Automatic differentiation of ruptured and unruptured intracranial aneurysms on computed tomography angiography based on deep learning and radiomics.

OBJECTIVES: Rupture of intracranial aneurysm is very dangerous, often leading to death and disability. In this study, deep learning and radiomics techniques were used to automatically detect and differentiate ruptured and unruptured intracranial aneurysms. MATERIALS AND METHODS: 363 ruptured aneurysms and 535 unruptured aneurysms from Hospital 1 were included in the training set. 63 ruptured aneurysms and 190 unruptured aneurysms from Hospital 2 were used for independent external testing. Aneurysm detection, segmentation and morphological features extraction were automatically performed with a 3-dimensional convolutional neural network (CNN). Radiomic features were additionally computed via pyradiomics package. After dimensionality reduction, three classification models including support vector machines (SVM), random forests (RF), and multi-layer perceptron (MLP) were established and evaluated via area under the curve (AUC) of receiver operating characteristics. Delong tests were used for the comparison of different models. RESULTS: The 3-dimensional CNN automatically detected, segmented aneurysms and calculated 21 morphological features for each aneurysm. The pyradiomics provided 14 radiomics features. After dimensionality reduction, 13 features were found associated with aneurysm rupture. The AUCs of SVM, RF and MLP on the training dataset and external testing dataset were 0.86, 0.85, 0.90 and 0.85, 0.88, 0.86, respectively, for the discrimination of ruptured and unruptured intracranial aneurysms. Delong tests showed that there was no significant difference among the three models. CONCLUSIONS: In this study, three classification models were established to distinguish ruptured and unruptured aneurysms accurately. The aneurysms segmentation and morphological measurements were performed automatically, which greatly improved the clinical efficiency. CLINICAL RELEVANCE STATEMENT: Our fully automatic models could rapidly process the CTA data and evaluate the status of aneurysms in one minute.

Sex differences in the association between suicidal ideation and neurocognitive function in Chinese patients with schizophrenia.

There is increasing evidence that sex differences exist in many clinical manifestations of patients with schizophrenia, including suicidal ideation (SI) and neurocognitive function. The present study was performed to explore the sex differences in the association between SI and neurocognitive function in Chinese patients with schizophrenia. A total of 1188 inpatients with schizophrenia were recruited from multicenter psychiatric hospitals. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was utilized to evaluate the neurocognitive function of all patients. The Positive and Negative Syndrome Scale (PANSS) was utilized to assess the psychopathology of patients. The Beck Scale for Suicide Ideation (BSSI) was used to assess the severity of SI. In male patients, the suicide risk score was significantly associated with PANSS negative symptoms (r = 0.167, p = 0.043), visuospatial subscale (r = - 0.261, p = 0.001), and RBANS total scores (r = - 0.172, p = 0.037). Furthermore, multivariate linear regression analysis showed that the visuospatial subscale (ß = - 0.490, t = - 3.273, p = 0.001) was independently associated with the suicide risk score in male patients. In female patients, the suicide risk score was significantly correlated with PANSS positive symptoms (r = 0.249, p = 0.021), negative symptoms (r = 0.394, p < 0.001), general psychopathology (r = 0.276, p = 0.01) and PANSS total score (r = 0.365, p = 0.001). Multivariate linear regression analysis showed that PANSS negative symptoms (ß = 1.849, t = 3.933, p = 0.001) were significantly associated with suicide risk scores in female patients. Our findings indicate that there are sex differences in the association between SI and neurocognitive function in patients with schizophrenia. Based on the findings of our study, gender-specific prevention and intervention strategies may make a difference in reducing SI in Chinese schizophrenia patients.

Integrated bulk and single-cell RNA-sequencing reveals SPOCK2 as a novel biomarker gene in the development of congenital pulmonary airway malformation.

BACKGROUND: Congenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM. METHODS: Tissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM. RESULTS: In total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11, and ZNF331 were highlighted in CPAM. CONCLUSIONS: Through our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM.

Transcriptomic profiling revealed important roles of amino acid metabolism in fruiting body formation at different ripening times in Hypsizygus marmoreus.

Introduction: Hypsizygus marmoreus is an industrial mushroom that is widely cultivated in East Asia. Its long postripening stage before fruiting severely limits its industrialized production. Methods: Five different mycelial ripening times (30, 50, 70, 90, and 100 d) were chosen and primordia (30P, 50P, 70P, 90P, and 110P) were collected for comparative transcriptomic analyses. The corresponding substrates (30F, 50F, 70F, 90F, and 110F) were used for nutrient content and enzyme activity determination. Results: In pairwise comparisons between 110P and other primordia, a total of 1,194, 977, 773, and 697 differentially expressed genes (DEGs) were identified in 30P_110P, 50P_110P, 70P_110P, and 90P_110P, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) functional enrichment analyses revealed that the DEGs were mainly associated with amino acid metabolism, and lipid and carbohydrate metabolism pathways. Tyrosine, tryptophan, phenylalanine and histidine metabolism were enriched in all groups. Among the main carbon nutrients, the contents of cellulose and hemicellulose were high, and the lignin content decreased with the extension of the ripening time. Laccase had the highest activity, and acid protease activity decreased with the extension of the ripening time. Discussion: The highly enrichment for amino acid metabolic pathways in primordia reveals that these pathways are essential for fruiting body formation in H. marmoreus, and these results will provide a basis for the optimization of its cultivation.

Prioritization of potential causative genes for schizophrenia in placenta.

Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits. The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness. These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies. Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone.

Improved diagnostic yield of symptom association probability involving only cough for gastroesophageal reflux-induced chronic cough.

Background: Use of symptom association probability (SAP) is recommended for identifying gastroesophageal reflux-induced chronic cough (GERC). This study aimed to compare the diagnostic yield of SAPs involving only cough (C-SAP) or total symptoms (T-SAP) for GERC identification. Methods: Patients with both chronic cough and other reflux-related symptoms underwent multichannel intraluminal impedance-pH monitoring (MII-pH) between January 2017 and May 2021. C-SAP and T-SAP were calculated based on the patient-reported symptoms. GERC was definitively diagnosed by the favorable response to anti-reflux therapy. The diagnostic yield of C-SAP in identifying GERC was evaluated by receiver operating characteristic curve analysis and compared with that of T-SAP. Results: MII-pH was performed in 105 patients with chronic cough, and GERC was confirmed in 65 (61.9%), including 27 (41.5%) cases of acid GERC and 38 (58.5%) cases of non-acid GERC. The positive rates of C-SAP and T-SAP were comparable (34.3% vs. 23.8%, P>0.05), but C-SAP exhibited a higher sensitivity (53.85% vs. 33.85%, χ2=8.117, P=0.004) and similar high specificities (97.5% vs. 92.5%, P>0.05) compared with T-SAP for GERC identification. C-SAP was also more sensitive for recognition of acid GERC (51.85% vs. 33.33%, χ2=7.386, P=0.007) and non-acid GERC (65.79% vs. 39.47%, χ2=14.617, P<0.001). More GERC patients with positive C-SAP needed intensified anti-reflux therapy for cough resolution when compared with those with negative C-SAP (82.9% vs. 46.7%, χ2=9.449, P=0.002). Conclusions: C-SAP was superior to T-SAP for the identification of GERC and may improve the diagnostic yield of GERC.

ß,ß-Directly Linked Porphyrin Rings: Synthesis, Photophysical Properties, and Fullerene Binding.

Cyclic porphyrin oligomers have been studied as models for photosynthetic light-harvesting antenna complexes and as potential receptors for supramolecular chemistry. Here, we report the synthesis of unprecedented ß,ß-directly linked cyclic zinc porphyrin oligomers, the trimer (CP3) and tetramer (CP4), by Yamamoto coupling of a 2,3-dibromoporphyrin precursor. Their three-dimensional structures were confirmed by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and single-crystal X-ray diffraction analyses. The minimum-energy geometries of CP3 and CP4 have propeller and saddle shapes, respectively, as calculated using density functional theory. Their different geometries result in distinct photophysical and electrochemical properties. The smaller dihedral angles between the porphyrin units in CP3, compared with CP4, result in stronger π-conjugation, splitting the ultraviolet-vis absorption bands and shifting them to longer wavelengths. Analysis of the crystallographic bond lengths indicates that the central benzene ring of the CP3 is partially aromatic [harmonic oscillator model of aromaticity (HOMA) 0.52], whereas the central cyclooctatetraene ring of the CP4 is non-aromatic (HOMA -0.02). The saddle-shaped structure of CP4 makes it a ditopic receptor for fullerenes, with affinity constants of (1.1 ± 0.4) × 105 M-1 for C70 and (2.2 ± 0.1) × 104 M-1 for C60, respectively, in toluene solution at 298 K. The formation of a 1:2 complex with C60 is confirmed by NMR titration and single-crystal X-ray diffraction.

Effects of brief exposure to campus environment on students' physiological and psychological health.

Experiences in natural environments can enhance human wellbeing and promote the recovery of physiological and psychological health. During the COVID-19 pandemic, university students' activity off-campus was limited, thus, the campus environment was particularly important for the recovery of students' physiological and psychological health. Although the benefits of sustained natural exposure are obvious for people's physiological and psychological health, the effects of brief exposure on physiological and psychological are unclear. In the present study, four types of campus environments, including square space, dense forest space, sparse forest space, and waterfront space, were selected to explore the transient recovery effects of different types of campus environments. Sixty university students were recruited, measuring their systolic blood pressure, diastolic blood pressure, and heart rate as physical parameters to assess stress recovery. Respondents also reported scores about their personal feelings in questionnaires to evaluate their psychological states. Both physiological and psychological indicators responded to the brief natural exposure (5 min), and physiological and psychological health was restored. However, only the recovery amounts of psychological indicators were significantly different in waterfront space, dense forest space, and sparse forest space. These results indicate that being compare with other spaces, the brief exposure in the waterfront space was the most beneficial to students' psychological health recovery. This recovery was attributed to the great role played by the sense of escape, but after the brief exposure, the attraction and compatibility of the environment would hinder the psychological health recovery. In conclusion, according to tests on both physiological and psychological aspects, the waterfront environment on campus is the best choice for students' transient health recovery.

Recent Progress in the Application of Metal Organic Frameworks in Surface-Enhanced Raman Scattering Detection.

Metal-organic framework (MOF) compounds are centered on metal ions or metal ion clusters, forming lattices with a highly ordered periodic porous network structure by connecting organic ligands. As MOFs have the advantages of high porosity, large specific surface area, controllable pore size, etc., they are widely used in gas storage, catalysis, adsorption, separation and other fields. SERS substrate based on MOFs can not only improve the sensitivity of SERS analysis but also solve the problem of easy aggregation of substrate nanoparticles. By combining MOFs with SERS, SERS performance is further improved, and tremendous research progress has been made in recent years. In this review, three methods of preparing MOF-based SERS substrates are introduced, and the latest applications of MOF-based SERS substrates in biosensors, the environment, gases and medical treatments are discussed. Finally, the current status and prospects of MOF-based SERS analysis are summarized.

Potential Effects of High Temperature and Heat Wave on Nanorana pleskei Based on Transcriptomic Analysis.

In the context of climate change, understanding how indigenous amphibians of the Qinghai-Tibet plateau react to stresses and their coping mechanisms could be crucial for predicting their fate and successful conservation. A liver transcriptome for Nanorana pleskei was constructed using high-throughput RNA sequencing, and its gene expression was compared with frogs acclimated under either room temperature or high temperature and also heat wave exposed ones. A total of 126,465 unigenes were produced, with 66,924 (52.92%) of them being annotated. Up to 694 genes were found to be differently regulated as a result of abnormal temperature acclimatization. Notably, genes belonging to the heat shock protein (HSP) family were down-regulated in both treated groups. Long-term exposure to high-temperature stress may impair the metabolic rate of the frog and trigger the body to maintain a hypometabolic state in an effort to survive challenging times. During heat waves, unlike the high-temperature group, mitochondrial function was not impaired, and the energy supply was largely normal to support the highly energy-consuming metabolic processes. Genes were more transcriptionally suppressed when treated with high temperatures than heat waves, and the body stayed in low-energy states for combating these long-term adverse environments to survive. It might be strategic to preserve initiation to executive protein activity under heat wave stress. Under both stress conditions, compromising the protection of HSP and sluggish steroid activity occurred in frogs. Frogs were more affected by high temperatures than by heat waves.

Self-Immolative Photosensitizers for Self-Reported Cancer Phototheranostics.

Photosensitizers to precise target and change fluorescence upon light illumination could accurately self-report where and when the photosensitizers work, enabling us to visualize the therapeutic process and precisely regulate treatment outcomes, which is the unremitting pursuit of precision and personalized medicine. Here, we report self-immolative photosensitizers by adopting a strategy of light-manipulated oxidative cleavage of C═C bonds that can generate a burst of reactive oxygen species, to cleave to release self-reported red-emitting products and trigger nonapoptotic cell oncosis. Strong electron-withdrawing groups are found to effectively suppress the C═C bond cleavage and phototoxicity via studying the structure-activity relationship, allowing us to elaborate NG1-NG5 that could temporarily inactivate the photosensitizer and quench the fluorescence by different glutathione (GSH)-responsive groups. Thereinto, NG2 with 2-cyano-4-nitrobenzene-1-sulfonyl group displays excellent GSH responsiveness than the other four. Surprisingly, NG2 shows better reactivity with GSH in weakly acidic condition, which inspires the application in weakly acidic tumor microenvironment where GSH elevates. To this end, we further synthesize NG-cRGD by anchoring integrin αvß3 binding cyclic pentapeptide (cRGD) for tumor targeting. In A549 xenografted tumor mice, NG-cRGD successfully deprotects to restore near-infrared fluorescence because of elevated GSH in tumor site, which is subsequently cleaved upon light irradiation releasing red-emitting products to report photosensitizer working, while effectively ablating tumors via triggered oncosis. The advanced self-immolative organic photosensitizer may accelerate the development of self-reported phototheranostics in future precision oncology.

Efficient CRISPR/Cas9-mediated gene editing in mammalian cells by the novel selectable traffic light reporters.

CRISPR/Cas9 is a powerful tool for gene editing in various cell types and organisms. However, it is still challenging to screen genetically modified cells from an excess of unmodified cells. Our previous studies demonstrated that surrogate reporters can be used for efficient screening of genetically modified cells. Here, we developed two novel traffic light screening reporters, puromycin-mCherry-EGFP (PMG) based on single-strand annealing (SSA) and homology-directed repair (HDR), respectively, to measure the nuclease cleavage activity within transfected cells and to select genetically modified cells. We found that the two reporters could be self-repaired coupling the genome editing events driven by different CRISPR/Cas nucleases, resulting in a functional puromycin-resistance and EGFP selection cassette that can be afforded to screen genetically modified cells by puromycin selection or FACS enrichment. We further compared the novel reporters with different traditional reporters at several endogenous loci in different cell lines, for the enrichment efficiencies of genetically modified cells. The results indicated that the SSA-PMG reporter exhibited improvements in enriching gene knockout cells, while the HDR-PMG system was very useful in enriching knock-in cells. These results provide robust and efficient surrogate reporters for the enrichment of CRISPR/Cas9-mediated editing in mammalian cells, thereby advancing basic and applied research.

PD-L1 exosomes electrochemical sensor based on coordination of AgNCs and Zr4+: Multivalent peptide enhancing target capture efficiency and antifouling performance.

Programmed death ligand 1 (PD-L1) exosomes are important biomarkers of immune activation in the initial stages of treatment and can predict clinical responses to PD-1 blockade in various cancer patients. However, traditional PD-L1 exosome bioassays face challenges such as high interface fouling in complex detection environments, limited detection specificity, and poor clinical serum applicability. Inspired by the multi-branched structure of trees, a biomimetic tree-like multifunctional antifouling peptide (TMAP)-assisted electrochemical sensor was developed for high-sensitivity exosomes detection. Multivalent interaction of TMAP significantly enhances the binding affinity of PD-L1 exosomes, thanks to the designed branch antifouling sequence, TMAPs antifouling performance is further improved. The addition of Zr4+ forms coordination bonds with the exosome's lipid bilayer phosphate groups to achieve highly selective and stable binding without interference from protein activity. The specific coordination between AgNCs and Zr4+ contributes to a dramatic change in the electrochemical signals, and lowing detection limit. The designed electrochemical sensor exhibited excellent selectivity and a wide dynamic response within the PD-L1 exosome concentration range from 78 to 7.8 × 107 particles/mL. Overall, the multivalent binding ability of TMAP and the signal amplification characteristics of AgNCs have a certain driving role in achieving clinical detection of exosomes.

In-situ construction of Cr2O3@ATO hybrid pigment towards synergetic enhancement of visible light-infrared-radar compatible stealth.

Multiband compatible stealth engineering with controllable visible light-infrared (VIS-IR) features and radar wave absorption is urgently needed to improve the survivability of advanced military equipment. Cr2O3 has good visible light stealth performance under green background, but it is lack of IR and radar multi-band stealth properties. Herein, a core-shelled Cr2O3@stannic antimony oxide (ATO) structure was developed to enhance the IR-radar compatible stealth properties of Cr2O3 by in-situ precipitation method, concurrently maintaining its visible light stealth property. The morphology, conductivity, and infrared stealth properties of the Cr2O3@ATO hybrids were influenced by the calcination temperature, and the IR and radar stealth performance were tunable by ATO content. The lowest emissivity of Cr2O3@ATO pigments is 0.852, reduced by 10% than pure Cr2O3. The Cr2O3@ATO filled silicone resin coatings possessed good thermal stability and IR stealth stability. Benefiting from the enhanced interfacial polarization and conductive loss, the Cr2O3@ATO exhibited an effective absorption bandwidth of 2 GHz in the X band, with respect to pure Cr2O3 without radar absorption property. The Cr2O3@ATO structure opens an avenue for advanced VIS-IR-Radar compatible stealth materials.

Coalescence of As(II) with •OH: The pivot for co-processing of As(III) and butyl xanthate.

Although water metalloid pollution is widely studied, the effect of the combined pollution of organic matter and metalloids in mining water and, especially, the possible interaction mechanisms between metalloids and flotation reagents, are both poorly understood. Existence of mixed pollution of metalloids and organic compounds tends to cause more serious harm to natural organisms. In this study, a synergistic removal of arsenite (As(III)) and butyl xanthate (Bx) in an advanced oxidation system was reported using biochar-based catalyst loaded with nano-zero-valent iron from an inexpensive iron source (iron slag) to activate peroxodisulfate. The removal efficiencies were improved by 30 % in the co-existence of As(III) and Bx compared to those of the single pollutant. The theoretical calculations, especially frontier molecular orbital theory, revealed the generation of [AsO2-OH]•- by the combination of As(II) with •OH. This [AsO2-OH]•- participated in the oxidative degradation of Bx with high activity and combined with the sulfur falling off Bx after the reaction to form a novel Fe-As-S complex as indicated by X-ray absorption +fine structure analysis. Overall, this study reports the generation of low-valent arsenic active substances of [AsO2-OH]•- and their effect on the removal of organic pollution containing S atoms in advanced oxidation systems under typical mining water conditions with the coexistence of As(III) and expands the understanding and application of traditional free radicals.

Sternal Pin Used to Close Sternum in Infants after Cardiac Surgery.

OBJECTIVE: A retrospective study was conducted to explore the efficacy of bioabsorbable poly-L-lactic acid sternal pins in sternal closure in infants after cardiac surgery. METHODS: A total of 170 infantile patients who underwent cardiac surgery were divided into the steel wire group (group A), the PDS cord group (group B), and the steel wire + sternal pin group (group C). The occurrence of the thoracic deformity was evaluated by vertebral index (VI), frontosagittal index (FSI), and Haller index (HI) values; the stability of the sternum was evaluated by detecting sternal dehiscence and displacement. RESULTS: By comparing the absolute values of the differences in VI, FSI, and HI in the three groups, it was found that the difference values of VI and HI in group C were significantly lower than those in group B (p = 0.028 and 0.005). For the highest deformation index, the deformation rate of infants in group C before discharge and during the 1-year follow-up was lower than that in group A and group B (p = 0.009 and 0.002, respectively). The incidence of sternal displacement in group C was also significantly lower than that in groups A and B (p = 0.009 and 0.009). During the 1-year follow-up, there was no sternal dehiscence, and the sternum healed completely in the three groups. CONCLUSION: The use of "steel wire + sternal pin" for sternal closure in infants after cardiac surgery can reduce the occurrence of sternal deformity, reduce anterior and posterior displacement of the sternum, and improve sternal stability.

Structural basis for the self-recognition of sDSCAM in Chelicerata.

To create a functional neural circuit, neurons develop a molecular identity to discriminate self from non-self. The invertebrate Dscam family and vertebrate Pcdh family are implicated in determining synaptic specificity. Recently identified in Chelicerata, a shortened Dscam (sDscam) has been shown to resemble the isoform-generating characters of both Dscam and Pcdh and represent an evolutionary transition. Here we presented the molecular details of sDscam self-recognition via both trans and cis interactions using X-ray crystallographic data and functional assays. Based on our results, we proposed a molecular zipper model for the assemblies of sDscam to mediate cell-cell recognition. In this model, sDscam utilized FNIII domain to form side-by-side interactions with neighboring molecules in the same cell while established hand-in-hand interactions via Ig1 domain with molecules from another cell around. Together, our study provided a framework for understanding the assembly, recognition, and evolution of sDscam.

Performance of Thermal-Oxidative Aging on the Structure and Properties of Ethylene Propylene Diene Monomer (EPDM) Vulcanizates.

A thermal-oxidative aging test at 120 °C was conducted on ethylene propylene diene monomer (EPDM) vulcanizates of the semi-efficient vulcanization system. The effect of thermal-oxidative aging on EPDM vulcanizates was systematically studied by curing kinetics, aging coefficient, crosslinking density, macroscopic physical properties, contact angle, Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric analysis (TGA) and thermal decomposition kinetics. The results show that the content of hydroxyl and carbonyl groups as well as the carbonyl index increased with increasing aging time, indicating that EPDM vulcanizates were gradually oxidized and degraded. As a result, the EPDM vulcanized rubber chains were crosslinked with limited conformational transformation and weakened flexibility. The thermogravimetric analysis demonstrates that the thermal degradation of EPDM vulcanizates had competitive reactions of crosslinking and degradation, and the thermal decomposition curve can be divided into three stages; meanwhile, the thermal stability of EPDM vulcanizates gradually decreased with increasing aging time. The introduction of antioxidants in the system can promote the crosslinking speed and reduce the crosslinking density of EPDM vulcanizates while inhibiting the surface thermal and oxygen aging reaction. This was attributed to the fact that the antioxidant can reduce the thermal degradation reaction level, but it is not conducive to the formation of a perfect crosslinking network structure and reduces the activation energy of thermal degradation of the main chain.

A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics.

Antibody-dependent enhancement of infection (ADE) is clinically relevant to Dengue virus (DENV) infection and poses a major risk to the application of monoclonal antibody (mAb)-based therapeutics against related flaviviruses such as the Zika virus (ZIKV). Here, we tested a two-tier approach for selecting non-cross-reactive mAbs combined with modulating Fc glycosylation as a strategy to doubly secure the elimination of ADE while preserving Fc effector functions. To this end, we selected a ZIKV-specific mAb (ZV54) and generated three ZV54 variants using Chinese hamster ovary cells and wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants as production hosts (ZV54CHO, ZV54WT, and ZV54ΔXF). The three ZV54 variants shared an identical polypeptide backbone, but each exhibited a distinct Fc N-glycosylation profile. All three ZV54 variants showed similar neutralization potency against ZIKV but no ADE activity for DENV infection, validating the importance of selecting the virus/serotype-specific mAbs for avoiding ADE by related flaviviruses. For ZIKV infection, however, ZV54CHO and ZV54ΔXF showed significant ADE activity while ZV54WT completely forwent ADE, suggesting that Fc glycan modulation may yield mAb glycoforms that abrogate ADE even for homologous viruses. In contrast to the current strategies for Fc mutations that abrogate all effector functions along with ADE, our approach allowed the preservation of effector functions as all ZV54 glycovariants retained antibody-dependent cellular cytotoxicity (ADCC) against the ZIKV-infected cells. Furthermore, the ADE-free ZV54WT demonstrated in vivo efficacy in a ZIKV-infection mouse model. Collectively, our study provides further support for the hypothesis that antibody-viral surface antigen and Fc-mediated host cell interactions are both prerequisites for ADE, and that a dual-approach strategy, as shown herein, contributes to the development of highly safe and efficacious anti-ZIKV mAb therapeutics. Our findings may be impactful to other ADE-prone viruses, including SARS-CoV-2.

Ligamentum teres hepatis as a graft for portal and/or superior mesenteric vein reconstruction: From bench to bedside.

BACKGROUND: Pancreaticoduodenectomy combined with portal vein (PV) and/or superior mesenteric vein (SMV) resection in patients with pancreaticobiliary malignancy has become a common surgical procedure. There are various grafts currently used for PV and/or SMV reconstruction, but each of these grafts have certain limitations. Therefore, it is necessary to explore novel grafts that have an extensive resource pool, are low cost with good clinical application, and are without immune response rejection or additional damage to patients. AIM: To observe the anatomical and histological characteristics of the ligamentum teres hepatis (LTH) and evaluate PV/SMV reconstruction using an autologous LTH graft in pancreaticobiliary malignancy patients. METHODS: In 107 patients, the post-dilated length and diameter in resected LTH specimens were measured. The general structure of the LTH specimens was observed by hematoxylin and eosin (HE) staining. Collagen fibers (CFs), elastic fibers (EFs), and smooth muscle (SM) were visualized by Verhoeff-Van Gieson staining, and the expression of CD34, factor VIII-related antigen (FVIIIAg), endothelial nitric oxide synthase (eNOS), and tissue type plasminogen activator (t-PA) were detected using immunohistochemistry in LTH and PV (control) endothelial cells. PV and/or SMV reconstruction using the autologous LTH was conducted in 26 patients with pancreaticobiliary malignancies, and the outcomes were retrospectively analyzed. RESULTS: The post-dilated length of LTH was 9.67 ± 1.43 cm, and the diameter at a pressure of 30 cm H2O was 12.82 ± 1.32 mm at the cranial end and 7.06 ± 1.88 mm at the caudal end. Residual cavities with smooth tunica intima covered by endothelial cells were found in HE-stained LTH specimens. The relative amounts of EFs, CFs and SM in the LTH were similar to those in the PV [EF (%): 11.23 ± 3.40 vs 11.57 ± 2.80, P = 0.62; CF (%): 33.51 ± 7.71 vs 32.11 ± 4.82, P = 0.33; SM (%): 15.61 ± 5.26 vs 16.74 ± 4.83, P = 0.32]. CD34, FVIIIAg, eNOS, and t-PA were expressed in both LTH and PV endothelial cells. The PV and/or SMV reconstructions were successfully completed in all patients. The overall morbidity and mortality rates were 38.46% and 7.69%, respectively. There were no graft-related complications. The postoperative vein stenosis rates at 2 wk, 1 mo, 3 mo and 1 year were 7.69%, 11.54%, 15.38% and 19.23%, respectively. In all 5 patients affected, the degree of vascular stenosis was less than half of the reconstructed vein lumen diameter (mild stenosis), and the vessels remained patent. CONCLUSION: The anatomical and histological characteristics of LTH were similar to the PV and SMV. As such, the LTH can be used as an autologous graft for PV and/or SMV reconstruction in pancreaticobiliary malignancy patients who require PV and/or SMV resection.