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Crocin-4 is a water-soluble carotenoid that exhibits cardiovascular protection effects through anti-inflammatory and antioxidant effects. However, the pharmacodynamic effects and mechanisms of its analogues crocin-1 and crocin-2' have not been reported. In this study, we evaluated the protective effects of rare crocins on cardiovascular systems. In ox-LDL induced HUVECs model, 0.02, 0.1, 0.5, 1, 2, 3, 4, 5, 6 μg/mL crocin-1 and crocin-2' can increase cell viability by up to 80 %. Meanwhile, rare crocins at concentrations between 25-100 μg/mL crocin-1 and crocin-2' reduced the lipid accumulation by 30 % in cholesterol-induced zebrafish larvae. What's more, the therapeutic potential of rare crocins on thrombosis has also been explored. In vitro experiments, rare crocin-1 and crocin-2' at concentrations of 0.02, 0.05, 0.2, 0.5, 1, 2, 5, 10 μg/mL protected Human Umbilical Vein Endothelial Cells (HUVECs) against lipopolysaccharides-induced oxidative stress and inflammation. In vivo studies revealed that rare crocins at concentrations of 25, 50, 100, 150, 200, and 300 μg/mL exerted significant antithrombotic effect on arachidonic acid (AA)-induced zebrafish and there was nearly no potential risk for the deformity of zebrafish at 300 μg/mL dosages. In brief, rare crocins was viewed as a potentially useful candidate for the treatment of cardiovascular diseases because of its anti-inflammatory, antioxidant, and anticoagulant properties., 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.)

Rationale: Anti-Myelin oligodendrocyte glycoprotein (MOG) and anti-metabotropic glutamate receptor 5 (mGluR5) double antibody positive encephalitis characterized by optic neuritis is extremely rare. We present a case of overlapping syndrome of MOG-IgG-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis., Patient Concerns: A 60-year-old Chinses woman presented to the hospital with progressive vision loss and headache for 1 week. The cerebrospinal fluid examination was within the normal range. Visual evoked potentials study disclosed prolonged latency of P100 bilaterally. Fundus examination revealed indistinct boundaries of both optic discs. Her brain magnetic resonance imaging showed patchy hyperintensity in the posterior horn of the left ventricle and the left optic nerve. Her serum was positive for anti-MOG and anti-mGluR5 antibodies., Diagnosis: The patient was diagnosed with overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis mainly based on the clinical symptoms and further test of the antibody in serum., Interventions and Outcomes: She was subsequently subjected to empirical treatment with intravenous methylprednisolone. After discharge, she was given a tapering dose of oral prednisone, alongside mycophenolate mofetil. On outpatient follow-up, her symptoms showed no relapse after 1 month, and her condition remained stable., Lessons: Early recognition of autoimmune encephalitis is crucial. The detection of cerebrospinal fluid and serum of autoimmune encephalitis and demyelinating diseases of the CNS, including MOG-IgG and mGluR5-IgG, should be strengthened in order to make a precise diagnosis and develop a comprehensive treatment plan in a timely manner., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: There are two major issues in the MRI image diagnosis task for Parkinson's disease. Firstly, there are slight differences in MRI images between healthy individuals and Parkinson's patients, and the medical field has not yet established precise lesion localization standards, which poses a huge challenge for the effective prediction of Parkinson's disease through MRI images. Secondly, the early diagnosis of Parkinson's disease traditionally relies on the subjective judgment of doctors, which leads to insufficient accuracy and consistency. This article proposes an improved YOLOv5 detection algorithm based on deep learning for predicting and classifying Parkinson's images., Methods: This article improves the YOLOv5s network as the basic framework. Firstly, the CA attention mechanism was introduced to enable the model to dynamically adjust attention based on local features of the image, significantly enhancing the sensitivity of the model to PD related small pathological features; Secondly, replace the dynamic full dimensional convolution module to optimize the multi-level extraction of image features; Finally, the coupling head strategy is adopted to improve the execution efficiency of classification and localization tasks separately., Results: We validated the effectiveness of the proposed method using a dataset of 582 MRI images from 108 patients. The results show that the proposed method achieves 0.961, 0.974, and 0.986 in Precision, Recall, and mAP, respectively, and the experimental results are superior to other algorithms., Conslusion: The improved model has achieved high accuracy and detection accuracy, and can accurately detect and recognize complex Parkinson's MRI images., Significance: This algorithm has shown good performance in the early diagnosis of Parkinson's disease and can provide clinical assistance for doctors in early diagnosis. It compensates for the limitations of traditional methods., (© 2024. The Author(s).)

Sailing robots can contribute significantly to maritime surface exploration, due to its potential for long-range and long-duration motions in the environment with abundant wind. However, energy, the critical factor for their long-term missions, shall be carefully investigated, so as to achieve sustainability in distance and time. In this survey, we have conducted a comprehensive investigation on numerous sailing robots, developed in academia and industry. Some of them have achieved long-term operation, and some are motivated by, but still on the way to this ambitious goal. Prototypes are grouped in each team, so as to view the development path. We further investigate the existing design and control strategies for energy sufficiency from three perspectives: actuation, harvesting, and energy management. In propulsion and steering, i.e., two major actuations, researchers have accumulated effective sail and rudder designs. The motorized propeller and wave-glider-inspired mechanism also contribute as compliments for propulsion. Electricity harvesting based on solar or wind energies is also discussed to gather more power from nature. Pros and cons in strategies of energy management, which are valuable tools to enhance power utilization efficiency, are elaborated. This article is hoped to provide researchers in long-term robotic sailing with a comprehensive reference from the perspectives of energy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Qi, Liu, Ji and Qian.)

Penicillin G acylase (PGA) was an important biocatalyst for enzymatic production of second-generation cephalosporin. PGA from Achromobacter xylosoxidans PX02 (AxPGA) showed relatively lower identity to EcPGA (54.9% in α subunit and 51.7% in β subunit), which could synthesize cefamandole in the kinetically controlled N-acylation (kcNa). Semi-rational design of AxPGA and "small and smart" mutant libraries were developed with minimal screening to improve cefamandole production. A triple mutant αR141A/αF142I/βF24G by combining the mutational sites (βF24, αR141, and αF142) from different subunits of AxPGA showed better performance in cefamandole production, with 4.2-fold of improvement in the (k cat /K m ) AD value for activated acyl donor (R)-Methyl mandelate. Meanwhile, the (k cat /K m ) Ps value for cefamandole by mutant αR141A/αF142I/βF24G was sharply dropped by 25.5 times, indicating its highly synthetic activity and extremely low hydrolysis of cefamandole. Strikingly, the triple mutant αR141A/αF142I/βF24G could form cefamandole with a yield of 85% at an economical substrate ratio (acyl donor/nucleophile) of 1.3:1 (82% at 1.1:1), which advanced the greener and more sustainable process of cefamandole production than the wild type. Furtherly, the improved synthetic ability and lower hydrolysis of cefamandole by mutant were rationalized using molecular docking., (Copyright © 2021. Published by Elsevier B.V.)

Context: Recent immunohistochemical studies have demonstrated Sry-related HMG-Box gene 10 (SOX10) expression in malignant melanomas, malignant peripheral nerve sheath tumors, a subset of breast carcinomas, and gliomas. SOX10 has shown important clinical utility in its ability to detect desmoplastic and spindle cell melanomas. To date, most publications have employed a research use-only goat polyclonal SOX10 antibody for immunohistochemical staining., Objective: To describe the development of a new mouse monoclonal SOX10 antibody (BC34) and evaluate its immunohistochemical staining profile in a wide range of normal and neoplastic tissues, with an emphasis on melanoma., Design: SOX10 antibody was optimized for staining using a polymer detection system and visualization with diaminobenzidine., Results: In normal tissues, SOX10 was expressed in skin melanocytes and eccrine cells, breast myoepithelial and lobular epithelial cells, salivary gland myoepithelial cells, peripheral nerve Schwann cells, and central nervous system glial cells. SOX10 was expressed in 238 of 257 melanomas (92.6%), including 50 of 51 of both spindle cell and desmoplastic melanomas (98%). SOX10 was expressed in 100% of nevi (20 of 20) and schwannomas (28 of 28). In other neoplasms, SOX10 was expressed in 18 of 109 invasive ductal breast carcinomas (16.5%). All other carcinomas were negative for SOX10. SOX10 was identified in 25 of 52 central nervous system neoplasms, primarily in astrocytomas (22 of 41; 53.7%), and in 4 of 99 various sarcomas examined (4.0%)., Conclusions: The newly developed mouse monoclonal SOX10 antibody BC34 is highly sensitive and specific for malignant melanoma, including desmoplastic and spindle cell variants, and appears highly suitable for clinical use.

Context: Uroplakin II is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. Studies have shown uroplakin II messenger RNA to be expressed in bladder cancer tissues and peripheral blood of patients with urothelial carcinoma. Little is known about the protein expression of uroplakin II in urothelial carcinoma, possibly because of the absence of a commercially available uroplakin II antibody. Pathologists have used the uroplakin III antibody (AU1) to identify tumors of urothelial origin; however, the use of AU1 is limited because of its poor sensitivity., Objectives: To evaluate a newly developed mouse monoclonal uroplakin II antibody (BC21) in urothelial carcinoma and to compare it with previously developed mouse monoclonal uroplakin III (BC17 and AU1)., Design: Uroplakin II and III antibodies were optimized for staining using a horseradish peroxidase-polymer detection system and were visualized with 3,3'-diaminobenzidine., Results: BC21, BC17, and AU1 demonstrated sensitivities in urothelial carcinoma of the bladder of 79% (44 of 56), 55% (31 of 56) (P = .002), and 34% (19 of 56) (P < .001), respectively. Subsequently, the increased staining sensitivity and intensity of BC21, compared with BC17, was validated in a larger study (134 of 174; 77% and 94 of 174; 54%, respectively) (P < .001). BC21 was found to be highly specific when evaluated in various normal and neoplastic tissues, including prostatic and renal carcinomas., Conclusions: The mouse monoclonal uroplakin II antibody (BC21) demonstrated superior sensitivity and specificity in urothelial carcinoma, compared with uroplakin III (BC17 and AU1), suggesting its advantages in the differential diagnosis of urothelial carcinoma and in the detection of tumors of unknown origin.

PAX8 is expressed in a high percentage of renal cell and ovarian cancers; however, the current existing anti-PAX8 rabbit polyclonal (P) antibodies also recognize B cells, pancreatic cancers, carcinoids, and some soft tissue tumors. Cross-reactivity with B cells can be especially troublesome in lymph nodes when identifying tumors of unknown origin. A new mouse monoclonal (M) anti-PAX8 antibody (Clone BC12) has been developed that recognizes PAX8 expression in a high percentage of renal cell and ovarian carcinomas, whereas exhibiting no staining of B cells. PAX8 (M) was tested for specificity and sensitivity in over 1300 cases of both normal and neoplastic tissues. PAX8 (M) demonstrated superior staining sensitivity in clear cell and papillary renal cell carcinomas (88.8% vs. 84.4%) and in serous and endometrioid ovarian carcinomas (87% vs. 83%), when compared with PAX8 (P). PAX8 (M) also stained a high percentage of endometrial and thyroid cancers, 67.5% and 60.7%, respectively. PAX8 (M) demonstrated low sensitivity in cervical and bladder cancers, 2.5% and 1.4%, respectively. All other cancers including lung, breast, prostate, stomach, liver, soft tissue, pancreas, testis, brain, colon, melanoma, lymphoma, adrenal, pituitary, and rectal were negative. In normal tissue, PAX8 (P) stained lymph nodes, pancreas, and neuroendocrine cells of stomach and colon. In contrast, PAX8 (M) was negative in each of these tissues. These results demonstrate that mouse monoclonal PAX8 [BC12] stains nuclei exclusively and performs well in formalin-fixed paraffin-embedded tissues. PAX8 (M) is a highly sensitive marker for thyroid, renal, and ovarian cancers. Importantly, PAX8 (M) does not stain B cells and does not seem to recognize epitopes of pancreatic origin and neuroendocrine cells in stomach and colon; thus, providing superior specificity and making PAX8 [BC12] an excellent marker for confirming primary tumor site and for differential diagnosis.

Objective: High hydrostatic pressure (HHP) could be synergized with Nisin in neutral food system to achieve commercial sterilization. The mechanism of synergistic inactivation by HHP treatment and Nisin was investigated at molecular level alongside ultramicroscopic structure., Methods: Bacillus subtilis strain was subjected to HHP (100 -500 MPa for 15 min) alone and in combination with Nisin (200 IU/mL) in PBS (pH 7.0). Membrane permeability was studied by fluorescent dye and ultraviolet absorption. Membrane lipid, protein and DNA changes were detected by Fourier Transform Infrared. Transmission Electron Microscope (TEM) was used to detect the morphological changes., Results: In neutral food system, the combined effect of HHP and Nisin reduced the population of the bacteria by 2.5 log, while at the same time increasing the membrane permeability by 10% - 60%. The physical state of membrane phospholipid molecules changed from liquid crystalline to gel state with a decrease in membrane fluidity. Treatments at elevated pressures were observed to cause protein denaturalization. Results from TEM demonstrate that cell content leaked owing to the synergistic effect., Conclusion: This confirms that Nisin is an effective bactericide when combined with HHP in neutral food and that the two inactivation methods have a synergistic effect.

In this paper, we describe the development of a novel rabbit monoclonal cytokeratin 7 (CK7) antibody. CK7 is widely used in immunohistochemical tests that are commonly performed in histopathology laboratories. Rabbits were immunized with a peptide corresponding to C-terminus of CK7. Recombinant monoclonal antibodies were developed using proprietary technology. Antibodies were screened by enzyme-linked immunosorbent assay against CK7 peptide, and the specificity of the antibody was verified by Western blotting on Hela cell lysates and by immunohistochemical staining on formalin-fixed paraffin-embedded tissue sections. One clone, designated as BC1 was selected and tested on a variety of human tissues. Its reactivity was tested and compared with a well-characterized mouse monoclonal CK7 antibody OV-TL 12/30 on lung, breast, ovarian, and colon cancers, and on a variety of normal tissues. The staining patterns and specificity were concordant with mouse monoclonal OV-TL 12/30. The BC1 clone, however, showed superior staining to OV-TL 12/30 in terms of intensity and staining of debris. CK7 combined with CK20 or CDX2 and TTF1 is a common panel used in histopathology laboratories in discrimination between primary adenocarcinomas and metastatic lung adenocarcinomas from colonic origin. We then developed a 4-step double stain (multiplex) assay by combining CDX-2 with CK7 in an antibody cocktail and tested the efficacy on lung, breast, and colon cancers. Results showed that this novel antibody can be used as a single component and/or in combination with CDX2 and TTF1 in applications for diagnostic pathology.