Metastatic Gastric Mucosal Melanoma: A Rare Case Presenting With Diffuse Gastric Polyposis.

We report a 66-year-old Chinese lady who presented with a three-month history of postprandial vomiting, early satiety, anorexia and weight loss, and significant physical findings of hepatomegaly and ascites. Gastroscopy revealed gastric polyposis with both hyperpigmented and unpigmented lesions over the gastric fundus, body, and proximal antrum, biopsies of which yielded malignant melanoma histologically. Cross-sectional imaging with CT also demonstrated extensive hepatic and bony metastases. No cutaneous or ocular primary was detected. She was treated with a combination of ipilimumab and nivolumab but developed interval progression of hepatic metastases after two cycles of immunotherapy. The patient eventually succumbed two months after diagnosis.

Somatic mutations in facial skin from countries of contrasting skin cancer risk.

The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK1-3, despite Singapore receiving 2-3 times more ultraviolet (UV) radiation4,5. Aging skin contains somatic mutant clones from which such cancers develop6,7. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations8-13. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes.

Power Efficiency Enhancement of Organic Light-Emitting Diodes Due to the Favorable Horizontal Orientation of a Naphthyridine-Based Thermally Activated Delayed Fluorescence Luminophore.

Four emitters based on the naphthyridine acceptor moiety and various donor units exhibiting thermally activated delayed fluorescence (TADF) were designed and synthesized. The emitters exhibited excellent TADF properties with a small ΔE ST and a high photoluminescence quantum yield. A green TADF organic light-emitting diode based on 10-(4-(1,8-naphthyridin-2-yl)phenyl)-10H-phenothiazine exhibited a maximum external quantum efficiency of 16.4% with Commission Internationale de L'éclairage coordinates of (0.368, 0.569) as well as a high current and power efficiency of 58.6 cd/A and 57.1 lm/W, respectively. The supreme power efficiency is a record-high value among the reported values of devices with naphthyridine-based emitters. This results from its high photoluminescence quantum yield, efficient TADF, and horizontal molecular orientation. The molecular orientations of the films of the host and the host doped with the naphthyridine emitter were explored by angle-dependent photoluminescence and grazing-incidence small-angle X-ray scattering (GIWAXS). The orientation order parameters (ΘADPL) were found to be 0.37, 0.45, 0.62, and 0.74 for the naphthyridine dopants with dimethylacridan, carbazole, phenoxazine, and phenothiazine donor moieties, respectively. These results were also proven by GIWAXS measurement. The derivative of naphthyridine and phenothiazine was shown to be more flexible to align with the host and to show the favorable horizontal molecular orientation and crystalline domain size, benefiting the outcoupling efficiency and contributing to the device efficiency.

Elastic mechanics solution of thermal expansion of bi-material curved beam and its application to negative thermal expansion metamaterials.

Thermal stress impacts various engineering fields significantly, such as aerospace and precision instruments. This adverse effect can be greatly reduced, if not eliminated, by the application of micro-thermal expansion materials, and bi-material beams are widely utilized in the design of micro-thermal expansion structures, thereby exhibiting great application potentials. The elasticity solution of bi-material curved beam under free thermal expansion has been proposed by scholars. Based on this solution, the simplified form is proposed in this paper, and extended to the case where the rotation angles at both ends of the circular arc are constrained under thermal loads. Besides, the geometric parameters and the nonlinear problems of the thermal expansion of bi-material curved beam are analyzed. In addition, a novel type of negative thermal expansion material has been designed by applying the bi-material curved beam to the tetra chiral and anti-tetra chiral materials. The proposed material has greater negative thermal expansion effect than the traditional tetra and anti-tetra chiral materials that are with straight beams.

Unusual Presentations of Eccrine Porocarcinomas.

Eccrine porocarcinomas (EPCs) are rare tumours, albeit the most common malignant adnexal tumours of the skin. They can present with very heterogeneous clinical and dermoscopic features, rendering diagnosis limited to histopathological examination alone. We share 2 cases of EPCs, one of which arose in a patient with a prior diagnosis of cutaneous squamous cell carcinoma (SCC) and another whose EPC was likely a malignant transformation of an existing poroma. An occurrence of porocarcinoma after the diagnosis of SCC may suggest the possibility of unknown risk factors for both. Positivity to androgen, oestrogen, and epidermal growth factor receptors was seen in a proportion of porocarcinomas, and this may prompt further research on combination therapy between conventional treatment modalities with hormone receptor antagonists. Malignant change of a poroma may be a more common phenomenon than we would expect based on the current literature.

Widely heterogeneous humoral and cellular immunity after mild SARS-CoV-2 infection in a homogeneous population of healthy young men.

BACKGROUND: We studied humoral and cellular responses against SARS-CoV-2 longitudinally in a homogeneous population of healthy young/middle-aged men of South Asian ethnicity with mild COVID-19. METHODS: In total, we recruited 994 men (median age: 34 years) post-COVID-19 diagnosis. Repeated cross-sectional surveys were conducted between May 2020 and January 2021 at six time points - day 28 (n = 327), day 80 (n = 202), day 105 (n = 294), day 140 (n = 172), day 180 (n = 758), and day 280 (n = 311). Three commercial assays were used to detect anti-nucleoprotein (NP) and neutralizing antibodies. T cell response specific for Spike, Membrane and NP SARS-CoV-2 proteins was tested in 85 patients at day 105, 180, and 280. RESULTS: All serological tests displayed different kinetics of progressive antibody reduction while the frequency of T cells specific for different structural SARS-CoV-2 proteins was stable over time. Both showed a marked heterogeneity of magnitude among the studied cohort. Comparatively, cellular responses lasted longer than humoral responses and were still detectable nine months after infection in the individuals who lost antibody detection. Correlation between T cell frequencies and all antibodies was lost over time. CONCLUSION: Humoral and cellular immunity against SARS-CoV-2 is induced with differing kinetics of persistence in those with mild disease. The magnitude of T cells and antibodies is highly heterogeneous in a homogeneous study population. These observations have implications for COVID-19 surveillance, vaccination strategies, and post-pandemic planning.

Establishment of a modified percutaneous CT-guided paraspinal intramuscular VX-2 squamous cell carcinoma dual tumor model in rabbits.

BACKGROUND: The rabbit VX-2 tumor model is a commonly used transplanted tumor model and is widely used in surgical, radiological, and interventional studies. Most of the known tumor models for each site are single solid tumors. This study aimed to establish an accurate and stable intramuscular dual tumor model guided by computed tomography (CT). METHODS: In this study, we compared three different inoculation methods to select the most appropriate dual tumor model. Six New Zealand White rabbits were used as tumor-carrying rabbits for tumor harvesting. Thirty rabbits were divided into three groups as experimental rabbits. Group A applied the tumor cell suspension method, in which the suspension was injected into the designated location with a syringe under CT guidance. Groups B and C used tumor tissue strips obtained in vivo or under direct in vitro vision. The tumor tissue strips were implanted into the designated locations using a guide needle under CT guidance. The differences in tumorigenic rate, the size difference between bilateral tumors, and metastasis between the three methods were compared. RESULTS: It was found that group A obtained a 100% tumor survival rate, but the size of the tumor was more variable, and needle tract implantation metastasis occurred in 5 cases. In group B, tumor tissue strips were taken in vivo for implantation, in which one case failed to survive. Tumor tissue strips in group C were obtained in vitro under direct vision. The tumor tissue strips obtained in vitro by puncture using a biopsy needle in group C had a 100% tumorigenicity rate and stable tumor size. No significant needle tract implantation metastases were found in either group B or C. The variance of tumor size obtained in group A was significantly higher than in groups B and C. The variance of tumor size in group C was the smallest. Group C had high tumorigenicity and a more stable size and morphology of the formed tumors. CONCLUSION: The results showed that the method of obtaining tumor tissue strips using in vitro direct vision puncture and implanting them into the muscle with CT guidance and guide needles can establish an accurate and stable dual tumor model. This dual tumor model can provide substantial support for relevant preclinical studies.

3D-printed cell-free PCL-MECM scaffold with biomimetic micro-structure and micro-environment to enhance in situ meniscus regeneration.

Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells, meniscus regeneration remains a great challenge in clinic. In this study, we found decellularized meniscal extracellular matrix (MECM) preserved native meniscal collagen and glycosaminoglycans which could be a good endogenous regeneration guider for stem cells. Moreover, MECM significantly promoted meniscal fibrochondrocytes viability and proliferation, increased the expression of type II collagen and proteoglycans in vitro. Meanwhile, we designed 3D-printed polycaprolactone (PCL) scaffolds which mimic the circumferential and radial collagen orientation in native meniscus. Taken these two advantages together, a micro-structure and micro-environment dually biomimetic cell-free scaffold was manipulated. This cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native meniscus. Strikingly, neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep models. Histological staining confirmed neo-menisci showed meniscus-like heterogeneous staining. Mankin scores showed PCL-MECM scaffold could protect articular cartilage well, and knee X-ray examination revealed same results. Knee magnetic resonance imaging (MRI) scanning also showed some neo-menisci in PCL-MECM scaffold group. In conclusion, PCL-MECM scaffold appears to optimize meniscus regeneration. This could represent a promising approach worthy of further investigation in preclinical applications.

Cell-Free Strategies for Repair and Regeneration of Meniscus Injuries through the Recruitment of Endogenous Stem/Progenitor Cells.

The meniscus plays a vital role in protecting the articular cartilage of the knee joint. The inner two-thirds of the meniscus are avascular, and injuries to this region often fail to heal without intervention. The use of tissue engineering and regenerative medicine techniques may offer novel and effective approaches to repairing meniscal injuries. Meniscal tissue engineering and regenerative medicine typically use one of two techniques, cell-based or cell-free. While numerous cell-based strategies have been applied to repair and regenerate meniscal defects, these techniques possess certain limitations including cellular contamination and an increased risk of disease transmission. Cell-free strategies attempt to repair and regenerate the injured tissues by recruiting endogenous stem/progenitor cells. Cell-free strategies avoid several of the disadvantages of cell-based techniques and, therefore, may have a wider clinical application. This review first compares cell-based to cell-free techniques. Next, it summarizes potential sources for endogenous stem/progenitor cells. Finally, it discusses important recruitment factors for meniscal repair and regeneration. In conclusion, cell-free techniques, which focus on the recruitment of endogenous stem and progenitor cells, are growing in efficacy and may play a critical role in the future of meniscal repair and regeneration.

[Construction of tissue engineered cartilage based on acellular cartilage extracellular matrix oriented scaffold and chondrocytes].

Objective: To observe the feasibility of acellular cartilage extracellular matrix (ACECM) oriented scaffold combined with chondrocytes to construct tissue engineered cartilage. Methods: Chondrocytes from the healthy articular cartilage tissue of pig were isolated, cultured, and passaged. The 3rd passage chondrocytes were labeled by PKH26. After MTT demonstrated that PKH26 had no influence on the biological activity of chondrocytes, labeled and unlabeled chondrocytes were seeded on ACECM oriented scaffold and cultivated. The adhesion, growth, and distribution were evaluated by gross observation, inverted microscope, and fluorescence microscope. Scanning electron microscope was used to observe the cellular morphology after cultivation for 3 days. Type Ⅱ collagen immunofluorescent staining was used to check the secretion of extracellular matrix. In addition, the complex of labeled chondrocytes and ACECM oriented scaffold (cell-scaffold complex) was transplanted into the subcutaneous tissue of nude mouse. After transplantation, general physical conditions of nude mouse were observed, and the growth of cell-scaffold complex was observed by molecular fluorescent living imaging system. After 4 weeks, the neotissue was harvested to analyze the properties of articular cartilage tissue by gross morphology and histological staining (Safranin O staining, toluidine blue staining, and typeⅡcollagen immunohistochemical staining). Results: After chondrocytes that were mainly polygon and cobblestone like shape were seeded and cultured on ACECM oriented scaffold for 7 days, the neotissue was translucency and tenacious and cells grew along the oriented scaffold well by inverted microscope and fluorescence microscope. In the subcutaneous microenvironment, the cell-scaffold complex was cartilage-like tissue and abundant cartilage extracellular matrix (typeⅡcollagen) was observed by histological staining and typeⅡcollagen immunohistochemical staining. Conclusion: ACECM oriented scaffold is benefit to the cell adhesion, proliferation, and oriented growth and successfully constructes the tissue engineered cartilage in nude mouse model, which demonstrates that the ACECM oriented scaffold is promise to be applied in cartilage tissue engineering.

Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model.

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

hWJECM-Derived Oriented Scaffolds with Autologous Chondrocytes for Rabbit Cartilage Defect Repairing.

Previously, we synthesized an articular cartilage extracellular matrix (ECM)-derived oriented scaffold for cartilage tissue engineering, which was biomimetic in terms of structure and biochemical composition. However, the limit resource of the cartilage-derived ECM is a hindrance for its application. In this study, we developed a new material for cartilage tissue engineering-human umbilical cord Wharton's jelly-derived ECM (hWJECM). The hWJECM has an abundant resource and similar biochemistry with cartilage ECM, and the use of it is not associated with ethical controversy. We adopted the method previously used in cartilage ECM-derived oriented scaffold preparation to generate the oriented hWJECM-derived scaffold, and the scaffold properties were tested in vitro and in vivo. The three-dimensional scaffold has a porous and well-oriented structure, with a mean pore diameter of ∼104 µm. Scanning electron microscopy and cell viability staining results demonstrated that the oriented scaffold has good biocompatibility and cell alignment. In addition, we used functional autologous chondrocytes to seed the hWJECM-derived oriented scaffold and tested the efficacy of the cell-scaffold constructs to repair the full-thickness articular cartilage defect in a rabbit model. Defects of 4 mm diameter were generated in the patellar grooves of the femurs of both knees and were implanted with chondrocyte-scaffold constructs (group A) or scaffolds alone (group B); rabbits with untreated defects were used as a control (group C). Six months after surgery, all defects in group A were filled completely with repaired tissue, and most of which were hyaline cartilage. In contrast, the defects in group B were filled partially with repaired tissue, and approximately half of these repaired tissues were hyaline cartilage. The defects in group C were only filled with fibrotic tissue. Histological grading score of group A was lower than those of groups B and C. Quantification of glycosaminoglycan indicated that newly formed cartilage in group A rabbits was comparable with normal cartilage. In conclusion, hWJECM-derived oriented scaffolds loaded with autologous chondrocytes induced cartilage repair in rabbit knees, which was comparable with native cartilage in terms of macroscopic view, microstructure, and biochemical composition.

Fabrication and In Vitro Study of Tissue-Engineered Cartilage Scaffold Derived from Wharton's Jelly Extracellular Matrix.

The scaffold is a key element in cartilage tissue engineering. The components of Wharton's jelly are similar to those of articular cartilage and it also contains some chondrogenic growth factors, such as insulin-like growth factor I and transforming growth factor-ß. We fabricated a tissue-engineered cartilage scaffold derived from Wharton's jelly extracellular matrix (WJECM) and compared it with a scaffold derived from articular cartilage ECM (ACECM) using freeze-drying. The results demonstrated that both WJECM and ACECM scaffolds possessed favorable pore sizes and porosities; moreover, they showed good water uptake ratios and compressive moduli. Histological staining confirmed that the WJECM and ACECM scaffolds contained similar ECM. Moreover, both scaffolds showed good cellular adherence, bioactivity, and biocompatibility. MTT and DNA content assessments confirmed that the ACECM scaffold tended to be more beneficial for improving cell proliferation than the WJECM scaffold. However, RT-qPCR results demonstrated that the WJECM scaffold was more favorable to enhance cellular chondrogenesis than the ACECM scaffold, showing more collagen II and aggrecan mRNA expression. These results were confirmed indirectly by glycosaminoglycan and collagen content assessments and partially confirmed by histology and immunofluorescent staining. In conclusion, these results suggest that a WJECM scaffold may be favorable for future cartilage tissue engineering.

Basaloid follicular hamartoma: clinical, dermoscopic, and histopathological characteristics of case.

Basaloid follicular hamartoma (BFH) is a rare benign adnexal tumor with variable clinical presentation. We report a case of a 64-year-old man, who presented with an incidental finding of a 3mm hyperpigmented macule on his cheek. Dermoscopy revealed a structureless blue lesion. Histopathology examination showed interconnecting lobules and cords of bland pigmented epithelial cells within the dermal stroma, with the presence of pseudohorncysts. The lesional cells were faintly positive for Bcl2on immunohistochemical staining. These findings were consistent with basaloid follicular hamartoma. Histological differential diagnoses include benign lesions such as trichoepithelioma, and malignant lesions such as basal cell carcinoma (BCC).