Endocrine disrupting and carcinogenic effects of decabromodiphenyl ether

BackgroundDecabromodiphenyl ether (BDE209), an essential industrial flame retardant that is widely used, has recently been reported to be increasing in human serum. Due to the structural similarity between BDE209 and thyroid hormones, its toxic effects on the thyroid are of particular concern.MethodsOriginal articles in the PubMed database were collected using the terms “BDE209”, “decabromodiphenyl ether”, “endocrine disrupting”, “thyroid”, “carcinogenesis”, “polybrominated diphenyl ethers”, “PBDEs,” and their synonyms from inception up to October of 2022.ResultsOf the 748 studies initially identified, 45 were selected, which emphasized the adverse effects of BDE209 on endocrine system. BDE209 may have a toxic effect not only on thyroid function but also on thyroid cancer tumorigenesis at multiple levels, such as by directly interfering with the TR, hypothalamic-pituitary-thyroid (HPT) axis, enzyme activity, and methylation. However, it is impossible to draw a definitive conclusion on the exact pathway of thyroid toxicity from BDE209.ConclusionsAlthough the toxic effects of BDE209 on the thyroid have been well investigated, its tumorigenic effects remain unclear and further research is necessary

Treatment-emergent neuroendocrine prostate cancer: molecularly driven clinical guidelines

An increasingly recognized mechanism of prostate cancer resistance is the transdifferentiation from adenocarcinoma to treatment-emergent neuroendocrine prostate cancer (t-NEPC), an extremely aggressive malignancy. The incidence of t-NEPC has been increasing in recent years, in part due to novel treatments that target the androgen receptor pathway. While clinicians historically had very few options for t-NEPC detection and treatment, recent research has uncovered key diagnostic tools and therapeutic targets that can be translated into improved patient care. In this article, we will outline the clinical features of t-NEPC and its molecular pathogenesis. Importantly, we will also discuss recently uncovered molecularly based strategies aimed at improving the diagnosis and treatment of t-NEPC. Finally, we will propose a unified algorithm that integrates clinical and molecular information for the clinical management of t-NEPC

Layered double hydroxide/poly(vinylpyrrolidone) coated solid phase microextraction Arrow for the determination of volatile organic compounds in water

Today, wide variety of adsorbents have been developed for sample pretreatment to concentrate and separate harmful substances. However, only a few solid phase microextraction Arrow adsorbents are commercially available. In this study, we developed a new solid phase microextraction Arrow coating, in which nanosheets layered double hydroxides and poly(vinylpyrrolidone) were utilized as the extraction phase and poly(vinyl chloride) as the adhesive. This new coating entailed higher extraction capacity for several volatile organic compounds (allyl methyl sulfide, methyl propyl sulfide, 3-pentanone, 2-butanone, and methyl isobutyl ketone) compared to the commercial Carboxen 1000/polydimethylsiloxane coating. Fabrication parameters for the coating were optimized and extraction and desorption conditions were investigated. The validation of the new solid phase microextraction Arrow coating was accomplished using water sample spiked with volatile organic compounds. Under the optimal conditions, the limits of quantification for the five volatile organic compounds by the new solid phase microextraction Arrow coating and developed gas chromatography with mass spectrometry method were in the range of 0.2-4.6 ng/mL. The proposed method was briefly applied for enrichment of volatile organic compounds in sludge.Peer reviewe

Research of the size effect on shear strength of metal-plate connector joints in China

According to the reliability theory, the size effect has a great impact on the design value on shear strength of metal-plate connector. But little research has been done. So, based on GB/T50329-2002 of China, firstly, determining the size of metal-plate at different conditions, size effect tests were then conducted on metal-plate connectors composed of a type of Chinese metal-plate and 2# SPF dimension lumber from North America. A total of 125 metal-plate connectors are tested at five angles (90°, 60°T, 120°C, 150°C, 30°T), with Five kinds of widths (50mm，85mm，125mm，150mm，180mm) for each angle. Based on the testing data, fitting curve of size effect is presented, and width-effect parameters are estimated with SPSS(Statistic Package for Social Science). Results indicate that the width effect is significant; shear strength increases with the increase of width, and stays stable after a certain width

Super-resolution microscopy and its applications in neuroscience

Optical microscopy promises researchers to see most tiny substances directly. However, the resolution of conventional microscopy is restricted by the diffraction limit. This makes it a challenge to observe subcellular processes happened in nanoscale. The development of super-resolution microscopy provides a solution to this challenge. Here, we briefly review several commonly used super-resolution techniques, explicating their basic principles and applications in biological science, especially in neuroscience. In addition, characteristics and limitations of each technique are compared to provide a guidance for biologists to choose the most suitable tool

Efficacy and safety of bevacizumab in patients with malignant melanoma: a systematic review and PRISMA-compliant meta-analysis of randomized controlled trials and non-comparative clinical studies

Background: Malignant melanoma is a highly aggressive cancer that spreads and metastasizes quickly. In recent years, the antiangiogenic drug bevacizumab has been trialed to treat malignant melanoma. We conducted the first meta-analysis to examine the efficacy and safety of bevacizumab combined with other drugs in malignant melanoma.Methods: We searched for randomized controlled trials (RCTs) and non-comparative clinical studies of bevacizumab combined with chemotherapy, targeted medicine, and interferon to treat malignant melanoma in PubMed, Embase, the Cochrane Library, and Web of Science. Meta-analysis of RCT was performed using Review Manager (version 5.4), and non-comparative meta-analysis was performed using R (version 4.0.3). The primary outcome was the objective response rate. Depending on the heterogeneity of the included studies, the pooled outcomes and 95% CI were calculated using either random-effects or fixed-effect models. Subgroup outcomes were calculated with possible relevant variables. Sensitivity analyses were carried out by excluding each study from the highly heterogeneous pooled results in turn. Funnel plot and Begg’s test were used to test the included studies' potential publication bias. The level of significance was set at p < 0.05.Results: This meta-analysis included 20 trials: five RCTs and 15 non-comparative clinical studies with a total of 23 bevacizumab intervention arms. In 14 treatment arms, bevacizumab was combined with chemotherapy drugs such as fotemustine, dacarbazine, carboplatin/paclitaxel, and temozolomide. In six treatment arms, bevacizumab was combined with targeted medicines such as imatinib, everolimus, sorafenib, erlotinib, and temsirolimus. There were also six treatment arms that used bevacizumab in combination with interferon. The pooled objective response rate was 15.8% (95% CI, 11.4%–20.2%). Bevacizumab plus carboplatin/paclitaxel significantly increased the overall survival compared to carboplatin/paclitaxel (HR = 0.64, 95% CI, 0.49-0.85, p < 0.01). Fatigue, nausea, leukopenia, thrombocytopenia, and neutropenia were the most common adverse events. The pooled incidence of hypertension of all bevacizumab arms in malignant melanoma was 32.4% (95% CI, 24.5%–40.3%).Conclusion: This study showed that bevacizumab combined with chemotherapy might be effective and well-tolerated in patients with stage III or IV unresectable malignant melanoma.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=304625], identifier [CRD42022304625]

Improved Dynamic Contrast-Enhanced MRI Using Low Rank with Joint Sparsity

This work presents a free-breathing dynamic contrast-enhanced (DCE) MRI reconstruction method called low-rank plus sparse (L+S) with joint sparsity. The proposed method improved dynamic contrast performance by integrating an additional temporal Fast Fourier Transform (FFT) constraint into the standard L+S decomposition method. In the proposed method, both temporal total variation (TV) sparsity constraint and temporal FFT constraint are integrated into a standard L+S decomposition model, forming L+S with joint sparsity. Temporal TV and Temporal FFT aim to suppress under-sampling artifacts and improve dynamic contrast in DCE-MRI, respectively. A fast composite splitting algorithm (FCSA) is adopted for solving the L+S model with multiple sparsity constraints, maintaining the reconstruction efficiency. A computer simulation framework was developed to compare the performance of L+S with joint sparsity and other reconstruction schemes. The performance of L+S with joint sparsity was tested using computer simulation and several liver DCE-MRI datasets. The proposed L+S based method achieved around four times faster reconstruction speed than the GRASP method. With the support of an additional sparsity constraint, the peak DCE signal in the proposed method was increased by more than 20% over that of a standard L+S decomposition

Cuff-Method Thigh Arterial Occlusion Counteracts Cerebral Hypoperfusion Against the Push–Pull Effect in Humans

Exposure to acute transition from negative (−Gz) to positive (+ Gz) gravity significantly impairs cerebral perfusion in pilots of high-performance aircraft during push—pull maneuver. This push—pull effect may raise the risk for loss of vision or consciousness. The aim of the present study was to explore effective countermeasures against cerebral hypoperfusion induced by the push—pull effect. Twenty healthy young volunteers (male, 21 ± 1 year old) were tested during the simulated push–pull maneuver by tilting. A thigh cuff (TC) pressure of 200 mmHg was applied before and during simulated push—pull maneuver (−0.87 to + 1.00 Gz). Beat-to-beat cerebral and systemic hemodynamics were measured continuously. During rapid −Gz to + Gz transition, mean cerebral blood flow velocity (CBFV) was decreased, but to a lesser extent, in the TC bout compared with the control bout (−3.1 ± 4.9 vs. −7.8 ± 4.4 cm/s, P < 0.001). Similarly, brain-level mean blood pressure showed smaller reduction in the TC bout than in the control bout (−46 ± 12 vs. −61 ± 13 mmHg, P < 0.001). The systolic CBFV was lower but diastolic CBFV was higher in the TC bout. The systemic blood pressure response was blunted in the TC bout, along with similar heart rate increase, smaller decrease, and earlier recovery of total peripheral resistance index than control during the gravitational transition. These data demonstrated that restricting thigh blood flow can effectively mitigate the transient cerebral hypoperfusion induced by rapid shift from −Gz to + Gz, characterized by remarkable improvement of cerebral diastolic flow