Full adherence to cirrhosis quality indicators is associated with lower mortality in acute variceal bleeding: Nationwide audit.

BACKGROUND AND AIMS: Acute variceal bleeding (AVB) is a major complication in patients with cirrhosis. Using a nationwide AVB audit, we performed a nested cohort study to determine whether full adherence to the AVB quality indicator (QI) improves clinical outcomes in patients with cirrhosis and AVB. APPROACH AND RESULTS: We assessed real-world adherence to AVB QI among patients with cirrhosis admitted for AVB in all public hospitals in Singapore between January 2015 and December 2020. Full adherence was considered when all 5 QIs were fulfilled: prophylactic antibiotics, vasoactive agents, timely endoscopy, endoscopic hemostasis during index endoscopy, and nonselective beta-blockers after AVB. We compare 6-week mortality between the full adherence and suboptimal adherence groups using a propensity-matched cohort.A total of 989 patients with AVB were included. Full adherence to all AVB QI was suboptimal (56.5%). Analysis of the propensity-matched cohort with comparable baseline characteristics showed that full adherence was associated with a lower risk of early infection (20.0% vs. 26.9%), early rebleeding (5.2% vs. 10.2%), and mortality at 6 weeks (8.2% vs. 19.7%) and 1 year (21.3% vs. 35.4%) ( p <0.05 for all). While full adherence was associated with a lower 6-week mortality regardless of the MELD score, nonadherence was associated with a higher 6-week mortality despite a lower predicted risk of 6-week mortality. Despite high adherence to the recommended process measures, patients with CTP-C remain at a higher risk of rebleeding, 6-week and 1-year mortality. CONCLUSIONS: Full adherence to the AVB QI should be the target for quality improvement in patients with cirrhosis.

Metal Valence State Modulation Strategy to Design Core@shell Hollow Carbon Microspheres@MoSe2/MoOx Multicomponent Composites for Anti-Corrosion and Microwave Absorption.

The exploitation of multicomponent composites (MCCs) has become the main pathway for obtaining advanced microwave absorption materials (MAMs). Herein, a metal valence state modulation strategy is proposed to tune the electromagnetic (EM) parameters and improve microwave absorption performances. Core@shell hollow carbon microspheres@MoSe2 and hollow carbon microspheres@MoSe2/MoOx MCCs with various mixed-valence states content are well-designed and produced by a simple hydrothermal reaction or/and heat treatment process. The results reveal that the thermal treatment of hollow carbon microspheres@MoSe2 in Ar and Ar/H2 leads to the in situ formation of MoOx and multivalence state, respectively, and the enhanced content of Mo4+ in the designed MCCs greatly boosts their impedance matching characteristics, polarization, and conduction loss capacities, which lead to their evidently improved EM wave absorption properties. Amongst, the as-prepared hollow carbon microspheres@MoSe2/MoOx MCCs achieve an effective absorption bandwidth of 5.80 GHz under a matching thickness of 1.97 mm and minimum reflection loss of -21.49 dB. Therefore, this work offers a simple and universal method to fabricate core@shell hollow carbon microspheres@MoSe2/MoOx MCCs, and a novel and feasible metal valence state modulation strategy is proposed to develop high-efficiency MAMs.

Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity.

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

Revealing the algicidal characteristics of Maribacter dokdonensis: An investigation into bacterial strain P4 isolated from Karenia mikimotoi bloom water.

Harmful algal blooms (HABs) are a global environmental concern, causing significant economic losses in fisheries and posing risks to human health. Algicidal bacteria have been suggested as a potential solution to control HABs, but their algicidal efficacy is influenced by various factors. This study aimed to characterize a novel algicidal bacterium, Maribacter dokdonensis (P4), isolated from a Karenia mikimotoi (Hong Kong strain, KMHK) HAB and assess the impact of P4 and KMHK's doses, growth phase, and algicidal mode and the axenicity of KMHK on P4's algicidal effect. Our results demonstrated that the algicidal effect of P4 was dose-dependent, with the highest efficacy at a dose of 25% v/v. The study also determined that P4's algicidal effect was indirect, with the P4 culture and the supernatant, but not the bacterial cells, showing significant effects. The algicidal efficacy was higher when both P4 and KMHK were in the stationary phase. Furthermore, the P4 culture at the log phase could effectively kill KMHK cells at the stationary phase, with higher algicidal efficacy in the bacterial culture than that of the supernatant alone. Interestingly, P4's algicidal efficacy was significantly higher when co-culturing with xenic KMHK (~90% efficacy at day 1) than that with the axenic KMHK (~50% efficacy at day 1), suggesting the presence of other bacteria could regulate P4's algicidal effect. The bacterial strain P4 also exhibited remarkable algicidal efficacy on four other dinoflagellate species, particularly the armored species. These results provide valuable insights into the algicidal effect of M. dokdonensis on K. mikimotoi and on their interactions.

Post-sepsis psychiatric disorder: Pathophysiology, prevention, and treatment.

Post-sepsis psychiatric disorder, encompassing anxiety, depression, post-traumatic stress disorder and delirium, is a highly prevalent complication secondary to sepsis, resulting in a marked increase in long-term mortality among affected patients. Regrettably, psychiatric impairment associated with sepsis is frequently disregarded by clinicians. This review aims to summarize recent advancements in the understanding of the pathophysiology, prevention, and treatment of post-sepsis mental disorder, including coronavirus disease 2019-related psychiatric impairment. The pathophysiology of post-sepsis psychiatric disorder is complex and is known to involve blood-brain barrier disruption, overactivation of the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, neurotransmitter dysfunction, programmed cell death, and impaired neuroplasticity. No unified diagnostic criteria for this disorder are currently available; however, screening scales are often applied in its assessment. Modifiable risk factors for psychiatric impairment post-sepsis include the number of experienced traumatic memories, the length of ICU stay, level of albumin, the use of vasopressors or inotropes, daily activity function after sepsis, and the cumulative dose of dobutamine. To contribute to the prevention of post-sepsis psychiatric disorder, it may be beneficial to implement targeted interventions for these modifiable risk factors. Specific therapies for this condition remain scarce. Nevertheless, non-pharmacological approaches, such as comprehensive nursing care, may provide a promising avenue for treating psychiatric disorder following sepsis. In addition, although several therapeutic drugs have shown preliminary efficacy in animal models, further confirmation of their potential is required through follow-up clinical studies.

Recent advances in the use of optical coherence tomography in neuro-ophthalmology: A review.

Optical coherence tomography (OCT) is an in vivo imaging modality that provides non-invasive, high resolution and fast cross-sectional images of the optic nerve head, retina and choroid. OCT angiography (OCTA) is an emerging tool. It is a non-invasive, dye-free imaging approach of visualising the microvasculature of the retina and choroid by employing motion contrast imaging for blood flow detection and is gradually receiving attention for its potential roles in various neuro-ophthalmic and retinal conditions. We will review the clinical utility of the OCT in the management of various common neuro-ophthalmic and neurological disorders. We also review some of the OCTA research findings in these conditions. Finally, we will discuss the limitations of OCT as well as introduce other emerging technologies.

Facile In Situ Assembly of Nanofibers within Three-Dimensional Porous Matrices with Arbitrary Characteristics for Creating Biomimetic Architectures.

It is challenging to recapitulate the natural extracellular matrix's hierarchical nano/microfibrous three-dimensional (3D) structure with multilevel pores, good mechanical and hydrophilic properties, and excellent bioactivity for designing and developing advanced biomimetic materials. This work reports a new facile strategy for the scalable manufacturing of such a 3D architecture. Natural polymers in an aqueous solution are interpenetrated into a 3D microfibrous matrix with arbitrary shapes and property characteristics to self-assemble in situ into a nanofibrous network. The collagen fiber-like hierarchical structure and interconnected multilevel pores are achieved by self-assembly of the formed nanofibers within the 3D matrix, triggered by a simple cross-linking treatment. The as-prepared alginate/polypropylene biomimetic matrices are bioactive and have a tunable mechanical property (compressive modulus from ∼17 to ∼24 kPa) and a tunable hydrophilicity (water contact angle from ∼94° to 63°). This facile and versatile strategy allows eco-friendly and scalable manufacturing of diverse biomimetic matrices or modification of any existing porous matrices using different polymers.

Ssu72 phosphatase deficiency leads to spindle crossing during the second meiotic division process.

Ssu72 is a component of the yeast cleavage/polyadenylation factor (CPF) complex, which catalyzes the dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II at S5-P and S7-P. It has been shown that Ssu72 phosphatase is involved in regulating chromosome cohesion during mitosis. To further clarify whether Ssu72 phosphatase affects chromosome separation during meiotic division in Schizosaccharomyces pombe, we utilized green fluorescent protein (GFP) to label centromeres and red fluorescent protein to label microtubule protein Atb2. The entire meiotic chromosome separation process of ssu72∆ cells was observed in real-time under fluorescence microscope. It was found that two spindles of ssu72∆ cells crossed during the metaphase and anaphase of the second meiotic division, and this spindle crossing led to a new type of spore defect distribution pattern. The results of this study can provide important reference significance for studying the roles of phosphatase Ssu72 in higher organisms.

Kinetic Resolution Polymerization Enabled Chemical Synthesis of Perfectly Isotactic Polythioesters.

Isotactic polythioesters (PTEs) that are thioester analogs to natural polyhydroxyalkanoates (PHAs) have attracted growing attention due to their distinct properties. However, the development of chemically synthetic methods for preparing isotactic PTEs has long been an intricate endeavour. Herein, we report the successful synthesis of perfectly isotactic PTEs via stereocontrolled ring-opening polymerization. This binaphthalene-salen aluminium (SalBinam-Al) catalyst promoted a robust polymerization of rac-α-substituted-ß-propiothiolactones (rac-BTL and rac-PTL) with highly kinetic resolution, affording perfectly isotactic P(BTL) and P(PTL) with Mn up to 276 kDa. Impressively, the isotactic P(BTL) formed a supramolecular stereocomplex with improved thermal property (Tm=204 °C). Ultimately, this kinetic resolution polymerization enabled the facile isolation of enantiopure (S)-BTL, which could efficiently convert to an important pharmaceutical building block (S)-2-benzyl-3-mercapto-propanoic acid. Isotactic P(PTL) served as a tough and ductile material comparable to the commercialized polyolefins. This synthetic system allowed to access of isotactic PTEs, establishing a powerful platform for the discovery of sustainable plastics.

Tailoring Fluorescence-Phosphorescence Emission with a Single Nanocavity.

Realizing the dual emission of fluorescence-phosphorescence in a single system is an extremely important topic in the fields of biological imaging, sensing, and information encryption. However, the phosphorescence process is usually in an inherently "dark state" at room temperature due to the involvement of spin-forbidden transition and the rapid non-radiative decay rate of the triplet state. In this work, we achieved luminescent harvesting of the dark phosphorescence processes by coupling singlet-triplet molecular emitters with a rationally designed plasmonic cavity. The achieved Purcell enhancement effect of over 1000-fold allows for overcoming the triplet forbidden transitions, enabling radiation enhancement with selectable emission wavelengths. Spectral results and theoretical simulations indicate that the fluorescence-phosphorescence peak position can be intelligently tailored in a broad range of wavelengths, from visible to near-infrared. Our study sheds new light on plasmonic tailoring of molecular emission behavior, which is crucial for advancing research on plasmon-tailored fluorescence-phosphorescence spectroscopy in optoelectronics and biomedicine.

Distinct Neural Representations and Cognitive Behaviors Attributable to Naturally Developed Active Avoidance or Reactive Escape Strategies in the Male Rat.

BACKGROUND: The high individual variability in coping with stress is often attributed to genetic background differences, sustained environmental conditions, or a combination of both. However, the neural mechanisms underlying coping style variability are still poorly understood. METHODS: Here we examined the impact of a single extended emotional challenge on coping style variability and the associated involvement of the hippocampus, medial prefrontal cortex (mPFC), and periaqueductal gray (PAG). Male Sprague-Dawley rats (n = 170) were trained in an extended 2-way shuttle avoidance (eTWSA) task for 7 days, and daily avoidance rates were measured. Forced swim test, elevated plus maze, or Morris water maze was tested before or after eTWSA exposure. Excitotoxic lesion of the hippocampal dentate gyrus (DG) was performed by Ibotenic infusion. Transient pharmacological blocking of DG, mPFC, or PAG was performed by muscimol or CNQX+TTX infusion. RESULTS: Exposing rats to eTWSA was found to lead to naturally developing dichotomous, not continuous, coping styles, which we termed active avoidance (AA) or reactive escape (RE). Prior emotional responses did not predict the developing coping style. AA was associated with beneficial outcomes, including reduced behavioral despair and improved spatial learning. RE led to impaired spatial retrieval. AA was abolished by lesioning or pharmacological blocking of the DG. RE was prevented by blocking mPFC or PAG. CONCLUSION: The results indicate that a single exposure to a significant emotional challenge can lead, in otherwise healthy individuals, to dichotomous development of an active or reactive coping style with distinctive neural correlates and subsequent behavioral significance.

High killing rate of nematode and promotion of rice growth by synthetic volatiles from Bacillus strains due to enhanced oxidative stress response.

The plant parasitic nematode Aphelenchoides besseyi is a major pest that poses serious threats to different vegetables and crop plants. In the present study, volatiles isolated from Bacillus spp. were utilized as green biocontrol agents to overcome nematodes. In in vitro experiment, Bacillus spp. GBSC56, SYST2, and FZB42 showed the strongest nematicidal activity with killing rates of 80.78%, 75.69%, and 60.45%, respectively, as compared with control. The selected synthetic volatile organic compounds (VOCs), namely albuterol, benzaldehyde (BDH), 1,2-benzisothiazol-3(2H)-one (1,2-HIT), dimethyl disulfide (DMDS), 2-undecanone (2-UD), and 1,3-propanediole (1,3-PD), exhibited strong nematicidal activity, with A. besseyi killing rate of 85.58%, 82.65%, 81.75%, 80.36%, 84.45%, and 82.36%, respectively, at 400 µg/mL. Microscopic analysis proved that the rapid mortality was due to the production of reactive oxygen species (ROS). Molecular docking attributed this ROS production to the nematicidal effect of synthetic VOCs on NADH DEHYDROGENASE SUBUNIT 2, which is known to play a critical role in the suppression of ROS in nematode models. In a greenhouse experiment, the Bacillus strains GBSC56, SYST2, and FZB42 and their synthetic VOCs significantly improved the physiological parameters in terms of growth promotion traits. In addition, selected genes related to growth promotion and defense genes showed a significant upregulation of their expression in rice seedlings treated with those synthetic VOCs. Overall, these findings revealed that the selected Bacillus strains and their synthetic VOCs possess high potential against A. besseyi. Moreover, this study also sheds new light on the mechanisms by which specific Bacillus nematicidal VOCs influence important genes involved in rice plant growth promotion and could effectively be used to suppress plant parasitic nematodes.

Deep Learning System Outperforms Clinicians in Identifying Optic Disc Abnormalities.

BACKGROUND: The examination of the optic nerve head (optic disc) is mandatory in patients with headache, hypertension, or any neurological symptoms, yet it is rarely or poorly performed in general clinics. We recently developed a brain and optic nerve study with artificial intelligence-deep learning system (BONSAI-DLS) capable of accurately detecting optic disc abnormalities including papilledema (swelling due to elevated intracranial pressure) on digital fundus photographs with a comparable classification performance to expert neuro-ophthalmologists, but its performance compared to first-line clinicians remains unknown. METHODS: In this international, cross-sectional multicenter study, the DLS, trained on 14,341 fundus photographs, was tested on a retrospectively collected convenience sample of 800 photographs (400 normal optic discs, 201 papilledema and 199 other abnormalities) from 454 patients with a robust ground truth diagnosis provided by the referring expert neuro-ophthalmologists. The areas under the receiver-operating-characteristic curves were calculated for the BONSAI-DLS. Error rates, accuracy, sensitivity, and specificity of the algorithm were compared with those of 30 clinicians with or without ophthalmic training (6 general ophthalmologists, 6 optometrists, 6 neurologists, 6 internists, 6 emergency department [ED] physicians) who graded the same testing set of images. RESULTS: With an error rate of 15.3%, the DLS outperformed all clinicians (average error rates 24.4%, 24.8%, 38.2%, 44.8%, 47.9% for general ophthalmologists, optometrists, neurologists, internists and ED physicians, respectively) in the overall classification of optic disc appearance. The DLS displayed significantly higher accuracies than 100%, 86.7% and 93.3% of clinicians (n = 30) for the classification of papilledema, normal, and other disc abnormalities, respectively. CONCLUSIONS: The performance of the BONSAI-DLS to classify optic discs on fundus photographs was superior to that of clinicians with or without ophthalmic training. A trained DLS may offer valuable diagnostic aid to clinicians from various clinical settings for the screening of optic disc abnormalities harboring potentially sight- or life-threatening neurological conditions.

Loss of Hap1 selectively promotes striatal degeneration in Huntington disease mice.

Huntington disease (HD) is an ideal model for investigating selective neurodegeneration, as expanded polyQ repeats in the ubiquitously expressed huntingtin (HTT) cause the preferential neurodegeneration in the striatum of the HD patient brains. Here we report that adeno-associated virus (AAV) transduction-mediated depletion of Hap1, the first identified huntingtin-associated protein, in adult HD knock-in (KI) mouse brains leads to selective neuronal loss in the striatum. Further, Hap1 depletion-mediated neuronal loss via AAV transduction requires the presence of mutant HTT. Rhes, a GTPase that is enriched in the striatum and sumoylates mutant HTT to mediate neurotoxicity, binds more N-terminal HTT when Hap1 is deficient. Consistently, more soluble and sumoylated N-terminal HTT is presented in HD KI mouse striatum when HAP1 is absent. Our findings suggest that both Rhes and Hap1 as well as cellular stress contribute to the preferential neurodegeneration in HD, highlighting the involvement of multiple factors in selective neurodegeneration.

Significant Zr isotope variations in single zircon grains recording magma evolution history.

Zircons widely occur in magmatic rocks and often display internal zonation finely recording the magmatic history. Here, we presented in situ high-precision (2SD <0.15‰ for δ94Zr) and high-spatial-resolution (20 µm) stable Zr isotope compositions of magmatic zircons in a suite of calc-alkaline plutonic rocks from the juvenile part of the Gangdese arc, southern Tibet. These zircon grains are internally zoned with Zr isotopically light cores and increasingly heavier rims. Our data suggest the preferential incorporation of lighter Zr isotopes in zircon from the melt, which would drive the residual melt to heavier values. The Rayleigh distillation model can well explain the observed internal zoning in single zircon grains, and the best-fit models gave average zircon-melt fractionation factors for each sample ranging from 0.99955 to 0.99988. The average fractionation factors are positively correlated with the median Ti-in-zircon temperatures, indicating a strong temperature dependence of Zr isotopic fractionation. The results demonstrate that in situ Zr isotope analyses would be another powerful contribution to the geochemical toolbox related to zircon. The findings of this study solve the fundamental issue on how zircon fractionates Zr isotopes in calc-alkaline magmas, the major type of magmas that led to forming continental crust over time. The results also show the great potential of stable Zr isotopes in tracing magmatic thermal and chemical evolution and thus possibly continental crustal differentiation.

Upregulation of Peridinin-Chlorophyll A-Binding Protein in a Toxic Strain of Prorocentrum hoffmannianum under Normal and Phosphate-Depleted Conditions.

Some strains of the dinoflagellate species Prorocentrum hoffmannianum show contrasting ability to produce diarrhetic shellfish poisoning (DSP) toxins. We previously compared the okadaic acid (OA) production level between a highly toxic strain (CCMP2804) and a non-toxic strain (CCMP683) of P. hoffmannianum and revealed that the cellular concentration of OA in CCMP2804 would increase significantly under the depletion of phosphate. To understand the molecular mechanisms, here, we compared and analyzed the proteome changes of both strains growing under normal condition and at phosphate depletion using two-dimensional gel electrophoresis (2-DE). There were 41 and 33 differential protein spots observed under normal condition and phosphate depletion, respectively, of which most were upregulated in CCMP2804 and 22 were common to both conditions. Due to the lack of matched peptide mass fingerprints in the database, de novo peptide sequencing was applied to identify the differentially expressed proteins. Of those upregulated spots in CCMP2804, nearly 60% were identified as peridinin-chlorophyll a-binding protein (PCP), an important light-harvesting protein for photosynthesis in dinoflagellates. We postulated that the high expression of PCP encourages the production of DSP toxins by enhancing the yields of raw materials such as acetate, glycolate and glycine. Other possible mechanisms of toxicity related to PCP might be through triggering the transcription of non-ribosomal peptide synthetase/polyketide synthase genes and the transportation of dinophysistoxin-4 from chloroplast to vacuoles.

[Quality status of Bombyx Batryticatus and suggestions for Chinese Pharmacopoeia (2025)].

To understand the current quality status and rearing situation of Bombyx Batryticatus, the authors collected 102 batches of Bombyx Batryticatus from different main producing areas and five major Chinese medicine markets from 2016 to 2018, and measured the properties and quality of the silk gland, to clarify the quality status of Bombyx Batryticatus from different producing areas and markets. In addition, 35 batches of Bombyx Batryticatus from 2019 to 2022 were used to verify the silk gland after revision. Moreover, Beauveria Bassiana was inoculated in the silkworm of 4-5 instars, and standardized rearing was carried out until they die. The death rate and the quality of Bombyx Batryticatus were measured to determine the differences in Bombyx Batryticatus of different instars, and explore the rationality of the infection age of Bombyx Batryticatus in Chinese Pharmacopoeia(2020). The results revealed that in the 102 batches of Bombyx Batryticatus, the qualification rate of silk gland was low; the content of total ash far exceeded the standard; the content of beauvericin varied greatly. The qualification rate of the silk gland of the 35 batches of Bombyx Batryticatus was only 47.49%, which could be increased to 73.00% if the number of silk gland was 2 to 4. The death rate of Bombyx Batryticatus at different infection ages was quite different, with uneven quality. Generally, the yield of Bombyx Batryticatus inoculated on the first day of the fifth instar was high with good quality. Therefore, in combination with the quality and actual production of Bombyx Batryticatus, the following suggestions were proposed for revision of Bombyx Batryticatus in Chinese Pharmacopoeia(2025): The number of silk gland should be revised as 2-4 bright brown or bright black silk glands, after which, the quality of Bombyx Batryticatus could be guaranteed, and the "quality identification based on character" could also be reflected scientifically; the content determination index that the content of beauvericin shall not be less than 0.017% should be added to better control the quality of Bombyx Batryticatus; the infection age should be revised as the first day of the fifth instar to narrow the age span, which could better fit the actual production and ensure the quality of Bombyx Batryticatus.

Interictal dynamic network transitions in mesial temporal lobe epilepsy.

OBJECTIVE: To reveal the possible routine of brain network dynamic alterations in patients with mesial temporal lobe epilepsy (mTLE) and to establish a predicted model of seizure recurrence during interictal periods. METHODS: Seventy-nine unilateral mTLE patients with hippocampal sclerosis and 97 healthy controls from two centers were retrospectively enrolled. Dynamic brain configuration analyses were performed with resting-state functional magnetic resonance imaging (MRI) data to quantify the functional stability over time and the dynamic interactions between brain regions. Relationships between seizure frequency and ipsilateral hippocampal module allegiance were evaluated using a machine learning predictive model. RESULTS: Compared to the healthy controls, patients with mTLE displayed an overall higher dynamic network, switching mainly in the epileptogenic regions (false discovery rate [FDR] corrected p-FDR < .05). Moreover, the dynamic network configuration in mTLE was characterized by decreased recruitment (intra-network communication), and increased integration (inter-network communication) among hippocampal systems and large-scale higher-order brain networks (p-FDR < .05). We further found that the dynamic interactions between the hippocampal system and the default-mode network (DMN) or control networks exhibited an opposite distribution pattern (p-FDR < .05). Strikingly, we showed that there was a robust association between predicted seizure frequency based on the ipsilateral hippocampal-DMN dynamics model and actual seizure frequency (p-perm < .001). SIGNIFICANCE: These findings suggest that the interictal brain of mTLE is characterized by dynamical shifts toward unstable state. Our study provides novel insights into the brain dynamic network alterations and supports the potential use of DMN dynamic parameters as candidate neuroimaging markers in monitoring the seizure frequency clinically during interictal periods.

Silk Hydrogel Electrostatically Functionalized with a Polycationic Antimicrobial Peptide: Molecular Interactions, Gel Properties, and Antimicrobial Activity.

Functionalization of silk fibroin hydrogel with antimicrobial activity is essential for promoting the applications of this excellent biomaterial. In this work, a simple approach based on electrostatic interaction is adopted to produce antimicrobial silk hydrogel containing an antimicrobial peptide (AMP), polymyxin B, an important last-line antibiotic to treat multidrug-resistant bacterial superbugs. The polycationic property of this peptide and the negative charge of silk fibroin lead to strong interactions between them, as demonstrated by changes in nanofibril structure, gelation kinetics, ζ-potential, fluorescence emission, and rheological properties of the gel. The hydrogels loaded with polymyxin B demonstrated antimicrobial activity against two Gram-negative bacterial strains. A combination of the results from the different characterizations suggests that the optimal molar ratio of polymyxin B to silk fibroin is 1:2.5. As most AMPs are cationic, this electrostatic approach is suitable for the straightforward functionalization of inert silk hydrogel with other AMPs.

Oxygen Challenge Imaging Reveals Differences in Metabolic Activity Between Kurtosis Lesion and Diffusion/Kurtosis Lesion Mismatch in a Rodent Model of Acute Stroke.

OBJECTIVE: Accurate identification of potentially salvageable tissues is critical for improving acute stroke treatment. A previous study showed that the kurtosis lesion exhibited insignificant response after prompt reperfusion treatment, while the diffusion/kurtosis lesion mismatch could recover after reperfusion. We hypothesized that these 2 regions are in different metabolic states. MATERIALS AND METHODS: Transient oxygen challenge (OC) is a procedure that uses oxygen as a metabolic bio-tracer and has been performed to explore metabolic activity in tissues. We combined OC with multiparameter magnetic resonance imaging (including diffusion kurtosis imaging and T2* mapping sequences) to study metabolic activity in the ischemic brain of Sprague Dawley rats. RESULTS: Oxygen challenge image analysis revealed changes in T2* values, most significantly in the mean diffusivity (MD)/mean kurtosis (MK) lesion mismatch (22.3 ± 1.6%) and least significantly in the MK lesions (6.6 ± 0.6%). The MD images acquired within 138 ± 9 minutes after ischemia showed a larger ischemic lesion (45.5 ± 3.0% of the total area) than the MK images (33.2 ± 4.2% of the total area). The change rate of the MK value (53.0 ± 4.4%) was higher than that of the MD value (37.5 ± 3.2%). CONCLUSIONS: The present study shows that MK lesion and MD/MK lesion mismatch exhibited different metabolic activity states. The MK lesion presented metabolic-related values close to the ischemic core, while at least part of the MD/MK mismatch area was comparable with ischemic penumbra metabolic activity. These findings are important to support image-guided individualized stroke therapies.