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The main challenge of fused deposition modeling (FDM) is the limited variety of commercially available semicrystalline polymer materials. Isotactic polypropylene (iPP), with a fast crystallization rate and high crystallinity, tends to undergo extensive volumetric shrinkage during the FDM process, further inducing severe deformation and poor dimensional accuracy in 3D‐printed parts. This study aims to develop desirable iPP‐based materials for the FDM technique through physically blending iPP and thermoplastic polyester elastomer (TPEE). TPEE retards the nonisothermal crystallization ability of iPP, as indicated by the significant decrease in crystallinity (Xc) from 47.7% for neat iPP to 28.5% for the iPP blend at a weight ratio of 30/70. The suppressed crystallization behavior accounts for a drastic decrease in the warpage degree of the 3D‐printed parts. The greater the content of TPEE is, the lower warpage the 3D‐printed parts have. Additionally, the presence of TPEE slightly influences the shear viscosity of iPP. As a result, iPP blends exhibit excellent extrudability during a typical FDM process. TPEE also enhances the impact strength of 3D‐printed parts by 168% compared to that of injection‐molded iPP. Taken together, the iPP blends developed in this work are promising FDM feedstock materials with good dimensional accuracy and excellent impact strength.

There are no effective pharmacological treatments for sarcopenia. We aim to identify potential therapeutic targets for sarcopenia by integrating various publicly available datasets. We integrated druggable genome data, cis‐eQTL/cis‐pQTL from human blood and skeletal muscle tissue, and GWAS summary data of sarcopenia‐related traits to analyse the potential causal relationships between drug target genes and sarcopenia using the Mendelian Randomization (MR) method. Sensitivity analyses and Bayesian colocalization were employed to validate the causal relationships. We also assessed the side effects or additional indications of the identified drug targets using a phenome‐wide MR (Phe‐MR) approach and investigated actionable drugs for target genes using available databases. MR analysis identified 17 druggable genes with potential causation to sarcopenia in human blood or skeletal muscle tissue. Six of them (HP, HLA‐DRA, MAP 3K3, MFGE8, COL15A1, and AURKA) were further confirmed by Bayesian colocalization (PPH4 > 90%). The up‐regulation of HP[higher ALM (beta: 0.012, 95% CI: 0.007–0.018, P= 1.2*10−5) and higher grip strength (OR: 0.96, 95% CI: 0.94–0.98, P= 4.2*10−5)], MAP 3K3[higher ALM (beta: 0.24, 95% CI: 0.21–0.26, P= 1.8*10−94), higher grip strength (OR: 0.82, 95% CI: 0.75–0.90, P= 2.1*10−5), and faster walking pace (beta: 0.03, 95% CI: 0.02–0.05, P= 8.5*10−6)], and MFGE8[higher ALM (muscle eQTL, beta: 0.09, 95% CI: 0.06–0.11, P= 6.1*10−13; blood pQTL, beta: 0.05, 95% CI: 0.03–0.07, P= 3.8*10−09)], as well as the down‐regulation of HLA‐DRA[lower ALM (beta: ‐0.09, 95% CI: −0.11 to −0.08, P= 5.4*10−36) and lower grip strength (OR: 1.13, 95% CI: 1.07–1.20, P= 1.8*10−5)] and COL15A1[higher ALM (muscle eQTL, beta: ‐0.07, 95% CI: −0.10 to −0.04, P= 3.4*10−07; blood pQTL, beta: ‐0.05, 95% CI: −0.06 to −0.03, P= 1.6*10−07)], decreased the risk of sarcopenia. AURKAin blood (beta: ‐0.16, 95% CI: −0.22 to −0.09, P= 2.1*10−06) and skeletal muscle (beta: 0.03, 95% CI: 0.02 to 0.05, P= 5.3*10−05) tissues showed an inverse relationship with sarcopenia risk. The Phe‐MR indicated that the six potential therapeutic targets for sarcopenia had no significant adverse effects. Drug repurposing analysis supported zinc supplementation and collagenase clostridium histolyticummight be potential therapeutics for sarcopenia by activating HPand inhibiting COL15A1, respectively. Our research indicated MAP 3K3, MFGE8, COL15A1, HP, and HLA‐DRAmay serve as promising targets for sarcopenia, while the effectiveness of zinc supplementation and collagenase clostridium histolyticumfor sarcopenia requires further validation.

Serious shrinkage and warpage are obstacles to the development of ideal isotactic polypropylene (iPP) materials for polymer‐based powder bed fusion (PBF) technique. In this work, the variations of the dimensional accuracy of the PBF‐printed iPP parts were investigated with various printing parameter and nucleating agent. The iPP parts printed at a scanning speed of 700 mm/s exhibit smaller extents of shrinkage and curling than those at lower speeds, due to a lower degree of crystallinity. Interestingly, iPP blended with the α‐ or β‐nucleating agent demonstrates more serious part deformation with respect to neat iPP. Especially, α‐nucleating agent tends to trigger the most severe curling under the investigated printing parameters. Based on X‐ray diffraction and differential scanning calorimetry (DSC) results, both neat iPP and α‐iPP parts crystallize into α‐crystal, while β‐iPP parts display the coexistence of β‐ and α‐crystals. And, the difference of the crystallinity is less than 3% in three specimens. This suggests that both crystallinity and crystalline structure are not the main reasons for the shrinkage and warpage in this case. Instead, the severe part deformation of the α‐iPP parts is assigned to the narrower sintering window as well as the higher onset crystallization temperature of α‐iPP, which hinder relaxation of residual stresses. This work provides insights into the part deformation mechanism for PBF‐processed polymer materials.

Objective: To explore whether the different phases of the nasal cycle have a significant effect on nasal temperature, the nasal mucosal clearance rate, and levels of nasal nitric oxide (nNO) and to investigate the correlation between these nasal conditions.Methods: The study participants were divided into 2 groups: the control group and the rhinitis group. The participants’ nasal temperature, cilia clearance rate, and nNO levels were measured during different phases of the nasal cycle (the congestion phase and decongestion phase) in the control group and before and after undergoing inferior turbinate ablation in the rhinitis group.Results: The temperature of the nasal cavity in the control group was significantly higher in the congestion phase than in the decongestion phase (P= .0025), while in the rhinitis group, the temperature of the nasal cavity decreased significantly after inferior turbinate ablation (P= .001). In the control group, the nasal mucosa clearance time was significantly shorter in the congestion phase than in the decongestion phase (P= .001), and in the rhinitis group, the clearance time of the nasal mucosa was significantly shortened after the operation (P= .0025). In the control group, the levels of nNO were significantly higher in the congestion phase than in the decongestion phase (P= .025), while in the rhinitis group, nNO levels decreased significantly after the operation (P= .005).Conclusion: The function of the nasal cavity changes in different phases of the nasal cycle. Therefore, when evaluating the impact of various factors on nasal function, factors associated with the nasal cycle should also be considered. Inferior turbinate plasma ablation can improve the ciliary function of the nasal mucosa, reduce the temperature of the nasal cavity, and reduce nNO levels.

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117Lvariant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.

A photoredox/copper-catalyzed cascade radical cyclization/phosphorothiolation reaction of N-allylbromoacetamides and P(O)SH compounds has been established. A broad range of novel nonfluorine- or difluoro-substituted 2-pyrrolidinones bearing the C(sp3)-SP(O)(OR)2moiety can be conveniently constructed in moderate to good yields under mild conditions. Importantly, most of the tested phosphorothiolated 2-pyrrolidinones showed potent inhibitory effects toward both AChE and BChE.

In recent years, the efficient and clean utilization of coal has been widely concerned by scholars at home and abroad. Despite the abundance of global coal resources, the deep utilization rate of coal is still insufficient. To address this challenge, it has been explored the development and preparation of coal-based high value-added carbonaceous materials. In the present study, a novel process was developed for the preparation of graphene using biphenyl sourced from low-rank coal. Using chemical vapor deposition (CVD) technology, it was successfully implemented for us to grow high-quality graphene on copper foils. The prepared graphene products were observed and characterized using Raman spectroscopy, optical microscopy and scanning electron microscopy techniques. The results of this research provide a new perspective for the utilization of low-rank coal resources.

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C15H16N2O6S, monoclinic, P21/n(no. 14), a= 11.1325(3) Å, b= 6.2088(2) Å, c= 23.8080(6) Å, β= 99.266(2)°, V= 1,624.12(8) Å3, Z= 4, Rgt(F) = 0.0431, wRref(F2) = 0.1271, T = 293(2) K.

C26H36N4O14Co, triclinic, P1̄ (no. 2), a= 7.1895(7) Å, b= 8.7773(9) Å, c= 10.9067(11) Å, α= 98.180(2)°, β= 104.0480(10)°, γ= 90.180(2)°, V= 660.37(11) Å3, Z= 1, Rgt(F) = 0.0287, wRref(F2) = 0.0751, T = 296.15 K.

Background: This study aimed to evaluate the long-term survival outcomes of esophagectomy with off-pump coronary artery bypass grafting (OPCABG) vs. esophagectomy alone. Methods: A total of 1798 patients who received esophagectomy between January 2010 and February 2020 were included and divided into the 38 patients who underwent OPCABG followed by esophagectomy (OP + ES group) and 1760 patients had only esophagectomy (ES group). Propensity score matching (PSM) and Cox multivariable analyses were performed to compare postoperative complications, disease-free survival (DFS), and overall survival (OS) between the two groups. Results: There were 37 patients in the OP + ES group matched with 74 in the ES group. The matched OP + ES group had higher total postoperative complications than the ES group, especially more pulmonary infections (P= 0.001) and arrhythmias (P= 0.018), but no other postoperative complications were the difference. The DFS was similar and the OS was a significant difference between the matching 2 groups (log-rank, P= 0.132 and 0.04, respectively). Although pT 3/4 stage, pN (+), and tumor length > 3.0 cm were independently associated with worse OS and DFS in multivariable analysis, CAD and EF < 55% were also found to be a predictive factor for OS and DFS in univariate analysis. Conclusion: OPCABG followed by esophagectomy for esophageal cancer associated with coronary artery disease has equivalent DFS and recurrence pattern to esophagectomy for esophageal cancer alone, but with a disadvantage in OS.

This article considers the consensus of a general class of second-order multiagent systems (MASs) with time delays, where the controller is of the common proportional and derivative (PD) type. All the delay and the controller gains are treated as free parameters in this article, and our objective is to develop a parameter-space approach that has not been reported in the literature. First, we adopt the complete stability analysis w.r.t. delay under a given PD controller for the corresponding characteristic equations. Next, we divide the controller parameter plane. For each divided region, the type concerning the consensus property can be qualitatively determined. Combining the above steps, we present a parameter-space approach. By using this approach, we can qualitatively as well as quantitatively identify all the consensus set in the whole space of delay plus controller parameters. Finally, the effectiveness and advantage will be clearly demonstrated by examples.

Biomarker discovery is essential for the understanding, diagnosis, targeted therapy and prognosis assessment of malignant diseases. However, it remains a huge challenge due to the lack of sensitive methods to identify disease-specific rare molecules. Here we present MORAC, molecular recognition based on affinity and catalysis, which enables the effective identification of candidate biomarkers with low abundance. MORAC relies on a class of DNAzymes, each cleaving a sole RNA linkage embedded in their DNA chain upon specifically sensing a complex system with no prior knowledge of the system’s molecular content. We show that signal amplification from catalysis ensures the DNAzymes high sensitivity (for target probing); meanwhile, a simple RNA-to-DNA mutation can shut down their RNA cleavage ability and turn them into a pure affinity tool (for target pulldown). Using MORAC, we identify previously unknown, low-abundance candidate biomarkers with clear clinical value, including apolipoprotein L6 in breast cancer and seryl-tRNA synthetase 1 in polyps preceding colon cancer.

The high crystallinity and fast crystallization rate of polypropylene (PP) often result in severe warpage of final parts prepared by means of material extrusion additive manufacturing (MEAM). In this work, the effect of bed temperature (Tb) and nozzle temperature (Tn) on the dimensional accuracy and mechanical property of MEAM‐printed PP copolymer parts was investigated. It is found that raising Tband Tncould significantly reduce the warpage of PP parts by regulating the crystallization behavior of PP. Specially, the amount of γ‐crystal grows obviously while the total crystallinity remains unchanged, as Tbor Tnincreases. Moreover, the more the content of γ‐crystal, the lower the warpage height of PP samples is. Hence, a close correlation between the content of γ‐crystal and part deformation of MEAM‐printed PP parts is successfully established. This is mainly related to the large rigidity of γ‐crystal, which significantly reduces the volume shrinkage of PP during MEAM process. Besides, the raise of Tbor Tnalso enhances the tensile strength, modulus and the elongation at break of PP parts. This wok provides an effective and convenient method for the manufacture of PP parts with good dimensional accuracy and excellent mechanical properties by means of MEAM techniques.

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Auditory hair cells (HCs) are the mechanosensory receptors of the cochlea, and HC loss or malfunction can result from genetic defects. Dock4, a member of the Dock180-related protein superfamily, is a guanine nucleotide exchange factor for Rac1, and previous reports have shown that Dock4mutations are associated with autism spectrum disorder, myelodysplastic syndromes, and tumorigenesis. Here, we found that Dock4 is highly expressed in the cochlear HCs of mice. However, the role of Dock4 in the inner ear has not yet been investigated. Taking advantage of the piggyBac transposon system, Dock4knockdown (KD) mice were established to explore the role of Dock4 in the cochlea. Compared to wild-type controls, Dock4KD mice showed significant hearing impairment from postnatal day 60. Dock4KD mice showed hair bundle deficits and increased oxidative stress, which eventually led to HC apoptosis, late-onset HC loss, and progressive hearing loss. Furthermore, molecular mechanism studies showed that Rac1/β-catenin signaling was significantly downregulated in Dock4KD cochleae and that this was the cause for the disorganized stereocilia and increased oxidative stress in HCs. Overall, our work demonstrates that the Dock4/Rac1/β-catenin signaling pathway plays a critical role in the maintenance of auditory HCs and hearing function.

Natural rotten wood is an excellent precursor to prepare porous carbon. Cellulose carbon of rotten wood (RWCC) has been prepared through carbonizing cellulose extracted from rotten wood followed by ZnCl2activation. RWCC exhibits a large specific surface area (SSA) of 1714.27 m2g-1and uniform microporous structure. RWCC shows a high specific capacitance of 350 F g-1at 1 A g-1in 6 M KOH electrolyte. Fungi-assisted method is low-cost and efficient for preparing porous carbon-based electrode materials.Cellulose carbon of rotten wood (RWCC) was prepared through carbonizing cellulose of rotten wood via fungi action. Attributed to high specific surface area and uniform micropores, RWCC exhibits higher specific capacitance (350 F g-1at 1 A g-1) and excellent rate performance. The capacitance retention of RWCC is 98.0% after 5000 cycles at 5 A g-1.

The wide dynamic range of serum proteome restrained discovery of clinically interested proteins in large cohort studies. Herein, we presented a high-sensitivity, high-throughput, and precise pan-targeted serum proteomic strategy for highly efficient cancer serum proteomic research and biomarker discovery. We constructed a resource of over 2000 cancer-secreted proteins, and the standard MS assays and spectra of at least one synthetic unique peptide per protein were acquired and documented (Cancer Serum Atlas, www.cancerserumatlas.com). Then, the standard peptide-anchored parallel reaction monitoring (SPA-PRM) method was developed with support of the Cancer Serum Atlas, achieving precise quantification of cancer-secreted proteins with high throughput and sensitivity. We directly quantified 325 cancer-related serum proteins in 288 serums of four cancer types (liver, stomach, lung, breast) and controls with the pan-targeted strategy and discovered considerable potential biomarker benefits for early detection of cancer. Finally, a proteomic-based multicancer detection model was built, demonstrating high sensitivity (87.2%) and specificity (100%), with 73.8% localization accuracy for an independent test set. In conclusion, the Cancer Serum Atlas provides a wide range of potential biomarkers that serve as targets and standard assays for systematic and highly efficient serological studies of cancer. The Cancer Serum Atlas-supported pan-targeted proteomic strategy enables highly efficient biomarker discovery and multicancer detection and thus can be a powerful tool for liquid biopsy.

ABSTRACTAminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. In the current study, we found that PINK1-PRKN-mediated mitophagy was impaired in neomycin-treated hair cells. Our data suggested that mitochondrial recruitment of PRKN and phagophore recognition of damaged mitochondria during mitophagy were blocked following neomycin treatment. In addition, the degradation of damaged mitochondria by lysosomes was significantly decreased as indicated by the mitophagic flux reporter mt-mKeima. Moreover, we demonstrated that neomycin disrupted mitophagy through transcriptional inhibition of Pink1expression, the key initiator of mitophagy. Moreover, we found that neomycin impaired mitophagy by inducing ATF3 expression. Importantly, treatment with a mitophagy activator could rescue neomycin-treated hair cells by increasing mitophagy, indicating that genetic modulation or drug intervention in mitophagy may have therapeutic potential for aminoglycoside-induced hearing loss.Abbreviations:AAV: adeno-associated virus; ABR: auditory brainstem response; ATF3: activating transcription factor 3; ATOH1/MATH1: atonal bHLH transcription factor 1; BafA1: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; COX4I1/COXIV: cytochrome c oxidase subunit 4I1; CTBP2/RIBEYE: C-terminal binding protein 2; DFP: deferiprone; EGFP: enhanced green fluorescent protein; FOXO3: forkhead box O3; GRIA2/GLUR2: glutamate receptor, ionotropic, AMPA2 (alpha 2); HC: hair cell; HSPD1/HSP60: heat shock protein 1 (chaperonin); IHC: inner hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MYO7A: myosin VIIA; OPTN: optineurin; OMM: outer mitochondrial membrane; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; RT-qPCR: real-time quantitative polymerase chain reaction; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling; USP30: ubiquitin specific peptidase 30; XBP1: X-box binding protein 1.

Ozone (O3) is ubiquitous in the environment and exposure to high levels of O3has been associated with various respiratory diseases, such as asthma, emphysema, and bronchitis. Therefore, it is necessary to develop a simple and efficient detection method for monitoring O3in the environment and living cells. In this study, an intramolecular charge-transfer (ICT) compound was designed and synthesized based on a phenol-type hemicyanine dye and 4-bromo-1-butene, which could specifically detect O3in aqueous solution. Due to the ICT process, the absorption spectrum, fluorescence spectrum, and color of the probe hemicyanine-butyl-3-enyl (HCB) changed significantly and thus the rapid and sensitive detection of O3was realized. The interaction between O3and the probe HCBcould be completed within 40 min, and the detection limit of O3was as low as 2.15 × 10−7mol L−1. Finally, the proposed method was successfully applied to the visual detection of O3in a simulated O3environment and living cells.

To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level.

Background: During postoperative follow-up, the visible range of maxillary sinus (MS) is limited, even combining 0° and 70° rigid endoscopes together. Flexible endoscope has been used in larynx examinations for a long time, but rarely in nasal cavity and sinus. We aimed to evaluate the application values of rigid and flexible endoscopes for visualization of MS. Methods: We followed up 70 patients with lesions in MS via both rigid and flexible endoscopes. In addition, we used thin-slice CT image of the sinus to create a MS model and divided it into two parts for 3D printing. The inner surface of the 3D-printed sinus was marked with grid papers of the same size (5 mm × 5 mm), then the visual range under rigid endoscopes with different angle and flexible endoscopes was calculated and analyzed. Results: In clinical follow-up, we found that flexible endoscopy can reach where rigid endoscopy cannot, which is more sensitive than medical imaging. Endoscopes showed the largest observation range of the posterolateral wall, more than half of which can be visualized by 0° endoscope. Almost all of the posterolateral wall can be revealed under 45° endoscope, 70° endoscope and flexible endoscope. The visual range of each wall under flexible endoscope is generally greater than that under rigid endoscopes, especially of the anterior wall, medial wall and inferior wall. Conclusion: There was obviously overall advantage of using flexible endoscope in postoperative follow-up of MS lesions. Flexible endoscopy can expand the range of observation, and improve the early detection of the recurrent lesion. We recommend flexible endoscope as a routine application. Graphical abstract:

Protein kinase C (PKC)[β.sub.2] is preferably overexpressed in the diabetic myocardium, which induces cardiomyocyte hypertrophy and contributes to diabetic cardiomyopathy, but the underlying mechanisms are incompletely understood. Caveolae are critical in signal transduction of PKC isoforms in cardiomyocytes. Caveolin (Cav)-3, the cardiomyocyte-specific caveolar structural protein isoform, is decreased in the diabetic heart. The current study determined whether PKC[β.sub.2] activation affects caveolae and Cav-3 expression. Immunoprecipitation and immunofluorescence analysis revealed that high glucose (HG) increased the association and colocalization of PKC[β.sub.2] and Cav-3 in isolated cardiomyocytes. Disruption of caveolae by methyl-β-cyclodextrin or Cav-3 small interfering (si)RNA transfection prevented HG-induced PKC[β.sub.2] phosphorylation. Inhibition of PKC[β.sub.2] activation by compound CGP53353 or knockdown of PKC[β.sub.2] expression via siRNA attenuated the reductions of Cav-3 expression and Akt/endothelial nitric oxide synthase (eNOS) phosphorylation in cardiomyocytes exposed to HG. LY333531 treatment (for a duration of 4 weeks) prevented excessive PKC[β.sub.2] activation and attenuated cardiac diastolic dysfunction in rats with streptozotocin-induced diabetes. LY333531 suppressed the decreased expression of myocardial NO, Cav-3, phosphorylated (p)-Akt, and p-eNOS and also mitigated the augmentation of [O.sub.2.sup.-], nitrotyrosine, Cav-1, and iNOS expression. In conclusion, hyperglycemia-induced PKC[β.sub.2] activation requires caveolae and is associated with reduced Cav-3 expression in the diabetic heart. Prevention of excessive PKC[β.sub.2] activation attenuated cardiac diastolic dysfunction by restoring Cav-3 expression and subsequently rescuing Akt/eNOS/NO signaling., Cardiovascular disease is the leading cause of diabetes-related death (1). While most diabetic heart failure etiology concerns coronary, disease associated with atherosclerosis, a diabetes-associated cardiomyopathy has been reported in humans [...]

Background Exposure to cigarette smoke is a major risk factor for lung cancer, but how it induces cancer is unclear. The overexpressed in lung cancer 1 (OLC1) gene is one of 50 candidate lung cancer genes identified by suppression subtractive hybridization as having higher expression in squamous cell carcinoma (SCC) than normal lung epithelia. Methods We used immunohistochemistry (IHC) to measure OLC1 protein levels in primary lung cancer samples from 559 patients and used fluorescence in situ hybridization to measure OLCl copy number in primary SCC samples from 23 patients. We compared OLC1 protein expression in SCC samples of 371 patients with and without a smoking history using the Pearson [chi square] test. We assayed OLC1 protein levels by immunoblotting in H1299 human lung cancer cells, immortalized human bronchial epithelial cells, and primary cultured normal human bronchial epithelial cells that were treated with cigarette smoke condensate. We assayed tumor formation in athymic mice using NIH3T3 mouse fibroblast cells transfected with OLC1 (eight mice) and analyzed apoptosis and colony formation of H1299 and H520 lung cancer cells transfected with scrambled (negative) or OLC1 small interfering RNAs (siRNAs) (s1). Results OLC1 protein was overexpressed in 387 of 464 (83.4%) of primary lung cancers, as detected by IHC, and OLC1 was amplified in 14 of 23 (60%) of SCC samples. OLC1 protein overexpression was more common in SCC patients with a smoking history than those without (77.1% vs 45.8%, P < .001). In addition, cigarette smoke condensate increased OLC1 protein levels in H1299 cells, immortalized human bronchial epithelial cells, and primary cultured normal human bronchial epithelial cells. Overexpression of OLC1 induced tumor formation in athymic mice (control vs OLC1, 0% vs 100%). Knockdown of OLC1 increased apoptosis (mean percentage of apoptotic H1299 cells, s1 vs negative: 30.3% vs 6.4%, difference = 23.9%, 95% confidence interval [CI] = 19.1% to 28.5%, P = .002; mean percentage of apoptotic H520 cells, s1 vs negative: 21.6% vs 4.9%, difference = 16.7%, 95% CI = 10.6% to 22.8%, P = .007) and decreased colony formation (mean no. of colonies of H1299 cells transfected with siRNAs, negative vs s1: 84 vs 4, difference = 80, 95% CI = 71 to 88, P < .001; mean no. of colonies of H520 cells transfected with siRNAs, negative vs s1: 103 vs 24, difference = 79, 95% CI = 40 to 116, P = .005). Conclusions OLC1 is a candidate oncogene in lung cancer whose expression may be regulated by exposure to cigarette smoke.

Background: Delayed neurocognitive recovery (dNCR) can result in unfavorable outcomes in elderly surgical patients. Physical activity (PA) has been shown to improve cognitive function, potentially by reducing systemic inflammatory responses. However, there is a lack of supportive data indicating whether PA has a protective effect against dNCR. Aims: To examine the correlation between dNCR and PA, and to further analyze if pro-inflammatory cytokines mediate this relationship. Methods: This study is a prospective nested case-control investigation of elderly patients who had knee replacement surgery. dNCR was defined as a decline in cognitive function compared with baseline by using a battery of neuropsychological tests. PA was assessed with the Physical Activity Scale for the Elderly (PASE). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of IL-6, IL-1β, and TNF-α. Multivariable logistic regression analysis was conducted to assess the association between PA and dNCR. Mediation analysis was employed to evaluate whether pro-inflammatory cytokines mediate the relationship between them. Results: A cohort of 152 patients was included, resulting in an incidence rate of dNCR of 23.68%. PA was associated with dNCR after full adjustment [OR = 0.199, (95% CI, 0.061; 0.649), P= 0.007]. Mediation analysis showed that the IL-6 mediated the statistical association between PA and dNCR, with mediation proportions (%) of 77.68 (postoperative concentration of IL-6) or 27.58 (the absolute change in IL-6 before and after surgery). Conclusions: PA serves as a protective factor against dNCR, possibly through the reduction of pro-inflammatory cytokine concentrations. The Chinese Clinical Trail Registry: : www.http://chictr.org.cn, Registration No. ChiCTR2300070834, Registration date: April 24, 2023.

To analyze the relationship between macro and meso parameters of the gas hydrate bearing coal (GHBC) and to calibrate the meso-parameters, the numerical tests were conducted to simulate the laboratory triaxial compression tests by PFC3D, with the parallel bond model employed as the particle contact constitutive model. First, twenty simulation tests were conducted to quantify the relationship between the macro–meso parameters. Then, nine orthogonal simulation tests were performed using four meso-mechanical parameters in a three-level to evaluate the sensitivity of the meso-mechanical parameters. Furthermore, the calibration method of the meso-parameters were then proposed. Finally, the contact force chain, the contact force and the contact number were examined to investigate the saturation effect on the meso-mechanical behavior of GHBC. The results show that: (1) The elastic modulus linearly increases with the bonding stiffness ratio and the friction coefficient while exponentially increasing with the normal bonding strength and the bonding radius coefficient. The failure strength increases exponentially with the increase of the friction coefficient, the normal bonding strength and the bonding radius coefficient, and remains constant with the increase of bond stiffness ratio; (2) The friction coefficient and the bond radius coefficient are most sensitive to the elastic modulus and the failure strength; (3) The number of the force chains, the contact force, and the bond strength between particles will increase with the increase of the hydrate saturation, which leads to the larger failure strength.

The rapid identification and antibiotic susceptibility testing (AST) of bacteria would help us to accurately identify the infectious sources as well as guide the use of antibiotics, which are crucial for improving the survival rate and antimicrobial resistance. Herein, a colorimetric sensor array for bacteria fingerprinting was constructed with d-amino acid (d-AA)-modified gold nanoparticles (AuNPs) as probes (Au/d-AA). Bacteria can metabolize the d-AA, triggering the aggregation of AuNPs. Making use of different metabolic capabilities of bacteria toward different d-AA, eight kinds of bacteria including antibiotic-resistant bacteria and strains of the same bacterial species are successfully differentiated via learning the response patterns. Meanwhile, the sensor array also performs well in quantitative analysis of single bacterium and differentiation of bacteria mixtures. More interestingly, a rapid colorimetric AST approach has been developed based on the Au/d-AA nanoprobes by monitoring the d-AA metabolic activity of bacteria toward various antibiotic treatments. In this regard, the outlined work here would promote clinical practicability and facilitate antibiotic stewardship.

Advanced and aggressive prostate cancer (PCa) depends on glutamine for survival and proliferation. We have previously shown that inhibition of glutaminase 1, which catalyzes the rate-limiting step of glutamine catabolism, achieves significant therapeutic effect; however, therapy resistance is inevitable. Here we report that while the glutamine carbon is critical to PCa survival, a parallel pathway of glutamine nitrogen catabolism that actively contributes to pyrimidine assembly is equally important for PCa cells. Importantly, we demonstrate a reciprocal feedback mechanism between glutamine carbon and nitrogen pathways which leads to therapy resistance when one of the two pathways is inhibited. Combination treatment to inhibit both pathways simultaneously yields better clinical outcome for advanced PCa patients.

MOF-derived porous materials Co3O4and Co/C with hierarchical structure (MHCo3O4&Co/C) were prepared by the self-sacrificial template strategy, and the surfaces of such materials were functionally modified with a “polydopamine (PDA)” bionic membrane for entrapping horseradish peroxidase (HRP) in this work. MHCo3O4was prepared under air atmosphere, and Co/C was prepared under nitrogen atmosphere based on the thermolysis of Co-MOF. HRP@PDA@MHCo3O4and HRP@PDA@Co/C could retain 96.8% and 93.7% catalytic activity compared to the free HRP, respectively, and exhibited better thermal stability and reusability. After 1 h incubation at 70 °C, HRP@PDA@MHCo3O4and HRP@PDA@Co/C retained 84.8% and 70.8% of the initial activity compared with less than 20% retained by free HRP. After 10 cycles, HRP@PDA@MHCo3O4and HRP@PDA@Co/C retained 92.4% and 85.4% of the initial activity. Moreover, HRP@PDA@MHCo3O4&Co/C exhibited extreme catalytic degradation efficiency for 2,4-dichlorophenol in simulated wastewater, and 2 mmol L−1of 2,4-dichlorophenol was completely degraded within 15 min. The superior properties of HRP@PDA@MHCo3O4&Co/C were researched by kinetics and thermodynamics analyses. The results suggested that the mass transfer resistance of the substrates was lower than that of the bulk solution for the reason that the substrates were originally enriched on the hierarchical porous carrier close to the enzyme. The specificity and binding affinity of the enzymatic reactors to substrates were enhanced by the functionalized “PDA” bionic membrane on the carrier surface, compared with free enzyme in bulk buffer.

BackgroundNephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases of monogenetically caused end-stage renal disease (ESRD) in children. Exploring the correlation between the phenotype and genotype of NPHP-RC is helpful for early diagnosis and management. We investigated the phenotype and genotype spectra of NPHP-RC in a Chinese multicentre cohort.MethodsCrosss-ectional and longitudinal data of 60 patients from 57 families with pathogenic NPHP-RC gene mutations distributed in 22 regions of China were collected into a unified, anonymous database. The mean observation time of this cohort was 3.5±3.1 years.ResultsMutations in NPHP1and NPHP3were the most common genetic defects. Overall, 45% of patients presented with isolated nephronophthisis (NPH), and 55% exhibited the extrarenal phenotype, which frequently involved the liver (41.7%, n=25), central nervous system (26.7%, n=16), eyes (26.7%, n=16) and skeletal system (11.7%, n=7). Accidental detection of elevated serum creatinine and non-specific symptoms caused by chronic kidney disease occurred in 65% of patients. Patients carrying NPHP1mutations mainly presented with isolated NPH (90%, 18/20) and progressed to ESRD at a mean age of 12.9±0.5 years. The mean age of ESRD onset in the non-NPHP1group was lower than that in the NPHP1group (6.2±1.4 years, p<0.001), especially for patients carrying NPHP3mutations (3.1±1.2 years), showing a heterogeneous phenotype characterised by Bardet-Biedl syndrome (12.5%, n=5), Joubert syndrome (7.5%, n=3), COACH syndrome (2.5%, n=1), Mainzer-Saldino syndrome (2.5%, n=1), short-rib thoracic dysplasia (2.5%, n=1) and unclassified symptoms (32.5%, n=13).ConclusionsThe Chinese Children Genetic Kidney Disease Database registry characterised the spectrum of the phenotype and genotype of NPHP-RC in the Chinese population. NPHP1and NPHP3were the most common pathogenic genes. Rapid progression to ESRD and liver involvement were noted in patients with NPHP3mutations.

The objective of this paper is to present a MATLAB-based toolbox called CSA-T-TDS (acronym for Complete Stability Analysis Toolbox for Time-Delay Systems). By using this toolbox, one can easily find the whole stability delay-set for a linear system with commensurate delays. For a better understanding of the methodology at the origin of the software, the theoretical core of CSA-T-TDS (the frequency-sweeping approach together with the auxiliary characteristic function) is discussed. Then, this application of the toolbox will be demonstrated along with some numerical examples.

A photoredox and copper-catalyzed fluoroalkylphosphorothiolation of activated and unactivated alkenes via a radical relay mechanism is reported. By employing fluoroalkyl halides as radical precursors and P(O)SH or P(S)SH compounds as coupling partners, a wide range of β-monofluoroalkyl-, -difluoroalkyl-, -trifluoromethyl-, or -perfluoroalkyl-substituted S-alkyl phosphorothioates and phosphorodithioates can be easily constructed under mild conditions with good functional group tolerance. Furthermore, this modular reaction system can be successfully applied to late-stage functionalization of bioactive molecules.

Background: The posterior tympanum approach of cochlear implantation is easy to damage the facial nerve and cord tympanic nerve. Therefore, we need to improve the safety of cochlear implantation.Objectives: To discuss the safety and feasibility of active and adequate transparent exposure of the facial nerve and chorda tympani nerve during the surgery.Methods: A retrospective analysis was performed on all 945 patients who underwent cochlear implantation from January 2011 to September 2017. All patients have been followed up for 14 months to 5 years postoperatively and postoperative complications have been observed.Results: All 945 patients received artificial cochlear implantation. The facial nerves of 76 cases were above the horizontal semicircular canal plane, while narrow facial recess was observed in 44 cases. Serious chorda tympani nerve variation was found in 1 case. No facial paralysis and facial nerve irritation and abnormal taste occurred after operation.Conclusions: Cochlear implantation with initiative and adequate exposure of facial nerve and the chorda tympani nerve can improve the safety of the cochlear implant surgery. Our study provide a safe and effective method for clinical cochlear implantation to reduce facial nerve and tympanic cord nerve injury.

With the development of Unmanned Aerial Vehicle (UAV) system autonomy, network communication technology and group intelligence theory, mission execution in the form of a UAV swarm will be an important realization of future applications. Traditional single-UAV mission reliability modeling methods have been unable to meet the requirements of UAV swarm mission reliability modeling. Therefore, the UAV swarm mission reliability modeling and evaluation method is proposed. First, aimed at the interdependence among the multiple layers, a multi-layer network model of a UAV swarm is established. At the same time, based on the system having the following characteristics—using a mission chain to complete the mission and applying the connectivity of the mission network—the mission network model of a UAV swarm is established. Second, vulnerability and connectivity are selected as two indicators to reflect the reliability of the mission, and aimed at random attack and deliberate attack, vulnerability and connectivity evaluation methods are proposed. Finally, the validity and accuracy of the constructed model are verified through simulations, and the model and selected indicators can meet the reliability requirements of the UAV swarm mission. In this way, this study provides quantitative reference for UAV-swarm-related decision-making work and supports the development of UAV-swarm-related work.

Purpose: The purpose of this paper is to investigate the literature on the treatment of primary pupils and inspecting the role of environmental psychology, e-learning, learning style and school design on the behavior of students in elementary schools. Design/methodology/approach: A questionnaire was designed to evaluate the components of the model. Experts with significant experiences in the field of students' behavior revised the surveys. Data were collected from 400 teachers of the elementary schools in Iran. The SMART-PLS 3.2 and SPSS 22 software package were used in the field of questionnaires' statistical analysis. Findings: Findings confirmed the suggested model's validity for elementary students' behavior assessment. The consequences of this research illustrated the effect of environmental psychology on the behavior of elementary students. In addition, the authors were concluded that intention to e-learning has a significant role in developing the action and behavior of the elementary students. Moreover, the learning style has an affirmative and considerable impact on the behavior of elementary students. Finally, school design has an affirmative and significant effect on the manner of the elementary students. Practical implications: The consequences of this research have provided some traces about the basic perspectives, which have to be in the center of attention of administrators. For instance, school design and learning style sound to be a decisive mechanism for improving action and learning behavior. In addition, educational leaders may use the findings to evaluate their school facilities and define where developments will have the most significant impact or planners may use the results to assist architects in the design and construction of new educational services. Originality/value: This study builds a valuable contribution by focusing on pupil environmental psychology, e-learning, learning style and school design in elementary schools by enlightening the connection between them and students' manner. [ABSTRACT FROM AUTHOR]

Herein, an interference-free surface-enhanced Raman scattering (SERS) platform with a “sandwich” structure has been developed for reliable detection and photothermal killing of bacteria with whole blood as the real sample. The multifunctional platform comprised a plasmonic gold film (pAu) functionalized with bacteria-capturing units of 4-mercaptophenylboronic acid and internal reference of 4-mercaptobenzonitrile as the SERS substrate and vancomycin-modified core (gold)–shell (Prussian blue) nanoparticles (Au@PB@Van NPs) as the SERS tag. The detected SERS signals were from the Raman-silent region where no background signals occurred from biological sources, eliminating the interference and improving the detection sensitivity and accuracy. As a proof-of-concept, model bacterial strain, Staphylococcus aureus, was captured and detected in the whole blood samples. Furthermore, high antibacterial efficiency of approximately 100% was reached under the synergistic photothermal effect from pAu and Au@PB@Van NPs. This study provides a new avenue for bacteria detection in real samples and their subsequent in situelimination.

Enzymes are efficient catalysts offering much more competitive processes than conventional chemical reactions. However, the lack of stability and reusability is a key issue on the use of enzymes in industrial applications. These drawbacks can generally be overcome by immobilization of the enzyme on a solid support. In this work, a Fe3O4/Fe-MOF core–shell with hierarchical pore sizes was prepared by growing Fe-MOF around Fe3O4nanoparticles viasolvothermal synthesis. Fe3O4/Fe-MOF integrates magnetic characteristics and hierarchical porous structure for supporting chloroperoxidase (CPO) or horseradish peroxidase (HRP). Immobilized CPO/HRP exhibited significantly enhanced stability against temperature stress and facilitated reuse. For example, HRP-Fe3O4/Fe-MOF can retain 94.1% activity after 10 reuses. Moreover, CPO/HRP-Fe3O4/Fe-MOFs were very efficient in the degradation of organic toxins, isoproturon or 2,4-dichlorophenol in simulated wastewater with a complete degradation within 15 min. The excellent performance of CPO/HRP-Fe3O4/Fe-MOF was investigated by kinetic and thermodynamic analysis. The results indicated that the diffusion resistance of substrates was reduced compared with that in a bulk solution because they were initially concentrated close to enzymes on the hierarchically porous support. The specificity and binding affinity of the immobilized enzymes are enhanced compared with the free enzymes.

A bifunctional lead(II)‐acylhydrazone coordination polymer featuring 3D hydrogen‐bonded framework exhibits intense blue luminescence and remarkable inhibitory effect on the fusarium fungi.

To screen the efficient media for CO2capture of flue gas from power plants, a strategy for improving the CO2capture capacity by dual functionalized ionic liquids (ILs) with multiple active sites is proposed. Three phosphonium dual functionalized ILs ([aP4443][2-Np], [aP4443][2-Op], and [aP4443][Triz]) have been prepared. The sorption capacities of the synthesized ILs under pure CO2atmosphere and the supported ILs under different loading amounts from 10 to 50%, temperatures of 30–80 °C, and CO2partial pressure varied from 10 to 15% were determined. Fourier transform infrared (FTIR) spectroscopy was applied to reveal the interaction between CO2and ILs, and the pseudo-second-order model and the intraparticle diffusion model were used for a better understanding of the CO2adsorption behavior. The results showed that a high capacity up to 1.88 mol of CO2/mol of IL for [aP4443][2-Np] is achieved, and 30% IL–MCM-41 can reach 3.19 mmol/g with excellent reversibility under the atmosphere of CO2:N2(15%:85%) at 30 °C and 0.1 MPa. Raising the temperature or decreasing the CO2concentration is not conducive to improving the CO2capacity. FTIR spectroscopy demonstrated that the amino and hydroxyl react with CO2to form NHCOO–or CO3–. Combined with the activation energy calculation, the kinetic analysis revealed that the CO2capture of supported ILs is an internal diffusion controlled physical adsorption.

Achieving efficient adsorption and desorption processes by controllably tuning the properties of adsorbents at different technical stages is extremely attractive. However, it is difficult for traditional adsorbents to reach the target because of their fixed active sites. Herein, we report on the fabrication of a smart adsorbent, which was achieved by introducing photoresponsive azobenzene derivatives with cis/transisomers to Ce-doped mesoporous silica. These photoresponsive groups serve as “molecular switches” by sheltering and exposing active sites, leading to efficient adsorption and desorption. Ce is also doped to provide additional active sites in order to enhance the adsorption performance. The results show that the cisisomers effectively shelter the active sites, leading to the selective adsorption of methylene blue (MB) over brilliant blue (BB), while the transisomers completely expose the active sites, resulting in the convenient release of the adsorbates. Both selective adsorption and efficient desorption can be realized controllably by these smart adsorbents through photostimulation. Moreover, the performance of the obtained materials is well maintained after five cycles.

ObjectiveTo investigate the correlation between the methylenetetrahydrofolate reductase (MTHFR) gene 677C> T polymorphism and fetal congenital defects.

Background Patients with moderate to severe allergic rhinitis (AR) who are treated according to the current rhinitis management guidelines may be inadequately controlled. These patients are at risk of serious comorbidities, such as asthma and chronic sinusitis. These symptoms, sneezing and an itchy, runny, stuffy nose, may have a negative impact on patients’ daily functioning. Omalizumab is being developed as a new choice for the treatment of AR. We therefore undertook a meta-analysis to assess the efficacy and safety of omalizumab in the treatment of AR.Methods We systematically searched PubMed, Cochrane Library, and MEDLINE databases for randomized controlled studies on the treatment of AR with omalizumab. Our evaluation outcomes were symptom scores, medication efficacy, combined symptom and medication scores, and adverse events. We descriptively summarized and quantitatively synthesized original data to evaluate the efficacy and safety of omalizumab in the treatment of AR by using Stata12.0 software for meta-analyses.Results The results of our meta-analysis showed that there were statistically significant differences between the omalizumab group and the control group in the following aspects: daily nasal symptom score (standardized mean difference [SMD] = –0.443, 95% confidence interval [CI]: –0.538 to –0.347, P< .001); daily ocular symptom score (SMD = –0.385, 95% CI: –0.5 to –0.269, P< .001); daily nasal medication symptom scores (SMD = –0.421, 95% CI: –0.591 to –0.251, P< .001); proportion of days of emergency drug use (risk ratio [RR] = 0.488, 95% CI: 0.307 to 0.788, P< .005); rhinoconjunctivitis-specific quality of life questionnaire (SMD = –0.286, 95% CI: –0.418 to –0.154, P< .001); and overall evaluation (RR = 1.435, 95% CI: 1.303–1.582, P< .001). There was no statistically significant difference in safety indicator: adverse events (RR = 1.026, 95% CI: 0.916–1.150, P= .655).Conclusion Omalizumab is effective and relatively safe in patients with AR; omalizumab used in conjunction with special immunotherapy has shown promising results, especially in reducing adverse events.

Cochlear implants are currently the most effective treatment for profound sensorineural hearing loss. However, their therapeutic effect is limited by the survival and proper physiological function of spiral ganglion neurons (SGNs), which are targeted by the cochlear implant. It is therefore critical to explore the mechanism behind the effect of electric-acoustic stimulation (EAS) on the targeted SGNs. In this work, a biocompatible cochlear implant/graphene EAS system was created by combining a cochlear implant to provide the electrically transformed sound stimulation with graphene as the conductive neural interface. SGNs were cultured on the graphene and exposed to EAS from the cochlear implant. Neurite extension of SGNs was accelerated with long-term stimulation, which might contribute to the development of growth cones. Our system allows us to study the effects of cochlear implants on SGNs in a low-cost and time-saving way, and this might provide profound insights into the use of cochlear implants and thus be of benefit to the populations suffering from sensorineural hearing loss.

Transforming growth factor β (TGF-β) is implicated as a key mediator of pathological fibrosis, but its pleiotropic activity in a range of homeostatic functions presents challenges to its safe and effective therapeutic targeting. There are three isoforms of TGF-β, TGF-β1, TGF-β2, and TGF-β3, which bind to a common receptor complex composed of TGF-βR1 and TGF-βR2 to induce similar intracellular signals in vitro.We have recently shown that the cellular expression patterns and activation thresholds of TGF-β2 and TGF-β3 are distinct from those of TGF-β1 and that selective short-term TGF-β2 and TGF-β3 inhibition can attenuate fibrosis in vivowithout promoting excessive inflammation. Isoform-selective inhibition of TGF-β may therefore provide a therapeutic opportunity for patients with chronic fibrotic disorders.

Nicotine is widely recognized as the primary contributor to tobacco dependence. Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area (VTA) neurons, and accumulating evidence suggests that glia play prominent roles in nicotine addiction. However, VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration. Here, a male mouse model of nicotine self-administration was established and the timing of three critical phases (pre-addiction, addicting, and post-addiction phase) was characterized. Single-nucleus RNA sequencing (snRNA-seq) in the VTA at each phase was performed to comprehensively classify specific cell subtypes. Adaptive changes occurred during the addicting and post-addiction phases, with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacted the transcription in each cell subtype. Furthermore, significant transcriptional changes in energy metabolism-related genes were observed, accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration. The results provide insights into mechanisms underlying the progression of nicotine addiction, serving as important resource for identifying potential molecular targets for nicotine cessation.

Objectives This study aimed to measure the supraorbital ethmoid cell (SOEC) and characterize the relationship between the degree of SOEC pneumatization and the position of the anterior ethmoidal artery (AEA) in relation to the skull base.Methods Computed tomography (CT) scans of 100 patients were analyzed. The correlation between the pneumatization of SOEC and the distance of the AEA from the skull base was explored by Spearman’s correlation rho efficient test.Results The distance of the AEA from skull base was 3.10 (2.60,3.60) mm in patients with SOEC compared with 0.6(0.40,2.10)mm in those without(P < .001). In 50.5% of the patients, the AEA was located below the skull base; the incidence of this localization was significantly higher in those with SOEC than in those without (78.79%vs22.77%, P < .001). Compared to female patients, male patients owned greater SOEC height (9.65vs8.20mm, P = .007). The SOECs volume (r = 0.45, P < .001), height (r = .30, P = .003), and transverse diameter (r = 0.28, P = .005) were all significantly correlated with the distance of the AEA from the skull base.Conclusions The pneumatization of SOEC critically impact the distance between the AEA and skull base. The higher the degree of pneumatization, the farther from the skull base the AEA will be, increasing the risk of complications during nasal endoscopic surgery. These results provide an important reference for protecting the AEA during nasal endoscopic surgery.

Accumulation of mutant proteins in cells can induce proteinopathies and cause functional damage to organs. Recently, the Cingulin (CGN) protein has been shown to maintain the morphology of cuticular plates of inner ear hair cells and a frameshift mutation in CGNcauses autosomal dominant nonsyndromic hearing loss. Here, we find that the mutant CGN proteins form insoluble aggregates which accumulate intracellularly and lead to cell death. Expression of the mutant CGN in the inner ear results in severe hair cell death and hearing loss in mice, resembling the auditory phenotype in human patients. Interestingly, a human-specific residue (V1112) in the neopeptide generated by the frameshift mutation is critical for the aggregation and cytotoxicity of the mutant human CGN. Moreover, the expression of heat shock factor 1 (HSF1) decreases the accumulation of insoluble mutant CGN aggregates and rescues cell death. In summary, these findings identify mutant-specific toxic polypeptides as a disease-causing mechanism of the deafness mutation in CGN, which can be targeted by the expression of the cell chaperone response regulator HSF1.