Engineering and environmental assessment of soilbag-based slope stabilisation for sustainable landslide mitigation in mountainous area.

Changes in land use significantly impact landslide occurrence, particularly in mountainous areas in northern Thailand, where human activities such as urbanization, deforestation, and slope modifications alter natural slope angles, increasing susceptibility to landslides. To address this issue, an appropriate method using soilbags has been widely used for slope stabilisation in northern Thailand, but their effectiveness and sustainability require assessment. This research highlights the need to evaluate the stability of the soilbag-based method. In this study, a case study was conducted in northern Thailand, focusing on an area characterised by high-risk landslide potential. This research focuses on numerical evaluation the slope stability of soilbag-reinforced structures and discusses environmental sustainability. The study includes site investigations using an unmanned aerial photogrammetric survey for slope geometry evaluation and employing the microtremor survey technique for subsurface investigation. Soil and soilbag material parameters are obtained from existing literatures. Modelling incorporates hydrological data, slope geometry, subsurface conditions, and material parameters. Afterwards, the pore-water pressure results and safety factors are analysed. Finally, the sustainability of soilbags is discussed based on the Sustainable Development Goals (SDGs). The results demonstrate that soilbags effectively mitigate pore-water pressures, improve stability, and align with several SDGs objectives. This study enhances understanding of soilbags in slope stabilisation and introduces a sustainable landslide mitigation approach for landslide-prone regions.

Embrittlement Fracture Behavior and Mechanical Properties in Heat-Affected Zone of Welded Maraging Steel.

In welded maraging steels, mechanical properties, particularly ductility and toughness, are often compromised in the heat-affected zone (HAZ). This study focuses on 300-grade maraging steel bars, solution annealed at 1123 K for 1.5 h (5.4 ks) and welded using gas tungsten arc welding, followed by a post-weld heat treatment at 753 K for 13.33 h (48 ks). In situ observations during three-point bending tests on HAZ samples featuring coarsened prior austenite grain sizes were conducted to examine damage behavior and the crack path near the crack tip. The main crack initiated at the peak applied load during the bending test and, upon further loading, exhibited significant deflection and extension accompanied by numerous microcracks and localized crack branching. Distinctive damage features, such as transgranular cracking across block regions, intense intergranular cracking along packet boundaries with a pronounced shear component, and crowding of microcracks ahead of the crack tip, were observed in the HAZ sample during the in situ test. The interaction between the main crack tip and microcracks and its influence on the local crack propagation driving force was discussed using fracture mechanics. Experimental results, including tensile fracture surface observations and in situ images, along with analysis of the stress anti-shielding effect by microcracks, suggest that the HAZ sample exhibits embrittlement fracture behavior with lower ductility and toughness compared to the base metal sample.

Add-on imeglimin versus metformin dose escalation regarding glycemic control in patients with type 2 diabetes treated with a dipeptidyl peptidase-4 inhibitor plus low-dose metformin: study protocol for a multicenter, prospective, randomized, open-label, parallel-group comparison study (MEGMI study).

INTRODUCTION: Imeglimin is a novel anti-hyperglycemic drug that improves both insulin resistance and insulin secretion. The effects of imeglimin on glycemic control were confirmed in phase III clinical trials, but little is known about its effectiveness in daily clinical practice settings, especially compared with metformin. Therefore, we aim to clarify the efficacy of imeglimin in patients with type 2 diabetes (T2D) being treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor plus low-dose metformin. RESEARCH DESIGN AND METHODS: This is a multicenter, randomized, prospective, open-label, parallel-group trial. Seventy participants with T2D treated with a DPP-4 inhibitor plus metformin (500-1000 mg/day) for more than 12 weeks and a glycated hemoglobin (HbA1c) level of 52-85 mmol/mol (7.0%-9.9%) will be randomized to receive add-on imeglimin 1000 mg two times per day or metformin dose escalation for 24 weeks. Biochemical analyses and physical assessments will be performed at baseline and at the end of the study, and adverse events will be recorded. The primary endpoint is the change in HbA1c after 24 weeks. The secondary endpoints comprise the changes in blood pressure, pulse rate, body weight, abdominal circumference, and other laboratory parameters; the relationship between improvements of biological parameters including glycemic control and patient background characteristics; and side effects. RESULTS: This study will reveal new insights into the incorporation of imeglimin into the diabetes treatment strategy. CONCLUSIONS: This will be the first randomized controlled trial to compare the efficacy of adding imeglimin versus metformin dose escalation on glycemic control in patients with T2D. TRIAL REGISTRATION NUMBER: jRCT1011220005.

Time-series transcriptome of Brachypodium distachyon during bacterial flagellin-induced pattern-triggered immunity.

Plants protect themselves from microorganisms by inducing pattern-triggered immunity (PTI) via recognizing microbe-associated molecular patterns (MAMPs), conserved across many microbes. Although the MAMP perception mechanism and initial events during PTI have been well-characterized, knowledge of the transcriptomic changes in plants, especially monocots, is limited during the intermediate and terminal stages of PTI. Here, we report a time-series high-resolution RNA-sequencing (RNA-seq) analysis during PTI in the leaf disks of Brachypodium distachyon. We identified 6,039 differentially expressed genes (DEGs) in leaves sampled at 0, 0.5, 1, 3, 6, and 12 hours after treatment (hat) with the bacterial flagellin peptide flg22. The k-means clustering method classified these DEGs into 10 clusters (6 upregulated and 4 downregulated). Based on the results, we selected 10 PTI marker genes in B. distachyon. Gene ontology (GO) analysis suggested a tradeoff between defense responses and photosynthesis during PTI. The data indicated the recovery of photosynthesis started at least at 12 hat. Over-representation analysis of transcription factor genes and cis-regulatory elements in DEG promoters implied the contribution of 12 WRKY transcription factors in plant defense at the early stage of PTI induction.

Tensile Examination and Strength Evaluation of Latewood in Japanese Cedar.

With the crisis awareness of global warming and natural disasters, utilization of local wood has drawn increasing attention in achieving the Sustainable Development Goals (SDGs). It is necessary to investigate the deformation and fracture of the structural tissue in wood in order to improve the safety and reliability of wood application. However, deformation and fracture mechanisms of the structural tissue in each annual ring are unknown. The mechanical characteristics of wood are reflected in the properties of earlywood and latewood. In the present study, microstructural observation and tensile tests were conducted to examine the relationship between the mechanical properties and fracture behavior of latewood in the growth direction in Japanese cedar. Brittle fracture behavior of the latewood specimen was confirmed based on the tensile stress-strain curve and features of the fracture surface. Moreover, two fracture modes, tensile fracture and shear fracture, were recognized. Weibull analysis of tensile strength in each fracture mode was performed to evaluate the reliability and utility of brittle latewood. Lastly, two fracture mechanisms were discussed based on the failure observation findings by a scanning electron microscope.

Optic nerve-associated connective tissue structures revisited: A histological study using human fetuses and adult cadavers.

Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve fibers into fascicles. We collected specimens from 25 adult cadavers and 15 fetuses and revisited the histological architecture of the optic and oculomotor nerves. In the optic chiasma, the meningeal layer of the dura joins the pia to form a thick SPM, and the periosteum of the sphenoid is continuous with the dural sheath at the orbital exit of the bony optic canal. The septa appeared as a cluster of irregularly arrayed fibrous plates in the intracranial course near the chiasma. Thus, the septa were not derived from either the SPM or the dural sheath. In the orbit, the central artery of the retina accompanies collagenous fibers from the dural sheath and the SPM to provide the vascular sheath in the optic nerve. These connective tissue configurations were the same between adult and fetal specimens. At the optic disk, the dural sheath and SPM merged with the sclera, whereas the septa appeared to end at the lamina cribrosa. However, in fetuses without lamina cribrosa, the septa extend into the nerve fiber layer of the retina. The SPM and septa showed strong elastin immunoreactivity, in contrast to the absence of reactivity in the sheaths of the oculomotor nerve. Each S100 protein-positive Schwann sheath of the oculomotor nerve was surrounded by collagenous endoneurium. Glial fibrillary acidic protein-positive astrocytes showed a linear arrangement along the septa.

Cerebrospinal fluid hypovolemia syndrome mimicking ocular myasthenia gravis: A case report.

Purpose: Cerebrospinal fluid hypovolemia syndrome (CHS) is a rare clinical entity that can be caused by spontaneous cerebrospinal fluid (CSF) leakage. The aim of this study is to report a rare case of CHS after a traffic accident in a patient who presented with diplopia and ptosis with fluctuation and was initially diagnosed with ocular myasthenia gravis. Observeations: A 29-year-old man exhibited fluctuating left ptosis and diplopia after a traffic accident. Although he was suspected of having myasthenia gravis and was treated using oral pyridostigmine bromide, his symptoms did not improve. He also had orthostatic headaches and malaise after the accident. His symptoms were suspected to be associated with traumatic cerebrospinal fluid hypovolemia. After 1000-mL fluid replacement, his diplopia and ptosis improved, and orbital T2-weghted MRI detected a high-signal zone around the optic nerve. We diagnosed him with oculomotor nerve paresis associated with cerebrospinal fluid hypovolemia. The symptoms, including ptosis, diplopia, orthostatic headaches, and malaise, disappeared after epidural blood patch therapy. Conclusions and Importance: When treating patients with fluctuating ocular symptoms, such as diplopia and ptosis, who have a history of trauma and orthostatic headaches, the possibility of CHS should be considered in the differential diagnosis.

Cerebrospinal fluid hypovolemia syndrome after a traffic accident with abnormal eye movements: A case report.

PURPOSE: To describe a rare case of cerebrospinal fluid hypovolemia syndrome after a traffic accident with abnormal eye movements. OBSERVATIONS: A 19-year-old man was referred to our clinic after being hit by a car five months ago while riding a bicycle. After the accident, he sometimes noticed oscillopsia, and had postural headaches and reading difficulties. His eye movement recording revealed square wave jerks during fixation and decreased pursuit gain during horizontal smooth pursuit. MR myelography detected cerebrospinal fluid leakage and the patient was diagnosed with cerebrospinal fluid hypovolemia. After undergoing epidural blood patch therapy, the leakage disappeared, and his postural headaches improved immediately. Square wave jerks and decreased pursuit gain improved, and his oscillopsia and reading difficulty also improved after therapy. CONCLUSIONS AND IMPORTANCE: A patient with cerebrospinal fluid hypovolemia presented with square wave jerks and decreased pursuit gain. Epidural blood patch therapy was effective for the symptoms. When treating patients with oscillopsia and postural headaches, we should consider the possibility of cerebrospinal fluid hypovolemia syndrome in the differential diagnosis.

QTL mapping using microsatellite linkage reveals target-site mutations associated with high levels of resistance against three mitochondrial complex II inhibitors in Tetranychus urticae.

The acaricides cyflumetofen, cyenopyrafen, and pyflubumide act as inhibitors of the mitochondrial electron transport system at complex II (succinate dehydrogenase; SDH), a new mode of action in arthropods. The development and mechanisms of low-level resistance against cyenopyrafen and cyflumetofen have been previously reported in Tetranychus urticae. In the present study, we investigated high levels of resistance against three SDH inhibitors in T. urticae field populations and clarify the genetic basis of resistance using quantitative trait locus (QTL) analysis. First, we constructed a microsatellite linkage map comprising 64 markers assembled into three linkage groups (LGs) with total length of 683.8 cM and average marker spacing of 11.03 cM. We then used the linkage map to perform QTL mapping, and identified significant QTLs contributing to resistance to cyflumetofen (one QTL on LG1), cyenopyrafen (one QTL on LG3), and pyflubumide (two QTLs on LG1 and LG3). The QTL peaks on LG1 for cyflumetofen and pyflubumide overlapped and included the SdhB locus. For cyenopyrafen resistance, the QTLs on LG3 included the SdhC locus. For cyflumetofen resistance, we found an I260T mutation in SdhB. For pyflubumide and cyenopyrafen resistance, we detected I260V and S56L substitutions in SdhB and SdhC, respectively, by direct sequencing. Both I260 in SdhB and S56 in SdhC were present in highly conserved regions of the ubiquinone binding site formed at the interface among SdhB, SdhC, and SdhD. Mutations at these positions have been implicated in resistance against fungicides that act as Sdh inhibitors in various pathogens. Therefore, we consider these mutations to be target-site resistance mutations for these acaricidal SDH inhibitors.

Preparation of Biodegradable Oligo(lactide)s-Grafted Dextran Nanogels for Efficient Drug Delivery by Controlling Intracellular Traffic.

Nanogels, nanometer-sized hydrogel particles, have great potential as drug delivery carriers. To achieve effective drug delivery to the active sites in a cell, control of intracellular traffic is important. In this study, we prepared nanogels composed of dextran with oligolactide (OLA) chains attached via disulfide bonds (Dex-g-SS-OLA) that collapse under the reductive conditions of the cytosol to achieve efficient drug delivery. In addition, we introduced galactose (Gal) residues on the nanogels, to enhance cellular uptake by receptor-mediated endocytosis, and secondary oligo-amine (tetraethylenepentamine) groups, to aid in escape from endosomes via proton sponge effects. The obtained Dex-g-SS-OLA with attached Gal residues and tetraethylenepentamine (EI4) groups, EI4/Gal-Dex-g-SS-OLA, formed a nanogel with a hydrodynamic diameter of ca. 203 nm in phosphate-buffered solution. The collapse of the EI4/Gal-Dex-g-SS-OLA nanogels under reductive conditions was confirmed by a decrease in the hydrodynamic diameter in the presence of reductive agents. The specific uptake of the hydrogels into HepG2 cells and their intercellular behavior were investigated by flow cytometry and confocal laser scanning microscopy using fluorescence dye-labeled nanogels. Escape from the endosome and subsequent collapse in the cytosol of the EI4/Gal-Dex-g-SS-OLA were observed. These biodegradable nanogels that collapse under reductive conditions in the cytosol should have great potential as efficient drug carriers in, for example, cancer chemotherapy.

Efficacy of Vonoprazan for Gastroesophageal Reflux Symptoms in Patients with Proton Pump Inhibitor-resistant Non-erosive Reflux Disease.

Objective Clinically, patients with proton pomp inhibitor (PPI)-resistant gastroesophageal reflux disease (GERD) are very challenging to treat. The aim of this study was to determine the rates of symptom relief and adverse events among PPI-resistant GERD patients that changed their therapy from a PPI to vonoprazan. Methods Patients with severe gastroesophageal reflux symptoms (total GERD-Q score ≥8) without endoscopic findings of mucosal breaks who changed their medication from a PPI to vonoprazan during a 12-week period from 2015 to 2016 at 2 hospitals were selected. The primary outcome was the self-reported relief of gastroesophageal reflux symptoms. The odds ratio (OR) for the improvement of symptoms was calculated based on an exact binomial distribution using a matched-pair analysis. The secondary outcome was the GERD-Q score and adverse events. Results Twenty-six patients (6 men) with a mean age of 67.5 years were analyzed. After the therapy was changed from a PPI to vonoprazan, 18 patients (69.2%) reported an improvement, 6 (23.1%) reported no change, and 2 (7.7%) reported an exacerbation of symptoms. A change in therapy was significantly associated with improved self-reported symptoms (OR 9.0, p<0.001). The mean total GERD-Q score during vonoprazan treatment was significantly lower than that during PPI therapy (11.96 vs. 8.92). There were no significant differences in the incidence of adverse events between the therapies. Conclusion Changing the medication from a PPI to vonoprazan was significantly associated with an improvement in gastroesophageal reflux symptoms. Vonoprazan is one of the most promising treatment options for patients with PPI-resistant GERD.

Successful endoscopic submucosal dissection of colon cancer with severe fibrosis after tattooing.

Endoscopic tattooing is often used to facilitate the identification of colorectal lesions before endoscopic treatments. However, tattooing under the lesion can result in technical difficulties because of the dark endoscopic field and submucosal fibrosis. A 65-year-old man with a non-granular-type laterally spreading tumor was referred to our hospital after tattooing with India ink for surgery. However, endoscopic submucosal dissection (ESD) was selected for the resection of this lesion because the findings of magnifying endoscopy suggested an intramucosal cancer. Dissection around a dense section was difficult because of the dark endoscopic field and non-lifting as a result of severe fibrosis. We performed ESD using the following strategy: (1) injection with a smaller amount of indigo carmine and (2) cut and dissection from the side of the thinly tattooed area. The lesion was curatively resected en bloc without any complications. This finding suggests that endoscopic tattooing before endoscopic treatment should be performed one or two folds away from the lesion.

Safety and efficacy of simultaneous colorectal ESD for large synchronous colorectal lesions.

BACKGROUND AND STUDY AIMS: Multiple large colorectal lesions are sometimes diagnosed during colonoscopy. However, there have been no investigations of the feasibility of simultaneous endoscopic submucosal dissection (ESD) for multiple lesions. This study aims to reveal the strategy of simultaneous ESD for multiple large colorectal lesions. PATIENTS AND METHODS: 246 patients who underwent ESD for 274 colorectal lesions were retrospectively evaluated in this study. Fifty-one large colorectal lesions among 23 patients were treated by ESD simultaneously (simultaneous group), and 223 patients were treated with ESD for a single lesion (single group). RESULTS: En-bloc resection and curative resection rates did not differ. Compared with the single group, each procedure time was faster (31.8 ±â€Š23.6 min vs. 45.8 ±â€Š44.8, P  = 0.002), but total procedure time was significantly longer in the simultaneous group (70.6 ±â€Š33.4 vs. 45.8 ±â€Š44.8 min, P  = 0.01). Rates of adverse events including bleeding and perforation were not higher in the simultaneous group but the mean blood pressure, incidence of bradycardia and the amount of sedative drug used during ESD were significantly higher in the simultaneous group. Multiple logistic regression analysis identified non-experienced physician, lesion size ≥ 40 mm and submucosal fibrosis as an independent risk factor for procedure duration (≥ 90 min) (Odds ratio 11.852, 18.280, and 3.672; P  < 0.05, respectively). CONCLUSIONS: Simultaneous ESD for multiple synchronous colorectal lesions is safe and feasible compared with single ESD and can reduce the burden to patients, length of hospital stay and medical expense. These results need to be elucidated by further studies.

More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance.

Genome instability triggers cellular senescence and is a common cause of cancer. The ribosomal RNA genes (rDNA), due to their repetitive structure, form a fragile site with frequent rearrangements. To identify eukaryotic factors that connect reduced genome stability to senescence we screened 4,876 strains of a Saccharomyces cerevisiae deletion library for aberrant rDNA and found 708 genes that contribute to its upkeep. 28 mutants caused abnormalities in non-rDNA chromosomes and among them 12 mutants have abnormalities both in rDNA and in non-rDNA chromosomes. Many mutated genes have not previously been implicated with genome maintenance nor their homologues with tumorigenesis in mammals. The link between rDNA state and senescence was broken after deletion of factors related with DNA polymerase ϵ. These mutations also suppressed the short lifespan phenotype of a sir2 mutant, suggesting a model in which molecular events at the heart of the replication fork induce abnormal rDNA recombination and are responsible for the emergence of an aging signal.

Multiple evanescent white dot syndrome associated with retinal vasculitis.

PURPOSE: A recent study revealed thickening of the inner retinal layers in acute stage of multiple evanescent white dot syndrome (MEWDS); however, the pathogenesis is still unknown. We report two cases with MEWDS whose funduscopy showed obvious retinal vasculitis. METHODS: Case reports. RESULTS: Healthy myopic 16- and 27-year-old women were the cases under study. In both cases, funduscopic examination revealed multiple, faint, small, subretinal white dots at the posterior pole to the midperiphery and macular granularity oculus dexter. Retinal vascular sheathing was also observed at midperiphery. Late-phase fluorescein angiography revealed leakages corresponding to the vascular sheathing. Enhanced depth imaging optical coherence tomography revealed the discontinuity of the ellipsoid zone corresponding to the white dots and increased macular choroidal thickness. One month later, these white dots and retinal sheathing spontaneously resolved in both cases. Three months later, impairments of the outer retinal morphology and the visual acuity were restored. CONCLUSION: These results suggest that retinal vasculitis possibly plays a role in the pathogenesis of thickened inner retinal layers in acute stage of MEWDS.

Impact of core-forming segment structure on drug loading in biodegradable polymeric micelles using PEG-b-poly(lactide-co-depsipeptide) block copolymers.

We synthesized series of amphiphilic AB-type block copolymers having systematic variation in the core-forming segments using poly(lactide-co-depsipeptide)s as a hydrophobic segment and prepared polymeric micelles using the block copolymers, PEG-b-poly(lactide-co-depsipeptide). We then discussed the relationship between the core-forming segment structure and drug loading efficiency for the polymeric micelles. PEG-b-poly(lactide-co-depsipeptide)s, PEG-b-PLGL containing L-leucine (Leu), and PEG-b-PLGF containing L-phenylalanine (Phe), with similar molecular weights and various mole fractions of depsipeptide units, were synthesized. Polymeric micelles entrapping model drug (fluorescein, FL) were prepared using these copolymers. As a result, PEG-b-poly(lactide-co-depsipeptide) micelles showed higher drug loading compared with PEG-b-PLLA and PEG-b-PDLLA as controls. The drug loading increased with increase in the mole fraction of depsipeptide unit in the hydrophobic segments. The introduction of aliphatic and aromatic depsipeptide units was effective to achieve higher FL loading into the micelles. PEG-b-PLGL micelle showed higher drug loading than PEG-b-PLGF micelle when the amount of FL in feed was high. These results obtained in this study should be useful for strategic design of polymeric micelle-type drug delivery carrier with high drug loading efficiency.

The effects of molecular structure on sol-to-gel transition of biodegradable poly(depsipeptide-co-lactide)-g-PEG copolymers.

We report on the effects of number and length of PEG chains in poly(depsipeptide-co-dl-lactide)-g-poly(ethylene glycol) (P(DG-dl-LA)-g-PEG) copolymers on their sol-to-gel transition behavior. The graft-type copolymer is suitable for the systematic study of the effects of molecular structure and hydrophilic/hydrophobic balance on its sol-to-gel transition. We prepared various P(DG-dl-LA)-g-PEG copolymers through coupling reactions between the pendant carboxylic acid groups of P(GD-dl-LA) and the end hydroxyl group of MeO-PEG having various molecular weights. Temperature-responsive sol-to-gel transition of the obtained copolymer solution in phosphate-buffered solution (pH 7.4, ionic strength = 0.14) was investigated by the test tube inverting method and rheological measurements. P(GD-dl-LA)-g-PEG copolymer prepared from higher molecular weight PEG showed higher sol-to-gel transition temperatures compared with the copolymers prepared from lower molecular weight PEG, although these copolymers have similar weight content of PEG (23-24 wt.%). Similar trends were observed for groups of copolymers whose PEG contents were 27 or 30 wt.%. These results are informative for providing strategies on rational design of thermo-gelling polymers.