Possible involvement of zinc transporter ZIP13 in myogenic differentiation.

Ehlers-Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13G64D) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.

Effects of flusulfamide on spore germination of Plasmodiophora brassicae.

Flusulfamide inhibits germination of Plasmodiophora brassicae resting spores to suppress clubroot disease, but its mechanism of action on the germination of P. brassicae resting spores remains unclear. In this study, P. brassicae resting spores were treated with flusulfamide and visualized using transmission electron microscopy (TEM). The gene expression of P. brassicae resting spores was analyzed using RT-PCR, followed by immunoblotting analysis. TEM results revealed that flusulfamide suppressed the primary zoosporogenesis of P. brassicae resting spores during the early phase, and RT-PCR results revealed that flusulfamide affected the gene expression during the germination of the resting spores. Immunoblot and RT-qPCR analyses revealed that PbCyp3, an immunophilin (peptidyl-prolyl-isomerase) gene, was highly expressed, resulting in the unusual accumulation of PbCYP3 protein in P. brassicae resting spores immediately after treatment with flusulfamide. This suggests that flusulfamide may cause aberrant folding of proteins involved in primary zoosporogenesis, thereby inhibiting germination.

Multiple parallel cell lineages in the developing mammalian cerebral cortex.

Cortical neurogenesis follows a simple lineage: apical radial glia cells (RGCs) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, such as human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret and barcoded lineage tracking to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not in mouse. Neurons followed parallel differentiation trajectories in the gyrus and sulcus, with different expressions of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex.

Facilely Fabricated Zero-Bias Silicon-Based Plasmonic Photodetector in the Near-Infrared Region with a Schottky Barrier Properly Controlled by Nanoalloys.

Plasmonic Schottky devices have attracted considerable attention for use in practical applications based on photoelectric conversion, because they enable light to be harvested below the bandgap of semiconductors. In particular, silicon-based (Si) plasmonic Schottky devices have great potential for useful photodetection in the near-infrared region. However, the internal quantum efficiency (IQE) values of previously reported devices are low because the Schottky barrier is excessively high. Here, we are the first to develop AuAg nanoalloy-n-type Si plasmonic Schottky devices by cathodic arc plasma deposition. Interestingly, it is found that a novel nanostructure, which leads to the improvement of responsivities, is formed. Moreover, these plasmonic nanostructures can be fabricated in only ∼1 min. The fabricated AuAg nanoparticle-film structure enables proper control of the Schottky barrier height and increases the area of the Schottky interface for electron transfer. As a result, the considerably enhanced IQE of our device at a telecommunication wavelength of 1310 nm (1550 nm) without external bias is 4.6 (6.5) times higher than those in previous reports, and these responsivities are a record high. This approach can be applied to realize efficient photodetection in the NIR region and extend the use of light below the bandgap of semiconductors. This paves the way for future application advancements in a variety of fields, including photodetection, imaging, photovoltaics, and photochemistry.

A case of anti-laminin γ1 (p200) pemphigoid developed after dipeptidyl peptidase-4 inhibitor administration.

A 73-year-old man with diabetes mellitus was referred to our department for ultraviolet treatment for erythematous skin lesions with itching. On dipeptidyl peptidase-4 inhibitor (DPP-4i) sitagliptin (Januvia®) for diabetes mellitus, the erythematous skin lesions appeared and spread to the whole body. At the initial visit, erythema multiforme-like skin lesions with crusts were observed on the trunk and extremities, and the patient was suspected to have drug eruption. Histopathology demonstrated eosinophilic infiltration in the superficial dermis and inflammatory cell infiltration in the epidermis. Sitagliptin was discontinued, and erythematous lesions improved with oral prednisolone. Thereafter the patient was treated with phototherapy and  betamethasone sodium phosphate infusion for residual prurigo. However, blistering skin lesions appeared 5 months later. Histopathological findings were subepidermal blisters with eosinophilic abscess, and bullous pemphigoid was suspected. CLEIAs for autoantibodies to desmoglein 1 (Dsg1), Dsg3 and BP180 were negative. Direct immunofluorescence showed linear depositions of immunoglobulin G (IgG) and C3 at the epidermal basement membrane zone, and indirect immunofluorescence detected IgG anti-epidermal basement membrane zone antibodies, reacting with the dermal side of 1M NaCl-split normal human skin. IgG antibodies reacted with 200 kDa laminin γ1 (p200) by immunoblotting using dermal extracts. These results indicated that this patient was diagnosed with anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration. Although reports of DPP-4i-related bullous pemphigoid have accumulated, cases of anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration are rarely reported.

Improvement of sleep and pain with lemborexant administration in patients with chronic pain: a retrospective observational study.

OBJECTIVE: Patients with chronic pain often have sleep disturbances, and many patients receive sleep medications in addition to analgesics. Although there have been scattered reports of negative pain-sleep interactions, only a few reports have investigated the efficacy of sleep medication interventions in patients with chronic pain for improving sleep disturbances and reducing pain. We retrospectively examined whether lemborexant, an orexin receptor antagonist, is effective in improving sleep disturbances and reducing pain in patients with chronic pain. This study was approved by the Ethics Committee of our hospital. METHODS: The subjects were 26 patients with chronic pain undergoing treatment at our pain clinic between July 2021 and March 2022, who had been diagnosed with insomnia, with an Athens Insomnia Scale (AIS) score of ≥6 and had been started on lemborexant. The AIS score and pain score (Numeric Rating Scale [NRS]) before and after 2 and 4 weeks of starting lemborexant were investigated. RESULTS: Patients who were already taking other sleep medications, such as benzodiazepines were switched to 5 mg of lemborexant after all the other sleep medications were discontinued. Those who had not yet used sleeping pills were started on 5 mg of lemborexant. During the study course, the dose of lemborexant was adjusted at the discretion of the attending physician, based on improvement of insomnia symptoms and secondary symptoms, such as daytime sleepiness and lightheadedness. The study finally included 21 patients, excluding 5 who could not continue taking lemborexant due to side effects, such as lightheadedness. The AIS scores significantly improved, decreasing from baseline (mean ± standard deviation: 12.5 ± 4.9) to 2 weeks (7.8 ± 3.1) and 4 weeks (5.3 ± 2.9) after the start of lemborexant. No significant difference was observed in the degree of improvement in sleep disturbance between patients with or without previous sleep medications, and there was also no statistically significant improvement in the NRS score before (6.1 ± 2.7) and after 2 weeks (5.5 ± 2.3) and 4 weeks (5.9 ± 2.2) from treatment initiation.

Corticotropin-releasing hormone signaling from prefrontal cortex to lateral septum suppresses interaction with familiar mice.

Social preference, the decision to interact with one member of the same species over another, is critical to optimize social interactions. Thus, adult rodents favor interacting with novel conspecifics over familiar ones, but whether this social preference stems from neural circuits facilitating interactions with novel individuals or suppressing interactions with familiar ones remains unknown. Here, we identify neurons in the infra-limbic area (ILA) of the mouse prefrontal cortex that express the neuropeptide corticotropin-releasing hormone (CRH) and project to the dorsal region of the rostral lateral septum (rLS). We show how release of CRH during familiar encounters disinhibits rLS neurons, thereby suppressing social interactions with familiar mice and contributing to social novelty preference. We further demonstrate how the maturation of CRH expression in ILA during the first 2 post-natal weeks enables the developmental shift from a preference for littermates in juveniles to a preference for novel mice in adults.

Bibliometric analysis of the 100 most cited articles in nonspecific neck pain research: A STROBE-compliant study.

The purpose of this study was to identify and analyze the top 100 cited articles in nonspecific neck pain (NSNP) research. A set of search terms was entered into the Web of Science database, and the articles with the highest citation counts in the field of NSNP were chosen. The top 100 articles were examined for total citation count, annual citations count, first author, year of publication, journal, study design, and country of origin. The citation count for the list final articles ranged from 181 to 2067, with an average of 291.9. The journal Spine contributed the most articles (25), followed by pain (16). Between 2001 and 2010, the most prolific years, 66 articles were published. In terms of country of origin, the majority of articles were from Australia (22). Vernon H., published the most cited article in the Journal of Manipulative & Physiological Therapeutics in 1991, reporting the first instrument developed to assess self-reported disability in patients with neck pain. The bibliographic analysis to identify the top 100 most cited articles related to NSNP acknowledges the field historical advances and provides insight into the types of articles that have provided these advances.

Enhancing performance of electron holography with mathematical and machine learning-based denoising techniques.

Electron holography is a useful tool for analyzing functional properties, such as electromagnetic fields and strains of materials and devices. The performance of electron holography is limited by the 'shot noise' inherent in electron micrographs (holograms), which are composed of a finite number of electrons. A promising approach for addressing this issue is to use mathematical and machine learning-based image-processing techniques for hologram denoising. With the advancement of information science, denoising methods have become capable of extracting signals that are completely buried in noise, and they are being applied to electron microscopy, including electron holography. However, these advanced denoising methods are complex and have many parameters to be tuned; therefore, it is necessary to understand their principles in depth and use them carefully. Herein, we present an overview of the principles and usage of sparse coding, the wavelet hidden Markov model and tensor decomposition, which have been applied to electron holography. We also present evaluation results for the denoising performance of these methods obtained through their application to simulated and experimentally recorded holograms. Our analysis, review and comparison of the methods clarify the impact of denoising on electron holography research.

Percutaneous retrocrural versus ultrasound-guided coeliac plexus neurolysis for refractory pancreatic cancer pain.

We report a successful case of fluoroscopic percutaneous retrocrural coeliac plexus neurolysis (PRCPN) for pancreatic cancer pain refractory to endoscopic ultrasound-guided coeliac plexus neurolysis (EUS-CPN). A 55-year-old man with upper abdominal pain due to end-stage pancreatic cancer underwent EUS-CPN. Although CT revealed distribution of the contrast medium with neurolytic agent around the left and cephalic sides of the coeliac artery, the pain did not improve and became even more severe. PRCPN was performed, resulting in the drastic improvement of pain immediately. PRCPN should be considered when EUS-CPN is not effective.

Molecular-Resolution Imaging of Interfacial Solvation of Electrolytes for Lithium-Ion Batteries by Frequency Modulation Atomic Force Microscopy.

Solvation structures formed by ions and solvent molecules at solid/electrolyte interfaces affect the energy storage performance of electrochemical devices, such as lithium-ion batteries. In this study, the molecular-scale solvation structures of an electrolyte, a solution of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in propylene carbonate (PC) at the electrolyte-mica interface, were measured using frequency-modulation atomic force microscopy (FM-AFM). The spacing of the characteristic force oscillation in the force versus distance curves increased with increasing ion concentration, suggesting an increase in the effective size of molecules at the interface. Molecular dynamics simulations showed that the effective size of molecular assemblies, namely, solvated ions formed at the interface, increased with increasing ion concentrations, which was consistent with the experimental results. Knowledge of molecular-scale structures of solid/electrolyte interfaces obtained by a combination of FM-AFM and molecular dynamics simulations is important in the design of electrolytes for future energy devices and in improving their properties.

A case of acute appendicitis incarcerated in obturator hernia.

An 85 year-old woman was transferred with a chief complaint of right thigh pain persisting for 5 days. Abdominal contrast-enhanced computed tomography clearly depicted a swollen appendix incarcerated in the right obturator cavity. She underwent an emergent laparoscopic appendectomy and the simultaneous repair of the obturator hernia. At laparoscopy, appendix was found to be incarcerated in the right obturator canal. The incarcerated appendix was successfully flushed out from the sac by spurting saline into the obturator hernia sac through the catheter inserted into the hernia sac. After a laparoscopic appendectomy, the hernia orifice was repaired using the uterine flap. The patient was discharged from the hospital without any sequelae. This report demonstrates a very rare case of obturator hernia incarcerated with appendix. Although patients with obturator hernia incarcerated with small intestine present with the symptoms related to bowel obstruction, patients with incarceration of appendix do not. Moreover, they would show no typical abdominal symptoms associated with acute appendicitis. Therefore, it is important to perform a radiological evaluation promptly to make a definitive diagnosis when a patient with persisting pain of the right thigh or right ileac fossa with a possibility of obturator hernia with incarceration of the appendix is encountered.

Relationship between scapular control during isometric shoulder flexion and scapular motion during baseball pitching: a cross-sectional study.

BACKGROUND: A baseball pitcher with decreased scapular control may not be able to achieve suitable scapular motion at maximum shoulder external rotation (MER) of baseball pitching during the pitching action. It is common clinically to compare scapular control of the throwing and non-throwing arms to detect side-to-side differences. However, it remains unclear whether scapular control is different between the throwing and non-throwing arms. Moreover, no data exist on the relationship between scapular control and scapular motion at MER of pitching. Primarily, this study aimed to compare scapular control during isometric shoulder flexion between the throwing and non-throwing arms. Secondly, this study aimed to investigate the relationship between scapular control during isometric shoulder flexion and scapular motion at MER of pitching. METHODS: Fifteen healthy collegiate baseball pitchers (age, 20.2 ± 1.9 years; height, 1.76 ± 0.05 m; body mass, 73.3 ± 6.7 kg) were recruited. An optical motion tracking system was used to assess scapular motion. Scapular control was defined as the amount of change in the scapular internal rotation angle, downward rotation angle, and anterior tilt angle during isometric shoulder flexion. We assessed scapular position at MER of pitching. RESULTS: No significant differences were detected for any of the scapular angles during isometric shoulder flexion between the throwing and non-throwing arms. The amount of change in the scapular internal rotation angle, scapular downward rotation angle, and scapular anterior tilt angle during isometric shoulder flexion had a significant relationship with the scapular downward rotation angle at MER. CONCLUSIONS: No side-to-side difference was noted in scapular control during isometric shoulder flexion in healthy collegiate baseball pitchers at the group level. Further studies are required to understand the side-to-side differences at the individual level. Additionally, there was a relationship between scapular control during isometric shoulder flexion and scapular position at MER. These findings suggest that clinicians may consider using isometric shoulder flexion to assess scapular control in baseball pitchers.

Secondary loss of miR-3607 reduced cortical progenitor amplification during rodent evolution.

The evolutionary expansion and folding of the mammalian cerebral cortex resulted from amplification of progenitor cells during embryonic development. This process was reversed in the rodent lineage after splitting from primates, leading to smaller and smooth brains. Genetic mechanisms underlying this secondary loss in rodent evolution remain unknown. We show that microRNA miR-3607 is expressed embryonically in the large cortex of primates and ferret, distant from the primate-rodent lineage, but not in mouse. Experimental expression of miR-3607 in embryonic mouse cortex led to increased Wnt/ß-catenin signaling, amplification of radial glia cells (RGCs), and expansion of the ventricular zone (VZ), via blocking the ß-catenin inhibitor APC (adenomatous polyposis coli). Accordingly, loss of endogenous miR-3607 in ferret reduced RGC proliferation, while overexpression in human cerebral organoids promoted VZ expansion. Our results identify a gene selected for secondary loss during mammalian evolution to limit RGC amplification and, potentially, cortex size in rodents.

Computational evaluation of sparse coding on off-axis electron holograms: comparison between charge-coupled device and direct-detection device cameras.

The effectiveness of sparse coding for image inpainting and denoising of off-axis electron holograms was examined computationally based on hologram simulations according to considerations of two types of electron detectors, namely charge-coupled device (CCD) and direct-detection device (DDD) cameras. In this simulation, we used a simple-phase object with a phase step such as a semiconductor p-n junction and assumed that the holograms recorded by the CCD camera include shot noise, dark-current noise and read-out noise, while those recorded by the DDD camera include only shot noise. Simulated holograms with various electron doses were sparsely coded. Even though interference fringes cannot be recognized in the simulated CCD and DDD holograms when subjected to electron doses (per pixel) equal to 1 and 0.01, respectively, both the corresponding sparse-coded holograms exhibit meaningful interference fringes. We demonstrate that a combination of the DDD camera and sparse coding reduces the requisite dose used to obtain holograms to values less than one-thousandth compared with the CCD camera without image postprocessing. This combination is expected to generate lower-dose and/or higher-speed electron holography.

Lithium Transport Pathways Guided by Grain Architectures in Ni-Rich Layered Cathodes.

Ni-rich layered cathodes have been used in commercial Li-ion batteries because of their high capacity and low cost. However, they suffer from crack formation at the grain boundaries owing to heterogeneous large volume changes during the reactions. To improve their performance, a comprehensive understanding of the grain architecture, Li transport pathways, and phase transitions is essential. Here, we show the correlations between these factors using in situ transmission electron microscopy. The results show that Li ions are extracted through tortuous paths connecting the Li-containing a-b planes in the crystals. Moreover, the grain boundary resistance depends not only on the misorientations of the neighboring grains. Even twins with misorientation angles of 70° are not decisive factors in Li movement. We also show the existence of two-phase separation in single crystals between two hexagonal phases during fast charging. These results provide valuable information for determining the optimal grain architecture and for material design, helping enhance high capacity and high stability.

Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice.

Autism spectrum disorder (ASD), characterized by profound impairment in social interactions and communication skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms underlying the development of ASD have focused on the serotonergic system; however, these studies have failed to completely elucidate the mechanisms. We previously identified N-ethylmaleimide-sensitive factor (NSF) as a new serotonin transporter (SERT)-binding protein and described its importance in SERT membrane trafficking and uptake in vitro. In the present study, we generated Nsf +/- mice and investigated their behavioral, neurotransmitter, and neurophysiological phenotypes in vivo. Nsf +/- mice exhibited abnormalities in sociability, communication, repetitiveness, and anxiety. Additionally, Nsf loss led to a decrease in membrane SERT expression in the raphe and accumulation of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors at the synaptic membrane surface in the hippocampal CA1 region. We found that postsynaptic density and long-term depression were impaired in the hippocampal CA1 region of Nsf +/- mice. Taken together, these findings demonstrate that NSF plays a role in synaptic plasticity and glutamatergic and serotonergic systems, suggesting a possible mechanism by which the gene is linked to the pathophysiology of autistic behaviors.

Passive transfer of fibromyalgia symptoms from patients to mice.

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.

Visualizing Lithiation of Graphite Composite Anodes in All-Solid-State Batteries Using Operando Time-of-Flight Secondary Ion Mass Spectrometry.

A fundamental understanding of lithiation dynamics in composite electrodes is essential for the development of all-solid-state batteries with high capacity and rate capability. However, a comprehensive methodology to monitor the time evolution of lithiation in a composite electrode has not been fully established because of the limitations of the characterization techniques currently employed. In this study, we demonstrate the visualization of the transient distribution of Li in composite graphite anodes during cell operation using operando time-of-flight secondary ion mass spectrometry. Selective detection of Li in the graphite electrode was successfully achieved by mapping the Li- fragment rather than the conventional mapping of positive Li-containing fragments. The results revealed the formation of a Li concentration gradient during charging, indicating that the reaction of the composite electrode is limited by the diffusion of Li ions inside the graphite. The demonstrated technique is expected to facilitate the investigation of the underlying lithiation mechanisms of composite electrodes in operating cells.

Pain induces stable, active microcircuits in the somatosensory cortex that provide a therapeutic target.

Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca2+ channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca2+ channels or other approaches, may provide ways to reduce inflammatory pain.