π-Diamond: A Diamondoid Superstructure Driven by π-Interactions.

Modulating the arrangement of superstructures through noncovalent interactions has a significant impact on macroscopic shape and the expression of unique properties. Constructing π-interaction-driven hierarchical three-dimensional (3D) superstructures poses challenges on account of limited directional control and weak intermolecular interactions. Here we report the construction of a 3D diamondoid superstructure, named π-Diamond, employing a ditopic strained Z-shaped building block comprising a porphyrin unit as bow-limb double-strapped with two m-xylylene units as bowstrings. This superstructure, reminiscent of diamond's tetrahedral carbon composition, is composed of double-walled tetrahedron (DWT) driven solely by π-interactions. Hetero-π-stacking interactions between porphyrin and m-xylylene panels drive the assembly of four building blocks predominantly into a DWT, which undergoes extension to create an adamantane unit and eventually a diamondoid superstructure wherein each porphyrin panel is shared by two neighboring tetrahedra through hetero-π-stacking. π-Diamond exhibits a solid-state fluorescent quantum yield 44 times higher than that of tetraphenylporphyrin along with excellent photocatalytic performance. The precise 3D directionality of π-interactions, achieved through strained multipanel building blocks, revolutionizes the assembly of hierarchical 3D superstructures driven by π-interactions.

Hybrid Autologous Costal Cartilage Grafting for Augmentation Rhinoplasty in Asian Patients.

BACKGROUND: Autologous costal cartilage has been used for augmentation rhinoplasty in Asia for many years. This study aimed to assess the effectiveness and safety of hybrid grafting of costal cartilage for dorsal augmentation, septal reconstruction, and tip augmentation for Asian patients. METHODS: A surgical technique was introduced and patients having rhinoplasty using this technique from April 2020 to March 2021 were retrospectively studied. In this technique, costal cartilage was meticulously carved or diced and grafted in various ways mainly based on the anatomic characteristics of nasal skin and subcutaneous soft tissues as well as bone and cartilage framework. The surgical outcomes, patient satisfaction, and complications retrieved from the documented medical records were reviewed and analyzed. RESULTS: Twenty-five patients having rhinoplasty with the proposed technique were followed up from 6 months to 12 months. As for cosmetic outcomes, 21 patients were graded as good, 3 patients were graded as fair, and only 1 patient was graded as poor. Those patients who were not graded as good had over-rotated tips, insufficient dorsal augmentation, or asymmetry of nostrils and soft tissue contracture. The overall patient satisfaction was as high as 96.0%. Local infection occurred in 1 patient and hematoma was not observed. Warping and visibility of costal cartilage were not observed in any patients. Slight displacement of diced cartilages was found in 2 patients near the radix 1 week postoperatively. CONCLUSIONS: Hybrid autologous costal cartilage grafts can be used for both tip refinement and dorsal augmentation for East Asian patients and achieve an outcome of a natural-looking nose with minimal complications. LEVEL OF EVIDENCE: Level IV.

Strain-Driven Formal [1,3]-Aryl Shift within Molecular Bows.

Delving into the influence of strain on organic reactions in small molecules at the molecular level can unveil valuable insight into developing innovative synthetic strategies and structuring molecules with superior properties. Herein, we present a molecular-strain engineering approach to facilitate the consecutive [1,2]-aryl shift (formal [1,3]-aryl shift) in molecular bows (MBs) that integrate 1,4-dimethoxy-2,5-cyclohexadiene moieties. By introducing ring strain into MBs through tethering the bow limb, we can harness the intrinsic mechanical forces to drive multistep aryl shifts from the para- to the meta- to the ortho-position. Through the use of precise intramolecular strain, the seemingly impractical [1,3]-aryl shift was realized, resulting in the formation of ortho-disubstituted products. The solvent and temperature play a crucial role in the occurrence of the [1,3]-aryl shift. The free energy calculations with inclusion of solvation support a feasible mechanism, which entails multistep carbocation rearrangements, for the formal [1,3]-aryl shift. By exploring the application of molecular strain in synthetic chemistry, this research offers a promising direction for developing new tools and strategies towards precision organic synthesis.

Cascade Synthesis of Benzotriazulene with Three Embedded Azulene Units and Large Stokes Shifts.

We report here the one-pot synthesis of benzo[1,2-a : 3,4-a' : 5,6-a'']triazulene (BTA), wherein three azulene units are embedded through a tandem reaction comprising two steps, Suzuki coupling and Knoevenagel condensation, between a readily available triborylated truxene precursor and 8-bromo-1-naphthaldehyde. Its nitration leads to a regioselective trinitrated product, namely, BTA-NO2 . Single-crystal X-ray crystallography revealed that the superstructure of BTA consists of a dimer stacked by two enantiomeric helicene conformers, while that of BTA-NO2 consists of an unprecedented π-tetramer stacked from two enantiomeric dimers, that is, four distinct helicene conformers. Both compounds show excellent stability and fluorescence with large Stokes shifts of up to 5100 cm-1 . In addition, BTA-NO2 exhibits a unique solvatochromic effect in different solvents and hydrogen-bonding-induced emission transfer in different ratios of THF/H2 O solutions.

Infinite Twisted Polycatenanes.

Poly[n]catenanes have exceptional mechanical bonding properties that give them tremendous potential for use in the development of molecular machines and soft materials. Synthesizing these compounds has, however, proven to be a formidable challenge. Herein, we describe a concise method for the construction of twisted polycatenanes. Our approach involves using preorganized double helicates as templates, linked crosswise in a linear fashion by either silver ions or triple bonds. By using this approach, we successfully synthesized twisted polycatenanes with both coordination and covalent bonding employing Ag(I) ions and ethynylene units, respectively, as the linkages and leveraging the same Ag(I)-templated double helicate in both cases. Synthesis with Ag(I) ions formed a single-crystalline one-dimensional (1D) coordination poly[n]catenane, and synthesis using ethynylene units generated 1D fibers which self-assembled with solvents to form a gel. Our results confirm the potential of multi-stranded metallohelicates for creating sophisticated mechanically interlocked molecules and polymers, which could pave the way for exploration in the realms of molecular nanotopology and materials design.

Association of novel MUC16, MAP3K15 and ABCA1 mutation with giant congenital melanocytic nevus.

BACKGROUND: Giant congenital melanocytic nevus (GCMN) is the benign nevomelanocytic proliferation. Mutations in NRAS have been previously detected in GCMN, but mutations in BRAF are generally lacking in the Chinese population. Mutated genes in this disease can estimate the risk of malignant transformation in GCMN. Therefore, it is worth investigating the genetic information of GCMN. METHODS: Here, we presented two cases of GCMN of the upper extremities. The clinical and histological data were analyzed. The whole exome sequencing (WES) was performed to investigate the mutational profile of peripheral venous blood (PB), normal skin (NS), small melanocytic nevus (SMN), deep penetrating and non-penetrating GCMN (dPGCMN and nPGCMN). RESULTS: We showed a reduction in the circumference of involved upper extremities in both patients. The clinical and histopathological data indicated the reduction of adipose tissue associated with the invasion of GCMN. The WES data revealed that MUC16, MAP3K15 and ABCA1 were novel potential candidate genes for the disease as well as biomarkers for predicting malignant transformation. CONCLUSION: The MUC16, MAP3K15 and ABCA1 may serve as novel biomarkers for predicting malignant transformation and targets for the diagnoses and therapy for the GCMN.

Linear Nonalternant Isomers of Acenes Fusing Multiple Azulene Units.

A modular approach to azulene building blocks was developed starting from readily available aryl-substituted cyclopentadiene and ortho-haloaryl aldehyde by dehydration condensation followed by palladium-catalyzed C-H coupling. It facilitates the synthesis of four nonalternant isomers of pentacene and hexacene, namely, dibenzo[e,g]azulene, benzo[1,2-f : 5,4-f']diazulene, benzo[1,2-f : 4,5-f']diazulene, and naphtho[2,3-f : 6,7-f']diazulene, which exhibit narrow band gaps with high stability in addition to protonation-caused enhanced near-infrared fluorescence. We discovered that in these isomers, i) constitutional isomerism influences significantly their photoelectric properties and ii) the elongation of the conjugation system does not necessarily lead to a narrowing in the band gap. Due to the easy modifiability of the nonazulene building blocks, this strategy can be extended to modularly prepare numerous multiazulene-fused aromatics.

Extracellular Vesicles in chondrogenesis and Cartilage regeneration.

Extracellular vesicles (EVs), mainly exosomes and microvesicles, are bilayer lipids containing biologically active information, including nucleic acids and proteins. They are involved in cell communication and signalling, mediating many biological functions including cell growth, migration and proliferation. Recently, EVs have received great attention in the field of tissue engineering and regenerative medicine. Many in vivo and in vitro studies have attempted to evaluate the chondrogenesis potential of these microstructures and their roles in cartilage regeneration. EVs derived from mesenchymal stem cells (MSCs) or chondrocytes have been found to induce chondrocyte proliferation and chondrogenic differentiation of stem cells in vitro. Preclinical studies have shown that exosomes derived from MSCs have promising results in cartilage repair and in cell-free therapy of osteoarthritis. This review will focus on the in vitro and in vivo chondrogenesis and cartilage regeneration of EVs as well as their potential in the treatment of osteoarthritis.

Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation.

In hypertrophic scar (HS) formation, the type 2 immune response induces the alternatively activated macrophages (M2), which manipulate fibroblasts to differentiate into myofibroblasts with active biologic functions and proliferation. Myofibroblasts express α-smooth muscle actin (α-SMA) and synthesize and produce additional collagen type I and collagen type III, inducing HS formation. However, studies on the mechanism of M2 macrophage modulation are only based on the recognition of profibrotic factors such as TGF-ß1 secreted by macrophages. The influence of exosomes from M2 macrophages on scar formation is still unknown. Both M2 macrophages and myofibroblasts highly express glutaminases (GLSs). GLS is a critical enzyme in glutaminolysis and is important for M2 macrophage and fibroblast polarization. In this study, we found that in a TGF-ß1-stimulated coculture system, a long noncoding RNA (lncRNA) named lncRNA-ASLNCS5088 was enriched in M2 macrophage-derived exosomes. This lncRNA could be transferred with high efficiency to fibroblasts and acted as an endogenous sponge to adsorb microRNA-200c-3p, resulting in increased GLS and α-SMA expression. Pretreatment with GW4869, which impairs M2 macrophage exosome synthesis, ameliorated these pathologic changes in fibroblasts in vitro. Local injection in the late scar formation period with GW4869 reduced α-SMA+ fibroblasts and alleviated the fibrosis of tissue after wound healing in vivo.-Chen, J., Zhou, R., Liang, Y., Fu, X., Wang, D., Wang, C. Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation.

Anti-miR-200b promotes wound healing by regulating fibroblast functions in a novel mouse model.

MicroRNA-200b (miR-200b) down-regulation has been found in wound-healing tissues. Fibroblasts are the predominant cells that orchestrate the production of collagen in wound healing. However, it is still unclear whether miR-200b can affect the wound healing by regulating the fibroblasts' function. The current rodent wound-healing models are not ideal due to their marked difference in structure compared with the human skin. In this study, we demonstrated that the murine plantar skin had similar anatomical features to the human skin. Using this model, the gain/loss-of-function studies showed that miR-200b caused a significantly delayed wound healing in vivo. Furthermore, using cell proliferation, migration and collagen synthesis assays, we found that miR-200b attenuated cell proliferation, migration and collagen synthesis of fibroblasts, which are critical aspects of wound healing. miR-200b also decreased the expression of Zeb1. Collectively, we established a new murine plantar skin model for the investigation of wound healing, and based on it we found that miR-200b affected the wound healing by regulating the biological function of fibroblasts, which provided a new insight for wound healing.

Proteomic characterization of the interactions between fish serum proteins and waterborne bacteria reveals the suppression of anti-oxidative defense as a serum-mediated antimicrobial mechanism.

Fish blood is one of the crucial tissues of innate immune system, but the full repertoire of fish serum components involved in antibacterial defense is not fully identified. In this study, we demonstrated that turbot serum, but not the heat-inactivated control, significantly reduced the number of Edwardsiella tarda (E. tarda). By conjugating serum proteins with fluorescent dyes, we showed that E. tarda were coated with multiple fish proteins. In order to identify these proteins, we used E. tarda to capture turbot serum proteins and subjected the samples to shotgun proteomic analysis. A total of 76 fish proteins were identified in high confidence, including known antimicrobial proteins such as immunoglobins and complement components. 34 proteins with no previously known immunological functions were also identified. The expression of one of these proteins, IQ motif containing H (IQCH), was exclusively in fish brain and gonads and was induced during bacterial infection. This approach also allowed the study of the corresponding proteomic changes in E. tarda exposed to turbot serum, which is a general decrease of bacterial protein expression except for an upregulation of membrane components after serum treatment. Interestingly, while most other known stresses stimulate bacterial antioxidant enzymes, fish serum induced a rapid suppression of antioxidant proteins and led to an accumulation of reactive oxygen species. Heat treatment of fish serum eliminated this effect, suggesting that heat labile factors in the fish serum overrode bacterial antioxidant defenses. Taken together, this work offers a comprehensive view of the interactions between fish serum proteins and bacteria, and reveals previously unknown factors and mechanisms in fish innate immunity.

Modification of the plasma complement protein profile by exogenous estrogens is indicative of a compromised immune competence in marine medaka (Oryzias melastigma).

Growing evidence suggests that the immune system of teleost is vulnerable to xenoestrogens, which are ubiquitous in the marine environment. This study detected and identified the major circulatory immune proteins deregulated by 17α-ethinylestradiol (EE2), which may be linked to fish susceptibility to pathogens in the marine medaka, Oryzias melastigma. Fish immune competence was determined using a host resistance assay to pathogenic bacteria Edwardsiella tarda. Females were consistently more susceptible to infection-induced mortality than males. Exposure to EE2 could narrow the sex gap of mortality by increasing infection-induced death in male fish. Proteomic analysis revealed that the major plasma immune proteins of adult fish were highly sexually dimorphic. EE2 induced pronounced sex-specific changes in the plasma proteome, with the male plasma composition clearly becoming "feminised". Male plasma was found to contain a higher level of fibrinogens, WAP63 and ependymin-2-like protein, which are involved in coagulation, inflammation and regeneration. For the first time, we demonstrated that expression of C1q subunit B (C1Q), an initiating factor of the classical complement pathway, was higher in males and was suppressed in both sexes in response to EE2 and bacterial challenge. Moreover, cleavage and post-translational modification of C3, the central component of the complement system, could be altered by EE2 treatment in males (C3dg down; C3g up). Multiple regression analysis indicated that C1Q is possibly an indicator of fish survival, which warrants further confirmation. The findings support the potential application of plasma immune proteins for prognosis/diagnosis of fish immune competence. Moreover, this study provides the first biochemical basis of the sex-differences in fish immunity and how these differences might be modified by xenoestrogens.

Tanshinone IIA Inhibits Proliferation and Induces Apoptosis Through the Downregulation of Survivin in Keloid Fibroblasts.

Keloids are considered benign dermal fibroproliferative tumors. Keloid fibroblasts (KFs) persistently proliferate and fail to undergo apoptosis, and no treatment is completely effective against these lesions. Tanshinone IIA induces apoptosis and inhibits the proliferation of various tumor cell types. In this study, we investigated the effect of tanshinone IIA on the regulation of proliferation, cell cycle, and apoptosis in KFs, and investigated potential mechanisms involved in the effects. First, KFs and normal skin fibroblasts (NSFs) were treated with various concentrations of tanshinone IIA. Cell counting kit-8 (CCK-8) was used to assess the proliferative activity of KFs and NSFs, and flow cytometry was used to investigate the cell cycle and apoptosis in KFs. We found that the proliferation of all tanshinone IIA-treated KFs was significantly decreased after treatment for 72 hours (P < 0.001). Also, NSFs treated with tanshinone IIA did not exhibit noticeable effects compared with KFs. In addition, the percentages of G0/G1 cells in all tanshinone IIA-treated KFs were significantly increased after treatment for 72 hours (P < 0.001). And the percentages of cells undergoing early apoptosis in all tanshinone IIA-treated KFs were significantly increased after treatment for 120 hours (P < 0.001). Furthermore, the apoptosis antibody array kit and Western blot analysis revealed that tanshinone IIA decreased survivin expression in KFs (P < 0.001). In conclusion, tanshinone IIA downregulates survivin and deactivates KFs, thus suggesting that tanshinone IIA could serve as a potential clinical keloid treatment.

ASH2L Mediates Epidermal Differentiation and Hair Follicle Morphogenesis through H3K4me3 Modification.

The processes of epidermal development in mammals are regulated by complex molecular mechanisms, such as histone modifications. Histone H3 lysine K4 methylation mediated by COMPASS (complex of proteins associated with Set1) methyltransferase is associated with gene activation, but its effect on epidermal lineage development remains unclear. Therefore, we constructed a mouse model of specific ASH2L (COMPASS methyltransferase core subunit) deletion in epidermal progenitor cells and investigated its effect on the development of mouse epidermal lineage. Furthermore, downstream target genes regulated by H3K4me3 were screened using RNA sequencing combined with Cleavage Under Targets and Tagmentation sequencing. Deletion of ASH2L in epidermal progenitor cells caused thinning of the suprabasal layer of the epidermis and delayed hair follicle morphogenesis in newborn mice. These phenotypes may be related to the reduced proliferative capacity of epidermal and hair follicle progenitor cells. ASH2L depletion may also lead to depletion of the epidermal stem cell pools in late mouse development. Finally, genes related to hair follicle development (Shh, Edar, and Fzd6), Notch signaling pathway (Notch2, Notch3, Hes5, and Nrarp), and ΔNp63 were identified as downstream target genes regulated by H3K4me3. Collectively, ASH2L-dependent H3K4me3 modification served as an upstream epigenetic regulator in epidermal differentiation and hair follicle morphogenesis in mice.

A 16-Year-Old Girl with Sinonasal Cutaneous Fistula Following Excision and Radiotherapy for Rhabdomyosarcoma Requiring Reconstructive Surgery Using an Expanded Forehead Flap.

BACKGROUND Sinonasal rhabdomyosarcoma (RMS) is a rare malignancy in children and adolescents. It is aggressive and locally invasive, and can require local postoperative radiotherapy. This report presents the case of a 16-year-old girl with a sinonasal-cutaneous fistula following excision and radiotherapy for rhabdomyosarcoma, which required reconstructive surgery using an expanded forehead flap. CASE REPORT We report the case of a16-year-old girl who was referred to our clinic with sinonasal-cutaneous fistula. Prior to presentation at our department, she presented with bilateral intermittent nasal congestion 3 years ago. At a local hospital, orbital computed tomography and nasal endoscopic biopsy revealed an embryonal rhabdomyosarcoma (ERMS). One month later, skull base tumor resection, nasal cavity and sinus tumor resection, and low-temperature plasma ablation were performed at a local hospital. Two weeks after the operation, the patient received intensity-modulated radiation therapy for a total of 50 Gy. Chemotherapy started 15 days after radiotherapy, using a vincristine, dactinomycin, and cyclophosphamide (VAC) regimen. Approximately 1 month later, an ulcer appeared at the nasal root and the lesion gradually expanded. The patient was referred to our hospital due to the defect. Firstly, a tissue expander was implanted at the forehead for 7 months. Then, the skin around the defect was trimmed and forehead flap was separated to repair the lining and external skin. The flap survived well 1-year after the operation. CONCLUSIONS This report highlights the challenges of post-radiation reconstructive surgery and describes how an expanded forehead flap can achieve an acceptable cosmetic outcome in a patient with a sinonasal-cutaneous fistula.

Advancement in the development of single chain antibodies using phage display technology.

Phage display technology has become an important research tool in biological research, fundamentally changing the traditional monoclonal antibody preparation process, and has been widely used in the establishment of antigen-antibody libraries, drug design, vaccine research, pathogen detection, gene therapy, antigenic epitope research, and cellular signal transduction research.The phage display is a powerful platform for technology development. Using phage display technology, single chain fragment variable (scFv) can be screened, replacing the disadvantage of the large size of traditional antibodies. Phage display single chain antibody libraries have significant biological implications. Here we describe the types of antibodies, including chimeric antibodies, bispecific antibodies, and scFvs. In addition, we describe the phage display system, phage display single chain antibody libraries, screening of specific antibodies by phage libraries and the application of phage libraries.