Critical new insights into the interactions of hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) with albumin at molecular and cellular levels.

A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking. Herein, the binding characteristics of bovine serum albumin (BSA) to GenX were explored at the molecular and cellular levels. It was found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid (PFOA). Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex. Consistent with its weaker affinity to albumin protein, the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA. In contrast to the significant effects of strong BSA-PFOA interaction, the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX. The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.

Effectiveness of digital health exercise interventions on muscle function and physical performance in older adults with possible, confirmed or severe sarcopenia: a protocol for a systematic review.

INTRODUCTION: Sarcopenia is characterised by the progressive weakening of muscle function that occurs with age. This condition frequently leads to frailty, disability and even death. Research on sarcopenia prevention is growing. Digital health exercise interventions are increasingly gaining attention in this field, with the rapid advancement of the internet and the influence of the COVID-19. However, there is a lack of empirical support for their effectiveness. Our study aims to assess the effect of digital health exercise intervention on sarcopenia in older persons, specifically focusing on its ability to improve muscle strength, muscle mass and physical performance. METHODS AND ANALYSIS: Searching will be performed in the following 11 databases (Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, WOS, Scopus, CBM, CNKI, WANFANG and VIP) for published trials and 2 trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) for unpublished trials. Google Scholar will be used to find grey literature. The criterion of inclusion will be clinical trials involving digital health exercise interventions in older adults (≥60 years) diagnosed with sarcopenia (possible, confirmed or severe sarcopenia). For data synthesis, we will use a summary table to show the major characteristics of selected trials and a summary graph to demonstrate the risk of bias for each outcome using RoB 2, which will be further discussed in a narrative synthesis. The possibility of meta-analysis for quantitative data will be assessed according to the homogeneity analysis of the trials, using the methods of fixed or random effects model. If meta-analysis is possible, subgroup analysis and sensitivity analysis will be performed as well. Publication bias will be assessed through the use of the funnel plot and Egger's linear regression test when an adequate number of trials are available. Finally, the Grading of Recommendations, Assessment, Development and Evaluation approach will be used to classify the certainty of evidence body into four categories (high, moderate, low and very low). ETHICS AND DISSEMINATION: The findings of the systematic review will be shared through publishing in a peer-reviewed journal and presentation at appropriate conferences. Since we will not be using specific patient data, ethical approval is unnecessary. PROSPERO REGISTRATION NUMBER: CRD42024516930.

PARP1 acetylation at K119 is essential in regulating the progression and proliferation of cervical cancer cells.

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function.

The Efficacy and Safety of the Rhomboid Intercostal Block for Postoperative Analgesia in Chest Surgery and Breast Surgery: A Systemic Review and Meta-Analysis.

BACKGROUND: Prior research has suggested that the rhomboid intercostal block (RIB) may contribute to postoperative analgesia after surgeries of the chest and breast. OBJECTIVE: To explore the effectiveness and safety of RIB for postoperative analgesia, as well as whether RIB is superior to other types of nerve blocks. STUDY DESIGN: A systematic review and meta-analysis. SETTING: Querying electronic databases, including the Cochrane Library, PubMed, Embase, and Web of Science, was part of the process in searching for eligible clinical trials for this meta-analysis and systematic review. METHODS: The Cochrane Collaboration's tool for quality evaluation was utilized in assessing the bias risk in the selected randomized controlled trials (RCTs). meta-analysis was facilitated through the utilization of Review Manager 5.3. The determination of the evidence's quality adhered to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: After the inclusion and exclusion criteria were established, the incorporation of 8 RCTs, encompassing 714 patients, took place. During the first 24 hours after the operation, patients in the RIB group exhibited lower pain scores and less opioid consumption than did those in the no-block group. Furthermore, a decrease in the incidence of postoperative vomiting and nausea was noted in the RIB group. Nevertheless, when comparing outcomes, it was revealed that the RIB group and the other nerve block group did not differ significantly. LIMITATIONS: No subgroup analysis to investigate the sources of heterogeneity was performed. The number of studies in this meta-analysis of RIB compared to those that focus on other types of nerve block is relatively small. The optimal concentrations and volumes of local anesthetics were not evaluated. CONCLUSIONS: RIB may be a new option for pain relief after chest and breast surgery.

Tumour cell-released autophagosomes promote lung metastasis by upregulating PD-L1 expression in pulmonary vascular endothelial cells in breast cancer.

PURPOSE: Establishing an immunosuppressive premetastatic niche (PMN) in distant organs is crucial for breast cancer metastasis. Vascular endothelial cells (VECs) act as barriers to transendothelial cell migration. However, the immune functions of PMNs remain unclear. Tumour cell-released autophagosomes (TRAPs) are critical modulators of antitumour immune responses. Herein, we investigated the mechanism through which TRAPs modulate the immune function of pulmonary VECs in lung PMN in breast cancer. METHODS: Immortalised mouse pulmonary microvascular endothelial cells were incubated with TRAPs in vitro. RNA sequencing, flow cytometry, and western blotting were employed to assess immunosuppressive function and mechanism. In vivo, TRAP-trained and autophagy-deficient tumour mice were used to detect immunosuppression, and high-mobility group box 1 (HMGB1)-deficient TRAP-trained and TLR4 knockout mice were utilised to investigate the underlying mechanisms of pulmonary VECs. Additionally, the efficacy of anti-programmed cell death ligand-1 (PD-L1) immunotherapy was evaluated in early tumour-bearing mice. RESULTS: HMGB1 on TRAPs surfaces stimulated VECs to upregulate PD-L1 via a TLR4-MyD88-p38/STAT3 signalling cascade that depended on the cytoskeletal movement of VECs. Importantly, PD-L1 on TRAP-induced VECs can inhibit T cell function, promote lung PMN immunosuppression, and result in more pronounced lung metastasis. Treatment with anti-PD-L1 reduces lung metastasis in early stage tumour-bearing mice. CONCLUSIONS: These findings revealed a novel role and mechanism of TRAP-induced immunosuppression of pulmonary VECs in lung PMN. TRAPs and their surface HMGB1 are important therapeutic targets for reversing immunosuppression, providing a new theoretical basis for the treatment of early stage breast cancer using an anti-PD-L1 antibody.

Psychosocial profiles influencing healthy dietary behaviors among adolescents in Shandong Province, China: a cross-sectional study.

Objectives: We aimed to assess the influence of psychosocial profiles on dietary behaviors among school-aged adolescents in China. Methods: A cross-sectional study was conducted involving 7,862 adolescents from 100 schools in Shandong, China. Psychosocial profiles and dietary behaviors were assessed using the Junior High School Students' Psychosocial Profiles Questionnaire (JPPQ) and the Chinese Diet Quality Questionnaire (DQQ), respectively. Linear regression models were used to investigate the association between adolescents' psychosocial profiles and dietary behaviors. Results: The mean age of the participants was 13.18 ± 1.15 years; 48.5% of them were boys. The majority of participants (97.90%) were Han Chinese, and approximately half of the participants (50.90%) resided in rural areas. After adjusting for sociodemographic characteristics and family computer and Internet ownership and usage, healthy dietary behavior was positively correlated with higher psychosocial profile scores (p < 0.05). The stratified analysis results revealed that the group with the highest psychosocial profile score was associated with an increased overall global dietary reference (GDR) score in "households without a family computer and Internet" ( ß : 5.357, 95% Cl: 4.931-5.784, p < 0.05). Conclusion: Good psychosocial profiles exhibit a positive influence on healthy dietary behaviors. Therefore, policymakers should focus on Internet usage to maximize the positive effects on global youth health behaviors.

The Different Concentrations of Applied Exogenous Sugars Widely Influence the Specificity, Significance and Physiological Relevance of Study Outcomings.

Plant growth and development are governed via signal networks that connect inputs from nutrient status, hormone signals, and environmental cues. Substantial researches have indicated a pivotal role of sugars as signalling molecules in plants that integrate external environmental cues and other nutrients with intrinsic developmental programmes regulated via multiple plant hormones. Therefore, plant growth and development are controlled through complication signalling networks. However, in many studies, to obtain more obviously experimental findings, excess concentrations of applied exogenous sugars have aggravated the complexity of this signalling networks. Once researchers underestimate this complexity, a series of contradictory or contrasting findings will be generated. More importantly, in terms of these contradictory findings, more contradictory study outcomings are derived. In this review, we carefully analyze some reports, and find that these reports have confused or neglected that the sugar-antagonism of ethylene signalling is specific or conditional. As a result, many contradictory conclusions are generated, which will in turn misdirect the scientific community.

Effect of Ginkgo tablets on the pharmacokinetics of metoprolol in rats: liquid chromatography-tandem mass spectrometry-based study.

OBJECTIVES: This study aimed to assess the interaction between metoprolol and Ginkgo tablets during their co-administration to provide a reference for clinical prescribing. METHODS: The co-administration of metoprolol (20 mg/kg) and Ginkgo tablets (2.4 mg/kg) was conducted in adult Sprague Dawley (SD) rats (n = 8). An optimized liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of plasma metoprolol to evaluate its pharmacokinetics. In vitro, the rat liver microsomes were employed to assess the effect of Ginkgo tablets on the metabolic stability of metoprolol and the activity of Cytochrome P450 2D6 (CYP2D6). RESULTS: The developed LC-MS/MS method was demonstrated of high sensitivity, accuracy, and precision. When co-administered with Ginkgo tablets, it increased the area under the curve (AUC, 59.01 ± 10.11 vs. 39.19 ± 10.21 µg/mL × min), the maximum plasma concentration (Cmax, 461.72 ± 44.64 vs. 276.35 ± 118.09 ng/mL), and the half-life (t1/2, 302.83 ± 91.52 vs. 262.34 ± 111.12 min) of metoprolol in rats and reduced the clearance rate (0.346 ± 0.057 vs. 0.539 ± 0.145 L/min/kg). In vitro, Ginkgo tablets improved the metabolic stability of metoprolol and suppressed the activity of CYP2D6 in a concentration-dependent manner with the IC50 value of 11.17 µM. CONCLUSION: Co-administration of metoprolol with Ginkgo tablets resulted in increasing its systemic exposure through inhibiting CYP2D6 activity.

p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.

Mechanisms underlying p53-mediated protection of the replicating genome remain elusive, despite the quintessential role of p53 in maintaining genomic stability. Here, we uncover an unexpected function of p53 in curbing replication stress by limiting PARP1 activity and preventing the unscheduled degradation of deprotected stalled forks. We searched for p53-dependent factors and elucidated RRM2B as a prime factor. Deficiency in p53/RRM2B results in the activation of an NRF2 antioxidant transcriptional program, with a concomitant elevation in basal PARylation in cells. Dissecting the consequences of p53/RRM2B loss revealed a crosstalk between redox metabolism and genome integrity that is negotiated through a hitherto undescribed NRF2-PARP1 axis, and pinpoint G6PD as a primary oxidative stress-induced NRF2 target and activator of basal PARylation. This study elucidates how loss of p53 could be destabilizing for the replicating genome and, importantly, describes an unanticipated crosstalk between redox metabolism, PARP1 and p53 tumor suppressor pathway that is broadly relevant in cancers and can be leveraged therapeutically.

Correlation between Vegetable and Fruit Intake and Cognitive Function in Older Adults: A Cross-Sectional Study in Chongqing, China.

OBJECTIVE: To explore the correlation between different types of vegetable and fruit intake and cognitive function among the older adults in Chongqing, China, and to provide a scientific basis for developing efficient lifestyle interventions for the prevention of Mild Cognitive Impairment (MCI). METHOD: Approximately 728 older adults in urban and rural areas of Chongqing were surveyed using face-to-face questionnaires. Cognitive function was assessed with the Montreal Cognitive Assessment-Basic (MoCA-B) scale, and the vegetable and fruit intake groups were investigated with the Simple Food Frequency Counting Survey Scale. Binary logistic regression was used to explore the effect of the vegetable and fruit intake group on cognitive function. Subgroup analysis was used to demonstrate the robustness of the results. RESULT: Of the 728 participants in the study, 36.40% were likely to have MCI, which is higher than the national average for this condition. After adjusting for confounders, compared to the Q1 group, fruit and root vegetable intake was a protective factor for MCI, showing a dose-response relationship (p < 0.05). Only lower intake (Q2) of total vegetables, medium intake (Q2, Q3) of solanaceous vegetables, and medium-high intake (Q2, Q4) of fungi and algae was protective against MCI, whereas the leafy vegetables showed no relation to MCI. Apart from this, participants who were older, female, unmarried, non-smoking, and engaged in physical labor, and who had an average monthly income of less than 3000 RMB were more likely to suffer from cognitive impairment. CONCLUSION: This suggested that the fruit-intake groups and some vegetable-intake groups showed a protective effect on cognitive function, and might behave differently depending on their different intake and demographic characteristics. A sensible, healthy diet can help prevent MCI.

Combined DeRitis ratio and alkaline phosphatase on the prediction of portal vein tumor thrombosis in patients with hepatocellular carcinoma.

Portal vein tumor thrombosis (PVTT) is one of the common complications of HCC and represents a sign of poor prognosis. PVTT signifies advanced liver cancer, deteriorating liver function, and heightened susceptibility to intrahepatic dissemination, systemic metastasis, and complications related to portal hypertension. It is important to seek novel strategies for PVTT arising from HCC. Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) represents a worse liver function, less treatment tolerance, and poor prognosis. This study aimed to investigate the diagnostic value of the combination of the DeRitis ratio (AST/ALT) and alkaline phosphatase (ALP) index (briefly named DALP) in predicting the occurrence risk of PVTT in patients with HCC. We performed a retrospective study enrolling consecutive patients with HCC from January 2017 to December 2020 in Hebei Medical University Third Hospital. ROC analysis was performed to estimate the predictive effectiveness and optimal cut-off value of DALP for PVTT occurrence in patients with HCC. Kaplan-Meier analysis revealed the survival probabilities in each subgroup according to the risk classification of DALP value. Univariate and multivariate Logistics regression analyses were applied to determine the independent risk for poor prognosis. ROC analysis revealed that the optimal cut-off value for DALP was 1.045, with an area under the curve (AUC) of 0.793 (95% CI 0.697-0.888). Based on the DALP classification (three scores: 0-2) with distinguishable prognoses, patients in the score 0 group had the best prognosis with a 1-year overall survival (OS) of 100%, whereas score 2 patients had the worst prognosis with 1-year OS of 72.4%. Similarly, there was a statistically different recurrence-free survival among the three groups. Besides, this risk classification was also associated with PVTT progression in HCC patients (odds ratio [OR] 5.822, P < 0.0001). Pathologically, patients in the score 2 group had more advanced tumors considering PVTT, extrahepatic metastasis, and ascites than those in score 0, 1 groups. Moreover, patients with a score of 2 had more severe hepatic inflammation than other groups. Combination of DeRitis ratio and ALP index presented a better predictive value for PVTT occurrence in patients with HCC, contributing to the tertiary prevention.

Effect of graphene oxide on carbon and nitrogen metabolism and growth of kidney bean at flowering stage.

Graphene oxide (GO) is a novel nanomaterial being applied in different fields, but was less used as foliar fertilizer in agriculture. We conducted a pot experiment to analyze the effects of foliar spraying GO from 0 (control), 50 (T1), 100 (T2), 150 (T3) and 200 mg·L-1 (T4) on the morphogenesis and carbon and nitrogen metabolism of kidney bean plants during the initiation of flowering to clarify the physiological effects of foliar spraying GO. The results showed that dry matter accumulation, the content of photosynthetic pigments, soluble sugars of T1 to T4 treatments, were significantly increased by 40.7%-43.4%, 10.4%-80.7%, 6.4%-9.1% in kidney bean plants compared with CK treatment, respectively. T3 treatment performed the best. Meanwhile, the activities of sucrose phosphate synthase, acid converting enzyme and neutral converting enzyme of T3 and T4 treatments were increased by 25.7%-45.5%, 17.4%-28.6%, and 14.7%-20.1%, and the activities of nitrate reductase, glutamine synthetase, and glutamate synthetase of T2 and T3 treatments were increased by 8.1%-15.2%, 11.5%-25.0%, and 89.7%-93.1%, respectively. In conclusion, foliar spraying of appropriate GO in early flowering stage of kidney bean could increase the content of photosynthetic pigments, improve the level of photosynthetic carbon and nitrogen metabolism, and increase dry matter accumulation. T3 treatment (150 mg·L-1) was the most effective in this study.

Zürich II Statement on Per- and Polyfluoroalkyl Substances (PFASs): Scientific and Regulatory Needs.

Per- and polyfluoroalkyl substances (PFASs) are a class of synthetic organic chemicals of global concern. A group of 36 scientists and regulators from 18 countries held a hybrid workshop in 2022 in Zürich, Switzerland. The workshop, a sequel to a previous Zürich workshop held in 2017, deliberated on progress in the last five years and discussed further needs for cooperative scientific research and regulatory action on PFASs. This review reflects discussion and insights gained during and after this workshop and summarizes key signs of progress in science and policy, ongoing critical issues to be addressed, and possible ways forward. Some key take home messages include: 1) understanding of human health effects continues to develop dramatically, 2) regulatory guidelines continue to drop, 3) better understanding of emissions and contamination levels is needed in more parts of the world, 4) analytical methods, while improving, still only cover around 50 PFASs, and 5) discussions of how to group PFASs for regulation (including subgroupings) have gathered momentum with several jurisdictions proposing restricting a large proportion of PFAS uses. It was concluded that more multi-group exchanges are needed in the future and that there should be a greater diversity of participants at future workshops.

Antibody glycan quality predicted from CHO cell culture media markers and machine learning.

N-glycosylation can have a profound effect on the quality of mAb therapeutics. In biomanufacturing, one of the ways to influence N-glycosylation patterns is by altering the media used to grow mAb cell expression systems. Here, we explore the potential of machine learning (ML) to forecast the abundances of N-glycan types based on variables related to the growth media. The ML models exploit a dataset consisting of detailed glycomic characterisation of Anti-HER fed-batch bioreactor cell cultures measured daily under 12 different culture conditions, such as changes in levels of dissolved oxygen, pH, temperature, and the use of two different commercially available media. By performing spent media quantitation and subsequent calculation of pseudo cell consumption rates (termed media markers) as inputs to the ML model, we were able to demonstrate a small subset of media markers (18 selected out of 167 mass spectrometry peaks) in a Chinese Hamster Ovary (CHO) cell cultures are important to model N-glycan relative abundances (Regression - correlations between 0.80-0.92; Classification - AUC between 75.0-97.2). The performances suggest the ML models can infer N-glycan critical quality attributes from extracellular media as a proxy. Given its accuracy, we envisage its potential applications in biomaufactucuring, especially in areas of process development, downstream and upstream bioprocessing.

Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys.

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.

Direct, Embedded, and Embodied Trade of Arsenic: 1990-2019.

International arsenic trade, physical and virtual, has resulted in considerable transfer of arsenic pollution across regions. However, no study has systematically captured, estimated, and compared physical and virtual arsenic trade and its relevant impacts. This study combines material flow analysis and embodied emission factors to estimate embedded (including direct and indirect trade) and embodied arsenic trade during 1990-2019, encompassing 18 arsenic-containing products among 244 countries. Global embedded arsenic trade increased considerably from 47 ± 7.3 to 450 ± 68 kilotonnes (kt) during this time and was dominated by indirect arsenic trade, contributing 94 and 90% to global arsenic trade in 1990 and 2019, respectively. Since the 1990s, global arsenic trade centers and the main flows have shifted from European and American markets to developing countries. The mass of arsenic involved in embodied trade increased from 87.5 ± 26 kt in 1990 to 800 ± 236 kt in 2019. Direct trade and indirect trade aggravate arsenic environmental emissions in major importing countries, like China, while embodied trade aggravates arsenic environmental emissions in major exporting countries, like Peru and Chile. The trade-related arsenic pollution transfer calls for a rational arsenic emission responsibility-sharing mechanism and corresponding policy recommendations for different trading countries.

Environmental pollution of paraben needs attention: A study of methylparaben and butylparaben co-exposure trigger neurobehavioral toxicity in zebrafish.

Parabens (PBs) are commonly utilized as preservatives in various commodities. Of all the PBs, methylparaben (MeP) and butylparaben (BuP) are usually found together at similar levels in the aqueous environment. Although a few studies have demonstrated that PBs are neurotoxic when present alone, the neurobehavioral toxic effects and mechanisms of coexisting MeP and BuP at environmental levels has not been determined. Neurobehavior is a sensitive indicator for identifying neurotoxicity of environmental pollutants. Therefore, adult female zebrafish (Danio rerio) were chronic co-exposure of MeP and BuP at environmental levels (5, 50, and 500 ng/L) for 60 d to investigate the effects on neurobehavior, histopathology, oxidative stress, mitochondrial function, neurotransmitters and gene expression. The results demonstrated that chronic co-exposure of MeP and BuP interfered with several behaviors (learning-memory, anxiety, fear, aggressive and shoaling behavior) in addition to known mechanisms of producing oxidative stress and disrupting energy. More intriguingly, chronic co-exposure of MeP and BuP caused retinal vacuolization and apoptosis in the optic tectum zone. It even has further effects on the phototransduction pathway, impairing optesthesia and leading to neurotransmitters dysregulation. These are critical underlying mechanisms resulting in neurobehavioral abnormalities. This study confirms that the pollution of multiple PBs by chronic co-exposure in aquatic environments can result neurobehavioral toxicity. It also suggests that the prolonged effects of PBs on aquatic ecosystems and health require close attention.

Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis.

Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, no studies have assessed their roles in mammalian meiosis of females, whose abnormality accounts for over 80% of the cases of gamete-originated human reproductive disease. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of KL2 significantly reduced chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. Importantly, we demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, eliminated KL2 from chromosomes completely. KL2 also interacted with phosphorylated eukaryotic elongation factor-2 kinase; they competed for chromosome binding. We also observed that the phosphorylated KL2 was localized at spindle poles, and that KL2 phosphorylation was regulated by extracellular signal-regulated kinase 1/2. In summary, our study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.

Efficient Functionalization of Organosulfones via Photoredox Catalysis: Direct Incorporation of α-Carbonyl Alkyl Side Chains into α-Allyl-ß-Ketosulfones.

A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-ß-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.