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Background: Animal models for the study of tendinopathy and bone-tendon (B-T) junction repair have been established in the past for sports medicine research. As healing at the B-T junction is difficult and sometimes delayed, establishing a delayed B-T healing experimental model is therefore essential to study the efficacy of potential biophysical and biological interventions for treatment of B-T junction healing. Objective: To test the hypothesis that a delay in B-T healing could be modelled by shielding the B-T healing interface for the initial few weeks. Methods: Using an established partial patellectomy model in rabbits, the B-T healing interface was shielded with a latex slice for the first 4 postoperative weeks in mature female rabbits. The characteristics of delay in B-T repair (n = 10) compared with controls (n = 10) were evaluated at 8 and 12 postoperative weeks. Results: Radiology showed consistent delay in osteogenesis at the healing interface in all samples in the delayed healing group; growth of new bone was only 25.8% and 50.1% of that in the control group at weeks 8 and 12, respectively. Bone mineral density was 56.0% lower in the delayed healing group at week 8, but this difference diminished at week 12. The quality of B-T healing was poor in the delayed healing group, with 22.9% and 24.2% lower failure load than the control group at weeks 8 and 12, respectively. The healing quality was also reflected by histological findings. Conclusions: A delayed B-T healing experimental model was established for the first time for future sports medicine research. [ABSTRACT FROM AUTHOR]

An on-line high performance liquid chromatography (HPLC)-diode array detector (DAD)-electrospray ionization mass spectrometry (ESI-MS) method has been developed to quantify simultaneously eight bioactive chemical components in Houttuynia cordata Thunb and related Saururaceae medicinal plants. Simultaneous separation of these eight compounds was achieved on a C(18) analytical column with gradient elution of acetonitrile and 0.2% acetic acid (v/v) at a flow rate of 0.6 mL/min and being detected at 280 nm. These eight compounds were completely separated within 90 min. Good linear regression relationship (r(2)>0.9978) within test ranges was shown in all calibration curves. Good repeatabilty for the quantification of these eight compounds in H.cordata was also demonstrated in this method, with intra- and inter-day variations less than 3.0%. The method established was successfully applied to quantify eight bioactive compounds in closely related species of H.cordata, which provides a new basis for quality assessment of H.cordata. [ABSTRACT FROM AUTHOR]

Aims This study evaluated the prevalence and reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence with a purpose to determine whether it is best conceptualized within the category of hallucinogens, amphetamines or its own category. Design Test-re-test study. Participants MDMA users (life-time use >5 times) were recruited in St Louis, Miami and Sydney ( n = 593). The median life-time MDMA consumption was 50 pills at the baseline. Measurements The computerized Substance Abuse Module for Club Drug (CD-SAM) was used to assess MDMA abuse and dependence. The Discrepancy Interview Protocol (DIP) was used to determine the reasons for the discrepant responses between the two interviews. Reliability of diagnoses, individual diagnostic criteria and withdrawal symptoms was examined using the kappa coefficient ([kappa]). Findings For baseline data, 15% and 59% met MDMA abuse and dependence, respectively. Substantial test-re-test reliability of the diagnoses was observed consistently across cities ([kappa] = 0.69). 'Continued use despite knowledge of physical/psychological problems' (87%) and 'withdrawal' (68%) were the two most prevalent dependence criteria. 'Physically hazardous use' was the most prevalent abuse criterion. Six dependence criteria and all abuse criteria were reported reliably across cities ([kappa]: 0.53-0.77). Seventeen of 19 withdrawal symptoms showed consistency in the reliability across cities. The most commonly reported reason for discrepant responses was 'interpretation of question changed'. Only a small proportion of the total discrepancies were attributed to lying or social desirability. Conclusion The adopted DSM-IV diagnostic classification for MDMA abuse and dependence was moderately reliable across cities. Findings on MDMA withdrawal support the argument that MDMA should be separated from other hallucinogens in DSM. [ABSTRACT FROM AUTHOR]

While the use of health food and over-the-counter drugs for health promotion and adjuvant therapy is becoming increasingly popular, the concern about adverse effects is mounting. The possible adverse effects that may arise from drug interactions between these herbal preparations and standard modem therapy are equally worrying. Herbal toxicity and adverse effects are well documented in classical Chinese medicinal volumes. Interactions between herbal preparations and standard modem therapy are known. Extensive work needs to be done before useful guidelines can be established. However, based on available reports and clinical observations, some commonly used herbs and Chinese medicines have already demonstrated the need for special attention when used together with modern therapy. This paper analyzes the important material already available, and would serve as a preliminary checklist for patients who are taking herbal preparations, while at the same time receiving treatment from modern medicine. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antrodia camphorata (AC) is an important fungus native to Taiwanese forested regions. Scientific studies have demonstrated that extracts of AC possess a variety of pharmacological functions. This study aims to identify the full profile fingerprint of nucleosides and nucleobases in mycelial AC and to assess the quality of two commercial mycelial AC products. METHODS: High-performance liquid chromatography coupled with diode array detector and mass spectrometry was employed to identify the major components in mycelial AC. The chemical separation was carried out using a gradient program on a reverse phase Alltima C18 AQ analytical column (250 x 4.6 mm, 5 mum) with the mobile phase consisting of deionized water and methanol. RESULTS: Ten nucleosides and nucleobases, two maleimide derivatives, and a sterol were identified as the major constituents in mycelial AC. These groups of chemical compounds constitute the first chromatographic fingerprint as an index for quality assessment of this medicinal fungus. CONCLUSIONS: This study provides the first chromatographic fingerprint to assess the quality of mycelial AC. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the mechanism of low-magnitude high-frequency vibration (LMHFV) treatment on angiogenesis and blood flow for enhancement of fracture healing. Nine-month-old ovariectomized (OVX) and sham-operated (Sham) rats received closed fractures creation at the femora and were randomized into LMHFV treatment (Sham-V, OVX-V) or control (Sham-C, OVX-C) groups. Pulsed-wave Doppler indicated an increase in blood flow velocity of the femoral artery at weeks 2 (OVX pair: p = 0.030) and 4 (OVX pair: p = 0.012; Sham pair: p = 0.020) post-treatment. Significantly enhanced vascular volume (VV) at the fracture site in the vibration groups was demonstrated by 3-D high-frequency power Doppler at week 2 (Sham pair: p = 0.021) and micro-computed tomography (microCT) microangiography at weeks 2 (OVX pair: p = 0.009) and 4 (OVX pair: p = 0.034), which echoed the osteogenesis findings by radiographic and microCT analysis. VV in the OVX groups was inferior to the Sham groups. However, OVX-V showed higher percentages of angiogenic enhancement than Sham-V. Despite impaired neo-angiogenesis in osteoporotic fractures, LMHFV could increase blood flow and angiogenesis in both normal and osteoporotic fractures, thus enhancing fracture healing. [ABSTRACT FROM AUTHOR]

Low-intensity pulsed ultrasound (LIPUS) with I(SATA)= 30 mW/cm(2) has been proven in facilitating fracture healing, which the spatial average intensity over the on period (I(SATP)) equals 150 mW/cm(2). As active ultrasound wave is only delivered during the on period, we postulate 150 mW/cm(2) is responsible for the beneficial effect of LIPUS. In this study, we compare the biologic effects of 30 mW/cm(2) and 150 mW/cm(2). We propose I(SATA) = 150 mW/cm(2) could further enhance fracture healing process. Closed femoral fractured Sprague-Dawley rats were randomized into control, LIPUS-30 (30 mW/cm(2)) and LIPUS-150 (150 mW/cm(2)) groups. Weekly radiographs and endpoint microCT, histomorphometry, and biomechanical tests were performed. The results show that LIPUS-30 had significantly higher low-density bone volume fraction and woven bone percentage than that of control and LIPUS-150 in microCT and histologic measurements, respectively. Mechanically, failure torque of LIPUS-30 was significantly higher than control and LIPUS-150 at week 6. In conclusion, LIPUS at I(SATA)= 150 mW/cm(2) did not further enhance fracture healing. [ABSTRACT FROM AUTHOR]

Quaternary ammonium compounds (QACs) are widely detected in the aquatic environment due to their extensive use in a wide array of antibacterial products during the pandemic. In the current study, UV/monochloramine (UV/NH 2 Cl) was used to degrade three typical QACs, namely benzalkonium compounds (BACs), dialkyl dimethyl ammonium compounds (DADMACs), and alkyl trimethyl ammonium compounds (ATMACs). This process achieved high efficiency in removing BACs from water samples. The transformation products of QACs treated with UV/NH 2 Cl were identified and characterized using a high-resolution mass spectrometer, and transformation pathways were proposed. The formation of N-nitroso-N-methyl-N-alkylamines (NMAs) and N-nitrosodimethylamine (NDMA) were observed during QAC degradation. The molar formation yield of NDMA from C 12 -BAC was 0.04 %, while yields of NMAs reached 1.05 %. The ecotoxicity of NMAs derived from QACs was predicted using ECOSAR software. The increased toxicity could be attributed to the formation of NMAs with longer alkyl chains; these NMAs, exhibited a one order of magnitude increase in toxicity compared to their parent QACs. This study provides evidence that QACs are the specific and significant precursors of NMAs. Greater attention should be given to NMA formation and its potential threat to the ecosystem, including humans., 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 © 2024 Elsevier B.V. All rights reserved.)

Using current water treatment systems, significant amounts of microplastics (MPs) are passing through and being released into the aquatic environment. However, we do not clearly know what effects disinfection processes have had on these particles. In this study, we applied inductively coupled plasma-mass spectrometry (ICP-MS) operating in time-resolved analysis (TRA) mode for quantifying changes in the chlorine (Cl) content of MPs under a variety of water treatment scenarios. Our results illustrated that time-resolved ICP-MS offers a potential method for sensitive and direct analysis of Cl content, including Cl mass and chlorine association (%Cl/C), of discrete particles in the MP suspension by the fast sequential measurements of signals from 35 Cl 1 H 2 and 12 C 1 H. Our research, across various water treatment scenarios, also showed that polystyrene (PS) MPs exhibited greater reactivity to Cl disinfectant after being pre-disinfected with UV light and in mildly acidic to neutral pH environments. It is noteworthy that about half of the particles in MP suspension exposed to 10 mg Cl 2 /L, a typical Cl dose applied in water treatment, were chlorinated, and had a Cl content comparable to that of particles subjected to extreme conditions. Of even greater concern is the fact that our cell viability tests revealed that chlorinated MPs induced considerably higher rates of cell death in both human A549 and Caco-2 cells, and that the effects were Cl dose- and polymer type-dependent. Overall, this study demonstrates the potential of time-resolved ICP-MS as a valuable technique for quantifying the Cl content of MP particles, which is crucial to assessing the fate and transformation of MPs in our water supply and treatment systems., 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 © 2024 Elsevier B.V. All rights reserved.)

Oxidative stress induces autooxidation of polyunsaturated fatty acids, producing numerous isoprostanoids and isofuranoids. These oxidized products are measurable in human plasma and urine and serve as oxidative stress biomarkers for chronic diseases. This chapter details the preparation and measurement of α-linolenic acid-derived phytoprostanes and phytofurans in human samples using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QToF-MS/MS)., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Nanoplastics (NPs) have raised concerns about the combined toxicity to living organisms due to their ability to adsorb heavy metals. There is still uncertainty, however, whether NPs combined with heavy metals exert adverse effects on intestinal microenvironment, especially the intestinal cells and microbiota. Herein, the combined effects of 500 nm spherical-shaped polystyrene nanoplastics (PSNPs) and copper ions (Cu 2+ ) on intestinal cells and gut microbiota were assessed using HCT-116 cells and zebrafish models. The combined exposure of PSNPs (10 mg/L) and Cu 2+ (0.5 mg/L) induced more severer hatching interference of zebrafish embryos, deformation, and mortality. In larval stage, PSNPs (10 mg/L) accumulated and carried more Cu 2+ in the gastrointestinal tract (GIT) of zebrafish after co-exposure for 5 days. Excessive neutrophil recruitment and oxidative stress in GIT of zebrafish larvae were observed. The mechanism of the combined toxicity was revealed by transmission electron microscopy (TEM) showing the injuries of GIT, transcriptome and 16S rDNA gene sequencing showing the toxicity pathways, including oxidative phosphorylation and respiratory electron transport chain, as well as microbial community analysis showing the induced microbiota dysbiosis. In vitro tests using HCT-116 cells showed that PSNPs (10 mg/L) and Cu 2+ (0.5 mg/L) increased cell death while decreasing ATP concentration and mitochondrial membrane potential after 48 h exposure. These findings may provide new insights into the combined toxicity of nanoplastics and heavy metals in the intestinal microenvironment., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition., Purpose: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms., Study Design and Methods: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds., Results: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms., Conclusion: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia., 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 © 2024. Published by Elsevier GmbH.)

The incidence of isoniazid (INH) resistant Mycobacterium tuberculosis is increasing globally. This study aimed to identify the molecular mechanisms behind the development of INH resistance in M. tuberculosis strains collected from the same patients during the standard course of treatment. Three M. tuberculosis strains were collected from a patient before and during antituberculosis (anti-TB) therapy. The strains were characterized using phenotypic drug susceptibility tests, Mycobacterial Interspersed Repeated Unit-Variable-Number Tandem Repeats (MIRU-VNTR), and whole-genome sequencing (WGS) to identify mutations associated with INH resistance. To validate the role of the novel mutations in INH resistance, the mutated katG genes were electroporated into a KatG-deleted M. tuberculosis strain (GA03). Three-dimensional structures of mutated KatG were modeled to predict their impact on INH binding. The pre-treatment strain was susceptible to INH. However, two INH-resistant strains were isolated from the patient after anti-TB therapy. MIRU-VNTR and WGS revealed that the three strains were clonally identical. A missense mutation (P232L) and a nonsense mutation (Q461Stop) were identified in the katG of the two post-treatment strains, respectively. Transformation experiments showed that katG of the pre-treatment strain restored INH susceptibility in GA03, whereas the mutated katG genes from the post-treatment strains rendered negative catalase activity and INH resistance. The protein model indicated that P232L reduced INH-KatG binding affinity while Q461Stop truncated gene transcription. Our results showed that the two katG mutations, P232L and Q461Stop, accounted for the co-emergence of INH-resistant clones during anti-TB therapy. The inclusion of these mutations in the design of molecular assays could increase the diagnostic performance.IMPORTANCEThe evolution of drug-resistant strains of Mycobacterium tuberculosis within the lung lesions of a patient has a detrimental impact on treatment outcomes. This is particularly concerning for isoniazid (INH), which is the most potent first-line antimycobacterial drug. However, the precise genetic factors responsible for drug resistance in patients have not been fully elucidated, with approximately 15% of INH-resistant strains harboring unknown genetic factors. This raises concerns about the emergence of drug-resistant clones within patients, further contributing to the global epidemic of resistance. In this study, we revealed the presence of two novel katG mutations, which emerged independently due to the stress exerted by antituberculosis (anti-TB) treatment on a parental strain. Importantly, we experimentally demonstrated the functional significance of both mutations in conferring resistance to INH. Overall, this research sheds light on the genetic mechanisms underlying the evolution of INH resistance within patients and provides valuable insights for improving diagnostic performance by targeting specific mutations., Competing Interests: The authors declare no conflict of interest.

There is an emerging potential for digital assessment of depression. In this study, Chinese patients with major depressive disorder (MDD) and controls underwent a week of multimodal measurement including actigraphy and app-based measures (D-MOMO) to record rest-activity, facial expression, voice, and mood states. Seven machine-learning models (Random Forest [RF], Logistic regression [LR], Support vector machine [SVM], K-Nearest Neighbors [KNN], Decision tree [DT], Naive Bayes [NB], and Artificial Neural Networks [ANN]) with leave-one-out cross-validation were applied to detect lifetime diagnosis of MDD and non-remission status. Eighty MDD subjects and 76 age- and sex-matched controls completed the actigraphy, while 61 MDD subjects and 47 controls completed the app-based assessment. MDD subjects had lower mobile time (P = 0.006), later sleep midpoint (P = 0.047) and Acrophase (P = 0.024) than controls. For app measurement, MDD subjects had more frequent brow lowering (P = 0.023), less lip corner pulling (P = 0.007), higher pause variability (P = 0.046), more frequent self-reference (P = 0.024) and negative emotion words (P = 0.002), lower articulation rate (P < 0.001) and happiness level (P < 0.001) than controls. With the fusion of all digital modalities, the predictive performance (F1-score) of ANN for a lifetime diagnosis of MDD was 0.81 and 0.70 for non-remission status when combined with the HADS-D item score, respectively. Multimodal digital measurement is a feasible diagnostic tool for depression in Chinese. A combination of multimodal measurement and machine-learning approach has enhanced the performance of digital markers in phenotyping and diagnosis of MDD., (© 2024. The Author(s).)

Manganese oxide (MnO 2 ) is one of the most abundant metal oxides, and it is renowned for its ability to degrade various phenolic micropollutants. However, under MnO 2 -mediated transformation, BP-3 transforms into 12 different radical-coupled transformation products (TPs) out of 15 identified TPs. These radical-coupled TPs are reported with adverse environmental impacts. This study explored the effects of MnO 2 on organic UV filter mixtures and different water constituents (i.e., bicarbonate ion (HCO 3 - ), humic acid (HA) and halide ions) in terms of degradation efficiency and transformation chemistry. When a mixture of benzophenone-3 (BP-3) and avobenzone (AVO) underwent transformation by MnO 2 , hybrid radical-coupled TPs derived from both organic UV filters were generated. These hybrid radical-coupled TPs were evaluated by an in silico prediction tool and Vibrio fischeri bioluminescence inhibition assay (VFBIA). Results showed that these TPs were potentially toxic to aquatic organisms, even more so than their parent compounds. The higher the concentration of HCO 3 - , HA, chloride ion (Cl - ) and bromide ion (Br - ), the greater the reduction in the efficiencies of degrading BP-3 and AVO. Contrastingly, in the presence of iodide ion (I - ), degradation efficiencies of BP-3 and AVO were enhanced; however, iodinated TPs and iodinated radical-coupled TPs were formed, with questionable toxicity. This study has revealed the environmental risks of hybrid radical-coupled TPs, iodinated TPs and iodinated radical-coupled TPs when the organic UV filters BP-3 and AVO are transformed by MnO 2 ., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 μM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca 2+ ]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA 2 ) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA 2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA 2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

We examined the effect of a nanoscale titanium surface topography (D) versus two hybrid micro/nanoscale topographies (B and OS) on adherent mesenchymal stem cells (MSCs) and bone marrow derived macrophages (BMMs) function in cell culture and in vivo. In the in vitro study, compared to OS and B surfaces, D surface induced earlier and greater cell spreading, and earlier and profound mRNA expression of RUNX2, Osterix and BMP2 in MSCs. D surface induced earlier and higher expression of RUNX2 and BMP2 and lower expression of inflammatory genes in implant adherent cells in vivo. Measurement of osteogenesis at implant surfaces showed greater bone-to-implant contact at D versus OS surfaces after 21 days. We explored the cell population on the D and OS implant surfaces 24 h after placement using single-cell RNA sequencing and identified distinct cell clusters including macrophages, neutrophils and B cells. D surface induced lower expression and earlier reduction of inflammatory genes expression in BMMs in vitro. BMMs on D, B and OS surfaces demonstrated a marked increase of BMP2 expression after 1 and 3 days, and this increase was significantly higher on D surface at day 3. Our data implicates a dynamic process that may be influenced by nanotopography at multiple stages of osseointegration including initial immunomodulation, recruitment of MSCs and later osteoblastic differentiation leading to bone matrix production and mineralization. The results suggest that a nanoscale topography (D) favorably modulates adherent macrophage polarization toward anti-inflammatory and regenerative phenotypes and promotes the osteoinductive phenotype of adherent mesenchymal stem cells. STATEMENT OF SIGNIFICANCE: Our manuscript contains original data developed to define effects of a novel nanotopography on the process of osseointegration at the cell and tissue level.  Few studies have compared the effects of a nanoscale surface versus the more typical hybrid micro/nano-scale surfaces used today. We have utilized single-cell RNA sequencing for the first time to identify earliest cell populations on implant surfaces in vivo. We provide data indicating that the nanoscale surface acts upon both osteoprogenitor and immune cell (macrophages) to alter the process of bone formation in a surface-specific manner. This work represents new observations regarding osseointegration and immunomodulation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LFC receives research grants and honorarium from Denstply Sirona. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Children are highly vulnerable to environmental pollutants, especially endocrine-disrupting chemicals (EDCs). Previous research has linked both organic UV filters and phthalates exposure to adiposity and pubertal development in children. Nevertheless, the individual and collective effects of these chemicals on this population remain poorly understood. In this study, twelve organic UV filters and metabolites, six phthalate metabolites and two oxidative stress biomarkers were analyzed in a prospective follow-up study in Shanghai, China after a baseline study conducted 1.5 years earlier. Results revealed a positive association between exposure to individual organic UV filters or their mixture and levels of 8-OHdG (β ranging from 0.242 to 0.588, P < 0.05), a marker of oxidative DNA damage. BP-3 and OD-PABA made a greater contribution to oxidative DNA damage than other UV filters. Levels of 8-OHdG were also positively correlated with single phthalate metabolites and their mixture, with MnBP and MMP contributing the most. Stratified analysis found that these associations were mainly observed in girls. Our mixture analysis revealed cumulative risks of oxidative DNA damage when there was co-exposure to these two kinds of EDCs. These results underscore the importance of considering the risks associated with organic UV filters and the necessity of evaluating the effects of all these pollutants, both individually and in mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Assessing patients' suicide risk is challenging, especially among those who deny suicidal ideation. Primary care providers have poor agreement in screening suicide risk. Patients' speech may provide more objective, language-based clues about their underlying suicidal ideation. Text analysis to detect suicide risk in depression is lacking in the literature., Objective: This study aimed to determine whether suicidal ideation can be detected via language features in clinical interviews for depression using natural language processing (NLP) and machine learning (ML)., Methods: This cross-sectional study recruited 305 participants between October 2020 and May 2022 (mean age 53.0, SD 11.77 years; female: n=176, 57%), of which 197 had lifetime depression and 108 were healthy. This study was part of ongoing research on characterizing depression with a case-control design. In this study, 236 participants were nonsuicidal, while 56 and 13 had low and high suicide risks, respectively. The structured interview guide for the Hamilton Depression Rating Scale (HAMD) was adopted to assess suicide risk and depression severity. Suicide risk was clinician rated based on a suicide-related question (H11). The interviews were transcribed and the words in participants' verbal responses were translated into psychologically meaningful categories using Linguistic Inquiry and Word Count (LIWC)., Results: Ordinal logistic regression revealed significant suicide-related language features in participants' responses to the HAMD questions. Increased use of anger words when talking about work and activities posed the highest suicide risk (odds ratio [OR] 2.91, 95% CI 1.22-8.55; P=.02). Random forest models demonstrated that text analysis of the direct responses to H11 was effective in identifying individuals with high suicide risk (AUC 0.76-0.89; P<.001) and detecting suicide risk in general, including both low and high suicide risk (AUC 0.83-0.92; P<.001). More importantly, suicide risk can be detected with satisfactory performance even without patients' disclosure of suicidal ideation. Based on the response to the question on hypochondriasis, ML models were trained to identify individuals with high suicide risk (AUC 0.76; P<.001)., Conclusions: This study examined the perspective of using NLP and ML to analyze the texts from clinical interviews for suicidality detection, which has the potential to provide more accurate and specific markers for suicidal ideation detection. The findings may pave the way for developing high-performance assessment of suicide risk for automated detection, including online chatbot-based interviews for universal screening., (© Tim M H Li, Jie Chen, Framenia O C Law, Chun-Tung Li, Ngan Yin Chan, Joey W Y Chan, Steven W H Chau, Yaping Liu, Shirley Xin Li, Jihui Zhang, Kwong-Sak Leung, Yun-Kwok Wing. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

Radical-coupled transformation products (TPs) have been identified as the byproducts of various transformation processes, including both natural attenuation and artificial treatments, of phenolic micropollutants. Benzophenone-3 (BP-3), an organic UV filter of emerging concern, has been previously reported with ubiquitous occurrence in the natural environment and water bodies. Current research has demonstrated how TPs are formed from BP-3 when it is treated with manganese oxide (MnO 2 ). The ecological and toxicological risks of these TPs have also been assessed. Polymerization of BP-3 through radical coupling was observed as the major pathway by which BP-3 is transformed when treated with MnO 2 . These radical-coupled TPs haven't shown further degradation after formation, suggesting their potential persistence once occurred in the environment. In silico experiments predict the radical-coupled TPs will increase in mobility, persistence and ecotoxicity. If true, they also represent an ever-increasing threat to the environment, ecosystems and, most immediately, aquatic living organisms. In addition, radical-coupled TPs produced by MnO 2 transformation of BP-3 have shown escalated estrogenic activity compared to the parent compound. This suggests that radical coupling amplifies the toxicological impacts of parent compound. These results provide strong evidence that radical-coupled TPs with larger molecular sizes are having potential adverse impacts on the ecosystem and biota., 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.)

While it is widely accepted that 2-butene-1,4-dial (BDA) is a toxic metabolite with genotoxic and carcinogenic properties, little is known about BDA and its analogues (BDAs) formation during water disinfection. In this study, the effects of different chlorination conditions on the formation of BDAs from bisphenol and its analogues (BPs analogues) were evaluated. A transformation pathway for the formation of BDAs upon chlorination of BPs analogues is proposed. The time profile of the transformation of BPs analogues into BDAs reveals that the generation of dichlorohydroquinone, dichloro-hydroxybenzenesulfonic acid and 2,4,6-trichlorophenol, are significantly associated with the formation of BDAs in the disinfected water. Owing to the different bridging groups contributing to the electrophilicity of BPs analogues in varying degrees, the stronger the electrophilicity of BPs analogues the more BDAs are formed. In addition, the type of BDAs produced is also affected. Four types of BDAs were detected in this study, one of which was newly identified. This study confirms that BPs analogues are an important source of BDAs and provides more insights into the formation of BDAs during chlorination. Greater attention should be given to the formation of BDAs in chlorinated water and their potential threat to humans and the ecosystem., 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.)

Background: HIV infections often develop drug resistance mutations (DRMs), which can increase the risk of virological failure. However, it has been difficult to determine if minor mutations occur in the same genome or in different virions using Sanger sequencing and short-read sequencing methods. Oxford Nanopore Technologies (ONT) sequencing may improve antiretroviral resistance profiling by allowing for long-read clustering., Methods: A new ONT sequencing-based method for profiling DRMs in HIV quasispecies was developed and validated. The method used hierarchical clustering of long amplicons that cover regions associated with different types of antiretroviral drugs. A gradient series of an HIV plasmid and 2 plasma samples was prepared to validate the clustering performance. The ONT results were compared to those obtained with Sanger sequencing and Illumina sequencing in 77 HIV-positive plasma samples to evaluate the diagnostic performance., Results: In the validation study, the abundance of detected quasispecies was concordant with the predicted result with the R2 of > 0.99. During the diagnostic evaluation, 59/77 samples were successfully sequenced for DRMs. Among 18 failed samples, 17 were below the limit of detection of 303.9 copies/μL. Based on the receiver operating characteristic analysis, the ONT workflow achieved an F1 score of 0.96 with a cutoff of 0.4 variant allele frequency. Four cases were found to have quasispecies with DRMs, in which 2 harbored quasispecies with more than one class of DRMs. Treatment modifications were recommended for these cases., Conclusions: Long-read sequencing coupled with hierarchical clustering could differentiate the quasispecies resistance profiles in HIV-infected samples, providing a clearer picture for medical care., (© American Association for Clinical Chemistry 2023.)

Cholesterol biosynthesis supports proliferation and drives resistance to tyrosine kinase inhibitor (TKI) therapy in hepatocellular carcinoma (HCC). Here, we present a protocol for using stable isotopic tracers to track the biosynthesis of cholesterol in cultured HCC cells. We describe steps for cell preparation, incubation, separation, and homogenization. We then detail lipid extraction and compound-specific isotope analysis for comparing and quantifying cholesterol synthesis between TKI-resistant HCC cells and their mock counterparts. This protocol can be expanded for use with other shorter-chained lipids., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)