% lower risk in all-cause mortality, compared with those engaging in a consistently unhealthy lifestyle. The benefit of improving lifestyle could be gained only after BMI change is considered further. This study provides further evidence from China around maintaining/improving healthy lifestyles to prevent CVD and early death.

Abstract Background Abdominal myomectomy (AM) and laparoscopic myomectomy (LM) are commonly see surgery for the uterine fibroids, several randomized controlled trials (RCTs) have compared the role of AM and LM, the results remained inconsistent. Therefore, we attempted this meta-analysis to analyze the role of LM versus AM in patients with uterine fibroids. Methods We searched PubMed et al. databases from inception date to July 31, 2019 for RCTs that compared LM versus AM in patients with uterine fibroids. Two authors independently screened the studies and extracted data from the published articles. Summary odd ratios(OR) or mean differences(MD) with 95% confidence intervals(CI) were calculated for each outcome by means of fixed- or random-effects model. Results Twelve RCTs with a total of 1783 patients were identified, with 887 patients for and 897 patients for AM. Compared with AM, LM could significantly decrease the blood loss (OR = − 29.78, 95% CI -57.62– − 0.95), shorten the duration of postoperative ileus (OR = − 10.91, 95% CI -18.72– − 3.11), reduce the length of hospital stay (OR = − 1.57, 95% CI -2.05– − 1.08), but LM was associated with longer duration of operation (OR = 16.10, 95% CI 6.52–25.67) and higher medical cost (OR = 17.61, 95% CI 7.34–27.88). Conclusions LM seems to be a better choice for patients with uterine fibroids, more related studies are needed to identify the role of LM and AM for the treatment of uterine fibroids.

With the highly-extensive integration of distributed renewable energy resources (DER) into the grid, the power distribution system has changed greatly in the structure, function and operating characteristics. On this ground, An AC-DC hybrid DER system becomes necessary for effective management and control over DER. This paper first summarizes the physical characteristics and morphological evolution of AC-DC hybrid DER system. The impact of these new features on system configuration planning is analyzed with respect to its flexible networking, rich operation control modes, and tight source-network-load-storage coupling. Then, based on a review of the existing research, problems and technical difficulties are figured out in terms of converter modeling, steady-state analysis, power flow calculation, operating scenarios management, and optimization model solution. In light of the problems and difficulties, a framework for the configuration optimization of AC-DC hybrid DER systems is proposed. At last, the paper provides a prospect of key technologies from six aspects including morphology forecasting, coupling interaction analysis, uncertainty modeling, operation simulation, optimization model solving algorithm and comprehensive scheme evaluation.

The mechanism of formation of lacustrine deposits within stable orogenic belts and their potential for shale oil and gas exploration are frontier themes of challenge in the fields of sedimentology and petroleum exploration. Orogenic belts witness strong tectonic activities and normally cannot host stable lacustrine basins and deep shale formations. Therefore, basins in orogenic belts are considered to have no potential to form shale hydrocarbon reservoirs. Here we investigate the Luanping Basin located in the Yanshan orogenic belt where previous studies regarded rivers and fan deltas as the major main Mesozoic deposits. Based on detailed field exploration and scientific drilling, we report the finding of a large number of lacustrine shale continental deep-water deposits in the Mesozoic strata. Our finding of the occurrence of active shale oil and gas also in this basin also subvert the previous perceptions.We report SHRIMP zircon U-Pb age that define the bottom boundary of the target interval as 127.6 ± 1.7 Ma belonging to the early Cretaceous strata. Tectonics and climate are considered to be the main factors that controlled the deep-water sedimentation during this period. The drill cores revealed evidence of shale gas and the TOC of shale is 0.33%–3.60%, with an average value of 1.39% and Ro is 0.84%–1.21%, with an average value of 1.002%. The brittleness index of shale is between 52.7% and 100%. After vertical well fracturing, the daily gas production is more than 1000 m3. Our findings show that the basin has considerable potential for shale oil and gas. The geological resources of the shale gas in the Xiguayuan Fm. are estimated as 1110.12 × 108 m3, with shale oil geological resources of 3340.152 × 104 t. Our findings indicate that the Yanshan orogenic belt has potential exploration prospect. This work not only redefines the Luanping Basin as a rift deep-water Mesozoic Lake Basin, but also rules out the previous notion that the basin is dominated by shallow water sediments. The discovery of shale oil and gas also provides an important reference for subsequent petroleum exploration and development in this basin. Our study shows that shale oil and gas reservoirs can be found in the lacustrine basins of orogenic belts which were strongly influenced by volcanism. These results have significant implications for the sedimentology and oil exploration in the Qinling and Xingmeng Orogenic Belts of China, as well as those in other terranes of the world including the New England Orogenic Belt in Australia.

BackgroundThymic epithelial tumors (TETs) are rare tumors originating from the thymic epithelial cells. SOX9, a member of the family of SOX (SRY-related high-mobility group box) genes, has been considered as an oncogene and therapeutic target in various cancers. However, its role in TETs remains uncertain.MethodsUsing the immunohistochemistry method, the expression of SOX9 was analyzed in TETs tissues, including 34 thymoma (8 cases with type A, 6 with type AB, 6 with type B1, 9 with type B2, and 5 with type B3 thymomas) and 20 thymic cancer tissues and the clinicopathologic and prognostic significances were evaluated. Further bioinformatics analysis of gene expression profiles of thymomas with high and low SOX9 expressions and the corresponding survival analyses were based on the thymoma cases identified in The Cancer Genome Atlas (TCGA) database, with the median expression level of SOX9 selected as cutoff.ResultsImmunohistochemistry staining showed that SOX9 was highly expressed in the nuclei of the epithelial cells of the Hassall’s corpuscles and of the TET tumor cells. SOX9 expression was significantly associated with histological type and high expression indicated unfavorable clinical outcomes of thymomas. Bioinformatics analysis revealed that genes positively associated with SOX9 expression were mapped in proteoglycans in cancer, cell adhesion molecules, and molecules involved in extracellular matrix-receptor interaction and the TGF-β signaling pathway, and that genes negatively associated with SOX9 expression were mapped in molecules involved in primary immunodeficiency, the T cell receptor signaling pathway, Th17 cell differentiation, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. In addition, SOX9 expression was positively associated with POU2F3 and TRPM5 expressions, the master regulators of tuft cells, suggesting that high SOX9 expression might be associated with the tuft cell phenotype of thymomas. Moreover, high SOX9 expression was associated with immune dysregulation of thymoma, and M2 macrophage significantly dominated in the high SOX9 expression group.ConclusionSOX9 may serve as a diagnostic and prognostic marker for TETs. Notably, high SOX9 expression in TETs may indicate a tuft cell phenotype and an immune suppressive microenvironment of thymomas.

A very attractive advantage of graphene is that its Fermi level can be regulated by electrostatic bias doping. It is of great significance to investigate and control the spatial location of graphene emission for graphene thermal emitters, in addition to tuning the emission intensity and emission spectrum. Here, we present a detailed theoretical model to describe the graphene emission characteristics versus gate voltages. The experimentally observed movement of the emission spot and temperature distribution of graphene emitters are basically in agreement with those from the theoretical model. Our results provide a simple method to predict the behavior of graphene emitters that is beneficial for achieving the spatial dynamic regulation of graphene infrared emission arrays.

As a rapid and efficient processing technology, CO2 laser processing has been applied to remove fused silica materials. However, thermal effect caused by CO2 laser would lead to thermal modification layer, thermal deformation and residual stress in processed fused silica optics. To reduce the thermal effect, high power and short pulse CO2 laser is applied to remove the surface material of fused silica. In this work, a model coupling the physical processes of heat transfer and phase transition was established to simulate the complex interaction of CO2 laser with fused silica. Then, the model was applied to investigate the evolutions of temperature distribution and surface morphology involved in the laser ablating and melting processes. The results indicate that with the increase of laser power and decrease of pulse width, positive effect would take place that the radius-depth ratio of ablating area increases and the heat-affected area becomes smaller. For the application of CO2 laser with 0.2 μs pulse width and 800 kW peak power, fused silica material would quickly reach the ablation state. The ablation depth is less than 1 μm, and the thickness of heat-affected area is about 80 nm. It means that the high power and short pulse CO2 laser is equivalent to a hot grinding ball head, which can remove the material rapidly with small heat-affected area on fused silica surface. The simulation results of line scanning processing with CO2 laser were finally compared with the experiment ones, which verified the feasibility of the established model. The suggestions and prospective for improving the model were put forward as well. Keywords: CO2 laser, Fused silica, Heat-affected area, Laser processing

A new method for optical multiple-image encryption based on polarization-resolved diffraction imaging is proposed in this study. A linearly polarized beam is split into two beams of orthogonal polarization to illuminate different images to be encrypted, and these images are then encrypted into a single white-noise-like intensity image in a single shot. A multi-mode iterative phase-retrieval algorithm is used in the decryption to reconstruct the amplitudes and phases of the secret images simultaneously. Both computer simulations and optical experiments are performed to demonstrate the feasibility and effectiveness of the proposed method.

When a graphene sheet is placed near a metal surface, it supports a special type of highly confined and low‐loss electromagnetic mode called acoustic graphene plasmons (AGPs). AGPs squeeze infrared photons into extremely confined areas down to a subnanometric scale and provides a unique platform for strong light–matter interactions. However, the efficient excitation of AGPs is a challenge due to the large momentum mismatch between free‐space light and AGPs. With theoretical analysis and numerical simulations, it is shown that the far‐field excitation of AGPs is realized by integrating graphene in a metal–insulator–metal (MIM) metamaterial with magnetic resonance (MR). More than ten graphene plasmonic modes are excited in the midinfrared range, resulting in a multiresonant spectra with Fano‐like characteristics at each resonant wavelength. The proposal opens a new door to explore the strong plasmonic coupling between graphene and metallic metamaterials down to atomic scale for extreme nanophotonics. The potential applications range from ultracompact tunable metamaterials and ultrasensitive infrared spectroscopy to single‐molecule optics, quantum plasmonics, and others.