Ameliorative Effect of Coenzyme Q10 on Phenotypic Transformation in Human Smooth Muscle Cells with FBN1 Knockdown.

Mutations of the FBN1 gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down FBN1 in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction. Furthermore, we incubated the shFBN1 SMCs with Coenzyme Q10 (CoQ10) to assess whether restoring mitochondrial function can reverse the phenotypic transformation. The results showed that shFBN1 SMCs had decreased TFAM (mitochondrial transcription factor A), mtDNA levels and mitochondrial mass, lost their contractile capacity and had increased synthetic phenotype markers. Inhibiting the mitochondrial function of SMCs can decrease the expression of contractile markers and increase the expression of synthetic genes. Imposing mitochondrial stress causes a double-hit effect on the TFAM level, oxidative phosphorylation and phenotypic transformation of FBN1-knockdown SMCs while restoring mitochondrial metabolism with CoQ10 can rapidly reverse the synthetic phenotype. Our results suggest that mitochondria function is a potential therapeutic target for the phenotypic transformation of SMCs in MFS.

Heterotopic pregnancy after a single embryo transfer with successful perinatal outcome: case report and literature review.

A heterotopic pregnancy is a rare and serious pathological pregnancy. In this paper, we report a rare case of heterotopic pregnancy and perform a literature review. A 30-year-old patient with a history of left adnexectomy presented with persistent lower abdominal pain and hemorrhagic shock after single embryo transfer. Emergency laparoscopic exploration revealed a ruptured mass in the right isthmus of the fallopian tube, for which right salpingectomy was performed. After anti-inflammatory treatment and fetal preservation, the intrauterine pregnancy progressed smoothly, and a healthy baby was delivered at 39 weeks gestation. In this case, the patient's heterotopic pregnancy was possibly due to a natural pregnancy caused by sexual intercourse during treatment, so we recommend that sexual intercourse be avoided during transfer cycles.

Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.

Cervical cancer is one of the leading causes of cancer death in women. Mitochondrial-mediated ferroptosis (MMF) is a recently discovered form of cancer cell death. However, the role and the underlying mechanism of MMF in cervical cancer remain elusive. Here, using an unbiased screening for mitochondrial transmembrane candidates, we identified mitochondrial carrier 1 (MTCH1) as a central mediator of MMF in cervical cancers. MTCH1-deficiency disrupted mitochondrial oxidative phosphorylation while elevated mitochondrial reactive oxygen species (ROS) by decreasing NAD+ levels. This mitochondrial autonomous event initiated a mitochondria-to-nucleus retrograde signaling involving reduced FoxO1 nuclear translocation and subsequently downregulation of the transcription and activity of a key anti-ferroptosis enzyme glutathione peroxidase 4 (GPX4), thereby elevating ROS and ultimately triggering ferroptosis. Strikingly, targeting MTCH1 in combination with Sorafenib effectively and synergistically inhibited the growth of cervical cancer in a nude mouse xenograft model by actively inducing ferroptosis. In conclusion, these findings enriched our understanding of the mechanisms of MMF in which MTCH1 governed ferroptosis though retrograde signaling to FoxO1-GPX4 axis, and provided a potential therapeutic target for treating cervical cancer.

Food groups and urologic cancers risk: a systematic review and meta-analysis of prospective studies.

Background: To assess the association between 12 food groups intake and the risk of urologic cancers. Methods: We scanned PubMed and Web of Science databases up to April 1st, 2023, and 73 publications met the inclusion criteria in the meta-analysis. We used a random effects model to estimate the summary risk ratios (RRs) and 95% confidence intervals (95% CI). Results: In the linear dose-response meta-analysis, an inverse association was found between each additional daily 100 g of fruits [RR: 0.89, 95%CI = (0.83, 0.97)], 100 g of vegetables [RR: 0.92, 95%CI = (0.85, 0.99)], 12 g of alcohol [RR: 0.91, 95%CI = (0.88, 0.94)] and 1 cup of coffee [RR: 0.95, 95%CI = (0.83, 0.97)] intake and the risk of renal cell carcinoma. Conversely, each additional daily 100 g of red meat intake was positively associated with renal cell carcinoma [RR: 1.41, 95%CI = (1.03, 2.10)]. Inverse associations were observed between each additional daily 50 g of egg [RR: 0.73, 95%CI = (0.62, 0.87)] and each additional daily 1 cup of tea consumption and bladder cancer risk [RR: 0.97, 95%CI = (0.94, 0.99)]. There were no significant associations for nonlinear dose-response relationships between 12 food groups and urological cancers. Conclusion: Our meta-analysis strengthens the evidence that appropriate intake of specific food groups, such as fruits, vegetables, alcohol, tea, and coffee, is associated with the risk of renal cell carcinoma or bladder cancer. More studies are required to fill the knowledge gap on the links between various food groups and urologic cancers because the evidence was less credible in this meta-analysis. Systematic Review Registration: This study was registered on PROSPERO (CRD42022340336).

Low Zinc Alleviates the Progression of Thoracic Aortic Dissection by Inhibiting Inflammation.

Vascular inflammation triggers the development of thoracic aortic dissection (TAD). Zinc deficiency could dampen tissue inflammation. However, the role of zinc as a nutritional intervention in the progression of TAD remains elusive. In this study, we employed a classical ß-aminopropionitrile monofumarate (BAPN)-induced TAD model in mice treated with low zinc and observed that the TAD progression was greatly ameliorated under low zinc conditions. Our results showed that low zinc could significantly improve aortic dissection and rupture (BAPN + low zinc vs. BAPN, 36% vs. 100%) and reduce mortality (BAPN + low zinc vs. BAPN, 22% vs. 57%). Mechanically, low zinc attenuated the infiltration of macrophages and inhibited the expression of inflammatory cytokines, suppressed the phenotype switch of vascular smooth muscle cells from contractile to synthetic types, and eventually alleviated the development of TAD. In conclusion, this study suggested that low zinc may serve as a potential nutritional intervention approach for TAD prevention.

Low-dose ketamine inhibits neuronal apoptosis and neuroinflammation in PC12 cells via α7nAChR mediated TLR4/MAPK/NF-κB signaling pathway.

Ketamine is commonly used for sedation, analgesia and anesthetics. Much evidence has shown that it has an immune-regulatory effect. The cholinergic anti-inflammatory pathway mediated by α7nAChR is a prominent target of anti-inflammatory therapy. However, whether ketamine suppresses inflammatory levels in nerve cells by activating α7nAChR remains unknown. Lipopolysaccharide (LPS) was used to establish the neuroinflammation model in PC12 cells in vitro, and α7nAChR siRNA was transfected into PC12 cells 30 min before LPS to inhibit gene expression of α7nAChR. PC12 cells were stimulated with LPS for 24 h, and the indicators were detected at 2 h after GTS-21 and ketamine were added. The results showed that LPS increased the proportion of PC12 cells apoptosis, activated TLR4/MAPK/NF-κB signaling pathway, and increased the expression of interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Ketamine reduced the ratio of early apoptosis and late apoptosis of PC12, inhibited the entry of P65 into the nucleus, decreased the activation of TLR4/MAPK/NF-κB and improved neuroinflammation. However, the ameliorating effects of ketamine on neuronal apoptosis and neuroinflammation were inhibited in the α7nAChRi group. This indicated that α7nAChR played a key role in the anti-inflammatory process of ketamine. Low-dose ketamine inhibited TLR4/MAPK/NF-κB by activating the α7nAChR-mediated cholinergic anti-inflammatory pathway, thereby producing the protective effect on neuronal apoptosis and neuroinflammation.

FISHERMAN: A Serious Game for Executive Function Assessment of Older Adults.

Executive functions (EFs) are essential for daily living activities but decline with age. Convenient assessment and timely intervention have particular significance for older adults. However, the traditional laboratory tasks of EFs are typically monotonous and inconvenient. The current study aimed to develop an interesting and convenient supplementary tool to assess EFs for older adults. According to the theory of EFs, we developed a serious game, FISHERMAN, to assess EFs. The game includes three subgames, Cautious Fisherman, Agile Fisherman, and Wise Fisherman, targeting core components of inhibition, shifting, and working memory, respectively. The current study aims to verify the reliability and validity of the game. One hundred and eight healthy older adults participated in this study and were tested through the FISHERMAN game and a battery of cognitive tests. The results show that the FISHERMAN game has high internal consistency reliability and good construct validity as well as criterion-related validity, suggesting that the game design is valid and can be used in EFs assessment for older adults. Future studies are warranted to establish the norm of the FISHERMAN game in older adults and investigate whether the FISHERMAN game can be generalized to other populations.

The Role and Mechanism of Polysaccharides in Anti-Aging.

The elderly proportion of the population is gradually increasing, which poses a great burden to society, the economy, and the medical field. Aging is a physiological process involving multiple organs and numerous reactions, and therefore it is not easily explained or defined. At present, a growing number of studies are focused on the mechanisms of aging and potential strategies to delay aging. Some clinical drugs have been demonstrated to have anti-aging effects; however, many still have deficits with respect to safety and long-term use. Polysaccharides are natural and efficient biological macromolecules that act as antioxidants, anti-inflammatories, and immune regulators. Not surprisingly, these molecules have recently gained attention for their potential use in anti-aging therapies. In fact, multiple polysaccharides have been found to have excellent anti-aging effects in different animal models including Caenorhabditis elegans, Drosophila melanogaster, and mice. The anti-aging qualities of polysaccharides have been linked to several mechanisms, such as improved antioxidant capacity, regulation of age-related gene expression, and improved immune function. Here, we summarize the current findings from research related to anti-aging polysaccharides based on various models, with a focus on the main anti-aging mechanisms of oxidative damage, age-related genes and pathways, immune modulation, and telomere attrition. This review aims to provide a reference for further research on anti-aging polysaccharides.

Fucoidan Protects against Doxorubicin-Induced Cardiotoxicity by Reducing Oxidative Stress and Preventing Mitochondrial Function Injury.

Doxorubicin (DOXO) is a potent chemotherapeutic drug widely used to treat various cancers. However, its clinical application is limited due to serious adverse effects on dose-dependent cardiotoxicity. Although the underlying mechanism has not been fully clarified, DOXO-induced cardiotoxicity has been mainly attributed to the accumulation of reactive oxygen species (ROS) in cardiomyocytes. Fucoidan, as a kind of sulphated polysaccharide existing in numerous brown seaweed, has potent anti-oxidant, immune-regulatory, anti-tumor, anti-coagulate and anti-viral activities. Here, we explore the potential protective role and mechanism of fucoidan in DOXO-induced cardiotoxicity in mice. Our results show that oral fucoidan supplement exerts potent protective effects against DOXO-induced cardiotoxicity by reducing oxidative stress and preventing mitochondrial function injury. The improved effect of fucoidan on DOXO-induced cardiotoxicity was evaluated by echocardiography, cardiac myocytes size and cardiac fibrosis analysis, and the expression of genes related to cardiac dysfunction and remodeling. Fucoidan reduced the ROS content and the MDA levels but enhanced the activity of antioxidant enzymes GSH-PX and SOD in the mouse serum in a DOXO-induced cardiotoxicity model. In addition, fucoidan also increased the ATP production capacity and restored the levels of a mitochondrial respiratory chain complex in heart tissue. Collectively, this study highlights fucoidan as a potential polysaccharide for protecting against DOXO-induced cardiovascular diseases.

The Regulatory Roles of Mitochondrial Calcium and the Mitochondrial Calcium Uniporter in Tumor Cells.

Mitochondria, as the main site of cellular energy metabolism and the generation of oxygen free radicals, are the key switch for mitochondria-mediated endogenous apoptosis. Ca2+ is not only an important messenger for cell proliferation, but it is also an indispensable signal for cell death. Ca2+ participates in and plays a crucial role in the energy metabolism, physiology, and pathology of mitochondria. Mitochondria control the uptake and release of Ca2+ through channels/transporters, such as the mitochondrial calcium uniporter (MCU), and influence the concentration of Ca2+ in both mitochondria and cytoplasm, thereby regulating cellular Ca2+ homeostasis. Mitochondrial Ca2+ transport-related processes are involved in important biological processes of tumor cells including proliferation, metabolism, and apoptosis. In particular, MCU and its regulatory proteins represent a new era in the study of MCU-mediated mitochondrial Ca2+ homeostasis in tumors. Through an in-depth analysis of the close correlation between mitochondrial Ca2+ and energy metabolism, autophagy, and apoptosis of tumor cells, we can provide a valuable reference for further understanding of how mitochondrial Ca2+ regulation helps diagnosis and therapy.

Pathological effect of different avian infectious bronchitis virus strains on the bursa of Fabricius of chickens.

Infectious bronchitis is an acute and highly contagious disease caused by avian infectious bronchitis virus (IBV). As well as the typical clinical respiratory signs, such as dyspnoea and tracheal rales, QX genotype strains can also cause damage to the urinary system and reproductive system. Our previous studies found that chickens infected with QX-type IBV also displayed damage to the bursa of Fabricius. To investigate the effects of different genotypes of IBV on the bursa of Fabricius, we challenged one-week-old SPF chickens with Mass, QX and TW genotype IBV strains and compared the clinical signs, gross lesions, histopathological damage, viral loads, and expression levels of inflammatory cytokines (IL-6, IL-8, IL-1ß, IFN-α,ß, γ and TNF-α). The results showed that all three strains caused tissue damage, while significant temporal variations in the viral loads of the different infected groups were detected. IBV infection seriously interfered with the natural immune response mediated by inflammatory cytokines (IFN-α, IFN-ß, IL-6 and IFN-γ) in chickens. Our results suggested that IBV has potential immunological implications for chickens that may lead to poor production efficiency. RESEARCH HIGHLIGHTSAvian coronavirus IBV is an important pathogen of chickens.IBV has potential immunological implications in chickens.The bursal viral load of different IBV strains varies significantly.

Addressing the social barriers to green stormwater infrastructure in residential areas from a socio-ecological perspective.

Despite the well-recognized financial limitations, social aspects can also impact the adoption of green stormwater infrastructure (GSI) as it is ingrained in the socio-ecological system we live in. Thus, this work focuses on gaining an understanding of the public's perceptions of GSI by considering cognitive biases that hinder its adoption. This work is composed of two forms of human-subject studies, including an online-based survey and a series of semi-structured interviews. The survey (n = 510) was conducted to gauge public opinions toward GSI, whereas the interviews with representatives of major local regulatory agencies were to learn about the logistics for GSI implementation in Mecklenburg County, NC. The results were interpreted using the theory of planned behavior of rational actors. Statistical results showed a weak interpretation through this theory to explain the survey participants' intention to adopt GSI measures. This could suggest that the incorporation of irrationality, such as cognitive biases, could further enhance the predictability of the theory. At the same time, an inconsistency between the findings from the survey and the interviews was identified: most survey participants showed an overall uniform positive attitude, intention, and behavior regarding GSI practice adoption, whereas the interviewed experts all suggested a wide diversity on such terms. Suggestions were made based on the findings for better policy-making on public engagement for local regulatory agencies. This research aims to help local stormwater management authorities explore shortcomings in current stakeholder engagement plans to gain sustainable support for GSI implementation in urbanized areas.

Natural Polysaccharide ß-Glucan Protects against Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress.

Doxorubicin (DOXO) can be used to treat a variety of human tumors, but its clinical application is limited due to severe cardiotoxic side effect. Here, we explore the role of ß-glucan in DOXO-induced cardiotoxicity in mice and study its underlying mechanism. When co-administered with DOXO, ß-glucan was observed to prevent left ventricular dilation and fibrosis. In fact, DOXO reduces the activity of mitochondrial respiratory chain complex and enhances oxidative stress, which in turn impairs heart function. DOXO decreases the ATP production capacity of the heart and increases the ROS content, while ß-glucan can restore the heart capacity and reduce oxidative stress. ß-glucan also increases the activity of antioxidant enzymes GSH-PX and SOD, and reduces the level of MDA in the serum. In addition, the mRNAs of cardiac dysfunction marker genes ANP, BNP and Myh7 were significantly increased after DOXO induction, however, they did not increase when combined with ß-glucan administration. In conclusion, our results indicate that ß-glucan can improve the antioxidant capacity of the heart, thereby serving as a potential therapeutic strategy to prevent DOXO-induced cardiotoxicity.

Two newly isolated GVI lineage infectious bronchitis viruses in China show unique molecular and pathogenicity characteristics.

During 2016 to 2020, GVI-1 type infectious bronchitis virus (IBV) strains were sporadically reported across China, indicating a new epidemic trend of the virus. Here we investigated the molecular characteristics and pathogenicity of two newly isolated GVI-1 type IBV virus strains (CK/CH/TJ1904 and CK/CH/NP2011) from infected chicken farms in China. Genetic evolution analysis of the S1 gene showed the highest homology with the GVI-1 representative strain, TC07-2. Phylogenetic analysis and recombination analysis of the virus genomes indicated that newly isolated strains in China may be independently derived from recombination events that occurred between GI-19 and GI-22 strains and early GVI-1 viruses. Interestingly, unlike the deduced parental GI-19 or GI-22 strains, CK/CH/TJ1904 and CK/CH/NP2011 showed affinity for the trachea rather than the kidney and were less pathogenic. This difference may be because of recombination events that occurred during the long co-existence of the GVI-1 viruses with prevalent GI-19 and GI-22 strains. Considering the new trend, it is very important to permanently monitor circulating strains and to develop new vaccines to counteract emerging new-type IBVs.

miR319c acts as a positive regulator of tomato against Botrytis cinerea infection by targeting TCP29.

miR319 family is one of the oldest and most conservative miRNA families in plant and plays an important role in plant development and abiotic stress response. In our previous study, the abundance of sly-miR319c was increased in tomatoes infected by B. cinerea, but the roles and regulatory mechanisms of sly-miR319c in B. cinerea-infected tomato remain unclear. In this study, we confirmed that miR319c was increased in tomato with B. cinerea infection. In contrast, A TCP transcript factor, TCP29, targeted by sly-miR319c was decreased in B. cinerea-infected tomato. Therefore, transgenic Arabidopsis overexpressing sly-miR319c or its target were generated for understanding the biological roles and molecular mechanism of miR319c in B.cinerea-infected plants. Results showed that miR319c overexpression improved the resistance of transgenic plants to B. cinerea, whereas TCP29 overexpression increased the susceptibility of transgenic plant to B. cinerea. So far, TCP transcription factors have been reported mainly in developmental processes. Our data indicate that TCP29 act as a negative regulator to B.cinerea infection. In conclusion, our results indicate that sly-miR319c is a positive regulator of tomato resistance to B. cinerea infection by targeting TCP29.

Functional Components, Antioxidant Activity and Hypoglycemic Ability Following Simulated Gastro-Intestinal Digestion of Pigments from Walnut Brown Shell and Green Husk.

To assess the effects of digestion on the functional components of walnut pigment and their bioactivities, we developed an in vitro model simulating gastro-intestinal digestion. Results showed an increase in the contents of flavonoids and conjugated phenols (with retention rates higher than 100%) in husk pigment after digestion. The lowest of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging abilities was reached in the group with the minimum flavonoid content after digestion. Close correlation was observed between free phenol content and total reducing power, as the reducing power among different groups of husk pigment was in consistent with free phenols changes. The inhibitory effect of walnut pigment on α-amylase with/without digestion enzyme was similar. However, shell pigment showed improved inhibitory effect on α-glucosidase activity, with an increased inhibitory rate of 5.42%. In general, the antioxidant activity and hypoglycemic ability of walnut pigment were prone to chemical and enzymatic changes during simulated digestion, which were also related to the alteration of flavonoids and phenols.

A rapid UHPLC-MS/MS method for quantitation of phytoestrogens and the distribution of enterolactone in an Alabama estuary.

Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that can interfere with the endocrine systems of humans and wildlife. EDCs can pass through wastewater treatment systems, or run off from urban areas or agricultural operations, into natural water bodies, exposing resident and migratory organisms to complex EDC mixtures. Some phytoestrogenic polyphenolics (PEPP) are known or suspected EDCs; however, their contribution to total EDC burden in natural surface water systems is largely unknown. We describe a rapid, sensitive, and reproducible quantitative method for analysis of 15 PEPP in estuarine sediment and water, using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS). The method provides excellent peak resolution, peak separation, and rapid run times (method separation/total run time: 8/12.5 min). With two exceptions, spiking experiments demonstrated that the percent recoveries for target PEPP in sediment and water samples were within acceptable analytical validation limits. LOD and LOQ values ranged from 0.004 to 0.010 ng/injection and 0.013-0.032 ng/injection, respectively. The validated method was used for PEPP analysis of sediment and water samples collected from 11 locations within the Perdido Bay estuary in coastal Alabama. No PEPP above the LOD were detected in sediment samples. The mammalian-derived lignin enterolactone was observed at low concentrations in water throughout the estuary, and significantly, at elevated concentrations at two locations associated with small-scale septic systems (3.66 ±â€¯0.27 ng L-1 and 4.01 ±â€¯0.33 ng L-1) and a large wastewater treatment system (4.56 ±â€¯0.24 ng L-1 and 5.69 ±â€¯0.43 ng L-1).

A rapid UHPLC-MS/MS method for simultaneous quantitation of 23 perfluoroalkyl substances (PFAS) in estuarine water.

Per- and polyfluoroalkyl substances (PFAS) represent a large group of synthetic organic compounds which, as a result of their unique chemical properties, render them extremely recalcitrant to environmental degradation. Research concerning the environmental, ecological, and human health effects of PFAS has focused on long aliphatic chain (> C7) compounds having no ether bonds. For new, less studied, or previously unknown PFAS (≤ C7 with ether bonds), there is little to no information about their environmental behavior, transport, fate, exposure, and toxicological effects. LC-MS/MS has proven effective for detection and quantitation of some PFAS, however, straightforward analytical methods for simultaneous trace quantitation of broad mixtures of PFAS in varied complex environmental media, available to a wide range of researchers and also suitable for routine monitoring, remain critical needs. Here we describe a simple, rapid, sensitive, and reproducible quantitative analytical method for trace analysis and monitoring of 23 PFAS in estuarine water, using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS). The developed MRM method allows simultaneous trace quantitation of a broad mixture of PFAS, including 13 perfluoroalkyl carboxylic acids, 8 perfluoroalkyl sulfonates, and 2 short-chain perfluoroethers. The method provides better peak resolution and peak separation, and shorter run times (method separation/total run time: 6/8 min) compared to those of existing analytical methods. Percent recoveries for the validated method ranged from 78.54 to 112.61. LOD and LOQ values ranged from 0.48 to 1.68 pg/injection and 1.71 to 5.40 pg/injection, respectively. The validated method was used for quantitative PFAS analysis of estuarine water samples collected from 16 locations within the Perdido Bay estuary in coastal Alabama.