Dual-channel fluorescent sensors based on chitosan-coated Mn-doped ZnS micromaterials to detect ampicillin.

The global threat of antibiotic resistance has increased the importance of the detection of antibiotics. Conventional methods to detect antibiotics are time-consuming and require expensive specialized equipment. Here, we present a simple and rapid biosensor for detecting ampicillin, a commonly used antibiotic. Our method is based on the fluorescent properties of chitosan-coated Mn-doped ZnS micromaterials combined with the ß-lactamase enzyme. The biosensors exhibited the highest sensitivity in a linear working range of 13.1-72.2 pM with a limit of detection of 8.24 pM in deionized water. In addition, due to the biological specificity of ß-lactamase, the proposed sensors have demonstrated high selectivity over penicillin, tetracycline, and glucose through the enhancing and quenching effects at wavelengths of 510 nm and 614 nm, respectively. These proposed sensors also showed promising results when tested in various matrices, including tap water, bottled water, and milk. Our work reports for the first time the cost-effective (Mn:ZnS)Chitosan micromaterial was used for ampicillin detection. The results will facilitate the monitoring of antibiotics in clinical and environmental contexts.

Optimization of Multiplex-PCR Technique To Determine Azf Deletions in infertility Male Patients.

Background: To optimize the multiplex polymerase chain reaction (M-PCR) technique to diagnose microdeletions of azoospermia factors (AZF) on the Y chromosome and initially apply the technique to diagnose male patients with sperm density less than 5×106 million sperm/mL was assigned to do a test to check for AZF microdeletions on the Y chromosome. Methods: Based on the positive control samples which belong to male subjects who have had 2 healthy children without any assisted reproductive technologies, the M-PCR method was developed to detect simultaneously and accurately AZF microdeletions on 32 male patients with sperm densities below 5×106 million sperm/mL of semen at the Department of Biology and Medical Genetics - Vietnam Military Medical University. Results: Successful optimization of the M-PCR technique including 7 reactions arranged according to each AZFabc region using 24 STS/gene on the Y chromosome. Initial application to diagnose AZF deletion on 32 azoospermic and oligospermic men reveals that AZFa deletion accounts for 6.25% (2/32); deletion of all 3 regions AZFa,b,c with 18.75% (6/32 cases); The combined deletion rate of AZFb,c is highest, accounting for 56.24% (18/32 patients). Conclusion: Successfully optimized the M-PCR technique in identifying AZF microdeletions using 24 sequence tagged sites (STS)/gene for azoospermic and oligozoospermic men. The M-PCR technique has great potential in the application of AZF deletion diagnosis.

Condensate-promoting ENL mutation drives tumorigenesis in vivo through dynamic regulation of histone modifications and gene expression.

Gain-of-function mutations in the histone acetylation 'reader' ENL, found in AML and Wilms tumor, are known to drive condensate formation and gene activation in cellular systems. However, their role in tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of myeloid progenitors, and triggers rapid onset of aggressive AML. Mutant ENL alters developmental and inflammatory gene programs in part by remodeling histone modifications. Mutant ENL forms condensates in hematopoietic stem/progenitor cells at key leukemogenic genes, and disrupting condensate formation via mutagenesis impairs its chromatin and oncogenic function. Moreover, treatment with an acetyl-binding inhibitor of mutant ENL displaces these condensates from target loci, inhibits mutant ENL-induced chromatin changes, and delays AML initiation and progression in vivo. Our study elucidates the function of ENL mutations in chromatin regulation and tumorigenesis, and demonstrates the potential of targeting pathogenic condensates in cancer treatment.

Structural Characterization of a Pathogenic Antibody Underlying Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT).

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but dangerous side effect of adenoviral-vectored COVID-19 vaccines. VITT had been linked to production of autoantibodies recognizing platelet factor 4 (PF4). Here, we characterize anti-PF4 antibodies obtained from a VITT patient's blood. Intact mass measurements indicate that a significant fraction of these antibodies represent a limited number of clones. MS analysis of large antibody fragments (the light chain and the Fc/2 and Fd fragments of the heavy chain) confirms the monoclonal nature of this component of the anti-PF4 antibodies repertoire and reveals the presence of a mature complex biantennary N-glycan within the Fd segment. Peptide mapping using two complementary proteases and LC-MS/MS was used to determine the amino acid sequence of the entire light chain and over 98% of the heavy chain (excluding a short N-terminal segment). The sequence analysis allows the monoclonal antibody to be assigned to the IgG2 subclass and verifies that the light chain belongs to the λ-type. Incorporation of enzymatic de-N-glycosylation into the peptide mapping routine allows the N-glycan in the Fab region of the antibody to be localized to the framework 3 region of the VH domain. This novel N-glycosylation site is the result of a single mutation within the germline sequence. Peptide mapping also provides information on lower-abundance (polyclonal) components of the anti-PF4 antibody ensemble, revealing the presence of all four subclasses (IgG1-IgG4) and both types of the light chain (λ and κ). This case study demonstrates the power of combining the intact, middle-down, and bottom-up MS approaches for meaningful characterization of ultralow quantities of pathogenic antibodies extracted directly from patients' blood.

Machine Learning Prediction of Lymph Node Metastasis in Breast Cancer: Performance of a Multi-institutional MRI-based 4D Convolutional Neural Network.

Purpose To develop a custom deep convolutional neural network (CNN) for noninvasive prediction of breast cancer nodal metastasis. Materials and Methods This retrospective study included patients with newly diagnosed primary invasive breast cancer with known pathologic (pN) and clinical nodal (cN) status who underwent dynamic contrast-enhanced (DCE) breast MRI at the authors' institution between July 2013 and July 2016. Clinicopathologic data (age, estrogen receptor and human epidermal growth factor 2 status, Ki-67 index, and tumor grade) and cN and pN status were collected. A four-dimensional (4D) CNN model integrating temporal information from dynamic image sets was developed. The convolutional layers learned prognostic image features, which were combined with clinicopathologic measures to predict cN0 versus cN+ and pN0 versus pN+ disease. Performance was assessed with the area under the receiver operating characteristic curve (AUC), with fivefold nested cross-validation. Results Data from 350 female patients (mean age, 51.7 years ± 11.9 [SD]) were analyzed. AUC, sensitivity, and specificity values of the 4D hybrid model were 0.87 (95% CI: 0.83, 0.91), 89% (95% CI: 79%, 93%), and 76% (95% CI: 68%, 88%) for differentiating pN0 versus pN+ and 0.79 (95% CI: 0.76, 0.82), 80% (95% CI: 77%, 84%), and 62% (95% CI: 58%, 67%), respectively, for differentiating cN0 versus cN+. Conclusion The proposed deep learning model using tumor DCE MR images demonstrated high sensitivity in identifying breast cancer lymph node metastasis and shows promise for potential use as a clinical decision support tool. Keywords: MR Imaging, Breast, Breast Cancer, Breast MRI, Machine Learning, Metastasis, Prognostic Prediction Supplemental material is available for this article. Published under a CC BY 4.0 license.

Controllable electronic properties, contact barriers and contact types in a TaSe2/WSe2 metal-semiconductor heterostructure.

Two-dimensional (2D) metallic TaSe2 and semiconducting WSe2 materials have been successfully fabricated in experiments and are considered as promising contact and channel materials, respectively, for the design of next-generation electronic devices. Herein, we design a metal-semiconductor (M-S) heterostructure combining metallic TaSe2 and semiconducting WSe2 materials and investigate the atomic structure, electronic properties and controllable contact types of the combined TaSe2/WSe2 M-S heterostructure using first-principles calculations. Our results reveal that the TaSe2/WSe2 M-S heterostructure can adopt four different stable stacking configurations, all of which exhibit enhanced elastic constants compared to the constituent monolayers. Furthermore, the TaSe2/WSe2 M-S heterostructure exhibits p-type Schottky contact (SC) with Schottky barriers ranging from 0.36 to 0.49 eV, depending on the stacking configurations. The TaSe2/WSe2 M-S heterostructure can be considered as a promising M-S contact for next-generation electronic Schottky devices owing to its small tunneling resistivity of about 2.14 × 10-9 Ω cm2. More interestingly, the TaSe2/WSe2 M-S heterostructure exhibits tunable contact types and contact barriers under the application of an electric field. A negative electric field induces a transition from Schottky contact type to ohmic contact (OC) type. On the other hand, a positive electric field leads to a transformation from p-type SC to n-type SC. Our findings provide valuable insights into the practical applications of the TaSe2/WSe2 M-S heterostructure towards next-generation electronic devices.

Growth patterns of preterm and small for gestational age children during the first 10 years of life.

Background: Preterm and small for gestational age (SGA) remain significant public health concerns worldwide. Yet limited evidence exists on their growth patterns during childhood from low-or middle-income countries. Objectives: We investigated the postnatal growth patterns of preterm and SGA compared to term appropriate for gestational age (AGA) children from birth to 10-11y, and examined the impact of birth status on child nutritional status during the school age years. Methods: Children born to women who participated in a double-blinded randomized controlled trial of preconception micronutrient supplementation in Vietnam were classified into three groups: preterm AGA (n = 130), full-term SGA (n = 165) and full-term AGA (n = 1,072). Anthropometric data (weight and height) were collected prospectively at birth, 3, 6, 12, 18, 24 months and at 6-7 and 10-11y. We used ANOVA and multiple regression models to examine the differences in growth patterns from birth to 10-11y as well as child undernutrition and overnutrition by birth status. Results: Children who were born preterm exhibited rapid postnatal growth, but still had lower HAZ at 1y and 2y and showed catch up to the AGA group at 6y. Compared to those born AGA, SGA infants had higher risk of thinness (BMIZ < -2) at 2y and 6y (adjusted Odds Ratio, AOR [95% CI] 2.5 [1.0, 6.1] and 2.6 [1.4, 4.6], respectively); this risk reduced at 10-11y (1.6 [0.9, 2.8]). The risk of stunting (HAZ < -2) was also 2.4 [1.5, 3.8] and 2.3 times [1.2, 4.1] higher in SGA than AGA group at ages 2y and 6-7y, respectively, with no differences at 10y. Although preterm children had higher rates of thinness and stunting at 2y compared to AGA children, these differences were not statistically significant. No associations were found between preterm or SGA and overweight /obesity at age 10-11y. Conclusion: Children who were born term-SGA continued to demonstrate deficits in weight and height during childhood whereas those born preterm showed catch-up growth by age 6-7y. Additional efforts to reduce the burden of these conditions are needed, particularly during school-age and early adolescents when children are exposed to challenging environments and have higher demands for nutrition.

Interactions and Transport of a Bioconjugated Peptide Targeting the Mitomembrane.

The Szeto-Schiller (SS) peptides are a subclass of cell-penetrating peptides that can specifically target mitochondria and mediate conditions caused by mitochondrial dysfunction. In this work, we constructed an iron-chelating SS peptide and studied its interaction with a mitochondrial-mimicking membrane using atomistic molecular dynamics (MD) simulations. We report that the peptide/membrane interaction is thermodynamically favorable, and the localization of the peptide to the membrane is driven by electrostatic interactions between the cationic residues and the anionic phospholipid headgroups. The insertion of the peptide into the membrane is driven by hydrophobic interactions between the aromatic side chains in the peptide and the lipid acyl tails. We also probed the translocation of the peptide across the membrane by applying nonequilibrium steered MD simulations and resolved the translocation pathway, free energy profile, and metastable states. We explored four distinct orientations of the peptide along the translocation pathway and found that one orientation was energetically more favorable than the other orientations. We tested a significantly slower pulling velocity on the most thermodynamically favorable system and compared metastable states during peptide translocation. We found that the peptide can optimize hydrophobic interactions with the membrane by having aromatic side chains interacting with the lipid acyl tails instead of forming π-π interactions with each other. The mechanistic insights emerging from our work will potentially facilitate improved peptide design with enhanced activity.

Disposable impedance sensors based on novel hybrid MoS2 nanosheets and microparticles to detect Escherichia Coli DNA.

The rapid and accurate detection of pathogenic bacteria is essential for food safety and public health. Conventional detection techniques, such as nucleic acid sequence-based amplification and polymerase chain reaction, are time-consuming and require specialized equipment and trained personnel. Here, we present quick, disposable impedance sensors based on the novel hybrid MoS2 nanomaterial for detecting Escherichia coli DNA. Our results indicate that the proposed sensors operate linearly between 10- 20 and 10-15 M concentrations, achieving an impressive detection limit of 10-20 M with the highest sensitivity observed at a 0.325 nM probe concentration sensor. Furthermore, the electrochemical impedance spectroscopy biosensors exhibited potential selectivity for Escherichia coli DNA over Bacillus subtilis and Vibrio proteolyticus DNA sequences. The findings offer a promising avenue for efficient and precise DNA detection, with potential implications for broader biotechnology and medical diagnostics applications.

Seasonal Change of Sediment Microbial Communities and Methane Emission in Young and Old Mangrove Forests in Xuan Thuy National Park.

Microbial communities in mangrove forests have recently been intensively investigated to explain the ecosystem function of mangroves. In this study, the soil microbial communities under young (<11 years-old) and old (>17 years-old) mangroves have been studied during dry and wet seasons. In addition, biogeochemical properties of sediments and methane emission from the two different mangrove ages were measured. The results showed that young and old mangrove soil microbial communities were significantly different on both seasons. Seasons seem to affect microbial communities more than the mangrove age does. Proteobacteria and Chloroflexi were two top abundant phyla showing >15%. Physio-chemical properties of sediment samples showed no significant difference between mangrove ages, seasons, nor depth levels, except for TOC showing significant difference between the two seasons. The methane emission rates from the mangroves varied depending on seasons and ages of the mangrove. However, this did not show significant correlation with the microbial community shifts, suggesting that abundance of methanogens was not the driving factor for mangrove soil microbial communities.

Alkali to alkaline earth metals: a DFT study of monolayer TiSi2N4 for metal ion batteries.

A significant problem in the area of rechargeable alkali ion battery technologies is the exploration of anode materials with overall high specific capacities and superior physical properties. By using first-principles calculations, we have determined that monolayer TiSi2N4 is precisely such a potential anode candidate. Its demonstrated dynamic, thermal, mechanical, and energetic stabilities make it feasible for experimental realization. An important benefit of the electrode conductivity is that the electronic structure reveals that the pristine system experiences a change from a semiconductor to a metal throughout the entire alkali adsorption process. What's more interesting is that monolayer TiSi2N4 can support up to double-sided 3-layer ad-atoms, resulting in extremely high theoretical capacities for Li, Na, Mg, and K of 1004, 854, 492 and 531 mA h g-1 and low average open-circuit voltages of 0.55, 0.25, 0.55, and -1.3 V, respectively. Alkali diffusion on the surface has been demonstrated to occur extremely quickly, with migration energy barriers for Li, Na, Mg, and K as low as 0.25, 0.14, 0.10, and 0.07 eV, respectively. The results reveal that the migration barrier energy is the lowest for Li and Mg from path-2 and Na and K from path-1. Overall, these findings suggest that monolayer TiSi2N4 is a suitable anode candidate for use in high-performance and low-cost metal-ion batteries.

Bacillus subtilis DNA fluorescent sensors based on hybrid MoS2 nanosheets.

Although sensor technology has advanced with better materials, biomarkers, and fabrication and detection methods, creating a rapid, accurate, and affordable bacterial detection platform is still a major challenge. In this study, we present a combination of hybrid-MoS2 nanosheets and an amine-customized probe to develop a fast, sensitive biosensor for Bacillus subtilis DNA detection. Based on fluorescence measurements, the biosensor exhibits a detection range of 23.6-130 aM, achieves a detection limit of 18.7 aM, and was stable over four weeks. In addition, the high selectivity over Escherichia coli and Vibrio proteolyticus DNAs of the proposed Bacillus subtilis sensors is demonstrated by the fluorescence quenching effect at 558 nm. This research not only presents a powerful tool for B. subtilis DNA detection but also significantly contributes to the advancement of hybrid 2D nanomaterial-based biosensors, offering substantial promise for diverse applications in biomedical research and environmental monitoring.

Antimicrobial resistance patterns of common Gram-negative microorganisms isolated from patients with lower respiratory tract infection in a Teaching Hospital in Vietnam.

This cross-sectional study investigated the antimicrobial resistance (AMR) patterns of Gram-negative pathogens isolated from 4,789 hospitalized patients with lower respiratory tract infections (LRTIs). Of the collected specimens, 1,325 (27.7%) specimens tested positive for Gram-negative bacteria. The most prevalent isolates were Acinetobacter baumannii (38.6%), Pseudomonas aeruginosa (33.5%), Klebsiella pneumoniae (18.7%), Escherichia coli (5.6%), and Klebsiella aerogenes (3.5%). Antimicrobial resistance analysis revealed high resistance rates among A. baumannii isolates, showing resistance (79.9%-100%) to multiple classes of antibiotics, except amikacin, trimethoprim/sulfamethoxazole, and colistin. P. aeruginosa displayed lower resistance to colistin (<10%), but resistance to other antibiotics was high. K. pneumoniae displayed elevated resistance rates against most penicillins, ranging from 90.0% to 100.0%. In contrast, the resistance rates were notably lower for colistin (7.1%) and amikacin (16.7%). K. aerogenes showed high resistance to various antibiotics, while sensitivity was observed for amikacin (95.1%), ampicillin (100.0%), and colistin (100.0%). E. coli exhibited resistance to ampicillin (96.9%) but showed maximum sensitivity to several antibiotics. The study identified significant antimicrobial resistance trends and highlighted the prevalence of multidrug-resistant strains (93.6% for K. aerogenes and 69.1%-92.4% for other isolates). These findings emphasize the urgent need for appropriate antibiotic stewardship practices to combat antimicrobial resistance in Gram-negative pathogens associated with LRTIs.

Reactive Vapor-Phase Inhibitors for Area-Selective Depositions at Tunable Critical Dimensions.

Area-selective depositions (ASD) take advantage of the chemical contrast between material surfaces in device fabrication, where a film can be selectively grown by chemical vapor deposition on metal versus a dielectric, for instance, and can provide a path to nontraditional device architectures as well as the potential to improve existing device fabrication schemes. While ASD can be accessed through a variety of methods, the incorporation of reactive moieties in inhibitors presents several advantages, such as increasing thermal stability and limiting precursor diffusion into the blocking layer. Alkyne-terminated small molecule inhibitors (SMIs)─propargyl, dipropargyl, and tripropargylamine─were evaluated as metal-selective inhibitors. Modeling these SMIs provided insight into the binding mechanism, influence of sterics, and complex polymer network formed from the reaction between inhibitors consisting of alkene, aromatic, and network branchpoints. While a significant contrast in the binding of the SMIs on copper versus a dielectric was observed, residual amounts were detected on the dielectric surfaces, leading to variable ALD growth rates dependent on pattern-critical dimensions. This behavior can be controlled and utilized to direct film growth on patterns only above a critical threshold dimension; below this threshold, both the dielectric and metal features are protected. This method provides another design parameter for ASD processes and may extend its application to broader-ranging device fabrication schemes.

Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Pasa: leveraging population pangenome graph to scaffold prokaryote genome assemblies.

Whole genome sequencing has increasingly become the essential method for studying the genetic mechanisms of antimicrobial resistance and for surveillance of drug-resistant bacterial pathogens. The majority of bacterial genomes sequenced to date have been sequenced with Illumina sequencing technology, owing to its high-throughput, excellent sequence accuracy, and low cost. However, because of the short-read nature of the technology, these assemblies are fragmented into large numbers of contigs, hindering the obtaining of full information of the genome. We develop Pasa, a graph-based algorithm that utilizes the pangenome graph and the assembly graph information to improve scaffolding quality. By leveraging the population information of the bacteria species, Pasa is able to utilize the linkage information of the gene families of the species to resolve the contig graph of the assembly. We show that our method outperforms the current state of the arts in terms of accuracy, and at the same time, is computationally efficient to be applied to a large number of existing draft assemblies.

A retrospective study of endogenous endophthalmitis-related pyogenic liver abscess: An increasing complication in North Vietnam.

Introduction: Endogenous endophthalmitis-related Klebsiella pyogenic liver abscess is a rare complication of metastatic infection. In most cases, visual acuity results are often impaired, even blind, and even with aggressive treatment with topical antibiotics, the final results are unsatisfactory. The objective of this study is to retrospectively based on medical records to describe clinical features, risk factors, and visual outcomes of patients with endogenous endophthalmitis-related pyogenic liver abscesses. Methods: We reported a case series of 12 endogenous endophthalmitis-related pyogenic liver abscess patients from March 2021 to 2023. All cases of endogenous endophthalmitis were diagnosed at admission or during the hospital stay. Results: From the medical records of 588 pyogenic liver abscess patients, we found 12 cases of endogenous endophthalmitis with 2.0%. The result showed a mean age of 61.5 ± 12.0 (41-78), diabetes mellitus (7 of 12), right lobe (7 of 12), single abscess (9 of 12), and the mean largest abscess diameter of 5.8 ± 1.7 cm (3.3-9). All patients had ocular symptoms such as eye pain (9 of 12), pus discharge (3 of 12), hypopyon (1 of 12), swollen eyelids (2 of 12), and corneal edema (2 of 12), pyogenic liver abscess before endogenous endophthalmitis (10 of 12), the median interval between endogenous endophthalmitis and pyogenic liver abscess 6.1 ± 1.9 days, ocular symptoms before diagnosis endogenous endophthalmitis 4.4 ± 2.3 days. All affected eyes were injected intravitreously with ceftazidime, amikacin, and vancomycin. Two patients underwent evisceration. Conclusions: Endogenous endophthalmitis has permanent morbidity, reducing visual acuity, poor quality of life, and lacks the warning signs, so it is essential for early detection of symptoms and referral to ophthalmologists.

Results of acute cerebral infarction treatment with hyperbaric oxygen therapy, 2020-2022.

BACKGROUND: Cerebral stroke is the third leading cause of death after cardiovascular disease, cancer and the leading cause of disability for patients. Hyperbaric oxygen is a non-drug treatment that has the potential to improve brain function for patients with ischaemic stroke. The objective of this study was to evaluate the results of treatment of acute cerebral infarction with hyperbaric oxygen therapy (HBOT). MATERIALS AND METHODS: This was a case-control study. One hundred ninety-five patients diagnosed with cerebral infarction, with signs of onset within 24 hours, were treated at the Centre for Underwater Medicine and Hyperbaric Oxygen of Vietnam National Institute of Maritime Medicine during the period from January 2020 to December 2022. Study group included 100 patients with acute cerebral infarction treated with a combination of HBOT and medication and reference group included 95 patients treated by medication only (antiplatelets drugs, statins, control of associated risks factors) RESULTS: After 7 days of treatment with hyperbaric oxygen (HBO), symptoms such as headache, dizziness, nausea, sensory disturbances, and Glasgow score of the study group improved better than that of the reference group (p < 0.01). Movement recovery in the study group was better than the reference group: the percentage of patients with mild and moderate paralysis in the study group increased higher than that of the reference group (86.0% and 68.4%), the degree of complete paralysis of the study group decreased more than that of the reference group (14.0% and 31.6%). The degree of independence in daily activities in the study group was better than the reference group. In the study group, the percentage of patients with complete independence in daily life increased from 27.0% to 84.0%. In the reference group, the rate of patients who were independent in their daily activities increased from 37.9% to 51.6%. The average number of treatment days of the study group was 10.32 ± 2.41 days and it the reference group 14.51 ± 3.24 days. CONCLUSIONS: Hyperbaric oxygen therapy is a non-drug treatment with many good effects in the treatment of cerebral infarction, especially acute cerebral infarction. HBOT reduces and improves functional symptoms, improves mobility, and reduces treatment time for patients.

Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome.

Short tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X chromosome in FXS patient-derived iPSCs, iPSC-derived neural progenitors, EBV-transformed lymphoblasts, and brain tissue with mutation-length CGG expansion. H3K9me3 domains connect via inter-chromosomal interactions and demarcate severe misfolding of TADs and loops. They harbor long synaptic genes replicating at the end of S phase, replication-stress-induced double-strand breaks, and STRs prone to stepwise somatic instability. CRISPR engineering of the mutation-length CGG to premutation length reverses H3K9me3 on the X chromosome and multiple autosomes, refolds TADs, and restores gene expression. H3K9me3 domains can also arise in normal-length iPSCs created with perturbations linked to genome instability, suggesting their relevance beyond FXS. Our results reveal Mb-scale heterochromatinization and trans interactions among loci susceptible to instability.

Reverse Engineering of a Pathogenic Antibody Reveals the Molecular Mechanism of Vaccine-Induced Immune Thrombotic Thrombocytopenia.

The massive COVID-19 vaccine roll-out campaign illuminated a range of rare side effects, the most dangerous of which─vaccine-induced immune thrombotic thrombocytopenia (VITT)─is caused by adenoviral (Ad)-vectored vaccines. VITT occurrence had been linked to the production of pathogenic antibodies that recognize an endogenous chemokine, platelet factor 4 (PF4). Mass spectrometry (MS)-based evaluation of the ensemble of anti-PF4 antibodies obtained from a VITT patient's blood indicates that the major component is a monoclonal antibody. Structural characterization of this antibody reveals several unusual characteristics, such as the presence of an N-glycan in the Fab segment and high density of acidic amino acid residues in the complementarity-determining regions. A recombinant version of this antibody (RVT1) was generated by transient expression in mammalian cells based on the newly determined sequence. It captures the key properties of VITT antibodies such as their ability to activate platelets in a PF4 concentration-dependent fashion. Homology modeling of the Fab segment reveals a well-defined polyanionic paratope, and the docking studies indicate that the polycationic segment of PF4 readily accommodates two Fab segments, cross-linking the antibodies to yield polymerized immune complexes. Their existence was verified with native MS by detecting assemblies as large as (RVT1)3(PF4)2, pointing out at FcγRIIa-mediated platelet activation as the molecular mechanism underlying VITT clinical manifestations. In addition to the high PF4 affinity, RVT1 readily binds other polycationic targets, indicating a polyreactive nature of this antibody. This surprising promiscuity not only sheds light on VITT etiology but also opens up a range of opportunities to manage this pathology.