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Robotic rehabilitation is a high-intensity intervention for upper limb paralysis after a stroke. This study explored the safety and feasibility of using a single-joint hybrid assistive limb (HAL-SJ) exoskeletal device for upper limb paralysis in patients with acute stroke. In total, 11 patients with stroke (6 with moderate paralysis and 5 with severe paralysis) were enrolled between October 2021 and October 2023 in a stroke care unit. The patients underwent HAL training 3 times a week for 6 sessions. No serious adverse events related to HAL-SJ occurred, and participants demonstrated significant improvements in the Fugl-Meyer Assessment Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT) (pre- vs. post-intervention; p < 0.05). The minimal clinically important difference (MCID) for FMA-UE was surpassed in 5 patients (83.3%) with moderate paralysis and 2 (40.0%) with severe paralysis. Regarding ARAT, 4 patients (66.7%) with moderate paralysis exceeded the MCID, whereas none (0.0%) with severe paralysis did. These findings suggest that HAL-SJ is both safe and feasible, particularly for individuals with moderate paralysis.

Per Food and Drug Administration (FDA) regulation, pembrolizumab can be administered as a 200mg dose every 3 weeks (Q3W) or as a 400mg dose every 6 weeks (Q6W) for various cancers. Little to no literature exists on time toxicity and transportation-related out-of-pocket expenditure for patients when considering the frequency of pembrolizumab infusions. We aimed to model differences in time toxicity and transportation costs between the status quo and institutionalized transitions to Q6W infusions for patients receiving care at United States (US) Veteran's Affairs (VA) hospitals using a simulation-based approach. Data was extracted from VA medical records of patients who received pembrolizumab infusions with or without chemotherapy or a tyrosine kinase inhibitor (TKI). Extracted data included driving distance from patient residence to the hospital, driving duration, type of infusion (pembrolizumab ± chemotherapy ± TKI), location of infusion site, and infusion dates. Distance and time data was extrapolated into scenarios defined by 1) pembrolizumab ± chemotherapy ± TKI transitioning to Q6W, i.e. "universal Q6W infusions" and 2) pembrolizumab-only infusions transitioning to Q6W, i.e. "monotherapy Q6W infusions." Gasoline expenditure was calculated as a multiplied product of patient driving distance, location-specific, monthly average gasoline price data from 2003 to 2023 and average light-duty US car fuel efficiency data published by US government agencies. Time toxicity was calculated as the sum of cumulative and per-infusion driving durations with published estimates of pembrolizumab infusion duration and associated duration of patient visits in the Q3W and Q6W setting. 7891 patients spanning 102 VA hospitals underwent treatment with pembrolizumab, comprising a total of 58639 infusions. Each hospital treated, on average, 77 (± 55) patients and delivered an average of 575 (± 421) infusions. Compared to the status quo, the mean total driving time for a complete treatment course was 71.4 minutes less per patient with a transition to universal Q6W infusions and 70.1 minutes less per patient with a transition to monotherapy Q6W infusions. Compared to the status quo, transitioning to universal and monotherapy Q6W infusions saved an average of 9.09 USD and 8.96 USD per patient respectively in gasoline costs for an entire treatment course. Additionally, transitioning to universal and monotherapy Q6W infusions saved an average of 361 minutes and 332 minutes per patient respectively for a complete treatment course. Our models show that transitioning from Q3W to Q6W infusions of pembrolizumab ± chemotherapy ± TKI lowers both transportation-related costs and time toxicity in VA patients. As such, Q6W infusions may represent a more cost-effective means of treatment delivery if deemed clinically appropriate. [ABSTRACT FROM AUTHOR]

We report on the electrical, ferroelectric, and magnetic properties of BiFeO3 (BFO)-La0.7Sr0.3MnO3 heterostructures deposited epitaxially onto Si(100) substrates. Temperature dependent (200-350 K) current-voltage (I-V), switching spectroscopy piezo-response force microscopy (SSPFM), and temperature dependent (5-300 K) anisotropic magnetization measurements have been performed. The BFO (100-nm thick)-based device structures were fabricated with a 250nm thick La0.7Sr0.3MnO3 bottom electrode and 200 lm circular top Pt electrodes. I-V measurements performed at various temperatures indicated that the devices retained their as-deposited characteristics and exhibited non-leaky behavior up to at least 50 cycles. The temperature-dependent measurements showed clear diode-like behavior and resistive (hysteretic) switching behaviour. Characteristic butterfly loops (of several cycles) were observed in the PFM amplitude signals of the BFofilm. In addition, the phase signal indicated a clear (180°) switching behavior at the switching voltage of 4-5V, providing unambiguous evidence for the occurrence of ferroelectricity in BFofilms integrated on Si (100). The temperature- and angledependent zerofield cooled isothermal (5 K) magnetization measurements were consistent with the presence of uniaxial magnetic anisotropy. This work makes an important step for the fabrication of CMOS-compatible BFO devices for memory applications. [ABSTRACT FROM AUTHOR]

We report the formation of NiO based single crystalline p-n junctions with enhanced photocatalytic activity induced by pulsed laser irradiation. The NiO epilayers were grown on Si(001) substrates buffered with cubic yttria-stabilized zirconia (c-YSZ) by using pulsed laser deposition. The NiO/c-YSZ/Si heterostructures were subsequently laser treated by 5 pulses of KrF excimer laser (pulse duration = 25 × 10-9 s) at lower energies. Microstructural studies, conducted by X-ray diffraction (θ-2θ and φ techniques) and high resolution transmission electron microscope, showed a cube-on-cube epitaxial relationship at the c-YSZ/Si interface; the epitaxial relationship across the NiO/c-YSZ interface was established as NiO<111 >||c-YSZ<001> and in-plane NiO<110>||c-YSZ<100>. Electron microscopy studies showed that the interface between the laser annealed and the pristine region as well as the NiO/c-YSZ interface was atomically sharp and crystallographically continuous. The formation of point defects, namely oxygen vacancies and NiO, due to the coupling of the laser photons with the NiO epilayers was confirmed by XPS. The p-type electrical characteristics of the pristine NiO epilayers turned to an n-type behavior and the electrical conductivity was increased by one order of magnitude after laser treatment. Photocatalytic activity of the pristine (p-NiO/c-YSZ/Si) and the laser-annealed (n-NiO/p-NiO/c-YSZ/Si) heterostructures were assessed by measuring the decomposition rate of 4-chlorophenol under UV light. The photocatalytic reaction rate constants were determined to be 0.0059 and 0.0092 min-1 for the as-deposited and the laser-treated samples, respectively. The enhanced photocatalytic efficiency was attributed to the suppressed charge carrier recombination in the NiO based p-n junctions and higher electrical conductivity. Besides, the oxygen vacancies ease the adsorption of 4-chlorophenol, hydroxyl, and water molecules to the surface. Thus, n-NiO/p-NiO single crystalline catalysts can be introduced as a potent candidate to remediate the environmental pollution. [ABSTRACT FROM AUTHOR]

Abstract The nervous system of the Asteroidea (starfish or seastar) consists of radial nerve cords (RNCs) that interconnect with a ring nerve. Despite its relative simplicity, it facilitates the movement of multiple arms and numerous tube feet, as well as regeneration of damaged limbs. Here, we investigated the RNC ultrastructure and its molecular components within the of Pacific crown-of-thorns starfish (COTS; Acanthaster sp.), a well-known coral predator that in high-density outbreaks has major ecological impacts on coral reefs. We describe the presence of an array of unique small bulbous bulbs (40–100 μm diameter) that project from the ectoneural region of the adult RNC. Each comprise large secretory-like cells and prominent cilia. In contrast, juvenile COTS and its congener Acanthaster brevispinus lack these features, both of which are non-corallivorous. Proteomic analysis of the RNC (and isolated neural bulbs) provides the first comprehensive echinoderm protein database for neural tissue, including numerous secreted proteins associated with signalling, transport and defence. The neural bulbs contained several neuropeptides (e.g., bombyxin-type, starfish myorelaxant peptide, secretogranin 7B2-like, Ap15a-like, and ApNp35) and Deleted in Malignant Brain Tumor 1-like proteins. In summary, this study provides a new insight into the novel traits of COTS, a major pest on coral reefs, and a proteomics resource that can be used to develop (bio)control strategies and understand molecular mechanisms of regeneration.

Some promoters, termed Epromoters, can display enhancer activity and regulate distal genes in their endogenous context. Here the authors report the broad involvement of Epromoters in the coordinated activation of interferon (IFN) response. They show activation of a number of IFN-inducible genes is a result of Epromoters regulating expression of an entire IFN response gene cluster.

Ascidians accumulate extremely high levels of vanadium (V) in their blood cells. Several V-related proteins, including V-binding proteins (vanabins), have been isolated from V-accumulating ascidians. In this study, to obtain a deeper understanding of vanabins, we performed de novo transcriptome analysis of blood cells from a V-rich ascidian, Ascidia sydneiensis samea, and constructed a database containing 8532 predicted proteins. We found a novel vanabin with a unique acidic amino acid–rich C-terminal domain, designated VanabinX, in the database and studied it in detail. Reverse-transcription polymerase chain reaction analysis revealed that VanabinX was detected in all adult tissues examined, and was most prominent in blood cells and muscle tissue. We prepared recombinant proteins and performed immobilized metal ion affinity chromatography and a NADPH-coupled V(V)-reductase assay. VanabinX bound to metal ions, with increasing affinity for Cu(II) > Zn(II) > Co(II), but not to V(IV). VanabinX reduced V(V) to V(IV) at a rate of 0.170 μM per micoromolar protein within 30 min. The C-terminal acidic domain enhanced the reduction of V(V) by Vanabin2 to 1.3-fold and of VanabinX itself to 1.7-fold in trans mode. In summary, we constructed a protein database containing 8532 predicted proteins expressed in blood cells; among them, we discovered a novel vanabin, VanabinX, which enhances V reduction by vanabins.

All the currently used type A botulinum neurotoxins for clinical uses are of subtype A1. We compared the efficacy and safety for the first time head-to-head between a novel botulinum toxin A2NTX prepared from subtype A2 and onabotulinumtoxinA (BOTOX) derived from A1 for post-stroke spasticity. We assessed the modified Ashworth scale (MAS) of the ankle joint, the mobility scores of Functional Independence Measure (FIM), and the grip power of the unaffected hand before and after injecting 300 units of BOTOX or A2NTX into calf muscles. The procedure was done in a blinded manner for the patient, the injecting physician, and the examiner. Stroke patients with chronic spastic hemiparesis (15 for A2NTX and 16 for BOTOX) were enrolled, and 11 for A2NTX and 13 for BOTOX (MAS of ankle; > or = 2) were entered for the MAS study. Area-under-curves of changes in MAS (primary outcome) were greater for A2NTX by day 30 (p = 0.044), and were similar by day 60. FIM was significantly improved in the A2NTX group (p = 0.005), but not in the BOTOX group by day 60. The hand grip of the unaffected limb was significantly decreased in the BOTOX-injected group (p = 0.002), but was unaffected in the A2NTX-injected group by day 60, suggesting there was less spread of A2NTX to the upper limb than there was with BOTOX. Being a small-sized pilot investigation with an imbalance in the gender of the subjects, the present study suggested superior efficacy and safety of A2NTX, and warrants a larger scale clinical trial of A2NTX to confirm these preliminary results.

Some sea slugs sequester chloroplasts from algal food in their intestinal cells and photosynthesize for months. This phenomenon, kleptoplasty, poses a question of how the chloroplast retains its activity without the algal nucleus. There have been debates on the horizontal transfer of algal genes to the animal nucleus. To settle the arguments, this study reported the genome of a kleptoplastic sea slug, Plakobranchus ocellatus, and found no evidence of photosynthetic genes encoded on the nucleus. Nevertheless, it was confirmed that light illumination prolongs the life of mollusk under starvation. These data presented a paradigm that a complex adaptive trait, as typified by photosynthesis, can be transferred between eukaryotic kingdoms by a unique organelle transmission without nuclear gene transfer. Our phylogenomic analysis showed that genes for proteolysis and immunity undergo gene expansion and are up-regulated in chloroplast-enriched tissue, suggesting that these molluskan genes are involved in the phenotype acquisition without horizontal gene transfer.

VO2(010)/NiO(111) epitaxial heterostructures were integrated with Si(100) substrates using a cubic yttria-stabilized zirconia (c-YSZ) buffer. The epitaxial alignment across the interfaces was determined to be VO2(010)|NiO(111)|c-YSZ(001)|Si(001) and VO2[100]|NiO<110>|c-YSZ<100>|Si<100>. The samples were subsequently treated by a single shot of a nanosecond KrF excimer laser. Pristine as-deposited film showed diamagnetic behavior, while laser annealed sample exhibited ferromagnetic behavior. The population of majority charge carriers (e-) and electrical conductivity increased by about two orders of magnitude following laser annealing. These observations are attributed to the introduction of oxygen vacancies into the VO2 thin films and the formation of V3+ defects. [ABSTRACT FROM AUTHOR]

The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-throughput enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus.

Umbilical vein catheterisation is a very common procedure in Neonatal Intensive Care Units. The tip of the umbilical vein catheter (UVC) should be located at the junction of inferior vena cava and right atrium, which is confirmed by an abdominal radiography or ultrasonography. The tip of the UVC can migrate to a different position because of a myriad of reasons. If hypertonic solutions are infused through an UVC which is malpositioned in the liver, it can result in serious complications. This is a case series of three neonates with malpositioned UVC and the resultant clinical presentations along with the characteristic ultrasonographic findings.

Many multicellular organisms rely on symbiotic associations for support of metabolic activity, protection, or energy. Understanding the mechanisms involved in controlling such interactions remains a major challenge. In an unbiased approach we identified key players that control the symbiosis between Hydra viridissima and its photosynthetic symbiont Chlorella sp. A99. We discovered significant up-regulation of Hydra genes encoding a phosphate transporter and glutamine synthetase suggesting regulated nutrition supply between host and symbionts. Interestingly, supplementing the medium with glutamine temporarily supports in vitro growth of the otherwise obligate symbiotic Chlorella, indicating loss of autonomy and dependence on the host. Genome sequencing of Chlorella sp. A99 revealed a large number of amino acid transporters and a degenerated nitrate assimilation pathway, presumably as consequence of the adaptation to the host environment. Our observations portray ancient symbiotic interactions as a codependent partnership in which exchange of nutrients appears to be the primary driving force.

Genome sequences of the reef-building coral, Acropora digitifera, have been decoded. Acropora inhabits an environment with intense ultraviolet exposure and hosts the photosynthetic endosymbiont, Symbiodinium. Acropora homologs of all four genes necessary for biosynthesis of the photoprotective cyanobacterial compound, shinorine, are present. Among metazoans, these genes are found only in anthozoans. To gain further evolutionary insights into biosynthesis of photoprotective compounds and associated coral proteins, we surveyed the Acropora genome for 18 clustered genes involved in cyanobacterial synthesis of the anti-UV compound, scytonemin, even though it had not previously been detected in corals. We identified candidates for only 6 of the 18 genes, including tyrP, scyA, and scyB. Therefore, it does not appear that Acropora digitifera can synthesize scytonemin independently. On the other hand, molecular phylogenetic analysis showed that one tyrosinase gene is an ortholog of vertebrate tyrosinase genes and that the coral homologs, scyA and scyB, are similar to bacterial metabolic genes, phosphonopyruvate (ppyr) decarboxylase and glutamate dehydrogenase (GDH), respectively. Further genomic searches for ppyr gene-related biosynthetic components indicate that the coral possesses a metabolic pathway similar to the bacterial 2-aminoethylphosphonate (AEP) biosynthetic pathway. The results suggest that de novo synthesis of carbon-phosphorus compounds is performed in corals.

The aim of this study was first to identify lysozymes paralogs in the deep sea mussel Bathymodiolus azoricus then to measure their relative expression or activity in different tissue or conditions. B. azoricus is a bivalve that lives close to hydrothermal chimney in the Mid-Atlantic Ridge (MAR). They harbour in specialized gill cells two types of endosymbiont (gram-bacteria): sulphide oxidizing bacteria (SOX) and methanotrophic bacteria (MOX). This association is thought to be ruled by specific mechanism or actors of regulation to deal with the presence of symbiont but these mechanisms are still poorly understood. Here, we focused on the implication of lysozyme, a bactericidal enzyme, in this endosymbiosis. The relative expression of Ba-lysozymes paralogs and the global anti-microbial activity, were measured in natural population (Lucky Strike--1700 m, Mid-Atlantic Ridge), and in in situ experimental conditions. B. azoricus individuals were moved away from the hydrothermal fluid to induce a loss of symbiont. Then after 6 days some mussels were brought back to the mussel bed to induce a re-acquisition of symbiotic bacteria. Results show the presence of 6 paralogs in B. azoricus. In absence of symbionts, 3 paralogs are up-regulated while others are not differentially expressed. Moreover the global activity of lysozyme is increasing with the loss of symbiont. All together these results suggest that lysozyme may play a crucial role in symbiont regulation.

Bathymodiolus mussels live in symbiosis with intracellular sulfur-oxidizing (SOX) bacteria that provide them with nutrition. We sequenced the SOX symbiont genomes from two Bathymodiolus species. Comparison of these symbiont genomes with those of their closest relatives revealed that the symbionts have undergone genome rearrangements, and up to 35% of their genes may have been acquired by horizontal gene transfer. Many of the genes specific to the symbionts were homologs of virulence genes. We discovered an abundant and diverse array of genes similar to insecticidal toxins of nematode and aphid symbionts, and toxins of pathogens such as Yersinia and Vibrio. Transcriptomics and proteomics revealed that the SOX symbionts express the toxin-related genes (TRGs) in their hosts. We hypothesize that the symbionts use these TRGs in beneficial interactions with their host, including protection against parasites. This would explain why a mutualistic symbiont would contain such a remarkable ‘arsenal’ of TRGs.

The light-harvesting complex (LHC) is an essential component in light energy capture and transduction to facilitate downstream photosynthetic reactions in plant and algal chloroplasts. The unicellular dinoflagellate alga Symbiodinium is an endosymbiont of cnidarian animals, including corals and sea anemones, and provides carbohydrates generated through photosynthesis to host animals. Although Symbiodinium possesses a unique LHC gene family, called chlorophyll a-chlorophyll c2-peridinin protein complex (acpPC), its genome-level diversity and evolutionary trajectories have not been investigated. Here, we describe a phylogenetic analysis revealing that many of the LHCs are encoded by highly duplicated genes with multi-subunit polyprotein structures in the nuclear genome of Symbiodinium minutum. This analysis provides an extended list of the LHC gene family in a single organism, including 80 loci encoding polyproteins composed of 145 LHC subunits recovered in the phylogenetic tree. In S. minutum, 5 phylogenetic groups of the Lhcf-type gene family, which is exclusively conserved in algae harboring secondary plastids of red algal origin, were identified. Moreover, 5 groups of the Lhcr-type gene family, of which members are known to be associated with PSI in red algal plastids and secondary plastids of red algal origin, were identified. Notably, members classified within a phylogenetic group of the Lhcf-type (group F1) are highly duplicated, which may explain the presence of an unusually large number of LHC genes in this species. Some gene units were homologous to other units within single loci of the polyprotein genes, whereas intergenic homologies between separate loci were conspicuous in other cases, implying that gene unit 'shuffling' by gene conversion and/or genome rearrangement might have been a driving force for diversification. These results suggest that vigorous intra- and intergenic gene duplication events have resulted in the genomic framework of photosynthesis in coral symbiont dinoflagellate algae.

Abstract Background The transplantation of neural stem/progenitor cells (NS/PCs) at the sub-acute phase of spinal cord injury, but not at the chronic phase, can promote functional recovery. However, the reasons for this difference and whether it involves the survival and/or fate of grafted cells under these two conditions remain unclear. To address this question, NS/PC transplantation was performed after contusive spinal cord injury in adult mice at the sub-acute and chronic phases. Results Quantitative analyses using bio-imaging, which can noninvasively detect surviving grafted cells in living animals, revealed no significant difference in the survival rate of grafted cells between the sub-acute and chronic transplantation groups. Additionally, immunohistology revealed no significant difference in the differentiation phenotypes of grafted cells between the two groups. Microarray analysis revealed no significant differences in the expression of genes encoding inflammatory cytokines or growth factors, which affect the survival and/or fate of grafted cells, in the injured spinal cord between the sub-acute and chronic phases. By contrast, the distribution of chronically grafted NS/PCs was restricted compared to NS/PCs grafted at the sub-acute phase because a more prominent glial scar located around the lesion epicenter enclosed the grafted cells. Furthermore, microarray and histological analysis revealed that the infiltration of macrophages, especially M2 macrophages, which have anti-inflammatory role, was significantly higher at the sub-acute phase than the chronic phase. Ultimately, NS/PCs that were transplanted in the sub-acute phase, but not the chronic phase, promoted functional recovery compared with the vehicle control group. Conclusions The extent of glial scar formation and the characteristics of inflammation is the most remarkable difference in the injured spinal cord microenvironment between the sub-acute and chronic phases. To achieve functional recovery by NS/PC transplantation in cases at the chronic phase, modification of the microenvironment of the injured spinal cord focusing on glial scar formation and inflammatory phenotype should be considered.