Benchmark Glycan Profile of Therapeutic Monoclonal Antibodies Produced by Mammalian Cell Expression Systems.

PURPOSE: This study aims to establish a benchmark glycan profile for commercial therapeutic monoclonal antibodies (mAbs) approved by the US Food and Drug Administration (FDA). METHODS: We conducted a rigorous comparison of glycosylation data from the regulatory submissions for FDA-approved therapeutic antibodies up to May 2023. This analysis includes over 150 mAbs produced by various mammalian cell expression systems. RESULTS: The study identified nine prevalent glycan epitopes across all FDA-approved monoclonal antibodies produced by different expression systems. These epitopes include terminal N-acetylglucosamine, core fucose, terminal galactose, high mannose, α-galactose, terminal α2,3-linked N-acetylneuraminic acid, terminal α2,6-linked N-glycolylneuraminic acid, triantennary structure, and bisecting N-acetylglucosamine, thus establishing a benchmark glycan profile. CONCLUSIONS: The findings of this study have significant implications for therapeutic antibody development, quality control, and regulatory compliance. The benchmark glycan profile enables the assessment of glycosylation consistency and comparability across a diverse range of antibody products, ensuring improved product quality within the biopharmaceutical industry.

Angiotensin IV ameliorates doxorubicin-induced cardiotoxicity by increasing glutathione peroxidase 4 and alleviating ferroptosis.

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in cancer patients treated with DOX. Angiotensin IV (Ang IV) has multiple protective effects against cardiovascular diseases, including diabetic cardiomyopathy and myocardial infarction, but its role in DOX-induced cardiotoxicity is currently unclear. In this study, we investigated the effects of Ang IV on DOX-induced cardiotoxicity. METHODS: The viability of primary cardiomyocytes was measured by Cell Counting Kit-8 assays and Hoechst 33342/propidium iodide staining in vitro. ELISAs (serum cTnT and CK-MB) and echocardiography were performed to assess myocardial injury and cardiac function in vivo. Phalloidin staining, haematoxylin and eosin staining and wheat germ agglutinin staining were conducted to detect cardiomyocyte atrophy. We also performed C11 BODIPY staining, measured the levels of Ptgs2 and malondialdehyde and detected the concentrations of ferrous ions, glutathione and oxidized glutathione to indicate ferroptosis. RESULTS: Ang IV not only attenuated DOX-induced atrophy and cardiomyocyte injury in vitro but also alleviated myocardial injury and improved cardiac function in DOX-treated mice in vivo. Moreover, Ang IV reversed DOX-induced downregulation of glutathione peroxidase 4 (GPX4) and inhibited ferroptosis both in vitro and in vivo. Knockdown of GPX4 by siRNA abolished the cardioprotective effects of Ang IV. Furthermore, Ang IV increased GPX4 levels and ameliorated ferroptosis in RAS-selective lethal 3-treated primary cardiomyocytes. CONCLUSIONS: Ang IV ameliorates DOX-induced cardiotoxicity by upregulating GPX4 and inhibiting ferroptosis. Ang IV may be a promising candidate to protect against DOX-induced cardiotoxicity in the future.

Exploration of glycosyltransferases mutation status in cervical cancer reveals PARP14 as a potential prognostic marker.

This study investigates the potential role of Glycosyltransferases (GTs) in the glycosylation process and their association with malignant tumors. Specifically, the study focuses on PARP14, a member of GTs, and its potential as a target for tumors in the diagnosis and treatment of cervical cancer. To gather data, the study used somatic mutation data, gene expression data and clinical information from TCGA-CESE dataset as well as tissue samples from cervical cancer patients. Further verification was conducted through RT-qPCR and immunohistochemistry staining on cervical cancer tissues to confirm the expression of PARP14. The study utilized Kaplan-Meier for survival analysis of cervical cancer patient and found significant mutational abnormalities in GTs. The high frequency mutated gene was identified as PARP14. RT-qPCR revealed significantly higher mRNA expression of PARP14 compared to precancerous tissue. Using IHC combined with Kaplan-Meier,patients in the PARP14 high expression group had a better prognosis than the low expression group. The study identified PARP14 as a frequently mutated gene in cervical cancer and proposed its potential role in diagnosis and treatment.

Informed MEG/EEG source imaging reveals the locations of interictal spikes missed by SEEG.

Determining the accurate locations of interictal spikes has been fundamental in the presurgical evaluation of epilepsy surgery. Stereo-electroencephalography (SEEG) is able to directly record cortical activity and localize interictal spikes. However, the main caveat of SEEG techniques is that they have limited spatial sampling (covering <5% of the whole brain), which may lead to missed spikes originating from brain regions that were not covered by SEEG. To address this problem, we propose a SEEG-informed minimum-norm estimates (SIMNE) method by combining SEEG with magnetoencephalography (MEG) or EEG. Specifically, the spike locations determined by SEEG offer as a priori information to guide MEG source reconstruction. Both computer simulations and experiments using data from five epilepsy patients were conducted to evaluate the performance of SIMNE. Our results demonstrate that SIMNE generates more accurate source estimation than a traditional minimum-norm estimates method and reveals the locations of spikes missed by SEEG, which would improve presurgical evaluation of the epileptogenic zone.

COVID-19 update: The race to therapeutic development.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents an unprecedented challenge to global public health. At the time of this review, COVID-19 has been diagnosed in over 40 million cases and associated with 1.1 million deaths worldwide. Current management strategies for COVID-19 are largely supportive, and while there are more than 2000 interventional clinical trials registered with the U.S. National Library of Medicine (clinicaltrials.gov), results that can clarify benefits and risks of candidate therapies are only gradually becoming available. We herein describe recent advances in understanding SARS-CoV-2 pathobiology and potential therapeutic targets that are involved in viral entry into host cells, viral spread in the body, and the subsequent COVID-19 progression. We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-CoV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-CoV-2, such as REGN-COV2 (an antibody cocktail), as well as recombinant human soluble ACE2 protein to counteract SARS-CoV-2 binding to the transmembrane ACE2 receptor in target cells. Finally, we discuss potential drug resistance mechanisms and provide thoughts regarding clinical trial design to address the diversity in COVID-19 clinical manifestation. Of note, preventive vaccines, cell and gene therapies are not within the scope of the current review.

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model.

BACKGROUND: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. METHODS: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. RESULTS: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam3CSK4. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. CONCLUSIONS: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2.

Simplified HIV Testing and Treatment in China: Analysis of Mortality Rates Before and After a Structural Intervention.

BACKGROUND: Multistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality. METHODS AND FINDINGS: In the "pre-intervention 2010" (from January 2010 to December 2010) and "pre-intervention 2011" (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the "post-intervention 2012" (from July 2012 to June 2013) and "post-intervention 2013" (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6-18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27-141)/43 d (IQR 15-113) to 5 d (IQR 2-12)/5 d (IQR 2-13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239-0.620] and 0.380 [95% CI 0.233-0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226-0.603] and 0.361 [95% CI 0.221-0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52. CONCLUSIONS: Our results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART.

[The practice and discussion of the physical knowledge stepping into genetics teaching].

Genetics, one of the core courses of biological field, play a key role in biology teaching and research. In fact, there exists high similarity between many genetic knowledge and physical knowledge. Due to strong abstract of genetic contents and the weak basis of genetics, some students lack of interests to study genetics. How to apply the strong physical knowledge which students had been learned in the middle school in genetics teaching is worthwhile for genetics teachers. In this paper, we would like to introduce an infiltrative teaching model on applying physical knowledge into genetic contents by establishing the intrinsic logistic relationship between physical knowledge and genetic knowledge. This teaching model could help students more deeply understand genetic knowledge and enhance students' self-studying ability as well as creating ability.

A tailored lectin microarray for rapid glycan profiling of therapeutic monoclonal antibodies.

Glycosylation plays a crucial role in determining the quality and efficacy of therapeutic antibodies. This necessitates a thorough analysis and monitoring process to ensure consistent product quality during manufacturing. In this study, we introduce a custom-designed lectin microarray featuring nine distinct lectins: rPhoSL, rOTH3, RCA120, rMan2, MAL_I, rPSL1a, PHAE, rMOA, and PHAL. These lectins have been specifically tailored to selectively bind to common N-glycan epitopes found in therapeutic IgG antibodies. By utilizing intact glycoprotein samples, our nine-lectin microarray provides a high-throughput platform for rapid glycan profiling, enabling comparative analysis of glycosylation patterns. Our results demonstrate the practical utility of this microarray in assessing glycosylation across various manufacturing batches or between biosimilar and innovator products. This capacity empowers informed decision-making in the development and production of therapeutic antibodies.

Constructing a Highly Robust Interface Film for Enhancing Rate Performance of Graphite Anode via a Novel Electrolyte Additive.

Solid electrolyte interphase (SEI) is regarded as a key factor to enable high power outputs of Lithium-ion batteries (LIBs). Herein, we demonstrate a modified electrolyte consisting of a novel electrolyte additive, 1H,1H,2H,2H-perfluorooctyltrimethoxysilane (FTMS) to construct a highly robust and stable SEI on a graphite anode for LIBs to enhance its rate performance. With 2% FTMS, the anode presents an improved capacity retention from 77.6 to 91.2% at 0.5 C after 100 cycles and an improved capacity from 86 to 229 mAh g-1 at 2 C. Experimental characterizations and theoretical calculations reveal that FTMS is preferentially absorbed and reduced on graphite to construct an interface chemistry with uniform fluoride-containing organic lithium salt and silicon-containing polymer, which exhibits high flexibility and conductivity and endows the SEI with high robustness and stability. This work provides an effective way to address the issue of slow lithium insertion/desertion kinetics of graphite anodes.

Metabolic profiling integrated with pharmacokinetics to reveal the material basis of Xiaokeyinshui extract combination in the treatment of type 2 diabetes in rats.

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.

Implanted cardiac pacemaker pulses as recorded from the body surface.

This study investigates the characteristics of contemporary pacemaker pulses as recorded from the body surface. Twelve-lead paced ECGs from 140 patients (68 ± 12 years, 71% males) were collected at 32,000 samples per second. Pacer pulses were manually annotated based on the high-sampling rate data stream. The results show that durations of the various pulses are stable, while amplitudes exhibit large variations. Also, more than 50% of pulses have either durations <0.5 ms or amplitudes <2 mV, which are the AAMI/IEC thresholds for detection and marking of pacemaker pulses on an ECG report. Therefore the current standards for pacemaker pulse detection are not fit for purpose and require to be updated. Further, this study suggests that a high-sampling rate database should be used as a standard test for pacemaker annotation and detection from body surface ECGs.

Proanthocyanidins-loaded complex coacervates-based drug delivery attenuates oral squamous cell carcinoma cells metastatic potential through down-regulating the Akt signaling pathway.

Oral cancer, constituted up to 90% by squamous cell carcinomas, is a significant health burden globally. Grape seed proanthocyanidins (PA) have been suggested as a potential chemopreventive agent for oral cancer. However, their efficacy can be restricted due to the low bioavailability and bioaccessibility. Inspired by sandcastle worm adhesive, we adapted the concept of complex coacervation to generate a new type of drug delivery platform. Complex coacervates are a dense liquid phase formed by the associative separation of a mixture of oppositely charged polyelectrolytes, can serve as a drug delivery platform to protect labile cargo. In this study, we developed a complex coacervates-based delivery of PA. The release kinetics was measured, and anticancer effects were determined in two human tongue squamous cell carcinoma cell lines. The results showed that complex coacervate successfully formed and able to encapsulate PA. Additionally, PA were steadily released from the system in a pH-dependent manner. The drug delivery system could significantly inhibit the cell proliferation, migration, and invasion of cancer cells. Moreover, it could markedly reduce the expression of certain matrix metalloproteinases (MMP-2, 9, and 13) crucial to metastatic processes. We also found that suppression of protein kinase B (Akt) pathway might be the underlying mechanism for these anticancer activities. Taken together, complex coacervates-based delivery of PA can act as an effective anticancer approach for oral cancer therapy.

Balance of Macrophage Activation by a Complex Coacervate-Based Adhesive Drug Carrier Facilitates Diabetic Wound Healing.

Uncontrolled and sustained inflammation disrupts the wound-healing process and produces excessive reactive oxygen species, resulting in chronic or impaired wound closure. Natural antioxidants such as plant-based extracts and natural polysaccharides have a long history in wound care. However, they are hard to apply to wound beds due to high levels of exudate or anatomical sites to which securing a dressing is difficult. Therefore, we developed a complex coacervate-based drug carrier with underwater adhesive properties that circumvents these challenges by enabling wet adhesion and controlling inflammatory responses. This resulted in significantly accelerated wound healing through balancing the pro- and anti-inflammatory responses in macrophages. In brief, we designed a complex coacervate-based drug carrier (ADC) comprising oligochitosan and inositol hexaphosphate to entrap and release antioxidant proanthocyanins (PA) in a sustained way. The results from in vitro experiments demonstrated that ADC is able to reduce LPS-stimulated pro-inflammatory responses in macrophages. The ability of ADC to reduce LPS-stimulated pro-inflammatory responses in macrophages is even more promising when ADC is encapsulated with PA (ADC-PA). Our results indicate that ADC-PA is able to polarize macrophages into an M2 tissue-healing phenotype via up-regulation of anti-inflammatory and resolution of inflammatory responses. Treatment with ADC-PA around the wound beds fine-tunes the balance between the numbers of inducible nitric oxide synthase-positive (iNOS+) and mannose receptor-negative (CD206-) M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment compared to controls. Achieving such a balance between the numbers of iNOS+CD206- M1 and iNOS-CD206+ M2 macrophages in the wound microenvironment has led to significantly improved wound closure in mouse models of diabetes, which exhibit severe impairments in wound healing. Together, our results demonstrate for the first time the use of a complex coacervate-based drug delivery system to promote timely resolution of the inflammatory responses for diabetic wound healing by fine-tuning the functions of macrophages.

Targeting cancer with antibody-drug conjugates: Promises and challenges.

Antibody-drug conjugates (ADCs) are a rapidly expanding class of biotherapeutics that utilize antibodies to selectively deliver cytotoxic drugs to the tumor site. As of May 2021, the U.S. Food and Drug Administration (FDA) has approved ten ADCs, namely Adcetris®, Kadcyla®, Besponsa®, Mylotarg®, Polivy®, Padcev®, Enhertu®, Trodelvy®, Blenrep®, and Zynlonta™ as monotherapy or combinational therapy for breast cancer, urothelial cancer, myeloma, acute leukemia, and lymphoma. In addition, over 80 investigational ADCs are currently being evaluated in approximately 150 active clinical trials. Despite the growing interest in ADCs, challenges remain to expand their therapeutic index (with greater efficacy and less toxicity). Recent advances in the manufacturing technology for the antibody, payload, and linker combined with new bioconjugation platforms and state-of-the-art analytical techniques are helping to shape the future development of ADCs. This review highlights the current status of marketed ADCs and those under clinical investigation with a focus on translational strategies to improve product quality, safety, and efficacy.

The fight against COVID-19: Striking a balance in the renin-angiotensin system.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by interacting with membrane-bound angiotensin-converting enzyme 2 (ACE2), a vital element in the renin-angiotensin system (RAS), which regulates blood pressure, fluid balance, and cardiovascular functions. We herein evaluate existing evidence for the molecular alterations within the RAS pathway (e.g., ACE2 and angiotensin II) during SARS-CoV-2 infection and subsequent Coronavirus Disease 2019 (COVID-19). This includes reports regarding potential effect of RAS blockade (e.g., ACE inhibitors and angiotensin II receptor blockers) on ACE2 expression and clinical outcomes in patients with co-morbidities commonly treated with these agents. The collective evidence suggests a dual role for ACE2 in COVID-19, depending on the stage of infection and the coexisting diseases in individual patients. This information is further discussed with respect to potential therapeutic strategies targeting RAS for COVID-19 treatment.

Novel green soybean shuidouchi fermented by Bacillus velezensis with multibioactivities.

Soybeans are usually fermented by Bacillus subtilis to produce shuidouchi, which is a traditional fermentation soybean product in China. In the study, green soybeans were fermented by Bacillus velezensis to make a novel green soybean shuidouchi with multibioactivities. The processing conditions were optimized as follows: initial moisture content 75%, inoculum concentration 7 log CFU/g, and incubation time 24 h for prefermentation; water addition 50%, salt addition 6%, temperature 45°C, 3 days for postfermentation. The fermented green soybean shuidouchi (FGSS) showed 234.8 FU/g dry weight (DW) for the fibrinolytic activity and IC50 of 0.33 mg/ml for the anticoagulant activity. FGSS had higher contents of chemical components including 3.6 mg rutin (RE)/g DW of total flavonoids, 8.2 mg gallic acid (GAE)/g DW of total phenolics, 63.7 mg/g DW of reducing sugars, and 163.8 mg/g DW of peptides than the unfermented green soybean shuidouchi (UGSS). Moreover, it exhibited high antioxidant activities of 29.8, 85.1 µmol trolox equivalent (TE)/g DW, and 12.8 µmol Fe2+/g DW through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), and ferric reducing antioxidant power (FRAP) experiments. Thus, a novel green soybean shuidouchi fermented by B. velezensis owing to multibioactivities can provide a theoretical basis for the further development of functional shuidouchi.

Magnetoencephalography STOUT Method Adapted to Radiofrequency Thermocoagulation for MR-Negative Insular Epilepsy: A Case Report.

Epilepsy is one of the most challenging neurologic diseases confronted by human society. Approximately 30-40% of the worldwide epilepsy patients are diagnosed with drug-resistant epilepsy and require pre-surgery evaluation. Magnetoencephalography (MEG) is a unique technology that provides optimal spatial-temporal resolution and has become a powerful non-invasive imaging modality that can localize the interictal spikes and guide the implantation of intracranial electrodes. Currently, the most widely used MEG source estimation method for clinical applications is equivalent current dipoles (ECD). However, ECD has difficulties in precisely locating deep sources such as insular lobe. In contrast to ECD, another MEG source estimation method named spatio-temporal unifying tomography (STOUT) with spatial sparsity has particular advantages in locating deep sources. In this case study, we recruited a 5 year-old female patient with insular lobe epilepsy and her seizure recurred in 1 year after receiving the radiofrequency thermocoagulation (RF-TC) therapy. The STOUT method was adopted to locate deep sources for identifying the epileptic foci in epilepsy evaluation. MEG STOUT method strongly supported a stereo-electroencephalographic (SEEG)-guided RF-TC operation, and the patient reported a satisfactory therapeutic effect. This case raises the possibility that STOUT method can be used particularly for the localization of deep sources, and successfully conducted RF-TC under the guidance of MEG STOUT results.

Methionine in proteins defends against oxidative stress.

A variety of reactive oxygen species react readily with methionine residues in proteins to form methionine sulfoxide, thus scavenging the reactive species. Most cells contain methionine sulfoxide reductases, which catalyze a thioredoxin-dependent reduction of methionine sulfoxide back to methionine. Thus, methionine residues may act as catalytic antioxidants, protecting both the protein where they are located and other macromolecules. To test this hypothesis directly, we replaced 40% of the methionine residues in Escherichia coli with norleucine, the carbon-containing analog, in which the sulfur of methionine is substituted by a methylene group (-CH2-). The intracellular free methionine and S-adenosylmethionine pools were not altered, nor was the specific activity of the key enzyme, glutamine synthetase. When unstressed, both control and norleucine-substituted cells survived equally well at stationary phase for at least 32 h. However, oxidative stress was more damaging to the norleucine-substituted cells. They died more rapidly than control cells when challenged by hypochlorite, hydrogen peroxide, or ionizing radiation. One of the most abundant proteins in the cell, elongation factor Tu, was found to be more oxidatively modified in norleucine-substituted cells, consistent with loss of the antioxidant defense provided by methionine residues. The results of these studies support the hypothesis that methionine in protein acts as an endogenous antioxidant in cells.

A review of electrocardiogram filtering.

Analog filtering and digital signal processing algorithms in the preprocessing modules of an electrocardiographic device play a pivotal role in providing high-quality electrocardiogram (ECG) signals for analysis, interpretation, and presentation (display, printout, and storage). In this article, issues relating to inaccuracy of ECG preprocessing filters are investigated in the context of facilitating efficient ECG interpretation and diagnosis. The discussion covers 4 specific ECG preprocessing applications: anti-aliasing and upper-frequency cutoff, baseline wander suppression and lower-frequency cutoff, line frequency rejection, and muscle artifact reduction. Issues discussed include linear phase, aliasing, distortion, ringing, and attenuation of desired ECG signals. Due to the overlapping power spectrum of signal and noise in acquired ECG data, frequency selective filters must seek a delicate balance between noise removal and deformation of the desired signal. Most importantly, the filtering output should not adversely impact subsequent diagnosis and interpretation. Based on these discussions, several suggestions are made to improve and update existing ECG data preprocessing standards and guidelines.