Inferring cellular contractile forces and work using deep morphology traction microscopy.

Traction-force microscopy (TFM) has emerged as a widely used standard methodology to measure cell-generated traction forces and determine their role in regulating cell behavior. While TFM platforms have enabled many discoveries, their implementation remains limited due to complex experimental procedures, specialized substrates, and the ill-posed inverse problem whereby low-magnitude high-frequency noise in the displacement field severely contaminates the resulting traction measurements. Here, we introduce deep morphology traction microscopy (DeepMorphoTM), a deep-learning alternative to conventional TFM approaches. DeepMorphoTM first infers cell-induced substrate displacement solely from a sequence of cell shapes and subsequently computes cellular traction forces, thus avoiding the requirement of a specialized fiduciarily marked deformable substrate or force-free reference image. Rather, this technique drastically simplifies the overall experimental methodology, imaging, and analysis needed to conduct cell-contractility measurements. We demonstrate that DeepMorphoTM quantitatively matches conventional TFM results while offering stability against the biological variability in cell contractility for a given cell shape. Without high-frequency noise in the inferred displacement, DeepMorphoTM also resolves the ill-posedness of traction computation, increasing the consistency and accuracy of traction analysis. We demonstrate the accurate extrapolation across several cell types and substrate materials, suggesting robustness of the methodology. Accordingly, we present DeepMorphoTM as a capable yet simpler alternative to conventional TFM for characterizing cellular contractility in two dimensions.

Value of [18F]AlF-NOTA-FAPI-04 PET/CT for differential diagnosis of malignant and various inflammatory lung lesions: comparison with [18F]FDG PET/CT.

OBJECTIVE: Uptake of the imaging tracers [18F]AlF-NOTA-FAPI-04 and [18F]FDG varies in some inflammatory lesions, which may result in false-positive findings for malignancy on PET/CT. Our aim was to compare the [18F]AlF-NOTA-FAPI-04 and [18F]FDG PET/CT imaging features of malignant and various inflammatory lung lesions and to analyze their value for differential diagnosis. METHODS: We retrospectively analyzed [18F]AlF-NOTA-FAPI-04 PET/CT scans from 67 cancer patients taken between December 2020 and January 2022, as well as the scans of 32 patients who also underwent [18F]FDG PET/CT imaging. The maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) and lesion-to-background ratio (LBR) were calculated. The predictive capabilities of semiquantitative PET/CT parameters were analyzed by receiver operating characteristic curve analysis. RESULTS: A total of 70 inflammatory and 37 malignant lung lesions were evaluated by [18F]AlF­NOTA­FAPI­04 PET/CT, and 33 inflammatory and 26 malignant lung lesions also were evaluated by [18F]FDG PET/CT. Inflammatory lesions exhibited lower [18F]AlF-NOTA-FAPI-04 and [18F]FDG uptake compared to malignant lesions, with statistically significant differences in SUVmax, SUVmean, and LBR (all p < 0.001). [18F]AlF-NOTA-FAPI-04 uptake also varied among different types of inflammatory lesions (SUVmax, p = 0.005; SUVmean, p = 0.008; LBR, p < 0.001), with the highest uptake observed in bronchiectasis with infection, followed by postobstructive pneumonia, and the lowest in pneumonia. [18F]FDG uptake was higher in postobstructive pneumonia than in pneumonia (SUVmax, p = 0.009; SUVmean, p = 0.016; LBR, p = 0.004). CONCLUSION: [18F]AlF-NOTA-FAPI-04/[18F]FDG PET/CT showed significantly lower uptake in inflammatory lesions than malignancies as well as variation in different types of inflammatory lesions, and thus, may be valuable for distinguishing malignant and various inflammatory findings. CLINICAL RELEVANCE STATEMENT: Our study confirmed that the uptake of [18F]AlF-NOTA-FAPI-04/[18F]FDG PET/CT in inflammatory and malignant lung lesions is different, which is beneficial to distinguish inflammatory and malignant lung lesions in clinic. KEY POINTS: • Malignant and different inflammatory lung lesions showed varying degrees of uptake of [18F]AlF-NOTA-FAPI-04 and [18F]FDG. • Inflammatory lung lesions showed significantly less uptake than malignancies, and uptake varied among different types of inflammatory lesions. • Both types of PET/CT could differentiate malignant and various inflammatory lung findings.

Integrated Bioinformatics-Based Identification and Validation of Neuroinflammation-Related Hub Genes in Primary Open-Angle Glaucoma.

Glaucoma is a leading cause of permanent blindness, affecting 80 million people worldwide. Recent studies have emphasized the importance of neuroinflammation in the early stages of glaucoma, involving immune and glial cells. To investigate this further, we used the GSE27276 dataset from the GEO (Gene Expression Omnibus) database and neuroinflammation genes from the GeneCards database to identify differentially expressed neuroinflammation-related genes associated with primary open-angle glaucoma (POAG). Subsequently, these genes were submitted to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analyses. Hub genes were picked out through protein-protein interaction networks and further validated using the external datasets (GSE13534 and GSE9944) and real-time PCR analysis. The gene-miRNA regulatory network, receiver operating characteristic (ROC) curve, genome-wide association study (GWAS), and regional expression analysis were performed to further validate the involvement of hub genes in glaucoma. A total of 179 differentially expressed genes were identified, comprising 60 upregulated and 119 downregulated genes. Among them, 18 differentially expressed neuroinflammation-related genes were found to overlap between the differentially expressed genes and neuroinflammation-related genes, with six genes (SERPINA3, LCN2, MMP3, S100A9, IL1RN, and HP) identified as potential hub genes. These genes were related to the IL-17 signaling pathway and tyrosine metabolism. The gene-miRNA regulatory network showed that these hub genes were regulated by 118 miRNAs. Notably, GWAS data analysis successfully identified significant single nucleotide polymorphisms (SNPs) corresponding to these six hub genes. ROC curve analysis indicated that our genes showed significant accuracy in POAG. The expression of these genes was further confirmed in microglia, Müller cells, astrocytes, and retinal ganglion cells in the Spectacle database. Moreover, three hub genes, SERPINA3, IL1R1, and LCN2, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the OGD/R-induced glaucoma model. This study suggests that the identified hub genes may influence the development of POAG by regulation of neuroinflammation, and it may offer novel insights into the management of POAG.

Early detection of radiation-induced myocardial damage by [18F]AlF-NOTA-FAPI-04 PET/CT imaging.

PURPOSE: Retrospective analysis revealed increased [18F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [18F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD). METHODS: Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50 Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [18F]AlF-NOTA-FAPI-04 PET/CT weekly for 12 weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [18F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted. RESULTS: Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [18F]FDG uptake and confirmed by autoradiography, hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. CONCLUSION: Through clinical phenomena and animal experimental studies, this study indicated that [18F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [18F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD.

LncRNA-MEG3 attenuates hyperglycemia-induced damage by enhancing mitochondrial translocation of HSP90A in the primary hippocampal neurons.

The diabetic cognitive impairments are associated with high-glucose (HG)-induced mitochondrial dysfunctions in the brain. Our previous studies demonstrated that long non-coding RNA (lncRNA)-MEG3 alleviates diabetic cognitive impairments. However, the underlying mechanism has still remained elusive. Therefore, this study was designed to investigate whether the mitochondrial translocation of HSP90A and its phosphorylation are involved in lncRNA-MEG3-mediated neuroprotective effects of mitochondrial functions in HG-treated primary hippocampal neurons and diabetic rats. The primary hippocampal neurons were exposed to 75 mM glucose for 72 h to establish a HG model in vitro. Firstly, the RNA pull-down and RNA immunoprecipitation (RIP) assays clearly indicated that lncRNA-MEG3-associated mitochondrial proteins were Annexin A2, HSP90A, and Plectin. Although HG promoted the mitochondrial translocation of HSP90A and Annexin A2, lncRNA-MEG3 over-expression only enhanced the mitochondrial translocation of HSP90A, rather than Annexin A2, in the primary hippocampal neurons treated with or without HG. Meanwhile, Plectin mediated the mitochondrial localization of lncRNA-MEG3 and HSP90A. Furthermore, HSP90A threonine phosphorylation participated in regulating mitochondrial translocation of HSP90A, and lncRNA-MEG3 also enhanced mitochondrial translocation of HSP90A through suppressing HSP90A threonine phosphorylation. Finally, the anti-apoptotic role of mitochondrial translocation of HSP90A was found to be associated with inhibiting death receptor 5 (DR5) in HG-treated primary hippocampal neurons and diabetic rats. Taken together, lncRNA-MEG3 could improve mitochondrial functions in HG-exposed primary hippocampal neurons, and the underlying mechanisms were involved in enhanced mitochondrial translocation of HSP90A via suppressing HSP90A threonine phosphorylation, which may reveal a potential therapeutic target for diabetic cognitive impairments.

The Application of MicroRNAs in Glaucoma Research: A Bibliometric and Visualized Analysis.

Glaucoma is similar to a neurodegenerative disorder and leads to global irreversible loss of vision. Despite extensive research, the pathophysiological mechanisms of glaucoma remain unclear, and no complete cure has yet been identified for glaucoma. Recent studies have shown that microRNAs can serve as diagnostic biomarkers or therapeutic targets for glaucoma; however, there are few bibliometric studies that focus on using microRNAs in glaucoma research. Here, we have adopted a bibliometric analysis in the field of microRNAs in glaucoma research to manifest the current tendencies and research hotspots and to present a visual map of the past and emerging tendencies in this field. In this study, we retrieved publications in the Web of Science database that centered on this field between 2007 and 2022. Next, we used VOSviewer, CiteSpace, Scimago Graphica, and Microsoft Excel to present visual representations of a co-occurrence analysis, co-citation analysis, tendencies, hotspots, and the contributions of authors, institutions, journals, and countries/regions. The United States was the main contributor. Investigative Ophthalmology and Visual Science has published the most articles in this field. Over the past 15 years, there has been exponential growth in the number of publications and citations in this field across various countries, organizations, and authors. Thus, this study illustrates the current trends, hotspots, and emerging frontiers and provides new insight and guidance for searching for new diagnostic biomarkers and clinical trials for glaucoma in the future. Furthermore, international collaborations can also be used to broaden and deepen the field of microRNAs in glaucoma research.

Postoperative Lactate Predicts In-Hospital Death in Patients with Acute Type A Aortic Dissection.

Several studies have found that lactate correlates with surgical outcomes in patients with heart disease. However, the prognostic value of postoperative lactate in patients with acute type A aortic dissection (AAAD) remains unclear. This study aimed to investigate the relationship between postoperative lactate and in-hospital mortality in patients with AAAD. Patients who underwent AAAD surgery at Fujian Cardiac Medical Center from February 2020 to January 2022 were enrolled in this retrospective study. Correlations between in-hospital mortality and various parameters, including lactate, were investigated. A total of 357 patients were included in this study, 58 of which died. Multivariate logistic regression analysis revealed that body mass index (BMI) (odds ratio [OR] = 1.099, 95% confidence interval [CI]: 1.017-1.188, P = 0.017), cardiopulmonary bypass (CPB) time (OR = 1.005; 95% CI: 1.000-1.010, P = 0.039), and lactate (OR = 1.291, 95% CI: 1.182-1.409, P < 0.001) were independent risk factors for in-hospital mortality in AAAD patients. Receiver operating characteristic (ROC) curve analysis showed that lactate had a moderate power for in-hospital mortality (area under the curve [AUC] = 0.729, 95% CI: 0.647-0.810, P < 0.001). Furthermore, the combination of lactate, BMI, and CPB time showed better performance (AUC = 0.780; 95% CI: 0.706-0.854, P < 0.001) in predicting in-hospital mortality than in using these variables independently. Among patients undergoing AAAD surgery, postoperative lactate was significantly associated with in-hospital mortality. Lactate can be used as a potential predictor of in-hospital mortality. The combination of lactate, BMI, and CPB time showed better performance in predicting in-hospital mortality than using single one.

Cell monolayer deformation microscopy reveals mechanical fragility of cell monolayers following EMT.

Tissue and cell mechanics are crucial factors in maintaining homeostasis and in development, with aberrant mechanics contributing to many diseases. During the epithelial-to-mesenchymal transition (EMT), a highly conserved cellular program in organismal development and cancer metastasis, cells gain the ability to detach from their original location and autonomously migrate. While a great deal of biochemical and biophysical changes at the single-cell level have been revealed, how the physical properties of multicellular assemblies change during EMT, and how this may affect disease progression, is unknown. Here we introduce cell monolayer deformation microscopy (CMDM), a new methodology to measure the planar mechanical properties of cell monolayers by locally applying strain and measuring their resistance to deformation. We employ this new method to characterize epithelial multicellular mechanics at early and late stages of EMT, finding the epithelial monolayers to be relatively compliant, ductile, and mechanically homogeneous. By comparison, the transformed mesenchymal monolayers, while much stiffer, were also more brittle, mechanically heterogeneous, displayed more viscoelastic creep, and showed sharp yield points at significantly lower strains. Here, CMDM measurements identify specific biophysical functional states of EMT and offer insight into how cell aggregates fragment under mechanical stress. This mechanical fingerprinting of multicellular assemblies using new quantitative metrics may also offer new diagnostic applications in healthcare to characterize multicellular mechanical changes in disease.

Effects of sand burial depth on Xanthium spinosum seed germination and seedling growth.

In desert habitats, sand burial is an important factor affecting germination of plant seeds and seedling growth. Xanthium spinosum has strong adaptability in arid desert areas, and is a common malignant invasive plant in Xinjiang, China. The effects of different sand burial depths on seed germination, seedling emergence, growth and biomass allocation were studied to provide a scientific basis for further control of X. spinosum. Six sand burial depths (1, 2, 3, 5, 7 and 9 cm) were established to explore the response of X. spinosum seed germination and seedling growth to sand burial. The first emergence time, peak emergence time, emergence rate, seedling growth height, biomass and biomass distribution of X. spinosum seeds was significantly different at sand burial depths (P < 0.05). The X. spinosum seeds had the highest emergence rate (71.5%) at 1 cm sand burial and the maximum seedling height (7.1 cm). As sand burial depth increased, the emergence rate and seedling height gradually decreased. Emergence rate (12.25%) and seedling height (2.9 cm) were lowest at 9 cm sand burial. The root length at 9 cm depth (13.6 cm) was significantly higher than that at other sand depths (P < 0.05). The sand burial depth affected the biomass accumulation and distribution of X. spinosum. As sand burial depth increased, the root biomass and rhizome ratio increased, and the most deeply buried seedlings allocated more biomass for root growth. The optimal sand burial depth for seed germination and seedling growth of X. spinosum was 1-3 cm, and high burial depth (5-9 cm) was not conducive to the germination and growth of X. spinosum seedlings. For prevention and control of X. spinosum, we suggest deeply ploughing crops before sowing to ensure X. spinosum seeds are ploughed into a deep soil layer.

Synthesis of 4-Tetrazolyl-Substituted 3,4-Dihydroquinazoline Derivatives with Anticancer Activity via a One-Pot Sequential Ugi-Azide/Palladium-Catalyzed Azide-Isocyanide Cross-Coupling/Cyclization Reaction.

A new one-pot preparation of 4-tetrazolyl-3,4-dihydroquinazolines has been reported. The Ugi-azide reactions of 2-azidobenzaldehydes, amines, trimethylsilyl azide, and isocyanides produced azide intermediates without separation, which were treated with isocyanides to give 4-tetrazolyl-3,4-dihydroquinazoline derivatives through a sequential Palladium-catalyzed azide-isocyanide cross-coupling/cyclization reaction in moderate to good yields. The biological evaluation demonstrated that compound 6c inhibited breast cancer cells well and displayed broad applications for synthesis and medicinal chemistry.

Usage of mobile health interventions among overweight/obese PCOS patients undergoing assisted reproductive technology treatment during the COVID-19 pandemic.

Objective: In the context of the coronavirus disease 2019 (COVID-19) pandemic, telemedicine is a promising tool for providing clinical care for patients. Since the first-line treatment for infertile women with polycystic ovarian syndrome (PCOS) is lifestyle modification, a mobile-based service that provides lifestyle modification education would be helpful in the treatment of PCOS patients. In this observational study, the effect of a mobile Health (mHealth) application for lifestyle modification on PCOS patients undergoing assisted reproductive technology (ART) treatment was evaluated.Methods: A total of 79 overweight/obese patients (40 in the paper group and 39 in the WeChat application group) with PCOS from the First Affiliated Hospital of University of Science and Technology of China were enrolled in the study. The changes in the outcomes of BMI and ART treatment were analyzed between the two groups.Results: After three months of intervention, the BMIs in the control and mHealth groups were 24.5 ± 3.3 and 23.7 ± 3.1, respectively. The percentage of patients who lost weight was higher in the WeChat group than in the control group (87.2% vs. 67.5%). Furthermore, PCOS patients in the WeChat group were found to have a higher live birth rate than those in the control group (p = 0.005).Conclusion: Lifestyle modifications for PCOS patients undergoing ART treatment using the WeChat application improved weight loss and oocyte quality. Infertile patients with PCOS were more likely to make lifestyle modifications based on the usage of mobile applications during the COVID-19 pandemic.

Sexually transmitted infections and semen quality from subfertile men with and without leukocytospermia.

BACKGROUND: The role of sexually transmitted infections (STIs) in semen parameters and male infertility is still a controversial area. Previous studies have found bacterial infection in a minority of infertile leukocytospermic males. This study aims to investigate the prevalence of STIs in semen from subfertile men with leukocytospermia (LCS) and without leukocytospermia (non-LCS) and their associations with sperm quality. METHODS: Semen samples were collected from 195 men who asked for a fertility evaluation. Infection with the above 6 pathogens was assessed in each sample. Sperm quality was compared in subfertile men with and without LCS. RESULTS: The LCS group had significantly decreased semen volume, sperm concentration, progressive motility, total motility and normal morphology. The infection rates of Ureaplasma urealyticum (Uuu), Ureaplasma parvum (Uup), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), herpes simplex virus-2 (HSV-2) and Neisseria gonorrhoeae (NG) were 8.7 %, 21.0 %, 8.2 %, 2.1 %, 3.6 %, 1.0 and 0 %, respectively. The STI detection rates of patients with LCS were higher than those of the non-LCS group (52.3 % vs. 39.3 %), although there was no statistically significant difference between the two groups (P = 0.07). All semen parameters were not significantly different between LCS with STIs and without STIs, except the semen volume in the MG-infected patients with LCS was significantly lower than that in the noninfected group. CONCLUSIONS: LCS was associated with a reduction in semen quality, but was not associated with STIs.

Algicidal Activity of Bacillamide Alkaloids and Their Analogues against Marine and Freshwater Harmful Algae.

Harmful algal blooms have become a great challenge to global aquatic ecosystems over the past decades. Given their low toxicity, high selectivity, and environment-friendly properties, the use of natural products and their analogues as algicides has proven to be particularly efficient. In the present study, algicidal activity of naturally occurring bacillamides A-C, alkaloid (1), and neobacillamide A, as well as their synthetic analogues were investigated intensively. Bioassay results showed that, relative to natural bacillamide alkaloids, aniline-derived analogue (10d) exhibited higher algicidal potential against three freshwater harmful algae Mycrocyctis aeruginosa, Scenedesmus obliquus, and Chlorella pyrenoidosa, suggesting that it could be used as a promising lead compound to develop novel algicide for controlling harmful algal blooms.

Discovery of (2-benzoylethen-1-ol)-containing 1,2-benzothiazine derivatives as novel 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibiting-based herbicide lead compounds.

A series of (2-benzoylethen-1-ol)-containing benzothiazine derivatives was synthesized, and their herbicidal activities were first evaluated. The bioassay results indicated that some of 3-benzoyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide derivatives displayed good herbicidal activity in greenhouse testing, especially, compound 4w had good pre-emergent herbicidal activities against Brassica campestris, Amaranthus retroflexus and Echinochloa crusgalli even at a dosage of 187.5 g ha(-1). More importantly, compound 4w displayed significant inhibitory activity against Arabidopsis thaliana HPPD and was identified as the most potent candidate with IC50 value of 0.48 µM, which is better than the commercial herbicide sulctrione (IC50=0.53 µM) and comparable with the commercial herbicide mesotrione (IC50=0.25 µM). The structure-activity relationships was studied and provided some useful information for improving herbicidal activity. The present work indicated that (2-benzoylethen-1-ol)-containing 1,2-benzothiazine motif could be a potential lead structure for further development of novel HPPD inhibiting-based herbicides.

Financial incentives for home-based health monitoring: a randomized controlled trial.

BACKGROUND: Home wireless device monitoring could play an important role in improving the health of patients with poorly controlled chronic diseases, but daily engagement rates among these patients may be low. OBJECTIVE: To test the effectiveness of two different magnitudes of financial incentives for improving adherence to remote-monitoring regimens among patients with poorly controlled diabetes. DESIGN: Randomized, controlled trial. (Clinicaltrials.gov Identifier: NCT01282957). PARTICIPANTS: Seventy-five patients with a hemoglobin A1c greater than or equal to 7.5% recruited from a Primary Care Medical Home practice at the University of Pennsylvania Health System. INTERVENTIONS: Twelve weeks of daily home-monitoring of blood glucose, blood pressure, and weight (control group; n = 28); a lottery incentive with expected daily value of $2.80 (n = 26) for daily monitoring; and a lottery incentive with expected daily value of $1.40 (n = 21) for daily monitoring. MAIN MEASURES: Daily use of three home-monitoring devices during the three-month intervention (primary outcome) and during the three-month follow-up period and change in A1c over the intervention period (secondary outcomes). KEY RESULTS: Incentive arm participants used devices on a higher proportion of days relative to control (81% low incentive vs. 58%, P = 0.007; 77% high incentive vs. 58%, P = 0.02) during the three-month intervention period. There was no difference in adherence between the two incentive arms (P = 0.58). When incentives were removed, adherence in the high incentive arm declined while remaining relatively high in the low incentive arm. In month 6, the low incentive arm had an adherence rate of 62% compared to 35% in the high incentive arm (P = 0.015) and 27% in the control group (P = 0.002). CONCLUSIONS: A daily lottery incentive worth $1.40 per day improved monitoring rates relative to control and had significantly better efficacy once incentives were removed than a higher incentive.

Individual- versus group-based financial incentives for weight loss: a randomized, controlled trial.

BACKGROUND: Data on the effectiveness of employer-sponsored financial incentives for employee weight loss are limited. OBJECTIVE: To test the effectiveness of 2 financial incentive designs for promoting weight loss among obese employees. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT01208350) SETTING: Children's Hospital of Philadelphia. PARTICIPANTS: 105 employees with a body mass index between 30 and 40 kg/m2. INTERVENTION: 24 weeks of monthly weigh-ins (control group; n = 35); individual incentive, designed as $100 per person per month for meeting or exceeding weight-loss goals (n = 35); and group incentive, designed as $500 per month split among participants within groups of 5 who met or exceeded weight-loss goals (n = 35). MEASUREMENTS: Weight loss after 24 weeks (primary outcome) and 36 weeks and changes in behavioral mediators of weight loss (secondary outcomes). RESULTS: Group-incentive participants lost more weight than control participants (mean between-group difference, 4.4 kg [95% CI, 2.0 to 6.7 kg]; P < 0.001) and individual-incentive participants (mean between-group difference, 3.2 kg [CI, 0.9 to 5.5 kg]; P = 0.008). Twelve weeks after incentives ended and after adjustment for 3-group comparisons, group-incentive participants maintained greater weight loss than control group participants (mean between-group difference, 2.9 kg [CI, 0.5 to 5.3 kg]; P = 0.016) but not greater than individual-incentive participants (mean between-group difference, 2.7 kg [CI, 0.4 to 5.0 kg]; P = 0.024). LIMITATION: Single employer and short follow-up. CONCLUSION: A group-based financial incentive was more effective than an individual incentive and monthly weigh-ins at promoting weight loss among obese employees at 24 weeks. PRIMARY FUNDING SOURCE: National Institute on Aging.

A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method for determination of phytohormones in the medicinal plant saffron.

Saffron (Crocus sativus L.) is a valuable Chinese herb with high medicinal value. Saffron pistils are used as medicine, so increasing the number of flowers can increase the yield. Plant hormones have essential roles in the growth and development of saffron, as well as the response to biotic and abiotic stresses (especially in floral initiation), which may directly affect the number of flowers. Quantitative analysis of plant hormones provides a basis for more efficient research on their synthesis, transportation, metabolism, and action. However, starch (which interferes with extraction) is present in high levels, and hormone levels are extremely low, in saffron corms, thereby hampering accurate determination of plant-hormone levels in saffron. Herein, we screened an efficient and convenient pre-treatment method for plant materials containing abundant amounts of starch. Also, we proposed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of abscisic acid (ABA) and auxin (IAA). Then, the method was applied for the detection of hormone-content differences between flowering and non-flowering top buds, as well as between lateral and top buds. Our method showed high sensitivity, reproducibility, and reliability. Specifically, good linearity in the range 2-100 ng ml-1 was achieved in the determination of ABA and IAA, and the correlation coefficient (R2) was >0.9982. The relative standard deviation was 2.956-14.51% (intraday) and 9.57-18.99% (interday), and the recovery range was 89.04-101.1% (n = 9). The matrix effect was 80.38-90.50% (n = 3). The method was thoroughly assessed employing various "green" chemistry evaluation tools: Blue Applicability Grade Index (BAGI), Complementary Green Analytical Procedure Index (Complex GAPI) and Red Green Blue 12 Algorithm (RGB12). These tools revealed the good greenness, analytical performance, applicability, and overall sustainability alignment of our method. Quantitative results showed that, compared with saffron with a flowering phenotype cultivated at 25 °C, the contents of IAA and ABA in the terminal buds of saffron cultivated at 16 °C decreased significantly. When cultivated at 25 °C, the IAA and ABA contents in the terminal buds of saffron were 1.54- and 4.84-times higher than those in the lateral buds, respectively. A simple, rapid, and accurate UPLC-MS/MS method was established to determine IAA and ABA contents. Using this method, a connection between the contents of IAA and ABA and the flowering phenotype was observed in the quantification results. Our data lay a foundation for studying the flowering mechanism of saffron.

O-sialoglycoprotein Endopeptidase (OSGEP) Suppresses Hepatic Ischemia-Reperfusion Injury-Induced Ferroptosis Through Modulating the MEK/ERK Signaling Pathway.

Hepatic ischemia-reperfusion injury (HIRI) was widely accepted as a critical complication of liver resection and transplantation. A growing body of evidence suggested that O-sialoglycoprotein endopeptidase (OSGEP) was involved in cell proliferation and mitochondrial metabolism. However, whether OSGEP could mediate the pathogenesis of HIRI has still remained unclarified. This study investigated whether OSGEP could be protective against HIRI and elucidated the potential mechanisms. The OSGEP expression level was detected in cases undergoing ischemia-related hepatectomy and a stable oxygen-glucose deprivation/reoxygenation (OGD/R) condition in hepG2 cells. Additionally, it was attempted to establish a mouse model of HIRI, thus, the function and mechanism of OSGEP could be analyzed. At one day after hepatectomy, the negative association of OSGEP expression level with the elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was noted. Moreover, it was attempted to carry out gain- and loss-of-function analyses of OSGEP in hepG2 cells to reveal its influences on OGD/R-induced injury and relevant signaling pathways. The findings suggested that OSGEP overexpression significantly protected hepG2 cells against ferroptotic cell death, while OSGEP consumption had opposite effects. Consistent with in vitro studies, OSGEP deficiency exacerbated liver functions and ferroptotic cell death in a mouse model of HIRI. The results also revealed that OSGEP mediated the progression of HIRI by regulating the MEK/ERK signaling pathway. Rescue experiments indicated that ERK1/2 knockdown or overexpression reversed the effects of OSGEP overexpression or knockdown on hepG2 cells under OGD/R condition. Taken together, the findings demonstrated that OSGEP could contribute to alleviate HIRI by mediating the MEK-ERK signaling pathway, which may serve as a potential prognostic marker and a therapeutic target for HIRI.

Microglia are necessary for probiotics supplementation to improve impaired fear extinction caused by pregnancy stress in adult offspring of rats.

The prevention and treatment of fear-related disorders in offspring affected by pregnancy stress remains challenging at clinic. Here, we examined the effects of gut microbiota of stressed pregnant rats on the fear extinction of their offsprings, and the potential mechanisms. We found that gut microbiota transplantation from rats with pregnancy stress to normal pregnant rats impaired fear extinction, induced microglial activation and synaptic phagocytosis, increased synapse loss in offsprings. Probiotics supplement during pregnancy stress partly normalized pregnancy stress-induced gut microbiota dysbiosis of pregnant rats, and promoted fear memory extinction, inhibited fear memory reappearance, and limited microglial activation and synaptic phagocytosis in offsprings. These data revealed that gut microbiota of stressed pregnant mother improved the development of fear-related disorders of offspring, which may be associated with microglial synaptic pruning.