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Hak Yung Ng Department of Paediatrics and Adolescent Medicine, Tseung Kwan O Hospital, Tseung Kwan O, Hong Kong, China Abstract: Obesity in adolescence is a public health priority because it usually tracks into adulthood, resulting in enormous medical and social costs. This underscores the importance of early identification and intervention. Acanthosis nigricans (AN) was once considered a rare paraneoplastic dermatosis, but is now frequently observed in obese adolescents. Current understanding suggests that it is associated with insulin resistance and has a unique role in secondary prevention. The purpose of this narrative review is to provide a comprehensive overview of AN in obese adolescents, covering its history, current knowledge on the condition, its clinical significance, management challenges, and the direction of future research. Keywords: Differential diagnosis, screening, insulin resistance, type 2 diabetes mellitus, metabolically healthy obesity, behavioral weight management, pharmacotherapy, bariatric surgery

Objective: The development of the Chinese Drug Involvement Scale for use in Chinese communities. Method: A battery of scales, including the Chinese Drug Involvement Scale and three mental health measures, were administered to 152 students of 13 to 18 years of age. Reliability and validity analyses were performed. The refined version was then cross-validated on a group of identified drug abusers (N = 77). Results: The final version of the Chinese Drug Involvement Scale is a 22-item scale. Validation results demonstrate that the Chinese Drug Involvement Scale has high reliability and a satisfactory level of validity. Conclusion: The Chinese Drug Involvement Scale is a global assessment of an individual's beliefs and values relating to drug use, apart from actual drug abuse behavior. The scale will be particularly useful for periodic assessments or outcome evaluation in treatment programs. [ABSTRACT FROM AUTHOR]

Carbon neutrality is a primary goal for wastewater treatment plants (WWTPs), as they are responsible for significant greenhouse gas (GHG) emissions as well as unpleasant odour emissions. The paper shows a new modular biotechnology that enables simultaneous treatment of gaseous emissions and biofixation of CO 2 . A comparative assessment of system performances in removing target pollutants (toluene, p-xylene and hydrogen sulphide) was implemented. Results showed that the highest removal efficiency (RE) was recorded for the toluene, equaling 99.9 ± 0.1 %, for an inlet load (IL) of 9.91 ± 3.44 g m -3 d -1 . During the experimental tests regarding hydrogen sulphide removal, the system recorded the highest CO 2 assimilation, equal to -3.03 ± 0.93 g m -3 d -1 . However, this assimilation rate did not correspond to the maximum volumetric biomass productivity (MVBP), equal to 1.3 g L -1 d -1 , recorded with toluene treatment, with a maximum lipid productivity (MLP) of 450 mg L -1 d -1 . The results demonstrated the complete adaptability of the investigated system, which can help to fill the gaps in the current technological landscape, providing an innovative biotechnology that can be directly implemented and environmentally sustainable., 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 B.V.)

Antibiotic resistome could be aerosolized under wastewater aeration processes, however, their seasonal variation, mobility, hosts, aerosolization behavior, and risk, are largely unknown. Herein, the antibiotic resistant pollution associated with fine particulate matter (PM 2.5 ) from the actual aeration tank (AerT), was analyzed using metagenomic assembly. The antibiotic resistance of AerT-PM 2.5 was characterized by significant seasonality. Antibiotic resistance genes (ARGs) in AerT-PM 2.5 , exhibited higher enrichment and mobility and were harbored more by pathogens than those in upwind-PM 2.5 , regardless of sampling season. Mobile ARGs were mainly flanked by transposase. Totally, 18 pathogenic antibiotic-resistant bacteria (PARB) carried more than one ARG, including 9 PARB with multiple ARG types. Although wastewater exerted a dominant source contribution for the airborne ARGs (47.31-55.56 %) and PARB (46.18-64.32 %), aeration endowed differential aerosolization capacity for various ARGs and PARB from wastewater. Airborne antibiotic resistome was mainly determined by bacterial community and indirectly influenced by meteorological conditions (i.e., relative humidity). Higher PM 2.5 -borne resistome risk was observed in AerT than upwind, and the most serious resistome risk of AerT-PM 2.5 was found in winter. This study emphasizes the importance of wastewater aeration processes in emission of airborne antibiotic resistome and offers referenced information for mitigating air pollution in wastewater treatment plants., 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.)

Bioaerosol contamination was considered as a potential health threat in sludge dewatering systems (SDSs), while emission and risk of airborne antibiotic resistome remain largely unclear. Herein, seasonal investigations of fine particulate matter (PM 2.5 ) were conducted using metagenomics-based methods within and around different SDSs, together with an analysis of sewage sludge. Featured with evident seasonality, antibiotic resistance genes (ARGs) in SDS-PM 2.5 also possessed greater accumulation, transfer, and pathogen accessibility than those in ambient air PM 2.5 . Mobile ARGs in SDS-PM 2.5 mainly encoded resistance to tetracycline, and most were flanked by integrase. Some pathogenic antibiotic resistant bacteria (PARB), including Enterobacter asburiae, Escherichia coli, Enterococcus faecium, and Staphylococcus aureus, also carried mobile genetic elements in SDS-PM 2.5 . Dewatering behavior actuated > 50.56% of ARG subtypes and > 42.86% of PARB in sewage sludge to aerosolize into air. Relative humidity, temperature, and PM 2.5 concentration collectively drove the evolution of bacterial community and indirectly promoted the antibiotic resistance of SDS-PM 2.5 . SDS-PM 2.5 posed more serious resistome risks than sewage sludge and ambient air PM 2.5 , and the highest levels were discovered in winter. These findings underline the role of dewatering behavior in facilitating resistome's aerosolization, and the need to mitigate this potential air pollution., 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 Ltd. All rights reserved.)

Objectives: To evaluate the learning gain and students' perceptions towards Jigsaw collaborative learning in comparison with lectures in learning about pharmacokinetic changes in special populations., Methods: Undergraduates learn about A-D-M-E of specific populations via Jigsaw collaborative learning and didactic lectures. Pre- and post-lesson quizzes were conducted to evaluate the effectiveness of the teaching method in terms of knowledge gain. Surveys comprising Likert scale statements and open-ended questions were conducted to elucidate students' perception towards the teaching methods., Results: From a class of 192 students, 118 (62%) and 110 (57%) students completed the pre- and post-lecture quizzes, respectively, while 176 (92%) and 168 (88%) students completed the pre- and post-Home Group discussion of Jigsaw quizzes, respectively. There was an improvement of 22.2% and 14.3% in median percentage quiz scores for the lecture and Jigsaw method respectively. Most students agreed that they have learned (54-60%) and collaborated (78-89%) through the Jigsaw method and rated Jigsaw as useful for their learning (54%). Open-ended survey responses offered a mixed conclusion where the didactic lecture was perceived to be as, or more effective than the Jigsaw method., Conclusion: Learning gains were observed through the Jigsaw collaborative learning method which relied solely on peer-teaching, despite students perceiving it to be not as effective as lecture. The method provided opportunities for active and peer-learning. Further studies are needed to evaluate the long-term effects of this teaching method., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In recent years, organophosphorus flame retardants (OPFRs) have been widely used as substitutes for brominated flame retardants with excellent properties, and their initial toxicological effects on the water ecosystem and human health have gradually emerged. However, to date, research on the cytotoxicity and health risks of OPFRs is still limited. Therefore, this study aims to systematically explore the cytotoxic effects and toxic mechanisms of OPFRs on cells. Human liver cancer (HepG2) cells were adopted as an ideal model for toxicity evaluation due to their rapid growth and metabolism. This study proposes a sensitive electrochemical cell-based sensor constructed on a graphitized multi-walled carbon nanotube/ionic liquid/gold nanoparticle-modified electrode. The sensor was used to detect the cytotoxicity of tri(2-butylxyethyl) phosphate (TBEP), tributyl phosphate (TnBP), triphenyl phosphate (TPhP), tri(1,3-dichloro-2-propyl) phosphate (TDCIPP), tri(2-chloropropyl) phosphate (TCPP) and tri(2-chloroethyl) phosphate (TCEP) in the liquid medium, providing insight into their toxicity in water environments. The half-maximal inhibitory concentration (IC 50 ) of TBEP, TnBP, TPhP, TDCIPP, TCPP and TCEP on HepG2 cells were 179.4, 194.9, 219.8, 339.4, 511.8 and 859.0 μM, respectively. Additionally, the cytotoxic mechanism of six OPFRs was discussed from the perspective of oxidative stress and apoptosis, and four indexes were correlated with toxicity. Furthermore, transcriptome sequencing was conducted, followed by a thorough analysis of the obtained sequencing results. This analysis demonstrated a significant enrichment of the p53 and PPAR pathways, both of which are closely associated with oxidative stress and apoptosis. This study presents a simplified and efficient technique for conducting in vitro toxicity studies on organophosphorus flame retardants in a water environment. Moreover, it establishes a scientific foundation for further investigation into the mechanisms of cytotoxicity associated with these compounds., 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 Ltd.)

Background and Aims: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus., Approach and Results: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05)., Conclusions: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261)., (Copyright © 2024 American Association for the Study of Liver Diseases.)

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%., Methods: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance., Results: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively., Conclusions: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection., Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Objective: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005-2010 and 2017-2021 inception cohorts., Methods: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan-Meier survival analysis and multivariable Cox regression., Results: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10)., Conclusion: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Membrane fouling has always been a critical constraint in the operation of the reverse osmosis (RO) process, and chemical cleaning is essential for mitigating membrane fouling and ensuring smooth operation of the membrane system. This paper presents an optimized chemical cleaning method for the efficient cleaning of RO membranes in full-scale applications. Compared to the regular cleaning method (cleaning with 0.1 % NaOH + 1 % ethylenediaminetetraacetic acid + 0.025 % sodium dodecyl benzene sulfonate followed by 0.2 % HCl), the optimized cleaning method improves the cleaning efficiency by adding sodium chloride to the alkaline cleaning solution and citric acid to the acid cleaning solution. Notably, the membrane flux recovery rate with the optimized cleaning method is 45.74 %, and it improves the cleaning efficiency by 1.65 times compared to the regular cleaning method. Additionally, the optimized cleaning method removes 30.46 % of total foulants (organic and inorganic), which is 2.11 times higher than the regular cleaning method. The removal of inorganic ions such as Fe, Ca, and Mg is significantly improved with the optimized cleaning method. For organic matter removal, the optimized cleaning method effectively removes more polysaccharides, proteins, and microbial metabolites by disrupting the complex structures of organic matter. Furthermore, it also changes the microbial community structure on the RO membrane surface by eliminating microorganisms that cannot withstand strong acids, bases, and high salt environments. However, Mycobacterium can adapt to these harsh conditions, showing a relative abundance of up to 84.13 % after cleaning. Overall, our results provide a new chemical cleaning method for RO membranes in full-scale applications. This method effectively removes membrane foulants and enhances the understanding of the removal characteristics of foulants on RO membrane surfaces by chemical cleaning., 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 Ltd. All rights reserved.)

Background: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2., Methods: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis., Results: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2-59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log 10 LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10 -5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log 10 LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log 10 LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log 10 LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log 10 LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10 -5 % vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log 10 LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log 10 LDA score = 2.14)., Conclusion: Among three-dose BNT162b2 recipients, S. parasanguinis , B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response.

The occurrence of biofouling restricts the widespread application of membrane bioreactors (MBRs) in wastewater treatment. Regulation of quorum sensing (QS) is a promising approach to control biofouling in MBRs, yet the underlying mechanisms are complex and remain to be illustrated. A fundamental understanding of the relationship between QS and membrane biofouling in MBRs is lacking, which hampers the development and application of quorum quenching (QQ) techniques in MBRs (QQMBRs). While many QQ microorganisms have been isolated thus far, critical criteria for selecting desirable QQ microorganisms are still missing. Furthermore, there are inconsistent results regarding the QQ lifecycle and the effects of QQ on the physicochemical characteristics and microbial communities of the mixed liquor and biofouling assemblages in QQMBRs, which might result in unreliable and inefficient QQ applications. This review aims to comprehensively summarize timely QQ research and highlight the important yet often ignored perspectives of QQ for biofouling control in MBRs. We consider what this "information" can and cannot tell us and explore its values in addressing specific and important questions in QQMBRs. Herein, we first examine current analytical methods of QS signals and discuss the critical roles of QS in fouling-forming microorganisms in MBRs, which are the cornerstones for the development of QQ technologies. To achieve targeting QQ strategies in MBRs, we propose the substrate specificity and degradation capability of isolated QQ microorganisms and the surface area and pore structures of QQ media as the critical criteria to select desirable functional microbes and media, respectively. To validate the biofouling retardation efficiency, we further specify the QQ effects on the physicochemical properties, microbial community composition, and succession of mixed liquor and biofouling assemblages in MBRs. Finally, we provide scale-up considerations of QQMBRs in terms of the debated QQ lifecycle, practical synergistic strategies, and the potential cost savings of MBRs. This review presents the limitations of classic QS/QQ hypotheses in MBRs, advances the understanding of the role of QS/QQ in biofouling development/retardation in MBRs, and builds a bridge between the fundamental understandings and practical applications of QQ technology.

Objectives: To describe treatment patterns and persistence of tofacitinib, interleukin 17 inhibitors (IL-17Ai) and tumour necrosis factor inhibitors (TNFi), in patients with psoriatic arthritis (PsA)., Methods: Data from adult patients with PsA and who had received at least one prescription of tofacitinib, IL-17Ai or TNFi between May 2019 and September 2021 were sourced from the Australian OPAL dataset. Persistence, analysed via Kaplan-Meier methods, and propensity score matching between tofacitinib and bDMARD (IL-17Ai and TNFi) groups were conducted., Results: Of 16,692 patients with PsA, 1486 (n = 406 tofacitinib, n = 416 IL-17Ai and n = 664 TNFi) were included. More females were in the tofacitinib group (75.4%) than in the IL-17Ai (61.1%) and TNFi (64.8%) groups. Overall, 19.2% of tofacitinib patients were first line, compared with 41.8% of IL-17Ai and 62.8% of TNFi patients. In the overall population, the median persistence was 16.5 months (95% CI 13.8 to 19.5 months), 17.7 months (95% CI 15.8 to 19.6 months) and 17.2 months (95% CI 14.9 to 20.5 months) in the tofacitinib, IL-17Ai and TNFi groups, respectively. Persistence was similar in the tofacitinib/IL-17Ai matched population; however, in the tofacitinib/TNFi matched population, persistence was longer in the tofacitinib group (18.7 months, 95% CI 15.6 to 21.4 months) compared with the TNFi group (12.2 months, 95% CI 19.9 to 14.9 months)., Conclusions: In this Australian real-world dataset, tofacitinib was more frequently used in later lines and among a slightly higher proportion of female patients than IL-17Ai or TNFi. Overall, treatment persistence was similar for tofacitinib, IL-17Ai and TNFi, but tofacitinib exhibited longer persistence than TNFi in a matched population. Key Points • This is the first, large real-world study from Australia investigating the demographics, treatment patterns and comparative treatment persistence of patients with psoriatic arthritis (PsA) treated with tofacitinib and biologic disease-modifying drugs (bDMARDs). • The study suggests that tofacitinib is an effective intervention in PsA with at least comparable persistence to bDMARDs: tumour necrosis factor inhibitors (TNFi) and interleukin-17 A inhibitors (IL-17Ai)., (© 2024. The Author(s).)

The release of nanoplastics (NPs) into the environment is growing due to the extensive use of plastic products. Numerous studies have confirmed the negative effects of NPs on microorganisms, which poses uncertainties concerning their impact on nanofiltration (NF) membrane biofouling. This study investigated the initial cell adhesion process, NF membrane biofouling kinetic processes and bacterial responses of Pseudomonas aeruginosa (P. aeruginosa) exposed to varied NPs concentrations (0-50 mg·L -1 ). Transcriptome analysis demonstrated that low concentration of NPs (0.1 mg·L -1 ) promoted bacterial quorum sensing, energy metabolism, exopolysaccharide biosynthesis and bacterial secretion systems. Correspondingly, the polysaccharide content increased remarkably to 2.77 times the unexposed control, which served as a protective barrier for bacteria to avoid the impact of NPs-induced stress. Suppressed homologous recombination, microbial metabolic potentials and flagellar assembly were detected in bacteria exposed to a high concentration (50 mg·L -1 ) of NPs, mainly due to the triggered reactive oxygen species (ROS) generation, genomic DNA damage, and decreased energy production. Overall, enhanced formation of the extracellular polymeric substances (EPS) and aggravated membrane flux decline were observed when NPs interacted with the membrane surface by cell secretions (low NPs levels) or cell lysis (high NPs levels). These findings shed light on understanding the microbial metabolism mechanism and membrane biofouling propensity with NPs stress at both the molecular and gene levels., 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 Ltd. All rights reserved.)

Membrane biofouling is a challenge to be solved for the stable operation of the seawater reverse osmosis (SWRO) membrane. This study explored the regulation mechanism of quorum sensing (QS) inhibition on microbial community composition and population-level behaviors in seawater desalination membrane biofouling. A novel antibiofouling SWRO membrane (MA&#95;m) by incorporating one of quorum sensing inhibitors (QSIs), methyl anthranilate (MA) was prepared. It exhibited enhanced anti-biofouling performance than the exogenous addition of QSIs, showing long-term stability and alleviating 22 % decrease in membrane flux compared with the virgin membrane. The results observed that dominant bacteria Epsilon- and Gamma-proteobacteria (Shewanella, Olleya, Colwellia, and Arcobacter), which are significantly related to (P ≤ 0.01) the metabolic products (i.e., polysaccharides, proteins and eDNA), are reduced by over 80 % on the MA&#95;m membrane. Additionally, the introduction of MA has a more significant impact on the QS signal-sensing pathway through binding to the active site of the transmembrane sensor receptor. It effectively reduces the abundance of genes encoding QS and extracellular polymeric substance (EPS) (exopolysaccharides (i.e., galE and nagB) and amino acids (i.e., ilvE, metH, phhA, and serB)) by up to 50 % and 30 %, respectively, resulting in a reduction of EPS by more than 50 %, thereby limiting the biofilm formation on the QSI-modified membrane. This study provides novel insights into the potential of QSIs to control consortial biofilm formation in practical SWRO applications., 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 Ltd. All rights reserved.)

Background: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac., Methods: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors., Results: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9-56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log 10 LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log 10 LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log 10 LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens , and S. salivarius was 0.03 (95% CI: 9.56 × 10 -4 -0.32), 0.03 (95% CI: 4.47 × 10 -4 -0.59), and 10.19 (95% CI: 0.81-323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log 10 LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions., Conclusion: E. rectale, C. aerofaciens , and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

In this study, two membrane-aerated biofilm reactors (MABRs) were constructed: one solely utilizing biofilm and another hybrid MABR (HMABR) incorporating both suspended-sludge and biofilm to treat low C/N aquaculture wastewater under varying lumen air pressure (LAP). Both HMABR and MABR demonstrated superior nitrogen removal than conventional aeration reactors. Reducing LAP from 10 kPa to 2 kPa could enhance denitrification processes without severely compromising nitrification, resulting in an increase in total inorganic nitrogen (TIN) removal from 50.2±3.1 % to 71.6±1.0 %. The HMABR exhibited better denitrification efficacy than MABR, underscoring its potential for advanced nitrogen removal applications. A decline in LAP led to decreased extracellular polymeric substance (EPS) production, which could potentially augment reactor performance by minimizing mass transfer resistance while maintaining microbial matrix stability and function. Gene-centric metagenomics analysis revealed decreasing LAP impacted nitrogen metabolic potentials and electron flow pathways. The enrichment of napAB at higher LAP and the presence of complete ammonia oxidation (Comammox) Nitrospira at lower LAP indicated aerobic denitrification and Comammox processes in nitrogen removal. Multifunctional microbial communities developed under LAP regulation, diversifying the mechanisms for simultaneous nitrification-denitrification. Increased denitrifying gene pool (narGHI, nirK, norB) and enzymatic activity at a low LAP can amplify denitrification by promoting denitrifying genes and electron flow towards denitrifying enzymes. Sulfamethoxazole (SMX) was simultaneously removed with efficiency up to 80.2 ± 3.7 %, mainly via biodegradation, while antibiotic resistome and mobilome were propagated. Collectively, these findings could improve our understanding of nitrogen and antibiotic removal mechanisms under LAP regulation, offering valuable insights for the effective design and operation of MABR systems in aquaculture wastewater treatment., 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 Ltd.)

CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8-61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. Bacteroides uniformis (log 10 LDA score = 4.39) and Bacteroides eggerthii (log 10 LDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with B. eggerthii (OR: 5.73; 95% CI: 1.32-29.55; p = 0.022) and B. uniformis with borderline significance (OR: 3.27; 95% CI: 0.73-14.72; p = 0.110). Additionally, B. uniformis was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (log 10 LDA score = 2.88) and II (log 10 LDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species ( B. eggerthii and B. uniformis ) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.

Objectives: To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using Janus kinase (JAKis) and TNF (TNFis) inhibitors., Method: A retrospective analysis of data from the Hong Kong Biologics Registry 2008-2021 was performed. RA patients who had ever used JAKis or TNFis were included. The incidence of MACEs, cancer and infections were compared between the two groups, with adjustment for confounding factors., Results: A total of 2471 courses of JAKis (n = 551) and TNFis (n = 1920) were used in 1732 RA patients (83.7% women, age 53.8 [12.5] years; follow-up 6431 patient-years). JAKi users had significantly older age, more atherosclerotic risk factors and higher frequency of past malignancies. A total of 15 and 40 MACEs developed in the JAKi and TNFi users, respectively (incidence 1.34 vs 0.75 per 100 patient-years; P = 0.22). There was no significant difference in the incidence of cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; P = 0.25). The adjusted hazard ratios of MACE and cancer in the JAKi users were 1.36 (95% CI: 0.62, 2.96) (P = 0.44) and 0.87 (95% CI: 0.39, 1.95) (P = 0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; P = 0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; P < 0.001)., Conclusions: In a real-life setting, there is no increase in MACEs or cancers in users of JAKis compared with TNFis. However, the incidence of non-serious infections, including herpes zoster, was increased in users of JAKis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Thromboembolic events resulting from disturbances in the body's balance of thrombotic and antithrombotic abilities are among the most life-threatening complications of nephrotic syndrome. Certain causes of nephrotic syndrome leave the patient particularly susceptible to thromboembolism. The severity of proteinuria and degree of hypoalbuminaemia are other common predictors of risk. Timely initiation of prophylactic therapy can help prevent morbidity and mortality associated with this complication in patients with nephrotic syndrome. The duration of treatment and choice of therapeutic agent depends on several factors, including the degree of hypoalbuminaemia, risk factors for thrombosis and risk of bleeding. This article reviews current understanding of the pathophysiology and risk factors for thromboembolism associated with nephrotic syndrome, and summarises recommendations and strategies for preventing and treating thromboembolic events in patients with nephrotic syndrome.

Introduction: Non-cognitive traits should be considered when selecting candidates to study medicine. However, evaluating these traits remains difficult. We explored whether measuring undesirable non-cognitive behaviour ('Red Flags') added value to a medical school admissions system. Red Flags included rudeness, ignoring the contributions of others, disrespectful behaviour, or poor communication., Methods: Following an admissions interview testing non-cognitive attributes in 648 applicants to a UK medical school, we measured the association between interview score and Red Flag frequency. We tested linear and polynomial regression models to evaluate whether the association was linear or non-linear., Results: In total, 1126 Red Flags were observed. While Red Flags were concentrated among low-scorers, candidates in the highest- and second-highest deciles for interview score still received Red Flags (six and twenty-two, respectively). The polynomial regression model indicated candidates with higher scores received fewer Red Flags, but the association was not linear ( F (3644) = 159.8, p  = .001, adjusted R 2 = 0.42)., Conclusions: The non-linear association between interview score and Red Flag frequency shows some candidates with desirable non-cognitive attributes will still display undesirable-or even exclusionary-non-cognitive attributes. Recording Red Flag behaviour reduces the likelihood such candidates will be offered a place at medical school.

Prediabetes, the precursor of type 2 diabetes mellitus, is an intermediate stage between normal glucose homeostasis and overt diabetes. This asymptomatic metabolic state is increasingly prevalent in pediatric population and is very difficult to detect without appropriate screening. Studies have shown that a certain proportion of children with prediabetes will develop diabetes in a few years. Even more alarming is the evidence that youth-onset diabetes has a more aggressive clinical course with progressive beta-cell decline and accelerated end-organ damage. Despite its importance, several aspects involving prediabetes in childhood are disputed or unknown. This review presents the latest insights into this challenging entity and outlines a simplified screening approach to aid clinical practice. In summary, childhood prediabetes is an important clinical condition indicating the need for proper screening and timely intervention., Competing Interests: Conflict-of-interest statement: All the authors report no conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Membrane aerated biofilm reactors (MABRs) can be used to treat domestic wastewater containing sulfamethoxazole (SMX) because of their favorable performance in the treatment of refractory pollutants. However, biologics are generally subjected to antibiotics stress, which induces the production of antibiotic resistance genes (ARGs). In this study, a simulated-sunlight assisted MABR (L-MABR) was used to promote SMX removal and reduce ARGs production. The SMX removal efficiency of the l-MABR system was 9.62 % superior to that of the MABR system (83.13 %). In contrast from MABR, in the l-MABR, only 28.75 % of SMX was removed through microbial activity because functional bacteria were inactivated through radiation by simulated sunlight. In addition, photolysis (64.61 %) dominated SMX removal, and the best performing indirect photolysis process was the excited state of effluent organic matters ( 3 EfOMs*). Through photolysis, ultraviolet (UV) and reactive oxygen species (ROS) enriched the SMX removal route, resulting in the SMX removal pathway in the l-MABR no longer being limited by enzyme catalysis. More importantly, because of the inactivation of functional bacteria, whether in the effluent or biofilm, the copy number of ARGs in the l-MABR was 1-3 orders of magnitude lower than that in the MABR. Our study demonstrates the feasibility of utilizing simulated-sunlight to enhance the antibiotic removal efficiency while reducing ARG production, thus providing a novel idea for the removal of antibiotics from wastewater., 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 Ltd. All rights reserved.)

Marine harmful algae bloom (HAB) is a growing threat to desalination plants worldwide. This work proposes ferrous iron/peroxymonosulfate (Fe 2+ /PMS) as a novel pretreatment technology for seawater reverse osmosis (SWRO) under HAB. Herein, Fe 2+ /PMS achieved a significantly higher reduction of negative charge of algae-laden seawater as compared to conventional coagulation (i.e., coagulant is Fe 3+ ), which thereby facilitated improved flocculation to remove algal cells, turbidity and algal organics matters (AOMs), and marine Ca 2+ (∼430 mg/L) could partially contribute to the enhanced coagulation performance. A new understanding of the improved coagulation efficiency achieved with Fe 2+ /PMS in seawater has been proposed as compared to freshwater: seawater matrix (e.g., 504 mM Cl - ) was demonstrated to significantly enhance the generation of high-valent iron (FeO 2+ ) as the main reactive intermediate instead of the long-recognized Fe 3+ and free radicals, as revealed by methyl phenyl sulfoxide (PMSO) probe, radicals scavenging analysis and electron spin resonance (ESR) spectra. This new mechanism is expected to provide valuable insights for the development of more novel oxidative seawater treatment technologies. Of note, while trade-off between particles and AOMs played an important role in membrane fouling reduction by different dosages of Fe 2+ /PMS, Fe 2+ /PMS with an optimal dosage of 0.1 mM/0.05 mM achieved an unprecedentedly higher reduction (95.26%) of modified fouling index (MFI) as compared to conventional coagulation (13.28%-42.36% with 0.1-0.2 mM of Fe 3+ ). Optical-photothermal infrared spectromicroscopy with sub-micron spatial resolution was employed to analyze membrane foulants for the first time, and Fe 2+ /PMS was found to mainly cause reduced cake layer resistance, which was attributed to the collectively reduced concentration of algae cells, micro-particles with sizes from 2 to 10 µm, humic substances and biopolymers. Moreover, Fe 2+ /PMS resulted in lower dissolved Fe 3+ (<0.027 mg/L) in ultrafiltration (UF) permeate, which would make it more reliable for SWRO operation as compared to conventional coagulation. When energy-intensive dissolved air flotation (DAF) was employed to withstand HAB, Fe 2+ /PMS outperformed it and was instrumental in achieving reduced MFI with 56.4% lower operational cost. In this context, Fe 2+ /PMS would facilitate a high-performance and low-cost pretreatment technology for seawater desalination plants under HAB., 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 Ltd. All rights reserved.)

The kidney plays a crucial role in glucose homeostasis by regulating glucose transport. We aimed to investigate the impact of alterations in glucose transport on glucose metabolism during ageing. Adult male Sprague Dawley rats were divided into five groups: 3-month, 6-month, and 12-month control groups, and 6- and 12-month groups receiving the hydrogen sulfide donor molecule GYY4137. The study found that, as age increased, daily urinary uric acid and protein levels increased in the 12-month group. Blood sugar level and HOMA-IR index increased in the 12-month group, and were partially improved by GYY4137. The kidney tissue showed mild glomerulosclerosis in the 12-month group, which was diminished by GYY4137. Gene expression analysis showed decreased sirtuin and increased p21 expression in the aging groups. Increased SGLT1 and SGLT2 expression was observed in the 12-month group, which was reversed by GYY4137. Both GLUT1 and GLUT2 expression was increased in the 6- and 12-month groups, and reversed by GYY4137 in the 12-month group. The study concluded that aging was associated with increased blood sugar levels and the HOMA-IR index, and the abundance of renal glucose transporters increased as aging progressed. GYY4137 effectively reversed aging-related alterations in glucose homeostasis and renal epithelial transporters.

We investigated the clinical significance of CTCs in cancer progression by detecting multiple cancer driver genes associated with epithelial-to-mesenchymal transition (EMT) at the transcript level. The 10-gene panel, comprising CCND1 , ECT2 , EpCAM , FSCN1 , KRT5 , KRT18 , MET , TFRC , TWIST1 , and VEGFC , was established for characterizing CTCs from mouse ESCC xenograft models and clinical ESCC peripheral blood (PB) samples. Correlations between gene expression in CTCs from PB samples ( n = 77) and clinicopathological features in ESCC patients ( n = 55) were examined. The presence of CTCs at baseline was significantly correlated with tumor size ( p = 0.031). The CTC-high patients were significantly correlated with advanced cancer stages ( p = 0.013) and distant metastasis ( p = 0.029). High mRNA levels of TWIST1 (Hazard Ratio (HR) = 5.44, p = 0.007), VEGFC (HR = 6.67, p < 0.001), TFRC (HR = 2.63, p = 0.034), and EpCAM (HR = 2.53, p = 0.041) at baseline were significantly associated with a shorter overall survival (OS) in ESCC patients. This study also revealed that TWIST1 facilitates EMT and enhances malignant potential by promoting tumor migration, invasion, and cisplatin chemoresistance through the TWIST1-TGFBI-ZEB1 axis in ESCC, highlighting the prognostic and therapeutic potential of TWIST1 in clinical ESCC treatment.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Esophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease., Objective: To examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival., Design, Setting, and Participants: This single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes., Intervention: Patients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT)., Main Outcomes and Measures: Detection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS)., Results: A total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10-6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre-cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10-4)., Conclusions and Relevance: The findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

Along with rapid urbanization and intensive human activities, polycyclic aromatic hydrocarbon (PAH) pollution in the Pearl River Estuary (PRE) and its effects on the microbial community have attracted extensive attention. However, the potential and mechanism of microbial degradation of PAHs across water and sediment habitats remain obscure. Herein, the estuarine microbial community structure, function, assembly process and co-occurrence patterns impacted by PAHs were comprehensively analyzed using environmental DNA-based approaches. The contamination and distribution of PAHs were jointly affected by anthropogenic and natural factors. Some of the keystone taxa were identified as PAH-degrading bacteria (i.e., genera Defluviimonas, Mycobacterium, families 67-14, Rhodobacteraceae, Microbacteriaceae and order Gaiellales in water) or biomarkers (i.e., Gaiellales in sediment) that were significantly correlated with PAH levels. The proportion of deterministic process in the high PAH-polluted water (76%) was much higher than that in the low pollution area (7%), confirming the significant effect of PAHs on the microbial community assembly. In sediment, the communities with high phylogenetic diversity demonstrated a great extent of niche differentiation, exhibited a stronger response to environmental variables and were strongly influenced by deterministic processes (40%). Overall, deterministic and stochastic processes are closely related to the distribution and mass transfer of pollutants, and substantially affect the biological aggregation and interspecies interaction within communities in the habitats., 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.)

Antibiotic resistome can be carried by the bioaerosols and propagate from wastewater treatment plants (WWTPs) to the atmosphere, but questions remain regarding their mobility, bacterial hosts, source, and resistome risk. Here, fine particulate matter (PM 2.5 ) was collected within and around a large WWTP and analyzed by the metagenomic assembly and binning. PM 2.5 was discovered with increasing enrichment of total antibiotic resistance genes (ARGs), potentially mobile ARGs, and antibiotic-resistant bacteria (ARB) along the WWTP-downwind-upwind gradient. Some ARGs were found to be flanked by certain mobile genetic elements and generally mediated by plasmids in WWTP-PM 2.5 . Totally, 198 metagenome assembled genomes assigning to seven phyla were identified as the ARB, and a contig-based analysis indicated that 32 pathogens were revealed harboring at least two ARGs. Despite disparate aerosolization potentials of ARGs or ARB at different WWTP units, high resistome risks were found, along with the dominant contribution of wastewater for airborne ARGs (44.79-62.82%) and ARB (35.03-40.10%). Among the detected WWTP matrices, the sludge dewatering room was characterized by the highest resistome risk associated with PM 2.5 . This study underscores the dispersion of ARGs and ARB from WWTPs to the atmosphere and provides a reference for managing risks of antibiotic resistance., 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 Ltd. All rights reserved.)

Thermophilic anaerobic digestion (TAD) provides a promising solution for sustainable high-strength waste treatment due to its enhanced methane-rich biogas recovery. However, high organic loading rates (OLR) exceeding 3.0 kgCOD/m 3 /day and short hydraulic retention times (HRT) below 10 days pose challenges in waste-to-energy conversion during TAD, stemming from volatile fatty acids (VFAs) accumulation and methanogenesis failure. In this study, we implemented a stepwise strategy for acclimatizing waste activated sludge (WAS) in a thermophilic anaerobic fixed-bed biofilm reactor (TA-FBBR) to optimize methanogen populations, thereby enhancing waste-to-energy efficiencies under elevated OLRs in food waste treatment. Results showed that following stepwise acclimatization, the TA-FBBR achieved stable methane production of approximately 5.8 L/L-reactor/day at an ultrahigh OLR of ∼20 kgCOD/m 3 /day and ∼15 kgVS/m 3 /day at 6-day HRT in food waste treatment. The average methane yield reached 0.45 m 3 /kgCOD removal , attaining the theoretical production in TAD. Moreover, VFA concentrations were stabilized below 1000 mg/L at the ultrahigh OLR under 6-day HRT, while maintaining an acetate/propionate ratio of > 1.8 and a VFA/TAK ratio of < 0.3 serving as effective indicators of system stability and methane yield potential. The microbial community analysis revealed that the WAS acclimatization strategy fostered the microbial diversity and abundance of Methanothermobacter and Methanosarcina. Methanosarcina in the biofilm were observed to be twice as abundant as Methanothermobacter, indicating a potential preference for biofilm existence among methanogens. The findings demonstrated an effective strategy, specifically the stepwise acclimatization of WAS in a thermophilic fixed-bed biofilm reactor, to enhance the food waste treatment performance at high OLRs, contributing valuable mechanistic and technical insights for future sustainable high-strength waste management., 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 Ltd.)

Clinically, most patients with poor wound healing suffer from generalized skin damage, usually accompanied by other complications, so developing therapeutic strategies for difficult wound healing has remained extremely challenging until now. Current studies have indicated that electrical stimulation (ES) to cutaneous lesions enhances skin regeneration by activating intracellular signaling cascades and secreting skin regeneration-related cytokine. In this study, we designed different concentrations of graphene in gelatin-methacrylate (GelMa) to form the conductive composite commonly used in wound healing because of its efficiency compared to other conductive thermo-elastic materials. The results demonstrated the successful addition of graphene to GelMa while retaining the original physicochemical properties of the GelMa bioink. In addition, the incorporation of graphene increased the interactions between these two biomaterials, leading to an increase in mechanical properties, improvement in the swelling ratio, and the regulation of degradation characteristics of the biocomposite scaffolds. Moreover, the scaffolds exhibited excellent electrical conductivity, increasing proliferation and wound healing-related growth factor secretion from human dermal fibroblasts. Overall, the HDF-laden 3D electroconductive GelMa/graphene-based hydrogels developed in this study are ideal biomaterials for skin regeneration applications in the future.

Despite the declining trend of Helicobacter pylori ( H. pylori ) prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing antibiotic resistance. The resistance of H. pylori to different antibiotics is caused by different molecular mechanisms, and advancements in sequencing technology have come a far way in broadening our understanding and in facilitating the testing of antibiotic susceptibility to H. pylori . In this literature review, we give an overview of the molecular mechanisms behind resistance, as well as discuss and compare different antibiotic susceptibility tests based on the latest research. We also discuss the principles of antibiotic stewardship and compare the performance of empirical therapies based on up-to-date resistance patterns and susceptibility-guided therapies in providing effective H. pylori treatment. Studies and clinical guidelines should ensure that the treatment being tested or recommended can reliably achieve a pre-agreed acceptable level of eradication rate and take into account the variations in antibiotic resistance across populations. Local, regional and international organizations must work together to establish routine antibiotic susceptibility surveillance programs and enforce antibiotic stewardship in the treatment of H. pylori , so that it can be managed in a sustainable and efficient manner.