Adaptive mask-based brain extraction method for head CT images.

Brain extraction is an important prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion identification, localization, and segmentation. To address the problem that the current traditional image segmentation methods are fast in extraction but poor in robustness, while the Full Convolutional Neural Network (FCN) is robust and accurate but relatively slow in extraction, this paper proposes an adaptive mask-based brain extraction method, namely AMBBEM, to achieve brain extraction better. The method first uses threshold segmentation, median filtering, and closed operations for segmentation, generates a mask for the first time, then combines the ResNet50 model, region growing algorithm, and image properties analysis to further segment the mask, and finally complete brain extraction by multiplying the original image and the mask. The algorithm was tested on 22 test sets containing different lesions, and the results showed MPA = 0.9963, MIoU = 0.9924, and MBF = 0.9914, which were equivalent to the extraction effect of the Deeplabv3+ model. However, the method can complete brain extraction of approximately 6.16 head CT images in 1 second, much faster than Deeplabv3+, U-net, and SegNet models. In summary, this method can achieve accurate brain extraction from head CT images more quickly, creating good conditions for subsequent brain volume measurement and feature extraction of intracranial lesions.

Computational Determination of the Mechanism of the Palladium-Catalyzed Domino Reaction of ortho-Iodostyrene, Oxanorbornadiene, and Phenylboronic Acid.

The palladium-catalyzed three-component domino reaction of ortho-iodostyrene, 2,3-dicarbomethoxy-7-oxanorbornadiene (ONBD), and phenylboronic acid discovered by the Lautens group provides a convenient method to synthesize indenes derivatives. Herein, density functional theory (DFT) calculations were employed to explore the detailed mechanism of this domino reaction. The computational results suggest that the alkene-insertion-first and the transmetalation-first mechanisms are competitive, and the former mechanism is slightly more favorable because of the difficult intramolecular alkene insertion of the alkyl-PdII-aryl than alkyl-PdII-I complex. Further analysis on substituents of ONBD unveils the impacts of noncovalent interactions and electronic effect on the rate-determining retro-Diels-Alder process. The understanding of this domino reaction has important implications for developing a novel palladium-catalyzed domino reaction with a retro-Diels-Alder strategy.

A fast and accurate brain extraction method for CT head images.

BACKGROUND: Brain extraction is an essential prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion recognition, location, and segmentation. Segmentation using a fully convolutional neural network (FCN) yields high accuracy but a relatively slow extraction speed. METHODS: This paper proposes an integrated algorithm, FABEM, to address the above issues. This method first uses threshold segmentation, closed operation, convolutional neural network (CNN), and image filling to generate a specific mask. Then, it detects the number of connected regions of the mask. If the number of connected regions equals 1, the extraction is done by directly multiplying with the original image. Otherwise, the mask was further segmented using the region growth method for original images with single-region brain distribution. Conversely, for images with multi-region brain distribution, Deeplabv3 + is used to adjust the mask. Finally, the mask is multiplied with the original image to complete the extraction. RESULTS: The algorithm and 5 FCN models were tested on 24 datasets containing different lesions, and the algorithm's performance showed MPA = 0.9968, MIoU = 0.9936, and MBF = 0.9963, comparable to the Deeplabv3+. Still, its extraction speed is much faster than the Deeplabv3+. It can complete the brain extraction of a head CT image in about 0.43 s, about 3.8 times that of the Deeplabv3+. CONCLUSION: Thus, this method can achieve accurate brain extraction from head CT images faster, creating a good basis for subsequent brain volume measurement and feature extraction of intracranial lesions.

Dual growth factor-modified microspheres nesting human-derived umbilical cord mesenchymal stem cells for bone regeneration.

BACKGROUND: Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue. RESULTS: Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis. CONCLUSIONS: The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.

Approach to Seven-Membered Carbocycles via a Lewis Acid Catalyzed Intramolecular Michael Addition of Allenone.

A straightforward strategy for constructing seven-membered carbocycles by employing a Lewis acid catalyzed intramolecular Michael addition of allenones is reported. It offers atom-economic access to synthetically important furan-fused bi- or tricyclic frameworks containing seven-membered carbocycles, which are widely found in natural products possessing various bioactivities. A number of seven-membered carbocycle-containing polycyclic frameworks bearing diverse functional groups were prepared in good to excellent yields. Furthermore, the application potential of this strategy was exemplified by the construction of the key skeletons of Caribenol A and Frondosin B.

Gold-Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor-Active Spirocyclic Oxindoles from Alkynes and Isatin-Derived Ketimines.

Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold-catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin-derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones.

Degradation of cyanobacterial neurotoxin ß-N-methylamino-L-alanine (BMAA) using ozone process: influencing factors and mechanism.

ß-N-methylamino-L-alanine (BMAA), which has been considered as an environmental factor that caused amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) or Alzheimer's disease, could be produced by a variety of genera cyanobacteria. BMAA is widely present in water sources contaminated by cyanobacteria and may threaten human health through drinking water. Although oxidants commonly used in drinking water plants such as chlorine, ozone, hydrogen peroxide, and hydroxyl radicals have been shown to effectively degrade BMAA, there are limited studies on the mechanism of BMAA degradation by different oxidants, especially ozone. This work systematically explored the effectiveness of BMAA ozonation degradation, investigated the effect of the operating parameters on the effectiveness of degradation, and speculated on the pathways of BMAA decomposition. The results showed that BMAA could be quickly eliminated by ozone, and the removal rates of BMAA were nearly 100% in pure water, but the removal rates were reduced in actual water. BMAA was primarily degraded by direct oxidation of ozone molecules in acidic and near-neutral conditions, and indirect oxidation of •OH accounted for the main part under strong alkaline conditions. The pH value had a significant effect on the decomposition of BMAA, and the degradation rate of BMAA was fastest at near-neutral pH value. The degradation rates of TOC were significantly lower than that of BMAA, indicating that by-products were generated during the degradation process. Three by-products ([M-H]+ = 105, 90, and 88) were identified by UPLC-MS/MS, and the degradation pathways of BMAA were proposed. The production of by-products was attributed to the fracture of the C-N bonds. This work is helpful for the in-depth understanding on the mechanism and demonstration of the feasibility of the oxidation of BMAA by the ozone process. HIGHLIGHTS: • The reaction of ozonation BMAA was easy to occur. • The degradation rate was fast under near-neutral conditions. • Direct oxidation under neural conditions was the main pathway for ozone degradation of BMAA. • Three products were detected, and the reaction path was inferred.

Gold-Catalyzed Regio- and Stereoselective α-Acyloxy-ß-Alkynylation of Ynol Ethers.

Enol esters and conjugated enynes are valuable structural motifs for synthetic chemistry and material sciences. Herein, the synthesis of tetra-substituted enol ester 2-iodobenzoate derivatives was achieved in good yields at room temperature through a gold-catalyzed acyloxyalkynylation of sensitive ynol ethers with ethynylbenziodoxolones (EBXs), the latter acting as bifunctional reactants. The conversion is highly regioselective with a broad substrate scope. Mechanistically, an Au(III) species is the key intermediate of an Au(I)/Au(III) redox cycle. The reaction is synthetically useful and can easily be scaled up to gram scale.

A cross-sectional study exploring the relationship between symptoms of anxiety/depression and P50 sensory gating in adult patients diagnosed with chronic fatigue syndrome/myalgic encephalomyelitis.

Introduction: Chronic fatigue syndrome (CFS) is a clinical disease that affects multiple body systems. It is characterized by persistent or recurring fatigue, which may be linked to immune, neuroendocrine, and energy metabolism dysfunctions. Individuals with CFS may experience pain, sleep disorders, anxiety, and depression. This research analyzed the fundamental characteristics of anxiety/depression symptoms in patients with CFS and investigated the association between these symptoms and the P50 SG (sensory gate) ratio. Methods: Two hundred and forty-nine subjects fulfilled the CDC-1994 criteria for CFS and were included in the study. The subjects successively completed the Symptom CheckList-90-Revised (SCL-90-R), Hamilton Anxiety Rating Scale-14 (HAMA-14), and Hamilton Depression Rating Scale-24 (HAMD-24). Auditory-evoked potential P50 were measured using the 128-lead-electroencephalograph. Result: According to HAMA and HAMD, 17.3% (n = 43) of the patients did not exhibit anxiety/depression, with a threshold score of 7 and 7 for HAMA and HAMD. When the threshold score was 14 and 20 respectively, 43.3% (n = 108) of the patients did not exhibit anxiety/depression. The SCL-90-R results indicated that 69.5% (n = 173) of these individuals with the score arranging from 0 to 160 did not present mental problems. There was a correlation between somatization scores and P50 SG ratio in the overall sample and no anxiety or depression (NAOD) group delimited by 14 and 20, respectively, (p < 0.05). Regression analysis showed that anxiety and depression were risk factors associated with an abnormal P50 SG ratio. Discussion: A significant correlation exists between the P50 SG ratio and clinical symptoms such as fatigue, anxiety, and depression. Abnormalities in brain function among patients with CFS may play a crucial role in the pathogenesis of the condition, leading to their classification as being prone to functional neurological disorders. The P50 SG ratio cannot be used as a diagnostic marker for CFS but show some significance on the mechanism, classification, treatment, and prognosis of CFS.

Merging photoredox with copper catalysis: enantioselective remote cyanation via 1,4-heteroaryl migration.

We have developed a photoredox/Cu dual catalyzed enantioselective remote cyanation via 1,4-heteroaryl migration. Experimental and computational studies have been carried out to reveal the reaction mechanism and explain the origins of the regio- and enantioselectivities of the remote cyanation process. This methodology exhibits mild conditions, a broad substrate scope and good regio- and enantioselectivities, which provides a unique approach for catalyst-controlled asymmetric backbone recombination of molecules via functional group migration.

Synthesis of Amide Enol 2-Iodobenzoates by the Regio- and Stereoselective Gold-Catalyzed Acyloxyalkynylation of Ynamides with Hypervalent Iodine Reagents.

Multisubstituted alkenes are accessible by a gold-catalyzed acyloxyalkynylation of ynamides with ethynylbenziodoxolones (EBXs) with perfect atom-economy. The EBX reagents transfer both the carboxylate as well as the alkynyl entity. Overall, this cascade comprises the in situ generation of an alkynyl gold(III) species, a stereoselective C(sp)-C(sp2) bond formation, and a C-O coupling at the alkynyl position of the ynamides. This reaction proceeds under mild conditions and accepts a wide range of substrates. A number of tetrasubstituted amide enol 2-iodobenzoates bearing different functional groups were obtained in good to excellent yields. DFT calculations explain the observed regioselectivity. The synthetic potential of the reaction was further demonstrated by a number of selected follow-up transformations.

Domestication and improvement genes reveal the differences of seed size- and oil-related traits in soybean domestication and improvement.

To address domestication and improvement studies of soybean seed size- and oil-related traits, a series of domesticated and improved regions, loci, and candidate genes were identified in 286 soybean accessions using domestication and improvement analyses, genome-wide association studies, quantitative trait locus (QTL) mapping and bulked segregant analyses in this study. As a result, 534 candidate domestication regions (CDRs) and 458 candidate improvement regions (CIRs) were identified in this study and integrated with those in five and three previous studies, respectively, to obtain 952 CDRs and 538 CIRs; 1469 loci for soybean seed size- and oil-related traits were identified in this study and integrated with those in Soybase to obtain 433 QTL clusters. The two results were intersected to obtain 245 domestication and 221 improvement loci for the above traits. Around these trait-related domestication and improvement loci, 7 domestication and 7 improvement genes were found to be truly associated with these traits, and 372 candidate domestication and 87 candidate improvement genes were identified using gene expression, SNP variants in genome, miRNA binding, KEGG pathway, DNA methylation, and haplotype analysis. These genes were used to explain the trait changes in domestication and improvement. As a result, the trait changes can be explained by their frequencies of elite haplotypes, base mutations in coding region, and three factors affecting their expression levels. In addition, 56 domestication and 15 improvement genes may be valuable for future soybean breeding. This study can provide useful gene resources for future soybean breeding and molecular biology research.

Ynamide-Mediated Thioamide and Primary Thioamide Syntheses.

Environmentally friendly ynamide-mediated thioamidation of monothiocarboxylic acids with amines or ammonium hydroxide for the syntheses of thioamides and primary thioamides is described. Simple and mild reaction conditions enable the reaction to tolerate a wide variety of functional groups such as hydroxyl group, ester, tertiary amine, ketone, and amide moieties. Readily available NaSH served as the sulfur source, avoiding the use of toxic, expensive, and malodorous organic sulfur reagents and making this strategy environmentally friendly and practical. Importantly, the stereochemical integrity of α-chiral monothiocarboxylic acids was maintained during the activation step and subsequent aminolysis process, thus offering a racemization-free strategy for peptide C-terminal modification. Furthermore, a number of thioamide-modified drugs were prepared in good yields by using this protocol and the synthesized primary thioamides were transformed into backbone thiazolyl modified peptides.

Penicillium fungi mediate behavioral responses of the yellow peach moth, Conogethes punctiferalis (Guenée) to apple fruits via altering the emissions of host plant VOCs.

Plant-associated microbes have been reported as important but overlooked drivers of plant-herbivorous insect interactions. Influence of plant-associated microbes on plant-insect interactions is diverse, including beneficial, detrimental, and neutral. Here, we determined the effects of three Penicillium fungi, including Penicillium citrinum, Penicillium sumatrense, and Penicillium digitatum, on the oviposition selection and behavior of the yellow peach moth (YPM), Conogethes punctiferalis (Guenée). Compared with fungi noninfected apples (NIA), mechanically damaged apples (MDA), and P. citrinum in potato dextrose agar medium (PC), the oviposition selection and four-arm olfactometer experiments both showed that mated YPM females preferred to P. citrinum-infected apples (PCA). For P. sumatrense or P. digitatum, we also found that mated YPM females preferred to P. sumatrense-infected apples (PSA) or P. digitatum-infected apples (PDA), respectively. Among three Penicillium fungi-infected apples, the selection rates including oviposition and olfactometer behavior of mated YPM females on PDA were both higher than those on PSA and PCA. Further analyses of host plant volatile organic compounds (VOCs) by GC-MS showed that the absolute contents of ethyl hexanoate and (Z, E)-α-farnesene in PCA, PSA, and PDA were all higher than those in NIA, and a total of 16 novel VOCs were detected in fungi-infected apples (PCA, PSA, and PDA), indicating that fungi infection changed the components and proportions of apple VOCs. Taken together, three Penicillium fungi play significant roles in mediating the host selection of YPMs via altering the emissions of VOCs. These findings will be beneficial for developing formulations for field trapping of YPMs in the future.

Valley Hall Elastic Edge States in Locally Resonant Metamaterials.

This paper presents a locally resonant metamaterial periodically rearranged as a local resonator, that is hexagonal holes arranged in a thin plate replace the elastic local resonator to achieve the quantum valley Hall effect. Due to the C3v symmetry in the primitive hexagonal lattice, one Dirac point emerges at high symmetry points in the Brillouin zone in the sub-wavelength area. Rotating the beam element of the resonator can break the spatial inversion symmetry to lift the Dirac degeneracy and form a new bandgap. Thus, the band inversion is discovered by computing the relationship between the associated bandgap and the rotational parameter. We also confirmed this result by analyzing the vortex chirality and calculating the Chern number. We can discover two kinds of edge states in the projected band obtained by computing the supercell composed of different topological microstructures. Finally, the propagation behavior in various heterostructures at low frequencies was analyzed. It is shown that these valley Hall elastic insulators can guide elastic waves along sharp interfaces and are immune to backscattering from defects or disorder. By utilizing elastic resonators, a simple reconfigurable topological elastic metamaterial is realized in the sub-wavelength area.

A Cas6-based RNA tracking platform functioning in a fluorescence-activation mode.

Given the fact that the localization of RNAs is closely associated with their functions, techniques developed for tracking the distribution of RNAs in live cells have greatly advanced the study of RNA biology. Recently, innovative application of fluorescent protein-labelled Cas9 and Cas13 into live-cell RNA tracking further enriches the toolbox. However, the Cas9/Cas13 platform, as well as the widely-used MS2-MCP technique, failed to solve the problem of high background noise. It was recently reported that CRISPR/Cas6 would exhibit allosteric alteration after interacting with the Cas6 binding site (CBS) on RNAs. Here, we exploited this feature and designed a Cas6-based switch platform for detecting target RNAs in vivo. Conjugating split-Venus fragments to both ends of the endoribonuclease-mutated Escherichia coli Cas6(dEcCas6) allowed ligand (CBS)-activated split-Venus complementation. We name this platform as Cas6 based Fluorescence Complementation (Cas6FC). In living cells, Cas6FC could detect target RNAs with nearly free background noise. Moreover, as minimal as one copy of CBS (29nt) tagged in an RNA of interest was able to turn on Cas6FC fluorescence, which greatly reduced the odds of potential alteration of conformation and localization of target RNAs. Thus, we developed a new RNA tracking platform inherently with high sensitivity and specificity.

Effective Picosecond Nd:YAG laser on seborrheic dermatitis and its mechanism.

BACKGROUND: The Picosecond Nd:YAG laser has advantages in skin rejuvenation, which has little damage to surrounding tissues due to the ultra-short pulse width. We perform clinical application of Picosecond Nd:YAG laser's tender skin mode, which could improve the seborrheic dermatitis. MATERIALS AND METHODS: Sixty-three subjects with facial seborrheic dermatitis are randomized to be control and observation groups. Records regarding skin subjective improvement, skin barrier function-related data, skin microbial status, and dermoscopy detection of the two patient groups before and after treatments are investigated. RESULTS: Improvements of erythema and scales in observation group are significant compared with controls (p < 0.05). In terms of skin barrier function, there are significant changes regarding transepidermal water loss and epidermal seborrhea content in observation group after the laser treatments. Skin microbial state, pityrosporum furfur, and Demodex significantly decrement in observation group. Microscopical findings of infiltration mode advise that scales and capillary congestion and dilatation are significantly improved in observation group. Compared with controls, epidermal gloss increases, pore fineness improves, and capillary density decreases in the observation group. CONCLUSIONS: Picosecond Nd:YAG laser could efficiently decrease erythema area and seborrheic dermatitis scales and reduce pruritus incidence. The sebaceous gland secretion of seborrhea and multiplying of epidermal parasitic microbiological are inhibited after laser treatment. Less epidermal seborrhea content and inflammation are induced by parasitic microbiology, which is helpful for skin barrier function and microvascular remodeling.

Dual Gold/Silver Catalysis: Indolizines from 2-Substituted Pyridine Derivatives via a Tandem C(sp3)-H Alkynylation/Iminoauration.

A dual gold/silver-catalyzed cascade C(sp3)-H alkynylation/iminoauration of 2-substituted pyridines with hypervalent iodine(III) reagents for the synthesis of indolizines is described. This novel reaction involves the formation of an alkynyl Au(III) species, a dual gold/silver-catalyzed C(sp3)-H functionalization, and a subsequent iminoauration process. A number of indolizines bearing diverse functionalities were prepared in good to excellent yield. Furthermore, a gram-scale reaction was efficiently conducted.

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Monoclonal Antibody (SCTA01) Targeting SARS-CoV-2 in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, Phase I Study.

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (n = 5; 3:2), cohort 2 (n = 8; 6:2), cohort 3, or cohort 4 (both n = 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in Cmax and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).

Tetrasubstituted 1,3-Enynes by Gold-Catalyzed Direct C(sp2)-H Alkynylation of Acceptor-Substituted Enamines.

A gold-catalyzed synthesis of tetrasubstituted 1,3-enynes from hypervalent iodine(III) reagents and activated alkenes is reported. This reaction involves an in situ formed alkynyl Au(III) species and a subsequent direct C(sp2)-H functionalization of alkenes, offering 26 enynes in 62-92% yield with excellent functional group tolerance.