Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATAC-seq and scRNA-seq.

Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during meiosis, especially in prophase I, are limited. Here, we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes. This event, conserved in mice, involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset. Furthermore, we identified 282 transcriptional regulators (TRs) that underwent activation or deactivation subsequent to this process. Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes, while secreted ENHO signals may alter metabolic patterns in these cells. Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia (NOA). This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.

Fluorescence fingerprint as an indicator to identify urban non-point sources in urban river during rainfall period.

Nowadays, the urban non-point source (NPS) pollution gradually evolved as the main contributor to urban water contamination since the point source pollution was effectively controlled. It was imperative to perform urban NPS identification in urban river to meet the requirements of precise source governance. In this study, the real-time detection about water quality parameters and fluorescence fingerprints (FFs) was performed for BX River and its outlets during rainfall period. EEM-PARAFAC and component similarity analyses discovered that the pollution encountered by BX River mainly came from road runoff and untreated municipal wastewater (UMWW) overflow. The C1 (tryptophan-like) and C3 (terrestrial humic-like) components located at Ex/Em = âˆ¼230(280)/340 and ∼275/430 nm were both detected in these two kinds of urban NPS. The C2 components of road runoff and UMWW overflow displayed remarkable differences, which located at Ex/Em = 250/385 and 245/365 nm, respectively, thus could be served as indicators for distinguishing them. During rainfall period, the outflow from rainwater outlets (RWOs) constantly showed similar FF features to road runoff, while the FFs of outflow from combined sewer outlets (CSOs) alternated between those of road runoff and UMWW overflow. The FF features of sections in BX River changed in response to the dynamic variations in FFs of the outlets, which revealed real-time pollution causes of BX River. This work not only realized the identification and differentiation of urban NPS, but also elucidated the dynamic variations of pollution characteristics throughout the entire process of "urban NPS-outlets-urban river", and demonstrated the feasibility of FF technique in quickly diagnosing the pollution causes of urban river during rainfall period, which provided important guidance for urban NPS governance.

Expression and tissue distribution analysis of vimentin and transthyretin proteins associated with coat colors in sheep (Ovis aries).

OBJECTIVE: Pigment production and distribution are controlled through multiple proteins, resulting in different coat color phenotypes of sheep. METHODS: The expression distribution of vimentin (VIM) and transthyretin (TTR) in white and black sheep skins was detected by liquid chromatography-electrospray ionization tandem MS (LC-ESI-MS/MS), gene ontology (GO) statistics, immunohistochemistry, Western blot, and quantitative real time polymerase chain reaction (qRT-PCR) to evaluate their role in the coat color formation of sheep. RESULTS: LC-ESI-MS/MS results showed VIM and TTR proteins in white and black skin tissues of sheep. Meanwhile, GO functional annotation analysis suggested that VIM and TTR proteins were mainly concentrated in cellular components and biological process, respectively. Further research confirmed that VIM and TTR proteins were expressed at significantly higher levels in black sheep skins than in white sheep skins by Western blot, respectively. Immunohistochemistry notably detected VIM and TTR in hair follicle, dermal papilla, and outer root sheath of white and black sheep skins. qRT-PCR results also revealed that the expression of VIM and TTR mRNAs was higher in black sheep skins than in white sheep skins. CONCLUSION: The expression of VIM and TTR were higher in black sheep skins than in white sheep skins and the transcription and translation were unanimous in this study. VIM and TTR proteins were expressed in hair follicles of white and black sheep skins. These results suggested that VIM and TTR were involved in the coat color formation of sheep.

Effect of short-term exposure to ambient air pollutants on non-accidental mortality in emergency department visits: a time-series study.

Objectives: Exposure to air pollution has been linked to an increased risk of premature mortality. However, the acute effects of air pollution on the risk of non-accidental mortality have not been extensively researched in developing countries, and the findings thus far have been inconsistent. Therefore, this study aimed to examine the association between short-term exposure to six pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and non-accidental mortality in Beijing, China. Methods: Daily data on non-accidental deaths were gathered from 1 January 2017 to 31 December 2018. Air pollution data for the same period were collected from 35 fixed-site air quality monitoring stations in Beijing. Generalized additive models (GAM) based on Poisson regression were used to investigate the association between non-accidental mortality in emergency department visits and the daily average levels of air pollutants. Results: There were 8,676 non-accidental deaths recorded during 2017-2018. After sensitivity analysis, short-term exposure to air pollutants, particularly gaseous pollutants, was linked to non-accidental mortality. Specifically, for every 10 µg/m3 increase (5 µg/m3 in SO2, 0.5 mg/m3 in CO) of SO2 (lag 04), NO2 (lag 04), O3 (lag 05), and CO (lag 04), the relative risk (RR) values were 1.054 (95% CI: 1.009, 1.100), 1.038 (95% CI: 1.013, 1.063), 1.032 (95% CI: 1.011, 1.054), and 1.034 (95% CI: 1.004, 1.066), respectively. In terms of causes of death, short-term exposure to NO2, SO2, and O3 increased the risk of circulatory mortality. Further stratified analysis revealed that the stronger associations were presented in females for O3 while in males for CO. People aged 65 and over were strongly associated with ambient air pollution. Conclusions: Our study showed that ambient air pollutants were associated with non-accidental mortality. Our findings suggested that efforts to control gaseous pollution should be stepped up, and vulnerable groups should be the focus of health protection education.

In situ gelling hydrogel loaded with berberine liposome for the treatment of biofilm-infected wounds.

Background: In recent years, the impact of bacterial biofilms on traumatic wounds and the means to combat them have become a major research topic in the field of medicine. The eradication of biofilms formed by bacterial infections in wounds has always been a huge challenge. Herein, we developed a hydrogel with the active ingredient berberine hydrochloride liposomes to disrupt the biofilm and thereby accelerate the healing of infected wounds in mice. Methods: We determined the ability of berberine hydrochloride liposomes to eradicate the biofilm by means of studies such as crystalline violet staining, measuring the inhibition circle, and dilution coating plate method. Encouraged by the in vitro efficacy, we chose to coat the berberine hydrochloride liposomes on the Poloxamer range of in-situ thermosensitive hydrogels to allow fuller contact with the wound surface and sustained efficacy. Eventually, relevant pathological and immunological analyses were carried out on wound tissue from mice treated for 14 days. Results: The final results show that the number of wound tissue biofilms decreases abruptly after treatment and that the various inflammatory factors in them are significantly reduced within a short period. In the meantime, the number of collagen fibers in the treated wound tissue, as well as the proteins involved in healing in the wound tissue, showed significant differences compared to the model group. Conclusion: From the results, we found that berberine liposome gel can accelerate wound healing in Staphylococcus aureus infections by inhibiting the inflammatory response and promoting re-epithelialization as well as vascular regeneration. Our work exemplifies the efficacy of liposomal isolation of toxins. This innovative antimicrobial strategy opens up new perspectives for tackling drug resistance and fighting wound infections.

Autoimmune Glial Fibrillary Acidic Protein (Gfap) Astrocytopa-Thy Accompanied with Reversible Splenial Lesion Syndrome (RESLES): A Case Report and Literature Review.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy usually presents as meningoencephalomyelitis. Many patients developed flu-like symptoms preceding the neurologic symptoms. Reversible lesion in the splenium of the corpus callosum (SCC) is a clinical and radiological syndrome secondary to many kinds of etiologies, including infections, which is termed RESLES. CASE PRESENTATION: we reported a case developing irregularly high fever, both temporal pain, low limbs fatigue with frequent urination admitted to our neurology department. CSF test showed GFAP-IgG positive, elevated WBC counts and protein, with low glucose and chlorine, while MRI showed a reversible lesion on SCC, leading us to diagnose autoimmune GFAP autocytopathy accompanied with RESLES. The boy had significantly improved after anti-virus and steroids therapy. DISCUSSION: Autoimmune GFAP autocytopathy accompanied with RESLES is rarely seen, and pathogenesis for the co-existence has not been clarified. Autoimmune GFAP autocytopathy and RESLES are both related to viral infection. Our case covered infectious symptoms and improved after antiviral treatment, suggesting virus infection may perform a key role in pathogenesis.

Exposure to bisphenol A induces neurotoxicity associated with synaptic and cytoskeletal dysfunction in neuro-2a cells.

Bisphenol A (BPA) has been reported to injure the developing and adult brain. However, the underlying mechanism still remains elusive. This study used neuro-2a cells as a cellular model to investigate the neurotoxic effects of BPA. Microtubule-associated protein 2 (MAP2) and tau protein maintain microtubule normal function and promote the normal development of the nervous system. Synaptophysin (SYP) and drebrin (Dbn) proteins are involved in regulating synaptic plasticity. Cells were exposed to the minimum essential medium (MEM), 0.01% (v/v) DMSO, and 150 µM BPA for 12, 24, or 36 h. Morphological analysis revealed that the cells in the BPA-treated groups shrank and collapsed compared with those in the control groups. CCK-8 and lactate dehydrogenase assay (LDH) assays showed that the mortality of neuro-2a cells increased as the BPA treatment time was prolonged. Ultrastructural analysis further revealed that cells demonstrated nucleolar swelling, dissolution of nuclear and mitochondrial membranes, and partial mitochondrial condensation following exposure to BPA. BPA also decreased the relative protein expression levels of MAP2, tau, and Dbn. Interestingly, the relative protein expression levels of SYP increased. These results indicated that BPA inhibited the proliferation and disrupted cytoskeleton and synaptic integrity of neuro-2a cells.

A conditional knockout rat resource of mitochondrial protein-coding genes via a DdCBE-induced premature stop codon.

Hundreds of pathogenic variants of mitochondrial DNA (mtDNA) have been reported to cause mitochondrial diseases, which still lack effective treatments. It is a huge challenge to install these mutations one by one. We repurposed the DddA-derived cytosine base editor to incorporate a premature stop codon in the mtProtein-coding genes to ablate mitochondrial proteins encoded in the mtDNA (mtProteins) instead of installing pathogenic variants and generated a library of both cell and rat resources with mtProtein depletion. In vitro, we depleted 12 of 13 mtProtein-coding genes with high efficiency and specificity, resulting in decreased mtProtein levels and impaired oxidative phosphorylation. Moreover, we generated six conditional knockout rat strains to ablate mtProteins using Cre/loxP system. Mitochondrially encoded ATP synthase membrane subunit 8 and NADH:ubiquinone oxidoreductase core subunit 1 were specifically depleted in heart cells or neurons, resulting in heart failure or abnormal brain development. Our work provides cell and rat resources for studying the function of mtProtein-coding genes and therapeutic strategies.

Exposure to fluoride induces apoptosis in the liver, kidney, and heart of Xenopus laevis by regulating the Caspase-8/3 signaling pathway.

Fluoride compounds are abundant and widely distributed in the environment at various concentrations, which can seriously injure the human body. In this study, we aim to evaluate the effects of excessive fluoride exposure on the liver, kidney, and heart tissues of healthy female Xenopus laevis by administering NaF (0, 100, and 200 mg/L) in drinking water for 90 days. The expression level of procaspase-8, cleaved-caspase-8, and procaspase-3 proteins were determined by Western blot. Compared with the control group, the group exposed to NaF exhibited expression levels of procaspase-8, cleaved-caspase-8, and procaspase-3 proteins that were considerably upregulated at a concentration of 200 mg/L in the liver and kidney. The cleaved-caspase-8 protein expression in the group exposed to a high concentration of NaF was lower than that in the control group in heart. Histopathological results by hematoxylin and eosin staining showed that excessive NaF exposure caused necrosis of hepatocytes and vacuolization degeneration. Granular degeneration and necrosis in renal tubular epithelial cells were also observed. Moreover, hypertrophy of myocardial cells, atrophy of myocardial fibers and disorder of myocardial fibers were detected. These results demonstrated that NaF-induced apoptosis and the mediated death receptor pathway activation ultimately damaged the liver and kidney tissues. This finding offers a fresh perspective on the effects of F-induced apoptosis in X. laevis.

Associations of Dietary Zinc-Vitamin B6 Ratio with All-Cause Mortality and Cardiovascular Disease Mortality Based on National Health and Nutrition Examination Survey 1999-2016.

Previous studies have suggested a possible association among dietary zinc and vitamin B6 intake and CVD mortality and all-cause mortality. However, evidence on the association of dietary zinc and vitamin B6 intake and their interactions with CVD mortality and all-cause mortality remains unclear. This prospective study utilized data from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. After a median follow-up of 10.4 years, 4757 deaths were recorded among 36,081 participants. Higher dietary zinc intake levels (≥9.87 mg/day) were associated with lower CVD mortality (hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.83−0.87). Vitamin B6 intake levels (≥1.73 mg/day) were associated with lower CVD mortality (HR = 0.91, 95% CI: 0.86−0.96) and all-cause mortality (HR = 0.91, 95% CI: 0.90−0.93). Higher dietary zinc intake and higher vitamin B6 intake were associated with a lower risk of CVD mortality, with an interaction between dietary zinc intake levels and vitamin B intake levels (LZLV group (HR, CI): 1.21,1.12−1.29; LZHV group (HR, CI): 1.42, 1.34−1.50; LZHV group (HR, CI): 1.28, 1.14−1.45; HZHV group (HR, CI): ref). There was also a J-type association (p for nonlinear < 0.001) between the dietary zinc−vitamin B6 ratio and CVD mortality, with a high dietary zinc−vitamin B6 ratio increasing the risk of CVD mortality (HR = 1.27, 95% CI: 1.19−1.35), whereas a moderate dietary zinc−vitamin B6 ratio appeared to be beneficial for CVD mortality. These results suggest that increasing the appropriate proportion of dietary zinc and vitamin B6 intake is associated with a lower risk of CVD mortality. Furthermore, precise and representative studies are needed to verify our findings.

Association Between IL10 Polymorphisms and the Susceptibility to Sepsis: A Meta-Analysis.

Many genetic variations have been identified to associate with sepsis in numerous studies, but the function of these variants in influencing sepsis is a complex process. We make use of mate-analysis and other analytic strategies (eQTL analysis and PPI network) to investigate the effect of interleukin-10 (IL10) on sepsis. Single-nucleotide polymorphisms (SNPs) in IL10 were analyzed in 3011 septic cases and 2976 controls from 22 studies. In results, the IL10-rs1800871 showed a significant association with sepsis in Asians (P < 0.05). Moreover, there is a association between rs1800896 and sepsis in pooled populations and Asians (P < 0.05). However, there is no association between rs1800872 and sepsis in different models. The three polymorphisms were also identified for the regulation of IL10 expression in an eQTL analyze, and the increased IL10 expression was related to the development of sepsis. Furthermore, the IL10 was discovered to associate with the expression of DRD1, TANK, MKL1, and STARD3NL genes in another independent cohort, which are functionally enriched for IRF3 (interferon regulatory factor 3)/IRF7 (interferon regulatory factor 7) and hormone pathways. In conclusion, the study confirmed the association between IL10 polymorphisms (rs1800871, rs1800872, rs1800896) and sepsis, and suggested the role of the variants in inflammatory pathologies.

Chitosan-wampee seed essential oil composite film combined with cold plasma for refrigerated storage with modified atmosphere packaging: A promising technology for quality preservation of golden pompano fillets.

The effect of chitosan-wampee seed essential oil (WSEO) composite film coating before cold plasma (CP) treatment on the quality preservation of golden pompano fillets during refrigerated storage was investigated and compared with that of chitosan and CP alone. The results indicated that the chitosan-WSEO composite film coating before CP treatment and modified atmosphere packaging (MAP), referred to as CPCW-M, exhibited the lowest total bacterial count, total volatile base nitrogen, and peroxide and thiobarbituric acid values of 4.03 log culture-forming units (CFU)/g, 13.45 mg/100 g, 24.65 meq/kg, and 1428.4 µg MDAeq/kg, respectively. Simultaneously, it contributed to the most profound inhibition of the lipid hydrolase, lipoxygenase, thus effectively preventing the oxidative deterioration of unsaturated fatty acids. Moreover, minimal color changes, drip loss, and texture deterioration of the fillets were observed. Therefore, the edible chitosan-WSEO composite film, together with CP and MAP, was effective in preserving golden pompano fillets and extending shelf life throughout the refrigerated storage period.

Effect of combined ultrasonic and enzymatic extraction technique on the quality of noni (Morinda citrifolia L.) juice.

In order to obtain noni juice with high yield and good quality, the effect of combined extraction technique of enzymatic treatment (EZ) and ultrasonication (US) on the overall quality of noni juice was investigated. Moreover, the extraction performance of the EZ-US combined extraction technique was compared with that of EZ-based extraction and the US-based extraction. Response surface methodology (RSM) was designed to optimize the parameters of ultrasonic treatment, by taking consideration of the extraction efficiency, quality parameters and bioactive ingredients of noni juice. The results indicated that combined ultrasonic and enzymatic treatment achieved a synergistic effect on promoting the quality of noni juice. The maximum juice yield of 67.95 % was obtained under ultrasonication for 10 min at 600 W after enzymatic treatment (EZU). In addition, EZU-treated juice exhibited the highest contents of total phenolic and flavonoid, which were 148.19 ± 2.53 mg gallic acid/100 mL and 47.19 ± 1.22 mg rutin/100 mL, respectively, thus contributing to better antioxidant activity. Moreover, the EZU treatment significantly reduced the particle size of noni juice, and improved its suspension stability and rheological properties. FTIR results indicated that the treatments did not bring major changes in the chemical structure and the functional groups of compounds in noni juice. Therefore, EZU treatment can be successfully applied to the extraction of noni juice with better nutritional properties and overall quality.

Spectroscopic and compositional profiles of dissolved organic matters in urban snow from 2019 to 2021: Focusing on pollution features identification.

Snow owns stronger adsorption capacity for organic pollutants compared with rain. Huge amounts of anthropogenic dissolved organic matters (DOMs) in the atmosphere may enter the water environment with urban snow and increase water pollution risk. Extracting stable pollution features of urban snow is conducive to identifying the urban snow pollution from the water environment. Herein, we systematically explored the spectroscopic and compositional profiles of urban snow in Beijing from three snow events by multiple analytical tools and extracted stable pollution features of urban snow for the first time. Results showed that conventional pollutants with high concentration were detected in urban snow. The fluorescence signals of humic-like and some protein-like materials, the molecular weight distributions of chromophoric DOM at 254 nm and humic-like materials, and 172 kinds of lignin-like molecular formulas were extracted as stable features for urban snow. These stable features of urban snow laid the foundation for the identification of urban snow pollution and the analysis of the impact mechanisms of atmospheric pollution sources on the water environment.

Traditional Chinese Nursing Using Fennel With Coarse Salt for Ironing and Umbilical Moxibustion for Epigastric Pain With Spleen-stomach Vacuity Cold.

Context: Spleen-stomach vacuity cold is the primary TCM pattern for epigastric pain, accounting for 75% of the patients. According to the TCM theory of treating both the tip and the root, epigastric pain requires the caregiver to dissipate cold and relieve pain, the treatments for the tip, which warm and supplement the spleen and stomach, the treatments for the root. Objective: This study aimed to explore effectiveness of traditional Chinese nursing care using fennel mixed with coarse salt for ironing,with umbilical moxibustion, for epigastric pain, with a pattern of spleen-stomach vacuity cold. Design: The research team designed a randomized control trial (RCT). Setting: The study was conducted at Ruikang Affiliated Hospital of Guangxi University of Chinese Medicine in the capital city of the Guangxi Zhuang autonomous region in the People's Republic of China. Participants: Participants were 96 patients who had been admitted to the hospital between October and November 2020 with epigastric pain resulting from the TCM spleen-stomach vacuity cold pattern, equivalent to chronic atrophic gastritis in Western medicine. Intervention: The research team randomly divided participants into an intervention group (n = 48) and a control group (n = 48) using a random digits table. The intervention group received fennel mixed with coarse salt for ironing, combined with umbilical moxibustion, whereas the control group received routine care. Outcome Measures: The study's instruments included the Traditional Chinese Medicine (TCM) Syndrome Score Scale (TCMSSS), Medical Outcome Study (MOS) Short Form 36 (SF-36), and Satisfaction with TCM Nursing Program (STCMNP). Data were collected and analyzed through descriptive statistics a Chi-square test and independent t test. A significance level of P < .05 was accepted for all statistical analyses. Results: The intervention group had mean scores that indicated significantly higher decreases in epigastric pain, and increases in quality of life and level of satisfaction with the traditional Chinese nursing care than the control group did (P < .05). Conclusions: The traditional Chinese nursing care was able to improve epigastric pain, enhance quality of life, and increase satisfaction with the traditional Chinese nursing care.

Genetic Algorithm-Based Optimization for Color Point Cloud Registration.

Point cloud registration is an important technique for 3D environment map construction. Traditional point cloud registration algorithms rely on color features or geometric features, which leave problems such as color affected by environmental lighting. This article introduced a color point cloud registration algorithm optimized by a genetic algorithm, which has good robustness for different lighting environments. We extracted the HSV color data from the point cloud color information and made the HSV distribution of the tangent plane continuous, and we used the genetic algorithm to optimize the point cloud color information consistently. The Gauss-Newton method was utilized to realize the optimal registration of color point clouds for the joint error function of color and geometry. The contribution of this study was that the genetic algorithm was used to optimize HSV color information of the point cloud and was applied to the point cloud registration algorithm, which reduces the influence of illumination on color information and improves the accuracy of registration. The experimental results showed that the square error of color information saturation and lightness optimized by the genetic algorithm was reduced by 14.07% and 37.16%, respectively. The color point cloud registration algorithm in this article was reduced by 12.53% on average compared with the optimal result algorithm RMSE.

A Comparative Study of Natural Language Processing Algorithms Based on Cities Changing Diabetes Vulnerability Data.

(1) Background: Poor adherence to management behaviors in Chinese Type 2 diabetes mellitus (T2DM) patients leads to an uncontrolled prognosis of diabetes, which results in significant economic costs for China. It is imperative to quickly locate vulnerability factors in the management behavior of patients with T2DM. (2) Methods: In this study, a thematic analysis of the collected interview materials was conducted to construct the themes of T2DM management vulnerability. We explored the applicability of the pre-trained models based on the evaluation metrics in text classification. (3) Results: We constructed 12 themes of vulnerability related to the health and well-being of people with T2DM in Tianjin. We considered that Bidirectional Encoder Representation from Transformers (BERT) performed better in this Natural Language Processing (NLP) task with a shorter completion time. With the splitting ratio of 6:3:1 and batch size of 64 for BERT, the test accuracy was 97.71%, the completion time was 10 min 24 s, and the macro-F1 score was 0.9752. (4) Conclusions: Our results proved the applicability of NLP techniques in this specific Chinese-language medical environment. We filled the knowledge gap in the application of NLP technologies in diabetes management. Our study provided strong support for using NLP techniques to rapidly locate vulnerability factors in T2DM management.

Bisphenol A induces apoptosis in response to DNA damage through c-Abl/YAPY357/ p73 pathway in P19 embryonal carcinoma stem cells.

Bisphenol A (2,2-bis(4'-hydroxyphenyl) propane, BPA) is a well-known endocrine-disrupting compound that is widely used in various daily products and exhibits embryonic development toxicity and genotoxicity. However, the affected signaling pathways involved in embryonic development especially the interactions of involved proteins remain unclear. In our previous study (Ge et al., 2021), BPA induces DNA damage and apoptosis in Xenopus embryos, resulting in multiple malformations of larvae. However, the signaling pathways induced for apoptosis response to DNA damage are still not well elucidated. Here, we systematically elucidated the enriched pathways affected by BPA and illustrated the interactions of involved proteins. Results indicated that BPA affected multiple embryonic development pathways including Hippo, TGF-ß, Wnt, and Notch pathways. Furthermore, the protein-protein interaction network suggested that the c-Abl/YAPY357/p73 pathway may play a key role in apoptosis induction in response to DNA damage. P19 embryonal carcinoma stem cells, as a developmental toxicity model, were treated with different BPA concentrations to establish an in vitro model to verify the role of the c-Abl/YAPY357/p73 pathway in apoptosis. BPA triggered DNA damage and significantly upregulated the expression levels of c-Abl, phosphorylated YAPY357, phosphorylated p73Y99, and cleaved caspase-3 protein (p < 0.05), thus decreasing cell viability and transcriptionally activating the p73 target genes Bax and Puma. These data suggested that BPA activated the c-Abl/YAPY357/p73 pathway in response to DNA damage. Imatinib, an inhibitor of tyrosine kinase c-Abl, significantly downregulated the elevated expression levels of p-YAPY357, p-p73Y99 and cleaved caspase-3 (p < 0.05) caused by BPA and then ameliorated the cell index of P19 cells in the BPA-treated group. Therefore, this substance restrained the phosphokinase activity of c-Abl and suppressed the c-Abl/YAPY357/p73 pathway. Results showed that the c-Abl/YAPY357/p73 pathway served as a mechanism for caspase-3 activation that induced the apoptosis response to DNA damage stress.

The effect of mindfulness and job demands on motivation and performance trajectories across the workweek: An entrainment theory perspective.

Employee performance is commonly investigated as a static, one-time snapshot of prior employee behaviors. For the studies that do acknowledge that performance fluctuates over time, the timeframe decision is disconnected from theoretical underpinnings. To make this connection clearer, we draw on entrainment theory and investigate trajectories in motivation and performance across the 5-day workweek. We hypothesize that both motivational control (i.e., staying on course and sustaining effort in pursuit of goals through the redirection of attention) and performance have a declining trajectory across the workweek. Drawing on self-determination theory, we also hypothesize that trait-based mindfulness (i.e., nonjudgmental present moment attention and awareness) negatively relates to the downward trajectory in performance across the workweek via its effect on the trajectory of motivational control. Finally, we take a trait activation theory perspective, hypothesizing that mindfulness is relevant as an indirect influence on performance trajectories through motivational control trajectories only when job demands are high. We test our model using 151 full-time employees in a medical device company. We collected data from participants twice daily across the 5-day workweek. We then use these daily scores to create between-person (e.g., person-centric) trajectories to investigate the proposed relationships. The hypotheses are generally supported. There is a downward trajectory of both motivational control and performance across the workweek. Furthermore, job demands conditionally moderate the indirect effect of mindfulness on performance trajectories through motivational control trajectories. Theoretical and practical implications specific to dynamic motivation and performance, entrainment, and mindfulness literature are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Health Care Costs and Treatment Patterns Associated with Uterine Fibroids and Heavy Menstrual Bleeding: A Claims Analysis.

Background: Heavy menstrual bleeding (HMB) is one of the most common distressing complications of uterine fibroids (UF); however, data on the health care costs for treatments in women experiencing HMB associated with UF are lacking. The objective of this study was to compare the direct costs and treatments patterns for women diagnosed with UF+HMB, UF only, and HMB only in the United States. Materials and Methods: The study design was retrospective matched cohort study using claims data. Women, aged 18-51 years, comprising four cohorts (HMB only, UF only, UF+HMB, and controls) were identified in the IBM MarketScan® Commercial Claims and Encounters Database (October 1, 2007‒September 30, 2018) and matched by demographics and Charlson Comorbidity Index score. Baseline characteristics and treatments during the 12 months post-diagnosis were summarized descriptively. Costs (2018 U.S. dollars) during the post-diagnosis year were compared using analysis of variance. Results: Before matching, women with UF+HMB represented 54% of UF cases. Following diagnosis, 32% in the matched UF+HMB cohort had no treatment, 49% underwent surgeries/procedures with (12%) or without (37%) medications, and 18% received medications only. The mean all-cause total costs for UF+HMB ($16,762) exceeded that for UF only by 24% ($13,506) and HMB only by 50% ($11,135), and almost tripled the mean cost for the control cohort ($6,691) (all, p < 0.001). The mean diagnosis-related costs were significantly higher for UF+HMB ($8,741) than for UF only ($4,550) and HMB only ($3,081) (all, p < 0.0001). Surgery/procedure costs comprised 80% of diagnosis-related medical costs for UF+HMB. Conclusions: UF with HMB were associated with significant economic burden, driven primarily by surgical/procedural costs and treatment patterns.