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[Objective] In order to improve the visualization and interactivity of the vehicle simulation system in rail transit, a digital twin simulation platform of rail transit vehicle is built based on VR (virtual reality) technology. [Method] Through the hierarchical construction method for digital twin 3D model and mechanism model of rail transit vehicles, and the hierarchical association mapping method, the fusion of 3D model and mechanism model is realized, and the digital twin 3D physical model is coupled and generated. On this basis, a digital twin simulation system and the system construction method for rail transit are proposed. With a metro vehicle and its operating line in Qingdao as the research object, the effectiveness of the digital twin simulation system is verified through the VR platform and the train automatic driving control algorithm. [Result & Conclusion] The test results show that the error between the actual running speed and the control running speed is within ±1.5 km/h, proving the validity of the model. The construction method of digital twin simulation platform for rail transit vehicles provides a new technical idea for improving the visualization and interactivity of the vehicle simulation system in rail transit.

BackgroundFrequent air pollution events in Northwest China pose a serious threat to human health. However, there is a lack of specific differences assessment in PM2.5-related disease burden. Therefore, we aimed to estimate the PM2.5-related premature deaths and health economic losses in this typical northwest region, taking into account disease-specific, age-specific, and region-specific factors.MethodsWe utilized the WRF-Chem model to simulate and analyze the characteristics and exposure levels of PM2.5 pollution in Gansu Province, a typical region of Northwest China. Subsequently, we estimated the premature mortality and health economic losses associated with PM2.5 by combining the Global Exposure Mortality Model (GEMM) and the Value of a Statistical Life (VSL).ResultsThe results suggested that the PM2.5 concentrations in Gansu Province in 2019 varied spatially, with a decrease from north to south. The number of non-accidental deaths attributable to PM2.5 pollution was estimated to be 14,224 (95% CI: 11,716–16,689), accounting for 8.6% of the total number of deaths. The PM2.5-related health economic loss amounted to 28.66 (95% CI: 23.61–33.63) billion yuan, equivalent to 3.3% of the regional gross domestic product (GDP) in 2019. Ischemic heart disease (IHD) and stroke were the leading causes of PM2.5-attributed deaths, contributing to 50.6% of the total. Older adult individuals aged 60 and above accounted for over 80% of all age-related disease deaths. Lanzhou had a higher number of attributable deaths and health economic losses compared to other regions. Although the number of PM2.5-attributed deaths was lower in the Hexi Corridor region, the per capita health economic loss was higher.ConclusionGansu Province exhibits distinct regional characteristics in terms of PM2.5 pollution as well as disease- and age-specific health burdens. This highlights the significance of implementing tailored measures that are specific to local conditions to mitigate the health risks and economic ramifications associated with PM2.5 pollution.

AbstractBackground Previous studies have shown that perioperative dexmedetomidine could reduce the incidence of postoperative AKI in cardiovascular surgery, however, its effectiveness in the non-cardiovascular surgery patient population has not been reported. The aim of this study was to investigate the effect of intraoperative dexmedetomidine on the incidence of postoperative AKI and postoperative ICU admissions in patients undergoing non-cardiovascular surgery.Design and setting A single-center retrospective cohort study obtained from the database of the Center for Anesthesia and Surgery, the Third Xiangya Hospital.Patients Inpatients between 18 and 75 years of age who were admitted to our hospital for non-cardiovascular surgery from 2012 to 2019.Results Overall 2391 patients who used dexmedetomidine intraoperatively were analyzed in comparison to 4552 patients who did not use dexmedetomidine after one-to-two matching. The two cohorts had similar baseline values and demographic characteristics. The incidence of AKI was lower in patients with intraoperative dexmedetomidine use than in the nonuse group (OR 0.60, p .05).Conclusion For non-cardiovascular surgery patient population, intraoperative use of dexmedetomidine was associated with a lower incidence and less severity of postoperative AKI. However, there was no significant correlation with postoperative ICU occupancy or in-hospital mortality. Further prospective RCTs are needed in the future.

Abstract Activating transcription factor 4 (ATF4) is one of the key effectors of endoplasmic reticulum stress (ERS), ATF4/CHOP pathway-mediated ERS plays an important role in the progression of acute kidney disease (AKI). We have previously reported that Vitamin D receptor (VDR) exert renoprotection in rodent AKI models. However, whether ATF4, as well as ERS, is involved in the protective effect of VDR in ischemia-reperfusion (I/R) induced AKI is unknown. Herein, we showed that VDR agonist paricalcitol and VDR overexpression alleviated I/R-induced renal injury and cells apoptosis with decreased ATF4 and attenuated ERS, while VDR deletion significantly resulted in further increased ATF4, more drastic ERS and renal injury in I/R mice models. In addition, paricalcitol remarkably reduced Tunicamycin (TM) induced ATF4 and ERS with attenuated renal injury, while VDR deletion aggravated the above changes in TM mice models. Moreover, overexpression of ATF4 partially abolished the effect of paricalcitol against TM-induced ERS and apoptosis, while inhibition of ATF4 enhanced the protective effect of paricalcitol. Bioinformatics analysis indicated potential VDR binding sites on ATF4 promotor sequence which were further confirmed by ChIP-qPCR and dual-luciferase reporter gene assay. In conclusion, VDR attenuated I/R-induced AKI by suppressing ERS partly via transcriptional regulation of ATF4.

Rice production is the agricultural activity with the highest energy consumption and carbon emission intensity. Water and fertilizer management constitutes an important part of energy input for rice production and a key factor affecting greenhouse gas emissions from paddy fields. Water–fertilizer integration management (AIM) is an automated water and fertilizer management system for large-scale rice production, which can effectively save water and fertilizer resources. At present, the energy utilization and environmental impact of AIM in rice production are not clear. To clarify whether AIM is a water and fertilizer management measure that combines energy conservation and carbon emission reduction, a comparative study between the widely used farmers’ enhanced water and fertilizer management (FEM) in China and AIM was conducted in this paper. Field experiments were conducted to evaluate the rice yield, carbon emission, energy utilization, and economic benefits of the two management methods. The results showed that AIM reduced water and fertilizer inputs, energy inputs, and economic costs by 12.18–28.57%, compared to FEM. The energy utilization efficiency, energy profitability, and energy productivity under AIM were improved by 11.30–12.61%. CH4 and N2O emissions and carbon footprint were reduced by 20.79%, 6.51%, and 16.39%, respectively. Compared with FEM, AIM can effectively improve the utilization efficiency of water and fertilizer resources and reduce carbon emissions. This study presents a mechanized water and fertilizer management approach suitable for large-scale rice production systems in China. By analyzing rice yield, resource utilization efficiency, and environmental benefits, AIM can serve as a crucial management strategy for enhancing productivity, economic returns, and environmental conservation within profitable rice production systems. In the future, further investigation into the impact of AIM on the microbial mechanisms underlying rice yield formation and greenhouse gas emissions is warranted.

Summary: Due to the enhanced labeling capability of maleimide-based fluorescent probes, lysine-cysteine-lysine (KCK) tags are frequently added to proteins for visualization. In this study, we employed an in vitro single-molecule DNA flow-stretching assay as a sensitive way to assess the impact of the KCK tag on the property of DNA-binding proteins. Using Bacillus subtilis ParB as an example, we show that, although no noticeable changes were detected by in vivo fluorescence imaging and chromatin immunoprecipitation (ChIP) assays, the KCK tag substantially altered ParB’s DNA compaction rates and its response to nucleotide binding and to the presence of the specific sequence (parS) on the DNA. While it is typically assumed that short peptide tags minimally perturb protein function, our results urge researchers to carefully validate the use of tags for protein labeling. Our comprehensive analysis can be expanded and used as a guide to assess the impacts of other tags on DNA-binding proteins in single-molecule assays. Motivation: Single-molecule fluorescence microscopy has been extensively used in modern biology to define the molecular action of proteins. Appending short peptide tags is a common strategy to enhance fluorescence labeling. Here, we evaluate the impact of a commonly used tag, the lysine-cysteine-lysine (KCK) tag, on protein behavior in single-molecule DNA flow-stretching assay, which is a sensitive and versatile method to understand the action of DNA-binding proteins. Our motivation is to provide researchers with an experimental framework to validate fluorescently labeled DNA-binding proteins in single-molecule methods.

ObjectiveTo explore the optimal bolus dose of oxycodone for patient controlled intravenous analgesia (PCIA) without background dose in elderly patients after laparoscopic surgery for gastrointestinal cancer.MethodsIn this prospective, randomized, double-blind, parallel-controlled study, we recruited patients aged 65 years or older. They underwent laparoscopic resection for gastrointestinal cancer and received PCIA after surgery. Eligible patients were randomly divided into 0.01, 0.02, or 0.03 mg/kg group according to the bolus dose of oxycodone in PCIA. The primary outcome was VAS scores of pain on mobilization at 48 h after surgery. Secondary endpoints included the VAS scores of rest pain, the total and effective numbers of press in PCIA, cumulative dose of oxycodone used in PCIA, the incidence of nausea, vomiting and dizziness, as well as patients’ satisfaction at 48 h after surgery.ResultsA total of 166 patients were recruited and randomly assigned to receive a bolus dose of 0.01 mg/kg (n = 55), 0.02 mg/kg (n = 56) or 0.03 mg/kg (n = 55) of oxycodone in PCIA. The VAS scores of pain on mobilization, the total and effective numbers of press in PCIA in 0.02 mg/kg group and 0.03 mg/kg group were lower than those in 0.01 mg/kg group (P 0.05).ConclusionFor elderly patients undergoing laparoscopic surgery for gastrointestinal cancer, 0.02 mg/kg bolus dose of oxycodone in PCIA without background infusion may be a better choice.

Immune checkpoint inhibitors (ICI) have dramatically transformed the treatment landscape for metastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) or high microsatellite instability (MSI-H). Envafolimab, a novel programmed death-1 ligand 1 (PD-L1) inhibitor, has been reported to be efficient and safe for the management of advanced MSI-H/dMMR solid tumors. Here, we report the case of a 35-year-old female patient with MSI-H/dMMR mCRC who was treated with envafolimab following mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) plus bevacizumab. While suffering from interstitial pneumonia after chemotherapy, the patient achieved a complete clinical response with the use of envafolimab without additional adverse events. Thus, PD-L1 inhibitors may be potential candidates for treating patients with MSI-H/dMMR mCRC.

Background: Our previous study showed that vitamin D (VD)-vitamin D receptor (VDR) plays a nephroprotective role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Recently, glucose metabolism reprogramming was reported to be involved in the pathogenesis of AKI.Objective: To investigate the role of VD-VDR in glucose metabolism reprogramming in LPS-induced AKI.Methods: We established a model of LPS-induced AKI in VDR knockout (VDR-KO) mice, renal proximal tubular-specific VDR-overexpressing (VDR-OE) mice and wild-type C57BL/6 mice. In vitro, human proximal tubular epithelial cells (HK-2 cells), VDR knockout and VDR overexpression HK-2 cell lines were used.Results: Paricalcitol (an active vitamin D analog) or VDR-OE reduced lactate concentration, hexokinase activity and PDHA1 phosphorylation (a key step in inhibiting aerobic oxidation) and simultaneously ameliorated renal inflammation, apoptosis and kidney injury in LPS-induced AKI mice, which were more severe in VDR-KO mice. In in vitro experiments, glucose metabolism reprogramming, inflammation and apoptosis induced by LPS were alleviated by treatment with paricalcitol or dichloroacetate (DCA, an inhibitor of p-PDHA1). Moreover, paricalcitol activated the phosphorylation of AMP-activated protein kinase (AMPK), and an AMPK inhibitor partially abolished the protective effect of paricalcitol in LPS-treated HK-2 cells.Conclusion: VD-VDR alleviated LPS-induced metabolic reprogramming in the kidneys of AKI mice, which may be attributed to the inactivation of PDHA1 phosphorylation via the AMPK pathway.

Advanced or recurrent mucinous carcinoma of the ovary minimally responds to current cytotoxic treatments and has a poor prognosis. Despite multimodal treatment with chemotherapy and surgery, most patients ultimately progress and require palliative systemic therapy. Anti-HER2 therapy has been demonstrated to be an effective strategy for the treatment of HER2-positive breast cancer. However, the role of anti-HER2 therapy in ovarian cancer remains largely unknown. Here, we report the case of a young woman with FIGO Stage IIIc recurrent mucinous ovarian carcinoma (MOC) who developed trastuzumab resistance and disease progression following cross-treatment with trastuzumab combined with pertuzumab. HER2 amplification was discovered using next-generation sequencing (NGS). The patient then received bevacizumab, and pyrotinib (an irreversible HER2 antagonist) plus capecitabine treatment, and achieved a long-term clinical benefit for 22 months. Pyrotinib combined with bevacizumab is a potential treatment for MOC patients who are heavily pretreated and harbor a HER2 amplification. Our case may provide valuable treatment information for patients with advanced or recurrent MOC.

Introduction: At present, the mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. The development of biomarkers is conducive to the early diagnosis and treatment of cancer. This research aimed to explore the role of microRNA-204-5p and downstream gene in ccRCC. Methods: We used bioinformatics analysis and qRT-PCR for measurement of microRNA-204-5p, qRT-PCR and western blot for GXYLT2 mRNA and protein levels, respectively. We conducted in vitro experiments like CCK8, colony formation, transwell, wound healing, and cell cycle assays to assess the role of microRNA-204-5p and GXYLT2 in ccRCC. Besides, the target relationship of microRNA-204-5p and GXYLT2 was confirmed through dual-luciferase assay. Results: This study disclosed that microRNA-204-5p was underexpressed in ccRCC cells and tissues, which was closely associated with prognosis of patients with ccRCC. Stable forced expression of microRNA-204-5p hindered malignant phenotypes of ccRCC cells. Further detection unfolded that microRNA-204-5p bound the 3’-UTR of GXYLT2 to repress its expression. Besides, forced expression of microRNA-204-5p restored the promoting impact of overexpression of GXYLT2 on malignant progression of ccRCC cells. Conclusion: These findings revealed the vital role of microRNA-204-5p and GXYLT2 in ccRCC progression, as well as the possibility of microRNA-204-5p in improving ccRCC prognosis and treatment.

ABSTRACT Many pathogens or symbionts of animals and plants contain multiple replicons, a configuration called a multipartite genome. Multipartite genomes enable those species to replicate their genomes faster and better adapt to new niches. Despite their prevalence, the mechanisms by which multipartite genomes are stably maintained are poorly understood. Agrobacterium tumefaciens is a plant pathogen that contains four replicons: a circular chromosome (Ch1), a linear chromosome (Ch2), and two large plasmids. Recent work indicates that their replication origins are clustered at the cell poles in a manner that depends on their ParB family centromeric proteins: ParB1 for Ch1 and individual RepB paralogs for Ch2 and the plasmids. However, understanding of these interactions and how they contribute to genome maintenance is limited. By combining genome-wide chromosome conformation capture (Hi-C) assays, chromatin-immunoprecipitation sequencing (ChIP-seq), and live cell fluorescence microscopy, we provide evidence here that centromeric clustering is mediated by interactions between these centromeric proteins. We further show that the disruption of centromere clustering results in the loss of replicons. Our data establish the role of centromeric clustering in multipartite genome stability. IMPORTANCE About 10% of sequenced bacteria have multiple replicons, also known as multipartite genomes. How these multipartite genomes are maintained is still poorly understood. Here, we use Agrobacterium tumefaciens as a model and show that the replication origins of the four replicons are clustered through direct interactions between the centromeric proteins; disruption of origin clustering leads to the loss of replicons. Thus, our study provided evidence that centromeric clustering is important for maintaining multipartite genomes.

Abstract Vascular smooth muscle cell (VSMC) phenotypic switching plays a critical role in the formation of abdominal aortic aneurysms (AAAs). FoxO3a is a key suppressor of VSMC homeostasis. We found that in human and animal AAA tissues, FoxO3a was upregulated, SM22α and α-smooth muscle actin (α-SMA) proteins were downregulated and synthetic phenotypic markers were upregulated, indicating that VSMC phenotypic switching occurred in these diseased tissues. In addition, in cultured VSMCs, significant enhancement of FoxO3a expression was found during angiotensin II (Ang II)-induced VSMC phenotypic switching. In vivo, FoxO3a overexpression in C57BL/6J mice treated with Ang II increased the formation of AAAs, whereas FoxO3a knockdown exerted an inhibitory effect on AAA formation in ApoE−/− mice infused with Ang II. Mechanistically, FoxO3a overexpression significantly inhibited the expression of differentiated smooth muscle cell (SMC) markers, activated autophagy, the essential repressor of VSMC homeostasis, and promoted AAA formation. Our study revealed that FoxO3a promotes VSMC phenotypic switching to accelerate AAA formation through the P62/LC3BII autophagy signaling pathway and that therapeutic approaches that decrease FoxO3a expression may prevent AAA formation.

We propose a continuous-variable quantum key distribution (CVQKD) scheme based on the atmosphere-to-seawater channel. In particular, an untrusted entanglement source (two modes of the compressed vacuum state, TMSV) is deployed on the surface of the seawater, each mode of TMSV is sent to one of the two legitimate parts, respectively. In this way, we can establish a trans-media CVQKD link between the atmosphere and the underwater. Meanwhile, a suitable non-Gaussian operation, namely photon subtraction, is introduced to enhance the performance of the trans-media CVQKD scheme. Security analysis shows that the proposed scheme can establish a trans-media quantum communication system on the atmosphere-to-seawater channel. Moreover, the maximum transmission distance can be further extended by using proper photon subtraction operation. Our scheme provides a guidance for applying CVQKD to trans-media channels.

Abstract Background Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. Methods This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. Results The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. Conclusions Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. Trial registration The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.

Abstract Background Chronic postsurgical pain (CPSP) is common and would reduce the quality of life of patients. Transversus abdominal plane (TAP) block has been widely used in lower abdominal surgery and many researches demonstrated that it could improve acute postsurgical pain. We aim to determine whether TAP block could improve chronic postoperative pain at 3 months and 6 months after colorectal surgery. Methods A total of 307 patients received selective colorectal surgery under general anesthesia between January, 2015 and January, 2019 in a single university hospital were included: 128 patients received TAP block combined with patient-controlled intravenous analgesia (PCIA) for postsurgical analgesia (group TP) and 179 only administrated with PCIA (group P). Main outcome was the NRS score of pain at 3 months after colorectal surgery. The data was analyzed by two-way repeated measures anova and the chi-square test. Results The NRS score at rest and during movement was decreased significantly at 24 h after surgery (rest NRS 1.07 ± 1.34 vs 1.65 ± 1.67, movement NRS 3.00 ± 1.45 vs 3.65 ± 1.89; all P = 0.003) in group TP than those of group P. There was no significant difference of NRS score at 48 h after surgery (P > 0.05). At 3 months after surgery, the NRS score during movement was also lower in group TP than that in group P (0.59 ± 1.23 vs 0.92 ± 1.65, P = 0.045). There was no significant difference of NRS score at 6 months after surgery (P > 0.05). The prevalence of CPSP was 19.5% (25/128) in group TP and 20.7% (37/179) in group P at 3 months after surgery. 13.2% (17/128) of patients suffered from CPSP in group TP and 13.9% (25/179) in group P at 6 months after surgery. Both at 3 months and 6 months after surgery, there was no statistical difference of the prevalence of CPSP between the two groups (all P > 0.05) . Conclusions TAP block reduced NRS during movement at 3 months after surgery but did not reduce the incidence of CPSP at 3 months and 6 months after selective colorectal surgery.

Abstract Background Flurbiprofen axetil (FA) is a commonly prescribed agent to relieve perioperative pain, but the relationship between FA and postoperative acute kidney injury (AKI) remains unclear. This study attempted to evaluate the effects of different dose of perioperative FA on postoperative AKI. Methods A total of 9915 patients were enrolled for this retrospective study. The clinical characteristics and the prevalence of postoperative AKI among patients non-using, using low dose (50-100 mg), middle dose (100-250 mg) and large dose (≧250 mg) of FA were analyzed respectively. The impact of different dose of FA on postoperative AKI was analyzed using univariable and multivariate logistic regression analysis. Results The prevalence of postoperative AKI was 6.7% in the overall subjects and 5.1% in 2446 cases who used FA. The incidence of AKI in low dose group was significantly less than that of non use group (4.5% vs 7.2%, P

BackgroundMinimally invasive techniques, such as percutaneous low-power laser discectomy (PLLD) and low-temperature plasma radiofrequency ablation (coblation) can be applied to treat degenerative cervical radiculopathy. However, less evidence supports the superiority of distinct minimally-invasive therapy. Our study aimed to evaluate the clinical and radiological characteristics of the PLLD and coblation for cervical radiculopathy.MethodsThis was a prospective, multicenter, cohort study (ChiCTR-ONC-17010356). The modified Macnab criteria was performed to assess the clinical improvement pre- and post-surgery. To evaluate the radiological effect, the Pfirrmann grading system and disk herniation index were applied with MRI.ResultsIn this study, 28 patients were enrolled in the coblation group and 30 patients in the PLLD group. The mean good-excellent rate at 3-month follow-up was 82.1% for PLLD group, and 66.7% for coblation group, respectively (p = 0.179). The PLLD group achieved higher good-excellent rate 6 and 12 months after discharge (92.9 vs. 70.0%, p = 0.026). Radiological data revealed that PLLD but not coblation treatment achieved significant reduction of disk herniation index (p < 0.0001). Coblation treatment did not change the Pfirrmann grades of cervical radiculopathy patients (n = 18), and 7 out of 17 (41.2%) patients achieved improvement after PLLD therapy. None obvious adverse event was observed in this study.ConclusionBoth PLLD and coblation are effective and safe option for patients with cervical radiculopathy. Better long-term clinical outcomes may be potentially associated with the improvement of disk degeneration after PLLD treatment.

Heart failure (HF) is a globally prevalent cardiovascular disease, but effective drug targets and diagnostic models are still lacking. This study was designed to investigate effective drug targets and diagnostic models for HF in terms of miRNA targets, hoping to contribute to the understanding and treatment of HF. Using HF miRNA and gene expression profile data from the GEO database, we analyzed differentially expressed miRNAs/gene identification in HF using Limma and predicted miRNA targets by the online TargetScan database. Subsequently, gene set enrichment analysis and annotation were performed using WebGestaltR package. Protein-protein interactions were identified using the STRING database. The proximity of drugs to treat HF was also calculated and predicted for potential target therapeutic drug. In addition, further drug identification was performed by molecular docking. Finally, diagnostic models were constructed based on differential miRNAs. The GEO dataset was used to screen 66 differentially expressed miRNAs, incorporating 56 downregulated miRNAs and 10 upregulated miRNAs. The JAK-STAT signaling pathway, MAPK signaling pathway, p53 signaling pathway, Prolactin signaling pathway, and TGF-beta signaling pathway were enriched, as shown by KEGG enrichment analysis on the target genes. In addition, we found that 83 genes were upregulated and 92 genes were downregulated in HF patients vs. healthy individuals. Based on the inflammation-related score, hypoxia-related score, and energy metabolism-related score, we identified key miRNA-mRNA pairs and constructed an interaction network. Following that, TAP1, which had the highest expression and network connectivity in acute HF with crystal and molecular docking studies, was selected as a key candidate gene in the network. And the compound DB04847 was selected to produce a large number of favorable interactions with TAP1 protein. Finally, we constructed two diagnostic models based on the differential miRNAs hsa-miR-6785-5p and hsa-miR-4443. In conclusion, we identified TAP1, a key candidate gene in the diagnosis and treatment of HF, and determined that compound DB04847 is highly likely to be a potential inhibitor of TAP1. The TAP1 gene was also found to be regulated by hsa-miR-6785-5p and hsa-miR-4443, and a diagnostic model was constructed. This provides a new promising direction to improve the diagnosis, prognosis, and treatment outcome and guide more effective immunotherapy strategies of HF.

A novel multiple-ring molecule containing P and N, called HCCP-SA, was successfully prepared by the nucleophilic substitution reaction of salicylamide (SA) and hexachlorocyclotriphosphazene (HCCP). Particularly, HCCP-SA possessed the dual functions of heat resistance and flame retardancy. The molecular structure of HCCP-SA was identified by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. HCCP-SA was bonded into the molecular chain of epoxy resin by the ring-opening curing reaction of epoxy resin, aiming to form a heat-resistant and flame-retardant composite (E-HS-x). In particular, the best-prepared E-HS-x composite with a 20 phr content of HCCP-SA (E-HS-20) presented excellent thermal stability, with an initial decomposition temperature of 267.94 °C and a max weight loss speed of only 0.95 mg·min−1. Moreover, E-HS-20 exhibited remarkable flame retardancy with a limiting oxygen index value of 27.1% and a V-2 rating in the UL94 flame retardancy test. The best-prepared E-HS-20 composite would be a suitable and potential candidate for heat-resistant and flame-retardant polymer materials.

Lithium-ion batteries (LIBs), used for energy supply and storage equipment, have been widely applied in consumer electronics, electric vehicles, and energy storage systems. However, the urgent demand for high energy density batteries and the shortage of lithium resources is driving scientists to develop high-performance materials and find alternatives. Low-volume expansion carbon material is the ideal choice of anode material. However, the low specific capacity has gradually become the shortcoming for the development of LIBs and thus developing new carbon material with high specific capacity is urgently needed. In addition, developing alternatives of LIBs, such as sodium ion batteries and potassium-ion batteries, also puts forward demands for new types of carbon materials. As is well-known, the design of high-performance electrodes requires a deep understanding on the working mechanism and the structural evolution of active materials. On this issue, ex-situ techniques have been widely applied to investigate the electrode materials under special working conditions, and provide a lot of information. Unfortunately, these observed phenomena are difficult to reflect the reaction under real working conditions and some important short-lived intermediate products cannot be captured, leading to an incomplete understanding of the working mechanism. In-situ techniques can observe the changes of active materials in operando during the charge/discharge processes, providing the concrete process of solid electrolyte formation, ions intercalation mechanism, structural evolutions, etc. Herein, this review aims to provide an overview on the characters of carbon materials in alkali ion batteries and the role of in-situ techniques in developing carbon materials.

Abstract Background Cholangiocarcinoma, or bile duct cancer, is a gastrointestinal cancer with limited therapeutic options and a poor outcome. Studies have revealed that some major driver genes are associated with cholangiocarcinoma, but no targeted therapies have been approved. Immune checkpoint inhibitors, which are represented by inhibitors of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), have emerged as a potential therapy for multiple types of solid cancers. Case presentation A 53-year-old female presented with postoperative recurrence of PD-L1-positive intrahepatic cholangiocarcinoma with a high tumour mutational burden. This patient exhibited a marked response to the combination of anti-PD-1 immunotherapy and chemotherapy. Conclusions As far as we know, this is the first case report on the success of the combination of immunotherapy and chemotherapy for advanced cholangiocarcinoma with PD-L1 positivity and a high tumour mutational burden.

Atmospheric continuous-variable quantum key distribution (ACVQKD) has been proven to be secure theoretically with the assumption that the signal source is well protected by the sender so that it cannot be compromised. However, this assumption is quite unpractical in realistic quantum communication system. In this work, we investigate a practical situation in which the signal source is no longer protected by the legitimate parts, but is exposed to the untrusted atmospheric channel. We show that the performance of ACVQKD is reduced by removing the assumption, especially when putting the untrusted source at the middle of the channel. To improve the performance of the ACVQKD with the untrusted source, a non-Gaussian operation, called photon subtraction, is subsequently introduced. Numerical analysis shows that the performance of ACVQKD with an untrusted source can be improved by properly adopting the photon subtraction operation. Moreover, a special situation where the untrusted source is located in the middle of the atmospheric channel is also considered. Under direct reconciliation, we find that its performance can be significantly improved when the photon subtraction operation is manipulated by the sender.

There is a growing interest in the security of underwater communication with the increasing demand for undersea exploration. In view of the complex composition and special optical properties of seawater, this paper deals with a performance analysis for continuous-variable quantum key distribution (CVQKD) over an underwater link. In particular, we focus on analyzing the channel transmittance and detection efficiency based on Monte Carlo simulation for different water types, link distances and transceiver parameters. A comparison between the transmittance obtained by simple Beer’s law and Monte Carlo simulation reveals that the transmittance of underwater link may be severely underestimated in the previous underwater CVQKD research. The effect of the receiver aperture and field of view (FOV) on detection efficiency under different water types is further evaluated based on Monte Carlo. Simulation results show that the transmission distance of the underwater CVQKD system obtained by Monte Carlo simulation in pure sea water, clear ocean water and coastal ocean water is larger than that obtained by Beer’s law, while the key rate of the system in all types of water is smaller than that obtained by Beer’s law because the size and FOV of the receiver aperture are taken into account. By considering the practical system parameters, this paper establishes a comprehensive model for evaluating the security of underwater CVQKD systems with different system configurations.

In practical quantum communication networks, the scheme of continuous-variable quantum key distribution (CVQKD) faces a challenge that the entangled source is controlled by a malicious eavesdropper, and although it still can generate a positive key rate and security, its performance needs to be improved, especially in secret key rate and maximum transmission distance. In this paper, we proposed a method based on the four-state discrete modulation and a heralded hybrid linear amplifier to enhance the performance of CVQKD where the entangled source originates from malicious eavesdropper. The four-state CVQKD encodes information by nonorthogonal coherent states in phase space. It has better transmission distance than Gaussian modulation counterpart, especially at low signal-to-noise ratio (SNR). Moreover, the hybrid linear amplifier concatenates a deterministic linear amplifier (DLA) and a noiseless linear amplifier (NLA), which can improve the probability of amplification success and reduce the noise penalty caused by the measurement. Furthermore, the hybrid linear amplifier can raise the SNR of CVQKD and tune between two types of performance for high-gain mode and high noise-reduction mode, therefore it can extend the maximal transmission distance while the entangled source is untrusted.

An aerosol shock tube has been developed for measuring the ignition delay times (tig) of aerosol mixtures of low-vapor-pressure fuels and for visualization of the auto-ignition flow-field. The aerosol mixture was formed in a premixing tank through an atomizing nozzle. Condensation and adsorption of suspended droplets were not observed significantly in the premixing tank and test section. A particle size analyzer was used to measure the Sauter mean diameter (SMD) of the aerosol droplets. Three pressure sensors and a photomultiplier were used to detect local pressure and OH emission respectively. Intensified charge-coupled device cameras were used to capture sequential images of the auto-ignition flow-field. The results indicated that stable and uniform aerosol could be obtained by this kind of atomizing method and gas distribution system. The averaged SMD for droplets of toluene ranged from 2 to 5 μ m at pressures of 0.14−0.19 MPa of dilute gases. In the case of a stoichiometric mixture of toluene/O2/N2, ignition delay times ranged from 77 to 1330 μs at pressures of 0.1−0.3 MPa, temperatures of 1432−1716 K and equivalence ratios of 0.5−1.5. The logarithm of ignition delay times was approximately linearly correlated to 1000/T. In contrast to the reference data, ignition delay times of aerosol toluene/O2/N2 were generally larger. Sequential images of auto-ignition flow-field showed the features of flame from generation to propagation.

We propose a novel scheme for discretely-modulated continuous-variable quantum key distribution (CVQKD) using machine learning technologies, which called multi-label learning-based CVQKD (ML-CVQKD). In particular, the proposed scheme divides the whole quantum system into state learning process and state prediction process. The former is used for training and estimating classifier, and the latter is used for generating final secret key. Meanwhile, a multi-label classification algorithm (MLCA) is also designed as an embedded classifier for distinguishing coherent state. Feature extraction for coherent state and related machine learning-based metrics for the quantum classifier are successively suggested. Security analysis based on the linear bosonic channel assumption shows that MLCA-embedded ML-CVQKD outperforms other existing discretely-modulated CVQKD protocols, such as four-state protocol and eight-state protocol, as well as the original Gaussian-modulated CVQKD protocol, and it will be further enhanced with the increase of modulation variance.

Mounting evidence shows that chronic stress can affect both the structure and function of the brain resulting in decreased synaptic plasticity and cognitive dysfunction. Although several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown how to prevent stress-induced memory deficits in aged animals. Neuroinflammation plays an important role in the pathogenesis of chronic stress-related brain dysfunction. Receptor-interacting protein 1 (RIP1) is a key molecule that can modulate inflammation, apoptosis, and necroptosis. Here, we investigated whether inhibiting RIP1 using necrostatin-1 during chronic stress could improve chronic stress-related brain dysfunction in D-galactose-induced aging mice. The stressed mice underwent restraint stress for 14 days. Necrostatin-1 (6.25 mg/kg) or vehicle was administered intraperitoneally once every 3 days during the stress period. Locomotor activity was tested using the open field test and cognitive function was assessed using the novel object recognition and Barnes maze tests. The hippocampus was collected to assess neuroinflammation (Iba1, IL-1α, IL-1β, TNF-α, and C1q), necroptosis [RIP1, RIP3, mixed lineage kinase domain-like (MLKL), and NF-κB], neuroplasticity (doublecortin, NR1, NR2A, NR2B, GluA1, and GluA2), and the expression of glucocorticoid and mineralocorticoid receptors. Blood samples were collected to quantify the levels of corticosterone. We found that chronic stress induced obvious memory impairment and neuroinflammation, decreased neurogenesis and GluA2 expression, and increased the expression of RIP1 and NF-κB. Inhibiting RIP1 by necrostatin-1 during chronic stress rescued the memory impairment and alleviated the pathological changes induced by stress. These suggest that inhibiting RIP1 using necrostatin-1 improves chronic stress-related brain dysfunction in D-galactose-induced aging mice. The potential mechanisms include limitation of neuroinflammation and the rescue of neurogenesis and GluA2 expression.

Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.

Considering the ocean water’s optical attenuation is significantly larger than that of Fiber Channel, we propose an approach to enhance the security of underwater continuous-variable quantum key distribution (CVQKD). In particular, the photon subtraction operation is performed at the emitter to enhance quantum entanglement, thereby improving the underwater transmission performance of the CVQKD. Simulation results show that the photon subtraction operation can effectively improve the performance of CVQKD in terms of underwater transmission distance. We also compare the performance of the proposed protocol in different water qualities, which shows the advantage of our protocol against water deterioration. Therefore, we provide a suitable scheme for establishing secure communication between submarine and submarine vehicles.

We propose a simultaneous classical communication and quantum key distribution (SCCQ) protocol based on plug-and-play configuration with an optical amplifier. Such a protocol could be attractive in practice since the single plug-and-play system is taken advantage of for multiple purposes. The plug-and-play scheme waives the necessity of using two independent frequency-locked laser sources to perform coherent detection, thus the phase noise existing in our protocol is small which can be tolerated by the SCCQ protocol. To further improve its capabilities, we place an optical amplifier inside Alice’s apparatus. Simulation results show that the modified protocol can well improve the secret key rate compared with the original protocol whether in asymptotic limit or finite-size regime.

To investigate the effects and underlying mechanism of dexmedetomidine on the cultured human dendritic cells (DCs).Human DCs and cytotoxic T lymphocytes (CTLs) were obtained from human cord blood mononuclear cells by density gradient centrifugation. Cultured DCs were divided into three groups: dexmedetomidine group, dexmedetomidine plus yohimbine (dexmedetomidine inhibitor) group and control group. DCs in the three groups were treated with dexmedetomidine, dexmedetomidine plus yohimbine and culture medium, respectively. After washing, the DCs were co-incubated with cultured CTLs. The maturation degree of DCs was evaluated by detecting (1) the ratios of HLA-DR-, CD86-, and CD80-positive cells (flow cytometry), and (2) expression of IL-12 and IL-23 (PCR and Elisa). The function of DCs was evaluated by detecting the proliferation (MTS assay) and cytotoxicity activity (the Elisa of IFN-γ) of CTLs. In addition, in order to explore the mechanisms of dexmedetomidine modulating DCs, α2-adrenergic receptor and its downstream signals in DCs were also detected.The ratios of HLA-DR-, CD86-, and CD80-positive cells to total cells were similar among the three groups (P>0.05). Compared to the control group, the protein levels of IL-12 and IL-23 in the culture medium and the mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the DCs all decreased in dexmedetomidine group (P

The scheme of the self-referenced continuous-variable quantum key distribution (SR CV-QKD) has been experimentally demonstrated. However, because of the finite dynamics of Alice’s amplitude modulator, there will be an extra excess noise that is proportional to the amplitude of the reference pulse, while the maximal transmission distance of this scheme is positively correlated with the amplitude of the reference pulse. Therefore, there is a trade-off between the maximal transmission distance and the amplitude of the reference pulse. In this paper, we propose the scheme of SR CV-QKD with virtual photon subtraction, which not only has no need for the use of a high intensity reference pulse to improve the maximal transmission distance, but also has no demand of adding complex physical operations to the original self-referenced scheme. Compared to the original scheme, our simulation results show that a considerable extension of the maximal transmission distance can be obtained when using a weak reference pulse, especially for one-photon subtraction. We also find that our scheme is sensible with the detector’s electronic noise at reception. A longer maximal transmission distance can be achieved for lower electronic noise. Moreover, our scheme has a better toleration of excess noise compared to the original self-referenced scheme, which implies the advantage of using virtual photon subtraction to increase the maximal tolerable excess noise for distant users. These results suggest that our scheme can make the SR CV-QKD from the laboratory possible for practical metropolitan area application.

We propose a long-distance continuous-variable quantum key distribution (CVQKD) with a four-state protocol using non-Gaussian state-discrimination detection. A photon subtraction operation, which is deployed at the transmitter, is used for splitting the signal required for generating the non-Gaussian operation to lengthen the maximum transmission distance of the CVQKD. Whereby an improved state-discrimination detector, which can be deemed as an optimized quantum measurement that allows the discrimination of nonorthogonal coherent states beating the standard quantum limit, is applied at the receiver to codetermine the measurement result with the conventional coherent detector. By tactfully exploiting the multiplexing technique, the resulting signals can be simultaneously transmitted through an untrusted quantum channel, and subsequently sent to the state-discrimination detector and coherent detector, respectively. Security analysis shows that the proposed scheme can lengthen the maximum transmission distance up to hundreds of kilometers. Furthermore, by taking the finite-size effect and composable security into account we obtain the tightest bound of the secure distance, which is more practical than that obtained in the asymptotic limit.

In the last couple of years, as the development of new imaging techniques, diffusion-weighted magnetic resonance imaging (DW-MRI) has been applied increasingly in the evaluation of various diseases in the body, and has been adopted frequently as an imaging tool in clinical tumor assessment. As a completely non-invasive, highly sensitive, well-tolerated and relatively low cost technique, diffusion-weighted imaging (DWI) can supply both quantitative and qualitative information at the cellular level by exploring irregular diffusion motion of water molecules within tissues in the body. In this article, we summarized the recent application and reliability of DWI in tumor evaluation including tumor detection, tumor features, and outcome of early treatment response.

It is known that age is an important factor for postoperative cognitive dysfunction (POCD) and the patients with POCD suffer from the impairment of multiple brain regions and multiple brain functions. However currently animal studies of POCD mainly focus on hippocampus region, therefore in this study we performed partial hepatectomy in young adult and aged rats to test the questions (1) whether POCD in animals involves other brain areas besides hippocampus; (2) how age influences POCD of young adult and aged animals. We found that (1) in young adult rats, the memory was not significantly affected (P>0.05) 1d, 3d and 7d after partial hepatectomy, but was significantly impaired (p0.05, respectively) 1d and 3d post-surgery, but the spine densities at CA1 and DG of aged rats were significant reduced 1d and 3d post-surgery (p0.05); (3) In young adult rats, surgery didn't affect the activation of microglia and levels of TNF-α and IL-1β at hippocampus (P>0.05), but significantly activated microglia and increased levels of TNF-α and IL-1β at hippocampus of aged rats (P

In the crystal of title compound, C16H19FN3O+·C10H5O8−·H2O, the water molecule and the ions are connected by intermolecular N—H...O and O—H...O hydrogen bonds and π–π stacking [centroid–centroid separation = 3.602 (1) Å] between the benzene ring and the pyridine ring, generating a three-dimensional supramolecular structure.

In order to study the efficacy of linear-polarized near-infrared light irradiation (LPNIR) on relieving chronic pain in conjunction with nerve block (NB) or local block (LB), a 3-week prospective, randomized, double-blind, controlled study was conducted to evaluate the pre- and post-therapy pain intensity. Visual analogue scales (VASs) were measured in all patients before and 6 months after therapy visiting the pain clinic during the period of August 2007 to January 2008. A total of 52 patients with either shoulder periarthritis or myofascial pain syndrome or lateral epicondylitis were randomly assigned into two groups by drawing lots. Patients in Group I were treated with NB or LB plus LPNIR; Group II patients, for their part, were treated with the same procedures as in Group I, but not using LPNIR. In both groups, the pain intensity (VAS score) decreased significantly immediately after therapy as compared to therapy. There was a significant difference between the test and control groups immediately after therapy (P

In the title compound, C16H19FN3O3+·C8H5O4−·0.5C8H6O4, the benzene-1,4-dicarboxylic acid molecule is located on a centre of symmetry. In the crystal, the molecules and ions are connected by intermolecular C—H...O and O—H...O hydrogen bonds and π–π stacking interactions [with a centroid–centroid distance of 3.402 (2) Å], generating a three-dimensional supramolecular structure.

Benzene, cyclohexane, and cyclohexene are essential raw materials in the petrochemical industry. Their separation and purification rely on traditional distillation processes that consume a large amount of energy due to their close boiling points. Here, we describe a new microporous metal azolate framework for mild adsorptive and kinetic separation of the three hexacyclic hydrocarbons. This metal azolate framework exhibits ultrafast benzene adsorption in a short saturation time within seconds and ultrafast kinetic adsorptive separation of benzene/cyclohexane and benzene/cyclohexene. Investigation into the adsorption kinetics of benzene, cyclohexane and cyclohexene reveals a two-step adsorption process, including steps of intraparticle diffusion and surface adsorption, respectively. Also, by adjusting the sample particle size, the adsorption behaviour can be significantly controlled. The large-particle sample achieves a high selectivity for benzene/cyclohexene (94.3) and an inverse selectivity for cyclohexane/cyclohexene, being opposite to the small-particle sample. This highlights the feasibility of controlling adsorption selectivity by manipulating the kinetic steps in porous materials. [ABSTRACT FROM AUTHOR]

lignin was modified by ultrasonic assisted Fenton oxidation, and high density polyethylene/lignin composites (HDPE/Lig) were prepared. The changes of functional groups and molecular weight of lignin before and after modification were analyzed, and the effects of lignin content before and after modification on mechanical properties, microstructure and rheological properties of the composites were discussed. The results show that the number average molecular weight (Mn) of lignin modified by ultrasonic-Fenton oxidation decreases from 15 034 g/mol to 6 375 g/mol, methoxy group decreases, phenolic hydroxyl group and carboxyl group increase. The tensile strength and impact strength of HDPE/Lig increase first and then decrease with the increase of lignin content. After modification, the optimum filling amount of lignin increases from 10% to 20%. After modification, the dispersity and compatibility of lignin are improved, the degree of microphase separation is reduced, and the physical forced compatibilization effect is better. The viscosity of HDPE is increased by lignin, and the viscosity, storage modulus and loss modulus of HDPE composites are decreased by ultrasonic-Fenton oxidation of lignin. [ABSTRACT FROM AUTHOR]

Background/aim: Urethroplasty is the preferred treatment for hypospadias but is affected by the severity of anomalies, making it a complex procedure with potential postoperative complications. Following surgery, parents receive instructions and recommendations, whether from nurses or physicians, regardless of complication rates. However, nurses play a crucial role in educating caregivers before surgery and providing postoperative care during follow-up. The study aims to assess parents' knowledge and practices, as well as the frequency of complications in boys who underwent urethroplasty for hypospadias and received postoperative nurse-led care and whose parents received preoperative education against those of boys who underwent urethroplasty under routine hospital care. Materials and methods: In this retrospective study, Han Chinese boys aged 21--41 months in Western China who underwent urethroplasty for hypospadias were divided into two groups: the NI cohort (n = 103), where they received postoperative nurse-led care and their parents received preoperative education, and the RH cohort (n = 142), where boys underwent routine hospital care. Results: After urethroplasty, higher numbers of caregivers with satisfactory knowledge (96 (93%) vs. 80 (56%), p < 0.0001) and practice (102 (99%) vs. 132 (93%), p = 0.0276) were reported in the NI cohort compared to the RH cohort. Additionally, a higher number of boys in the RH cohort experienced adverse effects such as moderate bleeding (13 (9%) vs. 1 (1%), p = 0.0052), wound infection (17 (12%) vs. 4 (4%), p = 0.0356), urinary obstruction (35 (25%) vs. 10 (10%), p = 0.0049), burning sensation (47 (33%) vs. 15 (15%), p = 0.0019), and urinary stent fall (32 (23%) vs. 6 (6%), p = 0.0008) compared to those in the NI cohort. Conclusion: Preoperative instructions enhance caregivers' knowledge and practices following urethroplasty, while postoperative nurseled care reduces immediate postoperative complications associated with hypospadias in boys. [ABSTRACT FROM AUTHOR]