Biochar alleviates inhibition effects of humic acid on anaerobic digestion: Insights to performances and mechanisms.

To recover methane from waste activated sludge through anaerobic digestion (AD) is one promising alternative to achieve carbon neutrality for wastewater treatment plants. However, humic acids (HAs) are one of the major compositions in waste activated sludge, and their accumulation performs inhibition effects on AD. This study investigated the potentials of biochar (BC) in alleviating inhibition effects of HAs on AD. Results showed that although the accumulated HAs reduced methane yield by 9.37% compared to control, the highest methane yield, 132.6 mL CH4/g VSS, was obtained after adding BC, which was 45.9% higher than that in HA group. Mechanism analysis showed that BC promoted the activities of hydrolase such as protease and α-glucosidase, which were 69.7% and 29.7% higher than those in HA group, respectively. The conversion of short-chain fatty acids was accelerated. In addition, the evolutions of electroactive microorganisms like Clostridium_sensu_stricto_13 and Methanosaeta were consistent with the activitiies of electron transfer and the contents of cytochrome c. Furthermore, parts of HAs rather than all of them were adsorbed by BC, and the remaining free HAs and BC formed synergistic effects on methanogenesis, then both CO2 reduction and acetoclastic methanogenesis pathways were improved. The findings may provide some solutions to alleviate inhibition effects of HAs on AD.

Novel PEI/Zein core-shell composite as mixed-mode stationary phase for high performance liquid chromatography.

Based on the adhesion of polyethyleneimine (PEI), a novel PEI/zein co-modified core-shell stationary phase (PEI/Zein@SiO2) was prepared by doping zein to form a composite modification layer. The stationary phase achieved effective separation of nucleosides, bases and antibiotics in hydrophilic interaction mode on account of the hydrophilic groups of composite coating. With the hydrophobicity of zein, the flavones could be separated in reversed-phase mode. In short, the separation and analysis of hydrophilic/hydrophobic compounds were accomplished excellently by the PEI/Zein@SiO2 column with mixed double mode. The prepared chromatographic stationary phase not only avoided the dissolution of zein, but also covered the strong adsorption of some analytes caused by silica hydroxyl groups on the surface of silica spheres. The morphological structure and specific surface area of the material were reflected by various characterization techniques. Hydrophilic/hydrophobic compounds were used as tested analytes to research separation performance and retention mechanisms of PEI/Zein@SiO2 column. The stability and reproducibility of the PEI/Zein@SiO2 stationary phase were satisfied. Therefore, the modification of zein could improve the separation selectivity of stationary phase effectively for complex samples, which had the potential to be one of the significant potential application materials in stationary phase packing.

An efficient ratiometric fluorescence and colorimetric dual-mode probe for convenient determination of nitrite in real samples and E. coli.

Developing an effective and convenient nitrite detection method is indispensable in food safety, environmental monitoring, clinical diagnosis of diseases, and many other areas. Herein, a dicyanoisophorone derivative, TMN-NH2 with large Stokes shift and near-infrared (NIR) emission, was proposed as a ratiometric fluorescence and colorimetric dual-mode probe for the rapid determination of NO2- in acidic media, showing excellent selectivity and high sensitivity. The sensing mechanism is based on the diazotization of TMN-NH2 with NO2- and subsequent diazonium salt hydrolysis to form a hydroxyl-substituted product (TMN-OH). Under the optimized conditions of reaction and detection, a new quantitative analysis method based on TMN-NH2 was established for NO2- detection, exhibiting good linear relationships to NO2- in the range of 0.5 to 15 µM with practical detection limits of 26.6 nM and 17.6 nM for the colorimetric and fluorescent readout, respectively. The quantitative detection of NO2- in real samples demonstrated satisfactory recoveries and repeatability. Moreover, TMN-NH2 was successfully applied for monitoring NO2- in Escherichia coli by confocal fluorescence imaging.

Bismuth Chelate-Mediated Digital Subtraction Angiography.

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time. Bi-DTPA Dimeglumine possesses a simple synthesis process without the need for purification, large-scale production ability (over 200 g in the lab), superior X-ray imaging capability, renal clearance capacity, and good biocompatibility. Bi-DTPA-enhanced DSA can clearly display the arteries of the rabbit's head and lower limbs, with a minimum vascular resolution of 0.5 mm. The displayed integrity of terminal vessels by Bi-DTPA-enhanced DSA is superior to that of iopromide-enhanced DSA. In a rabbit model of thrombotic disease, Bi-DTPA Dimeglumine-enhanced DSA enables the detection of embolism and subsequent reevaluation of vascular conditions after recanalization therapy. This proposed iodine-free DSA provides a promising and universal approach for diagnosing vascular diseases.

Zona Glomerulosa-Derived Klotho Modulates Aldosterone Synthase Expression in Young Female Mice.

Klotho plays a critical role in the regulation of ion and fluid homeostasis. A previous study reported that haplo-insufficiency of Klotho in mice results in increased aldosterone synthase (CYP11B2) expression, elevated plasma aldosterone, and high blood pressure. This phenotype was presumed to be the result of diminished Klotho expression in zona glomerulosa (zG) cells of the adrenal cortex; however, systemic effects on adrenal aldosterone production could not be ruled out. To examine whether Klotho expressed in the zG is indeed a critical regulator of aldosterone synthesis, we generated a tamoxifen-inducible, zG-specific mouse model of Klotho deficiency by crossing Klotho-flox mice with Cyp11b2-CreERT mice (zG-Kl-KO). Tamoxifen-treated Cyp11b2-CreERT animals (zG-Cre) served as controls. Rosa26-mTmG reporter mice were used for Cre-dependent lineage-marking. Two weeks after tamoxifen induction, the specificity of the zG-Cre line was verified using immunofluorescence analysis to show that GFP expression was restricted to the zG. RNA in situ hybridization revealed a 65% downregulation of Klotho messenger RNA expression in the zG of zG-Kl-KO female mice at age 12 weeks compared to control mice. Despite this significant decrease, zG-Kl-KO mice exhibited no difference in plasma aldosterone levels. However, adrenal CYP11B2 expression and the CYP11B2 promotor regulatory transcription factors, NGFIB and Nurr1, were enhanced. Together with in vitro experiments, these results suggest that zG-derived Klotho modulates Cyp11b2 but does not evoke a systemic phenotype in young adult mice on a normal diet. Further studies are required to investigate the role of adrenal Klotho on aldosterone synthesis in aged animals.

Role of phosphate in microalgal-bacterial symbiosis system treating wastewater containing heavy metals.

Phosphorus is one of the important factors to successfully establish the microalgal-bacterial symbiosis (MABS) system. The migration and transformation of phosphorus can occur in various ways, and the effects of phosphate on the MABS system facing environmental impacts like heavy metal stress are often ignored. This study investigated the roles of phosphate on the response of the MABS system to zinc ion (Zn2+). The results showed that the pollutant removal effect in the MABS system was significantly reduced, and microbial growth and activity were inhibited with the presence of Zn2+. When phosphate and Zn2+ coexisted, the inhibition effects of pollutants removal and microbial growth rate were mitigated compared to that of only with the presence of Zn2+, with the increasing rates of 28.3% for total nitrogen removal, 48.9% for chemical oxygen demand removal, 78.3% for chlorophyll-a concentration, and 13.3% for volatile suspended solids concentration. When phosphate was subsequently supplemented in the MABS system after adding Zn2+, both pollutants removal efficiency and microbial growth and activity were not recovered. Thus, the inhibition effect of Zn2+ on the MABS system was irreversible. Further analysis showed that Zn2+ preferentially combined with phosphate could form chemical precipitate, which reduced the fixation of MABS system for Zn2+ through extracellular adsorption and intracellular uptake. Under Zn2+ stress, the succession of microbial communities occurred, and Parachlorella was more tolerant to Zn2+. This study revealed the comprehensive response mechanism of the co-effects of phosphate and Zn2+ on the MABS system, and provided some insights for the MABS system treating wastewater containing heavy metals, as well as migration and transformation of heavy metals in aquatic ecosystems.

Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys.

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.

Biochar derived from alkali-treated sludge residue regulates anaerobic digestion: Enhancement performance and potential mechanisms.

Biochar produced from bio-wastes has been widely used to promote the performance of anaerobic digestion. Waste activated sludge (WAS) is considered as a kind of popular precursor for biochar preparation, but the abundant resources in WAS were neglected previously. In this study, the roles of biochar prepared from raw, pretreated, and fermented sludge on anaerobic digestion were investigated. That is, parts of carbon sources and nutrients like polysaccharides, proteins, and phosphorus were firstly recovered after sludge pretreatment or fermentation, and then the sludge residuals were used as raw material to prepare biochar. The methane yield improved by 22.1% with adding the biochar (AK-BC) prepared by sludge residual obtained from alkaline pretreatment. Mechanism study suggested that the characteristics of AK-BC like specific surface area and defect levels were updated. Then, the conversion performance of intermediate metabolites and electro-activities of extracellular polymeric substances were up-regulated. As a result, the activity of electron transfer was increased with the presence of AK-BC, with increase ratio of 21.4%. In addition, the electroactive microorganisms like Anaerolineaceae and Methanosaeta were enriched with the presence of AK-BC, and the potential direct interspecies electron transfer was possibly established. Moreover, both aceticlastic and CO2-reducing methanogenesis pathways were improved by up-regulating related enzymes. Therefore, the proposed strategy can not only obtain preferred biochar but also recover abundant resources like carbon source, nutrients, and bioenergy.

Multifunctional nanoparticles for enhanced sonodynamic-chemodynamic immunotherapy with glutathione depletion.

Aim: This study aimed to develop a sonodynamic-chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper-cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4+ and CD8+ T cells and promoting the expression of IL-2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.

Ionic regulation whey protein composition on membrane fouling during ultrafiltration process analyzed by HPLC.

In order to meet the market demand and avoid the increase of operation amount and cleaning cost in the process of ultrafiltration, it is particularly important to find more practical and efficient methods to control and improve membrane fouling. In this study, the ions in the ultrafiltration process were regulated to affect membrane surface proteins composition (lactoferrin, α-lactalbumin, ß-lactoglobulin A and ß-lactoglobulin B) and delay membrane fouling. It was found that Na+ (21 mmol/L), Zn2+ (0.25 mmol/L) and K+ (44 mmol/L) was added at 4 min, 8 min and 12 min, respectively during ultrafiltration process. The continuous regulation slowed down the decline rate of membrane flux and reduced the content of α-lactalbumin, ß-lactoglobulin A and ß-lactoglobulin B on the membrane surface analyzed by HPLC. This could reduce the irreversible membrane fouling of proteins cake resistance. Furthermore, the ions concentration was also investigated after filtration. The concentration of K+ was increased significantly and other ions concentration was not significantly changed after continuous regulation such Na+, Mg2+, Zn2+ and Ca2+ compared to control. Therefore, dynamic ionic regulation of whey protein ultrafiltration process is a simple and effective method, which provides technical theoretical basis for optimizing and improving membrane technology.

Highly dispersed amorphous nano-selenium functionalized carbon nanofiber aerogels for high-efficient uptake and immobilization of Hg(II) ions.

Owing to the strong Hg-Se interaction, Se-containing materials are promising for the uptake and immobilization of Hg(II) ions; compared with metal selenides or selenized compounds, elemental Se contains the highest ratio of Se. However, it remains a challenge to fully expose all the potential Se binding sites and achieve high utilization efficiency of elemental Se. Through rational design on the structure, dispersity, and size of materials, Se/CNF aerogels composed of abundant well-dispersed and amorphous nano-Se have been prepared and applied for the high-efficient uptake and immobilization of Hg(II) ions. The well-dispersion of nano-Se increases the exposure of Se sites, the amorphous structure benefits the easy cleavage of Se-Se bonds, the 3D porous networks of aerogels permit fast ions transport and easy operation. Benefiting from the combination effect of strong Hg-Se interaction and sufficient exposure of Se-enriched sites, the Se/CNF aerogels demonstrate strong binding ability (Kd = 3.8 ×105 mL·g-1), high capacity (943.4 mg·g-1), and preeminent selectivity (αMHg > 100) towards highly toxic Hg(II) ions. Notably, the utilization efficiency of Se in Se/CNF aerogels is as high as 99.5%. Moreover, the strong Hg-Se interaction and extraordinary stability of HgSe could minimize the environmental impact of the spent Se/CNF adsorbents after its disposal.

Multi-omics reveals aging-related pathway in natural aging mouse liver.

Aging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.

Single-cell transcriptomic atlas of distinct early immune responses induced by SARS-CoV-2 Proto or its variants in rhesus monkey.

Immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection play a critical role in the pathogenesis and outcome of coronavirus disease 2019 (COVID-19). However, the dynamic profile of immune responses postinfection by SARS-CoV-2 variants of concern (VOC) is not fully understood. In this study, peripheral blood mononuclear cells single-cell sequencing was performed to determine dynamic profiles of immune response to Prototype, Alpha, Beta, and Delta in a rhesus monkey model. Overall, all strains induced dramatic changes in both cellular subpopulations and gene expression levels at 1 day postinfection (dpi), which associated function including adaptive immune response, innate immunity, and IFN response. COVID-19-related genes revealed different gene profiles at 1 dpi among the four SARS-CoV-2 strains, including genes reported in COVID-19 patients with increased risk of autoimmune disease and rheumatic diseases. Delta-infected animal showed inhibition of translation pathway. B cells, T cells, and monocytes showed much commonality rather than specificity among the four strains. Monocytes were the major responders to SARS-CoV-2 infection, and the response lasted longer in Alpha than the other strains. Thus, this study reveals the early immune responses induced by SARS-CoV-2 Proto or its variants in nonhuman primates, which is important information for controlling rapidly evolving viruses.

[Analysis on Serology and FUT1 Gene of Para-Bombay Phenotype in Zhangzhou Area].

OBJECTIVE: To investigate blood group serological manifestations and molecular mechanism of para-Bombay phenotype. METHODS: The serological manifestations of para-Bombay phenotype was identified by serological assay. Molecular mechanism of para-Bombay phenotype was detected by PCR amplification. RESULTS: Eighteen cases of para-Bombay phenotype were detected through serology and PCR, including 5 cases of Amh, 4 cases of Bmh, and 10 cases of Omh. Eight cases produced anti-HI antibody. CONCLUSIONS: Blood group serology combined with molecular biology can accurately identify para-Bombay phenotype. Special transfusion strategy should be adopted for individual with para-Bombay phenotype to avoid hemolytic reactions.

Advances, challenges, and prospects in microalgal-bacterial symbiosis system treating heavy metal wastewater.

Heavy metal (HM) pollution, particularly in its ionic form in water bodies, is a chronic issue threatening environmental security and human health. The microalgal-bacterial symbiosis (MABS) system, as the basis of water ecosystems, has the potential to treat HM wastewater in a sustainable manner, with the advantages of environmental friendliness and carbon sequestration. However, the differences between laboratory studies and engineering practices, including the complexity of pollutant compositions and extreme environmental conditions, limit the applications of the MABS system. Additionally, the biomass from the MABS system containing HMs requires further disposal or recycling. This review summarized the recent advances of the MABS system treating HM wastewater, including key mechanisms, influence factors related to HM removal, and the tolerance threshold values of the MABS system to HM toxicity. Furthermore, the challenges and prospects of the MABS system in treating actual HM wastewater are analyzed and discussed, and suggestions for biochar preparation from the MABS biomass containing HMs are provided. This review provides a reference point for the MABS system treating HM wastewater and the corresponding challenges faced by future engineering practices.

Contribution identification of hydrolyzed products of potassium ferrate on promoting short-chain fatty acids production from waste activated sludge.

Potassium ferrate (K2FeO4) has been extensively employed to promote short-chain fatty acids (SCFAs) production from anaerobic fermentation of waste activated sludge (WAS) because of its potent oxidizing property and formation of alkaline hydrolyzed products (potassium hydroxide, KOH and ferric hydroxide, Fe(OH)3). However, whether K2FeO4 actually works as dual functions of both an oxidizing agent and an alkalinity enhancer during the anaerobic fermentation process remains uncertain. This study aims to identify the contributions of hydrolyzed products of K2FeO4 on SCFAs production. The results showed that K2FeO4 did not execute dual functions of oxidization and alkalinity in promoting SCFAs production. The accumulation of SCFAs using K2FeO4 treatment (183 mg COD/g volatile suspended solids, VSS) was less than that using either KOH (192 mg COD/g VSS) or KOH & Fe(OH)3 (210 mg COD/g VSS). The mechanism analysis indicated that the synergistic effects caused by oxidization and alkalinity properties of K2FeO4 did not happen on solubilization, hydrolysis, and acidogenesis stages, and the inhibition effect caused by K2FeO4 on methanogenesis stage at the initial phase was more severe than that of its hydrolyzed products. It was also noted that the inhibition effects of K2FeO4 and its hydrolyzed products on the methanogenesis stage could be relieved during a longer sludge retention time, and the final methane yields using KOH or KOH & Fe(OH)3 treatment were higher than that using K2FeO4, further confirming that dual functions of K2FeO4 were not obtained. Therefore, K2FeO4 may not be an alternative strategy for enhancing the production of SCFAs from WAS compared to its alkaline hydrolyzed products. Regarding the strong oxidization property of K2FeO4, more attention could be turned to the fates of refractory organics in the anaerobic fermentation of WAS.

Revealing mechanisms of triclosan on the removal and distribution of nitrogen and phosphorus in microalgal-bacterial symbiosis system.

Microalgal-bacterial symbiosis (MABS) system performs synergistic effect on the reduction of nutrients and carbon emissions in the water treatment process. However, antimicrobial agents are frequently detected in water, which influence the performance of MABS system. In this study, triclosan (TCS) was selected to reveal the effects and mechanisms of antimicrobial agents on MABS system. Results showed that the removal efficiencies of chemical oxygen demand, NH4+-N and total phosphorus decreased by 3.0%, 24.0% and 14.3% under TCS stress. In contrast, there were no significant decrease on the removal effect of total nitrogen. Mechanism analysis showed that both the growth rate of microorganisms and the nutrients retention capacity of extracellular polymeric substances were decreased. The intracellular accumulation for nitrogen and phosphorus was promoted due to the increased cytomembrane permeability caused by lipid peroxidation. Moreover, microalgae were dominant in MABS system with ratio between microalgae and bacteria of more than 5.49. The main genus was Parachlorella, with abundance of more than 90%. Parachlorella was highly tolerant to TCS, which might be conductive to maintain its survival. This study revealed the nutrients pathways of MABS system under TCS stress, and helped to optimize the operation of MABS system.

Natural zeolite enhances anaerobic digestion of waste activated sludge: Insights into the performance and the role of biofilm.

Anaerobic digestion is widely employed for the treatment of waste activated sludge (WAS) due to its advantages like simultaneous energy recovery and sludge stabilization, promoting carbon-neutral operation of wastewater treatment plants. Natural zeolite, a low-cost and eco-friendly additive, has the potential to improve methane production from anaerobic digestion. This study investigated the effects of natural zeolite on anaerobic digestion when the substrate was WAS. It was found that methane production potential in response to natural zeolite was dosage-dependent. The optimal dosage was 0.1 g zeolite/g volatile suspended solids (VSS), with a methane yield of 181.89 ± 6.75 mL/g VSS, which increased by 20.1% compared to that of the control. Although the methane yields with other dosages of natural zeolite were higher than that of control, they were lesser than that with 0.1 g zeolite/g VSS. Natural zeolite affected transfer and conversion of proteins much more than polysaccharides in liquid phase and extracellular polymeric substances. In anaerobic digestion, natural zeolite had with little effects on WAS solubilization, while it improved hydrolysis, acidification, and methanogenesis. The dosages of natural zeolite did have significant effects on bacterial communities in biofilm rather than suspension, while the archaeal communities in biofilm and suspension were all greatly related to natural zeolite dosages. The developed biofilms promoted richness and functionality of microbial communities. The syntrophic metabolism relationships between methanogens and bacteria were improved, which was proved by selective enrichment of Methanosarcina, Syntrophomonas, and Petrimonas. The findings of this work provided some new solutions for promoting methane production from WAS, and the roles of natural zeolite in anaerobic digestion.

Risk stratification of gallbladder masses by machine learning-based ultrasound radiomics models: a prospective and multi-institutional study.

OBJECTIVE: This study aimed to evaluate the diagnostic performance of machine learning (ML)-based ultrasound (US) radiomics models for risk stratification of gallbladder (GB) masses. METHODS: We prospectively examined 640 pathologically confirmed GB masses obtained from 640 patients between August 2019 and October 2022 at four institutions. Radiomics features were extracted from grayscale US images and germane features were selected. Subsequently, 11 ML algorithms were separately used with the selected features to construct optimum US radiomics models for risk stratification of the GB masses. Furthermore, we compared the diagnostic performance of these models with the conventional US and contrast-enhanced US (CEUS) models. RESULTS: The optimal XGBoost-based US radiomics model for discriminating neoplastic from non-neoplastic GB lesions showed higher diagnostic performance in terms of areas under the curves (AUCs) than the conventional US model (0.822-0.853 vs. 0.642-0.706, p < 0.05) and potentially decreased unnecessary cholecystectomy rate in a speculative comparison with performing cholecystectomy for lesions sized over 10 mm (2.7-13.8% vs. 53.6-64.9%, p < 0.05) in the validation and test sets. The AUCs of the XGBoost-based US radiomics model for discriminating carcinomas from benign GB lesions were higher than the conventional US model (0.904-0.979 vs. 0.706-0.766, p < 0.05). The XGBoost-US radiomics model performed better than the CEUS model in discriminating GB carcinomas (AUC: 0.995 vs. 0.902, p = 0.011). CONCLUSIONS: The proposed ML-based US radiomics models possess the potential capacity for risk stratification of GB masses and may reduce the unnecessary cholecystectomy rate and use of CEUS. CLINICAL RELEVANCE STATEMENT: The machine learning-based ultrasound radiomics models have potential for risk stratification of gallbladder masses and may potentially reduce unnecessary cholecystectomies. KEY POINTS: • The XGBoost-based US radiomics models are useful for the risk stratification of GB masses. • The XGBoost-based US radiomics model is superior to the conventional US model for discriminating neoplastic from non-neoplastic GB lesions and may potentially decrease unnecessary cholecystectomy rate for lesions sized over 10 mm in comparison with the current consensus guideline. • The XGBoost-based US radiomics model could overmatch CEUS model in discriminating GB carcinomas from benign GB lesions.

Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the persistent coronavirus disease 2019 (COVID-19) pandemic, which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden. The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2. In this study, the virological characteristics of the original SARS-CoV-2 strain and its variants of concern (VOCs; including Alpha, Beta, and Delta) in vitro, as well as differential transcriptomic landscapes in multiple organs (lung, right ventricle, blood, cerebral cortex, and cerebellum) from the infected rhesus macaques, were elucidated. The original strain of SARS-CoV-2 caused a stronger innate immune response in host cells, and its VOCs markedly increased the levels of subgenomic RNAs, such as N, Orf9b, Orf6, and Orf7ab, which are known as the innate immune antagonists and the inhibitors of antiviral factors. Intriguingly, the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did. Moreover, a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation- and immune-related RNAs. Furthermore, peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals. Collectively, these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.