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• The input population and output population are considered. • 108 scenarios are listed from the input population and quarantine strategies. • The second outbreak of disease is obtained. In this study, an epidemic model was developed to simulate and predict the disease variations of Guangdong province which was focused on the period from Jan 27 to Feb 20, 2020. To explore the impacts of the input population and quarantine strategies on the disease variations at different scenarios, four time points were assumed as Feb 6, Feb 16, Feb 24 and Mar 5 2020. The major results suggest that our model can well capture the disease variations with high accuracy. The simulated peak value of the confirmed cases is 1002 at Feb 10, 2020 which is mostly close to the reported number of 1007 at Feb 9, 2020. The disease will become extinction with peak value of 1397 at May 11, 2020. Moreover, the increased numbers of the input population can mainly shorten the disease extinction days and the increased percentages of the exposed individuals of the input population increase the number of cumulative confirmed cases at a small percentage. Increasing the input population and decreasing the quarantine strategy together around the time point of the peak value of the confirmed cases, may lead to the second outbreak. [ABSTRACT FROM AUTHOR]

The Coronavirus Disease 2019 (COVID-19) firstly announced in Wuhan of Hubei province, China is rapidly spreading to all the other 31 provinces of China and to more than 140 countries. Quarantine strategies play the key role on the disease controlling and public health in the world with this pandemic of the COVID-19 defined by the World Health Organization. In this study, a SEIRQ epidemic model was developed to explore the dynamic changes of COVID-19 in Wuhan and mainland China, from January 27, 2020 to March 5, 2020. Moreover, to investigate the effects of the quarantine strategies, two perspectives are employed from the different quarantine magnitudes and quarantine time points. The major results suggest that the COVID-19 variations are well captured by the epidemic model with very high accuracy in the cumulative confirmed cases, confirmed cases, cumulative recovered cases and cumulative death cases. The quarantine magnitudes in the susceptible individuals play larger roles on the disease control than the impacts of the quarantines of the exposed individuals and infectious individuals. For the quarantine time points, it shows that the early quarantine strategy is significantly important for the disease controlling. The time delayed quarantining will seriously increase the COVID-19 disease patients and prolongs the days of the disease extinction. Our model can simulate and predict the COVID-19 variations and the quarantine strategies are important for the disease controlling, especially at the early period of the disease outbreak. These conclusions provide important scientific information for the government policymaker in the disease control strategies. [ABSTRACT FROM AUTHOR]

Per-/polyfluoroalkyl substances (PFASs), which are widely used in industrial and commercial products, have been identified as global and ubiquitous pollutants. Despite this, limited data are available regarding the impacts of PFAS exposure and intake in non-human primates. Here, we report for the first time on the occurrence of PFASs in the blood and dietary sources of two rare and endangered primate species, namely, the golden snub-nosed monkey (Rhinopithecus roxellana) and Francois' leaf monkey (Trachypithecus francoisi). Results showed that perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) were dominant and found at the highest proportions in the blood of both species at the four study sites. The ∑PFAS levels in blood samples from captive golden snub-nosed monkeys in Tongling Zoo (mean: 2.51 ng/mL) and Shanghai Wild Zoo (3.52 ng/mL) near urbanized areas were one order of magnitude higher than the levels in wild monkeys from Shennongjia Nature Reserve (0.27 ng/mL). Furthermore, significant age positive relationships for perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonates (6:2 Cl-PFESA) were observed in both golden snub-nosed monkeys at Shanghai Wild Zoo and Francois' leaf monkeys at Wuzhou Breeding Center. In addition, PFAS levels in frequently consumed food and drinking water were analyzed for Francois' leaf monkeys. Results showed that tree leaves accounted for the highest percentage of total daily intake of PFASs, especially PFOA, thus highlighting tree leaf consumption as a primary PFAS exposure route for this species. Overall, however, dietary exposure to PFASs was of relatively low risk to Francois' leaf monkey health. Unlabelled Image • PFOA and PFNA were the predominant compounds in two colobine monkeys' blood. • F-53B was also detected in monkey's blood. • Levels of PFDA, PFOS, FOSA and F-53B in monkey blood increased with its age. • PFASs in monkey mainly were intake from tree leaves. [ABSTRACT FROM AUTHOR]

As a Chinese-specific alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the metal plating industry for over 40 years. This prevalence of use has resulted in its subsequent detection within the environment, wildlife, and humans. Despite this, however, its hepatotoxic effects on aquatic organisms remain unclear. Here, we characterized the impacts of long-term F-53B exposure on adult zebrafish liver and their offspring. Results showed that the concentration of F-53B was greater in the F0 liver than that in the gonads and blood. Furthermore, males had significantly higher liver F-53B levels than females. Hepatomegaly and obvious cytoplasmic vacuolation indicated that F-53B exposure induced liver injury. Compared to control, liver triglyceride levels decreased by 30% and 33.5% in the 5 and 50 μg/L-exposed males and 22% in 50 μg/L-exposed females. Liver transcriptome analysis of F0 adult fish found 2175 and 1267 differentially expressed genes (DEGs) in the 5 μg/L-exposed males and females, respectively. Enrichment analyses further demonstrated that the effects of F-53B on hepatic transcripts were sex-dependent. Gene Ontology showed that most DEGs were involved in multicellular organism development in male fish, whereas in female fish, most DEGs were related to metabolic processes and gene expression. qRT-PCR analysis indicated that the PPAR signaling pathway likely contributed to F-53B-induced disruption of lipid metabolism in F0 adult fish. In F1 larvae (5 days post fertilization), the transcription of pparα increased, like that in F0 adult fish, but most target genes showed the opposite expression trends as their parents. Taken together, our research demonstrated chronic F-53B exposure adversely impacts zebrafish liver, with disruption of PPAR signaling pathway dependent on sex and developmental stage. Image 1 • Accumulation of F-53B in zebrafish liver is sex-dependent. • F-53B exposure induces hepatomegaly and decreases liver triglyceride levels. • F-53B exposure results in differences between male and female hepatic transcripts. • F-53B interferes with the PPAR signal pathway in adult fish and their offspring. Long-term F-53B exposure induced hepatomegaly and disrupted lipid metabolism in F0 adult zebrafish and disturbed the transcriptional levels of genes involved in the PPAR signaling pathway in F1 larvae. [ABSTRACT FROM AUTHOR]

Abstract As an alternative to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used in the Chinese chrome plating industry for over four decades. It has been increasingly detected in environmental matrices in recent years, causing great concern regarding its potential health risks to humans and wildlife. However, its adverse effects on biota remain largely unknown. To explore the chronic toxicity of F-53B on reproduction, a two-generational study was conducted using zebrafish (Danio rerio). Adult zebrafish (F0 generation) were chronically exposed to different concentrations of F-53B (0, 5, 50, and 500 μg/L) for 180 d using a flow-through exposure system, with F1 and F2 generations reared without exposure. The reproductive toxicity endpoints were assessed in F0 and F1 adult fish. Results showed that F-53B accumulated in the F0 gonads and transferred to the F1 generation via maternal eggs, and even remained in F1 adult fish and their eggs (F2) after 180 d depuration. In the F0 generation, F-53B exposure significantly inhibited growth and induced reproductive toxicity, including decreased gonadosomatic index and egg production/female, changes in the histological structure of the gonads, and increased serum testosterone levels. In particular, serum estradiol and vitellogenin levels were significantly increased in 5 μg/L F-53B-exposed adult males. The transcriptional levels of several genes along the hypothalamic-pituitary-gonadal axis were altered in F0 generation fish. Testis transcriptome analysis revealed that F-53B exposure disrupted spermatogenesis in F0 male zebrafish. Maternal transfer of F-53B also induced adverse effects on growth and reproduction in the F1 generation. Furthermore, the higher occurrence of malformation and lower survival in F1 and F2 embryos indicated that parental exposure to F-53B could impair the embryonic development of offspring. Taken together, this study demonstrated that F-53B could induce reproductive toxicity in zebrafish similar to that induced by legacy PFOS, and its potential adverse effects on offspring deserve further investigation. Graphical abstract Image 1 Highlights • Bioconcentration of F-53B was gender-dependent, and transfer from parent to eggs. • Similar to PFOS, F-53B exposure inhibited the growth and reproduction of zebrafish. • F-53B exposure altered sex hormone level and expression of genes along HPGL axis. • Transcriptome analysis showed F-53B exposure disrupted spermatogenesis in male fish. • Parental exposure to F-53B could impair embryonic development of offspring. Long-term exposure to F-53B for one generation had adverse effects on reproduction in both F0 and F1 adult fish and impaired embryonic development of offspring. [ABSTRACT FROM AUTHOR]

Novel 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) and legacy PFASs, such as perfluorohexane sulfonate (PFHxS), have been used to replace perfluorooctane sulfonate (PFOS), a known persistent organic pollutant. Thus, it is critical to understand these PFOS alternatives regarding their sources and concentrations in the natural environment. In this study, 41 surface water samples as well as edible aquatic organisms were collected from Baiyangdian Lake, the largest freshwater lake in Hebei Province, China. Perfluorooctanoate acid (PFOA) and PFHxS were the predominant PFASs detected in the surface water, reaching concentrations of 8 397.23 ng/L and 1 478.03 ng/L, respectively, with PFHxS accounting for the greatest proportion (∼80.00%) in most water samples. PFHxS (mean: 87.53 ng/g) and PFOS (mean: 35.94 ng/g) were also the most prevalent compounds detected in aquatic organisms. Estimated daily intake (EDI) values of PFOS (16.56 ng/kg bw/d) and PFHxS (16.11 ng/kg bw/d) via aquatic food and drinking water were the highest among PFASs, indicating potential exposure risks to residents. In addition, fish product consumption was the important exposure pathway for residents to PFOA, PFHxS, PFOS, and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA). This study reports on the highest PFHxS levels ever recorded in surface water, suggesting that further quantification of PFHxS in human serum and assessment of its health risks to local residents are warranted and critical. [ABSTRACT FROM AUTHOR]

Saturated fluorotelomer carboxylic acids (FTCAs) are intermediates in the degradation of fluorotelomer alcohols (FTOHs) to perfluorinated carboxylic acids (PFCAs). Recent studies have detected FTCAs in precipitation, surface waters, and wildlife, but few studies have focused on their toxicity. In this study, zebrafish embryos were exposed to different concentrations of 6:2 FTCA (0, 4, 8, and 12 mg/L) from 6 to 120 h post-fertilization (hpf) to investigate its developmental toxicity. Results showed that 6:2 FTCA exposure decreased the hatching and survival percentages, reduced the heart rate, and increased the malformation of zebrafish embryos. The median lethal concentration of 6:2 FTCA was 7.33 mg/L at 120 hpf, which was lower than that of perfluorooctanoic acid (PFOA), thus indicating higher toxicity for zebrafish. The most common developmental malformation was pericardial edema, which appeared in the 8 and 12 mg/L 6:2 FTCA-exposed embryos from 60 hpf. Using o-dianisidine staining, we found that the hemoglobin content in embryos was reduced in a concentration-dependent manner after 6:2 FTCA exposure at 72 hpf. Based on quantitative real-time polymerase chain reaction (q-RT-PCR) and whole-mount in situ hybridization, the transcriptional levels of hemoglobin markers ( hbae1 , hbbe1 , and hbae3 ) were down-regulated at 48 and 72 hpf, even though no observed malformation appeared in zebrafish at 48 hpf. Moreover, 6:2 FTCA exposure decreased the protein level of gata1 , a principal early erythrocytic marker, in Tg ( gata1 :DsRed) transgenic zebrafish at 72 hpf. We analyzed the transcriptional level of other erythrocyte-related genes using q-RT-PCR assay. For heme formation, the transcription of alas2 , which encodes the key enzyme for heme biosynthesis, was down-regulated after 6:2 FTCA exposure, whereas the transcription of ho-1 , which is related to heme degradation, was up-regulated at 48 and 72 hpf. The transcriptional patterns of gata1 and gata2 , which are related to erythroid differentiation, differed. At 48 hpf, the mRNA level of gata2 was significantly increased, whereas that of gata1 exhibited no significant changes in any treatment group. At 72 hpf, the expressions of both were down-regulated in a concentration-dependent manner. Taken together, 6:2 FTCA exposure decreased the erythrocyte number and disrupted erythroid differentiation during zebrafish embryonic development. Our results suggest that 6:2 FTCA can cause developmental toxicity in zebrafish embryos, and that FTCAs exhibit greater toxicity than that of PFCAs. [ABSTRACT FROM AUTHOR]

As an alternative to perfluorooctanesulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used as a mist suppressant in Chinese electroplating industries for over 30 years. It has been found in the environment and fish, and one acute assay indicated F–53B was moderately toxic. However, the toxicological information on this compound was incomplete and insufficient for assessment of their environment impact. The object of this study was to examine the developmental toxicity of F–53B using zebrafish embryos. Zebrafish embryos were incubated in 6-well plates with various concentrations of F–53B (1.5, 3, 6, and 12 mg/L) from 6 to 132 h post fertilization (hpf). Results showed that F–53B exposure induced developmental toxicity, including delayed hatching, increased occurrence of malformations, and reduced survival. Malformations, including pericardial and yolk sac edemas, abnormal spines, bent tails, and uninflated swim bladders, appeared at 84 hpf, and increased with time course and dose. A decrease in survival percentages was noted in the 6 and 12 mg/L F-53B-treated groups at 132 hpf. Continuous exposure to 3 mg/L F–53B resulted in high accumulation levels in zebrafish embryos, suggesting an inability for embryos to eliminate this compound and a high cumulative risk to fish. We also examined the cardiac function of embryos at specific developmental stages following exposure to different concentrations, and found that F–53B induced cardiac toxicity and reduced heart rate. Even under low F–53B concentration, o-dianisidine staining results showed significant decrease of relative erythrocyte number at 72 hpf before the appearance of observed effects of F–53B on the heart. To elucidate the underlying molecular changes, genes involved in normal cardiac development were analyzed using real-time qPCR in the whole-body of zebrafish embryos. F–53B inhibited the mRNA expression of β-catenin ( ctnnb2 ) and wnt3a . The mRNA levels of β-catenin targeted genes ( nkx2.5 and sox9b ), which play critical roles in cardiogenesis, were also reduced after exposure. Thus, exposure to F–53B impaired the development of zebrafish embryos and disrupted cardiac development, which might be mediated by effects on the Wnt signaling pathway and decrease of erythrocyte numbers. [ABSTRACT FROM AUTHOR]

[Display omitted] • 3D thin wall with turgor pressure finite element model of bacterial cell was build. • The AFM indentation experiments of E. coli cell were simulated using 3D-TWTP-FEM. • Investigation of mechano-bactericidal mechanism of nanostructured surfaces. • This study reveals the maximum stress location of the cells adhered to nanopillars. • Optimal nanopillar geometry for mechanically killing bacteria. The mechano-bactericidal property of nanostructured surfaces has become the focus of intensive research toward the development of a new generation of antibacterial surfaces, especially in the current era of spreading antibiotic resistance. However, the mechanisms underlying nanostructured surfaces mechanically damaging bacteria remain unclear, which ultimately limits translational potential toward real-world applications. Using finite element simulation technique, we developed the three-dimensional thin wall with turgor pressure finite element model (3D-TWTP-FEM) of bacterial cell and verified the reliability of this model by the AFM indentation experiment simulation of the cell, and the cell model is able to simulate suspended bacterial cell and the process of cell adhering to the flat and nanopillar surfaces. Since bacterial cells suffer greater stress and deformation on the nanopillar surfaces, a two-stage model of the elastic and creep deformation stage of the cells on the nanostructured surfaces was developed. The calculations show that the location of the maximum stress/strain on the cells adhered to the nanopillar surfaces is at the liquid-cell-nanopillar three phase contact line. The computational results confirmed the ability of nanostructured surfaces to mechanically lyse bacteria and gave the effect of nanopillar geometry on the efficiency and speed of bacterial cell rupture. This study provides fundamental physical insights into how nanopillar surfaces can serve as effective and fast mechanical antimicrobial materials. [ABSTRACT FROM AUTHOR]

Given that per- and polyfluoroalkyl substances (PFASs) exhibit different distribution in the serum and semen of adult men, improving our understanding of the predictors of PFAS concentrations in paired serum and semen samples from an individual is essential. Here, we investigated and compared the effects of emerging and legacy PFAS concentrations in serum and semen on reproductive hormone levels in serum within a Chinese adult male population. We explored the relationships among perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorooctane sulfonate (PFOS), and chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) in serum and semen with reproductive hormones in serum among 651 adult men from Nanjing, China. Significant relationships among all analyzed serum and semen PFASs and decreased total testosterone (total T) were found. Serum and semen PFOA levels were associated with significant decreases in free T. Furthermore, the levels of sex hormone-binding globulin (SHBG) were significantly decreased in association with PFNA, PFOS, and 6:2 Cl-PFESA exposure. Negative relationships between the total T/luteinizing hormone (LH) ratio and semen concentrations of selected PFASs were also observed. After adjustment of PFAS concentrations (in both semen and serum), stronger associations of PFASs with total T, free T, estradiol (E2), SHBG, and total T/LH were observed in semen than in serum. We found that 84.8% of the associations between serum PFOA with total T were mediated by semen PFOA. Thus, elevated PFAS exposure may have negative effects on male reproductive health, and semen PFAS may be a better exposure indicator for the male reproductive system than serum PFAS. Image 1 • Paired serum and semen PFASs were simultaneously determined. • Studied semen and serum PFASs were significantly negative associated with Total T. • Significant negative associations were observed between semen PFASs and Total T/LH. • Stronger inverse associations were found for semen PFASs with reproductuive hormones. • Semen PFASs reflect exposures of reproductive system more directly than serum PFASs. This study explored the relationship of PFASs in serum and semen samples of male reproductive hormones, and suggested that semen PFASs can more directly reflect the actual exposure levels of the male reproductive system. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFASs) have been ubiquitously detected in the environment and marine animals. However, little is known about these substances and their associations with health parameters in wild terrestrial mammals. In this study, we determined PFAS levels and distribution in the blood of captive Siberian tigers in Harbin, China, and evaluated potential exposure pathways by daily intake. In addition, for the first time, we explored the associations between serum PFAS concentrations and clinical parameters. Results showed that perfluorooctanoate (PFOA) was the dominant PFAS compound in blood (accounting for 64%), followed by perfluorooctanesulfonate (PFOS). In addition, 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) concentrations were also detected in blood and dietary food. Furthermore, significant positive age relationships were observed for levels of perfluoroheptanoate (PFHpA), PFOA, PFOS, and 6:2 Cl-PFESA in the blood of female tigers. Results showed that PFOA and PFOS in dietary food accounted for over 70% of total daily intake of PFASs, indicating that meat consumption is a predominant exposure pathway in tigers. We also found positive associations between higher exposure to PFASs (including PFOA, PFOS, and 6:2 Cl-PFESA) and elevated serum levels of alanine transaminase (ALT), a marker of liver damage. Thus, comprehensive health assessments of PFAS burdens in wildlife are needed. Image 1 • Ten PFASs were detected in the blood of captive Siberian tigers, including PFOS alternative 6:2 Cl-PFESA. • PFOA has replaced PFOS as the predominant PFAS in captive Siberian tigers in China. • Dietary meat was the predominant PFAS exposure pathway for tigers. • Eight PFASs were significantly positively associated with serum ALT levels, a marker of liver damage. This study determined the bioaccumulation of legacy and emerging PFASs in captive Siberian tigers in China and identified eight PFASs that were positively associated with serum levels of ALT, a marker of liver damage. [ABSTRACT FROM AUTHOR]

Feature selection aims to select crucial features to improve classification accuracy in machine learning and data mining. Existing methods concentrate on the classification information from candidate features while seldom considering the changing information supported by selected features. In this paper, we construct a dynamic support ratio (DSR), which employs the new information of selected features to support classification. DSR explicitly describes the dynamic interactions between selected features and candidate features. Simultaneously, the feature relevance and feature redundancy are treated adaptively. Thus, distinctive features can be noticed sensitively. Afterward, a novel feature selection method based on a dynamic support ratio (DSRFS) is proposed. The proposed method is established on 18 benchmark data sets with four different classifiers. Classification accuracy, standard deviation, recall and statistical validations are employed to measure the classification performance. Extensive experiments demonstrate that DSRFS not only reduces the dimension of the feature space effectively, but also obtains the best average classification accuracy. [ABSTRACT FROM AUTHOR]

Abstract Although 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), an alternative to perfluorooctanesulfonate (PFOS), has been regularly detected in different environmental matrices, information regarding its toxicity remains limited. To explore the transgenerational thyroid-disrupting capacity of F-53B, adult zebrafish (F0) were exposed to different concentrations of F-53B (0, 5, 50, or 500 μg/L) for 180 d, with their offspring (F1 and F2) subsequently reared in uncontaminated water. Thyroid disturbances were then examined in the three (F0, F1, and F2) generations. For F0 adult fish, thyroxine (T4) increased in both sexes after exposure to 50 μg/L F-53B, whereas 3,5,3′-triiodothyronine (T3) decreased in all groups, except for 50 μg/L F-53B-treated males. For F1 embryos, parental exposure resulted in F-53B transfer as well as an increase in T4 content. At 5 days post-fertilization, the significant increase in T4 and decrease in T3 were accompanied by a decrease in body length, increase in mortality, and increase in uninflated posterior swim bladder occurrence in F1 larvae. Although thyroid hormone levels were not changed significantly in F1 adult fish or F2 offspring compared with the control, the transcription levels of several genes along the hypothalamus-pituitary-thyroid axis were significantly modified. Our study demonstrated that F-53B possesses transgenerational thyroid-disrupting capability in zebrafish, indicating it might not be a safer alternative to PFOS. Graphical abstract Unlabelled Image Highlights • F-53B exposure disrupted the balance of thyroid hormone levels in F0 adult fish. • Increased T4 levels in F1 eggs were consistent with the T4 level of F0 female serum. • Parental exposed to F-53B altered THs and the HPT axis genes expression in F1 larvae. • Change of TH levels companied with defected swim bladder in F1 larvae. • The change of some HPT axis genes expression still present in F1 adult and F2 larvae. [ABSTRACT FROM AUTHOR]

Feature selection is a crucial preprocessing technique in data mining and machine learning and has attracted increasing attentions. However, the relevance of existing methods only contains limited information. To enhance the classification ability of filter and information theory-based feature selection methods and reduce the redundancy of the selected subset, a relevant-redundant weight-based feature criterion (FSRRW) is proposed. In this paper, a feature relevant-redundant weight (RRW) is constructed to extract the important relevant and redundant information. Then, a novel feature relevance is defined based on the weight, which contains more comprehensive information from the dynamically changing features. Additionally, a feature evaluation criterion is presented via maximizing the feature relevance and minimizing the feature redundancy. The proposed algorithm and seven compared methods are tested on 20 benchmark datasets. Extensive experiments demonstrate that the proposed criterion exhibits better feature screening abilities, effectively facilitates classification, and has preferable applicability and robustness. • Design a feature relevant-redundant weight and define feature relevance. • Construct a novel feature evaluation criterion named FSRRW. • FSRRW is evaluated on 20 benchmark datasets under three classifiers. • The proposed method outperforms seven popular feature selection methods. [ABSTRACT FROM AUTHOR]

Because of the evolutionary variants of SARS-CoV-2, development of broad-spectrum neutralizing antibodies resilient to virus escape is urgently needed. We identified a group of high-affinity nanobodies from camels immunized with receptor-binding domain (RBD) of SARS-CoV-2 spike protein and resolved the structures of two non-competing nanobodies (NB1A7 and NB1B11) in complex with RBD using X-ray crystallography. The structures show that NB1A7 targets the highly conserved cryptic epitope shared by SARS-CoV-2 variants and some other coronaviruses and blocks ACE2 receptor attachment of the spike protein, and NB1B11 epitope overlaps with the contacting surface of ACE2 and is different from the binding site of NB1A7. These two nanobodies were covalently linked into multivalent and bi-paratopic formats, which significantly improved the avidity and neutralization potency and may further inhibit viral escape. The results contribute to the structure-guided design of antibodies against future variants of SARS-CoV-2 virus to combat coronavirus epidemics and pandemics. [Display omitted] • Two neutralizing nanobodies are generated against the RBD of SARS-CoV-2 • The crystal structures reveal that the two nanobodies have different epitopes • One nanobody targets the highly conserved epitope • Bispecific nanobodies improve neutralization potency to SARS-CoV-2 variants Shi et al. identify two neutralizing nanobodies against SARS-CoV-2. Crystal structures reveal how they prevent the virus and its variants from entering cells. The combination of two nanobodies significantly improves neutralization potency, which is a potential therapeutic candidate to reduce the probability of the emergence of escape variants of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two plasma proteins were adsorbed on three typical TiO 2 nanostructures. • Surface topographies of nanostructures can be affected by protein adsorption. • Bactericidal performance of nanostructures is weakened due to the changes in geometric dimensions after BSA adsorption. • Bactericidal efficiency of nanostructures against E. coli can be significantly improved due to the presence of HFN layer on the top of the nanostructures, which may cause higher stress of nanocones to cell membrane. Bionic nanostructures have broad potential applications for achieving the surface mechano-bactericidal performance especially for titanium extensively used as implants. However, the surface topographies of these nanostructures may be changed by protein adsorption in vivo, which possibly affects the sterilization of nanostructures. Herein, two plasma proteins, bovine serum albumin (BSA) and human serum fibronectin (HFN), were adsorbed onto three typical TiO 2 nanostructures respectively, and the topographies as well as the subsequent bacterial behavior of Escherichia coli and Staphylococcus aureus were investigated. The results show that after BSA adsorption, the height of the nanostructures is reduced and the radius of the nanocones is increased for three typical nanostructures, weakening the surface bactericidal performance. Whereas, after HFN adsorption, the proteins are adsorbed at different positions of nanostructures, affecting their bactericidal efficiency. Notably, the bactericidal efficiency of nanowire clusters and nanowire/sheet clusters against Escherichia coli is significantly improved from ∼ 49.64% and ∼ 83.25% to ∼ 64.89% and ∼ 93.67% due to the presence of HFN layer on the top of the nanostructures, which may cause higher stress to cell membrane by nanocones. Our results demonstrate that the bactericidal performance of implant is impacted by the combined effect of surface nanostructure and protein layer. [ABSTRACT FROM AUTHOR]

• Associations between 11 PFASs and 5 steroids in cord sera were assessed. • F-53B, as Chinese unique PFOS replacement, was associated with cortisol in girls. • PFBS, PFOS and PFHxS were positively associated with progesterone in newborns. • Seven PFASs were positively associated with 11-deoxycortisol, the precursor of cortisol. • The results indicate that PFOS and its replacements may influence neonatal steroids. Exposure to per-/polyfluoroalkyl substances (PFASs) can disrupt endocrine hormones in humans. Prior studies have focused on the harmful effects of the two traditional per-/polyfluoroalkyl substances (PFASs), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Other PFASs, used as the replacements of PFOS and PFOA, are widely and increasingly detected in humans. Whether these replacements influence glucocorticoids and progestogens in newborns remains unknown. To investigate the associations between exposures of PFOS, PFOA and their replacements and glucocorticoids and progestogens in newborns. We measured the concentrations of 13 PFASs, 3 glucocorticoids (11-deoxycortisol, cortisol and cortisone) and 2 progestogens [progesterone, 17-hydroxyprogesterone (17OHP)] in the cord sera of 374 neonates in a birth cohort from Wuhan, China, between 2013 and 2014. We evaluated the associations of each PFAS with glucocorticoids and progestogens using multiple linear regression models, and multiple comparisons were additionally corrected via false discovery rates (FDR). Out of the 13 PFASs, 9 were detected in over 95% of cord sera. The Chinese specific PFOS replacement − 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA, trade name F-53B) was positively associated with 13.13% change in cortisol in girls (95% CI = 4.47%, 22.52%, for each IQR increase in 6:2 Cl-PFESA). Seven PFASs had positive associations with the precursor of cortisol, namely 11-deoxycortisol (percent change ranged from 6.41% to 11.24%, for each IQR increase in PFASs). Perfluorobutane sulfonate (PFBS) in cord sera was positively associated with progesterone in the linear model, whereas PFOS and perfluorohexane sulfonate (PFHxS) levels were associated with progesterone in the quartile models. No PFASs were related to 17OHP or cortisone. In this study, PFOS, PFOA and/or their replacements were positively associated with progesterone, cortisol and 11-deoxycortisol in newborns. These results suggested that not only PFOS and PFOA, but also other PFASs have potential impacts on glucocorticoids and progestogens in newborns. [ABSTRACT FROM AUTHOR]