Reactive oxygen species-responsive nanocarrier ameliorates murine colitis by intervening colonic innate and adaptive immune responses.

Ulcerative colitis (UC) is a chronic or relapsing inflammatory disease with limited therapeutic outcomes. Pterostilbene (PSB) is a polyphenol-based anti-oxidant that has received extensive interest for its intrinsic anti-inflammatory and anti-oxidative activities. This work aims to develop a reactive oxygen species (ROS)-responsive, folic acid (FA)-functionalized nanoparticle (NP) for efficient PSB delivery to treat UC. The resulting PSB@NP-FA had a nano-scaled diameter of 231 nm and a spherical shape. With ROS-responsive release and ROS-scavenging properties, PSB@NP could effectively scavenge H2O2, thereby protecting cells from H2O2-induced oxidative damage. After FA modification, the resulting PSB@NP-FA could be internalized by RAW 264.7 and Colon-26 cells efficiently and preferentially localized to the inflamed colon. In dextran sulfate sodium (DSS)-induced colitis models, PSB@NP-FA showed a prominent ROS-scavenging capacity and anti-inflammatory activity, therefore relieving murine colitis effectively. Mechanism results suggested that PSB@NP-FA ameliorated colitis by regulating dendritic cells (DCs), promoting macrophage polarization, and regulating T cell infiltration. Both innate and adaptive immunity were involved. More importantly, the combination of the PSB and dexamethasone (DEX) enhanced the therapeutic efficacy of colitis. This ROS-responsive and ROS-scavenging nanocarrier represents an alternative therapeutic approach to UC. It can also be used as an enhancer for classic anti-inflammatory drugs.

Surgical Treatment for Extensive Postburn Facial Deformity Using Tube Flap and Cervicofacial Flap.

The current concept of facial unit reconstruction has evolved from simple coverage of defects to the reconstruction of the 3-dimensional structure and delicate features. The reshaping of the middle third of the face, including the nose and cheek, remains a challenge for plastic surgeons due to its complex structure and the dynamic relationship between each part. In this article, the authors describe a clinical report of extensive facial burns with skin lesions in the middle third of the face. The 30-year-old female patient sustained burns throughout the full thickness of the skin burns on the entire nose and left cheek with hypertrophic scar. The authors performed an expanded cervical-facial flap and tube flap of the upper extremity to reconstruct the entire nasal and cheek region. The patient underwent 8 stages of the operation successively resulting in a satisfactory level of appearance and function.

Deficient mismatch repair is detected in large-to-giant congenital melanocytic naevi: providing new insight into aetiology and diagnosis.

BACKGROUND: The aetiologies of large-to-giant congenital melanocytic naevi (LGCMN) remain ambiguous. A previous study discovered signatures associated with deficient mismatch repair (dMMR) in patients with LGCMN. However, a screening diagnostic immunohistochemistry (IHC) panel of dMMR in patients with LGCMN has not been performed to date. OBJECTIVES: To identify the MMR status and aetiologies of LGCMN. METHODS: A total of 110 patients with CMN, including 30 giant CMN, 30 large CMN, 30 medium CMN and 20 small CMN, underwent diagnostic IHC (for MSH6, MSH2, PMS2 and MLH1) screening of dMMR. The control group comprised normal skin samples from 20 healthy people. MMR proteins with little effect (MSH3 and PMS1) on the MMR system were stained in all samples. The surgical procedures conducted on each patient were noted because they might alter the behaviour of CMN and confound the results. Binary logistic regression analyses were performed between the phenotypic data and MMR status to identify associations. Whole-exome sequencing was performed on the main naevi, satellite naevi and normal skin tissues of four patients to detect variants. Mutational signature analyses were conducted to explore the aetiologies of LGCMN. RESULTS: dMMR was detected in 37% (11 of 30) of giant, 23% (7 of 30) of large and 7% (2 of 30) of medium CMNs, but were not identified in small CMNs or normal skin tissues. Moreover, multiple LGCMNs had a much higher dMMR rate than did single LGCMNs. The regression analyses showed that MMR status was significantly associated with CMN size and the presence of satellites, but was not correlated with age, sex, location, satellite diversity or tissue expansion. Notably, the pattern of protein loss in LGCMN mainly consisted of PMS2 loss. Mutational signature analyses detected dMMR-related signatures in patients with LGCMN. Additionally, rare deleterious germline mutations in DNA repair genes were detected in LGCMN, mainly in MSH6, ATM, RAD50, BRCA1 and ERCC8. These germline mutations were single-patient variants with unknown significance. CONCLUSIONS: dMMR is one of the aetiologies underlying LGCMN, particularly in patients with giant main lesions and multiple satellite lesions. Further studies are necessary to investigate the role of the DNA repair system, particularly MMR, in LGCMN.

Rational design of flower-like MnO2/Ti3C2Txcomposite electrode for high performance supercapacitors.

Combining the new two-dimensional conductive MXene with transition metal oxide to build composite structure is a promising path to improve the conductivity of metal oxide. However, a critical challenge still remains in how to achieve a good combination of MXene and metal oxide. Herein, we develop a facile hydrothermal route to synthesize the MnO2/Ti3C2Txcomposite electrode for supercapacitors by synergistically coupling MnO2nanowires with Ti3C2TxMXene nanoflakes. Compared with the pure MnO2electrode, the morphology of the MnO2/Ti3C2Txcomposite electrode changes from nanowires to nanoflowers. Moreover, the overall conductivity and electrochemical performance of the composite electrode are greatly improved due to an addition of Ti3C2TxMXene. The specific capacitance of the MnO2/Ti3C2Txcomposite electrode achieves 210.8 F·g-1at a scan rate of 2 mV·s-1, while that of the pure MnO2electrode is only 55.2 F·g-1. Furthermore, the specific capacitance of the MnO2/Ti3C2Txcomposite electrode still can remain at 97.2% even after 10 000 charge-discharge cycles, revealing an excellent cycle stability. The synthesis strategy of this work can pave the way for the research and practical application of the electrode materials for supercapacitors.

A chemokine regulatory loop induces cholesterol synthesis in lung-colonizing triple-negative breast cancer cells to fuel metastatic growth.

Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC.

Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1.

Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate the degradation of several key mitotic regulators independent of APC/C. We demonstrate that ordered progression through mitosis is orchestrated by two distinct E3 ligases through the shared use of Cdc20 and Cdh1. Furthermore, Parkin is phosphorylated and activated by polo-like kinase 1 (Plk1) during mitosis. Parkin deficiency results in overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis. These results suggest that the Parkin-Cdc20/Cdh1 complex is an important regulator of mitosis.

Customization of Soft Tissue Expanders: Improving Safety, Accuracy, and Efficiency for Treatment of Large and Complicated Skin Lesions.

BACKGROUND: Soft tissue expansion is a common technique for restoring large skin defects. Fixed-type expanders may be inappropriate for the following reasons: (1) the shapes and sizes of the defects vary in different patients; and (2) the bulged base of the fixed-type expander does not fit the curve of the human body, which may induce complications such as concave deformities or nerve palsy from continuous mechanical compression. The customized expander adjusts better to the shape and the topography of the expansion site compared with the fixed-type expander. It improves expansion efficiency and reduces complications caused by compression. METHODS: Between 2016 and 2022, customized soft tissue expansion was performed in 38 patients with skin lesions, including giant congenital melanocytic nevi and postburn scars. This series of patients included patients with a specific donor site shape that is unsuitable for fixed-type expanders. An expander was customized according to the shape of the donor site and then implanted in the subcutaneous pocket. After the expander reached a sufficient volume, the expander was removed, and the extra expanded skin flap was transferred to resurface the skin lesion. In the follow-up, the outcome and the complications were recorded. RESULTS: All the customized expanders fit not only the dimension but also the topography of the donor site. During expansion, 2 patients experienced leakage of the expander, and 3 patients suffered a skin rupture. In the remaining 33 patients, the expansion was successfully completed, and the expanded flaps restored the skin lesions as designed. The color and texture of the skin flaps remained satisfactory after long-term follow-up. CONCLUSIONS: Unlike fixed-type expanders, our customized expanders make it possible for "accurate" expansion, irrespective of the dimension and topography of the donor area. Customization of the expander helps increase efficiency and reduce complications caused by undue compression.

WSB1 promotes tumor metastasis by inducing pVHL degradation.

The von Hippel-Lindau tumor suppressor pVHL is an E3 ligase that targets hypoxia-inducible factors (HIFs). Mutation of VHL results in HIF up-regulation and contributes to processes related to tumor progression such as invasion, metastasis, and angiogenesis. However, very little is known with regard to post-transcriptional regulation of pVHL. Here we show that WD repeat and SOCS box-containing protein 1 (WSB1) is a negative regulator of pVHL through WSB1's E3 ligase activity. Mechanistically, WSB1 promotes pVHL ubiquitination and proteasomal degradation, thereby stabilizing HIF under both normoxic and hypoxic conditions. As a consequence, WSB1 up-regulates the expression of HIF-1α's target genes and promotes cancer invasion and metastasis through its effect on pVHL. Consistent with this, WSB1 protein level negatively correlates with pVHL level and metastasis-free survival in clinical samples. This work reveals a new mechanism of pVHL's regulation by which cancer acquires invasiveness and metastatic tendency.

Advances in Face-Lift Surgical Techniques: 2016-2021.

BACKGROUND: Face-lift surgery is the most crucial and constantly evolving technique of facial rejuvenation. Periodic reviews synthesizing the latest face-lift techniques may help surgeons sharpen their surgical procedures. METHODS: A literature search was conducted of the PubMed databases using the search term "face lift" and "rhytidectomy." Articles reporting rhytidectomy of the forehead/brow, midface, lower face, and neck were included. Sixty-nine articles were selected after independent screening by three of the authors. The Oxford Centre for Evidence-based Medicine scale was used for evaluating evidence level. RESULTS: Of the 69 candidate articles, 10 studies (15%) reported techniques of neck lifting; 10 studies (15%) introduced techniques of endoscopic brow lifting; 7 studies (10%) pertained to brow lifting without endoscopic techniques. The most frequently reported locations of rhytidectomy were the brow/forehead (20%), neck (19%), and face-neck (17%). Additionally, articles regarding Asian face-lifts (14%) have been increasing. The evidence level of the articles was generally low, with only 10 articles assessed as level 1-3 with 59 articles as level 4-5. CONCLUSIONS: Face-lift articles with high-level evidence are still lacking. Prominently, forehead lifting and neck lifting have become upward trends of rhytidectomy in recent years, and the techniques of short-scar face-lift have been more valued. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Flexible MXene-Based Composite Films: Synthesis, Modification, and Applications as Electrodes of Supercapacitors.

MXenes, as a 2D planar structure nanomaterial, were first reported in 2011. Due to their large specific surface area, high ductility, high electrical conductivity, strong hydrophilic surface, and high mechanical flexibility, MXenes have been extensively explored in the development of various functional materials with desired performances. This review is aimed to summarize the current progress in synthesis, modification, and applications of MXene-based composite films as electrode materials of flexible energy storage devices. In the synthesis of MXenes, the evolution and exploration of etchants are emphasized. Furthermore, in order to develop MXene-based composite films, the components used to modify the MXene nanoflakes, including 0D, 1D, and 2D nanomaterials, are summarized, and the perspectives and research direction of such materials are also discussed.

Discovery of novel MIF inhibitors that attenuate microglial inflammatory activation by structures-based virtual screening and in vitro bioassays.

Macrophage migration inhibitory factor (MIF) is a pluripotent pro-inflammatory cytokine and is related to acute and chronic inflammatory responses, immune disorders, tumors, and other diseases. In this study, an integrated virtual screening strategy and bioassays were used to search for potent MIF inhibitors. Twelve compounds with better bioactivity than the prototypical MIF-inhibitor ISO-1 (IC50 = 14.41 µM) were identified by an in vitro enzymatic activity assay. Structural analysis revealed that these inhibitors have novel structural scaffolds. Compound 11 was then chosen for further characterization in vitro, and it exhibited marked anti-inflammatory efficacy in LPS-activated BV-2 microglial cells by suppressing the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs). Our findings suggest that MIF may be involved in the regulation of microglial inflammatory activation and that small-molecule MIF inhibitors may serve as promising therapeutic agents for neuroinflammatory diseases.

circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFßR1/VEGF-D signaling.

Lymphatic metastasis constitutes a leading cause of recurrence and mortality in bladder cancer. Accumulating evidence indicates that lymphangiogenesis is indispensable to trigger lymphatic metastasis. However, the specific mechanism is poorly understood. In the present study, we revealed a pathway involved in lymphatic metastasis of bladder cancer, in which a circular RNA (circRNA) facilitated lymphangiogenesis in a vascular endothelial growth factor C (VEGF-C)-independent manner. Novel circRNA circEHBP1 was markedly upregulated in bladder cancer and correlated positively with lymphatic metastasis and poor prognosis of patients with bladder cancer. circEHBP1 upregulated transforming growth factor beta receptor 1 (TGFBR1) expression through physically binding to miR-130a-3p and antagonizing the suppression effect of miR-130a-3p on the 3' UTR region of TGFBR1. Subsequently, circEHBP1-mediated TGFßR1 overexpression activated the TGF-ß/SMAD3 signaling pathway, thereby promoting the secretion of VEGF-D and driving lymphangiogenesis and lymphatic metastasis in bladder cancer. Importantly, administration of VEGF-D neutralizing antibodies remarkably blocked circEHBP1-induced lymphangiogenesis and lymphatic metastasis in vivo. Our findings highlighted that the circEHBP1/miR-130a-3p/TGFßR1/VEGF-D axis contributes to lymphangiogenesis and lymphatic metastasis of bladder cancer independent of VEGF-C, which might lead to the development of circEHBP1 as a potential biomarker and promising therapeutic target for lymphatic metastasis in bladder cancer.

One-Stage Reconstruction of Large Upper Vermillion Defects Using a Lower to Upper Bipedicle Axial Cross-Lip Vermillion Flap.

BACKGROUND: Vermilion deformities after intralesional bleomycin A5 injections for hemangiomas of the upper lip have not been rare during the past 2 decades in China. In this article, we summarized our 10 years of experience using a lower to upper axial cross-lip musculomucosal flap with bipedicle lower labial coronary arteries for 1-stage reconstruction of large upper vermillion defects. Based on several years of experience, we also created some modified approaches to achieve satisfactory cosmetic outcomes. PATIENTS AND METHODS: From July 2006 to July 2016, a total of 25 patients with moderate and severe vermilion defects of the upper lip were treated with this method at the Department of Plastic and Reconstructive Surgery in Shanghai Ninth People's Hospital. The cosmetic outcomes and complications were reviewed. RESULTS: The overall mean follow-up time was 14.9 months. No patients had infection or hematoma. All the flaps survived, and all the patients were satisfied with the postoperative appearance. CONCLUSIONS: Our experience has proven that a lower to upper axial cross-lip musculomucosal flap with bipedicle lower labial coronary arteries is a safe and effective approach for correcting large upper vermillion defects. It is a 1-stage operation for the overall length of upper vermillion reconstruction. This method could improve upper-lip aesthetics and achieve reconstructive goals while avoiding lower-lip deformities.

CdS/TiO2 Nanocomposite-Based Photoelectrochemical Sensor for a Sensitive Determination of Nitrite in Principle of Etching Reaction.

The CdS/TiO2 nanocomposite (NC) photoelectrochemical (PEC) sensor was constructed based on a new sensing strategy for nitrite assay. The CdS etching process caused by nitrite-in-acid solution was confirmed and applied to nitrite sensing. The CdS etching phenomenon occurring on the sensor led to an obvious reduction in the photocurrent response under visible-light irradiation, which responded to the nitrite concentration. The CdS/TiO2 NC-based PEC sensor exhibited excellent performance on nitrite detection. The linear range for nitrite determination was from 1-100 and 100-500 µM, and the sensitivity of the PEC sensor was 2.91 and 0.186 µA µM-1 cm-2, respectively. The detection limit of the sensor was 0.56 µM (S/N = 3). In addition, the PEC sensor was also equipped with advantages such as good selectivity, excellent stability, low background, and recyclability. Satisfying results were obtained for the nitrite assay in real samples by such a PEC sensor. In summary, this work contributed a fresh idea to precisely determinate nitrite through PEC sensing.

Gene expression comparison between primary estrogen receptor-positive and triple-negative breast cancer with paired axillary lymph node metastasis.

The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER)-positive and triple-negative (TNBC) primary breast cancer (PBC). Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR-positive, HER2-negative PBC, and their paired ALN metastases were compared with TNBC and their paired ALN metastases. Fourteen pairs of ER-positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER-positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. Although ER-positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.

Facial Contour Rejuvenation by Reduction Malarplasty Combined With Second-Stage Fat Grafting.

BACKGROUND: With aging, the facial contour shows a double-concave deformity. Conventional facial contouring procedure, including face lifting and fat grafting, cannot yield a smooth facial contour line. This study was the first to propose a combination of reduction malarplasty and 2nd-stage autologous fat grafting so as to achieve the aesthetic goals of facial contour rejuvenation. METHODS: The study group comprised patients seeking facial contour rejuvenation from January 2017 to May 2018 (28 patients: 28 females and 0 males) at the Department of Plastic Surgery, Tian Tan Pu Hua Hospital. All of the cases underwent bilateral malarplasty with 2nd-stage autologous facial fat grafting. Radiologic and photographic documentation was completed preoperatively. The mean follow-up period was 12 months. Patients' pre-op photographs and 3 months follow-up pictures were blindly assessed. RESULTS: Most of the patients were satisfied with their results after 1-time fat grafting. Eleven patients demanded re-injection after the 1st fat grafting in temporal area, and 6 patients demanded 3rd time fat grafting in temporal area. Eleven patients demanded re-injection insubmalar area, and 8 patients demanded 3rd time fat grafting in submalar area. Meanwhile, 9 of those patients underwent fat grafting in other sites other than temporal and submalar region. The amount of fat injected was also recorded in this study. The appearance of double-concave deformity was greatly improved in all cases. Complications included infection (3.6%), hematoma (7.1%), and malar prominence relapse (7.1%), and so on. CONCLUSION: Reduction malarplasty combined with several times of fat grafting could effectively overcome the malar prominence and soft tissue deflation. Complications were minimal after these procedures. Therefore, this technique is useful to restore the youthful facial contour in Asian patients with aging double-concave deformity.

circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer.

BACKGROUND: Patients with lymph node (LN)-positive pancreatic ductal adenocarcinoma (PDAC) have extremely poor survival rates. Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNAs, have been proposed to mediate the progression of diverse types of tumors. However, the role and underlying regulatory mechanisms of circRNAs in the LN metastasis of PDAC remain unknown. METHODS: Next-generation sequencing was used to identify differentially expressed circRNAs between PDAC and normal adjacent tissues. In vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1. RNA pulldown and luciferase assays were performed to examine the binding of circNFIB1 and miR-486-5p. RESULTS: In the present study, we identified that a novel circRNA (circNFIB1, hsa_circ_0086375) was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients. Functionally, circNFIB1 knockdown promoted lymphangiogenesis and LN metastasis of PDAC both in vitro and in vivo. Mechanistically, circNFIB1 functioned as a sponge of miR-486-5p, and partially reversed the effect of miR-486-5p. Moreover, circNFIB1 attenuated the oncogenic effect of miR-486-5p and consequently upregulated PIK3R1 expression, which further downregulated VEGF-C expression through inhibition of the PI3K/Akt pathway, and ultimately suppressed lymphangiogenesis and LN metastasis in PDAC. CONCLUSIONS: Our findings provide novel insight into the underlying mechanism of circRNA-mediated LN metastasis of PDAC and suggest that circNFIB1 may serve as a potential therapeutic target for LN metastasis in PDAC.

Gene expression comparison between primary triple-negative breast cancer and paired axillary and sentinel lymph node metastasis.

Few studies examine the genomics of axillary lymph node (ALN) metastasis in triple-negative breast cancer (TNBC). The aim was to characterize and compare gene expression patterns of primary breast cancers and paired ALN metastases. Patients with stage 2-3 ER/PR negative, HER2 negative TNBC with ALN macrometastasis without neo-adjuvant therapy were selected. Tumor-specific area was isolated from breast and ALN tissue sections. Gene expression of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with Illumina next-generation sequencing (NGS). Seventeen pairs of TNBC and autologous ALN metastasis were analyzed. Compared with the primary, ALN metastasis had 257 statistically significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. Notably, there was an upregulation of anti-apoptosis and survival signaling genes (BIRC3, TCL1A, FLT3, and VCAM1) in the ALN metastasis. There was also an upregulation of chemotaxis genes (CCL19, CCL21, CXCL13, and TNFSF11). The most striking feature is the downregulation of genes known to regulate cell microenvironment interaction (MMP2, MMP 3, MMP 7, MMP 11, MMP14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, COL6A6, COL11A1, and COL17A1). In TNBC, ALN metastases have a distinct gene expression profile. Genes associated with anti-apoptosis, survival responses, and chemotaxis are upregulated, and genes associated with regulation of extracellular matrix are downregulated when compared to autologous primary cancer. TNBC cells metastatic to lymph nodes undergo a change in order to metastasize and survive in the new microenvironment, which may lead to insights into the metastatic process.

Solution-phase total synthesis of teixobactin.

The first solution-phase total synthesis of the cyclic depsipeptide teixobactin is described. Stereoselective construction of l-allo-enduracididine was established, and the protective groups for the peptide coupling reactions and conditions for the assembly of the fragments were also optimised. The longest linear sequence for the total synthesis was 20 steps from the known l-cis-4-hydroxyproline derivative and gave a 5.6% overall yield. This solution-phase total synthesis could serve as a complement to the current solid-phase synthesis of teixobactin.

A Penetrating Facial Wound With Burn Injury.

A patient presented with a complex penetrating facial wound by high temperature steel. The hot steel penetrated right temple, ethmoid bone, and maxillary sinus, and then exited from his left cheek. He kept his right eye but lost his sight. For functional and esthetic considerations, treatments were provided in a staged procedure. First, the debridement was performed under the endoscope. The dead bone was removed, broken teeth were extracted, and necrotic tissue was cleaned. The exposed wounds were cleaned, and dressing was changed daily until the exudation was widely reduced. Then, a 50-mL expander was placed in the left cheek, and an 80-mL expander was put in the scalp just before the defect in the temple area. Five months later, expander inflation was accomplished. Expanders were taken out and expanded flaps were transposed to cover the defect. At the same time, an anterolateral thigh flap was harvested to repair the inner lining of the cheek and the gingiva. Thereafter, several operations were performed to revise the wound scar and the remaining deformity. Both defects in the temple and left cheek were restored with a satisfactory functional and aesthetic outcome. The temporal area was repaired with haired expanded scalp, whereas the face was repaired with an expanded facial flap with similar texture and color. The oral commissure regained balance and integrity. The defect of the gingiva was repaired. A severe penetrating wound in the cranium and face can be nicely repaired using tissue expander and microvascular reconstruction.