Comorbidity of Myasthenia gravis and Graves' disease as immune reconstitution-associated autoimmune disease in HIV infection: A case report and literature review.

BACKGROUND: Comorbidity of Myasthenia gravis (MG) and Graves' disease (GD) in treated HIV-infected individuals has rarely been described and little study has been done on the link between HIV-related immune reconstitution and autoimmune diseases occurring post antiretroviral therapy. CASE PRESENTATION: Here we report on a 33-year-old Chinese man with HIV infection who had been virologically suppressed since 2018. The patient was diagnosed with GD and was treated in 2020. Early in 2022, he developed fluctuating weakness and fatigue involving the bilateral extraocular muscles and limbs. With a positive neostigmine test, he was considered to have MG, but showed a poor response to oral medication. After multiple failed medication attempts, a thymectomy was finally performed to resolve his symptoms. The consecutive onset of immunological events may have partially resulted from immune reconstitution after viral control. CONCLUSIONS: This is a rare case of HIV-related immune reconstitution-associated autoimmune disease (IRAD) with comorbidity of MG and GD which was reported initially. Cooperation with multidisciplinary teams is essential to avoid misdiagnosis and to promote the overall health of HIV-infected patients.

Hydrogel-Tissue Interface Interactions for Implantable Flexible Bioelectronics.

Hydrogels have emerged as multifunctional interface materials between implantable bioelectronic devices and biotissues. The soft and wet materials with low and alterable mechanical properties can match the mechanical, chemical, electrical, and biological properties of biotissues and thus diminish the mechanical and electrical mismatch. Interactions at the hydrogel-biotissue and hydrogel-device interfaces have attracted broad research interest. Great efforts have been devoted to establishing instant, strong, and conformal adhesion at the interface by chemical bonding, electrostatic interaction, hydrogen bonding, supramolecular recognition, hydrophobic association, and even topological entanglements at the interfaces. This Perspective provides a brief account of representative progress on the hydrogel-tissue adhesive that forms seamless and conformal interface adhesion and applications in implantable devices for physiological, cardiac, and neuronal signal collection and electrical stimulation. Major challenges such as wet adhesion and the stability of the adhesive hydrogel-tissue interface are identified for examination in future investigations.

Quantum vibration perturbation approach with polyatomic probe in simulating infrared spectra.

The quantitative prediction of vibrational spectra of chromophore molecules in solution is challenging and numerous methods have been developed. In this work, we present a quantum vibration perturbation (QVP) approach, which is a procedure that combines molecular quantum vibration and molecular dynamics with perturbation theory. In this framework, an initial Newtonian molecular dynamics simulation is performed, followed by a substitution process to embed molecular quantum vibrational wave functions into the trajectory. The instantaneous vibrational frequency shift at each time step is calculated using the Rayleigh-Schrödinger perturbation theory, where the perturbation operator is the difference in the vibrational potential between the reference chromophore and the perturbed chromophore in the environment. Semi-classical statistical mechanics is employed to obtain the spectral lineshape function. We validated our method using HCOOH·nH2O (n = 1-2) clusters and HCOOH aqueous solution as examples. The QVP method can be employed for rapid prediction of the vibrational spectrum of a specific mode in solution.

Genotypic diversity and antifungal susceptibility of Scedosporium species from clinical settings in China.

BACKGROUND: Scedosporium species have drawn significant interest as inhabitants of polluted soil and water and as cause of high mortality in near-drowning patients. So far, most cases have been reported from Europe and Australia, while knowledge on their prevalence and genotypic diversity from Asia is scant. OBJECTIVES: To increase the knowledge of the genetic diversity and in vitro antifungal susceptibility of Scedosporium species involved in human infections from China. METHODS: Here, we applied the ISHAM-MLST consensus scheme for molecular typing of Scedosporium species and revealed both high species diversity and high genotypic diversity among 45 Chinese clinical Scedosporium isolates. RESULTS: Among the five species, Scedosporium boydii (n = 22) was the most common, followed by S. apiospermum (n = 18), S. aurantiacum (n = 4) and S. dehoogii (n = 1). S. aurantiacum was reported for the first time from clinical samples in China. The predominant sequence types (STs) were ST17 in S. apiospermum, ST4 in S. boydii and ST92 in S. aurantiacum, including four novel STs (ST40, ST41, ST42 and ST43) in S. apiospermum. Based on the CLSI-M38 A2 criterion, voriconazole was the only antifungal compound with low MIC values (MIC90 ≤ 1 µg/ml) for all Scedosporium isolates in our study. CONCLUSIONS: The genetic diversity of clinical isolates of Scedosporium species from China is extremely high, with S. boydii being predominant and S. aurantiacum being firstly reported here. VOR was the only antifungal compound with low MIC values for all Scedosporium isolates in our study, which should be recommended as the firstline antifungal treatment against scedosporiosis in China.

Application of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Benign and Malignant Subpleural Pulmonary Lesions.

OBJECTIVE: To explore the clinical value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of benign and malignant subpleural pulmonary lesions (SPLs). METHODS: Among 959 patients with SPLs who were scheduled to undergo ultrasound-guided puncture in our department between January 2019 and June 2019, 506 patients were included and their B-mode ultrasound and CEUS features, including the lesion's location, size, margin, echo, perfusion pattern of ultrasound contrast agent, degree of enhancement, homogeneity, vascular signs, and necrosis, were retrospectively investigated. All malignant cases were diagnosed by pathology, while benign cases were diagnosed by two respiratory physicians after comprehensive analysis of pathology, etiology, imaging, and clinical symptoms. Statistical differences in these features between the benign and malignant groups were then analyzed. RESULTS: There were 506 cases in this study, including 219 benign cases and 287 malignant cases. Among them, 351 were males and 155 were females, with an average age of 59 ± 16 years. There were statistically significant differences between benign and malignant groups in the perfusion pattern, the degree of enhancement, and vascular signs. The features of the malignant group included local-to-whole perfusion pattern, hypo-enhancement, and curly hair sign, while those of the benign group included a centrifugal perfusion pattern, iso-enhancement and hyper-enhancement, and dendritic sign. There was no statistically significant difference between the two groups in homogeneity and necrosis. CONCLUSIONS: CEUS enhancement mode is different between benign and malignant SPLs, which can provide supplementary information for the differential diagnosis of SPLs in the existing imaging diagnosis.

The Accuracy of Semi-Empirical Quantum Chemistry Methods on Soot Formation Simulation.

Soot molecules are hazardous compounds threatening human health. Computational chemistry provides efficient tools for studying them. However, accurate quantum chemistry calculation is costly for the simulation of large-size soot molecules and high-throughput calculations. Semi-empirical (SE) quantum chemistry methods are optional choices for balancing computational costs. In this work, we validated the performances of several widely used SE methods in the description of soot formation. Our benchmark study focuses on, but is not limited to, the validation of the performances of SE methods on reactive and non-reactive MD trajectory calculations. We also examined the accuracy of SE methods of predicting soot precursor structures and energy profiles along intrinsic reaction coordinate(s) (IRC). Finally, we discussed the spin density predicted by SE methods. The SE methods validated include AM1, PM6, PM7, GFN2-xTB, DFTB2, with or without spin-polarization, and DFTB3. We found that the shape of MD trajectory profiles, the relative energy, and molecular structures predicted by SE methods are qualitatively correct. We suggest that SE methods can be used in massive reaction soot formation event sampling and primary reaction mechanism generation. Yet, they cannot be used to provide quantitatively accurate data, such as thermodynamic and reaction kinetics ones.

US Contrast Agent Arrival Time Difference Ratio for Benign versus Malignant Subpleural Pulmonary Lesions.

Background US has proven valuable in the diagnosis of subpleural pulmonary lesions (SPLs); however, existing US indicators have limitations. Purpose To propose and validate a revised contrast-enhanced (CE) US indicator for differential diagnosis of benign and malignant SPLs and to compare its performance with existing CE US diagnostic criteria. Materials and Methods This prospective study (Chinese clinical trial registry, ChiCTR1800019828) enrolled patients with SPLs between May 2019 and August 2020. They were divided into a developmental cohort (DC) and a validation cohort (VC). In the DC, the optimal indicator was selected from five CE US indicators. In the VC, the selected indicator was compared with existing CE US diagnostic criteria using the area under the receiver operating characteristic curve (AUC). Pathologic analysis, microbial evidence, and clinical follow-up were used as reference standards for all SPLs. Results A total of 902 participants (DC, 424 participants; VC, 478 participants) with SPLs (mean age, 56 years ± 17; 593 men) were evaluated. The arrival time (AT) difference ratio proved to be the optimal indicator to distinguish benign from malignant SPLs. In the overall (regardless of lesion size), large (vertical diameter >3 cm), and small (vertical diameter ≤3 cm) lesion groups, the cutoff values of the AT difference ratio were 43%, 42%, and 50% and the AUCs obtained from the VC were 0.91 (95% CI: 0.88, 0.93), 0.97 (95% CI: 0.94, 0.98), and 0.77 (95% CI: 0.71, 0.83) respectively, which were higher than those of lesion-lung AT difference greater than 2.5 seconds (0.81 [P < .001], 0.85 [P < .001], and 0.7 [P = .005], respectively), lesion AT greater than 7.5 seconds (0.65 [P < .001], 0.64 [P < .001], and 0.63 [P < .001], respectively), and lesion AT greater than 10 seconds (0.67 [P < .001], 0.68 [P < .001], and 0.64 [P < .001] respectively). Conclusion The US contrast agent arrival time difference ratio enables better differentiation of benign and malignant subpleural lesions when compared with existing diagnostic criteria. Online supplemental material is available for this article. Published under a CC BY 4.0 license.

Clinicopathological Analysis of Acquired Melanocytic Nevi and a Preliminary Study on the Possible Origin of Nevus Cells.

BACKGROUND: The pathogenesis of acquired melanocytic nevi (AMN) is still unclear, and the origin of nevus cells has not been clarified. OBJECTIVE: To analyze the clinical features and pathological types of AMN and identify the possible origin of nevus cells. METHODS: A retrospective study of 2929 cases of AMN was conducted, and 96 specimens of intradermal and junctional nevi were selected. Immunohistochemical assays were performed to detect the expression of basement membrane component receptor DDR-1 and the molecular markers on epidermal melanocytes, dermal stem cells (DSCs), and hair follicle stem cells. RESULTS: Junctional nevi and compound nevi were prone to occur on glabrous skin, such as the palms, soles, and vulva, and on the extremities in children, whereas intradermal nevi tended to develop on the trunk, head, and face of adults. The immunohistochemical data revealed that both junctional nevi and intradermal nevi expressed the epidermal melanocyte surface markers E-cadherin, DDR-1, and integrin α6 and the DSC molecular markers NGFRp-75 and nestin. CD34 was expressed only in junctional nevi, whereas K19 was not expressed in any type of melanocytic nevi. There was no significant difference in molecular expression at different sites or in different ages of onset. Nestin expression was markedly stronger in the intradermal nevi than in the junctional nevi, but there was no difference between the superficial and deep nevus cell nests of intradermal nevi. CONCLUSION: AMN may have a multicellular origin that commonly follows the mode of Abtropfung. Furthermore, DSCs may partly or independently participate in the formation of nevus cells.

The synergistic anti-tumor effect of schisandrin B and apatinib.

The synergistic anti-tumor effect of schisandrin B (Sch.B) and apatinib was investigated in vitro. The CCK-8 assay revealed that Sch.B enhanced the inhibition of apatinib on cell proliferation by arresting cell cycle in G0/G1 phase. Sch.B also potentiated the suppression of apatinib on cell migration and invasion, by means of wound-healing and transwell invasion assay. Flow cytometry results showed that Sch.B enhanced apoptosis induced by apatinib. The results were confirmed by western blot analysis of the proteins MMP-9, and Bax caspase-9, and -12. These results suggest that combining apatinib and Sch.B is an effective therapeutic strategy for preventing GC progression. [Formula: see text].

Retrospective comparison of stereotactic body radiotherapy versus intensity-modulated radiotherapy for stage III ultra-central squamous non-small-cell lung cancer.

Aim: To analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) versus intensity-modulated radiotherapy (IMRT) in stage III patients with ultra-central squamous non-small-cell lung cancer (sqNSCLC). Methods: Forty-four stage III patients with ultra-central sqNSCLC receiving SBRT (n = 15) or IMRT (n = 29) between December 2014 and August 2017 were reviewed. Results: At a median follow-up of 16.5 months, the 1-year local control rate of SBRT and IMRT was 60.8 and 37.5%, respectively (p = 0.23); the median overall survival was 17 versus 18 months (p = 0.48); ≥3 grade toxicity was 20 versus 24.1% (p = 0.83). Conclusion: SBRT is effective and patient friendly for stage III patients with ultra-central sqNSCLC. Toxicity might be tolerable with a moderate dose five to six fraction regimen. However, more prospective studies are warranted.

A novel murine antibody and an open sandwich immunoassay for the detection of clenbuterol.

Clenbuterol (CLEN) is a sympathomimetic amine used as a decongestant and bronchodilator while treating breathing disorders. It is also used in food-producing animals as it improves the rate of red meat production. However, it is prohibited in many countries nowadays due to human health and safety concerns. Unfortunately, the illegal use of CLEN is still rampant. Thus, monitoring it in food and livestock is important. Here, we report a novel murine antibody and an open sandwich enzyme linked immunosorbent assay (OS-ELISA) to detect CLEN based on antigen-antibody reactions. The genes of antibody variable regions in mice immunized with CLEN conjugated with bovine serum albumin were cloned into a phagemid (pDong1/Fab) to construct a phage-display antibody library, from which a novel antibody, A12, was selected. Then, an OS-ELISA was developed to detect CLEN using separated variable regions of the A12 antibody. The limit of detection of the assay was found to be 8 ng/mL, which was useful for monitoring CLEN usage.

Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats.

Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC-MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t1/2, mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC0-12h), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC0-12h of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t1/2. However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV.

Low BMI is correlated with increased TGF-ß and IL-10 mRNA levels in the peripheral blood of breast cancer patients.

Transforming growth factor-ß (TGF-ß), interleukin-10 (IL-10), and forkhead box P3 (Foxp3) have important roles in breast cancer development. Previous studies confirmed a correlation between these immune molecules and tumor characteristics, but their association with nutritional status in breast cancer is largely unknown. We aimed to investigate the association between body mass index (BMI), hemoglobin, total protein, albumin, globulin (GLB), albumin/GLB ratio (AGR), pre-albumin, prognostic nutritional index, and TGF-ß, IL-10, and Foxp3 mRNA expression in patients with breast cancer. Quantitative real-time PCR was used to detect the mRNA expression of TGF-ß, IL-10, and Foxp3 in the peripheral blood of 107 patients with breast cancer and 21 healthy controls. We found that TGF-ß mRNA levels were 2.6-fold, 3.2-fold, and 2.3-fold higher in patients with low BMI (<23), low AGR, and high GLB, respectively, than in their counterparts (P < 0.05). In addition, IL-10 mRNA expression levels in patients with normal BMI (<23) were 2.8-fold and 3.5-fold higher than in those who were overweight (23≤ BMI <25) and obese (BMI ≥ 25), respectively (P < 0.05). In addition, TGF-ß, IL-10, and Foxp3 mRNA levels were significantly higher in patients with breast cancer than in healthy controls (P < 0.05). In summary, our results suggest that nutritional status, especially BMI, may strongly affect systematic immune function in patients with breast cancer. © 2018 IUBMB Life, 70(3):237-245, 2018.

Acid Ceramidase Deficiency in Mice Results in a Broad Range of Central Nervous System Abnormalities.

Farber disease is a rare autosomal recessive disorder caused by acid ceramidase deficiency that usually presents as early-onset progressive visceral and neurologic disease. To understand the neurologic abnormality, we investigated behavioral, biochemical, and cellular abnormalities in the central nervous system of Asah1P361R/P361R mice, which serve as a model of Farber disease. Behaviorally, the mutant mice had reduced voluntary locomotion and exploration, increased thigmotaxis, abnormal spectra of basic behavioral activities, impaired muscle grip strength, and defects in motor coordination. A few mutant mice developed hydrocephalus. Mass spectrometry revealed elevations of ceramides, hydroxy-ceramides, dihydroceramides, sphingosine, dihexosylceramides, and monosialodihexosylganglioside in the brain. The highest accumulation was in hydroxy-ceramides. Storage compound distribution was analyzed by mass spectrometry imaging and morphologic analyses and revealed involvement of a wide range of central nervous system cell types (eg, neurons, endothelial cells, and choroid plexus cells), most notably microglia and/or macrophages. Coalescing and mostly perivascular granuloma-like accumulations of storage-laden CD68+ microglia and/or macrophages were seen as early as 3 weeks of age and located preferentially in white matter, periventricular zones, and meninges. Neurodegeneration was also evident in specific cerebral areas in late disease. Overall, our central nervous system studies in Asah1P361R/P361R mice substantially extend the understanding of human Farber disease and suggest that this model can be used to advance therapeutic approaches for this currently untreatable disorder.

An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats.

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

[Clinicopathologic characteristics of basal cell carcinoma of the prostate: analysis of 5 cases and review of the literature].

OBJECTIVE: To investigate the histogenesis, clinicopathologic characteristics, pathologic diagnosis, differential diagnosis, treatment and prognosis of basal cell carcinoma of the Prostate (BCCP). METHODS: We conducted clinicopathologic analysis on the manifestations of 5 cases of BCCP by HE staining and immunohistochemistry and reviewed relevant literature. RESULTS: Microscopically, the tumor cells were small in volume with ovoid karyomegaly and mitosis, some arranged like a solid nest or with a cribriform appearance. The tumors displayed an invasive growth, with positive expressions of 34betaE12, P63 and Cytokeratin 14, and negative expressions of PSA and P504s. No recurrence and metastasis were found in these patients during over 12 months of follow-up after surgery. CONCLUSION: BCCP is a rare neoplasm different from prostate adenocarcinoma. Immunohistochemistry is indispensable in distinguishing this tumor from other types of prostatic carcinoma. Its biological behavior remains to be further studied. The best treatment option may be radical surgery combined with chemo-radiotherapy at the present time.

Rethinking development and major research plans of Industrial Internet in China.

This paper gives a definition of the Industrial Internet and expounds on the academic connotation of the future Industrial Internet. From this foundation, we outline the development and current status of the Industrial Internet in China and globally. Moreover, we detail the avant-garde paradigms encompassed within the National Natural Science Foundation of China (NSFC)'s "Future Industrial Internet Fundamental Theory and Key Technologies" research plan and its corresponding management strategies. This research initiative endeavors to enhance interdisciplinary collaborations, aiming for a synergistic alignment of industry, academia, research, and practical implementations. The primary focus of the research plan is on the pivotal scientific challenges inherent to the future industrial internet. It is poised to traverse the "first mile", encompassing foundational research and pioneering innovations specific to the industrial internet, and seamlessly bridges to the "last mile", ensuring the effective commercialization of scientific and technological breakthroughs into tangible industrial market applications. The anticipated contributions from this initiative are projected to solidify both the theoretical and practical scaffolding essential for the cultivation of a globally competitive industrial internet infrastructure in China.

Machine Learning Approach Based on a Range-Corrected Deep Potential Model for Efficient Vibrational Frequency Computation.

As an ensemble average result, vibrational spectrum simulation can be time-consuming with high accuracy methods. We present a machine learning approach based on the range-corrected deep potential (DPRc) model to improve the computing efficiency. The DPRc method divides the system into "probe region" and "solvent region"; "solvent-solvent" interactions are not counted in the neural network. We applied the approach to two systems: formic acid C═O stretching and MeCN C≡N stretching vibrational frequency shifts in water. All data sets were prepared using the quantum vibration perturbation approach. Effects of different region divisions, one-body correction, cut range, and training data size were tested. The model with a single-molecule "probe region" showed stable accuracy; it ran roughly 10 times faster than regular deep potential and reduced the training time by about four. The approach is efficient, easy to apply, and extendable to calculating various spectra.

A Comprehensive Study of 3-D Vision-Based Robot Manipulation.

Robot manipulation, for example, pick-and-place manipulation, is broadly used for intelligent manufacturing with industrial robots, ocean engineering with underwater robots, service robots, or even healthcare with medical robots. Most traditional robot manipulations adopt 2-D vision systems with plane hypotheses and can only generate 3-DOF (degrees of freedom) pose accordingly. To mimic human intelligence and endow the robot with more flexible working capabilities, 3-D vision-based robot manipulation has been studied. However, this task is still challenging in the open world especially for general object recognition and pose estimation with occlusion in cluttered backgrounds and human-like flexible manipulation. In this article, we propose a comprehensive analysis of recent progress about the 3-D vision for robot manipulation, including 3-D data acquisition and representation, robot-vision calibration, 3-D object detection/recognition, 6-DOF pose estimation, grasping estimation, and motion planning. We then present some public datasets, evaluation criteria, comparisons, and challenges. Finally, the related application domains of robot manipulation are given, and some future directions and open problems are studied as well.

Sonocatalytic Optimization of Titanium-Based Therapeutic Nanomedicine.

Recent considerable technological advances in ultrasound-based treatment modality provides a magnificent prospect for scientific communities to conquer the related diseases, which is featured with remarkable tissue penetration, non-invasive and non-thermal characteristics. As one of the critical elements that influences treatment outcomes, titanium (Ti)-based sonosensitizers with distinct physicochemical properties and exceptional sonodynamic efficiency have been applied extensively in the field of nanomedical applications. To date, a myriad of methodologies has been designed to manipulate the sonodynamic performance of titanium-involved nanomedicine and further enhance the productivity of reactive oxygen species for disease treatments. In this comprehensive review, the sonocatalytic optimization of diversified Ti-based nanoplatforms, including defect engineering, plasmon resonance modulation, heterojunction, modulating tumor microenvironment, as well as the development of synergistic therapeutic modalities is mainly focused. The state-of-the-art Ti-based nanoplatforms ranging from preparation process to the extensive medical applications are summarized and highlighted, with the goal of elaborating on future research prospects and providing a perspective on the bench-to-beside translation of these sonocatalytic optimization tactics. Furthermore, to spur further technological advancements in nanomedicine, the difficulties currently faced and the direction of sonocatalytic optimization of Ti-based therapeutic nanomedicine are proposed and outlooked.