Skipping the Boundary Layer: High-Speed Droplet-Based Immunoassay Using Rayleigh Acoustic Streaming.

Acoustic mixing of droplets is a promising way to implement biosensors that combine high speed and minimal reagent consumption. To date, this type of droplet mixing is driven by a volume force resulting from the absorption of high-frequency acoustic waves in the bulk of the fluid. Here, we show that the speed of these sensors is limited by the slow advection of analyte to the sensor surface due to the formation of a hydrodynamic boundary layer. We eliminate this hydrodynamic boundary layer by using much lower ultrasonic frequencies to excite the droplet, which drives a Rayleigh streaming that behaves essentially like a slip velocity. At equal average flow velocity in the droplet, both experiment and three-dimensional simulations show that this provides a three-fold speedup compared to Eckart streaming. Experimentally, we further shorten a SARS-CoV-2 antibody immunoassay from 20 min to 40 s taking advantage of Rayleigh acoustic streaming.

Development and validation of a nomogram for postoperative sleep disturbance in adults: a prospective survey of 640 patients undergoing spinal surgery.

BACKGROUND: Postoperative sleep disturbance (PSD) is a prevalent clinical complication that may arise due to various factors. The purpose of this investigation is to identify the risk factors for PSD in spinal surgery and establish a risk prediction nomogram. METHODS: The clinical records of individuals who underwent spinal surgery from January 2020 to January 2021 were gathered prospectively. The least absolute shrinkage and selection operator (LASSO) regression, along with multivariate logistic regression analysis, was employed to establish independent risk factors. A nomogram prediction model was devised based on these factors. The nomogram's effectiveness was evaluated and verified via the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). RESULTS: A total of 640 patients who underwent spinal surgery were analyzed in this investigation, among which 393 patients experienced PSD with an incidence rate of 61.4%. After conducting LASSO regression and logistic regression analyses using R software on the variables in training set, 8 independent risk factors associated to PSD were identified, including female, preoperative sleep disorder, high preoperative anxiety score, high intraoperative bleeding volume, high postoperative pain score, dissatisfaction with ward sleep environment, non-use of dexmedetomidine and non-use of erector spinae plane block (ESPB). The nomogram and online dynamic nomogram were constructed after incorporating these variables. In the training and validation sets, the area under the curve (AUC) in the receiver operating characteristic (ROC) curves were 0.806 (0.768-0.844) and 0.755 (0.667-0.844), respectively. The calibration plots indicated that the mean absolute error (MAE) values in both sets were respectively 1.2% and 1.7%. The decision curve analysis demonstrated the model had a substantial net benefit within the range of threshold probabilities between 20% and 90%. CONCLUSIONS: The nomogram model proposed in this study included eight frequently observed clinical factors and exhibited favorable accuracy and calibration. TRIAL REGISTRATION: The study was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2200061257, 18/06/2022).

Comparative proteomics profiling revealed the involvement of GRB2-ROCK2 axis in Lyme neuroborreliosis caused by Borrelia Burgdorferi.

The zoonotic Lyme neuroborreliosis (LNB) disease is caused by Borrelia burgdorferi, with wide distribution, rapid dissemination and high disability rate. However, the molecular mechanism underlying B. burgdorferi mediated neuroborreliosis remains largely unknown. Here, the frontal cortex from rhesus brains was incubated with B. burgdorferi, and proteomics profiling was evaluated by isobaric tag for relative and absolute quantitation. Proteins were identified and quantified, and differentially expressed proteins (DEPs) were isolated by comparing co-cultured samples and control samples. A total of 43, 164 and 368 DEPs were significantly altered after 6, 12 and 24 h treatment with B. burgdorferi respectively. Gene ontology and KEGG pathway analyses revealed that chemokine biological process was significantly enriched. Two genes in chemokine pathway including GRB2 and ROCK2 were significantly up-regulated after B. burgdorferi co-culturing. By in vitro assay, we confirmed that the expression of GRB2 and ROCK2 was increased after B. burgdorferi infection. In conclusion, our study revealed the involvement of chemokine pathway in the pathogenesis of LNB. GRB2 and ROCK2 may be novel biomarkers and therapeutic targets for LNB.

Identification of Novel CD39 Inhibitors Based on Virtual Screening and Enzymatic Assays.

The accumulation of adenosine in the tumor microenvironment mediates immunosuppression and promotes tumor growth and proliferation. Intervention of the adenosine pathway is an important direction of antitumor immunity research. CD39 is an important ecto-nucleotidases for adenosine generation, therefore targeting the CD39-adenosine pathway is an emerging immune checkpoint for anticancer treatment. However, currently no CD39 inhibitor has been approved by the U.S. Food and Drug Administration. The development of CD39 drugs is urgent for clinical application. In this study, we combined homology modeling, virtual screening, and in vitro enzymatic activity to characterize the structural features of the CD39 protein and identify a triazinoindole-based compound as a CD39 inhibitor. The identified inhibitor and one of its analogues could effectively prevent the enzymatic activity of CD39 with IC50 values of 27.42 ± 5.52 and 79.24 ± 12.21 µM, respectively. At the same time, the inhibitor significantly inhibited the adenosine monophosphate production in colorectal cancer cell lines (HT29 and MC38) and thereafter prevented cell proliferation. Molecular docking studies, mutagenesis, and microscale thermophoresis indicated that residues such as R85 could be the main contributor in binding triazinoindole compounds. The binding mode can potentially be utilized for hit-to-lead optimization, and the identified inhibitor can be further tested for its anticancer activity in vivo or may serve as a chemical agent to study CD39-related functions.

Light Promotes the Immobilization of U(VI) by Ferrihydrite.

The environmental behaviors of uranium closely depend on its interaction with natural minerals. Ferrihydrite widely distributed in nature is considered as one main natural media that is able to change the geochemical behaviors of various elements. However, the semiconductor properties of ferrihydrite and its impacts on the environmental fate of elements are sometimes ignored. The present study systematically clarified the photocatalysis of U(VI) on ferrihydrite under anaerobic and aerobic conditions, respectively. Ferrihydrite showed excellent photoelectric response. Under anaerobic conditions, U(VI) was converted to U(IV) by light-irradiated ferrihydrite, in the form of UO2+x (x < 0.25), where •O2− was the dominant reactive reductive species. At pH 5.0, ~50% of U(VI) was removed after light irradiation for 2 h, while 100% U(VI) was eliminated at pH 6.0. The presence of methanol accelerated the reduction of U(VI). Under aerobic conditions, the light illumination on ferrihydrite also led to an obvious but slower removal of U(VI). The removal of U(VI) increased from ~25% to 70% as the pH increased from 5.0 to 6.0. The generation of H2O2 under aerobic conditions led to the formation of UO4•xH2O precipitates on ferrihydrite. Therefore, it is proved that light irradiation on ferrihydrite significantly changed the species of U(VI) and promoted the removal of uranium both under anaerobic and aerobic conditions.

Identification of Phelligridin-Based Compounds as Novel Human CD73 Inhibitors.

As an emerging immune checkpoint, CD73 has received more attention in the past decade. Inhibition of CD73 enzymatic activity can enhance antitumor immunity. Several CD73 inhibitors have been identified by in vitro assays in recent years, but they remain premature for clinical application, indicating that more novel CD73 inhibitors should be studied. Herein, we aimed to identify novel CD73 inhibitors that hopefully are suitable drug candidates by using computer-aided drug discovery and enzymatic-based assays. Five-hundred molecules with high binding affinity were retrieved from the Chemdiv-Plus database by using a structure-based virtual screening approach. Then, we analyzed the drug properties of these molecules and obtained 68 small molecules based on the oral noncentral nervous system (CNS) drug profile. The inhibition rates of these molecules against CD73 enzymatic activities were determined at a concentration of 100 µM, and 20 molecules had an inhibition rate greater than 20%, eight of which were dose-dependent, with IC50 values of 6.72-172.1 µM. Among the screening hits, phelligridin-based compounds had the best experimental inhibition values. Modeling studies indicate that the phelligridin group is sandwiched by the rings of F417 and F500 residues. The identified inhibitors have a molecular weight of approximately 500 Dal and are predicted to form primarily hydrogen bonds with CD73 in addition to hydrophobic stacking interactions. In conclusion, novel inhibitors with satisfactory drug properties may serve as lead compounds for the development of CD73-targeting drugs, and the binding modes may provide insight for phelligridin-based drug design.

Exploring the fate of heavy metals from mining and smelting activities in soil-crop system in Baiyin, NW China.

The activity and fate of heavy metals (HMs) from mining and smelting activities in farmland soil is of great significance to effectively prevent the excessive enrichment of HMs in crops. This study focuses on Baiyin area, a typical mining city in northwest China. In this example, the sources, speciation, and fate of HMs in the farmland soil, and the migration and enrichment characteristics of HMs in the different parts of crops planted in different areas were studied in detail combining the chemical sequential extraction and Pb isotope approaches. Results showed that the mean anthropogenic contributions of HMs in farmland soils were approximately 85%, 88%, 76%, and 41% for the ore district (OD), Xidagou sewage irrigation area (XSIA), Dongdagou sewage irrigation area, and the Yellow River irrigation area, respectively, and the risk that HMs were excessively accumulated in crops in OD and XSIA was high. Compared with soil residual fractions, the isotope ratios 206Pb/207Pb in non-residual fractions (1.1304-1.1669) were closer to the values of local ores, suggesting that anthropogenic HMs from mining and smelting activities were mainly enriched in the non-residual fractions. The isotope ratios 206Pb/207Pb in crops (1.1398-1.1686) further confirmed that those anthropogenic HMs were more easily absorbed and concentrated by crops. HMs contents in leaves from OD and XSIA were generally higher than that in roots, suggesting that atmospheric deposition in OD and XSIA had a greater impact on the HMs concentration of crop leaves，while the excess rate of HMs in grain/fruit was the lowest in all parts of crops. The division and classification of crop planting in mining area can effectively help minimize the risk that HMs from anthropogenic source enter the human body through the food chain.

Identification of key genes in prostate cancer gene expression profile by bioinformatics.

The aim of this study was to identify key candidate genes in prostate cancer. The gene expression profiles of GSE32448, GSE45016, GSE46602 and GSE104749 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between prostate cancer and normal samples were identified by R language. The gene ontology functional and pathway enrichment analyses of DEGs were performed by the Database for Annotation, Visualization and Integrated Discovery software followed by the construction of protein-protein interaction network. Hub gene identification was performed by the plug-in cytoHubba in Cytoscape software. The 217 DEGs were significantly enriched in biological processes including epithelial cell differentiation, response to estradiol and several pathways, mainly associated with protein digestion and absorption pathway in prostate cancer. Epithelial cell adhesion molecule, twist family basic helix-loop-helix transcription factor 1, CD38 molecule and vascular endothelial growth factor A were identified as hub genes. The expression levels of hub genes were consistent with data obtained in The Cancer Genome Atlas for prostate adenocarcinoma. These hub genes may be used as potential targets for prostate cancer diagnosis and treatment.

Borrelia burgdorferi basic membrane protein A stimulates murine macrophage to secrete specific chemokines.

In this study, we investigated the mechanisms that lead to the production of proinflammatory mediators by the murine macrophage cell line, RAW264.7, when these cells are exposed in vitro to recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). Using antibody protein microarray technology with high-throughput detection ability for detecting 25 chemokines in culture supernatant the RAW264.7 cell culture supernatants at 12 and 24 h post-stimulation with rBmpA, we identified two chemokines, a monocyte chemoattractant protein-5 (MCP-5/CCL12) and a macrophage inflammatory protein-2 (MIP-2/CXCL2), both of which increased significantly after stimulation. We then chose these two chemokines for further study. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction revealed that with the increase of rBmpA concentration, MCP-5/CCL12 and MIP-2/CXCL2 showed concentration-dependent increases (p <0.01).Our results indicate that the rBmpA could stimulate the secretion of several specific chemokines and induce Lyme arthritis.

Detecting a quasi-stable imine species on the reaction pathway of SHV-1 ß-lactamase and 6ß-(hydroxymethyl)penicillanic acid sulfone.

For the class A ß-lactamase SHV-1, the kinetic and mechanistic properties of the clinically used inhibitor sulbactam are compared with the sulbactam analog substituted in its 6ß position by a CH2OH group (6ß-(hydroxymethyl)penicillanic acid). The 6ß substitution improves both in vitro and microbiological inhibitory properties of sulbactam. Base hydrolysis of both compounds was studied by Raman and NMR spectroscopies and showed that lactam ring opening is followed by fragmentation of the dioxothiazolidine ring leading to formation of the iminium ion within 3 min. The iminium ion slowly loses a proton and converts to cis-enamine (which is a ß-aminoacrylate) in 1 h for sulbactam and in 4 h for 6ß-(hydroxymethyl) sulbactam. Rapid mix-rapid freeze Raman spectroscopy was used to follow the reactions between the two sulfones and SHV-1. Within 23 ms, a 10-fold excess of sulbactam was entirely hydrolyzed to give a cis-enamine product. In contrast, the 6ß-(hydroxymethyl) sulbactam formed longer-lived acyl-enzyme intermediates that are a mixture of imine and enamines. Single crystal Raman studies, soaking in and washing out unreacted substrates, revealed stable populations of imine and trans-enamine acyl enzymes. The corresponding X-ray crystallographic data are consonant with the Raman data and also reveal the role played by the 6ß-hydroxymethyl group in retarding hydrolysis of the acyl enzymes. The 6ß-hydroxymethyl group sterically hinders approach of the water molecule as well as restraining the side chain of E166 that facilitates hydrolysis.

"Mind the Gap": Raman Evidence for Rapid Inactivation of CTX-M-9 ß-Lactamase Using Mechanism-Based Inhibitors that Bridge the Active Site.

CTX-M ß-lactamases are one of the fastest growing extended-spectrum ß-lactamase (ESBL) families found in Escherichia coli rendering this organism extremely difficult to treat with ß-lactam antibiotics. Although they are grouped in class A ß-lactamases, the CTX-M family possesses low sequence identity with other enzymes. In addition, they have high hydrolytic activity against oxyimino-cephalosporins, despite having smaller active sites compared to other ESBLs in class A. Similar to most class A enzymes, most of the CTX-M ß-lactamases can be inhibited by the clinical inhibitors (clavulanic acid, sulbactam, and tazobactam), but the prevalence of inhibitor resistance is an emerging clinical threat. Thus, the mechanistic details of inhibition pathways are needed for new inhibitor development. Here, we use Raman microscopy to study the CTX-M-9 inactivation reaction with the three commercially available inhibitors and compare these findings to the analysis of the S130G variant. Characterization of the reactions in CTX-M-9 single crystals and solution show the formation of a unique cross-linked species, probably involving Ser70 and Ser130, with subsequent hydrolysis leading to an acrylate species linked to Ser130. In solution, a major population of this species is seen at 25 ms after mixing. Support for this finding comes from the CTX-M-9 S130G variant that reacts with clavulanic acid, sulbactam, and tazobactam in solution, but lacks the characteristic spectroscopic signature for the Ser130-linked species. Understanding the mechanism of inactivation of this clinically important ESBL-type class A lactamase permits us to approach the challenge of inhibitor resistance using knowledge of the bridging species in the inactivation pathway.

Mesenchymal stem cells in rabbit meniscus and bone marrow exhibit a similar feature but a heterogeneous multi-differentiation potential: superiority of meniscus as a cell source for meniscus repair.

BACKGROUND: The restoration of damaged meniscus has always been a challenge due to its limited healing capacity. Recently, bone marrow-derived mesenchymal stem cells (BMSCs) provide a promising alternative to repair meniscal defects. However, BMSCs are not ideal chondroprogenitor cells for meniscus repair because they have a high propensity for cartilage hypertrophy and bone formation. Our hypothesis is that mesenchymal stem cells (MSCs) reside in meniscus maintain specific traits distinct from others which may be more conducive to meniscus regeneration. METHODS: MSCs were isolated from bone marrow and menisci of the rabbits. The similarities and differences between BMSCs and MMSCs were investigated in vitro by a cell culture model, ex vivo by a rabbit meniscus defect model and in vivo by a nude rat implantation model using histochemistry, immunocytochemistry, qRT-PCR and western blotting. RESULTS: Our data showed that two types of MSCs have universal stem cell characteristics including clonogenicity, multi-potency and self-renewal capacity. They both express stem cell markers including SSEA-4, Nanog, nucleostemin, strol-1, CD44 and CD90. However, MMSCs differed from BMSCs. MMSC colonies were much smaller and grew more slowly than BMSC colonies. Moreover, fewer MMSCs expressed CD34 than BMSCs. Finally, MMSCs always appeared a pronounced tendency to chondrogenic differentiation while BMSCs exhibited significantly greater osteogenic potential, whatever in vitro and in vivo. CONCLUSIONS: This study shows the similarities and differences between MMSCs and BMSCs for the first time. MMSCs are a promising source of mesenchymal stem cells in repairing meniscus defect.

Probabilistic sunspot predictions with a gated recurrent units-based combined model guided by pinball loss.

Sunspots play a crucial role in both weather forecasting and the monitoring of solar storms. In this work, we propose a novel combined model for sunspot prediction using improved gated recurrent units (GRU) guided by pinball loss for probabilistic forecasts. Specifically, we optimize the GRU parameters using the slime mould algorithm and employ a seasonal-trend decomposition procedure based on loess to tackle challenges related to sequence prediction, such as self-correlations and non-stationarity. To address prediction uncertainty, we replace the traditional l 2 -norm loss with pinball loss. This modification extends the conventional GRU-based point forecasting to a probabilistic framework expressed as quantiles. We apply our proposed model to analyze a well-established historical sunspot dataset for both single- and multi-step ahead forecasting. The results demonstrate the effectiveness of our combined model in predicting sunspot values, surpassing the performance of other existing methods.

A mRNA Vaccine for Crimean-Congo Hemorrhagic Fever Virus Expressing Non-Fusion GnGc Using NSm Linker Elicits Unexpected Immune Responses in Mice.

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo Hemorrhagic virus (CCHFV), is listed in the World Health Organization's list of priority diseases. The high fatality rate in humans, the widespread distribution of CCHFV, and the lack of approved specific vaccines are the primary concerns regarding this disease. We used microfluidic technology to optimize the mRNA vaccine delivery system and demonstrated that vaccination with nucleoside-modified CCHFV mRNA vaccines encoding GnNSmGc (vLMs), Gn (vLMn), or Gc (vLMc) induced different immune responses. We found that both T-cell and B-cell immune responses induced by vLMc were better than those induced by vLMn. Interestingly, immune responses were found to be lower for vLMs, which employed NSm to link Gn and Gc for non-fusion expression, compared to those for vLMc. In conclusion, our results indicated that NSm could be a factor that leads to decreased specific immune responses in the host and should be avoided in the development of CCHFV vaccine antigens.

Combined effect of cold plasma-activated oxygen (CPAO) and microwave on microbial decontamination and quality of milkshake powder.

This study presents a new method combining cold plasma-activated oxygen (CPAO) and microwave (MW) to decontaminate milkshake powder, exploring its effectiveness, mechanisms, and quality impact. CPAO (6 min) alone reduced bacterial load by 0.419 log CFU/g, and MW (3 min) by 0.030 log CFU/g. However, their co-application significantly amplified decontamination, achieving a 1.265 log CFU/g reduction. CPAO-MW co-treatment inflicted more oxidative damage on bacterial cell membranes and intracellular antioxidant defense system, leading to higher mortality. It also raised protein and lipid oxidation, while decreasing vitamin C and A levels in the powder. Specifically, CPAO (6 min)-MW (3 min) co-treatment increased the carbonyl content from 0.438 to 0.891 nmol/mg protein, malondialdehyde from 0.824 to 0.996 mg/kg, and lowered vitamin C from 162.151 to 137.640 mg/kg, and vitamin A from 2.05 to 1.38 mg/kg. This study shows CPAO-MW is effective for decontaminating powdered foods but highlights a need to reduce negative effects.

Mitochondria-associated membranes contribution to exercise-mediated alleviation of hepatic insulin resistance: Contrasting high-intensity interval training with moderate-intensity continuous training in a high-fat diet mouse model.

OBJECTIVE: Mitochondria-associated membranes (MAMs) serve pivotal functions in hepatic insulin resistance (IR). Our aim was to explore the potential role of MAMs in mitigating hepatic IR through exercise and to compare the effects of different intensities of exercise on hepatic MAMs formation in high-fat diet (HFD) mice. METHODS: Male C57BL/6J mice were fed an HFD and randomly assigned to undergo supervised high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). IR was evaluated using the serum triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), glucose tolerance test (GTT), and insulin tolerance test (ITT). Hepatic steatosis was observed using hematoxylin-eosin (H&E) and oil red O staining. The phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K-AKT-GSK3ß) signaling pathway was assessed to determine hepatic IR. MAMs were evaluated through immunofluorescence (colocalization of voltage-dependent anion-selective channel 1 [VDAC1] and inositol 1,4,5-triphosphate receptor [IP3R]). RESULTS: After 8 weeks on an HFD, there was notable inhibition of the hepatic PI3K/Akt/GSK3ß signaling pathway, accompanied by a marked reduction in hepatic IP3R-VDAC1 colocalization levels. Both 8-week HIIT and MICT significantly enhanced the hepatic PI3K/Akt/GSK3ß signaling and colocalization levels of IP3R-VDAC1 in HFD mice, with MICT exhibiting a stronger effect on hepatic MAMs formation. Furthermore, the colocalization of hepatic IP3R-VDAC1 positively correlated with the expression levels of phosphorylation of protein kinase B (p-AKT) and phosphorylation of glycogen synthase kinase 3 beta (p-GSK3ß), while displaying a negative correlation with serum triglyceride/high-density lipoprotein cholesterol levels. CONCLUSION: The reduction in hepatic MAMs formation induced by HFD correlates with the development of hepatic IR. Both HIIT and MICT effectively bolster hepatic MAMs formation in HFD mice, with MICT demonstrating superior efficacy. Thus, MAMs might wield a pivotal role in exercise-induced alleviation of hepatic IR.

The impact of microplastics polystyrene on the microscopic structure of mouse intestine, tight junction genes and gut microbiota.

Microplastics, which are tiny plastic particles less than 5 mm in diameter, are widely present in the environment, have become a serious threat to aquatic life and human health, potentially causing ecosystem disorders and health problems. The present study aimed to investigate the effects of microplastics, specifically microplastics-polystyrene (MPs-PS), on the structural integrity, gene expression related to tight junctions, and gut microbiota in mice. A total of 24 Kunming mice aged 30 days were randomly assigned into four groups: control male (CM), control female (CF), PS-exposed male (PSM), and PS-exposed female (PSF)(n = 6). There were significant differences in villus height, width, intestinal surface area, and villus height to crypt depth ratio (V/C) between the PS group and the control group(C) (p <0.05). Gene expression analysis demonstrated the downregulation of Claudin-1, Claudin-2, Claudin-15, and Occludin, in both duodenum and jejunum of the PS group (p < 0.05). Analysis of microbial species using 16S rRNA sequencing indicated decreased diversity in the PSF group, as well as reduced diversity in the PSM group at various taxonomic levels. Beta diversity analysis showed a significant difference in gut microbiota distribution between the PS-exposed and C groups (R2 = 0.113, p<0.01), with this difference being more pronounced among females exposed to MPs-PS. KEGG analysis revealed enrichment of differential microbiota mainly involved in seven signaling pathways, such as nucleotide metabolism(p<0.05). The relative abundance ratio of transcriptional pathways was significantly increased for the PSF group (p<0.01), while excretory system pathways were for PSM group(p<0.05). Overall findings suggest that MPs-PS exhibit a notable sex-dependent impact on mouse gut microbiota, with a stronger effect observed among females; reduced expression of tight junction genes may be associated with dysbiosis, particularly elevated levels of Prevotellaceae.

Advances and perspectives in the development of vaccines against highly pathogenic bunyaviruses.

Increased human activities around the globe and the rapid development of once rural regions have increased the probability of contact between humans and wild animals. A majority of bunyaviruses are of zoonotic origin, and outbreaks may result in the substantial loss of lives, economy contraction, and social instability. Many bunyaviruses require manipulation in the highest levels of biocontainment, such as Biosafety Level 4 (BSL-4) laboratories, and the scarcity of this resource has limited the development speed of vaccines for these pathogens. Meanwhile, new technologies have been created, and used to innovate vaccines, like the mRNA vaccine platform and bioinformatics-based antigen design. Here, we summarize current vaccine developments for three different bunyaviruses requiring work in the highest levels of biocontainment: Crimean-Congo Hemorrhagic Fever Virus (CCHFV), Rift Valley Fever Virus (RVFV), and Hantaan virus (HTNV), and provide perspectives and potential future directions that can be further explored to advance specific vaccines for humans and livestock.

Improved Harmony Search Algorithm for Enhancing Efficiency and Quality in Optimization of the Distillation Process.

Reducing production costs is one of the main objectives of process intensification; in this work, production costs of the distillation process are reduced by reducing equipment size and utility consumption from the perspective of process optimization to achieve the purpose of process intensification. The application of intelligent optimization algorithms in the optimization process of distillation is vital to achieving high efficiency and low costs. Combining the harmony search algorithm with the characteristics of distillation optimization, a new distillation harmony search algorithm (DHSA) was proposed, which includes the self-adaptive adjustment of parameters, roulette selection strategy, and ratio optimization strategy. Benefiting from the DHSA, the optimal total annual cost and calculation times were remarkably reduced when compared with reported algorithms in the optimization of four distillation cases including the two-column model, three-column model, reactive distillation column model, and dividing-wall extractive distillation column model. In addition, the highest coefficient of variation of DHSA in 10 parallel calculations is 1.25%. These results indicate that DHSA has the advantages of a higher-quality solution, less computing time, and higher stability, which not only improves the optimization efficiency and quality but also inspires the optimization strategies for other algorithms.

Higher visceral adiposity index was associated with an elevated prevalence of gallstones and an earlier age at first gallstone surgery in US adults: the results are based on a cross-sectional study.

Objective: We sought to evaluate the association between visceral adiposity index (VAI) and the incidence of gallstones and the age at first gallstone surgery in adults in the United States. Methods: We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020 and evaluated the association between VAI and gallstone incidence and age at first gallstone surgery using logistic regression analysis, subgroup analysis, and dose-response curves. Results: A total of 7,409 participants aged >20 years were included in our study; 767 had a self-reported history of gallstones. After adjustment for all confounding factors, for each unit of VAI after Ln conversion, gallstone prevalence increased by 31% (OR = 1.31, 95% CI: 1.17, 1.48), while the first gallstone surgery was 1.97 years earlier (ß = -1.97, 95% CI: -3.35, -0.42). The dose-response curves showed a positive correlation between VAI and gallstone prevalence. There was a negative correlation between increased VAI and age at first gallstone surgery. Conclusion: A higher VAI is positively associated with the prevalence of gallstones and may lead to an earlier age at first gallstone surgery. This is worthy of attention, although causality cannot be established.