SARS-CoV-2 Protein Nanoparticle Vaccines Formed In Situ From Lyophilized Lipids.

The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) glycoprotein is an appealing immunogen, but associated vaccine approaches must overcome the hapten-like nature of the compact protein and adapt to emerging variants with evolving RBD sequences. Here, a vaccine manufacturing methodology is proposed comprising a sterile-filtered freeze-dried lipid cake formulation that can be reconstituted with liquid proteins to instantaneously form liposome-displayed protein nanoparticles. Mannitol is used as a bulking agent and a small amount of Tween-80 surfactant is required to achieve reconstituted submicron particles that do not precipitate prior to usage. The lipid particles include an E. coli-derived monophosphoryl lipid A (EcML) for immunogenicity, and cobalt porphyrin-phospholipid (CoPoP) for antigen display. Reconstitution of the lipid cake with aqueous protein results in rapid conversion of the RBD into intact liposome-bound format prior to injection. Protein particles can readily be formed with sequent-divergent RBD proteins derived from the ancestral or Omicron strains. Immunization of mice elicits antibodies that neutralize respective viral strains. When K18-hACE2 transgenic mice are immunized and challenged with ancestral SARS-CoV-2 or the Omicron BA.5 variant, both liquid liposomes displaying the RBD and rapid reconstituted particles protect mice from infection, as measured by the viral load in the lungs and nasal turbinates.

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing.

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

Chemical Constituents of the Fruits of Cornus Officinalis and Evaluation of their Neuroprotective Activity.

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.

Jacalin-related lectin 45 (OsJRL45) isolated from 'sea rice 86' enhances rice salt tolerance at the seedling and reproductive stages.

BACKGROUND: Rice (Oryza sativa L.) is one of the most widely cultivated grain crops in the world that meets the caloric needs of more than half the world's population. Salt stress seriously affects rice production and threatens food security. Therefore, mining salt tolerance genes in salt-tolerant germplasm and elucidating their molecular mechanisms in rice are necessary for the breeding of salt tolerant cultivars. RESULTS: In this study, a salt stress-responsive jacalin-related lectin (JRL) family gene, OsJRL45, was identified in the salt-tolerant rice variety 'sea rice 86' (SR86). OsJRL45 showed high expression level in leaves, and the corresponding protein mainly localized to the endoplasmic reticulum. The knockout mutant and overexpression lines of OsJRL45 revealed that OsJRL45 positively regulates the salt tolerance of rice plants at all growth stages. Compared with the wild type (WT), the OsJRL45 overexpression lines showed greater salt tolerance at the reproductive stage, and significantly higher seed setting rate and 1,000-grain weight. Moreover, OsJRL45 expression significantly improved the salt-resistant ability and yield of a salt-sensitive indica cultivar, L6-23. Furthermore, OsJRL45 enhanced the antioxidant capacity of rice plants and facilitated the maintenance of Na+-K+ homeostasis under salt stress conditions. Five proteins associated with OsJRL45 were screened by transcriptome and interaction network analysis, of which one, the transmembrane transporter Os10g0210500 affects the salt tolerance of rice by regulating ion transport-, salt stress-, and hormone-responsive proteins. CONCLUSIONS: The OsJRL45 gene isolated from SR86 positively regulated the salt tolerance of rice plants at all growth stages, and significantly increased the yield of salt-sensitive rice cultivar under NaCl treatment. OsJRL45 increased the activity of antioxidant enzyme of rice and regulated Na+/K+ dynamic equilibrium under salinity conditions. Our data suggest that OsJRL45 may improve the salt tolerance of rice by mediating the expression of ion transport-, salt stress response-, and hormone response-related genes.

Upregulation of HMGB1 in tumor-associated macrophages induced by tumor cell-derived lactate further promotes colorectal cancer progression.

BACKGROUND: Lactate accumulation leads to an acidic tumor microenvironment (TME), in turn promoting colorectal cancer (CRC) progression. Tumor-associated macrophages (TAMs) are the predominant cells in TME. This study aimed to reveal the regulation mechanism of CRC cell-derived lactate on TAMs and explore the mechanism underlying lactate accumulation-induced aggravation in CRC. METHODS: Cell growth and metastasis were evaluated by colony formation, Transwell, and wound healing assays. Western blot and RT-qPCR were applied to determine the protein and mRNA expression. Flow cytometry was used to analyze the polarization state and apoptotic rate of macrophages induced in THP-1 cells. The lactate in the cell supernatant was quantified using an ELISA kit. Immunofluorescence was performed to visualize the location of High Mobility Group Box 1 (HMGB1). H&E and Ki67 staining assays were used to assess tumorigenesis in nude mice bearing ectopic tumors. RESULTS: Cell growth and metastasis were promoted in the hypoxic CRC cells. The hypoxic cell supernatant stimulated the M2-type polarization of macrophages. The lactate level increased in hypoxic cancer cells. However, the inhibition of lactate using 3-hydroxy-butyrate (3-OBA) reversed the effects of hypoxia. Also, macrophages showed no promoting effect on cancer cell growth and migration in the presence of 3-OBA. HMGB1 was secreted into the extracellular space of lactate-induced macrophages, further enhancing the malignant behaviors of cancer cells. ERK, EMT, and Wnt signaling pathways were activated in cancer cells due to HMGB1 upregulation. CONCLUSIONS: The lactate metabolized by cancer cells stimulated M2 polarization and HMGB1 secretion by macrophages, aggravating the carcinogenic behaviors of cancer cells.

Interaction between two overall neutral charged microscopically patterned surfaces.

We study the interaction between heterogeneously charged surfaces in an electrolyte solution by employing classical Density Functional Theory (cDFT) and Monte Carlo simulations. We observe a consistent behavior between cDFT and Monte Carlo simulations regarding force curves and two-dimensional density profiles. Armed with the validated cDFT, we explore the system's behavior under parameters that are challenging to simulate directly. Our findings include the impacts of domain size, domain charge, domain charge configuration, and bulk electrolyte concentration on the osmotic pressure. Remarkably, the force curve is more sensitive to the domain size for an asymmetric configuration than a symmetry configuration; the bulk concentration weakly influences the force curve independent of the system configurations.

Low-light image enhancement based on Retinex-Net with color restoration.

Low-light images often suffer from a variety of degradation problems such as loss of detail, color distortions, and prominent noise. In this paper, the Retinex-Net model and loss function with color restoration are proposed to reduce color distortion in low-light image enhancement. The model trains the decom-net and color recovery-net to achieve decomposition of low-light images and color restoration of reflected images, respectively. First, a convolutional neural network and the designed loss functions are used in the decom-net to decompose the low-light image pair into an optimal reflection image and illumination image as the input of the network, and the reflection image after normal light decomposition is taken as the label. Then, an end-to-end color recovery network with a simplified model and time complexity is learned and combined with the color recovery loss function to obtain the correction reflection map with higher perception quality, and gamma correction is applied to the decomposed illumination image. Finally, the corrected reflection image and the illumination image are synthesized to get the enhanced image. The experimental results show that the proposed network model has lower brightness-order-error (LOE) and natural image quality evaluator (NIQE) values, and the average LOE and NIQE values of the low-light dataset images can be reduced to 942 and 6.42, respectively, which significantly improves image quality compared with other low-light enhancement methods. Generally, our proposed method can effectively improve image illuminance and restore color information in the end-to-end learning process of low-light images.

Temporal synchrony discrimination is abnormal in dichoptic but not monocular visual processing in treated anisometropic amblyopes.

PURPOSE: To evaluate whether temporal synchrony processing deficits remain when normal visual acuity is restored in adults with unilateral anisometropic amblyopia. METHODS: We recruited 14 clinically treated anisometropic amblyopes (mean age 23.17 ± 2.53 years) with best-corrected visual acuity ≤ 0.1 logMAR and 15 age-matched emmetropes (mean age 24.40 ± 1.92 years) with normal vision to participate in our experiment. We presented two pairs of flicking Gaussian dots (1 Hz) as visual stimuli: one pair of dots was synchronous (reference), and the other pair of dots was asynchronous (signal). Subjects were asked to determine the position of the asynchronous pair. We applied the constant stimuli method to measure the temporal synchrony threshold under monocular and dichoptic viewing conditions. There were eight temporal phase lags in the asynchronous pair. The minimum degree of the temporal phase at which a participant can discriminate a signal pair is defined as the temporal synchrony threshold. RESULTS: Under monocular viewing conditions where both the reference and signal pairs were presented to one eye, the temporal synchrony thresholds of previous amblyopic eyes and fellow eyes were not significantly different (p = 0.15). Under dichoptic viewing conditions where both the reference and signal pairs were dichoptically presented to both eyes, the temporal synchrony threshold in the treated anisometropic amblyopes was significantly higher than that of the controls (119.34 ± 20.43 vs. 99.78 ± 16.60 ms, p = 0.009). There was no significant correlation between the monocular and dichoptic viewing conditions in the treated amblyopes (r = -0.22, p = 0.94). CONCLUSIONS: Temporal synchrony discrimination is abnormal under dichoptic but not under monocular visual stimulation in treated anisometropic amblyopes with normalised visual acuity.

HS-GC-IMS Analysis of Volatile Organic Compounds in Different Varieties and Harvesting Times of Rhizoma gastrodiae (Tian Ma) in Yunnan Province.

Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) coupled with principal component analysis (PCA) was used to investigate the differences in volatile organic compounds (VOCs) in four different varieties of Yunnan Huang Tian Ma (containing both winter and spring harvesting times), Yunnan Hong Tian Ma, Yunnan Wu Tian Ma, and Yunnan Lv Tian Ma. The results showed that the flavor substances of different varieties and different harvesting times of Rhizoma gastrodiae were mainly composed of aldehydes, alcohols, ketones, heterocycles, esters, acids, alkenes, hydrocarbons, amines, phenols, ethers, and nitrile. Among them, the contents of the aldehydes, alcohols, ketones, and heterocyclic compounds are significantly higher than those of other substances. The results of cluster analysis and fingerprint similarity analysis based on principal component analysis and Euclidean distance showed that there were some differences between different varieties of Yunnan Rhizoma gastrodiae and different harvesting times. Among them, Yunnan Lv Tian Ma and Wu Tian Ma contained the richest volatile components. Winter may be the best harvesting season for Tian Ma. At the same time, we speculate that the special odor contained in Tian Ma should be related to the aldehydes it is rich in, especially benzene acetaldehyde, Benzaldehyde, Heptanal, Hexanal, Pentanal, and butanal, which are aldehydes that contain a strong and special odor and are formed by the combination of these aldehydes.

Degradome sequencing reveals an integrative miRNA-mediated gene interaction network regulating rice seed vigor.

BACKGROUND: It is well known that seed vigor is essential for agricultural production and rice (Oryza sativa L.) is one of the most important crops in the world. Though we previously reported that miR164c regulates rice seed vigor, but whether and how other miRNAs cooperate with miR164c to regulate seed vigor is still unknown. RESULTS: Based on degradome data of six RNA samples isolated from seeds of the wild-type (WT) indica rice cultivar 'Kasalath' as well as two modified lines in 'Kasalath' background (miR164c-silenced line [MIM164c] and miR164c overexpression line [OE164c]), which were subjected to either no aging treatment or an 8-day artificial aging treatment, 1247 different target transcripts potentially cleaved by 421 miRNAs were identified. The miRNA target genes were functionally annotated via GO and KEGG enrichment analyses. By STRING database assay, a miRNA-mediated gene interaction network regulating seed vigor in rice was revealed, which comprised at least four interconnected pathways: the miR5075-mediated oxidoreductase related pathway, the plant hormone related pathway, the miR164e related pathway, and the previously reported RPS27AA related pathway. Knockout and overexpression of the target gene Os02g0817500 of miR5075 decreased and enhanced seed vigor, respectively. By Y2H assay, the proteins encoded by five seed vigor-related genes, Os08g0295100, Os07g0633100, REFA1, OsPER1 and OsGAPC3, were identified to interact with Os02g0817500. CONCLUSIONS: miRNAs cooperate to regulate seed vigor in rice via an integrative gene interaction network comprising miRNA target genes and other functional genes. The result provided a basis for fully understanding the molecular mechanisms of seed vigor regulation.

Discovery of 3, 6-disubstituted isobenzofuran-1(3H)-ones as novel inhibitors of monoamine oxidases.

Monoamine oxidases A and B (MAO-A and MAO-B) play important roles in biogenic amine metabolism, oxidative stress, and chronic inflammation. Particularly, MAO-B selective inhibitors are promising therapeutic choices for the treatment of neurodegenerative diseases, such as Pakinson's disease and Alzheimer's disease. Herein, novel 3,6-disubstituted isobenzofuran-1(3H)-ones were designed, synthesized and evaluated in vitro as inhibitors of monoamine oxidases A and B. Structure-activity relationships were investigated, and all of the compounds with (R)-3-hydroxy pyrrolidine moiety on the 6-position displayed preferable inhibition toward the MAO-B isoform. Among them, compounds 6c with a 4'-fluorobenzyl ring and 6m bearing a 3',4'-difluorobenzyl ring on the 3-position were the most potent MAO-B inhibitors with IC50 values of 0.35 µM and 0.32 µM, respectively. The binding mode of compound 6m in MAO-B was predicted by CDOCKER program, revealing that (R)-3-hydroxypyrrolidine moiety is a critical structural feature for this series of MAO-B inhibitors. Compound 6m could serve as a new template structure for developing potent and selective MAO-B inhibitors.

Computational ghost imaging based on a conditional generation countermeasure network under a low sampling rate.

In this paper, an end-to-end depth neural network based on a conditional generative adversarial network for computational ghost imaging (CGANCGI) is proposed to restore clear object images with high quality at a sub-Nyquist sampling rate. The 2D light signal collected by a CMOS camera and the gray image of the original measured object are used as the input of the network model; then, the CGANCGI network is trained, and the measured object image is recovered directly from the 2D light signal. Experiments have verified that the proposed method only needs 1/10 of traditional deep learning samples to achieve fast image restoration with high-quality, and its peak signal-to-noise ratio and structural similarity are, respectively, four to six times and five to seven times higher than those of the original image, which prove that our method has practical application prospects in ghost imaging under low sampling rates.

Influence of optical zone on myopic correction in small incision lenticule extraction: a short-term study.

BACKGROUND: To evaluate the influence of preoperative optical zone on myopic correction in small incision lenticule extraction. METHODS: In this retrospective clinical study, 581 eyes from 316 patients underwent SMILE were selected, including 117 eyes in the small optical zone group (range from 6.0 to 6.4 mm) and 464 eyes in the large optical zone group (range from 6.5 to 6.8 mm). The measurements included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical, and cylinder were measured preoperatively and 3 months postoperatively. Propensity score match (PSM) analysis was performed with age, gender, eye (right/left), keratometry and preoperative spherical equivalent between two different groups. The influence of optical zones on postoperative refractive outcomes were evaluated using univariate regression analysis. RESULTS: In total, 78 pairs of eyes were selected by PSM (match ratio 1:1). There were no differences in the age, gender, eye (right/left), keratometry or preoperative spherical equivalent between the small and large optical zone groups. However, the difference of postoperative spherical equivalent was significantly between groups. Patients with larger optical zones had a trend towards less undercorrection (P = 0.018). Univariate linear regression model analysis found that each millimeter larger optical zone resulted in 8.13% or 0.39D less undercorrection (P < 0.001). The dependency between the optical zones and postoperative spherical equivalent was significant in the higher preoperative myopia group (r = 0.281, P < 0.001), but not significant in the lower myopia group (r = 0.028, P = 0.702). CONCLUSION: The diameter of optical zones would affect postoperative refractive outcomes in small incision lenticule extraction. This study indicated that larger optical zones induced less undercorrection, especially in patients with high myopia.

pH-responsive cinnamaldehyde-TiO2 nanotube coating: fabrication and functions in a simulated diabetes condition.

Current evidence has suggested that diabetes increases the risk of implanting failure, and therefore, appropriate surface modification of dental implants in patients with diabetes is crucial. TiO2 nanotube (TNT) has an osteogenic nanotopography, and its osteogenic properties can be further improved by loading appropriate drugs. Cinnamaldehyde (CIN) has been proven to have osteogenic, anti-inflammatory, and anti-bacterial effects. We fabricated a pH-responsive cinnamaldehyde-TiO2 nanotube coating (TNT-CIN) and hypothesized that this coating will exert osteogenic, anti-inflammatory, and anti-bacterial functions in a simulated diabetes condition. TNT-CIN was constructed by anodic oxidation, hydroxylation, silylation, and Schiff base reaction to bind CIN, and its surface characteristics were determined. Conditions of diabetes and diabetes with a concurrent infection were simulated using 22-mM glucose without and with 1-µg/mL lipopolysaccharide, respectively. The viability and osteogenic differentiation of bone marrow mesenchymal stem cells, polarization and secretion of macrophages, and resistance to Porphyromonas gingivalis and Streptococcus mutans were evaluated. CIN was bound to the TNT surface successfully and released better in low pH condition. TNT-CIN showed better osteogenic and anti-inflammatory effects and superior bacterial resistance than TNT in a simulated diabetes condition. These findings indicated that TNT-CIN is a promising, multifunctional surface coating for patients with diabetes needing dental implants. Graphical abstract.

Characteristic Volatile Organic Compound Analysis of Different Cistanches Based on HS-GC-IMS.

Cistanche is a medicinal and food homologous substance with a long history of consumption and medicinal use in China. In order to further understand the volatile organic compound differences between different cistanches, this study selected oil cistanche, blood cistanche and cistanche tubulosa in Xinjiang for HS-GC-IMS volatile organic compounds, and established the characteristic fingerprints of different cistanches for organic content and characteristic organic compound analysis. PCA and cluster analysis were used to study the similarity between different cistanches. After qualitative analysis, a total of 32 volatile organic compounds were identified, covering aldehydes (17), ketones (5), furans (1), alcohols (5), lactones (1) and esters (3), and the volatile organic compounds between samples a, b and c could be significantly distinguished, affecting the flavor of cistanche itself. It provides a basic theoretical basis for the study of cistanche flavor.

Neocornuside A-D, Four Novel Iridoid Glycosides from Fruits of Cornus officinalis and Their Antidiabetic Activity.

Four previously undescribed iridoid glycosides neocornuside A-D (1-4), along with six known ones (5-10), were isolated from Cornus officinalis fruit. Their structures were elucidated by extensive spectroscopic (NMR, UV, IR, and MS) analysis and comparison with data reported in the literature. All isolates were assessed for their antidiabetic activity on the relative glucose consumption in insulin-induced insulin-resistant HepG2 cells. The results showed that compounds 1, 3, and 7 exhibited significant antidiabetic activities with EC50 values of 0.582, 1.275, and 0.742 µM, respectively. Moreover, compounds 1, 3, and 7 could improve the ability of 2-NBDG uptake of insulin-induced HepG2 cells.

HPV-Associated Tumor Eradication by Vaccination with Synthetic Short Peptides and Particle-Forming Liposomes.

Human papilloma virus (HPV)-16 is associated with cervical cancers and induces expression of the E6 and E7 oncogenes. Using a murine cell line that expresses these, the genes are sequenced, and six predicted major histocompatibility complex (MHC) class I (MHC-I) epitopes are identified. A liposomal vaccine adjuvant based on cobalt-porphyrin-phospholipid (CoPoP) is admixed with synthetic 9-mer epitopes appended with three histidine residues, resulting in rapid formation of peptide-liposome particles. Immunization with multivalent peptides leads to protection from tumor challenge. Of the peptides screened, only the previously identified E749-57 epitope is functional. The peptide-liposome particles that form upon mixing E7HHH49-57 with CoPoP liposomes are stable in serum and are avidly taken up by immune cells in vitro. Immunization results in robust protection from tumor challenge and re-challenge. A 100 ng peptide dose protects mice in a therapeutic tumor challenge when admixed with CoPoP liposomes, whereas 200-fold higher peptide doses are ineffective with the polyinosinic-polycytidylic (poly(I:C)) adjuvant. CoPoP induces a strong infiltrating CD8+ T-cell response within the tumor microenvironment with an improved functional profile. Vaccine monotherapy using nanogram dosing of the E7HHH49-57 peptide admixed with CoPoP reverses the growth of large established tumors, eradicating subcutaneous tumors upwards of 100 mm3 . Immunization also eradicates lung tumors in a metastasis model.

Three-Dimensional Reconstruction of Light Field Based on Phase Similarity.

Light field imaging plays an increasingly important role in the field of three-dimensional (3D) reconstruction because of its ability to quickly obtain four-dimensional information (angle and space) of the scene. In this paper, a 3D reconstruction method of light field based on phase similarity is proposed to increase the accuracy of depth estimation and the scope of applicability of epipolar plane image (EPI). The calibration method of the light field camera was used to obtain the relationship between disparity and depth, and the projector calibration was removed to make the experimental procedure more flexible. Then, the disparity estimation algorithm based on phase similarity was designed to effectively improve the reliability and accuracy of disparity calculation, in which the phase information was used instead of the structure tensor, and the morphological processing method was used to denoise and optimize the disparity map. Finally, 3D reconstruction of the light field was realized by combining disparity information with the calibrated relationship. The experimental results showed that the reconstruction standard deviation of the two objects was 0.3179 mm and 0.3865 mm compared with the ground truth of the measured objects, respectively. Compared with the traditional EPI method, our method can not only make EPI perform well in a single scene or blurred texture situations but also maintain good reconstruction accuracy.

Cost-benefit analysis of low-impact development at hectare scale for urban stormwater source control in response to anticipated climatic change.

Investigation of the cost-effectiveness of low-impact development (LID) practices at the hectare scale in response to impacts of possible climate change was conducted using representative concentration pathways (RCPs). An LID project in Guangzhou has been selected to illustrate changes in the hydrologic performance for alternative source control strategies for a variety of future climate models and scenarios. Frequent storms of shorter duration in RCP 8.5 cause more dramatic fluctuation of hydrologic performance. Hydrologic performance of LID practices on reducing runoff volume and peak flow in test catchment are different in climate scenarios. Based on the constraints of life cycle costs and environmental impacts of LID alternatives, comprehensive strategies were found effective in managing surface runoff at the source to adapt to the influence of climate change. The methodology described herein could be useful in considering LID practices for critical source management with limited budgets and considering environmental impacts under long-term climate change.