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Chimeric antigen receptor (CAR‐T) cell therapy is a newly developed immunotherapy strategy and has achieved satisfactory outcomes in the treatment of hematological malignancies. However, some adverse effects related to CAR‐T cell therapy have to be resolved before it is widely used in clinics as a cancer treatment. Furthermore, the application of CAR‐T cell therapy in the treatment of solid tumors has been hampered by numerous limitations. Therefore, it is essential to explore novel strategies to improve the therapeutic effect of CAR‐T cell therapy. In this review, we summarized the recently developed strategies aimed at optimizing the generation of CAR‐T cells and improving the anti‐tumor efficiency of CAR‐T cell therapy. Furthermore, the discovery of new targets for CAR‐T cell therapy and the combined treatment strategies of CAR‐T cell therapy with chemotherapy, radiotherapy, cancer vaccines and nanomaterials are highlighted.

Objectives The current clinical pulse lavage technique for flushing fresh osteochondral allografts (OCAs) to remove immunogenic elements from the subchondral bone is ineffective. This study aimed to identify the optimal method for removing immunogenic elements from OCAs. Methods We examined five methods for the physical removal of immunogenic elements from OCAs from the femoral condyle of porcine knees. We distributed the OCAs randomly into the following seven groups: (1) control, (2) saline, (3) ultrasound, (4) vortex vibration (VV), (5) low‐pulse lavage (LPL), (6) high‐pulse lavage (HPL), and (7) high‐speed centrifugation (HSC). OCAs were evaluated using weight measurement, micro‐computed tomography (micro‐CT), macroscopic and histological evaluation, DNA quantification, and chondrocyte activity testing. Additionally, the subchondral bone was zoned to assess the bone marrow and nucleated cell contents. One‐way ANOVA and paired two‐tailed Student's t‐test are used for statistical analysis. Results Histological evaluation and DNA quantification showed no significant reduction in marrow elements compared to the control group after the OCAs were treated with saline, ultrasound, or VV treatments; however, there was a significant reduction in marrow elements after LPL, HPL, and HSC treatments. Furthermore, HSC more effectively reduced the marrow elements of OCAs in the middle and deep zones compared with LPL (p

Abstract Objective The purpose of the study is to construct meaningful nomogram models according to the independent prognostic factor for metastatic pancreatic cancer receiving chemotherapy. Methods This study is retrospective and consecutively included 143 patients from January 2013 to June 2021. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) is utilized to determine the optimal cut‐off value. The Kaplan–Meier survival analysis, univariate and multivariable Cox regression analysis are exploited to identify the correlation of inflammatory biomarkers and clinicopathological features with survival. R software are run to construct nomograms based on independent risk factors to visualize survival. Nomogram model is examined using calibration curve and decision curve analysis (DCA). Results The best cut‐off values of 966.71, 0.257, and 2.54 for the systemic immunological inflammation index (SII), monocyte‐to‐lymphocyte ratio (MLR), and neutrophil‐to‐lymphocyte ratio (NLR) were obtained by ROC analysis. Cox proportional‐hazards model revealed that baseline SII, history of drinking and metastasis sites were independent prognostic indices for survival. We established prognostic nomograms for primary endpoints of this study. The nomograms' predictive potential and clinical efficacy have been evaluated by calibration curves and DCA. Conclusion We constructed nomograms based on independent prognostic factors, these models have promising applications in clinical practice to assist clinicians in personalizing the management of patients.

Abstract Chloroplasts play a vital role in plant growth and development, which are the main sites of photosynthesis and the production of hormones and metabolites. Despite their significance, the regulatory mechanisms governing chloroplast development remain unclear. In our investigation, we identified a rice mutant with defective chloroplasts in rice (Oryza sativa L.), named albino lethal 13 (osal13), which displayed a distinct albino phenotype in leaves, ultimately resulting in seedling lethality. Molecular cloning revealed that OsAL13 encodes a novel rice protein with no homologous gene or known conserved domain. This gene was located in the chloroplast and exhibited constitutive expression in various tissues, particularly in green tissues and regions of active cell growth. Our study's findings reveal that RNAi‐mediated knockdown of OsAL13 led to a pronounced albino phenotype, reduced chlorophyll and carotenoid contents, a vesicle chloroplast structure, and a decrease in the expression of chloroplast‐associated genes. Consequently, the pollen fertility and seed setting rate were lower compared with the wild type. In contrast, the overexpression of OsAL13 resulted in an increased photosynthetic rate, a higher total grain number per panicle, and enhanced levels of indole‐3‐acetic acid (IAA) in the roots and gibberellin A3 (GA3) in the shoot. These outcomes provide new insights on the role of OsAL13 in regulating chloroplast development in rice.

Abstract Objective We aimed to reveal the role of structural and functional alterations of cingulate gyrus in early cognitive impairment in Type 2 diabetes mellitus (T2DM) patients. Methods Fifty‐six T2DM patients and 60 healthy controls (HCs) underwent a neuropsychological assessment and sagittal three‐dimensional T1‐weighted and resting‐state functional MRI. Differences in the cortical thickness of the cingulate cortex and the functional connectivity (FC) of the nine subregions of the cingulate gyrus and the whole brain were compared between T2DM patients and HCs. Correlation analysis was performed between cortex thickness and FC and the participants' clinical/cognitive variables. Results The cortical thickness of the cingulate gyrus was not significantly different between T2DM patients and HCs. However, the T2DM patients showed significantly lower FC between the pregenual ACC (pACC) and the bilateral hippocampus, significantly higher FC between the pACC and bilateral lateral prefrontal cortex (LPFC) and left precentral gyrus, and significantly lower FC between the retrosplenial cortex (RSC) and right cerebellar Crus I. The FC between the pACC and the left hippocampus was negatively correlated with the FC between the pACC and LPFC (r = −0.306, p = 0.022). Interpretation The pACC and the RSC show dysfunctional connectivity before the appearance of structural abnormalities in T2DM patients. Abnormal FC of the pACC with the bilateral hippocampus and LPFC may imply a neural compensatory mechanism for memory function. These findings provide valuable information and new directions for possible interventions for the T2DM‐related cognitive impairment.

Abstract Despite an alarming increase in the prevalence of hypertension among Chinese young adults, longitudinal studies investigating factors that affect the maintenance of normal blood pressure (BP) in this population are lacking. Our study aimed to address this knowledge gap. A total of 7100 participants from the Kailuan Study who had normal BP and were aged

Abstract INTRODUCTION The precise apolipoprotein E (APOE) ε4‐specific molecular pathway(s) for Alzheimer's disease (AD) risk are unclear. METHODS Plasma protein modules/cascades were analyzed using weighted gene co‐expression network analysis (WGCNA) in the Alzheimer's Disease Neuroimaging Initiative study. Multivariable regression analyses were used to examine the associations among protein modules, AD diagnoses, cerebrospinal fluid (CSF) phosphorylated tau (p‐tau), and brain glucose metabolism, stratified by APOE genotype. RESULTS The Green Module was associated with AD diagnosis in APOE ε4 homozygotes. Three proteins from this module, C‐reactive protein (CRP), complement C3, and complement factor H (CFH), had dose‐dependent associations with CSF p‐tau and cognitive impairment only in APOE ε4 homozygotes. The link among these three proteins and glucose hypometabolism was observed in brain regions of the default mode network (DMN) in APOE ε4 homozygotes. A Framingham Heart Study validation study supported the findings for AD. DISCUSSION The study identifies the APOE ε4–specific CRP–C3–CFH inflammation pathway for AD, suggesting potential drug targets for the disease. Highlights Identification of an APOE ε4 specific molecular pathway involving blood CRP, C3, and CFH for the risk of AD. CRP, C3, and CFH had dose‐dependent associations with CSF p‐Tau and brain glucose hypometabolism as well as with cognitive impairment only in APOE ε4 homozygotes. Targeting CRP, C3, and CFH may be protective and therapeutic for AD onset in APOE ε4 carriers.

Abstract After fertilization, sperm and oocyte fused and gave rise to a zygote which is the beginning of a new life. Then the embryonic development is monitored and regulated precisely from the transition of oocyte to the embryo at the early stage of embryogenesis, and this process is termed maternal‐to‐zygotic transition (MZT). MZT involves two major events that are maternal components degradation and zygotic genome activation. The epigenetic reprogramming plays crucial roles in regulating the process of MZT and supervising the normal development of early development of embryos. In recent years, benefited from the rapid development of low‐input epigenome profiling technologies, new epigenetic modifications are found to be reprogrammed dramatically and may play different roles during MZT whose dysregulation will cause an abnormal development of embryos even abortion at various stages. In this review, we summarized and discussed the important novel findings on epigenetic reprogramming and the underlying molecular mechanisms regulating MZT in mammalian embryos. Our work provided comprehensive and detailed references for the in deep understanding of epigenetic regulatory network in this key biological process and also shed light on the critical roles for epigenetic reprogramming on embryonic failure during artificial reproductive technology and nature fertilization.

Abstract Chinese herbal medicines (CHM) have been used to cure diseases for thousands of years. However, the bioactive ingredients of CHM are complex, and some CHM natural products cannot be directly absorbed by humans and animals. Moreover, the contents of most bioactive ingredients in CHM are low, and some natural products are toxic to humans and animals. Fermentation of CHM could enhance CHM bioactivities and decrease the potential toxicities. The compositions and functions of the microorganisms play essential roles in CHM fermentation, which can affect the fermentation metabolites and pharmaceutical activities of the final fermentation products. During CHM fermentation, probiotics not only increase the contents of bioactive natural products, but also are beneficial for the host gut microbiota and immune system. This review summarizes the advantages of fermentation of CHM using probiotics, fermentation techniques, probiotic strains, and future development for CHM fermentation. Cutting‐edge microbiome and synthetic biology tools would harness microbial cell factories to produce large amounts of bioactive natural products derived from CHM with low‐cost, which would help speed up modern CHM biomanufacturing.

Abstract While regular exercise exposure is considered the most effective therapy to reduce arterial stiffness, the effect of acute exercise training on arterial stiffness in adults with different blood pressure (BP) levels remains unclear. The authors aimed to investigate the effects of acute aerobic exercise on arterial stiffness in male with different BP levels. This cross‐sectional study utilized data for 1200 males aged 20–49 years from the Kailuan study cohort who participated in the fifth National Fitness Monitoring project. A total of 940 participants (621 in the non‐hypertensive group and 319 in the hypertensive group) aged 36.82 ± 7.76 who completed a twice‐quantitative cycle ergometer exercise and measure of brachial‐ankle pulse wave velocity (baPWV) at both the baseline and immediately after exercise were included in this study. The baPWV was decreased after acute aerobic exercise in the non‐hypertension and hypertension groups (Δ 40.29 [95% confidence interval [CI], −47.72 to −32.86] vs. Δ20.45 [95% CI, −31.32 to −9.58] cm/s). Participants without hypertension showed a greater decrease in baPWV (Δ 19.84 [95% CI, −33.83 to −5.84] cm/s) than participants with hypertension. Aerobic exercise had an acute positive effect on arterial stiffness. This study provides evidence of a greater reduction in arterial stiffness in individuals without hypertension than in those with hypertension.

With the continuous development of society and economy, energy consumption and exhaust emissions of high-speed trains have also gained more and more attention from the industry. Hence, optimizing the operation of high-speed trains is of pivotal significance to achieve optimization as required. On the basis of the intelligent robot palletizer technology, a spatial construction method and intelligent robot palletizer capable of operating through the dispatching of high-speed trains are put forward in this paper on the basis of the situation of high-speed trains assigned. The method of changing the arrival time of the trains and the order of departure are adopted to control the operation of the high-speed trains in an efficient and intelligent manner. With regard to the intervals of departure time, the overtaking of trains and other issues, a three-dimensional spatial travel route is established and used for processing. The intelligent robot palletizer is used to implement the dispatching of trains in the aspect of height. Subsequently, the minimum value method and secure network technology are used to verify that the technology of the intelligent robot palletizer is mature and reliable. Finally, a practical case analysis is carried out in this paper on some sections of the Harbin–Dalian high-speed railway to verify the accuracy and effectiveness of the method proposed in this paper. Through the comparative analysis with other methods, the advantages of the algorithm put forward in this paper can be observed.

Objective. This study is aimed at discussing the value of RNA interference technology on inhibiting lacrimal gland fibrosis in IgG4-related ocular disease (IgG4-ROD). Methods. Six patients with IgG4-ROD who came to the hospital for surgical treatment from October 2018 to August 2019 were selected, and their diseased lacrimal glands were taken for primary cell culture and fibroblast identification. High efficiency and specificity small interference RNA (siRNA) plasmid vector was constructed, its inhibitory effect on fibroblast proliferation was determined by CCK-8 assay, and the appropriate concentration was selected as the siRNA concentration for subsequent experiments. RT-PCR and Western blot detected the relative expression levels of Fibulin-5 mRNA and protein in the cells 48 hours after transfection. The apoptosis rate of each group of cells at 24 hours, 48 hours, and 72 hours after transfection was detected by flow cytometry, and the proliferation and apoptosis of cells after silencing Fibulin-5 were analyzed and compared. Results. 24 hours after transfection, there was no significant difference in the proliferation rate among the four groups (P>0.05); 48 hours and 72 hours after Fibulin-5 siRNA transfection, the proliferation activity of the transfected cells was significantly decreased compared with the 0 nM group, and the inhibitory effect of 75 nM siRNA was the strongest. The expression of Fibulin-5 mRNA and protein in the siRNA-transfected cells was significantly decreased compared with the blank and empty vector negative siRNA groups, and the difference was statistically significant (P

Abstract Background To investigate the efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non‐small cell lung cancer (NSCLC) through pooling of open published data. Methods The electronic databases of Medline (1960–2021.5), Cochrane central register of controlled trials (CENTRAL), EMBASE(1980–2021.5) and Wan fang (1986–2021.5) were systematically searched by two reviewers to identify the relevant clinical trials related to the above subject. The objective response rate (ORR), disease control rate (DCR) and drug relevant adverse reactions were pooled and demonstrated by risk ratio (RR) and 95% confidence interval (95% CI). The statistical heterogeneity across studies was assessed by I‐square test. The publication bias was evaluated by Egger's line regression test and demonstrated by Begg's funnel plot. Results Eleven prospective studies were included in the meta‐analysis. The pooled results indicated that the ORR (RR = 1.62, 95% CI: 1.32–2.00, p 0.05) except for hypertension (RR = 3.60, 95% CI: 1.26–10.31, p

Abstract Introduction Type 2 diabetes mellitus (T2DM) is a chronic disease with a high incidence worldwide. T2DM can cause cognitive impairment, but its neuropathological basis is unclear. A variety of neuropsychiatric studies have found that abnormal functional connectivity (FC) in the central executive network (CEN), default‐mode network (DMN), and salience network (SN) may be the neuropathological basis of cognitive dysfunction. The right dorsal anterior insula (dAI) is the core SN area. It plays an important role in regulating the CEN and the DMN. However, few studies have explored the relationship between cognitive impairment and FC among the right dAI, CEN, and DMN in patients with T2DM. Methods Resting‐state functional magnetic resonance imaging was used to investigate FC between the right dAI and the CEN and DMN in 44 patients with T2DM and 41 sex‐, age‐, and education‐matched healthy controls, as well as its relationship with clinical/cognitive variables. Results In patients with T2DM, FC between the right dAI and multiple brain regions of the CEN and DMN was generally decreased, and FC strength between the right dAI and the inferior frontal gyrus negatively correlated with trail making test A score (r = −0.421, p = 0.004). Conclusions Patients with T2DM exhibit abnormal FC between the right dAI and the CEN and DMN. This may be one of the neuromechanisms of cognitive impairment in patients with T2DM. In addition, reduced FC between the right dAI and the right inferior frontal gyrus may be related to abnormal attention regulation in patients with T2DM.

Ischemic stroke is a major condition that remains extremely problematic to treat. A cerebral reperfusion injury becomes apparent after an ischemic accident when reoxygenation of the afflicted area produces pathological side effects that are different than those induced by the initial oxygen and nutrient deprivation insult. Pyroptosis is a form of lytic programmed cell death that is distinct from apoptosis, which is initiated by inflammasomes and depends on the activation of Caspase-1. Then, Caspase-1 mobilizes the N-domain of gasdermin D (GSDMD), resulting in the release of cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). X-box binding protein l (XBP-1) is activated under endoplasmic reticulum (ER) stress to form an important transcription factor XBP-1 splicing (XBP-1s). The cerebral ischemia/reperfusion (CI/R) causes cytotoxicity, which correlates with the activation of splicing XBP-1 mRNA and NLRP3 (NOD-, LRR-, and pyrin domain-containing 3) inflammasomes, along with increases in the expression and secretion of proinflammatory cytokines and upregulation of pyroptosis-related genes in HT22 cells and in the middle cerebral artery occlusion (MCAO) rat model. However, whether XBP-1 plays a role in regulating pyroptosis involved in CI/R is still unknown. Our present study showed that behavior deficits, cerebral ischemic lesions, and neuronal death resulted from CI/R. CI/R increased the mRNA level of XBP-1s, NLRP3, IL-1β, and IL-18 and the expressions of XBP-1s, NLRP3, Caspase-1, GSDMD-N, IL-1β, and IL-18. We further repeated this process in HT22 cells and C8-B4 cells and found that OGD/R decreased cell viability and increased LDH release, XBP-1s, NLRP3, Caspase-1, GSDMD-N, IL-1β, IL-18, and especially the ratio of pyroptosis, which were reversed by Z-YVAD-FMK and downregulated XBP-1. Our results suggest that downregulated XBP-1 inhibited pyroptosis through the classical NLRP3/Caspase-1/GSDMD pathway to protect the neurons.

Purpose. Concurrent chemoradiotherapy (CCRT) has been widely applied to locally advanced cervical cancer (LACC) patients, inducing the massive release of antigen and systematic immunomodulatory effects. However, its effect on the soluble immune checkpoint proteins (sICPs) remains unclear, which might play a key role in the immune response. Therefore, the current study explored changes in the levels of 16 sICPs in LACC patients during CCRT. Methods. We prospectively enrolled fifty-one LACC patients treated with CCRT and collected patients’ blood before, during and after CCRT. The levels of 16 sICPs were measured using the Luminex platform, and the changes were measured using Friedman test with Bonferroni’s posttest. One month after CCRT, the tumor response was evaluated according to the RECIST 1.1 guidelines. Results. The levels of soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) significantly increased during CCRT (P=0.041), while those of the soluble B and T lymphocyte attenuator (sBTLA), sCD40, soluble glucocorticoid-induced tumor necrosis factor receptor ligand (sGITRL), sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and soluble inducible T-cell costimulator (sICOS) significantly increased after CCRT (all P0.05). 41 (80%), 8 (16%), and 2 (4%) patients showed complete response (CR), partial response (PR), and stable disease (SD) after CCRT, respectively. Interestingly, the level of soluble lymphocyte-activation gene 3 (sLAG-3) was significantly higher among the PR/SD patients as compared to the CR after CCRT (P=0.009). Conclusions. This study revealed that CCRT might elevate the serum levels of sTIM-3, sBTLA, sCD40, sGITRL, sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and sICOS in the patients with LACC. The sLAG-3 level was higher in the patients with poor response to CCRT. These findings revealed the dynamic changes in the sICPs levels during CCRT, which might be helpful in designing optimal treatment strategies for LACC patients.

In the process of stimulated reservoir volume of tight reservoir, horizontal well can form three zones, the inner zone is multistage fracturing zone, the middle zone is skin damage zone, and the outer zone is undamaged zone. In this paper, a transient well test analysis model of multistage fracturing horizontal well in three area composite reservoir is proposed. Based on Laplace transformation, point source integration, and superposition principle, the infinite conductivity multifracture model of three area composite reservoir is obtained. The linear equations of finite conductivity multifracture in Laplace space are established by using the equal conditions of flow and pressure at the fracture wall. Gauss-Newton iteration method and Stehfest number are used to obtain the solution of wellbore pressure. The accuracy of the results is verified by numerical simulation. Then, the flow characteristics of multistage fracturing horizontal wells in three area composite reservoirs are analyzed by type curves. The flow is divided into ten stages, which are the bilinear flow, the linear flow, the first radial flow stage, the inner zone linear flow, the inner zone radial flow, the middle zone linear flow, the middle zone radial flow, the outer zone linear flow, the outer zone radial flow, and the boundary dominated flow. The pressure derivative curves show different characteristics in different flow stages. The influences of fracture conductivity, fracture spacing, radius ratio of the middle zone to inner zone, radius ratio of the outer zone to the middle zone, permeability ratio of inner zone to the middle zone, permeability ratio of inner zone to outer zone, storage capacity ratio of inner zone to the middle zone, and storage capacity ratio of inner zone to outer zone on type curves are analyzed. Finally, the application and reliability of the proposed model are verified by a case example.

A bottom water reservoir is universal in all reservoirs in the world. In the exploitation process of the bottom water reservoir, because the reservoir is in complete contact with bottom water, the natural energy supply of the bottom water reservoir is sufficient. At the same time, in the production process, the pressure drop generated by the formation is mainly concentrated near the wellbore, which leads to a short period of waterless oil production, fast water breakthrough, and fast water cut rise, which seriously affects the overall recovery factor and increases the risk of oil filed exploitation. Since the distribution of an interlayer enhances the heterogeneity of the reservoir, it has a prominent impact on the flow of oil and water in the bottom water reservoir. However, people know little about the impact of the interlayer on the bottom water reservoir. In this paper, the mathematical model of two-phase flow in the bottom water reservoir with the interlayer is proposed, and the numerical solution of the model is obtained by a finite element method. The influence of the distribution of the interlayer on the water cut rising law of the bottom water reservoir is analyzed. The results show that the bottom water is blocked by the interlayer and its own gravity and the rising height of the bottom water is limited, so that the interlayer has a significant inhibitory effect on the coning of the bottom water. The closer the interlayer is to the oil-water interface, the faster the water cut will rise; the narrower the interlayer is, the faster the bottom water ridge will advance; when the width of the interlayer is the same as that of the reservoir, the water cone will not appear; the higher the permeability of the interlayer is, the faster the upper body of the water cut will be; when the permeability of the reservoir and the interlayer is over 1000, the influence of the interlayer on the water cut rise is not obvious; the thickness of the interlayer on the water cut rise law has little effect. Finally, through the case analysis, it is proposed that the new horizontal wells should be arranged in the position where the interlayer develops. The findings of this study can help for the better understanding of control laws of the interlayer on the bottom water and providing a crucial theoretical basis for the development of the bottom water reservoir.

We recently showed that inhibition of hypoxia-induced factor-1α (HIF-1α) decreased acute ischemic stroke-induced blood-brain barrier (BBB) damage. However, factors that induce the upregulation of HIF-1α expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a critical role in reperfusion-induced BBB damage after stroke. However, the role of NADPH oxidase in BBB injury during the acute ischemia stage remains unclear. This study is aimed at investigating the role of NADPH oxidase in BBB injury and the expression of HIF-1α after acute ischemic stroke. A sutured middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke in rats. Our results show that the inhibition of NADPH oxidase by apocynin can significantly reduce the BBB damage caused by 2 h ischemic stroke accompanied by reducing the degradation of tight junction protein occludin. In addition, treatment with apocynin significantly decreased the upregulation of HIF-1α induced by 2 h MCAO. More importantly, apocynin could also inhibit the MMP-2 upregulation. Of note, HIF-1α was not colocalized with a bigger blood vessel. Taken together, our results showed that inhibition of NADPH oxidase-mediated HIF-1α upregulation reduced BBB damage accompanied by downregulating MMP-2 expression and occludin degradation after 2 h ischemia stroke. These results explored the mechanism of BBB damage after acute ischemic stroke and may help reduce the associated cerebral hemorrhage transformation after thrombolysis and endovascular treatment after ischemic stroke.

Abstract Objective To explore the neural mechanisms of brain impairment in type 2 diabetes mellitus (T2DM), abnormal changes to the functional connections between brain regions in the resting state were investigated based on a meta‐analysis. Methods Resting‐state functional magnetic resonance imaging (fMRI) and neuropsychological assessment were performed on 38 patients with T2DM and 33 healthy controls (HCs). Functional connectivity between regions based on a meta‐analysis and other voxels in the brain was calculated and compared between the two groups using a two‐sample t test. A correlation analysis was conducted between clinical/cognitive variables and functional connection values from the regions with significant differences in the above comparison. Results Patients in the T2DM group showed a significantly decreased functional connection between the right posterior cerebellum and the right middle/inferior occipital gyrus, left middle temporal gyrus, left superior frontal gyrus, left middle frontal gyrus, left insula, left precuneus, and right paracentral lobule/left precuneus when compared with HC group. The functional connection values between the right insula and left medial frontal gyrus, left supplementary motor area, and between the left lingual gyrus and right middle/inferior occipital gyrus in patients with T2DM were significantly decreased. Moreover, the functional connection values between the right posterior cerebellum and left middle frontal gyrus, and between the right posterior cerebellum and left precuneus were negatively correlated with HbA1c in the T2DM group (r = −.356, p = .03; r = −.334, p = .043). Conclusions Our study showed a wide range of cerebellar–cerebral circuit abnormalities in patients with T2DM, which provides a new direction to investigate the neuropathological mechanisms of T2DM from the perspective of the cerebellum.

Abstract Introduction Previous voxel‐based morphometry (VBM) studies have revealed changes in brain structure in patients with vestibular migraine (VM); these findings have improved the present understanding of pathophysiology. Few other studies have assessed the association between structural changes and the severity of dizziness in VM. This study aimed to examine the structural changes and cortical morphometric features associated with migraine and vertigo attacks in patients with VM. Methods Twenty patients with VM and 20 healthy normal volunteers were scanned on a 3‐tesla MRI scanner. The gray matter volume (GMV) was estimated using the automated Computational Anatomy Toolbox (CAT12). The relationship between clinical parameters and morphometric abnormalities was also analyzed in VM. Results Compared with controls, VM patients have decreased GMV in the prefrontal cortex (PFC), posterior insula–operculum regions, inferior parietal gyrus, and supramarginal gyrus. Moreover, patient scores on the Dizziness Handicap Inventory (DHI) score showed a negative correlation with GMV in the posterior insula–operculum regions. Conclusion These findings demonstrated abnormality in the central vestibular cortex and correlations between dizziness severity and GMV in core regions of the vestibular cortex of VM patients, suggesting a pathophysiological role of these core vestibular regions in VM patients.

In this paper, a new rate decline analysis model of horizontal wells with variable conductivity and uneven distribution of multiple fractures is proposed. By Laplace transformation, point source integration, and superposition principle, solutions of multiple infinite conductivity fractures in closed reservoirs are obtained. By coupling Fredholm integral equation of variable conductivity, linear equations of variable conductivity fractures in Laplace space are obtained. Gauss-Newton iteration, Duhamel convolution, and Stehfest numerical inversion method are used to obtain the bottom hole production solution. The accuracy of the results is verified by comparing with Eclipse software simulation. Then, the influence of some important reservoir and fracture parameters on the production is analyzed. The calculative results show that the smaller the fracture spacing is, the earlier the fracture begins to decline, the more the production will decrease; the change of different fracture length with the total fracture length unchanged has almost no effect on the production; the angle between fracture and x-axis has an important effect on the production; the smaller the angle between fracture and x-axis is, the stronger the interference between fractures is, the higher the production; the initial fracture conductivity affects the early production behavior, and the higher the initial fracture conductivity, the higher the production; the larger the fracture declines index, the lower the production, but the decreasing range gradually decreases with the increase of the decline index; the larger the reservoir drainage radius, the later the energy depletion stage, the higher the production. At last, a good fitting effect is obtained by fitting an example of oil field. The model proposed in this paper enriches the model base of rate decline analysis of fractured horizontal wells and lays a theoretical foundation for efficient development and practice of tight reservoirs.

The distance Laplacian matrix of a connected graph G is defined as ℒG=TrG−DG, where DG is the distance matrix of G and TrG is the diagonal matrix of vertex transmissions of G. The largest eigenvalue of ℒG is called the distance Laplacian spectral radius of G. In this paper, we determine the graphs with maximum and minimum distance Laplacian spectral radius among all clique trees with n vertices and k cliques. Moreover, we obtainn vertices and k cliques.

Abstract Our previous studies revealed that the level of activated circulating endothelial cells (aCECs) was correlated with the progression‐free survival (PFS) in antiangiogenesis therapy. Anlotinib displayed affirmatory efficacies in several clinical trials of non‐small‐cell lung cancer (NSCLC). To find a marker predicting the efficacy of anlotinib treatment, we investigated the correlations of aCECs with PFS and overall survival (OS) in patients with NSCLC treated with anlotinib and the impact of anlotinib on human umbilical vascular endothelial cells (HUVECs). The blood samples of 78 patients with NSCLC were collected. aCECs were identified by flow cytometry as CD45−/CD146+/CD31+ cells and CD45−/CD146+/CD105+ cells. The mean value of baseline aCECs counts was defined as the cutoff value, according to which patients were divided into high and low baseline groups. Statistical correlation between high baseline CD31‐labeled aCECs counts and number of metastatic lesions (>3) (χ2 = 4.905, P = .027) was analyzed. The 49 patients treated with anlotinib were stratified according to the ratio of minimal aCECs counts at any time points to baseline (aCECs min/baseline) as

Small multi-rotor unmanned aerial vehicles (SMR-UAVs) are a promising platform for low-cost synthetic aperture radar (SAR) systems. However, SMR-UAVs usually suffer from serious position errors due to their unstable motion and low actuary position sensors, and autofocus is an indispensable step for their high-quality imaging. An efficient back-projection autofocus method is proposed for SMR-UAV SAR systems by the principle of minimum entropy. The position error estimation model via minimum entropy is derived. The conjugate-gradient method is used to efficiently estimate the position errors. Moreover, to improve the computing efficiency, the strong scatterer areas are estimated as the input of entropy estimation. The effectiveness of the algorithm is demonstrated using both simulation and experimental data.

Background Disrupted circadian rhythm of blood pressure is commonly observed in patients in the intensive care unit (ICU). This study assessed the association of nocturnal mean arterial pressure rising (NMAPR) with short‐ and long‐term mortality in critically ill adult patients. Methods and Results Adult patients with a complete record of mean arterial pressure monitoring during the first 24 hours of ICU stay in the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC‐II) database were included in this retrospective cohort study. All patients were divided into the non‐NMAPR group (≤1) or the NMAPR group (>1), according to the value of mean nighttime divided by daytime mean arterial pressure. The associations of NMAPR with ICU, hospital, 28‐day, and 1‐year mortality were assessed using multivariable logistic regression or a Cox proportional hazards model. Interaction and subgroup analyses were performed for those patients who had a first Sequential Organ Failure Assessment (SOFA) score of ≥8 or

A novel method for synthetic aperture radar (SAR) three-dimensional (3D) sparse imaging based on a coprime linear array (CLA) is proposed. To reduce the geometric resolution loss caused by under-sampled sparse SAR, a jointed sparse imaging approach is used. In this scheme, the coprime sampled data of CLA is separately processed via the iterative reweight least-squares approach, and their recovered results are combined to cancel the false targets and grating-lobes to improve the imaging quality. Both simulated and experimented results demonstrate the effectiveness of the method. It shows that the exploiting of CLA and sparse recovery can significantly reduce the linear array antenna amount and the geometric resolution loss compared with the conventional uniform linear array SAR.

Background Socioeconomic status (SES) is associated with health‐related quality of life (HRQOL) for children with critical congenital heart disease; however, literature from newly industrialized countries is scarce. Methods and Results This cross‐sectional study included 2037 surviving patients operated on for critical congenital heart disease at a tertiary hospital in China between May 2012 and December 2015. All eligible patients were aged 2 to 12 years. HRQOL was measured by the Pediatric Quality of Life Inventory 4.0 generic and 3.0 cardiac modules. Family SES was assessed by a composite of household income in the past year and occupation and education level of each parent in the family. Mean scores of major domains in HRQOL were significantly lower in the low‐SES group than in the medium‐ and high‐SES groups (total generic scores: 71.2±7.9 versus 75.0±8.0 and 76.0±7.9, respectively [P

The excessive use of inputs per unit of agricultural land poses a great threat to ecological sustainability. Using an input-oriented data envelopment analysis (DEA) model, this study analyzes ecoefficiency of intensive agricultural production in 31 provinces in China. The results show that the total efficiency of only six provinces can be considered fully efficient and that scale efficiencies are generally lower than technical efficiencies. Then, the spatial distribution of ecoefficiency is analyzed. The findings demonstrate that the provinces whose ecoefficiencies are maximal are primarily located in western China. The technical efficiencies in the western region are better than those in the eastern and middle regions. Imperfect scale efficiencies are distributed across all three regions. Furthermore, using the Tobit model, an analysis of the factors that influence ecoefficiency shows that the variables of farmland area per capita (FA), income per capita (IC), population per household (PH), and population burden coefficient (PB) have statistically significant impacts on total efficiency. The distinct effects of the variables on total efficiency are caused by their differential effects on technical efficiency and scale efficiency. Finally, suitable policies designed to improve ecoefficiency are proposed according to the local circumstances of each of the three regions.

This paper is concerned with transmission rate and control codesign of wireless sensor networked control systems (WSNCS) with time-varying delay. Jointly designing transmission rate and control is an attractive paradigm for WSNCS, since the control performance of WSNCS is highly sensitive to resource-constrained communication networks. The main idea of devised scheme is searching an optimal event-triggered transmission condition on the premise that wireless link capacity constraint is satisfied and stability of systems is guaranteed. The main aim of devised scheme is to greatly optimize control performance of WSNCS. First, two wireless network architectures characterized by multihop and star topology are put forward. Secondly, a model of WSNCS with event-triggered transmission mechanism is constructed. It is followed by stability analysis of WSNCS to obtain the asymptotical stability condition of systems. And then a search algorithm is presented for transmission rate and control codesign. Finally, numerical examples are given to illustrate the effectiveness of the proposed method.

The distributed strategy of Collaborative Optimization (CO) is suitable for large-scale engineering systems. However, it is hard for CO to converge when there is a high level coupled dimension. Furthermore, the discipline objectives cannot be considered in each discipline optimization problem. In this paper, one large-scale systems control strategy, the interaction prediction method (IPM), is introduced to enhance CO. IPM is utilized for controlling subsystems and coordinating the produce process in large-scale systems originally. We combine the strategy of IPM with CO and propose the Interaction Prediction Optimization (IPO) method to solve MDO problems. As a hierarchical strategy, there are a system level and a subsystem level in IPO. The interaction design variables (including shared design variables and linking design variables) are operated at the system level and assigned to the subsystem level as design parameters. Each discipline objective is considered and optimized at the subsystem level simultaneously. The values of design variables are transported between system level and subsystem level. The compatibility constraints are replaced with the enhanced compatibility constraints to reduce the dimension of design variables in compatibility constraints. Two examples are presented to show the potential application of IPO for MDO.

Let D denote the distance matrix of a connected graph G. The inertia of D is the triple of integers (n+(D), n0(D), n-(D)), where n+(D), n0(D), and n-(D) denote the number of positive, 0, and negative eigenvalues of D, respectively. In this paper, we mainly study the inertia of distance matrices of some graphs related to wheel graphs and give a construction for graphs whose distance matrices have exactly one positive eigenvalue.

Increased mobility coupled with a possible reduction of cabling costs and deployment time makes wireless communication an attractive alternative for the industrial process monitoring and control. The major obstacles toward the utilization of wireless industrial networks are predominantly the timeliness and reliability requirements. In this paper, orienting to clustered industrial wireless sensor networks, we analyze the performance bounds of the convergecast scheduling, which is a typical many-to-one communication in wireless industrial networks. The analysis aims to the cluster-line and cluster-tree topologies. Each kind is future divided into three scenarios according to an application parameter, named data update rate. Firstly, we establish the lower bounds on the number of timeslots to finish the intracluster and the intercluster convergecast transmissions. Secondly, we establish the lower bounds on the number of channels based on the lower bounds on the number of timeslots and maximum available channels in a multichannel scenario. Lastly, we carry out the extensive analysis-taking packet retransmissions into consideration so as to meet the reliability requirement. Experiment results validate the correctness and tightness of our theory analysis.