HMGB1 prefers to interact with structural RNAs and regulates rRNA methylation modification and translation in HeLa cells.

BACKGROUND: High-mobility group B1 (HMGB1) is both a DNA binding nuclear factor modulating transcription and a crucial cytokine that mediates the response to both infectious and noninfectious inflammation such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. HMGB1 has been proposed to control ribosome biogenesis, similar as the other members of a class of HMGB proteins. RESULTS: Here, we report that HMGB1 selectively promotes transcription of genes involved in the regulation of transcription, osteoclast differentiation and apoptotic process. Improved RNA immunoprecipitation by UV cross-linking and deep sequencing (iRIP-seq) experiment revealed that HMGB1 selectively bound to mRNAs functioning not only in signal transduction and gene expression, but also in axon guidance, focal adhesion, and extracellular matrix organization. Importantly, HMGB1-bound reads were strongly enriched in specific structured RNAs, including the domain II of 28S rRNA, H/ACA box snoRNAs including snoRNA63 and scaRNAs. RTL-P experiment showed that overexpression of HMGB1 led to a decreased methylation modification of 28S rRNA at position Am2388, Cm2409, and Gm2411. We further showed that HMGB1 overexpression increased ribosome RNA expression levels and enhanced protein synthesis. CONCLUSION: Taken together, our results support a model in which HMGB1 binds to multiple RNA species in human cancer cells, which could at least partially contribute to HMGB1-modulated rRNA modification, protein synthesis function of ribosomes, and differential gene expression including rRNA genes. These findings provide additional mechanistic clues to HMGB1 functions in cancers and cell differentiation.

Precise Construction of Nitrogen-Enriched Porous Ionic Polymers as Highly Efficient Sulfur Dioxide Adsorbent.

Porous ionic polymers with unique features have exhibited high performance in various applications. However, the fabrication of functional porous ionic polymers with custom functionality and porosity for efficient removal of low-concentration SO2 remains challenging. Herein, a novel nitrogen-enriched porous ionic polymer NH2Py-PIP is prepared featuring high-content nitrogen sites (15.9 wt.%), adequate ionic sites (1.22 mmol g-1), and a hierarchical porous structure. The proposed construction pathway relies on a tailored nitrogen-functionalized cross-linker NH2Py, which effectively introduces abundant functional sites and improves the porosity of porous ionic polymers. NH2Py-PIP with a well-engineered SO2-affinity environment achieves excellent SO2/CO2 selectivity (1165) and high SO2 adsorption capacity (1.13 mmol g-1 at 0.002 bar), as well as enables highly efficient and reversible dynamic separation performance. Modeling studies further elucidate that the nitrogen sites and bromide anions collaboratively promote preferential adsorption of SO2. The unique design in this work provides new insights into constructing functional porous ionic polymers for high-efficiency separations.

Flagellimonas halotolerans sp. nov., a novel bacterium isolated from the South China Sea.

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).

A Deep Learning Model for Accurate Diagnosis of Infection Using Antibody Repertoires.

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.

Predicting the therapeutic response to valproic acid in childhood absence epilepsy through electroencephalogram analysis using machine learning.

Childhood absence epilepsy (CAE) is a common type of idiopathic generalized epilepsy, manifesting as daily multiple absence seizures. Although seizures in most patients can be adequately controlled with first-line antiseizure medication (ASM), approximately 25 % of patients respond poorly to first-line ASM. In addition, an accurate method for predicting first-line medication responsiveness is lacking. We used the quantitative electroencephalogram (QEEG) features of patients with CAE along with machine learning to predict the therapeutic effects of valproic acid in this population. We enrolled 25 patients with CAE from multiple medical centers. Twelve patients who required additional medication for seizure control or who were shifted to another ASM and 13 patients who achieved seizure freedom with valproic acid within 6 months served as the nonresponder and responder groups. Using machine learning, we analyzed the interictal background EEG data without epileptiform discharge before ASM. The following features were analyzed: EEG frequency bands, Hjorth parameters, detrended fluctuation analysis, Higuchi fractal dimension, Lempel-Ziv complexity (LZC), Petrosian fractal dimension, and sample entropy (SE). We applied leave-one-out cross-validation with support vector machine, K-nearest neighbor (KNN), random forest, decision tree, Ada boost, and extreme gradient boosting, and we tested the performance of these models. The responders had significantly higher alpha band power and lower delta band power than the nonresponders. The Hjorth mobility, LZC, and SE values in the temporal, parietal, and occipital lobes were higher in the responders than in the nonresponders. Hjorth complexity was higher in the nonresponders than in the responders in almost all the brain regions, except for the leads FP1 and FP2. Using KNN classification with theta band power in the temporal lobe yielded optimal performance, with sensitivity of 92.31 %, specificity of 76.92 %, accuracy of 84.62 %, and area under the curve of 88.46 %.We used various EEG features along with machine learning to accurately predict whether patients with CAE would respond to valproic acid. Our method could provide valuable assistance for pediatric neurologists in selecting suitable ASM.

Brunonianines D-F, three new C19-diterpenoid alkaloids from the Delphinium brunonianum, with therapeutic effect on ovarian cancer in vitro and in vivo.

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.

Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet-Endothelium Interaction.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Liver transcriptomic and proteomic analyses provide new insight into the pathogenesis of liver fibrosis in mice.

BACKGROUND: Liver fibrosis (LF) is a kind of progressive liver injury reaction. The goal of this study was to achieve a more detailed understanding of the molecular changes in response to CCl4-induced LF through the identification of a differentially expressed liver transcriptomic and proteomic. RESULTS: A total of 1224 differentially expressed genes (DEGs) and 302 differentially expressed proteins (DEPs) were significantly identified at the transcriptomic and proteomic level, respectively, and 69 genes (hereafter "cor-DEGs-DEPs" genes) were detected at both levels. Pathway enrichment analysis showed that these cor-DEGs-DEPs genes were significantly enriched in 133 pathways. Importantly, among the cor-DEGs-DEPs genes, Gstm1, Gstm3, Ephx1 and Gstp1 were shown to be associated with metabolic pathways, and confirmed by RT-qPCR and parallel reaction monitoring (PRM) verification. CONCLUSIONS: Through the combined analysis of transcriptomic and proteomic data, this study provides valuable insights into the potential mechanism of the pathogenesis of LF, and lays a theoretical foundation for the further development of targeted therapy for LF.

LeGO-LOAM-FN: An Improved Simultaneous Localization and Mapping Method Fusing LeGO-LOAM, Faster_GICP and NDT in Complex Orchard Environments.

To solve the problem of cumulative errors when robots build maps in complex orchard environments due to their large scene size, similar features, and unstable motion, this study proposes a loopback registration algorithm based on the fusion of Faster Generalized Iterative Closest Point (Faster_GICP) and Normal Distributions Transform (NDT). First, the algorithm creates a K-Dimensional tree (KD-Tree) structure to eliminate the dynamic obstacle point clouds. Then, the method uses a two-step point filter to reduce the number of feature points of the current frame used for matching and the number of data used for optimization. It also calculates the matching degree of normal distribution probability by meshing the point cloud, and optimizes the precision registration using the Hessian matrix method. In the complex orchard environment with multiple loopback events, the root mean square error and standard deviation of the trajectory of the LeGO-LOAM-FN algorithm are 0.45 m and 0.26 m which are 67% and 73% higher than those of the loopback registration algorithm in the Lightweight and Ground-Optimized LiDAR Odometry and Mapping on Variable Terrain (LeGO-LOAM), respectively. The study proves that this method effectively reduces the influence of the cumulative error, and provides technical support for intelligent operation in the orchard environment.

Diabetes mellitus and hearing loss.

Diabetes mellitus (DM) is a major disease threatening human health and its incidence is increasing year on year. As a chronic complication of DM, hearing loss mostly occurs undetectably. However, the mechanism of this diabetes-related hearing loss (DRHL) remains unclear and there is no effective clinical treatment. Studies of animal or human pathology show that DM causes damage to the blood vessels, spiral ganglion neurons, afferent nerve fibers, the organ of Corti, and the stria vascularis of the inner ear. In recent years, more advances in pathological research have revealed the possible mechanism of DRHL. In addition, a large number of clinical studies suggest that the duration and severity of DM are closely related to the incidence and severity of DRHL. This review focuses on the relationship between DM and hearing loss. The clinical audiological characteristics of diabetic patients, risk factors for DRHL, typical pathology, and potential interventions of DRHL are summarized. This will help reveal the pathogenesis and intervention approaches for DRHL.

Flexible rotation of linear polarization conversion with a frequency selective surface.

A high-efficiency transmitted polarization converter based on a frequency selective surface (FSS) is proposed in this paper. The FSS-based polarization converter (FSS-PC) is designed based on receiving-via-transmitting (RVT) structure. The receiving and transmitting antenna structures are interconnected by the transmission line, designed in the form of metallized via holes. For any linearly polarized (LP) electromagnetic wave, our proposed FSS-PC has the capability to convert it into another LP electromagnetic wave. This converted wave will have a counterclockwise rotation angle of 2φ relative to the incident wave at 11 GHz. This is achieved by adjusting the relative azimuth φ between the polarization plane of the incident LP wave's electric field and the converter. Meanwhile, the FSS-PC can achieve exceptionally high polarization conversion above -0.30 dB at the central frequency of 11 GHz. Furthermore, as the azimuth of the incident electric field varies, this high-efficiency polarization conversion capability remains stable. The prototype has been fabricated and measured, and the measured results agree well with the simulated ones, thus confirming the effectiveness of the proposed design.

Effect of LGR4/EGFR signaling on cell growth and cancer stem cell-like characteristics in liver cancer.

PURPOSE: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Leucine-rich repeat containing G-protein-coupled receptors 4 (LGR4) participates in tumor progression, invasion, and metastasis. Our study aimed to investigate the effect of LGR4 with epidermal growth factor receptor (EGFR) in HCC cells. METHODS: We employed Hep3B and Huh7 cells to conduct our research. Comprehensive biological activities were characterized by CCK8 and transwell assay. Molecular biology techniques were used to determine the expression of proteins. Hep3B was employed to conduct subcutaneous tumor in mice. The tumor growth and the expression levels of proteins were assessed. RESULTS: LGR4 overexpression could promote the cells proliferation, migration, and invasion ability, while siLGR4 and siEGFR could inhibit cells biological activities. In addition, LGR4 overexpression promoted the expression levels of RSPO2, ß-catenin, EGFR and cancer stem cells (CSCs) markers, whereas silence of LGR4 or EGFR could diminish the expression levels of ß-catenin and CSCs markers. Furthermore, knockdown of LGR4 or EGFR also inhibited tumor growth and reduced the expression levels of RSPO2, CD133, CD44, Nanog, ß-catenin in vivo. CONCLUSION: Our data suggest that LGR4 /EGFR signaling in HCC leads to induce tumor growth, which then contributes to stem cell characteristics. It maybe a new perspective for the targeted therapy of HCC treatment.

Cereibacter flavus sp. nov., a novel member of the family Rhodobacteraceae isolated from seawater of the South China Sea and reclassification of Rhodobacter alkalitolerans as Cereibacter alkalitolerans comb. nov.

A Gram-stain-negative, aerobic, motile, ovoid-shaped and yellow-coloured strain, designated SYSU M79828T, was isolated from seawater collected from the South China Sea. Growth of this strain was observed at 4-37 °C (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-6% NaCl (optimum, 3.0 %, w/v). The respiratory quinone was found to be Q-10. Major fatty acid constituents were C18 : 1 ω7c/C18 : 1 ω6c, C18 : 1 ω7c11-methyl and C18 : 0 (>5 % of total). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphoglycolipid, two unidentified phospholipid, one unidentified lipid and an unidentified glycolipid. The genomic DNA G+C content was 64.5 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M79828T belonged to the genus Cereibacter and had the highest sequences similarity to 'Rhodobacter xinxiangensis' TJ48T (98.41 %). Based on 16S rRNA gene phylogeny, physiological and chemotaxonomic characterizations, we consider that strain SYSU M79828T represents a novel species of the genus Cereibacter, for which the name Cereibacter flavus sp. nov. is proposed. The type strain is SYSU M79828T (=GDMCC 1.3803T=KCTC 92893T). In addition, according to the results of phylogenetic analysis and similar taxonomic characteristics, we propose that Rhodobacter alkalitolerans should be reclassified as Cereibacter alkalitolerans comb. nov.

LncRNA HOTAIR promotes α-synuclein aggregation and apoptosis of SH-SY5Y cells by regulating miR-221-3p in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease. Here, the purpose of the study was to explore the function of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in PD and its underlying mechanism. An in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mouse model of PD was generated and the SH-SY5Y cells were treated with MPP + to induce neuronal damage in vitro. Quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot were used to detect the expression of HOTAIR, miR-221-3p, α-synuclein and apoptosis-related genes. MTT, flow cytometry and TUNEL assay was used to detect cell viability and apoptosis, respectively. The levels of inflammatory cytokines TNF-α,IL-1ß and IL-6 were detected by ELISA assay. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and superoxide dismutase (SOD) were determined using the appropriate assay kits. The interactions between miR-221-3p and HOTAIR or α-synuclein were determined by dual luciferase assay and RNA binding protein immunoprecipitation (RIP). Co-localization of HOTAIR and miR-221-3p was also proved by immunofluorescence staining. The results showed that HOTAIR was highly expressed, while miR-221-3p expression was decreased in PD model in vivo and in vitro. In SH-SY5Y cells treated with MPP+, the knockdown of HOTAIR increased cell viability and reduced cell apoptosis, the secretion of inflammatory cytokines and oxidative stress reaction, while HOTAIR overexpression led to opposite effects. Furthermore, HOTAIR sponged miR-221-3p which directly targeted α-synuclein and thus regulated the expression of α-synuclein. Meanwhile, inhibiting miR-221-3p could partially reverse the neuroprotective effects of HOTAIR knockdown. In conclusion, HOTAIR attenuated the injury of SH-SY5Y cells induced by MPP+ via miR-221-3p/α-synuclein axis, suggesting the potential therapeutic value of HOTAIR in PD.

Risk factors for intraoperative hemorrhage of Type I neurofibromatosis.

INTRODUCTION: Neurofibromatosis (NF) is an inherited disease and a benign tumor originating from nerve sheath cells. Neurofibromatosis type I (NF1) is the most common type, and most cases are characterized by neurofibromas. Neurofibromas in NF1 are mainly treated by surgery. Our study explores the risk factors for intraoperative hemorrhage in Type I neurofibromatosis patients who underwent neurofibroma resection. METHODS: A cross-sectional comparison of the patients who had undergone resection of neurofibroma for NF1. Data regarding patient characteristics and data about operative outcomes were recorded. The definition of intraoperative hemorrhage group was the intraoperative blood loss greater than 200 ml. RESULTS: Of 94 eligible patients, 44 patients were in the hemorrhage group and 50 patients were in the non-hemorrhage group. Multiple logistic regression analysis demonstrated that the area of excision, classification, surgical site, primary surgical, and organ deformation were significant independent predictors of hemorrhage. CONCLUSION: Early treatment can reduce the tumor cross-sectional area, avoid organ deformation, and reduce intraoperative blood loss. For plexiform neurofibroma or neurofibroma of the head and face, the amount of blood loss should be predicted correctly, and preoperative evaluation and blood preparation should be paid more attention to.

Expansion Technique for Reconstruction of Craniofacial Defect after Plexiform Neurofibroma Excision.

Reconstruction of large craniofacial defect after plexiform neurofibroma excision poses a continuous challenge for plastic surgeons, on account of characteristics of plexiform neurofibroma and patients' aesthetic requirements. Skin graft or free flap is hard to obtain satisfactory results or may pose technical challenges. In an attempt to provide the coverage with 'like tissue', we chose local tissue expansion technique. The expansion period was about an average of 3.4 months. We performed 19 expanded flaps located in the head, face, neck, forearm and superclavical regions to reconstruct the craniofacial defect and achieved satisfactory results. Preoperative endovascular embolism in some cases and several intraoperative hemostatic methods for all cases were undertaken to control the perioperative bleeding. For patients who request aesthetic results and are allowed two-staged operations, our method is viable.

Blood Supply of the Temporal Flap Pedicled With Orbicularis Oculi Muscle: Anatomy and Its Clinical Implications.

BACKGROUND: Traumatic injury or tumor resection can lead to eyelid defects, nasal defects, and cheek defects. The temporal flap pedicled with orbicularis oculi muscle (OOM) can be used to repair these defects. This cadaver-based anatomic study aimed to evaluate the blood supply of this flap and investigate its clinical implications. METHODS: Twenty hemifaces from 10 cadavers were used in this study. The number of arteries supplying OOM of the flap, the diameter of the artery entering OOM, and the maximum width of OOM were recorded. All data were presented as mean±SD values and analyzed using Student t -test. A P value<0.05 was considered statistically significant. RESULTS: Of these 10 specimens, 7 were males and 3 were females. The average age was 67.7 years (range, 53-78 y). The number of arteries supplying OOM was 8.5±1.4 in the male and 7.8±1.2 in the female. The diameter of the zygomatico-orbital artery was detected as 0.53±0.06 mm in the male and 0.40±0.11 mm in the female. The maximum width of OOM was detected as 2.5±0.1 cm in the male and 2.2±0.1 cm in the female. Males had significantly larger average values than females in the diameter of zygomatico-orbital artery and maximum width of OOM ( P =0.012, P <0.001, respectively). However, the number of arteries supplying OOM did not differ significantly between sex ( P =0.322). CONCLUSIONS: We conclude that the blood supply of the temporal flap pedicled with OOM is abundant and reliable. The findings provide surgeons with valuable anatomic knowledge for repairing facial defects with this flap.

Small-Incisional Techniques for Double-Eyelid Blepharoplasty: A Systematic Review.

BACKGROUND: Small-incisional double-eyelid surgery has increasingly gained popularity. In the published studies, the number of incisions, the debulking method, and the pretarsal fixation differ significantly among studies. Hence, this article was conducted to summarize the different techniques and compare their surgical results and complications. METHODS: The literature review was conducted using the PubMed and Cochrane databases from their inception to June 1, 2022. Clinical studies of small-incisional blepharoplasty with available full-text and extractable data were included and were grouped depending on the number of incisions. The number, length and location of the incisions, debulking method, fixation technique, and skin closure were concluded. The complications were statistically analyzed and compared. RESULTS: Finally, 13 articles and 4177 patients were eligible for reviewing, among which 5 studies (2460 patients) described single-incisional technique, 2 studies (645 patients) described two-incisional technique, 5 studies (700 patients) described three-incisional technique, and 1 study (372 patients) described four-incisional technique. Through the small incisions, the pretarsal soft tissue can be removed as appropriate, and the pretarsal fixation can be firm and exact. Both the single- and three-incisional studies had a pooled total complication rate of 5% and a pooled foldloss rate of 2%. No significant difference was found between groups. CONCLUSIONS: The small-incisional techniques offer a simple, safe, and reproducible approach to double-eyelids. It reduces post-op recovery time and allows a tenacious fixation. The fold-loss rate and other complication rate are acceptable when compared with the non-incisional and full-incisional techniques. 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.

The Dual Roles of Triiodothyronine in Regulating the Morphology of Hair Cells and Supporting Cells during Critical Periods of Mouse Cochlear Development.

Clinically, thyroid-related diseases such as endemic iodine deficiency and congenital hypothyroidism are associated with hearing loss, suggesting that thyroid hormones are essential for the development of normal hearing. Triiodothyronine (T3) is the main active form of thyroid hormone and its effect on the remodeling of the organ of Corti remain unclear. This study aims to explore the effect and mechanism of T3 on the remodeling of the organ of Corti and supporting cells development during early development. In this study, mice treated with T3 at postnatal (P) day 0 or P1 showed severe hearing loss with disordered stereocilia of the outer hair cells (OHCs) and impaired function of mechanoelectrical transduction of OHCs. In addition, we found that treatment with T3 at P0 or P1 resulted in the overproduction of Deiter-like cells. Compared with the control group, the transcription levels of Sox2 and notch pathway-related genes in the cochlea of the T3 group were significantly downregulated. Furthermore, Sox2-haploinsufficient mice treated with T3 not only showed excess numbers of Deiter-like cells but also a large number of ectopic outer pillar cells (OPCs). Our study provides new evidence for the dual roles of T3 in regulating both hair cells and supporting cell development, suggesting that it is possible to increase the reserve of supporting cells.

Acid/Base-Steered Cascade Cyclization: An Efficient One-Pot Access to Diverse Isobenzofuranone and Isoindolobenzoxazinone Derivatives.

We herein report the acid/base-steered two distinct reaction pathways of 2-acylbenzoic acids with isatoic anhydrides. In the presence of Na2CO3, the cascade process consists of the cyclization of 2-acetylbenzoic acid and nucleophilic ring-opening reaction of isatoic anhydride to furnish isobenzofuranone derivatives with high efficiency. However, p-toluenesulfonic acid can promote the product isobenzofuranones to undergo sequential intramolecular rearrangment, nucleophilic addition and cyclization reaction to produce diverse isoindolobenzoxazinones in good yields. The synthetic utility of this method was further demonstrated by the gram-scale preparation of the desired products and the facile transformations of the resulting products.