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Phthalic acid esters (PAEs), a class of typical endocrine disruptors, have received considerable attention due to their widespread applications and adverse effects on biological health. In this study, 30 water samples, along the mainstream of the Yangtze River (YR), were collected from Chongqing (upper stream) to Shanghai (estuary) from May to June in 2019. The total concentrations of 16 targeted PAEs ranged from 0.437 to 20.5 μg/L, with an average of 1.93 μg/L, where dibutyl phthalate (DBP, 0.222-20.2 μg/L), bis (2-ethylhexyl) phthalate (DEHP, 0.254-7.03 μg/L), and diisobutyl phthalate (DIBP, 0.0645-0.621 μg/L) were the most abundant PAEs. According to the pollution level in the YR to assess the ecological risk posed by PAEs, the results showed medium risk level of PAEs in the YR, among which DBP and DEHP posed a high ecological risk to aquatic organisms. The optimal solution for DBP and DEHP is found in ten fitting curves. The PNEC SSD of them is 2.50 μg/L and 0.34 μg/L, respectively., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bone metastasis is one of the main complications of lung cancer and most important factors that lead to poor life quality and low survival rate in lung cancer patients. However, the regulatory mechanisms underlying lung cancer bone metastasis are still poor understood. Here, we report that microRNA-182 (miR-182) plays a critical role in regulating osteoclastic metastasis of lung cancer cells. We found that miR-182 was significantly upregulated in both bone-metastatic human non-small cell lung cancer (NSCLC) cell line and tumor specimens. We further demonstrated that miR-182 markedly enhanced the ability of NSCLC cells for osteolytic bone metastasis in nude mice. Mechanistically, miR-182 promotes NSCLC cells to secrete Interleukin-8 (IL-8) and in turn facilitates osteoclastogenesis via activating STAT3 signaling in osteoclast progenitor cells. Importantly, systemically delivered IL-8 neutralizing antibody inhibits NSCLC bone metastasis in nude mice. Collectively, our findings identify the miR-182/IL-8/STAT3 axis as a key regulatory pathway in controlling lung cancer cell-induced osteolytic bone metastasis and suggest a promising therapeutic strategy that targets this regulatory axis to interrupt lung cancer bone metastasis., (© 2023. The Author(s).)

Background: The application of vedolizumab (VDZ) subcutaneous (SC) formulation has brought more convenience and hope to patients with moderate-to-severe inflammatory bowel diseases (IBDs) in the coronavirus disease 2019 context., Objective: This study aimed to systematically evaluate all previous studies that used VDZ SC formulation for maintenance therapy in patients with IBD., Design: Systematic review and meta-analysis., Data Sources and Methods: The search was conducted using the subject and free terms related to 'Vedolizumab', 'Subcutaneous', and 'IBD', in Embase, PubMed, Web of Science, Cochrane, and at ClinicalTrials.gov databases between 2008 and 2022. The methodological quality of randomized controlled trials (RCTs) and cohort studies was assessed using the Cochrane Handbook of Systematic Reviews and the Newcastle-Ottawa Scale, respectively. The endpoints included efficacy, safety, and immunogenicity., Results: A total of 60 studies and 2 completed clinical registry trials were retrieved, of which 3 RCTs with high methodological quality, and 3 cohort studies with large heterogeneity were included in the meta-analysis. In the RCT study design, patients with ulcerative colitis (UC) under different conditions after treated with VDZ SC were significantly distinct than those for placebo (PBO) in clinical remission, endoscopic remission, and biochemical remission. In Crohn's disease (CD), the aforementioned parameters were slightly higher than those for PBO, but there was not statistically significant in endoscopic remission and the efficacy of anti-tumor necrosis factor-naive patients. The clinical remission, endoscopic remission, and biochemical remission in patients with UC after VDZ SC treatment were similar to those after intravenous (IV) treatment. The risk ratios in patients experiencing adverse events (AEs) and serious AEs after VDZ SC and PBO treatments were 86% and 89% in UC, and 96% and 80% in CD, respectively. Compared with IV, safety was not statistically different. The risk of developing anti-VDZ antibody after VDZ SC treatment was only 20% of that after PBO in patients with UC, but it was 9.38 times in CD., Conclusion: VDZ SC treatment maintained the clinical efficacy of IV induction in patients with IBD without increasing the safety risk, and the efficacy was more pronounced in patients with UC. Immunogenicity might be a potential factor for the decrease in efficacy rate in patients with IBD., Registration: INPLASY 2022120115., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Purpose: Acupuncture has been widely used in the treatment of knee osteoarthritis (KOA), but the selection of acupoints is indeterminate and lacks biological basis. The skin temperature of acupoints can reflect the state of local tissue and may be a potential factor for guiding acupoint selection. This study aims to compare the skin temperature of acupoints between KOA patients and the healthy population., Study Design and Methods: This is a protocol for a cross-sectional case-control study with 170 KOA patients and 170 age- and gender-matched healthy individuals. Diagnosed patients aged 45 to 70 will be recruited in the KOA group. Participants in the healthy group will be matched with the KOA group based on mean age and gender distribution. Skin temperature of 11 acupoints (ST35, EX-LE5, GB33, GB34, EX-LE2, ST34, ST36, GB39, BL40, SP9, SP10) will be extracted from infrared thermography (IRT) images of the lower limbs. Other measurements will include demographic data (gender, age, ethnicity, education, height, weight, BMI) and disease-related data (numerical rating scale, pain sites, duration of pain, pain descriptors, pain activities)., Discussion: The results of this study will provide biological evidence for acupoint selection. This study is a precondition for follow-up studies, in which the value of optimized acupoint selection will be verified., Trial Registration: ChiCTR2200058867., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study explored the effectiveness and safety of low-volume polyethylene glycol electrolyte lavage solution (PEG-ELS) combined with ascorbic acid tablets (PEG-ELS/Asc) in bowel preparation for a colonoscopy., Methods: A total of 240 hospitalized patients who underwent a colonoscopy in Wenzhou People's Hospital, Wenzhou Third Clinical College of Wenzhou Medical University from July 2020 to June 2022 were randomly divided into two groups, with 120 patients each. All of the participants were given a low-residue or residue-free diet one day before the examination and fasted after dinner (completed before 18:00) the day before the examination. The 2-L PEG-ELS/Asc group took 2-L PEG-ELS plus 10 g ascorbic acid tablets once orally, while the 3-L PEG-ELS group took 3-L PEG orally on several occasions. The primary endpoint was the achievement of preparation adequacy and an overall colon cleansing score of ≥6, both assessed by blinded investigators using the Boston Bowel Preparation Scale (BBPS). The bowel cleansing effect, polyp detection rate, adverse reaction rate, oral drug tolerance rate, renal function, and electrolyte level changes were also compared between the two patient groups., Results: There were no significant differences in the success rate of bowel preparation, the detection rate of polyps, or the adverse reaction rate between the two groups ( P > 0.05). The tolerance rate of bowel preparation in the 2-L PEG-ELS/Asc group was significantly higher than that in the 3-L PEG-ELS group (93.3% vs. 80.23%) ( P < 0.05). The levels of creatinine, serum potassium, serum sodium, and serum chlorine of the two groups before and after bowel preparation were within the normal range. In addition, the intestinal cleaning effect of the two preparation schemes for the hospitalized patients with diabetes and constipation is worse than that of those without these conditions ( P < 0.05)., Conclusion: The effectiveness and safety of using 2-L PEG-ELS/Asc in bowel preparation for a colonoscopy in hospitalized patients were not inferior to using 3-L PEG-ELS. For patients with diabetes and constipation, the cleansing effect of the two bowel preparation options was not very satisfactory, and further clinical research is needed in this regard., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zheng, Sun, Lin, Pan and Lin.)

Terrestrial plants emit volatiles into the atmosphere to attract both pollinators and the enemies of herbivores, for defense. Phalaenopsis bellina is a scented orchid species in which the main scent components are monoterpenes, including linalool and geraniol, and their derivatives. Here, we investigated whether ABC transporters are involved in floral scent emission. We carried out whole-genome identification of ABC transporter-related genes using four floral transcriptomics libraries of P. bellina. We identified 86 ABC subfamily G genes related to terpenoid transport. After comparing the gene expression patterns of P. bellina with that of Phalaenopsis aphrodite subsp. formosana, a scentless species, followed by gene-to-gene correlation analysis, PbABCG1 and PbABCG2 were selected. The temporal expression of both PbABCG1 and PbABCG2 was highly correlated with that of the key enzyme PbGDPS and the major transcription factor PbbHLH4 in monoterpene biosynthesis, with optimal expression on day 5 post-anthesis. Spatial gene expression analysis showed that PbABCG1 was highly expressed in sepals, whereas PbABCG2 was expressed in the lip. Subcellular localization with a GFP fusion protein revealed that both PbABCG1 and PbABCG2 are cytoplasmic membrane proteins. Co-downregulation of PbABCG1 and PbABCG2 using both double-strand RNA interference and tobacco rattle virus-based gene silencing led to a significant decrease in monoterpene emission, accompanied by an increase in the internal monoterpene pools. Furthermore, ectopic expression of PbABCG1 and PbABCG2 in an ABC16 - mutant yeast strain rescued its tolerance to geraniol. Altogether, our results indicate that PbABCG1 and PbABCG2 play substantial roles in monoterpene transport/emission in P. bellina floral scent., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

The implementation of short-term traffic restriction policies (TRPs) during major events positively influences the traffic emission reduction. However, few studies explore the impact of diesel vehicle emissions on air quality during short-term TRP. In particular, the intertwined influences of short-term TRP and Spring Festival remains unclear. Based on Beijing 2022 Olympic Games, this study analyzed the spatiotemporal changes in urban air quality and diesel vehicle emission during short-term TRP. The results showed that the TRPs and Spring Festival contributed equally to the improvement of air quality and reduction of diesel vehicle emissions. The "interruption-recovery" pattern of short-term TRPs is characterized by a longer duration and a slower decline/recovery rate. Additionally, the individual contribution rate of diesel vehicle emissions to urban air pollutants was 15-20 % higher than that of meteorological factors during short-term TRPs., 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 Elsevier B.V. All rights reserved.)

The stem cell factor (SCF) binds to c-Kit in endothelial cells, thus activating downstream signaling and angiogenesis. Herein, we examined the role of G protein subunit alpha inhibitory (Gαi) proteins in this process. In MEFs and HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting c-Kit endocytosis, and binding of key adaptor proteins, subsequently transducing downstream signaling. SCF-induced Akt-mTOR and Erk activation was robustly attenuated by Gαi1/3 silencing or knockout (KO), or due to dominant negative mutations but was strengthened substantially following ectopic overexpression of Gαi1/3. SCF-induced HUVEC proliferation, migration, and capillary tube formation were suppressed after Gαi1/3 silencing or KO, or due to dominant negative mutations. In vivo , endothelial knockdown of Gαi1/3 by intravitreous injection of endothelial-specific shRNA adeno-associated virus (AAV) potently reduced SCF-induced signaling and retinal angiogenesis in mice. Moreover, mRNA and protein expressions of SCF increased significantly in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. SCF silencing, through intravitreous injection of SCF shRNA AAV, inhibited pathological retinal angiogenesis and degeneration of retinal ganglion cells in DR mice. Finally, the expression of SCF and c-Kit increased in proliferative retinal tissues of human patients with proliferative DR. Taken together, Gαi1/3 mediate SCF/c-Kit-activated signaling and angiogenesis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Exploring the effects of one-time amendment treatments on cadmium (Cd)-contaminated farmland soils is beneficial for providing a theoretical basis to effectively prevent Cd pollution in farmland soils and ensure the safe production of crops. Five amendments, including straw biochar, fly ash, sepiolite, white marble powder, and shale (particle size <0.2 mm, application rate 2.25 kg·m -2 ), were applied to the Cd-contaminated farmland soils. The soil nutrients, pH, soil available Cd, and Cd chemical forms in the soils and grain Cd concentration in the planted crops were determined to investigate the effects and persistence of one-time applications of the five amendments. The results showed that:① the application of the five amendments had little effect on soil nutrient content, but all of them could increase soil pH. Amendment treatments improved the transfer of Cd from the acid extraction fraction to residue fraction and further reduced the Cd availability in the soil. The decreasing amplitudes of straw biochar and white marble powder soil conditioner were 20.42%-22.53%, which was higher than those in the other treatments. ② The grain Cd concentrations in rice and wheat were significantly decreased under the amendment treatments with the decreasing amplitudes of 19.88%-48.77% and 5.06%-24.00%, respectively. The Cd concentrations in rice grains under the treatments of straw biochar, fly ash, and white marble powder soil conditioner were 0.195, 0.196, and 0.223 mg·kg -1 , respectively, which were lower than those under the other treatments and were close to or approached the National Standard of Food Safety(GB 2762-2017)(0.2 mg·kg -1 ). ③ The immobilization effects on Cd in farmland soils were decreasing with time under one-time application of the amendments. The available Cd concentrations in the soil and Cd concentrations in crop grains were still lower than those in the control after three rounds of rice-wheat rotation. The straw biochar and white marble powder soil conditioner had a good and long-term effect on reducing Cd availability in soils and Cd concentrations in crop grain, making them ideal materials for safe production in Cd-contaminated soils.

Objective: Long noncoding RNA WDFY3-AS2 has been shown to play dual roles in the modulation of cancer progression. This study aimed at clarifying the biological role of WDFY3-AS2 as well as the association between WDFY3-AS2 expression, β-catenin expression, and OSCC immunity in oral squamous cell carcinoma (OSCC)., Design: Bioinformatics analyses, CCK8, EdU, wound healing, transwell, RT-qPCR, western blot, immunofluorescence, in situ hybridization, and immunohistochemistry assays were adopted for exploring the role of WDFY3-AS2 in OSCC., Results: Bioinformatics analyses showed that WDFY3-AS2 conferred a poor prognosis for OSCC patients. Further analyses identified WDFY3-AS2 as an independent prognostic indicator for OSCC. Moreover, silencing WDFY3-AS2 inhibits OSCC cell proliferation, migration and invasion. Gene set enrichment analysis indicated that WDFY3-AS2 participated in the regulation of Wnt signaling. In addition, WDFY3-AS2 expression was positively associated with β-catenin mRNA levels, the key component of Wnt signaling. Interestingly, WDFY3-AS2 knockdown inhibited β-catenin expression and nuclear translocation, thus suppressing OSCC progression through Wnt signaling. Furthermore, WDFY3-AS2 expression correlated with an immunosuppressive phenotype in the tumor immune microenvironment. In situ hybridization and immunohistochemistry verified that WDFY3-AS2 was positively associated with total and nuclear β-catenin protein levels and negatively associated with CD4 expression., Conclusions: This study demonstrates that the immunity-associated WDFY3-AS2 augments OSCC proliferation and metastasis through Wnt/β-catenin signaling and may serve as a novel treatment target and a new prognostic factor for OSCC., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Enterohemorrhagic Escherichia coli O157:H7 is an important foodborne pathogen that forms biofilms. In this study, three quorum-sensing (QS) inhibitors (M414-3326, 3254-3286, and L413-0180) were obtained through virtual screening, and their in vitro antibiofilm activities were validated. Briefly, the three-dimensional structure model of LuxS was constructed and characterized using the SWISS-MODEL. High-affinity inhibitors were screened from the ChemDiv database (1,535,478 compounds) using LuxS as a ligand. Five compounds (L449-1159, L368-0079, M414-3326, 3254-3286, and L413-0180) with a good inhibitory effect (50% inhibitory concentration <10 μM) on type II QS signal molecule autoinducer-2 (AI-2) were obtained using a AI-2 bioluminescence assay. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties predicated that the five compounds had high intestinal absorption levels (high) and plasma protein binding (absorbent strong) and did not inhibit the metabolism of CYP2D6 metabolic enzymes. In addition, molecular dynamics simulation showed that compounds L449-1159 and L368-0079 could not stably bind with LuxS. Thus, these compounds were excluded. Furthermore, surface plasmon resonance results showed that the three compounds could specifically bind to LuxS. IN addition, the three compounds could effectively inhibit the biofilm formation without affecting the growth and metabolism of the bacteria. Finally, the reverse transcription-quantitative PCR results showed that the three compounds downregulated the expression of the LuxS gene. Overall, these results revealed that the three compounds obtained through virtual screening could inhibit biofilm formation of E. coli O157:H7 and are potential LuxS inhibitors that can be used to treat E. coli O157:H7 infections. IMPORTANCE E. coli O157:H7 is a foodborne pathogen of public health importance. Quorum sensing (QS) is a form of bacterial communication that can regulate various group behaviors, including biofilm formation. Here, we identified three QS AI-2 inhibitors (M414-3326, 3254-3286, and L413-0180) that can stably and specifically bind to LuxS protein. The three QS AI-2 inhibitors inhibited biofilm formation without affecting the growth and metabolic activity of E. coli O157:H7. The three QS AI-2 inhibitors are promising agents for treating E. coli O157:H7 infections. Further studies to identify the mechanism of the three QS AI-2 inhibitors are needed to develop new drugs to overcome antibiotic resistance.

Background: Ulcer area is a critical parameter in diabetic foot ulcer assessment but existing methods have deficiencies for routine measurement., Aim: We hypothesized that the Image J-based Computer Analysis method has a high level of agreement with the commonly used Maximum Length and Width and the Transparent Dressing-based Square Grid methods and aimed to test the consistency and verify the feasibility of the Image J-based Computer Analysis method in the routine assessment of ulcers., Methods: Outpatient attendees with diabetic foot ulcers at the Department of Endocrinology of Sun Yat-sen Memorial Hospital were enrolled between October 2020 and October 2021. The three methods sequentially assessed the area of 65 included ulcers. Results were analysed using one-way analysis of variance and Bland-Altman plots to perform consistency analysis., Results: The mean ± standard deviation ulcer area measured using the three methods were 14.79 ± 5.39, 14.35 ± 5.26, and 14.30 ± 5.26 cm 2 , respectively. The measurement differences among the three groups or between any two were not statistically significant. Bland-Altman plots showed good consistency between the Image J-based Computer Analysis and the other two methods., Conclusion: The Image J-based Computer Analysis method can be interchanged with the other methods to assess ulcer areas. It is freely accessible, accurate and home-operable, thus worth consideration by nurses for routine ulcer area assessment., (© 2022 John Wiley & Sons Australia, Ltd.)

Amphibians are facing population declines and extinctions, and protecting and supplementing refuges can help species survive. However, the microhabitat requirements of most species are unknown, and artificial shelters or burrows have not been well tested for amphibians. Some amphibians exhibit complex behaviour during the transition from post-reproductive dormancy to activity. However, little is known about the ecology, post-reproductive dormancy, and terrestrial activity of amphibians. Here, habitat site selection in experimental enclosures and the effects of shelters (stones, soil) and shade (with and without shade netting) on the activity, exposed body percentage, burrow depth, body-soil contact percentage, and survival of Rana dybowskii were investigated during post-reproductive dormancy and post-dormant activity. The results showed that R. dybowskii live individually under leaves, soil, stones or tree roots. Furthermore, although the dormant sites of frogs are significantly different, the distribution of male and female frogs in these sites is similar. Shading and shelter significantly affected the exposed body percentage, burrow depth and body-soil contact percentage of frogs compared with soil. In the stone group, soil and stone form the frog's refuge/burrow, whereas in the soil group, the refuge/burrow is composed entirely of soil. Even though the soil group has a deeper burrow and a larger area of soil contact with the body, it still has a higher exposure rate than the stone group. Frog activity frequency was affected by shelter and shade; the interaction of shelter and time and the interaction of shading and time were significant. The soil group had a higher activity frequency than the stone group, and the no-shade group had a higher activity frequency than the shade group. Shelter and shading differences do not significantly affect frog survival; however, the death rate during post-reproductive dormancy is lower than that during the active period., (© 2023. The Author(s).)

The aquatic environment, linked to the sustainable development of human existence and ecological environment, is influenced comprehensively by anthropogenic and natural activities. In light of the continuously low concentration of dissolved oxygen (DO) in surface water in plain river networks and the phenomenon of delay in the improvement of surface water quality, this research aims to introduce a method that may be utilized in identifying the critical driving forces of DO in surface water and their lagging characteristics, which will contribute to the assessment and adjustment of water quality drivers and/or policies. The research analyzes a typical small watershed in a river network region of the Yangtze River Delta plain as the study area, collecting 35-year (1986-2020) data on several water quality parameters, decades of anthropogenic activities, and two natural factors. The time series methods of vector autoregressive model, Granger causality tests, forecast error variance decompositions, and impulse response functions (hereinafter referred to as VAR+), which are rarely applied in related research, were employed in this study and proved helpful for screening out pivotal drivers and capturing the lagging responses of DO level to driving forces at each lagged time. Results show that there exists a fluctuating drop in DO level in surface water from 1986 to 2008 and a steady climb from 2008 to 2020, with the lowest DO level being present in 2008. The impulsive perturbations of phosphate fertilizer consumption (PFC), motor vessel number, and precipitation minimally increase DO concentration, while the impulsive perturbation of gross domestic product (GDP) causes the sharpest drop in DO level. With these perturbations, the driving force of PFC persists for approximately seven years, and the driving forces of water temperature, permanent population, and GDP persist for only five years. Future research could be conducted with spatial hysteresis, selection of lag order and variable quantity within the model, as well as intermediate variables between drivers and DO level for exploring driving pathways and mechanisms., 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 Elsevier Ltd. All rights reserved.)

The objective of this study is to observe the effect of high selenium on the antioxidant and immune functions of growing goats based on transcriptome sequencing. Eighteen goats were randomly divided into three groups: (1) the control (CON) group was fed a basal diet, and (2) the treatment 1 group (LS) and treatment 2 group (HS) were fed a basal diet with 2.4 and 4.8 mg/kg selenium-yeast (SY), respectively. The results indicate that HS treatment significantly (p < 0.05) increased the apparent digestibility of either extract and significantly increased (p < 0.05) total antioxidant capacity, whereas it significantly (p < 0.05) decreased plasma aspartate aminotransferase and malondialdehyde relative to the control group. The LS treatment had significantly (p < 0.05) increased glutathione S-transferase and catalase compared to CON. A total of 532 differentially expressed genes (DEGs) between the CON and HS were obtained using transcriptome sequencing. Kyoto Encyclopedia of Genes and Genomes analysis identified upregulated (p < 0.05) DEGs mainly related to vascular smooth muscle contraction, alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, the VEGF signalling pathway, and proteoglycans in cancer; downregulated (p < 0.05) DEGs mainly related to the NOD-like receptor signalling pathway, influenza A, cytokine-cytokine receptor interaction, haematopoietic cell lineage, and African trypanosomiasis. Ontology analyses of the top genes show that the identified DEGs are mainly involved in the regulation of granulocyte macrophage colony-stimulating factor production for biological processes, the external side of the plasma membrane for cellular components, and carbohydrate derivative binding for molecular functions. Seven genes are considered potential candidate genes for regulating antioxidant activity, including selenoprotein W, 1, glutathione peroxidase 1, glutathione S-transferase A1, tumour necrosis factor, tumour necrosis factor superfamily member 10, tumour necrosis factor superfamily member 8, and tumour necrosis factor superfamily member 13b. The experimental observations indicate that dietary supplementation with 4.8 mg/kg SY can enhance antioxidant and immune functions by improving muscle immunity, reducing the concentrations of inflammatory molecules, and modulating antioxidant and inflammatory signalling pathways in growing goats.

With the improvement of laparoscopic surgery, the feasibility and safety of laparoscopic hepatectomy have been affirmed, but intraoperative hepatic venous system hemorrhage and carbon dioxide gas embolism are the difficulties in laparoscopic hepatectomy. The incidence of preoperative hemorrhage and carbon dioxide gas embolism could be reduced through preoperative imaging evaluation, reasonable liver blood flow blocking method, appropriate liver-breaking device, controlled low-center venous pressure technology, and fine-precision precision operation. In the case of blood vessel rupture bleeding in the liver vein system, after controlling and reducing bleeding, confirm the type and severity of vascular damage in the liver and venous system, take appropriate measures to stop the bleeding quickly and effectively, and, if necessary, transfer the abdominal treatment in time. In addition, to strengthen the understanding, prevention and emergency treatment of severe CO2 gas embolism in laparoscopic hepatectomy is also the key to the success of surgery. This study aims to investigate the methods to deal with hepatic venous system hemorrhage and carbon dioxide gas embolization based on author's institutional experience and relevant literature. We retrospectively analyzed the data of 60 patients who received laparoscopic anatomical hepatectomy of hepatic vein approach for HCC. For patients with intraoperative complications, corresponding treatments were given to cope with different complications. After the operation, combined with clinical experience and literature, we summarized and discussed the good treatment methods in the face of such situations so that minimize the harm to patients as much as possible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qu, Wu, Feng, Shi, Chen, Sun, Duan, Chen and He.)

Objective: MED subunits have been reported to be associated with various types of tumors, however, the potential role of MED7 in hepatocellular carcinoma (HCC) was still unclear. The aim of the study was to explore the role of MED7 in HCC., Methods: In this study, MED7 mRNA expression levels between HCC and adjacent normal tissues were first analyzed by several public datasets. Then we utilized a tissue microarray (TMA) to investigate the clinical role of MED7 in HCC by immunohistochemistry (IHC). Meanwhile, the potential mechanisms of MED7 based on gene-gene correlation analyses were also explored., Results: High mRNA level of MED7 correlated with advanced stage and worse grade of differentiation. IHC results showed that MED7 protein level was upregulated in HCC and associated with Edmondson grade and Microvascular invasion in 330 cases of HCC. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that MED7 co-expressed genes participate primarily in ribonucleoprotein complex biogenesis, protein targeting, mRNA processing and nucleoside triphosphate metabolic process et cetera. Further analysis also revealed that MED7 mRNA level has significant correlation with immune cells infiltration levels., Conclusion: MED7 was upregulated in HCC and correlated with progression of HCC. Meanwhile, MED7 may promote HCC through participating in multiple gene networks to influence tumorigenesis as well as immune response in HCC microenvironment.

Snf5 (sucrose nonfermenting) is a core component of the SWI/SNF complexes and regulates diverse cellular processes in model eukaryotes. In plant pathogenic fungi, its biological function and underlying mechanisms remain unexplored. In this study, we investigated the biological roles of MoSnf5 in plant infection and fungal development in the rice blast pathogen Magnaporthe oryzae. The gene deletion mutants of MoSNF5 exhibited slower vegetative hyphal growth, severe defects in conidiogenesis, and impaired virulence and galactose utilization capacities. Domain dissection assays showed that the Snf5 domain and the N- and C-termini of MoSnf5 were all required for its full functions. Co-immunoprecipitation and yeast two-hybrid assays showed that MoSnf5 physically interacts with four proteins, including a transcription initiation factor MoTaf14. Interestingly, the ∆MoTaf14 mutants showed similar phenotypes as the ∆Mosnf5 mutants on fungal virulence and development. Moreover, assays on GFP-MoAtg8 expression and localization showed that both the ∆Mosnf5 and ∆MoTaf14 mutants were defective in autophagy. Taken together, MoSnf5 regulates fungal virulence, growth, and conidiation, possibly through regulating galactose utilization and autophagy in M. oryzae .

Objective: To analyze and compare the effect of the combination of energy and density parameters of CO 2 dot matrix laser in the hyperplastic stage of pediatric burn. Materials and Methods: A total of 160 pediatric patients with hypertrophic scar after limb burn from 2017 to 2020 were randomly divided into four parameter groups (n = 40). The patients were treated with ablative fraction carbon dioxide laser, once every 10 weeks. During the interval of laser treatment, Compound Heparin Sodium and Allantoin Gel (Contractubex) was applied externally, tid, and elastic cover or elastic bandage is attached to the affected limb. Scoring based on the Vancouver Scar Scale is performed before each laser treatment, The score before the first treatment was the initial score, which was scored by two people separately, and the average score was calculated. Subsequently, the patients were treated four times and scored. The differences between each treatment and the first score of each parameter group were compared. Under the same energy and different treatment density, the scores after each treatment were compared. Under the same density and different energy, the scores after each treatment were compared. The bleeding and pigmentation of each parameter group were compared. Results: The increase of density can show the therapeutic effect earlier than the increase of energy, and 25mj energy and 10% density have better intervention effect. With the course of disease and the progress of treatment, the correlation between intervention effect and parameters tends to weaken. Comparing the number of cases with different scores between each treatment and the first time, the score in the 5% density group was lower than that in the 10% density group, but there was no significant difference between the 25mj and 17.5mj energy levels in the same density group. The intervention effect of the increase of density on scar was better than that of energy, and the increase of energy and density could aggravate the pain. Conclusion: In pediatric burn hypertrophic scars treated by CO 2 dot matrix laser in exfoliation mode, the intervention effect of increasing density is better than that of energy. When setting laser treatment parameters, we should give priority to increasing density and adjust energy according to the effect of treatment and the condition of pain, bleeding and color precipitation. In this study, the best combination of parameters is 17.5mj/10%.

Purpose: The present study was performed to detect the prevalence of myopia among primary-school students in Xi'an, north-western of China., Methods: The present study was a school-based study with students aged from 6 to 13 years old. All the individuals underwent ophthalmological examination and spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Myopia was defined as a SE of ≤ -0.5 diopters (D), and further divided into three stratified groups based on SE: low myopia (≤ -0.5 to >-3.0 D), moderate myopia (≤ -3.0 to >-6.0 D), and high myopia (≤ -6.0 D). Relative risk factors, including age, sex, grade and ethnicity were investigated using questionnaire., Results: A total of 4,680 individuals were eligible for this survey and 4,654 (99.4% participation rate) were finally included (51.2% boys). The mean age of participants was 8.756 ± 1.727 years. The whole city-level prevalence of total myopia was 57.1% (95% CI: 55.7-58.6%). Additionally, the prevalence of low, moderate, and high myopia was 45.0% (95% CI: 43.5-46.4%), 11.1% (95% CI: 10.2-12.0%), and 1.0% (95% CI: 0.7-1.3%), respectively. Moreover, grade (education level) instead of age, sex and ethnicity was the most essential risk factor for prevalence of overall myopia (OR = 1.844, 95% CI: 1.605-2.119), and an increase of prevalence by 84.4% per grade was seen. Furthermore, similar associations of grade were significant with low myopia (OR = 1.613, 95% CI: 1.385-1.877) and moderate myopia (OR = 2.186, 95% CI: 1.693-2.823), meanwhile, prevalence of low myopia and moderate myopia demonstrated an increase of prevalence by 61.3 and 118.6% per grade, respectively. None of the factors included in the present study was significant risk factor for high myopia., Conclusions: The present study investigated a non-negligible high prevalence of myopia among primary-school students in Xi'an, north-western of China, and a gradual increasing in proportion with education level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ye, Yang, Zhang, Wang, Ren, Ge, Zhang, Zhang, Liu, Zhang, Tong, Lu, Lv, Zhou and Pei.)

A new antibacterial strategy based on inhibiting bacterial quorum sensing (QS) has emerged as a promising method of attenuating bacterial pathogenicity and preventing bacterial resistance to antibiotics. In this study, we screened Echinatin (Ech) with high-efficiency anti-QS from 13 flavonoids through the AI-2 bioluminescence assay. Additionally, crystal violet (CV) staining combined with confocal laser scanning microscopy (CLSM) was used to evaluate the effect of anti-biofilm against Escherichia coli (E. coli) . Further, the antibacterial synergistic effect of Ech and marketed antibiotics were measured by broth dilution and Alamar Blue Assay. It was found that Ech interfered with the phenotype of QS, including biofilm formation, exopolysaccharide ( EPS ) production, and motility, without affecting bacterial growth and metabolic activity. Moreover, qRT-PCR exhibited that Ech significantly reduced the expression of QS-regulated genes ( luxS , pfs , lsrB , lsrK , lsrR , flhC , flhD , fliC , csgD , and stx2 ). More important, Ech with currently marketed colistin antibiotics (including colistin B and colistin E) showed significantly synergistically increased antibacterial activity in overcoming antibiotic resistance of E. coli . In summary, these results suggested the potent anti-QS and novel antibacterial synergist candidate of Ech for treating E. coli infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bai, Shi, Wang, Wu, Bai, Li, Zhou and Zhang.)

Background: Cardiac fibrosis is a major structural change observed in the heart of patients with type 2 diabetes mellitus (T2DM), ultimately resulting in heart failure (HF). Suppression of inflammation is an effective therapeutic strategy for treating cardiac fibrosis and HF. Gentiopicroside (GPS), the primary component of Gentiana manshurica Kitagawa, possess potent anti-inflammatory activity. However, its cardioprotective role remains elusive., Purpose: We explored the potential cardioprotective role of GPS in T2DM rats and its underlying mechanisms., Methods: T2DM rats built by high-fat diet and streptozotocin were orally administered 25, 50, or 100 mg/kg GPS, daily for 8 weeks. The positive control drug was Metformin (200 mg/kg/day). Primary cardiac fibroblasts (CFs) were induced by high glucose (30 mM) and subsequently treated with GPS (100 μM). Cardiac function and pathological changes were analyzed using echocardiography and histological staining. Potential targets of GPS were predicted using Molecular docking. Real-time PCR as well as western blotting were applied to verify the expression of objective genes., Results: All three doses reduced fasting blood glucose levels, but only 50 and 100 mg/kg GPS improved cardiac function and alleviated inflammation and fibrosis in T2DM rats. GPS (100 mg/kg) exhibited a better effect, similar to that of metformin. Mechanistically, binding between GPS and the MH2 domain of Smad3 blocked high glucose-induced Smad3 phosphorylation, thus attenuating inflammation, oxidative stress, and activation in CFs., Conclusion: We, for the first time, demonstrated that GPS improved cardiac function in T2DM rats and elucidated the underlying mechanism through which GPS targeted Smad3 phosphorylation to suppress inflammation and activation in CFs, thereby revealing the potential application of GPS in HF therapy., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures., Methods: A retrospective cohort study was conducted to evaluate 70 consecutive patients [34 cases of robot-assisted percutaneous pedicle screw fixation (RAF) and 36 of conventional fluoroscopy-guided percutaneous pedicle screw fixation (FGF)]. Demographics, clinical characteristics, and radiological features were recorded. Pedicle screw length, diameter, and pedicle screw placement accuracy were assessed. The patients' sagittal kyphosis Cobb angles (KCA), anterior vertebral height ratios (VHA), and screw loosening rate were evaluated by radiographic data 1 year after surgery., Results: There was no significant difference in the mean computed tomography (CT) Hounsfield unit (HU) values, operation duration, or length of hospital stay between the groups. Compared with the FGF group, the RAF group had a lower fluoroscopy frequency [14 (12-18) vs. 21 (16-25), P < 0.001] and a higher "grade A + B" pedicle screw placement rate (96.5% vs. 89.4%, P < 0.05). The mean screw diameter was 6.04 ± 0.55 mm in the RAF group and 5.78 ± 0.50 mm in the FGF group (P < 0.001). The mean screw length was 50.45 ± 4.37 mm in the RAF group and 48.63 ± 3.86 mm in the FGF group (P < 0.001). The correction loss of the KCA and VHR of the RAF group was less than that of the FGT group at the 1-year follow-up [(3.8 ± 1.8° vs. 4.9 ± 4.2°) and (5.5 ± 4.9% vs. 6.4 ± 5.7%)], and screw loosening occurred in 2 out of 34 patients (5.9%) in the RAF group, and 6 out of 36 patients (16.7%) in the FGF group, but there were no significant differences (P > 0.05)., Conclusion: Compared with the fluoroscopy-guided technique, robotic-assisted spine surgery decreased radiation exposure and optimizes screw trajectories and dimensions intraoperatively. Although not statistically significant, the loosening rate of the RAF group was lower that of than the FGT group., (© 2022. The Author(s).)

Oncolytic viruses have found a good place in the treatment of cancer. Administering oncolytic viruses directly or by applying genetic changes can be effective in cancer treatment through the lysis of tumor cells and, in some cases, by inducing immune system responses. Moreover, oncolytic viruses induce antitumor immune responses via releasing tumor antigens in the tumor microenvironment (TME) and affect tumor cell growth and metabolism. Despite the success of virotherapy in cancer therapies, there are several challenges and limitations, such as immunosuppressive TME, lack of effective penetration into tumor tissue, low efficiency in hypoxia, antiviral immune responses, and off-targeting. Evidence suggests that oncolytic viruses combined with cancer immunotherapy-based methods such as immune checkpoint inhibitors and adoptive cell therapies can effectively overcome these challenges. This review summarizes the latest data on the use of oncolytic viruses for the treatment of cancer and the challenges of this method. Additionally, the effectiveness of mono, dual, and triple therapies using oncolytic viruses and other anticancer agents has been discussed based on the latest findings., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Global Challenges published by Wiley‐VCH GmbH.)

Background: Hemorrhagic fever with renal syndrome (HFRS) induced by Hantaan virus infection and heparin-induced thrombocytopenia (HIT) are associated with symptoms such as thrombocytopenia and thrombosis. However, related molecules, such as anti-platelet factor 4 (PF4)/heparin antibodies, in patients with HFRS have not been evaluated., Objectives: To test plasma levels of anti-PF4/heparin antibodies and study the possible role of these antibodies in HFRS pathogenesis., Methods: Indirect ELISA was used to determine plasma levels of anti-PF4/heparin antibodies in 75 patients with HFRS and 20 normal controls. The 4Ts (thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and other causes of thrombocytopenia) scoring system was used to determine the probability of HIT occurrence. A PF4-enhanced platelet activation assay was used to detect the pathological effects of anti-PF4/heparin antibodies. The laboratory/clinical features and viral load of all the patients were also assessed., Results: Of the 75 patients with HFRS enrolled in this study, 69 had thrombocytopenia. Platelet count was negatively correlated with Hantaan viral load. Moreover, the optical density (OD) values of plasma antibodies against PF4/heparin in normal controls were less than 0.65, 4 patients tested strongly positive for anti-PF4/heparin antibodies (OD values, 1.51-3.87), 21 patients were weakly positive (OD values, 0.66-0.74), and 50 patients were negative (OD values, 0.16-0.65). Moreover, all 4 patients who tested strongly positive for anti-PF4/heparin antibodies showed a low probability of HIT (4Ts score of 3 or less) and had negative results in the PF4-enhanced platelet activation assay., Conclusions: Hantaan virus infection produces nonpathogenic antibodies against PF4/heparin; however, the generation mechanism of these antibodies requires further study., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Repeated silica gel column chromatography, reversed-phase C&#95;(18) column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and semi-preparative medium pressure liquid chromatography were performed to separate and purify the chemical constituents of Hypericum lagarocladum. Spectroscopic methods such as mass spectrometry(MS) and nuclear magnetic resonance(NMR) combined with physicochemical properties were adopted in identifying the structure of the isolated compounds. Ten compounds were isolated from the ethyl acetate fraction of H. lagarocladum and identified as lagarxanthone A(1), 1,7-dihydroxyxanthone(2), 3,4,5-trihydroxyxanthone(3), 2,7-dihydroxy-1-methoxyxanthone(4), 1,3-dihydroxy-7-methoxyxanthone(5), 1,5-dihydroxy-8-methoxyxanthone(6), 3,4-dihydroxy-2-methoxyxanthone(7), 3,4-dihydroxy-5-methoxyxanthone(8), 2,3-dimethoxyxanthone(9), and 2,3,4-trimethoxyxanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from this plant for the first time. These ten compounds were tested for glucose uptake in L6 cells, and the results showed that all the compounds had no significant effect on glucose uptake.

Identifying how energy transfer proceeds from macroscales down to microscales in collisionless plasmas is at the forefront of astrophysics and space physics. It provides information on the evolution of involved plasma systems and the generation of high-energy particles in the universe. Here we report two cross-scale energy-transfer events observed by NASA's Magnetospheric Multiscale spacecraft in Earth's magnetosphere. In these events, hot ions simultaneously undergo interactions with macroscale (~[Formula: see text] km) ultra-low-frequency waves and microscale ([Formula: see text] km) electromagnetic-ion-cyclotron (EMIC) waves. The cross-scale interactions cause energy to directly transfer from macroscales to microscales, and finally dissipate at microscales via EMIC-wave-induced ion energization. The direct measurements of the energy transfer rate in the second event confirm the efficiency of this cross-scale transfer process, whose timescale is estimated to be roughly ten EMIC-wave periods about (1 min). Therefore, these observations experimentally demonstrate that simultaneous macroscale and microscale wave-ion interactions provide an efficient mechanism for cross-scale energy transfer and plasma energization in astrophysical and space plasmas., (© 2022. The Author(s).)

Glaucoma is characterized by the progressive loss of retinal ganglion cells (RGCs), although the pathogenic mechanism remains largely unknown. To study the mechanism and assess RGC degradation, mouse models are often used to simulate human glaucoma and specific markers are used to label and quantify RGCs. However, manually counting RGCs is time-consuming and prone to distortion due to subjective bias. Furthermore, semi-automated counting methods can produce significant differences due to different parameters, thereby failing objective evaluation. Here, to improve counting accuracy and efficiency, we developed an automated algorithm based on the improved YOLOv5 model, which uses five channels instead of one, with a squeeze-and-excitation block added. The complete number of RGCs in an intact mouse retina was obtained by dividing the retina into small overlapping areas and counting, and then merging the divided areas using a non-maximum suppression algorithm. The automated quantification results showed very strong correlation (mean Pearson correlation coefficient of 0.993) with manual counting. Importantly, the model achieved an average precision of 0.981. Furthermore, the graphics processing unit (GPU) calculation time for each retina was less than 1 min. The developed software has been uploaded online as a free and convenient tool for studies using mouse models of glaucoma, which should help elucidate disease pathogenesis and potential therapeutics.

Infectious diseases caused by bacteria and fungi are threatening human health all over the world. It is an increasingly serious problem that the efficacies of some antibacterial and antifungal agents have been weakened by the drug resistance of some bacteria and fungi, which makes a great need for new antibiotics. Sesquiterpenoids, with abundant structural skeleton types and a wide range of bioactivities, are considered as good candidates to be antibacterial and antifungal agents. In the past decades, many sesquiterpenoids were isolated from plants and fungi that exhibited good antibacterial and antifungal activities. In this review, the names, source, structures, antibacterial and antifungal degrees, and mechanisms of sesquiterpenoids with antibacterial and antifungal activity from 2012 to 2022 are summarized, and the structure-activity relationship of these sesquiterpenoids against bacteria and fungi is also discussed.

Neoneuromus ignobilis is an archaic holometabolous aquatic predatory insect. However, a lack of genomic resources hinders the use of whole genome sequencing to explore their genetic basis and molecular mechanisms for adaptive evolution. Here, we provided a high-contiguity, chromosome-level genome assembly of N. ignobilis using high coverage Nanopore and PacBio reads with the Hi-C technique. The final assembly is 480.67 MB in size, containing 12 telomere-ended pseudochromosomes with only 17 gaps. We compared 42 hexapod species genomes including six independent lineages comprising 11 aquatic insects, and found convergent expansions of long wavelength-sensitive and blue-sensitive opsins, thermal stress response TRP channels, and sulfotransferases in aquatic insects, which may be related to their aquatic adaptation. We also detected strong nonrandom signals of convergent amino acid substitutions in aquatic insects. Collectively, our comparative genomic analysis revealed the evidence of molecular convergences in aquatic insects during both gene family evolution and convergent amino acid substitutions., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In Taipu River, after being transformed from a drainage channel to a drinking water supply river in 1995, heavy metals that have accumulated in sediments have become an environmental issue. Herein, we collected sediments of Taipu River in 2018, 2020, and 2021 and analyzed the distribution of Sb, As, Cd, Cu, Pb, Cr, and Zn to identify their sources. The results revealed that the mean concentrations of heavy metals were above the background values, except for Cr and As. During the non-flood season, the midstream of Taipu River becomes a heavy metal hotspot, with their concentrations 2-5 times higher than those in upstream sediment. There were significant correlations (r = 0.79-0.99) among drainage, precipitation and flow rate, which indicated that drainage caused by both the opening of Taipu Gate and precipitation control the flow rate and, then, possibly influenced the distribution of heavy metals. Moreover, three sources (industrial sources, particle deposition sources, and natural sources) were characterized as the determinants for the accumulation of heavy metal by the Positive Matrix Factorization model, with the contribution rates of 41.7%, 32.9%, and 25.4%, respectively. It is recommended that the influence of hydrological conditions and industrial activities should be a key consideration when developing regulations for the management of heavy metals in rivers.

Purposes: To evaluate the postsurgical prognostic implication of contrast-enhanced ultrasound (CEUS) for combined hepatocellular-cholangiocarcinoma (CHC). To build a CEUS-based early recurrence prediction classifier for CHC, in comparison with tumor-node-metastasis (TNM) staging., Methods: The CEUS features and clinicopathological findings of each case were analyzed, and the Liver Imaging Reporting and Data System categories were assigned. The recurrence-free survival associated factors were evaluated by Cox proportional hazard model. Incorporating the independent factors, nomograms were built to estimate the possibilities of 3-month, 6-month, and 1-year recurrence and whose prognostic value was determined by time-dependent receiver operating characteristics, calibration curves, and hazard layering efficiency validation, comparing with TNM staging system., Results: In the multivariable analysis, the levels of carbohydrate antigen 19-9, prothrombin time and total bilirubin, and tumor shape, the Liver Imaging Reporting and Data System category were independent factors for recurrence-free survival. The LR-M category showed longer recurrence-free survival than did the LR-4/5 category. The 3-month, 6-month, and 1-year area under the curves of the CEUS-clinical nomogram, clinical nomogram, and TNM staging system were 0.518, 0.552, and 0.843 versus 0.354, 0.240, and 0.624 (P = .048, .049, and .471) vs. 0.562, 0.545, and 0.843 (P = .630, .564, and .007), respectively. The calibration curves of the CEUS-clinical model at different prediction time pionts were all close to the ideal line. The CEUS-clinical model effectively stratified patients into groups of high and low risk of recurrence in both training and validation set, while the TNM staging system only works on the training set., Conclusions: Our CEUS-clinical nomogram is a reliable early recurrence prediction tool for hepatocellular-cholangiocarcinoma and helps postoperative risk stratification., (© 2021 American Institute of Ultrasound in Medicine.)

A higher ratio of M1/M2 macrophages and an elevated chemerin level are both related to increased risk of preeclampsia. However, the crosstalk between these two events and their collective contribution to preeclampsia are not well understood. In this study, we assessed the impacts of chemerin chemokine-like receptor 1 (CMKLR1)/p-Akt/CEBPα axis in regulating macrophage polarization and mediating the pathogenic effects of chemerin on preeclampsia. We showed that chemerin, in a dose- and time-dependent manner, stimulated M1 macrophage polarization, inhibited macrophage-induced trophoblast invasion and migration, and suppressed macrophage-mediated angiogenesis. All these chemerin-induced phenotypes are essentially mediated by sequentially CMKLR1, Akt activation, and CEBPα. Mechanistically, CEBPα acted as a transcriptional activator for both IRF8 and chemerin. In vivo, chemerin aggravated preeclampsia, while α-NETA, an inhibitor for CMKLR1, significantly suppressed M1 macrophage polarization and alleviated preeclampsia. In summary, chemerin, by activating CMKLR1/Akt/CEBPα axis, forms a positive feedback loop, promotes M1 macrophage polarization, suppresses trophoblast migration/invasion and angiogenesis, and contributes to preeclampsia. Therefore, targeting chemerin signaling may benefit the prevention and/or treatment of preeclampsia., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

AbstractObjective: To investigate the effect of the axon guidance factor Netrin-1 on the expression of VEGFA in T cell acute lymphoblastic leukemia(T-ALL) and its related mechanism., Methods: ELISA assays were applied to detect the levels of Netrin-1 and VEGFA in the bone marrow (BM) samples from children in the T-ALL and control group. The level of Netrin-1 and VEGFA were compared between control children and patients, and the liner correlation between Netrin-1 and VEGFA was analyzed. The T-ALL cells Jurkat and Molt-4 were culture in vitro, and the cells were treated with different concentration of Netrin-1 (0, 25, 50, 100 ng/ml) for 24 h, quantitative RT-PCR (qRT-PCR) and Western blot were used to detect the VEGFA expression in Jurkat, Molt-4 cells. The expression of Netrin-1 receptors in T-ALL cells was detected by qRT-PCR and the interaction between Netrin-1 and receptor in each cells was detected by co-IP. Furthermore, Western blot was used to detect the phosphorylation level of key prateins of AKT signal transduction pathway including Akt and mTOR in T-ALL cells treated with Netrin-1 (100 ng/ml). The expression of VEGFA and phosphorylation of AKT pathway transducers were detected by Western blot, after T-ALL cells treated with Netrin-1 (100 ng/ml) combined with inhibitors specific to Akt or mTOR., Results: The expression level of Netrin-1 and VEGFA in T-ALL patients BM samples were both signi-ficantly higher than that of control group. And the expression level of Netrin-1 was positively correlated with that of VEGFA（r2=0974). With the increase of Netrin-1 concentration, the expression level of VEGFA also increased(P<0.05）. Netrin-1 interacted with its receptor, integrin-β4 at the Netrin-1 concentration of 100 ng/ml. Further, the treatment of Netrin-1 could increase the phosphorylation of Akt and mTOR, which were the key transducers of AKT pathway. After treatment of T-ALL cells with Netrin-1 (100 ng/mL) and Akt inhibitor, the expression of VEGFA and phosphorylation of Akt or mTOR decreased. When the cells were treated with Netrin-1(100 ng/ml) and mTOR inbititor, the phosphorylation level of mTOR and the expression of VEGFA decreased, the phosphorylation level of Akt increased., Conclusion: The expression of Netrin-1 and VEGFA in bone marrow of childred with T-ALL were abnormal, and there was a linear relationship between them. Netrin-1 can interact with its receptor, integrin-β4 and activate AKT transduction pathway to elevate the expression of VEGFA in T-ALL cells.

Objectives: This study aimed to assess the efficacy and safety of probiotics for Helicobacter pylori (H. pylori) eradication therapy as well as their effects on gastric microbiota., Methods: Patients who had failed H. pylori eradication therapy for at least twice were prospectively enrolled during March 2019 and March 2021. A 2-week administration of compound Lactobacillus acidophilus probiotic (1 g thrice daily) followed by a 10-day quadruple bismuth-containing H. pylori eradication therapy was administrated. Endoscopy was performed, and gastric biopsy samples were obtained for drug sensitivity testing and 16S rRNA gene sequencing before and after probiotic treatment. Eradication was evaluated by the 13 C-urea breath test at least 4 weeks after treatment completion. Adverse events (AEs) were recorded., Results: Thirty-seven patients were included. Probiotic supplementation had no effects on the diversity, community structure, and composition of gastric microbiota and no inhibition on H. pylori activity. However, it increased some of the beneficial bacteria such as Blautia, Dorea, and Roseburia (P < 0.05). The overall eradication rate was 97.3% (95% confidence interval [CI] 91.8%-100%). AEs, mainly dizziness, nausea, diarrhea, and chest distress, were detected in six individuals, all of which were resolved upon cessation of antibiotic administration. Dyspeptic symptoms were improved after probiotic supplementation and at treatment completion (both P < 0.001)., Conclusions: H. pylori-infected individuals might benefit from probiotics followed by a quadruple bismuth-containing eradication therapy. Further studies with large sample sizes are warranted., (© 2022 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Introduction: Hypertension is a common risk factor for cardiovascular disease. Transcutaneous electrical acupoint stimulation (TEAS) may be effective for hypertension, but the evidence remains limited. The aim of this study is to evaluate the effectiveness and safety of the smart phone-based TEAS as adjunctive therapy for hypertension., Methods and Analysis: This study is a 52-week cluster randomised controlled trial with 1600 hypertension patients in 32 community health service centres. Patients who meet the inclusion criteria will be randomised into usual care group or TEAS group in a 1:1 ratio. All patients will be provided with usual care as recommended by the guidelines. In addition to this, patients in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at home, 4 times weekly for 12 weeks. The primary outcome will be the mean difference in the changes in office systolic blood pressure from baseline to 12 weeks between TEAS and usual care groups. Secondary outcomes will include the change of mean diastolic blood pressure, proportion of patients with controlled blood pressure (blood pressure <140/90 mm Hg), proportion of patients taking antihypertensive drugs, change in number of antihypertensive drugs and changes in 12-item Short-Form. Tertiary outcomes will include change in body mass index, change in waist circumference, physical activity and medication adherence. Safety outcomes will be any serious adverse events and clinical events., Ethics and Dissemination: This study has been approved by ethics committee of Beijing University of Chinese Medicine (No. 2020BZHYLL0104). Written informed consent will be obtained from all patients before randomisation. Trial results will be disseminated in peer-reviewed publications., Trial Registration Number: ChiCTR2000039400., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Focusing on resistance trends and transmission patterns of pathogenic microorganisms is a major priority for national surveillance programs. The use of whole-genome sequencing for antimicrobial susceptibility testing (WGS-AST) is a powerful alternative to traditional microbiology laboratory methods. Yersinia enterocolitica antimicrobial resistance (AMR) in the Ningxia Hui Autonomous Region has yet to be described thoroughly in current studies. We assessed and monitored the development of Y. enterocolitica AMR in the Ningxia Hui Autonomous Region during 2007-2019 based on WGS-AST. Resistance genotypes were predicted based on WGS. Antimicrobial resistance testing using classical microbiology determined resistance to 13 antimicrobial agents in 189 Y. enterocolitica isolates from Ningxia. The highest resistance level was 97.88% for cefazolin, followed by ampicillin (AMP) (44.97%), ciprofloxacin (CIP) (25.40%), streptomycin (STR) (11.11%), and tetracycline (TET) (10.58%). Isolates emerged as chloramphenicol (CHL) and trimethoprim/sulfamethoxazole (SXT) resistant. The primary plasmid types were IncFII(Y) and ColRNAI. The TET, STR, and SXT resistance were mediated by the tet A, aph (6)-Id, aph (3″)-Ib, and sul 2 genes located on the IncQ1 plasmid. The resistant strains were predominantly biotype 4/O:3/ST429 and the hosts were pigs and patients. The number of multidrug-resistant (MDR) strains was of concern, at 27.51%. At present, the prediction of antimicrobial resistance based on WGS requires a combination of phenotypes. From 2007 to 2019, Y. enterocolitica isolates from the Ningxia Hui Autonomous Region showed a relatively high rate of resistance to cefazolin (CZO) and some resistance to AMP, CIP, STR, and TET. CIP, SXT, and TET showed a relatively clear trend of increasing resistance. Plasmids carrying multiple drug resistance genes are an important mechanism for the spread of antimicrobial resistance. Isolates with low pathogenicity were more likely to present an AMR phenotype than non-pathogenic isolates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yue, Shen, Liu, Hao, Kang, Che, Li, Chen, Xu, Jing, Li and Zhou.)

Background: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness., Methods: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses., Results: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified., Conclusions: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits., Trial Registration: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018)., (© 2022. The Author(s).)

Insects have sensitive olfactory systems to interact with environment and respond to the change in host plant conditions. Key genes in the system can be potential targets for developing new and efficient pest behaviour control methods. Riptortus pedestris is an important soybean pest in East Asia and has caused serious damage to the soybean plants in Huang-Huai-Hai region of China. However, the current treatment of pests is dominated by chemical insecticides and lacks efficient sustainable prevention and control technologies. In this study, we identified 49 putative odorant-binding proteins (OBPs) (43 were new genes) and 25 chemosensory proteins (CSPs) (17 were new genes) in R. pedestris genome. These OBP and CSP genes are clustered in highly conserved groups from other hemipteran species in phylogenetic trees. Most RpedOBPs displayed antennal-biased expression. Among the 49 RpedOBPs , 33 were significantly highly expressed in the antennae, including three male-biased and nine female-biased. While many RpedCSPs were detected both in the antennae and in non-antennal tissues, only 11 RpedCSPs displayed antennal-biased expression, in which four RpedCSPs were male-biased and five RpedCSPs were female-biased. Some OBP and CSP genes showed sex-biased expression profiles. Our results not only provide a foundation for future exploration of the functions of RpedOBPs and RpedCSPs but also aid in developing environmentally friendly insecticides in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yin, Yao, Ma, Dewer, Liu, Wang, Wang, Li and Zhu.)

Hearing loss is among the most common congenital sensory impairments. Genetic causes account for more than 50% of the cases of congenital hearing loss. The PTPRQ gene, encoding protein tyrosine phosphatase receptor Q, plays an important role in maintaining the stereocilia structure and function of hair cells. Mutations in the PTPRQ gene have been reported to cause hereditary sensorineural hearing loss. By using next-generation sequencing and Sanger sequencing, we identified a novel compound heterozygous mutation (c.997 G > A and c.6603-3 T > G) of the PTPRQ gene in a Chinese consanguineous family. This is the first report linking these two mutations to recessive hereditary sensorineural hearing loss. These findings contribute to the understanding of the relationship between genotype and hearing phenotype of PTPRQ -related hearing loss, which may be helpful to clinical management and genetic counseling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RC declared a past co-authorship with the authors SC and YS to the handling editor., (Copyright © 2022 Jin, Liu, Xie, Xie, Chen and Sun.)

Lay Abstract: Autism spectrum disorder has long been conceptualized as a disorder of "atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions)." However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6-30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

Xiangjiang (XJ) is a typical urban inland river that serves as a drinking water source, which may be affected by the currently used organochlorine pesticides (CUOCPs) originating from agricultural activities in the vicinity. On this basis, this study comprehensively explored the occurrence and distribution characteristics of CUOCPs in surface water and sediments under long-term precipitation and subsequent floods. Considering the low concentration of CUOCPs in water, a technique combining high-throughput organic analysis with high-volume solid phase extraction (High-throat/Hi-volume SPE) was introduced for effective analysis of CUCOPs. The results showed that the concentration of CUOCPs in the water and sediments of XJ ranged from 2.33 to 6.40 ng L -1 (average of 3.93 ± 1.15 ng L -1 ) and from 1.52 to 21.2 ng g -1 (average of 6.60 ± 4.31 ng g -1 dw), respectively. The distribution of CUOCPs in water was consistent throughout XJ, but that in sediments was not uniform, indicating a stronger impact of floods on water than on sediments. Water-sediment partition coefficients were generally >2 L g -1 , showing a tendency of CUOCP dominance in sediments. The results of principal component analysis and cluster analysis showed that the occurrence of CUOCPs is significantly affected by exogenous disturbance, which could be flood events; meanwhile, clusters of CUOCPs were found in both water and sediments in the source-limited middle reaches in urban areas. Redundancy analysis (RDA) showed that CUOCP occurrences were not positively correlated with nutrient elements (nitrogen and phosphorus), but related to pH and dissolved oxygen (DO), indicating complex sources., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mutations in the GJB2 gene (encoding Connexin26(Cx26)) are the most common cause of hereditary deafness, accounting for about a quarter of all cases. Sensory epithelial damage is considered to be one of the main causes of deafness caused by GJB2 gene mutation. Dexamethasone (DEX) is widely used in the treatment of a variety of inner ear diseases including sudden sensorineural hearing loss (SSNHL), noise-induced hearing loss (NIHL), and deafness caused by ototoxic drugs. Whether DEX has a direct therapeutic effect on hereditary deafness, especially GJB2-related deafness, remains unclear. In this study, we revealed that DEX can effectively prevent hair cell death caused by oxidative stress in cochlear explants. Additionally, two distinct Cx26-null mouse models were established to investigate whether systemic administration of DEX alleviate the cochlear sensory epithelial injury or deafness in these models. In a specific longitudinally Cx26-null model that does not cause deafness, systemic administration of DEX prevents the degeneration of outer hair cells (OHCs) induced by Cx26 knockout. Similarly, in a targeted-Deiter's cells (DCs) Cx26-null mouse model that causes deafness, treatment with DEX can almost completely prevent OHCs loss and alleviates auditory threshold shifts at some frequencies. Additionally, we observed that DEX inhibited the recruitment of CD45-positive cells in the targeted-DCs Cx26-null mice. Taken together, our results suggest that the protective effect of dexamethasone on cochlear sensory epithelial damage and partially rescue auditory function may be related to the regulation of inner ear immune response in Cx26 deficiency mouse models., (© 2022. The Author(s).)

The Warburg effect is a promising target for the diagnosis and treatment of cancer, referring to the ability of cancer cells to generate energy through high levels of glycolysis even in the presence of oxygen, allowing them to grow and proliferate rapidly. The antipsychotic Pimozide has strong anti-breast cancer effects both in vivo and in vitro, whether Pimozide has an inhibitory effect on aerobic glycolysis has not been elucidated. In this study, Pimozide inhibited the Warburg effect of breast cancer cells by hindering glucose uptake, ATP level and lactate production; reducing the extracellular acidification rate (ECAR); suppressing the expression of PKM2, a rate-limiting enzyme in glycolysis. Intriguingly, Pimozide was significantly involved in reprogramming glucose metabolism in breast cancer cells through a p53-dependent manner. Mechanistic studies demonstrated Pimozide increased the expression of p53 through inhibition of the PI3K/Akt/MDM2 signaling pathway, which in turn downregulated the expression of PKM2. In sum, our results suggest that Pimozide mediates the p53 signaling pathway through PI3K/AKT/MDM2 to inhibit the Warburg effect and breast cancer growth, and it may be a potential aerobic glycolysis inhibitor for the treatment of breast cancer., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Benign airway stenosis is a severe disease that can result in death with improper treatment. Clinicians must know about airway stents to choose the best one in their daily practice., Areas Covered: PubMed, Embase, and other electronic databases and websites were searched to identify relevant randomized controlled trials and meta-analyses. This review summarizes different types of airway stents and analyzes their advantages and disadvantages., Expert Opinion: Increasing attention has been given to the indications and prognosis of benign airway stenosis treated with different airway stents. With more investigations and data, better alternatives to silicone stents could be developed in the future.

Introduction: Many nanocarriers have been developed to react physicochemically to exterior stimuli like ultrasonic, light, heat, and magnetic fields, along with various internal stimuli including pH, hypoxia, enzyme, and redox potential. Nanocarriers are capable to respond various stimuli within the cancer cells to enable on-demand drug delivery, activation of bioactive compounds, controlled drug release, and targeting ligands, as well as size, charge, and conformation conversion, enabling sensing and signaling, overcoming multidrug resistance, accurate diagnosis, and precision therapy., Areas Covered: Carbohydrates are ubiquitous biomolecules with a high proclivity for supramolecular network formation. Numerous carbohydrate-based nanomaterials have been used in biological solicitations and stimuli-based responses. Particular emphasis has been placed on the utilization of carbohydrate-based NPs and nanogels in various fields including imaging, drug administration, and tissue engineering. Because the assembly process is irreversible, carbohydrate-based systems are excellent ingredients for the development of stimulus-responsive nanocarriers for cancer-targeted chemotherapy. This review aims to summarise current research on carbohydrate-based nanomaterials, with an emphasis on stimuli-sensitive nanocarriers for cancer-targeted chemotherapy., Expert Opinion: Carbohydrates-based stimulus-responsive nanomaterials have been proved highly efficient for targeted delivery of anticancer drugs, thus leading to effective chemotherapy with minimum off-target effects.

Objectives: To construct a preoperative model for survival prediction in intrahepatic cholangiocarcinoma (ICC) patients using ultrasound (US) based radiographic-radiomics signatures., Methods: Between April 2010 and September 2015, 170 patients with ICC who underwent curative resection were retrospectively recruited. Overall survival (OS)-related radiographic signatures and radiomics signatures based on preoperative US were built and assessed through a time-dependent receiver operating characteristic curve analysis. A nomogram was developed based on the selected predictors from the radiographic-radiomics signatures and clinical and laboratory results of the training cohort (n = 127), validated in an independent testing cohort (n = 43) by the concordance index (C-index), and compared with the Tumor Node Metastasis (TNM) cancer staging system as well as the radiographic and radiomics nomograms., Results: The median areas under the curve of the radiomics signature and radiographic signature were higher than that of the TNM staging system in the testing cohort, although the values were not significantly different (0.76-0.82 versus 0.62, P = .485 and .264). The preoperative nomogram with CA 19-9, sex, ascites, radiomics signature, and radiographic signature had C-indexes of 0.72 and 0.75 in the training and testing cohorts, respectively, and it had significantly higher predictive performance than the 8th TNM staging system in the testing cohort (C-index: 0.75 versus 0.67, P = .004) and a higher C-index than the radiomics nomograms (0.75 versus 0.68, P = .044)., Conclusions: The preoperative nomogram integrated with the radiographic-radiomics signature demonstrated good predictive performance for OS in ICC and was superior to the 8th TNM staging system., (© 2021 American Institute of Ultrasound in Medicine.)

We demonstrate the successful prediction of the continuous intensity time series and reproduction of the underlying dynamical behaviors for a chaotic semiconductor laser by reservoir computing. The laser subject to continuous-wave optical injection is considered using the rate-equation model. A reservoir network is constructed and trained using over 2 × 10 4 data points sampled every 1.19 ps from the simulated chaotic intensity time series. Upon careful optimization of the reservoir parameters, the future evolution of the continuous intensity time series can be accurately predicted for a time duration of longer than 0.6 ns, which is six times the reciprocal of the relaxation resonance frequency of the laser. Moreover, we demonstrate for the first time, to the best of our knowledge, that the predicted intensity time series allows for accurate reproduction of the chaotic dynamical behaviors, including the microwave power spectrum, probability density function, and the chaotic attractor. In general, the demonstrated approach offers a relatively high flexibility in the choice of reservoir parameters according to the simulation results, and it provides new insights into the learning and prediction of semiconductor laser dynamics based on measured intensity time series.

Characterizing the occurrence of organic contaminants (OCs) of environmental health concern in municipal sewage sludges is essential for safe handling and disposal of these abundant materials. This meta-analysis aimed to (i) summarize the extent of studies performed on the chemical composition of sewage sludges from China and the U.S., the world's two largest chemical producers, (ii) identify chemical groups of priority concern, (iii) quantitatively compare chemical abundance in sludge between nations, (iv) determine longitudinal contaminant accumulation trends in sludge, and (v) identify data gaps with regard to OC concentrations in sludge. A literature search was conducted on concentrations of OCs in U.S. sludges produced during treatment of domestic and industrial wastewater and compared statistically to contaminant levels in Chinese sludge abstracted from a recently established database. Longitudinal trends of OC occurrence were interpreted in the context of national chemical production, usage statistics, and regulations. A total of 105 studies on OCs in U.S. sewage sludge were found, while a total of 159 had been found in China. Among 1175 OCs monitored for, 23% of all analytes had been monitored in both countries (n = 269), 41% (n = 480) in China only, and the remaining 36% (n = 426) in the U.S. only. On average, concentrations of OCs were 4.0 times higher in U.S. than in Chinese sewage sludge, with the highest detection being observed for alkylphenol ethoxylates. Data from a new binational database on toxic OCs in sewage sludges suggest and reiterates the need for additional chemical monitoring in both countries, risk assessments for emerging OCs contained in sludges destined for application on land, and stronger enforcement of sludge disposal restrictions in China, where as much as 40% of sludge is currently being dumped improperly., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Halden and Mr. Steele are co-founders of AquaVitas LLC, an Arizona State University startup company that works in the intellectual space touched upon by this study. Dr. Halden is founder of Arizona State University Foundation's OneWaterOneHealth, a nonprofit project providing wastewater-based health assessments to underserved US communities., (Copyright © 2022 Elsevier B.V. All rights reserved.)