[Analysis of Regional Differences in Cadmium Ecological Risk in Surface Waters of the Yangtze River Basin].

This study primarily focused on the regional disparities in both water quality criteria and ecological risks attributed to cadmium presence within the surface waters of the Yangtze River Basin. In the initial phase, the long-term water quality criteria for cadmium were recalibrated in accordance with the guidelines outlined in China's "Water Quality Criteria for Freshwater Aquatic Organisms-Cadmium," accounting for the prevalent hardness distribution within the Yangtze River Basin's surface water. Subsequently, a more refined revision was undertaken considering the specific characteristics of the species residing within the Yangtze River Basin. This undertaking led to a comprehensive interpretation of the regional variations in both the distribution of long-term water quality criteria values and the risk quotient distribution of cadmium throughout the Yangtze River Basin. The incorporation of hardness and species-specific attributes resulted in a revised range of long-term water quality criteria for cadmium across different urban locales within the Yangtze River Basin. Notably, the recalibrated values ranged from 0.08 µg·L-1 as the lowest threshold to 0.75 µg·L-1 as the upper limit, signifying a tenfold differentiation. Correspondingly, the urban average annual risk quotient associated with cadmium exposure demonstrated a variation from 0.035 to 1.12, marking a significant 32-fold discrepancy between the lowest and highest values. It is essential to highlight that regions of paramount importance, such as the confluence area connecting the upper and middle stretches of the Yangtze River Basin and the intricate Dongting Lake system, exhibited noteworthy ecological risks attributed to cadmium presence. Consequently, further in-depth investigations into these critical regions are imperative for a comprehensive understanding of the associated risks.

Protocol for building an in vitro model of M2-like tumor-associated macrophages with lactic acid or conditioned medium from Lewis cells.

The model of M2-like tumor-associated macrophages (TAMs) is an increasingly attractive model for the study of TAMs. However, the detailed process of M2-like TAMs polarization induced by lactic acid or conditioned medium from Lewis cells (LCM) and the identification of M2-like TAMs is not yet available. In this protocol, we present the detailed methods to induce M2-like TAMs polarization and verify its functionality in order to better carry out related research. For complete details on the use and execution of this protocol, please refer to Fang et al.1.

A Hydrophilic Metal Azolate Coordination Polymer for In Situ Encapsulation of Haloalkane Dehalogenase with Enhanced Enzymatic Performance.

Encapsulating enzymes within metal-organic frameworks such as zeolitic imidazolate framework-8 (ZIF-8) has been demonstrated to enhance enzymatic performance under harsh conditions. However, by computer-aided analysis, we revealed that highly hydrophobic organic ligands and unfavorable metal ions could greatly impair the activity of haloalkane dehalogenase DhaA by directly interacting with the catalytic sites, causing an extremely low activity of DhaA after encapsulating within ZIF-8. We also found that the presence of a protecting polymer could protect DhaA from the damage of organic ligands and metal ions and that a positively charged amino acid could increase the DhaA activity. Based on the simulations and experimental observations, we have designed to coencapsulate DhaA with poly(vinylpyrrolidone) (PVP) and lysine (Lys) within the amorphous Co-based metal azolate coordination polymer (CoCP). The as-prepared immobilized enzyme (DhaA/PVP/Lys@CoCP) exhibited significantly increased activity (91.5 times higher than that of DhaA@ZIF-8), dramatically enhanced thermostability at 50-70 °C, greatly improved catalytic performance in several organic solvent solutions, and good recyclability (over 75% of the initial activity after 10 cycles). The superiority of the immobilized enzyme was also demonstrated with a substrate frequently detected in the real world. In addition to the protective effect of PVP and positive effect of Lys, experimental and computational investigations unveiled other two favorable aspects that contributed to the enhanced enzymatic performance: (1) high hydrophilicity of the immobilization material and (2) the use of Co2+ with a minimal negative effect on DhaA. The research has thus provided a promising immobilized DhaA with favorable catalytic performance and great potential in industrial applications.

Comparison of Patient Health Questionnaire-9, Edinburgh Postnatal Depression Scale and Hospital Anxiety and Depression - Depression subscale scores by administration mode: An individual participant data differential item functioning meta-analysis.

Administration mode of patient-reported outcome measures (PROMs) may influence responses. We assessed if Patient Health Questionnaire-9 (PHQ-9), Edinburgh Postnatal Depression Scale (EPDS) and Hospital Anxiety and Depression Scale - Depression subscale (HADS-D) item responses and scores were associated with administration mode. We compared (1) self-administration versus interview-administration; within self-administration (2) research or medical setting versus private; and (3) pen-and-paper versus electronic; and within interview-administration (4) in-person versus phone. We analysed individual participant data meta-analysis datasets with item-level data for the PHQ-9 (N = 34,529), EPDS (N = 16,813), and HADS-D (N = 16,768). We used multiple indicator multiple cause models to assess differential item functioning (DIF) by administration mode. We found statistically significant DIF for most items on all measures due to large samples, but influence on total scores was negligible. In 10 comparisons conducted across the PHQ-9, EPDS, and HADS-D, Pearson's correlations and intraclass correlation coefficients between latent depression symptom scores from models that did or did not account for DIF were between 0.995 and 1.000. Total PHQ-9, EPDS, and HADS-D scores did not differ materially across administration modes. Researcher and clinicians who evaluate depression symptoms with these questionnaires can select administration methods based on patient preferences, feasibility, or cost.

Neferine inhibits BMECs pyroptosis and maintains blood-brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α.

Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.

COVID-19 vaccinations and infections among individuals with systemic sclerosis: A Scleroderma Patient-centered Intervention Network (SPIN) Cohort study.

BACKGROUND/PURPOSE: We previously surveyed adults with systemic sclerosis (SSc) regarding COVID-19 vaccination in April-May 2021. The objective of the present study was to update through June-July 2022 and assess self-reported (1) COVID-19 vaccination rates, including boosters; (2) vaccine-related adverse events; (3) peri­vaccination immunosuppressive medication management; (4) vaccine hesitancy; and (5) prevalence and severity of COVID-19 infections. METHODS: In April-May 2021 and June-July 2022, SPIN Cohort participants completed surveys on COVID-19 vaccination and infection. Primary vaccine series was defined according to the standard for each COVID-19 vaccine; additional vaccine administrations were considered booster doses. Fully vaccinated was defined as having completed a primary vaccine series and at least one booster dose. RESULTS: 544 participants completed the 2021 survey only, 101 the 2022 survey only, and 388 both surveys. Among 489 participants with 2022 data, 437 (89 %) had received both primary and booster vaccines. Among all 1,033 participants, 960 (93 %) received at least one dose. At least one adverse reaction was reported by 34 % (330 of 960 participants) following first, 48 % (314 of 657 participants) following second, and 34 % (147 of 437 participants) following booster vaccine doses (primarily sore arm and fatigue); no severe adverse reactions were reported. SSc symptom worsening was reported in 6 % (53 of 960) after the first, 6 % after the second (39 of 657), and 4 % (17 of 437) after the booster dose. Of participants taking methotrexate or mycophenolate (including Cellcept or Myfortic), 34 of 266 (13 %) reported that they temporarily stopped or decreased their medication at the first dose, 32 of 215 (15 %) at the second dose, and 28 of 148 (19 %) for booster vaccination. Of 52 individuals not fully vaccinated with primary and booster doses in 2022, 29 (56 %) reported worry about vaccine related SSc flares. 172 of 489 (35 %) 2022 participants reported a history of at least one COVID-19 infection; 114 (66 %) occurred after receiving at least a primary vaccine series. Among initial COVID-19 infections, 9 (5 %) were asymptomatic, 66 (38 %) involved mild symptoms, 82 (48 %) moderate symptoms, and 15 (9 %) required hospitalization. CONCLUSION: Most people with SSc in the study were fully vaccinated, and most continued their methotrexate or mycophenolate post-primary and booster vaccinations. Over half of vaccine-hesitant participants were concerned regarding risk of SSc flare; however, few vaccinated participants reported this. These data may be useful for counselling people with SSc regarding COVID-19 vaccine safety and outcomes.

Biosafety assessment of laying hens fed different treatments of black soldier flies (Hermetia illucens) under doxycycline stress.

The black soldier fly (BSF, Hermetia illucens) is a resource insect that can utilize livestock and poultry feces. However, BSFs may also increase the risk of transmission of antibiotic resistance genes (AGRs) that are widespread in livestock and poultry farm environments. Therefore, we aimed to evaluate the biosecurity risks of different BSF treatments in the laying chicken food chain using the "chicken manure-BSF-laying hens" model. Our results indicated that different BSF treatments significantly affected antibiotic residue, ARGs, MGEs, bacterial antibiotic resistance, and bacterial microbial community composition in the food chain of laying hens fed BSFs. These risks can be effectively reduced through starvation treatment and high-temperature grinding treatment. Comprehensive risk assessment analysis revealed that starvation combined with high-temperature milling (Group H) had the greatest effect.

Individual Patient Data Meta-Analysis Estimates the Minimal Detectable Change of the Geriatric Depression Scale-15.

OBJECTIVE: To use individual participant data meta-analysis (IPDMA) to estimate the minimal detectable change (MDC) of the Geriatric Depression Scale-15 (GDS-15) and to examine whether MDC may differ based on participant characteristics and study-level variables. STUDY DESIGN AND SETTING: This was a secondary analysis of data from an IPDMA on the depression screening accuracy of the GDS. Datasets from studies published in any language were eligible for the present study if they included GDS-15 scores for participants aged 60 or older. MDC of the GDS-15 was estimated via random-effects meta-analysis using 2.77 (MDC95) and 1.41 (MDC67) standard errors of measurement (SEM). Subgroup analyses were used to evaluate differences in MDC by participant age and sex. Meta-regression was conducted to assess for differences based on study-level variables, including mean age, proportion male, proportion with major depression, and recruitment setting. RESULTS: 5,876 participants (mean age 76 years, 40% male, 11% with major depression) from 21 studies were included. The MDC95 was 3.81 points (95% confidence interval [CI] 3.59, 4.04), and MDC67 was 1.95 (95% CI 1.83, 2.03). The difference in MDC95 was 0.26 points (95% CI 0.04, 0.48) between ≥ 80-year-olds and < 80-year-olds; MDC95 was similar for females and males (0.05, 95% CI -0.12, 0.22). The MDC95 increased by 0.29 points (95% CI 0.17, 0.41) per 10% increase in proportion of participants with major depression; mean age had a small association (0.04 points, 95% CI 0.00 to 0.09) with MDC95, but sex and recruitment setting were not significantly associated. CONCLUSIONS: The MDC95 was 3.81 points and MDC67 was 1.95 points. MDC95 increased with the proportion of participants with major depression. Results can be used to evaluate individual changes in depression symptoms and as a threshold for assessing minimal clinical important difference estimates.

[Research progress in raw and processed Raphani Semen and prediction of quality markers].

Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.

The trial-by-trial fluctuations in primary motor cortex excitability during attentional bias among smokers: A transcranial magnetic stimulation study.

Background: A relatively new computational approach called trial-level bias score (TL-BS) has shown that attentional bias to smoking-related stimuli in smokers fluctuates temporally, trial by trial, during attention tasks. Here, we investigated the reliability of using TL-BS values to assess attentional bias and the electrophysiology mechanisms undergirding fluctuations in attentional bias among smokers. Method: In total, 26 male smokers and 26 male non-smokers performed a dot-probe task in Experiment 1. In Experiment 2, an additional 23 male smokers and 23 male non-smokers performed the same task while undergoing single-pulse transcranial magnetic stimulation, which was used to investigate corticospinal excitability. Results: It showed that assessing TL-BS parameters for reaction time (RT) was more reliable than calculating the traditional mean attentional bias score; however, this superior reliability was no longer apparent after controlling for general RT variability. There was a significant difference between smokers and non-smokers in TL-BS parameters calculated for both RT and motor-evoked potential (MEP) amplitude. However, TL-BS parameters for RT and MEP amplitude were strongly correlated with general RT variability and general MEP variability, respectively. Conclusions: Our findings indicated that TL-BS parameters may not be ideal for measuring attentional bias at either the behavioral or electrophysiology level; however, larger general RT and MEP amplitude variabilities in non-smokers may indicate dysregulation of cognitive processing in smokers.

Transcriptome Analysis of Sesame (Sesamum indicum L.) Reveals the LncRNA and mRNA Regulatory Network Responding to Low Nitrogen Stress.

Nitrogen is one of the important factors restricting the development of sesame planting and industry in China. Cultivating sesame varieties tolerant to low nitrogen is an effective way to solve the problem of crop nitrogen deficiency. To date, the mechanism of low nitrogen tolerance in sesame has not been elucidated at the transcriptional level. In this study, two sesame varieties Zhengzhi HL05 (ZZ, nitrogen efficient) and Burmese prolific (MD, nitrogen inefficient) in low nitrogen were used for RNA-sequencing. A total of 3964 DEGs (differentially expressed genes) and 221 DELs (differentially expressed lncRNAs) were identified in two sesame varieties at 3d and 9d after low nitrogen stress. Among them, 1227 genes related to low nitrogen tolerance are mainly located in amino acid metabolism, starch and sucrose metabolism and secondary metabolism, and participate in the process of transporter activity and antioxidant activity. In addition, a total of 209 pairs of lncRNA-mRNA were detected, including 21 pairs of trans and 188 cis. WGCNA (weighted gene co-expression network analysis) analysis divided the obtained genes into 29 modules; phenotypic association analysis identified three low-nitrogen response modules; through lncRNA-mRNA co-expression network, a number of hub genes and cis/trans-regulatory factors were identified in response to low-nitrogen stress including GS1-2 (glutamine synthetase 1-2), PAL (phenylalanine ammonia-lyase), CHS (chalcone synthase, CHS), CAB21 (chlorophyll a-b binding protein 21) and transcription factors MYB54, MYB88 and NAC75 and so on. As a trans regulator, lncRNA MSTRG.13854.1 affects the expression of some genes related to low nitrogen response by regulating the expression of MYB54, thus responding to low nitrogen stress. Our research is the first to provide a more comprehensive understanding of DEGs involved in the low nitrogen stress of sesame at the transcriptome level. These results may reveal insights into the molecular mechanisms of low nitrogen tolerance in sesame and provide diverse genetic resources involved in low nitrogen tolerance research.

Anisotropic optical property of ferroelectric Bi2O2X(X = S,Se,Te) monolayer and strain engineering.

Based on the first-principles calculations, ferroelectricBi2O2X(X=S,Se,Te)monolayers with unequivalent in-plane lattice constants are confirmed to be the ground state, which is consistent with the experiment result (Ghoshet al2019Nano Lett.195703-09), and the anisotropic optical property is firstly investigated. We find that the polarizations ofBi2O2Xmonolayers points along the direction ofa-axis, andBi2O2Temonolayer process the largest polarization. Furthermore, both the biaxial and uniaxial strains are favor for the enhancement of polarization ofBi2O2Xmonolayers. It should be mentioned that the type of band gap will convert from indirect to direct forBi2O2Temonolayer when thea-axial tensile strain is larger than 2%. At last, the optical absorption coefficient forBi2O2Xmonolayers are calculated, and we obtain thatBi2O2Temonolayer has the strongest optical absorption within the range of visible light, the anisotropy and possible strain engineering to improve the optical absorption are discussed in detail. Our findings are significant in fields of optoelectronics and photovoltaics.

Poria acid inhibit the growth and metastasis of renal cell carcinoma by inhibiting the PI3K/akt/NF-κb signaling pathway.

Background: Poria acid (PAC) is a triterpene compound found in Poria cocos, a traditional Chinese medicine (TCM). The current study aims to explore the therapeutic effects and potential mechanisms of PAC on the migration and proliferation of human renal cell carcinoma (RCC) cells as well as tumor growth in animal model. Methods: Cell viability and proliferative capacity of normal renal cells and RCC cells were investigated by MTT assay. In addition, 786-O cells were divided into four groups and treated with different concentrations of PAC (0, 20, 40, and 60 µM) for 48 h. Cell scratch test and cell invasion assay were performed to evaluate the effects of PAC on the invasion and migration of RCC cells, respectively. The effects of PAC on apoptosis of RCC cells and expression levels of PI3K/Akt/NF-kB signaling pathway-related biomarkers were investigated using TUNEL staining and Western blotting methods, respectively. Effects of PAC on the inhibitory activity of RCC tumor in mice were evaluated in a 786-O CDX model. Results: The study found that PAC inhibited the viability of RCC cells in a dose-dependent manner, as demonstrated by in vitro cell assays (p < 0.05). However, PAC showed no significant inhibitory effect on normal renal cells (p > 0.05). PAC also significantly inhibited the migration and invasion of RCC via EMT/MMP signaling pathways (p < 0.05). Immunofluorescence and immunoblotting results showed that PAC induced the apoptosis of RCC, which was accompanied by changes in the expression levels of apoptosis-related proteins (p < 0.05). Moreover, PAC significantly downregulated the PI3K/Akt/NF-kB signaling pathway in a concentration-dependent manner (p < 0.05). The effect of PAC on RCC apoptosis was dramatically reversed by 740Y-P (PI3K agonist) (p < 0.05) but significantly enhanced in the presence of LY294002 (PI3K inhibitor) (p < 0.05). The results of in vivo experiment also demonstrated that the antitumor activity of PAC was achieved by affecting the PI3K/Akt/NF-kB signaling pathway. Conclusions: PAC can effectively suppress the proliferation, invasion and migration of RCC cells, and exhibit anti-tumor effects in RCC model by inhibiting the PI3K/Akt/NF-kB signaling pathway.

A Multimodal Feature Fusion Brain Fatigue Recognition System Based on Bayes-gcForest.

Modern society increasingly recognizes brain fatigue as a critical factor affecting human health and productivity. This study introduces a novel, portable, cost-effective, and user-friendly system for real-time collection, monitoring, and analysis of physiological signals aimed at enhancing the precision and efficiency of brain fatigue recognition and broadening its application scope. Utilizing raw physiological data, this study constructed a compact dataset that incorporated EEG and ECG data from 20 subjects to index fatigue characteristics. By employing a Bayesian-optimized multi-granularity cascade forest (Bayes-gcForest) for fatigue state recognition, this study achieved recognition rates of 95.71% and 96.13% on the DROZY public dataset and constructed dataset, respectively. These results highlight the effectiveness of the multi-modal feature fusion model in brain fatigue recognition, providing a viable solution for cost-effective and efficient fatigue monitoring. Furthermore, this approach offers theoretical support for designing rest systems for researchers.

B1 inhomogeneity corrected CEST MRI based on direct saturation removed omega plot model at 5T.

PURPOSE: CEST can image macromolecules/compounds via detecting chemical exchange between labile protons and bulk water. B1 field inhomogeneity impairs CEST quantification. Conventional B1 inhomogeneity correction methods depend on interpolation algorithms, B1 choices, acquisition number or calibration curves, making reliable correction challenging. This study proposed a novel B1 inhomogeneity correction method based on a direct saturation (DS) removed omega plot model. METHODS: Four healthy volunteers underwent B1 field mapping and CEST imaging under four nominal B1 levels of 0.75, 1.0, 1.5, and 2.0 µT at 5T. DS was resolved using a multi-pool Lorentzian model and removed from respective Z spectrum. Residual spectral signals were used to construct the omega plot as a linear function of 1/ B 1 2 $$ {B}_1^2 $$ , from which corrected signals at nominal B1 levels were calculated. Routine asymmetry analysis was conducted to quantify amide proton transfer (APT) effect. Its distribution across white matter was compared before and after B1 inhomogeneity correction and also with the conventional interpolation approach. RESULTS: B1 inhomogeneity yielded conspicuous artifact on APT images. Such artifact was mitigated by the proposed method. Homogeneous APT maps were shown with SD consistently smaller than that before B1 inhomogeneity correction and the interpolation method. Moreover, B1 inhomogeneity correction from two and four CEST acquisitions yielded similar results, superior over the interpolation method that derived inconsistent APT contrasts among different B1 choices. CONCLUSION: The proposed method enables reliable B1 inhomogeneity correction from at least two CEST acquisitions, providing an effective way to improve quantitative CEST MRI.

Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023.

Background and aim: The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. Methods: A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. Results: There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). Conclusion: IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.

Multimodal approach utilising a weight management programme prior to bariatric surgery in patients with BMI ≥50 kg/m2: A propensity score matching retrospective cohort study.

We evaluated preoperative weight loss and days from initial consult to surgery in patients with BMI ≥50 kg/m2 who were and were not enrolled in medical weight management (MWM) prior to laparoscopic sleeve gastrectomy. We retrospectively identified patients with BMI ≥50 kg/m2 who had primary sleeve gastrectomy between 2014 and 2019 at two bariatric surgery centres in our healthcare system. Patients presenting after 2017 that received preoperative MWM (n = 28) were compared to a historical cohort of non-MWM patients (n = 118) presenting prior to programme initiation in 2017 on preoperative percent total body weight loss (%TBWL) and days from initial consult to surgery. A total of 151 patients (MWM, 33; non-MWM, 118) met inclusion criteria. BMI was significantly greater in MWM versus non-MWM (p = .018). After propensity score matching, median BMI at initial consult in non-MWM versus MWM no longer differed (p = .922) neither were differences observed on the basis of weight, age, sex, race or ethnicity. After PSM, MWM had significantly lower BMI at surgery (p = .018), lost significantly more weight from consult to surgery (p < .001) and achieved significantly greater median %TBWL from consult to surgery (p < .001). We noted no difference between groups on 6-month weight loss (p = .533). Days from initial consult to surgery did not differ between groups (p < .863). A preoperative MWM programme integrated into multimodal treatment for obesity in patients with a BMI ≥50 kg/m2 resulted in clinically significant weight loss without prolonging time to surgery.

Lysophosphatidic Acid Receptor 1 (LPA1) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer.

Metastasis is responsible for about 90 % of cancer deaths. Anti-metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis-specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive. Lysophosphatidic acid receptor 1 (LPA1) is activated by an endogenous lipid molecule LPA, leading to a diverse array of cellular activities. Previous studies have shown that the LPA/LPA1 axis supports the progression of metastasis for many types of cancer. In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12 f, the most potent and highly selective in this series with an IC50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migrastatic target. Consequently, the LPA1 antagonists developed in this study hold promise as potential migrastatic candidates for TNBC.