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IMPORTANCE: Early onset of myopia increases the risk of high myopia, which can lead to irreversible retinal damage and even loss of central vision. OBJECTIVE: To investigate the efficacy and safety of naked-eye 3-dimensional vision training (NVT) in preventing the progression of myopia in children. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in 3 hospitals from May 25, 2022, to February 24, 2023. Participants were children (aged 6-18 years) who had a diagnosis of myopia with a spherical equivalent refraction of −0.75 to −6.00 diopters (D). INTERVENTION: Children in the intervention group received 20 minutes of NVT treatment every day, whereas children in the control group lived as usual without vision training. MAIN OUTCOME AND MEASURE: The primary outcome was the change in axial length at 6 months. Spherical equivalent refraction (SER) was included as a secondary outcome. RESULTS: Among 263 participants, 125 (47.5%) were male and 138 (52.5%) were female; the mean (SD) age was 10.3 (1.9) years (range, 6.1-15.6 years). A total of 227 patients (86.3%) completed the 6-month follow-up, including 102 in the intervention group and 125 in the control group. In the intervention group, the changes in axial length and SER at 6 months were 0.18 mm (95% CI, 0.16 to 0.20 mm) and −0.25 D (95% CI, −0.31 to −0.19 D), respectively. In the control group, the changes in axial length and SER at 6 months were 0.23 mm (95% CI, 0.21 to 0.25 mm) and −0.35 D (95% CI, −0.41 to −0.30 D), respectively. The differences in AL and SER between the 2 groups were significant (AL difference: −0.06 mm; 95% CI, −0.09 to −0.03; P < .001; SER difference: 0.10 D; 95% CI, 0.02 to 0.19; P = .02). No study-related adverse reactions were reported during follow-up. CONCLUSIONS AND RELEVANCE: NVT is a safe and promising means to control myopia progression in children with good adherence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05468775

In the treatment of unresectable advanced hepatocellular carcinoma (HCC), cisplatin is administered transhepatic arterially for local treatment, but the clinical application of cisplatin drugs is frequently hindered by the emergence of drug resistance. Kinesin family member 2C(KIF2C) has been shown as oncogene in a variety of tumors. Nevertheless, its effect on cisplatin sensitivity has yet to be ascertained. Herein, we aim to investigate the impact of the KIF2Cgene on cisplatin sensitivity within HCC and the plausible underlying molecular mechanism. We examined the expression level of the KIF2Cgene in HCC cells by real-time quantitative reverse transcription PCR and Western blot analysis, and analyzed bioinformatically by The Gene Expression Omnibus database and The Cancer Genome Atlas database. The KIF2Cgene was silenced using the small interfering RNA technology, and its effect on cisplatin drug sensitivity in HCC cells was evaluated by flow cytometry, cell proliferation, cell migration, and invasion assays. Our results indicated that KIF2Cwas highly expressed in HCC cells. KIF2Csilencing inhibits HCC cell proliferation, migration and invasion, promotes apoptosis, and keeps the cell cycle in G2 phase. In addition, KIF2Csilencing enhanced the sensitivity of HCC cells to cisplatin. KIF2Csilencing down-regulates the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mitogen-activated protein kinase 3 (MAPK3) proteins. In conclusion, KIF2Csilencing amplifies the sensitivity of HCC cells to cisplatin by regulating the PI3K/AKT/MAPK signaling pathway. Consequently, targeting KIF2Cshows great application potential as a strategy for enhancing the effectiveness of HCC treatment.

Episodic memory is fundamental to the brain’s cognitive function, but how neuronal activity is temporally organized during its encoding and retrieval is still unknown. In this article, combining hippocampus structure with a spiking neural network (SNN), a new bionic spiking temporal memory (BSTM) model is proposed to explore the encoding, formation, and retrieval of episodic memory. For encoding episodic memory, the spike-timing-dependent-plasticity (STDP) learning algorithm and a proposed minicolumn selection algorithm are used to encode each input item into several active minicolumns. For the formation of episodic memory, a sequential memory algorithm is proposed to store the contexts between items. For retrieval of episodic memory, the local retrieval algorithm and the global retrieval algorithm are proposed to retrieve sequence information, achieving multisentence prediction and multitime step prediction. All functions of BSTM are based on bionic spiking neurons, which have biological characteristics including columnar and dendritic structures, firing and receiving spikes, and delaying transmission. To test the performance of the BSTM model, the Children’s Book Test (CBT) data set was used to conduct a series of experiments under different settings, including changing the number of minicolumns, neurons and sequences, modifying sequence items, etc. Compared to other sequence memory algorithms, the experimental results show that the proposed BSTM achieves higher accuracy and better robustness.

PurposeTo evaluate the characteristics and associated factors of choroidal thickness (ChT) and choriocapillaris flow deficit percentage (CC FD%) in children with Marfan syndrome (MFS).MethodsThis is a cross-sectional study. The ChT of the subfoveal area and other areas 0.5, 1.5, and 2.5 mm away from the fovea were assessed. The CC FD% of quadrant and circular regions with diameters of 0.5, 1.5 and 2.5 mm were assessed with 3×3 mm macular choriocapillaris images. Best-corrected visual acuity (BCVA) and cardiac function factor such as Z score were measured to analyse the associations with ChT and CC FD%.Results51 MFS children and 50 healthy controls were enrolled in this study. Compared with the healthy controls, the ChT in the MFS group was thinner in the subfoveal area, temporal 0.5, 1.5 and 2.5 mm (all p<0.001). The CC FD% was higher in circle 0.5, 1.5 and 2.5 mm (all p<0.001). Multivariate regression analysis showed that CC FD% in the circle 2.5 mm when the Z score ≥2 was associated with BCVA (β=9.08 (95% CI 3.96 to 14.20); p=0.005) and Z score (β=4.19 (95% CI 1.28 to 12.00); p=0.012).ConclusionsThinner ChT and a higher CC FD% were observed in children with MFS, and an increased CC FD% in circle 2.5 mm was significantly associated with worse BCVA and cardiac function. These findings may help identify future visual impairment and early cardiac events in MFS children.

Most studies assume the ramp to be a single lane regardless of the possibility of multiple lanes on a freeway ramp. This assumption limits the application of previous ramp metering strategies in the real world. Therefore, this paper proposes a strategy for a centralized controller to efficiently merge connected automated vehicles from a multiple-lane ramp. The proposed strategy aims to allow vehicles from different lanes to pass through the conflict point with the objective of minimum delay and fuel consumption. Numerical experiments are carried out to compare the proposed strategy with first-in-first-out (FIFO) and Vissim built-in strategies. Simulation results indicate that the proposed strategy can reduce more delay than FIFO and Vissim-based strategies. Furthermore, the proposed strategy is also found to be the most reliable in various scenarios with different traffic demand splits, safe headways, and numbers of lanes.

The brain-inspired spiking neural networks (SNNs) hold the advantages of lower power consumption and powerful computing capability. However, the lack of effective learning algorithms has obstructed the theoretical advance and applications of SNNs. The majority of the existing learning algorithms for SNNs are based on the synaptic weight adjustment. However, neuroscience findings confirm that synaptic delays can also be modulated to play an important role in the learning process. Here, we propose a gradient descent-based learning algorithm for synaptic delays to enhance the sequential learning performance of single spiking neuron. Moreover, we extend the proposed method to multilayer SNNs with spike temporal-based error backpropagation. In the proposed multilayer learning algorithm, information is encoded in the relative timing of individual neuronal spikes, and learning is performed based on the exact derivatives of the postsynaptic spike times with respect to presynaptic spike times. Experimental results on both synthetic and realistic datasets show significant improvements in learning efficiency and accuracy over the existing spike temporal-based learning algorithms. We also evaluate the proposed learning method in an SNN-based multimodal computational model for audiovisual pattern recognition, and it achieves better performance compared with its counterparts.

Graphical abstract: The synergistic effect of GNPs and f-CNTs varies with the microstructural conductive network evolution at different filler ratios.

In this study, we found the vessel density and foveal avascular zone circularity index of superficial microvascular plexuses were significantly decreased in children with Marfan syndrome in comparison to the controls. Alterations of microvascular flow are associated with visual acuity, central macular thickness, aortic diameters, and left ventricular ejection fraction.

Trip purpose information plays a significant role in transportation systems. Existing trip purpose information is traditionally collected through human observation. This manual process requires many personnel and a large amount of resources. Because of this high cost, automated trip purpose estimation is more attractive from a data-driven perspective, as it could improve the efficiency of processes and save time. Therefore, a hybrid-data approach using taxi operations data and point-of-interest (POI) data to estimate trip purposes was developed in this research. POI data, an emerging data source, was incorporated because it provides a wealth of additional information for trip purpose estimation. POI data, an open dataset, has the added benefit of being readily accessible from online platforms. Several techniques were developed and compared to incorporate this POI data into the hybrid-data approach to achieve a high level of accuracy. To evaluate the performance of the approach, data from Chengdu, China, were used. The results show that the incorporation of POI information increases the average accuracy of trip purpose estimation by 28% compared with trip purpose estimation not using the POI data. These results indicate that the additional trip attributes provided by POI data can increase the accuracy of trip purpose estimation.

Purpose: The purpose of this study is to compare the lesion detection rates of ocular toxocariasis (OT) between ultra-wide-field scanning laser ophthalmoscopy (UWF-SLO) and conventional fundus photography (CFP), and to evaluate the potential diagnostic ability of UWF-SLO in OT. Methods: A total of 56 patients with serological/immunological confirmed unilateral OT were enrolled. The presence of OT characteristic features included the posterior granuloma (postG), peripheral granuloma (periG), tractional retinal detachment (TRD), retinal folds (RF), and vitreous strands (VS) and was analyzed in 36 patients with UWF-SLO and 56 patients with CFP. Diagnostic tests were employed using the clinical examination as gold standard. Results: In total of the 56 OT eyes, granulomas were identified in 91.1% (51/56) of eyes, including postG in 46.4% (26/56) of eyes, periG in 41.1% (23/56) of eyes, and combined granulomas in 3.6% (2/56) of eyes. TRD, RF, and VS were found in 28.6% (16/56), 51.8% (29/56), and 83.9% (47/56) of patients, respectively. Although the specificities of the diagnosis in clinical features were similar by the diagnostic tests, the sensitivities of postG, periG, TRD, RF, and VS using UWF-SLO were 100%, 100%, 66.7%, 95%, and 81.8%, respectively, which were significantly higher those of CFP (72.2%, 31.3%, 11.1%, 55%, and 48.5%). Additionally, the extent of vitreous haze was milder graded by UWF-SLO compared to CFP (p= 0.0099). Conclusions: The diagnostic ability of UWF-SLO was superior to CFP using clinical examination as gold standard for the ascertainment of the characteristic manifestations of OT, especially for granulomas and RF.

Recent studies have suggested that lincRNA-ROR is involved in the tumorigenesis of different types of cancers. However, the role of lincRNA-ROR in retinoblastoma has not been determined. We investigated lincRNA-ROR levels in 58 retinoblastoma and adjacent non-tumor tissues by quantitative reverse transcription PCR. Recurrence-free survival was analyzed using Cox regression analyses. Cell migration and invasion abilities were detected by wound-healing, Transwell invasion, and bioluminescence imaging assays. Western blotting was performed to detect epithelial–mesenchymal transition markers. Interactions between lincRNA-ROR, miR-32-5p, and Notch1 were confirmed by Luciferase, RNA pull-down, and RIP assays. Histone acetylation was detected by chromatin immunoprecipitation assays. We showed that lincRNA-ROR was significantly upregulated in retinoblastoma tissues, and overexpression of lincRNA-ROR was significantly correlated with optic nerve invasion, nodal or distant metastasis, and recurrence. We also showed that lincRNA-ROR is a critical promoter of retinoblastoma cell metastasis, both in vivo and in vitro. Further, we demonstrated that lincRNA-ROR activates the Notch signaling pathway by acting as a sponge of miR-32-5p. Upregulation of lincRNA-ROR was attributed to the CBP-mediated H3K27 acetylation at the promoter region. Our results reveal a potential competing endogenous RNA regulatory pathway, in which lincRNA-ROR modulates the epithelial–mesenchymal transition program by competitively binding to endogenous miR-32-5p and regulating Notch signaling pathway activity in retinoblastoma cells, which may provide new insights into novel molecular therapeutic targets for retinoblastoma.

Background/AimsTo describe some novel vitreoretinal microstructural findings in patients with mild familial exudative vitreoretinopathy (FEVR) on ultra-wide-field scanning laser ophthalmoscopy (UWF-SLO) and UWF optical coherence tomography (UWF-OCT) and to evaluate their clinical significance.MethodsA total of 32 patients and 32 healthy controls were studied. An additional independent 40 FEVR patients, 44 patients with non-FEVR retinopathies and 40 healthy controls participated in a diagnostic test to validate the abilities of novel findings in FEVR screening.ResultsA novel anatomic change, named Temporal Mid-Peripheral Vitreoretinal Interface Abnormality (TEMPVIA), was found on UWF-SLO in 88.3% of FEVR patients and in none of the healthy controls. The clinical significance of TEMPVIA was further validated by a diagnostic test in new independent cases, with satisfying sensitivity (91.5%) and specificity (98.8%) and Youden Index 0.90. In addition to foveal hypoplasia, some previously unrecognised, novel clinical changes in FEVR, for instance, retinoschisis, focal retinal thickening, sudden thinning of the retina and retinal ridge, were identified using UWF-OCT.ConclusionThe results of this study have led to an update of the clinical spectrum of FEVR and have improved our understanding of its pathogenesis. TEMPVIA is therefore suggested to be a useful biomarker in the screening strategy for mild FEVR.

A novel copper-catalyzed stereodefined procedure for the selective synthesis of cyclopropyl bis(boronates) from terminal alkenes has been developed. Various aliphatic alkenes were transformed into the desired bis(boronate ester)-substituted cyclopropanes in moderate to good yields. Synthetic transformations of the resulting cyclopropyl bis(boronates) demonstrate their utility. A possible reaction mechanism is proposed.

Spin engineering provides a powerful strategy for manipulating the interaction between electrons in the d orbital and oxygen-containing adsorbates, while a little endeavor was performed to understand whether such a strategy can make a prosperous enhancement for fuel electrooxidations. Herein, we demonstrate that spin engineering of trimetallic Pd–Fe–Pt nanomeshes (NMs) can achieve superior enhancement for fuel electrooxidations. Magnetization characterizations reveal that Pd59Fe27Pt14NMs own the highest number of polarized spins (μb= 0.85 μB/f.u.), playing an important role on facilitating the adsorption of OHadsto promote the oxidation of COads, as confirmed by theoretical results. Consequently, the optimized Pd59Fe27Pt14NMs exhibit excellent methanol oxidation reaction activity and stability with a mass activity of 1.61 A mgPt–1, 2.6-fold and 7.3-fold larger than those of PtRu/C and Pt/C. Such catalysts also present exceptional performances in ethanol oxidation and formic acid oxidation reactions. Our work highlights a new strategy for designing efficient electrocatalysts for fuel electrooxidations and beyond.

Background:Employing non-family paid helpers has become a prevalent practice across North America, Europe, and Asia, which families adopt to alleviate the stroke care burden, allowing family to take a break from their obligations and perform other social activities. However, paid helpers’ experiences of providing palliative care to stroke patients are under-explored. This study aimed to explore the caregiving experiences of non-family paid helpers providing palliative care to stroke patients. Method:A qualitative descriptive study was undertaken using purposive sampling and semi-structured individual in-depth interviews. Thematic analysis was used for data analysis. Results:Seventeen participants (mean age: 51.23 years) were included, predominantly being female (88%), and their caregiving experiences with patients ranged from four to 26 years. Participants shared that monetary compensation offset the exhaustion, familial and health sacrifices of palliative caregiving. They emphasized emotional self-management through accepting and coping or avoiding and distancing, and appreciated rewarding appraisals from stroke patients and family members. They also expressed a lack of recognition from the public, being invisible to the healthcare system/professionals, and insecurity in employment rights. Conclusions:Findings support the need for governmental initiatives to subsidize families in employing helpers to provide palliative care. Helpers perceived monetary compensation and a reciprocal caregiving relationship as the primary motives for providing care. Public recognition of this role as a helper in caregiving, contractual employment rights, and being recognized by the healthcare system and healthcare professionals are considerations in promoting quality care and alleviating a health care burden. The findings may contribute to further understanding of the experiences of non-family paid helpers in a job lacking recognition when delivering palliative care in a hospital for stroke patients. Evidence-based interventions that enhance reciprocity and recognition should be considered as part of the global initiatives to support paid helpers in palliative care.

Contact guidance in fibroblasts is preserved following loss of NM2B, and expression of NM2A alone is sufficient to establish an appropriate orientation of the cells. Loss of NM2B, and overexpression of NM2A, results in prominent cell polarization that is found to be linked to the increased alignment of microtubules with the actomyosin scaffold.

Efficiently designed limited-stop transit service is an attractive way to respond to high commuter travel demand in which trips concentrate on a few origin–destination pairs during peak hours. Such service is redesigned in many metropolises in China. Some research has dealt with this situation; bus fleet size was assumed to be unlimited, and the research was concerned with the average daily passenger flow rather than the specific average peak hour travel demand. In contrast to previous work, this paper presents an approach to design limited-stop transit service with the existing available fleet size from current normal service and focuses only on peak hour travel demand extracted through exploitation of transit data. First, a model for limited-stop service was proposed to minimize user costs through existing fixed fleet size. A heuristic algorithm was developed to search the transit line structure for limited-stop service instead of selecting lines from the predefined set. Next, a case in Chengdu, China, was tested. The results indicate that up to 9.32% of total travel time can be saved with the fixed fleet size when limited-stop transit service is applied. Finally, different proportions of commuter flow and different travel behaviors are discussed to illustrate the performance of limited-stop service for different scenarios.

Efficiently designed limited-stop transit service is an attractive way to respond to high commuter travel demand in which trips concentrate on a few origin–destination pairs during peak hours. Such service is redesigned in many metropolises in China. Some research has dealt with this situation; bus fleet size was assumed to be unlimited, and the research was concerned with the average daily passenger flow rather than the specific average peak hour travel demand. In contrast to previous work, this paper presents an approach to design limited-stop transit service with the existing available fleet size from current normal service and focuses only on peak hour travel demand extracted through exploitation of transit data. First, a model for limited-stop service was proposed to minimize user costs through existing fixed fleet size. A heuristic algorithm was developed to search the transit line structure for limited-stop service instead of selecting lines from the predefined set. Next, a case in Chengdu, China, was tested. The results indicate that up to 9.32% of total travel time can be saved with the fixed fleet size when limited-stop transit service is applied. Finally, different proportions of commuter flow and different travel behaviors are discussed to illustrate the performance of limited-stop service for different scenarios.

Background: Ankylosing spondylitis is a progressive, disabling joint disease that affects millions worldwide. Given its unclear etiology, studies of ankylosing spondylitis relied heavily on drug-induced or transgenic rodent models which retain only partial clinical features. There is obviously a lack of a useful disease model to conduct comprehensive mechanistic studies. Methods: We followed a group of cynomolgus monkeys having joint lesions reported of spinal stiffness for 2 years by conducting hematological testing, radiographic examination, family aggregation analysis, pathological analysis, and genetic testing. Results: The results confirmed that these diseased animals suffered from spontaneous ankylosing spondylitis with clinical features recapitulating human ankylosing spondylitis disease progression, manifested by pathological changes and biochemical indicators similar to that of ankylosing spondylitis patients. Conclusion: The study offers a promising non-human primate model for spontaneous ankylosing spondylitis which may serve as an excellent substitute for its pre-clinical research.

The boiler “Four Tubes” in a boiler occupies a very important position, according to incomplete statistics of a thermal power plant accident occurrence of unplanned outage, the boiler “Four Tubes” leakage caused by unplanned outage times 60%. Seriously study the boiler “Four Tubes” leakage causes and corresponding preventive measures that are put forward have some practical engineering significance.

Considering actual steel structures as research background, with emphasis on the effect of initial imperfections, the bending stability of stiffened plates was analyzed by ANSYS finite element. The results show that the moment of stiffening rib are different with the angle changing, and the ability of channel steel is more reinforced than L angles steel. With the thickness of the plate simply supported on four sides decreasing, the influence of imperfection becomes more obvious and the initial imperfection decreases the deflections of the skew plates. Finally through the comparative analysis with monitoring results, the numerically simulated results have a certain reference value.

Abstract: Using the plane wave ultrasoft pseudopotential method based on the first-principles density functional theory (DFT), the influence on the electronic structure and dehydrogenation properties of VH2 doped with Zr, Cu and Zn has been studied. The results show that the negative heat of formation increases and the valence electron number at the Fermi level E F, N(E F) decreases in the Zr-doped model, indicating the higher stability of VH2 after Zr alloying. On the other hand, the negative heat of formation of VH2 decreases and the N(E F) increases in Cu- or Zn-doped systems, suggesting the lower stability of VH2 after Cu or Zn alloying. The calculated overlap populations and electron densities of the V-H bond demonstrate that the bonding is strengthened by Zr doping and weakened by Cu or Zn doping. The results predict that the maximum capacity to absorb and desorb hydrogen can be raised by the introduction of Zr and reduced by the introduction of Cu or Zn, while the dehydrogenation properties will be poorer in Zr-doped systems and enhanced in Cu- or Zn-doped systems. These predictions are consistent with the experimental results. Mulliken populations were also calculated and it was found that the Mulliken population of the V 3d orbitals decreased as a result of Zr doping, and increased after Cu or Zn doping.

•Highly mesoporous carbons were prepared from corn silks.•High surface area over 2400 m2g-1and pore volume >1.89 cm3g-1were achieved.•A high energy density of 25 Wh kg-1was maintained at 23,070 W kg-1for EDLCs.•A high energy density of 38.5 Wh kg-1was achieved at 14, 741 W kg-1for ZICs.

Objectives Diabetic macular edema (DME) is a complication of diabetes mellitus that leads to diabetic retinopathy. Thus far, the role of serum exosomal microRNAs (miRNAs) in DME progression remains elusive. This study investigated serum exosomal miRNAs from patients with type 2 diabetes (T2D) and DME to identify miRNAs associated with expression of vascular endothelial growth factor (VEGF), a pivotal component in DME progression; it also evaluated the diagnostic values of these miRNAs for DME.Methods Serum was collected from patients with T2D who did (n = 20) and did not have DME (n = 24). Exosomes were isolated from serum and subjected to real-time polymerase chain reaction, western blotting, luciferase reporter, and miRNA profiling analyses.Results VEGF was significantly upregulated in ARPE-19 cells treated with exosomes from patients with T2D and DME, compared with exosomes from patients with T2D alone. Among the top 10 downregulated miRNAs identified during exosomal miRNA profiling, miR-377-3p inhibited the expression of VEGF. Luciferase reporter assays confirmed that miR-377-3p could directly regulate VEGF expression. Receiver operating characteristic analysis identified serum exosomal miR-377-3p as a potential biomarker for DME.Conclusion Serum exosomal miR-377-3p inhibits VEGF expression to suppress retinal pigment epithelium proliferation and offers a diagnostic biomarker for DME.

Aim. Portal hypertension is a series of syndrome commonly seen with advanced cirrhosis, which seriously affects patient’s quality of life and survival. This study was designed to access the efficacy and safety of selective esophagogastric devascularization in the modified Sugiura procedure for patients with cirrhotic hemorrhagic portal hypertension. Methods. Sixty patients with hepatitis B cirrhotic hemorrhagic portal hypertension and meeting the inclusion criteria were selected and randomly divided by using computer into the selective modified Sugiura group (sMSP group, n = 30) and the modified Sugiura group (MSP group, n = 30). The primary endpoint measurement is the postoperative rebleeding rate. Secondary endpoint measurements included free portal venous pressure, liver Child–Pugh score, liver volume, portal vein width and blood flow velocity, survival rate, quality of life, and dysphagia as well as other complications one year postoperatively. This trial is registered with ChiCTR, number ChiCTR2000033468. Results. There was no statistically significant difference in rebleeding rates within one year after surgery between patients in the sMSP and MSP groups (χ = 0.11, p=0.73). In comparison with the MSP group, the Child–Pugh score of liver function in the sMSP group significantly increased (χ = 6.4, p=0.04) and the incidence of dysphagia was significantly reduced (χ = 6.23, p=0.01) one year after surgery. There was a statistically significant difference in the quality of life between the two groups. However, there were no statistically significant differences in free portal venous pressure (MD = −3.44, 95% CI: −7.87 to 0.98, p=0.12), postoperative liver volume (3 months: MD = -258.81, 95% CI: −723.21 to 205.57, p=0.24; 1 year: MD = −320.12, 95% CI: −438.43 to 102.78, p=0.16), postoperative portal vein width (3 months: MD = −0.06, p=0.50; 1 year: MD = 0.17, p=0.21), portal vein flow velocity (3 months: MD = 1.64, p=0.21; 1 year: MD = −1.19, p=0.57), 1-year survival rate (χ = 1.01, p=0.31), and other complications between the two groups. Conclusions. Selective esophagogastric devascularization in the modified Sugiura procedure may not lower the incidence of rebleeding in the short term based on our findings. However, it may significantly improve quality of life of patients with cirrhotic hemorrhagic portal hypertension, improve liver function, and reduce postoperative dysphagia.

Physical Properties of the two-dimensional tellurium were discussed in detail, including electrical properties, optical properties, thermoelectric properties, and outstanding environmental stability.Emerging applications based on atomically thin tellurene flakes were presented, such as photodetector, transistors, piezoelectric device, modulator, and energy harvesting devices.The challenges encountered and prospects were presented.

MEK inhibition decreases cell viability and induces differentiation in RAS-driven rhabdomyosarcoma via an epigenetic mechanism.

ABSTRACTTumors evade host immune surveillance through multiple mechanisms, including the generation of a tumor microenvironment that suppresses immune effector function. Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1). We demonstrate that M7824 reduces plasma TGFβ1, binds to PD-L1 in the tumor, and decreases TGFβ-induced signaling in the tumor microenvironment in mice. In murine breast and colon carcinoma models, M7824 decreased tumor burden and increased overall survival as compared to targeting TGFβ alone. M7824 treatment promoted CD8+ T cell and NK cell activation, and both of these immune populations were required for optimal M7824-mediated tumor control. M7824 was superior to TGFβ- or αPD-L1-targeted therapies when in combination with a therapeutic cancer vaccine. These findings demonstrate the value of using M7824 to simultaneously target TGFβ and PD-L1/PD-1 immunosuppressive pathways to promote anti-tumor responses and efficacy. The studies also support the potential clinical use of M7824 as a monotherapy or in combination with other immunotherapies, such as therapeutic cancer vaccines, including for patients who have progressed on αPD-L1/αPD-1 checkpoint blockade therapies.

No relevant conflicts of interest to declare.

Abstract 1453

Direct intratumoral introduction of therapeutic or regulatory genes is a developing technology with potential application for cancer gene therapy. Macrophage inflammatory protein-1 beta (MIP-1b) is a chemokine which can chemoattract immune cells such as T cells. In the present study, murine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus (AdhMIP-1b) carrying the human MIP-1b gene. 24h post-transfection, hMIP-1b levels reached approximately 980 pg/ml in supernatants of 106 hMIP-1b-transfected CT26 cells. Moreover, the supernatants exhibited chemotactic activity for CD8+ T cells, CD4+ T cells, NK cells and immature DCs. Intratumoral injection of AdhMIP-1b significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice. Intratumoral hMIP-1b gene transfer also induced powerful tumor-specific CTL responses in vivo. The therapeutic effects of hMIP-1b gene therapy were greatly reduced following in vivo depletion of both CD4+ and CD8+ T cells, but were unaffected by depletion of single T cell subsets. Immune cell depletion experiments also revealed that NK cells played an important role in hMIP-1b-induced anti-tumor responses. These results suggest that intratumoral expression of hMIP-1b has the potential effect to induce host anti-tumor immunity and may prove to be a useful form of cancer gene therapy.

Direct intratumoral introduction of therapeutic or regulatory genes is a developing technology with potential application for cancer gene therapy. Macrophage inflammatory protein-1 beta (MIP-1b) is a chemokine which can chemoattract immune cells such as T cells. In the present study, murine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus (AdhMIP-1b) carrying the human MIP-1b gene. 24h post-transfection, hMIP-1b levels reached approximately 980 pg/ml in supernatants of 106hMIP-1b-transfected CT26 cells. Moreover, the supernatants exhibited chemotactic activity for CD8+T cells, CD4+T cells, NK cells and immature DCs. Intratumoral injection of AdhMIP-1b significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice. Intratumoral hMIP-1b gene transfer also induced powerful tumor-specific CTL responses in vivo. The therapeutic effects of hMIP-1b gene therapy were greatly reduced following in vivodepletion of both CD4+and CD8+T cells, but were unaffected by depletion of single T cell subsets. Immune cell depletion experiments also revealed that NK cells played an important role in hMIP-1b-induced anti-tumor responses. These results suggest that intratumoral expression of hMIP-1b has the potential effect to induce host anti-tumor immunity and may prove to be a useful form of cancer gene therapy.