Cullin-3 proteins be a novel biomarkers and therapeutic targets for hyperchloremia induced by oral poisoning.

Oral poisoning can trigger diverse physiological reactions, determined by the toxic substance involved. One such consequence is hyperchloremia, characterized by an elevated level of chloride in the blood and leads to kidney damage and impairing chloride ion regulation. Here, we conducted a comprehensive genome-wide analysis to investigate genes or proteins linked to hyperchloremia. Our analysis included functional enrichment, protein-protein interactions, gene expression, exploration of molecular pathways, and the identification of potential shared genetic factors contributing to the development of hyperchloremia. Functional enrichment analysis revealed that oral poisoning owing hyperchloremia is associated with 4 proteins e.g. Kelch-like protein 3, Serine/threonine-protein kinase WNK4, Serine/threonine-protein kinase WNK1 and Cullin-3. The protein-protein interaction network revealed Cullin-3 as an exceptional protein, displaying a maximum connection of 18 nodes. Insufficient data from transcriptomic analysis indicates that there are lack of information having direct associations between these proteins and human-related functions to oral poisoning, hyperchloremia, or metabolic acidosis. The metabolic pathway of Cullin-3 protein revealed that the derivative is Sulfonamide which play role in, increasing urine output, and metabolic acidosis resulted in hypertension. Based on molecular docking results analysis it found that Cullin-3 proteins has the lowest binding energies score and being suitable proteins. Moreover, no major variations were observed in unbound Cullin-3 and all three peptide bound complexes shows that all systems remain compact during 50 ns simulations. The results of our study revealed Cullin-3 proteins be a strong foundation for the development of potential drug targets or biomarker for future studies.

Halogen Bond-Assisted Supramolecular Dimerization of Pyridinium-Fused 1,2,4-Selenadiazoles via Four-Center Se2N2 Chalcogen Bonding.

The synthesis and structural characterization of α-haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles with various counterions is reported herein, demonstrating a strategy for directed supramolecular dimerization in the solid state. The compounds were obtained through a recently discovered 1,3-dipolar cycloaddition reaction between nitriles and bifunctional 2-pyridylselenyl reagents, and their structures were confirmed by the X-ray crystallography. α-Haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles exclusively formed supramolecular dimers via four-center Se···N chalcogen bonding, supported by additional halogen bonding involving α-haloalkyl substituents. The introduction of halogens at the α-position of the substituent R in the selenadiazole core proved effective in promoting supramolecular dimerization, which was unaffected by variation of counterions. Additionally, the impact of cocrystallization with a classical halogen bond donor C6F3I3 on the supramolecular assembly was investigated. Non-covalent interactions were studied using density functional theory calculations and topological analysis of the electron density distribution, which indicated that all ChB, XB and HB interactions are purely non-covalent and attractive in nature. This study underscores the potential of halogen and chalcogen bonding in directing the self-assembly of functional supramolecular materials employing 1,2,4-selenadiazoles derived from recently discovered cycloaddition between nitriles and bifunctional 2-pyridylselenyl reagents.

Influence of Various Strontium Formulations (Ranelate, Citrate, and Chloride) on Bone Mineral Density, Morphology, and Microarchitecture: A Comparative Study in an Ovariectomized Female Mouse Model of Osteoporosis.

Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms-strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)-for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium's potential in bone health, emphasizing variations in efficacy among its forms.

[Chemical Design of Radiohalogenated Agents Using Neopentyl Structure].

Many useful radionuclides exist among the halogen elements. Fluorine-18 (18F) is used for positron emission tomography (PET) diagnosis, iodine-123 and iodine-131 (131I) for single photon emission computed tomography (SPECT) diagnosis, 131I for nuclear medicine therapy, and iodine-125 (125I) for research. Astatine-211 (211At), which can be produced by a cyclotron and is attracting attention as a versatile α-ray emitting radionuclide, also belongs to the halogen family. Therefore, if a labeling agent that can stably hold radio-halogens can be developed, it would be useful for the development of radiotheranostic agents that can be expanded from nuclear medicine diagnosis using PET and SPECT to nuclear medicine therapy using ß--rays and even α-rays. Currently, benzoic acid derivatives are widely used as labeling agents for radio-halogens. The compounds labeled with 18F or radioiodine using this structure retain the radionuclide stably in vivo, but when 211At is labeled using this structure, 211At is rapidly released from the structure in vivo. Therefore, it is desirable to develop labeling agents that can stably hold 18F to 211At. Under these circumstances, we have found that a neopentyl structure with diol can stably retain 211At and 125I in vivo. Furthermore, this structure can also stably retain 18F in vivo. In this review, I would like to introduce the characteristics of neopentyl diol as a radio-halogens labeling agent and the development of radiotheranositc agents using neopentyl diol.

Macroalgal microbiomes unveil a valuable genetic resource for halogen metabolism.

BACKGROUND: Macroalgae, especially reds (Rhodophyta Division) and browns (Phaeophyta Division), are known for producing various halogenated compounds. Yet, the reasons underlying their production and the fate of these metabolites remain largely unknown. Some theories suggest their potential antimicrobial activity and involvement in interactions between macroalgae and prokaryotes. However, detailed investigations are currently missing on how the genetic information of prokaryotic communities associated with macroalgae may influence the fate of organohalogenated molecules. RESULTS: To address this challenge, we created a specialized dataset containing 161 enzymes, each with a complete enzyme commission number, known to be involved in halogen metabolism. This dataset served as a reference to annotate the corresponding genes encoded in both the metagenomic contigs and 98 metagenome-assembled genomes (MAGs) obtained from the microbiome of 2 red (Sphaerococcus coronopifolius and Asparagopsis taxiformis) and 1 brown (Halopteris scoparia) macroalgae. We detected many dehalogenation-related genes, particularly those with hydrolytic functions, suggesting their potential involvement in the degradation of a wide spectrum of halocarbons and haloaromatic molecules, including anthropogenic compounds. We uncovered an array of degradative gene functions within MAGs, spanning various bacterial orders such as Rhodobacterales, Rhizobiales, Caulobacterales, Geminicoccales, Sphingomonadales, Granulosicoccales, Microtrichales, and Pseudomonadales. Less abundant than degradative functions, we also uncovered genes associated with the biosynthesis of halogenated antimicrobial compounds and metabolites. CONCLUSION: The functional data provided here contribute to understanding the still largely unexplored role of unknown prokaryotes. These findings support the hypothesis that macroalgae function as holobionts, where the metabolism of halogenated compounds might play a role in symbiogenesis and act as a possible defense mechanism against environmental chemical stressors. Furthermore, bacterial groups, previously never connected with organohalogen metabolism, e.g., Caulobacterales, Geminicoccales, Granulosicoccales, and Microtrichales, functionally characterized through MAGs reconstruction, revealed a biotechnologically relevant gene content, useful in synthetic biology, and bioprospecting applications. Video Abstract.

Effects of Halides on Organic Compound Degradation during Plasma Treatment of Brines.

Plasma has been proposed as an alternative strategy to treat organic contaminants in brines. Chemical degradation in these systems is expected to be partially driven by halogen oxidants, which have been detected in halide-containing solutions exposed to plasma. In this study, we characterized specific mechanisms involving the formation and reactions of halogen oxidants during plasma treatment. We first demonstrated that addition of halides accelerated the degradation of a probe compound known to react quickly with halogen oxidants (i.e., para-hydroxybenzoate) but did not affect the degradation of a less reactive probe compound (i.e., benzoate). This effect was attributed to the degradation of para-hydroxybenzoate by hypohalous acids, which were produced via a mechanism involving halogen radicals as intermediates. We applied this mechanistic insight to investigate the impact of constituents in brines on reactions driven by halogen oxidants during plasma treatment. Bromide, which is expected to occur alongside chloride in brines, was required to enable halogen oxidant formation, consistent with the generation of halogen radicals from the oxidation of halides by hydroxyl radical. Other constituents typically present in brines (i.e., carbonates, organic matter) slowed the degradation of organic compounds, consistent with their ability to scavenge species involved during plasma treatment.

Impact of Halogen Bonds on Protein-Peptide Binding and Protein Structural Stability Revealed by Computational Approaches.

Halogen bonds (XBs) are essential noncovalent interactions in molecular recognition and drug design. Current studies on XBs in drug design mainly focus on the interactions between halogenated ligands and target proteins, lacking a systematic study of naturally existing and artificially prepared halogenated residue XBs (hr_XBs) and their characteristics. Here, we conducted a computational study on the potential hr_XBs in proteins/peptides using database searching, quantum mechanics calculations, and molecular dynamics simulations. XBs at the protein-peptide interaction interfaces are found to enhance their binding affinity. Additionally, the formation of intramolecular XBs (intra_XBs) within proteins may significantly contribute to the structural stability of structurally flexible proteins while having a minor impact on proteins with inherently high structural rigidity. Impressively, introducing halogens without the formation of intra_XBs may lead to a decrease in the protein structural stability. This study enriches our understanding of the roles and effects of halogenated residue XBs in biological systems.

Controlled synthesis of sulfhydryl-dendritic mesoporous silica nanospheres for ultrafast extraction and sensitive analysis of organochlorine herbicides containing amide groups.

The distinctive morphology of dendritic mesoporous silica nanoparticles (DMSN) has recently attracted considerable attention in scientific community. However, synthesis of DMSN with well-defined structure and uniform size for ultrafast extraction of trace herbicide residues from environmental and food samples remains to be a compelling challenge. In this study, sulfhydryl functionalized dendritic mesoporous silica (SH-DMSN) was synthesized and the SH-DMSN showcases monodisperse microspheres with flower shape and precisely tailored and controllable pore sizes. This distinctive structural configuration accelerates mass transfer within the silica layer, resulting in heightened adsorption efficiencies. Furthermore, the particle sizes (455, 765, and 808) of the adsorbent can be meticulously fine-tuned by introducing distinct templates. Specifically, when the particle size is 765 nm, the optimized SH-DMSN exhibits a substantial specific surface area (691.32 m²/g), outstanding adsorption efficiencies (>90 %), remarkably swift adsorption and desorption kinetics (2 min and 3 min, respectively), and exceptional stability. The superior adsorption capabilities of this novel adsorbent, ranging from 481.65 to 1021.7 µg/g for organochlorine herbicides containing amide groups, can be attributed to the interplay of S-π interactions, halogen bonding, and electrostatic attraction interaction. These interactions involve the lone pair electrons of sulfhydryl and silanol groups with the π-electrons, halogen atoms and amide groups in herbicide molecules. This study not only offers a new perspective on advancing the practical utilization of dendritic mesoporous silica but also provides a pragmatic strategy for the separation and analysis of herbicides in diverse sample matrices.

Structural Insights on the Role of Halogen Bonding in Protein MEK Kinase-Inhibitor Complexes.

Kinases are enzymes that play a critical role in governing essential biological processes. Due to their pivotal involvement in cancer cell signaling, they have become key targets in the development of anti-cancer drugs. Among these drugs, those containing the 2,4-dihalophenyl moiety demonstrated significant potential. Here we show how this moiety, particularly the 2-fluoro-4-iodophenyl one, is crucial for the structural stability of the formed drug-enzyme complexes. Crystallographic analysis of reported kinase-inhibitor complex structures highlights the role of the halogen bonding that this moiety forms with specific residues of the kinase binding site. This interaction is not limited to FDA-approved MEK inhibitors, but it is also relevant for other kinase inhibitors, indicating its broad relevance in the design of this class of drugs.

Detection of Bromochloro Alkanes in Indoor Dust Using a Novel CP-Seeker Data Integration Tool.

Bromochloro alkanes (BCAs) have been manufactured for use as flame retardants for decades, and preliminary environmental risk screening suggests they are likely to behave similarly to polychlorinated alkanes (PCAs), subclasses of which are restricted as Stockholm Convention Persistent Organic Pollutants (POPs). BCAs have rarely been studied in the environment, although some evidence suggests they may migrate from treated-consumer materials into indoor dust, resulting in human exposure via inadvertent ingestion. In this study, BCA-C14 mixture standards were synthesized and used to validate an analytical method. This method relies on chloride-enhanced liquid chromatography-electrospray ionization-Orbitrap-high resolution mass spectrometry (LC-ESI-Orbitrap-HRMS) and a novel CP-Seeker integration software package for homologue detection and integration. Dust sample preparation via ultrasonic extraction, acidified silica cleanup, and fractionation on neutral silica cartridges was found to be suitable for BCAs, with absolute recovery of individual homologues averaging 66 to 78% and coefficients of variation ≤10% in replicated spiking experiments (n = 3). In addition, a total of 59 indoor dust samples from six countries, including Australia (n = 10), Belgium (n = 10), Colombia (n = 10), Japan (n = 10), Thailand (n = 10), and the United States of America (n = 9), were analyzed for BCAs. BCAs were detected in seven samples from the U.S.A., with carbon chain lengths of C8, C10, C12, C14, C16, C18, C24 to C28, C30 and C31 observed overall, though not detected in samples from any other countries. Bromine numbers of detected homologues in the indoor dust samples ranged Br1-4 as well as Br7, while chlorine numbers ranged Cl2-11. BCA-C18 was the most frequently detected, observed in each of the U.S.A. samples, while the most prevalent degrees of halogenation were homologues of Br2 and Cl4-5. Broad estimations of BCA concentrations in the dust samples indicated that levels may approach those of other flame retardants in at least some instances. These findings suggest that development of quantification strategies and further investigation of environmental occurrence and health implications are needed.

Machine learning framework for predicting cytotoxicity and identifying toxicity drivers of disinfection byproducts.

Drinking water disinfection can result in the formation disinfection byproducts (DBPs, > 700 have been identified to date), many of them are reportedly cytotoxic, genotoxic, or developmentally toxic. Analyzing the toxicity levels of these contaminants experimentally is challenging, however, a predictive model could rapidly and effectively assess their toxicity. In this study, machine learning models were developed to predict DBP cytotoxicity based on their chemical information and exposure experiments. The Random Forest model achieved the best performance (coefficient of determination of 0.62 and root mean square error of 0.63) among all the algorithms screened. Also, the results of a probabilistic model demonstrated reliable model predictions. According to the model interpretation, halogen atoms are the most prominent features for DBP cytotoxicity compared to other chemical substructures. The presence of iodine and bromine is associated with increased cytotoxicity levels, while the presence of chlorine is linked to a reduction in cytotoxicity levels. Other factors including chemical substructures (CC, N, CN, and 6-member ring), cell line, and exposure duration can significantly affect the cytotoxicity of DBPs. The similarity calculation indicated that the model has a large applicability domain and can provide reliable predictions for DBPs with unknown cytotoxicity. Finally, this study showed the effectiveness of data augmentation in the scenario of data scarcity.

Enhanced uranium removal from aqueous solution by core-shell Fe0@Fe3O4: Insight into the synergistic effect of Fe0 and Fe3O4.

In this study, Fe0@Fe3O4 was synthesized and used to remove U(VI) from groundwater. Different experimental conditions and cycling experiments were used to investigate the performance of Fe0@Fe3O4 in the U(VI) removal, and the XRD, TEM, XPS and XANES techniques were employed to characterize the Fe0@Fe3O4. The results showed that the U(VI) removal efficiency of Fe0@Fe3O4 was 48.5 mg/g that was higher than the sum of removal efficiency of Fe0 and Fe3O4. The uranium on the surface of Fe0@Fe3O4 mainly existed as U(IV), followed by U(VI) and U(V). The Fe0 content decreased after reaction, while the Fe3O4 content increased. Based on the results of experiments and characterization, the enhanced removal efficiency of Fe0@Fe3O4 was attributed to the synergistic effect of Fe0 and Fe3O4 in which Fe3O4 accelerated the Fe0 corrosion that promoted the progressively formation of Fe(II) that promoted the reduction of adsorbed U(VI) to U(IV) and incorporated U(VI) to U(V). The performance of Fe0@Fe3O4 at near-neutrality condition was better than at acidic and alkalic conditions. The chloride ions, sulfate ions and nitrate ions showed minor effect on the Fe0@Fe3O4 performance, while carbonate ions exhibited significant inhibition. The metal cations showed different effect on the Fe0@Fe3O4 performance. The removal efficiency of Fe0@Fe3O4 decreased with the number of cycling experiment. Ionizing radiation could regenerate the used Fe0@Fe3O4. This study provides insight into the U(VI) removal by Fe0@Fe3O4 in aqueous solution.

Comparative analysis of chlorine-resistant bacteria after chlorination and chloramination in drinking water treatment plants.

Chlorine-resistant bacteria (CRB) in drinking water treatment plants (DWTPs) jeopardize water quality and pose a potential risk to human health. However, the specific response of CRB to chlorination and chloramination remains uncharacterized. Therefore, we analyzed 16 S rRNA sequencing data from water samples before and after chlorination and chloramination taken between January and December 2020. Proteobacteria and Firmicutes dominated all finished water samples. After chloramination, Acinetobacter, Pseudomonas, Methylobacterium, Ralstonia, and Sphingomonas were the dominant CRB, whereas Ralstonia, Bacillus, Acinetobacter, Pseudomonas, and Enterococcus were prevalent after chlorination. Over 75% of the CRB e.g. Acinetobacter, Pseudomonas, Bacillus, and Enterococcus were shared between the chlorination and chloramination, involving potentially pathogens, such as Acinetobacter baumannii and Pseudomonas aeruginosa. Notably, certain genera such as Faecalibacterium, Geobacter, and Megasphaera were enriched as strong CRB after chloramination, whereas Vogesella, Flavobacterium, Thalassolituus, Pseudoalteromonas, and others were enriched after chlorination according to LEfSe analysis. The shared CRB correlated with temperature, pH, and turbidity, displaying a seasonal pattern with varying sensitivity to chlorination and chloramination in cold and warm seasons. These findings enhance our knowledge of the drinking water microbiome and microbial health risks, thus enabling better infectious disease control through enhanced disinfection strategies in DWTPs.

Effects of dissolved organic matter and halogen ions on phototransformation of pharmaceuticals and personal care products in aquatic environments.

Photochemical reactions contribute to the attenuation and transformation of pharmaceuticals and personal care products (PPCPs) in surface natural waters. Nevertheless, effects of DOM and halogen ions on phototransformation of PPCPs remain elusive. This work selected disparate PPCPs as target pollutants to investigate their aquatic phototransformation processes. Results show that PPCPs containing multiple electron-donating groups (-OH, -NH2, -OR, etc.) are more reactive with photochemically produced reactive intermediates (PPRIs) such as triplet DOM (3DOM*), singlet oxygen (1O2), and reactive halogen species (RHSs), relative to PPCPs containing electron-withdrawing groups (-NOR, -COOR, -OCR, etc.). The generation of RHSs as a result of the coexistance of DOM and halide ions changed the contribution of PPRIs to the photochemical conversion of PPCPs during their migration from fresh water to seawater. For PPCPs (AMP, SMZ, PN, NOR, CIP, etc) with highly reactive groups toward RHSs, the generation of RHSs facilitated their photolysis in halide ion-rich waters, where Cl- plays a critical role in the photochemical transformation of PPCPs. Density functional theory (DFT) calculations showed that single electron transfer and H-abstraction are main reaction pathways of RHSs with the PPCPs. These results demonstate the irreplaceable roles of PPRIs and revealing the underlying reaction mechanisms during the phototransformation of PPCPs, which contributes to a better understanding of the environmental behaviors of PPCPs in complex aquatic environments.

How to achieve adequate quenching for DBP analysis in drinking water?

Quenching is an important step to terminate disinfection during preparation of disinfected water samples for the analysis of disinfection byproducts (DBPs). However, an incomplete quenching might result in continued reactions of residual chlorine, whereas an excessive quenching might decompose target DBPs. Therefore, an adequate quenching to achieve simultaneous disinfection termination and DBP preservation is of particular importance. In this study, the two-stage reaction kinetics of chlorine and three commonly used quenching agents (i.e., ascorbic acid, sodium thiosulfate, and sodium sulfite) were determined. Stopping quenching during the first stage prevented interactions of residual chlorine with natural organic matter. Complete quenching was achieved by minimizing the quenching time for ascorbic acid and sodium sulfite, while limiting the quenching time to less than 3 min for sodium thiosulfate. At the optimized quenching times, the molar ratios (MRs) of quenching agent to chlorine were 1.05, 1.10, and 0.75 for ascorbic acid, sodium sulfite, and sodium thiosulfate, respectively. The destructive effects of the three quenching agents on total organic halogen (TOX) followed the rank order of ascorbic acid (33.7-64.8 %) < sodium sulfite (41.6-72.8 %) < sodium thiosulfate (43.3-73.2 %), and the destructive effects on aliphatic DBPs also followed the rank order of ascorbic acid (29.5-44.5 %) < sodium sulfite (34.9-51.9 %) < sodium thiosulfate (46.9-53.2 %). For total organic chlorine (TOCl) and aliphatic DBPs, the quenching behavior itself had more significant destructive effect than the quenching agent type/dose and quenching time, but for total organic bromine (TOBr), the destructive effect caused by quenching agent type/dose and quenching time was more significant. High-dose, long-duration quenching enhanced the reduction of TOX, but had little effect on aliphatic DBPs. Additionally, the three quenching agents reduced the levels of halophenols (except for tribromophenol), while maintained or increased the levels of tribromophenol, halobenzoic/salicylic acids, and halobenzaldehydes/salicylaldehydes. To achieve adequate quenching for overall DBP analysis in chlorinated water samples, it is recommended to use ascorbic acid at a quenching agent-to-chlorine MR of 1.0 for a quenching time of < 0.5 h.

Recent advances in eco-friendly technology for decontamination of pulp and paper mill industrial effluent: a review.

The economic development of a country directly depends upon industries. But this economic development should not be at the cost of our natural environment. A substantial amount of water is spent during paper production, creating water scarcity and generating wastewater. Therefore, the Pollution Control Board classifies this industry into red category. Water is used in different papermaking stages such as debarking, pulping or bleaching, washing, and finishing. The wastewater thus generated contains lignin and xenobiotic compounds such as resin acids, chlorinated lignin, phenols, furans, dioxins, chlorophenols, adsorbable organic halogens (AOX), extractable organic halogens (EOCs), polychlorinated biphenyls, plasticizers, and polychlorinated dibenzodioxins. Nowadays, several microorganisms are used in the detoxification of these hazardous effluents. Researchers have found that microbial degradation is the most promising treatment method to remove high biological oxygen demand (BOD) and chemical oxygen demand (COD) from wastewater. Microorganisms also remove AOX toxicity, chlorinated compounds, suspended solids, color, lignin, derivatives, etc. from the pulp and paper mill effluents. But in the current scenario, mill effluents are known to deteriorate the environment and therefore it is highly desirable to deploy advanced technologies for effluent treatment. This review summarizes the eco-friendly advanced treatment technologies for effluents generated from pulp and paper mills.

Insights into microbial contamination and antibiotic resistome traits in pork wholesale market: An evaluation of the disinfection effect of sodium hypochlorite.

Chlorine and its derivatives, such as sodium hypochlorite (NaClO) and chlorine dioxide, are frequently employed as disinfectants throughout the pork supply chain in China. Nevertheless, the extensive use of NaClO has the potential to cause the creation of 'chlorine-tolerant bacteria' and accelerate the evolution of antibiotic resistance. This study evaluated the efficacy of NaClO disinfection by examining alterations in the microbiome and resistome of a pork wholesale market (PWM), and bacteria isolation and analysis were performed to validate the findings. As expected, the taxonomic compositions of bacteria was significantly different before and after disinfection. Notably, Salmonella enterica (S. enterica), Salmonella bongori (S. bongori), Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa) were observed on all surfaces, indicating that the application of NaClO disinfection treatment in PWM environments for pathogenic bacteria is limited. Correlations were identified between antibiotic resistance genes (ARGs) associated with aminoglycosides (aph(3'')-I, aph(6')-I), quinolone (qnrB, abaQ), polymyxin (arnA, mcr-4) and disinfectant resistance genes (emrA/BD, mdtA/B/C/E/F). Furthermore, correlations were found between risk Rank I ARGs associated with aminoglycoside (aph(3')-I), tetracycline (tetH), beta_lactam (TEM-171), and disinfectant resistance genes (mdtB/C/E/F, emrA, acrB, qacG). Importantly, we found that Acinetobacter and Salmonella were the main hosts of disinfectant resistance genes. The resistance mechanisms of the ARGs identified in PWM were dominated by antibiotic deactivation (38.7%), antibiotic efflux (27.2%), and antibiotic target protection (14.4%). The proportion of genes encoding efflux pumps in the PWM resistome increased after disinfection. Microbial cultures demonstrated that the traits of microbial contamination and antibiotic resistane were consistent with those observed by metagenomic sequencing. This study highlights the possibility of cross-resistance between NaClO disinfectants and antibiotics, which should not be ignored.

Pioneering Piezoelectric-Driven Atomic Hydrogen for Efficient Dehalogenation of Halogenated Organic Pollutants.

The electrocatalytic hydrodehalogenation (EHDH) process mediated by atomic hydrogen (H*) is recognized as an efficient method for degrading halogenated organic pollutants (HOPs). However, a significant challenge is the excessive energy consumption resulting from the recombination of H* to H2 production in the EHDH process. In this study, a promising strategy was proposed to generate piezo-induced atomic H*, without external energy input or chemical consumption, for the degradation and dehalogenation of HOPs. Specifically, sub-5 nm Ni nanoparticles were subtly dotted on an N-doped carbon layer coating on BaTiO3 cube, and the resulted hybrid nanocomposite (Ni-NC@BTO) can effectively break C-X (X = Cl and F) bonds under ultrasonic vibration or mechanical stirring, demonstrating high piezoelectric driven dehalogenation efficiencies toward various HOPs. Mechanistic studies revealed that the dotted Ni nanoparticles can efficiently capture H* to form Ni-H* (Habs) and drive the dehalogenation process to lower the toxicity of intermediates. COMSOL simulations confirmed a "chimney effect" on the interface of Ni nanoparticle, which facilitated the accumulation of H+ and enhanced electron transfer for H* formation by improving the surface charge of the piezocatalyst and strengthening the interfacial electric field. Our work introduces an environmentally friendly dehalogenation method for HOPs using the piezoelectric process independent of the external energy input and chemical consumption.

Chlorination of antiviral drug ribavirin: Kinetics, nontargeted identification, and concomitant toxicity evolution.

Residual antiviral drugs in wastewater may increase the risk of generating transformation products (TPs) during wastewater treatment. Therefore, chlorination behavior and toxicity evolution are essential to understand the secondary ecological risk associated with their TPs. Herein, chlorination kinetics, transformation pathways, and secondary risks of ribavirin (RBV), one of the most commonly used broad-spectrum antivirals, were investigated. The pH-dependent second-order rate constants k increased from 0.18 M-1·s-1 (pH 5.8) to 1.53 M-1·s-1 (pH 8.0) due to neutral RBV and ClO- as dominant species. 12 TPs were identified using high-resolution mass spectrometry in a nontargeted approach, of which 6 TPs were reported for the first time, and their chlorination pathways were elucidated. The luminescence inhibition rate of Vibrio fischeri exposed to chlorinated RBV solution was positively correlated with initial free active chlorine, probably due to the accumulation of toxic TPs. Quantitative structure-activity relationship prediction identified 7 TPs with elevated toxicity, concentrating on developmental toxicity and bioconcentration factors, which explained the increased toxicity of chlorinated RBV. Overall, this study highlights the urgent need to minimize the discharge of toxic chlorinated TPs into aquatic environments and contributes to environmental risk control in future pandemics and regions with high consumption of antivirals.

Hybrid 2D Supramolecular Organic Frameworks (SOFs) Assembled by the Cooperative Action of Hydrogen and Halogen Bonding and π⋯π Stacking Interactions.

The cis- and trans-isomers of 6-(3-(3,4-dichlorophenyl)-1,2,4-oxadiazol-5-yl)cyclohex-3-ene-1-carboxylic acid (cis-A and trans-A) were obtained by the reaction of 3,4-dichloro-N'-hydroxybenzimidamide and cis-1,2,3,6-tetrahydrophthalic anhydride. Cocrystals of cis-A with appropriate solvents (cis-A‧½(1,2-DCE), cis-A‧½(1,2-DBE), and cis-A‧½C6H14) were grown from 1,2-dichloroethane (1,2-DCE), 1,2-dibromoethane (1,2-DBE), and a n-hexane/CHCl3 mixture and then characterized by X-ray crystallography. In their structures, cis-A is self-assembled to give a hybrid 2D supramolecular organic framework (SOF) formed by the cooperative action of O-H⋯O hydrogen bonding, Cl⋯O halogen bonding, and π⋯π stacking. The self-assembled cis-A divides the space between the 2D SOF layers into infinite hollow tunnels incorporating solvent molecules. The energy contribution of each noncovalent interaction to the occurrence of the 2D SOF was verified by several theoretical approaches, including MEP and combined QTAIM and NCIplot analyses. The consideration of the theoretical data proved that hydrogen bonding (approx. -15.2 kcal/mol) is the most important interaction, followed by π⋯π stacking (approx. -11.1 kcal/mol); meanwhile, the contribution of halogen bonding (approx. -3.6 kcal/mol) is the smallest among these interactions. The structure of the isomeric compound trans-A does not exhibit a 2D SOF architecture. It is assembled by the combined action of hydrogen bonding and π⋯π stacking, without the involvement of halogen bonds. A comparison of the cis-A structures with that of trans-A indicated that halogen bonding, although it has the lowest energy in cis-A-based cocrystals, plays a significant role in the crystal design of the hybrid 2D SOF. The majority of the reported porous halogen-bonded organic frameworks were assembled via iodine and bromine-based contacts, while chlorine-based systems-which, in our case, are structure-directing-were unknown before this study.