Ready-to-use ratiometric bioluminescence immunosensor for detection of ochratoxin a in pepper.

Rapid, portable, and accurate detection tools for monitoring ochratoxin A (OTA) in food are essential for the guarantee of food safety and human health. Herein, as a proof-of-concept, this study proposed a ratiometric bioluminescence immunosensor (RBL-immunosensor) for homogeneous detection of OTA in pepper. The construct of the RBL-immunosensor consists of three components, including the large fragment of the split nanoluciferase (NanoLuc)-tagged nanobody (NLg), the small fragment of the split NanoLuc-tagged mimotope peptide heptamer (MPSm), and the calibrator luciferase (GeNL). The specific nanobody-mimotope peptide interaction between NLg and MPSm induces the reconstitution of the NanoLuc, which catalyzes the Nano-Glo substrate and produces a blue emission peak at 458 nm. Meanwhile, GeNL can produce a green emission peak at 518 nm upon substrate conversion via bioluminescent resonance energy transfer (BRET). Therefore, the concentration of OTA can be linked to the variation of the bioluminescence signal (λ458/λ518) measured by microplate reader and the variation of the blue/green ratio measured by smartphone via the competitive immunoreaction where OTA competes with MPSm to bind NLg. The immunosensor is ready-to-use and works by simply mixing the components in a one-step incubation of 10 min for readout. It has a limit of detection (LOD) of 0.98 ng/mL by a microplate reader and an LOD of 1.89 ng/mL by a smartphone. Good selectivity and accuracy were confirmed for the immunosensor by cross-reaction analysis and recovery experiments. The contents of OTA in 10 commercial pepper powder samples were tested by the RBL-immunosensor and validated by high-performance liquid chromatography. Hence, the ready-to-use RBL-immunosensor was demonstrated as a highly reliable tool for detection of OTA in food.

Drug resistance­related gene targets and molecular mechanisms in the A2780/Taxol­resistant epithelial ovarian cancer cell line.

Epithelial ovarian cancer (EOC) is a fatal gynecological malignant tumor with a low 5-year survival rate. The use of the first-line chemotherapeutic drug, paclitaxel, for the treatment of EOC is associated with resistance, often leading to treatment failure. The present study investigated the gene targets in an A2780 paclitaxel-resistant EOC cell line (A2780/Taxol), and the potential underlying mechanisms using transcriptome sequencing technology and bioinformatics analysis. The transcriptome of the A2780/Taxol cell line was sequenced, and 498 differentially expressed genes were obtained contained in the Gene Expression Omnibus dataset. Further bioinformatics analysis revealed that matrix metalloproteinase 1 (MMP1), zyxin (ZYX) and Unc-5 netrin receptor C (UNC5C) may be gene targets related to paclitaxel resistance. Moreover, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that a potential mechanism associated with paclitaxel resistance was related to cell migration. Furthermore, the expression levels of MMP1, ZYX and UNC5C were verified using western blotting, immunofluorescence and immunohistochemistry in vitro. The results revealed that the expression levels of MMP1 and ZYX were significantly increased in A2780/Taxol cells, while UNC5C expression was significantly decreased, which was consistent with the results of the transcriptome sequencing. The present study demonstrated that MMP1, ZYX and UNC5C may be the gene targets associated with paclitaxel resistance in EOC. These genes have potential to be used as molecular markers for EOC drug therapy, targeted elimination of drug resistance, and evaluation of treatment efficacy and patient prognosis.

Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature.

BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457). METHODS: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2. RESULTS: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved. CONCLUSION: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.

[Inhibition of Autophagy Augments the Anticancer Activity of KPT-330 in Mantle Cell Lymphoma Cells].

OBJECTIVE: To investigate the influence of novel CRM1 inhibitor KPT-330 on the autophagy of mantle cell lymphoma (MCL) cells, and effect of KPT-330 on the prolifiration of MCL cells in the presence or absence of autophagy inhibitor. METHODS: CCK-8 assay was used to detect the effect of KPT-330 on MCL cell lines Z-138， Jeko-1， Granta-519， Rec-1. The effect of KPT-330 on autophagy features were determined by detecting acidic vesicular organelles (AVO) by MDC staining under fluorescence microscope and detecting protein expression of LC3B-II assessed by Western blot. Further combined application of lysosomal inhibitor Chloroquine (CQ) was used to observe its effect on the increase of LC3B-Ⅱ caused by KPT-330. CalcuSyn 2.0 software was used to detected the Combination index (CI) of KPT-330 combined with CQ. RESULTS: The proliferation of MCL cell lines （Z-138, Jeko-1, Grant-519, Rec-1） could be inhibited by KPT-330 in a dose-dependent manner (r =0.930, 0.946, 0.691, 0.968 respectively). The number of acidic vesicular organelles (AVO) and the expression of LC3B-II were increased in KPT-330 treated Jeko-1 and Granta-519 cells in a dose-dependent manner (r Jeko-1=0.993, r Granta-519=0.971). LC3B-II protein amounts still increased upon KPT-330 treatment with the existence of lysosomal inhibitor CQ in Jeko-1 and Granta-519 cells, which was higher than CQ or KPT-330 single drug group. The combination of KPT-330 and CQ produced the synergistic effects on cells proliferation inhibition with CalcuSyn 2.0 analysis. CONCLUSION: KPT-330 can inhibit MCL cell proliferation and induce autophagy. KPT-330 combined with autophagy inhibitor CQ could produce synergistic anti MCL effects, providing experimental basis for clinical combination therapy.

Fast high quality computational ghost imaging based on saliency variable sampling detection.

Fast computational ghost imaging with high quality and ultra-high-definition resolution reconstructed images has important application potential in target tracking, biological imaging and other fields. However, as far as we know, the resolution (pixels) of the reconstructed image is related to the number of measurements. And the limited resolution of reconstructed images at low measurement times hinders the application of computational ghost imaging. Therefore, in this work, a new computational ghost imaging method based on saliency variable sampling detection is proposed to achieve high-quality imaging at low measurement times. This method physically variable samples the salient features and realizes compressed detection of computational ghost imaging based on the salient periodic features of the bucket detection signal. Numerical simulation and experimental results show that the reconstructed image quality of our method is similar to the compressed sensing method at low measurement times. Even at 500 (sampling rate 0.76 % ) measurement times, the reconstructed image of the method still has the target features. Moreover, the 2160 × 4096 (4K) pixels ultra-high-definition resolution reconstructed images can be obtained at only a sampling rate of 0.11 % . This method has great potential value in real-time detection and tracking, biological imaging and other fields.

Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes.

Tomosyns are widely thought to attenuate membrane fusion by competing with synaptobrevin-2/VAMP2 for SNARE-complex assembly. Here, we present evidence against this scenario. In a novel mouse model, tomosyn-1/2 deficiency lowered the fusion barrier and enhanced the probability that synaptic vesicles fuse, resulting in stronger synapses with faster depression and slower recovery. While wild-type tomosyn-1m rescued these phenotypes, substitution of its SNARE motif with that of synaptobrevin-2/VAMP2 did not. Single-molecule force measurements indeed revealed that tomosyn's SNARE motif cannot substitute synaptobrevin-2/VAMP2 to form template complexes with Munc18-1 and syntaxin-1, an essential intermediate for SNARE assembly. Instead, tomosyns extensively bind synaptobrevin-2/VAMP2-containing template complexes and prevent SNAP-25 association. Structure-function analyses indicate that the C-terminal polybasic region contributes to tomosyn's inhibitory function. These results reveal that tomosyns regulate synaptic transmission by cooperating with synaptobrevin-2/VAMP2 to prevent SNAP-25 binding during SNARE assembly, thereby limiting initial synaptic strength and equalizing it during repetitive stimulation.

The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis.

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.

The construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments.

BACKGROUND: Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. METHODS: Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells. For this purpose, we initially screened healthy donors and cultured their T cells to obtain a higher proportion of stem cell-like memory T (TSCM) cells, which exhibit robust self-renewal capacity, sustainability and cytotoxicity. To reduce the alloreactivity, the T cells were further edited by double knockout of the T cell receptor (TCR) and class I human leukocyte antigen (HLA-I) genes utilizing the CRISPR/Cas9 system. The well-growing and genetically stable universal cells carrying the CAR-moiety were then stored as a stable and unified cell bank. Subsequently, the SDcatcher/GVoptiTag system, which generate an isopeptide bond, was used to covalently connect the purified scFvs of antibody targeting different antigens to the recovered CAR-T cells. RESULTS: The resulting CAR-T cells can perform different functions by specifically targeting various cells, such as the eradication of human immunodeficiency virus type 1 (HIV-1)-latenly-infected cells or elimination of T lymphoma cells, with similar efficiency as the traditional CAR-T cells did. CONCLUSION: Taken together, our strategy allows the production of CAR-T cells more modularization, and makes the quality control and pharmaceutic manufacture of CAR-T cells more feasible.

Ivermectin for treatment of COVID-19: A systematic review and meta-analysis.

The effect of ivermectin (IVM) in treating coronavirus disease 2019 (COVID-19) is still controversial, yet the drug has been widely used in the world. The aim of this review was to systematically evaluate the clinical outcomes of IVM in patients with COVID-19. From inception to June 22, 2023, the PubMed, EMBASE, Web of Science (WOS), and scopus databases were searched for relevant observational studies on the risk of RA in migraineurs. We searched PubMed/Medline, EMBASE, the Cochrane Library, Web of Science, medRxiv, and bioRxiv to collect all relevant publications from inception to June 22, 2023. Primary outcomes were all-cause mortality rate, mechanical ventilation (MV) requirement, PCR negative conversion, and adverse events (AEs). Revman 5.4 was used to assess the risk of bias (RoB) and quality of evidence. Thirty-three RCTs (n = 10,489) were included. No significant difference in all-cause mortality rates or PCR negative conversion between IVM and controls. There were significant differences in MV requirement (RR 0.67, 95% CI 0.47-0.96) and AEs (RR 0.87, 95% CI 0.80-0.95) between the two groups. Ivermectin could reduce the risk of MV requirement and AEs in patients with COVID-19, without increasing other risks. In the absence of a better alternative, clinicians could use it with caution.

Development of Shark Single Domain Antibodies Specific for Human α-Fetoprotein and the Multimerization Strategy in Serum Detection.

Sensitive detection of cancer biomarkers can contribute to the timely diagnosis and treatment of diseases. In this study, the whitespotted bamboo sharks were immunized with human α-fetoprotein (AFP), and a phage-displayed variable new antigen receptor (VNAR) single domain antibody library was constructed. Then four unique VNARs (VNAR1, VNAR11, VNAR21, and VNAR25) against AFP were isolated from the library by biopanning for the first time. All of the sequences belong to type II of VNAR, and the VNAR11 was much different from the rest of the three sequences. Then VNAR1 and VNAR11 were selected to fuse with the C4-binding protein α chain (C4bpα) sequence and efficiently expressed in the Escherichia coli system. Furthermore, a VNAR-C4bpα-mediated sandwich chemiluminescence immunoassay (VSCLIA) was developed for the detection of AFP in human serum samples. After optimization, the VSCLIA showed a limit of detection of 0.74 ng/mL with good selectivity and accuracy. Moreover, the results of clinical serum samples detected by the VSCLIA were confirmed by an automatic immunoanalyzer in the hospital, indicating its practical application in actual samples. In conclusion, the novel antibody element VNAR exhibits great potential for immunodiagnosis, and this study also provides a new direction and experimental basis for AFP detection.

Characterization of CD8+ T cells in immune-privileged organs of ZIKV-infected Ifnar1-/- mice.

Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in Ifnar1-/- mice, based on an immunodominant epitope E294-302 tetramer. The distinct kinetics and functions of virus-specific CD8+ T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E294-302-specific T cells can account for 20-60% of the total CD8+ T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E294-302-specific TCRαßs within the IPOs are featured with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains, but with distinct αß paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors, Ccr2 and Ccr5, were selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8+ T cells after infection. Overall, this study adds to the understanding of virus-specific CD8+ T cell responses for controlling and clearing ZIKV infection in IPOs.IMPORTANCEThe immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8+ T cells. Our data show that CD8+ T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first ex vivo comparative analyses of the composition and diversity related to TCRα/ß clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRα/ß clonotypes in tissues utilize TRAV9N-3 with conservation. Specific chemokine expression, including Ccr2 and Ccr5, was found to be selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8+ T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8+ T cells after ZIKV infection in different IPOs.

Lipid osmosis, membrane tension, and other mechanochemical driving forces of lipid flow.

Nonvesicular lipid transport among different membranes or membrane domains plays crucial roles in lipid homeostasis and organelle biogenesis. However, the forces that drive such lipid transport are not well understood. We propose that lipids tend to flow towards the membrane area with a higher membrane protein density in a process termed lipid osmosis. This process lowers the membrane tension in the area, resulting in a membrane tension difference called osmotic membrane tension. We examine the thermodynamic basis and experimental evidence of lipid osmosis and osmotic membrane tension. We predict that lipid osmosis can drive bulk lipid flows between different membrane regions through lipid transfer proteins, scramblases, or other similar barriers that selectively pass lipids but not membrane proteins. We also speculate on the biological functions of lipid osmosis. Finally, we explore other driving forces for lipid transfer and describe potential methods and systems to further test our theory.

Profiles and transplacental transfer of per- and polyfluoroalkyl substances in maternal and umbilical cord blood: A birth cohort study in Zhoushan, Zhejiang Province, China.

Per- and polyfluoroalkyl substances (PFAS) can pass through the placental barrier and pose health risks to fetuses. However, exposure and transplacental transfer patterns of emerging PFAS remain unclear. Here, 24 PFAS were measured in paired maternal whole blood (n = 228), umbilical cord whole blood (n = 119) and serum (n = 120). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to differentiate PFAS between different matrices. The transplacental transfer (TPT) of PFAS was calculated using cord to maternal whole blood concentration ratios. PFOS and PFOA were still the dominant PFAS in maternal samples. The emerging PFAS had higher TPT than PFOS and PFOA. Moreover, PFAS with the same chain length but different functional groups and C-F bonds showed different TPT, such as PFOS and PFOSA (C8, median: 0.090 vs. 0.305, p < 0.05) and PFHxS and 4:2 FTS (C6, median: 0.220 vs. 1.190, p < 0.05). A significant sex difference in 4:2 FTS (median: boys 1.250, girls 1.010, p < 0.05) were found. Furthermore, we observed a significant U-shaped trend for the TPT of carboxylates with increasing carbon chain length. PFAS showed a compound-specific transfer through placental barrier and a compound-specific distribution between different matrices in this study.

Mesenchymal Stem Cell-Derived Exosomes Promote Recovery of The Facial Nerve Injury through Regulating Macrophage M1 and M2 Polarization by Targeting the P38 MAPK/NF-Κb Pathway.

Facial nerve (FN) injury seriously affects human social viability and causes a heavy economic and social burden. Although mesenchymal stem cell-derived exosomes (MSC-Exos) promise therapeutic benefits for injury repair, there has been no evaluation of the impact of MSC-Exos administration on FN repair. Herein, we explore the function of MSC-Exos in the immunomodulation of macrophages and their effects in repairing FN injury. An ultracentrifugation technique was used to separate exosomes from the MSC supernatant. Administrating MSC-Exos to SD rats via local injection after FN injury promoted axon regeneration and myelination and alleviated local and systemic inflammation. MSC-Exos facilitated M2 polarization and reduced the M1-M2 polarization ratio. miRNA sequencing of MSC-Exos and previous literature showed that the MAPK/NF-κb pathway was a downstream target of macrophage polarization. We confirmed this hypothesis both in vivo and in vitro. Our findings show that MSC-Exos are a potential candidate for treating FN injury because they may have superior benefits for FN injury recovery and can decrease inflammation by controlling the heterogeneity of macrophages, which is regulated by the p38 MAPK/NF-κb pathway.

Study on optimization of layout parameters of high-level boreholes in Pingdingshan coal mine.

To reduce the gas disaster of high gas coal seam and improve the efficiency of gas extraction by high drilling, the layout parameters of drilling holes in Pingdingshan coal mine are optimized. Based on the analysis and calculation of the "three zones" of the movement towards the overly strata of No.10 coal in Pingdingshan coal mine, the height of caving zone and fissure zone in 24,130 working face are 10.06-14.46 m and 38.75-49.95 m respectively. The elevation angle, azimuth angle and the length of high-level boreholes are studied and analyzed by COMSOL numerical simulation software. The simulation results show that the optimum layout parameters of high-level boreholes are as follows: The elevation angle of borehole should be controlled at 9°-12°, the azimuth angle should be 30°-45°, and the length of borehole should be 150 m. Then the optimum layout parameters of high-level boreholes are determined for engineering application of 24,130 working face. Borehole data onto actual mine show that the optimum layout parameters of high-level boreholes were elevation angle between 8°and 11°, azimuth angle between 30° and 42°, and length of boreholes between 145 and 155 m. The simulation results are basically consistent with the measured data. The maximum gas concentration in working face, upper corner and return air roadway is stably controlled below 1%. The safe mining of 24,130 working face is ensured, which provided a certain reference value of gas control in the goaf of Pingdingshan mine and adjacent mines.

Effect of silver sulfadiazine on mature mixed bacterial biofilms on voice prostheses.

BACKGROUND: Biofilm formation on voice prostheses disrupts the function and limits the lifespan of voice prostheses. There is still no effective clinical strategy for inhibiting or removing these biofilms. Silver sulfadiazine (SSD), as an exogenous antibacterial agent, has been widely used in the prevention and treatment of infection, however, its effect on voice prosthesis biofilms is unknown. The purpose of this study was to explore the effect of SSD on the mature mixed bacterial biofilms present on voice prostheses. METHODS: Quantitative and qualitative methods, including the plate counting method, real-time fluorescence quantitative PCR, crystal violet staining, the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) (XTT) reduction assay, scanning electron microscopy, and laser confocal microscopy, were used to determine the effect of SSD on the number of bacterial colonies, biofilm formation ability, metabolic activity, and ultrastructure of biofilms in a mature mixed bacterial (Staphylococcus aureus, Streptococcus faecalis and Candida albicans) voice prosthesis biofilm model. The results were verified in vitro on mature mixed bacterial voice prosthesis biofilms from patients, and the possible mechanism of action was explored. RESULTS: Silver sulfadiazine decreased the number of bacterial colonies on mature mixed bacterial voice prosthesis biofilm, significantly inhibited the biofilm formation ability and metabolic activity of mature voice prosthesis biofilms, inhibited the formation of the complex spatial structure of voice prosthesis biofilms, and inhibited the synthesis of polysaccharides and proteins in the biofilm extracellular matrix. The degree of inhibition and removal effect increased with SSD concentration. CONCLUSIONS: Silver sulfadiazine can effectively inhibit and remove mature mixed bacterial voice prosthesis biofilms and decrease biofilm formation ability and metabolic activity; SSD may exert these effects by inhibiting the synthesis of polysaccharides and proteins among the extracellular polymeric substances of voice prosthesis biofilms.

Prognostic Factors Affecting Hearing in Otitis Media With ANCA-Associated Vasculitis Patients: A Systematic Review and Meta-Analysis.

Objectives: To conduct a systematic review and meta-analysis of clinical studies describing the possible prognostic factors affecting hearing outcomes in Otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) patients. To provide guidance for clinical work, avoiding profound irreversible hearing loss affecting patients' lives. Methods: A literature search was performed in PubMed, MEDLINE, EMBASE, Cochrane, Scopus, and Web of Science to identify English articles published before December 1, 2022. After screening the articles, the Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the extracted literature, and studies with high quality (score > 6) were included. Results: Four studies were included: 1 was a retrospective cohort study, and 3 were case-control studies. We performed a meta-analysis of 4 factors: facial palsy, hypertrophic pachymeningitis, ANCA-negative status, and the period from onset to diagnosis. The results showed that there was a significant association between facial palsy [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.07-2.15; I2 = 0%; P = .02], hypertrophic pachymeningitis (OR 1.73; 95% CI 1.18-2.53; I2 = 24%; P = .005), ANCA negativity (OR 1.75; 95% CI 1.11-2.77; I2 = 33; P = .02), and poor hearing prognosis in OMAAV patients. However, the period from onset to diagnosis (SEM ± SD 2.54; 95% CI -1.56 to 6.64; I2 = 98%; P = .22) of OMAAV was not significantly associated with poor hearing outcomes. Conclusion: We found that OMAAV patients with facial palsy, hypertrophic pachymeningitis, and ANCA negativity have a significant association with poor hearing prognosis, which provides diagnosis and treatment guidance in protecting patients' hearing.

Force redistribution in clathrin-mediated endocytosis revealed by coiled-coil force sensors.

Forces are central to countless cellular processes, yet in vivo force measurement at the molecular scale remains difficult if not impossible. During clathrin-mediated endocytosis, forces produced by the actin cytoskeleton are transmitted to the plasma membrane by a multiprotein coat for membrane deformation. However, the magnitudes of these forces remain unknown. Here, we present new in vivo force sensors that induce protein condensation under force. We measured the forces on the fission yeast Huntingtin-Interacting Protein 1 Related (HIP1R) homolog End4p, a protein that links the membrane to the actin cytoskeleton. End4p is under ~19-piconewton force near the actin cytoskeleton, ~11 piconewtons near the clathrin lattice, and ~9 piconewtons near the plasma membrane. Our results demonstrate that forces are collected and redistributed across the endocytic machinery.

Effect of organic carbon structures on the degradation of nonylphenol by hydrogen peroxide in sediment-water system.

A laboratory experiment is conducted to investigate the effects of organic carbon (OC) from riverine and marine sediments on the degradation of ring-14 C-labeled nonylphenol (14 C-NP) by hydrogen peroxide (H2 O2 ). Researchers have isolated demineralized OC (DM) before and after oxidation, namely, DM and resistant OC (ROC) fractions, respectively. The structures of DM and ROC are characterized using solid-state 13 C nuclear magnetic resonance. Unstable structures (O-alkyl, OCH3 /NCH, and COO/NC=O) show a significant and positive correlation with the degradation of 14 C-NP (R2  > 0.73, p < 0.05), thus suggesting that the NP absorbed in the unstable structures is easily degraded because of the decomposition of unstable components. The stable structures (alkyl C and non-protonated aromatic C [Arom C─C]) exhibit a significant and negative correlation with the degradation of 14 C-NP (R2  > 0.69, p < 0.05), thus suggesting that the NP absorbed and protected in these resistant structures is minimally degraded. The significant correlations among the degradation kinetic parameters (Frap and Fslow ), OC structures (Falip and Farom ), and microporosity further illustrate the important protective roles of OC structures and micropores in the degradation of 14 C-NP by H2 O2 (R2  > 0.69, p < 0.05). The parent NP fraction that desorbed into the aqueous solution or extracted is completely degraded, indicating preferential degradation of the easily desorbed NP. This study provides important insights into the NP degradation mechanism in sediment-water systems, particularly regarding sediment OC structures and microporosity.