Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach in Double-Eyelid Blepharoplasty Revision.

BACKGROUND: Incisional double-eyelid blepharoplasty is the main surgical technique to obtain an artificial crease. Postoperative complications decrease patients' satisfaction, and patients with prominent depressed groove and persistent pretarsal swelling (sausage phenomenon) usually need revision surgery. To resolve the sausage phenomenon after blepharoplasty, we adopt Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach to create natural double eyelids. METHODS: We included 68 patients in the study. The inclusion criteria for revision surgery were as follows: (1) pretarsal OOM remained after primary surgery, (2) prominent depressed surgical scar/groove and persistent pretarsal bulge (sausage phenomenon), (3) postsurgical abnormally wide crease. The surgical procedure involved releasing the pretarsal OOM, forming OFOOM-OOM flap, and OFOOM-OOM flap fixed with aponeurosis. Outcome observations were assessed using the FACE-Q questionnaire, and the follow-up period ranged from 6 to 36 months (mean=18 months). RESULTS: The depressed groove and pretarsal bulge showed significant improvements, and FACE-Q scores of the 68 patients before surgery (mean scores=66) compared with those after surgery (mean scores=90) were significantly different (P<0.01). Four patients with palpebral fold asymmetry and two patients with shallow eyelids received revision surgery, and patients were satisfied with the secondary surgery effects. Six patients presented with unnatural curves of folds and revision surgery alleviated these situations. CONCLUSIONS: Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach is an effective way to resolve the sausage phenomenon. The OFOOM-OOM flap is a reliable and flexible structure to create natural double eyelids. LEVEL OF EVIDENCE IV: 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 .

Aesthetic Sideburn Reconstruction Using an Expanded Hair Bearing Skin Flap With Natural Hairline.

BACKGROUND: Hairline is the marginal line of hair growth on the scalp. Patients with sideburn defects, caused by tumor resection, severe infection, or burns, might have low self-esteem and mental stress. The purpose of this article was to explore a surgical method of applying the expanded scalp flap with natural hairline for cosmetic reconstruction of hairline, so as to provide reference for future clinical work. METHODS: In this study, a retrospective analysis was conducted on 23 patients in the plastic surgery ward of the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from January 2015 to December 2018, who underwent expanded scalp flap cosmetic reconstruction of the sideburns with natural hairline (14 males and 9 females; average age, 18.7 ± 13.7 years). The follow-up time was 8 to 44 months. RESULTS: Patient satisfaction rate (scored 4 or more) was 95.7%, with an average score of 4.59. A total of 16 patients were very satisfied, and 6 were satisfied. There were 21 patients who had good flap survival, and 2 patients who had venous congestion at the distal end of the flap. One case relieved voluntarily 3 days postsurgery, and the other case had partial skin necrosis at the distal end, healing phase II. These 2 cases were classified as grade I according to the Clavien-Dindo classification. In 9 of the patients, the reconstructed sideburn presented a natural look with good hair angle and great size and shape, with average scores of 4.61, 4.52, and 4.48. The scars at the donor site were inconspicuous, and there were no complaints (average score, 4.61). The rest of the patients received satisfactory appearances after surgery. CONCLUSION: In conclusion, the technique described above presented a fine method for sideburn reconstruction. Based on the achieved aesthetic scores of our study, as well as the high patient satisfaction rate (95.7%), the aforementioned technique is acceptable for both surgeons and patients.

A New Technique for Chondrolaryngoplasty in Patients Assigned Female at Birth.

BACKGROUND: Chondrolaryngoplasty is a classical facial feminization surgery for transgender women. In recent years, however, an increasing number of patients assigned female at birth are seeking chondrolaryngoplasty for esthetic purposes. Traditional chondrolaryngoplasty can no longer cope with problems of the growing group whose leading cause of laryngeal prominence differs from the transgender population. METHODS: A modified technique is designed as a supplement to the classical procedure. After the cartilage reduction process, paired platysma flaps are raised and advanced successively, resulting in an overlapped area over the thyroid notch, to further camouflage the thyroid prominence. To evaluate the efficiency of the new technique, a retrospective survey of 34 patients (5 men and 29 women) who underwent the surgery from 2016 to 2021 was performed, via a 5-point Likert scale including 7 questions. Physician assessment was also accomplished to provide an extra estimation. Complications were followed up and analyzed to evaluate the safety of modified surgery as well. RESULTS: Although only half of the patients graded prominence changes more than "moderately changed," as many as 75.0% of them still expressed "completely satisfied" or "satisfied very much" with the outcome. Similarly, physician assessment indicated a satisfactory result in appearance improvement. No severe and irreversible complications occurred after surgery, but lasting scar-related issues were reported by 4 patients and should be paid more attention to. CONCLUSIONS: Generally speaking, the new technique is both safe, efficient, and satisfying for most patients, especially ones assigned females at birth with esthetic demand.

Three-Dimensional Z-Epicanthoplasty Retains the Depth of the Medial Canthus With Scars That Are Less Visible.

BACKGROUND: Traditional coronal Z-epicanthoplasty usually generates visible scars, and V-Y advancement or skin redraping can damage the normal shape of the lower eyelid. In addition, these methods usually lead to loss of the medial canthus depth, which is important for the natural appearance of East Asians. This report aims to describe a 3-dimensional Z-epicanthoplasty that can maintain the depth of the medial canthus with fewer visible scars. METHODS: Patients who underwent 3-dimensional Z-epicanthoplasty from January 2016 to December 2019 were included. In our method, excess skin in the horizontal direction was first rotated to the vertical position and then turned inward from a coronal to a sagittal orientation to supplement the skin deficiency of the medial canthus in the sagittal orientation. The skin flap turned in the sagittal orientation and maintained the depth of the medial canthus and the natural appearance of the eye. RESULTS: In total, 138 patients were included, and the follow-up interval ranged from 6 to 36 months. After the surgery, the epicanthi were removed, and the shapes of the patients' eyes were significantly improved and appeared natural. The surgical scars were hidden in the sagittal orientation rather than in the coronal orientation, which cannot be seen easily. The depth of the medial canthus was well preserved without any lower eyelid destruction. Patients were satisfied with the natural appearance of the medial canthus. CONCLUSIONS: This method could not only correct the epicanthal fold effectively with scars that are less visible but also maintain the depth of the medial canthus and make the appearance of the eye look more natural.

Different Transfer Forms of the Expanded Forehead Flap Pedicled With Superficial Temporal Vessels to Treat Chin and Submental Scar Deformities.

BACKGROUND: The chin and submental regions are located at the junction of the face and neck. Its function and aesthetic appearance can be seriously affected when scar deformities cause the cervico-mental angle to disappear. The expanded forehead flap pedicled with superficial temporal vessel(s) is a surgical treatment for chin and submental scar deformities. Different transfer types have developed for this flap based on individual situations. At present, there is no unified treatment strategy for applying this forehead flap to treat different regions and ranges of chin and submental scar deformities. METHODS: Ninety one cases were collected from patients with chin and submental scar deformities that were treated using the expanded forehead flap pedicled with superficial temporal vessels from January 2008 to December 2018. The authors divided the chin and submental scar deformities into 4 types according to different regions and ranges, and summarized flap survival and complications of 5 different transfer forms used to treat scars for creating feasible treatment strategies. We followed up 76 cases, investigating the satisfaction of appearance and texture of the flaps, improvement of neck movement, and scar recurrence. RESULTS: Expanded forehead flaps were used to repair 91 cases of chin and submental scar deformities. According to the postoperative flap survival and complications of flap blood supply, the treatment strategies are as follows: Bilateral cutaneous and subcutaneous pedicled forehead flaps are applied to treat scars in bilaterally symmetrical large-scale scars in Zone LCL. Unilateral pedicled forehead flaps are applied to treat small-scale scars in Zone C and Zone L. Unilateral pedicled plus contralateral vascular anastomosis and unilateral pedicled plus contralateral super thin forehead flaps are applied to treat the moderate-scale scars of Zone LC. Mean follow-up period was 81 months (range 28-131), 93.4% (71/76) was satisfied with appearance and texture of the flaps, 97.4% (74/ 76) was satisfied with the improvement of neck movement, and 2.6% (2/76) occurred scar recurrence. CONCLUSIONS: Five different types of expanded forehead flaps pedicled with superficial temporal vessels can be used to repair differential scar deformities of the chin and submental regions and achieve good therapeutic effects.

Infraeyebrow Blepharoplasty Using Dynamic Suspension Technique Between Dermis-Fascia Flap and Frontalis in Upper Eyelid Lifting and Eyebrow Augmentation.

OBJECTIVE: Upper eyelid laxity affects facial aesthetics and the eyebrow arch in the East Asian population is generally low. The authors developed infraeyebrow blepharoplasty using a dynamic suspension technique between the dermis-fascia flap and frontalis for upper eyelid lifting and eyebrow augmentation. METHODS: A retrospective study was performed on 43 female patients with upper eyelid laxity from August 2015 to October 2019. The epidermis and superficial dermis of the infraeyebrow was removed from the surgical marking area with the deep dermis and fascia preserved. The eyebrow skin flap was separated from the frontalis surface which fully exposed the area around eyebrow arch. The preserved dermis-fascia flap was folded and suspended to frontalis in the superior margin of eyebrow arch. RESULTS: Forty-three patients (median age 54 years [range, 38-70]) underwent this operation. Mean follow-up was 25 months (range, 8-42) was assessed. All incisions healed well and were almost invisible. The eyebrow area improved with upper eyelid skin lift and eyebrow augmentation; 40 cases were "very satisfied" with their appearance. Three cases were "not very satisfied," including 1 case with numbness in surgical area. 2 cases had slight bilateral asymmetry of the upper eyelids. CONCLUSIONS: The dynamic suspension technique is worthy of clinical application because it can correct upper eyelid laxity, augment the low eyebrow arch, and obtain an invisible scar by reducing the incision tension.

Inhibiting Warburg Effect Can Suppress the Biological Activity and Secretion Function of Keloid Fibroblasts.

BACKGROUND: Keloids have always been a difficult problem in the clinic. In our previous study, we demonstrated a Warburg effect in keloid fibroblasts (KFs), like tumors. In this study, we aimed to investigate the effects of the suppression of the Warburg effect on the biological activity and function of KFs. METHODS: KFs were isolated and cultured with different concentrations of oxamate, a classical competitive lactate dehydrogenase A (LDHA) inhibitor. First, the suppression effect of oxamate on the Warburg effect in KFs was verified. After treatment with oxamate, a scratch wound assay, real-time PCR, flow cytometry, CCK8 kit, and western blotting were used to detect the migration ability, collagen production, apoptosis, cell proliferation, cell cycle distribution, and related molecular mechanisms in KFs. RESULTS: As expected, oxamate inhibited the Warburg effect in KFs in a dose-dependent manner. After the inhibition of the Warburg effect in KFs, the cell migration rate decreased significantly, the mRNA transcription levels of type I collagen and α-SMA were significantly lower, the cell apoptosis rate increased significantly, the cell proliferation activity decreased significantly, and G0/G1 phase cells in KFs increased significantly. The expression of cyclin D1 and its upstream regulatory factors, Akt protein and GSK3 ß (phospho S9), decreased significantly. CONCLUSION: Inhibiting the Warburg effect in KFs significantly suppressed cell proliferation, enhanced cell apoptosis, inhibited cell migration ability, reduced collagen secretion, and induced G0/G1 arrest through the Akt-GSK3ß-Cyclin D1 pathway. Therefore, inhibiting the Warburg effect in KFs may provide a new option for the prevention and treatment of keloids. LEVEL OF EVIDENCE IV: 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 .

Combining photo-redox and enzyme catalysis for the synthesis of 4H-pyrimido[2,1-b] benzothiazole derivatives in one pot.

A novel strategy combining visible-light and enzyme catalysis in one pot for the synthesis of 4H-pyrimido[2,1-b] benzothiazole derivatives from alcohols is described for the first time. Fourteen 4H-pyrimido[2,1-b] benzothiazole derivatives were prepared with yields of up to 98% under mild reaction conditions by a simple operation. The photoorgano catalyst rose Bengal (rB) was employed to oxyfunctionalise alcohols to aldehydes. Compared with aldehydes, alcohols with more stable properties and lower cost, thus we used photocatalysis to oxidize alcohols into aldehydes. Next, the enzyme was used to further catalyze the reaction of Biginelli to produce the target product of 4H-pyrimidine [2,1-b] benzothiazole. Experimental results show that this method provides a more efficient and eco-friendly strategy for the synthesis of 4H-pyrimido[2,1-b] benzothiazole derivatives.

Fast and high-efficiency synthesis of 2-substituted benzothiazoles via combining enzyme catalysis and photoredox catalysis in one-pot.

An efficient and green method, combining enzymatic and visible-light catalysis for synthesis of the widely applicable 2-substituted benzothiazoles, has been developed. This method features a relay catalysis protocol consisting of biocatalytic promiscuity and visible-light-induced subsequent oxidization of 2-phenyl benzothiazolines. The whole reaction process is very high-efficiency, achieving 99% yield in just 10 min, under an air atmosphere, nearly 100% atomic utilization, and the 2-substituted benzothiazole products were obtained in good to excellent yields with a wide range of substrates. This reaction is the other example of combining the non-natural catalytic activity of hydrolases with visible-light catalysis for organic synthesis and the catalytic system does not require additional oxidants or metals, which is good for the environment.

Aesthetic Design of Expanded Bilateral Superficial Temporal Vascular Fascial Pedicled Flap for Repairing Maxillocervical Scars.

BACKGROUND: Large-scale maxillocervical scars impair face and neck function and damage appearance. The forehead expanded bilateral superficial temporal pedicled flap is a good treatment strategy for this area; however, the traditional cutaneous pedicled flap damages the temporal hair area. This impairs aesthetics and causes alopecia; furthermore, requires an additional pedicle-cut operation. METHODS: A retrospective study was performed on 7 patients with large-scale maxillocervical scars from January 2014 to August 2018. Forehead expanders were implanted in the first-stage operation for all patients. After the injection and rest period, patients were treated using the forehead expanded bilateral superficial temporal vascular fascial pedicled flap. Superficial temporal vascular fascia pedicles were carefully harvested. The use of an intralesional or hidden retrotragus incision was determined by the presence of a preauricular scar. Patient satisfaction with postoperative neck activity and the incision scar was evaluated. RESULTS: Intralesional and retrovagus incisions were used in 4 and 3 cases, respectively. One flap developed hematoma, which recovered completely after conservative treatment; all other cases had no complications. All flaps healed well. The neck mobility of the patients was significantly improved with no visible scar in the temporal region. Six cases reported being "very satisfied" and one was "relatively satisfied" with their improvement in neck mobility. All cases reported being "very satisfied" with frontotemporal morphology. CONCLUSIONS: The forehead expanded bilateral superficial temporal vascular fascial pedicled flap is a good choice for patients with large-scale maxillocervical scars. This technique can maintain the aesthetics of temporal hair and reduce patients extra surgical injury.

Nanofat Injection for the Treatment of Depressed Facial Scars.

BACKGROUND: Patients with depressed facial scars complain of their negative effects. However, the efficacy of optional treatment techniques is never completely adequate. This study aimed to assess the efficacy of nanofat injection in the improvement of depressed facial scars. METHODS: This retrospective study included patients who underwent depressed facial scar filling with nanofat between November 2017 and January 2020. The FACE-Q scale was sent to patients for feedback regarding satisfaction. Evaluations of the results were also performed by three plastic surgeons. RESULTS: Among the 52 included patients, 44 patients (29 women and 15 men) completed the questionnaire. Obvious and stable effects were usually acquired 3 months after surgery. Temporary erythema appeared at the injection site to varying degrees, lasting 2 to 3 weeks in 93% of the patients. No other serious postoperative complications were observed in the injection area. The FACE-Q outcomes showed that patients who completed injection therapy more than 1 year prior were significantly more satisfied with the decision to undergo this therapy than those who completed the treatment less than 1 year prior. Furthermore, according to the physicians' evaluations, 91% of patients experienced improvement in scar appearance after treatment. CONCLUSIONS: The low rate of injection-site complications and the safety of this procedure both support the current implementation of nanofat in the treatment of depressed facial scars. The results of the physicians' evaluations and patient satisfaction surveys confirmed the stable effect of nanofat injection in the treatment of depressed facial scars. LEVEL OF EVIDENCE IV: 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.

The Application of Temporal-Fasciae-Complex Sheet in Treating Severe Blepharoptosis.

AIM: To introduce the application of the temporal-fasciae-complex sheet in treating severe blepharoptosis by frontalis suspension and evaluate its postoperative effect. METHODS: Between 2008 and 2016, 25 patients (33 eyelids) underwent this procedure. A 3-cm incision in the temporal region was made to harvest a sheet of deep temporal fascia with the loose aponeurosis attached on both sides. The sheet was then grafted through a preseptal tunnel to perform the suspension. The margin reflex distance 1 after suspension (MRD1S), the margin reflex distance 1 as lifting eyebrow forcefully (MRD1F), the eyelid excursion and the closable eyelid function were used to evaluate the postoperative effect. RESULTS: A total of 22 patients (30 eyelids) completed the study with a mean follow-up period of 23 ± 8.78 months. There was a statistically significant difference between the MRD1 and MRD1S (p < 0.05), the preoperative and postoperative MRD1F (p < 0.05), the preoperative and postoperative eyelid excursion (p < 0.05). All the upper palpebral margins were located above the pupils and no longer affected visual acuity in primary gaze. No severe complication and recurrence were documented within a maximum follow-up period of 36 months. CONCLUSIONS: Frontalis suspension with the temporal-fasciae-complex sheet is an efficient method to correct severe blepharoptosis with less complications and recurrences. The application of the sheet can not only overcome the influence of adhesion but also lift the eyelid both functionally and cosmetically. LEVEL OF EVIDENCE IV: 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 .

Sustained hedgehog signaling in medulloblastoma tumoroids is attributed to stromal astrocytes and astrocyte-derived extracellular matrix.

Aberrant activation of the hedgehog (Hh) signaling pathway is associated with the formation of medulloblastoma (MB), the most common malignant pediatric brain tumor. However, tumor cells from human and mouse MB can not be passaged or preserved after being adherently cultured. Moreover, Hh signaling in MB cells is inactivated in such culture. Here we demonstrate that MB cells are capable of forming tumoroids (tumor spheroids) in vitro under optimized conditions, which can be further passaged and cryopreserved. More importantly, MB cells maintain Hh pathway activation and cell proliferation in tumoroids. Our studies further reveal that tumoroids-forming capacity of MB cells relies on astrocytes, a major component of the MB microenvironment. Astrocytes facilitate the formation of MB tumoroids by secreting sonic hedgehog (Shh) and generating astrocyte-derived extracellular matrix. These findings demonstrate the critical role of stromal astrocytes in supporting the survival and proliferation of MB cells in vitro. This study establishes a valid model for long-term culture of primary MB cells, which could be greatly beneficial for future investigation of MB tumorigenicity and the development of improved approaches to treat MB.

Effect of Mechanical Tension on the circRNA Expression Profile of Human Skin Tissue.

Skin soft tissue dilatation has emerged as one of the most prominent methods to skin defects spanning large areas. However, effective expansion of additional skin tissue is still the most challenging problem. This study aimed to understand the potential role of circular RNAs (circRNAs) in gene regulation during skin regeneration via analysis of the circRNA expression profile of skin tissue during skin regeneration under mechanical tension. In total, 1039 circRNAs were identified, of which 126 were newly identified. Furthermore, 48 circRNAs were differentially expressed between the experimental and control groups, which were annotated with gene ontology and kyoto encyclopedia of genes and genomes functions, and the regulatory network of microRNA (miRNA)-circRNA was established. The present results provide a theoretical basis for future studies on the mechanism underlying skin regeneration.

Faciocervical Reconstruction Using a Large Expanded Forehead Island Flap Grafted Using a Microsurgical Technique for Burned Cicatricial Contracture Correction.

Extrinsic cicatricial contracture is still one of the most common and frustrating complications in the faciocervical area after severe burns. Because of these contractured scars, patients not only suffer from aesthetic issues but also local dysfunction, especially when it comes to the faciocervical region. Esthetical and functional reconstruction of these regions remains a great challenge for reconstructive surgeons. This report presents a 28-year-old man with postburn mentocervical adhesion treated successfully with a large expanded forehead island flap. Cosmetic and functional results have been achieved in this patient during long-term follow-ups.

Low-level laser treatment stimulates hair growth via upregulating Wnt10b and ß-catenin expression in C3H/HeJ mice.

This study was conducted in order to evaluate the role of low-level laser treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were randomly divided into two groups: with and without low-level laser treatment. The skin color of each mouse was observed each day. Skin samples were collected for H&E, immunofluorescence, PCR, and western blot analysis, to observe the morphology of hair follicles and detect the expression levels of Wnt10b and ß-catenin. Observation of skin color demonstrated that black pigmentation started significantly earlier in the laser group than in the control group. Hair follicle number in both groups showed no difference; however, the hair follicle length presented a significant difference. Wnt10b protein was detected on the second day in hair matrix cells in the LLLT group but not in the control group. PCR and western blot results both illustrated that expression of Wnt10b and ß-catenin was significantly higher in the LLLT group than in the control group. Our study illustrated that low-level laser treatment can promote hair regrowth by inducing anagen phase of hair follicles via initiating the Wnt10b/ß-catenin pathway.

N-myc alters the fate of preneoplastic cells in a mouse model of medulloblastoma.

Studying the early stages of cancer can provide important insight into the molecular basis of the disease. We identified a preneoplastic stage in the patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma. Preneoplastic cells (PNCs) are found in most ptc mutants during early adulthood, but only 15% of these animals develop tumors. Although PNCs are found in mice that develop tumors, the ability of PNCs to give rise to tumors has never been demonstrated directly, and the fate of cells that do not form tumors remains unknown. Using genetic fate mapping and orthotopic transplantation, we provide definitive evidence that PNCs give rise to tumors, and show that the predominant fate of PNCs that do not form tumors is differentiation. Moreover, we show that N-myc, a gene commonly amplified in medulloblastoma, can dramatically alter the fate of PNCs, preventing differentiation and driving progression to tumors. Importantly, N-myc allows PNCs to grow independently of hedgehog signaling, making the resulting tumors resistant to hedgehog antagonists. These studies provide the first direct evidence that PNCs can give rise to tumors, and demonstrate that identification of genetic changes that promote tumor progression is critical for designing effective therapies for cancer.

Novel Magnetic Cross-Linked Cellulase Aggregates with a Potential Application in Lignocellulosic Biomass Bioconversion.

The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has been developed and applied for biomass bioconversion. The crosslinked aggregates could purify and immobilize enzymes in a single operation, and could then be combined with magnetic nanoparticles (MNPs), which provides easy separation of the materials. The immobilized cellulase showed a better activity at a wider temperature range and pH values than that of the free cellulase. After six cycles of consecutive reuse, the immobilized cellulase performed successful magnetic separation and retained 74% of its initial activity when carboxylmethyl cellulose (CMC) was used as the model substrate. Furthermore, the structure and morphology of the immobilized cellulase were studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, the immobilized cellulase was shown to hydrolyze bamboo biomass with a yield of 21%, and was re-used in biomass conversion up to four cycles with 38% activity retention, which indicated that the immobilized enzyme has good potential for biomass applications.

NGL-2 Is a New Partner of PAR Complex in Axon Differentiation.

Neuronal polarization is pivotal for neural network formation during brain development. Axon differentiation is a hallmark of initial neuronal polarization. Here, we report that the leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2) as a polarity regulator that localizes asymmetrically in rat hippocampal neurons and is required for differentiation of the future axon. NGL-2 was associated with PAR complex, and this interaction resulted in local stabilization of axonal microtubules. Further study showed that the C terminal of NGL-2 binds to the PDZ domain of PAR6, and NGL-2 interacts with PAR3 and atypical PKCζ (aPKCζ), with PAR6 acting as a bridge or modifier. Then, NGL-2 regulates the local stabilization of microtubules and promotes axon differentiation by the aPKCζ/microtubule affinity-regulating kinase 2 pathway. These findings reveal the critical role of NGL-2 in regulating axon differentiation in rat hippocampal neurons and reveal a novel partner of the PAR complex.

Subtypes of medulloblastoma have distinct developmental origins.

Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.