Explore the vast range of titles available.

Ternary Optical Computer (TOC) is unique in the development of optical computers, in terms of principle, experiment, algorithm and application. After 20 years of development, six generations of prototypes have been developed. At present, tri-state optical signal storage is the main problem faced by TOC. According to the characteristics of tri-state optical signals and the ternary optical processor’s special requirements for storage systems, we design and implement the interface structure of TOC memory system, including the overall structure of the interface, the address generation module for memory access, the data input and output channels, the read/write timing, and the working process of the memory interface. Finally, the correctness of the memory system interface design is verified by the experiments, which are carried out on FPGA, of reading and writing operational result data of the SD16 TOC prototype. This work tries to improve the theoretical system and practical basis of TOC.

Cancer immunotherapy has made unprecedented breakthrough in the fields of chimeric antigen receptor-redirected T (CAR T) cell therapy and immune modulation. Combination of CAR modification and the disruption of endogenous inhibitory immune checkpoints on T cells represent a promising immunotherapeutic modality for cancer treatment. However, the potential for the treatment of hepatocellular carcinoma (HCC) has not been explored. In this study, the gene expressing the programmed death 1 receptor (PD-1) on the Glypican-3 (GPC3)-targeted second-generation CAR T cells employing CD28 as the co-stimulatory domain was disrupted using the CRISPR/Cas9 gene-editing system. It was found that, , the CAR T cells with the deficient PD-1 showed the stronger CAR-dependent anti-tumor activity against native programmed death 1 ligand 1-expressing HCC cell PLC/PRF/5 compared with the wild-type CAR T cells, and meanwhile, the CD4 and CD8 subsets, and activation status of CAR T cells were stable with the disruption of endogenous PD-1. Additionally, the disruption of PD-1 could protect the GPC3-CAR T cells from exhaustion when combating with native PD-L1-expressing HCC, as the levels of Akt phosphorylation and anti-apoptotic protein Bcl-xL expression in PD-1 deficient GPC3-CAR T cells were significantly higher than those in wild-type GPC3-CAR T cells after coculturing with PLC/PRF/5. Furthermore, the anti-tumor activity of the CAR T cells with the deficient PD-1 was investigated using the subcutaneous xenograft tumor model established by the injection of PLC/PRF/5 into NOD-scid-IL-2Rγ-/- (NSG) mice. The results indicated that the disruption of PD-1 enhanced the anti-tumor activity of CAR T cells against HCC, improved the persistence and infiltration of CAR T cells in the NSG mice bearing the tumor, and strengthened the inhibition of tumor-related genes expression in the xenograft tumors caused by the GPC3-CAR T cells. This study indicates the enhanced anti-tumor efficacy of PD-1-deficient CAR T cells against HCC and suggests the potential of precision gene editing on the immune checkpoints to enhance the CAR T cell therapies against HCC.

In the process of long-distance pressurized pipeline water transmission, in addition to the problem of water hammer hazards that can easily occur in the pipeline, the safety of the pipeline before the pump also presents hidden dangers. When excessive water hammer pressure occurs in the whole pipeline, it can easily lead to pipeline leakage or even pipe bursting. In this work, we analyze the pressure head in the pipeline of a long-distance pumping station using modeling calculations from KY PIPE software, combined with data from an actual water transmission project, to study the effect of stopping the pump water hammer. The use of two-phase check valves can effectively solve the problem of pump inversion when the pump water hammer stops, and the installation of an air valve and regulating tower can effectively reduce the pressure head of the pipeline. At the same time, the negative pressure in the pipeline can be eliminated, and the installation of a water hammer relief valve can effectively reduce the volume of the bladder surge tank by 77.5%. The results show that the use of joint protection equipment in a long-distance water transmission project has a better effect on the water hammer pressure in the pipeline. It is proposed that the joint protection equipment device can effectively reduce the volume of the surge tank. This provides reference significance for similar projects.

Globally, natural wetlands have suffered severe ecological degradation (vegetation, soil, and biotic community) due to multiple factors. Understanding the spatiotemporal dynamics and driving forces of natural wetlands is the key to natural wetlands’ protection and regional restoration. In this study, we first investigated the spatiotemporal evolutionary trends and shifting characteristics of natural wetlands in the Northeast Plain of China from 1990 to 2020. A dataset of driving-force evaluation indicators was constructed with nine indirect (elevation, temperature, road network, etc.) and four direct influencing factors (dryland, paddy field, woodland, grassland). Finally, we built the driving force analysis model of natural wetlands changes to quantitatively refine the contribution of different driving factors for natural wetlands’ dynamic change by introducing the sparrow search algorithm (SSA) and extreme gradient boosting algorithm (XGBoost). The results showed that the total area of natural wetlands in the Northeast Plain of China increased by 32% from 1990 to 2020, mainly showing a first decline and then an increasing trend. Combined with the results of transfer intensity, we found that the substantial turn-out phenomenon of natural wetlands occurred in 2000–2005 and was mainly concentrated in the central and eastern parts of the Northeast Plain, while the substantial turn-in phenomenon of 2005–2010 was mainly located in the northeast of the study area. Compared with a traditional regression model, the SSA-XGBoost model not only weakened the multicollinearity of each driver but also significantly improved the generalization ability and interpretability of the model. The coefficient of determination (R2) of the SSA-XGBoost model exceeded 0.6 in both the natural wetland decline and rise cycles, which could effectively quantify the contribution of each driving factor. From the results of the model calculations, agricultural activities consisting of dryland and paddy fields during the entire cycle of natural wetland change were the main driving factors, with relative contributions of 18.59% and 15.40%, respectively. Both meteorological (temperature, precipitation) and topographic factors (elevation, slope) had a driving role in the spatiotemporal variation of natural wetlands. The gross domestic product (GDP) had the lowest contribution to natural wetlands’ variation. This study provides a new method of quantitative analysis based on machine learning theory for determining the causes of natural wetland changes; it can be applied to large spatial scale areas, which is essential for a rapid monitoring of natural wetlands’ resources and an accurate decision-making on the ecological environment’s security.

The peripheral nerve system has an intrinsic regenerative capacity in response to traumatic injury. To better understand the molecular events occurring after peripheral nerve injury, in the current study, a rat model of sciatic nerve crush injury was used. Injured nerves harvested at 0, 1, 4, 7, and 14 days post injury were subjected to deep RNA sequencing for examining global gene expression changes. According to the temporally differential expression patterns of a huge number of genes, 3 distinct phases were defined within the post-injury period of 14 days: the acute, sub-acute, and post-acute stages. Each stage showed its own characteristics of gene expression, which were associated with different categories of diseases and biological functions and canonical pathways. Ingenuity pathway analysis revealed that genes involved in inflammation and immune response were significantly up-regulated in the acute phase, and genes involved in cellular movement, development, and morphology were up-regulated in the sub-acute stage, while the up-regulated genes in the post-acute phase were mainly involved in lipid metabolism, cytoskeleton reorganization, and nerve regeneration. All the data obtained in the current study may help to elucidate the molecular mechanisms underlying peripheral nerve regeneration from the perspective of gene regulation, and to identify potential therapeutic targets for the treatment of peripheral nerve injury.

We measured the levels of High‐Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child‐care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme‐linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)‐17, IL‐6, transforming growth factor β (TGF‐β), IL‐10, and NT‐proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage ( P  < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL‐17, and IL‐6 and was negatively correlated with TGF‐β and IL‐10 ( P  < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.

Study objective To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. Design A prospective, randomized, controlled trial study. Setting A tertiary university hospital. Patients A total of 130 patients with moderate (American Fertility Society [AFS] score of 5–8) and severe (AFS score of 9–12) intrauterine adhesions were recruited. Interventions 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). Measurements and main results The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased( P <0.05), whereas endometrial thickness was significantly increased across the three groups( P <0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group( P <0.01), with no significant difference between the IUD groups( P  = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness( P  = 0.502) and the pregnancy outcomes( P  = 0.803) in the three groups were not significantly different. Conclusion Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. Trial registration This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.

Periodic groundwater table fluctuations are found frequently in natural aquifers due to sea tides or seasonal recharge. However, their impact on the transport of volatile organic compounds in the vadose zone released from a groundwater contaminant source (i.e., vapor intrusion) has not been well known. A 2D numerical model was developed to explore vapor intrusion processes in the sandy vadose zone, subject to a fluctuating groundwater table with a range of fluctuation amplitudes and periods. A carcinogenic compound, Trichloroethylene (TCE), was chosen as the groundwater contaminant of interest in the current study and assumed to transport into the dwelling through a crack at the corner of the basement. Results showed that the resistant effect caused by high soil moisture contents in the thin capillary fringe is weakened by periodic groundwater table fluctuations, resulting in a higher concentration of gaseous TCE at the building foundation crack, in comparison with that under a static groundwater table. The increase of the gaseous TCE concentration was induced by the enhancement of diffusion and advection due to groundwater table fluctuations. Sensitivity analyses indicated that a higher amplitude and frequency of fluctuations lead to a higher TCE concentration at the crack under the dynamic equilibrium condition. Specifically, compared with the static groundwater table condition, the TCE concentration at the crack increased by one order of magnitude under the condition of groundwater table fluctuations with an amplitude of 0.2 m and a period of one day. The results obtained could provide insights into the importance of the amplitude and frequency of groundwater table fluctuations on vapor intrusion.

Objective To analyze the infection status and subtype distribution of high-risk human papillomavirus (hrHPV) and their relationship with cervical lesions among women undergoing cervical cancer screening in Guizhou Province, thereby informing HPV vaccine selection and optimizing cervical cancer screening strategies. Methods Data were sourced from the 2024 Guizhou Province free cervical cancer screening program for women. The prevalence of hrHPV-positive samples was analyzed, and age-specific associations between HPV genotypes and severe lesions were explored. Furthermore, the co-infection propensity for any two HPV genotypes was assessed by calculating the infection rate ratio. Results The overall hrHPV infection rate in the Guizhou region of China was 10.09%. Among hrHPV-positive individuals, the detection rate of cervical lesions was 11.49%. In hrHPV-positive women with cervical lesions, the most common genotypes were HPV16, 52, and 58. HPV16 was predominant across the entire spectrum of cervical lesions, and its prevalence increased significantly with the severity of cervical lesions, from 21.7% in LSIL to 39.4% in HSIL, and to 56.7% in cervical cancer (p < 0.001). However, the primary HPV types leading to cervical cancer were HPV16, 18, and 33. The infection pattern was predominantly single genotype (71.8%), with multiple genotypes accounting for only 28.2%. Among multiple infections, dual infection was the most common. The most frequent mixed genotype combinations were HPV16 + 52, 52 + 58, and 16 + 58. Significant co-infection preferences were observed for HPV16 with 33, HPV16 with 58, and HPV18 with 59. Analysis of the association between HPV genotype risk grouping and age across different cervical lesion grades showed that in the LSIL group, women aged 55–65 had a significantly 24% higher risk of HPV16 infection compared to those aged 35–45 (P = 0.023), while the risk of ‘Other hrHPV’ infection was significantly reduced by 8% (P = 0.019). In the HSIL group, the 45–55 age group had a significantly 11% lower risk of ‘Other hrHPV’ infection compared to the 35–45 age group. Conclusion HPV16 predominates across the entire cervical lesion spectrum, with its prevalence significantly increasing with lesion severity. Furthermore, the nonavalent HPV vaccine covers all prevalent oncogenic hrHPV genotypes in this region (except for HPV56). These findings provide crucial epidemiological evidence for optimizing HPV vaccination strategies and cervical cancer screening programs.

Background Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by recurring structural chromosomal alterations and genetic alterations, whose detection is critical in diagnosis, risk stratification and prognostication. However, the genetic mechanisms that give rise to ALL remain poorly understood. Methods Using next-generation sequencing (NGS) in matched germline and tumor samples from 140 pediatric Chinese patients with ALL, we landscaped the gene mutations and estimated the mutation frequencies in this disease. Results Our results showed that the top driver oncogenes having a mutation prevalence over 5% in childhood ALL included KRAS (8.76%), NRAS (6.4%), FLT3 (5.7%) and KMT2D (5.0%). While the most frequently mutated genes were KRAS , NRAS and FLT3 in B cell ALL (B-ALL), the most common mutations were enriched in NOTCH1 (23.1%), FBXW7 (23.1%) and PHF6 (11.5%) in T cell ALL (T-ALL). These mutant genes are involved in key molecular processes, including the Ras pathway, the Notch pathway, epigenetic modification, and cell-cycle regulation. Strikingly, more than 50% of mutations occurred in the high-hyperdiploid (HeH) ALL existed in Ras pathway, especially FLT3 (20%). We also found that the epigenetic regulator gene KMT2D , which is frequently mutated in ALL, may be involved in driving leukemia transformation, as evidenced by an in vitro functional assay. Conclusion Overall, this study provides further insights into the genetic basis of ALL and shows that Ras mutations are predominant in childhood ALL, especially in the high-hyperdiploid subtype in our research.