Celine, a long interspersed nuclear element retrotransposon, colonizes in the centromeres of poplar chromosomes.

Centromeres in most multicellular eukaryotes are composed of long arrays of repetitive DNA sequences. Interestingly, several transposable elements, including the well-known long terminal repeat (LTR) retrotransposon CRM (centromeric retrotransposon of maize), were found to be enriched in functional centromeres marked by the centromeric histone H3 (CENH3). Here we report a centromeric long interspersed nuclear element (LINE), Celine, in Populus species. Celine has colonized preferentially in the CENH3-associated chromatin of every poplar chromosome, with 84% of the Celine elements localized in the CENH3-binding domains. By contrast, only 51% of the CRM elements were bound to CENH3 domains in Populus trichocarpa. These results suggest different centromere targeting mechanisms employed by Celine and CRM elements. Nevertheless, the high target specificity seems to be detrimental to further amplification of the Celine elements, leading to a shorter life span and patchy distribution among plant species compared to the CRM elements. Using a phylogenetically guided approach we were able to identify Celine-like LINE elements in tea plant (Camellia sinensis) and green ash tree (Fraxinus pennsylvanica). The centromeric localization of these Celine-like LINEs was confirmed in both species. We demonstrate that the centromere targeting property of Celine-like LINEs is of primitive origin and has been conserved among distantly related plant species.

Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Neutrophil extracellular traps as a unique target in the treatment of inflammatory pain.

Pain is a widespread motivation for seeking healthcare and stands as a substantial global public health concern. Despite comprehensive investigations into the mechanisms of pain sensitization induced by inflammation, efficacious treatments options remain scarce. Neutrophil extracellular traps (NETs) have been associated with the progression and tissue damage of diverse inflammatory diseases. This study aims to explore the impact of NETs on the progression of inflammatory pain and explore potential therapeutic approaches. Initially, we observed neutrophil infiltration and the formation of NETs in the left hind paw of mice with inflammatory pain induced by complete Freund's adjuvant (CFA). Furthermore, we employed the peptidyl arginine deiminase 4 (PAD4) inhibitor Cl-amidine (diluted at 50 mg/kg in saline, administered via tail vein injection once daily for three days) to impede NETs formation and administered DNase1 (diluted at 10 mg/kg in saline, once daily for three days) to break down NETs. We investigated the pathological importance of peripheral NETs formation in inflammatory pain and its influence on the activation of spinal dorsal horn microglia. The findings indicate that neutrophils infiltrating locally generate NETs, leading to an increased release of inflammatory mediators that worsen peripheral inflammatory reactions. Consequently, this results in the transmission of more harmful peripheral stimuli to the spinal cord, triggering microglial activation and NF-κB phosphorylation, thereby escalating neuroinflammation and fostering pain sensitization. Suppression of peripheral NETs can mitigate peripheral inflammation in mice with inflammatory pain, reverse mechanical and thermal hypersensitivity by suppressing microglial activation in the spinal cord, ultimately diminishing inflammatory pain. In conclusion, these discoveries propose that obstructing or intervening with NETs introduces a novel therapeutic avenue for addressing inflammatory pain.

Safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of Exendin-4-IgG4-Fc in healthy subjects: A phase 1, single-centre, randomized, double-blind, dose escalation study.

AIM: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects. METHODS: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level. RESULTS: E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose-dependent relationship between frequency, severity or causality of treatment-emergent adverse events. Cmax and area under the curve of E4F4 were dose proportional over the 0.45-14.85 mg dose range. Median Tmax and t1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose-dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose-response relationship in the 1.8-10.35 mg dose range, with an increased response at the higher doses. CONCLUSION: E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5-10.35 mg once every 2 weeks.

LECT2 mediates antibacterial immune response induced by Nocardia seriolae infection in the northern snakehead.

Leukocyte-derived chemotaxin-2 (LECT2) is a multifunctional immunoregulator that plays several pivotal roles in the host's defense against pathogens. This study aimed to elucidate the specific functions and mechanisms of LECT2 (CaLECT2) in the northern snakehead (Channa argus) during infections with pathogens such as Nocardia seriolae (N. seriolae). We identified CaLECT2 in the northern snakehead, demonstrating its participation in the immune response to N. seriolae infection. CaLECT2 contains an open reading frame (ORF) of 459 bp, encoding a peptide of 152 amino acids featuring a conserved peptidase M23 domain. The CaLECT2 protein shares 62%-84% identities with proteins from various other fish species. Transcriptional expression analysis revealed that CaLECT2 was constitutively expressed in all examined tissues, with the highest expression observed in the liver. Following intraperitoneal infection with N. seriolae, CaLECT2 transcription increased in the spleen, trunk kidney, and liver. In vivo challenge experiments showed that injecting recombinant CaLECT2 (rCaLECT2) could protect the snakehead against N. seriolae infection by reducing bacterial load, enhancing serum antibacterial activity and antioxidant capacity, and minimizing tissue damage. Moreover, in vitro analysis indicated that rCaLECT2 significantly enhanced the migration, respiratory burst, and microbicidal activity of the head kidney-derived phagocytes. These findings provide new insights into the role of LECT2 in the antibacterial immunity of fish.

A prospective comparison of a modified miniaturised hand-held epifluorescence microscope and touch imprint cytology for evaluation of axillary sentinel lymph nodes intraoperatively in breast cancer patients.

BACKGROUND: The management of axillary lymph nodes in early-stage breast cancer patients has changed considerably, with the primary focus shifting from the examination of sentinel lymph nodes (SLNs) to toward the detection of all macro-metastases. However, current methods, such as touch imprint cytology (TIC) and frozen sections, are inadequate for clinical needs. To address this issue, we proposed a novel miniaturised epifluorescence widefield microscope (MEW-M) to assess SLN status intraoperatively for improved diagnostic efficiency. METHODS: A prospective, side-by-side comparison of intraoperative SLN evaluation between MEW-M and TIC was performed. RESULTS: A total of 73 patients with 319 SLNs consecutive enrolled in this study. MEW-M showed significantly superior image quality compared to TIC (median score 3.1 vs 2.1, p < 0.0001) and had a shorter time to issue results (10.3 vs 19.4 min, p < 0.0001). Likelihood ratio analysis illustrated that the positive likelihood ratio value of MEW-M compared with TIC was infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 1 (classifying results into negative/positive), infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 2 (classifying results into macro-metastasis/others, and TIC results followed the same classification as model 1), respectively. Similarly, the negative likelihood ratio values of MEW-M compared with TIC were 0.055 (95% CI, 0.018-0.160) and 0.074 (95% CI, 0.029-0.190) in model 1; and 0.019 (95% CI, 0.003-0.130) vs 0.020 (95% CI, 0.003-0.140) in model 2, respectively. CONCLUSIONS: MEW-M is a promising technique that can be utilised to provide a rapid and accurate intraoperative assessment of SLN in a clinical setting to help improve decision-making in axillary surgery.

Comprehensive quality evaluation of Lysimachia christinae Hance via fingerprint, spectrum-effect relationship, and quantitative analyses of multiple components by single marker.

BACKGROUND: Lysimachia christinae Hance (LCH) is a traditional medicine used to treat gallstone disease and cholecystitis. Despite its known anti-inflammatory and choleretic effects, its quality has not been extensively evaluated. OBJECTIVE: In this study, we aimed to establish a reliable quality evaluation method for LCH via fingerprint, spectrum-effect relationship, and quantitative analyses of multicomponents by a single marker (QAMS). METHODS: First, the fingerprints and anti-inflammatory and choleretic activities of 14 LCH batches were determined. Then, the gray relation analysis method was used to analyze the peak areas of the fingerprint profile and pharmacodynamic data. Subsequently, the characteristic peaks were tentatively identified using high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Finally, rutin was selected as the internal reference material, and QAMS was used to analyze the LCH components. RESULTS: Pharmacodynamic experiments confirmed that LCH exerted anti-inflammatory and choleretic effects. Moreover, 15 flavonoids related to the anti-inflammatory and choleretic effects of LCH were identified. Notably, relative error percentage between the QAMS and external standard method was less than 5%. CONCLUSION: This study successfully established a comprehensive evaluation method for the qualitative and quantitative analyses of LCH.

Scalp Composite Tissue Transplantation for Repairing Upper Lip Defect: A Feasible Clinical Study.

BACKGROUND: The repair of upper lip defects is difficult and can result in asymmetry. The authors have developed a postauricular scalp composite tissue for the repair of upper lip defects. Herein, the authors, present the feasibility of scalp composite tissue grafts for repairing of upper lip defects. METHODS: The authors conducted a retrospective study of 10 patients who underwent scalp composite tissue transplantation for upper lip repair. The surgical procedure consisted of the excision of skin lesions or scar tissue from the upper lip to prepare the recipient area, and then the scalp composite tissue was excised behind the ear and transplanted to the upper lip defect. The authors reviewed the photographs and clinical notes of these patients. The patients' self-reported satisfaction with the repair effect was assessed. Tissue sections and hematoxylin and eosin staining of the scalp composite tissues were performed. RESULTS: All patients successfully underwent lesion resection and scalp composite tissue transplantation to repair the wound. There was no necrosis of the scalp composite tissue in the early postoperative period. The lip wound healed completely within 2 weeks. The mean follow-up time was 16 months, ranging from 12 to 20 months. Histologic sections and hematoxylin and eosin staining showed that the scalp composite tissue had abundant capillaries and dense fibrous connective tissue. All 10 patients were satisfied with the clinical effect of the procedure. CONCLUSION: Scalp composite tissue transplantation is a viable method for repairing upper lip defects. The special histomorphological characteristics of the scalp provide the basis for clinical application. LEVEL OF EVIDENCE: IV.

Nasofacial Groove Pedicled Flap for the Reconstruction of Lateral Alar Defect.

BACKGROUND: The repair of nasal alar defects is challenging for plastic surgeons, and there is currently no standard operation. Herein, the authors reported the clinical outcomes of a nasofacial groove pedicled flap for the reconstruction of alar defect. METHODS: This retrospective study included patients who underwent the nasofacial groove pedicled flap for the reconstruction of alar defect between January 2018 and June 2020. Photographs of standard facial postures were taken before and after surgery to record the surgical results of the patients. The patient's medical history was reviewed retrospectively. Self-reported satisfaction of patients on scar morphology and reconstructive effect were evaluated with a questionnaire survey. RESULTS: There were 26 eligible patients enrolled, and all patients were followed up for more than 1 year after surgery. All flaps were free of ischemia and necrosis and healed well. No patient experienced restricted nostril ventilation. Eight patients underwent reoperation to trim the flap pedicle and the scar. Eight patients (8/26) reported "very satisfied," and 17 patients (17/26) reported "satisfied" with the repair effect and scar morphology. One patient went through multiple laser treatments to improve her scars but still remained visible hyperpigmentation. She was dissatisfied with postoperative flap pigmentation but was satisfied with the correction effect. CONCLUSIONS: The clinical results indicated that the nasal groove flap was safe for the treatment of the lateral alar defect, and the patients were satisfied with the clinical results. The authors believe that this flap can be used as an alternative method for repairing the lateral alar defect. LEVEL OF EVIDENCE: Level -IV, therapeutic study.

Cardiomyocyte peroxisome proliferator-activated receptor α prevents septic cardiomyopathy via improving mitochondrial function.

Clinically, cardiac dysfunction is a key component of sepsis-induced multi-organ failure. Mitochondria are essential for cardiomyocyte homeostasis, as disruption of mitochondrial dynamics enhances mitophagy and apoptosis. However, therapies targeted to improve mitochondrial function in septic patients have not been explored. Transcriptomic data analysis revealed that the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the heart was the most significantly decreased in the cecal ligation puncture-treated mouse heart model, and PPARα was the most notably decreased among the three PPAR family members. Male Pparafl/fl (wild-type), cardiomyocyte-specific Ppara-deficient (PparaΔCM), and myeloid-specific Ppara-deficient (PparaΔMac) mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce endotoxic cardiac dysfunction. PPARα signaling was decreased in LPS-treated wild-type mouse hearts. To determine the cell type in which PPARα signaling was suppressed, the cell type-specific Ppara-null mice were examined. Cardiomyocyte- but not myeloid-specific Ppara deficiency resulted in exacerbated LPS-induced cardiac dysfunction. Ppara disruption in cardiomyocytes augmented mitochondrial dysfunction, as revealed by damaged mitochondria, lowered ATP contents, decreased mitochondrial complex activities, and increased DRP1/MFN1 protein levels. RNA sequencing results further showed that cardiomyocyte Ppara deficiency potentiated the impairment of fatty acid metabolism in LPS-treated heart tissue. Disruption of mitochondrial dynamics resulted in increased mitophagy and mitochondrial-dependent apoptosis in Ppara△CM mice. Moreover, mitochondrial dysfunction caused an increase of reactive oxygen species, leading to increased IL-6/STAT3/NF-κB signaling. 3-Methyladenine (3-MA, an autophagosome formation inhibitor) alleviated cardiomyocyte Ppara disruption-induced mitochondrial dysfunction and cardiomyopathy. Finally, pre-treatment with the PPARα agonist WY14643 lowered mitochondrial dysfunction-induced cardiomyopathy in hearts from LPS-treated mice. Thus, cardiomyocyte but not myeloid PPARα protects against septic cardiomyopathy by improving fatty acid metabolism and mitochondrial dysfunction, thus highlighting that cardiomyocyte PPARα may be a therapeutic target for the treatment of cardiac disease.

Molecular insight into the transformation of dissolved organic matter during sewage sludge composting: An investigation of a full-scale composting plant.

The aim of the study was to explore the molecular dynamics and transformation pathways of dissolved organic matter (DOM) in sewage sludge (SS) during composting, and the DOM of raw material, material experiencing thermophilic phase and material collected from humification phase were characterized using electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. The results indicated that there were approximately 85% of aliphatic/proteins and 75% of carbohydrate preferentially decomposed in the thermophilic phase. Moreover, lignins/carboxylic-rich alicyclic molecules (CRAM) were the main N-containing substances evolved in the decomposition, which leading to a reduction of N/C ratio from 0.073 to 0.041. Whereas aliphatic acids and tryptophan in lignins/CRAM with high oxidizing capacities are preferentially decomposed in the thermophilic phase. As for maturity phase, the carbon of the newly generated compounds (belonging to lignins/CRAM and tannins), possessed an oxidation state that similar to sulfonates and sulfonamides, and these DOM are beneficial for the humic substances formation. Moreover, it was found that the newly formed N2Ox and N3Ox compounds had a more significant contribution to the double bond equivalent (DBE) of the compost, corresponding to 1.0 and 1.7 DBE, respectively. The results would help explore the understanding of DOM transformation and humification during SS composting in the microscopic molecular level.

Targeting mitochondrial transcription factor A sensitizes pancreatic cancer cell to gemcitabine.

BACKGROUND: The survival of pancreatic cancer cells, particularly cancer stem cells which are responsible for tumor relapse, depends on mitochondrial function. Mitochondrial transcription factor A (TFAM) is critical for the regulation of mitochondrial DNA and thus mitochondrial function. However, the possible involvement of TFAM in pancreatic cancer is unknown. METHODS: Human samples were obtained from pancreatic cancers and their adjacent tissues; human pancreatic cell lines were cultured in RPMI1640 medium. TFAM expressions in pancreatic tissues and cultured cells were determined using immunohistochemistry, ELISA, and reverse transcription polymerase chain reaction (RT-PCR). The effect of TFAM on cell growth, migration, colony formation and apoptosis were evaluated. Mitochondrial biogenesis in pancreatic cancer and normal cells were examined. RESULTS: The majority of pancreatic cancer tissues exhibited higher TFAM expression compared to the adjacent counterparts. Consistently, TFAM mRNA and protein levels were higher in pancreatic cancer cell lines than in immortalized normal pancreatic epithelial cells. There was no difference on TFAM level between gemcitabine-sensitive and resistant pancreatic cancer cells. Functional analysis demonstrated that TFAM overexpression activated pancreatic normal and tumor cells whereas TFAM inhibition effectively inhibited the growth of pancreatic cancer cells. TFAM inhibition enhanced gemcitabine's cytotoxicity and suppressed growth, anchorage-independent colony formation and survival of gemcitabine-resistant pancreatic cancer cells. Mechanistic studies showed that TFAM inhibition resulted in remarkable mitochondrial dysfunction and energy crisis followed by oxidative stress. The basal mitochondrial biogenesis level correlated well with TFAM level in pancreatic cancer cells. CONCLUSIONS: TFAM played essential roles in pancreatic cancer via regulating mitochondrial functions which highlighted the therapeutic value of inhibiting TFAM to overcome gemcitabine resistance.

Quality evaluation of Hawk tea from different months and regions based on quantitative analysis of multiple components with a single marker (QAMS) combined with HPLC fingerprint.

BACKGROUND: Hawk tea, a medicinal and edible plant, has been consumed for thousands of years in Southwest China. To date, no unified food safety standard for Hawk tea has been established, and systematic research on the quality of Hawk tea is lacking. OBJECTIVE: The aim of this study was to develop a comprehensive evaluation method for the quality of Hawk tea based on inclusions content, high-performance liquid chromatography (HPLC) fingerprinting combined with the quantitative analysis of multiple components with a single marker (QAMS) method. METHODS: The contents of total flavonoids, total phenols, total polysaccharides, and total protein were determined using the colorimetric method. An effective comprehensive evaluation method was established to classify the 16 batches of samples based on HPLC fingerprint analysis combined with similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), partial least-squares discrimination analysis (PLS-DA), and the QAMS method. RESULTS: Flavonoids were the main chemical components of Hawk tea. The accuracy of the QAMS method was verified by comparing the calculated results with those of the external standard method (ESM). No significant differences were found between the two methods. Additionally, the fingerprint of Hawk tea was also established. CONCLUSION: The method established in this study can be used for the comprehensive quality evaluation of Hawk tea and can also provide a reference for the quality evaluation of other herbal medicines.

Nasal Tip and Alar Groove Plasty Through External Nasal Cutting in Asians: A Clinical Study.

OBJECTIVE: Nasal tip hypertrophy is common in Asians, and its reshaping is very critical in rhinoplasty. For patients who refuse any implant placed in the nose, there are limited options for tip reshaping. Herein, we introduce a new procedure of nasal tip and alar groove plasty through external nasal cutting in Asians. METHODS: A total of 20 patients who had hypertrophic nasal tip and refused to have any implants were included in this study. They were performed this procedure of nasal tip and alar groove plasty through external nasal cutting. The authors carefully reviewed the patients' medical records and preoperative and postoperative photographs. Self-reported satisfactions of patients with the scar morphology and correction effect were assessed at postoperative every follow-up using a questionnaire survey. RESULTS: All of the patients' procedures were completely successful, and the hypertrophic nasal tip was improved. In the long-term postoperative follow-up, the patients' wound showed no abnormalities such as scar contracture deformity, scar bumps, and nasal deformation. In 1 patient, the nasal wound developed significant scarring, and we performed reoperation to remove the superficial scar tissue. Surgical scars in the remaining patients were not obvious. Eight patients (8/20) reported "very satisfied" with scar shape and nasal tip shape improvement results, and 10 patients (10/20) reported "satisfied" with the outcomes. CONCLUSIONS: This procedure of nasal tip and alar groove plasty could be an alternative for making the nasal tip more refined. However, the surgical indications for this procedure need to be strictly limited to specific patients. LEVEL OF EVIDENCE: Level IV.

Complications and Treatments of Pseudomonas aeruginosa Infection After Rhinoplasty With Implants: A Clinical Study.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen, and because of its specificity, its treatments appear tricky in postrhinoplasty infections with internal implants. This study summarizes the clinical characteristics and treatment of this type of infections to provide some reference for clinical work. METHODS: We retrospectively analyzed 10 patients who were diagnosed with a nasal infection of P. aeruginosa after implant nasal augmentation. The results of the bacterial culture and drug sensitivity test of the patients' wound secretions were summarized and analyzed. We summarized the characteristics of the patients' infection and the treatments, and we also summarized the patients' prognosis. RESULTS: In these 10 cases, their implants included rib cartilage and ear cartilage alone, as well as their own cartilage combined with expanded polytetrafluoroethylene and silicone. All patients developed wound infections within 1 month after rhinoplasty, with bacterial cultures of P. aeruginosa . Prolonged use of sensitive antibiotics, as well as wound dressing changes, failed to keep the infection well under control. Patients whose implant was removed and thoroughly debrided within 1 week of infection did not experience any serious complications. In patients who were infected for >1 week before surgery to remove the implants, complications such as nasal column necrosis and nasal contracture occurred, and later the nasal repair was performed after multiple surgeries. CONCLUSIONS: For bacterial infections in postrhinoplasty wounds with implants, we recommend early bacterial culture. If the infection is clearly P. aeruginosa , the implant should be removed and thoroughly debrided as soon as possible to avoid serious complications. LEVEL OF EVIDENCE: Level IV.

External Z-plasty Technique for Correction of Alar Retraction in Asian Patients.

BACKGROUND: Current strategies for correcting alar retraction mainly include cartilage grafting and composite grafting, which are relatively complicated and may produce injury to the donor site. Herein, we introduce a simple and effective external Z-plasty technique for correcting alar retraction in Asian patients with poor skin malleability. METHODS: Twenty-three patients were presented with alar retraction and poor skin malleability, and they were very concerned about the shape of the nose. These patients undergoing external Z-plasty surgery were analyzed retrospectively. In this surgery, no grafts were needed, and the location of the Z-plasty was according to the highest point of the retracted alar rim. We reviewed the clinical medical notes and photographs. During the postoperative follow-up period, patients' reported satisfaction with aesthetic outcome were also evaluated. RESULTS: The alar retraction of all the patients was successfully corrected. The postoperative mean follow-up period was 8 months (range: 5-28 mo). No incidents of flap loss, recurrence of alar retraction, or nasal obstruction were observed during postoperative follow-up. Within postoperative 3-8 weeks, minor red scarring was visible at the operative incisions in most patients. However, these scars turned unobvious after postoperative 6 months. There were 15 cases (15/23) being very satisfied with the aesthetic outcome of this procedure. Seven patients (7/23) were satisfied with the effect and the invisible scar of this operation. Only one patient was dissatisfied with the scar, but she was satisfied with the correction effect of the retraction. CONCLUSION: This external Z-plasty technique can be an alternative method for correction of alar retraction with no need of cartilage grafting, and the scar can be unobvious with fine surgical suture. However, the indications should be limited in patients with severe alar retraction and poor skin malleability, who should not particularly care about the scars.

An Innovative Stent Consisting of Expanded Polytetrafluoroethylene and Ear Cartilage in Rhinoplasty For Asians: Application I of Dai's Exogenous Extension Stent Concept.

BACKGROUND: Restricted ventilation is common after rhinoplasty with an endogenous extension stent. The authors proposed an exogenous extension stent concept for Asian rhinoplasty patients to avoid this problem. Herein, we introduce an innovative stent in rhinoplasty for Asians, which is an application of this concept. METHODS: An L-shaped expanded polytetrafluoroethylene is hand-carved, and the long arm is placed at the nose back to improve the flatness of the nose, while the short arm supports the nasal column to raise the nose tip. The prosthesis does not occupy nasal volume and therefore theoretically does not affect nasal ventilation. The fan-shaped ear cartilage was placed at the nasal tip to prevent visualization of the nasal tip. The safety and effectiveness of this method were verified through 20 years of clinical practice. The difficulty of learning and popularizing the method was tested through the course of rhinoplasty among 22 plastic surgeons. RESULTS: After 20 years of clinical practice, it was found that this stent could not only effectively improve the nasal dorsum and tip morphology, but also did not actually affect the nasal volume and thus did not affect the nasal ventilation of patients. Among the trainees in plastic surgery, we found that it was not difficult to learn this method of rhinoplasty and the trainees could complete the prosthesis carving well after standardized training. CONCLUSION: This stent consisting of expanded polytetrafluoroethylene and ear cartilage is suitable in rhinoplasty for Asians with significant advantages, one of which is that it has no risk of resulting in restricted nasal ventilation. LEVEL OF EVIDENCE: Level IV.

ANKRD49 promotes the invasion and metastasis of lung adenocarcinoma via a P38/ATF-2 signalling pathway.

Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ2 test, Spearman correlation analysis, Kaplan-Meier, log-rank test, and Cox's proportional hazard model were used to analyse the clinical cases. The effect of ANKRD49 on the LUAD was investigated using CCK-8, clonal formation, would healing, transwell assays, and nude mice experiment. Expressions of ANKRD49 and its associated downstream protein molecules were verified by real-time PCR, Western blot, immunohistochemistry, and/or immunofluorescence analyses. ANKRD49 expression was highly elevated in LUAD. The survival rate and Cox's modelling analysis indicated that there may be an independent prognostic indicator for LUAD patients. We also found that ANKRD49 promoted the invasion and migration in both in in vitro and in vivo assays, through upregulating matrix metalloproteinase (MMP)-2 and MMP-9 activities via the P38/ATF-2 signalling pathway Our findings suggest that ANKRD49 is a latent biomarker for evaluating LUAD prognosis and promotes the metastasis of A549 cells via upregulation of MMP-2 and MMP-9 in a P38/ATF-2 pathway-dependent manner.

Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. METHODS: A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. CONCLUSIONS: In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA-MB-468 Cells by Altering Cell Energy Metabolism.

Triple-negative breast cancer (TNBC) is a serious health issue for women worldwide and there is still no suitable treatment option. AA005, a structurally simplified mimic of natural Annonaceous acetogenins, presents outstanding properties with impressive cytotoxicity and cell-type selective actions. The present study was aimed at evaluating the potential of AA005 as a therapeutic agent for TNBC. AA005 potently inhibited the growth of TNBC cells at 50 nM level. Inspired by the finding of the phosphatase and tensin homologue (PTEN) tumor suppressor, the effect of AA005 on aerobic glycolysis was investigated in TNBC MDA-MB-468 cells. A short-term AA005 exposure markedly suppressed mitochondrial function in MDA-MB-468 cells, thus activating the aerobic glycolysis to lessen the risk of decreased ATP generation in mitochondria. Prolonging the incubation time of AA005 clearly weakened the aerobic glycolysis in the cells. This was in part attributed to the PI3K-AKT pathway inactivation and subsequent declined glucose uptake. As a consequence, the energy supply was completely cut from the two major energy-producing pathways. Further experiments showed that AA005 resulted in irreversible damage on cell activity including cell cycle and growth, inducing mitochondrial oxidative stress and ultimately leading to cell death. In addition, the in vivo therapeutic efficacy of AA005 was proved on 4T1 xenograft tumor mice model. Our data demonstrate that AA005 exhibited a great potential for future clinical applications in TNBC therapy.