Genetic deletion of the apoptosis associated speck like protein containing a card in LysM+ macrophages attenuates spinal cord injury by regulating M1/M2 polarization through ASC-dependent inflammasome signaling axis.

Apoptosis associated speck like protein containing a card (ASC), the key adaptor protein of the assembly and activation of canonical inflammasomes, has been found to play a significant role in neuroinflammation after spinal cord injury (SCI). The previous studies indicated that widely block or knockout ASC can ameliorate SCI. However, ASC is ubiquitously expressed in infiltrated macrophages and local microglia, so further exploration is needed on which type of cell playing the key role. In this study, using the LysMcre;Ascflox/flox mice with macrophage-specifc ASC conditional knockout (CKO) and contusive SCI model, we focus on evaluating the specific role of ASC in lysozyme 2 (LysM)+ myeloid cells (mainly infiltrated macrophages) in this pathology. The results revealed that macrophage-specifc Asc CKO exhibited the follow effects: (1) A significant reduction in the numbers of infiltrated macrophages in the all phases of SCI, and activated microglia in the acute and subacute phases. (2) A significant reduction in ASC, caspase-1, interleukin (IL)-1ß, and IL-18 compared to control mice. (3) In the acute and subacute phases of SCI, M1 subset differentiation was inhibited, and M2 differentiation was increased. (4) Histology and hindlimb motor recoveries were improved. In conclusion, this study elucidates that macrophage-specific ASC CKO can improve nerve function recovery after SCI by regulating M1/M2 polarization through inhibiting ASC-dependent inflammasome signaling axis. This indicates that ASC in peripheral infiltrated macrophages may play an important role in SCI pathology, at least in mice, could be a potential target for treatment.

Shaping Adoption and Sustained Use Across the Maternal Journey: Qualitative Study on Perceived Usability and Credibility in Digital Health Tools.

BACKGROUND: Maternal and child health outcomes are positively influenced by early intervention, and digital health (DH) tools provide the potential for a low-cost and scalable solution such as informational platforms or digital tracking tools. Despite the wide availability of DH tools out there for women from before to after pregnancy, user engagement remains low. OBJECTIVE: This study aims to explore the factors that shape women's DH adoption and sustained use across the maternal journey from preconception to postbirth, to improve user engagement with DH tools. METHODS: One-hour semistructured qualitative interviews were conducted with 44 women from before to after pregnancy (age range 21-40 years) about their experiences with DH. This study is part of a larger study on women's maternal experiences with health care and DH and focuses on the factors that affected women's DH adoption and sustained use. Interviews were audio recorded, transcribed verbatim, and analyzed using inductive thematic analysis. RESULTS: Five main themes and 10 subthemes were identified that affected women's adoption and sustained use of DH tools. These included themes on their preexisting attitudes to DH, perceived ease of use, perceived usefulness, perceived credibility, and perceived value of the tool. CONCLUSIONS: The themes that emerged were fully or partially mapped according to the Unified Theory of Acceptance and Use of Technology 2 model. The applicability of the model and the need to consider specific cultural nuances in the Asian context (such as the importance of trust and social influence) are discussed. The interaction of the 5 themes with DH adoption and sustained use are explored with different themes being relevant at various points of the DH adoption journey. The insights gained serve to inform future DH design and implementation of tools for women to optimize their DH engagement and the benefits they derive from it. TRIAL REGISTRATION: ClinicalTrials.gov NCT05099900; https://clinicaltrials.gov/study/NCT05099900.

Injectable Gel-PEG hydrogels as promising delivery system for intravitreal PACAP release: Novel therapeutics for unilateral common carotid artery occlusion induced retinal ischemia.

Retinal ischemia is an ophthalmic emergency often caused by cardiovascular diseases, leading to irreversible vision loss and even blindness. Innovative retinal ischemia treatments are needed due to limited options. The pathological mechanisms involve retinal cell apoptosis and microglial activation. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a well distributed neuropeptide found in both central nervous system and peripheral organs. Though it shows great anti-apoptosis and anti-microglia activation properties, it is rapidly cleared by intravitreal injection. Herein, we established a novel poly(ethylene glycol) (PEG) hydrogel system by cross-linking 4arm-PEG-NHS and 4arm-PEG-NH2 to load PACAP (PACAP@Gel-PEG), which exhibited great fluidity, injectability, structural recovery ability, moderate swelling ratio and drug release ability that were appropriate for drug delivery. Then the safety and effectiveness of the PACAP@Gel-PEG were evaluated in vitro in three retinal cell lines (ARPE-19, 661 W and rRMC) and in vivo using the unilateral common carotid artery occlusion (UCCAO) mice model. The CCK-8 test and live/dead staining demonstrated that PACAP@Gel-PEG exhibited excellent biocompatibility in three retinal cell lines. Furthermore, after PACAP@Gel-PEG treatment, a great anti-apoptotic effect was observed in cells treated by CoCl2. Application of PACAP@Gel-PEG greatly improved the therapeutic efficacy of PACAP in restoring retinal function, maintaining retinal integrity, and suppressing apoptosis and microglia activation in retinal tissues. Moreover, in mice, the biosafety of PACAP@Gel-PEG was confirmed by H&E staining of systemic organs. Taken together, our results demonstrated PACAP@Gel-PEG as a promising therapeutic option for retinal ischemia, providing new strategies for vision restoration.

An Overview of Interactions between Goat Milk Casein and Other Food Components: Polysaccharides, Polyphenols, and Metal Ions.

Casein is among the most abundant proteins in milk and has high nutritional value. Casein's interactions with polysaccharides, polyphenols, and metal ions are important for regulating the functional properties and textural quality of dairy foods. To improve the functional properties of casein-based foods, a deep understanding of the interaction mechanisms and the influencing factors between casein and other food components is required. This review started by elucidating the interaction mechanism of casein with polysaccharides, polyphenols, and metal ions. Thermodynamic incompatibility and attraction are the fundamental factors in determining the interaction types between casein and polysaccharides, which leads to different phase behaviors and microstructural types in casein-based foods. Additionally, the interaction of casein with polyphenols primarily occurs through non-covalent (hydrogen bonding, hydrophobic interactions, van der Waals forces, and ionic bonding) or covalent interaction (primarily based on the oxidation of proteins or polyphenols by enzymatic or non-enzymatic (alkaline or free radical grafting) approaches). Moreover, the selectivity of casein to specific metal ions is also introduced. Factors affecting the binding of casein to the above three components, such as temperature, pH, the mixing ratio, and the fine structure of these components, are also summarized to provide a good foundation for casein-based food applications.

Rational Design of an Artificial Metalloenzyme by Constructing a Metal-Binding Site Close to the Heme Cofactor in Myoglobin.

In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching a nonnative metal-binding ligand of bipyridine to Cys46 through the F46C mutation in the heme distal site. The X-ray structure of the designed enzyme, termed F46C-mBpy Mb, was solved in the Cu(II)-bound form, which revealed the formation of a heterodinuclear center of Cu-His-H2O-heme. Cu(II)-F46C-mBpy Mb exhibits not only nitrite reductase reactivity but also cascade reaction activity involving both hydrolysis and oxidation. Furthermore, F46C-mBpy Mb displays Mn-peroxidase activity by the oxidation of Mn2+ to Mn3+ using H2O2 as an oxidant. This study shows that the construction of a nonnative metal-binding site close to the heme cofactor is a convenient approach to creating an artificial metalloenzyme with a heterodinuclear center that confers multiple functions.

Construction and validation of a risk prediction model for soldiers with frostbite in northeast China: a cross-sectional study.

BACKGROUND: One of the challenges of physical training in extreme condition is frostbite, especially in Northeast China. In this study, we aimed to construct a risk prediction model for frostbite among soldiers in Northeast China, and verify its effect. METHODS: 698 participants were selected via convenience sampling from Northeast China from December 2021 to January 2022 (winter). They were randomly divided into a training set (N = 479) and a testing set (N = 202) in a ratio of 7:3. All participants completed a researcher-made questionnaire on frostbite. The prediction model was constructed through the use of Logistic regression analysis, which was used to predict the independent risk factors for frostbite formation and screen significant indicators. The model's performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) to evaluate the prediction efficiency and goodness of fit. RESULTS: The incidence of frostbite in the training set was 19.83% (95 people), all of which were first-degree frostbite. Among them, frostbite in multiple parts was the most common (58.95%), followed by singular body parts like hands (24.21%), ears (11.58%) and feet (5.26%). Single factor logistic regression analyses showed that ambient temperature, ambient wind speed, outdoor stationary time, stationary status, and history of frostbite are independent risk factors that affect the occurrence of frostbite. Furthermore, we constructed the frostbite risk prediction model for soldiers in the northeastern region of China. The area under the receiver operating characteristic curve (AUC) for the risk of frostbite in the training set and testing set was 0.816 (95% CI, 0.770 ~ 0.862) and 0.787 (95% CI, 0.713 ~ 0.860), respectively. The Hosmer-Lemeshow test of the model showed χ2 = 11.328 and P = 0.184 (> 0.05). The DCA curve indicated that most of the clinical net benefits of the model are greater than 0, demonstrating good clinical usefulness. CONCLUSION: The constructed frostbite prediction model can effectively identify soldiers with a higher risk of frostbite. It provided theoretical support for commanders to take preventive measures to reduce the incidence of frostbite among soldiers and was of great clinical guiding significance.

Elevated Risk of Adverse Prognosis in Patients with T2-3 Stage Breast Cancer Exhibiting Non-Pathological Complete Response Following Neoadjuvant Chemotherapy: Significance of Regenerating Islet-Derived Family Member 4.

Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR). Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes. Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR. Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

Clinical value of ACR O-RADS combined with CA125 in the risk stratification of adnexal masses.

Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

The Use of Novel Colorimetric Films to Monitor the Freshness of Pork, Utilizing Konjac Glucomannan With Curcumin/Alizarin.

In this study, different proportions of curcumin (CUR) and alizarin (ALI) were added to konjac glucomannan (KG)/ polyvinyl alcohol (PVA) to prepare an active intelligent packaging film and evaluate its potential to indicate pork freshness. The mixed indicator had a richer color hierarchy in the buffer solution with pH = 2-12. The surface of the KG-2C2A and KG-1C3A films is smoother and has fewer cross-section faults. With the increase of CUR content in the film, the crystal structure becomes more prominent, leading to poor compatibility with KG. The WAC of KG-3C1A and KG-1C3A films was significantly higher than that of the other groups, and they had better hydrophobicity. With the increase of CUR content in the films, the thermal stability of the films was enhanced, and the KG-C films showed the highest thermal stability. Among them, the KG-2A2C and KG-1C3A films showed the most significant color change during pork spoiling and could be used to monitor the freshness of pork. As a pH colorimetric indicator, CUR and ALI-coated KG films might be of great potential in fresh meat monitoring.

Influencing factors for pediatric eye disorders and health related quality of life: a cross-sectional study in Shanghai, China.

Background: Myopia, strabismus, and ptosis are common pediatric eye diseases, which have a negative impact on children and adolescents in terms of visual function, mental health, and health-related quality of life (HRQoL). Therefore, this study focused on those pediatric eye diseases by analyzing their risk factors and HRQoL for the comprehensive management of myopia, strabismus, and ptosis. Methods: A total of 363 participants (2-18 years old) were included in this study for risk factors analysis of myopia, strabismus, and ptosis. We collected demographic characteristics, lifestyle habits and eye care habits of these children and analyzed them by using univariable and multivariable logistic regression. In addition, we applied the Chinese version of Pediatric Quality of Life Inventory-Version 4.0 (PedsQL 4.0) to assess HRQoL in 256 children with strabismus and ptosis. Univariable and multivariable linear regression models were applied to evaluate potential influencing factors of HRQoL. Results: Of all the participants, 140 had myopia, 127 had strabismus, and 145 had ptosis. Based on the multivariable logistic regression analysis model, we found that the history of parental myopia and daily average near-distance eye usage time were risk factors for myopia, and increased body mass index (BMI) was identified as a risk factor for strabismus and ptosis. Individuals with ptosis possessed decreased HRQoL. The multivariable linear regression model suggested that daily average near-distance eye usage time, light intensity during visual tasks, and daily average sleep duration had potential influences on HRQoL. Conclusion: This is the first study to assess the risk factors and HRQoL of myopia, strabismus, and ptosis together. We identified risk factors for these common pediatric eye diseases to help doctors, parents, and teachers better manage them. Our study discovered that children with eye disorders exhibit a notably diminished HRQoL. Consequently, it emphasizes the necessity for increased social attention and mental health assistance for these children.

Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The Astragalus-Coptis drug pair is frequently employed in the management of DKD. However, the precise molecular mechanism underlying its therapeutic effect remains elusive. AIM: To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways. METHODS: The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform. The targets were predicted using the SwissTargetPrediction database, while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database. DKD targets were acquired from the GeneCards, Online Mendelian Inheritance in Man database, and DisGeNET databases, with common targets identified through the Venny platform. The protein-protein interaction network and the "disease-active ingredient-target" network of the common targets were constructed utilizing the STRING database and Cytoscape software, followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients. Gene Ontology (GO) function and Kyoto Ency-clopedia of Genes and Genomes (KEGG) pathway enrichments were performed using the DAVID database. The tissue and organ distributions of key targets were evaluated. PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets. Finally, molecular dynamics (MD) simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins. RESULTS: A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified. There were 273 common targets between DKD and the Astragalus-Coptis drug pair. Through protein-protein interaction network topology analysis, we identified 9 core active ingredients and 10 key targets. GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes, including protein phosphorylation, negative regulation of apoptosis, inflammatory response, and endoplasmic reticulum unfolded protein response. These pathways are mainly associated with the advanced glycation end products (AGE)-receptor for AGE products signaling pathway in diabetic complications, as well as the Lipid and atherosclerosis. Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets. Notably, the quercetin-AKT serine/threonine kinase 1 (AKT1) and quercetin-tumor necrosis factor (TNF) protein complexes exhibited exceptional stability. CONCLUSION: This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients, targets, and signaling pathways. We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD. Furthermore, we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF, providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Artificial Intelligence for Early Detection of Pediatric Eye Diseases Using Mobile Photos.

IMPORTANCE: Identifying pediatric eye diseases at an early stage is a worldwide issue. Traditional screening procedures depend on hospitals and ophthalmologists, which are expensive and time-consuming. Using artificial intelligence (AI) to assess children's eye conditions from mobile photographs could facilitate convenient and early identification of eye disorders in a home setting. OBJECTIVE: To develop an AI model to identify myopia, strabismus, and ptosis using mobile photographs. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted at the Department of Ophthalmology of Shanghai Ninth People's Hospital from October 1, 2022, to September 30, 2023, and included children who were diagnosed with myopia, strabismus, or ptosis. MAIN OUTCOMES AND MEASURES: A deep learning-based model was developed to identify myopia, strabismus, and ptosis. The performance of the model was assessed using sensitivity, specificity, accuracy, the area under the curve (AUC), positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios (P-LR), negative likelihood ratios (N-LR), and the F1-score. GradCAM++ was utilized to visually and analytically assess the impact of each region on the model. A sex subgroup analysis and an age subgroup analysis were performed to validate the model's generalizability. RESULTS: A total of 1419 images obtained from 476 patients (225 female [47.27%]; 299 [62.82%] aged between 6 and 12 years) were used to build the model. Among them, 946 monocular images were used to identify myopia and ptosis, and 473 binocular images were used to identify strabismus. The model demonstrated good sensitivity in detecting myopia (0.84 [95% CI, 0.82-0.87]), strabismus (0.73 [95% CI, 0.70-0.77]), and ptosis (0.85 [95% CI, 0.82-0.87]). The model showed comparable performance in identifying eye disorders in both female and male children during sex subgroup analysis. There were differences in identifying eye disorders among different age subgroups. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the AI model demonstrated strong performance in accurately identifying myopia, strabismus, and ptosis using only smartphone images. These results suggest that such a model could facilitate the early detection of pediatric eye diseases in a convenient manner at home.

Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus.

OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

Hepatocellular carcinoma: An analysis of the expression status of stress granules and their prognostic value.

BACKGROUND: Hepatocellular carcinoma (HCC) is a global popular malignant tumor, which is difficult to cure, and the current treatment is limited. AIM: To analyze the impacts of stress granule (SG) genes on overall survival (OS), survival time, and prognosis in HCC. METHODS: The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE25097, and GSE36376 datasets were utilized to obtain genetic and clinical information. Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach, and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression, respectively. The prognostic model's receiver operating characteristic (ROC) curve was produced and plotted utilizing the time ROC software package. Nomogram models were constructed to predict the outcomes at 1, 3, and 5-year OS prognostications with good prediction accuracy. RESULTS: We identified seven SG genes (DDX1, DKC1, BICC1, HNRNPUL1, CNOT6, DYRK3, CCDC124) having a prognostic significance and developed a risk score model. The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group (P < 0.001). The nomogram model's findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort. Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle, RNA editing, and other biological processes. CONCLUSION: Based on the impact of SG genes on HCC prognosis, in the future, it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

Assisted Reproductive Technology During COVID-19: A Population-Based Study Of Pregnancy Outcomes.

We assessed the impact of the COVID-19 pandemic on the pregnancy outcomes of patients who used assisted reproductive technology. We conducted a population-based cohort study of 443,101 patients who conceived naturally or with assisted reproductive technology between December 2015 and July 2021 and had a delivery in hospitals of Quebec, Canada. The main exposure measure was use of assisted reproductive technology before or during the pandemic. Outcomes included preeclampsia, preterm birth, and other pregnancy complications. We used adjusted log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of assisted reproductive technology with adverse pregnancy outcomes compared with natural conception before vs. during the pandemic. In secondary analyses, we examined the association of COVID-19 infection with pregnancy outcomes among women who used assisted reproductive technology. Compared with natural conception, assisted reproductive technology was associated with an increased risk of preeclampsia (RR 1.43; 95% CI 1.21-1.68), preterm birth (RR 2.07; 95% CI 1.84-2.33), and low birth weight (RR 1.94; 95% CI 1.72-2.20) during the pandemic. However, the same risks were also present before the pandemic. Compared with no infection, COVID-19 infection was not associated with adverse outcomes among women who conceived with assisted reproductive technology. This study suggests that the COVID-19 pandemic did not significantly impact the pregnancy outcomes of women who underwent assisted reproductive procedures in Quebec. The findings are reassuring for patients concerned about the potential reproductive effects of the pandemic.

An isocratic HPLC-UV analytical procedure for assessment of glutathione and its related substances.

Reduced glutathione (GSH) is an endogenous tripeptide antioxidant which plays a crucial role in a variety of physiological and pathological activities. Although GSH is not present in any FDA-approved drug product, GSH dietary supplement products and compounded GSH drugs are available to patients in the US. Several incidents of toxicity have occurred in recent years due to endotoxin or otherwise contaminated GSH in compounded drugs. Efficient and sensitive analytical methods are needed for assessing and ensuring the quality of GSH substance and associated drug or dietary supplement products. Impurities A (L-cysteinylglycine), B (cysteine), C (oxidized L-glutathione) and D (γ-L-glutamyl-L-cysteine) are the main related impurities for GSH drug substance which have been detected and quantified by capillary electrophoresis and qNMR analytical procedures. However, there are no reported HPLC methods for detecting or quantifying the three main related impurities A, B and D even though numerous HPLC analytical methods have been reported for analyzing GSH and impurity C. In this report, an isocratic HPLC-UV analytical procedure was developed and validated for separating and identifying GSH and related impurities A-D as well as a newly identified degradant, L-pyroglutamic acid (pGlu), within 10 minutes with resolution (RS) more than 3. The LOD and LOQ were determined to be 0.02 % w/w and 0.05 % w/w, respectively, for impurities A-D and pGlu. Importantly, the optimized HPLC analytical procedure for GSH assay does not have interference from impurities A, B and D, providing highly specific results compared to the commonly used iodine titration method. The newly validated analytical procedure was applied to assess different commercial GSH bulk substance samples. The results suggest that the analytical procedure described in this work is suitable for quality assessment of GSH samples.

Design of Mn-based nanozymes with multiple enzyme-like activities for identification/quantification of glyphosate and green transformation of organophosphorus.

A Mn-based nanozyme, Mn-uNF/Si, with excellent alkali phosphatase-like activity was designed by in-situ growth of ultrathin Mn-MOF on the surface of silicon spheres, and implemented as an effective solid Lewis-Brønsted acid catalyst for broad-spectrum dephosphorylation. H218O-mediated GC-MS studies confirmed the cleavage sites and the involvement of H2O in the new bonds. DRIFT NH3-IR and in-situ ATR-FTIR confirmed the coexistence of Lewis-Brønsted acid sites and the adjustment of adsorption configurations at the interfacial sites. In addition, a green transformation route of "turning waste into treasure" was proposed for the first time ("OPs→PO43-→P food additive") using edible C. reinhardtii as a transfer station. By alkali etching of Mn-uNF/Si, a nanozyme Mn-uNF with laccase-like activity was obtained. Intriguingly, glyphosate exhibits a laccase-like fingerprint-like response (+,-) of Mn-uNF, and a non-enzyme amplified sensor was thus designed, which shows a good linear relationship with Glyp in a wide range of 0.49-750 µM, with a low LOD of 0.61 µM, as well as high selectivity and anti-interference ability under the co-application of phosphate fertilizers and multiple pesticides. This work provides a controllable methodology for the design of bifunctional nanozymes, which sheds light on the highly efficient green transformation of OPs, and paves the way for the selective recognition and quantification of glyphosate. Mechanistically, we also provided deeper insights into the structure-activity relationship at the atomic scale.

Development and validation of a neoadjuvant chemotherapy pathological complete remission model based on Reg IV expression in breast cancer tissues: a clinical retrospective study.

OBJECTIVE: To develop and authenticate a neoadjuvant chemotherapy (NACT) pathological complete remission (pCR) model based on the expression of Reg IV within breast cancer tissues with the objective to provide clinical guidance for precise interventions. METHOD: Data relating to 104 patients undergoing NACT were collected. Variables derived from clinical information and pathological characteristics of patients were screened through logistic regression, random forest, and Xgboost methods to formulate predictive models. The validation and comparative assessment of these models were conducted to identify the optimal model, which was then visualized and tested. RESULT: Following the screening of variables and the establishment of multiple models based on these variables, comparative analyses were conducted using receiver operating characteristic (ROC) curves, calibration curves, as well as net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Model 2 emerged as the most optimal, incorporating variables such as HER-2, ER, T-stage, Reg IV, and Treatment, among others. The area under the ROC curve (AUC) for Model 2 in the training dataset and test dataset was 0.837 (0.734-0.941) and 0.897 (0.775-1.00), respectively. Decision curve analysis (DCA) and clinical impact curve (CIC) further underscored the potential applications of the model in guiding clinical interventions for patients. CONCLUSION: The prediction of NACT pCR efficacy based on the expression of Reg IV in breast cancer tissue appears feasible; however, it requires further validation.

Microplastic exposure inhibits nitrate uptake and assimilation in wheat plants.

Microplastic (MP) contamination in soil severely impairs plant growth. However, mechanisms underlying the effects of MPs on plant nutrient uptake remain largely unknown. In this study, we revealed that NO3- content was significantly decreased in shoots and roots of wheat plants exposed to high concentrations (50-100 mg L-1) of MPs (1 µm and 0.1 µm; type: polystyrene) in the hydroponic solution. Isotope labeling experiments demonstrated that MP exposure led to a significant inhibition of NO3- uptake in wheat roots. Further analysis indicated that the presence of MPs markedly inhibited root growth and caused oxidative damage to the roots. Additionally, superoxide dismutase and peroxidase activities in wheat roots decreased under all MP treatments, whereas catalase and ascorbate peroxidase activities significantly increased under the 100 mg L-1 MP treatment. The transcription levels of most nitrate transporters (NRTs) in roots were significantly downregulated by MP exposure. Furthermore, exposure to MPs distinctly suppressed the activity of nitrate reductase (NR) and nitrite reductase (NiR), as well as the expression levels of their coding genes in wheat shoots. These findings indicate that a decline in root uptake area and root vitality, as well as in the expression of NRTs, NR, and NiR genes caused by MP exposure may have adverse effects on NO3- uptake and assimilation, consequently impairing normal growth of plants.