Cancer-associated fibroblasts-secreted exosomal miR-92a-3p promotes tumor growth and stemness in hepatocellular carcinoma through activation of Wnt/ß-catenin signaling pathway by suppressing AXIN1.

Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor-promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR-92a-3p expression was then measured using reverse transcriptase quantitative real-time PCR in CAFs, NFs, CAFs-derived exosomes (CAFs-Exo), and NF-derived exosomes (NFs-Exo). Compared to NFs or NF-Exo, CAFs and CAFs-Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF-Exo, miR-92a-3p level was notably higher in CAFs and CAFs-Exo, respectively. Exosomal miR-92a-3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR-92a-3p. Exosomal miR-92a-3p could activate ß-catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR-92a-3p notably promoted tumor growth and stemness through targeting AXIN1/ß-catenin axis. Collectively, CAFs secreted exosomal miR-92a-3p was capable of promoting growth and stemness in HCC through activation of Wnt/ß-catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs-derived miR-92a-3p may be a potential strategy for treating HCC.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence.

The dual catalysis strategy is an efficient and powerful tool to fulfill the stereodivergent synthesis of stereoisomeric products from the same set of starting materials. Great attention has been given to the construction of chiral compounds with two contiguous stereocenters. However, the synthesis of two remote noncontiguous stereocenters is more challenging and is less developed, despite the high demand for synthetic tactics. We herein developed an unprecedented example of the stereodivergent preparation of synthetically useful and biologically important chiral ζ-hydroxy amino ester derivatives containing remote 1,6-noncontiguous stereocenters and a unique ß,γ-unsaturation moiety. This cascade dehydrogenation/1,6-Michael addition/hydrogenation protocol between readily-available ketoimine esters and racemic branched dienyl carbinols was rationally realized with bimetallic copper/ruthenium relay catalysis. The key features of the process were atom economy, step economy, and redox-neutrality. All four stereoisomers of chiral ζ-hydroxy amino ester derivatives were easily achieved by the orthogonal permutations of a chiral copper catalyst and chiral ruthenium catalyst. Importantly, a much more challenging stereodivergent synthesis of all eight stereoisomers of chiral peptide products containing three remote stereocenters was accomplished with excellent results through the cooperation of two chiral catalyst pairs and substrate enantiomers.

Exploring the bidirectional causal associations between pain and circulating inflammatory proteins: A Mendelian randomization study.

Multisite chronic pain (MCP) and site-specific chronic pain (SSCP) may be influenced by circulating inflammatory proteins, but the causal relationship remains unknown. To overcome this limitation, two-sample bidirectional Mendelian randomization (MR) analysis was used to analyse data for 91 circulating inflammatory proteins, MCP and SSCP encompassing headache, back pain, shoulder pain, hip pain, knee pain, stomach abdominal pain and facial pain. The primary MR method used was inverse variance weighting, sensitivity analyses included weighted median, MR pleiotropy residual sum and outlier and the Egger intercept method. Heterogeneity was also detected using Cochrane's Q test and leave-one-out analyses. Finally, a causal relationship between 29 circulating inflammatory proteins and chronic pain was identified. Among these proteins, 14 exhibited a protective effect, including MCP (T-cell surface glycoprotein cluster of differentiation 5), headache (4E-binding protein 1 [4EBP1], cluster of differentiation 40, cluster of differentiation 6 and C-X-C motif chemokine [CXCL] 11), back pain (leukaemia inhibitory factor), shoulder pain (fibroblast growth factor [FGF]-5 and interleukin [IL]-18R1), stomach abdominal pain (tumour necrosis factor [TNF]-α), hip pain (CXCL1, IL-20 and signalling lymphocytic activation molecule 1) and knee pain (IL-7 and TNF-ß). Additionally, 15 proteins were identified as risk factors for MCP and SSCP: MCP (colony-stimulating factor 1, human glial cell line-derived neurotrophic factor and IL-17C), headache (fms-related tyrosine kinase 3 ligand, IL-20 receptor subunit α [IL-20RA], neurotrophin-3 and tumour necrosis factor receptor superfamily member 9), facial pain (CXCL1), back pain (TNF), shoulder pain (IL-17C and matrix metalloproteinase-10), stomach abdominal pain (IL-20RA), hip pain (C-C motif chemokine 11/eotaxin-1 and tumour necrosis factor ligand superfamily member 12) and knee pain (4EBP1). Importantly, in the opposite direction, MCP and SSCP did not exhibit a significant causal impact on circulating inflammatory proteins. Our study identified potential causal influences of various circulating inflammatory proteins on MCP and SSCP and provided promising treatments for the clinical management of MCP and SSCP.

Microstructure Evolution of Reactive Polyurethane Films During In Situ Polyaddition and Film-Formation Processes.

Due to the advantages of low energy consumption, no air and water pollutions, the reactive polyurethane films (RPUFs) are replacing the solvated and waterborne PUFs nowadays, which significantly promotes the green and low-carbon production of PU films. However, the microstructure evolution and in situ film-formation mechanism of RPUFs in solvent-free media are still unclear. Herein, according to time-temperature equivalence principle, the in situ polyaddition and film-formation processes of RPUFs generated by the typical polyaddition of diisocyanate terminated prepolymer (component B) and polyether glycol (component A) are thoroughly investigated at 25 °C. According to the temporal change of viscosity, the RPUFs gradually transfer from liquid to gel and finally to solid state. Further characterizing the molecular weight, hydrogen bonds, crystallinity, gel content, and phase images, the polyaddition and film-formation processes can be divided into three stages as 1) chain extension and microcrystallization; 2) gelation and demicrocrystallization; 3) microphase separation and film-formation. This work promotes the understanding of the microstructure evolution and film-formation mechanism of RPUFs, which can be used as the theoretical guidance for the controllable preparation of high-performance products based on RPUFs.

Insights into starch synthesis and amino acid composition of common buckwheat in response to phosphate fertilizer management strategies.

To investigate the response and the regulatory mechanism of common buckwheat starch, amylose, and amylopectin biosynthesis to P management strategies, field experiments were conducted in 2021 and 2022 using three phosphorus (P) levels. Results revealed that the application of 75 kg hm-2 phosphate fertilizer significantly enhanced amylopectin and total starch content in common buckwheat, leading to improved grain weight and starch yield, and decreased starch granule size. The number of upregulated differentially expressed proteins induced by phosphate fertilizer increased with the application rate, with 56 proteins identified as shared differential proteins between different P levels, primarily associated with carbohydrate and amino acid metabolism. Phosphate fertilizer inhibited amylose synthesis by downregulating granule-bound starch synthase protein expression and promoted amylopectin accumulation by upregulating 1,4-alpha-glucan branching enzyme and starch synthase proteins expression. Additionally, Phosphate fertilizer primarily promoted the accumulation of hydrophobic and essential amino acids. These findings elucidate the mechanism of P-induced starch accumulation and offer insights into phosphate fertilizer management and high-quality cultivation of common buckwheat.

Effect of a Thermosensitive Hydroxybutyl Chitosan Hydrogel on Postoperative Sequalae and Quality of Life After Impacted Mandibular Third Molar Extraction.

BACKGROUND: Third molar (M3) extraction is a common surgery in oral and maxillofacial surgery, and composite wound dressings such as hydroxybutyl chitosan (HBC) may improve postoperative sequala following M3 removal. PURPOSE: The study purpose was to measure and compare differences in pain, swelling, trismus, wound healing, and quality of life (QOL) between the HBC and the control sides in patients undergoing M3 removal. STUDY DESIGN, SETTING, SAMPLE: This study is a double-blind, split-mouth, randomized clinical trial. Patients who required M3 removal between June 2022 and May 2023 were included. Exclusion criteria included seafood allergies, smoking, poor oral hygiene, and systemic diseases. PREDICTOR VARIABLE: The predictor variable was the socket treatment technique. Subjects were randomly assigned to the HBC or control (physiological saline) side. MAIN OUTCOME VARIABLE: The primary outcome variables, including pain assessed by visual analog scale, swelling, and maximal incisional opening, were measured on the first, third, and seventh postoperative days. The secondary outcome variables included QOL and wound healing score measured on the third and seventh days after surgery. COVARIATES: The covariates included age, sex, and operation time. ANALYSES: The Shapiro‒Wilk test was used to evaluate the normality of the data distribution. The paired t test or Wilcoxon signed-rank test was adopted. Statistical significance was set at P < .05. RESULTS: The study included 60 patients (mean age: 25.81 ± 4.91; 23 (38%) males, 37 (62%) females). A statistically significant difference in the level of pain (HBC: 37.58 ± 4.39 mm, control: 47.00 ± 4.33 mm, day 1, P < .001; 21.88 ± 3.25 mm, 35.95 ± 1.57 mm, day 3, P < .001), maximal incisional opening (23.92 ± 1.38 mm, 18.22 ± 1.82 mm, day 1, P < .001; 30.00 ± 1.61 mm, 23.78 ± 1.70 mm, day 3, P < .001), and swelling (6.86 ± 0.70 mm, 7.15 ± 0.80 mm, day 3, P = .006) was detected after surgery. A statistically significant difference in QOL was detected (HBC: 13.70 ± 1.65, control: 18.60 ± 2.14, day 3, P < .001). CONCLUSION AND RELEVANCE: The application of HBC hydrogels to wounds after impacted mandibular M3 extraction reduces postoperative sequalae, promotes wound healing and improves postoperative QOL.

Identification of lignans as selective cyclooxygenase-2 inhibitors from the extract of Acanthopanacis cortex.

Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1-4) and 12 known lignans (5-16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1-16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1-16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6∼8 and 13∼16 demonstrate better COX-2 inhibitory effects with IC50 values from 0.75 to 8.17 µΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors.

Covalent Bonding of Salen Metal Complexes with Pyrene Chromophores to Porous Polymers for Photocatalytic Hydrogen Evolution.

The development of low-cost and efficient photocatalysts to achieve water splitting to hydrogen (H2) is highly desirable but remains challenging. Herein, we design and synthesize two porous polymers (Co-Salen-P and Fe-Salen-P) by covalent bonding of salen metal complexes and pyrene chromophores for photocatalytic H2 evolution. The catalytic results demonstrate that the two polymers exhibit excellent catalytic performance for H2 generation in the absence of additional noble-metal photosensitizers and cocatalysts. Particularly, the H2 generation rate of Co-Salen-P reaches as high as 542.5 µmol g-1 h-1, which is not only 6 times higher than that of Fe-Salen-P but also higher than a large amount of reported Pt-assisted photocatalytic systems. Systematic studies show that Co-Salen-P displays faster charge separation and transfer efficiencies, thereby accounting for the significantly improved photocatalytic activity. This study provides a facile and efficient way to fabricate high-performance photocatalysts for H2 production.

Metabolites of blueberry roots at different developmental stages strongly shape microbial community structure and intra-kingdom interactions at the root-soil interface.

The rhizosphere microorganisms of blueberry plants have long coexisted with their hosts under distinctively acidic soil conditions, exerting a profound influence on host performance through mutualistic symbiotic interactions. Meanwhile, plants can regulate rhizosphere microorganisms by exerting host effects to meet the functional requirements of plant growth and development. However, it remains unknown how the developmental stages of blueberry plants affect the structure, function, and interactions of the rhizosphere microbial communities. Here, we examined bacterial communities and root metabolites at three developmental stages (flower and leaf bud development stage, fruit growth and development stage, and fruit maturation stage) of blueberry plants. The results revealed that the Shannon and Chao 1 indices as well as community composition varied significantly across all three developmental stages. The relative abundance of Actinobacteria significantly increased by 10 % (p < 0.05) from stage 1 to stage 2, whereas that of Proteobacteria decreased significantly. The co-occurrence network analysis revealed a relatively complex network with 1179 edges and 365 nodes in the stage 2. Niche breadth was highest at stage 2, while niche overlap tended to increase as the plant developed. Furthermore, the untargeted metabolome analysis revealed that the number of differential metabolites of vitamins, nucleic acids, steroids, and lipids increased between stage 1 to stage2 and stage 2 to stage 3, while those for differential metabolites of carbohydrates and peptides decreased. Significant changes in expression levels of levan, L-glutamic acid, indoleacrylic acid, oleoside 11-methyl ester, threo-syringoylglycerol, gingerglycolipid B, and bovinic acid were highly correlated with the bacterial community structure. Collectively, our study reveals that significant alterations in dominant bacterial taxa are strongly correlated with the dynamics of root metabolites. These findings lay the groundwork for developing prebiotic products to enhance the beneficial effects of root microorganisms and boosting blueberry productivity via a sustainable approach.

Ultrathin carbon film as ultrafast rechargeable cathode for hybrid sodium dual-ion capacitor.

The development of electrochemical energy storage devices has a decisive impact on clean renewable energy. Herein, novel ultrafast rechargeable hybrid sodium dual-ion capacitors (HSDICs) were designed by using ultrathin carbon film (UCF) as the cathode material. The UCF is synthesized by a simple low temperature catalytic route followed by an acid leaching process. UCF owns a large adsorption interface and number of additional active sites, which is due to the nitrogen doping. In addition, there exists several short-range order carbons on the surface of UCF, which are beneficial for anionic storage. An ultrafast rechargeable remarkable performance, remarkable anion hybrid storage capability and outstanding structure stability is fully tapped employing UCF as cathode for HSDICs. The electrochemical performance of UCF in a half-cell system at the operating voltage between 1.0 and 4.8 V, achieving an admirable specific discharge capacity of 358.52 mAh·g-1at 500 mA·g-1, and a high capacity retention ratio of 98.42% after cycling 2500 times at 1000 mA·g-1, respectively. Besides, with the support ofex-situTEM and EDS mapping, the structural stability principle and anionic hybrid storage mechanism of UCF electrode are investigated in depth. In the full-cell system, HSDICs with the UCF as cathode and hard carbon as anode also presents a super-long cycle stability (80.62% capacity retention ratio after cycling 1300 times at 1000 mA·g-1).

Ameliorated Effects of Fucoidan on Dextran Sulfate Sodium-Induced Ulcerative Colitis and Accompanying Anxiety and Depressive Behaviors in Aged C57BL/6 Mice.

Fucoidan has shown better effects on the improvement of acute ulcerative colitis (UC). However, the specific mechanisms by which fucoidan improves UC-related behavioral disorders in aged mice, especially its effect on the gut-brain axis, remain to be further explored. C57BL/6 male mice aged 8 months were gavaged with 400 or 100 mg/kg bw day fucoidan for five consecutive weeks, with UC being induced by ad libitum to dextran sulfate sodium (DSS) solution in the fifth week. The results showed that fucoidan ameliorated UC and accompanying anxiety- and depressive-like behaviors with downregulated expressions of (NOD)-like receptor family and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteine aspartate-specific protease-1 (Caspase-1) and interlekin-1ß (IL-1ß), and elevated mRNA levels of brain-derived neurotrophic factor (Bdnf) and postsynaptic-density protein 95 (Psd-95) in cortex and hippocampus. Furthermore, fucoidan improved the permeability of intestinal barrier and blood-brain barrier and restored the abnormal structure of the gut microbiota with a significantly decreased ratio of Firmicutes to Bacteroidota (F/B) and obviously increased abundance of Akkermansia. As a diet-derived bioactive ingredient, fucoidan might be a better alternative for the prevention of UC and accompanying anxiety- and depressive-like behaviors.

Exciton-Phonon Coupling Induces a New Pathway for Ultrafast Intralayer-to-Interlayer Exciton Transition and Interlayer Charge Transfer in WS2-MoS2 Heterostructure: A First-Principles Study.

Despite the weak, van der Waals interlayer coupling, photoinduced charge transfer vertically across atomically thin interfaces can occur within surprisingly fast, sub-50 fs time scales. An early theoretical understanding of charge transfer is based on a noninteracting picture, neglecting excitonic effects that dominate optical properties of such materials. We employ an ab initio many-body perturbation theory approach, which explicitly accounts for the excitons and phonons in the heterostructure. Our large-scale first-principles calculations directly probe the role of exciton-phonon coupling in the charge dynamics of the WS2/MoS2 heterobilayer. We find that the exciton-phonon interaction induced relaxation time of photoexcited excitons at the K valley of MoS2 and WS2 is 67 and 15 fs at 300 K, respectively, which sets a lower bound to the intralayer-to-interlayer exciton transfer time and is consistent with experiment reports. We further show that electron-hole correlations facilitate novel transfer pathways that are otherwise inaccessible to noninteracting electrons and holes.

Modulating built-in electric field via Bi-VO4-Fe interfacial bridges to enhance charge separation for efficient photoelectrochemical water splitting.

Photoelectrochemical (PEC) water splitting on semiconductor electrodes is considered to be one of the important ways to produce clean and sustainable hydrogen fuel, which is a great help in solving energy and environmental problems. Bismuth vanadate (BiVO4) as a promising photoanode for photoelectrochemical water splitting still suffers from poor charge separation efficiency and photo-induced self-corrosion. Herein, we develop heterojunction-rich photoanodes composed of BiVO4 and iron vanadate (FeVO4), coated with nickel iron oxide (NiFeOx/FeVO4/BiVO4). The formation of the interface between BiVO4 and FeVO4 (Bi-VO4-Fe bridges) enhances the interfacial interaction, resulting in improved performance. Meanwhile, high-conductivity FeVO4 and NiFeOx oxygen evolution co-catalysts effectively enhance bulk electron/hole separation, interface water's kinetics and photostability. Concurrently, the optimized NiFeOx/FeVO4/BiVO4 possesses a remarkable photocurrent density of 5.59 mA/cm2 at 1.23 V versus reversible hydrogen electrode (vs RHE) under AM 1.5G (Air Mass 1.5 Global) simulated sunlight, accompanied by superior stability without any decreased of its photocurrent density after 14 h. This work not only reveals the crucial role of built-in electric field in BiVO4-based photoanode during PEC water splitting, but also provides a new guide to the design of efficient photoanode for PEC.

Urbanization significantly increases greenhouse gas emissions from a subtropical headwater stream in Southeast China.

Streams are disproportionately significant contributors to increases in greenhouse gas (GHG) effluxes in river networks. In the context of global urbanization, a growing number of streams are affected by urbanization, which has been suggested to stimulate the water-air GHG emissions from fluvial systems. This study investigated the seasonal and longitudinal profiles of GHG (N2O, CH4, and CO2) concentrations of Jiuxianghe Stream, a headwater stream undergoing urbanization, and estimated its GHG diffusive fluxes and global warming potentials (GWPs) using the boundary layer method. The results showed that N2O, CH4, and CO2 concentrations in Jiuxianghe Stream were 0.45-7.19 µg L-1, 0.31-586.85 µg L-1, and 0.16-11.60 mg L-1, respectively. N2O, CH4, and CO2 concentrations in the stream showed 4.55-, 23.70-, and 7.68-fold increases from headwaters to downstream, respectively, corresponding to the forest-urban transition within the watershed. Multiple linear regression indicated that NO3--N, NH4+-N, and DOC:NO3--N accurately predicted N2O and CO2 concentrations, indicating that N nutrients were the driving factors. The Jiuxianghe Stream was a source of atmospheric GHGs with a daily GWP of 7.31 g CO2-eq m-2 d-1 on average and was significantly positively correlated with the ratio of construction land and forest in the sub-watershed. This study highlights the critical role of urbanization in amplifying GHG emissions from streams, thereby augmenting our understanding of GHG emissions from river networks. With global urbanization on the rise, streams experiencing urbanization are expected to make an unprecedentedly significant contribution to riverine GHG budgets in the future.

Research on the mechanism of Guanyu Zhixie Granule in intervening gastric ulcers in rats based on network pharmacology and multi-omics.

Objective: Guanyu Zhixie Granule (GYZXG) is a traditional Chinese medicine compound with definite efficacy in intervening in gastric ulcers (GUs). However, the effect mechanisms on GU are still unclear. This study aimed to explore its mechanism against GU based on amalgamated strategies. Methods: The comprehensive chemical characterization of the active compounds of GYZXG was conducted using UHPLC-Q/TOF-MS. Based on these results, key targets and action mechanisms were predicted through network pharmacology. GU was then induced in rats using anhydrous ethanol (1 mL/200 g). The intervention effects of GYZXG on GU were evaluated by measuring the inhibition rate of GU, conducting HE staining, and assessing the levels of IL-6, TNF-α, IL-10, IL-4, Pepsin (PP), and epidermal growth factor (EGF). Real-time quantitative PCR (RT-qPCR) was used to verify the mRNA levels of key targets and pathways. Metabolomics, combined with 16S rRNA sequencing, was used to investigate and confirm the action mechanism of GYZXG on GU. The correlation analysis between differential gut microbiota and differential metabolites was conducted using the spearman method. Results: For the first time, the results showed that nine active ingredients and sixteen targets were confirmed to intervene in GU when using GYZXG. Compared with the model group, GYZXG was found to increase the ulcer inhibition rate in the GYZXG-M group (p < 0.05), reduce the levels of IL-6, TNF-α, PP in gastric tissue, and increase the levels of IL-10, IL-4, and EGF. GYZXG could intervene in GU by regulating serum metabolites such as Glycocholic acid, Epinephrine, Ascorbic acid, and Linoleic acid, and by influencing bile secretion, the HIF-1 signaling pathway, and adipocyte catabolism. Additionally, GYZXG could intervene in GU by altering the gut microbiota diversity and modulating the relative abundance of Bacteroidetes, Bacteroides, Verrucomicrobia, Akkermansia, and Ruminococcus. The differential gut microbiota was strongly associated with serum differential metabolites. KEGG enrichment analysis indicated a significant role of the HIF-1 signaling pathway in GYZXG's intervention on GU. The changes in metabolites within metabolic pathways and the alterations in RELA, HIF1A, and EGF mRNA levels in RT-qPCR experiments provide further confirmation of this result. Conclusion: GYZXG can intervene in GU induced by anhydrous ethanol in rats by regulating gut microbiota and metabolic disorders, providing a theoretical basis for its use in GU intervention.

Enhancing corn stalk-based anaerobic digestion with different types of zero-valent iron added during the acidification stage: Performance and mechanism.

Anaerobic digestion has been defined as a competitive approach to facilitate the recycling of corn stalks. However, few studies have focused on the role of direct interspecies electron transfer (DIET) pathway in the acidification stage under the addition of different particle sizes of zero-valent iron (ZVI). In this study, three types of ZVI, namely iron filings, iron powder and nanoscale iron, were investigated, respectively, to enhance its high-value conversion. Variations in volatile fatty acids (VFAs) and methane (CH4) production associated with the underlying mechanisms were emphatically determined. Results indicated that the addition of ZVI could increase the concentration of VFAs, with the most outstanding performance observed with the use of nanoscale iron. Importantly, the conversion of propionic acid to acetic acid was driven by adding ZVI with no between-group differences in acidizing phase. Conversely, the substrate was more fully utilized when supplied with iron powder compared with other groups in methanogenic phase, thereby displaying the maximum CH4 yield with a value of 263.1 mL/(g total solids (TS)). However, adding nanoscale iron could signally shorten the digestion time (T80), saving 7 days in comparison to the group of iron powder.

Targeting Nr2e3 to Modulate Tet2 Expression: Therapeutic Potential for Depression Treatment.

Epigenetic mechanisms such as DNA methylation and hydroxymethylation play a significant role in depression. This research has shown that Ten-eleven translocation 2 (Tet2) deficiency prompts depression-like behaviors, but Tet2's transcriptional regulation remains unclear. In the study, bioinformatics is used to identify nuclear receptor subfamily 2 group E member 3 (Nr2e3) as a potential Tet2 regulator. Nr2e3 is found to enhance Tet2's transcriptional activity by binding to its promoter region. Nr2e3 knockdown in mouse hippocampus leads to reduced Tet2 expression, depression-like behaviors, decreased hydroxymethylation of synaptic genes, and downregulation of synaptic proteins like postsynaptic density 95 KDa (PSD95) and N-methy-d-aspartate receptor 1 (NMDAR1). Fewer dendritic spines are also observed. Nr2e3 thus appears to play an antidepressant role under stress. In search of potential treatments, small molecule compounds to increase Nr2e3 expression are screened. Azacyclonal (AZA) is found to enhance the Nr2e3/Tet2 pathway and exhibited antidepressant effects in stressed mice, increasing PSD95 and NMDAR1 expression and dendritic spine density. This study illuminates Tet2's upstream regulatory mechanism, providing a new target for identifying early depression biomarkers and developing treatments.

Supragingival microbiome variations and the influence of Candida albicans in adolescent orthodontic patients with gingivitis.

Introduction: Gingivitis is a prevalent complication in adolescents undergoing fixed orthodontic treatments. However, changes in the supragingival microbiome associated with gingivitis and the impact of Candida albicans remain elusive. Therefore, we investigated supragingival microbiome discrepancy and C. albicans colonization in adolescent orthodontic patients with gingivitis. Methods: Dental plaques were collected from 30 gingivitis patients and 24 healthy adolescents, all undergoing fixed orthodontic treatment. The supragingival microbiome composition was analyzed using 16S rRNA sequencing. C. albicans colonization was determined using fungal culture and real-time quantitative polymerase chain reaction. Results: Our analysis revealed significantly heightened microbial diversity in the Gingivitis group. Notably, patients with gingivitis exhibited an enrichment of periodontal pathogens, such as Saccharibacteria (TM7) [G-1], Selenomonas, Actinomyces dentalis, and Selenomonas sputigena. Additionally, 33% of the gingivitis patients tested positive for C. albicans, exhibiting significantly elevated levels of absolute abundance, while all healthy patients tested negative. Significant differences in microbial composition were also noted between C. albicans-positive and -negative samples in the Gingivitis group. Conclusion: Significant disparities were observed in the supragingival microbiome of adolescent orthodontic patients with and without gingivitis. The presence of C. albicans in the supragingival plaque may alter the microbiome composition and potentially contribute to gingivitis pathogenesis.

• Adolescent patients undergoing fixed orthodontic treatment, with and without gingivitis, show significant differences in their marginal supragingival plaque microbiomes. • Adolescent patients with gingivitis exhibit a significantly higher rate of Candida albicans colonization than healthy individuals. • The colonization of C. albicans alters the composition of the marginal supragingival plaque microbiome in patients with gingivitis.

Genetic link between depression and musculoskeletal disorders: insights from Mendelian randomization analysis.

Background: The association between depression and musculoskeletal diseases has long been a subject of contentious debate. However, the causal relationship between the two remains uncertain. This study employs a two-sample Mendelian randomization (MR) analysis to investigate the causality between depression and six musculoskeletal diseases. Methods: In this study, we performed MR analysis to systematically explore the causal relationship between depression and six musculoskeletal disorders. Single nucleotide polymorphisms (SNPs) that are linked to depression were employed as instrumental variables. To ensure robust and reliable conclusions, multiple analytical approaches were utilized, including inverse variance weighting(IVW), weighted median, and MR-Egger regression. Additionally, sensitivity analysis methods such as the MR-Egger intercept test, Cochran's Q test, leave-one-out analysis, and funnel plot were employed. Results: Our MR analysis revealed a significant association between depression and cervical spondylosis (depression: OR 1.003, 95% CI 1.002-1.005, P = 8.32E-05; major depressive disorder: OR 1.003, 95% CI 1.001-1.005, P = 0.0052). Furthermore, a strong correlation was noted between major depressive disorder (MDD) and knee osteoarthritis (KOA) (OR 1.299, 95% CI 1.154-1.463, P = 1.50E-5). Sensitivity analysis confirmed the robustness of these findings. Our independent validation study also corroborated these results. Conclusion: The MR analysis conducted in this study provides evidence supporting a genetic link between depression and cervical spondylosis, as well as KOA. Targeted interventions to manage depression in susceptible populations may contribute to lowering the risk of cervical spondylosis and KOA in these cohorts.