Application of Epithelial Growth Factor Receptor-Targeted Magnetic Resonance Imaging and Near-Infrared II Dual-Modal Probe in Lung Cancer Diagnosis and Surgical Resection.

There has been an increase in the use of molecular probe diagnostic techniques for lung cancer, and magnetic resonance imaging (MRI) offers specific advantages for diagnosing pulmonary carcinoma. Furthermore, advancements in near-infrared II (NIR-II) fluorescence have provided a new method for precise intraoperative tumor resection. However, few probes combine preoperative diagnosis with intraoperative imaging. This study aims to fill this research void by employing a dual-modal probe that targets the epidermal growth factor receptor for MR and NIR-II imaging, enabling the preoperative diagnosis of lung cancer using MRI and precise intraoperative tumor localization using NIR-II with a single probe. The imaging effects and targeting ability of the probe were confirmed in cell lines, mouse models, and clinical samples. The MR signal decreased within 24 h in the patient-derived xenograft mouse model. The average signal-to-background ratio of NIR-II reached 3.98 ± 0.27. The clinical sample also showed a decrease in the T2 signal using MRI, and the NIR-II optical signal-to-background ratio was 3.29. It is expected that this probe can improve the diagnostic rate of lung cancer using MRI and enable precise intraoperative tumor resection using NIR-II.

Flow-diverter stents in intracranial aneurysm treatment: impact on covered cerebral artery branches.

OBJECTIVE: Flow diverter stents (FDSs) have attracted interest for intracranial aneurysm (IA) treatment; however, occlusion of side branches and related complications have been reported. This study aimed to investigate the effects of FDSs in IA management when different branches of intracranial arteries are covered. MATERIALS AND METHODS: A cross-sectional study was conducted using PUBMED, Embase, Web of Science, and Cochrane databases to include randomized or nonrandomized comparative-designed studies from January 2000 to August 2022 which reported outcomes of occlusion/narrowing of branches after IA treatment using FDSs. The PRISMA guidelines were used for our report. A random-effects meta-analysis was conducted to pool the outcomes, which included incidence rates of occlusion/narrowing of FDS-covered branches, branch occlusion-related symptoms, obliteration of IAs, and ideal clinical outcomes (modified Rankin Scale score ≤2). RESULTS: The authors identified 57 studies involving 3789 patients with IA managed by FDSs covering different branches. During the median imaging follow-up at 12 months, the IA obliteration rate was satisfactory (>70%) when covering the ophthalmic artery (OA), posterior communicating artery (PComA), anterior choroidal artery (AChoA) or anterior cerebral artery (ACA), but not the middle cerebral artery-M2 segment (MCA-M2; 69.5%; 95% CI: 60.8-77.5%) and posterior inferior cerebellar artery (PICA; 59.1%, 13/22). The overall ideal clinical outcome was observed in 97.4% of patients (95% CI: 95.5-98.9%). Higher rates of occlusion/narrowing of branches were identified when FDSs covered the ACA (66.6%; 95% CI: 45.1-85.3%), PComA (44.3%; 95% CI: 34.2-54.6%), or MCA-M2 (39.2%; 95% CI: 24.5-54.7%); the risks were lower when covering the OA (11.8%; 95% CI: 8.8-15.1%), PICA (6.8%; 95% CI: 1.5-14.5%), and AchoA (0.5%; 95% CI: 0.0-2.9%). The risk of branch occlusion-related complications was low (incidence rate <5%) for each of the six evaluated branches. CONCLUSIONS: Acceptable outcomes were identified following treatment of IAs when FDSs were placed across each of the six studied cerebral arteries. Treatment decisions regarding FDS placement across branch arteries should be made with the risk of complications from branch occlusion in mind.

Transcriptome and metabolomics analysis of adaptive mechanism of Chinese mitten crab (Eriocheir sinensis) to aflatoxin B1.

Aflatoxin B1 (AFB1), with the strong toxicity and carcinogenicity, has been reported to great toxicity to the liver and other organs of animals. It cause huge economic losses to breeding industry, including the aquaculture industry. Chinese mitten crabs (Eriocheir sinensis), as one of important species of freshwater aquaculture in China, are deeply disturbed by it. However, the molecular and metabolic mechanisms of hepatopancreas and ovary in crabs underlying coping ability are still unclear. Hence, we conducted targeted injection experiment with or without AFB1, and comprehensively analyzed transcriptome and metabolomics of hepatopancreas and ovary. As a result, 210 and 250 DEGs were identified in the L-C vs. L-30 m and L-C vs. L-60 m comparison, among which 14 common DEGs were related to six major functional categories, including antibacterial and detoxification, ATP energy reaction, redox reaction, nerve reaction, liver injury repair and immune reaction. A total of 228 and 401 DAMs in the ML-C vs. ML-30 m and ML-C vs. ML-60 m comparison both enriched 12 pathways, with clear functions of cutin, suberine and wax biosynthesis, tyrosine metabolism, purine metabolism, nucleotide metabolism, glycine, serine and threonine metabolism, ABC transporters and tryptophan metabolism. Integrated analysis of metabolomics and transcriptome in hepatopancreas discovered three Co-enriched pathways, including steroid biosynthesis, glycine, serine and threonine metabolism, and sphingolipid metabolism. In summary, the expression levels and functions of related genes and metabolites reveal the regulatory mechanism of Chinese mitten crab (Eriocheir sinensis) adaptability to the Aflatoxin B1, and the findings contribute to a new perspective for understanding Aflatoxin B1 and provide some ideas for dealing with it.

Oblique lateral internal fusion combined with percutaneous pedicle screw fixation in severe lumbar spinal stenosis: clinical and radiographic outcome.

BACKGROUND: Oblique lumbar interbody fusion (OLIF) has been a popular technique for treating lumbar degenerative diseases. Previous studies have shown its efficiency in lumbar spinal stenosis; yet, only a few studies have investigated its application to severe lumbar spinal stenosis. Herein, we investigated the clinical and radiographic outcome of OLIF with percutaneous pedicle screws in the treatment of severe lumbar spinal stenosis. METHODS: A total of 15 patients who underwent OLIF with percutaneous pedicle screws were retrospectively analysed. All patients were diagnosed with severe lumbar stenosis (Schizas grade C or D) through preoperative magnetic resonance image (MRI) and received OLIF combined with percutaneous pedicle screw surgery. Clinical outcomes, including visual analogue scale (VAS)-back and VAS-leg scores, and Oswestry Disability Index (ODI), as well as mean disc height (DH), mean foraminal height (FH), segmental lumbar lordosis (SLL) and cross-sectional area (CSA) of the spinal canal, were analysed before and after surgery and at the last follow-up. Intraoperative data, complications and fusion rate were also investigated. RESULTS: OLIF combined with percutaneous pedicle screws was performed on 18 segments in 15 patients. Mean follow-up was 23.1 ± 4.6 months (range 15-29 months). VAS-back, VAS-leg, and ODI scores were significantly improved at the last follow-up. DH increased from 8.86 ± 3.06 mm before surgery to 13.31 ± 2.14 mm after; at the last follow-up, DH was 11.69 ± 1.87 mm. FH increased from 17.85 ± 2.26 mm before surgery to 22.09 ± 1.36 mm after; at the last follow-up, FH was 20.41 ± 0.99 mm. CSA of the spinal canal increased from 30.83 ± 21.15 mm2 before surgery to 74.99 ± 33.65 mm2 after the operation and 81.22 ± 35.53 mm2 at the last follow-up. The segmental LL before surgery, after surgery and at last follow-up was 20.27 ± 6.25 degrees, 20.83 ± 6.52 degrees and 19.75 ± 5.87 degrees, respectively. All patients have gained fusion at the last follow-up. CONCLUSION: OLIF with percutaneous pedicle screws could achieve satisfactory clinical and radiographic effects through indirect compression by increasing DH, FH and CSA of the spinal canal in severe lumbar stenosis patients.

Effects of 24-Epibrassinolide, melatonin and their combined effect on cadmium tolerance in Primula forbesii Franch.

This study aimed to investigate the interaction between 24-Epibrassinolide (EBR) and melatonin (MT) and their effects on cadmium (Cd)-stressed Primula forbesii Franch. P. forbesii seedlings were hydroponically acclimatized at 6-7 weeks, then treated with Cd (200 µmol L-1), 24-EBR (0.1 µmol L-1), and MT (100 µmol L-1) after two weeks. Cd stress significantly reduced crown width, shoot, root length, shoot fresh weight, and fresh and dry root weights. Herein, 24-EBR, MT, and 24-EBR+MT treatments attenuated the growth inhibition caused by Cd stress and improved the morphology, growth indexes, and ornamental characteristics of P. forbesii under Cd stress. 24-EBR had the best effect by effectively alleviating Cd stress and promoting plant growth and development. 24-EBR significantly increased all growth parameters compared to Cd treatment. In addition, 24-EBR significantly improved the gas exchange parameters, activities of antioxidant enzymes, and the cycle efficiency of AsA-GSH. Furthermore, 24-EBR increased the activities of ascorbate peroxidase (APX), glutathione reductase (GR), dehydroascorbate reductase (DHAR), and monodehydroascorbate reductase (MDHAR) by 127.29%, 61.31%, 61.22%, and 51.04%, respectively, compared with the Cd treatment. Therefore, 24-EBR removed the reactive oxygen species produced by stress, thus protecting plants against stress damage. These results indicate that 24-EBR can effectively enhance the tolerance of P. forbesii to Cd stress.

Comparison of total corneal power measurements obtained with different devices after myopic keratorefractive surgery.

AIM: To analyze the differences, agreements, and correlation among total corneal power parameters generated by different instruments after myopic keratorefractive surgery. METHODS: The prospective cross-sectional study included patients who underwent myopic keratorefractive surgery and received measurements of corneal power 3mo after surgery. Automated keratometer was used for the measurement of simulated keratometry (SimK), swept-source optical coherence tomography (SS-OCT) based biometer for total keratometry (TK), anterior segment-OCT for real keratometry (RK), and Scheimpflug keratometer for the true net power (TNP), the total corneal refractive power (TCRP) and equivalent K-readings (EKR). The differences among these parameters were analyzed, and the agreements and correlation between SimK and other total corneal power parameters were investigated. RESULTS: A total of 70 eyes of 70 patients after myopic keratorefractive surgery were included. The evaluated corneal power parameters were as follows: SimK 38.32±1.93 D, TK 37.54±2.12 D, RK 36.64±2.09 D, TNP 36.56±1.97 D, TCRP 36.70±2.01 D, and EKR 37.55±2.00 D. Pairwise comparison showed that there were significant differences (P<0.001) among all parameters except for between TK and EKR, RK and TNP, RK and TCRP (P=1.000, 1.000, 1.000, respectively). The limits of agreement between SimK and TK, RK, TNP, TCPR, and EKR were 1.08, 1.08, 1.43, 1.48, and 1.73 D, respectively. All parameters showed good correlation with SimK, and the correlation coefficients were 0.995, 0.994, 0.983, 0.982, and 0.975. CONCLUSION: Among the corneal power parameters after myopic keratorefractive surgery, the value of SimK is the largest, followed by TK and EKR, with TCRP, RK, and TNP being the smallest. The differences among the parameters may be attributable to the different calculation principles. Correct understanding and evaluation of corneal power parameters can provide a theoretical basis for taking advantage of the total corneal power to improve the accuracy of intraocular lens calculation after keratorefractive surgery.

Comparative analysis of ultrasonic elastosonography and contrast-enhanced ultrasonography in the diagnosis of benign and malignant intraocular tumors.

PURPOSE: To compare the diagnostic value of ultrasonic elastosonography (UE) and contrast-enhanced ultrasonography (CEUS) for benign and malignant intraocular tumors. METHODS: This retrospective study enrolled patients with intraocular tumors at Beijing Tongren Hospital, Capital Medical University (August 2016 to January 2020). The strain rate ratio (strain rate of tumor tissue divided by strain rate of surrounding normal tissue) was measured by UE. CEUS was performed using SonoVue® contrast agent. The performance of each method at differentiating benign from malignant intraocular tumors was evaluated by receiver operating characteristic curve analysis. RESULTS: The analysis included 147 eyes in 145 patients (45.6 ± 13.4 years-old; 66 males): 117 patients (119 eyes) with malignant tumors and 28 patients (28 eyes) with benign tumors. At an optimal cutoff of 22.67 for the strain rate ratio, UE distinguished benign from malignant tumors with a sensitivity of 86.6% and a specificity of 96.4%. CEUS showed that 117 eyes with malignant tumors had a fast-in, fast-out time-intensity curve, and only two eyes with malignant tumors had a fast-in, slow-out curve, while all 28 eyes with benign tumors had a fast-in, slow-out curve. CEUS differentiated benign from malignant tumors with a sensitivity of 98.3% and a specificity of 100%. The diagnostic results differed significantly between the two methods (P = 0.004, McNemar test). The diagnostic performances of the two tests were moderately consistent (κ = 0.657, P < 0.001). CONCLUSION: Both CEUS and UE have good diagnostic value in the differentiation of benign intraocular tumors from malignant intraocular tumors.

Value of the strain ratio in the differential diagnosis of intraocular tumors by elastosonography: A retrospective case-control study.

Purpose: To examine the role of the strain ratio in elastosonography for the differential diagnosis of common intraocular tumors such as choroidal melanoma, choroidal hemangioma, choroidal metastatic carcinoma, and retinoblastoma. Methods: This study included patients suffering from intraocular space-occupying lesions and who visited Beijing Tongren Eye Center of Beijing Tongren Hospital affiliated to Capital Medical University from June 2016 to March 2020. All patients underwent a physical examination, fundus examination with mydriasis, color Doppler ultrasonography, elastosonography, magnetic resonance imaging (MRI), and fundus angiography within 1 week. All patients were grouped as choroidal melanoma, choroidal metastatic carcinoma, retinoblastoma, choroidal hemangioma, and optic disk melanocytoma. A receiver operating characteristic (ROC) curve analysis was performed to assess the strain ratio for diagnosing malignant intraocular tumors. Results: A total of 155 patients (161 eyes) were recruited. The strain ratios measured were 39.59 ± 15.92 for choroidal melanoma, 36.85 ± 13.64 for choroidal metastatic carcinoma, 38.93 ± 17.27 for retinoblastoma, 13.42 ± 10.93 for choroidal hemangioma, and 3.84 ± 1.32 for optic disk melanocytoma. The strain ratios of the three malignant lesions were significantly higher than those of the two benign lesions (all P < 0.001). The area under the ROC curve was 0.95 ± 0.028. The optimal cutoff point was 22.67, with 85.7% sensitivity and 96.4% specificity. Conclusion: There were significant differences in elasticity between the malignant and benign intraocular tumors. The strain ratio using elastosonography could serve as an important auxiliary examination to distinguish between benign and malignant intraocular tumors.

Thermal treatment affects aptamers' structural profiles.

Using anion-exchange high performance liquid chromatography under non-denaturing conditions, the conformational flexibility of adenosine-, ampicillin-, and quinine aptamers were studied. It was found that all three aptamers showed more than one species when not subjected to thermal anneal. Addition of ligand to untreated aptamers did not significantly change the structural distribution. Upon heating followed by slow cooling, however, all three aptamers were found to exist virtually solely in one structure, presumably the partial hairpin species. It was also found that sonication of quinine aptamer, but not adenosine and ampicillin aptamer, led to its elution off HPLC as virtually a single species. These changes in conformational distribution as a result of thermal anneal or sonication were further confirmed by UV/vis and circular dichroism spectroscopy, as well as melt curves. The findings provided basis for future optimization of aptamer selection and preparation, where thermal anneal can help optimize selection efficiency and improve the consistency in the interpretation of results.

Can machine learning 'transform' peptides/peptidomimetics into small molecules? A case study with ghrelin receptor ligands.

There has been considerable interest in transforming peptides into small molecules as peptide-based molecules often present poorer bioavailability and lower metabolic stability. Our studies looked into building machine learning (ML) models to investigate if ML is able to identify the 'bioactive' features of peptides and use the features to accurately discriminate between binding and non-binding small molecules. The ghrelin receptor (GR), a receptor that is implicated in various diseases, was used as an example to demonstrate whether ML models derived from a peptide library can be used to predict small molecule binders. ML models based on three different algorithms, namely random forest, support vector machine, and extreme gradient boosting, were built based on a carefully curated dataset of peptide/peptidomimetic and small molecule GR ligands. The results indicated that ML models trained with a dataset exclusively composed of peptides/peptidomimetics provide limited predictive power for small molecules, but that ML models trained with a diverse dataset composed of an array of both peptides/peptidomimetics and small molecules displayed exceptional results in terms of accuracy and false rates. The diversified models can accurately differentiate the binding small molecules from non-binding small molecules using an external validation set with new small molecules that we synthesized previously. Structural features that are the most critical contributors to binding activity were extracted and are remarkably consistent with the crystallography and mutagenesis studies.

Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation.

BACKGROUND: The pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in bAVM. This study examined genetic variants associated with bAVM through quantitative synthesis and qualitative description of literature. METHODS: Five databases were searched to gather potentially relevant articles published up to January 2022. STATA 14.0 software was used for statistical analyses. Pooled odds ratios and 95% confidence intervals were calculated with random effect models, and heterogeneity was assessed using the Cochran Q test and quantified with the I 2 test. Sensitivity and publication bias were analyzed to test the robustness of the associations. Variants identified in only one study or with great heterogeneity were not suitable for pooling association analysis, and therefore a qualitative systematic review was performed. RESULTS: In total, 30 papers were included in a systematic review involving 4709 cases and 7832 controls, where 17 papers were in a meta-analysis. A suggested association of bAVM was observed with ACVRL1 rs2071219 in the additive model and CDKN2B-AS1 rs1333040 in the recessive and additive models. Other variants of genes that could not be analyzed were summarized by qualitative description. These genes were mostly involved in bone morphogenic protein/transforming growth factor beta (BMP/TGF-ß), vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), and RAS-mitogen activated protein kinase (MAPK) signaling and inflammation. CONCLUSIONS: According to our meta-analysis, ACVRL1 rs2071219 and CDKN2B-AS1 rs1333040 were potentially associated with bAVM. Multiple pathological signaling pathways could affect disease development. Future studies should aim to determine the interaction of candidate genes with environmental risk factors and to elucidate detailed mechanisms of action of variants and genes.1.

Gas Diffusion Layer for Proton Exchange Membrane Fuel Cells: A Review.

Proton exchange membrane fuel cells (PEMFCs) are an attractive type of fuel cell that have received successful commercialization, benefitted from its unique advantages (including an all solid-state structure, a low operating temperature and low environmental impact). In general, the structure of PEMFCs can be regarded as a sequential stacking of functional layers, among which the gas diffusion layer (GDL) plays an important role in connecting bipolar plates and catalyst layers both physically and electrically, offering a route for gas diffusion and drainage and providing mechanical support to the membrane electrode assemblies. The GDL commonly contains two layers; one is a thick and rigid macroporous substrate (MPS) and the other is a thin microporous layer (MPL), both with special functions. This work provides a brief review on the GDL to explain its structure and functions, summarize recent progress and outline future perspectives.

A Cyclen-Functionalized Cobalt-Substituted Sandwich-Type Tungstoarsenate with Versatility in Removal of Methylene Blue and Anti-ROS-Sensitive Tumor Cells.

Oxidative degradation by using reactive oxygen species (ROS) is an effective method to treat pollutants. The synthesis of artificial oxidase for the degradation of dyes is a hot spot in molecular science. In this study, a nanoscale sandwich-type polyoxometalate (POM) on the basis of a tetra-nuclear cobalt cluster and trivacant B-α-Keggin-type tungstoarsenate {[Co(C8H20N4)]4}{Co4(H2O)2[HAsW9O34]2}∙4H2O (abbreviated as CAW, C8H20N4 = cyclen) has been synthesized and structurally examined by infrared (IR) spectrum, ultraviolet-visible (UV-Vis) spectrum, X-ray photoelectron spectrum (XPS), single-crystal X-ray diffraction (SXRD), and bond valence sum (Σs) calculation. According to the structural analysis, the principal element of the CAW is derived from modifying sandwich-type polyanion {Co4(H2O)2 [HAsW9O34]2}8- with four [Co(Cyclen)]2+, in which 1,4,7,10-tetraazacyclododecane (cyclen) is firstly applied to modify POM. It is also demonstrated that CAW is capable of efficiently catalyzing the production of ROS by the synergistic effects of POM fragments and Co-cyclen complexes. Moreover, CAW can interfere with the morphology and proliferation of sensitive cells by producing ROS and exhibits ability in specifically eliminating methylene blue (MB) dyes from the solution system by both adsorption and catalytic oxidation.

CHO cathepsin B identified as the protease responsible for a target bispecific antibody fragmentation.

In a previous work we demonstrated that CHO protease caused fragmentation of an expressed bispecific antibody (bsAb) and this detrimental host cell protein (HCP) can be effectively removed through an optimized Protein A wash step. In addition, preliminary evidence suggested that the responsible protease belongs to the threonine or cysteine protease family. In the current study, this protease was further identified as cathepsin B. First, we identified several CHO proteases in the further fractionated Protein A wash using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this allowed us to select four candidate proteases. Next, by examining the cleavage pattern of each individual protease and comparing it with that observed during purification, cathepsin B was identified as the protease responsible for the observed bsAb fragmentation.

Viral removal by column chromatography in downstream processing of monoclonal antibodies.

For monoclonal antibodies (mAbs) produced in mammalian cells, viral safety is a critical concern. The downstream process, in addition to removing other impurities, needs to ensure robust clearance (removal or inactivation) of potential endogenous and adventitious viruses. In general, Protein A and polishing chromatography steps all can provide certain level of virus removal. Chromatographic removal combined with virus inactivation and nanofiltration usually provides adequate virus clearance across the overall downstream process. This article reviews the virus clearance capability of commonly used column chromatography, with attention to possible interference of virus-mAb interaction on virus removal. In addition, the potential of using viral surrogate as a safe alternative to live virus for assessing viral clearance is briefly discussed.

LncRNA HAND2-AS1 attenuates glioma cell proliferation, invasion and migration by targeting CDK6.

OBJECTIVE: Long non-coding RNA (lncRNA) HAND2-AS1 has been indicated to play biological roles in several cancers. However, whether HAND2-AS1 could exert its role in glioma remains unknown. We aimed to investigate the function of HAND2-AS1 in the proliferation, invasion and migration and to explore its underlying molecular mechanism in glioma cells. METHODS: Reverse transcription-quantitative polymerase chain reaction analysis was conducted to determine the expression of HAND2-AS1 and cyclin-dependent kinases 6 (CDK6) in tissues or cells. Western blot analysis was used to detect the CDK6 protein expression. CCK-8 assay was adopted to determine the proliferation in glioma cell lines. Transwell assay was taken to evaluate the invasion and migration in glioma cell lines. RESULTS: Our results revealed that HAND2-AS1 expression was significantly downregulated in the glioma tissues and cell lines. Moreover, overexpression of HAND2-AS1 attenuated the proliferation, invasion, and migration in glioma cell lines. However, overexpression of CDK6 could partially block the inhibitory role of HAND2-AS1 on cell proliferation as well as cell invasion and migration in glioma cell lines. CONCLUSION: LncRNA HAND2-AS1 may play a critical anti-tumorigenic role in glioma by negatively regulating CDK6 expression.