Photoelectrochemical and electrochemical ratiometric aptasensing: a case study of streptomycin

There has been much interest in constructing ratiometric sensors using different sensing techniques because of their synergistic effect, although the simultaneous collection of the signals is challenging. Herein, we propose a ratiometric aptasensing strategy based on the dual-detection model with a photoelectrochemical (PEC) “signalon” and an electrochemical (EC) “signal-off”. As a proof-of-concept study, CdTe quantum dots (CdTe QDs) and a methylene blue-labeled aptamer (MB-Apt) were used to generate PEC and EC signals in the sensing system. The target-induced conformational change of MB-Apt pushed MB away from the electrode, thereby decreasing the EC signal; at the same time, the reduced steric hindrance favored the restoration of the PEC signal from the CdTe QDs. Thus, this PEC-EC strategy can achieve the PEC “signal-on” and EC “signal-off” states simultaneously, as well as allowing quantitative analysis of the target based on the ratio of the current intensities. As a model application, an aptasensor fabricated for streptomycin detection showed a wide linear range from 0.03 to 100 μM with a detection limit of 10 nM (S/N = 3). The proposed sensing platform displayed superior analytical properties compared with methods based on PEC or EC alone. Our work provides an efficient dual-detection modelbased ratiometric strategy for advanced analysis, and paves the way to the simultaneous acquisition of signals

Step pyrolysis of N-rich industrial biowastes: Regulatory mechanism of NOx precursor formation via exploring decisive reaction pathways

Step pyrolysis of N-rich industrial biowastes was used to explore decisive reaction pathways and regulatory mechanisms of NOx precursor formation. Three typical ones involving medium-density fiberboard waste (MFW), penicillin mycelia waste (PMW) and sewage sludge (SS) were employed to compare the formation characteristics of NOx precursors during one-step and two-step pyrolysis. Results demonstrated that considerable NH3-N pre-dominated NOx precursors for one-step pyrolysis at low temperatures, depending on primary pyrolysis of labile amide-N/inorganic-N in fuels. Meanwhile, NOx precursors differed in the increment of each species yield while resembled in the total yield of 20-45 wt.% among three samples at high temperatures, due to specific prevailing reaction pathways linking with distinctive amide-N types. Subsequently, compared with one-step pyrolysis uniformly (800 degrees C), by manipulating intensities of reaction pathways at different stages (selecting differential intermediate feedstocks), two-step pyrolysis was capable of minimizing NOx precursor-N yield by 36-43% with a greater impact on HCN-N (75-85%) than NH3-N (9-37%), demonstrating its great capacity on regulating the formation of NOx precursors for industrial biowaste pyrolysis. These observations were beneficial to develop effective insights into N-pollution emission control during their thermal reutilization

(meso-5,7,7,12,14,14-Hexamethyl-1,4,8,11-tetra­aza­cyclo­tetra­deca-4,11-diene)nickel(II) dibromide dihydrate

The asymmetric unit of the title compound, [Ni(C16H32N4)]Br2·2H2O, consists of one half [Ni(C16H32N4)]2+ cation, one Br− anion and one water mol­ecule of crystallization. The NiII ion lies on an inversion centre in a square-planar environment formed by the four macrocyclic ligand N atoms. In the crystal structure, the cations, anions and water mol­ecules are linked via inter­molecular N—H⋯Br and O—H⋯Br hydrogen bonds, forming discrete chains with set-graph motif D(2)D 2 2(7)D 2 1(3)D 3 2(8). The water mol­ecules and Br− ions are linked with set-graph motif R 4 2(8)

Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy: a comparative study

Background and Aim: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. Methods: Search of the Cleveland Clinic’s CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. Results: Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn’s disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35–1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54–1.4; P = 0.58) between IBD and non-IBD patients. Conclusion: Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions

Surrogate-based optimization with improved support vector regression for non-circular vent hole on aero-engine turbine disk

Abstract(#br)This paper investigates a structural optimization for the non-circular vent hole on an aero-engine turbine disk. A novel optimization approach, namely SO-ISVR (the surrogate-based optimization using an improved support vector regression), for the vent hole design is developed. ISVR (the improved support vector regression) is proposed to extract some ignored valuable information from the existing training data by using the least squares method, so as to improve the performance of SVR (support vector regression). To validate the advantages of SO-ISVR, another two optimization approaches are also developed. They are SO-SVR (the surrogate-based optimization using SVR) and FEMO (the finite element method based optimization). The results show that ISVR is suitable and valuable in engineering optimization. Compared to the initial scheme, the maximum von Mises stress of the optimal scheme obtained by SO-ISVR is reduced from 1189.488 MPa to 948.530 MPa. Further comparative study for SO-ISVR, SO-SVR, and FEMO demonstrates that SO-ISVR possesses some advantages in both computational efficiency and optimization effect

Ceftazidime-avibactam induced renal disorders: past and present

With the increasing prevalence of multidrug-resistant Gram-negative bacterial pathogens worldwide, antimicrobial resistance has become a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) exhibited excellent in vitro activity against many carbapenemase-producing pathogens, and was widely used for the treatment of various complicated infections. CAZ-AVI is well tolerated across all dosing regimens, and its associated acute kidney injury (AKI) in phase II/III clinical trials is rare. However, recent real-world studies have demonstrated that CAZ-AVI associated AKI was more frequent in real-world than in phase II and III clinical trials, particularly in patients receiving concomitant nephrotoxic agents, with critically ill patients being at a higher risk. Herein, we reviewed the safety data related to renal impairment of CAZ-AVI, and discussed its pharmacokinetic/pharmacodynamic targets and dosage adjustment in patients with impaired renal function. This review aimed to emphasize the importance for healthcare professionals to be aware of this adverse event of CAZ-AVI and provide practical insights into the dosage optimization in critically ill patients with renal dysfunction

Gastrodin attenuates renal injury and collagen deposition via suppression of the TGF-β1/Smad2/3 signaling pathway based on network pharmacology analysis

Background: Gastrodin has been widely used clinically in China as an antihypertensive drug. However, its effect on hypertensive renal injury is yet to be elucidated. The current study aimed to investigate the effects of gastrodin on hypertensive renal injury and its underlying mechanisms by network pharmacology analysis and validation in vivo and in vitro.Methods: A total of 10 spontaneously hypertensive rats (SHRs) were randomly categorized into the following two groups: SHR and SHR + Gastrodin groups. Wistar Kyoto (WKY) rats were used as the control group (n = 5). The SHR + Gastrodin group was intragastrically administered gastrodin (3.5 mg/kg/day), and the rats in both WKY and SHR groups were intragastrically administered an equal amount of double-distilled water for 10 weeks. Hematoxylin-eosin, Masson’s trichrome, and Sirius red staining were used to detect the pathological changes and collagen content in the renal tissues. Network pharmacology analysis was performed to explore its potential targets and related pathways. In vitro, the CCK-8 assay was used to determine the cell viability. Immunohistochemistry and western-blotting analyses were employed to assess the protein expression associated with renal fibrosis and transforming growth factor-β1 (TGF-β1) pathway-related proteins in the renal tissues or in TGF-β1-stimulated rat kidney fibroblast cell lines (NRK-49F).Results: Gastrodin treatment attenuates renal injury and pathological alterations in SHRs, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilation. Gastrodin also reduced the accumulation of collagen in the renal tissues of SHRs, which were confirmed by downregulation of α-SMA, collagen I, collagen III protein expression. Network pharmacology analysis identified TGFB1 and SMAD2 as two of lead candidate targets of gastrodin on against hypertensive renal injury. Consistently, gastrodin treatment downregulated the increase of the protein expression of TGF-β1, and ratios of both p-Smad2/Smad2 and p-Samd3/Smad3 in renal tissues of SHRs. In vitro, gastrodin (25–100 μM) treatment significantly reversed the upregulation of α-SMA, fibronectin, collagen I, as well as p-Smad2 and p-Smad3 protein expressions without affecting the cell viability of TGF-β1 stimulated NRK-49F cells.Conclusion: Gastrodin treatment significantly attenuates hypertensive renal injury and renal fibrosis and suppresses TGF-β1/Smad2/3 signaling in vivo and in vitro

Characterization of Chronic Gastritis in Lynch Syndrome Patients With Gastric Adenocarcinoma

Background: Gastric cancer is one of the Lynch syndrome (LS)-associated malignancies. Previous studies have suggested that LS patients with gastric cancer also had chronic atrophic gastritis in the background mucosa, but further histologic characterization was not attempted. This study aims to understand the histologic features of background chronic gastritis in LS patients with gastric adenocarcinoma. Methods: Eleven LS-associated gastric cancer cases were collected from five institutions. Demographics and clinical features were retrieved by review of medical charts. Pathological material was reviewed for tumor location and histologic type. In addition, non-neoplastic gastric mucosa was assessed for inflammation (chronic and active), atrophy, intestinal metaplasia (IM) in the antrum and body, as well as pyloric gland metaplasia and enterochromaffin-like (ECL) cell hyperplasia in the body. Results: Eleven LS patients with gastric cancer (four male and seven female) with a mean age of 63 years (range: 23 - 83) were included. Ten (90.9%) had personal cancer histories; however none of the patients had family history of gastric cancer. Eight (72.7%) patients underwent gastrectomy and three had endoscopic resection. Nine (81.8%) patients had tumor in the fundus and/or body and two had tumor present in the antrum. Seven (63.6%) cases were intestinal type or mixed type carcinoma, and the remaining four were signet ring cell carcinoma. Eight (of 11, 72.7%) patients had chronic gastritis, five (45.4%) had atrophy, and four (36.3%) had intestinal metaplasia. Four of five patients with both antrum and body mucosa available for evaluation (80%), demonstrated body-predominant chronic gastritis. Four patients had germline MLH1 alterations and all of these patients had chronic gastritis, including one Helicobacter pylori (H. pylori) gastritis and three H. pylori-negative gastritis. Conclusions: None of LS patients with gastric cancer in our cohort had a family history of gastric cancer. Gastric adenocarcinomas in LS patients were primarily located in the fundus and/or body. Two-thirds of these tumors were of intestinal type and had a background chronic, H. pylori-negative gastritis. These results support a chronic atrophic gastritis with intestinal metaplasia-dysplasia-carcinoma sequence in LS-related gastric tumorigenesis, particularly in MLH1-mutated LS patients

Multiplex LNA probe-based RAP assay for rapid and highly sensitive detection of rifampicin-resistant Mycobacterium tuberculosis

ObjectivesThe World Health Organization (WHO) Global tuberculosis Report 2021 stated that rifampicin-resistant tuberculosis (RR-TB) remains a major public health threat. However, the in-practice diagnostic techniques for RR-TB have a variety of limitations including longer time, lack of sensitivity, and undetectable low proportion of heterogeneous drug resistance.MethodsHere we developed a multiplex LNA probe-based RAP method (MLP-RAP) for more sensitive detection of multiple point mutations of the RR-TB and its heteroresistance. A total of 126 clinical isolates and 78 sputum samples collected from the National Tuberculosis Reference Laboratory, China CDC, were tested by MLP-RAP assay. In parallel, qPCR and Sanger sequencing of nested PCR product assay were also performed for comparison.ResultsThe sensitivity of the MLP-RAP assay could reach 5 copies/μl using recombinant plasmids, which is 20 times more sensitive than qPCR (100 copies/μl). In addition, the detection ability of rifampicin heteroresistance was 5%. The MLP-RAP assay had low requirements (boiling method) for nucleic acid extraction and the reaction could be completed within 1 h when placed in a fluorescent qPCR instrument. The result of the clinical evaluation showed that the MLP-RAP method could cover codons 516, 526, 531, and 533 with good specificity. 41 out of 78 boiled sputum samples were detected positive by MLP-RAP assay, which was further confirmed by Sanger sequencing of nested PCR product assay, on the contrary, qPCR was able to detect 32 samples only. Compared with Sanger sequencing of nested PCR product assay, both the specificity and sensitivity of the MLP-RAP assay were 100%.ConclusionMLP-RAP assay can detect RR-TB infection with high sensitivity and specificity, indicating that this assay has the prospect of being applied for rapid and sensitive RR-TB detection in general laboratories where fluorescent qPCR instrument is available