The long-term outcomes in drug-resistant epilepsy patients who underwent subtotal hemispherotomy: A single-center retrospective cohort study.

OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68 %) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63 %) patients; seven (37 %) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.

Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8 weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.

Surgical outcomes of patients with genetically refractory epilepsy: A systematic review and meta-analysis.

OBJECTIVE: To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes. METHODS: A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines. RESULTS: Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55-0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00-0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55-0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline. CONCLUSION: Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy.

Seizure, Motor, and Cognitive Outcomes After Epilepsy Surgery for Patients With Sturge-Weber Syndrome: Results From a Multicenter Study.

BACKGROUND AND OBJECTIVES: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes. METHODS: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China. Longitudinal postoperative seizures were classified by Engel class, and Engel class I was regarded as seizure-free outcome. Functional (motor and cognitive) outcomes were evaluated using the SWS neurologic score, and improved or unchanged scores between baseline and follow-up were considered to have stable outcomes. Outcomes were analyzed using Kaplan-Meier analyses. Multivariate Cox regression was used to identify factors associated with outcomes. RESULTS: A total of 214 patients with a median age of 2.0 (interquartile range 1.2-4.6) years underwent surgery (focal resection, FR [n = 87]; hemisphere surgery, HS [n = 127]) and completed a median of 3.5 (1.7-5.0) years of follow-up. The overall estimated probability for being seizure-free postoperatively at 1, 2, and 5 years was 86.9% (95% CI 82.5-91.6), 81.4% (95% CI 76.1-87.1), and 70.7% (95% CI 63.3-79.0), respectively. The overall estimated probability of being motor stable at the same time post operatively was 65.4% (95% CI 58.4-71.2), 80.2% (95% CI 73.8-85.0), and 85.7% (95% CI 79.5-90.1), respectively. The overall probability for being cognition stable at 1, 2, and 5 years was 80.8% (95% CI 74.8-85.5), 85.1% (95% CI 79.3-89.2), and 89.5% (95% CI 83.8-93.2), respectively. Both FR and HS were effective at ensuring seizure control. For different HS techniques, modified hemispherotomy had comparable outcomes but improved safety compared with anatomical hemispherectomy. Regarding FR, partial resection (adjusted hazard ratio [aHR] 11.50, 95% CI 4.44-29.76), acute postoperative seizure (APOS, within 30 days of surgery; aHR 10.33, 95% CI 3.94-27.12), and generalized seizure (aHR 3.09, 95% CI 1.37-6.94) were associated with seizure persistence. For HS, seizure persistence was associated with APOS (aHR 27.61, 9.92-76.89), generalized seizure (aHR 7.95, 2.74-23.05), seizure frequency ≥30 times/month (aHR 4.76, 1.27-17.87), and surgical age ≥2 years (aHR 3.78, 1.51-9.47); motor stability was associated with severe motor defects (aHR 5.23, 2.27-12.05) and postoperative seizure-free status (aHR 3.09, 1.49-6.45); and cognition stability was associated with postoperative seizure-free status (aHR 2.84, 1.39-5.78) and surgical age <2 years (aHR 1.76, 1.13-2.75). DISCUSSION: FR is a valid option for refractory epilepsy in patients with SWS and has similar outcomes to those of HS, with less morbidity associated with refractory epilepsy. Early surgical treatment (under the age of 2 years) leads to better outcomes after HS, but there is insufficient evidence that surgical age affects FR outcomes. These findings warrant future prospective multicenter cohorts with international cooperation and prolonged follow-up in better exploring more precise outcomes and developing prognostic predictive models. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in children with SWS and refractory seizures, surgical resection-focal, hemispherectomy, or modified hemispherotomy-leads to improved outcomes.

Effect of biochar-derived DOM on contrasting redistribution of chromate during Schwertmannite dissolution and recrystallization.

Biochar-derived dissolved organic matter (BDOM), is extensively involved in the recrystallization of minerals and the speciation alteration of associated toxic metals. This study investigates how BDOM extracted from tobacco petiole (TP) or tobacco stalk (TS) biochar influences the speciation repartitioning of Cr(VI) in environments impacted by acid mine drainage (AMD), focusing on interactions with secondary minerals during Schwertmannite (Sch) dissolution and recrystallization. TP-BDOM, rich in lignin-like substances, slowed down the Cr-Sch dissolution and Cr release under acidic conditions compared to TS-BDOM. TP-BDOM's higher O/C component exerts a delayed impact on Cr-Sch stability and Cr(VI) reduction. In-situ ATR-FTIR and 2D-COS analysis showed that carboxylic and aromatic N-OH groups in BDOM could interact with Cr-Sch surfaces, affecting sulfate and Cr(VI) release. It was also observed that slight recrystallization occurred from Cr-Sch to goethite, along with increased Cr incorporation into secondary minerals within TS-BDOM. This enhances our understanding of BDOM's role in Cr(VI) speciation changes in AMD-contaminated sites.

Engineering strategies for enhanced 1', 4'-trans-ABA diol production by Botrytis cinerea.

BACKGROUND: Currently, industrial fermentation of Botrytis cinerea is a significant source of abscisic acid (ABA). The crucial role of ABA in plants and its wide range of applications in agricultural production have resulted in the constant discovery of new derivatives and analogues. While modifying the ABA synthesis pathway of existing strains to produce ABA derivatives is a viable option, it is hindered by the limited synthesis capacity of these strains, which hinders further development and application. RESULTS: In this study, we knocked out the bcaba4 gene of B. cinerea TB-31 to obtain the 1',4'-trans-ABA-diol producing strain ZX2. We then studied the fermentation broth of the batch-fed fermentation of the ZX2 strain using metabolomic analysis. The results showed significant accumulation of 3-hydroxy-3-methylglutaric acid, mevalonic acid, and mevalonolactone during the fermentation process, indicating potential rate-limiting steps in the 1',4'-trans-ABA-diol synthesis pathway. This may be hindering the flow of the synthetic pathway. Additionally, analysis of the transcript levels of terpene synthesis pathway genes in this strain revealed a correlation between the bchmgr, bcerg12, and bcaba1-3 genes and 1',4'-trans-ABA-diol synthesis. To further increase the yield of 1',4'-trans-ABA-diol, we constructed a pCBg418 plasmid suitable for the Agrobacterium tumefaciens-mediated transformation (ATMT) system and transformed it to obtain a single-gene overexpression strain. We found that overexpression of bchmgr, bcerg12, bcaba1, bcaba2, and bcaba3 genes increased the yield of 1',4'-trans-ABA-diol. The highest yielding ZX2 A3 strain was eventually screened, which produced a 1',4'-trans-ABA-diol concentration of 7.96 mg/g DCW (54.4 mg/L) in 144 h of shake flask fermentation. This represents a 2.1-fold increase compared to the ZX2 strain. CONCLUSIONS: We utilized metabolic engineering techniques to alter the ABA-synthesizing strain B. cinerea, resulting in the creation of the mutant strain ZX2, which has the ability to produce 1',4'-trans-ABA-diol. By overexpressing the crucial genes involved in the 1',4'-trans-ABA-diol synthesis pathway in ZX2, we observed a substantial increase in the production of 1',4'-trans-ABA-diol.

Purification of gamma-cyclodextrin via selective coordination with potassium ions to form metal-organic frameworks.

Efficient purification of gamma-cyclodextrin (γ-CD) is always challenging due to its structural similarity to other CDs and low crystallinity in water. In addressing this issue, an approach was proposed based on the formation mechanism of cyclodextrin metal-organic frameworks (CD-MOFs). This method involved the selective coordination of CDs mixture with potassium ions in water, facilitated by ethanol-induced crystallization, leading to the purification of γ-CD. The results showed that potassium ions enhanced γ-CD crystallization, and ethanol was crucial to selectively coordinating potassium ions with γ-CD. The characterizations revealed that the resulting CD-MOFs exhibited a small particle size, high surface area, and high thermal stability, and was identical to γ-CD-MOF, further indicating the final γ-CD with high purity. The separation factors of γ-CD/α-CD and γ-CD/ß-CD were 309 and 260, respectively. Moreover, this method was validated through its application to the industrial enzymatic CDs mixture. The purification of γ-CD could achieve 99.99 ± 0.01 % after four crystallization cycles. Therefore, selectively coordinating with potassium ions to form MOFs provided a valuable reference for the purification of γ-CD and even the direct synthesis of γ-CD-MOF from CDs mixture. This advancement will also benefit the future production and application of γ-CD.

Implementing a Barcode-Based Whole-Life Cycle Management Process to Improve Robotic Instrument Tracking.

Minimally invasive surgery can involve the use of robotics to improve patient outcomes. Some robotic systems require special instruments with a designated number of uses. In China, during the reprocessing of the robotic instruments, health care personnel determined that the existing tracking processes were inadequate. They conducted a quality improvement project with the goal of establishing a barcode-based standardized process for tracking robotic instruments. They implemented technology that generated a unique identifier each time a robotic instrument was reprocessed after use. Nurses scanned the identifier when surgeons used the instrument. The findings included the increased accuracy of use documentation and decreases in untraceable sterilization and use records, charging concerns, and average daily and monthly inventory times. An increase in adverse event reports associated with robotic instruments also was noted. The use of barcode technology for robotic instrument tracking continues at the facility and may be expanded for additional specialty instruments.

Supramolecular Structure of the ß-Cyclodextrin Metal-Organic Framework Optimizes Iodine Stability and Its Co-delivery with l-Menthol for Antibacterial Applications.

The spread of upper respiratory tract (URT) infections harms people's health and causes social burdens. Developing targeted treatment strategies for URT infections that exhibit good biocompatibility, stability, and strong antimicrobial effects remains challenging. The dual antimicrobial and antiviral effects of iodine (I2) in combination with the cooling sensation of l-menthol in the respiratory tract can simultaneously alleviate URT inflammation symptoms. However, as both I2 and l-menthol are volatile, addressing stability issues is crucial. In this study, a potassium iodide ß-cyclodextrin metal-organic framework [ß-CD-POF(I)] with appropriate particle size was used to coload and deliver I2 and l-menthol. Primarily, ß-CD-POF(I) was employed as the most efficient carrier to significantly enhance the stability of I2, surpassing any other known protection strategies in the pharmaceutical field (CD complexations, PVP conjugations, and cadexomer iodine). The mechanism underlying the improvement in stability of I2 by ß-CD-POF(I) was investigated through scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular docking. The results revealed that the key processes involved in improving stability were the inclusion of I2 by ß-CD cavities in ß-CD-POF(I) and the formation of polyiodide anion between iodine ions and I2. Furthermore, the potential of ß-CD-POF(I) to load and deliver drugs was validated, and coloading of l-menthol and I2 demonstrated reliable stability. ß-CD-POF(I) achieved a rate of URT deposition ≥95% in vitro, and the combined antibacterial effects of coloaded I2 and l-menthol was better than I2 or PVP-I alone, with no irritation noted following URT administration in rabbits. Therefore, the stable coloading of drugs by ß-CD-POF(I), leading to enhanced antimicrobial effects, provides a new strategy for treating URT infections.

Predictors of seizure outcomes in stereo-electroencephalography-guided radio-frequency thermocoagulation for MRI-negative epilepsy.

Background: One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery. Objective: This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy. Design: This was a single-center retrospective cohort study. Methods: We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis. Results: With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387). Conclusion: Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

Normal distribution of H3K9me3 occupancy co-mediated by histone methyltransferase BcDIM5 and histone deacetylase BcHda1 maintains stable ABA synthesis in Botrytis cinerea TB-31.

Abscisic acid (ABA) is a conserved and important "sesquiterpene signaling molecule" widely distributed in different organisms with unique biological functions. ABA coordinates reciprocity and competition between microorganisms and their hosts. In addition, ABA also regulates immune and stress responses in plants and animals. Therefore, ABA has a wide range of applications in agriculture, medicine and related fields. The plant pathogenic ascomycete B. cinerea has been extensively studied as a model strain for ABA production. Nevertheless, there is a relative dearth of research regarding the regulatory mechanism governing ABA biosynthesis in B. cinerea. Here, we discovered that H3K9 methyltransferase BcDIM5 is physically associated with the H3K14 deacetylase BcHda1. Deletion of Bcdim5 and Bchda1 in the high ABA-producing B. cinerea TB-31 led to severe impairment of ABA synthesis. The combined analysis of RNA-seq and ChIP-seq has revealed that the absence of BcDIM5 and BcHda1 has resulted in significant global deficiencies in the normal distribution and level of H3K9me3 modification. In addition, we found that the cause of the decreased ABA production in the ΔBcdim5 and ΔBchda1 mutants was due to cluster gene repression caused by the emergence of hyper-H3K9me3 in the ABA gene cluster. We concluded that the ABA gene cluster is co-regulated by BcDIM5 and BcHda1, which are essential for the normal distribution of the B. cinerea TB-31 ABA gene cluster H3K9me3. This work expands our understanding of the complex regulatory network of ABA biosynthesis and provides a theoretical basis for genetic improvement of high-yielding ABA strains.

Higher Expression of Human Endogenous Retrovirus-K was Observed in Peripheral B Lymphocytes of Leukemia and Lymphoma Patients.

Hematological malignant tumors (HMTs) are serious diseases that threaten human health and life with high mortality. Therefore, it is necessary to develop novel strategies for diagnosis and treatment. Human endogenous retroviruses (HERVs) have recently attracted increasing attention as potential targets for cancer diagnosis and therapy. In this study, we explored the association between HERV-K expression levels and HMTs development. Clinical data and peripheral blood samples were collected from 236 leukemia, 384 lymphoma patients, and 69 healthy controls. Quantitative polymerase chain reaction was used to detect the expression of HERV-K gag, pol, and env genes in peripheral blood mononuclear cells or different cell subpopulations. Differently expressed HERV-K genes were further tested by using deep sequencing method, and further analyzed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. B cell- and T cell-related cytokines in patients were also detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the expression levels of the HERV-K gag, pol, and env genes in patients were significantly higher than in healthy controls. There was a correlation between the expression level of HERV-K and the clinicopathological parameters of leukemia patients. HERV-K expression was increased in the B lymphocytes of leukemia and lymphoma patients, but not in the T cells or neutrophils. The GO and KEGG analyses showed that abnormal expression of the HERV-K locus in patients affected immune regulation. The analysis of cytokines proved that the B cell-related cytokines, including interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon-gamma, were significantly decreased in patients, while the T cell-related cytokines, including IL-3, IL-12, and TNF-ß, were not significantly changed. In conclusion, HERV-K genes might participate in the occurrence and development of leukemia and lymphoma, and might be biomarkers for the detection or evaluation of leukemia and lymphoma.

Filter-Informed Spectral Graph Wavelet Networks for Multiscale Feature Extraction and Intelligent Fault Diagnosis.

Intelligent fault diagnosis has been increasingly improved with the evolution of deep learning (DL) approaches. Recently, the emerging graph neural networks (GNNs) have also been introduced in the field of fault diagnosis with the goal to make better use of the inductive bias of the interdependencies between the different sensor measurements. However, there are some limitations with these GNN-based fault diagnosis methods. First, they lack the ability to realize multiscale feature extraction due to the fixed receptive field of GNNs. Second, they eventually encounter the over-smoothing problem with increase of model depth. Finally, the extracted features of these GNNs are hard to understand due to the black-box nature of GNNs. To address these issues, a filter-informed spectral graph wavelet network (SGWN) is proposed in this article. In SGWN, the spectral graph wavelet convolutional (SGWConv) layer is established upon the spectral graph wavelet transform, which can decompose a graph signal into scaling function coefficients and spectral graph wavelet coefficients. With the help of SGWConv, SGWN is able to prevent the over-smoothing problem caused by long-range low-pass filtering, by simultaneously extracting low-pass and band-pass features. Furthermore, to speed up the computation of SGWN, the scaling kernel function and graph wavelet kernel function in SGWConv are approximated by the Chebyshev polynomials. The effectiveness of the proposed SGWN is evaluated on the collected solenoid valve dataset and aero-engine intershaft bearing dataset. The experimental results show that SGWN can outperform the comparative methods in both diagnostic accuracy and the ability to prevent over-smoothing. Moreover, its extracted features are also interpretable with domain knowledge.

Structural and functional specializations of human fast-spiking neurons support fast cortical signaling.

Fast-spiking interneurons (FSINs) provide fast inhibition that synchronizes neuronal activity and is critical for cognitive function. Fast synchronization frequencies are evolutionary conserved in the expanded human neocortex despite larger neuron-to-neuron distances that challenge fast input-output transfer functions of FSINs. Here, we test in human neurons from neurosurgery tissue, which mechanistic specializations of human FSINs explain their fast-signaling properties in human cortex. With morphological reconstructions, multipatch recordings, and biophysical modeling, we find that despite threefold longer dendritic path, human FSINs maintain fast inhibition between connected pyramidal neurons through several mechanisms: stronger synapse strength of excitatory inputs, larger dendrite diameter with reduced complexity, faster AP initiation, and faster and larger inhibitory output, while Na+ current activation/inactivation properties are similar. These adaptations underlie short input-output delays in fast inhibition of human pyramidal neurons through FSINs, explaining how cortical synchronization frequencies are conserved despite expanded and sparse network topology of human cortex.

In Situ Characterization of 17-4PH Stainless Steel by Small-Angle Neutron Scattering.

17-4PH martensitic steel is usually used as valve stems in nuclear power plants and it suffers from thermal aging embrittlement due to long-time service in a high-temperature and high-pressure environment. Here, we characterized the evolution of microstructures at the nano-scale in 17-4PH steel by in situ small-angle neutron scattering (SANS) with a thermo-mechanically coupled loading device. The device could set different temperatures and tensile so that an in situ SANS experiment could dynamically characterize the process of nanoscale structural changes. The results showed that with increasing thermal aging time, the ε-Cu phase precipitates and grows as the temperature is 475 °C and 590 °C, and the ε-Cu phase is spherical at 475 °C but became elongated cylinders at 590 °C. Moreover, the loading stress could aid in the growth of the ε-Cu phase at 475 °C.

Ectopic expression of neuronal adenosine kinase, a biomarker in mesial temporal lobe epilepsy without hippocampal sclerosis.

AIMS: Mesial temporal lobe epilepsy without hippocampal sclerosis (no-HS MTLE) refers to those MTLE patients who have neither magnetic resonance imaging (MRI) lesions nor definite pathological evidence of hippocampal sclerosis. They usually have resistance to antiepileptic drugs, difficulties in precise seizure location and poor surgical outcomes. Adenosine is a neuroprotective neuromodulator that acts as a seizure terminator in the brain. The role of adenosine in no-HS MTLE is still unclear. Further research to explore the aetiology and pathogenesis of no-HS MTLE may help to find new therapeutic targets. METHODS: In surgically resected hippocampal specimens, we examined the maladaptive changes of the adenosine system of patients with no-HS MTLE. In order to better understand the dysregulation of the adenosine pathway in no-HS MTLE, we developed a rat model based on the induction of focal cortical lesions through a prenatal freeze injury. RESULTS: We first examined the adenosine system in no-HS MTLE patients who lack hippocampal neuronal loss and found ectopic expression of the astrocytic adenosine metabolising enzyme adenosine kinase (ADK) in hippocampal pyramidal neurons, as well as downregulation of neuronal A1 receptors (A1 Rs) in the hippocampus. In the no-HS MTLE model rats, the transition of ADK from neuronal expression to an adult pattern of glial expression in the hippocampus was significantly delayed. CONCLUSIONS: Ectopic expression of neuronal ADK might be a pathological hallmark of no-HS MTLE. Maladaptive changes in adenosine metabolism might be a novel target for therapeutic intervention in no-HS MTLE.

Dynamic evolution of the anterior cingulate-insula network during seizures.

OBJECTIVES: In physiological situations, the anterior cingulate cortex (ACC) and anterior insular cortex (AIC) are prone to coactivation. The functional connectivity and interaction between ACC and AIC in the context of epilepsy remain unclear. This study aimed to investigate the dynamic coupling between these two brain regions during seizures. METHODS: Patients who underwent stereoelectroencephalography (SEEG) recording were included in this study. The SEEG data were visually inspected and quantitatively analyzed. The narrowband oscillations and aperiodic components at seizure onset were parameterized. The frequency-specific non-linear correlation analysis was applied to the functional connectivity. The excitation/inhibition ratio (E:I ratio) reflected by the aperiodic slope was performed to evaluate the excitability. RESULTS: Twenty patients were included in the study, with 10 diagnosed with anterior cingulate epilepsy and 10 with anterior insular epilepsy. In both types of epilepsy, the correlation coefficient (h2 ) between the ACC and AIC at seizure onset exhibited a significantly higher value than that during interictal and preictal periods (p < 0.05). The direction index (D) showed a significant increase at seizure onset, serving as an indicator for the direction of information flow between these two brain regions with up to 90% accuracy. The E:I ratio increased significantly at seizure onset, with the seizure-onset zone (SOZ) demonstrating a more pronounced increase compared to non-SOZ (p < 0.05). For seizures originating from AIC, the E:I ratio was significantly higher in the AIC than in the ACC (p = 0.0364). CONCLUSIONS: In the context of epilepsy, the ACC and AIC are dynamically coupled during seizures. The functional connectivity and excitability exhibit a significant increase at seizure onset. By analyzing connectivity and excitability, the SOZ in ACC and AIC can be identified. The direction index (D) serves as an indicator for the direction of information flow from SOZ to non-SOZ. Notably, the excitability of SOZ changes more significantly than that of non-SOZ.

Effects of altered excitation-inhibition imbalance by repetitive transcranial magnetic stimulation for self-limited epilepsy with centrotemporal spikes.

Objectives: Patients with self-limited epilepsy with centrotemporal spikes (SeLECTS) with electrical status epilepticus in sleep (ESES) have generalized cognitive impairment, yet treatment options are limited. Our study aimed to examine the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on SeLECTS with ESES. In addition, we applied electroencephalography (EEG) aperiodic components (offset and slope) to investigate the improvement of rTMS on the excitation-inhibition imbalance (E-I imbalance) in the brain of this group of children. Methods: Eight SeLECTS patients with ESES were included in this study. Low-frequency rTMS (≤1 Hz) was applied for 10 weekdays in each patient. To assess the clinical efficacy and changes in E-I imbalance, EEG recordings were performed both before and after rTMS. Seizure-reduction rate and spike-wave index (SWI) were measured to investigate the clinical effects of rTMS. The aperiodic offset and slope were calculated to explore the effect of rTMS on E-I imbalance. Results: Five of the eight patients (62.5%) were seizure-free within 3 months after stimulation, with treatment effects decreasing with longer follow-ups. The SWI decreased significantly at 3 and 6 months after rTMS compared with the baseline (P = 0.0157 and P = 0.0060, respectively). The offset and slope were compared before rTMS and within 3 months after stimulation. The results showed a significant reduction in the offset after stimulation (P < 0.0001). There was a remarkable increase in slope after the stimulation (P < 0.0001). Conclusion: Patients achieved favorable outcomes in the first 3 months after rTMS. The ameliorative effect of rTMS on SWI may last up to 6 months. Low-frequency rTMS could reduce firing rates in neuronal populations throughout the brain, which was most pronounced at the site of stimulation. A significant reduction in the slope after rTMS treatment suggested an improvement in the E-I imbalance in the SeLECTS.

WPConvNet: An Interpretable Wavelet Packet Kernel-Constrained Convolutional Network for Noise-Robust Fault Diagnosis.

Deep learning (DL) has present great diagnostic results in fault diagnosis field. However, the poor interpretability and noise robustness of DL-based methods are still the main factors limiting their wide application in industry. To address these issues, an interpretable wavelet packet kernel-constrained convolutional network (WPConvNet) is proposed for noise-robust fault diagnosis, which combines the feature extraction ability of wavelet bases and the learning ability of convolutional kernels together. First, the wavelet packet convolutional (WPConv) layer is proposed, and constraints are imposed to convolutional kernels, so that each convolution layer is a learnable discrete wavelet transform. Second, a soft threshold activation is proposed to reduce the noise component in feature maps, whose threshold is adaptively learned by estimating the standard deviation of noise. Third, we link the cascaded convolutional structure of convolutional neutral network (CNN) with wavelet packet decomposition and reconstruction using Mallat algorithm, which is interpretable in model architecture. Extensive experiments are carried out on two bearing fault datasets, and the results show that the proposed architecture outperforms other diagnosis models in terms of interpretability and noise robustness.