Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.

Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation.

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin-proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.

UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b.

Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome encoded fewer accessory proteins, among which the ORF4b protein had anti-immunity ability in both the cytoplasm and nucleus. Our work for the first time revealed that ORF4b protein was unstable in the host cells and could be degraded by the ubiquitin proteasome system. After extensive screenings, it was found that UBR5 (ubiquitin protein ligase E3 component N-recognin 5), a member of the HECT E3 ubiquitin ligases, specifically regulated the ubiquitination and degradation of ORF4b. Similar to ORF4b, UBR5 can also translocate into the nucleus through its nuclear localization signal, enabling it to regulate ORF4b stability in both the cytoplasm and nucleus. Through further experiments, lysine 36 was identified as the ubiquitination site on the ORF4b protein, and this residue was highly conserved in various MERS-CoV strains isolated from different regions. When UBR5 was knocked down, the ability of ORF4b to suppress innate immunity was enhanced and MERS-CoV replication was stronger. As an anti-MERS-CoV host protein, UBR5 targets and degrades ORF4b protein through the ubiquitin proteasome system, thereby attenuating the anti-immunity ability of ORF4b and ultimately inhibiting MERS-CoV immune escape, which is a novel antagonistic mechanism of the host against MERS-CoV infection. IMPORTANCE ORF4b was an accessory protein unique to MERS-CoV and was not present in SARS-CoV and SARS-CoV-2 which can also cause severe respiratory disease. Moreover, ORF4b inhibited the production of antiviral cytokines in both the cytoplasm and the nucleus, which was likely to be associated with the high lethality of MERS-CoV. However, whether the host proteins regulate the function of ORF4b is unknown. Our study first determined that UBR5, a host E3 ligase, was a potential host anti-MERS-CoV protein that could reduce the protein level of ORF4b and diminish its anti-immunity ability by inducing ubiquitination and degradation. Based on the discovery of ORF4b-UBR5, a critical molecular target, further increasing the degradation of ORF4b caused by UBR5 could provide a new strategy for the clinical development of drugs for MERS-CoV.

Effectiveness and degradation pathways of bisphenol A (BPA) initiated by hydroxyl radicals and sulfate radicals in water: Initial reaction sites based on DFT prediction.

Bisphenol A (BPA), one of the widely known endocrine-disrupting chemicals, can be effectively degraded by advanced oxidation processes in water because of the powerful reactive oxygen species. In this study, Fenton, UV/Fenton, and metal ion/peroxymonosulfate (PMS) processes were compared to investigate BPA degradation efficiency and pathways initiated by hydroxyl radicals and sulfate radicals. In contrast to the Fenton system, which only degraded 60% of BPA within 15 min, the UV/Fenton system could degrade greater than 80% of BPA, because more hydroxyl radicals (•OH) were generated under the reduction of Fe3+ to Fe2+. The optimized parameters of the UV/Fenton system were as follows: 8 µmol/L of Fe2+, 80 µmol/L of H2O2, and a pH value of 3.0. As for the metal ion/PMS system, the BPA degradation efficiency was closely associated with the applied metal ions, and the order was as follows: Co2+/PMS (∼100%) > Fe2+/PMS (∼80%) > Cu2+/PMS (∼79%). The degradation pathways of BPA were theoretically interpreted through density functional theory prediction and degradation products during various processes. Two major initial reaction sites (4C and 6C) for •OH initiated using the UV/Fenton system and one initial reaction site (4C) for sulfate radicals (SO4•-) using the metal ion/PMS system were recognized for BPA degradation processes. The degradation products by •OH showed a larger average molecular weight than those by SO4•-. These studies are instructive for the application of different advanced oxidation systems in the treatment process of BPA in wastewater.

M6A-mediated upregulation of circMDK promotes tumorigenesis and acts as a nanotherapeutic target in hepatocellular carcinoma.

BACKGROUND: Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. METHODS: RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. RESULTS: Hsa_circ_0095868, derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m6A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (ß-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. CONCLUSIONS: CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC.

SARS-CoV-2: Mechanism of infection and emerging technologies for future prospects.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally to over 200 countries with more than 23 million confirmed cases and at least 800,000 fatalities as of 23 August 2020. Declared a pandemic on March 11 by World Health Organization, the disease caused by SARS-CoV-2 infection, called coronavirus disease 2019 (COVID-19), has become a global public health crisis that challenged all national healthcare systems. This review summarized the current knowledge about virologic and pathogenic characteristics of SARS-CoV-2 with emphasis on potential immunomodulatory mechanism and drug development. With multiple emerging technologies and cross-disciplinary approaches proving to be crucial in our global response against COVID-19, the application of PROteolysis TArgeting Chimeras strategy, CRISPR-Cas9 gene editing technology, and Single-Nucleotide-Specific Programmable Riboregulators technology in developing antiviral drugs and detecting infectious diseases are proposed here. We also discussed the available but still limited epidemiology of COVID-19 as well as the ongoing efforts on vaccine development. In brief, we conducted an in-depth analysis of the pathogenesis of SARS-CoV-2 and reviewed the therapeutic options for COVID-19. We also proposed key research directions in the future that may help uncover more underlying molecular mechanisms governing the pathology of COVID-19.

Effect of crystalline structure on terbuthylazine degradation by H2O2-assisted TiO2 photocatalysis under visible irradiation.

Various methods for shifting the optical response of TiO2 into the visible (Vis) range have been reported. Herein, we reported the application of a TiO2/H2O2/Vis process and the effects of TiO2 crystalline structure on the degradation of terbuthylazine. The results indicated that TiO2 crystalline structure and H2O2 addition had significant effects on terbuthylazine degradation: its degradation rate could be increased from 7% to 70% with H2O2 addition after 180 min of reaction, the synergistic degradation of terbuthylazine by TiO2-Fe3+ was substantially accelerated, with the degradation rate reaching up to 100% after 20 min of reaction, and rutile TiO2 showed better photocatalytic activity and a more obvious synergistic effect than anatase TiO2. The addition of free-radical scavengers (tert-butyl alcohol or methanol) inhibited the degradation efficiency of rutile TiO2, but had a relatively minor effect on anatase TiO2. Fluorescence spectrophotometry analysis indicated that hydroxyl free radicals could be continuously produced when using rutile TiO2 as the photocatalyst. Degradation of terbuthylazine catalyzed by rutile TiO2 occurred mainly in solution, but occurred on the particle surface of the photocatalyst when catalyzed by anatase TiO2. This study provides new insight into the role of TiO2 crystalline structure on the degradation of terbuthylazine and its photocatalytic degradation mechanism.

A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication.

The ORF9b protein, derived from the nucleocapsid's open-reading frame in both SARS-CoV and SARS-CoV-2, serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response. Despite its significance, the precise regulatory mechanisms underlying its function remain elusive. In the present study, we unveil that the ORF9b protein of SARS-CoV-2, including emerging mutant strains like Delta and Omicron, can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway, despite certain mutations present among these strains. Moreover, our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70 (TOM70) as a substrate receptor, bridging ORF9b with heat shock protein 90 alpha (HSP90α) and Cullin 5 (CUL5) to form a complex. Within this complex, CUL5 triggers the ubiquitination and degradation of ORF9b, acting as a host antiviral factor, while HSP90α functions to stabilize it. Notably, treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b, leading to a pronounced inhibition of SARS-CoV-2 replication. Single-cell sequencing data revealed an up-regulation of HSP90α in lung epithelial cells from COVID-19 patients, suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90α to evade the host immunity. Our study identifies the CUL5-TOM70-HSP90α complex as a critical regulator of ORF9b protein stability, shedding light on the intricate host-virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.

Performance of short-cut denitrifying phosphorus removal and microbial community structure in the A2SBR process.

ABSTRACTAcclimatization of short-cut denitrifying polyphosphate accumulating organisms (SDPAOs), metabolic mechanism, and operating parameters were analyzed to investigate the performance of the anaerobic/anoxic sequencing batch reactor (A2SBR) process. The high-throughput sequencing technology was employed to explore the microbial community structures of activated sludge systems. The experimental results illustrated that SDPAOs were successfully enriched with three-phase inoculation for 36 days. The removal rates of TP and NO2--N were 93.22% and 91.36%, respectively, under the optimal parameters of a pH of 7.5, an SRT of 26 days, a temperature of 24 ℃ and a COD of 200.00 mg·L-1 using acetate as the carbon source. In the anaerobic stage, 82.20% external carbon source was converted into 88.78 mg·g-1 PHB, and the removal rate of NO2--N in the anoxic stage was characterized by ΔNO2--N/ΔPHB, anoxic ΔP/ΔPHBeffective was 0.289, which was higher than anaerobic ΔP/ΔCODeffective of 0.203. Ignavibacterium and Povalibacter with significant phosphorus removal ability were the dominant bacterial genera. The nitrogen and phosphorus removal could be realized simultaneously in an anaerobic/anoxic sequencing batch reactor. Therefore, this study provided an important understanding of the removal of nitrogen and phosphorus from low-carbon nitrogen wastewater.

Transformation of hydroxylamine to nitrosated and nitrated products during advanced oxidation process.

Recently, hydroxylamine (HAm) was introduced to drive advanced oxidation processes (AOPs) for removing organic contaminants. However, we found that HAm-driven Cu(II)/peroxymonosulfate oxidation of phenol produced p-nitrosophenol, 2-nitrophenol and 4-nitrophenol. The total nitro(so) products accounted for approximately 25.0 % of the phenol transformation at certain condition. SO4•- and •OH were identified as the primary and second significant oxidants, respectively. Reactive nitrogen species (RNS) were involved in phenol transformation. The pathway and mechanism of HAm transformation in HAm-driven transition metal ion-catalyzed AOPs were proposed for the first time in this study. The product of HAm via twice single-electron oxidation by Cu(II) is nitroxyl (HNO/NO-), which is a critical oxidation intermediate of HAm. Further oxidation of HNO by SO4•- or •OH is the initial step in propagating radical chain reactions, leading to nitric oxide radical (•NO) and nitrogen dioxide radical (•NO2) as the primary RNS. HAm is a critical intermediate in natural nitrogen cycle, suggesting that HAm can drive the oxidation processes of pollutants in natural environments. Nitro(so) products will be readily produced when AOPs are applied for ecological remediation. This study highlights the formation of toxic nitrosated and nitrated products in HAm-driven AOPs, and the requirement of risk assessments to evaluate the possible health and ecological impacts.

Overlooked roles of Cl2O and Cl2 in micropollutant abatement and DBP formation by chlorination.

This study investigated the roles of diverse free available chlorine (FAC) species including HOCl/OCl-, H2OCl+, Cl2O, and Cl2 in the degradation of micropollutants. The degradation of 5 micropollutants was significantly affected by pH, FAC dosage, and chloride (Cl-) concentration. The reaction orders in FAC (n) of 5 micropollutants (acetaminophen, carbamazepine, naproxen, gemfibrozil, and mecoprop) ranged from 1.4 ± 0.2 to 2.1 ± 0.3 at pH 3 - 5, evidencing the importance of Cl2O and Cl2 for micropollutant abatement. A simplified method for the determination of second-order rate constants (k) of specific FAC species with micropollutants was developed. Herein, the k for neutral/dissociated forms of 5 micropollutants with Cl2 and Cl2O were determined in the ranges of 9.3 (± 0.2) × 102 ∼ 2.9 (± 0.2) × 109 M-1 s-1 and 1.8 (± 0.1) × 104 ∼ 3.7 (± 0.6) × 109 M-1 s-1, respectively. They were 4 - 7 orders of magnitude higher than those of HOCl, whereas those of OCl- and H2OCl+ were negligible. By using kinetic modeling, Cl2 was more important under acidic conditions and higher Cl- levels with contributions of 37.9 - 99.2% at pH 5 in pure water. Cl2O played a dominant role in micropollutant degradation in pure water (56.4 - 87.3%) under neutral conditions. Furthermore, both Cl2 and Cl2O played vital roles in the formation of disinfection byproducts (DBPs) during chlorination of carbamazepine and natural organic matter. This study highlights the overlooked roles of Cl2O and Cl2 in micropollutant abatement and DBP formation during chlorination.

Testing of worn face mask and saliva for SARS-CoV-2.

Background: Exhaled SARS-CoV-2 can be detected on face masks. We compared tests for SARS-CoV-2 RNA on worn face masks and matched saliva samples. Methods: We conducted this prospective, observational, case-control study between December 2021 and March 2022. Cases comprised 30 in-center hemodialysis patients with recent COVID-19 diagnosis. Controls comprised 13 hemodialysis patients and 25 clinic staff without COVID-19 during the study period and the past 2 months. Disposable 3-layer masks were collected after being worn for 4 hours together with concurrent saliva samples. ThermoFisher COVID-19 Combo Kit (A47814) was used for RT-PCR testing. Results: Mask and saliva testing specificities were 99% and 100%, respectively. Test sensitivity was 62% for masks, and 81% for saliva (p = 0.16). Median viral RNA shedding duration was 11 days and longer in immunocompromised versus non-immunocompromised patients (22 vs. 11 days, p = 0.06, log-rank test). Conclusion: While SARS-CoV-2 testing on worn masks appears to be less sensitive compared to saliva, it may be a preferred screening method for individuals who are mandated to wear masks yet averse to more invasive sampling. However, optimized RNA extraction methods and automated procedures are warranted to increase test sensitivity and scalability. We corroborated longer viral RNA shedding in immunocompromised patients.

A novel nanofibrous PAN ultrafiltration membrane embedded with ZIF-8 nanoparticles for effective removal of Congo red, Pb(II), and Cu(II) in industrial wastewater treatment.

A novel Polyacrylonitrile (PAN) composite membrane involving ZIF-8 nanoparticles, named as ZIF-8/PAN membrane, was obtained via electrospinning to remove the Congo red (CR), Pb(II) and Cu(II) ions in industrial wastewaters, during which the adsorption mechanisms were examined in this study. The adsorption efficiency of the electrospun ZIF-8/PAN membrane was as high as 89%, 92% and 76% for CR, Pb(II) and Cu(II), respectively. Comparative analysis showed that ZIF-8 nanoparticles embedded in the ZIF-8/PAN membrane accounted for these enhanced adsorption capabilities. The adsorption behaviors of the ZIF-8 nanoparticles were investigated through experiments and theoretical analysis, and the results unraveled that the adsorption for CR by the ZIF-8 was mainly including electrostatic interaction, hydrogen bonding and π-π interaction, while those for Pb(II) and Cu(II) were mainly caused by ion-exchange and chemical adsorption. Parametric studies were conducted to optimize the conditions for removing CR, Pb(II), and Cu(II) by ZIF-8 nanoparticles, during which all of pollutants showed different reactions to the solution pH. This work not only develops a novel ZIF-8/PAN composite membrane for effective removals of pollutants, but also reveals the underlying mechanisms of pollutants adsorption in terms of molecular interactions, providing important understandings on fibrous materials design for efficient heavy metals and dyes removals in industrial wastewater treatment.

Efficient degradation and deiodination of iopamidol by UV/sulfite process: Assessment of typical process parameters and transformation paths.

Iopamidol (IPM) is widely used in medical clinical examination and treatment and has immeasurable harm to the ecological environment. The combination of UV and sulfite (UV/sulfite) process was developed to degrade IPM in this study. In contrast to that almost no removal of IPM was observed under sulfite reduction alone, the UV/sulfite process could efficiently reductively degrade IPM with the observed rate constant (kobs) of 2.08 min-1, which was nearly 4 times that of UV irradiation alone. The major active species in the UV/sulfite process were identified as hydrated electrons (eaq-) by employing active species scavengers. The influence of the initial pH, sulfite dosage, IPM concentration, UV intensity and common water matrix were evaluated. The degradation of IPM reached nearly 100% within only 2.5 min at pH 9, and kobs increased at higher initial sulfite dosages and greater UV intensities. HCO3- had a limited effect on the degradation of IPM, while humic acid (HA) was found to be a strong inhibitor in the UV/sulfite process. With the synergistic action of UV/sulfite, most of the iodine in IPM was found to release in the form of iodide ions (up to approximately 98%), and a few formed iodide-containing organic compounds, reducing significantly the toxicity of degradation products. Under direct UV irradiation and free radical reduction (mainly eaq-), 15 transformation intermediates of IPM were produced by amide hydrolysis, deiodination, hydroxyl radical addition and hydrogen abstraction reactions, in which free radical attack accounted for the main part. Consequently, the UV/sulfite process has a strong potential for IPM degradation in aquatic environments.

Virtual mouse brain histology from multi-contrast MRI via deep learning.

1H MRI maps brain structure and function non-invasively through versatile contrasts that exploit inhomogeneity in tissue micro-environments. Inferring histopathological information from magnetic resonance imaging (MRI) findings, however, remains challenging due to absence of direct links between MRI signals and cellular structures. Here, we show that deep convolutional neural networks, developed using co-registered multi-contrast MRI and histological data of the mouse brain, can estimate histological staining intensity directly from MRI signals at each voxel. The results provide three-dimensional maps of axons and myelin with tissue contrasts that closely mimic target histology and enhanced sensitivity and specificity compared to conventional MRI markers. Furthermore, the relative contribution of each MRI contrast within the networks can be used to optimize multi-contrast MRI acquisition. We anticipate our method to be a starting point for translation of MRI results into easy-to-understand virtual histology for neurobiologists and provide resources for validating novel MRI techniques.

Ethiodized poppyseed oil-based contrast medium is superior to water-based contrast medium during hysterosalpingography regarding image quality improvement and fertility enhancement: A multicentric, randomized and controlled trial.

Background: The efficacy of ethiodized poppyseed oil in hysterosalpingography (HSG) image quality and fertility enhancement has been revealed, but whether this HSG modality has similar effects in the Chinese population is still unclear. Methods: Between July 18, 2017, and December 29, 2019, this multicentric, randomized, two-arm, clinical trial was performed involving 15 medical centers. Infertile women meeting HSG indications were randomly assigned to an oil group and a water group. The coprimary outcome included HSG image quality during HSG and fertility-enhancing effects of HSG. This study was registered on ClinicalTrials.gov (NCT03370575). Findings: A total of 1026 subjects were randomly assigned to an oil group (N = 508) and a water group (N = 518). HSG image quality revealed that the oil group had outstanding visualization (all P < 0.001); total image quality scores for uterus opacification or uterine outline (2.9 ± 0.4 vs. 2.7 ± 0.5), fallopian tube outline (2.3 ± 0.8 vs. 1.7 ± 0.7), fimbrial rugae (1.7 ± 1.0 vs. 1.3 ± 0.8), fallopian tube spillage (2.1 ± 0.9 vs. 1.6 ± 0.8), peritoneal distribution (2.6 ± 0.9 vs. 2.1 ± 1.0) and diagnostic quality (11.6 ± 3.4 vs. 9.5 ± 3.1) (all P < 0.001) were higher in the oil group than in the water group. Regarding fertility-enhancing evaluation, the oil group showed an increased cumulative on-going pregnancy rate, on-going pregnancy within 6 months (29.1% vs. 20.1%), clinical pregnancy (39.5% vs. 29.1%) and live birth ≥ 24 weeks of gestation (36.1% vs. 27.7%) but a shorter time to pregnancy than the water group (all P < 0.01). Concerning adverse events, the oil group showed a lower occurrence rate of abdominal pain and vaginal bleeding after HSG (both P < 0.01). Interpretation: Ethiodized poppyseed oil-based contrast is superior to water-based contrast during HSG in terms of image quality improvement and fertility enhancement. This study indicates the priority of the application of ethiodized poppyseed oil-based contrast during the HSG procedure in infertile patients. Funding: No funding was received.

Sample pooling: burden or solution?

BACKGROUND: Pool-testing strategies combine samples from multiple people and test them as a group. A pool-testing approach may shorten the screening time and increase the test rate during times of limited test availability and inadequate reporting speed. Pool testing has been effectively used for a wide variety of infectious disease screening settings. Historically, it originated from serological testing in syphilis. During the current coronavirus disease 2019 (COVID-19) pandemic, pool testing is considered across the globe to inform opening strategies and to monitor infection rates after the implementation of interventions. AIMS: This narrative review aims to provide a comprehensive overview of the global efforts to implement pool testing, specifically for COVID-19 screening. SOURCES: Data were retrieved from a detailed search for peer-reviewed articles and preprint reports using Medline/PubMed, medRxiv, Web of Science, and Google up to 21st March 2021, using search terms "pool testing", "viral", "serum", "SARS-CoV-2" and "COVID-19". CONTENT: This review summarizes the history and theory of pool testing. We identified numerous peer-reviewed articles that describe specific details and practical implementation of pool testing. Successful examples as well as limitations of pool testing, in general and specifically related to the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies, are reviewed. While promising, significant operational, pre-analytical, logistical, and economic challenges need to be overcome to advance pool testing. IMPLICATIONS: The theory of pool testing is well understood and numerous successful examples from the past are available. Operationalization of pool testing requires sophisticated processes that can be adapted to the local medical circumstances. Special attention needs to be paid to sample collection, sample pooling, and strategies to avoid re-sampling.

Unexpected degradation and deiodination of diatrizoate by the Cu(II)/S(IV) system under anaerobic conditions.

Transition metal catalyzed sulfite auto-oxidation is a promising technology used in water and wastewater treatment for the elimination of contaminants. In the literature, this process has been reported to be efficient only in the presence of oxygen. However, in this study, we unexpectedly found that the degradation of diatrizoate (DTZ) by a system based on the combination of copper ion and sulfite (Cu(II)/S(IV)) reached over 95% under anaerobic conditions, but was considerably retarded under aerobic conditions at pH 7. Furthermore, it was found that Cu(I), generated from the cleavage of the CuSO3 complex, was the main reactive species responsible for the degradation of DTZ by the Cu(II)/S(IV) system under anaerobic conditions. In fact, the absence of oxygen promoted the accumulation of Cu(I). The concomitant release of the iodide ion with the degradation of DTZ indicated that the anaerobic degradation of DTZ by the Cu(II)/S(IV) system mainly proceeded through the deiodination pathway, which was also confirmed by the detection of deiodinated products. The anaerobic degradation of DTZ was favored at higher initial concentrations of Cu(II) or sulfite in this system. Since the CuSO3 complex, the precursor of Cu(I), was formed mainly at pH 7, the highest anaerobic degradation of DTZ was achieved at pH 7. An increase in reaction temperature considerably enhanced the degradation of DTZ by the Cu(II)/S(IV) system with an apparent activation energy of 119.4 kJ/mol. The presence of chloride, bicarbonate and humic acid slightly influenced the anaerobic degradation of DTZ. The experiments with real water samples also demonstrated the effectiveness of the degradation of DTZ by the Cu(II)/S(IV) system under anaerobic conditions.

A novel diagnostic method for distinguishing between Fe(IV) and •OH by using atrazine as a probe: Clarifying the nature of reactive intermediates formed by nitrilotriacetic acid assisted Fenton-like reaction.

In this work, we found that the distribution of two specific atrazine (ATZ) oxidation products (desethyl-atrazine (DEA) and desisopropyl-atrazine (DIA)) was different in oxidation processes involving aqueous ferryl ion (Fe(IV)) species and •OH. Specifically, the molar ratio of produced DEA to DIA (i.e., [DEA]/[DIA]) increased from 7.5 to 13 with increasing pH from 3 to 6 when ATZ was oxidized by Fe(IV), while the treatment of ATZ by •OH led to the [DEA]/[DIA] value of 2 which was independent of pH. Moreover, ATZ showed high reactivity towards Fe(IV) over a wide pH range, especially at near-neutral pH, at which ATZ oxidation in Fe(II)/peroxydisulfate system was even much faster than another well-defined Fe(IV) scavenger, the sulfoxides. By using this approach, it was obtained that the [DEA]/[DIA] value remained at 2 during ATZ transformation by the nitrilotriacetic acid (NTA) assisted Fenton-like (Fe(III)/H2O2) system, which was independent of solution pH and reactants dosage. This result clarified that •OH was the primary reactive intermediate formed in the NTA assisted Fe(III)/H2O2 system. This study not only developed a novel sensitive diagnostic tool for distinguishing Fe(IV) from •OH, but also provided more credible evidence to the nature of reactive intermediate in a commonly controversial system.

Formation of nitrosated and nitrated aromatic products of concerns in the treatment of phenols by the combination of peroxymonosulfate and hydroxylamine.

Recently, the combination of peroxymonosulfate (PMS) and hydroxylamine (HA) has been proposed as a green and efficient sulfate radical ()-based advanced oxidation process (AOP) for eliminating organic contaminants. However, we found that toxic nitrosated and nitrated aromatic compounds were generated during the treatment of phenolic compounds by PMS/HA system, indicating the involvement of reactive nitrogen species (RNS) during the interaction of PMS with HA. Specifically, considerable production of p-nitrosophenol (p-NSP) and mononitrophenol were obtained when phenol was oxidized by PMS/HA system under various conditions. At the molar ratio between HA and PMS of 1.0 and pH 5.0, sum of the yields of p-NSP and nitrophenols reached their maxima (around 50%). Moreover, production of p-NSP was inhibited while that of nitrophenols was promoted when applied NH2OH1/2H2SO4 was replaced by NH2OHHCl, which was possibly related to the formation of secondary reactive species induced by the reaction of with chloride ion. Further, formation of undesirable nitrosated and nitrated aromatic products was obtained in the treatment of other phenolic compounds including acetaminophen, bisphenol A, and bisphenol S by PMS/HA system. Considering the toxicity of nitrosated and nitrated aromatic compounds, practical application of PMS/HA system for environmental decontamination should be scrutinized.