Abstract Objective : To study the effects of 2,2′,4,4′,5,5′-hexa-brominated diphenyl ether (BDE-153) exposure during lactation on the learning and memory abilities, spontaneous behavior and brain ...cells of adult rats and to elicit basic information on PBDE’s developmental neurotoxicity. Methods : Newborn male rat pups were randomly categorized into the following groups (15 pups per group), according to their weights and litters: a control group, and 1 mg/kg, 5 mg/kg and 10 mg/kg BDE-153 groups. At postnatal day 10 (PND10), the pups in the BDE-153 groups were intraperitoneally injected once with BDE-153 plant oil solutions at 0.1 ml/10 g body weight, and the controls were injected with plant oil. Throughout the entire experiment, physiological measures were recorded, such as food and water consumption, body weight and clinical symptoms. At 1 month and 2 months after treatment, the learning and memory abilities of the rats were tested by the Morris water maze test, the step-down test, and the step-through test; spontaneous behavior was tested by the open-field test. After all tests were accomplished, rats were weighed and sacrificed, and the brain tissue was immediately isolated and divided into two parts. Sections were fabricated from one part, and changes in the morphology and ultrastructure in CA3 region of hippocampus were observed under an optical microscope and transmission electron microscope, along with the detection of apoptotic cells with the terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method. The tissue of the second part was digested into single-cell suspension liquid, and the cell apoptosis was assayed with flow cytometry and the lactate dehydrogenase (LDH) leakage was detected with spectrophotometry. Results : There was no obvious change in food and water consumption, body weight and the ratio of brain to body weight, or any overt clinical symptoms in the BDE-153-treated rats. Compared to the control group, rats' latency time in the test session (LT2) in the step-down test was significantly increased in the 10 mg/kg BDE-153 group at 2 months after treatment ( P <0.05), and the BDE-153-treated rats' swimming times and distances in the target quadrant were significantly decreased at 1 month and 2 months after treatment ( P <0.05 or P <0.01). These parameters were also significantly increased in the opposite quadrant at 1 month after treatment ( P <0.05 or P <0.01). The spontaneous behavior was significantly reduced in the treated groups compared to the controls ( P <0.05 or P <0.01). The severity of neurobehavioral dysfunction was dependent on the exposure dose of BDE-153, and worsened with age. Under an optical microscope, the treated rats' neurons in the CA3 region of the hippocampus were observed to be reduced and disarranged, and the cell junctions were loosened and the intercellular spaces were enlarged. Under a transmission electron microscope, the cell nucleus was observed to shrink; the chromatin was condensed and gathered near the nuclear membrane, the Nissl bodies and other organelles in the perikaryon were reduced, and the vacuole was observed to degenerate and even disappear. Moreover, compared to the controls, the cell apoptosis rates were significantly increased in the 5 and 10 mg/kg BDE-153 groups ( P <0.05), and the LDH activity was significantly increased in the 10 mg/kg BDE-153 groups ( P <0.01). Conclusion : Lactation exposure to BDE-153 damaged adult rats' learning and memory abilities, disrupted their spontaneous behavior (hypoactivity) and induced hippocampus neuron apoptosis.
Metal-organic frameworks (MOFs) as promising materials have been widely used in drug delivery, disease diagnosis and therapy; however, their effects on the reproductive system remain unknown, which ...hinders their further clinical applications. Here we show that repeated subcutaneous injections of copper MOFs (HKUST-1) induce higher toxicity into the male reproductive system relative to the female reproductive system, with disrupted seminiferous tubule histology, sperm generation disorder, irreversible sperm morphological abnormities and reduced pregnancy rate but only slight follicle dysfunction and pregnancy complications in female mice. Interestingly, the modification of HKUST-1 with folic acid attenuates the reproductive toxicity and even improves pregnancy and fetus development. This study confirms the gender-dependent toxicity of HKUST-1 to the reproductive system, and that folic acid modification could relieve the reproductive toxicity, thus providing us a deep understanding of reproductive toxicity of copper MOFs, and also a guideline and feasible way to improve the biocompatibility of copper MOFs for potential medical use.
HKSUT-1 is more toxic in male mice than that in female mice, affecting testis histology, sperm development and pregnancy rate. F-HKSUT-1 with folic acid modification relieves reproductive toxicity and even improves pregnancy and fetus development.
The least absolute shrinkage and selection operator (LASSO) is an established sparse representation approach for variable selection, and its performance relies on finding a good value for the ...regularization parameter, typically through cross-validation. However, cross-validation is a computationally intensive step and requires a properly determined search range and step size. In the present study, the ridge-adding homotopy (RAH) algorithm is applied with LASSO to overcome the aforementioned shortcomings. The homotopy algorithm can fit the entire solution of the LASSO problem by tracking the Karush-Kuhn Tucker (KKT) conditions and yields a finite number of potential regularization parameters. Considering the singularities, a M×1 random ridge vector will be added to the KKT conditions, which ensures that only one element is added to or removed from the active set. Finally, we can select the optimal regularization parameter by traversing the potential parameters with modelling and evaluation metrics. The selected variables are the nonzero elements in the sparse regression coefficient vector derived by the optimal regularization parameter. The proposed method has been demonstrated on three near-infrared (NIR) datasets with regard to wavelength selection and calibration. The results suggested that the “RAH-LASSO + PLS” outperforms “LASSO + PLS” and “full-wavelength PLS” in most cases. Importantly, the RAH method provides a systematic, as opposed to trial-and-error, procedure to determine the regularization parameter in LASSO.
•A novel spectral variable selection method named RAH –LASSO was proposed.•Provide a systematic procedure to determine the regularization parameter with KKT optimal conditions.•Require no trial-and-error or random procedure to determine the regularization parameter in LASSO.•The superiority of the proposed RAH-LASSO over exist scheme is demonstrated through numerical examples.
Physical exercise is effective in enhancing cognitive function, reducing anxiety and depressive symptoms, reducing cravings, and improving quality of life in methamphetamine (METH) addiction. ...However, little is known about the effect of exercise on metabolic profiles. We performed LC/MS-based targeted metabolic profiling on serum samples to investigate the metabolic characteristics of METH dependence and find the differences between METH-dependent individuals and nonusers and evaluated the metabolomic profiles of individuals with METH dependence following aerobic exercise training. We identified a total of 201 metabolites, among which 115 were differentially expressed under METH use. Among the differentially regulated metabolites, 72 were selected as potential biomarkers. Further analysis identified 19 pathways, among which glyoxylate and dicarboxylate metabolism; alanine, aspartate, and glutamate metabolism; and citrate cycle were most significantly affected by METH. The aerobic exercise intervention differentially regulated 55 metabolites, of which 51 were selected as potential biomarkers and were mainly enriched in 10 pathways. Interestingly, alanine, aspartate, and glutamate metabolism and nitrogen metabolism were the remarkably affected pathways. Furthermore, METH increased the serum levels of glutamate and decreased GABA, whereas exercise decreased the serum levels of glutamate and increased GABA. Results suggested that METH dependency disturbed normal metabolic homeostasis, whereas exercise restored metabolism.
Gastric cancer (GC), an acknowledged malignant neoplasm, threatens life and digestive system functionality if not detected and addressed promptly in its nascent stages. The indispensability of early ...detection for GC to augment treatment efficacy and survival prospects forms the crux of this investigation. Our study introduces an innovative wrapper-based feature selection methodology, referred to as bCIFMVO-FKNN-FS, which integrates a crossover-information feedback multi-verse optimizer (CIFMVO) with the fuzzy k-nearest neighbors (FKNN) classifier. The primary goal of this initiative is to develop an advanced screening model designed to accelerate the identification of patients with early-stage GC. Initially, the capability of CIFMVO is validated through its application to the IEEE CEC benchmark functions, during which its optimization efficiency is measured against eleven cutting-edge algorithms across various dimensionalities—10, 30, 50, and 100. Subsequent application of the bCIFMVO-FKNN-FS model to the clinical data of 1632 individuals from Wenzhou Central Hospital—diagnosed with either early-stage GC or chronic gastritis—demonstrates the model's formidable predictive accuracy (83.395%) and sensitivity (87.538%). Concurrently, this investigation delineates age, gender, serum gastrin-17, serum pepsinogen I, and the serum pepsinogen I to serum pepsinogen II ratio as parameters significantly associated with early-stage GC. These insights not only validate the efficacy of our proposed model in the early screening of GC but also contribute substantively to the corpus of knowledge facilitating early diagnosis.
•Proposes CIFMVO algorithm with crossover-information feedback.•Augments CIFMVO to escape local optima effetively.•Outperforms others on IEEE CEC 2017, CEC 2020.•Enhances GC prediction accuracy using FS method.
•Uniform PB/ITO composite films are prepared by an in-situ replacement method.•The process is completed under atmospheric pressure without requests of sealed spaces.•The films achieve 59.9% ...transmittance modulation within 12 s.•After 1200 bleaching/coloring cycles, 77% of transmittance modulation ability remained.•This method is friendly to large-areal and scale-up fabrication.
As an attractive electrochromic (EC) material, Prussian blue (PB) holds many praiseworthy merits such as environmental benignity, low cost, proper redox potential, and fast electrochemical kinetics, thanks to their unique open framework structure consisting of common elements. However, restricted by the available synthetic methods and the formation of crystallographic imperfects, facile fabrication of large areal and high performance PB EC layers is still challenging. In this article, we establish a simple yet effective protocol to prepare PB EC layers with the assistance of ITO nanoparticle (ITO-np). This preparation method involves just an interfacial precipitation reaction between Fe(CN)64- from the electrolyte and Fe3+ from the acid-etched sacrifice layers. The ITO-np, as a transparent conductive additive, is used to enhance not only electrical conductivity but also adhesion strength of the prepared PB EC layers. The whole processes can be completed under atmospheric pressure without requests of any sealed reaction spaces, and thus should be very friendly to scale up fabrication. The as-prepared PB layers demonstrate decent EC performances with a transmittance modulation of 59.9% at 633 nm, a bleaching/coloring time of 12 s/8s, a cycling lifetime with 77% transmittance modulating ability remained after 1200 cycles, along with a remarkable charge storage/release ability. This work provides an alternative approach for the facile preparation of PB-based films for applications of both EC devices and smart-supercapatteries.
Background
Chemotherapy is the standard of treatment for metastatic gallbladder carcinoma (GBC). It is unclear whether chemotherapy plus surgery improves the survival outcomes of patients with ...isolated liver metastases from GBC. We aimed to investigate the survival benefits of chemotherapy plus surgery in GBC with isolated liver metastases compared to those of chemotherapy alone.
Methods
We identified 406 patients with isolated liver metastases from GBC who underwent chemotherapy alone or chemotherapy plus surgery between 2010 and 2015 from Surveillance, Epidemiology, and End Results. Patients were divided into 3 subgroups: group I, chemotherapy alone (n = 263); group II, chemotherapy combined with cholecystectomy (n = 116); and group III, chemotherapy combined with cholecystectomy plus hepatectomy (n = 27). The cancer-specific survival and overall survival were evaluated.
Results
Compared with group I, group II revealed a longer survival time (P < .001). In addition, the survival time of the group III was also prolonged (P < .001). Multivariate cox analysis showed that treatment strategy was an independent prognostic factor.
Conclusion
Chemotherapy combined with resection of the primary tumor plus or not plus resection of the metastatic lesions may be beneficial in GBC with isolated liver metastases.
Ceftazidime/avibactam (CAZ/AVI) is regarded as an effective alternative antibiotic for the clinical treatment of Klebsiella pneumoniae carbapenemase (KPC)-producing isolates. As resistance has been ...reported in some strains, it is critical to understand the key mechanisms contributing to the acquired resistance to CAZ/AVI. From January 2018 to April 2020, 127 KPC-producing carbapenem-resistant Klebsiella pneumoniae strains (CRKPs) were isolated at a university hospital in Chongqing, China, and 25 strains showed reduced susceptibility to CAZ/AVI. All reduced-susceptibility CRKPs were deficient in Ompk35 and Ompk36 porins, and 24 strains had a premature termination at amino acid position 63 in Ompk35 and 134 to 135 glycine and aspartic acid (GD) insertion in OmpK36, while the blaKPC-2 expression level showed no significant difference compared to that of strain BAA-1705. Four reduced-susceptibility strains evolved resistance under selective pressure of CAZ/AVI with the blaKPC-2 expression level increased, and two of these strains had mutations in the Ω-loop. The study found a strain of CRKP55 with changes in the resistance phenotype during conjugation, evolving from reduced sensitivity to high-level resistance to CAZ/AVI. Through plasmid sequencing and reverse transcription-quantitative PCR, it was speculated that insertion sequence (IS)26-mediated blaKPC-2 gene amplification caused the MIC value change in the conjugant JKP55. Our findings illustrated the potential of CAZ/AVI resistance under antibiotic stress and demonstrated that IS26 may mediate blaKPC-2 replication transposition, leading to high-level resistance during horizontal gene transfer. Investigation of CAZ/AVI resistance mechanisms may offer a unique opportunity to study the horizontal evolutionary trajectories of K. pneumoniae high-risk clones. IMPORTANCE Klebsiella pneumoniae carbapenemase (KPC) production is the most common mechanism of K. pneumoniae resistance to carbapenems in China. Currently, CAZ/AVI is considered a potential alternative therapeutic option for infections caused by these isolates. However, there have been increasing reports of resistant or reduced-sensitivity strains since the approval of this agent. In this study, resistance to CAZ/AVI was induced under drug-selective pressure and was caused by blaKPC-2 overexpression and/or substitutions in the Ω-loop of KPC. Additionally, it was demonstrated that a conjugative plasmid carrying blaKPC-2 could transfer horizontally between species, and perhaps, IS26-derived tandem amplification of blaKPC-2 during this period led to high-level resistance to CAZ/AVI. Our research suggests that IS26-mediated resistance evolution may have important implications in guiding clinical antibiotic use.
Porous carbon is one of the most promising alternatives to traditional graphite materials in lithium-ion batteries. This is not only attributed to its advantages of good safety, stability and ...electrical conductivity, which are held by all the carbon-based electrodes, but also especially ascribed to its relatively high capacity and excellent cycle stability. Here we report the design and synthesis of a highly porous pure carbon material with multifractal structures. This material is prepared by the vacuum carbonization of a zinc-based metal-organic framework, which demonstrates an ultrahigh lithium storage capacity of 2458 mAh g
and a favorable high-rate performance. The associations between the structural features and the lithium storage mechanism are also revealed by small-angle X-ray scattering (SAXS), especially the closed pore effects on lithium-ion storage.
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