Reconstruction of perianal skin defect using modified keystone flap after perianal tumor resection.

Purpose: The large resection area of perianal tumor makes the skin defect hard to reconstruct. The keystone flap has demonstrated a growing application in skin defects. Herein, we aimed to explore the efficacy of keystone flap in the repair of skin defect after perianal tumor resection. Methods: This study is a retrospective review of patients diagnosed with perianal tumor from January 2010 to November 2021. A standardized data collection template was used to collect variables. The detailed process of the reconstructive surgery is carefully described in this article. After surgery, the healing process was closely observed. Results: Twenty patients underwent keystone flap repair. The average wound size before closure measured 3.5 × 4.9 cm2. Primary wound healing was achieved, and the flap survived during the follow up period, which ranged from 6 to 24 months. No severe complications occurred; slight edema was noticed in one patient. Conclusion: The application of keystone flap is a promising way to repair skin defect after tumor removal, and the complications rate was low after surgery. It can be concluded that this method is an effective and reliable way to repair perianal skin defect.

HD-Zip proteins modify floral structures for self-pollination in tomato.

Cleistogamy is a type of self-pollination that relies on the formation of a stigma-enclosing floral structure. We identify three homeodomain-leucine zipper IV (HD-Zip IV) genes that coordinately promote the formation of interlocking trichomes at the anther margin to unite neighboring anthers, generating a closed anther cone and cleistogamy (flower morphology necessitating strict self-pollination). These HD-Zip IV genes also control style length by regulating the transition from cell division to endoreduplication. The expression of these HD-Zip IV genes and their downstream gene, Style 2.1, was sequentially modified to shape the cleistogamy morphology during tomato evolution and domestication. Our results provide insights into the molecular basis of cleistogamy in modern tomato and suggest targets for improving fruit set and preventing pollen contamination in genetically modified crops.

A gradient of the HD-Zip regulator Woolly regulates multicellular trichome morphogenesis in tomato.

Homeodomain (HD) proteins regulate embryogenesis in animals such as the fruit fly (Drosophila melanogaster), often in a concentration-dependent manner. HD-leucine zipper (Zip) IV family genes are unique to plants and often function in the L1 epidermal cell layer. However, our understanding of the roles of HD-Zip IV family genes in plant morphogenesis is limited. In this study, we investigated the morphogenesis of tomato (Solanum lycopersicum) multicellular trichomes, a type of micro-organ in plants. We found that a gradient of the HD-Zip IV regulator Woolly (Wo) coordinates spatially polarized cell division and cell expansion in multicellular trichomes. Moreover, we identified a TEOSINTE BRANCHED1, CYCLOIDEA, and PROLIFERATING CELL NUCLEAR ANTIGEN BINDING FACTOR (TCP) transcription factor-encoding gene, SlBRANCHED2a (SlBRC2a), as a key downstream target of Wo that regulates the transition from cell division to cell expansion. High levels of Wo promote cell division in apical trichome cells, whereas in basal trichome cells, Wo mediates a negative feedback loop with SlBRC2a that forces basal cells to enter endoreduplication. The restricted high and low activities of Wo patterns the morphogenesis of tomato multicellular trichomes. These findings provide insights into the functions of HD-Zip IV genes during plant morphogenesis.

Crosstalk between gut microbiota and metastasis in colorectal cancer: implication of neutrophil extracellular traps.

Primary colorectal cancer (CRC) often leads to liver metastasis, possibly due to the formation of pre-metastatic niche (PMN) in liver. Thus, unravelling the key modulator in metastasis is important for the development of clinical therapies. Gut microbiota dysregulation is a key event during CRC progression and metastasis. Numerous studies have elucidated the correlation between specific gut bacteria strains (e.g., pks + E. coli and Bacteroides fragilis) and CRC initiation, and gut bacteria translocation is commonly witnessed during CRC progression. Gut microbiota shapes tumor microenvironment (TME) through direct contact with immune cells or through its functional metabolites. However, how gut microbiota facilitates CRC metastasis remains controversial. Meanwhile, recent studies identify the dissemination of bacteria from gut lumen to liver, suggesting the role of gut microbiota in shaping tumor PMN. A pro-tumoral PMN is characterized by the infiltration of immunosuppressive cells and increased pro-inflammatory immune responses. Notably, neutrophils form web-like structures known as neutrophil extracellular traps (NETs) both in primary TME and metastatic sites, NETs are involved in cancer progression and metastasis. In this review, we focus on the role of gut microbiota in CRC progression and metastasis, highlight the multiple functions of different immune cell types in TME, especially neutrophils and NETs, discuss the possible mechanisms of gut microbiota in shaping PMN formation, and provide therapeutical indications in clinic.

Liquid nitrogen frozen cells for chemotherapy drug delivery and vaccination of melanoma.

PURPOSE: Cancer vaccine (CV) has thrived as a promising tool for cancer prevention and treatment. However, how to maintain the integrity and diversity of individualized vaccine antigens and activate the adaptive immune system is still challenging. METHODS: Herein, a preventive and therapeutic vaccine platform for in situ effective multi-model synergistic therapy is developed. In our study, we process B16F10 cells by liquid nitrogen frozen (LNF) to obtain LNF cells, the characterization of LNF cells were conducted. Moreover,  the anti-tumor effect and immune activation ability were studied, and the role as a CV were investigated. RESULTS: The LNF cells preserve intact cellular structure and tumor-associated self-antigen gp100. Moreover, LNF cells have the ability of loading and releasing doxorubicin (DOX). Except for the anti-tumor effect of chemotherapy brought by DOX, the LNF cells can promote the maturation of dendritic cells (DCs) and induce immune response by activating CD4+ and CD8+ T cells, particularly with the existence of adjuvant, R848. Specifically, the CD8+ T cells of mice in LNF-DOX/R848 group are 6 times of that in PBS group in tumor microenvironment, and twice in spleen. Therefore, LNF cells can also be utilized as a CV. Vaccination with LNF/R848 cells effectively suppress the tumor growth in mice by fivefold as compared to the control group. CONCLUSION: In this work, we obtain the LNF cells with a simple procedure. The LNF cells not only provides a tumor cells-based multi-modal system for cancer therapy but inspires new insights into future development of individualized CVs strategies. This study processes live B16F10 cells by liquid nitrogen frozen to obtain LNF cells, which preserve cell integrity and homologous targeting ability. The LNF cells can load and deliver drug and can serve as tumor vaccine. Results demonstrated the LNF cells have effective prophylactic ability, and ideal anti-tumor ability with the loaded drug and adjuvant.

Metformin promotes angiogenesis by enhancing VEGFa secretion by adipose-derived stem cells via the autophagy pathway.

Human adipose tissue-derived stem cell (ADSC) derivatives are cell-free, with low immunogenicity and no potential tumourigenicity, making them ideal for aiding wound healing. However, variable quality has impeded their clinical application. Metformin (MET) is a 5' adenosine monophosphate-activated protein kinase activator associated with autophagic activation. In this study, we assessed the potential applicability and underlying mechanisms of MET-treated ADSC derivatives in enhancing angiogenesis. We employed various scientific techniques to evaluate the influence of MET on ADSC, assess angiogenesis and autophagy in MET-treated ADSC in vitro, and examine whether MET-treated ADSC increase angiogenesis. We found that low MET concentrations exerted no appreciable effect on ADSC proliferation. However, MET was observed to enhance the angiogenic capacity and autophagy of ADSC. MET-induced autophagy was associated with increased vascular endothelial growth factor A production and release, which contributed to promoting the therapeutic efficacy of ADSC. In vivo experiments confirmed that in contrast to untreated ADSC, MET-treated ADSC promoted angiogenesis. Our findings thus indicate that the application of MET-treated ADSC would be an effective approach to accelerate wound healing by promoting angiogenesis at wound sites.

The Application of Double-Layer-Vacuum-Assisted Closure Therapy With Flap Repair of Soft Tissue Defects Near the Eyes or EarDL-VAC Therapy.

OBJECTIVE: We aimed to introduce and evaluate the safety of double-layer-vacuum-assisted closure (DL-VAC) therapy with flap repair of the wound near the eyes or ears. METHODS: This study is case reports of 2 patients who underwent DL-VAC therapy for tissue defects near the eyes or ears. The detailed process of the DL-VAC therapy is carefully described in this study. The postoperative wound healing process was closely observed. The biggest concern was the treatment outcome of DL-VAC therapy on the eyes and ears. RESULTS: Two patients underwent DL-VAC therapy due to their soft tissue defects close to the eyes or ears. Both patients achieved primary wound healing and the flaps survived during the follow-up period, which ranged from 1 to 24 months. Patients did not receive any dressing change until the VAC device was removed on the 5th to 7th postoperative day. No severe complications appeared and the patients were satisfied with both appearance and function. CONCLUSIONS: Double-layer-vacuum-assisted closure therapy is an effective and safe option for the treatment of wounds near the eyes and ears.

A HD-ZIP transcription factor specifies fates of multicellular trichomes via dosage-dependent mechanisms in tomato.

Hair-like structures are shared by most living organisms. The hairs on plant surfaces, commonly referred to as trichomes, form diverse types to sense and protect against various stresses. However, it is unclear how trichomes differentiate into highly variable forms. Here, we show that a homeodomain leucine zipper (HD-ZIP) transcription factor named Woolly controls the fates of distinct trichomes in tomato via a dosage-dependent mechanism. The autocatalytic reinforcement of Woolly is counteracted by an autoregulatory negative feedback loop, creating a circuit with a high or low Woolly level. This biases the transcriptional activation of separate antagonistic cascades that lead to different trichome types. Our results identify the developmental switch of trichome formation and provide mechanistic insights into the progressive fate specification in plants, as well as a path to enhancing plant stress resistance and the production of beneficial chemicals.

Adipose-Derived Stem Cells Exosomes Improve Fat Graft Survival by Promoting Prolipogenetic Abilities through Wnt/ß-Catenin Pathway.

Autologous fat grafting has been widely used in plastic surgery in recent years, but the unstable retention of fat graft has always been a key clinical problem. Adipose tissue has poor tolerant to ischemia, so the transplanted adipose tissue needs to rebuild blood supply at an early stage in order to survive stably. Our previous study has found that comparing to human foreskin fibroblast exosome (HFF-Exo), human adipose-derived stem cells exosome (hADSC-Exo) can significantly improve the proliferation of vascular endothelial cells and the angiogenic effect of artificial dermal preconstructed flaps. Therefore, the ability of hADSC-Exo to improve the retention of adipose grafts and its potential regenerative mechanism aroused our strong interest. In this study, we applied hADSC-Exo and HFF-Exo to adipose grafts and explored the potential regeneration mechanism through various means such as bioinformatics, immunofluorescence, immunohistochemistry, and adipogenic differentiation. The results showed that hADSC-Exo can significantly promote grafts angiogenesis and adipogenic differentiation of ADSC to improve the retention of fat grafts and may downregulate the Wnt/ß-catenin signaling pathway to promote the adipogenic differentiation. In summary, our results provide a theoretical basis for the clinical translation of hADSC-Exo in fat grafting.

The surgical strategies of vaginoplasty for vaginal agenesis patients with or without functional uterus.

BACKGROUND: Vaginal agenesis is a rare condition worldwide. Most reported cases were accompanied by the absence of uterus or uterine hypoplasia; for patients with functional endometrium, hysterectomy was most likely to be conducted to lower postoperative complications. OBJECTIVE: Based on our successful experience in vaginoplasty with autologous buccal mucosal, the purpose of this article is to discuss the surgical strategies in the reconstruction of neovaginal for vaginal agenesis patients with functional uterus and cervical hypoplasia. METHODS: The uterus was preserved in our procedure, and the cervicoplasty was performed to connect the uterine cavity with the neovagina. After the vaginal cavity was formed, the cervix was confirmed and fixed. With the assistance of laparoscope, the direction and angle of the cervix and the uterine body were observed and confirmed. An incision was made in cervix to connect the uterine cavity, and a Foley's catheter was inserted. The newly formed opening of cervix and neovagina was covered by autologous buccal mucosal. RESULTS: The connection between neovagina and cervix uteri was successfully conducted in patient with functional uterus. Unimpeded and regular menstrual was achieved, and the cyclic abdominal pain was disappeared. No complications were observed. CONCLUSION: For patients without functional uterus, vaginoplasty with autologous buccal mucosal can be conducted. However, fertility-preserving surgery should be the primary choice in patients with functional endometrium. It can be concluded from our experience that the utero-vaginal connection with the assistance of laparoscope and the use of autologous buccal mucosa is a promising way to achieve ideal outcomes.

At The Forefront of Penile Surgical Reconstruction: A Bibliometric Study of the 100 Most-Cited Articles.

PURPOSE: The citation count of a scientific article is considered as the recognition it received from this field. The purpose of this bibliometric analysis was to identify the top 100 most-cited scientific articles in penile surgical reconstruction. METHODS: The Web of Science database was used to extract the top 100 most-cited articles. Individual articles were reviewed to identify the authorship, published journal, journal impact factor (IF), primary disease, article type, institution and country of origin, and year of publication. RESULTS: The top 100 most-cited articles were published between 1947 and 2013. The number of citations ranged from 23 to 233. Journal of Urology contributed the most articles (n = 36). Articles with a high level of evidence like prospective analysis (n = 5), systematic review and meta-analysis (n = 2), and guideline (n = 1) were all published after 2000. The average citation per year of articles published in high-IF journals was significantly higher than that of other articles (p = 0.0129). There was a positive linear correlation between citation count per year and publication year (r2 = 0.26, p < 0.001). Among the top 100 articles, 74 articles were interlinked via citation of each other. The major topic of co-citation network was the application of flaps in penile reconstruction. CONCLUSIONS: The analysis of top 100 most-cited articles facilitates the comprehensive recognition of current focus in the field of penile surgical reconstruction, which is the exploration of flaps and development of new techniques in penile reconstruction. In the future, more attention should be paid to evidence-based medicine to provide high-level evidence for research. 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 .

MiR-206 promotes extracellular matrix accumulation and relieves infantile hemangioma through targeted inhibition of DNMT3A.

MiR-206 is abnormally expressed in infant hemangioma endothelial cells (HemECs), but the mechanism is not clear. We explored the intervention of miR-206 in HemECs in relation to extracellular matrix (ECM) metabolism. We selected 48 cases of infantile hemangioma (IH) from volunteer organizations. After the isolated and extracted HemECs were interfered with overexpressed or silenced miR-206, the effects of miR-206 on the proliferation, migration and invasion of HemECs were examined through basic cell function experiments. The expression differences of miR-206, DNA Methyltransferase 3A (DNMT3A) and ECM-related genes were analyzed as needed by qRT-PCR or Western blot. TargetScan and dual-luciferase experiments were applied to predict and confirm the binding relationship between miR-206 and DNMT3A. The correlation between miR-206 and DNMT3A was analyzed in IH tissues by Pearson correlation coefficient, and further confirmed in HemECs by conducting rescue experiments. A nude mouse model of xenograft tumor was constructed to verify the results of in vitro experiments. MiR-206, which was downregulated in proliferative hemangioma, suppressed the malignant development of HemECs by regulating ECM-related genes. As the target gene of miR-206, DNMT3A was high-expressed in IH tissues and was negatively correlated with miR-206. Overexpressed DNMT3A counteracted the inhibitory effect of miR-206 mimic on HemECs and its regulatory effect on ECM. The results of in vivo experiments were consistent with those from cell experiments. Thus, miR-206 could promote ECM accumulation through targeted inhibition of DNMT3A, further inhibiting the malignant development of HemECs and relieving IH.

APICAL SPIKELET ABORTION (ASA) Controls Apical Panicle Development in Rice by Regulating Salicylic Acid Biosynthesis.

Panicle degradation causes severe yield reduction in rice. There are two main types of panicle degradation: apical spikelet abortion and basal degeneration. In this study, we isolated and characterized the apical panicle abortion mutant apical spikelet abortion (asa), which exhibits degeneration and defects in the apical spikelets. This mutant had a pleiotropic phenotype, characterized by reduced plant height, increased tiller number, and decreased pollen fertility. Map-based cloning revealed that OsASA encodes a boric acid channel protein that showed the highest expression in the inflorescence, peduncle, and anther. RNA-seq analysis of the asa mutant vs wild-type (WT) plants revealed that biological processes related to reactive oxygen species (ROS) homeostasis and salicylic acid (SA) metabolism were significantly affected. Furthermore, the asa mutants had an increased SA level and H2O2 accumulation in the young panicles compared to the WT plants. Moreover, the SA level and the expression of OsPAL3, OsPAL4, and OsPAL6 genes (related to SA biosynthesis) were significantly increased under boron-deficient conditions in the asa mutant and in OsASA-knockout plants. Collectively, these results suggest that the boron distribution maintained by OsASA is required for normal panicle development in a process that involves modulating ROS homeostasis and SA biosynthesis.

Dual-targeted and MRI-guided photothermal therapy via iron-based nanoparticles-incorporated neutrophils.

Nanoparticle-mediated photothermal therapy (PTT) has shown promising capability for tumor therapy through the high local temperature at the tumor site generated by a photothermal agent (PTA) under visible or near-infrared (NIR) irradiation. Improving the accumulation of PTA at the tumor site is crucial to achieving effective photothermal treatment. Here, we developed temperature-activatable engineered neutrophils (Ne) by combining indocyanine green (ICG)-loaded magnetic silica NIR-sensitive nanoparticles (NSNP), which provide the potential for dual-targeted photothermal therapy. The combined effect of neutrophil targeting and magnetic targeting increased the accumulation of PTA at the tumor site. According to magnetic resonance imaging (MRI), the retention of intravenous injected NSNP-incorporated neutrophils within the tumor site was markedly augmented as compared to free NSNP. Furthermore, when irradiated by NIR, NSNP could cause a high local temperature at the tumor site and the thermal stimulation of neutrophils. The heat can kill tumor cells directly, and also lead to the death of neutrophils, upon which active substances with tumor-killing efficacy will be released to kill residual tumor cells and thus reduce tumor recurrence. Thereby, our therapy achieved the elimination of malignancy in the mouse model of the pancreatic tumor without recurrence. Given that all materials used in this system have been approved for use in humans, the transition of this treatment method to clinical application is plausible.

An innovative technique of hydrosurgery in the treatment of osmidrosis.

BACKGROUND: We aimed at evaluating the effects of hydrosurgery and traditional surgical approach with two parallel incisions in the treatment of osmidrosis. METHODS: This prospective study enrolled patients with axillary osmidrosis between January 2015 and November 2016. For hydrosurgery, a 1-cm-long incision was made in the middle of the posterior long axis. The hand piece was turned upside down and processed in a 'W-O' way. For traditional method, two 3-cm-long parallel incisions were made transversely. Patient demographics, complications, duration of procedures and the outcomes were collected and compared. All patients had a follow-up period of 24-36 months. RESULTS: A total of 93 patients were included: 41 patients in hydrosurgery group and 52 patients in traditional method group. No severe complications occurred in the hydrosurgery group, while necrosis occurred in six sides of axillae of traditional surgical group. No recurrence occurred in both groups. Both groups showed similar odor and hair growth reduction rate. Only one in 82 sides occurred slight scar formation, while in traditional group, 22 sides of axillae formed scars (p < .001). CONCLUSIONS: The application of hydrosurgery in the treatment of osmidrosis is efficient and effective. Moreover, it has less postoperative complications, and high patient satisfaction rates.

Mediation of JA signalling in glandular trichomes by the woolly/SlMYC1 regulatory module improves pest resistance in tomato.

Almost all plants form trichomes, which protect them against insect herbivores by forming a physical barrier and releasing chemical repellents. Glandular trichomes produce a variety of specialized defensive metabolites, including volatile terpenes. Previous studies have shown that the defence hormone jasmonic acid (JA) affects trichome development and induces terpene synthases (TPSs) but the underlying molecular mechanisms remain unclear. Here, we characterized a loss-of-function allele of the HD-ZIP IV transcription factor woolly (wo) and analysed its role in mediating JA signalling in tomato. We showed that knockout of wo led to extensive trichome defects, including structural and functional changes in type VI glandular trichomes, and a dramatic reduction in terpene levels. We further found that wo directly binds to TPS gene promoters to recruit SlMYC1, a JA signalling modulator, and that together these transcription factors promote terpene biosynthesis in tomato trichomes. The wo/SlMYC1 regulatory module is inhibited by SlJAZ2 through a competitive binding mechanism, resulting in a fine-tuned JA response in tomato trichomes. Enhanced expression of SlMYC1 substantially increased terpene levels and improved tomato resistance to spider mites. Interestingly, we also found that SlMYC1 plays an additional role in glandular cell division and expansion in type VI trichomes, independent of JA. Together, our results reveal a novel, JA-mediated regulatory mechanism that promotes insect resistance in tomato.

Vaginoplasty With Mesh Autologous Buccal Mucosa in Vaginal Agenesis: A Multidisciplinary Approach and Literature Review.

BACKGROUND: Vaginal agenesis, a rare condition, is treated by various surgical techniques to achieve neovaginal reconstruction. The main difference between the approaches lies in the graft material used to cover the newly formed cavity. OBJECTIVES: The purpose of this retrospective study was to describe the surgical procedure and outcomes of autologous buccal mucosal grafting in neovaginal reconstruction. METHODS: Sixteen patients with vaginal agenesis admitted to our department between January 2016 and January 2019 were included in our study. A reconstruction procedure, described in detail here, involving autologous buccal mucosa as graft material was successfully conducted in all of the patients. Long-term anatomic and functional outcomes were evaluated. RESULTS: The blood loss during operation was estimated to be 15 to 20 mL in all cases. No rectal or bladder injury occurred. The buccal mucosal wound completely healed 10 to 14 days after the operation. All patients had a well-formed neovagina 8 to 10 cm in length, with a mean diameter of >3 finger-breadths. CONCLUSIONS: The application of autologous buccal mucosa in neovaginal construction is a simple procedure. Autologous buccal mucosa is an ideal material to achieve excellent cosmetic and functional results in patients with vaginal agenesis.

Melanoma Cell Membrane Biomimetic Versatile CuS Nanoprobes for Homologous Targeting Photoacoustic Imaging and Photothermal Chemotherapy.

Modulating the surface properties of nanoparticles (NPs) is an important approach to accomplish immune escape, prolonged the blood retention time, and enhance the ability of targeted drug delivery. The camouflage of cancer cell membrane onto nanoparticles has been proved to be an ideal approach to enhance active targeting ability of NPs. Herein, we isolated the membrane of melanoma cells to coat doxorubicin (DOX) and indocyanine green (ICG)-loaded hollow copper sulfide NPs (ID-HCuSNP@B16F10) for targeted photothermal therapy, photoacoustic imaging, and chemotherapy. A remarkable in vitro anticancer effect after irradiation and homologous targeting can be observed in B16F10 cells after the treatment of ID-HCuSNP@B16F10. Moreover, ID-HCuSNP@B16F10 exhibits excellent photothermal effect in melanoma animal models and achieves a high tumor ablation rate. This biomimetic system can realize high drug loading efficiency, enhanced targeting ability, and ideal antitumor efficiency.

Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps.

Large prefabricated flaps often suffer from necrosis or poor healing due to a lack of new blood vessels and related factors that promote angiogenesis. The innovative use of adipose-derived stem cell exosomes (ADSC-Exo) resolves the problem of vascularization of prefabricated flaps. We analyzed the differential microRNA (miRNA) expression in ADSC-Exo using next-generation sequencing (NGS) technology to explore their potential mechanisms in promoting vascularization. We observed that ADSC-Exo could significantly promote the vascularization of artificial dermis prefabricated flaps compared with human foreskin fibroblast exosomes. NGS indicated that there were some differentially expressed miRNAs in both exosomes. Bioinformatics analysis suggested that significantly upregulated hsa-miR-760 and significantly downregulated hsa-miR-423-3p in ADSC-Exo could regulate the expression of the ITGA5 and HDAC5 genes, respectively, to promote the vascularization of skin flaps. In summary, ADSC-Exo can promote skin-flap vascularization, and thereby resolve the problem of insufficient neovascularization of artificial dermis prefabricated flaps, thus expanding the application of prefabricated skin-flap transplantation.