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Numerous studies have shown that the expression of circular RNA (circRNA) is closely related to the malignant progression of cancer. However, the role of circ-MFN2 in colorectal cancer (CRC) is unclear. Our study aims to explore the role and mechanism of circ-MFN2 in CRC progression. The relative expression levels of circ-MFN2, microRNA (miR)-574-3p and insulin-like growth factor 1 receptor (IGF1R) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was determined using 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The colony number and radioresistance of cells were assessed using colony formation assay. Moreover, the migration and invasion of cells were measured using transwell assay. Tumor xenograft model was constructed to evaluate the effect of circ-MFN2 knockdown on CRC tumor growth. Furthermore, dual-luciferase reporter assay was used to verify the interaction between miR-574-3p and circ-MFN2 or IGF1R. In addition, the protein level of IGF1R was evaluated by western blot (WB) analysis. Circ-MFN2 expression was elevated in CRC tissues and cells. Knockdown of circ-MFN2 restrained the proliferation, migration, invasion, and radioresistance of CRC cells in vitro. Furthermore, silenced circ-MFN2 also reduced the tumor volume and weight of CRC in vivo. MiR-574-3p could be sponged by circ-MFN2, and its inhibitor reversed the suppression effect of circ-MFN2 silencing on CRC progression. Moreover, IGF1R was a target of miR-574-3p, and its overexpression reversed the inhibition effect of miR-574-3p mimic on CRC progression. In addition, circ-MFN2 could positively regulate IGF1R expression by sponging miR-574-3p. Our results revealed that circ-MFN2 promoted the proliferation, metastasis and radioresistance of CRC through regulating the miR-574-3p/IGF1R axis, suggesting that circ-MFN2 might be a novel therapeutic biomarker for CRC.

MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. PiggyBac transposon system, with an inclination to memory T cells, offers a more convenient and economical alternative for transgene delivery. We herein report the first case of triple-hit RR DLBCL with TP53 mutation who was treated with piggyBac-generated CAR19-T cells and accompanied by grade 2 cytokine release syndrome. The patient obtained a complete remission (CR) in the 2nd month post-infusion and demanded maintenance therapy. Whether maintenance therapy is favorable and how to administrate it after CAR-T cell infusion remain controversial. Preclinical studies demonstrated that lenalidomide could enhance antitumor activity of CAR19-T cells. Therefore, we pioneered oral lenalidomide after CAR19-T therapy in the patient from the 4th month, and he discontinued after one cycle due to side effects. The patient has still kept sustained CR for over 24 months. Our case have firstly demonstrated the feasibility, preliminary safety and efficacy of piggyBac-produced CAR19-T cell therapy in triple-hit lymphoma. The innovative combination with lenalidomide warrants further investigation. Our findings shed new light on the possible solutions to improve short-term relapse after CAR19-T cell therapy in RR DLBCL. ChiCTR, number ChiCTR1800018111.

Objective: To present our primary experience of robotic-assisted laparoscopic pyeloplasty (RALP) for severe ureteropelvis junction obstruction (UPJO) infants under 3 months.Methods: We performed a retrospective study of 9 infants under 3 months who underwent RALP for severe UPJO between April 2017 and March 2019 in our center. The severe UPJO was defined as infants with severe hydronephrosis (Society of Fetal Urology grades III or IV, anteroposterior diameter >3 cm or split renal function 20 min) involving bilateral, solitary kidney, or contralateral renal hypoplasia UPJO at the same time. All clinical, perioperative, and postoperative information was collected.Results: There were four bilateral UPJO cases, two solitary kidney UPJO cases and three unilateral UPJO with contralateral renal hypoplasia cases included. One single surgeon performed RALP on all of the infants. The mean age of the infants was 1.62 ± 0.54 months. The mean operative time was 109.55 ± 10.47 min. The mean estimated blood loss was 19.29 ± 3.19 ml, and the mean length of hospital stay was 5.57 ± 0.73 days. According to the ultrasonography results, all patients had a significant recovery of renal function at 12 months after the operation.Conclusions: To maximize the protection of renal function, early RALP is a safe and feasible option for the treatment of severe UPJO in infants under 3 months.

RNA modification of N6-methyladenosine (m6A) plays critical roles in various biological processes, such as cancer development, inflammation, and the anticancer immune response. However, the role played by a comprehensive m6A modification pattern in regulating anticancer immunity in kidney renal clear cell carcinoma (KIRC) has not been fully elucidated. In this study, we identified two independent m6A modification patterns with distinct biological functions, immunological characteristics, and prognoses in KIRC. Next, we developed an m6A score algorithm to quantify an individual's m6A modification pattern, which was independently validated in external cohorts. The m6A cluster 1 and low m6A score groups were characterized by a hot tumor microenvironment with an increased infiltration level of cytotoxic immune cells, higher tumor mutation burden, higher immune checkpoint expression, and decreased stroma-associated signature enrichment. In general, the m6A cluster 1 and low m6A score groups reflected an inflammatory phenotype, which may be more sensitive to anticancer immunotherapy. The m6A cluster 2 and high m6A score groups indicated a non-inflammatory phenotype, which may not be sensitive to immunotherapy but rather to targeted therapy. In this study, we first identified m6A clusters and m6A scores to elucidate immune phenotypes and to predict the prognosis and immunotherapy response in KIRC, which can guide urologists for making more precise clinical decisions.

In order to explore the deformation and failure evolution characteristics of the surrounding rock during the connection process of the deep rock burst drivage roadway under the dynamic load disturbance, and based on this, the catastrophe mechanism of the roadway is analyzed, taking the rock burst accident of Longyun Coal Industry in Shandong Province on October 20, 2018, as the engineering background. FLAC3D was used to study the distribution evolution law of displacement, plastic zone, and stress field in the whole process of “Roadway Drivage-Deformation and Failure-Instability and Disaster” in the surrounding rock of deep roadway. The research results show that under the conditions of high stress and dynamic load disturbance, the surrounding rock deformation and failure are significant during the connection of the thick-top-coal roadway in deep, the roof is the most, the two ribs are the second, and the roadway top-coal is in an “inverted trapezoid” sag pattern. When the length of the bolts is limited or the anchoring force of the cables is not enough to effectively restrain the roof, the impact of dynamic disturbance on the plastic damage of the roof is greater than that of the two ribs and the floor, and the plastic damage of the coal seam roof affecting the surrounding rock deformation of the roadway drivage played a leading role.

Background. There is a positive association between serum magnesium and hemoglobin levels in the general population. However, no studies have evaluated the association between serum magnesium and hemoglobin levels in patients with primary hyperparathyroidism (PHPT). We aimed to investigate whether there is a relationship between serum magnesium and hemoglobin levels in the patient population with PHPT. Methods. This retrospective study included 307 hospitalized PHPT patients who were continuously admitted to the Second Xiangya Hospital of Central South University, from January 2010 to August 2020. Laboratory and demographic data of patients were collected. Hypomagnesemia was defined as serum magnesium

Degeneration of the locus coeruleus (LC) is recognized as a critical hallmark of Parkinson's disease (PD). Recent studies have reported that noradrenaline produced from the LC has critical effects on brain functional organization. However, it is unknown if LC degeneration in PD contributes to cognitive/motor manifestations through modulating brain functional organization. This study enrolled 94 PD patients and 68 healthy controls, and LC integrity was measured using the contrast-to-noise ratio of the LC (CNRLC) calculated from T1-weighted magnetic resonance imaging. We used graph-theory-based network analysis to characterize brain functional organization. The relationships among LC degeneration, network disruption, and cognitive/motor manifestations in PD were assessed. Whether network disruption was a mediator between LC degeneration and cognitive/motor impairments was assessed further. In addition, an independent PD subgroup (n = 35) having functional magnetic resonance scanning before and after levodopa administration was enrolled to evaluate whether LC degeneration-related network deficiencies were independent of dopamine deficiency. We demonstrated that PD patients have significant LC degeneration compared to healthy controls. CNRLC was positively correlated with Montreal Cognitive Assessment score and the nodal efficiency (NE) of several cognitive-related regions. Lower NE of the superior temporal gyrus was a mediator between LC degeneration and cognitive impairment in PD. However, levodopa treatment could not normalize the reduced NE of the superior temporal gyrus (mediator). In conclusion, we provided evidence for the relationship between LC degeneration and extensive network disruption in PD, and highlight the role of network disorganization in LC degeneration-related cognitive impairment.

With the increasing depth of coal mining and expanding mining scale, the rocks surrounding deep roadways are in a complex mechanical condition of frequent dynamic disturbance. The heterogeneity has an important influence on rock mass failure under dynamic loads. Therefore, it is necessary to study the deformation and failure of heterogeneous roadway under dynamic load. In this paper, the effect of heterogeneity on stability of roadway under static and different dynamic loads is studied. According to the results, the effect of rock mass heterogeneity on the deformation and failure of surrounding rock varies with different degrees of heterogeneity. Under static loading conditions, the stability of roadway is negatively correlated with the degree of heterogeneity of the rock mass. Under dynamic loading conditions, the change of heterogeneity degree has significant influence on the stability of surrounding rock. With the increase in dynamic load strength, the change in variation difference in the average value of roof sag, stress distribution, and plastic zone caused by variations in heterogeneity will increase. This study contributes to understanding the deformation and failure characteristics of heterogeneous roadways under dynamic loads and can be used to analyze heterogeneous roadways under dynamic loads.

High-G MEMS accelerometer (HGMA) is a new type of sensor; it has been widely used in high precision measurement and control fields. Inevitably, the accelerometer output signal contains random noise caused by the accelerometer itself, the hardware circuit and other aspects. In order to denoise the HGMA’s output signal to improve the measurement accuracy, the improved VMD and TFPF hybrid denoising algorithm is proposed, which combines variational modal decomposition (VMD) and time-frequency peak filtering (TFPF). Firstly, VMD was optimized by the multi-objective particle swarm optimization (MOPSO), then the best decomposition parameters [kbest, abest] could be obtained, in which the permutation entropy (PE) and fuzzy entropy (FE) were selected for MOPSO as fitness functions. Secondly, the accelerometer voltage output signals were decomposed by the improved VMD, then some intrinsic mode functions (IMFs) were achieved. Thirdly, sample entropy (SE) was introduced to classify those IMFs into information-dominated IMFs or noise-dominated IMFs. Then, the short-window TFPF was selected for denoising information-dominated IMFs, while the long-window TFPF was selected for denoising noise-dominated IMFs, which can make denoising more targeted. After reconstruction, we obtained the accelerometer denoising signal. The denoising results of different denoising algorithms in the time and frequency domains were compared, and SNR and RMSE were taken as denoising indicators. The improved VMD and TFPF denoising method has a smaller signal distortion and stronger denoising ability, so it can be adopted to denoise the output signal of the High-G MEMS accelerometer to improve its accuracy.

With the aim of solving the problems of ship trajectory classification and channel identification, a ship trajectory classification method based on deep a convolutional neural network is proposed. First, the ship trajectory data are preprocessed using the improved QuickBundle clustering algorithm. Then, data are converted into ship trajectory image data, a dataset is established, a deep convolutional neural network-based ship trajectory classification model is constructed, and the manually annotated dataset is used for training. The fully connected neural network model and SVM model with latitude and longitude data as input are selected for comparative analysis. The results show that the ship trajectory classification model based on a deep convolutional neural network can effectively distinguish ship trajectories in different waterways, and the proposed method is an effective ship trajectory classification method.

The fast and accurate prediction of crop yield at the regional scale is of great significance to food policies or trade. In this study, a new model is developed to predict the yield of oilseed rape from high-resolution remote sensing images. In order to derive this model, the ground experiment and remote sensing data analysis are carried out successively. In the ground experiment, the leaf area index (LAI) of four growing stages are measured, and a regression model is established to predict yield from ground LAI. In the remote sensing analysis, a new model is built to predict ground LAI from Gaofen-1 images where the simple ratio vegetation index at the bolting stage and the VARIgreen vegetation index at the flowering stage are used. The WOFOSTWOrld FOod STudy (WOFOST) crop model is used to generate time-series ground LAI from discontinuous ground LAI, which is calibrated coarsely with the MODerate resolution imaging spectroradiometer LAI product and finely with the ground-measured data. By combining the two conclusive formulas, an estimation model is built from Gaofen-1 images to the yield of oilseed rape. The effectiveness of the proposed model is verified in Wuxue City, Hubei Province from 2014 to 2019, with the pyramid bottleneck residual network to extract oilseed rape planting areas, the proposed model to estimate yields, and the China statistical yearbooks for comparison. The validation shows that the prediction error of the proposed algorithm is less than 5.5%, which highlights the feasibility of our method for accurate prediction of the oilseed rape yield in a large area.

L-2-hydroxyglutarate (L-2HG) is an oncometabolite found elevated in renal tumors. However, this molecule might have physiological roles that extend beyond its association with cancer, as L-2HG levels are elevated in response to hypoxia and during Drosophila larval development. L-2HG is known to be metabolized by L-2HG dehydrogenase (L2HGDH), and loss of L2HGDH leads to elevated L-2HG levels. Despite L2HGDH being highly expressed in the kidney, its role in renal metabolism has not been explored. Here, we report our findings utilizing a novel CRISPR/Cas9 murine knockout model, with a specific focus on the role of L2HGDH in the kidney. Histologically, L2hgdh knockout kidneys have no demonstrable histologic abnormalities. However, GC-MS metabolomics demonstrates significantly reduced levels of the TCA cycle intermediate succinate in multiple tissues. Isotope labeling studies with [U-13C] glucose demonstrate that restoration of L2HGDH in renal cancer cells (which lowers L-2HG) leads to enhanced incorporation of label into TCA cycle intermediates. Subsequent biochemical studies demonstrate that L-2HG can inhibit the TCA cycle enzyme α-ketoglutarate dehydrogenase. Bioinformatic analysis of mRNA expression data from renal tumors demonstrates that L2HGDH is co-expressed with genes encoding TCA cycle enzymes as well as the gene encoding the transcription factor PGC-1α, which is known to regulate mitochondrial metabolism. Restoration of PGC-1α in renal tumor cells results in increased L2HGDH expression with a concomitant reduction in L-2HG levels. Collectively, our analyses provide new insight into the physiological role of L2HGDH as well as mechanisms that promote L-2HG accumulation in disease states.

BackgroundThe corpus callosum (CC) is an important feature of Parkinson’s disease (PD) not only in motor but also in non-motor functions. However, CC is not a homogeneous component, and the damage of specific subsection may contribute to corresponding clinical deficit.ObjectiveThe objective of the study is to investigate the structural alterations of different callosal subsections cross-sectionally and longitudinally in PD and evaluate their relationships to clinical performance.MethodsThirty-nine PD patients who had been longitudinally reexamined and 82 normal controls (NC) were employed. According to their specific callosal–cortical connectivity, 3D CC was divided into five subsections (including prefrontal, premotor, motor, somatosensory, and temporal–parietal–occipital subsection). The fractional anisotropy (FA), mean diffusivity (MD), and volume of whole CC and its subsections were computed and compared between groups. Regression model was constructed to explore the relationships between callosal structure and clinical performance.ResultsAt baseline, PD did not show any significant macro/microstructural difference compared with NC. During disease course, there was a decreased FA and increased MD of whole CC as well as its subsections (except temporal–parietal–occipital subsection), and the volume of motor subsection was decreased. Moreover, the FA of temporal–parietal–occipital subsection and volume of motor subsection were correlated with the mood domain at baseline, and the MD of somatosensory subsection was associated with the motor domain at follow-up.ConclusionThe structure of CC and its connectivity-specific subsections remain preserved at a relatively early stage in PD and are progressively disrupted during disease course. Besides, different callosal subsections possess specific associations with clinical performance in PD.

Background: Statins have multiple protective effects on inflammation, immunity and coagulation, and may help alleviate pneumonia. However, there was no report focusing on the association of statin use with in-hospital outcomes of patients with coronavirus disease 2019 (COVID-19). We investigated the association between the use of statins and in-hospital outcomes of patients with COVID-19.Methods: In this retrospective case series, consecutive COVID-19 patients admitted at 2 hospitals in Wuhan, China, from March 12, 2020 to April 14, 2020 were analyzed. A 1:1 matched cohort was created by propensity score-matched analysis. Demographic data, laboratory findings, comorbidities, treatments and in-hospital outcomes were collected and compared between COVID-19 patients taking and not taking statins.Result: A total of 2,147 patients with COVID-19 were enrolled in this study. Of which, 250 patients were on statin therapy. The mortality was 2.4% (6/250) for patients taking statins while 3.7% (70/1,897) for those not taking statins. In the multivariate Cox model, after adjusting for age, gender, admitted hospital, comorbidities, in-hospital medications and blood lipids, the risk was lower for mortality (adjusted HR, 0.428; 95% CI, 0.169–0.907; P = 0.029), acute respiratory distress syndrome (ARDS) (adjusted HR, 0.371; 95% CI, 0.180–0.772; P = 0.008) or intensive care unit (ICU) care (adjusted HR, 0.319; 95% CI, 0.270–0.945; P = 0.032) in the statin group vs. the non-statin group. After propensity score-matched analysis based on 18 potential confounders, a 1:1 matched cohort (206:206) was created. In the matched cohort, the Kaplan-Meier survival curves showed that the use of statins was associated with better survival (P = 0.025). In a Cox regression model, the use of statins was associated with lower risk of mortality (unadjusted HR, 0.254; 95% CI, 0.070–0.926; P = 0.038), development of ARDS (unadjusted HR, 0.240; 95% CI, 0.087–0.657; P = 0.006), and admission of ICU (unadjusted HR, 0.349; 95% CI, 0.150–0.813; P = 0.015). The results remained consistent when being adjusted for age, gender, total cholesterol, triglyceride, low density lipoprotein cholesterol, procalcitonin, and brain natriuretic peptide. The favorable outcomes in statin users remained statistically significant in the first sensitivity analysis with comorbid diabetes being excluded in matching and in the second sensitivity analysis with chronic obstructive pulmonary disease being added in matching.Conclusion: In this retrospective analysis, the use of statins in COVID-19 patients was associated with better clinical outcomes and is recommended to be continued in patients with COVID-19.

BackgroundExcessive aggregation of α-synuclein is the key pathophysiological feature of Parkinson’s disease (PD). Rapid eye movement sleep behavior disorder (RBD) is also associated with synucleinopathies and considered as a powerful predictor of PD. Growing evidence suggests the diminished clearance of α-synuclein may be partly attributable to poor interstitial fluid drainage, which can be reflected by magnetic resonance imaging (MRI)-visible enlarged perivascular space (EPVS). However, the effect of MRI-visible EPVS on iRBD and PD, and their correlation with clinical characteristics remain unclear.ObjectiveTo evaluate the clinical and neuroimaging significance of MRI-visible EPVS in iRBD and PD patients.MethodsWe enrolled 33 iRBD patients, 82 PD (with and without RBD) patients, and 35 healthy controls (HCs), who underwent clinical evaluation and 3.0 Tesla MRI. Two neurologists assessed MRI-visible EPVS in centrum semiovale (CSO), basal ganglia (BG), substantia nigra (SN), and brainstem (BS). Independent risk factors for iRBD and PD were investigated using multivariable logistic regression analysis. Spearman analysis was used to test the correlation of MRI-visible EPVS with clinical characteristics of patients.ResultsiRBD patients had significantly higher EPVS burdens (CSO, BG, SN, and BS) than PD patients. Higher CSO-EPVS and BS-EPVS burdens were independent risk factors for iRBD. Furthermore, higher CSO-EPVS and SN-EPVS burdens were positively correlated with the severity of clinical symptom in iRBD patients, and higher BG-EPVS burden was positively correlated with the severity of cognitive impairment in PD patients.ConclusioniRBD and PD patients have different MRI-visible EPVS burdens, which may be related with a compensatory mechanism in glymphatic system. Lower MRI-visible EPVS burden in PD patients may be a manifestation of severe brain waste drainage dysfunction. These findings shed light on the pathophysiologic relationship between iRBD and PD with respect to neuroimaging marker of PD.

Vascular-targeted PDT (vPDT) has produced promising results in the treatment of many cancers, including drug-resistant ones, but little is known about its efficacy in lymphoma. Unfortunately, the lack of a specific therapeutic target and a hypoxic microenvironment for lymphoma jeopardizes the efficacy of vPDT severely. In this study, we designed a lymphoma tissue factor-targeted “O2-evolving” strategy combining PDT with catalase and HMME-encapsulated, EGFP-EGF1-modified PEG-PLGA nanoparticles (CENPs) to boost PDT efficiency; this combination takes advantage of the low oxygen tension of lymphoma. In our results, CENPs accumulated effectively in the vascular lymphoma in vivo and in vitro, and this accumulation increased further with PDT treatment. Per positron emission tomography imaging, combining CENPs with PDT inhibited lymphoma glucose metabolism significantly. The expression of hypoxia-inducible factor (HIF)-1α in the entrapped catalase groups reduced markedly. These data show that the combined administration of PDT and CENPs can prompt tissue factor-cascade-targeted and self-supply of oxygen and that it has a good therapeutic effect on malignant lymphoma.

Shikonin (SHI) is an anti-inflammatory agent extracted from natural herbs. It is still unknown whether SHI ameliorates lipopolysaccharide (LPS)-induced cardiac dysfunction. This study aims to explore the protective effects of SHI on LPS-induced myocardial injury and its mechanism. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of SHI. In the present study, we found that SHI treatment improved the survival rate and cardiac function and remarkably ameliorated the release of inflammatory cytokines and macrophage infiltration in heart tissue of LPS-treated mice. SHI also reduced lactate dehydrogenase (LDH) and cardiac troponin (cTn) release, cell inflammation, and apoptosis in LPS plus adenosine triphosphate (ATP)-treated H9c2 cells. In addition, SHI significantly upregulated silent information regulator 1 (SIRT1) expression and suppressed the upregulation of NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Meanwhile, we got the same results in LPS plus ATP-treated H9c2 cells in vitro. Further, SIRT1 inhibitor or siRNA partially blocked SHI-mediated upregulation of SIRT1 expression and downregulation of NLRP3, cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Therefore, we conclude that SHI ameliorates LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes and might be a promising therapeutic strategy for the treatment of LPS-induced cardiac dysfunction.

In nature, plant viruses are mostly transmitted by hemipteran insects, such as aphids, leafhoppers, and whiteflies. However, the molecular mechanisms underlying the interactions between virus and insect vector are poorly known. Here, we investigate the proteomic interactions between tomato yellow leaf curl virus (TYLCV, genus Begomovirus, family Geminiviridae), a plant virus, and its vector whitefly (Bemisia tabaci) species complex. First, using a yeast two-hybrid system, we identified 15 candidate whitefly proteins interacting with the coat protein of TYLCV. GO and KEGG pathway analysis implicated that these 15 whitefly proteins are of different biological functions/processes mainly including metabolic process, cell motility, signal transduction, and response to stimulus. We then found that the whitefly protein tumorous imaginal discs (Tid), one of the 15 whitefly proteins identified, had a stable interaction with TYLCV CP in vitro, and the DnaJ_C domain of Tid301−499aa may be the viral binding site. During viral retention, the expression of whitefly protein Tid was observed to increase at the protein level, and feeding whiteflies with dsRNA or antibody against Tid resulted in a higher quantity of TYLCV in the whitefly body, suggesting the role of Tid in antiviral infection. Our data indicate that the induction of Tid following viral acquisition is likely a whitefly immune response to TYLCV infection.

Purpose: To investigate the structural covariance network disruption in Parkinson’s disease (PD), and explore the functional alterations of disrupted structural covariance network.Methods: A cohort of 100 PD patients and 70 healthy participants underwent structural and functional magnetic resonance scanning. Independent component analysis (ICA) was applied separately to both deformation-based morphometry (DBM) maps and functional maps with the same calculating parameters (both decomposed into 20 independent components (ICs) and computed 20 times the Infomax algorithm in ICASSO). Disrupted structural covariance network in PD patients was identified, and then, we performed goodness of fit analysis to obtain the functional network that showed the highest spatial overlap with it. We investigated the relationship between structural covariance network and functional network alterations. Finally, to further understand the structural and functional alterations over time, we performed a longitudinal subgroup analysis (51 patients were followed up for 2 years) with the same procedures.Results: In a cross-sectional analysis, PD patients showed decreased structural covariance between anterior and posterior cingulate subnetworks. The functional components showed best overlap with anterior and posterior cingulate structural subnetworks were selected as anterior and posterior cingulate functional subnetworks. The functional connectivity between them was significantly increased [assessed by Functional Network Connectivity (FNC) toolbox]; and the increased functional connectivity was negatively correlated with cingulate structural covariance network integrity. Longitudinal subgroup analysis showed cingulate structural covariance network disruption was worse at follow-up, while the functional connectivity between anterior and posterior cingulate network was increased at baseline and decreased at follow-up.Conclusion: This study indicated that the cingulate structural covariance network displayed a high susceptibility in PD patients. This study indicated that the cingulate structural covariance network displayed a high susceptibility in PD patients. Considering that disrupted structural covariance network coexisted with enhanced/remained functional activity during disease development, enhanced functional activity underlying the disrupted cingulate structural covariance network might represent a temporal compensation for maintaining clinical performance.

Statin is the medication most widely prescribed to reduce plasma cholesterol levels. Yet, how the medication contributes to diabetes risk and impaired glucose metabolism is not clear. This study aims to examine the epigenetic mechanisms of ABCG1 through which statin use associates with risk of type 2 diabetes. We determined the association between the statin use, DNA methylation at ABCG1 and type 2 diabetes/glycemic traits in the Framingham Heart Study Offspring (FHS, n = 2741), with validation in the Women’s Health Initiative Study (WHI, n = 2020). The causal effect of statin use on the risk of type 2 diabetes was examined using a two-step Mendelian randomization approach. Next, based on transcriptome analysis, we determined the links between the medication-associated epigenetic status of ABCG1 and biological pathways on the pathogenesis of type 2 diabetes. Our results showed that DNA methylation levels at cg06500161 of ABCG1 were positively associated with the use of statin, type 2 diabetes and related traits (fasting glucose and insulin) in FHS and WHI. Two-step Mendelian randomization suggested a causal effect of statin use on type 2 diabetes and related traits through epigenetic mechanisms, specifically, DNA methylation at cg06500161. Our results highlighted that gene expression of ABCG1, ABCA1 and ACSL3, involved in both cholesterol metabolism and glycemic pathways, was inversely associated with statin use, CpG methylation, and diabetic signatures. We concluded that DNA methylation site cg06500161 at ABCG1 is a mediator of the association between statins and risk of type 2 diabetes.

As one of the abiotic stresses, low temperature severely threatens rice production during its entire growth period, especially during the booting stage. In the present study, transcriptome analysis was performed comparing Longjing (LJ) 25 (chilling-tolerant) and LJ 11 (chilling-sensitive) rice varieties to identify genes associated with chilling tolerance in rice spikelets. A total of 23 845 expressed genes and 13 205 differentially expressed genes (DEGs) were identified, respectively. Gene ontology (GO) enrichment analyses revealed ‘response to cold’ (containing 180 DEGs) as the only category enriched in both varieties during the entire cold treatment period. Through MapMan analysis, we identified nine and six DEGs related to the Calvin cycle and antioxidant enzymes, respectively, including OsRBCS3, OsRBCS2, OsRBCS4, OsAPX2 and OsCATC, that under chilling stress were markedly downregulated in LJ11 compared with LJ25. Furthermore, we predicted their protein–protein interaction (PPI) network and identified nine hub genes (the threshold of co-expressed gene number ≥ 11) in Cytoscape, including three RuBisCO-related genes with 14 co-expressed genes. Under chilling stress, antioxidant enzyme activities (peroxidase (POD) and catalase (CAT)) were downregulated in LJ11 compared with LJ25. However, the content of malondialdehyde (MDA) was higher in LJ11 compared with LJ25. Collectively, our findings identify low temperature responsive genes that can be effectively used as candidate genes for molecular breeding programmes to increase the chilling tolerance of rice.

Summary: Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

Related to ABSCISIC ACID INSENSITIVE3 (ABI3)/VIVIPAROUS1(VP1)(RAV) transcription factors, which encode a B3 domain and an APETALA2(AP2) domain, belong to the APETALA2/ethylene-responsive element binding factor(AP2/ERF) or B3 superfamily and play an important role in regulating plant growth and development and responding to abiotic stress. Although there have been many functional studies on RAV, the functional differences between RAVs are not clear. Therefore, in this study, the functional differences of RAVs of Medicago truncatula were analyzed. Based on sequence data from the plant transcription factor database and the M. truncatula genome database, we cloned three RAV genes from M. truncatula, named MtRAV1, MtRAV2, and MtRAV3. The cis-acting elements of these genes promoters were predicted, and the expression patterns of MtRAVs under exogenous conditions (4°C, NaCl, Polyethylene Glycol, Abscisic acid) were analyzed. MtRAVs transgenic Arabidopsis thaliana were obtained and subjected to adversity treatment. Subcellular localization results indicated that MtRAVs were located in the nucleus. A much lower expression level was observed for MtRAV3 than the levels of MtRAV1 and MtRAV2 in M. truncatula for growth in normal conditions, but under 4°C or PEG and NaCl treatment, the expression level of MtRAV3 was significantly increased. Only the MtRAV3 overexpression transgenic plants showed strong cold resistance, but the overexpressed MtRAV1 and MtRAV2 transgenic plants showed no difference from wild type plants. MtRAV transgenic plants exhibited similar response to exogenous mannitol, NaCl, and ABA, and the expression of some adverse-related marker genes were up-regulated, such as COLD REGULATED 414 THYLAKOID MEMBRANE 1 (COR414-TM1), Arabidopsis thaliana drought-induced 21 (AtDI21), and Arabidopsis thaliana phosphatidylinositol-specific phospholipase C (ATPLC). MtRAVs transgenic Arabidopsis thaliana exhibited increasing of branch number. These results indicated that there was some function redundancy during MtRAVs proteins of M. truncatula, and MtRAV3 has increased function compared to the other two genes. The results of this study should provide the foundation for future application of MtRAVs in legumes.

Uveal melanoma (UM) is the most common primary intraocular carcinoma in adults. Cinobufagin, secreted by the Asiatic toad Bufo gargarizans, is a traditional Chinese medicine, widely used in tumor treatment. Here, we explored the potential antitumor function of cinobufagin and investigated its biochemical mechanisms in UM cells. The antitumor potential of cinobufagin was determined via cell viability, cell cycle, and apoptosis assays. Colony formation assays confirmed that cinobufagin exerted potent antitumor activity in a dose-dependent manner. We found that cinobufagin could induce cell apoptosis and upregulate the expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), and cleaved caspase-9 in vivo and in vitro. In addition, after treatment with increased concentrations of cinobufagin, the intrinsic mitochondrial apoptosis pathway was also activated, which was demonstrated by increased cell apoptosis with increased expression of Bad and Bax, decreased expression of Bcl-2 and Bcl-xl, and reduced mitochondrial membrane potential (MMP) in OCM1 cells. Taken together, the results of this preclinical study suggest that cinobufagin can both inhibit cell survival and induce cell apoptosis in a dose-dependent manner in UM cells, which provides new insights into the biochemical mechanism of cinobufagin and its potential as a future chemotherapeutic agent for UM.

BackgroundDepression is common in patients with Parkinson’s disease (PD). Our previous studies suggest that depressed PD patients have altered insula structures. It is, however, still unknown whether the altered structures cause disruption of insula functional networks, further contributing to depression in PD.MethodsIn the present study, 17 depressed PD patients, 17 non-depressed PD patients, and 17 normal controls were enrolled. All subjects went through neurological and psychiatric clinical assessments. Resting-state functional magnetic resonance imaging and seed-based insula functional analyses were performed to examine the insula functional connectivity alterations in PD patients.ResultsWe found that compared with normal controls, PD patients exhibited significantly decreased insula functional connectivity widely across the whole brain. Compared with non-depressed PD patients, depressed patients showed further decreased functional connectivity in the middle frontal gyrus and inferior parietal lobe. Furthermore, connectivity between the left anterior insula and middle frontal gyrus was positively correlated with the cognitive scale score.ConclusionThese results suggest that insula networks were severely damaged in PD patients, and that the disrupted connection between the salience network and executive control network might contribute to depression in PD.

Micron-MnO2 powder has unique thermal decomposition process compared with other metal oxides, and the different characteristics of components in thermite could affect the thermal performance of the whole system directly. In this work, the Al powder with different three particle sizes was combined with micron-MnO2 to prepare the Al-MnO2 thermite system, and the effect of Al powder particle sizes on the whole thermal behavior was studied. Firstly, the thermal decomposition process of micron-MnO2 and purity of Al powder are tested by TG-DSC. By using ultrasonic dispersion method, the fuel-rich thermite samples were prepared and characterized by SEM and TG-DSC at different heating rates. The Kissinger method was also employed to calculate the activation energy for the first exothermic peak. It was found that the thermal decomposition process of MnO2 in the thermite system can be significantly disturbed by different Al particles size. In other words, the effect of Al particle sizes on the thermite can be magnified due to the unique decomposition properties of micron-MnO2 instead of onset temperature of exothermic reaction changing simply. The activation energy of thermite system decreased with the reduction of Al particle sizes in micron-level, while in nanolevel the activation energy markedly increased. Finally, the possible reasons for phenomenon were discussed.

Fault activation triggers local deformation and dislocation, releasing a large amount of energy that can easily cause mining disasters, such as rock bursts and roadway instability. To study the changing characteristics of overburden structures and the evolution law of mining-induced stress as panel advances towards a fault from a footwall, two similar models were established, namely, a simulation experimental model and a numerical simulation model. In addition, the relationship among mining, mining stress, and rock bursts induced by fault activation was investigated. The results of this study reveal that when the working face is 30 m away from the fault, the high-position rock mass near the fault turns to the goaf where the fault is activated, and the two walls display relatively obvious dislocation. During the process of footwall panel mining to the fault, the abutment stress of the coal pillar tends to increase initially, followed by a decrease. When the working face is 20 m away from the fault, the abutment stress ahead of the working face reaches its maximum. When the width of the coal pillar is within the range of 10–40 m, the coal pillar accumulates a large amount of energy, and the working face affected by the fault easily induces a rock burst. Before fault activation, disturbances arising from the mining activities destroy the equilibrium stress environment of the rock system surrounding the fault, and the fault continuously accumulates energy. When the accumulated energy reaches a certain threshold, under the action of normal stress or shear stress, the fault will be activated, and a large amount of energy will be released, which can easily induce a rock burst. The research results in this paper provide a scientific basis for the classification, prediction, and prevention of rock bursts under similar geological conditions.

Objective. To estimate the relationship between obesity (defined by both BMI and SAD) and various levels of depressive symptoms in women in the United States. Methods. This is a cross-sectional design. All data were collected from NHANES 2011-2012 and 2013-2014. The Patient Health Questionnaire (PHQ-9) was the primary variable used to index depressive symptoms. SAD was assessed using an abdominal caliper. We stratified participates into three groups according to SAD (trisection): T1: low (11.8-18.4 cm), T2: middle (18.5-22.8 cm), and T3: high (22.9-40.1 cm). Other data were collected following the NHANES protocols. We aimed to investigate the effects of obesity on the depression in the NHANES populations. Results. A total of 4477 women were enrolled in the final study population. Participants with a high SAD had the highest risk of clinical depression symptoms (OR=1.2, 95% CI: 1.1-1.4), which was, in particular, the case for moderate-severe depression (OR=1.4, 95% CI: 1.1-1.7) and severe depression (OR=1.4, 95% CI: 1.0-1.9). We also found a significant relationship between SAD and BMI (r=0.836). We did, however, not find a significant relationship between BMI and severe depression. Conclusions. SAD had a better correlation with clinical depression symptoms than BMI, especially regarding severe depression symptoms.

To investigate the potential applications and the molecular mechanisms of transcranial direct current stimulation (tDCS) on cognitive impairment in a vascular dementia (VD) animal model. Sprague-Dawley rats were used in this study. VD rat model was induced by modified permanent bilateral common carotid artery occlusion (2-VO) approach. Anodal tDCS was applied to the animals. Morris water maze was used to analyze spatial memory and navigation ability. The pathological changes in the hippocampal CA1 region and cerebral cortex were examined via Hematoxylin-Eosin staining. The rats were sacrificed for the measurement of the level of superoxide (SOD), glutathione (GSH), reactive oxidative species (ROS), malondialdehyd (MDA), Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α level in the hippocampus. Western blot was carried out to measure the hippocampal expression of microtubule-associated protein 1 light chain 3 (LC-3) and p62. Rats with VD have decreased number of neurons in the hippocampus and cerebral cortex, as well as worse cognitive impairment. The proliferation of activated microglia and astroglia, accompanied with attenuation of myelination were observed in the white matter about 1 month after 2-VO operation. These abnormalities were significantly ameliorated by tDCS treatment. Further study revealed that anodal tDCS could suppress the MDA and ROS level, while enhance the SOD and GSH level to reduce the oxidative stress. Anodal tDCS could inhibit hypoperfusion-induced IL-1β, IL-6, and TNF-α expression to attenuate inflammatory response in hippocampus. Moreover, anodal tDCS treatment could alleviate autophagy level. The study has demonstrated a possible therapeutic role of tDCS in the treatment of cognitive impairment in VD.

Disruption of brain circuits is one of the core mechanisms of Parkinson’s disease (PD). Understanding structural connection alterations in PD is important for effective treatment. However, due to methodological limitations, most studies were unable to account for confounding factors such as crossing fibers and were unable to identify damages to specific fiber tracts. In the present study, we aimed to demonstrate tract-specific white matter structural changes in PD patients and their relationship with clinical symptoms. Ninety-eight PD patients, divided into early (ES) and middle stage (MS) groups, and 76 healthy controls (HCs) underwent brain magnetic resonance imaging scans and clinical assessments. Fixel-based analysis was used to investigate fiber tract alterations in PD patients. Compared to HCs, the PD patients showed decreased fiber density (FD) in the corpus callosum (CC), increased FD in the cortical spinal tract (CST), and increased fiber-bundle cross-section (FC, log-transformed: log-FC) in the superior cerebellar peduncle (SCP). Analysis of variance (ANOVA) revealed significant differences in FD in the CST and log-FC in the SCP among the three groups. Post-hoc analysis revealed that the mean FD values of the CST were higher in ES and MS patient groups compared to HCs, and the mean log-FC values of the SCP were higher in ES and MS patient groups compared to HCs. Additionally, the FD values of the CC in PD patients were negatively correlated with the Unified Parkinson’s Disease Rating Scale part-III (UPDRS-III) scores (r = -0.257, p = 0.032), Hamilton Depression Rating Scale 17 Items (HAMD-17) scores (r = -0.230, p = 0.033), and Hamilton Anxiety Scale (HAMA) scores (r = -0.248, p = 0.032). Moreover, log-FC values of the SCP (r = 0.274, p = 0.028) and FD values of the CST (r = 0.384, p

Leaf senescence is a complex organized developmental stage limiting the yield of crop plants, and alfalfa is an important forage crop worldwide. However, our understanding of the molecular mechanism of leaf senescence and its influence on biomass in alfalfa is still limited. In this study, RNA sequencing was utilized to identify differentially expressed genes (DEGs) in young, mature, and senescent leaves, and the functions of key genes related to leaf senescence. A total of 163,511 transcripts and 77,901 unigenes were identified from the transcriptome, and 5,133 unigenes were differentially expressed. KEGG enrichment analyses revealed that ribosome and phenylpropanoid biosynthesis pathways, and starch and sucrose metabolism pathways are involved in leaf development and senescence in alfalfa. GO enrichment analyses exhibited that six clusters of DEGs are involved in leaf morphogenesis, leaf development, leaf formation, regulation of leaf development, leaf senescence and negative regulation of the leaf senescence biological process. The WRKY and NAC families of genes mainly consist of transcription factors that are involved in the leaf senescence process. Our results offer a novel interpretation of the molecular mechanisms of leaf senescence in alfalfa.

The vortex rope in the draft tube is considered as the major contributor to pressure pulsation at partial load (PL) conditions, which causes the hydro unit to operate unstably. Based on the prototype Francis turbine HLA551-LJ-43 in the laboratory, J-grooves are designed on its conical section in this paper. We used numerical simulation to study the effect of the J-grooves on vortex suppression and energy dissipation in the draft tube. Four typical operating conditions were chosen to analyze the vortex suppression; the corresponding flow ratios Q* are 100%, 82%, 69%, and 53%, respectively. Entropy production theory is used to calculate the energy losses and assess the effect of the J-groove on energy dissipation under part-load conditions. By comparing entropy production, circumferential and axial velocity components, swirl intensity, pressure pulsation, and vortex distribution in a draft tube with and without J-grooves at different operating conditions, it can be concluded that the entropy production on the wall containing a conical section with J-grooves is obviously smaller than that without J-grooves, the effects of J-grooves on reducing circumferential velocity component Vu, pressure pulsation, and weakening vortex intensity and vortex rope in the conical section are obvious, especially at part load and deep part-load operating conditions. Using J-grooves shows better performance on vortex control and energy dissipation in the draft tube of a Francis turbine at partial load conditions.

Human activity recognition is becoming increasingly important. As contact with oneself and the environment accompanies almost all human activities, a Smart-Sleeve, made of soft and stretchable textile pressure sensor matrix, is proposed to sense human contact with the surroundings and identify performed activities in this work. Additionally, a dataset including 18 activities, performed by 14 subjects in 10 repetitions, is generated. The Smart-Sleeve is evaluated over six classical machine learning classifiers (support vector machine, k-nearest neighbor, logistic regression, random forest, decision tree and naive Bayes) and a convolutional neural network model. For classical machine learning, a new normalization approach is proposed to overcome signal differences caused by different body sizes and statistical, geometric, and symmetry features are used. All classification techniques are compared in terms of classification accuracy, precision, recall, and F-measure. Average accuracies of 82.02% (support vector machine) and 82.30% (convolutional neural network) can be achieved in 10-fold cross-validation, and 72.66% (support vector machine) and 74.84% (convolutional neural network) in leave-one-subject-out validation, which shows that the Smart-Sleeve and the proposed data processing method are suitable for human activity recognition.

Photodynamic therapy (PDT) is a treatment modality that uses light to target tumors and minimize damage to normal tissues. It offers advantages including high spatiotemporal selectivity, low side effects, and maximal preservation of tissue functions. However, the PDT efficiency is severely impeded by the hypoxic feature of tumors. Moreover, hypoxia may promote tumor metastasis and tumor resistance to multiple therapies. Therefore, addressing tumor hypoxia to improve PDT efficacy has been the focus of antitumor treatment, and research on this theme is continuously emerging. In this review, we summarize state-of-the-art advances in strategies for overcoming hypoxia in tumor PDTs, categorizing them into oxygen-independent phototherapy, oxygen-economizing PDT, and oxygen-supplementing PDT. Moreover, we highlight strategies possessing intriguing advantages such as exceedingly high PDT efficiency and high novelty, analyze the strengths and shortcomings of different methods, and envision the opportunities and challenges for future research.

With the rapid expansion of graphs and networks and the growing magnitude of data from all areas of science, effective treatment and compression schemes of context-dependent data is extremely desirable. A particularly interesting direction is to compress the data while keeping the “structural information” only and ignoring the concrete labelings. Under this direction, Choi and Szpankowski introduced the structures (unlabeled graphs) which allowed them to compute the structural entropy of the Erdős–Rényi random graph model. Moreover, they also provided an asymptotically optimal compression algorithm that (asymptotically) achieves this entropy limit and runs in expectation in linear time. In this paper, we consider the stochastic block models with an arbitrary number of parts. Indeed, we define a partitioned structural entropy for stochastic block models, which generalizes the structural entropy for unlabeled graphs and encodes the partition information as well. We then compute the partitioned structural entropy of the stochastic block models, and provide a compression scheme that asymptotically achieves this entropy limit.

In recent years,telecom operators have begun to make strategic transformation and layout to the smart home ecosystem.Telecom operators hope to build a smart home open platform to realize business ecology and intelligent operation,provide users with innovative business models and consumption experience.How to build an open platform for smart home based on the characteristics of operators has become a hot topic in the industry.The architecture mode and the existing problems of the mainstream open platform for smart home were firstly analyzed,then the key elements of open platform of telecom operators were studied.Finally,the key technical direction and application practice was proposed to build the open platform for the operators.

Wi-Fi mesh is a kind of suitable for large or complex home wireless self-organizing network solution.It can provide users with full coverage,self-handoff and easy installation of high-quality wireless network.Wi-Fi mesh has many advantages,such as self-organizing,self-management,self-repair and self-balance.But the existing Wi-Fi mesh product implementation scheme is not uniform,complex,high terminal capability requirement and unable to interoperate.The realization of multi AP collaborative work in home network was firstly discussed,then the main current technology development of Wi-Fi mesh was analyzed,and the technical scheme and comparative analysis of home Wi-Fi mesh was focused on.Then,aiming at home application scenario,a Wi-Fi mesh technology implementation scheme for operators was presented,which was modularized,easy to realize,with low terminal capability requirement and good interoperability.

Abstract In a supersymmetric extension of the standard model with local gauged baryon and lepton numbers (BLMSSM), there are new sources for lepton flavor violation, because the right-handed neutrinos, new gauginos and Higgs are introduced. We investigate muon conversion to electron in nuclei within the BLMSSM in detail. The numerical results indicate that the $$\mu \rightarrow e $$ μ→e conversion rates in nuclei within the BLMSSM can reach the experimental upper bound, which may be detected in the future experiments.

Abstract Background Increasing evidence suggests a critical role for long noncoding RNAs (LncRNAs) and pseudogenes in cancer. Renal cell carcinoma (RCC), the most common primary renal neoplasm, is highly aggressive and difficult to treat because of its resistance to chemotherapy and radiotherapy. Despite many identified LncRNAs and pseudogenes, few have been clearly elucidated. Methods This study provides new insights into LncRNAs and pseudogenes in the prognosis of RCC. We searched an online database to interrogate alterations and clinical data on cBioPortal. We analysed LncRNA and pseudogene signatures to predict the prognosis of RCC based on a Cox model. We also found potential serum biomarkers of RCC and validated them in 32 RCC patients, as well as healthy controls. Results Alterations were found in 2553 LncRNAs and 8901 pseudogenes and occurred in up to 23% of all cases. Among these, 27 LncRNAs and 45 pseudogenes were closely related to prognosis. We also identified signatures of LncRNAs and pseudogenes that can predict overall survival and recurrence of RCC. We then validated the relative levels of these LncRNAs and pseudogenes in the serum of 32 patients. Six of these, including LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P, could be non-invasive biomarkers of RCC. Finally, we selected PIK3CD-AS1 to determine its role in RCC and found that upregulation of PIK3CD-AS1 was closely associated with higher tumour stage and metastasis. Conclusions These signatures of LncRNAs and pseudogenes can predict overall survival and recurrence of RCC. LINC00520, PIK3CD-AS1, LINC01559, CEACAM22P, MSL3P1 and TREML3P could be non-invasive biomarkers of RCC. These data suggest the important roles of LncRNAs and pseudogenes in RCC, and therefore provides us new insights into the prognosis of RCC.

Abstract Background Many applications of CRISPR/Cas9-mediated genome editing require Cas9-induced non-homologous end joining (NHEJ), which was thought to be error prone. However, with directly ligatable ends, Cas9-induced DNA double strand breaks may be repaired preferentially by accurate NHEJ. Results In the repair of two adjacent double strand breaks induced by paired Cas9-gRNAs at 71 genome sites, accurate NHEJ accounts for about 50% of NHEJ events. This paired Cas9-gRNA approach underestimates the level of accurate NHEJ due to frequent + 1 templated insertions, which can be avoided by the predefined Watson/Crick orientation of protospacer adjacent motifs (PAMs). The paired Cas9-gRNA strategy also provides a flexible, reporter-less approach for analyzing both accurate and mutagenic NHEJ in cells and in vivo, and it has been validated in cells deficient for XRCC4 and in mouse liver. Due to high frequencies of precise deletions of defined “3n”-, “3n + 1”-, or “3n + 2”-bp length, accurate NHEJ is used to improve the efficiency and homogeneity of gene knockouts and targeted in-frame deletions. Compared to “3n + 1”-bp, “3n + 2”-bp can overcome + 1 templated insertions to increase the frequency of out-of-frame mutations. By applying paired Cas9-gRNAs to edit MDC1 and key 53BP1 domains, we are able to generate predicted, precise deletions for functional analysis. Lastly, a Plk3 inhibitor promotes NHEJ with bias towards accurate NHEJ, providing a chemical approach to improve genome editing requiring precise deletions. Conclusions NHEJ is inherently accurate in repair of Cas9-induced DNA double strand breaks and can be harnessed to improve CRISPR/Cas9 genome editing requiring precise deletion of a defined length.

Steam Assisted Gravity Drainage (SAGD) is widely used in the Athabasca oil sands deposit to recover bitumen. Since the viscosity of bitumen is high at original reservoir conditions, heat is required to lower its viscosity to the point it becomes mobile enough to be recovered under gravity drainage. To heat the reservoir, steam is injected into the formation and thus SAGD is energy intense. Given that the fuel used to generate steam is the largest operating cost, the steam-to-oil ratio is one of the key parameter for evaluating the economics of any SAGD project. Here, the use of dynamic distributed steam injection within a pad of SAGD wellpairs is explored. The results demonstrate that feedback control leads to improvements of the SOR over that of constant pressure. The results show that the controller is able to detect the “sweet spots” (oil zones with better geological properties) in the reservoir and dynamically deliver more steam to that region. Meanwhile, it reduces the steam injection towards relatively worse quality zones to lower the local SOR. Keywords: Steam-assisted gravity drainage, SAGD pad, Control strategies, PID, cSOR, Oil sands emissions

Seed germination and early seedling growth are important agricultural traits for developing populations of both irrigated and directly seeded rice (DSR). To investigate the genetic mechanisms underlying seed germination and early seedling growth in rice, 275 recombinant inbred lines (RILs) were genotyped in this study via the genotyping-by-sequencing (GBS) approach to construct a high-density linkage bin map based on the parent-independent genotyping method. Quantitative trait loci (QTLs) for 12 traits related to seed germination and early seedling growth were analyzed. Totally, 22 additive loci were detected, after analysis of the interaction between additive QTLs and environments, five stable additive loci were obtained. Among them, loci 4, 5, 12 and 14 exhibited clear pleiotropic effects that were associated with multiple traits. Analysis of the effects of the five additive stable loci showed that a single locus increased the corresponding phenotypic value. Ten of the 275 RILs pyramided the excellent alleles of the five stable genetic loci. Most phenotypic values of the ten RILs were greater than the average values. Four RILs (G260, G342, G371, and G401) with more excellent phenotypic values were subsequently selected; these RILs could serve as donor parents of favorable alleles in the breeding process. Due to the existence of pleiotropy, the use of these genetic loci for pyramid breeding can further increase the efficiency to reach breeding goals. In addition, these five stable loci have an average physical interval of only 170 kb, we also further identified five promising candidate genes by qRT-PCR, which provides us with a basis for future cloning of these genes. Overall, this work will help broaden our understanding of the genetic control of seed germination and early seedling growth, and this study provides both a good theoretical basis and a new genetic resource for the breeding of direct-seeded rice.

Abstract Background Resveratrol, a plant phenol, affords protection against inflammation and oxidative stress. The objective of this study was to investigate the effects of dietary resveratrol supplementation during pregnancy and lactation on the antioxidant status of sows and piglets and on antioxidant gene expression and pathway in placenta. Methods Forty sows were allotted to 2 dietary treatments 20 d after breeding. Sows were fed a control diet and a control diet with 300 mg/kg resveratrol. Oxidative stress biomarkers and antioxidant enzymes were measured in the placenta, milk, and plasma of sows and piglets. Antioxidant gene expression and protein expression of Kelch-like ECH-associated protein 1-Nuclear factor E2-related factor 2 (Keap1-Nrf2), nuclear factor kappa B-p65 (NFκB-p65) and sirtuin1 (Sirt1) were quantified in the placenta. Results Dietary resveratrol increased the litter and piglets weaning weights. Antioxidant status in the milk, placenta and plasma of sows and piglets was partially improved by dietary resveratrol. In placenta, Nrf2 protein expression was increased and Keap1 protein expression was decreased by dietary resveratrol. The mRNA expression of antioxidant genes including catalase (CAT), glutathione peroxidase 1 (GPX1), GPX4, superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO1), and phase 2 detoxification genes, including glutamate-cysteine ligase modifier (GCLM), microsomal glutathione S-transferase 1(MGST1) and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), was increased by dietary resveratrol. Dietary resveratrol also increased Sirt1 and phosphorylated NFκB-p65 protein expression in the placenta. We failed to observe any influences of dietary resveratrol on pro-inflammatory cytokine levels, including those of interleukin 1β (IL-1β), IL-6, IL-8 and tumor necrosis factor α (TNF-α). However, we observed that the mRNA expression of IL-8 in placenta was reduced by maternal resveratrol. In addition, dietary resveratrol showed interactive effects with day of lactation on activities of SOD and CAT and levels of malonaldehyde (MDA) and hydrogen peroxide (H2O2) in milk. Conclusions Dietary resveratrol supplementation during pregnancy and lactation improves the antioxidant status of sows and piglets, which is beneficial to the reproductive performance of sows. Dietary resveratrol regulates placental antioxidant gene expression by the Keap1-Nrf2 pathway and Sirt1 in placenta.

Abstract Purpose: To investigate the impact of different hypoxia reoxygenation (HR) times on autophagy of rat cardiomyocytes (H9C2). Methods: Rat cardiomyocytes were randomly divided into normal control group (group A), hypoxia group (group B), 2 h HR group (group C), 12 h HR group (group D), and 24 h HR group (group E). LC3 II/LC3 I was determined via western blotting, and cell viabilities of cardiomyocytes were measured using methyl thiazolyl tetrazolium (MTT) assay. Results: Cell viabilities in HR model groups were significantly lower than those of group A (P

Blast resistance and grain quality are major problems in hybrid rice production in China. In this study, two resistance (R) genes, Pi46 and Pita, along with the gene Wxb, which mainly affects rice endosperm amylose content (AC), were introgressed into an elite indica restoring line, R8166, which has little blast resistance and poor grain quality through marker-assisted selection (MAS). Eight improved lines were found to have recurrent genome recovery ratios ranging from 88.68 to 96.23%. Two improved lines, R163 and R167, were selected for subsequent studies. R167, which has the highest recovery ratio (96.23%), showed no significant differences in multiple agronomic traits. In contrast, R163 with the lowest recovery ratio (88.68%) exhibited significant differences in heading date and yield per plant compared with the recurrent parent. At two developmental stages, R163 and R167 had greatly enhanced resistance to blast over the recurrent parent. Similar trends were also observed for agronomic traits and blast resistance in R163- and R167-derived hybrids when compared with the counterparts from R8166. In addition, R163, R167, and their derived hybrids significantly improved the grain quality traits, including amylose content (AC), gel consistency (GC), chalky grain rate (CGR), and degree of endosperm chalkiness (DEC). It confirmed the success of efficiently developing elite restoring lines using MAS in this study.

A novel hybrid PKS–NRPS alkaloid, xylarialoid A (1), containing a 13-membered macrocyclic moiety and [5,5,6] fused tricarbocyclic rings, together with ten known cytochalasins (2–11), was isolated from a plant-derived endophytic fungus, Xylaria arbuscula. The chemical structures of all compounds were elucidated using 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculation. Compounds 1–3 and 10 exhibited significant antitumor activities against A549 and Hep G2 cell lines, with IC50 values of 3.6–19.6 μM. In addition, compound 1 showed potent anti-inflammatory activity against LPS-induced nitric oxide (NO) production in macrophage RAW 264.7 cells (IC50, 6.6 μM).

Rapid, non-destructive methods for determining the biochemical composition of straw are crucial in ruminant diets. In this work, ground samples of corn stover (n = 156) and wheat straw (n = 135) were scanned using near-infrared spectroscopy (instrument NIRS DS2500). Samples were divided into two sets, with one set used for calibration (corn stover, n = 126; wheat straw, n = 108) and the remaining set used for validation (corn stover, n = 30; wheat straw, n = 27). Calibration models were developed utilizing modified partial least squares (MPLS) regression with internal cross validation. Concentrations of moisture, crude protein (CP), and neutral detergent fiber (NDF) were successfully predicted in corn stover, and CP and moisture were in wheat straw, but other nutritional components were not predicted accurately when using single-crop samples. All samples were then combined to form new calibration (n = 233) and validation (n = 58) sets comprised of both corn stover and wheat straw. For these combined samples, the CP, NDF, and ADF were predicted successfully; the coefficients of determination for calibration (RSQC) were 0.9625, 0.8349, and 0.8745, with ratios of prediction to deviation (RPD) of 6.872, 2.210, and 2.751, respectively. The acid detergent lignin (ADL) and moisture were classified as moderately useful, with RSQC values of 0.7939 (RPD = 2.259) and 0.8342 (RPD = 1.868), respectively. Although the prediction of hemicellulose was only useful for screening purposes (RSQC = 0.4388, RPD = 1.085), it was concluded that NIRS is a suitable technique to rapidly evaluate the nutritional value of forage crops.

Water Resource Sustainability Management plays a vitally important role in ensuring sustainable development, especially in water-stressed arid regions throughout the world. In order to achieve sustainable development, it is necessary to study and monitor the water quality in the arid region of Central Asia, an area that is increasingly affected by climate change. In recent decades, the rapid deterioration of water quality in the Ebinur Lake basin in Xinjiang (China) has severely threatened sustainable economic development. This study selected the Ebinur Lake basin as the study target, with the purpose of revealing the response between the water quality index and water body reflectivity, and to describe the relationship between the water quality index and water reflectivity. The methodology employed remote sensing techniques that establish a water quality index monitoring model to monitor water quality. The results of our study include: (1) the Water Quality Index (WQI) that was used to evaluate the water environment in Ebinur Lake indicates a lower water quality of Ebinur Lake, with a WQI value as high as 4000; (2) an introduction of the spectral derivative method that realizes the extraction of spectral information from a water body to better mine the information of spectral data through remote sensing, and the results also prove that the spectral derivative method can improve the relationship between the water body spectral and WQI, whereby R2 is 0.6 at the most sensitive wavelengths; (3) the correlation between the spectral sensitivity index and WQI was greater than 0.6 at the significance level of 0.01 when multi-source spectral data were integrated with the spectral index (DI, RI and NDI) and fluorescence baseline; and (4) the distribution map of WQI in Ebinur Lake was obtained by the optimal model, which was constructed based on the third derivative data of Sentinel 2 data. We concluded that the water quality in the northwest of Ebinur Lake was the lowest in the region. In conclusion, we found that remote sensing techniques were highly effective and laid a foundation for water quality detection in arid areas.

The inter-blade passage vortex, the vortex rope of the draft tube, and the vortex in the guide apparatus are the characteristics of flow instability of the Francis turbine, which may lead to fatigue failure in serious cases. In the current study, in order to accurately capture the transient turbulent characteristics of flow under different conditions and fully understand the flow field and vortex structure, we conduct a simulation that adopts sliding grid technology and the large-eddy simulation (LES) method based on the wall-adapting local eddy viscosity (WALE) model. Using the pressure iso-surface method, the Q criterion, and the latest third-generation Liutex vortex identification method, this study analyzes and compares the inter-blade passage vortex, the vortex rope of the draft tube, and the outflow and vortex in the guide apparatus, focusing on the capture ability of flow field information by various vortex identification methods and the unique vortex structure under the condition of a small opening. The results indicate that the dependence of Liutex on the threshold is small, and the scale range of the flow direction vortex captured by Liutex is wider, but the ability of the spanwise vortex is relatively weak. The smaller the opening, the more disorderly the vortexes generated in each component and the more unstable the flow field. In the draft tube, the original shape of the vortex rope is destroyed due to the interaction between vortexes. Under the condition of a small opening, an inter-blade passage vortex is generated, affecting the efficient and stable operation of the turbine.