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Abstract Background This study aimed to investigate clinical features and treatment strategies for intracranial aneurysm (IA) associated with pituitary adenoma (PA). Methods We enrolled patients with lesions in the sellar region and age-matched general population who were confirmed with IA from two hospitals. Four types of treatment strategies were performed, which included Type I (both IA and PA were treated with surgery), Type II (IA was treated with surgery and PA was performed by non-surgical treatment), Type III (PA was performed with surgery and observation was available for IA) and Type IV (both IA and PA were performed with non-surgical treatment). Results The incidence of IA was 2.2% in the general population, 6.1% in patients with PA, 4.3% in patients with Rathke cleft cyst, 2.8% in patients with meningioma and none were found with IA in patients with craniopharyngioma. Age over 50 years (OR, 2.69; 95% CI, 1.20–6.04; P = 0.016), female (OR, 3.83, P = 0.003), and invasive tumor (OR, 3.26, P = 0.003) were associated with a higher incidence of IA in patients with PA. During the mean follow-up of 49.2 months, no patients experienced stroke, and recurrence of aneurysms and aneurysms treated with observation were stable. Of four patients with recurrence of PA, three patients were treated for type I and one patient for type III. Conclusions Preoperative evaluation for aneurysm screening is necessary due to the high incidence of IA in PA patients. Our current treatment strategies may provide a benefit for these patients.

The use of wheeled mobile robots (MRs) with symmetrical structure in engineering is rapidly increasing, with applications in various fields, such as industry, agriculture, forestry, healthcare, mining, rehabilitation, search and rescue, household tasks, remote locations, and entertainment. As MRs become more common, researchers are focusing on developing better ways to model and control these robots to improve their performance and adaptability. The main challenges in this area include uncertain dynamics, non-holonomic constraints, and various perturbations, which complicate the design of the control system. This paper presents a new predictive control scheme for MRs that is independent of the dynamics and the robot’s working environment. A Type-3 fuzzy logic system is developed to identify the MR dynamics online. The designed predictive scheme improves accuracy and speeds up convergence, while also addressing uncertainties and considering constraints on control input. Additionally, a chaotic-based system is proposed for secure path planning, generating a complex and unpredictable reference trajectory that is useful for patrol MR applications. The effectiveness of the suggested controller is demonstrated through simulations and experiments.

Summary: Background: Highly pathogenic respiratory RNA viruses such as SARS-CoV-2 and its associated syndrome COVID-19 pose a tremendous threat to the global public health. Innate immune responses to SARS-CoV-2 depend mainly upon the NF-κB-mediated inflammation. Identifying unknown host factors driving the NF-κB activation and inflammation is crucial for the development of immune intervention strategies. Methods: Published single-cell RNA sequencing (scRNA-seq) data was used to analyze the differential transcriptome profiles of bronchoalveolar lavage (BAL) cells between healthy individuals (n = 27) and patients with severe COVID-19 (n = 21), as well as the differential transcriptome profiles of peripheral blood mononuclear cells (PBMCs) between healthy individuals (n = 22) and severely ill patients with COVID-19 (n = 45) or influenza (n = 16). Loss-of-function and gain-of-function assays were performed in diverse viruses-infected cells and male mice models to identify the role of TOMM34 in antiviral innate immunity. Findings: TOMM34, together with a list of genes encoding pro-inflammatory cytokines and antiviral immune proteins, was transcriptionally upregulated in circulating monocytes, lung epithelium and innate immune cells from individuals with severe COVID-19 or influenza. Deficiency of TOMM34/Tomm34 significantly impaired the type I interferon responses and NF-κB-mediated inflammation in various human/murine cell lines, murine bone marrow-derived macrophages (BMDMs) and in vivo. Mechanistically, TOMM34 recruits TRAF6 to facilitate the K63-linked polyubiquitination of NEMO upon viral infection, thus promoting the downstream NF-κB activation. Interpretation: In this study, viral induction of TOMM34 is positively correlated with the hyperinflammation in severely ill patients with COVID-19 and influenza. Our findings also highlight the physiological role of TOMM34 in the innate antiviral signallings. Funding: A full list of funding sources can be found in the acknowledgements section.

Background Cancer has surpassed infectious diseases and heart ailments, taking the top spot in the disease hierarchy. Cervical cancer is a significant concern for women due to high incidence and mortality rates, linked to the human papillomavirus (HPV). HPV infection leads to precancerous lesions progressing to cervical cancer. The cervix’s external os, near the vagina, hosts various microorganisms. Evidence points to the link between vaginal microbiota and HPV-induced cervical cancer. Cervical cancer onset aligns with an imbalanced Th1/Th2 immune response, but the role of vaginal microbiota in modulating this imbalance is unclear. Methods In this study, we collected vaginal samples from 99 HPV-infected patients across varying degrees of lesions, alongside control groups. These samples underwent bacterial DNA sequencing. Additionally, we employed Elisa kits to quantify the protein expression levels of Th1/Th2 cytokines IL2, IL12, IL5, IL13, and TNFa within the centrifuged supernatant of vaginal-cervical secretions from diverse research subjects. Subsequently, correlation analyses were conducted between inflammatory factors and vaginal microbiota. Results Our findings highlighted a correlation between decreased Lactobacillus and increased Gardenerella presence with HPV-induced cervical cancer. Functionally, our predictive analysis revealed the predominant enrichment of the ABC transporter within the vaginal microbiota of cervical cancer patients. Notably, these microbiota alterations exhibited correlations with the production of Th1/Th2 cytokines, which are intimately tied to tumor immunity. Conclusions This study suggests the potential involvement of vaginal microbiota in the progression of HPV-induced cervical cancer through Th1/Th2 cytokine regulation. This novel insight offers a fresh perspective for early cervical cancer diagnosis and future prevention strategies.

BackgroundCardio-Facio-Cutaneous syndrome (CFCS) is a rare autosomal dominant genetic disorder primarily caused by BRAF gene mutations, posing diagnostic challenges due to its multifaceted clinical presentation.ObjectiveTo elucidate the clinical characteristics of pediatric CFCS patients, expanding the phenotypic spectrum to enhance early diagnostic capabilities, while also presenting the relationship between genotye and corresponding phenotype severity.MethodsFrom January 2015 to March 2022, four children diagnosed with CFCS in Children's Hospital of Chongqing Medical University were included for analysis. Whole exome sequencing (WES) was conducted to identify the types and locations of possible gene mutations. Neurological development was assessed using electroencephalography (EEG), magnetic resonance imaging (MRI) and Gesell developmental evaluation.ResultsAll four CFCS patients exhibited de novo BRAF gene mutations, manifesting with cardiac malformations, distinctive facial features, skin and hair changes, and neurological abnormalities. WES revealed that the specific BRAF mutations were closely linked to their clinical severity. Three patients displayed milder symptoms (case 1–3, genotype I or II), demonstrating stability or slight improvement, whereas one patient (case 4, genotype III) suffered from a severe phenotype characterized by profound neurological and digestive system impairments, leading to a significantly reduced quality of life and a grim prognosis.ConclusionIn CFCS patients, severe developmental delay and seizures are predominant neurological features, possibly accompanied by continuous spike-and-wave during sleep (CSWS) and severe sleep disturbances. CFCS generally carries a poor prognosis, underscoring the importance of disease awareness and early genetic testing.

Abstract With the annual increases in the morbidity and mortality rates of tumors, the use of biomarkers for early diagnosis and real-time monitoring of tumor cells is of great importance. Biomarkers used for tumor cell detection in body fluids include circulating tumor cells, nucleic acids, protein markers, and extracellular vesicles. Among them, circulating tumor cells, circulating tumor DNA, and exosomes have high potential for the prediction, diagnosis, and prognosis of tumor diseases due to the large amount of valuable information on tumor characteristics and evolution; in addition, in situ monitoring of telomerase and miRNA in living cells has been the topic of extensive research to understand tumor development in real time. Various techniques, such as enzyme-linked immunosorbent assays, immunoblotting, and mass spectrometry, have been widely used for the detection of these markers. Among them, the detection of tumor cell markers in body fluids based on electrochemical biosensors and fluorescence signal analysis is highly preferred because of its high sensitivity, rapid detection and portable operation. Herein, we summarize recent research progress in the detection of tumor cell biomarkers in body fluids using electrochemical and fluorescence biosensors, outline the current research status of in situ fluorescence monitoring and the analysis of tumor markers in living cells, and discuss the technical challenges for their practical clinical application to provide a reference for the development of new tumor marker detection methods.

Background & Aims: Cognitive dysfunction is an increasingly recognised manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanistic link remains unclear. The aim of this study was to investigate the hypothesis that experimental MASLD leads to cognitive dysfunction via systemic inflammation and neuroinflammation. Methods: Twenty male Sprague Dawley rats were randomised to a high-fat high-cholesterol (HFHC) diet to induce MASLD, or a standard diet (n = 10/group), for 16 weeks. Assessments included: MASLD severity (histology), neurobehaviour, inflammation (liver, plasma and cerebrospinal fluid), brain microglia and astrocyte activation, and synaptic density. Results: The HFHC diet induced MASLD with extensive steatosis and lobular inflammation without fibrosis. Several plasma cytokines were elevated (CXCL1, IL-6, IL-17, MIP-1α, MCP-1, IL-10; all p

Abstract Postoperative cerebral ischemic complication is the most common complication of revascularization surgery for patients with moyamoya disease (MMD). This retrospective study was conducted on 63 patients with ischemic MMD. Postoperative ischemia occurred in 15 of the 70 revascularization operations performed for patients after surgical revascularization, translating to an incidence of 21.4%. Univariate analysis revealed that onset infarction (p = 0.015), posterior cerebral artery involvement (p = 0.039), strict perioperative management (p = 0.001), interval time between transient ischemic attack (TIA) or infarction presentation and operation (p = 0.002) and preoperatively cerebral infarction extent score (CIES) (p = 0.002) were significantly associated with postoperative cerebral ischemia. Multivariate analysis revealed that strict perioperative management (OR = 0.163; p = 0.047), and preoperatively CIES (OR = 1.505; p = 0.006) were independently associated with postoperative cerebral ischemia-related complications. After comprehensive improvement of perioperative management protocol, the incidence of symptomatic infarction declined to 7.4% (4 out of 54). Analysis of the area under the receiver operating characteristic curve (AUROC) indicated CIES was a predictor for both postoperative ischemia and high follow-up modified Rankin Scale scores. In summary, strict perioperative management and CIES were identified as independent risk factors for postoperative ischemic complications in ischemic MMD, demonstrating that comprehensive and individualized perioperative management improve postoperative outcomes in patients with MMD. Furthermore, application of CIES to evaluate pre-existing cerebral infarction can improve the management of patients.

The development of functional materials for catalysis applications is a continuing issue, particularly in aqueous-phase catalysis. The creation of inexpensive catalysts with improved catalytic activity is still difficult. In this study, the hollow structured Cu nanospheres decorated on the reduced graphene oxide sheets (h-CuNS/rGO) nanocomposites were successfully prepared and applied in the catalytic reduction of p-nitrophenol (p-NP) in water using sodium borohydride as the reducing agent to obtain industrially useful p-aminophenol (p-AP) within a short time. The structure and morphology of h-CuNS/rGO were studied in order to get a full knowledge of the mechanism underlying the creation of its distinctive hollow structure. In the reduction of p-NP, the h-CuNS/rGO demonstrated significant catalytic activity and reusability. The catalytic hydrogenation mechanism on the surface of h-CuNS/rGO was shown to exhibit a synergistic effect between the catalytic h-CuNS and the supporting rGO. The hollow structure, abundant oxygen vacancies as well as the supported rGO worked together to enhance the catalytic activity during p-NP reduction. Therefore, this work proposes a strategy for the simple synthesis of nanocatalyst with high catalytic performance, which endows the potential applications including catalysis.

Pressure hulls play an important role in deep-sea underwater vehicles. However, in the ultra-high pressure environment, a highly destructive phenomenon could occur to them which is called implosion. To study the characteristics of the flow field of the underwater implosion of hollow ceramic pressure hulls, the compressible multiphase flow theory, direct numerical simulation, and adaptive mesh refinement are used to numerically simulate the underwater implosion of a single ceramic pressure hull and multiple linearly arranged ceramic pressure hulls. Firstly, the feasibility of the numerical simulation method is verified. Then, the results of the flow field of the underwater implosion of hollow ceramic pressure hulls in 11000 m depth is analyzed. There are the compression-rebound processes of the internal air cavity in the implosion. In the rebound stage, a shock wave that is several times the ambient pressure is generated outside the pressure hull, and the propagation speed is close to the speed of sound. The pressure peak of the shock wave has a negative exponential power function relationship with the distance to the center of the sphere. Finally, it is found that the obvious superimposed effect between spheres exists in the chain-reaction implosion which enhances the implosion shock wave.

Summary: Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and leads to progressive motor dysfunction. While studies have focused on the basal ganglia network, recent evidence suggests neuronal systems outside the basal ganglia are also related to PD pathogenesis. The zona incerta (ZI) is a predominantly inhibitory subthalamic region for global behavioral modulation. This study investigates the role of GABAergic neurons in the ZI in a mouse model of 6-hydroxydopamine (6-OHDA)-induced PD. First, we found a decrease in GABA-positive neurons in the ZI, and then the mice used chemogenetic/optogenetic stimulation to activate or inhibit GABAergic neurons. The motor performance of PD mice was significantly improved by chemogenetic/optogenetic activation of GABAergic neurons, and repeated chemogenetic activation of ZI GABAergic neurons increased the dopamine content in the striatum. Our work identifies the role of ZI GABAergic neurons in regulating motor behaviors in 6-OHDA-lesioned PD model mice.

Background The anti-Müllerian hormone (AMH) is gaining attention as a key factor in determining ovarian reserve and polycystic ovarian syndrome, and its clinical applications are becoming more widespread worldwide. Objective To identify the most accurate formula for converting AMH assay results between different platforms, so that the developed AMH converter can be used to reduce the need for multiple AMH tests at different hospitals. Methods Assuming that the Beckman Access, Kangrun, and Roche Elecsys® AMH assays fit a linear relationship from the lowest to the highest concentration (a global relationship), we used Passing–Bablok regression to determine the conversion equation between each two assays. When the relationship between two AMH assays was a local one, spline regression was used. Bland–Altman plots were drawn to check systemic bias and heterogeneity of variance across different ranges of values. The fitting effects of the models were evaluated using the squared coefficient of determination (r2), adjusted r2, root mean square error (RMSE), Akaike information criterion (AIC), and corrected AIC. Results The coefficient of variance for multiple controls in the Kangrun, Roche, and Beckman assays was lower than 5%, and the bias of multiple controls was lower than 7%. A global linear relationship was observed between the Kangrun and Roche assays, with the intercept being zero, for which Passing-Bablok regression was employed for data conversion between the two platforms. For the other two pairs of platforms, i.e., Roche and Kangrun or Beckman and Kangrun, spline regression was applied, with the intercepts not including zero. The six corresponding formulas were developed into an online AMH converter (http://121.43.113.123:8006/). Conclusion This is the first time Passing–Bablok plus spline regression has been used to convert AMH concentrations from one assay to another. The formulas have been developed into an online tool, which makes them convenient to use in practical applications.

Crystallization selectivity is an important principle in polymorph control. Ribavirin Form I, Form II, DMSO solvate, and amorphous ribavirin are prepared, and the short-range order similarities between these solid forms and ribavirin aqueous solution and DMSO solution are compared via mid-frequency Raman difference spectra (MFRDS). The crystallization process from amorphous ribavirin to Form I and from solution to amorphous phase is explained. Reasons for the difficulty in preparing the DMSO solvate are proposed. The rationale provided for the crystallization selectivity provides a foundation for the synthesis of metastable phases with a robust and convenient method.

Guanine crystals with unique optical properties in organisms have been extensively studied and the biomineralization principles of guanine are being established. This review summarizes the fundamental physicochemical properties (solubility, tautomers, bands, and refractivity), polymorphs, morphology of biological and synthetic forms, and the reported biomineralization principles of guanine (selective recrystallization of amorphous precursor, preassembled scaffolds, additives, twinning, hypoxanthine doping, fluorescence, and assembly). The biomineralization principles of guanine will be helpful for the synthesis of guanine crystals with excellent properties and the design of functional organic materials for drugs, dyes, organic semiconductors, etc.

Non-holonomic wheeled robots (NWR) comprise a type of robotic system; they use wheels for movement and offer several advantages over other types. They are efficient, highly, and maneuverable, making them ideal for factory automation, logistics, transportation, and healthcare. The control of this type of robot is complicated, due to the complexity of modeling, asymmetrical non-holonomic constraints, and unknown perturbations in various applications. Therefore, in this study, a novel type-3 (T3) fuzzy logic system (FLS)-based controller is developed for NWRs. T3-FLSs are employed for modeling, and the modeling errors are considered in stability analysis based on the symmetric Lyapunov function. An observer is designed to detect the error, and its effect is eliminated by a developed terminal sliding mode controller (SMC). The designed technique is used to control a case-study NWR, and the results demonstrate the good accuracy of the developed scheme under non-holonomic constraints, unknown dynamics, and nonlinear disturbances.

Abstract Background Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na+/H+ exchanger-1 (NHE1) in reactive astrocytes causes astrocytic hypertrophy and swelling. In this study, we examined the role of NHE1 protein in astrogliosis, white matter demyelination, and cognitive function in a murine CCH model with bilateral carotid artery stenosis (BCAS). Methods Sham, BCAS, or BCAS mice receiving vehicle or a selective NHE1 inhibitor HOE642 were monitored for changes of the regional cerebral blood flow and behavioral performance for 28 days. Ex vivo MRI-DTI was subsequently conducted to detect brain injury and demyelination. Astrogliosis and demyelination were further examined by immunofluorescence staining. Astrocytic transcriptional profiles were analyzed with bulk RNA-sequencing and RT-qPCR. Results Chronic cerebral blood flow reduction and spatial working memory deficits were detected in the BCAS mice, along with significantly reduced mean fractional anisotropy (FA) values in the corpus callosum, external capsule, and hippocampus in MRI DTI analysis. Compared with the sham control mice, the BCAS mice displayed demyelination and axonal damage and increased GFAP+ astrocytes and Iba1+ microglia. Pharmacological inhibition of NHE1 protein with its inhibitor HOE642 prevented the BCAS-induced gliosis, damage of white matter tracts and hippocampus, and significantly improved cognitive performance. Transcriptome and immunostaining analysis further revealed that NHE1 inhibition specifically attenuated pro-inflammatory pathways and NADPH oxidase activation. Conclusion Our study demonstrates that NHE1 protein is involved in astrogliosis with pro-inflammatory transformation induced by CCH, and its blockade has potentials for reducing astrogliosis, demyelination, and cognitive impairment.

The fluorescent carbon dots (CDs) have found their extensive applications in sensing, bioimaging, and photoelectronic devices. In general terms, the synthesis of CDs is straight-forward, though their subsequent purification can be laborious. Therefore, there is a need for easier ways to generate solid CDs with a high conversion yield. Herein, we used collagen waste as a carbon source in producing solid CDs through a calcination procedure without additional chemical decomposition treatment of the raw material. Considering a mass of acid has destroyed the original protein macromolecules into the assembled structure with amino acids and peptide chains in the commercial extraction procedure of collagen product. The residual tissues were assembled with weak intermolecular interactions, which would easily undergo dehydration, polymerization, and carbonization during the heat treatment to produce solid CDs directly. The calcination parameters were surveyed to give the highest conversion yield at 78%, which occurred at 300°C for 2 h. N and S atomic doping CDs (N-CDs and S-CDs) were synthesized at a similar process except for immersion of the collagen waste in sulfuric acid or nitric acid in advance. Further experiments suggested the prepared CDs can serve as an excellent sensor platform for Fe3+ in an acid medium with high anti-interference. The cytotoxicity assays confirmed the biosafety and biocompatibility of the CDs, suggesting potential applications in bioimaging. This work provides a new avenue for preparing solid CDs with high conversion yield.

Epilepsy accounts for a significant proportion of the burden of neurological disorders. Neuroinflammation acting as the inflammatory response to epileptic seizures is characterized by aberrant regulation of inflammatory cells and molecules, and has been regarded as a key process in epilepsy where mTOR signaling serves as a pivotal modulator. Meanwhile, accumulating evidence has revealed that non-coding RNAs (ncRNAs) interfering with mTOR signaling are involved in neuroinflammation and therefore articipate in the development and progression of epilepsy. In this review, we highlight recent advances in the regulation of mTOR on neuroinflammatory cells and mediators, and feature the progresses of the interaction between ncRNAs and mTOR in epileptic neuroinflammation.

Quinone organic materials are promising electrodes for the next lithium-ion batteries (LIBs) owing to their versatile molecular designs, high theoretical capacity, flexibility, sustainability, and environmental friendliness. However, quinone organic electrode materials can easily dissolve in organic electrolytes during the cycling process, which leads to the decay of capacity and poor cycling stability. Here, two metal-organic frames (MOFs), one-dimensional (1D) linear structural anthraquinone-2,3-dicarboxylate zinc coordination polymer (ZnAQDC) and two-dimensional (2D) structural anthraquinone-2,3-dicarboxylate manganese coordination polymer (MnAQDC), are synthesized by using anthraquinone 2,3-dicarboxylic acid, zinc acetate, and manganese acetate in a simple hydrothermal reaction. The formed 1D and 2D structures facilitate the insertion and extraction of lithium ions in and from carbonyl groups of anthraquinone. When MnAQDC is used as cathodes for LIBs, MnAQDC electrodes show an initial discharge capacity of ~63 mAh g−1 at 50 mA g−1. After 200 cycles, the MnAQDC electrode still maintains the specific capacity of ~45 mA h g−1, which exhibits good cycle stability. the ZnAQDC electrode displays a initial discharge capacity of ~85 mA h g−1 at 50 mA g−1, and retains the specific capacity of ~40 mA h g−1 after 200 cycles, showing moderate cyclic performance. The lithium-inserted mechanism shows that lithium ions are inserted and extracted in and from the carbonyl groups, and the valences of the Zn and Mn ions in the two MOFs do not change, and coordination metals do not contribute capacities for the two MOFs electrodes. The strategy of designing and synthesizing MOFs with 1D and 2D structures provides guidance for suppressing the dissolution and improving the electrochemical performance of quinone electrode materials.

A key research topic in the field of robotics is the formation control of a group of robots in trajectory tracking problems. Using organized robots has many advantages over using them individually, such as efficient use of resources, increased reliability due to cooperation, and better resistance against defects. To achieve this, a controller is proposed that steers the leader robot and subsequent follower robots asymptotically to a reference trajectory. The basic controller is feedback linearization. To ensure stability against perturbations, a compensator based on type-3 fuzzy logic systems (T3-FLSs) and a data-driven control strategy is designed. The approach involves employing a finite number of open-loop data and using the model-based predictive controller (MPC) approach to acquire sufficient criteria for stability. An infinite-horizon function is minimized online, which allows the data-based control policy to be considered the optimal control method. The gains of the constrained data-based control signal are computed at each time step to enhance accuracy. Applying the data-based state feedback controller to the system yields positive and stable state trajectories with appropriate transient responses. The suggested data-driven compensator is guaranteed to handle constraints. A practical example is simulated to evaluate the proposed strategy.

Abstract Background In many cases, both the rupture rate of cerebral arteriovenous malformation (bAVM) in patients and the risk of endovascular or surgical treatment (when radiosurgery is not appropriate) are not low, it is important to assess the risk of rupture more cautiously before treatment. Based on the current high-risk predictors and clinical data, different sample sizes, sampling times and algorithms were used to build prediction models for the risk of hemorrhage in bAVM, and the accuracy and stability of the models were investigated. Our purpose was to remind researchers that there may be some pitfalls in developing similar prediction models. Methods The clinical data of 353 patients with bAVMs were collected. During the creation of prediction models for bAVM rupture, we changed the ratio of the training dataset to the test dataset, increased the number of sampling times, and built models for predicting bAVM rupture by the logistic regression (LR) algorithm and random forest (RF) algorithm. The area under the curve (AUC) was used to evaluate the predictive performances of those models. Results The performances of the prediction models built by both algorithms were not ideal (AUCs: 0.7 or less). The AUCs from the models built by the LR algorithm with different sample sizes were better than those built by the RF algorithm (0.70 vs 0.68, p 0.1). Conclusions Based on the current risk predictors, it may be difficult to build a stable and accurate prediction model for the hemorrhagic risk of bAVMs. Compared with sample size and algorithms, meaningful predictors are more important in establishing an accurate and stable prediction model.

In this paper, the main concepts of interval type-2 (IT2), generalized type-2 (GT2), and interval type-3 (IT3) fuzzy logic systems (FLSs) are mathematically and graphically studied. In representation approaches of fuzzy sets (FSs), the main differences between IT2, GT2, and IT3 fuzzy sets were investigated. For the first time, the simple Matlab Simulink and M-files by illustrative examples and symmetrical FSs are presented for the practical use of IT3-FLSs. The computations were simplified for the practical use of IT3-FLSs. By the use of various examples, such as online identification, offline time series modeling, and a robotic control system, the design of IT3-FLSs is elaborated. The required derivative equations are also presented to design the adaptation laws for the rule parameters easily in other learning schemes. Some simulation examples show that the designed M-files and Simulink work well and result in a good performance.

Abstract One-dimensional (1D) nanomaterials with specific architectures have received increasing attention for both scientific and technological interests for their applications in catalysis, sensing, and energy conversion, etc. However, the development of an operable and simple method for the fabrication of 1D nanostructures remains a challenge. In this work, we developed an “anion-regulated morphology” strategy, in which anions could regulate the dimensionally-restricted anisotropic growth of ZnO nanomaterials by adjusting the surface energy of different growth facets. ZnO 1D necklace-like nanostructures (NNS) could be prepared through a hydrothermal treatment of zinc acetate and urea mixture together with a subsequent calcination procedure at 400 °C. While replacing the acetate ions to nitrate, sulfate, and chlorion ions produced ZnO nanoflowers, nanosheets and hexagonal nanoplates, respectively. Density functional theory calculations were carried out to explain the mechanism behind the anions-regulating anisotropic crystal growth. The specified ZnO 1D NNS offered improved electron transport while the grain surface could supply enlarged specific surface area, thus providing advanced photocatalytic ability in the following photodegradation of methyl orange (MO). Among the four photocatalysts with different morphologies, ZnO 1D NNS, possessing the highest catalytic activity, degraded 57.29% MO in the photocatalytic reaction, which was 2 times, 10 times and 17 times higher than nanoflowers, nanosheets and hexagonal nanoplates, respectively. Our work provides new ideas for the construction and application of ZnO 1D nanomaterials.

Abstract Background Retinal degeneration is a leading cause of blindness in the world; its etiology is complex and involves genetic defects and stress-associated aging. In addition to gene therapies for known genetically defective retinal degeneration, cellular therapies have been widely explored for restoring vision in both preclinical animal models and clinical trials. Stem cells of distinct tissue sources and their derived lineages have been tested for treating retinal degeneration; most of them were reported to be effective to some extent in restoring/improving deteriorated vision. Whether this visual improvement is due to a functional integration of grafted cells to substitute for lost retinal neurons in recipients or due to their neuroprotective and neurotrophic effects to retain recipient functional neurons, or both, is still under debate. Methods We compared the results of subretinal transplantation of various somatic cell types, such as stem cells and differentiated cells, into RhoP23H/+ mice, a retinal degeneration model for human retinitis pigmentosa (RP) by evaluating their optokinetic response (OKR) and retinal histology. We identified some paracrine factors in the media that cultured cells secreted by western blotting (WB) and functionally evaluated the vascular endothelial growth factor Vegfa for its potential neurotrophic and neuroprotective effects on the neuroretina of model animals by intravitreal injection of VEGF antibody. Results We found that live cells, regardless of whether they were stem cells or differentiated cell types, had a positive effect on improving degenerating retinas after subretinal transplantation; the efficacy depended on their survival duration in the host tissue. A few paracrine factors were identified in cell culture media; Vegfa was the most relevant neurotrophic and neuroprotective factor identified by our experiments to extend neuron survival duration in vivo. Conclusions Cellular therapy-produced benefits for remediating retinal degeneration are mostly, if not completely, due to a paracrine effect of implanted cells on the remaining host retinal neurons.

Electrochemical sensors benefit from low cost and fast detection speeds, which makes them suitable for routine analysis of small biological molecules such as dopamine (DA). DA is a neurotransmitter that plays an important physiological role and can be used as a marker for conditions such as depressive disorder and Parkinson’s disease. In this communication, electrodes modified with self-assembled gold nanoparticles (SA-AuNPs) were used as electrochemical sensors for the detection of DA with the aim of achieving better signal stability among the same batch of electrodes. High signal reproducibility among the SA-AuNP-modified electrodes was obtained due to the more orderly packing of AuNPs leading to relatively consistent electrochemical resistance and homogeneous mass transport.

Members of the family Zoogloeaceae within the order Rhodocyclales are found to play vital roles in terrestrial and aquatic ecosystems by participating in biofloc formation in activated sludge, polycyclic aromatic hydrocarbon degradation, and nitrogen metabolism, such as denitrification and nitrogen fixation. Here, two bacterial strains designated H1-1-2AT and ZN11-R3-1 affiliated to the family Zoogloeaceae were isolated from coastal wetland habitats. The 16S rRNA gene sequences of the two strains were 100% identical and had maximum similarity with Nitrogeniibacter mangrovi M9-3-2T of 98.4% and ≤94.5% with other species. Phylogenetic analysis suggested that the two strains belonged to a single species and formed a novel monophyletic branch affiliated to the genus Nitrogeniibacter. The average nucleotide identity (ANI) value and digital DNA-DNA hybridization (dDDH) estimate between the two strains and N. mangrovi M9-3-2T were 78.5–78.7% and 21.4–21.6%, respectively, indicating that the two strains represent a novel species. The genomes of strain H1-1-2AT (complete genome) and ZN11-R3-1 (draft genome) were 4.7Mbp in length encoding ~4,360 functional genes. The DNA G+C content was 62.7%. Nitrogen fixation genes were found in the two strains, which were responsible for the growth on nitrogen-free medium, whereas denitrification genes found in N. mangrovi M9-3-2T were absent in the two strains. The respiratory quinone was ubiquinone-8. The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, and aminophospholipid. The major fatty acids were summed feature 3 (C16:1ω7c and C16:1ω6c), C16:0, C12:0, and C10:0 3-OH. Based on genomic, phenotypic, and chemotaxonomic characterizations, strains H1-1-2AT and ZN11-R3-1 represent a novel species of the genus Nitrogeniibacter, for which the name Nitrogeniibacter aestuarii sp. nov. is proposed. The type strain is H1-1-2AT (=MCCC 1K04284T=KCTC 82672T), and additional strain is ZN11-R3-1 (=MCCC 1A17971=KCTC 82671). Additionally, phylogenomic analysis of the members of the family Zoogloeaceae including type strains and uncultivated bacteria was performed, using the Genome Taxonomic Database toolkit (GTDB-Tk). Combined with the 16S rRNA gene phylogeny, four novel genera, Parazoarcus gen. nov., Pseudazoarcus gen. nov., Pseudothauera gen. nov., and Cognatazoarcus gen. nov., were proposed. This study provided new insights to the taxonomy of the family Zoogloeaceae.

Partly because of extensions in lifespan, the incidence of neurodegenerative diseases is increasing, while there is no effective approach to slow or prevent neuronal degeneration. As we all know, neurons cannot self-regenerate and may not be replaced once being damaged or degenerated in human brain. Astrocytes are widely distributed in the central nervous system (CNS) and proliferate once CNS injury or neurodegeneration occur. Actually, direct reprogramming astrocytes into functional neurons has been attracting more and more attention in recent years. Human astrocytes can be successfully converted into neurons in vitro. Notably, in vivo direct reprogramming of astrocytes into functional neurons were achieved in the adult mouse and non-human primate brains. In this review, we briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for CNS diseases, mainly focusing on neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). We highlight and outline the advantages and challenges of direct neuronal reprogramming from astrocytes in vivo for future neuroregenerative medicine.

The linear parameter-varying (LPV) models have broad applications in advanced mathematics and modern control systems. This paper introduces a new method for controlling the LPV systems. This method includes the gain-scheduled state-feedback technique and a fuzzy system to calculate the state-feedback gain. The main goal of the control system is to stabilize the system and bring its states to equilibrium points. Linear matrix inequalities calculate feedback gains to stabilize the system. On the other hand, a fuzzy control system also produces a combined signal with the primary controller signal to speed up this operation. Lyapunov’s theory is used to guarantee the control system’s stability. Finally, to evaluate the performance of the proposed control system, the inverted pendulum has been investigated as a case study. The results show that the proposed method has good efficiency and performance.

Intracranial atherosclerosis (ICAS) is a progressive pathological process that causes progressive stenosis and cerebral hypoperfusion and is a major cause of stroke occurrence and recurrence around the world. Multiple factors contribute to the development of ICAS. Angiography imaging techniques can improve the diagnosis of and the selection of appropriate treatment regimens for ICAS. Neither aggressive medication nor endovascular interventions can eradicate stroke recurrence in patients with ICAS. Non-pharmacological therapies such as remote ischemic conditioning and hypothermia are emerging. Comprehensive therapy with medication in combination with endovascular intervention and/or non-pharmacological treatment may be a potential strategy for ICAS treatment in the future. We summarized the epidemiology, pathophysiological mechanisms, risk factors, biomarkers, imaging and management of ICAS.

The construction of heavy polar icebreakers is usually done with special hull steels, which require comprehensive properties such as good low-temperature toughness, high strength, and superior fatigue resistance. Reasonable and satisfactory heat treatments should be investigated and applied to acquire the required high strength and superior low-temperature toughness, since this is deemed an effective approach to ameliorate the combined properties of high-strength hull steels. Regarding this, the present study specifically explores the effects of different laboratory-based quenching (850 to 930 °C) and tempering (580 to 660 °C) heat treatments on the final low-temperature toughness of the high-strength hull steels. The low-temperature toughness is eventually improved without significantly sacrificing the strength. The results show that a favourable combination of properties can be obtained in the specimens under 900 °C quenching and 660 °C tempering processes. Additionality, the specimens tempered at 620 °C present the highest hardness, owing to the higher percentage of tempered martensite. Detailed mechanisms of the enhanced properties of the typical specimens subjected to the corresponding quenching and tempering processing are analysed and explicated.

Membrane fouling markedly influences the service life and performance of the membrane during the using process. Herein, hydrophilic polyvinylidene fluoride (PVDF) nanocomposite (P-GO-DAA) membranes with antifouling and anti-biofouling characteristics were fabricated by employing graphene oxide (GO) and different concentrations of D-Tyrosine. The structural properties of the prepared nanocomposite membranes as well as pure PVDF membranes were characterized using FTIR, XPS, SEM, AFM, and contact angle analysis. It was found that the introduction of GO fillers made an excellent antifouling performance compared to pure PVDF indicated by the pure water flux, flux recovery rate, and rejection rate during ultrafiltration experiments as a result of the formation of the hydrophilic and more porous membrane. In particular, the nanocomposite membranes showed an increased flux of 305.27 L/(m2·h) and the rejection of 93.40% for the mixed pollutants solution (including Bull Serum Albumin, Sodium Alginate, and Humic Acid). Besides, the outstanding anti-biofouling activity was shown by the P-GO-DAA membrane with the properties of D-Tyrosine for inhibiting biofilm formation during the bacterial adhesion experiments. Furthermore, the adhesion ratio of bacteria on the membrane was 26.64% of the P-GO-DAA membrane compared to 84.22% of pure PVDF. These results were confirmed by CLSM.

BackgroundImmunotherapy has significantly improved patient outcomes, but encountered obstacles recently. CD96, a novel immune checkpoint expressed on T cells and natural killer (NK) cells, is essential for regulating immune functions. However, how CD96 correlating with immune infiltration and patient prognosis in pan-cancer remains unclear.MethodsHPA, TCGA, GEO, GTEx, Oncomine, TIMER2.0, PrognoScan, Linkedomics, Metascape, and GEPIA2 databases were used to analyze CD96 in cancers. Visualization of data was mostly achieved by R language, version 4.0.2.ResultsIn general, CD96 was differentially expressed between most cancer and adjacent normal tissues. CD96 significantly impacted the prognosis of diverse cancers. Especially, high CD96 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in the TCGA lower grade glioma (LGG) cohort (OS, HR = 2.18, 95% CI = 1.79–2.66, P < 0.001). The opposite association was significantly observed in skin cutaneous melanoma (SKCM) cohort (OS, HR = 0.96, 95% CI = 0.94–0.98, P < 0.001). Notably, SKCM samples demonstrated the highest CD96 mutation frequency among all cancer types. Furthermore, in most cancers, CD96 expression level was significantly correlated with expression levels of recognized immune checkpoints and abundance of multiple immune infiltrates including CD8+ T cells, dendric cells (DCs), macrophages, monocytes, NK cells, neutrophils, regulatory T cells (Tregs), and follicular helper T cells (Tfh). CD96 was identified as a risk factor, protective factor, and irrelevant variable in LGG, SKCM and adrenocortical carcinoma (ACC), respectively. CD96 related genes were involved in negative regulation of leukocyte in LGG, however, involved in multiple positive immune processes in SKCM. Furthermore, CD96 was significantly associated with particular immune marker subsets. Importantly, it strongly correlated with markers of type 1 helper T cell (Th1) in SKCM, but not in LGG or ACC either.ConclusionsCD96 participates in diverse immune responses, governs immune cell infiltration, and impacts malignant properties of various cancer types, thus standing as a potential biomarker for determining patient prognosis and immune infiltration in multiple cancers, especially in glioma and melanoma.

Orbitocranial penetrating injury (OPI) with multiple vascular invasions is a rare occurrence. To our knowledge, experience with its clinical treatment is rather limited, especially for infants. This case report describes an infant who fell from a 0.5 m high bed and landed on a toy with a keen-edged plastic rod. The fractured end of the rod was noted at the medial aspect of the left eyelid, and she was experiencing impaired consciousness. Computed tomography showed that the foreign body penetrated the cavernous sinus with internal carotid artery involvement, and compressed the transverse sinus through the cerebellum. Emergency surgery was performed with temporal occlusion of the left common carotid artery. The rod was removed from the orbital side, and bleeding from cavernous sinus region was effectively controlled under direct inspection via a sub-temporal approach. The patient was successfully treated and recovered consciousness after 17 days. This is the first report of successful management of OPI combined with multiple vascular injury in an infant. Herein, we highlight the anatomical imaging features of the injuries and also the individualized strategy concerning vascular invasion.

Background: The retinal pigment epithelium (RPE) has the potential to regenerate the entire neuroretina upon retinal injury in amphibians. In contrast, this regenerative capacity has been lost in mammals. The reprogramming of differentiated somatic cells into induced pluripotent stem cells (iPSCs) by viral transduction of exogenous stem cell factors has triggered a revolution in regenerative medicine. However, the risks of potential mutation(s) caused by random viral vector insertion in host genomes and tumor formation in recipients hamper its clinical application. One alternative is to immortalize adult stem cells with limited potential or to partially reprogram differentiated somatic cells into progenitor-like cells through non-integration protocols. Methods: Sphere-induced RPE stem cells (iRPESCs) were generated from adult mouse RPE cells. Their stem cell functionality was studied in a mouse model of retinal degeneration. The molecular mechanism underlying the sphere-induced reprogramming was investigated using microarray and loss-of-function approaches. Findings: We provide evidence that our sphere-induced reprogramming protocol can immortalize and transform mouse RPE cells into iRPESCs with dual potential to differentiate into cells that express either RPE or photoreceptor markers both in vitro and in vivo. When subretinally transplanted into mice with retinal degeneration, iRPESCs can integrate to the RPE and neuroretina, thereby delaying retinal degeneration in the model animals. Our molecular analyses indicate that the Hippo signaling pathway is important in iRPESC reprogramming. Interpretation: The Hippo factor Yap1 is activated in the nuclei of cells at the borders of spheres. The factors Zeb1 and P300 downstream of the Hippo pathway are shown to bind to the promoters of the stemness genes Oct4, Klf4 and Sox2, thereby likely transactivate them to reprogram RPE cells into iRPESCs. Fund: National Natural Science Foundation of China and the National Institute of Health USA. Keywords: RPE stem cells, Sphere-induced reprogramming, Retina degeneration, Cell transplantation

The association of residual myometrium thickness (RMT) and scar defect depth (D) with menstrual abnormalities and the effectiveness of vaginal repair remain to be determined in patients with cesarean section scar diverticulum (CSD). To assess the value of ultrasound to predict vaginal repair effectiveness. This was a retrospective study of patients with CSD treated with vaginal repair between 01/2014 and 02/2016 at Shanghai First Maternity and Infant Hospital (Tongji University). Transvaginal ultrasound was performed before and 3 months after surgical repair. RMT, D, scar defect length (L), and scar defect width (W) were measured. Width (W), D, and L increased along the duration of menstrual period (P

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder that affects nearly all organs and tissues. As knowledge about the mechanism of SLE has increased, some immunosuppressive agents have become routinely used in clinical care, and infections have become one of the direct causes of mortality in SLE patients. To identify the risk factors indicative of infection in SLE patients, a case control study of our hospital's medical records between 2011 and 2013 was performed. We reviewed the records of 117 SLE patients with infection and 61 SLE patients without infection. Changes in the levels of T cell subsets, immunoglobulin G (IgG), complement C3, complement C4, globulin, and anti-double-stranded DNA (anti-ds-DNA) were detected. CD4+ and CD4+/CD8+ T cell levels were significantly lower and CD8+ T cell levels were significantly greater in SLE patients with infection than in SLE patients without infection. Additionally, the concentrations of IgG in SLE patients with infection were significantly lower than those in SLE patients without infection. However, complement C3, complement C4, globulin, and anti-ds-DNA levels were not significantly different in SLE patients with and without infection. Therefore, clinical testing for T cell subsets and IgG is potentially useful for identifying the presence of infection in SLE patients and for distinguishing a lupus flare from an acute infection.