Butyryl group distribution modulates the structure and properties of butyrylated maize starch focused on amylose contents.

In this study, four types of maize starch with different amylose contents (3 %, 25 %, 40 %, and 70 %) were used to prepare butyrylated starches. Based on amylose contents, the influence of butyryl group distribution on the structure, thermal and digestive properties of butyrylated maize starch was investigated. The butyrylation reaction mainly substituted butyryl groups on amylose, and the butyryl groups were most easily substituted for the hydroxyl group at the C6 position. The degree of substitution of butyrylated starch reached its maximum when the amylose content was 40 %, and the degree of substitution did not correlate linearly with the amylose content. The butyrylation reaction increased the surface roughness, decreased the crystallinity, enthalpy value and molecular weight of native starch granules, resulting in a decrease in the degree of internal order of the starch and inducing the rearrangement of the amylose molecular chains in the amorphous region of the starch. The combination of the amylose content and the substitution of butyryl groups on amylose affected the digestibility of starch and ultimately increased its resistance. The Pearson correlation coefficient further confirmed the correlation between the distribution of butyryl groups and the structure and properties of butyrylated starch.

Effect of lotus seed resistant starch on the bioconversion pathway of taurocholic acid by regulating the intestinal microbiota.

Taurocholic acid (TCA) is abundant in the rat intestine and has multiple health benefits. In the gut, intestinal microbiota can transform TCA into different bile acid (BA) derivatives, with the composition of microbiota playing a crucial role in the transformation process. This study aims to investigate how lotus seed resistant starch (LRS) can regulate microbiota to influence BA transformation. A fecal fermentation study was conducted in vitro, using either LRS, high-amylose maize starch (HAMS), or glucose (GLU) to analyze microbiota composition, BA content, and metabolic enzyme activities over different fermentation times. Bioinformatics analysis found that LRS increased the relative abundance of Enterococcus, Bacillus, and Lactobacillus, and decreased Escherichia-Shigella, compared with HAMS and GLU. LRS also reduced total BA content and accelerated the conversion of TCA to cholic acid, deoxycholic acid, and other derivatives. These results reveal that LRS and GLU tend to mediate the dehydroxy pathway, whereas HAMS tends to secrete metabolic enzymes in the epimerization pathway. Therefore, the evidence that LRS may regulate TCA bioconversion may benefit human colon health research and provide an important theoretical basis, as well as offer new concepts for the development of functional foods.

Pressure-dominated steam explosion for modifying textured soy proteins: Structure and in vitro digestion kinetics.

Textured Soy Proteins (TSPs) have been employed as building blocks in various food processes, but their availability remains limited. In this research, influence of Steam Explosion (SE) with pressure ranges (0, 0.5, 1.0, 1.5 MPa) on the structure and in vitro digestibility of TSPs was investigated. The results showed that 0.5 and 1.0 MPa significantly increased the relative content of ß-sheets and decreased the relative content of α-helices and ß-turns. Correlation analysis revealed that the structural changes made the TSP brittle, with lower thermal stability and resistance to digestion. Moreover, SE decreased the degree of hydrolysis of TSPs in the gastric stage, with the lowest degree observed for the TSP at 0.5 MPa. However, in the intestinal phase, 1.0 and 1.5 MPa significantly increased the hydrolysis degree. These findings provide a better understanding of the SE pressure-modulated quality characteristics of TSPs and suggest the processing potential of modified TSPs as functional ingredients.

Quality properties of fish ball with abalone and its relationship with sensory properties.

In this work, whiteness, water-holding capacity, gel strength, textural profile analysis were performed to examine the quality of fish balls with abalone (FBA). In addition, a correlation between quality and sensory properties was established. The addition of abalone significantly increased the water holding capacity, gel strength and textural properties of FBA, and decreased their whiteness, the best overall quality was achieved at 9 % w/w abalone addition. The E-nose and E-tongue results revealed that the addition of abalone changed the flavour of FBA. HS-SPME-GC-MS identified 65 volatile organic compounds (VOCs) and proved to be effective in reducing fishy flavour. E-nose can distinguish between the VOCs in FBA. Moreover, Umami and 1-octen-3-ol can serve as important indicators to observe changes in the quality of FBA, as they were positively connected with WHC, gumminess, chewiness, resilience, a*, hexanal, etc. The results provided a theoretical basis for the development of abalone and surimi products.

The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.

Endometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive. This study demonstrates that the hot POLE P286R mutation impedes endometrial tumorigenesis by inducing DNA breakage and activating the cGAS-STING signaling pathway. The POLE mutations were found to inhibit the proliferation and stemness of primary human EC cells. Mechanistically, the POLE mutants enhance DNA damage and suppress its repair through the interaction with DNA repair proteins, leading to genomic instability and the upregulation of cytoplasmic DNA. Additionally, the POLE P286R mutant also increases cGAS level, promotes TBK1 phosphorylation, and stimulates inflammatory gene expression and anti-tumor immune response. Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective cancer therapy.

Association of tirofiban treatment with outcomes following endovascular therapy in cardioembolic stroke: insights from the RESCUE BT randomized trial.

BACKGROUND AND PURPOSE: The efficacy and safety of tirofiban in endovascular therapy for cardioembolic ischemic stroke patients remain controversial. This study aimed to evaluate the role of intravenous tirofiban before endovascular therapy in cardioembolic stroke. METHODS: This post hoc analysis utilized data from the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke) trial, which was an investigator-initiated, randomized, double-blind, placebo-controlled trial. Participants were randomized to receive either tirofiban or a placebo in a 1:1 ratio before undergoing endovascular therapy. The study included patients aged 18 years or older, presenting with occlusion of the internal carotid artery or middle cerebral artery (MCA) M1/M2 within 24 h of the last known well time, and with a stroke etiology of cardioembolism. The primary efficacy outcome was global disability at 90 days, assessed using the modified Rankin Scale (mRS). The safety outcome included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days. RESULTS: A total of 406 cardioembolic stroke patients were included in this study, with 212 assigned to the tirofiban group and 194 assigned to the placebo group. Tirofiban treatment did not correlate with a favorable shift towards a lower 90-day mRS score (adjusted common odds ratio [OR], 0.91; 95% CI 0.64-1.3; p = 0.617). However, the tirofiban group had a significantly higher risk of symptomatic intracranial hemorrhage (sICH) within 48 h (adjusted OR, 3.26; 95% CI 1.4-7.57; p = 0.006) compared to the placebo group. The adjusted odds ratio (aOR) for mortality within 90 days was 1.48 (95% CI 0.88-2.52; p = 0.143). CONCLUSIONS: Tirofiban treatment was not associated with a lower level of disability and increased the incidence of sICH after endovascular therapy in cardioembolic stroke patients.

Structural and Physicochemical Properties of a Chinese Yam Starch-Tea Polyphenol Complex Prepared Using Autoclave-Assisted Pullulanase Treatment.

Interactions between food components have a positive impact in the field of food science. In this study, the effects of tea polyphenol on the structural and physicochemical properties of Chinese yam starch using autoclave-assisted pullulanase treatment were investigated. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, rapid visco analysis, differential scanning calorimetry, and the 3,5-dinitrosalicylic acid method were applied in this study. The results showed that the Chinese yam starch-tea polyphenol complex formed a structural domain with higher thermal stability along with lower pasting viscosities than native starch. The in vitro digestibility of Chinese yam starch decreased with the addition of the tea polyphenol, and the amount of resistant starch content in the complex was 56.25 ± 1.37%, significantly higher than that of native starch (p < 0.05). In addition, the complex showed a B+V-type crystalline structure, which confirmed that the interaction modes between the starch and tea polyphenol include hydrogen bonding and hydrophobic interactions. Moreover, the appearance of an irregular sponge network structure of the complex further supported the interactions between the starch and tea polyphenol. This study provides a theoretical basis for the development of functional foods using Chinese yam starch.

Bile acid and its bidirectional interactions with gut microbiota: a review.

Bile acids (BAs) are an important metabolite produced by cholesterol catabolism. It serves important roles in glucose and lipid metabolism and host-microbe interaction. Recent research has shown that different gut-microbiota can secrete different metabolic-enzymes to mediate the deconjugation, dehydroxylation and epimerization of BAs. In addition, microbes mediate BAs transformation and exert physiological functions in metabolic diseases may have a potentially close relationship with diet. Therefore, elaborating the pathways by which gut microbes mediate the transformation of BAs through enzymatic reactions involved are principal to understand the mechanism of effects between dietary patterns, gut microbes and BAs, and to provide theoretical knowledge for the development of functional foods to regulate metabolic diseases. In the present review, we summarized works on the physiological function of BAs, as well as the classification and composition of BAs in different animal models and its organs. In addition, we mainly focus on the bidirectional interactions of gut microbes with BAs transformation, and discuss the effects of diet on microbial transformation of BAs. Finally, we raised the question of further in-depth investigation of the food-gut microbial-BAs relationship, which might contribute to the improvement of metabolic diseases through dietary interventions in the future.

AHEGC: Adaptive Hindsight Experience Replay With Goal-Amended Curiosity Module for Robot Control.

With shaped reward functions, reinforcement learning (RL) has recently been successfully applied to several robot control tasks. However, designing a task-relevant and well-performing reward function takes time and effort. Still, if RL can train an agent to complete a task in a sparse reward environment, it is an effective way to address the difficulty of reward function design, but it is still a significant challenge. To address this issue, the pioneering hindsight experience replay (HER) method dramatically enhances the probability of acquiring skills in sparse reward environments by transforming unsuccessful experiences into helpful training samples. However, HER still requires a lengthy training period. In this article, we propose a new technique based on HER termed adaptive HER with goal-amended curiosity module (AHEGC) for further enhancing sample and exploration efficiency. Specifically, an adaptive adjustment strategy of hindsight experience (HE) sampling rate and reward weights is developed to enhance sample efficiency. Furthermore, we introduce a curiosity mechanism to encourage more efficient exploration of the environment and propose a goal-amended (GA) curiosity module as a solution to the problem of over-seeking novelty caused by the curiosity introduced. We conducted experiments on six demanding robot control tasks with binary rewards, including Fetch and Hand environments. The results show that the proposed method outperforms existing methods regarding learning ability and convergence speed.

Fraxin inhibits melanogenesis by suppressing the ERK/MAPK pathway and antagonizes oxidative stress by activating the NRF2 pathway.

Hyperpigmentation disorders, such as melasma and freckles, are highly prevalent and draw increasing attention. Patients thus tend to seek effective and safe cosmetic whitening agents. Fraxin, a bioactive substance extracted from Cortex Fraxini, possesses anti-inflammation and antioxidant properties. In this study, we further explored the anti-melanogenic activities of fraxin were explored in vitro and in vivo. We found that pretreatment with fraxin decreased the melanin content of MNT1 cells and zebrafishes. In MNT1 cells, melanogenesis-related proteins, such as MITF, TYR, TYRP1, and DCT were down-regulated and tyrosinase activity was reduced under fraxin treatment. Further exploration of the mechanism revealed that fraxin could inhibit the phosphorylation of ERK, which is closely related to melanogenesis. Besides, fraxin also protected MNT1 cells from H2O2-induced apoptosis via scavenging reactive oxygen species (ROS) in cells. Further experimentation revealed that fraxin could activate NRF2 and upregulate antioxidase CAT and HO-1. In conclusion, fraxin could be an effective agent with anti-melanogenesis and antioxidant properties for hyperpigmentation disorders.

Fuzhuan brick tea ameliorates hepatic steatosis and steatohepatitis through gut microbiota-derived aryl hydrocarbon receptor ligands in high-fat diet-induced obese mice.

High-fat diet (HFD) induced obesity and its associated conditions, such as hepatic steatosis and steatohepatitis, are major health concerns worldwide. Previous studies have reported the excellent efficiency of Fuzhuan brick tea (FBT) in attenuating HFD-induced obesity and metabolic disorders. In this study, we investigated the effects of FBT on hepatic steatosis and simple steatohepatitis in HFD-induced obese mice, as well as the metabolic function of the gut microbiome using metagenomics and metabolomics. The results showed that FBT ameliorated dyslipidemia, hepatic steatosis and steatohepatitis in HFD-induced obese mice by normalizing the gut microbiota structure and tryptophan metabolism. FBT increased the cecal abundance of aryl hydrocarbon receptor (AhR)-ligand producing bacteria such as Lactobacillus_reuteri and Lactobacillus_johnsonii, at the expense of AhR-ligand consuming bacteria, such as Faecalibaculum_rodentium and Escherichia_coli, and elevated the cecal contents of AhR-ligands such as IAA, IPA, and KYNA. Furthermore, FBT regulated the expressions of AhR and its targeted lipometabolic genes such as Pemt, Fasn, and SREBP-1c, as well as other inflammatory genes including TNF-α, IL-6, and IL-1ß in the liver of mice. Overall, these findings highlight the beneficial effects of FBT on obesity-related hepatic steatosis and steatohepatitis via microbiota-derived AhR signaling.

Physiochemical Quality, Microbial Diversity, and Volatile Components of Monascus-Fermented Hairtail Surimi.

In order to study the effects and mechanism of Monascus on the quality of hairtail surimi, high-throughput sequencing technology, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC/MS), and electronic nose techniques were used to investigate the changes in the quality, microbial diversity, and volatile flavor compounds of Monascus-fermented hairtail surimi (MFHS) during fermentation. The results showed that the total volatile basic nitrogen (TVB-N) index of hairtail surimi fermented by Monascus for 0-5 h met the requirements of the national standard. Among them, the 1 h group showed the best gel quality, which detected a total of 138 volatile substances, including 20 alcohols, 7 aldehydes, 12 olefins, 4 phenols, 12 alkanes, 8 ketones, 15 esters, 6 acids, 16 benzenes, 4 ethers, and 8 amines, as well as 26 other compounds. In addition, the dominant fungal microorganisms in the fermentation process of MFHS were identified, and a Spearman correlation analysis showed that 16 fungal microorganisms were significantly correlated with the decrease in fishy odor substances in the fermented fish and that 8 fungal microorganisms were significantly correlated with the increase in aromatic substances after fermentation. In short, Monascus fermentation can eliminate and reduce the fishy odor substances in hairtail fish, increase and improve the aromatic flavor, and improve the quality of hairtail surimi gel. These findings are helpful for revealing the mechanism of the quality formation of fermented surimi and provide guidance for the screening of starter culture in the future.

Ratiometric and discriminative visualization of autophagic processes with a novel dual-responded lysosome-specific fluorescent probe.

BACKGROUND: Autophagy is a critical self-eating pathway involved in numerous physiological and pathological processes. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fluctuations in the lysosomal microenvironment is vital for tracking the dynamic process of autophagy. Although much effort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy. METHODS: Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the performance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury. RESULTS: We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual-wavelength emission, and small background interference. The ratiometric fluorescent signal (R = I 610/I 460) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion effect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starvation or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible effect of hepatoprotective drugs on this event. CONCLUSIONS: In this study, we developed the first ratiometric dual-responsive fluorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety.

UVB promotes melanogenesis by regulating METTL3.

Ultraviolet (UV) radiation is the primary exogenous inducer of skin pigmentation, although the mechanism has not been fully elucidated. N6-methyladenosine (m6 A) modification is one of the key epigenetic form of gene regulation that affects multiple biological processes. The aim of this study was to explore the role and underlying mechanisms of m6 A modification in UVB-induced melanogenesis. Low-dose UVB increased global m6 A modification in melanocytes (MCs) and MNT1 melanoma cell line. The GEPIA database predicted that methyltransferase METTL3 is positively correlated with the melanogenic transcription factor MITF in the sun-exposed skin tissues. After METTL3 respectively overexpressed and knocked down in the MNT1, the melanin content and melanogenesis-related genes were significantly upregulated after overexpression of METTL3, especially with UVB irradiation, and downregulated after METTL3 knockdown. METTL3 levels were also higher in melanocytic nevi with high melanin content. METTL3 overexpression and knockdown also altered the protein level of YAP1. SRAMP analysis predicted four high-potential m6 A modification sites on YAP1 mRNA, of which three were confirmed by methylated RNA immunoprecipitation. Inhibition of YAP1 expression can partially reverse melanogenesis induced by overexpression of METTL3. In conclusion, UVB irradiation promotes global m6 A modification in MCs and upregulates METTL3, which increases the expression level of YAP1 through m6 A modification, thereby activating the co-transcription factor TEAD1 and promoting melanogenesis.

Proteomic analysis reveals that Polygonatum cyrtonema Hua polysaccharide ameliorates mice muscle atrophy in chemotherapy-induced cachexia.

Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64 mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.

Correlation Study between Quality and Sensory Characteristics of Kelp Paste by Aspergillus oryzae and Aspergillus niger during Fermentation.

In order to clarify the relationship between quality and sensory characteristics of kelp paste during fermentation, this study analyzed the quality and sensory characteristics of kelp paste through physicochemical indexes, nutritional components, electronic nose and electronic tongue. The results showed that with the extension of fermentation time, the contents of amino nitrogen, total acid, ammonium salt and ash increased gradually, while the pH value, moisture, fat, protein and carbohydrate decreased gradually. Short-chain alkanes such as nitrogen oxides and methane were the main causes of odor. Freshness, salinity and richness were the main indexes of kelp paste taste. Many quality indexes, such as amino nitrogen and protein, were significantly related to the odor sensor, which can better reflect the odor produced in the fermentation process of kelp paste. There was a significant correlation between quality indicators and important taste indicators such as umami, richness and salty taste, which can better reflect the taste of kelp paste during fermentation. To sum up, there was a significant correlation between the quality characteristics and sensory quality of kelp paste, so the relationship between quality characteristics and sensory characteristics in kelp paste can be clarified.

Effects of Porphyra haitanensis polysaccharides on gelatinization and gelatinization kinetics of starches with different crystal types.

The effects of Porphyra haitanensis polysaccharide (PHP) on the gelatinization and gelatinization kinetics of corn starch (CS), potato starch (PS) and lotus seed starch (LS) were studied. The gelatinization, rheological and thermal enthalpy properties of the samples were measured by a rapid viscosity analyzer (RVA), a rheometer, and a differential scanning calorimeter (DSC), respectively. And the kinetic equations were further established. RVA confirmed that the addition of 0.4 %, 0.8 % and 1.2 % PHP elevated the gelatinization viscosity of CS and LS but decreased that of the PS, and also elevated the thermal balance of CS, PS, and LS, especially PS (The breakdown viscosity was decreased to 363.00 ± 6.08, 370.00 ± 1.15, and 362.00 ± 0.58, respectively). And the rheometer indicated that the addition of 0.4 %, 0.8 % and 1.2 % PHP improved the apparent viscosity of CS, PS and LS, especially PS (The consistency coefficient was increased to 18.26 ± 0.02, 21.71 ± 0.04, and 23.26 ± 0.01, respectively). Eventually, DSC displayed that the addition of 0.4 %, 0.8 % and 1.2 % PHP extended the gelatinization temperature and enthalpy of CS, PS, and LS, especially PS. Among them, the gelatinization temperature (63.40 ± 0.03, 70.26 ± 0.02 and 74.61 ± 0.01, respectively) and the gelatinization enthalpy (1.55 ± 0.01) of PS increased the most with 1.2 % PHP. Moreover, gelatinization kinetics displayed that the addition of 0.4 %, 0.8 % and 1.2 % PHP decreased the rate constants of CS, PS, and LS and accelerated the activation energies of CS (666.37 ± 4.23, 623.89 ± 4.21 and 558.39 ± 2.35, respectively) and PS (752.53 ± 4.13, 699.61 ± 3.78 and 662.15 ± 4.52, respectively) while reducing that of the LS (938.87 ± 3.38, 669.98 ± 4.61 and 491.48 ± 4.29, respectively). Therefore, the addition of PHP at all concentrations inhibited the gelatinization procedure of CS and PS but promoted that of the LS. This study provided a theoretical basis for the creation of new products based on PHP and starch.

Effect of Imaging Selection Paradigms on Endovascular Thrombectomy Outcomes in Patients With Acute Ischemic Stroke.

BACKGROUND: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China. METHODS: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021). Patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early, 0-6 hours versus extended, 6-24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin Scale score of 0-2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after endovascular treatment at each time windows. RESULTS: A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.99 [95% CI, 0.84-1.16]; P=0.91; extended window: adjusted relative risk, 1.00 [95% CI, 0.84-1.20]; P=0.97). CONCLUSIONS: In this post hoc analysis of 2 randomized clinical trial pooled data involving patients with large vessel occlusion stroke, an association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows was not detected. Our study adds to the growing body of literature on simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Gut microbiota-metabolic axis insight into the hyperlipidemic effect of lotus seed resistant starch in hyperlipidemic mice.

We investigated the hyperlipidemic effect of different doses of lotus seed resistant starch (low-, medium and high-dose LRS, named as LLRS, MLRS and HLRS, respectively) in hyperlipidemic mice using gut microbiota-metabolic axis compared to high-fat diet mice (model control group, MC). Allobaculum was significantly decreased in LRS groups compared to MC group, while MLRS promoted the abundance of norank_f_Muribaculaceae and norank_f_Erysipelotrichaceae. Moreover, supplementation of LRS promoted cholic acid (CA) production and inhibited deoxycholic acid compared to MC group. Among, LLRS promoted formic acid, MLRS inhibited 20-Carboxy-leukotriene B4, while HLRS promoted 3, 4-Methyleneazelaic acid and inhibited Oleic acid and Malic acid. Finally, MLRS regulate microbiota composition, and this promoted cholesterol catabolism to form CA, which inhibited serum lipid index by gut microbiota-metabolic axis. In conclusion, MLRS can promote CA and inhibit medium chain fatty acids, so as to play the best role in lowering blood lipids in hyperlipidemia mice.

Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway.

Global warming and rising temperature significantly increase the incidence of heat stress, which is known to affect the process of inflammation and aging. However, the effect of heat stress on skin melanogenesis is not fully known. We found that healthy foreskin tissues underwent significant pigmentation when exposed to 41°C. Furthermore, heat stress promoted melanogenesis in pigment cells by increasing the paracrine effects of keratinocytes. High-throughput RNA sequencing showed that heat stress activates the Hedgehog (Hh) signaling pathway in keratinocytes. The agonists of Hh signaling promote the paracrine effect of keratinocytes on melanogenesis. In addition, transient receptor potential vanilloid (TRPV) 3 agonists activate the Hh signaling in keratinocytes and augment its paracrine effect on melanogenesis. The heat-induced activation of Hh signaling is dependent on TRPV3-mediated Ca2+ influx. Heat exposure promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway. Our findings provide insights into the mechanisms of heat-induced skin pigmentation.