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A new synthetic methodology for the synthesis of 5

KN026 is a novel human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody that binds two distinct domains of HER2. We report the safety and efficacy results of the phase 2 trial in patients with advanced HER2-expressing gastric or gastroesophageal junction cancer who failed from at least one prior line of standard treatment.In this open-label, multicentre, phase 2 trial, eligible patients were enrolled in the high-level HER2 cohort or low-level HER2 cohort and assigned to receive KN026 10 mg/kg (once a week), 20 mg/kg (once every two weeks) or 30 mg/kg (once every three weeks) intravenously. The primary end-points were the objective response rate (ORR) and duration of response assessed according to Response Evaluation Criteria in Solid Tumours (version 1.1).Between 17th June 2019 and 23rd August 2021, 45 patients were enrolled and received at least one dose of KN026, including 27 patients in the high-level HER2 cohort, 14 patients in the low-level HER2 cohort and four patients who had no HER2 expression. The ORR in the high-level HER2 cohort was 56% (95% confidence interval [CI] 35%-76%), with a durable response duration of 9.7 months (95% CI 4.2-not evaluable); while for the patients with low-level HER2, the ORR was 14% (95% CI 2%-43%). The most frequent ≥ grade 3 treatment-emergent adverse events were gastrointestinal disorders (five patients, 11%). No drug-related deaths were reported.KN026 showed a favourable safety profile and promising anti-tumour activity. Our results support further studies evaluating KN026 and the combination treatment with other active drugs in patients with advanced gastric or gastroesophageal junction cancer having high-level HER2 expression.

MXene has drawn considerable attention in energy storage due to particular physicochemical properties. At present, among most near-ambient temperature preparation methods, water is usually served as the main solvent. However, MXene is usually subjected to fast structural degradation on account of water molecules attacking in aqueous solution. Herein, we report a novel water-free etching strategy for synthesizing few-layered Ti

Background: MET gene amplification is associated with poor prognosis in gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ). Savolitinib is a potent and highly selective oral MET tyrosine-kinase inhibitor. Here we reported the preliminary efficacy and safety from a phase 2 trial of savolitinib monotherapy in patients (pts) with MET-amplified advanced or metastatic GC/GEJ. (NCT04923932). Methods: Eligible pts had 2L+ GEJ or GC, with MET amplification and measurable lesions. Pts received savolitinib at 600 mg QD for body weight (BW) ≥50 kg, while 400 mg QD for BW Results: As of IA, 20 pts were enrolled for QD regimen. Demographics and clinical outcomes are shown in table 1. The mean relative dose intensity of 93.07%. Median duration of exposure was 2.09 months. Confirmed ORR by IRC was 45%, and reached 50% in 16 patients with MET GCN (high) while only 1 PR was observed in 4 patients with MET GCN (low). Duration of response rate at 4-month was 85.7% with median follow up time of 5.5 months. The most common Gr≥3 TRAE (≥5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. In all pts, only 1 patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE. Conclusion: Savolitinib monotherapy had manageable safety and showed promising efficacy in pts with MET-amplified GEJ or GC, particularly in pts with MET high GCN. BID regimen is being investigated to further evaluate the efficacy and safety of savolitinib in pts with MET high GCN. Table 1. Pts baseline characteristics and clinical efficacy Baseline Characteristics ITT in IA (n=20) Median age (min, max), yearsSex (male/female), nECOG (0/1/2)Median BMI (min, max), (kg/m2)Primary location of tumor (GC/GEJ)Tumor stage (IV)Prior line of therapy (1/2/≥3)MET GCN (high/low) 57.00 (39.5, 76.8)17/33/15/220.8 (14.9, 25.8)16/4205/10/516/4 Clinical Efficacy By IRC By Investigator Confirmed objective response rateDisease control rate4m-DoR rate,% (95% CI) 45%65%85.7 (33.4, 97.9) 40%55%71.4 (25.8, 92.0) Citation Format: Zhi Peng, Hua Wang, Baorui Liu, Huiting Xu, Zhenyang Liu, Tianshu Liu, Jun Zhang, Yuxian Bai, Ying Yuan, Tao Wu, Feng Ye, Qinghua Pan, Jufeng Wang, Enxiao Li, Diansheng Zhong, Yueyin Pan, Yanru Qin, Yan Yang, Yusheng Wang, Aiping Zhou, Yongshun Chen, Dianbao Zhang, Hongli Liu, Xiujuan Qu, Shubin Wang, Ning Liu, Jinsheng Wu, Wei Li, Kejun Nan, Hongming Pan, Jianming Xu, Chunmei Bai, Heling Liu, Jia Wei, Runzhi Chen, Rongrong Li, Wei Li, Jinghong Zhou, Hongyan Yin, Qian Xu, Songhua Fan, Yongxin Ren, Weiguo Su, Lin Shen. A multicenter Phase II study of savolitinib in patients with MET-amplified gastroesophogeal junction adenocarcinomas or gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT152.

Aqueous zinc ion batteries have attracted extensive concern as a promising candidate for large-scale energy storage because of their high theoretical specific capacity, low cost and inherent safety. However, the lacking of applicable cathode materials with outstanding electrochemical performance have severely hindered the further development of aqueous zinc ion batteries. Herein, we report a hierarchical accordion-like manganese oxide@carbon (MnO@C) hybrid with strong interaction heterointerface and comprehensively inquire into its electrochemical performance as cathode materials for aqueous zinc ion batteries. The unique hierarchical accordion-like layered structure coupling with strong interaction heterointerface between small MnO and carbon matrix efficaciously improve the ion/electron transfer process and enhance structure stability of the MnO@C hybrid. Benefitting from these unique advantages, the MnO@C hybrid bestows excellent specific capacity of 456 mAh g

Conventional CRISPR approaches for precision genome editing rely on the introduction of DNA double-strand breaks (DSB) and activation of homology-directed repair (HDR), which is inherently genotoxic and inefficient in somatic cells. The development of base editing (BE) systems that edit a target base without requiring generation of DSB or HDR offers an alternative. Here, we describe a novel BE system called Pin-point(TM) that recruits a DNA base-modifying enzyme through an RNA aptamer within the gRNA molecule. Pin-point is capable of efficiently modifying base pairs in the human genome with precision and low on-target indel formation. This system can potentially be applied for correcting pathogenic mutations, installing premature stop codons in pathological genes, and introducing other types of genetic changes for basic research and therapeutic development.

Quadriplegia is an extremely serious disease. Due to the impaired function of patients' limbs, it is difficult for them to move freely by a wheelchair. This dilemma has become a huge obstacle to the rehabilitation of the disabled, and meanwhile added extra burden to society. To improve the quality of their lives, our team designs a vision-controlled automatic wheelchair based on the pupil center and cornea reflection (PCCR) technique. By constructing a multi-sensor real-time intelligent control system, the wheelchair realizes eye-controlled movements and other auxiliary functions such as emergency communication and rollover alarm. Through continuous optimization of multiple versions, a more intelligent, highly reliable, and low-cost wheelchair is manufactured.

397 Background: ASKB589 is a humanized IgG1 monoclonal antibody against Claudin 18.2 (CLDN18.2) with high affinity and enhanced antibody-dependent cellular cytotoxicity activity. We report preliminary safety and efficacy data from an ongoing Phase I/II, first-in-human, dose-escalation and expansion study of ASKB589 in patients (pts) with advanced solid tumors (NCT04632108). Methods: A two-part study was initiated to determine the maximum tolerated dose (MTD), safety and tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ASKB589 as monotherapy (Part A) and in combination with chemotherapy (Part B). Each part used a modified 3 + 3 dose escalation design. Responses were assessed per RECIST 1.1 every 2 cycles (6 weeks). Adverse events (AEs) were graded using CTCAE v5.0. In Part A, pts with heavily pre-treated solid tumors received ASKB589 intravenously (IV) at doses of 0.3, 1, 3, 6, 10,15 or 20mg/kg every 3 weeks (Q3W). In Part B, pts with gastric/gastro-esophageal junction (G/GEJ) cancers received ASKB589 IV at doses of 3, 6, 10 or 15 mg/kg Q3W in combination with capecitabine plus oxaliplatin. Results: As of September 9, 2022, 51 pts received ASKB589 and no drug limiting toxicity (DLT) was observed. In expansion, pts have been enrolled into 6, 10, 15 mg/kg doses. In Part A, 17 pts were enrolled in escalation and 13 in expansion. All pts had metastatic disease, and most (90%) had ≥2 lines of prior therapy. 24 (80%) pts had treatment-related adverse events (TRAEs), the most common being nausea (53%), vomiting (43%), hypoalbuminemia (40%) and loss of appetite (30%). While the majority of TRAEs were grade 1 or 2, 3 pts (10%) had grade 3 events. For the 9 evaluable pts (G/GEJ cancer who received ≥10 mg/kg ASKB589 with at least one post-baseline tumor assessment), 5 pts (45%) had decreases in tumor size (range 1-38% from baseline). 2 pts achieved a partial response (PR) for an objective response rate (ORR) of 22%. In addition, 6 pts had stable disease (SD) for a disease control rate (DCR) of 89%. In Part B, 13 pts were enrolled in escalation and 8 in expansion. These pts were with advanced disease (95% stage IV) and had no prior systemic treatment in this setting. 17 (81%) pts had TRAEs, the most common being nausea (76%), vomiting (66%), hypoalbuminemia (52%), granulocytopenia (38%) and hypoleukemia (33%). While the majority of TRAEs were grade 1 or 2, 8 pts (38%) had grade 3 events. For the 12 evaluable pts (G/GEJ cancer who received ≥6 mg/kg ASKB589 with at least one post-baseline tumor assessment), all had decreases in tumor size (range 6-66% from baseline). 9 pts achieved PR for an ORR of 75%. In addition, 3 pts had SD for a DCR of 100%. The PK profile showed dose-related increases in drug exposure across study doses. Conclusions: ASKB589 showed a manageable safety profile up to doses of 20 mg/kg and promising antitumor activity, both as monotherapy and in combination with chemotherapy. Clinical trial information: NCT04632108 .

Aqueous zinc-ion batteries receive more and more attentions on account of their low cost, high theoretical density and inherent safety. Nevertheless, the lack of suitable cathode materials with excellent performance still severely impedes the development of aqueous zinc-ion batteries. Herein, an in-situ electrochemical induction strategy is developed to prepare hollow nanotube-like amorphous vanadium oxide and carbon (a-V

Tartary buckwheat shows health benefits with its high antioxidant activity and abundant flavonoid content. However, glycosylated flavonoid accumulation patterns and their molecular basis remain unidentified in Tartary buckwheat. Here, our metabolomics analysis revealed that F3'H branching was the major flavonoid metabolic flux in Tartary buckwheat. Interestingly, metabolome results also showed that the most abundant flavonoids were mainly in the glycosylated form, including flavonoid glycosides and flavonoid diglycosides in Tartary buckwheat. However, the flavonoid glycosides glycosyltransferase (GGT) gene catalyzing the second glycosylation step of flavonoid diglycoside has not been discovered yet in Tartary buckwheat. Thus, we explored GGT genes in the transcriptome-metabolome correlation network and confirmed that FtUGT79A15 showed the rhamnosyltransferase activity to catalyze quercetin 3-O-glucoside to rutin invitro and inplanta. Overall, FtUGT79A15 was identified to involve in the flavonoid diglycoside biosynthesis pathway in Tartary buckwheat.

Although sophisticated radiotherapy (RT) technology has been widely applied in clinical oncotherapy, unsatisfactory therapeutic effects due to hypoxic tumor microenvironments and complications are still prevalent. Herein, copper sulphide nanoparticles (CuS NPs) wrapped on the surface of upconversion nanoparticles (UCNPs)

The aim of this study is to explore the prognostic values and optimal cutoff point of time to positivity (TTP) of blood culture in children with Klebsiella pneumoniae (K. pneumoniae) bloodstream infection. Ninety-four children with K. pneumoniae bloodstream infection hospitalized in Children's Hospital of Chongqing Medical University from April 2014 to January 2019 were enrolled retrospectively. TTP and risk factors were determined and analyzed by receiver operating characteristic (ROC) analysis and logistic regression analysis. The standard cutoff point of TTP was 13 h. Patients in early TTP (≤ 13 h) group had significantly higher in-hospital mortality (37.93% vs 6.15%, P = 0.000), higher incidence of septic shock (44.83% vs 6.15%, P = 0.000), higher proportion of PRISM III scores ≥ 10 (48.28% vs 20.00%, P = 0.005), and higher proportion of hypoalbuminemia on admission (44.83% vs 18.46%, P = 0.008). Multivariate analysis indicated PRISM III scores ≥ 10, early TTP, and hypoalbuminemia on admission were independent risk factors of in-hospital mortality (OR 8.36, 95% CI 1.80-38.92, P = 0.007; OR 5.85, 95% CI 1.33-25.61, P = 0.019; OR 5.73, 95% CI 1.30-25.22, P = 0.021, respectively) and septic shock (OR 14.04, 95% CI 2.63-75.38, P = 0.002; OR 11.26, 95% CI 2.10-60.22, P = 0.005; OR 10.27, 95% CI 2.01-52.35, P = 0.005, respectively).Conclusion: Early TTP (TTP ≤ 13 h), PRISM III scores ≥ 10, and hypoalbuminemia on admission appeared to be associated with worse outcomes for K. pneumoniae bloodstream infection children. What is Known: • Klebsiella pneumoniae bloodstream infection is an important cause of infectious disease morbidity and mortality worldwide in children. • Short duration of time to positivity indicated poor clinical outcomes. What is New: • Time to positivity ≤ 13 h, along with PRISM III scores ≥ 10 and hypoalbuminemia on admission, indicated higher in-hospital mortality and incidence of septic shock in Klebsiella pneumoniae bloodstream infection children. • The cut-off point of TTP in this pediatric study was much longer than that reported in adult patients.

Nonalcoholic fatty liver disease (NAFLD) has a developmental origin and is influenced in utero. We aimed to evaluate if maternal diet intervention before pregnancy would be beneficial to reduce the risk of offspring NAFLD. In our study, female mice were either on a normal-fat diet (NF group), or a high-fat diet for 12 weeks and continued on this diet throughout pregnancy and lactation (HF group), or switched from HF-to-NF diet 1 week (H1N group), or 9 weeks (H9N group) before pregnancy. Compared with the NF offspring, the H1N and HF, but not the H9N offspring, displayed more severe hepatic steatosis and glucose intolerance. More specifically, an abnormal blood lipid panel was seen in the H1N offspring and abnormal hepatic free fatty acid composition was present in both the HF and H1N offspring, while the H9N offspring displayed both at normal levels. These physiological changes were associated with desensitized hepatic insulin/AKT signaling, increased expression of genes and proteins for de novo lipogenesis and cholesterol synthesis, decreased expression of genes and proteins for fatty acid oxidation, increased Pcsk9 expression, and hypoactivation of 5′ AMP-activated protein kinase (AMPK) signaling in the HF and H1N offspring. However, these effects were completely or partially rescued in the H9N offspring. In summary, we found that early maternal diet intervention is effective in reducing the risk of offspring NAFLD caused by maternal HF diet. These findings provide significant support to develop effective diet intervention strategies and policies for prevention of obesity and NAFLD to promote optimal health outcomes for mothers and children. The authors evaluated the efficiency of different maternal diet interventions on reducing the risk for offspring nonalcoholic fatty liver disease due to maternal overnutrition. They found that that different maternal diet interventions prime the lipid metabolism differently via changes in lipogenesis and β-oxidation through insulin/AKT signaling and 5′ AMP-activated protein kinase signaling.

Gluconeogenesis (GNG) is de novo production of glucose from endogenous carbon sources. Although it is a commonly studied pathway, particularly in disease, there is a lack of consensus about substrate preference. Moreover, primary hepatocytes are the current gold standard for in vitro liver studies, but no direct comparison of substrate preference at physiological fasting concentrations has been performed. We show that mouse primary hepatocytes prefer glycerol to pyruvate/lactate in glucose production assays and 13C isotope tracing studies at the high concentrations commonly used in the literature, as well as at more relevant fasting, physiological concentrations. In addition, when glycerol, pyruvate/lactate, and glutamine are all present, glycerol is responsible for over 75% of all glucose carbons labeled. We also found that glycerol can induce a rate-limiting enzyme of GNG, glucose-6-phosphatase. Lastly, we suggest that glycerol is a better substrate than pyruvate to test in vivo production of glucose in fasting mice. In conclusion, glycerol is the major carbon source for GNG in vitro and in vivo and should be compared with other substrates when studying GNG in the context of metabolic disease states.

Little is known if and how maternal diet affects the liver phospholipid profiles that contribute to non-alcoholic fatty liver disease (NAFLD) development in offspring. We examined NAFLD phenotypes in male offspring mice of either maternal normal-fat diet (NF group), maternal high-fat diet (HF group), maternal methionine supplement (H1S group), or complete one-carbon supplement (H2S group) added to the maternal HF diet during gestation and lactation. HF offspring displayed worsened NAFLD phenotypes induced by post-weaning HF diet, however, maternal one-carbon supplement prevented such outcome. HF offspring also showed a distinct phospholipid profile from the offspring exposed to H1S or H2S diet. Whole genome bisulfite sequencing (WGBS) analysis further identified five pathways involved in phospholipid metabolism altered by different maternal diet interventions. Furthermore, differential methylated regions (DMRs) on Prkca, Dgkh, Plcb1 and Dgki were identified comparing between HF and NF offspring; most of these DMRs were recovered in H2S offspring. These methylation pattern changes were associated with gene expression changes: HF diet significantly reduced while H1S and H2S diet recovered their levels. Maternal HF diet disrupted offspring phospholipid profiles contributing to worsened hepatic steatosis. The maternal one-carbon supplement prevented such effects, probably through DNA methylation modification.

BackgroundThe dynamic of soil-borne disease is closely related to the rhizosphere microbial communities. Maize-soybean intercropping can suppress soybean root rot as compared to monoculture. However, it is still unknown whether rhizosphere microbial community participates in the regulation of intercropped soybean root rot.MethodsIn this study, the difference of rhizosphere Fusarium and Trichoderma community was compared between healthy or root-rotted soybean rhizosphere soil from soybean monoculture and maize-soybean intercropping, and the inhibitory effect of potential biocontrol Trichoderma against pathogenic Fusarium were examined.ResultsThe abundance of rhizosphere Fusarium was remarkably different between intercropping and monoculture, while Trichoderma was largely accumulated in healthy rhizosphere soil of intercropping rather than monoculture. Four rhizosphere Fusarium species identified were all pathogenic to soybean but displayed distinct composition and isolation proportion in the corresponding soil types. As the dominant and most aggressive species, F. oxysporum was more frequently isolated in diseased soil of monoculture. Furthermore, of three Trichoderma species identified, T. harzianum dramatically increased in the rhizosphere of intercropping rather than monoculture as compared to T. virens and T. afroharzianum. For in-vitro antagonism test, Trichoderma strains had antagonistic effects on F. oxysporum with the percentage of mycelial inhibition ranging of 50.59%-92.94%, and they displayed good mycoparasitic abilities against F. oxysporum through coiling around and entering into the hyphae, expanding along cell-cell lumen and even dissolving cell walls of target fungus.Conclusion These results indicate maize-soybean intercropping significantly increase the density and composition proportion of beneficial Trichoderma to antagonist the pathogenic Fusarium species, thus contributing to the suppression of soybean root rot under intercropping.

Fasting hyperglycemia in diabetes mellitus is caused by unregulated glucagon secretion that activates gluconeogenesis (GNG) and increases the use of pyruvate, lactate, amino acids, and glycerol. Studies of GNG in hepatocytes, however, tend to test a limited number of substrates at non-physiologic concentrations. Therefore, we treated cultured primary hepatocytes with three identical substrate mixtures of pyruvate/lactate, glutamine, and glycerol at serum fasting concentrations, where a different U

BackgroundErlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, demonstrated therapeutic efficacy against pancreatic cancer. However, acquired resistance to erlotinib in pancreatic cancer is widely observed, and the exact mechanisms have not been fully explored until now. We examined the role of circular RNA circ_0013587 in the acquired resistance to erlotinib in pancreatic cancer cells and explored the underlying mechanisms.MethodsWe selected erlotinib-resistant pancreatic cancer cells from the AsPC-1 cell line. The expression of circ_0013587 was examined by qRT-PCR assays. The effects of circ_0013587 on pancreatic cancer cell proliferation, invasion, and erlotinib resistance were assessed by cell functional assays. Bioinformatic analysis and dual-luciferase reporter assays identified circ_0013587 and E-cadherin as direct targets of miR-1227. Mouse xenograft models were employed to investigate the function of circ_0013587 in erlotinib resistance of tumors in vivo.ResultsCirc_0013587 expression was significantly reduced in erlotinib-resistant AsPC-1 cells. We found that increasing circ_0013587 levels in erlotinib-resistant AsPC-1 cells re-sensitized them, whereas reducing circ_0013587 levels in erlotinib-sensitive AsPC-1 cells made them resistant. Mechanically, circ_0013587 released E-cadherin from the suppression of miR-1227, leading to E-cadherin up-regulation. Rescue assays highlighted that circ_0013587 reversed erlotinib resistance in pancreatic cancer cells by increasing E-cadherin levels through reducing the expression of miR-1227. Furthermore, circ_0013587 overexpression sensitized erlotinib-resistant AsPC-1 cells to erlotinib in xenograft models.ConclusionsOur results demonstrated that down-regulation of circ_0013587 contributes to acquired resistance to erlotinib in pancreatic cancer cells through mediating the miR-1227/E-cadherin pathway and that circ_0013587 is a potential target molecular to overcome erlotinib resistance.

We aim to evaluate the effects of time to appropriate therapy (TTAT) on outcomes in children with nosocomial K. pneumoniae bloodstream infection, and to find an optimal time window for empiric antibiotics administration. Children with nosocomial K. pneumoniae bloodstream infection hospitalized in Children’s Hospital of Chongqing Medical University from April 2014 to December 2019 were enrolled retrospectively. TTAT cutoff point and risk factors were determined and analyzed by Classification and Regression Tree (CART) analysis and Logistic Regression analysis. Overall, sixty-seven patients were enrolled. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 hours. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), PRISM III scores ≥ 10, early TTP (TTP ≤ 13 h), and need for invasive mechanical ventilation were independent risk factors of septic shock (OR 9.87, 95% CI 1.46-66.59, P = 0.019; OR 9.69, 95% CI 1.15-81.39, P = 0.036; OR 8.28, 95% CI 1.37-50.10, P = 0.021; OR 6.52, 95% CI 1.08-39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25-393.94, P = 0.035; OR 40.06, 95% CI 2.32-691.35, P = 0.011; OR 22.60, 95% CI 1.78-287.27, P = 0.016; OR 12.21, 95% CI 1.06-140.67, P = 0.045; respectively). Conclusions: TTAT is an independent predictor of poor outcome in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antibiotic therapy should begin within 10.7 hours from the onset of bloodstream infection.

Background: Renal cell carcinoma (RCC) is one of the most common malignancies worldwide. Noninvasive imaging techniques, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), have been involved in increasing evolution to detect RCC. This meta-analysis aims to compare to compare the value of MRI, SPECT, and PET in the diagnosis of RCC, and to provide evidence for decision-making in terms of further research and clinical settings.Methods: Electronic databases including PubMed, Web of Science, Embase, and Cochrane Library were systemically searched. Studies concerning MRI, SPECT, and PET for the detection of RCC were included. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), with their respective 95% confidence interval (CIs) and the area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated.Results: A total of 44 articles were finally detected for inclusion in this meta-analysis. The pooled sensitivities of MRI, SPECT, and PET were 0.80, 0.81, and 0.88, respectively. Their respective overall specificities were 0.90, 0.54, and 0.87. Results in the subgroup analysis of the performance of SPECT that the pooled sensitivity, specificity, and AUC of the prospective SPECT studies included were 0.80, 0.42, 0.80, respectively. In the analysis of 18F-FDG PET, the pooled sensitivity, specificity, and AUC were 0.88, 0.86, and 0.92, respectively. PET studies showed a pooled sensitivity, specificity, and AUC of 0.80, 0.85, and 0.85, respectively in the diagnosis of primary RCC. The pooled sensitivity, specificity, and AUC of PET studies in detecting recurrent or metastatic RCC were 0.93, 0.88, and 0.94.Conclusion: Our meta-analysis manifests that MRI and PET present better diagnostic value for the detection of RCC in comparison with SPECT. PET is superior in the diagnosis of recurrent or metastatic RCC.

Anaerobic digestion (AD) comprises a series of biochemical reactions, with methane as one of the target products. Amino acids (AAs) are important molecular and primary intermediate products when protein is the main component of organic waste/wastewater. The L (levorotatory, left-handed)-configuration is natural for AAs, while D (dextrorotatory, right-handed) -AAs also widely exist in the natural environment and can be generated by racemization. However, the effects and underlying mechanisms of natural AAs and their enantiomers on the methane yield and the underlying mechanisms remain unclear. In this study, the effects of certain widespread L-AAs and their enantiomers on two-stage AD and the mechanisms therein were investigated. The AAs enantiomers showed variable or even opposite effects on different processes. The methane yield from a model monosaccharide (glucose) decreased by 57% with D-leucine addition. The butyrate generation and the methane yield from propionate were sensitive to the AA configuration and were inhibited by D-leucine by 80% and 61.8%, respectively, with D-leucine addition, while the volatile fatty acids concentration was slightly increased with the addition of L-leucine. The related mechanisms were further investigated in terms of key enzymes and microbial communities. The addition of D-Leucine decreased acetic acid production from homoacetogens by 30.2% due to the inhibition of key enzymes involved in hydrogen generation and consumption. The transform of butyryl CoA to butyryl phosphate was the rate-limiting step, with the related enzyme (phosphotransbutylase) was inhibited by D-leucine. Furthermore, the bacteria related to butyric acid generation and organic matter degradation were inhibited by D-leucine, while the methanogenic archaea remained stable irrespective of leucine addition. The effect of D-AAs on microorganisms is related to the type of sludge. In this study, the methanogenetic seed sludge was granular and did not dissociate after treatment; however, the D-AAs could trigger biofilm disassembly and reduce the stability of the sludge floc. The study provides a novel method for regulating AD by adding specific AAs with L or D configuration.

Although photothermal therapy (PTT) has been extensively applied in the treatment of cancer using various types of nanomaterials, low penetration of excitation light, low nanoparticle concentration enrichment and abominable nanoparticle permeation still remain huge obstacles in cancer therapy. Herein, we synthesized stable cupric sulfide nanoparticles (CuS NPs) with small size, which after functionalization with a MnO2 coating, were employed for diagnosing and treating tumors. After reacting with an RGD peptide, the nanoparticles were able to target and focus on tumor sites. Once the nanoparticles were enriched in tumors by RGD targeting, the MnO2 coating decomposed to Mn2+ ions in the tumor microenvironment. Meanwhile, the decomposition of MnO2 allowed the dispersion of aggregated CuS NPs to enter deep tumors, and a 1064 nm laser with powerful penetration was utilized to activate CuS NPs in deep tumors for PTT. More importantly, the generated Mn2+ ions were used for stimuli-enhanced T1-weighted magnetic resonance imaging (T1-MRI) and agminated CuS NPs in tumors were accepted for computed tomography (CT) imaging. It was found that these nanocomposites can accurately indicate tumor sites after being intravenously injected, and in vitro and in vivo experiments illustrated the tremendous potential of these nanoplatforms for use in imaging-guided PTT against HepG2 tumors.

4040 Background: Outcomes of second or later-line treatment for pts with advanced GC/GEJC remain inferior. KN026 is a novel HER2-targeted bispecific antibody composed of VH regions of trastuzumab and pertuzumab, targeting the HER2 juxtamembrane domain (IV) and the dimerization domain (II) simultaneously. KN026 has shown promising antitumor efficacy in preclinical and phase I studies. Here we present the results of KN026 monotherapy in previously treated, advanced HER2-expressing GC/GEJC. Methods: In this multi-center, single-arm, open-label, 2-cohort phase II study, adult pts with previously treated, advanced GC/GEJC were assigned into a HER2 high-level cohort (Cohort 1: IHC3+ or IHC 2+ ISH+) or a HER2 low-level cohort (Cohort 2: IHC 1+/2+ ISH- or IHC 0/1+ISH+). KN026 was given intravenously in 10 mg/kg QW, 20 mg/kg Q2W, or 30 mg/kg Q3W. Primary endpoints were objective response rate (ORR) and duration of response (DoR) assessed by investigators per RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety outcomes. This trial is registered at ClinicalTrials.gov (NCT03925974). Results: At data cut-off (Oct. 29, 2021), 45 pts were enrolled and treated with KN026; 39 were eligible for response evaluation (25 pts in Cohort 1 and 14 pts in Cohort 2). In Cohort 1, ORR was 56% (95%CI 35%-76%) with 14 PR; the median DoR was 9.7 months (mo) (95%CI 4.2-not evaluable (NE)). At a median follow-up of 14.7 mo (95%CI 9.4-16.5), the median PFS was 8.3 mo (95%CI 4.2-11.4), and median OS was 16.3 mo (95% CI 11.0- NE). In Cohort 2, ORR was 14% (95%CI 2%-43%), with median DoR being 6.2 mo (95%CI 3.2-NE). At a median follow-up of 27.5 mo (95%CI 4.1-NE), the median PFS was 1.4 mo (95%CI 1.4-4.1), and median OS was 9.6 mo (95% CI 3.5-14.9). The table shows efficacy in Cohort 1 pts who have progressed on the prior trastuzumab treatment. KN026-related adverse events (TRAEs) were observed in 37 (82%) pts; the most common TRAEs (any grade) were increased aspartate aminotransferase (12, 27%), increased alanine aminotransferase (9, 20%), rash (7,16%), anemia (7,16%), and infusion-related reaction (7,16%). Four pts reported 5 grade 3 TRAEs, including infusion-related reaction, renal hydrocele, ureteral stenosis, increased blood pressure, and abnormal hepatic function (1 each). No grade 4 or 5 TRAEs occurred. Conclusions: KN026 monotherapy yielded promising efficacy with mild to moderate toxicities in pts with previously treated, advanced GC/GEJC. Further investigation is warranted. Clinical trial information: NCT03925974. [Table: see text]

BACKGROUND: Vancomycin trough concentrations are associated with clinical outcomes and drug adverse effects. This study investigates the effects of continuous venovenous hemofiltration (CVVH) on vancomycin trough concentrations in critically ill children with a vancomycin dosage of 40–60 mg/kg/day. METHODS: Children with steady-state vancomycin trough concentrations admitted to the pediatric intensive care unit (PICU) between January 2016 and December 2019 were retrospectively enrolled. Patients were divided into CVVH and non-CVVH groups according to treatment differences and renal function. Vancomycin trough concentrations were then compared between the groups, and risk factors for supratherapeutic trough concentrations (>20 mg/L) were analyzed with logistic regression. RESULTS: Of the 119 patients included, 35 were enrolled in the CVVH group and 84 in the non-CVVH group. Median vancomycin trough concentrations were significantly higher in the CVVH group than those in the non-CVVH group [14.9 (IQR =9.6–19.6) vs. 9.3 (IQR =7.0–13.4), P

Background & aims Pregnant women may transmit their metabolic phenotypes to their offspring, enhancing the risk for nonalcoholic fatty liver disease (NAFLD); however, the molecular mechanisms remain unclear. Methods Prior to pregnancy female mice were fed either a maternal normal-fat diet (NF-group, "no effectors"), or a maternal high-fat diet (HF-group, "persistent effectors"), or were transitioned from a HF to a NF diet before pregnancy (H9N-group, "effectors removal"), followed by pregnancy and lactation, and then offspring were fed high-fat diets after weaning. Offspring livers were analysed by functional studies, as well as next-generation sequencing for gene expression profiles and DNA methylation changes. Results The HF, but not the H9N offspring, displayed glucose intolerance and hepatic steatosis. The HF offspring also displayed a disruption of lipid homeostasis associated with an altered methionine cycle and abnormal one-carbon metabolism that caused DNA hypermethylation and L-carnitine depletion associated with deactivated AMPK signalling and decreased expression of PPAR-α and genes for fatty acid oxidation. These changes were not present in H9N offspring. In addition, we identified maternal HF diet-induced genes involved in one-carbon metabolism that were associated with DNA methylation modifications in HF offspring. Importantly, the DNA methylation modifications and their associated gene expression changes were reversed in H9N offspring livers. Conclusions Our results demonstrate for the first time that maternal HF diet disrupted the methionine cycle and one-carbon metabolism in offspring livers which further altered lipid homeostasis. CpG islands of specific genes involved in one-carbon metabolism modified by different maternal diets were identified.

This paper aims to solve the problem of optimal portfolio of venture capital investment by intelligent algorithm. Using the actual data, this paper constructs the optimal portfolio models based on different risk measures and termination conditions: unit risk return maximization model, VaR risk control model, risk and return preference model. Genetic algorithm and simulated annealing algorithm are used to optimize the models.

Objectives: To evaluate the effects of time to appropriate therapy (TTAT) on outcomes in children with nosocomial K. pneumoniae bloodstream infection, and to find an optimal time window for empiric antibiotics administration. Methods: Children with nosocomial K. pneumoniae bloodstream infection hospitalized in Children’s Hospital of Chongqing Medical University from April 2014 to December 2019 were enrolled retrospectively. TTAT cutoff point and risk factors were determined and analyzed by Classification and Regression Tree (CART) analysis and Logistic Regression analysis. Results: Overall, sixty-seven patients were enrolled. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 hours. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), PRISM III scores ≥ 10, early TTP (TTP ≤ 13 h), and need for invasive mechanical ventilation were independent risk factors of septic shock (OR 9.87, 95% CI 1.46-66.59, P = 0.019; OR 9.69, 95% CI 1.15-81.39, P = 0.036; OR 8.28, 95% CI 1.37-50.10, P = 0.021; OR 6.52, 95% CI 1.08-39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25-393.94, P = 0.035; OR 40.06, 95% CI 2.32-691.35, P = 0.011; OR 22.60, 95% CI 1.78-287.27, P = 0.016; OR 12.21, 95% CI 1.06-140.67, P = 0.045; respectively). Conclusions: TTAT is an independent predictor of poor outcome in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antibiotic therapy should begin within 10.7 hours from the onset of bloodstream infection.

282 Background: Albumin-bound paclitaxel has been proven to be an active agent in advanced gastric cancer, and was approved by PMDA Japan for use as a second-line treatment of advanced gastric cancer. The aim of this study was to evaluated the efficacy and safety of AS and SOX in the first-line treatment of advanced gastric cancer. Methods: Patients diagnosed with unresectable locally advanced, recurrent or metastatic human epidermal growth factor receptor type 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma were randomized (1:1) to either AS group (albumin-bound paclitaxel 260mg/m2 d1 or 130mg/m2 d1, 8; S-1 40 mg [BSA < 1.25 m2], 50 mg [1.25 ≤ BSA < 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks) or SOX group (oxaliplatin 130mg/m2 d1; S-1 40 mg [BSA < 1.25 m2], 50 mg [1.25 ≤ BSA < 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks). Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: Between March 2019 and March 2021, 96 patients were enrolled and 85 patients (AS group, n = 43; SOX group, n = 42) who received at least one dose of study drug and had at least one postbaseline efficacy evaluation were included in the final analysis. 34 (79.0%) patients in the AS group and 35 (83.3%) in the SOX group had discontinued treatment. Of these 85 patients, 78.8% had two or more organs involved, 61.2% had peritoneal dissemination, and more than 1/4 had massive ascites. Patient demographics and disease characteristics were generally balanced between arms. With median follow-up 15.4 months (95% CI, 8.8-21.9), the median PFS of AS group vs. SOX group was 9.2 vs.5.1 months (HR = 0.58 [95% CI 0.36-0.96], p = 0.034); and the median OS was 14.4 vs. 15.4 months (HR = 0.73 [95%CI 0.40-1.34], p = 0.375). Tumor response was assessable in 33 patients according to RECIST V1.1 in both cohorts, the ORR and DCR were similar in AS vs. SOX arm (ORR: 54.5% vs. 51.5%, P = 0.805; DCR: 78.8% vs. 78.8%, P = 1.000). The main grade 3 or worse treatment-related adverse events were neutropenia (30.2% vs 23.8%), Leucopenia (11.6% vs 11.9%) and peripheral sensory neuropathy (4.7% vs 7.1%) in AS and SOX group. The study was planned to be adjusted, due to the widespread use of immunotherapy in first-line treatment of gastric cancer. Conclusions: The results of this study indicated that in previously untreated patients with unresectable locally advanced, recurrent or metastatic HER2-negative gastric or GEJ adenocarcinoma, AS achieved better PFS than SOX, with an inadequate power. The toxicities were controllable and consistent with previously reported. Clinical trial information: NCT03801668.

BACKGROUND: For metastatic colorectal cancer (mCRC) patients for whom at least 2 lines of previous standard therapies have failed, the prognosis is often unfavorable due to very limited subsequent treatment options. We sought to explore the efficacy of apatinib, an oral small-molecule vascular endothelial growth factor receptor-2 inhibitor, plus 5-fluorouracil (5-FU) as a third- or subsequent-line treatment for mCRC. METHODS: In this phase-II, single-arm, prospective study, the eligible patients had been histologically confirmed to have adenocarcinoma of the colon or rectum for which at least 2 previous regimens of standard therapies had failed. All the patients were treated with a daily dose of 250 mg of apatinib, in combination with capecitabine, Tegafur Gimeracil Oteracil Potassium Capsule (S-1), or 5-FU, until disease progression, unacceptable toxicity, or consent withdrawal. RESULTS: From June 2017 to April 2018, 16 patients were enrolled in this study. Among them, 4 achieved partial response, 7 had stable disease, and 5 had progression disease, resulting in an objective response rate of 25.00% [95% confidence interval (CI): 7.27–52.38%], and a disease control rate of 68.75% (95% CI: 41.34–88.98%). The median progression-free survival (PFS) was 4.83 months (95% CI: 2.17–8.90 months), and the median overall survival (OS) was 9.10 months (95% CI: 5.59–15.18 months). The common treatment-related adverse events (AEs) were hand-foot syndrome (56.25%), hypertension (37.50%), proteinuria (37.50%), gingival bleeding (18.75%) and abdominal pain (18.75%). Grade 3 AEs, including hand-foot syndrome (18.75%), hypertension (12.50%), and proteinuria (12.50%), were observed in 7 patients. CONCLUSIONS: The combination regimen of apatinib plus 5-FU had encouraging anti-tumor efficacy, and is a feasible third- or subsequent-line treatment option for mCRC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03210064.

Background Pseudomonas aeruginosa (P. aeruginosa) is a major Gram-negative pathogen, which has been reported to result in high mortality. We aim to investigate the prognostic value and optimum cut-off point of time-to-positivity (TTP) of blood culture in children with P. aeruginosa bacteremia. Methods From August 2014 to November 2018, we enrolled the inpatients with P. aeruginosa bacteremia in a 1500-bed tertiary teaching hospital in Chongqing, China retrospectively. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off point of TTP, and logistic regression were employed to explore the risk factors for in-hospital mortality and septic shock. Results Totally, 52 children with P. aeruginosa bacteremia were enrolled. The standard cut-off point of TTP was18 h. Early TTP (≤18 h) group patients had remarkably higher in-hospital mortality (42.9% vs 9.7%, P = 0.014), higher incidence of septic shock (52.4% vs12.9%, P = 0.06), higher Pitt bacteremia scores [3.00 (1.00–5.00) vs 1.00 (1.00–4.00), P = 0.046] and more intensive care unit admission (61.9% vs 22.6%, P = 0.008) when compared with late TTP (> 18 h) groups. Multivariate analysis indicated TTP ≤18 h, Pitt bacteremia scores ≥4 were the independent risk factors for in-hospital mortality (OR 5.88, 95%CI 1.21–21.96, P = 0.035; OR 4.95, 95%CI 1.26–27.50, P = 0.024; respectively). The independent risk factors for septic shock were as follows: TTP ≤18 h, Pitt bacteremia scores ≥4 and hypoalbuminemia (OR 6.30, 95%CI 1.18–33.77, P = 0.032; OR 8.15, 95%CI 1.15–42.43, P = 0.014; OR 6.46, 95% CI 1.19–33.19 P = 0.031; respectively). Conclusions Early TTP (≤18 hours) appeared to be associated with worse outcomes for P. aeruginosa bacteremia children.

Industrial wireless sensor networks have been widely deployed in many industrial systems. The main communication paradigm of such systems, known as convergecast, is to converge sensing data to a centralized manager. The rapid and reliable data convergecast is essential to the industrial production. Multiple radio interfaces on a network device and convergecast scheduling algorithms can effectively reduce convergecast delay. Existing works confine to the convergecast based on linear- and tree-based routing. Compared to the two routing schemes, graph routing is more reliable. Although the graph routing gains more popularity in industrial networks due to its better reliability, few works have addressed its temporality performance. On the other hand, the number of radio interfaces also impacts on the convergecast delay. In this paper, we present a holistic framework to solve how to use multiple radio interfaces to converge data. First, we propose a convergecast scheduling algorithm for industrial wireless sensor networks with multiple radio interfaces. Second, based on our proposed scheduling algorithm, we propose an optimal algorithm and a fast heuristic algorithm to minimize the number of radio interfaces under the temporality constraint of industrial production. Evaluations show that all our algorithms perform closely to the optimal solution.

Dominant TBX5 mutation causes Holt-Oram syndrome (HOS), which is characterized by limb defects in humans, but the underlying mechanistic basis is unclear. We used a mouse model with Tbx5 conditional knockdown in Hh-receiving cells (marked by Gli1+) during E8 to E10.5, a previously established model to study atrial septum defects, which displayed polydactyly or hypodactyly. The results suggested that Tbx5 is required for digit identity in a subset of limb mesenchymal cells. Specifically, Tbx5 deletion in this cell population decreased cell apoptosis and increased the proliferation of handplate mesenchymal cells. Furthermore, Tbx5 was found to negatively regulate the Hh-signaling activity through transcriptional regulation of Ptch1, a known Hh-signaling repressor. Repression of Hh-signaling through Smo co-mutation in Tbx5 heterozygotes rescued the limb defects, thus placing Tbx5 upstream of Hh-signaling in limb defects. This work reveals an important missing component necessary for understanding not only limb development but also the molecular and genetic mechanisms underlying HOS.

Waste emissions have increased the amount of water and soil contaminated with heavy metals such as Pb. To broaden the methods for the recycling and environmental usage of cow manure (CM) and its vermicompost (CV), CM, CV, and their derived biochars produced by the pyrolysis of CM or CV at 350 and 700 °C were used as adsorbents for Pb

Although photothermal therapy (PTT) has been extensively applied in the treatment of cancer using various types of nanomaterials, low penetration of excitation light, low nanoparticle concentration enrichment and abominable nanoparticle permeation still remain huge obstacles in cancer therapy. Herein, we synthesized stable cupric sulfide nanoparticles (CuS NPs) with small size, which after functionalization with a MnO

Purpose To compare 3D liver acceleration volume acquisition (LAVA) and digital subtraction angiography (DSA) for evaluating the presence of accessory hepatic veins (AHV) in Budd-Chiari syndrome (BCS). Materials and Methods This was a retrospective study in 228 patients with BCS who underwent 3.0T magnetic resonance imaging (MRI) with the 3D LAVA sequence. Two reviewers noted AHV: openings located in the inferior vena cava (IVC), caliber, and the angle of entering into the IVC. MRI results were compared to DSA. Kappa statistics were calculated to quantify intrareader variability in detecting AHVs. Results On MRI, 63 patients demonstrated no AHV on LAVA images, 70 had one AHV, 62 had two AHVs, 26 patients had three AHVs, six patients had four AHVs, and one patient had five AHVs (P < 0.05 vs. DSA). The mean caliber of the AHVs was 8.3 ± 4.0 mm compared to 9.9 ± 3.2 for DSA (P < 0.001). Among the 301 AHVs, there were 140 with acute angles (46.5%), 71 with right angles (23.6%), and 90 with obtuse angles (29.8%). The prevalence of AHVs on DSA was 54.8% (125/228), while MRI demonstrated 301 AHVs in 165 patients, for a prevalence of 72.4% (165/228) compared to 54.8% for DSA (P = 0.001). The two methods were concordant in only 116/228 (50.9%) patients. The kappa coefficient demonstrated good intrareader consistency for all documented MRI findings of AHVs (κ = 0.626 for caliber and κ = 0.65 for angles). Conclusion More AHVs were visible on MRI LAVA sequences than on conventional DSA. Level of Evidence: 4 J. Magn. Reson. Imaging 2017;45:401–409.

The authors regrets that there is a typo error on the Abbreviation section of their published paper. "Area under the curve" should have been abbreviated to "AUC" instead of "A". The authors have requested that this be noted. The original article has been corrected.

Waste emissions have increased the amount of water and soil contaminated with heavy metals such as Pb. To broaden the methods for the recycling and environmental usage of cow manure (CM) and its vermicompost (CV), CM, CV, and their derived biochars produced by the pyrolysis of CM or CV at 350 and 700 °C were used as adsorbents for Pb2+ removal in this batch adsorption experiment to reveal their different Pb2+ removal efficiencies and the underlying mechanisms. The batch experiment results revealed that all adsorbents rapidly removed Pb2+ within 30 min. A pH between 2.0 and 6.0 positively affected Pb2+ removal by CM and its biochar, whereas that by CV and its biochar was only positively affected by pH between 2.0 and 3.0. CV-derived biochar was more effective in the removal of Pb2+ than the other absorbents, with the maximum adsorption capacities (Qm) fitted from the Langmuir model reaching approximately 230.0 mg·g−1 and the desorption rate (DR) being approximately 0.00–0.02%. Material physiochemical characterization, including X-ray diffraction analysis, showed that high pH, high ash content, rich mineral content, and high mineral contents might have been the main reasons for more effective removal of Pb2+ from aqueous solutions by CV-derived biochar. Fourier-transform infrared analysis indicated that surface functional groups such as –OH, C O, –COO–, and C–O; original and newly produced carbonate; and phosphate in CV also led to more effective Pb2+ removal efficiency from aqueous solution via surface functional group binding. Thus, pyrolyzing CVs may be used to produce biochar as a cost-effective adsorbent for heavy metal remediation in soil and water in the future.

The layered high-pressure hydrogen vessels are widely used in hydrogen refueling stations. The head of the high-pressure vessel is made of austenitic stainless steel, and has thick walls, a pipe with a small diameter on the top and a butt-weld structure. It’s difficult to detect effectively, using conventional methods in the inspection of the butt weld on the head. To effectively detect the weld joint, a detecting method was investigated using ultrasonic phased array technique from the inner surface of the small-diameter pipe. By axial focusing and circumferential focusing, the ultrasonic field in austenitic stainless steel could satisfy the specific inspection requirement. Some ultrasonic field analysis and defect detection simulations were carried out with CIVA, for artificial defects such as side-drilled holes. Meanwhile, the test specimen and probe were designed and manufactured, and experiments were conducted. Furthermore, the feasibility and rationality of the detecting method and the simulation method were verified, and the detecting process parameters were determined.

In this work, a mixture of pig manure and

Magnetic resonance imaging (MRI) as a noninvasive diagnostic technology with high spatial resolution has been widely used in clinics. However, the relatively low sensitivity is the main shortcoming of this technology. To address this issue, we would like to develop a molecular MRI nanoprobe for the sensitive and specific MRI of renal carcinoma cells with BSA-Gd2O3 nanoparticles as MRI contrast agents, mesoporous silica nanoparticles (mSiO2 NPs) as nanocarriers and the AS1411 aptamer as a targeting molecule. To achieve this aim, BSA-Gd2O3 NPs were assembled onto mSiO2 NPs with the help of anionic polyelectrolyte, sodium polystyrene sulfonate (PSS), and cationic polyelectrolyte, poly dimethyl diallyl ammonium chloride (PDDA) layer by layer. Such successful assembly was confirmed by transmission electron microscopy (TEM), FT-IR spectroscopy, zeta-potential analysis, hydrodynamic diameter determination and gel electrophoresis. After assembly, the mSiO2/PSS/PDDA/BSA-Gd2O3 nanoprobe presented a larger longitudinal relaxivity (r1) (26.1 s−1 mM−1 Gd) than BSA-Gd2O3 NPs (11.8 s−1 mM−1 Gd) and commercially used Gd–DTPA (3.87 s−1 mM−1 Gd). Additionally, with the AS1411 aptamer as a targeting molecule, our fabricated mSiO2/PSS/PDDA/BSA-Gd2O3-AS1411 nanoprobes could recognize clear cell renal carcinoma cells (ccRCC) specifically by MRI in vitro.