Flexible High Lithium-Ion Conducting PEO-Based Solid Polymer Electrolyte with Liquid Plasticizers for High Performance Solid-State Lithium Batteries.

Lithium-ion secondary batteries (LIB) with high energy density have attracted much attention for electric vehicle (EV) applications. However, LIBs have a safety problem because these batteries contain a flammable organic electrolyte. As such, all-solid secondary batteries that are not flammable have been extensively reported recently. In this study, we have focused on polymer electrolytes, which is flexible and is expected to address the safety problem. However, the conventional polymer electrolytes have low electrial conductivity at room temperature. Various attempts have been made to solve this problem, such as the addition of inorganic fillers and ionic liquids; however, these composite polymer electrolytes have not yet reached a practical level of lithium-ion conductivity. In this study, high electrical conductivity and lithium dendrite formation-free PEO based composite electrolytes are developed with both a filler of Li6,4La3Zr1.4Ta0.6O12 and liquid plasticizers of tetraethylene glycol dimethyl ether and 1,2 dimethoxyethane. The proposed flexible polymer electrolyte shows a high electrical conduciviy of 6.01×10-4 S cm-1 at 25 °C.

Nerve Regeneration and Gait Function Recovery with Implantation of Glucose/Mannose Conduits Using a Rat Model: Efficacy of Glucose/Mannose as a New Neurological Guidance Material.

Therapy with clinical nerve guidance conduits often causes functional incompleteness in patients. With the aim of better therapeutic efficacy, nerve regeneration and gait function were investigated in this study using a novel nerve guidance conduit consisting of glucose/mannose. The glucose/mannose nerve guidance conduits were prepared by filling the conduits with the glucose/mannose aqueous solutions for different kinematic viscosity, which were applied to sciatic nerve defects (6 mm gap) in a rat model. The nerve regeneration effect and the gait function recovery with the fabricated nerve guidance conduits were examined. From the results of the XRD measurement, the glucose/mannose conduits were identified as crystal structures of cellulose type II. Young's modulus and the maximum tensile strength of the crystalline glucose/mannose conduits demonstrated good strength and softness for the human nerve. Above 4 weeks postoperative, macroscopic observation revealed that the nerve was regenerated in the defective area. In various staining results of the nerve tissue removed at 4 weeks postoperative, myelinated nerves contributing to gait function could not be observed in the proximal and distal sites to the central nerve. At 8-12 weeks postoperative, myelinated nerves were found at the proximal and distal sites in hematoxylin/eosin staining. Glia cells were confirmed by phosphotungstic acid-hematoxylin staining. Continuous nerve fibers were observed clearly in the sections of the regenerated nerves towards the longitudinal direction at 12 weeks postoperative. The angle between the metatarsophalangeal joint and the ground plane was approximately 93° in intact rats. At 4 weeks postoperative, walking was not possible, but at 8 weeks postoperative, the rats were able to walk, with an angle of 53°. At 12 weeks postoperative, the angle increased further, reaching 65°, confirming that the rats were able to walk more quickly than at 8 weeks postoperative. These results demonstrated that gait function in rats treated with glucose/mannose nerve guidance conduits was rapidly recovered after 8 weeks postoperative. The glucose/mannose nerve guidance conduit could be applied as a new promising candidate material for peripheral nerve regeneration.

Wound Healing Performance in a Moist Environment of Crystalline Glucose/Mannose Film as a New Dressing Material Using a Rat Model: Comparing with Medical-Grade Wound Dressing and Alginate.

Although medical wound dressings produced using hydrocolloids and alginate were effective in wound healing, adhesion at the wound site and the resulting delayed healing have been a problem. As a new wound dressing material, crystalline wound dressings produced from glucose/mannose were used in this study, which aimed to clarify the properties, adhesion reduction, and wound healing performance of a new wound dressing. Crystalline glucose/mannose films were obtained via alkali treatment using the solution casting method. The structure of the crystalline glucose/mannose films was analogous to the cellulose II polymorph, and the crystallinity decreased with time in hydrated conditions. The crystalline glucose/mannose films had adequate water absorption of 34 × 10-4 g/mm3 for 5 min. These allowed crystalline glucose/mannose films to remove excess wound exudates while maintaining a moist wound healing condition. This in vivo study demonstrated the healing effects of three groups, which were crystalline glucose/mannose group > alginate group > hydrocolloid group. At 1 week, the crystalline glucose/mannose group was also found to be non-adhesive to the portion of wound healing. This was evidenced by the earlier onset of the healing process, which assisted in re-epithelization and promotion of collagen formation and maturation. These results implied that crystalline glucose/mannose films were a promising candidate that could accelerate the wound healing process, compared with medical-grade wound dressing and alginate.

Ultrastructural and morphological analysis during progression of Bowen disease reveals a complex interplay between hyperkeratosis, cytokeratin expression, host immunity and amyloid deposition.

BACKGROUND: Bowen disease, one of the common skin cancers, is defined as squamous cell carcinoma in situ, characterized by atypical keratinocytes occupying the full thickness of the epidermis, and predominantly occurs on sun-protected skin. There is no existing data on the impact of tumour and immune cell interactions or cytokeratin expression on the pathology of Bowen disease. OBJECTIVES: We analysed dynamic changes in cytokeratin expression and immune cell composition during the development and progression of Bowen disease. MATERIALS & METHODS: Analysis was performed using immunohistochemistry and electron microscopy for samples from 140 patients with Bowen disease and 20 patients with invasive squamous cell carcinoma. We evaluated cytokeratin expression, the number of infiltrating immune cells and amyloid deposition by immunohistochemistry, and the ultrastructural relationship between tumour cells and immune cells by electron microscopy. RESULTS: The results showed that the expression of CK14 is associated with tumour progression, keratotic status and amyloid deposition and that the expression of CK10 is associated with accumulation of immune cells in Bowen disease. The findings of electron microscopy indicated repeated battles involving immune cells in response to tumour invasion. CONCLUSION: The expression of cytokeratins, hyperkeratosis, inflammatory infiltration and amyloid deposition are useful findings indicating the "stage" in Bowen disease.

Clinical guidance of pyoderma gangrenosum 2022.

Pyoderma gangrenosum (PG) is a rare, neutrophilic skin disease. For the purpose of accurate diagnosis and proper treatment of PG, the Japanese clinical practice guidance for PG developed by the Japanese Dermatological Association was published in 2022. In this guidance, clinical aspects, pathogenesis, current therapies, and clinical questions on PG are described from the viewpoints of current knowledge and evidence-based medicine. Here, the English version of the Japanese clinical practice guidelines for PG is presented and is intended to be widely referred to in the clinical examination and treatment of PG.

The Significant Potential of Simonkolleite Powder for Deep Wound Healing under a Moist Environment: In Vivo Histological Evaluation Using a Rat Model.

In the present work, simonkolleite powder consisting of Zn5(OH)8Cl2·H2O composition was proposed as a new candidate material for the healing of deep wounds in a moist environment. The powder was synthesized using a solution process and evaluated for wound-healing effects in rats. The pH value of physiological saline at 37 °C using the simonkolleite powder was 7.27, which was the optimal pH value for keratinocyte and fibroblast proliferation (range: 7.2-8.3). The amount of Zn2+ ions sustainably released from simonkolleite powder into physiological saline was 404 mmol/L below cytotoxic ion concentrations (<500 mmol/L), and the rhombohedral simonkolleite was accordingly converted to monoclinic Zn5(OH)10·2H2O. To evaluate the wound-healing effect of simonkolleite powder, the powder was applied to a full-thickness surgical wound reaching the subcutaneous tissue in the rat's abdomen. The histological analysis of the skin tissues collected after 1, 2, and 4 weeks found that angiogenesis, collagen deposition, and maturation were notedly accelerated due to the Zn2+ ions released from simonkolleite powder. The simonkolleite regenerated collagen close to autologous skin tissue after 4 weeks. The hair follicles, one of the skin appendages, were observed on the regenerative skin in the simonkolleite group at 4 weeks but not in the control group. Therefore, simonkolleite was hypothesized to stimulate the early regeneration of skin tissue in a moist environment, compared with commercial wound dressing material. These results suggested that simonkolleite could offer great potential as new wound dressing material.

Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F.

The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1ß, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis.

Examining the usefulness of the brain network marker program using fMRI for the diagnosis and stratification of major depressive disorder: a non-randomized study protocol.

BACKGROUND: Although many studies have reported the biological basis of major depressive disorder (MDD), none have been put into practical use. Recently, we developed a generalizable brain network marker for MDD diagnoses (diagnostic marker) across multiple imaging sites using resting-state functional magnetic resonance imaging (rs-fMRI). We have planned this clinical trial to establish evidence for the practical applicability of this diagnostic marker as a medical device. In addition, we have developed generalizable brain network markers for MDD stratification (stratification markers), and the verification of these brain network markers is a secondary endpoint of this study. METHODS: This is a non-randomized, open-label study involving patients with MDD and healthy controls (HCs). We will prospectively acquire rs-fMRI data from 50 patients with MDD and 50 HCs and anterogradely verify whether our diagnostic marker can distinguish between patients with MDD and HCs. Furthermore, we will longitudinally obtain rs-fMRI and clinical data at baseline and 6 weeks later in 80 patients with MDD treated with escitalopram and verify whether it is possible to prospectively distinguish MDD subtypes that are expected to be effectively responsive to escitalopram using our stratification markers. DISCUSSION: In this study, we will confirm that sufficient accuracy of the diagnostic marker could be reproduced for data from a prospective clinical study. Using longitudinally obtained data, we will also examine whether the "brain network marker for MDD diagnosis" reflects treatment effects in patients with MDD and whether treatment effects can be predicted by "brain network markers for MDD stratification". Data collected in this study will be extremely important for the clinical application of the brain network markers for MDD diagnosis and stratification. TRIAL REGISTRATION: Japan Registry of Clinical Trials ( jRCTs062220063 ). Registered 12/10/2022.

Verification of the brain network marker of major depressive disorder: Test-retest reliability and anterograde generalization performance for newly acquired data.

BACKGROUND: Recently, we developed a generalizable brain network marker for the diagnosis of major depressive disorder (MDD) across multiple imaging sites using resting-state functional magnetic resonance imaging. Here, we applied this brain network marker to newly acquired data to verify its test-retest reliability and anterograde generalization performance for new patients. METHODS: We tested the sensitivity and specificity of our brain network marker of MDD using data acquired from 43 new patients with MDD as well as new data from 33 healthy controls (HCs) who participated in our previous study. To examine the test-retest reliability of our brain network marker, we evaluated the intraclass correlation coefficients (ICCs) between the brain network marker-based classifier's output (probability of MDD) in two sets of HC data obtained at an interval of approximately 1 year. RESULTS: Test-retest correlation between the two sets of the classifier's output (probability of MDD) from HCs exhibited moderate reliability with an ICC of 0.45 (95 % confidence interval,0.13-0.68). The classifier distinguished patients with MDD and HCs with an accuracy of 69.7 % (sensitivity, 72.1 %; specificity, 66.7 %). LIMITATIONS: The data of patients with MDD in this study were cross-sectional, and the clinical significance of the marker, such as whether it is a state or trait marker of MDD and its association with treatment responsiveness, remains unclear. CONCLUSIONS: The results of this study reaffirmed the test-retest reliability and generalization performance of our brain network marker for the diagnosis of MDD.

Dual role of basophils in the pathogenesis of bullous pemphigoid elucidated by pathological and ultrastructural studies

Background: Bullous pemphigoid (BP), one of the most common autoimmune blistering disorders, is characterized by early erythematous and bullous lesions. Histopathologically, eosinophilia in the dermal tissue is a common finding in BP. In addition, basophils infiltrate the BP skin lesion. Although basophils are involved in the induction of type 2 immunity along with eosinophils, their role in both the erythema and blister, as well as the chronology of their involvement, have not been investigated. Objectives: To elucidate the role of basophils in BP development and resolution by performing early- and late-phase histopathological analysis of BP. Materials & Methods: A total of 25 patients with BP who underwent biopsy for both erythema and bullous lesions and were not taking oral steroids at the time of biopsy, were selected. Biopsy specimens of the erythematous (inflammatory) and bullous (resolution) phases were compared by histopathology, immunohistochemistry and electron microscopy. Results: During the early phase of BP, the number of basophils positively correlated with the number of eosinophils compared with other immune cells. In the late phase (bullous phase) of BP, the number of basophils significantly increased and more cell-cell contact between the basophils and M2 macrophages was noted, compared to the early phase Conclusions: Basophils are involved in the development of BP and its resolution, in part, via cell-cell contact with eosinophils or M2 macrophages, as demonstrated by pathological analysis.

[A Case of Surgically Treated Primary Anorectal Malignant Melanoma Detected by Colorectal Cancer Screening].

Anorectal malignant melanoma(AMM)is a relatively rare disease with an extremely poor prognosis. We experienced a case of this disease detected by colorectal cancer screening and report it here with a literature review. Our 67-year-old female patient was referred to the Department of Gastroenterology at our hospital for a thorough examination of the gastrointestinal tract after an abnormal fecal occult blood count(+/+ on 2 occasions)was noted during a colorectal cancer screening. Lower gastrointestinal endoscopy revealed a small easily bleeding lesion near the anal verge for which endoscopic mucosal resection was performed. A histopathological examination revealed a primary malignant melanoma of the rectum, and the patient underwent abdominoperineal rectal amputation. According to the rules for the treatment of T1b (1,200 µm), N0, P0, H0, M(-), StageⅠ, Cur A colorectal cancer. A histopathological examination of the resected specimen showed no remnant tumor cells. About 2 years have passed since the surgery, and the patient is still alive without recurrence. Considering its characteristics, patients with AMM will require further careful follow-up. Here we summarize our experience diagnosing and treating a case of early-stage AMM.

Infiltrative Erythemas and Nodules on a Unilateral Cheek Following Inappropriate Use of a Topical Steroid.

A 50-year-old Japanese woman referred to us with erythematous nodules on her left cheek. She had been treated with topical corticosteroids on her left cheek at a previous local clinic for 4 years. A skin biopsy specimen from a nodule showed perifolliculitis and folliculitis with a destruction of hair follicle without epidermal involvement. Based on the patient's history of the long-term topical corticosteroids and physical examination, we finally diagnosed this case as unilateral steroid-induced rosacea-like dermatitis (SIRD). She stopped topical steroid and was treated with topical application of benzoyl peroxide. One and a half year after starting the treatment, the nodules were flattened. Use of long-term and only unilateral application of topical corticosteroids probably resulted in unique clinical findings in our case. Given the broad clinical differential diagnosis, our case highlights the importance of appropriate application of topical steroids as well as histopathological analysis on any facial erythematous nodules.

Corrigendum: Bullous pemphigoid IgG induces cell dysfunction and enhances the motility of epidermal keratinocytes via Rac1/proteasome activation.

[This corrects the article DOI: 10.3389/fimmu.2019.00200.].