Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients). METHODS: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied. RESULTS: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and ß-lactam/ß-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment. CONCLUSIONS: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients.

Antiplatelet drug ticagrelor suppresses triple negative breast cancer metastasis by targeting PI3K.

Metastatic recurrence is still a major challenge in breast cancer treatment. Patients with triple negative breast cancer (TNBC) develop early recurrence and relapse more frequently. Due to the lack of specific therapeutic targets, new targeted therapies for TNBC are urgently needed. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is one of the active pathways involved in chemoresistance and survival of TNBC, being considered as a potential target for TNBC treatment. Our present study identified ticagrelor, an anti-platelet drug, as a pan-PI3K inhibitor with potent inhibitory activity against four isoforms of class I PI3K. At doses normally used in clinic, ticagrelor showed weak cytotoxicity against a panel of breast cancer cells, but significantly inhibited the migration, invasion and the actin cytoskeleton organization of human TNBC MDA-MB-231 and SUM-159PT cells. Mechanistically, ticagrelor effectively inhibited PI3K downstream mTOR complex 1 (mTORC1) and mTORC2 signaling by targeting PI3K and decreased the protein expression of epithelial-mesenchymal transition (EMT) markers. In vivo, ticagrelor significantly suppressed tumor cells lung metastasis in 4T1 tumor bearing BALB/c mice model and experimental lung metastasis model which was established by tail vein injection of GFP-labeled MDA-MB-231 cells. The above data demonstrated that ticagrelor can inhibit the migration and invasion of TNBC both in vitro and in vivo by targeting PI3K, suggesting that ticagrelor, a pan-PI3K inhibitor, might represent a promising therapeutic agent for the treatment of metastatic TNBC.

Cytomegalovirus and Epstein-Barr virus infections in patients with neuromyelitis optica spectrum disorder.

OBJECTIVES: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in patients with Neuromyelitis optica spectrum disorder (NMOSD) remain unclear. The objective of this study was to investigate CMV and EBV infections in patients with NMOSD. METHODS: Serum immunoglobin (Ig) G antibodies against CMV and EBV were measured in patients with NMOSD and healthy controls (HCs), including anti-CMV, anti-EBV nuclear antigen-1 (EBNA-1), anti-EBV virus capsid antigen (VCA), and anti-EBV early antigen (EA) IgGs. The immune status ratio (ISR) was used to evaluate the serum anti-CMV and anti-EBV IgG levels and ISR ≧1.10 was defined as seropositivity. RESULTS: In total, 238 serum samples were collected from 94 patients with NMOSD and 144 HCs, and no significant difference of sex and age between NMOSD and HCs. Comparing to the HCs, patients with NMOSD exhibited significantly higher serum anti-CMV IgG level. In contrast, the serum anti-EBNA1 IgG level was significantly lower in patients with NMOSD than in HCs. The serum anti-VCA and anti-EA IgG levels did not differ between the two groups, but the anti-EA seropositivity was significantly higher in NMOSD group than that in HC group. We did not find associations between serum anti-CMV or anti-EBV IgG levels and NMOSD disease stage, immunotherapy, or disability score. CONCLUSIONS: Our findings indicated that increased CMV infection and EBV recent infection, as well as reduced EBV latency infection were associated with the risk of NMOSD. Prospective cohort studies are needed to verify our findings and clarify the correlation between CMV and EBV infections and clinical characteristics of NMOSD.

Integrating genetic and proteomic data to elucidate the association between immune system and blood-brain barrier dysfunction with multiple sclerosis risk and severity.

BACKGROUND: Immune system dysfunction and blood-brain barrier (BBB) impairment are implicated in multiple sclerosis (MS) risk and severity. However, the causal relationships and potential therapeutic targets remain unclear. METHODS: Leveraging the MRC IEU OpenGWAS data infrastructure, we extracted 1254 peripheral immune systems and 792 BBB biomarkers as genetic instruments for exposure. MS risk data from the International Multiple Sclerosis Genetics Consortium (IMSGC) (47,429 MS cases, 68,374 controls) served as one outcome, replicated in FinnGen (1048 cases, 217,141 controls) and the UK Biobank (1679 cases, 461,254 controls). Genetic associations with MS severity derived from IMSGC and MultipleMS Consortium GWAS data (12,584 cases). Two-sample, bidirectional, and protein drug-target MR analyses were conducted, along with interaction analysis of identified proteins and druggability assessment. RESULTS: Causal relationships between 45 immunological markers, 15 BBB markers, and MS risk were strongly supported. In peripheral immunity, the causal associations with MS are predominantly concentrated in CD4+ T cells and CD8+ T cells. Notably, anti-Epstein-Barr virus nuclear antigen (EBNA) IgG levels exhibited the most significant causal effect on MS risk (OR = 225.62, P = 5.63E-208), replicated in the MS severity (OR = 1.11, P = 0.04). Weak causal evidence was found between 62 immunological markers, 35 BBB markers, and MS severity. Reverse MR analysis suggested potential causal effects of MS risk on 8 markers. Drug-targeted MR analysis indicated potential therapeutic benefits in reducing MS risk for CD40 (OR = 0.71, P = 7.24E-13, PPH4 = 97.6 %), AHSG (OR = 0.88, P = 2.91E-05, PPH4 = 94.4 %), and FCRL3 (Sun BB et al.: OR = 0.83, P = 8.93E-09, PPH4 = 94.2 %, Suhre K et al.: OR = 0.88, P = 5.20E-08, PPH4 = 99.2 %). CONCLUSIONS: This study provides evidence supporting the causal effects of immune system and BBB dysfunction on MS risk and severity. It emphasizes the significant role of anti-EBNA IgG levels, CD4+ T cells, and CD8+ T cells in MS, and delineates the potential therapeutic benefits of targeting three proteins associated with MS risk: CD40, AHSG, and FCRL3.

Exploring treatment options in cancer: Tumor treatment strategies.

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical and psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive and remarkable transformation. Emerging as fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, and gene therapy. These cutting-edge treatment modalities not only afford personalized and precise tumor targeting, but also provide patients with enhanced therapeutic comfort and the potential to impede disease progression. Nonetheless, it is acknowledged that these therapeutic strategies still harbour untapped potential for further advancement. Gaining a comprehensive understanding of the merits and limitations of these treatment modalities holds the promise of offering novel perspectives for clinical practice and foundational research endeavours. In this review, we discussed the different treatment modalities, including small molecule targeted drugs, peptide drugs, antibody drugs, cell therapy, and gene therapy. It will provide a detailed explanation of each method, addressing their status of development, clinical challenges, and potential solutions. The aim is to assist clinicians and researchers in gaining a deeper understanding of these diverse treatment options, enabling them to carry out effective treatment and advance their research more efficiently.

Hydroxylamine-induced activation of permanganate for enhanced oxidation of sulfamethoxazole: Mechanism and products.

Recently, many reagents have been introduced to accelerate the formation of highly reactive intermediate Mn species from permanganate (KMnO4), thereby improving the oxidation activity of KMnO4 towards pollutants. However, most studies have mainly focused on sulfur-containing reducing agents (e.g., bisulfite and sodium sulfite), with little attention paid to nitrogen-containing reducing agents. This study found that hydroxylamine (HA) and hydroxylamine derivatives (HAs) can facilitate KMnO4 in pollutant removal. Taking sulfamethoxazole (SMX) as a target contaminant, the effect of pH, SMX concentration, KMnO4 and HA dosages, and the molar ratio of HA and KMnO4 on the degradation of SMX in the KMnO4/HA process was systematically investigated. Quenching experiments and probe analysis revealed MnO2-catalyzed KMnO4 oxidation, Mn(III) and reactive nitrogen species as the primary active species responsible for SMX oxidation in the KMnO4/HA system. Proposed transformation pathways of SMX in the KMnO4/HA system mainly involve hydroxylation and cleavage reactions. The KMnO4/HA system was more conducive to selective oxidation of SMX, 2,4-dichlorophenol, and several other pollutants, but reluctant to bisphenol S (BPS). Overall, this study proposed an effective system for eliminating pollutants, while providing mechanistic insight into HA-driven KMnO4 activation for environmental remediation.

Overlooked Impacts of Alcohols in Electro-H2O2 and Fenton Chemistry.

Alcohols are promising fuels for direct alcohol fuel cells and are common scavengers to identify reactive oxygen species (ROS) in electro-Fenton (EF) systems. However, the side impacts of alcohols on oxygen reduction reactions and ROS generation are controversial due to the complex interactions between electrodes and alcohol-containing electrolytes. Herein, we employed synchrotron-Fourier-transform infrared spectroscopy and electron paramagnetic resonance technologies to directly observe the changes of chemical species and electrochemical properties on the electrode surface. Our studies suggested that alcohols exhibited different limiting degrees on proton (H+) mass transfer toward the catalytic surface, following an order of methanol < ethanol < isopropanol < tert-butyl alcohol (TBA). In addition, the formation of hydrophobic TBA clusters at high concentrations (>400 mM) resulted in a significant reduction in ionic conductivity and an elevation in charge transfer resistance, which impedes H+ mass transfer and raises the energy barrier for 2e- oxygen reduction reaction processes. Moreover, the organic radical •CH2(CH3)2CH2OH produced by the interaction of Fe3+ and •OH with the alcohol in the EF system serves as a crucial intermediate in facilitating H2O2 regeneration, which complicates the quenching effect of alcohols on •OH identification. Therefore, it is recommended that methanol should be used as the scavenger instead of TBA and the concentration should be less than 400 mM in EF systems.

A rare adverse effect in inebilizumab therapy for neuromyelitis optica spectrum disorder: a case report.

Inebilizumab is one of the monoclonal antibodies approved as maintenance therapy for aquaporin-4 immunoglobulin G-seropositive neuromyelitis optica spectrum disorder (NMOSD). It is a humanized monoclonal antibody targeting cluster of differentiation 19 (CD19). Common adverse reactions include urinary tract infections, nasopharyngitis, arthralgia, infusion reactions, headaches and a decrease in immunoglobulin levels. Here, we present a case of an NMOSD patient who experienced transient hyperCKaemia after the use of inebilizumab. The adverse reactions of this very rare monoclonal antibody drug improved after discontinuation.

Hybrid nanoflower-based electrochemical lateral flow immunoassay for Escherichia coli O157 detection.

An electrochemical biosensor has been developed for detection of Escherichia coli O157 by integrating lateral flow with screen-printed electrodes. The screen-printed electrodes were attached under the lateral flow detection line, and organic-inorganic nanoflowers prepared from E. coli O157-specific antibodies as an organic component were attached to the lateral flow detection line. In the presence of E. coli O157, an organic-inorganic nanoflower-E. coli O157-antimicrobial peptide-labelled ferrocene sandwich structure is formed on the lateral flow detection line. Differential pulse voltammetry is applied using a smartphone-based device to monitor ferrocene on the detection line. The resulting electrochemical biosensor could specifically detect E. coli O157 with a limit of detection of 25 colony-forming units mL-1. Through substitution of antibodies of organic components in organic-inorganic nanoflowers, biosensors have great potential for the detection of other pathogens in biomedical research and clinical diagnosis.

Associations Between Multiparametric US-Based Indicators and Pathological Status in Patients with Metabolic Associated Fatty Liver Disease.

OBJECTIVE: Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) using ultrasonography holds significant clinical value. The associations between ultrasound (US)-based parameters and the pathological spectra remain unclear and controversial. This study aims to investigate the associations thoroughly. METHODS: The participants with MAFLD undergoing liver biopsy and multiparametric ultrasonography were prospectively recruited from December 2020 to September 2022. Three US-based parameters, namely attenuation coefficient (AC), liver stiffness (LS) and dispersion slope (DS) were obtained. The relationship between these parameters and steatosis grades, inflammation grades and fibrosis stages was examined. RESULTS: In this study with 116 participants, AC values significantly differed across distinct steatosis grades (p < 0.001), while DS and LS values varied among inflammation grades (p < 0.001) and fibrosis stages (p < 0.001). The area under the receiver operating characteristic curves (AUCs) of AC ranged from 0.82 to 0.84 for differentiating steatosis grades, while AUCs of LS ranged from 0.62 to 0.76 for distinguishing inflammation grades and 0.83-0.95 for discerning fibrosis stages. AUCs for DS ranged from 0.79 to 0.81 in discriminating inflammation grades and 0.80-0.88 for differentiating fibrosis stages. Subgroup analysis revealed that LS demonstrated different trends in inflammation grade but consistent trends in fibrosis stage across subgroups, whereas DS showed consistent trends for both inflammation grade and fibrosis stage across all subgroups. CONCLUSION: AC values indicate the degree of hepatic steatosis but not inflammation or fibrosis. LS values are determined only by fibrosis stage and are not associated with inflammation grades. DS values are associated with both fibrosis and inflammation grades.

Identification and Characterization of Metastasis-Initiating Cells in ESCC in a Multi-Timepoint Pulmonary Metastasis Mouse Model.

Metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. Single-cell RNA sequencing analyses are applied to investigate lung metastatic ESCC cells isolated from pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. A small population of parental KYSE30 cell line (Cluster S) resembling metastasis-initiating cells (MICs) is identified because they survive and colonize at lung metastatic sites. Differential expression profile comparisons between Cluster S and other subpopulations identified a panel of 7 metastasis-initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs in ESCC. Functional studies demonstrated MICs (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), migration, invasion, stemness, and in vivo lung metastasis capabilities, while bioinformatics analyses revealed enhanced organ development, stress responses, and neuron development, potentially remodel early metastasis microenvironment. Meanwhile, early metastasizing cells demonstrate quasi-epithelial-mesenchymal phenotype to support both invasion and anchorage. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC clinical samples demonstrated differential MIS expression scores (dMISs) predict lymph node metastasis, overall survival, and risk of carcinothrombosis.

Causal effects of gut microbiota on multiple sclerosis: A two-sample Mendelian randomization study.

BACKGROUND: Gut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear. OBJECTIVE: We performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS. METHODS: Independent genetic variants associated with 211 gut microbiota phenotypes were selected as instrumental variables from the largest genome-wide association studies (GWAS) previously published by the MiBioGen study. GWAS data for MS were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC) for primary analysis and the FinnGen consortium for replication and collaborative analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. RESULTS: After inverse-variance-weighted and sensitivity analysis filtering, seven gut microbiota with potential causal effects on MS were identified from the IMSGC. Only five metabolites remained significant associations with MS when combined with the FinnGen consortium, including genus Anaerofilum id.2053 (odds ratio [OR] = 1.141, 95% confidence interval [CI]: 1.021-1.276, p = .021), Ruminococcus2 id.11374 (OR = 1.190, 95% CI: 1.007-1.406, p = .042), Ruminococcaceae UCG003 id.11361 (OR = 0.822, 95% CI: 0.688-0.982, p = .031), Ruminiclostridium5 id.11355 (OR = 0.724, 95% CI: 0.585-0.895, p = .003), Anaerotruncus id.2054 (OR = 0.772, 95% CI: 0.634-0.940, p = .010). CONCLUSION: Our MR analysis reveals a potential causal relationship between gut microbiota and MS, offering promising avenues for advancing mechanistic understanding and clinical investigation of microbiota-mediated MS.

Preliminary study on diagnosis of gallbladder neoplastic polyps based on contrast-enhanced ultrasound and grey scale ultrasound radiomics.

Objective: Neoplastic gallbladder polyps (GPs), including adenomas and adenocarcinomas, are considered absolute indications for surgery; however, the distinction of neoplastic from non-neoplastic GPs on imaging is often challenging. This study thereby aimed to develop a CEUS radiomics nomogram, and evaluate the role of a combined grey-scale ultrasound and CEUS model for the prediction and diagnosis of neoplastic GPs. Methods: Patients with GPs of ≥ 1 cm who underwent CEUS between January 2017 and May 2022 were retrospectively enrolled. Grey-scale ultrasound and arterial phase CEUS images of the largest section of the GPs were used for radiomics feature extraction. Features with good reproducibility in terms of intraclass correlation coefficient were selected. Grey-scale ultrasound and CEUS Rad-score models were first constructed using the Mann-Whitney U and LASSO regression test, and were subsequently included in the multivariable logistic regression analysis as independent factors for construction of the combined model. Results: A total of 229 patients were included in our study. Among them, 118 cholesterol polyps, 68 adenomas, 33 adenocarcinomas, 6 adenomyomatoses, and 4 inflammatory polyps were recorded. A total of 851 features were extracted from each patient. Following screening, 21 and 15 features were retained in the grey-scale and CEUS models, respectively. The combined model demonstrated AUCs of 0.88 (95% CI: 0.83 - 0.93) and 0.84 (95% CI: 0.74 - 0.93) in the training and testing set, respectively. When applied to the whole dataset, the combined model detected 111 of the 128 non-neoplastic GPs, decreasing the resection rate of non-neoplastic GPs to 13.3%. Conclusion: Our proposed combined model based on grey-scale ultrasound and CEUS radiomics features carries the potential as a non-invasive, radiation-free, and reproducible tool for the prediction and identification of neoplastic GPs. Our model may not only guide the treatment selection for GPs, but may also reduce the surgical burden of such patients.

The comparison of contrast-enhanced ultrasound and gadoxetate disodium-enhanced MRI LI-RADS for nodules ≤2 cm in patients at high risk for HCC: a prospective study.

Objectives: To investigate the consistency of LI-RADS of CEUS and EOB-MRI in the categorization of liver nodules ≤2cm in patients at high risk for HCC. Methods: Patients at high risk for HCC with nodules ≤2cm who underwent CEUS and EOB-MRI in our hospital were prospectively enrolled. The CEUS images and EOB-MRI imaging of each liver nodule were observed to evaluate inter-observer consistency and category according to CEUS LI-RADS V2017 and CT/MRI LI-RADS V2017 criteria double blinded. Pathology and/or follow-up were used as reference standard. Results: A total of 127 nodules in 119 patients met the inclusion criteria. The inter-observer agreement was good on CEUS and EOB-MRI LI-RADS (kappa = 0.76, 0.76 p < 0.001). The inter-modality agreement was fair (kappa=0.21, p < 0.001). There was no statistical difference in PPV and specificity between CEUS and EOB-MRI LR-5 for HCC, while the difference in AUC was statistically significant. We used new criteria (CEUS LR-5 and EOB-MRI LR-4/5 or CEUS LR-4/5 and EOB-MRI LR-5) to diagnose HCC. The sensitivity, specificity, and AUC of this criteria was 63.4%, 95.6%, and 0.80. Conclusions: CEUS and EOB-MRI showed fair inter-modality agreement in LI-RADS categorization of nodules ≤2 cm. The inter-observer agreement of CEUS and EOB-MRI LI-RADS were substantial. CEUS and EOB-MRI LR-5 have equally good positive predictive value and specificity for HCC ≤ 2cm, and combining these two modalities may better diagnose HCC ≤ 2 cm. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04212286.

Comparisons between Caucasian-validated photo-numeric scales and Korean-validated photo-numeric scales for photo-ageing. Insights from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort.

BACKGROUND: Photo-ageing is a form of skin ageing which affects the entire face. A photo-aged skin has a diverse variety of wrinkles and dyspigmentation all over the face. Here, we discuss photo-ageing on the Chinese skin evaluated using a photo-numeric scale developed and validated on Caucasian skin (i.e., Caucasian scale) and evaluated using a photo-numeric scale developed and validated on Korean skin (i.e., Korean scale). The Korean scale can be subdivided into two scales that separately address the wrinkling and dyspigmentation constituents of photo-ageing. AIM: As there are currently no photo-ageing scales for Chinese skin, the main objective of this study is to adapt existing photo-ageing photo-numeric scales for use on ethnic Chinese skin. METHOD: Three trained assessors studied facial photo-ageing on 1,081 ethnic Chinese young adults from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort. RESULTS: All assessors are highly internally consistent (Weighted Kappa (κw) values≥0.952). We found that the Caucasian scale and Korean scale give nearly synonymous results for the wrinkling constituent of photo-ageing (R2 = 0.9386). The two scales are strongly concordant (Spearman's Rank Correlation (ρ) value: 0.62 ± 0.06, p = 1.31×10-84). A weak-to-moderate inter-scalar level of agreement (Cohen's Kappa (κ) values: 0.38 ± 0.05, p = 8.87×10-53) persists and is statistically significant after accounting for agreements due to chance. When tested on ethnic Chinese skin, both scales detect photo-ageing consistently (Area under curve [AUC] values: 0.76-0.84). Additionally, the Korean scale for the dyspigmentation constituent of photo-ageing is concordant with both the Caucasian scale (R2 = 0.7888) and the Korean scale for the wrinkling constituent of photo-ageing (R2 = 0.7734). CONCLUSION: Our results show that the Caucasian scale is suitable for capturing photo-ageing on Chinese skin, especially wrinkle variations. The Korean dyspigmentation scale supplements the Caucasian scale to capture dyspigmentation patterns on Chinese skin that may be absent on Caucasian skin. Currently, photo-ageing scales for Chinese skin are absent. When developed, these photo-ageing scales must be properly validated for their ability to capture photo-ageing of the entire face.

High-valent metal-oxo species transformation and regulation by co-existing chloride: Reaction pathways and impacts on the generation of chlorinated by-products.

High-valent metal-oxo species (HMOS) have been extensively recognized in advanced oxidation processes (AOPs) owing to their high selectivity and high chemical utilization efficiency. However, the interactions between HMOS and halide ions in sewage wastewater are complicated, leading to ongoing debates on the intrinsic reactive species and impacts on remediation. Herein, we prepared three typical HMOS, including Fe(IV), Mn(V)-nitrilotriacetic acid complex (Mn(V)NTA) and Co(IV) through peroxymonosulfate (PMS) activation and comparatively studied their interactions with Cl- to reveal different reactive chlorine species (RCS) and the effects of HMOS types on RCS generation pathways. Our results show that the presence of Cl- alters the cleavage behavior of the peroxide OO bond in PMS and prohibits the generation of Fe(IV), spontaneously promoting SO4•- production and its subsequent transformation to secondary radicals like Cl• and Cl2•-. The generation and oxidation capacity of Mn(V)NTA was scarcely influenced by Cl-, while Cl- would substantially consume Co(IV) and promote HOCl generation through an oxygen-transfer reaction, evidenced by density functional theory (DFT) and deuterium oxide solvent exchange experiment. The two-electron-transfer standard redox potentials of Fe(IV), Mn(V)NTA and Co(IV) were calculated as 2.43, 2.55 and 2.85 V, respectively. Due to the different reactive species and pathways in the presence of Cl-, the amounts of chlorinated by-products followed the order of Co(II)/PMS > Fe(II)/PMS > Mn(II)NTA/PMS. Thus, this work renovates the knowledge of halide chemistry in HMOS-based systems and sheds light on the impact on the treatment of salinity-containing wastewater.

Comparisons between wrinkles and photo-ageing detected and self-reported by the participant or identified by trained assessors reveal insights from Chinese individuals in the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort.

BACKGROUND: Changes develop on the facial skin as a person ages. Other than chronological time, it has been discovered that gender, ethnicity, air pollution, smoking, nutrition, and sun exposure are notable risk factors that influence the development of skin ageing phenotypes such as wrinkles and photo-ageing. These risk factors can be quantified through epidemiological collection methods. We previously studied wrinkles and photo-ageing in detail using photo-numeric scales. The analysis was performed on the ethnic Chinese skin by three trained assessors. Recent studies have shown that it is possible to use self-reported data to identify skin-related changes including skin colour and skin cancer. In order to investigate the association between risk factors and skin ageing phenotypic outcomes in large-scale epidemiological studies, it would be useful to evaluate whether it is also possible for participants to self-report signs of ageing on their skin. AIM: We have previously identified several validated photo-numeric scales for wrinkling and photo-ageing to use on ethnic Chinese skin. Using these scales, our trained assessors grade wrinkling and photo-ageing with moderately high inter-assessor concordance and agreement. The main objective of this study involves letting participants grade self-reported wrinkling and photo-ageing using these same scales. We aim to compare the concordance and agreement between signs of skin ageing by the participant and signs of ageing identified by our assessors. METHOD: Three trained assessors studied facial photo-ageing on 1081 ethnic Chinese young adults from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort. Self-reported facial photo-ageing data by the same 1081 participants were also collated and the two sets of data are compared. RESULTS: Here, we found that self-reported signs of photo-ageing are concordant with photo-ageing detected by our assessors. This finding is consistent whether photo-ageing is evaluated through studying wrinkle variations (Spearman's rank correlation (ρ) value: 0.246-0.329) or through studying dyspigmentation patterns (Spearman's rank correlation (ρ) value 0.203-0.278). When studying individual wrinkles, both participants and assessors often detect the presence of the same wrinkle (Spearman's rank correlation (ρ) value 0.249-0.366). A weak-to-fair level of agreement between both participants and assessors (Cohen's kappa (κ) values: 0.041-0.233) persists and is statistically significant after accounting for agreements due to chance. Both the participant and the assessor are largely consistent in evaluating the extent of photo-ageing (area under curve (AUC) values 0.689-0.769) and in discerning between the presence or absence of a given facial wrinkle (area under curve (AUC) values 0.601-0.856). CONCLUSION: When we analyse the overall appearance of the face, our results show that signs of photo-ageing identified by the participant are concordant with signs of photo-ageing identified by our assessors. When we focused our analysis on specific areas of the face, we found that participants were more likely to identify and self-report the same wrinkles that our assessors have also detected. Here, we found that self-reported signs of skin ageing provide a satisfactory approximation to the signs of skin ageing identified by our assessors. The ability to use self-reported signs of skin ageing should also be evaluated on scales beyond the ones discussed in this study. Currently, there are not as many photo-numeric scales for quantifying dyspigmentation patterns as there are for quantifying wrinkle variations. As Chinese skin is known to become dyspigmented more easily with age, more photo-numeric scales need to be developed and properly validated.

A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.