Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.

The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping that is highly concordant with knowledge-based structural classifications3-5. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A-D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)6 and group F (for example, CR3022)7, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.

Nanobodies as negative allosteric modulators for human calcium sensing receptor.

Human calcium sensing receptor (CaSR) senses calcium ion concentrations in vivo and is an important class of drug targets. Mutations in the receptor can lead to disorders of calcium homeostasis, including hypercalcemia and hypocalcemia. Here, 127 CaSR-targeted nanobodies were generated from camels, and four nanobodies with inhibitory function were further identified. Among these nanobodies, NB32 can effectively inhibit the mobilization of intracellular calcium ions (Ca2+i) and suppress the G12/13 and ERK1/2 signaling pathways downstream of CaSR. Moreover, it enhanced the inhibitory effect of the calcilytics as a negative allosteric modulator (NAM). We determined the structure of complex and found NB32 bound to LB2 (Ligand-binding 2) domain of CaSR to prevent the interaction of LB2 domains of two protomers to stabilize the inactive state of CaSR.

Identification of a novel orthonairovirus from ticks and serological survey in animals near China-North korea border.

Emerging pathogenic tick-borne viruses (TBVs) have attracted a great deal of attention due to their significant impact on human and animal health. A novel orthonairovirus named Dadong virus (DDV) was isolated from Haemaphysalis concinna ticks in the Changbai Mountain region on the China-North Korea border. DDV can induce cytopathic effects in mammalian and human cell lines. Phylogenetic analysis showed that it belongs to the genus Orthonairovirus, family Nairoviridae, exhibiting 72.4%-81.3% nucleic acid identity to Tofla orthonairovirus, known to cause lethal infection in IFNAR KO mice. The first serological evidence of DDV circulating in cattle and mice was also obtained, with 4.0% (1/25) of cattle and 2.27% (1/44) of mice seropositive for DDV. Further investigations, including serological surveys using human samples, are required to assess the public health risk posed by DDV.

Roles of varying carbon chains and functional groups of legacy and emerging per-/polyfluoroalkyl substances in adsorption on metal-organic framework: Insights into mechanism and adsorption prediction.

Metal-organic frameworks (MOFs) are promising adsorbents for legacy per-/polyfluoroalkyl substances (PFASs), but they are being replaced by emerging PFASs. The effects of varying carbon chains and functional groups of emerging PFASs on their adsorption behavior on MOFs require attention. This study systematically revealed the structure-adsorption relationships and interaction mechanisms of legacy and emerging PFASs on a typical MOF MIL-101(Cr). It also presented an approach reflecting the average electronegativity of PFAS moieties for adsorption prediction. We demonstrated that short-chain or sulfonate PFASs showed higher adsorption capacities (µmol/g) on MIL-101(Cr) than their long-chain or carboxylate counterparts, respectively. Compared with linear PFASs, their branched isomers were found to exhibit a higher adsorption potential on MIL-101(Cr). In addition, the introduction of ether bond into PFAS molecule (e.g., hexafluoropropylene oxide dimeric acid, GenX) increased the adsorption capacity, while the replacement of CF2 moieties in PFAS molecule with CH2 moieties (e.g., 6:2 fluorotelomer sulfonate, 6:2 FTS) caused a decrease in adsorption. Divalent ions (such as Ca2+ and SO42-) and solution pH have a greater effect on the adsorption of PFASs containing ether bonds or more CF2 moieties. PFAS adsorption on MIL-101(Cr) was governed by electrostatic interaction, complexation, hydrogen bonding, π-CF interaction, and π-anion interaction as well as steric effects, which were associated with the molecular electronegativity and chain length of each PFAS. The average electronegativity of individual moieties (named Me) for each PFAS was estimated and found to show a significantly positive correlation with the corresponding adsorption capacity on MIL-101(Cr). The removal rates of major PFASs in contaminated groundwater by MIL-101(Cr) were also correlated with the corresponding Me values. These findings will assist with the adsorption prediction for a wide range of PFASs and contribute to tailoring efficient MOF materials.

Structure basis of two nanobodies neutralizing SARS-CoV-2 Omicron variant by targeting ultra-conservative epitopes.

The evolving SARS-CoV-2 Omicron strain has repeatedly caused widespread disease epidemics, and effective antibody drugs continue to be in short supply. Here, we identified a batch of nanobodies with high affinity for receptor binding domain (RBD) of SARS-CoV-2 spike protein, separated them into three classes using high performance liquid chromatography (HPLC), and then resolved the crystal structure of the ternary complexes of two non-competing nanobodies (NB1C6 and NB1B5) with RBD using X-ray crystallography. The structures showed that NB1B5 and NB1C6 bind to the left and right flank of the RBD, respectively, and that the binding epitopes are highly conserved cryptic sites in all SARS-CoV-2 mutant strains, as well as that NB1B5 can effectively block the ACE2. These two nanobodies were covalently linked into multivalent and bi-paratopic formats, and have a high affinity and neutralization potency for omicron, potentially inhibiting viral escape. The binding sites of these two nanobodies are relatively conserved, which help guide the structural design of antibodies targeting future variants of SARS-CoV-2 to combat COVID-19 epidemics and pandemics.

CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation.

BACKGROUND: Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200-CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown. METHODS: The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging. RESULTS: We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS. CONCLUSIONS: Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.

Long-term variations and potency of neutralizing antibodies against Omicron subvariants after CoronaVac-inactivated booster: A 7-month follow-up study.

The long-term protective efficacy of neutralizing antibodies (Nabs) against Omicron subvariants after inactivated booster vaccines remains elusive. During the follow-up study, 54 healthy volunteers aged 20-31 years received inactivated CoronaVac booster vaccinations and were monitored for 221 days. The dynamic efficacy and durability of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.2, and BA4/5 were assessed using a pseudotyped virus neutralization assay at up to nine time points post immunization. The antibody response against Omicron subvariants was substantially weaker than D614G, with BA.4/5 being the least responsive. The geometric mean titer (GMT) of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.1, and BA.4/5 was 2.2-, 1.7-, 1.8-, and 2.2-fold lower than that against D614G (ps < 0.0001). The gap in Nab response between Omicron subvariants was pronounced during the 2 weeks-2 months following booster vaccination (ps < 0.05). Seven months post booster, the antibody potency against D614G was maintained at 100% (50% for Nab titers ≥ 100 50% inhibitory dilution [EC50 ]), whereas at 77.3% for BA.1, 90.9% for BA.2, 86.4% for BA.2.12.1, and 86.4% for BA.4/5 (almost 20% for Nab titers ≥ 100 EC50 ). Despite the inevitable immune escape, Omicron subvariants maintained sustained and measurable antibody potency post-booster vaccination during long-term monitoring, which could help optimize immunization strategies.

A procedure for producing an anti-AXL nanobody in E. coli.

As one of the receptors of the TAM family, AXL plays a vital role in stem cell maintenance, angiogenesis, immune escape of viruses and drug resistance against tumors. In this study, the truncated extracellular segment containing two immunoglobulin-like domains of human AXL (AXL-IG), which has been confirmed to bind growth arrest specific 6 (GAS6) by structural studies [1], was expressed in a prokaryotic expression system and then purified. Immunizing camelid with the purified AXL-IG as antigen could lead to the production of unique nanobodies composed of only variable domain of heavy chain of heavy-chain antibody (VHH), which are around 15 kD and stable. We screened out a nanobody A-LY01 specific binding to AXL-IG. We further determined the affinity of A-LY01 to AXL-IG and revealed that A-LY01 could specifically recognize full-length AXL on the surface of HEK 293T/17 cells. Our study provides appropriate support for the development of diagnostic reagents and antibody therapeutics targeting AXL.

Application of Pseudotyped Viruses.

Highly pathogenic emerging and reemerging viruses have serious public health and socioeconomic implications. Although conventional live virus research methods can more reliably investigate disease pathogenicity and evaluate antiviral products, they usually depend on high-level biosafety laboratories and skilled researchers; these requirements hinder in vitro assessments of efficacy, as well as efforts to test vaccines and antibody drugs. In contrast, pseudotyped viruses (i.e., single-round infectious viruses that mimic the membrane structures of various live viruses) are widely used in studies of highly pathogenic viruses because they can be handled in biosafety level 2 facilities. This chapter provides a concise overview of various aspects of pseudotyped virus technologies, including (1) exploration of the mechanisms of viral infection; (2) evaluation of the efficacies of vaccines and monoclonal antibodies based on pseudovirion-based neutralization assay; (3) assessment of antiviral agents (i.e., antibody-based drugs and inhibitors); (4) establishment of animal models of pseudotyped virus infection in vivo; (5) investigation of the evolution, infectivity, and antigenicity of viral variants and viral glycosylation; and (6) prediction of antibody-dependent cell-mediated cytotoxic activity.

Novel Photoelectrochemical Biosensing Platform Based on a Double Type II CdLa2S4/SnIn4S8/Sb2S3 Ternary Heterojunction as Photoactive Materials and NiCo2O4 Nanospheres as a Photoquencher for CA19-9 Detection.

A novel signal-off biosensing platform based on the CdLa2S4/SnIn4S8/Sb2S3 heterojunction as photoactive materials and NiCo2O4 nanospheres as a photoquencher was developed to achieve the sensitive detection of CA19-9. First, the narrow band gap hydrangea-like CdLa2S4/SnIn4S8/Sb2S3 not only provided excellent photocurrent response but also supplied a mass of active sites that facilitated the loading of capture antibody (Ab1). Second, a double type II CdLa2S4/SnIn4S8/Sb2S3 heterojunction promoted the fast separation and migration of photogenerated e-/h+ and overcame the problem of short carrier lifetime caused by the recombination of photogenerated carriers. In addition, to improve the sensitivity of the constructed sensor to detect CA19-9, signal tags (p-type NiCo2O4) with large steric hindrance were introduced to accomplish signal amplification by the effect of double signal quenching. On one hand, NiCo2O4, which was strongly responsive to visible light, utilized its own advantages to compete for AA with CdLa2S4/SnIn4S8/Sb2S3, resulting in a decrease in the hole scavenging rate of the substrate. On the other hand, the photoquencher NiCo2O4 also prevented AA from contacting the matrix and further aggravated the photoelectrochemical (PEC) signal-damping effect. The PEC immunosensor was prepared with brilliant selectivity and splendid stability to detect CA19-9 (0.001-50 U/mL), and the detection limit was 0.0004 U/mL (S/N = 3).

Hippocampal CD39/ENTPD1 promotes mouse depression-like behavior through hydrolyzing extracellular ATP.

Emerging evidence implicates that low levels of ATP in the extracellular space may contribute to the pathophysiology of major depressive disorder (MDD). The concentration of extracellular ATP is regulated by its hydrolase ectonucleotide tri(di)phosphohydrolase (ENTPD). However, the role of ENTPD in depression remains poorly understood. Here we examine the role of CD39 (known as ENTPD1) in mouse depression-like behavior induced by chronic social defeat stress (CSDS). We demonstrate that CSDS enhances the expression and activity of CD39 in hippocampus. The CD39 functional analog apyrase also induces depression-like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD39 has an antidepressant-like effect via increasing hippocampal extracellular ATP concentration, accompanied with an increase in hippocampal neurogenesis and dendritic spine numbers in defeated mice. These results suggest that hippocampal CD39 contributes to CSDS-induced depression-like behavior via hydrolyzing extracellular ATP, indicating that CD39 may be a promising new target for the treatment of depression.

Genome-wide association study of the level of blood components in Pekin ducks.

Blood components are considered to reflect nutrient metabolism and immune activity in both humans and animals. In this study, we measured 12 blood components in Pekin ducks and performed genome-wide association analysis to identify the QTLs (quantitative trait locus) using a genotyping-by-sequencing strategy. A total of 54 QTLs were identified for blood components. One genome-wide significant QTL for alkaline phosphatase was identified within the intron-region of the OTOG gene (P = 1.31E-07). Moreover, 21 genome-wide significant SNPs for the level of serum cholinesterase were identified on six different scaffolds. In addition, for serum calcium, one genome-wide significant QTL was identified in the upstream region of gene RAB11B. These results provide new markers for functional studies in Pekin ducks, and several candidate genes were identified, which may provide additional insights into specific mechanisms for blood metabolism in ducks and their potential application for duck breeding programs.

Accumulation, Biotransformation, and Endocrine Disruption Effects of Fluorotelomer Surfactant Mixtures on Zebrafish.

As an alternative to perfluorooctanesulfonate (PFOS), novel fluorotelomer surfactants (6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB) and 6:2 fluorotelomer sulfonamide alkylamine (6:2 FTAA)) are widely used in aqueous film-forming foams and are frequently found to coexist in the environment. However, their potential toxicities remain unknown. Here, we investigated the chronic toxicity of 6:2 FTAB (65%) and 6:2 FTAA (35%) coexposure on adult zebrafish at doses of 0, 5, 50, or 500 µg/L using a flow-through exposure system for 180 days. Results showed that 6:2 FTAB was undetected in adult tissue and their offspring, while 6:2 FTAA was highly dominant, accounting for ∼92% of total quantified poly/perfluoroalkyl substances (PFASs), and their metabolic products (6:2 fluorotelomer sulfonamide and 6:2 fluorotelomer sulfonate) further accounting for 2.8%-8.5%. 6:2 FTAA accumulation exhibited a sex-bias, with higher levels found in male livers than that in female, but in gonad showed an opposite pattern. Co-exposure to 6:2 FTAB and 6:2 FTAA mixture (50 and 500 µg/L) could decrease the average number of eggs production and increase the malformation and mortality in their offspring. Testosterone (T) and 17 ß-estradiol (E2) levels increased in the 50 and 500 µg/L exposed females, but T level decreased in the 500 µg/L exposed males. Correspondingly, the transcriptional pattern of hypothalamus-pituitary-gonad axis genes was different between male and female. Increased liver vitellogenin levels in the 50 and 500 µg/L-exposed males indicated that these compounds might possess estrogen-like activity. Furthermore, 3,5,3'-triiodothyronine (T3) and thyroxine (T4) levels decreased in the 50 and 500 µg/L females and increased T4 level in 500 µg/L exposed males. These results suggest that 6:2 FTAB is extensively metabolized in fish, whereas 6:2 FTAB and 6:2 FTAA coexposure disrupted the adult endocrine system and impaired offspring development.

Primary Acute Angle-Closure Glaucoma: Three-Dimensional Reconstruction Imaging of Optic Nerve Heard Structure in Based on Optical Coherence Tomography (OCT).

BACKGROUND In glaucoma, the cup to plate ratio enlargement is a recognized pathological phenomenon. At present, the research on optic nerve in China and abroad mainly focuses on 2-dimensional research, and the measurement of 3-dimensional volume data is less well studied. Therefore, the recognition of 3-dimensional morphological changes is conducive to timely clinical intervention to prevent or slow down progressive vision loss. MATERIAL AND METHODS In this paper, optical coherence tomography (OCT) volume imaging technology was used to analyze and compare the morphological changes of primary acute angle-closure glaucoma in three-dimensional morphology, reconstruct the volume data of three-dimensional optic nerve head (ONH), and make morphological measurements. RESULTS The rim width of the glaucoma group was significantly lower than that of the control group, and the average volume and intraocular pressure of the optic cup were significantly increased (P<0.05), while the rim width and intraocular pressure of the other group were not significantly changed (P>0.05). CONCLUSIONS We used three-dimensional reconstruction to identify OCT images between glaucoma patients and the control group with significant differences.

Penetration of PFASs Across the Blood Cerebrospinal Fluid Barrier and Its Determinants in Humans.

Laboratory studies indicate that exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) can induce neurobehavioral effects in animals. However, the penetration of PFASs across the brain barrier and its determining factors are yet to be clarified in humans. We studied PFAS levels in 223 matched-pair serum and cerebrospinal fluid (CSF) samples from hospital in-patients using UPLC/MS/MS. Among the 21 target analytes, PFOA, PFOS, and 6:2 Cl-PFESA were dominant in serum, with mean concentrations of 7.4, 6.8, and 6.2 ng/mL, respectively, contributing 79% to the total PFAS burden in serum. In CSF, PFOA, PFOS, and 6:2 Cl-PFESA were again the dominant PFASs, with mean concentrations of 0.078, 0.028, and 0.051 ng/mL contributing 36%, 13%, and 24%, respectively, to the total PFAS burden in CSF. Furthermore, PFAS penetration ( RPFAS, PFASCSF/PFASserum) was positively correlated with the barrier permeability index RAlb (AlbuminCSF/Albuminserum), indicating that barrier integrity was the main determinant of PFAS penetration across the blood-CSF barrier. Positive associations between the RPFAS values of the main PFASs and serum C-reactive protein were observed, implying that inflammation facilitates the penetration of PFASs across the brain barrier.

Occurrence and Tissue Distribution of Novel Perfluoroether Carboxylic and Sulfonic Acids and Legacy Per/Polyfluoroalkyl Substances in Black-Spotted Frog (Pelophylax nigromaculatus).

Research on perfluoroalkyl substances (PFASs) continues to grow. However, very little is known about these substances in amphibians. Here we report for the first time on the occurrence, tissue distribution, and bioaccumulation of two novel PFASs, chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide trimer acid (HFPO-TA), in the black-spotted frog (Pelophylax nigromaculatus) from China. Frogs from cities with large-scale fluorochemical industries had significantly greater liver ∑PFAS levels (mean 54.28 ng/g in Changshu; 31.22 ng/g in Huantai) than those from cities without similar industry (9.91 ng/g in Zhoushan; 7.68 ng/g in Quzhou). Females had significantly lower liver PFAS levels than males, and older frogs tended to have lower PFAS levels than younger frogs. Skin, liver, and muscle contributed nearly 80% to the whole body burden of 6:2 Cl-PFESA in males, whereas the female ovary alone accounted for 58.4%. These results suggest substantial maternal transfer of 6:2 Cl-PFESA to eggs, raising concern regarding its developmental toxicity on frogs and other species. The bioaccumulation factor results (6:2 Cl-PFESA > PFOS; HFPO-TA > PFOA) suggest a stronger accumulative potential in the black-spotted frog for these alternative substances compared to their predecessors. Future studies on their toxicity and ecology risk are warranted.

Subchronic Hepatotoxicity Effects of 6:2 Chlorinated Polyfluorinated Ether Sulfonate (6:2 Cl-PFESA), a Novel Perfluorooctanesulfonate (PFOS) Alternative, on Adult Male Mice.

The compound 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative to perfluorooctanesulfonate (PFOS) in the metal-plating industry, has been widely detected in various environmental matrices. However, its hepatotoxicity has yet to be clarified. Here, male mice were exposed to 0.04, 0.2, or 1 mg/kg/day of 6:2 Cl-PFESA for 56 days. Results demonstrated that relative liver weight increased significantly in the 0.2 and 1 mg/kg/day 6:2 Cl-PFESA groups, whereas liver lipid accumulation increased in all 6:2 Cl-PFESA groups. Serum enzyme activities of alanine transaminase and alkaline phosphatase were increased. Serum triglycerides and low-density lipoprotein cholesterol both increased, whereas serum total cholesterol and high-density lipoprotein cholesterol decreased following 6:2 Cl-PFESA exposure. A total of 264 differentially expressed proteins (127 up-regulated and 137 down-regulated), mainly involved in lipid metabolism, xenobiotic metabolism, and ribosome biogenesis, were identified by quantitative proteomics. Bioinformatics analysis highlighted the de-regulation of PPAR and PXR, which may contribute to the hepatotoxicity of 6:2 Cl-PFESA. Additionally, 6:2 Cl-PFESA induced both cell apoptosis and proliferation in the mouse liver. Compared to the overt toxicity of PFOS, 6:2 Cl-PFESA exhibited more-serious hepatotoxicity. Thus, caution should be exercised in the application of 6:2 Cl-PFESA as a replacement alternative to PFOS in industrial areas.

Worldwide Distribution of Novel Perfluoroether Carboxylic and Sulfonic Acids in Surface Water.

Driven by increasingly stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), novel fluorinated compounds have emerged on the market. Here we report on the occurrences of several perfluoroalkyl ether carboxylic and sulfonic acids (PFECAs and PFESAs), including hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA), ammonium 4,8-dioxa-3 H-perfluorononanoate (ADONA), chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), and its hydrogen-substituted analogue (6:2 H-PFESA) in surface waters from China ( n = 106), the United States ( n = 12), the United Kingdom ( n = 6), Sweden ( n = 10), Germany ( n = 14), The Netherlands ( n = 6), and Korea ( n = 6). Results showed that HFPO-DA, HFPO-TA, and 6:2 Cl-PFESA (median = 0.95, 0.21, and 0.31 ng/L, respectively) were frequently detected in all countries, indicating ubiquitous dispersal and distribution in global surface waters. The presence of 6:2 H-PFESA was widely detected in China (detection rate > 95%) but not in any other country. Only trace levels of ADONA (0.013-1.5 ng/L) were detected in the Rhine River flowing through Germany. The estimated total riverine mass discharges of HFPO-DA, HFPO-TA, and ΣPFESAs reached 2.6, 6.0, and 4.3 ton/year in five of the major river systems in China. Our results indicated that novel PFECAs and PFESAs might become global contaminants, and future investigations are warranted.

First Report on the Occurrence and Bioaccumulation of Hexafluoropropylene Oxide Trimer Acid: An Emerging Concern.

Here, we report on the occurrence of a novel perfluoroalkyl ether carboxylic acid, ammonium perfluoro-2-[(propoxy)propoxy]-1-propanoate (HFPO-TA), in surface water and common carp (Cyprinus carpio) collected from the Xiaoqing River and in residents residing near a fluoropolymer production plant in Huantai County, China. Compared with the levels upstream of the Xiaoqing River, HFPO-TA concentrations (5200-68500 ng/L) were approximately 120-1600-times higher downstream after receiving fluoropolymer plant effluent from a tributary. The riverine discharge of HFPO-TA was estimated to be 4.6 t/yr, accounting for 22% of total PFAS discharge. In the wild common carp collected downstream from the point source, HFPO-TA was detected in the blood (median: 1510 ng/mL), liver (587 ng/g ww), and muscle (118 ng/g ww). The log BCFblood of HFPO-TA (2.18) was significantly higher than that of PFOA (1.93). Detectable levels of HFPO-TA were also found in the sera of residents (median: 2.93 ng/mL). This is the first report on the environmental occurrence and bioaccumulation of this novel chemical. Our results indicate an emerging usage of HFPO-TA in the fluoropolymer manufacturing industry and raise concerns about the toxicity and potential health risks of HFPO-TA to aquatic organisms and humans.

Novel Chlorinated Polyfluorinated Ether Sulfonates and Legacy Per-/Polyfluoroalkyl Substances: Placental Transfer and Relationship with Serum Albumin and Glomerular Filtration Rate.

Per- and polyfluoroalkyl substances (PFASs) may cross the placental barrier and lead to fetal exposure. However, little is known about the factors that influence maternal-fetal transfer of these chemicals. PFAS concentrations were analyzed in 100 paired samples of human maternal sera collected in each trimester and cord sera at delivery; these samples were collected in Wuhan, China, 2014. Linear regression was used to estimate associations of transfer efficiencies with factors. Chlorinated polyfluorinated ether sulfonates (Cl-PFAESs, 6:2 and 8:2) were frequently detected (>99%) in maternal and cord sera. A significant decline in PFAS levels during the three trimesters was observed. A U-shape trend for transfer efficiency with increasing chain length was observed for both carboxylates and sulfonates. Higher transfer efficiencies of PFASs were associated with advancing maternal age, higher education, and lower glomerular filtration rate (GFR). Cord serum albumin was a positive factors for higher transfer efficiency (increased 1.1-4.1% per 1g/L albumin), whereas maternal serum albumin tended to reduce transfer efficiency (decreased 2.4-4.3% per 1g/L albumin). Our results suggest that exposure to Cl-PFAESs may be widespread in China. The transfer efficiencies among different PFASs were structure-dependent. Physiological factors (e.g., GFR and serum albumin) were observed for the first time to play critical roles in PFAS placental transfer.