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Wastewater treatment plants (WWTPs) pose a potential threat to the environment because of the accumulation of antibiotic resistance genes (ARGs) and microplastics (MPs). However, the interactions between ARGs and MPs, which have both indirect and direct effects on ARG dissemination in WWTPs, remain unclear. In this study, spatiotemporal variations in different types of MPs, ten ARGs (sul1, sul2, tetA, tetO, tetM, tetX, tetW, qnrS, ermB, and ermC), class 1 integron integrase (intI1) and transposon Tn916/1545 in three typical WWTPs were characterized. Sul1, tetO, and sul2 were the predominant ARGs in the targeted WWTPs, whereas the intI1 and transposon Tn916/1545 were positively correlated with most of the targeted ARGs. Saccharimonadales (4.15 %), Trichococcus (2.60 %), Nitrospira (1.96 %), Candidatus amarolinea (1.79 %), and SC-I-84 (belonging to phylum Proteobacteria) (1.78 %) were the dominant genera. Network and redundancy analyses showed that Trichococcus, Faecalibacterium, Arcobacter, and Prevotella copri were potential hosts of ARGs, whereas Candidatus campbellbacteria and Candidatus kaiserbacteria were negatively correlated with ARGs. The potential hosts of ARGs had a strong positive correlation with polyethylene terephthalate, silicone resin, and fluor rubber and a negative correlation with polyurethane. Candidatus campbellbacteria and Candidatus kaiserbacteria were positively correlated with polyurethane, whereas potential hosts of ARGs were positively correlated with polypropylene and fluor rubber. Structural equation modeling highlighted that intI1, transposon Tn916/1545 and microbial communities, particularly microbial diversity, dominated the dissemination of ARGs, whereas MPs had a significant positive correlation with microbial abundance. Our study deepens the understanding of the relationships between ARGs and MPs in WWTPs, which will be helpful in designing strategies for inhibiting ARG hosts in WWTPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Rationale: Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG) is an antibody-mediated and complement-involved acquired autoimmune disorder of the post-synaptic neuromuscular junction. There have been few reports about if there is related between the 2. In this study, we present the case of a man who was diagnosed as FOSMN with MG in continuity., Patient Concerns: The patient chief complaints were right-side facial numbness and right-eyelid incomplete closure, followed by slurred speech and dysphagia, and the symptoms gradually progressed. The patient serum was positive for anti-AchR and anti-Titin antibodies., Diagnoses: The patient was diagnosed FOSMN with MG., Interventions: The patient symptoms were relieved after pyridostigmine bromide and prednisolone treatment., Outcomes: Symptoms have improved., Lessons: Facial-onset sensory and motor neuronopathy and MG have disparate clinical features. Therefore, we reported a rare case in which the 2 conditions concurrently existed. Immune dysfunction might be the pathogenesis of this association, while there is no definite evidence to support it, further studies are needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Prenatal fine particulate matter (PM 2.5 ) exposure has been linked to infant cognitive and motor functions, but the effects of PM 2.5 chemical composition remain unclear., Objectives: We aimed to explore the associations of prenatal PM 2.5 and its composition exposure with infant cognitive and motor functions., Methods: We studied 2,435 mother-infant pairs in the Shanghai Birth Cohort Study. PM 2.5 and its seven compositions [primary particles (black carbon, mineral dust and sea salts) and secondary particles (NH 4 + , NO 3 - , SO 4 2- and organic matter)] during thethreetrimesters ofpregnancy were retrieved from the V4.CH.03 product developed by using a combined geoscience-statistical method. At the 12-month-old follow-up, infant cognitive and motor functions in five domains were assessed using the Ages and Stages Questionnaire (ASQ). We used multivariable linear regressions to estimate the effects of PM 2.5 and its composition on the ASQ scores, for all infants and stratifying by sex and breastfeeding duration., Results: PM 2.5 exposure was negatively associated with gross motor, problem-solving and personal-social scores for all infants. PM 2.5 compositions were inversely associated with ASQ scores in all five domains, and the effects of different compositions varied across domains. Specifically, all compositions except organic matter were correlated with lower problem-solving scores [e.g., ( [Formula: see text]  =  - 10.79, 95 % CI: -17.40, -4.18) ∼ ( [Formula: see text]  =  - 4.68, 95 % CI: -7.84, -1.53); for each 10 μg/m 3 increase in PM 2.5 compositions during the third trimester]. Primary and some secondary particles (organic matter, NO 3 - ) were related to lower gross motor scores. Secondary particles were also inversely associated with communication (organic matter and NO 3 - ), fine motor (NH 4 + , NO 3 - , SO 4 2- ) and personal-social (NH 4 + ) scores. Additionally, boys and infants breastfed for < 6 months appeared to be more susceptible., Conclusions: We found negative associations of PM 2.5 and its compositions with infant cognitive and motor functions over a range of domains, especially the problem-solving domain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

This study aimed to compare the differences between oral administration and intravenous injection of polygalacturonic acid (PGA) in the regulation of immune and intestinal microflora in ulcerative colitis (UC) mice. PGA was administered orally or intravenously. PGA in the high-dose ig group was the most effective in treating UC by increasing colon length and downregulating disease activity index, histopathological score and proinflammatory cytokine levels. In spleen, the efficacy of PGA on restoring Th17/Treg balance in the high-dose iv group was better than that in the high-dose ig group, the opposite was observed in the lamina propria. The level of colonic IL-17A in the high-dose ig group was lower than that in the high-dose iv group, the opposite was observed for that of colonic IL-10. Western blot and immunohistochemistry analysis revealed that PGA in the high-dose ig group decreased the protein expression of RORγt, and increased that of FOXP3. Furthermore, PGA in the high-dose ig group was more effective than that in the high-dose iv group in improving the intestinal microflora structure. Our results suggest that in immune regulation, oral PGA is more effective in the lamina propria and gut microbiota while intravenous PGA is more effective in the spleen., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To systematically evaluate the efficacy and safety of Huangqin Tang (HQT) combined with mesalazine for the treatment of ulcerative colitis (UC)., Methods: The China Knowledge Network, Wanfang Data, VIP, PubMed, SinoMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) of UC with HQT in Chinese and English. The search time was from the establishment of the database to October 2021. The included literature was evaluated for data extraction and risk of bias, efficacy and safety were evaluated using the RevMan5.3 software, and the quality of evidence was evaluated using GRADE., Results: Six studies with a total of 565 subjects were included, and a meta-analysis showed that HQT combined with mesalazine for UC significantly improved the cure rate (RR = 1.56, 95% CI [1.23, 1.98), P =0.0003) and overall efficacy rate (RR = 1.24, 95% CI [1.14, 1.35], P =0.00001), which significantly reduced the clinical symptom scores; however, all had high heterogeneity. HQT combined with mesalazine modulated the patients' serum IL-6, IL-10, IgA, and IgG levels. HQT combined with mesalazine for UC tended to reduce adverse effects; however, the difference was not statistically significant. All GRADE ratings of the quality of evidence were of low quality., Conclusions: HQT combined with mesalazine in the treatment of UC significantly improved the cure rate and overall treatment efficiency and regulated the expression levels of serum IL-6, IL-10, IgA, and IgG., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Chengyu Pan et al.)

Background: Few studies have examined the adverse birth sizes of preconception exposure to organophosphate pesticides (OPs) in women undergoing in vitro fertilization (IVF)., Objectives: We investigated the relationship of preconception OP exposure with birth sizes among Chinese women undergoing IVF., Methods: This study included 302 couples seeking infertility treatment in the China National Birth Cohort Study, from Shanghai, China, who gave birth to singleton infants between 2018 and 2021. Clinical data were collected from medical records. We measured the concentrations of six nonspecific dialkyl phosphates (DAP) metabolites of OPs [diethylthiophosphate (DETP), diethylphosphate (DEP), diethyldithiophosphate (DEDTP), dimethyldithiophosphate (DMTP), dimethylphosphate (DMP), and dimethyldithiophosphate (DMDTP)] in maternal urine. DMDTP and DEDTP were precluded from further analyses due to the low detection rates. Generalized linear models (GLMs) and weighted quantile sum (WQS) regression analyses were performed to examine the individual and joint effects of OP exposures on gestational age, birth weight, body length, and ponderal index. Odder ratio (OR) of preterm birth were estimated using logistic regression models., Results: Women in the highest as compared with lowest quartile of DEP had shorter gestational age (β = - 0.68; 95% CI = -1.24, -0.11). The association was modified by sex, with boys showing larger decreases in gestational age (β = - 0.86; 95% CI = -1.60, -0.13). No associations were found between other DAP metabolites and birth sizes. Results from linear models with individual DAP metabolites were corroborated by the WQS regression where DEP had the largest contribution to the overall mixture effect on gestational age (weight = 0.70). Moreover, DEP concentration was associated with an elevated risk of preterm birth (OR = 1.35, 95% CI = 1.11, 2.25)., Conclusion: Preconception DEP concentration was associated with shortened gestational age and increased risk of preterm birth, and the association was more pronounced among boys than girls., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Humans are typically exposed to mixtures of environmental endocrine-disrupting chemicals simultaneously, but most studies have considered only a single chemical or a class of similar chemicals., Objectives: We examined the association of exposure to mixtures of 7 chemicals, including 2 phenols [bisphenol A (BPA) and bisphenol S (BPS)], 2 parabens [methylparaben (MeP) and propyl paraben (PrP)], and 3 phthalate metabolites [Mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP), mono (carboxyoctyl) phthalate (MCOP)] with sex steroid hormones., Methods: A total of 1179 children aged 6-19 years who had complete data on both 7 chemicals and sex steroid hormones of estradiol (E 2 ), total testosterone (TT), and sex hormone-binding globulin (SHBG) were analyzed from the U.S. National Health and Nutrition Examination Survey 2013-2016. Free androgen index (FAI) calculated by TT/SHBG, and the ratio of TT to E 2 (TT/E 2 ) were also estimated. Puberty was defined if TT ≥ 50 ng/dL in boys, E 2 ≥ 20 pg/mL in girls; otherwise prepuberty was defined. Linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were performed to estimate the associations of individual chemical or chemical mixtures with sex hormones., Results: The linear regression showed that 2 phenols, 2 parabens, and 3 phthalate metabolites were generally negatively associated with E 2 , TT, FAI, and TT/E 2 , while positively with SHBG. Moreover, these associations were more pronounced among pubertal than prepubertal children. The aforementioned associations were confirmed when further applying WQS and BKMR, and the 3 phthalates metabolites were identified to be the most heavily weighing chemicals., Conclusions: Exposure to phenols, parabens, and phthalates, either individuals or as a mixture, was negatively associated with E 2 , TT, FAI and TT/E 2 , while positively with SHBG. Those associations were stronger among pubertal children., Competing Interests: Declaration of competing interest The authors declare no actual or potential conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: An increasing number of studies have reported neonicotinoid insecticides (NEOs), the emerging alternatives to conventional insecticides, may increase oxidative stress and cause adverse health effects, but limited is known about the prenatal NEOs exposures and their impact on birth outcomes., Objectives: We investigated the levels of prenatal exposure to NEOs/metabolites, to assess their associations with birth outcomes, and investigate whether these associations could be mediated by oxidative stress using 8-OHdG as the biomarker., Methods: We studied 296 mother-infant pairs recruited from Laizhou Wan Birth Cohort in 2010 - 2013. Two NEOs (IMI and ACE), three metabolites (6-CN, ND-ACE, and 2CTCA), and 8-OHdG were measured in maternal urine collected before delivery. Birth outcomes including birth weight, birth length, ponderal index (PI), head circumference, and gestational age, were acquired. We examined the associations between NEOs/metabolites and birth outcomes using multivariable linear regression. Mediation analysis was conducted to clarify the role of 8-OHdG on the association of NEOs/metabolites exposure and birth outcomes., Results: Highest detection rate was observed for ACE (100.0%), followed by IMI (98.3%) and 6-CN (98.0%), suggesting the common exposure of pregnant women. The highest median concentration was observed for 6-CN with creatinine-adjusted median levels of 9.58 μg/g creatinine. A decrease in newborns' head circumference was observed with a 10-fold increase in IMI (β = -1.83; 95% CI = -3.04, -0.62) and ACE (β = -2.27; 95% CI = -3.56, -0.98). An increase in newborns' PI was observed with a 10-fold increase in IMI (β = 0.40; 95% CI = 0.03, 0.75). Maternal 8-OHdG demonstrated 38.5-65.5% mediating effects in the negative association of IMI, ACE, 2-CTCA with head circumference. These associations might differ between boys and girls., Conclusions: Pregnant women were widely exposed to NEOs/metabolites in China. Results suggested the potential impacts of prenatal exposure to certain neonicotinoid insecticides on head circumference. Urinary 8-OHdG may partly mediate these associations., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Per- and polyfluoroalkyl substances (PFAS) are believed to impair early neurodevelopment and disrupt thyroid hormone (TH) levels. However, there are limited epidemiological data on the neurodevelopmental effects in infancy of prenatal PFAS exposure and the potential mediating effects of TH., Objectives: To evaluate potential associations between prenatal PFAS exposure and early neurodevelopmental deficiencies, and assess mediator effects of TH., Methods: From 2010 to 2013, 274 mother-infant pairs were recruited to the Laizhou Wan Birth Cohort in China. Ten PFAS and five TH were measured in cord serum. Developmental quotient (DQ) from 5 domains (adaptive, social, language, gross and fine motor) was assessed using Gesell Developmental Schedules for each child at 1 year of age. The associations between PFAS and DQs were evaluated using multivariable linear regressions. TH-mediated effects of PFAS on DQs were calculated by mediation analyses., Results: Among our study population, PFAS exposures were common and associated with DQ decrement in infants. For each 10-fold increase in PFBS concentrations, gross motor and adaptive DQ decreased by 8.56 (95%CI: -15.15, -1.97) and 5.87 (95%CI: -8.07, -3.67) points, respectively. TSH mediated 12.90% of the association of PFBS with gross motor DQ and FT4 explained 19.63% of the association of PFBS with adaptive DQ. The negative association was also found between PFHxS exposure and gross motor DQ (β = 8.14, 95%CI: -15.39, -0.98)., Conclusions: PFBS and PFHxS were negatively associated with early neurodevelopment, especially consistent in gross motor domain. The associations were partly explained by TSH and FT4., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Pregnant women are ubiquitously exposed to per- and polyfluoroalkyl substances (PFAS). Prenatal exposure to PFAS has been associated with lower birth weight but also with excess adiposity and higher weight in childhood. These mixed findings warrant investigation of the relationship between PFAS and dynamic offspring growth., Objectives: To investigate the association between prenatal PFAS exposure and early-life growth trajectories during the first 2 y., Methods: Pregnant women ( n = 3,426 ) were recruited from 2013 to 2016 from the Shanghai Birth Cohort (SBC) Study, and their children were followed up from birth to 2 y of age. Seven PFAS congeners were quantified in pregnant women's serum during the first trimester. Our study population was restricted to 1,350 children who had five repeated measurements for at least one anthropometric measure. Four anthropometric measures, including weight, length/height, weight-for-length, and head circumference, were evaluated at birth, 42 d, 6 months, 12 months, and 24 months, and standardized into z -scores using the World Health Organization reference. Trajectories of each measure were classified into five groups using group-based trajectory modeling. Multinomial logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for trajectory groups according to log 2 -transformed PFAS concentrations, and the moderate-stable group was selected as the reference group for all measures., Results: Higher prenatal exposure to PFAS was associated with elevated odds for the low-rising weight-for-age z -score (WAZ) trajectory, and the high-rising length-for-age z -score (LAZ) trajectory. Meanwhile, PFAS levels were associated with decreased odds for the low-rising and high-rising weight-for-length z -score (WLZ) trajectories. In addition, the associations of PFAS with growth trajectory groups differed by sex, where males had greater odds for the low-rising and low-stable WAZ trajectories and for the high-stable and low-rising WLZ trajectories. In contrast, inverse associations were consistently observed with trajectories of the high-stable, low-stable, and low-rising head-circumference-for-age z -score (HCZ) in relation to most individual PFAS congeners. PFAS mixtures analysis further confirmed the above findings., Discussion: Trajectory analysis approach provided insight into the complex associations between PFAS exposure and offspring growth. Future studies are warranted to confirm the present findings with trajectory modeling strategies and understand the clinical significance of these trajectory groups. https://doi.org/10.1289/EHP9875.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-632). The authors have no conflicts of interest to declare.

Background: Perfluoroalkyl substances (PFASs) are persistent and bio-accumulative compounds that have been recognized as important immune hazards by animal studies. However, epidemiological studies regarding the impact on infant infections were inconsistent., Objectives: We investigated the associations between prenatal exposure to PFASs and acute infectious diseases including common cold, bronchitis/pneumonia, and diarrhea in early childhood., Methods: Participating 235 mother-infant pairs were recruited from the Laizhou Wan (Bay) birth cohort (LWBC), a prospective study in Shandong, China between September 2010 and 2013. Ten selected PFASs congeners including PFOA, PFOS, PFNA, PFDA, PFUA, PFDoA, PFHxS, PFBS, PFHpA, and PFOSA were measured from maternal serum by HPLC-MS/MS. Detailed information on parent-reported frequency of acute infectious diseases was collected from questionnaires at 1-year follow-up, which was confirmed by the medical records. Logistic and Poisson regression models were used on binary health outcomes (yes/no) and the number of episodes of outcomes, which were reported as odds ratio (OR) and incidence rate-ratio (IRR), respectively., Results: The risk of diarrhea increased by 4.99 (95% CI = 1.86, 13.39) per log-unit increase in PFOA. The frequencies of diarrhea increased by 97%-116% for each 10-fold increase in PFOA, PFNA, and PFDA. Moreover, when stratified by exclusively breastfeeding duration (at least 4 months or not), the adverse effects of PFASs exposures on diarrhea were more pronounced among the breastfed infants. There were no associations between prenatal PFASs exposure and common cold or bronchitis/pneumonia., Conclusions: Exposure to PFASs was associated with increased risks of diarrhea during the first year of life, and these effects were stronger among the breastfed infants. Due to the small sample size, our results should be interpreted with caution and additional studies on larger populations are needed to confirm our findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Although maternal perfluoroalkyl and polyfluroalkyl substances (PFASs) were associated with adverse birth outcomes, much less is known about their impact on infant growth during early infancy., Objectives: We investigated the association between maternal PFASs exposure and infant growth during the first 12 months of life., Methods: Participating 2395 pregnancies were recruited from Shanghai Birth Cohort between 2013 and 2016. Ten PFASs were quantified from maternal plasma collected during early pregnancy (median, 15 gestational weeks). We measured infant length, weight, and head circumference at birth, 42 days, 6 months, and 12 months. Linear mixed regression model was used to estimate the associations between PFAS concentrations and repeated measurements of infant growth. Effect modification by infant sex was estimated., Results: Elevated perfluoroheptanoic acid (PFHpA) concentration was negatively associated with infant length-for-age Z score (LAZ) (β = -0.06, 95% confidence interval (CI): -0.11, -0.01) during the first year. Adverse associations were also observed for perfluorobutane sulfonate (PFBS) and weight-for-length Z score (WFL) (β = -0.02, 95% CI: -0.04, -0.00) and BMI-for-age Z score (BAZ) (β = -0.02, 95% CI: -0.04, -0.00). However, perfluorododecanoic acid (PFDoA) was positively associated with WFL (β = 0.03, 95% CI: 0.00, 0.06) and BAZ (β = 0.03, 95% CI: 0.00, 0.06). The adverse association of PFHpA and LAZ was more pronounced among males (β = -0.06; 95% CI: -0.11, -0.00) than females (β = 0.06; 95% CI: 0.01, 0.12)., Conclusions: In our study, negative associations were found for maternal PFHpA exposure and infant LAZ, PFBS and WFL and BAZ. Meanwhile, maternal PFDoA exposure was positively related with WFL and BAZ. The adverse association of maternal PFHpA exposure and infant LAZ was more pronounced among males. The results should be interpreted with caution, further prospective cohort studies with longitudinal and detailed measures are warranted to confirm these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)