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Aims: This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults. Methods: The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023. Results: The results revealed that vitamin K supplementation increased BMD at the lumbar spine (p = 0.035). Moreover, the pooled effects demonstrated a notable increase in carboxylated osteocalcin (cOC) (p = 0.004), a decrease in uncarboxylated osteocalcin (ucOC) (p < 0.001), and no significant effect on total osteocalcin (tOC) (p = 0.076). Accordingly, the ratio of cOC to ucOC (p = 0.002) significantly increased, while the ratio of ucOC to tOC decreased (p = 0.043). However, there was no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (NTx), bone alkaline phosphatase (BAP), and procollagen I N-terminal propeptide (PINP). Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine BMD (p = 0.028) and decreasing ucOC (p < 0.001). Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC. Conclusion: This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of OC rather than altering the total amount of OC. Cite this article: Bone Joint Res 2024;13(12):750–763.

BackgroundVagus nerve stimulation (VNS) has emerged as a promising therapeutic approach for stroke treatment, drawing significant attention due to its potential benefits. However, despite this growing interest, a systematic bibliometric analysis of the research landscape is yet to be conducted.MethodsWe performed a comprehensive search of the Web of Science Core Collection (WoSCC) database for literature published between January 1, 2005, and August 31, 2024. CiteSpace and the Bibliometrix package in R software were used to generate knowledge maps and conduct a bibliometric analysis. This analysis focused on publication output, geographic distribution, institutional involvement, author and co-cited author networks, journal and co-cited journal relationships, co-cited references, and keyword trends.ResultsDuring the study period, 316 publications on VNS in stroke were identified, authored by 1,631 researchers from 1,124 institutions across 172 countries or regions. The number of publications showed steady growth, with the United States of America (USA) leading as the primary contributor. The University of Texas System emerged as the most active research institution. Frontiers in Neuroscience published the highest number of articles, while Stroke had the most citations. Professor Michael P. Kilgard authored the largest number of papers and was also the most frequently cited researcher. The main research trends focus on investigating VNS mechanisms via animal models and exploring its application in improving post-stroke sensorimotor function in the upper limbs. Moreover, VNS is showing promise in enhancing non-motor functions, such as swallowing, speech, and cognition, while addressing complications like post-stroke insomnia, depression, and disruptions in gut microbiota.ConclusionThis bibliometric study offers a comprehensive overview of the research landscape and emerging trends in VNS for stroke rehabilitation, providing a solid foundation and reference point for future research directions in this field.

The Saihanba Mechanical Forest is an artificial national forest park with a forest-steppe landscape. The flora and fauna have been extensively studied, but a comprehensive understanding of the bacterial community composition and structure of the natural rainwater lakes present in the area has rarely been reported. In this study, the structure and functional characteristics of bacterial communities in lake sediments and water samples in the Saihanba artificial forest were investigated using 16s rRNA high-throughput sequencing. Microbial diversity analyses revealed that Proteobacteria, Acidobacteria, Bacteroidota and Verrucomicrobiota microbiota dominated. The abundance of Proteobacteria and Actinobacteriota was significantly higher (p

Abstract Aim To evaluate the potential role of serum and tissue hsa_circ_0008621 as a prognostic biomarker for CRC patients. Focused on the functional role of hsa_circ_0008621 in colorectal cancer (CRC). Methods Serum and tissue hsa_circ_0008621 expression were quantified by qRT‐PCR in 157 CRC patients, as well as 100 serums from healthy controls. Serum and tissue hsa_circ_0008621 expression was evaluated for their prognostic role in CRC patients using Kaplan–Meier curves and Multivariate Cox proportional hazards analysis. To further characterize the biological role of hsa_circ_0008621 expression in CRC, in vitro hsa_circ_0008621 inhibition was performed and the effects on cellular growth, migration, invasion, apoptosis, and glycolysis were explored. Next, the downstream molecules for hsa_circ_0008621 were predicted. Results Hsa_circ_0008621 expression was significantly upregulated in CRC tissues and serums. Serum hsa_circ_0008621 levels were significantly up‐regulated in advanced‐staged samples. High serum hsa_circ_0008621 expression was associated with shorter overall survival and recurrence‐free survival in CRC patients. Multivariate Cox regression analysis identified a high level of serum hsa_circ_0008621 expression as an independent prognostic factor with respect to overall survival and recurrence‐free survival. Loss of function assays for hsa_circ_0008621 in vitro led to a significant decrease in cell proliferation, migration, invasion, and glycolysis, but an increase in cell apoptosis. Hsa_circ_0008621 can sponge miR‐532‐5p, which targets SLC16A3. Conclusion High level of serum hsa_circ_0008621 is associated with poor survival in CRC and promotes CRC progression, suggesting it to be a promising non‐invasive prognostic biomarker and novel therapeutic target in CRC patients.

Hepatic myelopathy (HM) is a rare complication of end-stage chronic liver disease, primarily presenting as symmetrical lower limb weakness that progresses to spastic paralysis without sensory or sphincter dysfunction. We report a case of decompensated cirrhosis associated with hepatitis B virus and HM. The patient showed significant recovery after liver transplantation (LT) and comprehensive rehabilitation training. We summarize the patient’s clinical characteristics post-diagnosis and the assessment outcomes following integrated treatment.

Abstract Most deaths in breast cancer patients are attributed to metastasis, and lung metastasis is associated with a particularly poor prognosis; therefore it is imperative to identify potential target for intervention. The transforming growth factor‐β (TGF‐β) pathway plays a vital role in breast cancer metastasis, in which Smad3 is the key mediator and performs specific functions by binding with different cofactors. However, Smad3 cofactors involved in lung metastasis have not yet been identified. This study first establishes the interactome of Smad3 in breast cancer cells and identifies ZNF8 as a novel Smad3 cofactor. Furthermore, the results reveal that ZNF8 is closely associated with breast cancer lung metastasis prognosis, and specifically facilitates TGF‐β pathway‐mediated breast cancer lung metastasis by participating in multiple processes. Mechanistically, ZNF8 binds with Smad3 to enhance the H3K4me3 modification and promote the expression of lung metastasis signature genes by recruiting SMYD3. SMYD3 inhibition by BCI121 effectively prevents ZNF8‐mediated lung metastasis. Overall, the study identifies a novel cofactor of TGF‐β/Smad3 that promotes lung metastasis in breast cancer and introduces potential therapeutic strategies for the early management of breast cancer lung metastasis.

Objective: TPMS porous structures have adjustable stiffness, a smooth surface, and highly connected pores, which help avoid stress concentration within the dot-matrix structure and promote cell adhesion and proliferation. A cervical interbody cage based on this type of porous structure was designed and fabricated, and its mechanical properties and biocompatibility were evaluated. Methods: TPMS porous structures have adjustable stiffness, a smooth surface, and highly connected pores, which help avoid stress concentration within the dot-matrix structure and promote cell adhesion and proliferation. A cervical interbody cage based on this type of porous structure was designed and fabricated, and its mechanical properties and biocompatibility were evaluated. Results: The volume fraction of the 3D-printed TC4-based Tubular-G structure was linearly related to compressive strength. Adjusting the volume fraction resulted in a Tubular-G structure with a modulus and yield strength similar to human bone, without stress concentration within the structure. The designed and fabricated TC4-based Tubular-G porous cervical interbody cage demonstrated excellent anti-sagging properties and biocompatibility. Conclusions: The volume fraction of the 3D-printed TC4-based Tubular-G structure was linearly related to compressive strength. Adjusting the volume fraction resulted in a Tubular-G structure with a modulus and yield strength similar to human bone, without stress concentration within the structure. The designed and fabricated TC4-based Tubular-G porous cervical interbody cage demonstrated excellent anti-sagging properties and biocompatibility.

Abstract Gossypium purpurascens is a member of the Malvaceae family, holds immense economic significance as a fiber crop worldwide. Abiotic stresses harm cotton crops, reduce yields, and cause economic losses. Generating high-quality reference genomes and large-scale transcriptomic datasets across diverse conditions can offer valuable insights into identifying preferred agronomic traits for crop breeding. The present research used leaf tissues to conduct PacBio Iso-seq and RNA-seq analysis. We carried out an in-depth analysis of DEGs using both correlations with cluster analysis and principal component analysis. Additionally, the study also involved the identification of both lncRNAs and CDS. We have prepared RNA-seq libraries from 75 RNA samples to study the effects of drought, salinity, alkali, and saline-alkali stress, as well as control conditions. A total of 454.06 Gigabytes of transcriptome data were effectively validated through the identification of differentially expressed genes and KEGG and GO analysis. Overwhelmingly, gene expression profiles and full-length transcripts from cotton tissues will aid in understanding the genetic mechanism of abiotic stress tolerance in G. purpurascens.

Alternative splicing has been shown to participate in tumor progression, including hepatocellular carcinoma. The poor prognosis of patients with HCC calls for molecular classification and biomarker identification to facilitate precision medicine. We performed ssGSEA analysis to quantify the pathway activity of RNA splicing in three HCC cohorts. Kaplan–Meier and Cox methods were used for survival analysis. GO and GSEA were performed to analyze pathway enrichment. We confirmed that RNA splicing is significantly correlated with prognosis, and identified an alternative splicing-associated protein LUC7L3 as a potential HCC prognostic biomarker. Further bioinformatics analysis revealed that high LUC7L3 expression indicated a more progressive HCC subtype and worse clinical features. Cell proliferation-related pathways were enriched in HCC patients with high LUC7L3 expression. Consistently, we proved that LUC7L3 knockdown could significantly inhibit cell proliferation and suppress the activation of associated signaling pathways in vitro. In this research, the relevance between RNA splicing and HCC patient prognosis was outlined. Our newly identified biomarker LUC7L3 could provide stratification for patient survival and recurrence risk, facilitating early medical intervention before recurrence or disease progression.

Decision-making for autonomous maneuvering in dynamic, uncertain, and nonlinear environments represents a challenging frontier problem. Deep deterministic policy gradient (DDPG) is an effective method to solve such problems, but it is found that complex strategies require extensive computation and time in the learning process. To address this issue, we propose a node clustering (NC) method, inspired by grid clustering, integrated into the DDPG algorithm for the learning of complex strategies. In the NC method, the node membership degree is defined according to the specific characteristics of the maneuvering decision-making problem, and error handling strategies are designed to reduce the number of transitions in the replay database effectively, ensuring that the most typical transitions are retained. Then, combining NC and DDPG, an autonomous learning and decision-making algorithm of maneuvering is designed. The algorithm flow and the pseudo-code of the algorithm are given. Finally, the NC_DDPG algorithm is applied to a typical short-range air combat maneuvering decision problem for verification. The results show that the NC_DDPG algorithm significantly accelerates the autonomous learning and decision-making process under both balanced and disadvantageous conditions, taking only about 77% of the time required by Vector DDPG. The scale of NC impacts learning speed; the simulation results across five scales indicate that smaller clustering scales significantly increase learning time, despite a high degree of randomness. Compared with Twin Delayed DDPG (TD3), NC_DDPG consumes only 0.58% of the time of traditional TD3. After applying the NC method to TD3, NC_DDPG requires approximately 20–30% of the time of NC_TD3.

The novel deubiquitinase enzyme, motif interacting with ubiquitin-containing novel DUB family-1 (MINDY1), is highly expressed in liver cancer tissues and plays a crucial role in maintaining the stemness of liver cancer cells. Programmed death ligand-1 (PD-L1) is an immunosuppressive molecule overexpressed by tumour cells. The potential role of MINDY1 in inhibiting the stemness of liver cancer cells by deubiquitinating PD-L1 has not yet been reported. To investigate the mechanism by which MINDY1 mediates immune escape in liver cancer through the regulation of PD-L1 ubiquitination, we examined the expression levels of MINDY1 and PD-L1 in liver cancer and adjacent tissues from 50 hepatocellular carcinoma (HCC) patients using protein imprinting and immunohistochemistry. We analyzed the relationship between the expression levels of MINDY1 and PD-L1 in liver cancer tissues and their correlation with the 5-year tumor-free survival rates of patients. Subsequently, MINDY1 expression was knocked down in Huh7 cells using small interfering RNA (siRNA) interference or upregulated through transfection with a MINDY1 overexpression plasmid. The effects of MINDY1 knockdown or overexpression on the proliferation, apoptosis, migration, and invasion of HCC cells, as well as the regulation of PD-L1 binding and ubiquitination, were assessed. The 5-year tumor-free survival rates were significantly lower in both the high MINDY1 expression group and the high PD-L1 expression group (χ2 = 4.919 and 13.158, respectively). A significant difference in survival was observed between the high and low MINDY1 expression groups (χ2= 27.415). MINDY1 was found to directly interact with PD-L1, with MINDY1 gene knockdown promoting PD-L1 ubiquitination and MINDY1 overexpression inhibiting PD-L1 ubiquitination. All comparisons yielded statistically significant results (P < 0.05). In conclusion, MINDY1 inhibits the malignant progression of liver cancer by inhibiting PD-L1 ubiquitination and mediating immune escape.

Al–Li alloy has a wide range of application prospects in aerospace and rail transportation fields. Friction stir welding (FSW) is suitable for joining of Al–Li alloy. The microstructure evolution in FSW of Al–Li alloy determines the final joint properties. However, it is difficult to directly observe the microstructure evolution in FSW of Al–Li alloy only by experimental methods. Therefore, a Monte Carlo model in cooperation with a thermomechanical finite element model was proposed to study the microstructure evolution in FSW of 2195 Al–Li alloy. The validated thermomechanical finite element model was first used to calculate the temperature field, strain rate and strain evolution during the FSW process. Then, the achieved thermomechanical history was used in the Monte Carlo model to predict the transient microstructure evolution and the final morphology of the grain structure. It is found that the plastic materials on the advancing side experience a higher strain compared with that on the retreating side with the same distance from the joint line. The plastic material in the middle of the weld nugget zone (WNZ) experiences a relatively high temperature with more severe plastic deformation. Therefore, fully dynamic recrystallization takes place for the material at this region as it flows across the tool during FSW, which results in a fine recrystallization grain in the middle of WNZ. However, the material on the advancing side at 2 mm away from the joint line experiences a lower strain rate, which results in partial recrystallization with some relatively large grains of the base materials. The simulated average grain size and grain morphology were in good agreement with the measured results by EBSD method.

Abstract Background High-fat diet (HFD) is closely associated with the increased prevalence of inflammatory bowel disease (IBD). Excessive gut microbial metabolite deoxycholic acid (DCA) caused by HFD plays significant roles in eliciting intestinal inflammation, however, the mechanism underlining the induction of inflammatory response by DCA has not been fully elucidated. The purpose of this study was to investigate the role of DCA in the triggering of inflammation via affecting CD4+ T cell differentiation. Results Murine CD4+T cells were cultured under Th1, Th2 or Th17-polarizing conditions treated with or without different dosage of DCA, and flowcytometry was conducted to detect the effect of DCA on CD4+ T cell differentiation. Alteration of gene expression in CD4+ T cells upon DCA treatment was determined by RNA-sequencing and qRT-PCR. Bioinformatic analysis, cholesterol metabolic profiling, ChIP assay and immuno-fluorescent staining were further applied to explore the DCA-regulated pathway that involved in CD4+T cell differentiation. The results showed that DCA could dose-dependently promote the differentiation of CD4+ T cell into Th17 linage with pathogenic signature. Mechanistically, DCA stimulated the expression of cholesterol biosynthetic enzymes CYP51 and led to the increased generation of endogenous RORγt agonists, including zymosterol and desmosterol, therefore facilitating Th17 differentiation. Up-regulation of CYP51 by DCA was largely mediated via targeting transcription factor SREBP2 and at least partially through bile acid receptor TGR5. In addition, DCA-supplemented diet significantly increased intestinal Th17 cell infiltration and exacerbated TNBS-induced colitis. Administration of cholestyramine to eliminate fecal bile acid obviously alleviated colonic inflammation accompanied by decreased Th17 cells in HFD-fed mice. Conclusions Our data establish a link between DCA-induced cholesterol biosynthesis in immune cells and gut inflammation. Modulation of bile acid level or targeting cholesterol metabolic pathway may be potential therapeutic measurements for HFD-related colitis.

Genome-wide physical protein–protein interaction (PPI) mapping remains a major challenge for current technologies. Here, we reported a high-efficiency BiFC-seq method, yeast-enhanced green fluorescent protein-based bimolecular fluorescence complementation (yEGFP-BiFC) coupled with next-generation DNA sequencing, for interactome mapping. We first applied yEGFP-BiFC method to systematically investigate an intraviral network of the Ebola virus. Two-thirds (9/14) of known interactions of EBOV were recaptured, and five novel interactions were discovered. Next, we used the BiFC-seq method to map the interactome of the tumor protein p53. We identified 97 interactors of p53, more than three-quarters of which were novel. Furthermore, in a more complex background, we screened potential interactors by pooling two BiFC libraries together and revealed a network of 229 interactions among 205 proteins. These results show that BiFC-seq is a highly sensitive, rapid, and economical method for genome-wide interactome mapping.

The mechanism of aerosol pollution transport remains highly elusive owing to the myriad of influential factors. In this study, ground station data, satellite data, ground-based LiDAR remote sensing data, sounding data, ERA5 reanalysis and a backward trajectory model were combined to investigate the formation process and optical properties of winter aerosol pollution in Beijing and surrounding areas. The analysis of ground station data shows that compared to 2019 and 2021, the pandemic lockdown policy resulted in a decrease in the total number of pollution days and a decrease in the average concentration of particulate matter in the Beijing area in 2020. The terrain characteristics of the Beijing-Tianjin-Hebei (BTH) made it prone to northeast and southwest winds. The highest incidence of aerosol pollution in Beijing occurs in February and March during the spring and winter seasons. Analysis of a typical heavy aerosol pollution process in the Beijing area from 28 February to 5 March 2019 shows that dust and fine particulate matter contributed to the primary pollution; surface air temperature inversion and an average wind speed of less than 3 m/s were conducive to the continuous accumulation of pollutants, which was accompanied by the oxidation reaction of NO2 and O3, forming photochemical pollution. The heavy aerosol pollution was transmitted and diffused towards the southeast, gradually eliminating the pollution. Our results provide relevant research support for the prevention and control of aerosol pollution.

PROTAC is a rapidly developing engineering technology for targeted protein degradation using the ubiquitin–proteasome system, which has promising applications for inflammatory diseases, neurodegenerative diseases, and malignant tumors. This paper gives a brief overview of the development and design principles of PROTAC, with a special focus on PROTAC-based explorations in recent years aimed at achieving controlled protein degradation and improving the bioavailability of PROTAC, as well as TPD technologies that use other pathways such as autophagy and lysosomes to achieve targeted protein degradation.

Abstract Background Dysfunctional p53 signaling is one of the major causes of hepatocellular carcinoma (HCC) tumorigenesis and development, but the mechanisms underlying p53 inactivation in HCC have not been fully clarified. The role of Krüppel-associated box (KRAB)-type zinc-finger protein ZNF498 in tumorigenesis and the underlying mechanisms are poorly understood. Methods Clinical HCC samples were used to assess the association of ZNF498 expression with clinicopathological characteristics and patient outcomes. A mouse model in which HCC was induced by diethylnitrosamine (DEN) was used to explore the role of ZNF498 in HCC initiation and progression. ZNF498 overexpression and knockdown HCC cell lines were employed to examine the effects of ZNF498 on cellular proliferation, apoptosis, ferroptosis and tumor growth. Western blotting, immunoprecipitation, qPCR, luciferase assays and flow cytometry were also conducted to determine the underlying mechanisms related to ZNF498 function. Results ZNF498 was found to be highly expressed in HCC, and increased ZNF498 expression was positively correlated with advanced pathological grade and poor survival in HCC patients. Furthermore, ZNF498 promoted DEN-induced hepatocarcinogenesis and progression in mice. Mechanistically, ZNF498 directly interacted with p53 and suppressed p53 transcriptional activation by inhibiting p53 Ser46 phosphorylation. ZNF498 competed with p53INP1 for p53 binding and suppressed PKCδ- and p53INP1-mediated p53 Ser46 phosphorylation. In addition, functional assays revealed that ZNF498 promoted liver cancer cell growth in vivo and in vitro in a p53-dependent manner. Moreover, ZNF498 inhibited p53-mediated apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation. Conclusions Our results strongly suggest that ZNF498 suppresses apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation in hepatocellular carcinogenesis, revealing a novel ZNF498-PKCδ-p53INP1-p53 axis in HCC cells that would enrich the non-mutation p53-inactivating mechanisms in HCC.

Summary: Endoplasmic reticulum (ER) homeostasis has been implicated in the pathogenesis of various forms of cancer; however, our understanding of the role of ER quality control mechanisms in tumorigenesis remains incomplete. Here, we show that the SEL1L-HRD1 complex of ER-associated degradation (ERAD) suppresses hepatocyte proliferation and tumorigenesis in mice. Hepatocyte-specific deletion of Sel1L or Hrd1 predisposed mice to diet/chemical-induced tumors. Proteomics screen from SEL1L-deficient livers revealed WNT5A, a tumor suppressor, as an ERAD substrate. Indeed, nascent WNT5A was misfolding prone and degraded by SEL1L-HRD1 ERAD in a quality control capacity. In the absence of ERAD, WNT5A misfolds is largely retained in the ER and forms high-molecular weight aggregates, thereby depicting a loss-of-function effect and attenuating WNT5A-mediated suppression of hepatocyte proliferation. In humans, SEL1L-HRD1 ERAD expression correlated positively with survival time for patients with liver cancer. Overall, our data reveal a key role of SEL1L-HRD1 ERAD in suppressing hepatocyte proliferation and liver cancer.

Excessive fructose intake from desserts and beverages may influence bone development among adolescents. The gut microbiota (GM) and energy metabolism play important roles in bone development. In this study, 40 female adolescent rats were randomly assigned to the control group, the fructose group with two concentrations, and the glucose group as the positive control group. After 10 weeks, serum glucose and lipids were detected by means of an automatic analyzer, and the bone microstructure was analyzed by Micro-CT. Then, the GM was determined via 16S rRNA sequencing analysis, and energy metabolism was detected by measuring serum carbohydrate metabolites. At last, bone metabolism markers were measured via ELISA kits. The results showed that excessive fructose intake could increase body weight and influence the glucolipid metabolism of female adolescent rats. Meanwhile, the bone microstructures were impaired with excessive fructose intake. Mechanistically, excessive fructose intake shifted the GM of rats with the decrease of Lachnospiraceae, Ruminococcaceae, and increase of Allobaculum, Lachnospiraceae. Energy metabolism analysis suggested that most metabolites of fructose did not enter the tricarboxylic acid cycle to provide energy for the body’s development. Furthermore, serum bone metabolism markers showed that excessive fructose intake could decrease both bone formation and resorption. Our results suggested that excessive fructose intake could inhibit skeletal development in adolescents. One potential mechanism might be that it affected the intestinal microbiota homeostasis in the juvenile body, thus changing the energy metabolism level, and ultimately affecting the bone metabolic balance.

High-fat diet (HFD) leads to systemic low-grade inflammation, which has been involved in the pathogenesis of diverse metabolic and inflammatory diseases. Colon is thought to be the first organ suffering from inflammation under HFD conditions due to the pro-inflammatory macrophages infiltration, however, the mechanisms concerning the induction of pro-inflammatory phenotype of colonic macrophages remains unclear. In this study, we show that HFD increased the percentage of gram-positive bacteria, especially genus Clostridium, and resulted in the significant increment of fecal deoxycholic acid (DCA), a gut microbial metabolite produced by bacteria mainly restricted to genus Clostridium. Notably, reducing gram-positive bacteria with vancomycin diminished fecal DCA and profoundly alleviated pro-inflammatory macrophage infiltration in colon, whereas DCA-supplemented feedings to vancomycin-treated mice provoked obvious pro-inflammatory macrophage infiltration and colonic inflammation. Meanwhile, intra-peritoneal administration of DCA also elicited considerable recruitment of macrophages with pro-inflammatory phenotype. Mechanistically, DCA dose-dependently promoted M1 macrophage polarization and pro-inflammatory cytokines production at least partially through toll-like receptor 2 (TLR2) transactivated by M2 muscarinic acetylcholine receptor (M2-mAchR)/Src pathway. In addition, M2-mAchR mediated increase of TLR2 transcription was mainly achieved via targeting AP-1 transcription factor. Moreover, NF-κB/ERK/JNK signalings downstream of TLR2 are involved in the DCA-induced macrophage polarization. In conclusion, our findings revealed that high level DCA induced by HFD may serve as an initiator to activate macrophages and drive colonic inflammation, thus offer a mechanistic basis that modulation of gut microbiota or intervening specific bile acid receptor signaling could be potential therapeutic approaches for HFD-related inflammatory diseases.

The fractionation of components of lignocellulosic biomass is important to be able to take advantage of biomass resources. The hydrothermal–ethanol method has significant advantages for fraction separation. The first step of hydrothermal treatment can separate hemicellulose efficiently, but hydrothermal treatment affects the efficiency of ethanol treatment to delignify lignin. In this study, the efficiency of lignin removal was improved by an ultrasonic-assisted second-step ethanol treatment. The effects of ultrasonic time, ultrasonic temperature, and ultrasonic power on the ultrasonic ethanol treatment of hydrothermal straw were investigated. The separated lignin was characterized by solid product composition analysis, FT-IR, and XRD. The hydrolysate was characterized by GC-MS to investigate the advantage on the products obtained by ethanol treatment. The results showed that an appropriate sonication time (15 min) could improve the delignification efficiency. A proper sonication temperature (180 °C) can improve the lignin removal efficiency with a better retention of cellulose. However, a high sonication power 70% (840 W) favored the retention of cellulose and lignin removal.

For hydrothermal liquefaction of dry biomass to produce liquid fuels, water needs to be added or the aqueous phase products can be recycled. This paper focuses on understanding the relationship between hydrothermal degradation of the dry biomass and oil formation under the condition of accumulative recycling of the aqueous phase. Completely dried corn stalk and deionized water were used for the hydrothermal liquefaction (HTL) experiment. The aqueous products for subsequent recycling were not diluted. It was demonstrated that the recycling of the aqueous can promote the enrichment of organic acids and the conversion of ketones and phenols in the aqueous, improving the yield and quality of Bio-crude oil. After recycling, the yield of Bio-crude oil increased from 20.42% to 24.31% continuously, and the oxygen content decreased from 13.34% to 9.90%. Although the process was accompanied by solid deposition and had a negative impact on the hydrothermal degradation efficiency, the formation of carbon microspheres during the deposition enhanced the utilization of nondegradable solids, while the formation of metal salt particles had a positive impact on oil production. After three rounds of recycling, the solid deposition effect was weakened. At this time, oil production and solids degradation can be promoted simultaneously.

We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1β production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

Biomass energy is becoming increasingly important, owing to the decreasing supply of fossil fuels and growing environmental problems. Hydrothermal carbonization (HTC) is a promising technology for producing solid biofuels from agricultural and forestry residues because of its lower fossil-fuel consumption. In this study, HTC was used to upgrade red jujube branch (RJB) to prepare hydrochar at six temperatures (220, 240, 260, 280, 300, and 320 °C) for 120 min, and at 300 °C for 30, 60, 90, and 120 min. The results showed that the energy recovery efficiency (ERE) reached maximum values of 80.42% and 79.86% at a residence time of 90 min and a reaction temperature of 220 °C, respectively. X-ray diffraction results and Fourier transform infrared spectroscopy measurements show that the microcrystal features of RJB were destroyed, whereas the hydrochar contained an amorphous structure and mainly lignin fractions at increased temperatures. Thermogravimetric analysis shows that the hydrochar had better fuel qualities than RJB, making hydrochar easier to burn.

A westernized high-fat diet (HFD) is associated with the development of inflammatory bowel disease (IBD). High level fecal deoxycholic acid (DCA) caused by HFD contributes to the colonic inflammatory injury of IBD, however, the mechanism concerning the initiation of inflammatory response by DCA remains unclear. In this study, we sought to investigate the role and mechanism of DCA in the induction of inflammation via promoting NLRP3 inflammasome activation. Here we for the first time showed that DCA dose-dependently induced NLRP3 inflammasome activation and highly pro-inflammatory cytokine-IL-1β production in macrophages. Mechanistically, DCA triggered NLRP3 inflammasome activation by promoting cathepsin B release at least partially through sphingosine-1-phosphate receptor 2 (S1PR2). Colorectal instillation of DCA significantly increased mature IL-1β level in colonic tissue and exacerbated DSS-induced colitis, while in vivo blockage of NLRP3 inflammasome or macrophage depletion dramatically reduced the mature IL-1β production and ameliorated the aggravated inflammatory injury imposed by DCA. Thus, our findings show that high level fecal DCA may serve as an endogenous danger signal to activate NLRP3 inflammasome and contributes to HFD-related colonic inflammation. NLRP3 inflammasome may represent a new potential therapeutical target for treatment of IBD.