Genetic causal association between physical activities and epilepsy: A Mendelian randomization study.

BACKGROUND: Despite numerous investigations into the relationship between physical activities (PA) and epilepsy, the causal effects remain contentious. Thus, we conducted a two-sample Mendelian randomization (MR) study to assess the potential causality. METHODS: Single-nucleotide polymorphisms (SNPs) predisposed to self-reported moderate and vigorous physical activities (MPA and VPA) and overall acceleration average (OAA) calculated through wrist-worn accelerometers were selected as exposure instrumental variables. Five subtypes of epilepsy, including all epilepsy, focal epilepsy and generalized epilepsy (with or without each other), focal epilepsy-strict definition and generalized epilepsy-strict definition (without overlap), were chosen as the outcomes. The MR study utilized the inverse-variance weighted (IVW) method as the primary analytical tool, supplemented by MR-Egger, simple mode, weighted mode, and weighted median methods. Cochran's Q and MR-Egger intercept tests were employed to assess heterogeneity and pleiotropy, while MR pleiotropy residual sum and outlier and leave-one-out analyses were conducted to identify potential SNP outliers. RESULTS: The study indicated that OAA was genetically linked to a decreased risk of both focal epilepsy (OR = 0.812, 95% CI: 0.687-0.960, p = .015, IVW) and focal epilepsy-strict definition (OR = 0.732, 95% CI: 0.596-0.900, p = .003, IVW; OR = 0.749, 95% CI: 0.573-0.979, p = .035, Weighted median). Genetically predicted MPA and VPA did not exhibit a causal association with all epilepsy or its subtypes (p>.05). No evidence of heterogeneity, pleiotropy, or SNP outlier was observed. CONCLUSIONS: Our findings suggested that PA with accelerometer monitoring may potentially reduce the risk of focal epilepsy, while there is no evidence supporting causal association between self-reported MPA or VPA and either focal or generalized epilepsy.

Rhizopus microsporus and Mucor racemosus coinfection following COVID-19 detected by metagenomics next-generation sequencing: A case of disseminated mucormycosis.

Mucormycosis is an invasive opportunistic fungal infection, which may be lethal and mostly affects patients with immunodeficiency or diabetes mellitus. Among Mucorales fungi, Rhizopus spp. is the most common cause of mucormycosis, followed by genera such as Mucor and Lichtheimia. Here we report a patient with severe COVID-19 infection who developed nasal pain, facial swelling, prominent black eschar on the nasal root. CT scan revealed pansinusitis along the maxillary, ethmoidal, and sphenoid sinuses. Mixed mold infection with Rhizopus microsporus and Mucor racemosus was detected by blood metagenomics next-generation sequencing (mNGS) and later nasal mucosa histological investigation confirmed mucormycosis. Severe COVID-19 infection led to the patient's thrombocytopenia and leukopenia. Later disseminated mucormycosis aggravated the infection and sepsis eventually resulted in death. It is the first case report of mucormycosis in which R. microsporus and M. racemosus as the etiologic agents were found simultaneously in one patient. COVID-19 infection combined with disseminated mucormycosisis can be fatal and mNGS is a fast, sensitive and accurate diagnostic method for fungi detection.

Identification of bidirectional causal links between gut microbiota and narcolepsy type 1 using Mendelian randomization.

STUDY OBJECTIVES: Narcolepsy type 1 (NT1), characterized by cataplexy and orexin deficiency, is a rare and frequently debilitating neurological disorder. It has been noted to have connections with the gut microbiota, yet the exact causal relationships remain unclear. METHODS: We conducted a comprehensive bidirectional Mendelian randomization (MR) study to rigorously investigate the causal links between the gut microbiota and NT1, utilizing genetic datasets from the MiBioGen consortium and FinnGen consortium, respectively. The inverse-variance weighted (IVW) method was employed to obtain the primary MR estimates, supplemented by several alternative methods as well as sensitivity analyses including Cochran's Q, MR-Egger, MR pleiotropy residual sum and outlier, leave-one-out, and genetic colocalization. RESULTS: Our findings indicated that an increased relative abundance of five genera including Blautia (p = 4.47E-5), Collinsella (p = 0.036), Gordonibacter (p = 0.047), Hungatella (p = 0.015), and Lachnospiraceae UCG010 (p = 0.027) may be associated with a decreased risk of NT1. Conversely, an increased relative abundance of class Betaproteobacteria (p = 0.032), genus Alloprevotella (p = 0.009), and genus Ruminiclostridium6 (p = 0.029) may potentially heighten the risk of NT1. The onset of NT1 may lead to a decrease in the relative abundance of genus Eubacterium eligens group (p = 0.022), while a increase in the family Family XI (p = 0.009), genus Hungatella (p = 0.005), genus Prevotella (p = 0.013), and unknown genus id.2001 (p = 0.019). These findings remained robust under all sensitivity analyses. CONCLUSIONS: Our results offer robust evidence for the bidirectional causal links between particular gut microbial taxa and NT1, underscoring the significance of the microbiota-gut-brain axis in the pathological process of NT1.

Open-loop analog programmable electrochemical memory array.

Emerging memories have been developed as new physical infrastructures for hosting neural networks owing to their low-power analog computing characteristics. However, accurately and efficiently programming devices in an analog-valued array is still largely limited by the intrinsic physical non-idealities of the devices, thus hampering their applications in in-situ training of neural networks. Here, we demonstrate a passive electrochemical memory (ECRAM) array with many important characteristics necessary for accurate analog programming. Different image patterns can be open-loop and serially programmed into our ECRAM array, achieving high programming accuracies without any feedback adjustments. The excellent open-loop analog programmability has led us to in-situ train a bilayer neural network and reached software-like classification accuracy of 99.4% to detect poisonous mushrooms. The training capability is further studied in simulation for large-scale neural networks such as VGG-8. Our results present a new solution for implementing learning functions in an artificial intelligence hardware using emerging memories.

A phase I clinical trial of sonodynamic therapy combined with temozolomide in the treatment of recurrent glioblastoma.

PURPOSE: The prognosis of recurrent glioblastoma (rGBM) is poor, and there is currently no effective treatment strategy. Sonodynamic therapy (SDT) is a new method for cancer treatment that uses a combination of low-frequency ultrasound and sonosensitisers to produce antitumor effects, which have shown good therapeutic effects in preclinical studies. Therefore, we initiated an open, prospective pilot study to evaluate the safety, tolerability, and efficacy of SDT for the treatment of rGBM. METHODS: Nine patients with rGBM were enrolled who had received multiple treatments, but the nidus continued to progress without additional standard treatments. After MRI localisation, porphyrin drugs were injected, and intermittent low-frequency ultrasound therapy was performed for five days. RESULTS: None of the nine patients in this clinical trial showed any clinical, neurological, haematological, or skin-targeted adverse effects associated with SDT. After the completion of the trial, one patient maintained stable disease, and eight patients experienced disease progression. Among the eight with progressive disease, the median progression-free survival time was 84 days. Four patients died, and the median overall survival duration after recurrence was 202.5 days. CONCLUSION: The number of patients in this study was small; therefore, a long-term survival benefit was not demonstrated. However, this study suggests that SDT has potential as a treatment for rGBM and warrants further exploration. Trial information: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ): ChiCTR2200065992. November 2, 2022, retrospectively registered.

CircMAN1A2 contributes to nasopharyngeal carcinoma progression via enhancing the ubiquitination of ATMIN through miR-135a-3p/UBR5 axis.

Recently, the dysregulation of circRNAs has been increasingly implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). Among these circRNAs, circMAN1A2 has been highlighted for the up-regulated expression in NPC, whereas the underlying mechanisms have not been clearly established. Thus, the aim of this study was to delineate the tumor-supporting role of circMAN1A2 in the oncogenesis and metastases of NPC. We validated through qRT-PCR that circMAN1A2 was highly expressed in NPC tissues and NPC cells. Survival analysis through Kaplan-Meier method showed that the overall survival, disease-free survival, and distant metastasis-free survival of patients was negatively correlated with the expression of circMAN1A2. Then, gain- and loss-of function assays demonstrated that circMAN1A2 knockdown could impede the proliferation, migration, invasion, and EMT in NPC cells. Further, we conducted dual luciferase reporter gene, RIP, and RNA pull down assays, unveiling that circMAN1A2 functioned as a sponge of miR-135a-3p, and miR-135a-3p targeted UBR5. Additionally, UBR5 interacted with ATMIN to foster the ubiquitination of ATMIN, thereby expediting the malignant behaviors of NPC cells as well as the lung and inguinal lymph node metastases of NPC tumors in vivo. Together, our study uncovered the tumor-initiating and pro-metastatic role of circMAN1A2-miR-135a-3p-UBR5-ATMIN axis in NPC regulation that may be a potential therapeutic target for human NPC.

Evidence for genetic causal relationships between gut microbiome, metabolites, and myasthenia gravis: a bidirectional Mendelian randomization study.

Background: Myasthenia gravis (MG) is an autoimmune disease observed to have connections with gut microbiome. We aimed to systematically assess the causal relationships between gut microbiome, gut microbiome-derived metabolites, and MG using Mendelian randomization (MR) approach. Methods: Summary-level genetic datasets from large-scale genome-wide association studies regarding 196 gut microbial taxa from the MiBioGen consortium (n=18,340), 72 derived metabolites from the TwinsUK and KORA studies (n=7,824), and antiacetylcholine receptor (AChR) antibody-positive MG (case=1,873, control=36,370) were employed for MR causal estimates. The inverse-variance weighted (IVW) method was utilized as the main analysis with MR-Egger, maximum likelihood, simple mode, and weighted median as complements. The tests of Cochran's Q, MR-Egger intercept, Steiger, MR-PRESSO and leave-one-out were implemented for sensitivity analyses. Results: The forward MR estimates of IVW revealed significant causal associations of the abundance of phylum Actinobacteria, class Gammaproteobacteria, family Defluviitaleac, family Family XIII, and family Peptococcaceae with a reduced risk of MG. Conversely, the abundance of phylum Lentisphaerae, order Mollicutes RF9, order Victivallales, and genus Faecalibacterium was causally associated with an increased risk of MG. The reversed MR analysis proved negative causal correlations between the MG and the abundance of family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum. Regarding the derived metabolites, the IVW estimates revealed that elevated levels of beta-hydroxyisovalerate and methionine were causally associated with a decreased risk of MG, while increased levels of choline and kynurenine were linked to an increased risk of MG. Furthermore, genetically predicted MG was associated with a decreased level of cholesterol. The results obtained from complementary MR methods were similar. These findings remained robust in all sensitivity analyses. Conclusion: Our MR findings support the causal effects of specific gut microbiome taxa and derived metabolites on AChR antibody-positive MG, and vice versa, yielding novel insights into prevention and therapy targets of MG. Future studies may be warranted for validation and pursuing the precise mechanisms.

[The changes in subjective visual vertical after otolith reduction in patients with BPPV].

Objective:To observe and analyze the changes in subjective visual vertical（SVV） after otolith reduction in patients with BPPV. Methods:46 patients with confirmed BPPV recieving successful otolith reduction were selected as the test group. 31 cases of posterior canal stones and 15 cases of horizontal semicircular canal stones, 29 cases of right ear and 17 cases of left ear. Fifty cases of healthy young volunteers were in the control group. Using the virtual reality SVV examination system, 0° SVV in the positive head were tested in the test group patients before and after the reduction of SVV , and were tested in the control group .The deviation angle of the SVV before and after the otolith reduction in the test group were analyzed. Results:Before otoliths reduction, the SVV was （0.08±3.83）° of right BPPV and was （-1.69±2.23）° of left BPPV. After otoliths reduction, the SVV was （-1.52±3.74）° of right BPPV and was （-1.04±2.50）° of left BPPV. In the control group, the SVV was（-1.57±2.28）° . The changes of SVV deflection angle between the control group and the right BPPV before the otolith reduction, and before and after the otolith reduction in the right BPPV were analyzed, and the differences were all statistically significant. There was no significant difference in SVV deflection angle between the left BPPV（before and after reduction） and the control group. In the test group, after the otolith reduction, 18 cases had larger bias angles, 28 cases had smaller bias angle among which 13 cases the deviation angle even turned to the contralateral side. Conclusion:Utriculare dysfunction in patients with BPPV leads to the judgment error of SVV. Reduction of otolithoid can cause new stimulation to the eutricule and affect its functional status. SVV detection can provide help for the evaluation of utricular function in patients with BPPV.

Case Report: Anti-NF186+ CIDP After Receiving the Inactivated Vaccine for Coronavirus Disease (COVID-19).

Corona Virus Disease 2019 (COVID-19), the novel coronavirus disease, is now a global pandemic. Vaccination can significantly reduce the mortality rate caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). There are currently several effective vaccines that have been introduced. Inactivated COVID-19 vaccine is one of these options and is generally considered safe. Neurofascin (NF) plays an important role in keeping the functionality of the node of Ranvier. We report here a rare case of anti-NF186+ chronic inflammatory demyelinating polyneuropathy (CIDP) in a 23-year-old male patient who was vaccinated with inactivated COVID-19 vaccine prior to the onset. This report adds a new possible rare side effect of a COVID-19 vaccine and provides a case for the clinical effectiveness of rituximab (RTX) in patients with anti-NF186+ CIDP.

Demographic, Virological Characteristics and Prognosis of Asymptomatic COVID-19 Patients in South China.

BACKGROUND: Asymptomatic transmission is a major concern for SARS-CoV-2 community spread; however, little information is available on demographic, virological characteristics and prognosis of asymptomatic cases. METHODS: All COVID-19 patients hospitalized in Guangdong Province from September 1, 2020 to February 28, 2021, were included and were divided into asymptomatic and symptomaticgroup. The source country of all patients, clinical laboratory test results, the genotype of virus and the time of SARS-CoV-2 RNA turning negative or hospitalization were confirmed. RESULTS: Total 233 patients from 57 different countries or regions were included, with 83 (35.6%) asymptomatic and 150 (64.4%) symptomatic patients. Asymptomatic cases were younger (P = 0.019), lower rate in comorbidities (P = 0.021) such as hypertension (P = 0.083) and chronic liver disease (P = 0.045), lower PCT (P = 0.021), DDI (P < 0.001) and ALT (P = 0.029), but higher WBC count (P = 0.002) and lymphocyte (P = 0.011) than symptomatic patients. As for SARS-CoV-2 subtypes, patients infected with B.1.1 (53.8%), B.1.351 (81.8%) and B.1.524 (60%) are mainly asymptomatic, while infected with B, B.1, B.1.1.63, B.1.1.7, B.1.36, B.1.36.1, B.1.36.16, B.1.5 and B.6 were inclined to be symptomatic. Patients infected with variant B.1.351 and B.1.524 spent longer time in SARS-CoV-2 RNA turn negative (26 days, P = 0.085; 41 days, P = 0.007) and hospitalization (28 days, P = 0.085; 43 days, P = 0.004). CONCLUSIONS: The asymptomatic cases are prone to develop in patients with younger age, less comorbidities andinfected with B.1.1 and B.1.524 variants. More attention should be paid for lineage B.1.524 because it can significantly prolong the SARS-CoV-2 RNA negative conversion time and hospitalization in infected cases.

Remaining Useful Life Prognostics of Bearings Based on a Novel Spatial Graph-Temporal Convolution Network.

As key equipment in modern industry, it is important to diagnose and predict the health status of bearings. Data-driven methods for remaining useful life (RUL) prognostics have achieved excellent performance in recent years compared to traditional methods based on physical models. In this paper, we propose a novel data-driven method for predicting the remaining useful life of bearings based on a deep graph convolutional neural network with spatiotemporal domain convolution. This network uses the average sliding root mean square (ASRMS) as the health factor to identify the healthy and degraded states, and then uses correlation coefficient analysis on the hybrid features of the degraded data to construct a spatial graph according to the strength of the correlation between the obtained features. In the time domain, we introduce historical data as the input to the temporal convolution. After the data are processed by the spatial map and the temporal dimension, we perform the prediction of the remaining useful life. The experimental results show the accuracy of the method.

Dynamic Tannic Acid Hydrogel with Self-Healing and pH Sensitivity for Controlled Release.

Dynamic hydrogels constructed with dynamic chemical bonds often have mechanical strength and self-healing properties. In this paper, tannic acid is combined with lysine-containing F127 through Schiff base. A series of FLaT hydrogels cross-linked by hydrogen bonds and dynamic chemical bonds is prepared, and the influence of Schiff base amount on the performance is discussed. The FLaT hydrogel exhibits reversible sol-gel transition, self-healing, injectability, and pH sensitivity. Increasing the amount of Schiff base can improve the strength, stability, and self-healing ability of the hydrogel. Owing to their low cytotoxicity, linear release pattern, and pH-controlled release rate, the FLaT hydrogels show potential use in drug delivery systems for cancer treatment.

Thermally induced and physically cross-linked hydrogel doped with graphene oxide for controlled release.

Graphene oxide (GO) is an ideal hydrogel material because of its water solubility, non-toxicity, and excellent mechanical properties. Here, we added GO to oligo(lysine)-modified F127 to prepare a series of FLGO composite hydrogels. The FLGO hydrogel was thermally induced, stable and injectable. And the content of GO would affect the sol-gel transition, rheological properties and glass transition temperature of the FLGO hydrogel. GO was connected to the matrix through electrostatic interactions and hydrogen bonds. The cross-linking effect of GO enhanced the FLGO hydrogel. We also studied the release properties of the FLGO hydrogel loaded with anticancer drug 5-fluorouracil. Compared with F127 hydrogel, the FLGO hydrogel showed a linear, slower and stable release pattern within one week. The release rate of FLGO hydrogel could be adjusted by the pH and it was faster under acidic conditions. Therefore, the FLGO hydrogel is expected to be used as a drug release system in the field of biomedicine.

Effects of Emulsifier Type and Post-Treatment on Stability, Curcumin Protection, and Sterilization Ability of Nanoemulsions.

Curcumin has a high inhibitory effect on many potential diseases caused by bacteria and fungi. However, its degradability and low water solubility limit its application. Loading curcumin with an emulsion delivery system can overcome these problems. Five different types of emulsifiers were used to prepare the curcumin-loaded nanoemulsions, namely, Tween 80 (T80), Span 80 (S80), sodium dodecyl sulfate (SDS), soybean protein isolate (SPI), and lecithin (LEC). The effects of emulsifier types and post-treatment methods on emulsion stability and curcumin-load efficiency were studied. In addition, photodynamic inactivation was used to test the antibacterial effect of nanoemulsions on Escherichia coli under blue light excitation. The five types of emulsifiers could form uniform emulsions with good storage stability and with antibacterial capacity on Escherichia coli. Among them, the T80 and LEC emulsions had good stability, coating effect, and sterilization performance under heating or room temperature. Both curcumin-loaded bactericidal emulsions had the potential for large-scale applications. A nanoemulsions delivery system could effectively improve the dispersion and chemical stability of curcumin in water. An emulsion loaded with antibacterial photosensitizer represents a new idea for the storage and preservation of food commodities.

A green self-assembled organic supermolecule as an effective flame retardant for epoxy resin.

Toxicity and environmental issues have elicited research attention regarding the need to prepare a green flame retardant with high flame retardancy. Here, a supermolecular self-assembly technology was used to prepare nickel phytate as shell materials aggregated on aminated silica nanotemplates through electrostatic interactions as a green novel flame retardant (Ni@SiO2-PA). After incorporating the obtained core-shell structured Ni@SiO2-PA into epoxy resin (EP), the supermolecular shell effectively enhanced the adhesive property between the nanoparticles and the EP matrix. The thermal stability was improved, and the peak heat release rate decreased significantly after introducing the well-characterized Ni@SiO2-PA. The absorbance intensity of the toxic aromatic compounds also decreased. Moreover, the char yield of the EP composites was improved because of the synergetic coupled effects between the nickel phytate supermolecules and SiO2 nanotemplates. The possible fire-retardancy mechanism was hypothesized as follows. The crosslinking structure of the silica initially enabled the formation of a polymer network to prevent further decomposition. The N-P synergistic flame-retardancy system then generated a gas barrier and P-rich intumescent char. Besides, char-residue generation was catalyzed by introducing Ni2+, which isolated the heat and the exchange between oxygen and the matrix. Overall, this study proposes a novel green flame retardant that may enable significant improvements in preparing environmentally friendly organic-inorganic materials with applications in the fields of flame-retardant composites.

Covalently functionalized graphene oxide wrapped by silicon-nitrogen-containing molecules: preparation and simultaneous enhancement of the thermal stability, flame retardancy and mechanical properties of epoxy resin nanocomposites.

A novel functionalized graphene oxide (FGO) wrapped with Si-N-containing flame retardant (FR-fGO) was successfully synthesized via a chemical modification process and applied to enhance the thermal stability, fire resistance, and mechanical properties of epoxy resin (EP). Herein, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were used to explore the structure and morphology of FR-fGO to overcome the fact that the FGO cannot strongly bond with the polymer matrix. With the incorporation of FR-fGO into EP, the thermal stability improved and the total heat release decreased compared with pure EP. Meanwhile, FR-fGO composites significantly reduced the amount of flammable and toxic volatiles. A possible flame-retardant mechanism of FR-fGO was deduced from a theoretical analysis of the chemical bond energy and the experimental results of thermal decomposition: namely, well-dispersed FR-fGO nanosheets constituted a physical barrier, with an Si-N-containing synergy system forming a highly graphitized residual char with an Si-containing cross-linked network. The enhancement in mechanical properties demonstrated that the composites had remarkable compatibility. This study provides a novel modification strategy to improve the dispersion and flame retardance of graphene.

Dual responsive oligo(lysine)-modified Pluronic F127 hydrogels for drug release of 5-fluorouracil.

Peptide-containing hydrogels have become a research hotspot due to their unique secondary structure and biocompatibility. Herein, we used amino-terminated F127 as a macroinitiator to initiate the ring-opening polymerization of l-lysine(z)-NCA, and the obtained oligo(lysine)-modified F127 (FL) had degrees of polymerization of lysine of 2, 5, and 8. The results showed that the FL hydrogels had reversible temperature-dependent sol-gel transitions, and the introduction of lysine increased the critical gel temperature. In the dilute solution of FL, the micelle size increased and aggregated as the pH increased; the micelle grew into a rod-like shape under alkaline conditions. Scanning electron micrographs showed that the interior of the FL hydrogel had a more complete porous structure. The FL-2 hydrogel loaded with 5-fluorouracil exhibited an approximately linear release trend within 12 h and has good biocompatibility. Therefore, FL hydrogels have potential applications in the field of biomedicine.

Eliminating Phase Drift for Distributed Optical Fiber Acoustic Sensing System with Empirical Mode Decomposition.

Phase-drift elimination is crucial to vibration recovery in the coherent detection phase-sensitive optical time domain reflectometry system. The phase drift drives the whole phase signal fluctuation as a baseline, and its negative effect is obvious when the detection time is long. In this paper, empirical mode decomposition (EMD) is presented to extract and eliminate the phase drift adaptively. It decomposes the signal by utilizing the characteristic time scale of the data, and the baseline is eventually obtained. It is validated by theory and experiment that the phase drift deteriorates seriously when the length of the vibration region increases. In an experiment, the phase drift was eliminated under the conditions of different vibration frequencies of 1 Hz, 5 Hz, and 10 Hz. The phase drift was also eliminated with different vibration intensities. Furthermore, the linear relationship between phase and vibration intensity is demonstrated with a correlation coefficient of 99.99%. The vibrations at 0.5 Hz and 0.3 Hz were detected with signal-to-noise ratios (SNRs) of 55.58 dB and 64.44 dB. With this method, when the vibration frequency is at the level of Hz or sub-Hz, the phase drift can be eliminated. This contributes to the detection and recovery of low-frequency perturbation events in practical applications.