Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Transcriptomic Profiling and Cellular Composition of Creeping Fat in Crohn's disease.

BACKGROUND AND AIMS: Creeping fat [CF] is a poorly understood feature of Crohn's disease [CD], characterized by the wrapping of mesenteric adipose tissue [MAT] around the inflamed intestine. The aim of this study was to investigate the transcriptional profile and compositional features of CF. METHODS: We collected 59 MAT samples: 23 paired samples from patients with CD (CF [CD-CF] and MAT around the uninflamed intestine [CD-MAT]) and 13 MAT samples from non-CD patients [Con-MAT]. Differentially expressed gene [DEG], functional pathway, cell deconvolution, and gene co-expression network analyses were performed. RESULTS: By comparing three different MAT samples, we identified a total of 529 DEGs [|log2FoldChange| > 1.5; false discovery rate < 0.05]. Of these, 323 genes showed an incremental pattern from Con-MAT to CD-MAT, and to CD-CF, while 105 genes displayed a decremental pattern. Genes with an incremental pattern were related to immune cell responses, including B- and T-cell activation, while genes with a decremental pattern were involved in cell trafficking and migration. Cell deconvolution analysis revealed significant changes in cellular composition between the CD-CF and Con-MAT groups, with increased proportions of B-cells/plasma cells [p = 1.16 × 10-4], T-cells [p = 3.66 × 10-3], and mononuclear phagocytes [p = 3.53 × 10-2] in the CD-CF group. In contrast, only the B-cell/plasma cell component showed a significant increase [p = 1.62 × 10-2] in the CD-MAT group compared to Con-MAT. CONCLUSION: The distinct transcriptional profiles and altered cellular components of each MAT found in our study provide insight into the mechanisms behind CF and highlight its possible role in the pathogenesis of CD.

Holistic energy landscape management in 2D/3D heterojunction via molecular engineering for efficient perovskite solar cells.

Constructing two-dimensional (2D) perovskite atop of 3D with energy landscape management is still a challenge in perovskite photovoltaics. Here, we report a strategy through designing a series of π-conjugated organic cations to construct stable 2D perovskites and to realize delicate energy level tunability at 2D/3D heterojunctions. As a result, the hole transfer energy barriers can be reduced both at heterojunctions and within 2D structures, and the preferable work function shift reduces charge accumulation at interface. Leveraging these insights and also benefitted from the superior interface contact between conjugated cations and poly(triarylamine) (PTAA) hole transporting layer, a solar cell with power conversion efficiency of 24.6% has been achieved, which is the highest among PTAA-based n-i-p devices to the best of our knowledge. The devices exhibit greatly enhanced stability and reproducibility. This approach is generic to several hole transporting materials, offering opportunities to realize high efficiency without using the unstable Spiro-OMeTAD.

Case-case genome-wide association analysis identifying genetic loci with divergent effects on Crohn's disease and ulcerative colitis.

Crohn's disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of these two diseases, we performed a genome-wide association study (GWAS) between CD (n = 2359) and UC (n = 2175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergent effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2. In addition, the seven established susceptibility loci [major histocompatibility complex (MHC), TNFSF15, OTUD3, USP12, IL23R, FCHSD2 and RIPK2] reached genome-wide significance. Of the nine loci, six (MHC, TNFSF15, OTUD3, USP12, IL23R and CD200) were replicated in the case-case GWAS of European populations. The proportion of variance explained in CD-UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver-operating characteristic curve value was 0.74, suggesting acceptable discrimination between CD and UC. This CD-UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.

Reactive Oxygen Species Suppressive Kraft Lignin-Gelatin Antioxidant Hydrogels for Chronic Wound Repair.

Chronic wound is difficult to repair because the normal wound healing mechanism is inhibited by the continuous inflammatory response. The delayed inflammatory responses generate high level of reactive oxygen species (ROS) at the wound sites, which leads to a longer inflammatory phase and induces a vicious cycle that interferes with the normal wound healing process. Therefore, ROS scavenging is an important factor for chronic wound healing. In this study, antioxidant hydrogel is developed by cross-linking kraft lignin, an antioxidant agent, and gelatin (Klig-Gel). Klig-Gel hydrogel is fabricated via ring opening reaction with epichlorohydrin as a cross-linker. High ROS scavenging activities are confirmed by various antioxidant evaluations, and in vitro natural antioxidant expression tests show reduction of oxidative stress. Mechanical properties of Klig-Gel hydrogel are tailorable by introducing different amount of kraft lignin to the hydrogel system. Biocompatibility is confirmed regardless of the kraft lignin content. Klig-Gel hydrogel is a promising ROS scavenging material that can be applied in various chronic wound healing applications.

Exogenous Ligand-Free NiH-Catalyzed Hydroacylation of Aryl Alkenes with Aroyl Fluorides.

Acyl fluorides have emerged as efficient acyl group donors, but these attractive reagents have rarely been utilized in transition-metal-catalyzed hydroacylation. Herein we report a nickel hydride-catalyzed hydroacylation of aryl alkenes using aroyl fluorides. The reaction proceeds without recourse to an exogenous ligand under mild conditions. The synthetic utility of the present method is demonstrated by the glovebox-free, gram-scale reaction and the late-stage derivatization of complex molecules containing pharmaceutical frameworks.

Discrete Infomax Codes for Supervised Representation Learning.

For high-dimensional data such as images, learning an encoder that can output a compact yet informative representation is a key task on its own, in addition to facilitating subsequent processing of data. We present a model that produces discrete infomax codes (DIMCO); we train a probabilistic encoder that yields k-way d-dimensional codes associated with input data. Our model maximizes the mutual information between codes and ground-truth class labels, with a regularization which encourages entries of a codeword to be statistically independent. In this context, we show that the infomax principle also justifies existing loss functions, such as cross-entropy as its special cases. Our analysis also shows that using shorter codes reduces overfitting in the context of few-shot classification, and our various experiments show this implicit task-level regularization effect of DIMCO. Furthermore, we show that the codes learned by DIMCO are efficient in terms of both memory and retrieval time compared to prior methods.

A multidisciplinary assessment of the impact of spilled acids on geoecosystems: an overview.

We developed and applied a multidisciplinary approach to the impact of an accidentally spilled acid on the underlying geomedia and subsurface environment, based on the concept of geoecosystem. We used mineralogical, geochemical, microbiological, and ecotoxicological techniques to identify and assess the multiple aspects involved. First, we constructed a conceptual model for the acid interactions with the underlying subsurface environment by introducing the concept of a geoecosystem-a multicomponent system composed of inorganic, organic, and biological components to describe the subsurface environment. Second, we designed and manufactured a two dimensional cell to visualize acid transport through geomedia. Third, we hypothesized that the acids are neutralized through dissolution of minerals and protonation of functional groups on the surfaces of minerals and organic matter. We tested this hypothesis by conducting batch-type geomedia-acid reaction and surface titration experiments. Fourth, we observed changes in soil microbial communities before and after the acid exposure and neutralization treatment. Fifth, we performed flow-through experiments using columns packed with soil samples pre-contaminated with arsenic to investigate potential longer term, secondary effects of remnant acids on geoecosystems. Finally, we conducted ecotoxicological investigations using various geomedia and observed that suitability of the geoecosystem as a habitat deteriorated to different degrees depending on the respective systems' acid neutralizing power. We conclude that a holistic understanding of the interactions among the multiple components of geoecosystems and subsequent estimation of the influenced area requires a multidisciplinary approach such as those used in this study. Based on the findings of this study, we propose geoecosystems' vulnerability defined as the reciprocal of their acid-neutralizing capacity against the moving acid fronts and present this concept as central to a quantitative assessment of the impact of acid spills on geoecosystems. We also inventoried the essential components, factors, and parameters necessary in developing geoecosystems' acid vulnerability assessment system.

The effects of diabetes on mental health in South Korean adults.

BACKGROUND: The changes in dietary habits can affect mental health problems, such as depressive disorder, due to the occurrence of diabetes. OBJECTIVE: This study aimed to determine the effects of diabetes on mental health (Patient Health Questionnaire-9: PHQ-9). METHODS: A secondary data analysis of cross-sectional design based on the raw data from KNHANES VII-1 was performed, which were disclosed by MOHW and KCDC. Of 8,150 respondents, 5,661 respondents aged ⩾ 20 years were included, thus excluding 2,489 respondents. Data were analyzed using an SPSS version 20.0 program. RESULTS: The respondents scored high for diabetes diagnosis status (3.65), suicide planning status for a year (8.56), mental problem counseling for a year (7.80), and the degree of daily stress awareness (8.27) in PHQ-9. They scored higher for suicide planning status for a year, mental problem counseling for a year, and the degree of daily stress awareness than for diabetes diagnosis status in PHQ-9. Positive correlation was found among diabetes diagnosis status, suicide planning status for a year, mental problem counseling for a year, and daily stress awareness in PHQ-9 (p< 0.01). Diabetes diagnosis status (p< 0.01), suicide planning status for a year (p< 0.001), mental problem counseling for a year (p< 0.001), and the degree of daily stress awareness (p< 0.001) affected PHQ-9. CONCLUSION: PHQ-9 for screening depressive disorder based on diabetes diagnosis status had low scoring distribution. However, because diabetes diagnosis status significantly affected PHQ-9 for depression screening, it is necessary to pay attention to health care related to diabetes. Further research should be conducted on the association with diverse causes of the low scoring distribution in PHQ-9 in relation to diabetes.

One-Stage Treatment for Adult Patients With Crouzonoid Appearance by Orthognathic and Face Contouring Surgery.

Crouzon syndrome is a rare genetic disorder with autosomal-dominant inheritance that shows a triad of hallmark characteristics: craniosynostosis, exophthalmos, and midface retrusion. General treatment protocol for patients with Crouzon syndrome has already been established, but there is no standard treatment strategy for adult patients with Crouzonoid appearance. The authors present clinical patients of 1-stage orthognathic and face contouring surgery to achieve functional and aesthetic improvement.One-stage surgery was performed in adult patients with Crouzonoid appearance without a history of facial surgery. Orthognathic 2-jaw surgery was first performed to treat class III malocclusion. Face contouring surgery was conducted next to improve the aesthetic appearance using midface augmentation with onlay rib bone graft, advancement genioplasty, augmentation rhinoplasty, and ancillary procedures such as neck lift, fat graft, or fillers.Five patients (2 men, 3 women) were enrolled in this study. The mean age at the time of surgery was 19.0 years. No specific surgery-related complications such as infection, nerve injury, or recurred malocclusion were observed during the 3.5 years of follow-up. Normal class I occlusion was reached in all patients. The frontonasal angle, nasolabial angle, and labiomental angle improved from 125.1° to 135.1° (P > 0.05), 60.9° to 86.3° (P = 0.018), and 146.3° to 125.0° (P = 0.018), respectively. The Global Aesthetic Improvement Scale score was 4.75 and 5.00 in frontal and profile views, respectively.One-stage orthognathic and face contouring surgery may be an effective surgical option with good postoperative functional and aesthetic improvement in adult patients with Crouzonoid appearance.

Effect of the redox dynamics on microbial-mediated As transformation coupled with Fe and S in flow-through sediment columns.

Arsenic (As) biogeochemistry coupled with iron (Fe) and sulfur (S) was studied using columns packed with As(V)-contaminated sediments under two phases: a reduction phase followed by an oxidation phase. During the reduction phase, four identical columns inoculated with G. sulfurreducens were stimulated with 3mM acetate for 60days. The As(III) in the effluent rapidly increased then gradually decreased. The Fe(II) and sulfate concentration indicated ferrous sulfide precipitation inside the column after day 14 and X-ray absorption near edge structure spectra showed that As(III) was enriched at the column outlet. The genera Desulfosporosinus and Anaeromyxobacter as well as the Geobacter inoculum played a primary role in As reduction. During the oxidation phase, dissolved oxygen was consumed by heterotrophic aerobes belonging to the phylum Cloroflexi in the column with acetate, resulting in more As in the effluent. When only nitrate was injected, sulfur-oxidizing bacteria such as Thiobacillus thioparus instantly oxidized the sulfide formed during the first phase, resulting in less As(V) in the aqueous phase compared to the column with dissolved oxygen alone. This study showed that redox gradients and dynamics linked to Fe and S biogeochemistry have an important role in controlling As mobility in subsurface environments.

Development of Facial Rejuvenation Procedures: Thirty Years of Clinical Experience with Face Lifts.

Facial rejuvenation procedures can be roughly divided into face lift surgery and nonoperative, less invasive procedures, such as fat grafts, fillers, botulinum toxin injections, thread lifts, or laserbrasion. Face lift surgery or rhytidectomy is the procedure most directly associated with rejuvenation, due to its fundamental ability to restore the anatomical changes caused by aging. Various methods of face lift surgery have been developed over the last hundred years, thanks to advances in the understanding of facial anatomy and the mechanisms of aging, as well as the dedication of innovative surgeons. However, no generally applicable standard method exists, because the condition of each patient is different, and each operative method has advantages and disadvantages. Specific characteristics of the skin of Asians and their skeletal anatomy should be considered when determining the operative method to be used on Asian patients. Plastic surgeons should improve their ability to analyze the original aesthetic properties and problem areas of each patient, drawing on scientific knowledge about the aging process, and they should develop the skills necessary to perform various rejuvenative techniques. In the present article, we reviewed various face lift procedures and the current methods of modified double plane face lift, based on our clinical experience of over 30 years.

Use of scar and capsule flap for preventing the contour deformity after applying tissue expansion in patients with scar.

BACKGROUND: Tissue expansion is a reconstruction method often used to repair the tissue loss that results after removing soft tissue lesions such as scars, tumors, and giant hairy nevi. However, because the pressure of a tissue expander applies in all directions almost equally, along with the desired expansion of skin and subcutaneous fat tissue, the muscle and bone underneath the expander become depressed simultaneously. Even with a successful expansion of the tissue itself, the conventional surgical procedure results to frequent aesthetically dissatisfying outcomes because of contour irregularities. However, no studies have been conducted regarding the correction of these secondary deformities. METHODS: A surgical method to prevent secondary depression deformity was performed on a total of 80 patients who had undergone scar revision using tissue expansion between May 2002 and April 2012. First, the scar tissue was de-epithelized and transposed to fill the depressed area as a buried flap. Second, the capsule formed around a tissue expander was elevated as a flap and turned over to fill the depressed area. Lastly, the thickened capsule at the margins of the expander was used as a free capsule graft, which provides additional supports. Four plastic surgeons analyzed the postoperative aesthetic results after the surgery in an outpatient follow-up clinic. RESULTS: There were complications of tissue expansion in 7 patients: 5 had minor complications, which were successfully addressed with conservative treatments, and 2 had major complications, which required tissue expander removal during the course. In more than 85% of the patients, satisfactory postoperative aesthetic results were achieved without any perceivable depression or asymmetry. CONCLUSIONS: Secondary depression deformity induced by a tissue expander can be effectively prevented with a simple operative technique using capsule flaps, scar tissue flaps, and free capsule grafts.

Face reconstruction using lateral intercostal artery perforator-based adipofascial free flap.

BACKGROUND: The aim of this study was to determine the efficacy of lateral intercostal artery perforator-based adipofascial free flaps for facial reconstruction in patients with facial soft tissue deficiency. METHODS: We conducted a retrospective study of five consecutive patients diagnosed with facial soft tissue deficiency who underwent operations between July 2006 and November 2011. Flap design included the area containing the perforators. A linear incision was made along the rib, which had the main intercostal pedicle. First, we dissected below Scarpa's fascia as the dorsal limit of the flap. Then, the adipofascial flap was elevated from the medial to the lateral side, including the perforator that pierces the serratus anterior muscle after emerging from the lateral intercostal artery. After confirming the location of the perforator, pedicle dissection was performed dorsally. RESULTS: Dominant perforators were located on the sixth to eighth intercostal space, and more than four perforators were found in fresh-cadaver angiography. In the clinical case series, the seventh or eighth intercostal artery perforators were used for the free flaps. The mean diameter of the pedicle artery was 1.36 mm, and the mean pedicle length was 61.4 mm. There was one case of partial fat necrosis. No severe complications occurred. CONCLUSIONS: This is the first study of facial contour reconstruction using lateral intercostal artery perforator-based adipofascial free flaps. The use of this type of flap was effective and can be considered a good alternative for restoring facial symmetry in patients with severe facial soft tissue deficiency.

Umbilical reconstruction using a modified inverted C-V flap with conjoint flaps.

The umbilicus is an important aesthetic feature of the abdomen. Because of its location, the umbilicus can be injured after abdominal surgical procedures. Various methods have been devised to reconstruct the umbilicus by using local flaps, purse-string sutures, or a cartilage graft, but there are no ideal methods. The authors have created a modified inverted C-V flap with conjoint flaps. A 10-year-old boy presented with deformed umbilicus because he had undergone surgical correction of an omphalocele. The drawback of the traditional C-V flap method is the transverse long abdominal scar because of the long length of the V flap. However, by using two conjoint flaps at the superior part of the C-V flap, the length of V flap can be more short and the umbilical wall can be reconstructed by rotation of two conjoint flaps. It is also good for making a sinusoidal pocket and it makes the umbilicus deeper and more natural-looking. After the operation, there were no complications like flap necrosis, infection, haematoma, and so on. The patient was satisfied with the results The patient had a more attractive umbilicus than the one with the other previous technique. This new method makes a natural-looking umbilicus with less of a transverse scar and an adequate sinusoidal pocket and umbilical wall.

Onlay rib bone graft in elevation of reconstructed auricle: 17 years of experience.

BACKGROUND: A cartilage wedge block and covering flap are standard procedures for firm elevation of the ear in microtia correction. However, using costal cartilage for elevation of the reconstructed auricle can be insufficient, and the fixed cartilage wedge block may be absorbed or may slip out. Furthermore, elevating covering flaps is time-consuming and uses up fascia, a potential source of reconstruction material. Therefore, we propose an innovative method using autologous onlay rib bone graft for auricular elevation of microtia. METHODS: From February 1995 to August 2012, 77 patients received a first stage operation with a rib cartilage framework graft. In the second stage operation, a small full thickness of rib bone was harvested through the previous donor scar. The bihalved rib bone was inserted into the subperiosteal pocket beneath the cartilage framework. RESULTS: The follow-up time ranged from 1 month to 17 years, with a mean of 3 years. All of the patients sustained the elevation of their ears very well during the follow-up period. Donor site problems, except for hypertrophic scars, were not observed. Surgery-related complications, specifically skin necrosis, infection, or hematoma, occurred in 4 cases. CONCLUSIONS: Onlay rib bone graft used to elevate the reconstructed auricle is a more anatomically appropriate material than cartilage, due to the bone-to-bone contact between the bone graft and the temporal bone. Postoperative minor correction of the elevation degree is straightforward and the skin graft survives better. Therefore, reconstructed auricle elevation using onlay rib bone graft is a useful and valuable method.

Treatment strategy for intracranial primary pure germinoma.

OBJECT: This prospective randomized clinical study will address the efficacy of radiation (RT)-alone and combined with pre-RT chemotherapy (CTX) treatments and propose the novel standard treatment strategy for intracranial primary pure germinoma. MATERIALS AND METHODS: Between 2005 and 2008, there were 54 patients diagnosed with intracranial primary pure germinomas in a single institute. Twenty-eight patients were enrolled. The mean age of the patients was 16.2 years (range 6-31 years). There were 19 men and 9 women (men/women ratio = 2.1:1). There were 21 patients with solitary tumors and 7 with multiple tumors. These patients were randomized as RT-only treatment group (11 solitary and 3 multiple tumors) and combined (10 solitary and 4 multiple tumors, neo-adjuvant CTX followed by response-adapted RT) treatment group. The follow-up period for RT only group has a median of 58 months (mean 58.2 months, range 41-82 months), and for combine therapy group, the median was 68.5 months (mean 67.8 months, range 41-88 months). All 14 patients in the RT-only group showed complete response (CR) and no recurrence. Eleven patients in the combined group had CR and three patients had partial response after neo-adjuvant CTX. All patients responded to RT as CR without recurrence. At the time of analysis, all 28 patients were alive without evidence of disease. CONCLUSION: Neo-adjuvant CTX for localized germinomas seems to be unnecessary as a method to reduce radiation dose in our RT protocol. However, the effective control of multifocal or disseminated germinoma can be achieved by neo-adjuvant CTX followed by response-adapted reduced dose RT.

Human cutaneous protothecosis: report of a case and literature review.

The Prototheca species is achlorophyllic algae and rarely causes human infection. Human protothecosis presents clinically as a cutaneous infection, olecranon bursitis, and disseminated systemic disease. We report a case of human cutaneous protothecosis involving the left wrist. A 68-year-old man presented with an ill-defined erythematous lesion with crust at the dorsal aspect of his left wrist. A punch biopsy was performed to reveal the histologic features of granulomatous inflammation with necrosis at the upper dermis, containing Prototheca organisms, of which, the characteristic features were highlighted by special staining. Through a molecular study, the Prototheca zopfii species was identified.

Reconstruction of defects after excision of facial skin cancer using a venous free flap.

After extensive excision of skin cancer on the face, or when skin cancer is located on the 3-dimensional structures of the face, reconstruction with a local flap can be impossible, or clinicians are reluctant to reconstruct defects with a skin graft because of postoperative contraction, hyperpigmentation, or other complication. Instead, an arterialized venous free flap can be used as an alternative method of reconstruction to prevent distortion and recurrence. Eight patients underwent surgery with an arterialized venous-free flap. We evaluated the cosmetic results using ordinary scale methods on the basis of 4 categories (color, contour, texture, and distortion of surrounding structures) and recurrence and metastases of skin cancer physically. The follow-up period ranged between 24 and 48 months, with an average of 33 months. All of the soft-tissue defects made by excising the tumor were reconstructed with good outcomes, except for 1 case. Regarding the cosmetic evaluation, the color was fair, the contour and texture were good, absence of distortion of surrounding structures was excellent, and the overall results in most all cases were good. There were no recurrences or metastases during the follow-up period. The arterialized venous free flap is an alternative plan among several reconstruction methods when skin cancer on the face is extensively excised.