Regulating Catalytic Oxidation Enantiomers Behavior by Imparting Chiral Microenvironment in Zr-Based Metal-Organic Frameworks.

Chiral inversions of enantiomers have significantly different biological activities, so it is important to develop simple and effective methods to efficiently identify optically pure compounds. Inspired by enzyme catalysis, the construction of chiral microenvironments resembling enzyme pockets in the pore space structure of metal-organic frameworks (MOFs) to achieve asymmetric enantioselective recognition and catalysis has become a new research hotspot. Here, a super-stable porphyrin-containing material PCN-224 is constructed by solvothermal method and a chiral microenvironment around the existing catalytic site of the material is created by post-synthesis modifications of the histidine (His) enantiomers. Experimental and theoretical calculations results show that the modulation of chiral ligands around Zr oxide clusters produces different spatial site resistances, which can greatly affect the adsorption and catalytic level of the enantiomeric molecules of tryptophan guests, resulting in a good enantioselective property of the material. It provides new ideas and possibilities for future chiral recognition and asymmetric catalysis.

Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis.

Ischemic stroke is one of the most vital causes of high neurological morbidity and mortality in the world. Preconditioning exercise is considered as the primary prevention of stroke to resistance to subsequent injury. We tried to research the underlying biological mechanisms of this exercise. Forty-two SD rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO) group, exercise group with MCAO (EX + MCAO) group, and sham group, with 14 rats in each group. The EX + MCAO group underwent exercise preconditioning for 3 weeks before occlusion, and the other two groups were fed and exercised normally. After 3 weeks, MCAO model was made by thread plug method in the EX + MCAO group and MCAO group. After successful modeling, the Longa scale was used to evaluate the neurological impairment of rats at day 0, day 1, and day 2. The rats in each group were killed on the third day after modeling. TTC staining measured the infarct volume of each group. The morphology and apoptosis of cortical cells were observed by HE and Tunel staining. Three rats in each group underwent high-throughput sequencing. Bioinformatic analysis was used to find the deferentially expressed genes (DEGs) and predict the transcription factor binding sites (TFBS) of the next-generation sequencing results. Gene enrichment (GSEA) was used to analyze potential functional genes and their corresponding signaling pathways. The Longa scale showed EX + MCAO group had the neurological function better than the modeling group (P < 0.001). TTC staining showed that the infarct size of EX + MCAO group was less than MCAO group (P < 0.05). HE and Tunel staining showed that the cells in the EX + MCAO group and the sham group had normal morphology and fewer apoptotic cells than MCAO group. A new gene named 7994 was discovered and TFBS of this gene was predicted, which could interact with key genes such as Foxd3, Foxa2, NR4A2, SP1, CEBPA, and SOX10. GSEA showed that EX + MCAO group could promote and regulate angiogenesis and apoptosis through PI3K-AKT pathway. Preconditioning exercise could improve nerve function and reduce infarct size in rats. The underlying mechanism is to regulate the PI3K-AKT pathway through several key genes, promote cerebral angiogenesis, and reduce apoptosis.

The STAT3 inhibitor stattic overcome bortezomib-resistance in multiple myeloma via decreasing PSMB6.

Bortezomib, an FDA approved drug in 2003 for newly diagnosed and relapsed/refractory MM, had showed great efficacy in different clinical settings. However, many patients still developed resistance to Bortezomib, and the mechanism of action remains unelucidated. Here, we showed that Bortezomib resistance can be partially overcome by targeting a different subunit of 20 S complex - PSMB6. PSMB6 knock down by shRNA increased sensitivity to Bortezomib in resistant and sensitive cell line. Interestingly, a STAT3 inhibitor, Stattic, is shown to selectively inhibit PSMB6 and induce apoptosis in Bortezomib resistant and sensitive MM cells, even with IL-6 induction. Therefore, PSMB6 is a novel target for Bortezomib resistance and Stattic may offer a potential therapeutic strategy.

Two-component system LiaSR negatively regulated the acid resistance and pathogenicity of Listeria monocytogenes 10403S.

The glutamate decarboxylase (GAD) system is one of the acid-resistant systems of Listeria monocytogenes (L. monocytogenes), while the regulatory mechanism of GadT2/GadD2, which plays the major role in the GAD system for acid resistance, is not clear. The two-component system (TCS) is a signal transduction system that is also involved in regulating acid resistance in bacteria. By screening the TCSs of L. monocytogenes 10403S, we found that knocking out the TCS LisSR (encoded by lmo1021/lmo1022) led to a significant increase in the transcription and expression of the gadT2/gadD2 cluster. Subsequently, we constructed a complemental strain CΔliaSR. and a complemental strain with LiaS His157 to Ala, which was designated as CΔliaSRH157A. Survival assay, transcriptional and expression analysis and pathogenicity assay revealed that liaSR deletion significantly enhanced the acid resistance and pathogenicity of 10403S and significantly increased the gadT2/gadD2 transcription and expression. Mutating LiaS His157 to Ala significantly enhanced the acid resistance and pathogenicity of CΔliaSR and significantly increased the gadT2/gadD2 transcription and expression. The results suggest that the two-component system LiaSR mediates the acid resistance and pathogenicity in 10403S by inhibiting the gadT2/gadD2 cluster, and the key activation site of LiaS is His157. This study provides novel knowledge on the regulation of GAD system and the control of this foodborne pathogen.

Latent class analysis of the sleep quality of night shift nurses and impact of shift-related factors on the occupational stress and anxiety.

AIMS: The objective of this study is to explore the various latent categories within the sleep quality of night shift nurses and to investigate whether shift-related factors predispose nurses to higher levels of occupational stress and anxiety. DESIGN: This is a cross-sectional study. METHODS: From November to December 2020, registered nurses from 18 tertiary hospitals and 16 secondary hospitals in Chongqing were selected through convenience sampling for this study. Latent class analysis was used to investigate the sleep quality of nurses working night shifts. Furthermore, univariate analysis and logistic multivariate analysis were utilized to identify the contributing factors to occupational stress and anxiety. RESULTS: The four latent categories of Pittsburgh Sleep Quality Index for night shift nurses were identified as 'Low Sleep Disorder Group' (56.34%), 'Moderate Sleep Disorder Group' (37.27%), 'High Sleep Disorder Non-Reliant on Sleeping medication Group' (4.89%) and 'High Sleep Disorder Reliant on Sleeping medication Group' (1.50%). The results showed that having a night-shift frequency of 3-4 times per month, night-shift durations of 9-12 h, sleep time delay after night shift (≥2 h), total sleep time after night shift less than 4 h were shift-related factors that increased the levels of occupational stress and anxiety. CONCLUSION: The sleep quality of night shift nurses demonstrates heterogeneity and can be classified into four latent categories. Higher frequency of night shifts, extended work hours and insufficient rest time are all associated with increased levels of occupational stress and anxiety. IMPACT: By identifying the four latent categories of sleep quality among night shift nurses, this study sheds light on the relationship between sleep patterns and levels of occupational stress and anxiety. These findings have important implications for healthcare institutions in the management of nurse well-being and work schedules. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Defect-engineered chiral metal-organic frameworks.

Chirality has an important impact on chemical and biological research, as most active substances are chiral. In recent decades, metal-organic frameworks (MOFs), which are assembled from metal ions or clusters and organic linkers via metal-ligand bonding, have attracted considerable scientific interest due to their high crystallinity, exceptional porosity and tunable pore sizes, high modularity, and diverse functionalities. Since the discovery of the first functional chiral metal-organic frameworks (CMOFs), CMOFs have been involved in a variety of disciplines such as chemistry, physics, optics, medicine, and pharmacology. The introduction of defect engineering theory into CMOFs allows the construction of a class of defective CMOFs with high hydrothermal stability and multi-stage pore structure. The introduction of defects not only increases the active sites but also enlarges the pore sizes of the materials, which improves chiral recognition, separation, and catalytic reactions, and has been widely investigated in various fields. This review describes the design and synthesis of various defective CMOFs, their characterization, and applications. Finally, the development of the materials is summarized, and an outlook is given. This review should provide researchers with an insight into the design and study of complex defective CMOFs.

Fabrication strategies for chiral self-assembly surface.

Chiral self-assembly is the spontaneous organization of individual building blocks from chiral (bio)molecules to macroscopic objects into ordered superstructures. Chiral self-assembly is ubiquitous in nature, such as DNA and proteins, which formed the foundation of biological structures. In addition to chiral (bio) molecules, chiral ordered superstructures constructed by self-assembly have also attracted much attention. Chiral self-assembly usually refers to the process of forming chiral aggregates in an ordered arrangement under various non-covalent bonding such as H-bond, π-π interactions, van der Waals forces (dipole-dipole, electrostatic effects, etc.), and hydrophobic interactions. Chiral assembly involves the spontaneous process, which followed the minimum energy rule. It is essentially an intermolecular interaction force. Self-assembled chiral materials based on chiral recognition in electrochemistry, chiral catalysis, optical sensing, chiral separation, etc. have a broad application potential with the research development of chiral materials in recent years.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Transcriptional networks orchestrating red and pink testa color in peanut.

BACKGROUND: Testa color is an important trait of peanut (Arachis hypogaea L.) which is closely related with the nutritional and commercial value. Pink and red are main color of peanut testa. However, the genetic mechanism of testa color regulation in peanut is not fully understood. To elucidate a clear picture of peanut testa regulatory model, samples of pink cultivar (Y9102), red cultivar (ZH12), and two RNA pools (bulk red and bulk pink) constructed from F4 lines of Y9102 x ZH12 were compared through a bulk RNA-seq approach. RESULTS: A total of 2992 differential expressed genes (DEGs) were identified among which 317 and 1334 were up-regulated and 225 and 1116 were down-regulated in the bulk red-vs-bulk pink RNA pools and Y9102-vs-ZH12, respectively. KEGG analysis indicates that these genes were divided into significantly enriched metabolic pathways including phenylpropanoid, flavonoid/anthocyanin, isoflavonoid and lignin biosynthetic pathways. Notably, the expression of the anthocyanin upstream regulatory genes PAL, CHS, and CHI was upregulated in pink and red testa peanuts, indicating that their regulation may occur before to the advent of testa pigmentation. However, the differential expression of down-stream regulatory genes including F3H, DFR, and ANS revealed that deepening of testa color not only depends on their gene expression bias, but also linked with FLS inhibition. In addition, the down-regulation of HCT, IFS, HID, 7-IOMT, and I2'H genes provided an alternative mechanism for promoting anthocyanin accumulation via perturbation of lignin and isoflavone pathways. Furthermore, the co-expression module of MYB, bHLH, and WRKY transcription factors also suggested a fascinating transcriptional activation complex, where MYB-bHLH could utilize WRKY as a co-option during the testa color regulation by augmenting anthocyanin biosynthesis in peanut. CONCLUSIONS: These findings reveal candidate functional genes and potential strategies for the manipulation of anthocyanin biosynthesis to improve peanut varieties with desirable testa color.

Asynchronous measurement-device-independent quantum key distribution with hybrid source.

The linear constraint of secret key rate capacity is overcome by the twin-field quantum key distribution (QKD). However, the complex phase-locking and phase-tracking technique requirements throttle the real-life applications of the twin-field protocol. The asynchronous measurement-device-independent (AMDI) QKD, also called the mode-pairing QKD, protocol can relax the technical requirements and keep the similar performance of the twin-field protocol. Here, we propose an AMDI-QKD protocol with a nonclassical light source by changing the phase-randomized weak coherent state to a phase-randomized coherent-state superposition in the signal state time window. Simulation results show that our proposed hybrid source protocol significantly enhances the key rate of the AMDI-QKD protocol, while exhibiting robustness to imperfect modulation of nonclassical light sources.

All-photonic quantum repeater for multipartite entanglement generation.

Quantum network applications such as distributed quantum computing and quantum secret sharing represent a promising future network equipped with quantum resources. Entanglement generation and distribution over long distances are critical and unavoidable when utilizing quantum technology in a fully connected network. The distribution of bipartite entanglement over long distances has seen some progress, while the distribution of multipartite entanglement over long distances remains unsolved. Here we report a two-dimensional quantum repeater protocol for the generation of multipartite entanglement over long distances with an all-photonic framework to fill this gap. The entanglement generation yield remains proportional to the transmission efficiency regardless of the number of network users and shows long transmission distance under various numbers of network users. With the improved efficiency and flexibility of extending the number of users, we anticipate that our protocol can work as a significant building block for quantum networks in the future.

Experimental Quantum Communication Overcomes the Rate-Loss Limit without Global Phase Tracking.

Secure key rate (SKR) of point-point quantum key distribution (QKD) is fundamentally bounded by the rate-loss limit. Recent breakthrough of twin-field (TF) QKD can overcome this limit and enables long distance quantum communication, but its implementation necessitates complex global phase tracking and requires strong phase references that not only add to noise but also reduce the duty cycle for quantum transmission. Here, we resolve these shortcomings, and importantly achieve even higher SKRs than TF-QKD, via implementing an innovative but simpler measurement-device-independent QKD that realizes repeaterlike communication through asynchronous coincidence pairing. Over 413 and 508 km optical fibers, we achieve finite-size SKRs of 590.61 and 42.64 bit/s, which are respectively 1.80 and 4.08 times of their corresponding absolute rate limits. Significantly, the SKR at 306 km exceeds 5 kbit/s and meets the bitrate requirement for live one-time-pad encryption of voice communication. Our work will bring forward economical and efficient intercity quantum-secure networks.

Neuroprotective Roles of Apelin-13 in Neurological Diseases.

Apelin is a natural ligand for the G protein-coupled receptor APJ, and the apelin/APJ system is widely distributed in vivo. Among the apelin family, apelin-13 is the major apelin isoform in the central nervous system and cardiovascular system, and is involved in the regulation of various physiopathological mechanisms such as apoptosis, neuroinflammation, angiogenesis, and oxidative stress. Apelin is currently being extensively studied in the nervous system, and apelin-13 has been shown to be associated with the onset and progression of a variety of neurological disorders, including stroke, neurodegenerative diseases, epilepsy, spinal cord injury (SCI), and psychiatric diseases. This study summarizes the pathophysiological roles of apelin-13 in the development and progression of neurological related diseases.

Cryptogenic hepatocellular carcinoma: characteristics, outcome, and prognostic role of albumin-bilirubin (ALBI) grade vs easy ALBI grade.

BACKGROUND: The characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC) remain unclear. The albumin-bilirubin (ALBI) grade and its updated version, the easy ALBI (EZ-ALBI) grade, are important prognostic predictors for HCC. We aimed to investigate the long-term survival of patients with cryptogenic HCC and the prognostic role of ALBI and EZ-ALBI grade in these patients. METHODS: A prospective cohort of 2,937 HCC patients with viral or cryptogenic etiology were retrospectively analyzed. The multivariate Cox model was used to determine prognostic predictors. RESULTS: Cryptogenic HCC patients were often older and diabetic, had lower serum ɑ-fetoprotein (AFP) levels, larger tumor burden, poor performance status, advanced cancer stage, and received non-curative treatments compared with hepatitis B or C-related HCC. The Cox analysis showed that age > 65 years, serum AFP > 400 ng/mL, presence of vascular invasion or distant metastasis, presence of ascites, performance status 2-4, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatment, were independent predictors of decreased survival in cryptogenic HCC (p < .001). Significant survival differences were found across ALBI grade and EZ-ALBI grade in cryptogenic HCC and subgroup patients receiving curative or non-curative treatments. The Cancer of Liver Italian Program was the best staging system for patients with cryptogenic HCC. CONCLUSIONS: Patients with cryptogenic HCC have a larger tumor burden and advanced cancer stage at disease presentation compared with those with viral HCC. The ALBI and EZ-ALBI score are robust models to evaluate liver functional reserve for these patients independent of treatment modality.

Effective treatment of hydrogen boride sheets for long-term stabilization.

Two-dimensional hydrogen boride (HB) sheets prepared via the ion-exchange reaction from magnesium diboride (MgB2) are known to possess several intriguing properties for a wide range of applications; however, previous reports have shown that the sheets prepared using this method contain small amounts of reactive components, making them unsuitable for certain applications. Therefore, developing a method for preparing HB sheets that exhibit long-term stability and do not contain reactive species is essential. In this study, we developed an effective treatment method for achieving long-term stabilization of HB sheets. We found that by pre-treating the HB sheets with water and then filtering the dried product from an acetonitrile dispersion, we could achieve excellent long-term stability over nine months. This stability was maintained even outside of a glovebox, with no H2 released by the decomposition and/or reaction. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) absorption spectroscopy measurements revealed that the sample exhibited pure HB characteristics with negatively charged boron and B-H-B and terminal B-H bonds, even after nine months of storage. Furthermore, based on thermal desorption spectroscopy (TDS) measurements, the presence of reactive species in the as-prepared HB sheets is attributed to fluctuating B-H bonds with relatively weak binding energies that can be removed using the method developed in this study.

The Underappreciated Placebo Effects and Responses in Randomized Controlled Trials on Neck Pain: A Systematic Review With Meta-analysis.

OBJECTIVE: To quantify placebo effects and responses in randomized controlled trials (RCTs) on neck pain and explore how they would influence the treatment of neck pain. DATA SOURCES: We searched MEDLINE (PubMed), EMBASE (Ovid), CINAHL (EBSCO), Physiotherapy Evidence Database (PEDro), and World Health Organization International Clinical Trials Registry Platform from the inception of August 15, 2021, to identify relevant RCTs. STUDY SELECTION AND DATA EXTRACTION: The abstracts and full texts of potential studies were independently screened, and data extraction was also independently performed by 2 researchers. Scales of the score measuring neck pain and the scores both at baseline and the endpoint were extracted. DATA SYNTHESIS: A total of 60 RCTs were included. The mean improvement in the pain score after placebo treatment was 15.65 (mean difference [MD]=-15.65, 95% confidence interval; CI [-19.19, -12.12]; P<.05), which we defined as the placebo response. In the active groups, it was 25.91 (MD=-25.91, 95% CI [-29.15, -22.68]; P<.05), and in the no-treatment groups, it was 5.80 (MD=-5.80, 95% CI [13.28, 1.69]; P=.13). Using the 3 MDs from the 3 groups, the placebo effect was calculated to account for 38.0% of the pain score improvement in the active group. CONCLUSIONS: The pain scores of patients with neck pain were reduced after treatment with placebos, but the magnitude of pain score reduction was not clinically significant enough. The 38.0% amount of pain score reduction in patients treated with active interventions was caused by placebo. Interventions with considerable clinically significance for neck pain were still required.

GadR4 mediates the acid resistance and pathogenicity of Listeria monocytogenes 10403S by negatively regulating the gadT2/gadD2 cluster.

Listeria monocytogenes is an important foodborne pathogen that can survive under acidic conditions. The glutamate decarboxylase (GAD) system is one of the acid resistance systems of L. monocytogenes. It usually comprises two glutamate transporters (GadT1/T2) and three glutamate decarboxylases (GadD1/D2/D3). Among them, gadT2/gadD2 contributes most significantly to the acid resistance of L. monocytogenes. However, the regulation mechanisms of gadT2/gadD2 still remain unclear. The results of this study indicated that gadT2/gadD2 deletion significantly decreases the survival rate of L. monocytogenes under different acidic conditions, including brain and heart infusion (BHI) broth, with a pH of 2.5, 2% citric acid, 2% acetic acid and 2% lactic acid. Further, gadT2/gadD2 cluster was expressed in the representative strains in response to alkaline stress rather than acid stress. To explore the regulation of gadT2/gadD2, we knocked out the five transcriptional factors belonging to the Rgg family in L. monocytogenes 10403S. We found that the deletion of gadR4, which exhibits the highest homology with the gadR of Lactococcus lactis, resulted in a significant increase in the survival rate of L. monocytogenes upon acid stress. Western blot analysis showed that gadR4 deletion significantly increased the gadD2 expression of L. monocytogenes under alkaline and neutral conditions. Furthermore, the gfp reporter gene showed that gadR4 deletion significantly increased the expression of the gadT2/gadD2 cluster. Adhesion and invasion assays indicated that gadR4 deletion significantly increased the rates of adhesion and invasion of L. monocytogenes to epithelial Caco-2 cells. Virulence assays showed that gadR4 knockout significantly improved the colonization ability of L. monocytogenes in the livers and spleens of the infected mice. Taken together, our results showed that GadR4, a transcription factor belonging to the Rgg family, negatively regulates the gadT2/gadD2 cluster, thus, reducing the acid stress tolerance and pathogenicity of L. monocytogens 10403S. Our results provide a better understanding of the regulation of the GAD system of L. monocytogenes and a novel approach to potentially prevent and control listeriosis.

Sleep quality mediates the relationship between lower urinary tract symptoms and health-related quality of life in women with type-II diabetes.

AIM: To examine the mediating effect of sleep quality on the relationship between lower urinary tract symptoms and health-related quality of life in women with type-II diabetes. DESIGN: A cross-sectional study. METHODS: A study questionnaire comprising three valid instruments was used to obtain data about lower urinary tract symptoms, sleep quality and physical and mental component summary health-related quality of life between July 2017 and December 2018 (n = 343). Pearson's correlation coefficients were estimated initially to examine the relationships between the three variables. Multiple regression models were tested using a regression-based approach Hayes PROCESS macro for SPSS to examine the significance of proposed mediation effects. RESULTS: Most participants experienced at least one urinary symptom (n = 268, 78.1%). The total number of types of lower urinary tract symptoms experienced by participants was significantly inversely correlated with physical and mental component summary health-related quality of life, and sleep quality. Participants' sleep quality was significantly correlated with physical and mental component summary health-related quality of life. The relationships of lower urinary tract symptoms with physical and mental component summary health-related quality of life were, respectively, fully and partially mediated by sleep quality. CONCLUSION: Sleep quality played a mediating role on the relationship between lower urinary tract symptoms and health-related quality of life. Our findings could lead to improvements of diabetes care in nursing and healthcare practices. IMPACT: Understanding the role of sleep quality in the adverse effects of lower urinary tract symptoms on health-related quality of life contributes to the development and delivery of appropriate strategies to promote optimal health-related quality of life. We recommended including assessments of lower urinary tract symptoms, sleep and health-related quality of life in routine diabetes management. Nurses and healthcare professionals should concurrently reduce lower urinary tract symptoms and improve sleep to achieve this population's optimal health-related quality of life. PATIENTS OR PUBLIC CONTRIBUTION: We recruited a sample of older women with type-II diabetes at the endocrinology and metabolism outpatient departments of two hospitals. Study participants provided responses on the study questionnaires. The two hospitals provided needed supports (e.g., height/weight scales, suitable places for interview) during the data collection process.

Application of Auricular Cartilage-Skin Graft in the Reconstruction of Unilateral Cleft Lip Nasal Deformity.

BACKGROUND: Autologous cartilage grafts are increasingly used in the treatment of cleft lip nasal deformity, but nasal alar retraction caused by lining defects often occurs after surgery. We designed a new graft to treat unilateral cleft lip nasal deformity while avoiding nasal alar retraction. METHODS: Nineteen patients in our hospital underwent unilateral cleft lip nasal deformity repair surgery with an auricular cartilage-skin graft. The effect of surgery was evaluated in four aspects: satisfaction with postoperative appearance, nasal aesthetic subunit indices, position of the nasal alar rim and three-dimensional spatial difference. RESULTS: Overall satisfaction with each index was above 90%. The nasal tip angle and nasolabial angle of patients were significantly smaller after surgery than before surgery (P < 0.01). The height of the nostril on the affected side and the length of the nasal columella were greater after surgery than before surgery (P < 0.01). The spatial differences in soft tissue between the unaffected side and the affected side after surgery were significantly smaller than before surgery (P < 0.01). According to the follow-up results of 1-2 years, there were no significant retraction of the nasal alar rim (P > 0.05) and no obvious auricular deformity. All patients had a noticeable improvement in their nasal appearance. CONCLUSION: The auricular cartilage-skin graft, which can not only improve the appearance of the nose but also avoid nasal alar retraction, is an ideal graft to cure unilateral cleft lip nasal deformity. 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 .

RNA binding protein RPS3 mediates microglial polarization by activating NLRP3 inflammasome via SIRT1 in ischemic stroke.

BACKGROUND: Ischemic stroke is the obstruction of cerebral blood flow with a high morbidity. Microglial polarization is a contributing factor for ischemic stroke-induced injury. Here, we focused on function and mechanism of RNA binding protein RPS3 in microglial polarization after ischemic stroke. METHODS: Transient middle cerebral artery occlusion (tMCAO) was conducted in SD rats. Infarct area was detected by TTC staining and neurological score was assessed. Fluorescence staining tested neuronal apoptosis and microglial differentiation. Oxygen and glucose deprivation/reoxygenation (OGD/R) was applied for treating microglia. Levels of RPS3, SIRT1, M1 and M2 polarization markers (CD86, iNOS, CD206, Arg-1) were determined by RT-qPCR. Western blot detected RPS3, SIRT1, NLRP3, ASC and Cleaved-caspase-1 expression. RIP assay validated that RPS3 interacted with SIRT1. CCK-8 measured cell viability. Flow cytometry and ELISA assessed M1 and M2 polarization markers. LDH release was detected using colorimetric CytoTox 96 Cytotoxicity kit. RESULTS: RPS3 depletion improved neurological dysfunction and reduced infarction area in rats after tMCAO. Knockdown of RPS3 resulted in increased SIRT1 expression and decreased NLRP3 inflammasome activation, and induced microglia M2 polarization after ischemia-reperfusion (I/R). Besides, RPS3 directly targeted SIRT1 and reduced its expression in microglia. RPS3 silencing suppressed OGD/R-triggered neuronal and microglial cell death through SIRT1. Moreover, RPS3 activated NLRP3 inflammasome and regulated microglial polarization via SIRT1. CONCLUSION: RPS3 regulates microglial polarization and neuronal injury through SIRT1/NLRP3 pathway, suggesting a novel target for ischemic stroke treatment.