Preparation and Properties of Multi-Responsive Liquid Crystalline Poly(urethane-acrylate)s and Its Composite Membranes.

In this work, a kind of side chain liquid crystalline poly(urethane-acrylate)s was synthesized by free polymerization based on self-made liquid crystalline monomers, and a series of liquid crystalline polyurethane/shape memory polyurethane composite membranes were prepared by electrospinning. The synthesized liquid crystalline poly(urethane-acrylate)s have excellent thermal stability. Due to the regular arrangement of azobenzene on the side chains, polymers can rapidly undergo a photoinduced transition from trans-isomerism to cis-isomerism in THF solution and restore reversible configurational changes under visible light. The composite membranes prepared by electrospinning can also undergo photoinduced deformation within 6 s, and the deformation slowly returns under visible light. Meanwhile, the composites have shape memory, and after deformation caused by stretching, the membranes can quickly recover their original shape under thermal stimulation. These results indicate that the composites have triple response performances of photoinduced deformation, photo-, and thermal recovery.

Construction of an interface interaction in a g-C3N4/CdS/NiS for photoreforming of plastic and clean hydrogen regeneration.

Converting plastics into organic matter by photoreforming is an emerging way to deal with plastic pollution and produce valuable organic matter. Water shortage can be alleviated by using seawater resources. To solve these problems, we synthesize a ternary heterostructure composite g-C3N4/CdS/NiS. Heterojunctions are formed between graphitized carbon nitride (g-C3N4), cadmium sulfide (CdS) and nickel sulfide (NiS), which effectively improve the problem of fast charge recombination of pure g-C3N4 and CdS. The results of the g-C3N4/CdS/NiS photocatalytic tests show that the hydrogen production rates in seawater and pure water for 5 h are 30.44 and 25.79 mmol/g/h, respectively. In stability test, the hydrogen production rate of the g-C3N4/CdS/NiS in seawater and pure water is similar. This suggests that seawater can replace pure water as a source of hydrogen. While H2 is generated, the lactate obtained by polylactic acid (PLA) hydrolysis is oxidized to form small organic compounds such as formate, acetate and pyruvate. Our study shows that g-C3N4/CdS/NiS can not only use seawater as a hydrogen source to produce H2, but also photoreformate plastics dissolved in seawater into valuable small organic molecules. This has a positive impact on the production and use of clean energy, as well as on plastic pollution and water scarcity.

Nanofiber-Reinforced MXene/rGO Composite Aerogel for a High-Performance Piezoresistive Sensor and an All-Solid-State Supercapacitor Electrode Material.

The assembly of two-dimensional (2D) nanomaterials into a three-dimensional (3D) aerogel can effectively prevent the problem of restacking. Here, nanofiber-reinforced MXene/reduced graphene oxide (rGO) conductive aerogel is prepared via the hydrothermal reduction of GO using pyrrole and in situ composite with MXene. Combined with low-content 2D conductive nanosheets (MXene and rGO) as "brick", conductive polypyrrole as "mortar", and one-dimensional (1D) nanofiber as "rebar", a strong interfacial cross-linking of MXene and rGO nanosheets is realized through covalent and noncovalent bonds to synergistically improve its mechanical performance. Based on the prepared MXene/rGO aerogel, a high-performance piezoresistive sensor with a sensitivity of up to 20.80 kPa-1 in a wide pressure range of 15.6 kPa is obtained, and it can withstand more than 5000 cyclic compressions. Besides, the sensor shows a stable output and can be applied to monitor various human motion signals. In addition, an all-solid-state supercapacitor electrode is also fabricated, which shows a high area-specific capacitance of up to 274 mF/cm2 at a current density of 1 mA/cm2.

Discovery and engineering of ChCas12b for precise genome editing.

Many clustered regularly interspaced short palindromic repeat and CRISPR-associated protein 12b (CRISPR-Cas12b) nucleases have been computationally identified, yet their potential for genome editing remains largely unexplored. In this study, we conducted a GFP-activation assay screening 13 Cas12b nucleases for mammalian genome editing, identifying five active candidates. Candidatus hydrogenedentes Cas12b (ChCas12b) was found to recognize a straightforward WTN (W = T or A) proto-spacer adjacent motif (PAM), thereby dramatically expanding the targeting scope. Upon optimization of the single guide RNA (sgRNA) scaffold, ChCas12b exhibited activity comparable to SpCas9 across a panel of nine endogenous loci. Additionally, we identified nine mutations enhancing ChCas12b specificity. More importantly, we demonstrated that both ChCas12b and its high-fidelity variant, ChCas12b-D496A, enabled allele-specific disruption of genes harboring single nucleotide polymorphisms (SNPs). These data position ChCas12b and its high-fidelity counterparts as promising tools for both fundamental research and therapeutic applications.

Causal association of sarcopenia with hepatocellular carcinoma risk in European population: a Mendelian randomization study.

Background: The causal association of sarcopenia with the incidence risk of hepatocellular carcinoma (HCC) in the European population, and the potential mediating role of C-reactive protein (CRP), remains unclear. This study employed a bidirectional two-sample, two-step Mendelian randomization (MR) analysis to investigate the causality and identify the mediator. Methods: Summary statistics for HCC, CRP, and sarcopenia-related traits, including appendicular lean mass (ALM), hand grip strength (HGS), and walking pace (WP), were acquired from publicly available databases. We conducted bidirectional MR and Steiger tests of directionality to check the presence of reverse causality. Additionally, a two-step MR analysis was used to assess the mediating effect of CRP in the causality between sarcopenia and HCC. Tests for heterogeneity and horizontal pleiotropy were performed. Results: As ALM increases, the risk of HCC occurrence decreases [odds ratio (OR), 95% confidence interval (CI): 0.703, 0.524-0.943; P = 0.019]. And, genetically predicted low-HGS (OR, 95%CI: 2.287, 1.013-5.164; P = 0.047) was associated with an increased incidence risk of HCC, with no reverse causality. However, we found no evidence supporting a causality between WP and HCC. CRP was identified as the mediator of the causal effect of ALM and low-HGS on HCC, with corresponding mediating effects of 9.1% and 7.4%. Conclusions: This MR study effectively demonstrates that lower ALM and low-HGS are linked to an elevated risk of HCC within the European population, and the causality was not bidirectional. Furthermore, CRP serves as a mediator in the associations. These findings may help mitigate HCC risk among individuals with sarcopenia.

Nontoxigenic Bacteroides fragilis: A double-edged sword.

The contribution of commensal microbes to human health and disease is unknown. Bacteroides fragilis (B. fragilis) is an opportunistic pathogen and a common colonizer of the human gut. Nontoxigenic B. fragilis (NTBF) and enterotoxigenic B. fragilis (ETBF) are two kinds of B. fragilis. NTBF has been shown to affect the host immune system and interact with gut microbes and pathogenic microbes. Previous studies indicated that certain strains of B. fragilis have the potential to serve as probiotics, based on their observed relationship with the immune system. However, several recent studies have shown detrimental effects on the host when beneficial gut bacteria are found in the digestive system or elsewhere. In some pathological conditions, NTBF may have adverse reactions. This paper presents a comprehensive analysis of NTBF ecology from the host-microbe perspective, encompassing molecular disease mechanisms analysis, bacteria-bacteria interaction, bacteria-host interaction, and the intricate ecological context of the gut. Our review provides much-needed insights into the precise application of NTBF.

Anterior segment optical coherence tomography for superficial keratectomy.

PURPOSE: To report the use of anterior segment optical coherence tomography (AS-OCT) for superficial keratectomy (SK) in anterior corneal opacity. METHODS: The characteristics of 43 eyes (39 patients) with various lesions responsible for anterior corneal opacity were included in this retrospective non-comparative study. AS-OCT was performed on all eyes before surgery. The thickness of corneal opacity and the underlying healthy stroma were measured. SK was performed on each individual. RESULTS: Four types of anterior corneal opacity were evaluated, including corneal degeneration (26/43), Reis-Bücklers corneal dystrophy (8/43), alkali burn (1/43) and corneal tumors (8/43). Based on AS-OCT images, all eyes showed abnormal hyper-reflective signals in the superficial cornea to less than one-third of the normal corneal thickness in the deepest corneal opacity. All 43 eyes underwent an SK procedure. In addition, 1 eye with alkali burns and 7 eyes with corneal tumors were combined with amniotic membrane transplantation. All eyes restored transparency without significant complications. CONCLUSION: AS-OCT is a valuable method for objective preoperative and noninvasive assessments of anterior corneal opacities and is useful for guiding SK.

Engineering of a high-fidelity Cas12a nuclease variant capable of allele-specific editing.

CRISPR-Cas12a, often regarded as a precise genome editor, still requires improvements in specificity. In this study, we used a GFP-activation assay to screen 14 new Cas12a nucleases for mammalian genome editing, successfully identifying 9 active ones. Notably, these Cas12a nucleases prefer pyrimidine-rich PAMs. Among these nucleases, we extensively characterized Mb4Cas12a obtained from Moraxella bovis CCUG 2133, which recognizes a YYN PAM (Y = C or T). Our biochemical analysis demonstrates that Mb4Cas12a can cleave double-strand DNA across a wide temperature range. To improve specificity, we constructed a SWISS-MODEL of Mb4Cas12a based on the FnCas12a crystal structure and identified 8 amino acids potentially forming hydrogen bonds at the target DNA-crRNA interface. By replacing these amino acids with alanine to disrupt the hydrogen bond, we tested the influence of each mutation on Mb4Cas12a specificity. Interestingly, the F370A mutation improved specificity with minimal influence on activity. Further study showed that Mb4Cas12a-F370A is capable of discriminating single-nucleotide polymorphisms. These new Cas12a orthologs and high-fidelity variants hold substantial promise for therapeutic applications.

Fecal Microbiota Transplantation Attenuates Frailty via Gut-Muscle Axis in Old Mice.

Targeting adverse pathogenic gut microbiota regulation through fecal microbiota transplantation (FMT) may restore health and has been validated in some aging-related diseases. However, the mechanisms of the gut microbiota's role in frailty and whether modulation of the gut microbiota can treat age-related frailty remain largely unknown. To assess the effects of FMT on frailty, we used bidirectional fecal microbiota transplantation in young and old mice. We demonstrated that fecal bacteria transplanted from old mice into young mice reduced body weight and grip strength (p=0.002), and led to elevated inflammatory factors in young mice, but had no significant effect on intestinal barrier function. Notably, FMT treatment in older mice not only improved frailty (grip strength: p=0.036, low physical activity: p=0.020, running speed: p=0.048, running time: p=0.058, frailty score: p=0.027) and muscle mass, but also improved intestinal ecological imbalances, intestinal barrier function, and systemic inflammation (serum TNF-α: p=0.002, and IL-6: p<0.001). KEGG enrichment analysis of fecal metabolites showed that FMT may ameliorate frailty through the sphingolipid metabolism pathway. In addition, aged mice given FMT treatment showed a significant increase in the abundance of SCFA-producing bacteria and increased levels of short-chain fatty acids (butyric acid: p=0.084, propionic acid: p=0.028). Subsequent further verification found that FMT ameliorating frailty may be achieved through SCFAs metabolism. Another mechanism study found that FMT reduces lipopolysaccharide levels (p<0.001), thereby inhibiting the TLR4/NF-κB signaling pathway and its downstream pro-inflammatory products. Therefore, regulating SCFAs metabolism by altering gut microbial composition and targeting the gut-muscle axis with LPS/TLR4 pathways may be potential strategies to treat frailty in older adults.

Green and efficient extraction of flavonoids from Perilla frutescens (L.) Britt. leaves based on natural deep eutectic solvents: Process optimization, component identification, and biological activity.

In this study, an ultrasonic-assisted natural deep eutectic solvent (NaDES) was used to extract flavonoids from Perilla frutescens (L.) Britt. leaves. Of 10 tested NaDESs, that comprising D-(+)-glucose and glycerol exhibited the best total flavonoid extraction rate. Response surface methodology (RSM) was used for extraction modeling and optimization, and the total flavonoid content reached 87.48 ± 1.61 mg RE/g DW, which was a significant increase of 5.36% compared with that of 80% ethanol extraction. Morphological changes in P. frutescens leaves before and after extraction were analyzed by scanning electron microscopy (SEM), and the mechanism of NaDES formation was studied by Fourier transform infrared (FT-IR) spectroscopy. Furthermore, 10 flavonoids were identified by UPLC-Q-TOF-MS. In addition, the NaDES extract had better biological activity according to five kinds of antioxidant capacity measurements, cyclooxygenase-2 (COX-2) and hyaluronidase (Hyal) inhibition experiments. Moreover, the stability test revealed that the total flavonoid loss rate of the NaDES extract after four weeks was 37.75% lower than that of the ethanol extract. These results indicate that the NaDES can effectively extract flavonoids from P. frutescens leaves and provide a reference for further applications in the food, medicine, health product and cosmetic industries.

Hhatl ameliorates endoplasmic reticulum stress through autophagy by associating with LC3.

Endoplasmic reticulum (ER) stress, a common cellular stress response induced by various factors that interfere with cellular homeostasis, may trigger cell apoptosis. Autophagy is an important and conserved mechanism for eliminating aggregated proteins and maintaining protein stability of cells, which is closely associated with ER stress and ER stress-induced apoptosis. In this paper, we report for the first time that Hhatl, an ER-resident protein, is downregulated in response to ER stress. Hhatl overexpression alleviated ER stress and ER stress induced apoptosis in cells treated with tunicamycin or thapsigargin, whereas Hhatl knockdown exacerbated ER stress and apoptosis. Further study showed that Hhatl attenuates ER stress by promoting autophagic flux. Mechanistically, we found that Hhatl promotes autophagy by associating with autophagic protein LC3 (microtubule-associated protein 1A/1B-light chain 3) via the conserved LC3-interacting region motif. Noticeably, the LC3-interacting region motif was essential for Hhatl-regulated promotion of autophagy and reduction of ER stress. These findings demonstrate that Hhatl ameliorates ER stress via autophagy activation by interacting with LC3, thereby alleviating cellular pressure. The study indicates that pharmacological or genetic regulation of Hhatl-autophagy signaling might be potential for mediating ER stress and related diseases.

Exploration of quantitative-effectiveness association between acupuncture temporal parameters and stable chronic obstructive pulmonary disease: A systematic review and dose-response meta-analysis of randomized controlled trials.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a globally common chronic respiratory disease with a high morbidity and mortality rate. Acupuncture has been proven effective for COPD. A dose-response meta-analysis was conducted to assess the correlation between the acupuncture temporal parameters(session, frequency, and duration) and its effectiveness in patients with stable COPD. METHODS: Acupuncture randomized controlled trials on COPD were searched in eight databases from their inception to June 2023. The "doses" were defined as the acupuncture session, frequency, and duration. The outcomes mainly included Forced Expiratory Volume in one-second rate (FEV1%) and Six-minute Walking Distance (6MWD). The assessment of bias risk and literature quality were conducted independently using the Cochrane risk of bias tool and the Standards for reporting interventions in clinical trials of acupuncture. The dose-response relationship was modeled using robust error element regression, and meta-analysis was operated by R 4.3.1 and Stata 15.0. The protocol was registered in PROSPERO with the registration number CRD42023401406. RESULT: Out of 1669 records, 17 RCTs with 1165 participants were finally included in the meta-analysis. There was notable heterogeneity among the studies, but sensitivity analysis demonstrated good robustness. The findings revealed a significant improvement in the following outcomes for stable COPD patients in the acupuncture group: FEV1% (MD=3.50, 95%CI: 2.05-4.95), 6MWD (MD=47.39, 95%CI: 29.29-65.50), St. George's respiratory questionnaire (SGRQ; MD=-8.25, 95%CI: -11.38 to -5.12); COPD assessment test (CAT; MD=-2.91, 95%CI: -3.99 to -1.83). The relationship between the acupuncture session, duration, and FEV1%, 6MWD followed a "Λ" curve pattern, while the relationship between acupuncture frequency and FEV1%, 6MWD exhibited logarithmic growth. Firstly, After 12 acupuncture sessions, FEV1% and 6MWD increased by 7.06% (95%CI: 4.56-9.55) and 36.28 m (95%CI: 20.37-52.20), respectively. The peak improvement in FEV1% and 6MWD was observed after 18 acupuncture sessions (MD=7.89, 95% CI: 5.33-10.45) and 45 sessions (MD=125.43, 95% CI: 72.80-178.07) each. Additionally, weekly acupuncture resulted in a 4.14% improvement in FEV1% (95% CI: 2.55-5.72) and a 42.49 m increase in 6MWD (95%CI: 17.16-67.81). Notably, the maximum effects on FEV1% and 6MWD improvement were achieved with different acupuncture frequencies, specifically three times a week (MD=6.00, 95% CI: 5.34-6.66) and once a day(MD=112.41, 95% CI: 77.27-147.56), respectively. Furthermore, after a 28-day duration of acupuncture treatment, FEV1% increased by 4.74% (95% CI: 3.73-5.75) and 6MWD increased by 47.34 m (95%CI: 22.01-72.67). During 60 days of acupuncture treatment, the FEV1% and 6MWD improvement reached their highest levels at 8.76% (95% CI: 7.05-10.47) and 88.06 m (95% CI: 45.96-130.16), respectively. CONCLUSION: Acupuncture was effective in improving FEV1%, 6MWD, SGRQ, and CAT in patients with stable COPD. There was a dose-response relationship between the time parameters of acupuncture (session, frequency, and duration) and the efficacy of COPD treatment (FEV1% and 6MWD). The minimal clinically important difference could be achieved after 12 acupuncture sessions. Acupuncture with a medium-frequency (2-3 times per week) over 60 days may result in the greatest improvement in FEV1%, while higher-frequency acupuncture (5-7 times per week) for 2 months may lead to the maximum improvements in 6MWD. It indicated that the optimal acupuncture duration for different indicators remains consistent, while the optimal frequencies may differ. To confirm these results, it is necessary to conduct multicenter, large-scale randomized controlled trials. ETHICS AND DISSEMINATION: Ethical approval is not required for literature-based studies. The results will be published in peer-reviewed journals or conferences.

Inhibition of LPS-Induced Skin Inflammatory Response and Barrier Damage via MAPK/NF-κB Signaling Pathway by Houttuynia cordata Thunb Fermentation Broth.

Houttuynia cordata Thunb is rich in active substances and has excellent antioxidant and anti-inflammatory activity. Scanning electron microscopy and gel permeation chromatography were used to analyze the molecular characteristics of the fermentation broth of Houttuynia cordata Thunb obtained through fermentation with Clavispora lusitaniae (HCT-f). The molecular weight of HCT-f was 2.64265 × 105 Da, and the polydispersity coefficient was 183.10, which were higher than that of unfermented broth of Houttuynia cordata Thunb (HCT). By investigating the active substance content and in vitro antioxidant activity of HCT-f and HCT, the results indicated that HCT-f had a higher active substance content and exhibited a superior scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals and hydroxyl radicals, with IC50 values of 11.85% and 9.01%, respectively. Our results showed that HCT-f could effectively alleviate the increase in the secretion of inflammatory factors and apoptotic factors caused by lipopolysaccharide (LPS) stimulation, and had a certain effect on repairing skin barrier damage. HCT-f could exert an anti-inflammatory effect by down-regulating signaling in the MAPK/NF-κB pathway. The results of erythrocyte hemolysis and chicken embryo experiments showed that HCT-f had a high safety profile. Therefore, this study provides a theoretical basis for the application of HCT-f as an effective ingredient in food and cosmetics.

Reusable magnetic molecular imprinted polymers based on magnetic graphene oxide for selective identification and detection of eugenol in environmental water samples.

In this study, a reliable method for determining eugenol content in environmental water samples was established by combining magnetic solid-phase extraction with high-performance liquid chromatography. Magnetic molecular imprinted polymers MGO@MIPs were prepared through surface molecular imprinting technique with eugenol as the template molecule. The material displayed good superparamagnetic properties and magnetic responsiveness in favor of rapid separation. The adsorption properties of MGO@MIPs for eugenol were evaluated through adsorption kinetics and selectivity experiments. MGO@MIPs were found to have favorable reusability and obvious selectivity for eugenol. In addition, adsorption and elution conditions were investigated. Under optimal conditions, a linear relationship was obtained between the concentration of eugenol and its peak area in the range of 0.02-5 mg/L (R2 = 0.9998) and the limit of detection was 4.0 × 10-6 mg/mL. The performance of the established method was assessed with the average recovery of 96.59-102.20% and the relative standard deviation (RSD) below 3.5%. The application of this method provides a new perspective for the separation, enrichment and detection of eugenol in water environment.

[Screening for Characteristic Genes of Different Traditional Chinese Medicine Syndromes of Psoriasis Vulgaris: A Study Based on Bioinformatics and Machine Learning]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­›é€‰é“¶å±‘ç— ä¸­åŒ»è¯åž‹ç‰¹å¾åŸºå› .

Objective: To screen for the key characteristic genes of the psoriasis vulgaris (PV) patients with different Traditional Chinese Medicine (TCM) syndromes, including blood-heat syndrome (BHS), blood stasis syndrome (BSS), and blood-dryness syndrome (BDS), through bioinformatics and machine learning and to provide a scientific basis for the clinical diagnosis and treatment of PV of different TCM syndrome types. Methods: The GSE192867 dataset was downloaded from Gene Expression Omnibus (GEO). The limma package was used to screen for the differentially expressed genes (DEGs) of PV, BHS, BSS, and BDS in PV patients and healthy populations. In addition, KEGG (Kyoto Encyclopedia of Genes and Genes) pathway enrichment analysis was performed. The DEGs associated with PV, BHS, BSS, and BDS were identified in the screening and were intersected separately to obtain differentially characterized genes. Out of two algorithms, the support vector machine (SVM) and random forest (RF), the one that produced the optimal performance was used to analyze the characteristic genes and the top 5 genes were identified as the key characteristic genes. The receiver operating characteristic (ROC) curves of the key characteristic genes were plotted by using the pROC package, the area under curve (AUC) was calculated, and the diagnostic performance was evaluated, accordingly. Results: The numbers of DEGs associated with PV, BHS, BSS, and BDS were 7699, 7291, 7654, and 6578, respectively. KEGG enrichment analysis was focused on Janus kinase (JAK)/signal transducer and activator of transcription (STAT), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), apoptosis, and other pathways. A total of 13 key characteristic genes were identified in the screening by machine learning. Among the 13 key characteristic genes, malectin (MLEC), TUB like protein 3 (TULP3), SET domain containing 9 (SETD9), nuclear envelope integral membrane protein 2 (NEMP2), and BTG anti-proliferation factor 3 (BTG3) were the key characteristic genes of BHS; phosphatase 15 (DUSP15), C1q and tumor necrosis factor related protein 7 (C1QTNF7), solute carrier family 12 member 5 (SLC12A5), tripartite motif containing 63 (TRIM63), and ubiquitin associated protein 1 like (UBAP1L) were the key characteristic genes of BSS; recombinant mouse protein (RRNAD1), GTPase-activating protein ASAP3 Protein (ASAP3), and human myomesin 2 (MYOM2) were the key characteristic genes of BDS. Moreover, all of them showed high diagnostic efficacy. Conclusion: There are significant differences in the characteristic genes of different PV syndromes and they may be potential biomarkers for diagnosing TCM syndromes of PV.

The relationship between different fatty acids intake and the depressive symptoms: A population-based study.

BACKGROUND: Depression is a common psychological disorder worldwide, affecting mental and physical health. Previous studies have explored the benefits of polyunsaturated fatty acids (PUFAs) intake in depressive symptoms; however, few studies have focused on the association between all types of fatty acids intake and depressive symptoms. Therefore, we explored the relationship between the intake of different fatty acids intake and the risk of depressive symptoms. METHODS: The study was based on the data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a large US-based database. We used a nutrient residual model and multi-nutrient density model for the analysis. We calculated the nutrient density and residual in men and women separately, and the fatty acids intake was divided into quartiles based on the sex distribution. The relationship between the depressive symptoms and the intake of different fatty acids was examined using logistic regression; furthermore, we explored the relationships separately in men and women. RESULTS: The intake of monounsaturated fatty acids (MUFAs) and PUFAs, particularly n-3 and n-6 PUFAs, were associated with reduced odds ratios for depressive symptoms. The inverse relationship between the intake of MUFAs, PUFAs, n-3, and n-6 PUFAs and depressive symptoms was stronger in women. The inverse relationship between total fatty acid (TFAs) intake and depressive symptoms existed only in a single model. In contrast, saturated fatty acid (SFAs) intake was not related to depressive symptoms. CONCLUSION: Consuming MUFAs and PUFAs can counteract the depressive symptoms, especially in women.

Maternal RNA transcription in Dlk1-Dio3 domain is critical for proper development of the mouse placental vasculature.

The placenta is a unique organ for ensuring normal embryonic growth in the uterine. Here, we found that maternal RNA transcription in Dlk1-Dio3 imprinted domain is essential for placentation. PolyA signals were inserted into Gtl2 to establish a mouse model to prevent the expression of maternal RNAs in the domain. The maternal allele knock-in (MKI) and homozygous (HOMO) placentas showed an expanded junctional zone, reduced labyrinth and poor vasculature impacting both fetal and maternal blood spaces. The MKI and HOMO models displayed dysregulated gene expression in the Dlk1-Dio3 domain. In situ hybridization detected Dlk1, Gtl2, Rtl1, miR-127 and Rian dysregulated in the labyrinth vasculature. MKI and HOMO induced Dlk1 to lose imprinting, and DNA methylation changes of IG-DMR and Gtl2-DMR, leading to abnormal gene expression, while the above changes didn't occur in paternal allele knock-in placentas. These findings demonstrate that maternal RNAs in the Dlk1-Dio3 domain are involved in placental vasculature, regulating gene expression, imprinting status and DNA methylation.

Protective Effect of Panax notoginseng Extract Fermented by Four Different Saccharomyces cerevisiae Strains on H2O2 Induced Oxidative Stress in Skin Fibroblasts.

Purpose: To produce Panax notoginseng extract as a cosmetic ingredient through Saccharomyces cerevisiae fermentation. Methods: We first compared the total sugar content, polysaccharide content, reducing sugar content, total phenolic content, total saponin content, DPPH free radical, ABTS free radical, hydroxyl free radical scavenging ability and ferric reducing antioxidant power (FRAP) of Panax notoginseng fermented extract (pnFE) and unfermented extract (pnWE). Their potential correlations were analyzed by Pearson's correlation analysis. Then, the oxidative stress model of H2O2-induced MSFs was used to evaluate the effects of different pnFE on MSF viability, reactive oxygen species (ROS), malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) to explore their protective effects on MSFs subjected to H2O2-induced cellular oxidative damage. Finally, their safety and stability were evaluated by using the red blood cell (RBC) test and hen's egg test-chorioallantoic membrane (HET-CAM) assay, and changes in pH and content of soluble solids, respectively. Results: Compared with pnWE, pnFE has more active substances and stronger antioxidant capacity. In addition, pnFE has a protective effect on H2O2-induced oxidative stress in MSFs with appropriate safety and stability. Conclusion: PnFE has broad application prospects in the field of cosmetics.

Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability.

Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated. MYC family oncoproteins coordinate nucleotide synthesis and ROS generation to drive the development of numerous cancers. We herein perform a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based functional screen targeting metabolic genes and identified nudix hydrolase 1 (NUDT1) as a MYC-driven dependency. Mechanistically, MYC orchestrates the balance of two metabolic pathways that act in parallel, the NADPH oxidase 4 (NOX4)-ROS pathway and the Polo like kinase 1 (PLK1)-NUDT1 nucleotide-sanitizing pathway. We describe LC-1-40 as a potent, on-target degrader that depletes NUDT1 in vivo. Administration of LC-1-40 elicits excessive nucleotide oxidation, cytotoxicity and therapeutic responses in patient-derived xenografts. Thus, pharmacological targeting of NUDT1 represents an actionable MYC-driven metabolic liability.