Dynamical and statistical features of soliton interactions in the focusing Gardner equation.

In this paper, the dynamical properties of soliton interactions in the focusing Gardner equation are analyzed by the conventional two-soliton solution and its degenerate cases. Using the asymptotic expressions of interacting solitons, it is shown that the soliton polarities depend on the signs of phase parameters, and that the degenerate solitons in the mixed and rational forms have variable velocities with the time dependence of attenuation. By means of extreme value analysis, the interaction points in different interaction scenarios are presented with exact determination of positions and occurrence times of high transient waves generated in the bipolar soliton interactions. Next, with all types of two-soliton interaction scenarios considered, the interactions of two solitons with different polarities are quantitatively shown to have a greater contribution to the skewness and kurtosis than those with the same polarity. Specifically, the ratios of spectral parameters (or soliton amplitudes) are determined when the bipolar soliton interactions have the strongest effects on the skewness and kurtosis. In addition, numerical simulations are conducted to examine the properties of multi-soliton interactions and their influence on higher statistical moments, especially confirming the emergence of the soliton interactions described by the mixed and rational solutions in a denser soliton ensemble.

Design of hepadnavirus core protein-based chimeric virus-like particles carrying epitopes from respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an "epitope-focused" vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design.

Remodeling the Electronic Structure of Metallic Nickel and Ruthenium via Alloying in a Molecular Template for Sustainable Hydrogen Evolution.

The reasonably constructed high-performance electrocatalyst is crucial to achieve sustainable electrocatalytic water splitting. Alloying is a prospective approach to effectively boost the activity of metal electrocatalysts. However, it is a difficult subject for the controllable synthesis of small alloying nanostructures with high dispersion and robustness, preventing further application of alloy catalysts. Herein, we propose a well-defined molecular template to fabricate a highly dispersed NiRu alloy with ultrasmall size. The catalyst presents superior alkaline hydrogen evolution reaction (HER) performance featuring an overpotential as low as 20.6 ± 0.9 mV at 10 mA·cm-2. Particularly, it can work steadily for long periods of time at industrial-grade current densities of 0.5 and 1.0 A·cm-2 merely demanding low overpotentials of 65.7 ± 2.1 and 127.3 ± 4.3 mV, respectively. Spectral experiments and theoretical calculations revealed that alloying can change the d-band center of both Ni and Ru by remodeling the electron distribution and then optimizing the adsorption of intermediates to decrease the water dissociation energy barrier. Our research not only demonstrates the tremendous potential of molecular templates in architecting highly active ultrafine nanoalloy but also deepens the understanding of water electrolysis mechanism on alloy catalysts.

Impact of deoxynivalenol on rumen function, production, and health of dairy cows: Insights from metabolomics and microbiota analysis.

Deoxynivalenol contamination in feed and food, pervasive from growth, storage, and processing, poses a significant risk to dairy cows, particularly when exposed to a high-starch diet; however, whether a high-starch diet exacerbates these negative effects remains unclear. Therefore, we investigated the combined impact of deoxynivalenol and dietary starch on the production performance, rumen function, and health of dairy cows using metabolomics and 16 S rRNA sequencing. Our findings suggested that both high- and low-starch diets contaminated with deoxynivalenol significantly reduced the concentration of propionate, isobutyrate, valerate, total volatile fatty acids (TVFA), and microbial crude protein (MCP) concentrations, accompanied by a noteworthy increase in NH3-N concentration in vitro and in vivo (P < 0.05). Deoxynivalenol altered the abundance of microbial communities in vivo, notably affecting Oscillospiraceae, Lachnospiraceae, Desulfovibrionaceae, and Selenomonadaceae. Additionally, it significantly downregulated lecithin, arachidonic acid, valine, leucine, isoleucine, arginine, and proline metabolism (P < 0.05). Furthermore, deoxynivalenol triggered oxidative stress, inflammation, and dysregulation in immune system linkage, ultimately compromising the overall health of dairy cows. Collectively, both high- and low-starch diets contaminated with deoxynivalenol could have detrimental effects on rumen function, posing a potential threat to production performance and the overall health of cows. Notably, the negative effects of deoxynivalenol are more pronounced with a high-starch diet than a low-starch diet.

Chimeric virus-like particles of human norovirus constructed by structure-guided epitope grafting elicit cross-reactive immunity against both GI.1 and GII.4 genotypes.

IMPORTANCE: Human norovirus (HuNoV) is highly infectious and can result in severe illnesses in the elderly and children. So far, there is no effective antiviral drug to treat HuNoV infection, and thus, the development of HuNoV vaccines is urgent. However, NoV evolves rapidly, and currently, at least 10 genogroups with numerous genotypes have been found. The genetic diversity of NoV and the lack of cross-protection between different genotypes pose challenges to the development of broadly protective vaccines. In this study, guided by structural alignment between GI.1 and GII.4 HuNoV VP1 proteins, several chimeric-type virus-like particles (VLPs) were designed through surface-exposed loop grafting. Mouse immunization studies show that two of the designed chimeric VLPs induced cross-immunity against both GI.1 and GII.4 HuNoVs. To our knowledge, this is the first designed chimeric VLPs that can induce cross-immune activities across different genogroups of HuNoV, which provides valuable strategies for the development of cross-reactive HuNoV vaccines.

Assessment of Blood Volume in Liposuction Fluids Using Colorimetry.

OBJECTIVE: The possibility of using a color contrast method to evaluate blood loss during liposuction was assessed. A color chart of blood-lipid content associated with different blood volumes was developed. METHODS: Three color cards with different concentrations of blood were developed based on clinical parameters. The color cards were used to evaluate the volume of blood present in liposuction solutions obtained from 60 clinical liposuction patients. The red blood cell count also was evaluated for each patient. The data obtained using each evaluation method were compared and statistically analyzed to determine the most accurate calculation formula. RESULTS: The red blood cell counts were compared to the color card results. The paired t test results for the calculated values for the 3:1, 2:1, and 1:1 color cards and the red blood cell count values were comparable (44.3 ± 22.1 ml vs. 53.6 ± 25.0 ml, t = 10.5; 45.4 ± 19.0 ml vs. 55.2 ± 20.7 ml, t = 18.1; 41.9 ± 25.6 ml vs. 52.8 ± 28.3 ml, t = 14.0). The P values were < 0.05, and the difference between the two groups was statistically significant. The average standard error of the mean was 0.90, 0.54, and 0.77, respectively. Sixty samples were evaluated in a scatter diagram using the two detection methods. Trend analysis revealed that the two results demonstrated a linear increase (y = 5.6 + 1.1x), R2 = 0.989, indicating that the two inspection methods were highly correlated with only small errors. CONCLUSION: The colorimetric card protocol developed in this study could quickly, accurately, and conveniently calculate blood volumes in liposuction fluids, which has considerable clinical significance. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Optimizing the Spatial Density of Single Co Sites via Molecular Spacing for Facilitating Sustainable Water Oxidation.

Advances in single-atom (-site) catalysts (SACs) provide a new solution of atomic economy and accuracy for designing efficient electrocatalysts. In addition to a precise local coordination environment, controllable spatial active structure and tolerance under harsh operating conditions remain great challenges in the development of SACs. Here, we show a series of molecule-spaced SACs (msSACs) using different acid anhydrides to regulate the spatial density of discrete metal phthalocyanines with single Co sites, which significantly improve the effective active-site numbers and mass transfer, enabling one of the msSACs connected by pyromellitic dianhydride to exhibit an outstanding mass activity of (1.63 ± 0.01) × 105 A·g-1 and TOFbulk of 27.66 ± 1.59 s-1 at 1.58 V (vs RHE) and long-term durability at an ultrahigh current density of 2.0 A·cm-2 under industrial conditions for oxygen evolution reaction. This study demonstrates that the accessible spatial density of single atom sites can be another important parameter to enhance the overall performance of catalysts.

Identification of key mutations responsible for the enhancement of receptor-binding affinity and immune escape of SARS-CoV-2 Omicron variant.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised concerns worldwide due to its enhanced transmissibility and immune escapability. The first dominant Omicron BA.1 subvariant harbors more than 30 mutations in the spike protein from the prototype virus, of which 15 mutations are located at the receptor binding domain (RBD). These mutations in the RBD region attracted significant attention, which potentially enhance the binding of the receptor human angiotensin-converting enzyme 2 (hACE2) and decrease the potency of neutralizing antibodies/nanobodies. This study applied the molecular dynamics simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method, to investigate the molecular mechanism behind the impact of the mutations acquired by Omicron on the binding affinity between RBD and hACE2. Our results indicate that five key mutations, i.e., N440K, T478K, E484A, Q493R, and G496S, contributed significantly to the enhancement of the binding affinity by increasing the electrostatic interactions of the RBD-hACE2 complex. Moreover, fourteen neutralizing antibodies/nanobodies complexed with RBD were used to explore the effects of the mutations in Omicron RBD on their binding affinities. The calculation results indicate that the key mutations E484A and Y505H reduce the binding affinities to RBD for most of the studied neutralizing antibodies/nanobodies, mainly attributed to the elimination of the original favorable gas-phase electrostatic and hydrophobic interactions between them, respectively. Our results provide valuable information for developing effective vaccines and antibody/nanobody drugs.

Characteristics of culprit intracranial plaque without substantial stenosis in ischemic stroke using three-dimensional high-resolution vessel wall magnetic resonance imaging.

Background and aims: We aim to analyze the difference in quantitative features between culprit and non-culprit intracranial plaque without substantial stenosis using three-dimensional high-resolution vessel wall MRI (3D hr-vw-MRI). Methods: The patients with cerebral ischemic symptoms of the unilateral anterior circulation were recruited who had non-stenotic intracranial atherosclerosis (<50%) confirmed by computed tomographic angiographic (CTA) or magnetic resonance angiography (MRA). All patients underwent 3D hr-vw MRI within 1 month after symptom onset. 3D hr-vw-MRI characteristics, including wall thickness, plaque burden, enhancement ratio, plaque volume and intraplaque hemorrhage, and histogram features were analyzed based on T2-, precontrast T1-, and post-contrast T1-weighted images. Univariate and multivariate logistic regression analysis were used to identify key determinates differentiating culprit and non-culprit plaques and to calculate the odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 150 plaques were identified, of which 133 plaques (97 culprit and 36 non-culprit) were in the middle cerebral artery, three plaques (all culprit) were in the anterior cerebral artery (ACA) and 14 (11 culprit and three non-culprit) were in the internal carotid artery (ICA). Of all the quantitative parameters analyzed, plaque volume, maximum wall thickness, minimum wall thickness, plaque burden, enhancement ratio, coefficient of variation of the most stenotic site, enhancement ratio of whole culprit plaque in culprit plaques were significantly higher than those in non-culprit plaques. Multivariate logistic regression analysis found that plaque volume [OR, 1.527 (95% CI, 1.231-1.894); P < 0.001] and enhancement ratio of whole plaque [OR, 1.095 (95% CI, 1.021-1.175); P = 0.011] were significantly associated with culprit plaque. The combination of the two features obtained a better diagnostic efficacy for culprit plaque with sensitivity and specificity (0.910 and 0.897, respectively) than each of the two parameters alone. Conclusion: 3D hr-vw MRI features of intracranial atherosclerotic plaques provided potential values over prediction of ischemic stroke patients with non-stenotic arteries. The plaque volume and enhancement ratio of whole plaque of stenosis site were found to be effective predictive parameters.

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants.

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to pose a serious threat to public health and has so far resulted in over six million deaths worldwide. Mass vaccination programs have reduced the risk of serious illness and death in many people, but the virus continues to persist and circulate in communities across the globe. Furthermore, the current vaccines may be less effective against the new variants of the virus, such as Omicron and Delta, which are continually emerging and evolving. Therefore, it is urgent to develop effective vaccines that can provide broad protection against existing and future forms of SARS-CoV-2. There are several different types of SARS-CoV-2 vaccine, but they all work in a similar way. They contain molecules that induce immune responses in individuals to help the body recognize and more effectively fight SARS-CoV-2 if they happen to encounter it in the future. These immune responses may be so specific that new variants of a virus may not be recognized by them. Therefore, a commonly used strategy for producing vaccines with broad protection is to make multiple vaccines that each targets different variants and then mix them together before administering to patients. Here, Zhang et al. took a different approach by designing a new vaccine candidate against SARS-CoV2 that contained three different versions of part of a SARS-CoV2 protein ­ the so-called spike protein ­ all linked together as one molecule. The different versions of the spike protein fragment were designed to include key features of the fragments found in Omicron and several other SARS-CoV-2 variants. The experiments found that this candidate vaccine elicited a much higher immune response against Omicron and other SARS-CoV-2 variants in rats than an existing SARS-CoV-2 vaccine. It was also effective as a booster shot after a first vaccination with the existing SARS-CoV-2 vaccine. These findings demonstrate that the molecule developed by Zhang et al. induces potent and broad immune responses against different variants of SARS-CoV-2 including Omicron in rats. The next steps following on from this work are to evaluate the safety and immunogenicity of this vaccine candidate in clinical trials. In the future, it may be possible to use a similar approach to develop new broad-spectrum vaccines against other viruses.

The Tumor Plastic Surgery Technology versus Traditional Repair Technology on the Repair of Large-Area Skin Defects after Maxillofacial Tumor Resection: A Randomized Controlled Trial.

Objective: To explore the effect of tumor plastic surgery on the repair of large-area skin defects after maxillofacial tumor resection. Methods: 90 patients undergoing maxillofacial tumor resection in our hospital from March 2019 to March 2020 were selected and randomized 1 : 1 to receive either tumor plastic surgery (experimental group) or traditional repair (control group). The clinical efficacy and facial cosmetic improvement of the two groups were compared. The Patient and Observer Scar Assessment Scale (POSAS) was used to evaluate the surgical outcomes of the two groups, the Profile of Mood States (POMS) was used to evaluate the patients' psychological status, and the Generic Quality of Life Inventory-74 (GQOLI-74) was used to assess the quality of life of patients. Results: Total clinical effective rate of the experimental group was significantly higher than that of the control group (p < 0.001). A higher excellent rate of facial cosmetic improvement was observed in the experimental group versus the control group (p < 0.001). Significantly lower POSAS scores of the experimental group than the control group were observed (p < 0.001). The POMS scores of the experimental group after treatment were lower than those of the control group (p < 0.001). Tumor plastic surgery resulted in a remarkably higher GQOLI-74 score in the patients versus traditional repair (p < 0.001). Conclusion: Tumor plastic surgery is a promising alternative for patients undergoing maxillofacial tumor resection. It can effectively promote the recovery of facial morphology and physiological function of patients, with high clinical efficacy, so it merits promotion and application.

Impact of heat stress on milk yield, antioxidative levels, and serum metabolites in primiparous and multiparous Holstein cows.

This study aimed to access the effect of heat stress on milk yield, antioxidative levels, and serum metabolites in primiparous and multiparous Holstein dairy cows during the early lactation stage. A total of 200 cows were selected based on their month of calving (June, temperature humidity index (THI) = 66.72; July, THI = 70.30; August, THI = 69.32; September, THI = 67.20; October, THI = 59.45). Blood samples were collected on days 0, 21, 50, 80, and 100 after calving for serum oxidative status analysis and milk yield was recorded daily. The lower average daily milk yield was recorded among the cows that calved in June and July (P < 0.05), and the average daily milk yield of multiparous cows was higher than that of primiparous cows that calved in the same month (P < 0.05) from d1 to d100, suggesting that seasonal (June, July) heat stress negatively affected milk yield in both primiparous and multiparous cows at early lactation. The study also indicated that there was seasonal variation in most of the serum metabolites across the studied months. The study shows that heat stress (average THI = 70.30) was higher among the cows calving in June vis-à-vis those calving in October and differences were also observed among the primiparous cows and multiparous cows, respectively. These metabolites (e.g., glycine, serine, etc.) which showed significant variations were mainly involved in the pathways of aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism, and the metabolism of glycine, serine and threonine. These data suggested that heat stress negatively affected the elevation of the serum oxidative and antioxidative index and thus badly influence milk yield. Metabolic biomarkers in serum associated with heat stress could be a reliable way to identify heat stress of primiparas and multiparas dairy cows.

Floquet Engineering Hz-Level Rabi Spectra in Shallow Optical Lattice Clock.

Quantum metrology with ultrahigh precision usually requires atoms prepared in an ultrastable environment with well-defined quantum states. Thus, in optical lattice clock systems deep lattice potentials are used to trap ultracold atoms. However, decoherence, induced by Raman scattering and higher order light shifts, can significantly be reduced if atomic clocks are realized in shallow optical lattices. On the other hand, in such lattices, tunneling among different sites can cause additional dephasing and strongly broadening of the Rabi spectrum. Here, in our experiment, we periodically drive a shallow ^{87}Sr optical lattice clock. Counterintuitively, shaking the system can deform the wide broad spectral line into a sharp peak with 5.4 Hz linewidth. With careful comparison between the theory and experiment, we demonstrate that the Rabi frequency and the Bloch bands can be tuned, simultaneously and independently. Our work not only provides a different idea for quantum metrology, such as building shallow optical lattice clock in outer space, but also paves the way for quantum simulation of new phases of matter by engineering exotic spin orbit couplings.

Confinement synthesis in porous molecule-based materials: a new opportunity for ultrafine nanostructures.

A balance between activity and stability is greatly challenging in designing efficient metal nanoparticles (MNPs) for heterogeneous catalysis. Generally, reducing the size of MNPs to the atomic scale can provide high atom utilization, abundant active sites, and special electronic/band structures, for vastly enhancing their catalytic activity. Nevertheless, due to the dramatically increased surface free energy, such ultrafine nanostructures often suffer from severe aggregation and/or structural degradation during synthesis and catalysis, greatly weakening their reactivities, selectivities and stabilities. Porous molecule-based materials (PMMs), mainly including metal-organic frameworks (MOFs), covalent organic frameworks (COFs) and porous organic polymers (POPs) or cages (POCs), exhibit high specific surface areas, high porosity, and tunable molecular confined space, being promising carriers or precursors to construct ultrafine nanostructures. The confinement effects of their nano/sub-nanopores or specific binding sites can not only effectively limit the agglomeration and growth of MNPs during reduction or pyrolysis processes, but also stabilize the resultant ultrafine nanostructures and modulate their electronic structures and stereochemistry in catalysis. In this review, we highlight the latest advancements in the confinement synthesis in PMMs for constructing atomic-scale nanostructures, such as ultrafine MNPs, nanoclusters, and single atoms. Firstly, we illustrated the typical confinement methods for synthesis. Secondly, we discussed different confinement strategies, including PMM-confinement strategy and PMM-confinement pyrolysis strategy, for synthesizing ultrafine nanostructures. Finally, we put forward the challenges and new opportunities for further applications of confinement synthesis in PMMs.

Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

Plasma ADAM-10 levels and functional outcome of acute primary basal ganglia hemorrhage.

BACKGROUND: The a-secretase A disintegrin and metalloprotease-10 (ADAM-10) may have deleterious effects in acute brain injury. This study was designed to discern if a relationship between plasma ADAM-10 levels and functional outcome exists in patients with intracerebral hemorrhage (ICH). METHODS: A total of 109 patients with basal ganglia hemorrhage and 100 healthy controls were included. Their plasma ADAM-10 levels were gauged. Ninety-day prognosis was assessed and poor outcome was defined as death or major disability (modified Rankin Scale score of 3 or greater). RESULTS: Plasma ADAM-10 levels were substantially elevated in patients, as compared to controls. ADAM-10 levels were independently correlated with hematoma size and National Institutes of Health Stroke Scale (NIHSS) score. Plasma ADAM-10, NIHSS score and hematoma size emerged as the independent predictors for 90-day poor outcome. Under receiver operating characteristic curve, plasma ADAM-10 levels exhibited similar prognostic capability, as compared to hematoma size and NIHSS score; moreover, it significantly improved prognostic abilities of NIHSS and hematoma size. CONCLUSIONS: Rising plasma ADAM-10 levels are independently related to increasing severity and poor long-term functional outcome after hemorrhagic stroke, substantializing serum ADAM-10 as a useful prognostic biomarker of ICH.

Lung ultrasound to quantitatively evaluate extravascular lung water content and its clinical significance.

BACKGROUND: As we all know, pulmonary edema can be diagnosed by lung ultrasound (LUS), but how to accurately and quantitatively evaluate lung water content by ultrasound is a difficult problem that needs to be solved urgently. B-line assessment with LUS has recently been proposed as a reliable, noninvasive semiquantitative tool for evaluating extravascular lung water (EVLW). To date, however, there has been no easy quantitative method to evaluate EVLW by LUS. OBJECTIVE: (1) To explore the feasibility of establishing a rabbit model with increased EVLW by injecting warm normal saline (NS) into the lungs via the endotracheal tube. (2) To establish a simple, accurate and clinically operable method for quantitative assessment of EVLW using LUS. (3) To develop LUS into a resource for guiding the clinical treatment of patients with increased EVLW. METHODS: Forty-five New Zealand rabbits were randomized into nine groups (n = 5). After anesthesia, each group of rabbits was injected with different amounts of warm sterile NS (0 ml/kg, 2 ml/kg, 4 ml/kg, 6 ml/kg, 8 ml/kg, 10 ml/kg, 15 ml/kg, 20 ml/kg, 30 ml/kg) via the endotracheal tube. Each rabbit was examined by LUS before and after NS injection. At the same time, the spontaneous respiratory rate (RR, breaths per minute), heart rate (HR, bpm) and arterial blood gas (ABG) of the rabbits were recorded. Then, both lungs were dissected to obtain the wet and dry weight and conduct a complete histological examination. RESULTS: Injecting NS into the lungs through a tracheal tube can successfully establish a rabbit model with increased EVLW. The extent of EVLW increase is related to the volume of NS injected into the lungs. As the EVLW increases, three different types of B-lines can be seen in the LUS. When the NS injection volume is 2-6 ml/kg, comet-tail artifacts and B-lines are the main patterns found on LUS; as additional NS is injected into the lungs, the rabbits' RR gradually increases, while their HR gradually decreases, ABG remains normal or shows mild metabolic acidosis (MA). Confluent B-lines grow gradually but significantly, reaching a dominant position when the NS injection volume reaches 6-8 ml/kg and predominating almost entirely when the NS injection volume is 8-15 ml/kg; at that time, rabbits' RRs and HRs decrease sharply, and the ABG indicated type I respiratory failure (RF).Compact B-lines occur and predominate almost entirely when the NS injection volume reaches 10 ml/kg and 15-20 ml/kg, respectively. At that time, rabbits begin to enter cardiac and respiratory arrest, and ABG shows type II RF and MA. CONCLUSION: In this study, the establishment of an animal model with increased EVLW confirmed that different lung water content had corresponding manifestations in ultrasound and was associated with different degrees of clinical symptoms, and the study results can be used to guide clinical practice.

Neurocognitive deficits and sequelae following severe hand, foot, and mouth disease from 2009 to 2017, in JiangSu Province, China: a long-term follow-up study.

BACKGROUND: The aim of this study was to evaluate the long-term sequelae and cognitive profiles resulting from severe hand, foot, and mouth disease (HFMD) with central nervous system (CNS) involvement. METHODS: 294 HFMD cases were included in a retrospective follow-up study. Physical examinations were conducted. The Chinese Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to assess intelligence. RESULTS: 58 mild HFMD cases and 99 severe HFMD cases with mild CNS involvement did not present any neurological sequelae. In comparison, the sequelae incidence for severe HFMD with more severe CNS complications was 50.0%. The proportion of full-scale intelligence quotient (FSIQ) impairment was 45.0%. In the 2:6-3:11 age group, severe HFMD with more severe CNS complications and lower maternal education level were risk factors for verbal comprehension disorder. Urban-rural residence and lower paternal education level were risk factors for FSIQ disorder. Furthermore, in the 4:0-6:11 age group, severe HFMD with more severe CNS complication was a risk factor for visual spatial disorder and fluid reasoning disorder. Lower paternal education level was a risk factor for FSIQ disorder. CONCLUSION: Early assessment and intervention among severe HFMD patients with more severe CNS involvement at a very young age will prove beneficial for their future performance.

Effects of Different Combinations of Sugar and Starch Concentrations on Ruminal Fermentation and Bacterial-Community Composition in vitro.

High levels of starch is known to have positive effects on both energy supply and milk yield but increases the risk of rumen acidosis. The use of sugar as a non-structural carbohydrate could circumvent this risk while maintaining the benefits, but its effects and that of the simultaneous use of both sugar and starch are not as well-understood. This study aimed to evaluate the effects of different combinations of sugar and starch concentrations on ruminal fermentation and bacterial community composition in vitro in a 4 ×4 factorial experiment. Sixteen dietary treatments were formulated with 4 levels of sugar (6, 8, 10, and 12% of dietary dry matter), and 4 levels of starch (21, 23, 25, and 27% of dietary dry matter). Samples were taken at 0.5, 1, 3, 6, 12, and 24 h after cultivation to determine the disappearance rate of dry matter, rumen fermentation parameters and bacterial community composition. Butyric acid, gas production, and Treponema abundance were significantly influenced by the sugar level. The pH, acetic acid, and propionic acid levels were significantly influenced by starch levels. However, the interactive effect of sugar and starch was only observed on the rate of dry matter disappearance. Furthermore, different combinations of starch and sugar had different effects on volatile fatty acid production rate, gas production rate, and dry matter disappearance rate. The production rate of rumen fermentation parameters in the high sugar group was higher. Additionally, increasing the sugar content in the diet did not change the main phylum composition in the rumen, but significantly increased the relative abundance of Bacteroidetes and Firmicutes phyla, while the relative abundance of Proteobacteria was reduced. At the genus level, the high glucose group showed significantly higher relative abundance of Treponema (P < 0.05) and significantly lower relative abundance of Ruminobacter, Ruminococcus, and Streptococcus (P < 0.05). In conclusion, different combinations of sugar and starch concentrations have inconsistent effects on rumen fermentation characteristics, suggesting that the starch in diets cannot be simply replaced with sugar; the combined effects of sugar and starch should be considered to improve the feed utilization rate.