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Aim: To evaluate the outcomes of eye-sparing surgery for lacrimal gland adenoid cystic carcinoma and the impact on tumor recurrence and orbital integrity., Methods: The study enrolled four patients with recurrent lacrimal gland adenoid cystic carcinoma. The outcome focused on the relevance of the integrity of the lateral orbital wall to the occurrence of extraorbital metastasis in the local recurrence of lacrimal gland adenoid cystic carcinoma., Results: Three patients underwent eye-sparing surgery via lateral orbitotomy without postoperative radiotherapy, and one patient who underwent eye-sparing surgery via sub-brow approach. These four patients all demonstrated a recurrence involving the invasion of extraorbital tissues as metastatic form through surgical bone seams., Conclusion: Preserving intact orbital bone tissue is crucial for mitigating direct cross-organ metastasis of lacrimal gland adenoid cystic carcinoma. The findings suggest avoiding the lateral orbitotomy approach with no or limited orbital bone wall invasion., Competing Interests: Conflicts of Interest: Ma MS, None; Ren TT, None; Luan FX, None; Li J, None; Wang N, None; Tao Y, None; Ma JM, None., (International Journal of Ophthalmology Press.)

Accurate segmentation of thyroid nodules is essential for early screening and diagnosis, but it can be challenging due to the nodules' varying sizes and positions. To address this issue, we propose a multi-attention guided UNet (MAUNet) for thyroid nodule segmentation. We use a multi-scale cross attention (MSCA) module for initial image feature extraction. By integrating interactions between features at different scales, the impact of thyroid nodule shape and size on the segmentation results has been reduced. Additionally, we incorporate a dual attention (DA) module into the skip-connection step of the UNet network, which promotes information exchange and fusion between the encoder and decoder. To test the model's robustness and effectiveness, we conduct the extensive experiments on multi-center ultrasound images provided by 17 local hospitals. The model is trained using the federal learning mechanism to ensure privacy protection. The experimental results show that the Dice scores of the model on the data sets from the three centers are 0.908, 0.912 and 0.887, respectively. Compared to existing methods, our method demonstrates higher generalization ability on multi-center datasets and achieves better segmentation results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Facile immobilization is essential for the wide application of enzymes in large-scale catalytic processes. However, exploration of suitable enzyme supports poses an unmet challenge, particularly in the context of scale-up biocatalyst fabrication. In this study, we present facile and scale-up syntheses of high-performance enzyme biocatalysts via in situ encapsulation of cytochrome c (Cyt-c) as mono-enzyme and glucose oxidase (GOx)-horseradish peroxidase (HRP) as dual-enzyme cascade (GOx&HRP) systems, respectively, into a stable mesoporous hydrogen-bonded organic framework (meso-HOF) matrix. In situ encapsulation reactions occur under ambient conditions, and facilitate scale up (∼3 g per reaction) of enzyme@meso-HOF within a very short period (5-10 min). The resultant biocatalysts not only exhibit high enzyme loading (37.9 wt% for mono-enzyme and 22.8 wt% for dual-enzyme) with minimal leaching, but also demonstrate high catalytic activity, superior reusability, and durability. This study represents an example of scale-up fabrication of enzyme@meso-HOF biocatalysts on the gram level and highlights superior meso-HOFs as suitable host matrices for biomolecular entities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to PKM2-dependent conventional caspase-3/GSDME cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-PD-1. In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press.)

Purpose: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions., Methods: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3)., Results: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis., Conclusion: In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

Ethnopharmacological Relevance: Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases (Shang Han Lun) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood., Aim of the Study: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas., Materials and Methods: The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro. Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo. Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model., Results: The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1-S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro. Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 μg mL -1 ) in vivo. q-PCR data demonstrated that DGSN decoction (500 μg mL -1 ) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo., Conclusion: The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases., Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765)., Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification ( P  = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P  = 0.0025) and general dermatologists (AUC, 0.838; P  = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P  = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P  = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P  = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases., Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers., Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Author(s).)

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

In recent years, the association between portal vein thrombosis and liver transplantation has extensive attention from physicians worldwide. However, there is no available literature on bibliometric analysis in this research area. Herein, we aimed to conduct a bibliometric analysis to identify the hotspots and frontiers of research related to portal vein thrombosis and liver transplantation. Documents published between 2002 and 2022 were retrieved and downloaded from the Web of Science Core Collection database. VOSviewer was utilized to generate a visualization network map of authors, nations, institutions, journals, and keyword co-occurrence/clustering. Additionaly, CiteSpace was used to analyze the keywords with the strongest bursts. A total of 1272 articles and reviews were extracted from the database. The author Marco Senzolo published the largest number of papers. The United States was the most prolific country, and Hope-Bochon (France) was the top productive institution. Liver Transplantation was the most prolific journal in the field. The most commonly identified keywords in the study were cirrhosis, risk factors, portal vein thrombosis, and management, as revealed by the keyword co-occurrence analysis. It is suggested that patients with cirrhosis, portal vein thrombosis prevention, and management measures for portal vein thrombosis have been prominet topics in recent years. Furthermore, an analysis of keywords with the strongest citation bursts highlighted pediatric liver transplantation, direct oral anticoagulants, and nonalcoholic fatty liver disease as current research trends. Research in portal vein thrombosis and liver transplantation exhibits a general upward trend. The latest hot topics within this area of study involve pediatric patients and nonalcoholic fatty liver disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to investigate the intervention effect and mechanism of Xiaoyao Kangai Jieyu Recipe(XKJR) on hip-pocampal microglia and neuronal damage in mice with breast cancer related depression. The mouse model of breast cancer related depression was established by inoculation of 4T1 breast cancer cells in axilla and subcutaneous injection of corticosterone(30 mg·kg~(-1)). The successfully modeled mice were randomly divided into a model group, a positive drug group(capecitabine 60 mg·kg~(-1)+fluoxetine 19.5 mg·kg~(-1)), and XKJR group(19.5 mg·kg~(-1) crude drug), with 6 in each group. Another 6 normal mice were taken as a normal group. The administration groups were given corresponding drugs by gavage, while the normal and model groups were given an equal volume of distilled water, once a day for 21 consecutive days. The depressive behavior of mice was assessed by glucose consumption test, open field test and novelty-suppressed feeding test. Hematoxylin and eosin(HE) staining and tumor suppression rate were used to evaluate the changes of axillary tumors. The mRNA expressions and the relative protein expressions of interleukin-1β(IL-1β), interleukin-18(IL-18), cyclooxyganese-2(COX-2) and glutamyl-prolyl-tRNA synthetase(EPRs) in the hippocampus of mice were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and immunohistochemistry, respectively. Immunofluorescence was performed to detect the mean fluorescence intensity of CD11b, a marker of hippocampal microglia activation. Nissler staining and transmission electron microscopy were employed to observe the morphological changes and the ultramorphological changes of hippocampal neurons, respectively. The experimental results indicated that compared with the normal group, the model group had reduced glucose consumption and lowered number of total activities in open field test(P<0.05, P<0.01), prolonged first feeding latency in no-velty-suppressed feeding test(P<0.01), and significant depression-like behavior; the contents of IL-1β, IL-18, COX-2, and EPRs in hippocampus were increased(P<0.05, P<0.01), with hippocampal microglia activation and obvious neuronal damage. Compared with the model group, the positive drug group and the XKJR group presented an improvement in depressive behaviors, a decrease in the contents of IL-1β, IL-18, COX-2 and EPRs in hippocampus, and an alleviation in the activation of hippocampal microglia and neuronal damage; the tumor suppression rates of positive drug and XKJR were 40.32% and 48.83%, respectively, suggesting a lower tumor growth rate than that of the model group. In summary, XKJR may improve hippocampal microglia activation and neuronal damage in mice with breast cancer related depression through activating COX signaling pathway.

Optic nerve glioma (ONG) is a relatively rare central nervous system tumor that mainly affects children and adolescents. It can be classified into sporadic and neurofibromatosis type 1 (NF1)-associated types. The histological type is mainly a low-grade pilocytic astrocytoma. The typical clinical manifestations are visual impairment and painless eye protrusion, and the imaging features mainly present as fusiform swelling or irregular masses. Chemotherapy is still the first-line treatment for ONG, and other treatment options include radiotherapy, surgical resection, and molecular targeted therapy. Screening and monitoring of NF1 patients are also crucial. The prognosis of ONG is difficult to predict, and close monitoring and timely effective intervention are necessary.

Quinazoline and its derivatives have drawn much attention in the development of potential antitumor agents. Here, we synthesized a series of 1,2,3-triazole derivatives of quinazoline at the C6 position and evaluated for their cytotoxic activity in various human cancer cell lines. We found that compound 5a was the most cytotoxic to HCT-116 cells (IC 50 , 0.36 μM). Target profiling found that 5a directly binds to both the autophagy-associated protein SQSTM1/P62 and the E3 ligase RNF168, promoting their interaction. Consistently, 5a treatment induces a decrease in RNF168-mediated H2A ubiquitination and compromises homologous recombination-mediated DNA repair, thus increasing the sensitivity of HCT-116 to X-ray radiation. Moreover, 5a suppressed xenografted tumor growth in mice in a dose-dependent manner. Taken together, the 1,2,3-triazole derivative of quinazoline 5a may serve as a novel compound for tumor therapy based on its role in promoting a P62/RNF168 interaction.

Astragalin (AST) is a natural flavonoid with excellent antioxidant and anti-inflammatory activities. However, whether AST is an effective chemical for neuronal protection and its underlying mechanisms remain to be elucidated. In this study, we established a mouse model of cognitive impairment and aging-like phenotype induced by sequential administration of AlCl 3 and D-galactose (Gal). We found that AST effectively ameliorated cognitive impairment in the model mice and improved their learning and memory performance in the Morris water maze (MWM) test. AlCl 3 /Gal-induced activation of astrocytes and microglia and inflammation were observed by immunohistochemistry and immunofluorescence, but could be attenuated by AST. In addition, alterations in oxidative stress-regulating enzymes or markers, including T-SOD, T-AOC, CAT, GSH-Px, and MDA, as well as the pro-inflammatory factors TNF-α, IL-1β, and IL-6, were restored. At the mechanistic level, AlCl 3 /Gal-intoxicated mice showed a significant elevation of Notch/HES-1 and NF-κB signaling axis corresponding to microglia activation and inflammation. AST attenuated the activation of Notch/HES-1 and NF-κB signaling axis, thus reducing the inflammation. In summary, AST is a promising natural product to protect neurons from toxin-induced injury, indicating its therapeutic potential for neurological disorders., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Tibetan ginseng named Wangla (tuber of Coeloglossum viride var. bracteatum) is a traditional tonic that has Yang-strengthening and qi-enhancing, tranquilizing, intelligence-enhancing and longevity-enhancing properties. It has been used to treat impotence, spermatorrhea, anemia and insomnia. Therefore, its characteristic components and neuronal modulating effects were studied., Aim of the Study: To investigate the elimination of Aβ-induced toxicity by CE and to elucidate the molecular mechanisms involving BDNF, FGF2, and their related signaling axis, and the RIP1-driven inflammatory pathway., Materials and Methods: We established Aβ-induced toxicity models in cultured neurons and ICR mice, respectively. MWM and fear conditioning tests were performed for behavioral analysis of cognitive functions in mice. Western blot was used to investigate the levels of BDNF, FGF2, and their downstream effector TrkB/Akt/Bcl-2, as well as the RIP1-driven RIP1/RIP3/MLKL pathway. Immunofluorescence assay is used to examine the status of glial cells., Results: CE abrogated Aβ toxicity and inhibited apoptosis in cultured neurons, mainly by regulating the BDNF, FGF2, and TrkB/Akt signaling pathways as well as RIP1-driven inflammation and necroptosis. Similarly, mice injected intracerebrally with Aβ exhibited cognitive deficits and had elevated oxidative stress and inflammatory factors detected in their serum and brain. However, CE-treated mice showed recovery of cognitive abilities and quelled levels of oxidative stress and inflammatory factors. Moreover, Aβ toxicity led to a reduction in BDNF, FGF2, and related signaling regulators in the hippocampus and prefrontal cortex, accompanied by activation of RIP1-driven inflammatory signaling pathways, and a reduction in TBK1 and Bcl-2. However, CE restored the levels of BDNF, FGF2, and TrkB/Akt signaling pathway, while inhibiting RIP1-induced RIP1/RIP3/MLKL pathway, thereby antagonizing apoptosis and maintaining neuronal activity., Conclusions: CE effectively eliminated the toxicity of Aβ in cultured neurons and mouse models, which holds promise for drug development., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Gisenoside Rg1 is a potent neuroprotectant in ginseng. The aim of this study was to investigate the elimination effect of Rg1 on cadmium (Cd)-induced neurotoxicity., Materials and Methods: A cumulative Cd exposure mouse model was established. Also, the toxicity of Cd and the protective effect of Rg1 were examined in vitro using cultured neurons and microglia., Results: We found that Cd-intoxicated mice exhibited significant injury in the liver, kidney, small intestine, and testis, along with cognitive impairment. Antioxidant enzymes such as SOD, GSH-Px and CAT were reduced in the blood and brain, and correspondingly, the lipid peroxidation product MDA was elevated. In the brain, astrocytes and microglia were activated, characterized by an increase in inflammatory factors such as TNF-α, IL-1β and IL-6, as well as their protein markers GFAP and IBA1. However, Rg1 eliminated Cd-induced toxicity and restored oxidative stress and inflammatory responses, correspondingly restoring the behavioral performance of the animals. Meanwhile, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the Rg1-mediated elimination of Cd-induced toxicity., Conclusion: Rg1 is a promising agent for the elimination of Cd-induced toxicity., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Preoperative determination of breast cancer molecular subtypes facilitates individualized treatment plan-making and improves patient prognosis. We aimed to develop an assembled convolutional neural network (ACNN) model for the preoperative prediction of molecular subtypes using multimodal ultrasound (US) images., Methods: This multicentre study prospectively evaluated a dataset of greyscale US, colour Doppler flow imaging (CDFI), and shear-wave elastography (SWE) images in 807 patients with 818 breast cancers from November 2016 to February 2021. The St. Gallen molecular subtypes of breast cancer were confirmed by postoperative immunohistochemical examination. The monomodal ACNN model based on greyscale US images, the dual-modal ACNN model based on greyscale US and CDFI images, and the multimodal ACNN model based on greyscale US and CDFI as well as SWE images were constructed in the training cohort. The performances of three ACNN models in predicting four- and five-classification molecular subtypes and identifying triple negative from non-triple negative subtypes were assessed and compared. The performance of the multimodal ACNN was also compared with preoperative core needle biopsy (CNB)., Finding: The performance of the multimodal ACNN model (macroaverage area under the curve [AUC]: 0.89-0.96) was superior to that of the dual-modal ACNN model (macroaverage AUC: 0.81-0.84) and the monomodal ACNN model (macroaverage AUC: 0.73-0.75) in predicting four-classification breast cancer molecular subtypes, which was also better than that of preoperative CNB (AUC: 0.89-0.99 vs. 0.67-0.82, p < 0.05). In addition, the multimodal ACNN model outperformed the other two ACNN models in predicting five-classification molecular subtypes (AUC: 0.87-0.94 vs. 0.78-0.81 vs. 0.71-0.78) and identifying triple negative from non-triple negative breast cancers (AUC: 0.934-0.970 vs. 0.688-0.830 vs. 0.536-0.650, p < 0.05). Moreover, the multimodal ACNN model obtained satisfactory prediction performance for both T1 and non-T1 lesions (AUC: 0.957-0.958 and 0.932-0.985)., Interpretation: The multimodal US-based ACNN model is a potential noninvasive decision-making method for the management of patients with breast cancer in clinical practice., Funding: This work was supported in part by the National Natural Science Foundation of China (Grants 81725008 and 81927801), Shanghai Municipal Health Commission (Grants 2019LJ21 and SHSLCZDZK03502), and the Science and Technology Commission of Shanghai Municipality (Grants 19441903200, 19DZ2251100, and 21Y11910800)., Competing Interests: Declaration of Competing Interest T. Wu is an employee of GE Healthcare. D. Li is an employee of XiaoBaiShiJi Network Technical Co., Ltd. They do not hold any other financial interests in these companies. These companies had no role in the study design, data collection, analysis, patient recruitment or writing of the manuscript, the decision to submit the manuscript for publication or any aspect pertinent to the study. No products from this company were used in this study. The other authors declare that they have no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The neurotoxicity caused by cadmium (Cd) is well known in humans and experimental animals. However, there is no effective treatment for its toxicity. In this study, we established Cd toxicity models in cultured cells or mice to investigate the detoxification effect of edaravone (Eda). We found that Eda protected GL261 cells from Cd toxicity and prevented the loss of cell viability. In Cd-exposed mice, liver, kidney and testicular damage, as well as cognitive dysfunction were observed. Oxidative stress and inflammatory responses, such as decreased SOD and CAT, increased LDH and MDA, and abnormal changes in the inflammatory factors TNF-α, IL-1β, IL-6 and IL-10 were detected in serum and brain tissue. Eda protected mice from Cd-induced toxicity and abrogated oxidative stress and inflammatory responses. Also, Eda prevented inflammatory activation of microglia and astrocytes and was accompanied by restoration of the neuronal marker protein MAP2, indicating restoration of neuronal function. In addition, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the response of Eda to the elimination of Cd toxicity. In conclusion, Eda does contribute to the clearance of Cd-induced toxicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The risk stratification system of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for thyroid nodules is affected by low diagnostic specificity. Machine learning (ML) methods can optimize the diagnostic performance in medical image analysis. However, it is unknown which ML-based diagnostic pattern is more effective in improving diagnostic performance for thyroid nodules and reducing nodule biopsies. Therefore, we compared ML-assisted visual approaches and radiomics approaches with ACR TI-RADS in diagnostic performance and unnecessary fine-needle aspiration biopsy (FNAB) rate for thyroid nodules. Methods: This retrospective study evaluated a data set of ultrasound (US) and shear wave elastography (SWE) images in patients with biopsy-proven thyroid nodules (≥1 cm) from the Shanghai Tenth People's Hospital (743 nodules in 720 patients from September 2017 to January 2019) and an independent test data set from the Ma'anshan People's Hospital (106 nodules in 102 patients from February 2019 to April 2019). Six US features and five SWE parameters from the radiologists' interpretation were used for building the ML-assisted visual approaches. The radiomics features extracted from the US and SWE images were used with ML methods for developing the radiomics approaches. The diagnostic performance for differentiating thyroid nodules and the unnecessary FNAB rate of the ML-assisted visual approaches and the radiomics approaches were compared with ACR TI-RADS. Results: The ML-assisted US visual approach had the best diagnostic performance than the US radiomics approach and ACR TI-RADS (area under the curve [AUC]: 0.900 vs. 0.789 vs. 0.689 for the validation data set, 0.917 vs. 0.770 vs. 0.681 for the test data set). After adding SWE, the ML-assisted visual approach had a better diagnostic performance than US alone (AUC: 0.951 vs. 0.900 for the validation data set, 0.953 vs. 0.917 for the test data set). When applying the ML-assisted US+SWE visual approach, the unnecessary FNAB rate decreased from 30.0% to 4.5% in the validation data set and from 37.7% to 4.7% in the test data set in comparison to ACR TI-RADS. Conclusions: The ML-assisted dual modalities visual approach can assist radiologists to diagnose thyroid nodules more effectively and considerably reduce the unnecessary FNAB rate in the clinical management of thyroid nodules.

Objective: Coronavirus disease 2019 (COVID-19) has elevated mortality in severe and critical patients globally. This study examined the effect of glucocorticoids (GCS) on the time of virus clearance and absorption of lung lesions in severe and critical COVID-19 patients., Patients and Methods: Severe and critical COVID-19 cases diagnosed in Wuhan Pulmonary Hospital from January 7 to February 10, 2020 were analyzed. The generalized linear model was utilized to assess the effects of GCS therapy on the times of nucleic acid test turning negative and improved pulmonary imaging, respectively., Results: Of 66 patients, 51 (77.3%) and 15 (22.7%) were severe and critical cases, respectively, and aged 62 ± 11 years. A total of 58 patients (87.9%) tested negative, and 56 (84.8%) showed improved lung imaging. Age, thrombocytopenia, CD8 + T cell count, course of GCS therapy, and total dose were correlated with the time of nucleic acid test turning negative (p < 0.05), and sex was correlated with the time of initial pulmonary imaging improvement (p < 0.05). The time of nucleic acid test turning negative in individuals with GCS therapy course ≤ 10 days was shorter than that of the GCS therapy course > 10 days group (p=0.001). No statistical difference was found in the dose, course of GCS, and initial time of improved lung imaging., Conclusions: Increasing the dose of GCS and prolonging the course of treatment do not shorten the time of nucleic acid test turning negative or improved absorption of pulmonary lesions. Thus, the rational use of GCS is particularly important.

2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is the major active ingredient in Plygonum multiflorum that displays a great deal of health-benefits including anti-oxidation, anti-hyperlipidemia, anti-cancer, anti-inflammation and neuroprotection. However, it is unclear whether THSG exerts neuroprotective functions by regulating neurotrophic factors and their associated signaling pathways. In this study, hippocampal neurons were challenged with staurosporine (STS) to establish a neural damage model. We found that STS-induced cytotoxicity introduced significant morphological collapse and initiating cell apoptosis, along with the down regulation of BDNF and TrkB/Akt signaling axis. In contrast, neurons pretreated with THSG showed resistance to STS-induced toxicity and maintained cell survival. THSG rescued STS induced dysfunctions of BDNF and its associated TrkB/Akt signaling, and restored the expression of Bcl-2 and Caspase-3. However, inhibition of TrkB activity by K252a or Akt signaling by LY294002 abolished the neuroprotective effects of THSG. Therefore, BDNF and TrkB/Akt signaling axis is a promise target for THSG mediated neuroprotective functions., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Tea polyphenols (TP) are the major ingredients in tea beverages that display health-benefits including anti-oxidation, anti-inflammation, anti-aging, attenuating blood pressure and deflating. In this study, we investigated the neuroprotective effects of TP to attenuate staurosporine (STS)-induced cytotoxicity. Rat hippocampal neurons were isolated, cultured and incubated with STS to induce neurite collapse and apoptosis, however, the medication of TP eliminated these adverse effects and maintained the morphology of neurons. STS decreased the expression of pro-BDNF, downregulated the TrkB/Akt/Bcl-2 signaling axis and promoted the activation of Erk1/2 and caspase-3. In contrast, TP rescued the expression of pro-BDNF and antagonistically restored the biochemistry of aforementioned signaling effectors. Consistently, the activity of TP can be attenuated by the inhibition of TrkB or Akt by small chemicals K252a and LY294002. Therefore, BDNF-TrkB and Akt signaling axis is essential for TP-mediated neuroprotective effects. In summary, TP showed beneficial effects to protect neurons from exogenous insults such as STS-induced neural cytotoxicity and cell death., (© 2020 The Author(s).)

Micro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (T 2 DM), but whether intensive glucose control decreases the risk of diabetic cardiovascular complications remains uncertain. Many studies have confirmed that impaired quality and quantity of mesenchymal stem cells (MSCs) plays a pathogenic role in diabetes. Our previous study found that the abundance of circulating MSCs was significantly decreased in patients with T 2 DM, which was correlated with the progression of diabetic complications. In addition, metformin-induced MSC apoptosis is one of the reasons for the decreased quantity of endogenous or exogenous MSCs during intensive glucose control. However, the role of glucose in metformin-induced MSC apoptosis during intensive glucose control in T 2 DM remains unknown. In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner. Thus, our results indicate that the poorer clinical benefit of the intensive glucose control strategy may be related to an adverse effect due to metformin-induced MSC apoptosis during intensive glucose control therapy in patients with T 2 DM.

Background: Cardiovascular complications, especially myocardial infarctions (MIs), are the leading mortality cause in diabetic patients. The transplantation of stem cells into damaged hearts has had considerable success as a treatment for MI, although whether antidiabetic drugs affect the therapeutic efficacy of stem cell transplantation is still unknown. This study aims to understand whether and how metformin, one of the first-line drugs used to treat type 2 diabetes mellitus (T 2 DM), induces mesenchymal stromal cell (MSC) apoptosis and dampens their cardioprotective effect after transplantation into infarcted hearts., Methods: A mouse MI model was generated via permanent ligation of the left anterior descending (LAD) coronary artery. MSCs with or without metformin treatment were transplanted after MI in diabetic mice. Echocardiography was used to assess cardiac function and determine cardiac remodeling, and TTC staining was performed to evaluate infarction size. A mouse gavage model was performed to evaluate bone marrow MSCs for flow cytometry assay., Results: Metformin dampened MSC therapeutic efficacy, which increased infarct size and restricted functional cardiac recovery. Specifically, metformin induced the activation of AMP-activated protein kinase (AMPK)-mediated apoptosis through the inhibition of S6K1-Bad-Bcl-xL cell survival signaling, resulting in the upregulated expression of apoptosis-associated proteins and increased MSC apoptosis. Accordingly, counteracting AMPK attenuated metformin-induced apoptosis in MSCs and partially restored their cardioprotective effects in diabetic mice with MI. Furthermore, a decrease in peripheral blood MSCs was found in patients with T 2 DM who had a metformin medication history., Conclusions: Our results highlight an unexpected adverse effect of metformin-induced MSC apoptosis through AMPK-mediated mTOR suppression, which is attenuated by an AMPK inhibitor. Moreover, AMPK inhibition may be a novel strategy for enhancing the effectiveness of stem cell therapy after MI in diabetes.

A Gram-stain-positive, aerobic, non-motile, non-spore-forming, and rod-shaped bacterium, designated strain CHu64-6-1 T , was isolated from a 67-cm-long sediment core collected from the Daechung Reservoir at a water depth of 17-m in Daejeon, Republic of Korea. Comparative 16S rRNA gene sequence studies placed the new isolate in the class Sphingobacteriia, and the isolate is notably most closely related to Flavihumibacter sediminis CJ663 T (98.1% similarity), Flavihumibacter solisilvae 3-3 T (97.8%), Flavihumibacter petaseus T41 T (97.5%), Flavihumibacter cheonanensis WS16 T (97.4%), and Flavihumibacter stibioxidans YS-17 T (97.2%). The cells of strain CHu64-6-1 T formed yellow colonies on R2A agar and contained MK-7 as the only menaquinone, phosphatidylethanolamine, an unidentified phospholipid, and two unidentified aminolipids as the major polar lipids, and C 15:0 iso, C 17:0 iso 3-OH, C 15:1 iso G, and C 16:1 ω5c as the major fatty acids (> 5%). The DNA G + C content of the genome was determined to be 46.5 mol%. The DNA-DNA hybridization values of strain CHu64-6-1 T with F. sediminis CJ663 T , F. solisilvae 3-3 T , F. petaseus T41 T , F. cheonanensis WS16 T , and F. stibioxidans YS-17 T were 12.4-33.2%. Based on the combined genotypic and phenotypic data, we propose that strain CHu64-6-1 T represents a novel species of the genus Flavihumibacter, for which the name Flavihumibacter profundi sp. nov. is proposed. The type strain is CHu64-6-1 T (= KCTC 62290 T = CCTCC AB 2018060 T ).

Two series of thieno[2,3-d]pyrimidine derivatives bearing a dithiocarbamate side chain at the C2 position were synthesized and evaluated for cytotoxic activity in human lung cancer A549 and colon cancer HCT-116 cell lines. Compound 3n exhibited the most cytotoxic effect on A549 cells with an IC 50 value of 4.87 μM, inducing a cell cycle arrest at G2/M phase and activating the spindle assembly checkpoint (SAC). To identify the target protein(s) of 3n, we incorporated biotin with 3n through a three-carbon chain and an amide bond to synthesize probe 10. The targeted proteins were pulled down from the A549 total cell lysate by biotin-streptavidin affinity purification and analyzed by mass spectrometry. Tubulin was the only protein identified, which is related to the SAC and directly binds to probe 10 both in vivo and in vitro. Furthermore, compound 3n inhibited tubulin polymerization in vitro in a dose-dependent manner, competed with taxol in binding to tubulin, exerting cytotoxic activity toward taxol-resistant A549 cells. These results demonstrate that thieno[2,3-d]pyrimidine derivative 3n exhibits cytotoxicity in cancer cells by targeting tubulin to activate the SAC and potentially acts as a therapeutic lead compound for taxol-resistant cancers., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Two main theories have been used to explain the arithmetic split effect: decision-making process theory and strategy choice theory. Using the inequality paradigm, previous studies have confirmed that individuals tend to adopt a plausibility-checking strategy and a whole-calculation strategy to solve large and small split problems in complex addition arithmetic, respectively. This supports strategy choice theory, but it is unknown whether this theory also explains performance in solving different split problems in complex subtraction arithmetic. This study used small, intermediate and large split sizes, with each split condition being further divided into problems requiring and not requiring borrowing. The reaction times (RTs) for large and intermediate splits were significantly shorter than those for small splits, while accuracy was significantly higher for large and middle splits than for small splits, reflecting no speed-accuracy trade-off. Further, RTs and accuracy differed significantly between the borrow and no-borrow conditions only for small splits. This study indicates that strategy choice theory is suitable to explain the split effect in complex subtraction arithmetic. That is, individuals tend to choose the plausibility-checking strategy or the whole-calculation strategy according to the split size., (© 2016 International Union of Psychological Science.)

The linear relationship between the concentration of either bovine serum albumin (BSA) or sodium alginate (SA) and the intensity of a resonance light scattering (RLS) spectrum was established by using Congo red and neutral red as the dye probes, respectively. Moreover, the linear relationship between the concentration of humic acids (HA) and UV absorbance was determined by using toluidine blue (TB) as the dye probe. The detection of concentration range and the pH value of three kinds of standard substances were optimized. The recovery rate of bi-and tri-element samples of the standard objects was investigated by means of the dye probe analysis method. The results show that, in the appropriate concentration range, the linear correlation coefficients between the concentration of BSA, HA, or SA and the intensity of its corresponding dye probe spectrum were all high, at 0.98. The recovery rates of the three kinds of standard objects in mixed samples were all greater than 95%, and the standard errors were all less than 0.11%. Based on qualitative analysis of the proteins, polysaccharides, and humic acids in the secondary water discharge samples of urban sewage obtained via UV and RLS spectra, the dominant pollutants were confirmed in the four kinds of secondary effluent. The relative deviations of the concentration of polysaccharides and proteins measured using the dye probe technique and the national standard method ranged were from 1.2% to 0.04%.

Sulfadimidine (SM2) is commonly used in the swine industry and enters the environment via faeces. In recent years, advances in the ecotoxicology of SM2 have become a popular research interest with two common research methods including swine manure collection from swine fed with a diet containing SM2 and directly adding SM2. The purpose of this experiment was to compare SM2 degradation behaviour in pig manure with two different SM2 addition methods. The results showed that the degradation half-lives of SM2 in manure from SM2-fed swine treatment were 33.2 and 32.0 days at the initial addition level of SM2 at 32.1 and 64.3 mg/kg, respectively. This was significantly longer than that in manure directly adding SM2 treatment with the half-lives of 21.4 and 14.8 days. The metabolite of SM2 N 4 -acetyl-sulfamethazine occurred in manure from SM2-fed swine treatment but was not detected in directly adding SM2 treatment. The pH in manure from SM2-fed swine treatment was significantly lower than that in directly adding SM2 treatment, but the values of organic carbon, total nitrogen, and electrical conductivity in manure from SM2-fed swine treatment were significantly higher than those in manure directly adding SM2 treatment. Meanwhile, although the copy number of bacteria had no significant difference between two treatments, there was a significant difference in bacteria diversity. Results of the present study demonstrated that the presence of the metabolites, chemical property, and microbial diversity might be the reason for different SM2 degradation behaviours on different addition methods. Thus, the method using manure with SM2 collected from swine could obtain more accurate results for the ecotoxicological study of SM2.

A series of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at the C4-position were synthesized using piperidine and 1-bromo-3-chloropropane as starting materials via eight steps. Final compounds 8a-q and 9a-i were evaluated for their antiproliferative activity against human lung cancer A549, breast adenocarcinoma MCF-7, and colorectal cancer HCT-116 cell lines. The results showed that fourteen of twenty-six final compounds inhibited the proliferation of three cancer cell lines with IC50 values less than 10μM. When treated with a representative compound 8n, HCT-116 cells were arrested at G0/G1 phase of the cell cycle. This provided a clue to further investigation of the mechanism of action., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Bone morphogenetic protein receptors (BMPRs) are multifunctional proteins; they have indispensible roles in the process of BMP signaling. However, their function in dedifferentiated chondrosarcoma is uncertain. It has been reported that BMPR2 is associated with chondrosarcoma. Moreover, the detection of BMPR2 is more frequent in dedifferentiated chondrosarcomas (DDCS) than in conventional chondrosarcomas (CCS). BMPR2, phospho-SMAD1/5 (pSMAD1/5), and runt-related transcription factor 2 (RUNX2) expressions were found to be associated with the pathological grades of chondrosarcoma and could be a promising target of treatment outcome. Moreover, BMPR2 was found to induce the RUNX2 expression via pSmad1/5. Knockdown of BMPR2 and pSmad1/5 results in the downregulation of RUNX2 expression in DDCS cells, while the upregulation of BMPR2 and Smad1/5 in CCS cells leads to increased RUNX2 expression. The luciferase reporter gene assay suggested that BMPR2 can induce the RUNX2 expression at the transcriptional level. By chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assay (EMSA), it was found that pSmad1/5 combined directly to RUNX2. The in vivo tumorigenicity assay in mice showed that the inhibition of BMPR2 or Smad1/5 in DDCS cell line reduced tumor growth, while the upregulation of BMPR2 or Smad1/5 in CCS cell line increased tumor growth. Furthermore, a BMPR signaling inhibitor, LDN-193189, was introduced to investigate its role as a potential drug to treat DDCS. Taken together, the present-study results suggest that BMPR2-pSmad1/5 signaling pathway has an important role in regulating not only the RUNX2 expression but also the tumorigenesis of DDCS.

In order to compare the chronic toxicity of pollutants to organisms in an aquatic environment under different food densities, the cladoceran Moina macrocopa was used as test animal to investigate the effects of Hg²⁺ concentrations (0, 0.4, 1.1, 1.8, 2.5, 3.2 and 3.9 µg · L⁻¹) on its life table demography under low (0.5 x 10⁶ cells · mL⁻¹), medium (1.0 x 10⁶ cells · mL⁻¹) and high (2.0 x 10⁶ cells · mL⁻¹) densities of Scenedesmus obliquus. The results showed that at low and high food levels, certain concentrations of Hg²⁺ had inhibitory effects on survival, reproduction and population growth of M. macrocopa. However, at the medium food level, the inhibitory effects disappeared. Compared with the control, at the low food level, Hg²⁺ at 0.4-2.5 and 3.9 µg · L⁻¹ significantly decreased the life expectancy at hatching, Hg²⁺ at 0.4, 1.1, 2.5 and 3.9 µg · L⁻¹ decreased the generation time, Hg²⁺ at 1.1, 2.5 and 3.9 µg · L⁻¹ decreased the net reproduction rate, and Hg²⁺ at 3.9 µg · L⁻¹ decreased the gross reproduction rate of M. macrocopa. At the high food level, Hg²⁺ at 1.1 µg · L⁻¹ decreased the intrinsic rate of population increase, and Hg²⁺ at 3.9 µg · L⁻¹ decreased the life expectancy at hatching and the net reproduction rate of M. macrocopa. However, at the medium food level, Hg²⁺ at 3.2 µg · L⁻¹ increased the life expectancy at hatching of M. macrocopa. When S. obliquus density was 0.5 x 10⁶ cells · mL⁻¹, there were significant dose-effect relationships between Hg²⁺ concentration and the life expectancy at hatching, the generation time as well as the cross reproduction rate of M. macrocopa. However, when S. obliquus density was 1.0 x 10⁶ or 2.0 x 10⁶ cells · mL⁻¹, there were no any significant dose-effect relationships between Hg²⁺ concentration and each of the life table demographic parameters of M. macrocopa.

Background and Aim: Chronic kidney disease has recently been shown to be a major risk factor for cardiovascular disease and carotid intima-media thickness has been widely used as a biomarker for early detection of cardiovascular disease. The aim of this study was to confirm whether carotid thickening and carotid plaque are associated with preclinical chronic kidney disease in individuals without clinical cardiovascular disease and chronic kidney disease., Material and Methods: We conducted a cross-sectional study on participants from Maanshan City, China. All participants underwent carotid ultrasonography. Kidney function was measured using cystatin C, serum creatinine, blood urea nitrogen and blood uric acid. Demographics and risk factors for cardiovascular diseases were obtained from each participant., Results: A total of 927 subjects were surveyed; 453 (48.87%) were men and 474 (51.13%) were women. A total of 525 (56.63%) of the participants were found to have carotid thickening of which 281 (53.52%) were men and 244 (46.48%) were women. Kidney function was strongly associated with carotid thickening and plaque in the unadjusted analysis. However, cystatin C was the only measure of kidney function that was significantly associated with carotid thickening and plaque in the adjusted analysis (in order to select risk factors from sex, age, BMI, hypertension, diabetes, smoking, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein A, apolipoprotein B, cystatin C, creatinine, blood urea nitrogen, blood uric, estimated GFR)., Conclusion: Cystatin C, an alternative measure of kidney function, was more strongly associated with carotid thickening and plaque than other measures of kidney function.

In this paper, it is shown that the proposed quantum algorithm for implementing Boolean circuits generated from the DNA-based algorithm solving the vertex-cover problem of any graph G with m edges and n vertices is the optimal quantum algorithm. Next, it is also demonstrated that mathematical solutions of the same biomolecular solutions are represented in terms of a unit vector in the finite-dimensional Hilbert space. Furthermore, for testing our theory, a nuclear magnetic resonance (NMR) experiment of three quantum bits to solve the simplest vertex-cover problem is completed.

In this laboratory study, an advanced flow visualization technique - particle image velocimetry (PIV) - was employed to investigate the change of shape of activated sludge flocs in water and its influence on the material transport characteristics of the flocs. The continuous shape change of the bio-flocs that occurred within a very short period of time could be captured by the PIV system. The results demonstrate that the fluid turbulence caused the shift of parts of a floc from one side to the other in less than 200 ms. During the continuous shape change, the liquid within the floc was forced out of the floc, which was then refilled with the liquid from the surrounding flow. For the bio-flocs saturated with a tracer dye, it was shown that the dye could be released from the flocs at a faster rate when the flocs were swayed around in water. The experimental results indicate that frequent shape change of bio-flocs facilitates the exchange of fluid and materials between the floc interior and the surrounding water. This mass transfer mechanism can be more important than molecular diffusion and internal permeation to the function and behavior of particle aggregates, including bio-flocs, in natural waters and treatment systems.

A laboratory study was conducted to investigate the production of quorum sensing (QS) molecules by aerobic granules in membrane-partitioned bioreactor. Flow-chamber (FC) tests with Escherichia coli K12 demonstrated that granules induced more attached growth of E. coli cells than activated sludge flocs, leading to more cell adhesion and biofilm formation on the FC cover slide. Using the thin-layer chromatography, N-acy-l-homoserine lactones (AHLs) with acyl chains shorter than 10 carbons were detected in the liquid phase of granular sludge. Organic substances extracted with acidified ethyl acetate from the supernatant of granular sludge promoted the adhesion and growth of E. coli cells on the glass surface. AHL-like signal molecules were apparently produced by granules and might be involved in the formation of granules and the maintenance of granular structures during wastewater treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Synthetically useful α,β-unsaturated carbonyl compounds were obtained from gold-catalyzed oxidative rearrangement of homopropargylic ether under mild reaction conditions. Gold carbenoid and oxonium ylide are proposed as key intermediates.

Aim: To investigate the expression and clinical significance of CEACAM1 and HBx in HBV related hepatocellular carcinoma., Methods: The expression of CEACAM1 and HBx in 81 HBV related hepatocellular carcinoma were detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. The expression of CEACAM1 in the human normal hepatocyte cell line QZG, HepG2 and HepG2-X were detected by Western blot., Results: The positive rate of CEACAM1 and HBx in 81 HBV related hepatocellular carcinoma tissues were 71.60%(58/81) and 74.07%(60/81) respectively. The expression of CEACAM1 and HBx were correlated with portal vein invasion, nodal metastasis and TNM staging. The expression of CEACAM1 was negative correlated with HBx(r(s);=-0.310, P<0.01). CEACAM1 protein was significantly down regulated in HepG2-X than in HepG2-PC and human normal hepatocyte cell line QZG., Conclusion: The higher expression of HBx and lower expression of CEACAM1 are correlated with invasion and metastasis of HBV related hepatocelular carcinoma, CEACAM1 may be a effect molecule in HBV related hepatocarcinogenesis.

Ewing's sarcoma is the second most frequent primary malignant bone tumor, mainly affecting children and young adults. The notorious metastatic capability of this tumor aggravates patient mortality and remains a problem to be overcome. We investigated the effect of arsenic trioxide (As₂O₃) on the metastasis capability of Ewing's sarcoma cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide assays to choose appropriate concentrations of As₂O₃ for the experiments. Migration, invasion, and adhesion assays were performed to assess the effect of As₂O₃ on the metastasis of Ewing's sarcoma. Immunofluorescent staining was used to observe cytoskeleton reorganization in Ewing's sarcoma cells treated with As₂O₃. Changes in matrix metalloproteinase-9 expression and the mitogen-activated protein kinase (MAPK) pathway were investigated using western blot. Inhibitors of p38(MAPK) (sb202190) and c-Jun NH₂-terminal kinase (JNK, sp600125) were used in invasion assays to determine the effect of p38(MAPK) and JNK. We found that As₂O₃ may markedly inhibit the migration and invasion capacity of Ewing's sarcoma cells with structural rearrangements of the actin cytoskeleton. The expressions of matrix metalloproteinase-9, phosphor-p38(MAPK), and phosphor-JNK were suppressed by As₂O₃ treatment in a dose-dependent manner. The inhibitors of p38(MAPK) (sb202190) and JNK (sp600125) enhanced the inhibition induced by As₂O₃, which was counteracted by anisomycin, an activating agent of p38(MAPK) and JNK. Taken together, our results demonstrate that As₂O₃ can inhibit the metastasis capability of RD-ES and A-673 cells and may have new therapeutic value for Ewing's sarcoma.

In this work, nitrogen loss in the nitrite oxidation step of the nitrification process in an aerobic-granule-based reactor was characterized with both experimental and modeling approaches. Experimental results showed that soluble microbial products (SMP) were released from the nitrite-oxidizing granules and were utilized as a carbon source by the heterotrophs for denitrification. This was verified by the fluorescence in situ hybridization (FISH) analysis. Microelectrode tests showed that oxygen diffusion limitation did result in an anoxic micro-zone in the granules and allowed sequential utilization of nitrate as an electron acceptor for heterotrophic denitrification with SMP as a carbon source. To further elucidate the nitrogen loss mechanisms, a mathematic model was formulated to describe the growth of nitrite oxidizers, the formation and consumption of SMP, the anoxic heterotrophic growth on SMP and nitrate, as well as the oxygen transfer and the substrate diffusion in the granules. The results clearly indicate that the heterotrophs grown on the SMP released by the autotrophs are responsible for the nitrogen loss in the nitrifying granules, and give us a better understanding of the aerobic granules for nitrogen removal. Biotechnol. Bioeng. 2011;108: 2844-2852. © 2011 Wiley Periodicals, Inc., (Copyright © 2011 Wiley Periodicals, Inc.)

In the title compound, C(15)H(10)Cl(2)N(4)O(2), the dichloro-pyrimidine and meth-oxy-phen-oxy parts are approximately perpendicular [dihedral angle = 89.9 (9)°]. The dihedral angle between the two pyrimidine rings is 36.3 (4)° In the crystal, there are no hydrogen bonds but the mol-ecules are held together by short inter-molecular C⋯N [3.206 (3) Å] contacts and C-H⋯π inter-actions.

Quorum sensing (QS) through signal chemical molecules is known to be essential to bacterial adhesion and biofilm formation. In this study, the QS ability of aerobic granules--a special form of biofilms used for biological wastewater treatment--was investigated and compared with that of conventional activated sludge flocs. A novel sectional membrane bioreactor was used together with a flow-cell to evaluate the possible influence of signal chemicals produced by the source sludge on the growth mode of bacterial cells. The results demonstrate the apparent production of QS chemicals from granules and its impact on initial cell attachment and granule formation. When granules were used as the signal-producing biomass, the attached-growth mode was dominant for the free cells, and the biofilm formation rate in the flow-cell was about ten times faster than in cases which used activated sludge as the signal source biomass. In addition, the intracellular extract from mature granules significantly accelerated the sludge granulation process. It is argued that the production and expression of QS signal chemicals from granules and granule precursors might have induced the gene expression of bacteria in suspension for attached growth rather than suspended growth, leading to granule formation and its stable structure.

Purpose: Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The regulatory mechanisms for the rapid proliferation of chondrosarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. In this study, we investigate the effect of epigallocatechin-3-gallate (EGCG) on growth and apoptosis of chondrosarcoma cells., Methods: The chondrosarcoma cell lines, SW1353 and CRL-7891, were cultured with and without EGCG. The MTT assay was used to test the cytotoxicity of EGCG. Flow cytometry and DAPI staining were used to observe cell apoptosis caused by EGCG. To explore the effect of EGCG on the Indian Hedgehog signaling pathway and apoptosis-related proteins, RT-PCR and Western blotting were used to detect the expression of PTCH and Gli-1 in the Indian Hedgehog signaling pathway. Meanwhile, expression of Bcl-2, Bax, and caspase-3 were also evaluated by Western blot analysis., Results: EGCG effectively inhibited cellular proliferation and induced apoptosis of SW1353 and CRL-7891. EGCG inhibited the human Indian Hedgehog pathway, down-regulated PTCH and Gli-1 levels, and induced apoptosis as confirmed by DAPI staining followed by flow cytometry. Protein expression levels of caspase-3 were unchanged in response to EGCG treatment in chondrosarcoma cells; however, the expression levels of Bcl-2 were significantly decreased and the levels of Bax were significantly increased., Conclusions: Our findings demonstrate that EGCG is effective for growth inhibition of a chondrosarcoma cell lines in vitro, and suggest that EGCG may be a new therapeutic option for patients with chondrosarcoma.

Since a certain level of hydrodynamic shear force is needed in the formation of microbial granules for wastewater treatment, a method for quantifying the shear stresses in a microbial granular sludge reactor is highly desirable. In this work a novel energy-dissipation-based model was established and validated to quantitatively describe the shear stresses in a granular sludge sequencing batch reactor (SBR). With this model, the shear stress at the solid-liquid interface in an SBR was estimated and the relative magnitudes of shear stresses induced by fluid, gas bubble and collision on granules were evaluated. The results demonstrate that the effect of reactor geometry on the global shear stress was significant. Both the shear stress at the microbial granule surface and the biomass-loss rate increased with an increase in biomass concentration in the SBR. The gas bubble and the collision were found to be the main source for the shear stress at the granule surface.

In this paper, we demonstrate that the logic computation performed by the DNA-based algorithm for solving general cases of the satisfiability problem can be implemented more efficiently by our proposed quantum algorithm on the quantum machine proposed by Deutsch. To test our theory, we carry out a three-quantum bit nuclear magnetic resonance experiment for solving the simplest satisfiability problem.

Calcium-rich aerobic granules were cultivated after 3-month operation. The chemical form and spatial distribution of calcium in the granules and their physicochemical characteristics were explored. Examination with a scanning electron microscope combined energy dispersive X-ray detector (SEM-EDX) shows that Ca was mainly accumulated in the core of the granules. CaCO(3) was found to be the main calcium precipitate in the granules. The fluorescent in situ hybridization (FISH) analysis shows that the cells were crowded in the outer layer and gathered in clusters. Compared with the granules without Ca accumulation, the Ca-rich granules had more rigid structure and a higher strength. However, their specific oxygen uptake rate (SOUR) reduced after the Ca accumulation inside them. Comparison between the SOUR values of the granules with and without Ca accumulation suggests that Ca accumulated in the aerobic granules might have a negative effect on their bioactivity.

Settling velocity of microbial aggregates, such as anaerobic and aerobic granules, in biological wastewater treatment systems is highly related to their drag coefficient. In this work a new approach, taking the porosity and the permeability into account, was established to evaluate the drag coefficient of porous and permeable microbial granules. The effectiveness of this approach was demonstrated by the experimental results with both the anaerobic and the aerobic granules. The drag coefficient of the microbial granules was found to be less than that of smooth rigid spheres and Biofilm-covered particles. In addition, this study demonstrates that the drag coefficient of microbial granules depended heavily on their permeability and porosity. A fractal-cluster model was found to be able to predict the distribution of the primary particles in the microbial granules.

Objective: To compare characteristics of better responders to new regimen therapy with non-responders., Methods: In a 12-week, two-center, open, parallel group clinical trial, 80 type 2 diabetic patients treated with twice-daily premixed 30 R insulin with or without OAD (s) [fasting blood glucose (FBG) 7.8 - 16.7 mmol/L, HbA1c 7% - 10%] were randomized to once-daily morning insulin glargine plus glimepiride 3 mg or premixed 30 R insulin (70/30) twice-daily plus glimepiride 3 mg. Insulin dosage was titrated to target FBG 8.0% vs 8.9%-->7.8%, P > 0.05). However, hypoglycemic episodes were significantly higher in premixed-insulin-treated subjects than in glargine-treated subjects [total: 123 vs 57; proved hypoglycemic episodes 94 (76%) vs 21 (47%), chi(2) = 23.692, P < 0.01], The frequency of hypoglycemia before lunch was especially greater in premixed-insulin-treated subjects 64 (52%) vs 17 (30%), chi(2) = 7.762, P = 0.005. Several subjects from the premixed arm experienced too frequent hypoglycemic episodes to be recorded during 10AM-11AM almost every day. Subgroup analysis for patients treated with glargine: 28.2% (11 cases) of the patients in this group attained HbA1c 8.5% at 12 weeks, mean daily dosage for glargine were (0.66 +/- 0.30) U.kg(-1).d(-1). There were significant differences of baseline HbA1c, diabetes duration and baseline postprandial C-peptide between the two subgroups in glargine arm (HbA1c: 8.1% +/- 0.8% vs 9.6% +/- 1.2%; duration: 10 (6 - 14.5) years vs 13 (8 - 19.5) years; postprandial c peptide: 2.5 nmol/L (1.4 - 3.3) vs 1.4 (1.2 - 2.6) nmol/L, all P < 0.05)., Conclusion: Type 2 diabetic patients treated with twice-daily injection of premixed 30 R insulin with or without OAD (s) can be effectively and safely switched to basal insulin plus OAD. Pretreatment HbA1c, diabetes duration and postprandial C peptide are the key factors that closely related to efficacy of this new regimen.

A digital light modulation microscope (DLMM) that utilizes a digital micromirror device (DMD) on an epifluorescence microscope has been developed to modulate excitation light in spatial and temporal domains for phosphorescence lifetime detection. Local O2 concentration can be inferred through the detected lifetime around an O2-quenching phosphorescent porphyrin microsensor. Combined with microsensor arrays, the DLMM can sequentially address light to each microsensor element to construct a discrete lifetime image or O2 distribution. In contrast to conventional phosphorescence lifetime imaging, the new method eliminates the need for a pulsed light source and a time-gated camera. To demonstrate O2 sensing with lab-on-a-chip devices, an array of 150-mum-diameter micro-wells coated with phosphorescent porphyrin were observed. The locations of the sensor elements were automatically identified though image analysis. The goal of this platform is to measure the O2 consumption of individual cells trapped in the microwells.

p37 protein is a membrane lipoprotein of Mycoplasma hyorhinis, and our previous work showed that there was high ratio of M. hyorhinis infection in human gastric carcinoma. To investigate the possible functions of p37 in cancer development, the nucleotide sequence of p37 gene was modified and expressed well in transfected cells. We found that p37 localized at the Golgi apparatus and could be secreted out of the cell. Human gastric cancer cells AGS, after being transfected with the p37 gene, were smaller, more spherical and easy to detach from each other. Their adhesion to matrix was also diminished and cytoskeleton in these stable p37 AGS cell was rearranged and transcription co-factor beta-actin was transferred to nucleolus with down-regulation of ICAM-1 and integrin beta1. These findings will be helpful for us to elucidate the effects of p37 on eukaryotic cells as well as to better understand the potential relationship between cancer and mycoplasma infection.