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Key messageA plant-derived secretory component conferred protease-resistance to Shiga toxin-specific mammalian immunoglobulin A. The protease-resistance was functionally demonstrated by a toxin neutralization assay.Secretory component (SC) is believed to play roles in such as the protease-resistance of secretory immunoglobulin A (SIgA), allowing it to function on mucosae. Although the use of a plant expression system for SIgA production has been increasing, it has not been sufficiently assessed as to whether heterologously expressed SC could functionally contribute to the protease-resistance of SIgA. Here, we reconstituted SIgA using plant-derived SC and tested for changes in vulnerability to protease challenge. With glutathione redox buffers, plant-derived SC and mammalian cell-derived dimeric IgA (dIgA) specific for Shiga toxin 1 (Stx1) efficiently formed SIgA. Prior ammonium sulfate precipitation of dIgA was also shown to be useful to enhance the formation of SIgA. The reconstituted SIgA was treated with two gastrointestinal proteases, pepsin and trypsin. After 2-h pepsin treatment, the signal from SIgA remained at 42% with plant-derived SC-reconstitution while that from dIgA remained at 12% without SC-reconstitution on western blot analysis. Similarly, the signal from SIgA remained at 74% with SC but that from dIgA remained at 36% without SC after 4-h trypsin treatment. Furthermore, an effect of SC-reconstitution of dIgA on pepsin-resistance was observed in a toxin neutralization assay involving Vero cells. These results indicated that the plant-derived SC could contribute to the production of orally applicable SIgA.

Meteorites from interplanetary space often include high-pressure polymorphs of their constituent minerals, which provide records of past hypervelocity collisions. These collisions were expected to occur between kilometre-sized asteroids, generating transient high-pressure states lasting for several seconds to facilitate mineral transformations across the relevant phase boundaries. However, their mechanisms in such a short timescale were never experimentally evaluated and remained speculative. Here, we show a nanosecond transformation mechanism yielding ringwoodite, which is the most typical high-pressure mineral in meteorites. An olivine crystal was shock-compressed by a focused high-power laser pulse, and the transformation was time-resolved by femtosecond diffractometry using an X-ray free electron laser. Our results show the formation of ringwoodite through a faster, diffusionless process, suggesting that ringwoodite can form from collisions between much smaller bodies, such as metre to submetre-sized asteroids, at common relative velocities. Even nominally unshocked meteorites could therefore contain signatures of high-pressure states from past collisions. Meteorites from space often include denser polymorphs of their minerals, providing records of past hypervelocity collisions. An olivine mineral crystal was shock-compressed by a high-power laser, and its transformation into denser ringwoodite was time-resolved using an X-ray free electron laser.

Acute pancreatitis often results in life-threatening situations, making a prompt and accurate diagnosis cardinally important. To achieve these, it is crucial to correctly identify characteristic symptoms and test findings. However, when patients do not exhibit distinctive symptoms during a physician's examination, in addition to limited resources, these can become challenging. In this manuscript, we present an instructive case.A male in his twenties, who complained of generalized malaise, was admitted to our hospital. Unfortunately, however, he passed away within two days prior to undergoing detailed examinations or receiving therapeutic interventions. We performed an autopsy in order to ascertain the reasons for this outcome. The findings revealed that pulmonary edema and diffuse alveolar hemorrhage were the causative factors of his demise, with acute pancreatitis observed in the background.The occurrence of acute pancreatitis leading to death in youths is infrequent. Where could we have intervened to halt such an unfortunate course in a young individual? This patient probably had diabetic ketoacidosis and hyperlipidemia, both of which are known to be closely associated with acute pancreatitis. In retrospect, we should have noticed this point. In this case, the condition progressed too rapidly for appropriate therapeutic interventions. We believe that this case would provide educational instruction for similar situations that could arise in the future.

Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO. Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.

Laser-induced periodic surface structure (LIPSS), which has a period smaller than the laser wavelength, is expected to become a potential technique for fine surface processing. We report the microscopic and macroscopic observations of the crystallinity of LIPSSs, where the characteristics such as defects generation and residual strain were analyzed, respectively. The LIPSSs were formed on a Si substrate using two different femtosecond pulses from Ti:Sapphire laser with near-infrared wavelength (0.8 μm) and free-electron laser (FEL) with mid-infrared wavelength (11.4 μm). The photon energies of the former and latter lasers used here are higher and lower than the Si bandgap energies, respectively. These LIPSSs exhibit different crystalline states, where LIPSS induced by Ti:Sapphire laser show residual strain while having a stable crystallinity; in contrast, FEL-LIPSS generates defects without residual strain. This multiple analysis (microscopic and macroscopic observations) provides such previously-unknown structural characteristics with high spatial resolution. To obtain LIPSS with suitable properties and characteristics based on each application it is paramount to identify the laser sources that can achieve such properties. Therefore, identifying the structural information of the LIPSS generated by each specific laser is of great importance.

In Japan, programs to monitor antimicrobial use in companion animals have not been established. To fill this gap, the Japan Veterinary Medical Association has conducted surveys of actual use. The aims of this paper are to clarify the frequency and factors associated with the use of human antimicrobials in Japanese small-animal clinics. Antimicrobial usage and awareness surveys were conducted at 260 veterinary clinics between November 2021 and February 2022 using two questionnaires. The annual use of each antimicrobial drug was categorized by frequency, and the median value of each category, with a score of 50 for the choice ≥50, was used to quantify usage frequency. Important antimicrobial drugs for human use were defined as rank I antibiotics of the Food Safety Commission. Knowledge and awareness factors associated with the use of important antimicrobial drugs for human use were analyzed using three approaches. First, the use of important drugs was examined using a generalized linear model (GLM) with binomial errors. Second, a vector generalized linear and additive model with zero-inflated binomial errors was used to evaluate the proportion of important drugs among the annual frequency of use of human antimicrobial drugs. Third, at the drug level, selecting veterinary clinics using important human drugs, univariable GLMs with Poisson errors were used to evaluate the frequency of important human drug use, with the log number of employees as the offset term. The response rates were 71.2 and 72.3% for the antimicrobial usage and awareness surveys, respectively. All of the facilities used human antimicrobial drugs, and 57.1% (93/163) of facilities used important human antimicrobial drugs. Important human antimicrobial drugs accounted for 21.7% of the frequency of use of human antimicrobial drugs annually (7,342/33,896 times). In terms of the proportion of important human drugs and frequency of important human drug use, the use of important human antimicrobial drugs was low in cases of high awareness of prudent use of antimicrobial drugs and where tests for evidence-based judgment were introduced, but was high when price and ease of use were emphasized. Antibiotic stewardship should be further promoted in Japanese small-animal clinics through educational and information dissemination activities.

Over the past century, understanding the nature of shock compression of condensed matter has been a major topic. About 20 years ago, a femtosecond laser emerged as a new shock-driver. Unlike conventional shock waves, a femtosecond laser-driven shock wave creates unique microstructures in materials. Therefore, the properties of this shock wave may be different from those of conventional shock waves. However, the lattice behaviour under femtosecond laser-driven shock compression has never been elucidated. Here we report the ultrafast lattice behaviour in iron shocked by direct irradiation of a femtosecond laser pulse, diagnosed using X-ray free electron laser diffraction. We found that the initial compression state caused by the femtosecond laser-driven shock wave is the same as that caused by conventional shock waves. We also found, for the first time experimentally, the temporal deviation of peaks of stress and strain waves predicted theoretically. Furthermore, the existence of a plastic wave peak between the stress and strain wave peaks is a new finding that has not been predicted even theoretically. Our findings will open up new avenues for designing novel materials that combine strength and toughness in a trade-off relationship.

The Japanese National Action Plan on Antimicrobial Resistance (AMR) was adopted to strengthen AMR surveillance and monitoring in companion animals. The Japanese Veterinary Antimicrobial Resistance Monitoring (JVARM) system monitors the sale of veterinary antimicrobial drugs by pharmaceutical companies, and the sale of human drugs by principal wholesale companies to companion animal (dogs and cats) clinics. However, the data do not include sales by local drug suppliers and personal importation to companion animal clinics in Japan. The purposes of this study were to estimate total antimicrobial drug use by companion animal clinics in Japan and to identify the factors associated with their use. In 2018, questionnaires gathering data on attributes of the clinic and volumes of antimicrobial drugs used were sent to 212 clinics across Japan by the Japan Veterinary Medical Association. Out of the clinics, 170 valid questionnaires were returned (80.2% response rate). Antimicrobial drugs were categorized first as human, veterinary, or imported drugs and then further categorized as important drugs (critically important drugs for humans and second-choice veterinary drugs) or others. Total antimicrobial drug use was estimated based on the number of clinics reported in 2016. The relationships between antimicrobial drug use and various questionnaire items were analyzed using non-parametric regression analysis. Total antimicrobial drug use was estimated at 29.9t, which was 2.1 times higher than reported by the JVARM survey on the sales of antimicrobial drugs. In terms of total use, important drugs and human drugs accounted for 12.6 and 61.8%, respectively. Clinic income per veterinarian was associated with total antimicrobial use per veterinarian. The proportion of important drugs among all antimicrobial drugs used in a clinic was high in recently established clinics with middle-aged and older directors.

ObjectivesMultiple system atrophy (MSA) is a refractory neurodegenerative disease, but novel treatments are anticipated. An accurate natural history of MSA is important for clinical trials, but is insufficient. This regional registry was launched to complement clinical information on MSA.SettingPatient recruitment started in November 2014 and is ongoing at the time of submission. The number of participating facilities was 66. Postal surveys were sent to medical facilities and patients with MSA in Hokkaido, Japan.ParticipantsAfter obtaining written consent from 196 participants, 184 overview surveys and 115 detailed surveys were conducted.Primary and secondary outcome measuresAn overview survey evaluated conformity to diagnostic criteria and a detailed survey implemented an annual assessment based on the Unified Multiple System Atrophy Rating Scale (UMSARS).ResultsAt the time of registration, 58.2% of patients were diagnosed with cerebellar symptoms predominant type MSA (MSA-C) and 29.9% were diagnosed with parkinsonism predominant type MSA (MSA-P). UMSARS Part Ⅳ score of 4 or 5 accounted for 53.8% of participants. The higher the UMSARS Part Ⅳ score, the higher the proportion of MSA-P. At baseline, levodopa was used by 69 patients (37.5%) and the average levodopa dose was 406.7 mg/day. The frequency of levodopa use increased over time. Eleven cases changed from MSA-C to MSA-P during the study, but the opposite was not observed. Information about survival and causes of death was collected on 54 cases. Half of deaths were respiratory-related. Sudden death was recorded even in the group with UMSARS Part Ⅳ score of 1.ConclusionsThis study is the first large-scale prospective MSA cohort study in Asia. MSA-C was dominant, but the use of antiparkinsonian drugs increased over the study period. Changes from MSA-C to MSA-P occurred, but not vice versa.

Here, we report, that by means of direct irradiation of lithium fluoride a (LiF) crystal, in situ 3D visualization of the SACLA XFEL focused beam profile along the propagation direction is realized, including propagation inside photoluminescence solid matter. High sensitivity and large dynamic range of the LiF crystal detector allowed measurements of the intensity distribution of the beam at distances far from the best focus as well as near the best focus and evaluation of XFEL source size and beam quality factor M 2 . Our measurements also support the theoretical prediction that for X-ray photons with energies ~10 keV the radius of the generated photoelectron cloud within the LiF crystal reaches about 600 nm before thermalization. The proposed method has a spatial resolution ~ 0.4–2.0 μm for photons with energies 6–14 keV and potentially could be used in a single shot mode for optimization of different focusing systems developed at XFEL and synchrotron facilities.