Wood Cell Wall Nanoengineering toward Anisotropic, Strong, and Flexible Cellulosic Hydrogel Sensors.

Achieving highly ionic conductive hydrogels from natural wood remains challenging owing to their insufficient surface area and low number of active sites on the cell wall. This study proposes a viable strategy to design a strong and anisotropic wood-based hydrogel through cell wall nanoengineering. By manipulating the microstructure of the wood cell wall, a flexible cellulosic hydrogel is achieved through Schiff base bonding via the polyacrylamide and cellulose molecular chains. This results in excellent flexibility and mechanical properties of the wood hydrogel with tensile strengths of 22.3 and 6.1 MPa in the longitudinal and transverse directions, respectively. Moreover, confining aqueous salt electrolytes within the porous structure gives anisotropic ionic conductivities (19.5 and 6.02 S/m in the longitudinal and transverse directions, respectively). The wood-based hydrogel sensor has a favorable sensitivity and a stable working performance at a low temperature of -25 °C in monitoring human motions, thereby demonstrating great potential applications in wearable sensor devices.

The new function of FaSRT2-1 protein in energy metabolism: Promoting strawberry fruit quality and ripening.

Sirtuins (SRTs) are nicotinamide adenine dinucleotide (NAD+) dependent II histone deacetylases (HDACs) that have been understudied in horticultural crops. However, their functions in regulating mitochondrial energy metabolism and influencing fruit development and quality formation remain unclear. In this study, we found that FaSRT2-1 exhibits diverse subcellular localizations. Overexpression of FaSRT2-1 promoted strawberry fruit quality formation (soluble sugars, organic acids, anthocyanins) and accelerated ripening. Conversely, knockout of FaSRT2-1 yielded opposite results. During fruit ripening, ATP content and ATP/ADP ratio gradually increased, and FaSRT2-1 promoted ATP accumulation and decreased before and after the deep red stage, respectively, indicating its role in fruit ripening and senescence. FaSRT2-1 interacted with energy-related proteins (FaRPT4a, FaATPß and FaATPγ) to increase ATP content and the ATP/ADP ratio. Additionally, FaSRT2-1 collaborated with FaGDH2 and FaWDR5B to increase the accumulation of soluble sugars, organic acids and anthocyanins. Meanwhile, FaRPT4a, FaATPγ, FaGDH2 and FaWDR5B were co-localized with FaSRT2-1, while FaATPß was localized in both the cytoplasm and mitochondria. Transient overexpression experiments further highlight the roles of FaRPT4a and FaGDH2/FaWDR5B in modulating ATP accumulation and fruit ripening, respectively. In summary, FaSRT2-1 plays important roles in promoting strawberry fruit ripening, senescence and quality formation by regulating energy metabolism.

Maternal sleep deprivation disrupts glutamate metabolism in offspring rats.

Maternal sleep deprivation (MSD) has emerged as a significant public health concern, yet its effects on offspring metabolism remain poorly understood. This study investigated the metabolomic implications of MSD on offspring cognitive development, with a particular focus on alterations in glutamate metabolism. Pregnant rats were subjected to sleep deprivation during late gestation. Plasma and brain samples from their offspring were collected at different postnatal days (P1, P7, P14, and P56) and analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry. Metabolomic analysis revealed significant differences in various amino acids, including L-glutamate, L-phenylalanine, L-tyrosine, and L-tryptophan, which are crucial for cognitive function. Subsequent differential analysis and partial least squares discriminant analysis (sPLS-DA) demonstrated a gradual reduction in these metabolic differences in the brain as the offspring underwent growth and development. KEGG pathway analysis revealed differential regulation of several pathways, including alanine, aspartate, and glutamate metabolism, glutathione metabolism, arginine biosynthesis, aminoacyl-tRNA biosynthesis, histidine metabolism, and taurine and hypotaurine metabolism, at different developmental stages. Mantel and Spearman analyses indicated that the observed changes in metabolites in MSD progeny may be related to various gut microbes, Ruminococcus_1, Ruminococcaceae_UCG-005, and Eubacterium_coprostanoligenes_group. Biochemical assays further demonstrated developmental changes in the L-glutamate metabolic pathway. Collectively, these findings suggest that MSD not only affects maternal well-being but also has enduring metabolic consequences for offspring, particularly impacting pathways linked to cognitive function. This highlights the importance of addressing maternal sleep health to mitigate potential long-term consequences for offspring.

Birth Outcomes After Pertussis and Influenza Diagnosed in Pregnancy: A Retrospective, Population-Based Study.

OBJECTIVE: Adverse birth outcomes and the maternal severity of influenza in pregnancy are well documented but information on pertussis is limited. DESIGN: Population-based linkage data were collected during 2001-2016. SETTING: New South Wales, Australia. POPULATION OR SAMPLE: A total of 1 453 037 singleton births. METHODS: Cox regression was used to estimate the associations between pertussis or influenza during pregnancy and birth outcomes with adjustment of covariates. MAIN OUTCOME MEASURES: Adverse birth outcomes (preterm birth and low birth weight). RESULTS: Among 1 453 037 singleton births over 16 years, we identified pertussis in 925 (49; 5.3% hospitalised) and influenza in 2850 (1092; 38.3% hospitalised) women during pregnancy. Cases of pertussis were similarly distributed by trimester (32% 3rd) whereas 46% of influenza cases were in the 3rd trimester. Younger age, previous birth, and being overseas-born were associated with both pertussis and influenza, whereas identifying as Aboriginal or Torres Strait Islander, hypertension or diabetes before and during pregnancy, and a number of other factors were only associated with influenza. Both pertussis and influenza in pregnancy were associated with increased risk of preterm birth (pertussis: aHR = 1.30, 95% CI 1.01-1.68; influenza: aHR = 1.56, 95% CI 1.36-1.79) and these increased risks were greater when infections in the period within 2 weeks of birth were considered (pertussis: aHR = 2.36, 95% CI 1.26-4.41; influenza: aHR = 2.29, 95% CI 1.78-2.96). CONCLUSIONS: Maternal pertussis and influenza infections close to the time of birth were associated with adverse birth outcomes. These findings highlight the benefits of vaccination during pregnancy.

Oriented 1D Metal-Organic Frameworks for Selective Chemisorption by a Substitution-Insertion Mechanism.

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and purification of targeted systems. Herein, oriented 1D NH2-CuBDC·H2O metal-organic frameworks (MOFs) featuring accessible CuII sites are successfully fabricated by bottom-up interfacial polymerization. The prepared MOFs, as deliberately self-assembled secondary particles, exhibit a visually detectable coordination-responsive characteristic induced by the nucleophilic substitution and competitive coordination of guest molecules. As a versatile phase-change chemosorbent, the MOFs exhibit unprecedented NH3 capture (18.83 mmol g-1 at 298 K) and bioethanol dehydration performance (enriching ethanol from 99% to 99.99% within 10 min by direct adsorption separation of liquid mixtures of ethanol and water). Furthermore, the raw materials for preparing the 1D MOFs are inexpensive and readily available, and the facile regeneration with water washing at room temperature effectively minimizes the energy consumption and cost of recycling, enabling it to be the most valuable adsorbent for the removal and separation of target substances.

Simiao Wan attenuates high-fat diet-induced hyperlipidemia in mice by modulating the gut microbiota-bile acid axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is a lipid metabolism disorder and a risk factor for obesity, diabetes, and coronary heart disease. It occurs mostly in the old adults; however, its incidence rate is increasing annually and there is a trend towards younger adults. Current clinical drugs for treating hyperlipidemia have multiple side effects. Therefore, it is necessary to develop safe and effective drugs from natural products to prevent and treat hyperlipidemia. Simiao Wan (SMW) is a classic Chinese medicine prescription first recorded in the Cheng Fang Bian Du of the Qing Dynasty. Studies have shown that SMW has excellent efficacy in metabolic diseases, which can effectively improve hyperlipidemia combined with other metabolic diseases. However, its underlying mechanism in hyperlipidemia treatment is yet to be clarified. AIM OF THE STUDY: To investigate the hypolipidemic effect of SMW on hyperlipidemic mice and explore whether the gut microbiota-bile acid (BA) axis is the potential mechanism. MATERIALS AND METHODS: A hyperlipidemic mouse model was established using a high-fat diet (HFD), and the hypolipidemic effect of SMW was detected in vivo. We performed 16S ribosomal RNA sequencing and BA metabolism analysis to explore the hypolipidemic mechanisms of SMW. Western blotting was conducted to detect the expression of proteins involved in the gut microbiota-bile acid axis to determine the potential lipid-lowering pathway. RESULTS: Excessive obesity in hyperlipidemic mice was alleviated after 8 weeks of SMW treatment. The total cholesterol and low-density lipoprotein cholesterol levels decreased significantly, whereas high-density lipoprotein cholesterol levels increased. SMW also reduced hepatic lipid and inguinal white adipose tissue accumulation in HFD-induced hyperlipidemic mice. Furthermore, intestinal bile saline hydrolase (BSH) level, associated with BA excretion, decreased. Meanwhile, SMW decreased the abundance of BSH-enriched microbes in hyperlipidemic mice. SMW increased the intestinal conjugated-BAs contents in hyperlipidemic mice, especially tauro-ß-muricholic acid and tauro-ursodeoxycholic acid, which are ileac farnesoid X receptor (FXR) antagonists. Inhibited intestinal FXR signaling with SMW was accompanied by a decreased expression of intestinal fibroblast growth factor 15 and the activation of hepatic FXR, which promoted hepatic cholesterol conversion to BA. CONCLUSION: SMW indirectly attenuated HFD-induced hyperlipidemia in mice by regulating the gut microbiota-BA axis. Our results provide a pharmacological basis for SMW treating hyperlipidemia and suggest a new idea for developing lipid-lowering drugs.

Efficacy of natural duct specimen extraction versus conventional laparoscopic surgery for rectal cancer: a single-centre retrospective analysis.

OBJECTIVE: Rectal cancer has a high incidence and its onset age is getting younger. Currently, conventional laparoscopic surgery can no longer meet the clinical requirements for surgical incisions. Natural orifice specimen extraction surgery (NOSES) is less invasive, but there have been few studies on the effectiveness of this procedure for rectal cancer. Therefore, this study aimed to explore the efficacy of NOSES and conventional laparoscopic surgery in rectal cancer treatment. METHODS: In this retrospective analysis, we collected clinical data of 150 rectal cancer patients. Patients who received NOSES were included in a NOSES group and those underwent routine laparoscopic surgery were in a control group. Then, the observation group was matched with the control group at a ratio of 1:1 by using the propensity score matching method. We compared the surgical indicators, postoperative recovery indicators, physical indicators, pain, surgical stress-related indicators, inflammation indicators, immune indicators, quality of life, and postoperative complications between the two groups. RESULTS: We found that compared with the control group, the NOSES group had a shorter exhaust start time, getting out-of-bed activity time, length of hospital stay, bowel sound recovery time, and gastrointestinal peristalsis time. The Pittsburgh Sleep Quality Index (PSQI) and Positive and Negative Affect Schedule (PANAS) scores decreased in both groups after surgery, with the NOSES group showing a more significant reduction. The Visual Analogue Scale (VAS) scores decreased in both groups, and the NOSES group had lower VAS scores. Additionally, the NOSES group exhibited a significant interaction effect with time (intergroup effect: F = 497.800; time effect: F = 163.100; interaction effect: F = 5.307). Superoxide dismutase (SOD) levels decreased and malondialdehyde (MDA) levels increased in both groups postoperatively; however, the NOSES group had higher SOD levels and lower MDA levels. All the above comparisons were statistically significant (P < 0.05). There was no statistically significant difference in the total complication rates between the NOSES group and the control group (Z = -0.768, P = 0.442; χ2 = 2.333, P = 0.127). CONCLUSION: Compared to conventional laparoscopic surgery, NOSES results in less pain and injury, a more stable mood, faster recovery, and comparable safety.

Smart Implantable Hydrogel for Large Segmental Bone Regeneration.

Large segmental bone defects often lead to nonunion and dysfunction, posing a significant challenge for clinicians. Inspired by the intrinsic bone defect repair logic of "vascularization and then osteogenesis", this study originally reports a smart implantable hydrogel (PDS-DC) with high mechanical properties, controllable scaffold degradation, and timing drug release that can proactively match different bone healing cycles to efficiently promote bone regeneration. The main scaffold of PDS-DC consists of polyacrylamide, polydopamine, and silk fibroin, which endows it with superior interfacial adhesion, structural toughness, and mechanical stiffness. In particular, the adjustment of scaffold cross-linking agent mixing ratio can effectively regulate the in vivo degradation rate of PDS-DC and intelligently satisfy the requirements of different bone defect healing cycles. Ultimately, PDS hydrogel loaded with free desferrioxamine (DFO) and CaCO3 mineralized ZIF-90 loaded bone morphogenetic protein-2 (BMP-2) to stimulate efficient angiogenesis and osteogenesis. Notably, DFO is released rapidly by free diffusion, whereas BMP-2 is released slowly by pH-dependent layer-by-layer disintegration, resulting in a significant difference in release time, thus matching the intrinsic logic of bone defect repair. In vivo and in vitro results confirm that PDS-DC can effectively realize high-quality bone generation and intelligently regulate to adapt to different demands of bone defects.

Covalent Organic Framework Membranes with Regulated Orientation for Monovalent Cation Sieving.

Continuous covalent organic framework (COF) thin membranes have garnered broad concern over the past few years due to their merits of low energy requirements, operational simplicity, ecofriendliness, and high separation efficiency in the application process. This study marks the first instance of fabricating two distinct, self-supporting COF membranes from identical building blocks through solvent modulation. Notably, the precision of the COF membrane's separation capabilities is substantially enhanced by altering the pore alignment from a random to a vertical orientation. Within these confined channels, the membrane with vertically aligned pores and micron-scale stacking thickness demonstrates rapid and selective transportation of Li+ ions over Na+ and K+ ions, achieving Li+/K+ and Li+/Na+ selectivity ratios of 38.7 and 7.2, respectively. This research not only reveals regulated orientation and layer stacking in COF membranes via strategic solvent selection but also offers a potent approach for developing membranes specialized in Li+ ion separation.

Prevalence and treatment of autism spectrum disorder in the United States, 2016-2022.

This study aims to assess the prevalence of Autism Spectrum Disorder (ASD) and its treatment. The study population was children aged 3-17 years with information on current ASD from National Survey of Children's Health, 2016-2022. Analysis of treatment was also conducted within the population of children with a current ASD diagnosis. A multivariate log-binomial regression model was used to assess the change of current ASD prevalence and ASD treatment by two study period (prior to COVID-19 pandemic: 2016-2019; during COVID-19 pandemic: 2020-22) and sociodemographic information. Compared to the current ASD at 2.5% in 2016, it increased to 3.6% in 2022. The treatment has decreased from 70.5% in 2016 to 61.6% in 2022 for any treatment and from 27.2% in 2016 to 20.4% in 2022 for medication treatment. Compared to children from 2016-2019, children from the following group were more likely to have ASD diagnosis during the pandemic (2020-2022), including those aged 3-5 years (aPR = 1.66, 95%CI 1.29-2.13), non-Hispanic white children, children from family with above national family income, and those with private insurance. However, medication treatment almost halved during the pandemic for non-Hispanic black children (aPR = 0.49, 95%CI 0.26-0.93) and children born overseas. In conclusion, higher prevalence of ASD might indicate a better awareness of ASD. The reduction in treatment correlates to the health service disruption caused by the pandemic, highlighting the needs of policy efforts to improve treatment for ASD.

Four novel species of Pleurotheciaceae collected from freshwater habitats in Jiangxi Province, China.

During an investigation of fungal diversity from freshwater environments in different regions in Jiangxi Province, China, four interesting species were collected. Morphology coupled with combined gene analysis of an ITS, LSU, SSU, and rpb2 DNA sequence data showed that they belong to the family Pleurotheciaceae. Four new species, Pleurotheciella ganzhouensis, Pla. irregularis, Pla. verrucosa, and Pleurothecium jiangxiense are herein described. Pleurotheciella ganzhouensis is characterized by its capsule-shaped conidia and short conidiophores, while Pla. irregularis has amorphous conidiophores and 3-septate conidia. Pleurotheciella verrucosa has cylindrical or verrucolose conidiogenous cells, 1-septate, narrowly fusiform, meniscus or subclavate conidia. Pleurothecium jiangxiense characterized in having conidiogenous cells with dense cylindrical denticles and short conidiophores. Pleurothecium obovoideum was transferred to Neomonodictys based on phylogenetic evidence. All species are compared with other similar species and comprehensive descriptions, micrographs, and phylogenetic data are provided.

A DNA machine-based magnetic resonance imaging nanoprobe for in vivo microRNA detection.

In situ monitoring microRNA (miRNA) expression in vivo holds immense potential for directly visualizing the occurrence and progression of tumors. However, the significant barrier to developing a probe that can overcome the low abundance of miRNAs while providing an output signal with unlimited tissue penetration depth remains formidable. In this study, we developed a DNA machine-based magnetic resonance imaging nanoprobe (MRINP) for amplified detection of miR-21 in vivo. The MRINP was constructed with superparamagnetic Fe3O4 nanoparticles (NPs), paramagnetic Gd-DOTA complexes, and miR-21-activated DNA machines; the DNA machine was composed of hairpin DNAzyme (HD) strands serving as the DNAzyme walker and hairpin substrate (HS) strands serving as the track. Once uptake into tumor cells, the intracellular miR-21 specifically recognized and hybridized with the HD strand, restoring the activity of DNAzyme. Subsequently, the DNAzyme walker autonomously traveled on the surface of MRINP, and each step movement of the DNAzyme walker resulted in the cleavage of its substrate strands and the ensued release of the Gd-DOTA complex-labeled oligonucleotides, turning on the T1 signal of Gd-DOTA complexes for in situ imaging of miR-21 in tumor-bearing mice. This strategy would offer a promising approach for mapping tumor-specific biomarkers in vivo with unlimited penetration depth.

Transcriptomic profiling reveals the complex interaction between a bipartite begomovirus and a cucurbitaceous host plant.

BACKGROUND: Begomoviruses are major constraint in the production of many crops. Upon infection, begomoviruses may substantially modulate plant biological processes. While how monopartite begomoviruses interact with their plant hosts has been investigated extensively, bipartite begomoviruses-plant interactions are understudied. Moreover, as one of the major groups of hosts, cucurbitaceous plants have been seldom examined in the interaction with begomoviruses. RESULTS: We profiled the zucchini transcriptomic changes induced by a bipartite begomovirus squash leaf curl China virus (SLCCNV). We identified 2275 differentially-expressed genes (DEGs), of which 1310 were upregulated and 965 were downregulated. KEGG enrichment analysis of the DEGs revealed that many pathways related to primary and secondary metabolisms were enriched. qRT-PCR verified the transcriptional changes of twelve selected DEGs induced by SLCCNV infection. Close examination revealed that the expression levels of all the DEGs of the pathway Photosynthesis were downregulated upon SLCCNV infection. Most DEGs in the pathway Plant-pathogen interaction were upregulated, including some positive regulators of plant defenses. Moreover, the majority of DEGs in the MAPK signaling pathway-plant were upregulated. CONCLUSION: Our findings indicates that SLCCNV actively interact with its cucurbitaceous plant host by suppressing the conversion of light energy to chemical energy and inducing immune responses. Our study not only provides new insights into the interactions between begomoviruses and host plants, but also adds to our knowledge on virus-plant interactions in general.

Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.

Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice. In this study we investigated whether ginsenoside Rg1, a principal compound in ginseng notable for soothing the mind, could alleviate PD deterioration induced by psychological stress. Ten-month-old transgenic hαSyn A53T mice were subjected to 4 weeks' restraint stress to simulate chronic stress conditions that worsen PD, meanwhile the mice were treated with Rg1 (40 mg· kg-1 ·d-1, i.g.), and followed by functional magnetic resonance imaging (fMRI) and a variety of neurobehavioral tests. We showed that treatment with Rg1 significantly alleviated both motor and non-motor symptoms associated with PD. Functional MRI revealed that Rg1 treatment enhanced connectivity between brain regions implicated in PD, and in vivo multi-channel electrophysiological assay showed improvements in dyskinesia-related electrical activity. In addition, Rg1 treatment significantly attenuated the degeneration of dopaminergic neurons and reduced the pathological aggregation of αSyn in the striatum and SNc. We revealed that Rg1 treatment selectively reduced the level of the stress-sensitive protein RTP801 in SNc under chronic stress conditions, without impacting the acute stress response. HPLC-MS/MS analysis coupled with site-directed mutation showed that Rg1 promoted the ubiquitination and subsequent degradation of RTP801 at residues K188 and K218, a process mediated by the Parkin RING2 domain. Utilizing αSyn A53T+; RTP801-/- mice, we confirmed the critical role of RTP801 in stress-aggravated PD and its necessity for Rg1's protective effects. Moreover, Rg1 alleviated obstacles in αSyn autophagic degradation by ameliorating the RTP801-TXNIP-mediated deficiency of ATP13A2. Collectively, our results suggest that ginsenoside Rg1 holds promise as a therapeutic choice for treating PD-sensitive individuals who especially experience high levels of stress and self-imposed expectations.

Enrichment of antioxidant peptide from rice protein hydrolysates via rice husk derived biochar.

In this study, rice husk biochar was engineered with abundant iron ion sites to enhance the enrichment of antioxidant peptides from rice protein hydrolysates through metal-chelating interactions. The π-π interactions and metal ion chelation were identified as the primary mechanisms for the enrichment process. Through peptide sequencing, four peptides were identified: LKFL (P1: Leu-Lys-Phe-Leu), QLLF (P2: Gln-Leu-Leu-Phe), WLAYG (P3: Trp-Leu-Ala-Tyr-Gly), and HFCGG (P4: His-Phe-Cys-Gly-Gly). The vitro analysis and molecular docking revealed that peptides P1-P4 possessed remarkable scavenging ability against radicals and Fe2+ chelating ability. Notably, peptide P4 showed radical scavenging activity comparable to glutathione (GSH) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals. Cellular experiments further confirmed that peptide P4 effectively protected HepG2 cells from oxidative stress-induced damage. The modified rice husk biochar proved to be an effective means for enriching rice antioxidant peptides from protein hydrolysates.

Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism.

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence.

The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.

Enzymatic Synthesis of a Novel Antioxidant Octacosanol Lipoate and Its Antioxidant Potency in Sunflower Oil.

α-Lipoic acid possesses remarkable antioxidant activity; however, its poor lipid solubility greatly restricts its practical utilization. The present study was the first (i) to synthesize a novel lipophilic antioxidant of octacosanol lipoate and (ii) to assess its antioxidant potency in sunflower oil by hydrogen nuclear magnetic resonance (1H NMR) spectroscopy. In brief, octacosanol lipoate was successfully synthesized using octacosanol and lipoic acid as substrates and Candida sp. 99-125 lipase as a catalyst. The conversion of octacosanol lipoate could reach as high as 98.1% within merely 2 h, with an overall yield of 87.9%. The hydrophobicity of lipoic acid was significantly enhanced upon esterification with octacosanol. Interestingly, both traditional methods and 1H NMR analysis consistently indicated that octacosanol lipoate exhibited superior antioxidant activity compared with butyl hydroxytoluene at high temperatures. It was concluded that octacosanol lipoate has the potential to be developed into a safe and efficient natural antioxidant which can be utilized not only in daily cooking oils but also in frying oils.

Efficacy and safety of ritlecitinib in vitiligo patients across Fitzpatrick skin types with biomarker analyses.

Efficacy and safety of ritlecitinib (an oral JAK3/TEC family kinase inhibitor) were evaluated in patients with nonsegmental vitiligo (NSV) across Fitzpatrick skin types (FSTs). Patients with FST I-III ('light skin'; n = 247) and FST IV-VI ('dark skin'; n = 117) received once-daily ritlecitinib 50 mg (with/without 4-week loading dose), low-dose ritlecitinib or placebo for 24 weeks. At baseline, patients with light skin displayed higher CLM-1 and NCR1 serum levels than patients with dark skin (p < 0.05). At 24 weeks, ritlecitinib 50 mg improved the extent of depigmentation measured by percent change from baseline in facial-vitiligo area scoring index (placebo-adjusted mean difference [90% CI]) in patients with light (-15.2 [-24.7, -5.8]; p = 0.004) and dark (-37.4 [-50.3, -24.4]; p < 0.0001) skin, with continuous re-pigmentation through week 48. Treatment-emergent adverse events were similar across FSTs. At weeks 4 and 24, ritlecitinib 50 mg reduced CXCL11 serum levels (p < 0.001) in patients with light skin, whereas patients with dark skin had increased levels at week 4 (p = 0.05) and no significant change at week 24. Ritlecitinib 50 mg decreased IL-9 and IL-22 expression levels in dark skin compared with light skin (qPCR; p < 0.05). These differences in immune dysregulations may explain why NSV patients with dark skin respond to therapy earlier than patients with light skin.

Oral administration of astilbin mitigates acetaminophen-induced acute liver injury in mice by modulating the gut microbiota.

Acetaminophen (APAP) overdose-induced acute liver injury (ALI) is characterized by extensive oxidative stress, and the clinical interventions for this adverse effect remain limited. Astilbin is an active compound found in the rhizome of Smilax glabra Roxb. with anti-inflammatory and antioxidant activities. Due to its low oral bioavailability, astilbin can accumulate in the intestine, which provides a basis for the interaction between astilbin and gut microbiota (GM). In the present study we investigated the protective effects of astilbin against APAP-induced ALI by focusing on the interaction between astilbin and GM. Mice were treated with astilbin (50 mg·kg-1·d-1, i.g.) for 7 days. After the last administration of astilbin for 2 h, the mice received APAP (300 mg/kg, i.g.) to induce ALI. We showed that oral administration of astilbin significantly alleviated APAP-induced ALI by altering the composition of GM and enriching beneficial metabolites including hydroxytyrosol (HT). GM depletion using an "antibiotics cocktail" or paraoral administration of astilbin abolished the hepatoprotective effects of astilbin. On the other hand, administration of HT (10 mg/kg, i.g.) caused similar protective effects in APAP-induced ALI mice. Transcriptomic analysis of the liver tissue revealed that HT inhibited reactive oxygen species and inflammation-related signaling in APAP-induced ALI; HT promoted activation of the Nrf2 signaling pathway to combat oxidative stress following APAP challenge in a sirtuin-6-dependent manner. These results highlight that oral astilbin ameliorates APAP-induced ALI by manipulating the GM and metabolites towards a more favorable profile, and provide an alternative therapeutic strategy for alleviating APAP-induced ALI.