Rational Design of NIR-II G-Quadruplex Fluorescent Probes for Accurate In Vivo Tumor Metastasis Imaging.

Accurate in vivo imaging of G-quadruplexes (G4) is critical for understanding the emergence and progression of G4-associated diseases like cancer. However, existing in vivo G4 fluorescent probes primarily operate within the near-infrared region (NIR-I), which limits their application accuracy due to the short emission wavelength. The transition to second near-infrared (NIR-II) fluorescent imaging has been of significant interest, as it offers reduced autofluorescence and deeper tissue penetration, thereby facilitating more accurate in vivo imaging. Nonetheless, the advancement of NIR-II G4 probes has been impeded by the absence of effective probe design strategies. Herein, through a "step-by-step" rational design approach, we have successfully developed NIRG-2, the first small-molecule fluorescent probe with NIR-II emission tailored for in vivo G4 detection. Molecular docking calculations reveal that NIRG-2 forms stable hydrogen bonds and strong π-π interactions with G4 structures, which effectively inhibit twisted intramolecular charge transfer (TICT) and, thereby, selectively illuminate G4 structures. Due to its NIR-II emission (940 nm), large Stokes shift (90 nm), and high selectivity, NIRG-2 offers up to 47-fold fluorescence enhancement and a tissue imaging depth of 5 mm for in vivo G4 detection, significantly outperforming existing G4 probes. Utilizing NIRG-2, we have, for the first time, achieved high-contrast visualization of tumor metastasis through lymph nodes and precise tumor resection. Furthermore, NIRG-2 proves to be highly effective and reliable in evaluating surgical and drug treatment efficacy in cancer lymphatic metastasis models. We are optimistic that this study not only provides a crucial molecular tool for an in-depth understanding of G4-related diseases in vivo but also marks a promising strategy for the development of clinical NIR-II G4-activated probes.

Correction: Mechanisms of the ethanol extract of Gelidium amansii for slow aging in high-fat male Drosophila by metabolomic analysis.

Correction for 'Mechanisms of the ethanol extract of Gelidium amansii for slow aging in high-fat male Drosophila by metabolomic analysis' by Yushi Chen et al., Food Funct., 2022, 13, 10110-10120, https://doi.org/10.1039/D2FO02116A.

Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS: Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS: The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.

Worldwide productivity and research trend of publications concerning SIAD: a bibliometric study.

Background: Syndrome of inappropriate antidiuretic(SIAD) occurs secondary to various diseases, which is characterised by hypotonic hyponatremia and impaired urinary diluting capacity. Research on SIAD in both domestic and international contexts has a long history. This study objectively and comprehensively analyses the research trends, hotspots and development of SIAD research of the past 20 years using the method of bibliometric analysis. Methods: The 2003-2022 data in the Web of Science Core Collection database were searched. The Bibliometrix software package, VOSviewer and CiteSpace were used to mine, extract and visualise the retrieved literature, and the generated maps were used in analysing the main topics and trends in the field of SIAD research. Results: A total of 1215 articles published in 623 journals were included in the analysis, with a total of 18,886 citations. Results showed that the research output on SIAD has continuously increased in the past 20 years, and the United States had the highest number of publications and citations. Keywords with the highest burst strength in recent years were the most mentioned keywords, in addition to the search terms 'hyponatremia', 'covid-19', and 'mortality'. Thus, the relationship among SIAD, covid-19 and mortality may become research frontiers and trends. Fifteen milestone articles were identified through co-citation analysis, which mainly focused on the pathophysiology and treatment of SIAD. Conclusion: Based on bibliometric analysis and knowledge mapping, this study summarises development trends in the field of SIAD research, providing references for current and future research into SIAD.

Guanine nucleotide exchange factor RABGEF1 facilitates TNF-induced necroptosis by targeting cIAP1.

Necroptosis is a form of regulated cell death that depends on the receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL). The molecular mechanisms underlying distinct instances of necroptosis have only recently begun to emerge. In the present study, we characterized RABGEF1 as a positive regulator of RIPK1/RIPK3 activation in vitro. Based on the overexpression and knockdown experiments, we determined that RABGEF1 accelerated the phosphorylation of RIPK1 and promoted necrosome formation in L929 cells. The pro-necrotic effect of RABGEF1 is associated with its E3 ubiquitin ligase activity and guanine nucleotide exchange factor (GEF) activity. We further confirmed that RABGEF1 interacts with cIAP1 protein by inhibiting its function and plays a regulatory role in necroptosis, which can be abolished by treatment with the antagonist Smac mimetic (SM)-164. In conclusion, our study highlights a potential and novel role of RABGEF1 in promoting TNF-induced cell necrosis.

Anti-necroptosis and anti-ferroptosis compounds from the Deep-Sea-Derived fungus Aspergillus sp. MCCC 3A00392.

Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.

Saracatinib inhibits necroptosis and ameliorates psoriatic inflammation by targeting MLKL.

Necroptosis is a kind of programmed cell death that causes the release of damage-associated molecular patterns and inflammatory disease including skin inflammation. Activation of receptor-interacting serine/threonine kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) is the hallmark of tumour necrosis factor α (TNF)-induced necroptosis. Here, we screened a small-molecule compound library and found that saracatinib inhibited TNF-induced necroptosis. By targeting MLKL, Saracatinib interfered with the phosphorylation, translocation, and oligomerization of MLKL induced by TNF. Consistently, mutation of the saracatinib-binding site of MLKL reduced the inhibitory effect of saracatinib on TNF-induced necroptosis. In an imiquimod (IMQ)-induced psoriasis mouse model, saracatinib effectively blocked MLKL phosphorylation and inflammatory responses in vivo. Taken together, these findings indicate that saracatinib inhibits necroptosis by targeting MLKL, providing a potential therapeutic approach for skin inflammation-related diseases such as psoriasis.

The contribution of a novel PHEX gene mutation to X-linked hypophosphatemic rickets: a case report and an analysis of the gene mutation dosage effect in a rat model.

A Chinese family was identified to have two patients with rickets, an adult female and a male child (proband), both exhibiting signs related to X-linked hypophosphatemic rickets (XLH). Gene sequencing analysis revealed a deletion of adenine at position 1985 (c.1985delA) in the PHEX-encoding gene. To investigate the relationship between this mutation and the pathogenicity of XLH, as well as analyze the effects of different dosages of PHEX gene mutations on clinical phenotypes, we developed a rat model carrying the PHEX deletion mutation. The CRISPR/Cas9 gene editing technology was employed to construct the rat model with the PHEX gene mutation (c.1985delA). Through reproductive procedures, five genotypes of rats were obtained: female wild type (X/X), female heterozygous (-/X), female homozygous wild type (-/-), male wild type (X/Y), and male hemizygous (-/Y). The rats with different genotypes underwent analysis of growth, serum biochemical parameters, and bone microstructure. The results demonstrated the successful generation of a stable rat model inheriting the PHEX gene mutation. Compared to the wild-type rats, the mutant rats displayed delayed growth, shorter femurs, and significantly reduced bone mass. Among the female rats, the homozygous individuals exhibited the smallest body size, decreased bone mass, shortest femur length, and severe deformities. Moreover, the mutant rats showed significantly lower blood phosphorus concentration, elevated levels of FGF23 and alkaline phosphatase, and increased expression of phosphorus regulators. In conclusion, the XLH rat model with the PHEX gene mutation dosage demonstrated its impact on growth and development, serum biochemical parameters, and femoral morphology.

Neoadjuvant chemotherapy for breast cancer: an evaluation of its efficacy and research progress.

Neoadjuvant chemotherapy (NAC) for breast cancer is widely used in the clinical setting to improve the chance of surgery, breast conservation and quality of life for patients with advanced breast cancer. A more accurate efficacy evaluation system is important for the decision of surgery timing and chemotherapy regimen implementation. However, current methods, encompassing imaging techniques such as ultrasound and MRI, along with non-imaging approaches like pathological evaluations, often fall short in accurately depicting the therapeutic effects of NAC. Imaging techniques are subjective and only reflect macroscopic morphological changes, while pathological evaluation is the gold standard for efficacy assessment but has the disadvantage of delayed results. In an effort to identify assessment methods that align more closely with real-world clinical demands, this paper provides an in-depth exploration of the principles and clinical applications of various assessment approaches in the neoadjuvant chemotherapy process.

Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis.

Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases.

Correlation of Nonalcoholic Fatty Liver Disease with Dietary Folate and Serum Folate in U.S. Adults: Cross-Sectional Analyses from National Health and Nutrition Examination Survey 2009-2018.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a global health problem, and dietary intervention is still considered one of the primary interventions. This study aimed to examine cross-sectional associations between dietary and serum levels of folate and NAFLD. Methods: We conducted a study of 7543 adults who participated in the National Health and Nutrition Examination Survey, 2009-2018. NAFLD status was determined by a fatty liver index (FLI) value ≥60. Multivariable logistic regression models were used to estimate associations between folate and NAFLD. Results: Almost half (45%) of the patients were classified as having NAFLD based on the FLI. In the fully adjusted model, participants in the highest quartile of dietary total folate and food folate were found to have a lower prevalence of NAFLD than those in the lowest quartile [odds ratio (OR)quartile 4 versus 1 = 0.582; 95% confidence interval (CI) = 0.350-0.968; and ORquartile 4 versus 1 = 0.737; 95% CI = 0.611-0.888, respectively], and the fourth quartile values of serum total folate and 5-methyl-tetrahydrofolate were significantly negatively associated with NAFLD prevalence (ORquartile 4 versus 1 = 0.664; 95% CI = 0.495-0.891; and ORquartile 4 versus 1 = 0.712; 95% CI = 0.532-0.954, respectively). Subgroup analyses revealed that this beneficial association was more significant in women (ORquartile 4 versus 1 = 0.526; 95% CI = 0.329-0.843; pinteraction < 0.001) than in men (ORquartile 4 versus 1 = 0.805; 95% CI = 0.546-1.186). Conclusions: Higher dietary folate intake and serum folate levels are associated with a lower NAFLD prevalence among U.S. adults and the trend is more pronounced among women, indicating opportunities for dietary NAFLD interventions.

Branched-chain amino acids prevent obesity by inhibiting the cell cycle in an NADPH-FTO-m6A coordinated manner.

Obesity has become a major health crisis in the past decades. Branched-chain amino acids (BCAA), a class of essential amino acids, exerted beneficial health effects with regard to obesity and its related metabolic dysfunction, although the underlying reason is unknown. Here, we show that BCAA supplementation alleviates high-fat diet (HFD)-induced obesity and insulin resistance in mice and inhibits adipogenesis in 3T3-L1 cells. Further, we find that BCAA prevent the mitotic clonal expansion (MCE) of preadipocytes by reducing cyclin A2 (CCNA2) and cyclin-dependent kinase 2 (CDK2) expression. Mechanistically, BCAA decrease the concentration of nicotinamide adenine dinucleotide phosphate (NADPH) in adipose tissue and 3T3-L1 cells by reducing glucose-6-phosphate dehydrogenase (G6PD) expression. The reduced NADPH attenuates the expression of fat mass and obesity-associated (FTO) protein, a well-known m6A demethylase, to increase the N6-methyladenosine (m6A) levels of Ccna2 and Cdk2 mRNA. Meanwhile, the high m6A levels of Ccna2 and Cdk2 mRNA are recognized by YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), which results in mRNA decay and reduction of their protein expressions. Overall, our data demonstrate that BCAA inhibit obesity and adipogenesis by reducing CDK2 and CCNA2 expression via an NADPH-FTO-m6A coordinated manner in vivo and in vitro, which raises a new perspective on the role of m6A in the BCAA regulation of obesity and adipogenesis.

Patient-reported outcomes of neurologic and neuropsychiatric symptoms in mild COVID-19: a prospective cohort study.

BACKGROUND: Various neurologic manifestations have been reported in patients with COVID-19, mostly in retrospective studies of patients admitted to hospital, but there are few data on patients with mild COVID-19. We examined the frequency and persistence of neurologic/neuropsychiatric symptoms in patients with mild COVID-19 in a 1-year prospective cohort study, as well as assessment of use of health care services and patient-reported outcomes. METHODS: Participants in the Alberta HOPE COVID-19 trial (hydroxychloroquine v. placebo for 5 d), managed as outpatients, were prospectively assessed 3 months and 1 year after their positive test result. They completed detailed neurologic/neuropsychiatric symptom questionnaires, the telephone version of the Montreal Cognitive Assessment (T-MoCA), the Kessler Psychological Distress Scale (K10) and the EuroQol EQ-5D-3L (measure of quality of life). Close informants completed the Mild Behavioural Impairment Checklist (MBI-C) and the Informant Questionnaire on Cognitive Decline in the Elderly. We also tracked use of health care services and neurologic investigations. RESULTS: The cohort consisted of 198 participants (87 female [43.9%] median age 45 yr, interquartile range 37-54 yr). Of the 179 participants with symptom assessments, 139 (77.6%) reported at least 1 neurologic symptom, the most common being anosmia/dysgeusia (99 [55.3%]), myalgia (76 [42.5%]) and headache (75 [41.9%]). Forty patients (22.3%) reported persistent symptoms at 1 year, including confusion (20 [50.0%]), headache (21 [52.5%]), insomnia (16 [40.0%]) and depression (14 [35.0%]); 27/179 (15.1%) reported no improvement. Body mass index (BMI), a history of asthma and lack of full-time employment were associated with the presence and persistence of neurologic/neuropsychiatric symptoms; female sex was independently associated with both (presence: odds ratio [OR] adjusted for age, race, BMI, history of asthma and neuropsychiatric history 5.04, 95% confidence interval [CI] 1.58 to 16.10). Compared to participants without persistent symptoms, those with persistent symptoms had more hospital admissions and family physician visits, and worse MBI-C scores and less frequent independence for instrumental activities at 1 year (83.8% v. 97.8%, p = 0.005). Patients with any or persistent neurologic symptoms had worse psychologic distress (K10 score ≥ 20: adjusted OR 12.1, 95% CI 1.4 to 97.2) and quality of life (median EQ-5D-3L visual analogue scale rating 75 v. 90, p < 0.001); 42/84 (50.0%) had a T-MoCA score less than 18 at 3 months, as did 36 (42.9%) at 1 year. Participants who reported memory loss were more likely than those who did not report such symptoms to have informant-reported cognitive-behavioural decline (1-yr MBI-C score ≥ 6.5: adjusted OR 15.0, 95% CI 2.42 to 92.60). INTERPRETATION: Neurologic/neuropsychiatric symptoms were commonly reported in survivors of mild COVID-19, and they persisted in 1 in 5 patients 1 year later. Symptoms were associated with worse participant- and informant-reported outcomes. Trial registration: ClinicalTrials.gov, no. NCT04329611.

Automatic Classification of Histopathology Images across Multiple Cancers Based on Heterogeneous Transfer Learning.

BACKGROUND: Current artificial intelligence (AI) in histopathology typically specializes on a single task, resulting in a heavy workload of collecting and labeling a sufficient number of images for each type of cancer. Heterogeneous transfer learning (HTL) is expected to alleviate the data bottlenecks and establish models with performance comparable to supervised learning (SL). METHODS: An accurate source domain model was trained using 28,634 colorectal patches. Additionally, 1000 sentinel lymph node patches and 1008 breast patches were used to train two target domain models. The feature distribution difference between sentinel lymph node metastasis or breast cancer and CRC was reduced by heterogeneous domain adaptation, and the maximum mean difference between subdomains was used for knowledge transfer to achieve accurate classification across multiple cancers. RESULT: HTL on 1000 sentinel lymph node patches (L-HTL-1000) outperforms SL on 1000 sentinel lymph node patches (L-SL-1-1000) (average area under the curve (AUC) and standard deviation of L-HTL-1000 vs. L-SL-1-1000: 0.949 ± 0.004 vs. 0.931 ± 0.008, p value = 0.008). There is no significant difference between L-HTL-1000 and SL on 7104 patches (L-SL-2-7104) (0.949 ± 0.004 vs. 0.948 ± 0.008, p value = 0.742). Similar results are observed for breast cancer. B-HTL-1008 vs. B-SL-1-1008: 0.962 ± 0.017 vs. 0.943 ± 0.018, p value = 0.008; B-HTL-1008 vs. B-SL-2-5232: 0.962 ± 0.017 vs. 0.951 ± 0.023, p value = 0.148. CONCLUSIONS: HTL is capable of building accurate AI models for similar cancers using a small amount of data based on a large dataset for a certain type of cancer. HTL holds great promise for accelerating the development of AI in histopathology.

Industrial Regenerator Model for SMTO Technology.

In order to alleviate the current domestic oil shortage, China has studied the technology of using coal as the source to produce low carbon olefins, among which methanol to olefin (MTO) is an important process. Since the coke deposition of MTO catalyst is inevitable, the deactivated MTO catalysts need to be regenerated by continuous coke combustion to recover the activity. This paper used the actual industrial data to study the gas-solid two-phase fluidized bed of a SMTO regenerator and the coke combustion kinetics of the deactivated SAPO-34 catalyst, and established the mathematical model of the SMTO industrial regenerator. The kinetic parameters in the model were obtained and validated with different data, which showed that the model is reliable and can accurately predict the industrial reaction results and provide guidance for the SMTO production operation.

Mathematical Model for the Industrial SMTO Reactor with a SAPO-34 Catalyst.

The methanol-to-olefins (MTO) technology creates a new non-oil route to produce light olefins. This paper reports a 14-lump MTO kinetic model for SAPO-34 catalyst, combined with the hydrodynamic model for the fast fluidized bed reactor of the industrial SMTO process. Selective deactivation is considered to quantify the product selectivity and abrupt catalytic activity change. Moreover, referring to the parallel compartment (PC) model, the activity difference between the circulating spent catalyst and the regenerated catalyst is considered. The validation results with the optimized kinetic parameters showed good agreement between the calculated value and the actual value. Sensitivity analysis of the industrial SMTO process was performed. According to the results, the established mathematical model can provide guidance for industrial production operations.

miR-197-3p Promotes Osteosarcoma Stemness and Chemoresistance by Inhibiting SPOPL.

First-line treatment for osteosarcoma includes chemotherapy and surgery. However, the five-year survival rate of refractory osteosarcoma remains unsatisfactory. Osteosarcoma cancer stem cells, possessing stemness and chemoresistance, are one of the critical causes of poor response to chemotherapy. Elucidating regulatory signaling pathways of osteosarcoma cancer stem cells may provide a rationale for improving regimens against chemoresistant osteosarcoma. Methotrexate (MTX)-resistant osteosarcoma cells were established. microRNA expression profiles were used for detecting differentially expressed microRNA in resistant clones and the parental cells. microRNA target databases were employed to predict potential microRNA and mRNA interactions. Flow cytometry was performed to measure stem cell marker Prominin-1 (CD133)-positive cells. Immunofluorescence staining was applied to detect CD133 expression. miR-197-3p mimic or anti-miR-197-3p stably transfected cells were used to generate xenograft models. In the study, we found that miR-197-3p was increased in MTX-resistant cell lines. Overexpression of miR-197-3p enhanced the expression of cancer stem cell markers CD133, Octamer-binding protein 4 (OCT4), Transcription factor SOX-2 (SOX2), and Homeobox protein NANOG (NANOG), as well as chemoresistance-associated genes ATP-dependent translocase ABCB1 (ABCB1) and Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2), whereas miR-197-3p knockdown inhibited stemness and recovered sensitivity to MTX. We also classified the tumor suppressor Speckle-type POZ protein-like (SPOPL) as a target of miR-197-3p. The miR-197-3p mutation that could not combine SPOPL promoter regions was unable to sustain stemness or chemoresistance. Collectively, we discovered miR-197-3p conferred osteosarcoma stemness and chemotherapy resistance by targeting SPOPL, prompting promising therapeutic candidates for refractory osteosarcoma treatment.

The incidence, risk factors, characteristics, and prognosis of recurrent deep venous thrombosis in the contralateral lower extremity.

BACKGROUND: Recurrent events after a first symptomatic deep venous thrombosis (DVT) are relatively frequent, but little is known about contralateral recurrent DVT (RDVT). METHODS: We retrospectively reviewed the medical records of patients with a first symptomatic lower extremity DVT between January 2017 and April 2021. The incidence, demographics, risk factors, and prognosis of RDVT were analyzed, with differences compared between patients with contralateral RDVT and those with ipsilateral RDVT. RESULTS: In 570 consecutive patients with DVT, 28 patients (4.91%) developed contralateral RDVT, and 49 patients (8.60%) developed ipsilateral RDVT during a mean follow-up of 27.62 ± 14.84 months. Contralateral RDVT was more frequently found in the right lower extremity, whereas ipsilateral RDVT had more left lower extremity involvement. The median follow-up was 12 months until ipsilateral RDVT and 26.5 months until contralateral RDVT. In multivariate Cox analysis, inherited thrombophilia, stent extension with 50% to 100% coverage, autoimmune disease and anticoagulation noncompliance were identified as risk factors for contralateral RDVT. During follow-up, 5 patients (17.86%) with contralateral RDVT and 10 patients (20.41%) with ipsilateral RDVT died (P > .05), with 12 of 15 dying of an underlying malignancy. CONCLUSIONS: The incidence of contralateral RDVT after a first symptomatic DVT is relatively low, and contralateral DVT is strongly associated with stent extension with 50% to 100% coverage, autoimmune disease, anticoagulation noncompliance, and inherited thrombophilia. Compared with ipsilateral RDVT, contralateral RDVT occurs later and is more often in the right lower extremity. Survival following contralateral RDVT is similar to survival following ipsilateral RDVT, with underlying malignancy being the leading cause of death.

Mechanisms of the ethanol extract of Gelidium amansii for slow aging in high-fat male Drosophila by metabolomic analysis.

Gelidium amansii (GA) is a kind of red alga homologous to medicine and food and is distributed all over the world. Studies on GA are mainly focused on its polysaccharides, with little research on the ethanol extract. The ethanol extract of Gelidium amansii (GAE) was subjected to a reverse-phase column to obtain 7 components. Among them, 100% methanol solution (GAM), enriched with phytene-1,2-diol, exhibited the strongest DPPH free radical scavenging activity (IC50 = 0.17 mg mL-1). Subsequently, high-fat male flies (HMFs) were used as a model to explore the antioxidant and anti-aging effects of GAM in vivo. Studies showed that GAM can effectively prolong the lifespan of HMFs. When GAM concentrations were 0.2 and 1.0 mg mL-1, the average lifespan of HMFs was increased by 28.7 and 40.7%, respectively, while the longest lifespan of HMFs was increased by 20.55% and 32.88%, respectively. Further research revealed that GAM can significantly downregulate the levels of malondialdehyde (MDA) and protein carbonyl (PCO), and can significantly upregulate the levels of catalase (CAT) and total superoxide dismutase (T-SOD). In addition, by analyzing differential metabolites, we found that GAM relieves aging caused by oxidative stress by regulating amino acid, lipid, sugar, and energy metabolism. The GAM group significantly regulated the levels of adenine, cholic acid, glutamate, L-proline, niacin, and stachyose which tend to recover to the levels of the normal diet male fly (NMF) group. In general, our research provides ideas for the high-value utilization of GA and provides a lead compound for the research and development of anti-aging food or medicine.

mRNA m5C inhibits adipogenesis and promotes myogenesis by respectively facilitating YBX2 and SMO mRNA export in ALYREF-m5C manner.

Although 5-methylcytosine (m5C) has been identified as a novel and abundant mRNA modification and associated with energy metabolism, its regulation function in adipose tissue and skeletal muscle is still limited. This study aimed at investigating the effect of mRNA m5C on adipogenesis and myogenesis using Jinhua pigs (J), Yorkshire pigs (Y) and their hybrids Yorkshire-Jinhua pigs (YJ). We found that Y grow faster than J and YJ, while fatness-related characteristics observed in Y were lower than those of J and YJ. Besides, total mRNA m5C levels and expression rates of NSUN2 were higher both in backfat layer (BL) and longissimus dorsi muscle (LDM) of Y compared to J and YJ, suggesting that higher mRNA m5C levels positively correlate with lower fat and higher muscle mass. RNA bisulfite sequencing profiling of m5C revealed tissue-specific and dynamic features in pigs. Functionally, hyper-methylated m5C-containing genes were enriched in pathways linked to impaired adipogenesis and enhanced myogenesis. In in vitro, m5C inhibited lipid accumulation and promoted myogenic differentiation. Furthermore, YBX2 and SMO were identified as m5C targets. Mechanistically, YBX2 and SMO mRNAs with m5C modification were recognized and exported into the cytoplasm from the nucleus by ALYREF, thus leading to increased YBX2 and SMO protein expression and thereby inhibiting adipogenesis and promoting myogenesis, respectively. Our work uncovered the critical role of mRNA m5C in regulating adipogenesis and myogenesis via ALYREF-m5C-YBX2 and ALYREF-m5C-SMO manners, providing a potential therapeutic target in the prevention and treatment of obesity, skeletal muscle dysfunction and metabolic disorder diseases.