Effect of Dental Implant System-Assisted Tooth Intentional Replantation in the Treatment of Anterior Teeth with Pathological Tooth Flaring, Drifting and Elongation in Patients with Stage III/IV Periodontitis: a Case Series.

OBJECTIVE: To investigate the clinical effect of implant-assisted dental intentional replantation (IR) for the treatment of "drifted" anterior periodontally hopeless teeth (PHT). METHODS: The present authors recruited 22 patients with stage III/IV periodontitis who suffered drifting of the maxillary anterior teeth, with a total of 25 teeth. The PHT were extracted for in vitro root canal treatment (RCT). The root surface was smoothed and the shape was trimmed, and the alveolar socket was scratched. The dental implant system was used to prepare the alveolar socket according to the direction, depth and shape of the tooth implantation. The PHT were reimplanted into the prepared alveolar socket. The periodontal indicators were analysed statistically before and after surgery. RESULT: Twenty-two patients who completed the full course of treatment, with a total of 25 PHT, had a successful retention rate of 88%. Mean periodontal probing depth (PPD) decreased by 2.880 ± 0.556 mm and 3.390 ± 0.634 mm at 6 months and 1 year, respectively, and clinical attachment loss (CAL) decreased by 2.600 ± 0.622 mm and 2.959 ± 0.731 mm at the same time points, respectively, showing significant improvement (P < 0.05). CONCLUSION: Dental implant system-assisted IR can effectively preserve "drifted" natural PHT in patients with stage III/IV periodontitis.

Exploring auditory temporal resolution and dichotic listening skills among individuals with type 2 diabetes mellitus.

The study aimed to explore the auditory temporal resolution and dichotic listening skills in patients with type 2 diabetes mellitus (T2DM) and identify associated health-related factors. Using a cross-sectional design, 87 adults with T2DM and 48 non-diabetic controls, all with normal hearing, participated. The two central auditory processing (CAP) skills were assessed through the Gaps-In-Noise (GIN) and Dichotic-Digits Listening (DDL) tests. T2DM participants underwent blood tests to measure various health-related factors. In the GIN test, the shortest gap threshold (GapTh) obtained across both ears was significantly higher in the diabetic group (9.1 ± 2.4 ms) compared to the non-diabetic group (7.5 ± 1.5 ms), and the score of correctly identified gaps (GapSc) in the diabetic group (45±11 %) was significantly lower than GapSc in the non-diabetic group (52±9 %), p < 0.001. In the DDL test, the free-recall score (73.8 ± 18.5 %) across both ears and the right-ear advantage (-1.3 ± 20.6 %) in the diabetic group were significantly lower than the free-recall score (85.8 ± 11.9 %) and right-ear advantage (6.9 ± 11.9 %) in the non-diabetic group, p < 0.005. Furthermore, the duration of diabetes, eGFR level, retinopathy, carotid plaque, fasting blood glucose level, and HDL-C (good cholesterol) level were factors significantly associated with performances in the GIN and/or DDL tests for T2DM participants. In conclusion, individuals with T2DM are at risk of reduced auditory processing skills in temporal resolution and dichotic listening, impacting their speech understanding. Six health-related factors were identified as significantly associated with CAP skills in T2DM patients.

[Spatiotemporal Simulation and Prediction of Soil Organic Carbon Density in Gannan Grassland Under Future Climate Scenarios].

To study the temporal and spatial distribution characteristics of soil organic carbon density in grassland and explore the relationship between organic carbon density and influencing factors is of great significance to the management and maintenance of grassland ecosystems in Gannan Autonomous Prefecture, which is conducive to realizing the goal of "double carbon," promoting carbon sink, and mitigating climate change. Taking Gannan Tibetan Autonomous Prefecture of Gansu Province as the research object, based on data from two CMIP6 future climate scenarios (SSP126 and SSP585), the CENTURY model was used to simulate and predict the temporal and spatial changes in soil organic carbon density in grassland of Gannan during 2023-2100. The main conclusions were as follows:① From 2023 to 2100, total organic carbon density, slow organic carbon density, and inert organic carbon density all showed a downward trend, whereas active organic carbon density fluctuated first and then increased. Meanwhile, the total organic carbon density, active organic carbon density, slow organic carbon density, and inert organic carbon density under the SSP585 scenario were higher than those under the SSP126 scenario. ② Mann-Kendall mutation analysis showed that the abrupt change in the difference of soil total organic carbon density (Δsomtc) occurred in 2030. The abrupt change in the difference of soil active carbon density (Δsom1c) occurred in 2027. ③ During the study period, the average soil organic carbon density of Gannan grassland was 7 505.69 g·m-2 under the SSP126 scenario and 7 551.87 g·m-2 under the SSP585 scenario. Gannan grassland soil organic carbon density was higher in the west and lower in the east, and the coefficient of variation was relatively stable. ④ The results of partial correlation analysis showed that precipitation was positively correlated with soil organic carbon density, whereas temperature was significantly negatively correlated with soil organic carbon density under future climate scenarios. ⑤ The results of the Theil-Sen Median trend analysis and Mann-Kendall test showed that under the two climate scenarios, the soil organic carbon density in Gannan showed an overall downward trend, in which Luqu County showed the fastest downward trend and Dibe County showed the slowest.

Crocin's role in modulating MMP2/TIMP1 and mitigating hypoxia-induced pulmonary hypertension in mice.

To explore the molecular pathogenesis of pulmonary arterial hypertension (PAH) and identify potential therapeutic targets, we performed transcriptome sequencing of lung tissue from mice with hypoxia-induced pulmonary hypertension. Our Gene Ontology analysis revealed that "extracellular matrix organization" ranked high in the biological process category, and matrix metallopeptidases (MMPs) and other proteases also played important roles in it. Moreover, compared with those in the normoxia group, we confirmed that MMPs expression was upregulated in the hypoxia group, while the hub gene Timp1 was downregulated. Crocin, a natural MMP inhibitor, was found to reduce inflammation, decrease MMPs levels, increase Timp1 expression levels, and attenuate hypoxia-induced pulmonary hypertension in mice. In addition, analysis of the cell distribution of MMPs and Timp1 in the human lung cell atlas using single-cell RNAseq datasets revealed that MMPs and Timp1 are mainly expressed in a population of fibroblasts. Moreover, in vitro experiments revealed that crocin significantly inhibited myofibroblast proliferation, migration, and extracellular matrix deposition. Furthermore, we demonstrated that crocin inhibited TGF-ß1-induced fibroblast activation and regulated the pulmonary arterial fibroblast MMP2/TIMP1 balance by inhibiting the TGF-ß1/Smad3 signaling pathway. In summary, our results indicate that crocin attenuates hypoxia-induced pulmonary hypertension in mice by inhibiting TGF-ß1-induced myofibroblast activation.

Tip60-FOXO regulates JNK signaling mediated apoptosis in Drosophila.

The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism Drosophila and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into Drosophila effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from Drosophila to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.

All-in-One Electrokinetic Strategy Coupled with a Miniaturized Chip for SERS Detection of Multipesticides.

Complexed and tiresome pretreatment processes have significantly impeded in-field analysis of environmental specimens. Herein, an all-in-one sample separation and enrichment strategy based on a compact charge-selective capture/nanoconfined enrichment (CSC/NCE) device is exploited for marker-free surface-enhanced Raman spectroscopy (SERS) detection of charged pesticides in matrix specimens. This tactic incorporating in situ separations, seizing, and nanoconfined enhancement can greatly elevate the effectiveness of sample pretreatment. Importantly, CSC/NCE with excellent adsorption performances and excellent plasmonic features facilitates concentration and signal amplification of electrically charged pesticides. With the introduction of an electric field on this integrated CSC/NCE, the matrix effect in samples could be significantly eradicated, and a distinct SERS response is witnessed for targeted analytes. Accurate quantification of multipesticides is achieved by synergizing the CSC/NCE chip and chemometrics, and the contents found by the CSC/NCE-based sensing strategy agree with those obtained from chromatography assays with relative deviations lower than 10%. The facile and versatile all-in-one tactic infused in a compact chip exhibits enormous potential for field-test application in chemical measurement and food safety.

Interfacing data science with cell therapy manufacturing: where we are and where we need to be.

Although several cell-based therapies have received FDA approval, and others are showing promising results, scalable, and quality-driven reproducible manufacturing of therapeutic cells at a lower cost remains challenging. Challenges include starting material and patient variability, limited understanding of manufacturing process parameter effects on quality, complex supply chain logistics, and lack of predictive, well-understood product quality attributes. These issues can manifest as increased production costs, longer production times, greater batch-to-batch variability, and lower overall yield of viable, high-quality cells. The lack of data-driven insights and decision-making in cell manufacturing and delivery is an underlying commonality behind all these problems. Data collection and analytics from discovery, preclinical and clinical research, process development, and product manufacturing have not been sufficiently utilized to develop a "systems" understanding and identify actionable controls. Experience from other industries shows that data science and analytics can drive technological innovations and manufacturing optimization, leading to improved consistency, reduced risk, and lower cost. The cell therapy manufacturing industry will benefit from implementing data science tools, such as data-driven modeling, data management and mining, AI, and machine learning. The integration of data-driven predictive capabilities into cell therapy manufacturing, such as predicting product quality and clinical outcomes based on manufacturing data, or ensuring robustness and reliability using data-driven supply-chain modeling could enable more precise and efficient production processes and lead to better patient access and outcomes. In this review, we introduce some of the relevant computational and data science tools and how they are being or can be implemented in the cell therapy manufacturing workflow. We also identify areas where innovative approaches are required to address challenges and opportunities specific to the cell therapy industry. We conclude that interfacing data science throughout a cell therapy product lifecycle, developing data-driven manufacturing workflow, designing better data collection tools and algorithms, using data analytics and AI-based methods to better understand critical quality attributes and critical-process parameters, and training the appropriate workforce will be critical for overcoming current industry and regulatory barriers and accelerating clinical translation.

Development and validation of a predictive model for acute-on-chronic liver failure after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a cause of acute-on-chronic liver failure (ACLF). AIM: To investigate the risk factors of ACLF within 1 year after TIPS in patients with cirrhosis and construct a prediction model. METHODS: In total, 379 patients with decompensated cirrhosis treated with TIPS at Nanjing Drum Tower Hospital from 2017 to 2020 were selected as the training cohort, and 123 patients from Nanfang Hospital were included in the external validation cohort. Univariate and multivariate logistic regression analyses were performed to identify independent predictors. The prediction model was established based on the Akaike information criterion. Internal and external validation were conducted to assess the performance of the model. RESULTS: Age and total bilirubin (TBil) were independent risk factors for the incidence of ACLF within 1 year after TIPS. We developed a prediction model comprising age, TBil, and serum sodium, which demonstrated good discrimination and calibration in both the training cohort and the external validation cohort. CONCLUSION: Age and TBil are independent risk factors for the incidence of ACLF within 1 year after TIPS in patients with decompensated cirrhosis. Our model showed satisfying predictive value.

Unraveling early recurrence of risk factors in Gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER). METHODS: A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity. RESULTS: Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER. CONCLUSION: This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.

SLC7A11 as a therapeutic target to attenuate phthalates-driven testosterone level decline in mice.

INTRODUCTION: Phthalates exposure is a major public health concern due to the accumulation in the environment and associated with levels of testosterone reduction, leading to adverse pregnancy outcomes. However, the relationship between phthalate-induced testosterone level decline and ferroptosis remains poorly defined. OBJECTIVES: Herein, we aimed to explore the mechanisms of phthalates-induced testosterone synthesis disorder and its relationship to ferroptosis. METHODS: We conducted validated experiments in vivo male mice model and in vitro mouse Leydig TM3 cell line, followed by RNA sequencing and metabolomic analysis. We evaluated the levels of testosterone synthesis-associated enzymes and ferroptosis-related indicators by using qRT-PCR and Western blotting. Then, we analyzed the lipid peroxidation, ROS, Fe2+ levels and glutathione system to confirm the occurrence of ferroptosis. RESULTS: In the present study, we used di (2-ethylhexyl) phthalate (DEHP) to identify ferroptosis as the critical contributor to phthalate-induced testosterone level decline. It was demonstrated that DEHP caused glutathione metabolism and steroid synthesis disorders in Leydig cells. As the primary metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP) triggered testosterone synthesis disorder accompanied by a decrease in the expression of solute carri1er family 7 member 11 (SLC7A11) protein. Furthermore, MEHP synergistically induced ferroptosis with Erastin through the increase of intracellular and mitochondrial ROS, and lipid peroxidation production. Mechanistically, overexpression of SLC7A11 counteracts the synergistic effect of co-exposure to MEHP-Erastin. CONCLUSION: Our research results suggest that MEHP does not induce ferroptosis but synergizes Erastin-induced ferroptosis. These findings provide evidence for the role of ferroptosis in phthalates-induced testosterone synthesis disorder and point to SLC7A11 as a potential target for male reproductive diseases. This study established a correlation between ferroptosis and phthalates cytotoxicity, providing a novel view point for mitigating the issue of male reproductive disease and "The Global Plastic Toxicity Debt".

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Long non-coding RNA MSL3P1 regulates CUL3 mRNA cytoplasmic transport and stability and promotes lung adenocarcinoma metastasis.

Lung adenocarcinoma (LUAD) is the most prevalent histological type of lung cancer. Previous studies have reported that specific long non-coding RNAs (lncRNAs) are involved in cancer development and progression. The phenotype and mechanism of ENST00000440028, named MSL3P1, a lncRNA which we referring to a cancer-testis gene with potential roles in tumorigenesis and progression, have not been reported. We found that MSL3P1 is overexpressed in LUAD tumor tissues, which is significantly associated with clinical characteristics, metastasis, and poor clinical prognosis. MSL3P1 promotes the metastasis of LUAD in vitro and in vivo. The enhancer reprogramming in LUAD tumor tissue is the major driver of the aberrantly expression of MSL3P1. Mechanistically, due to the competitive binding to CUL3 mRNA with ZFC3H1 protein (a protein involved in targeting polyadenylated RNA to exosomes and promoting the degradation of target mRNA), MSL3P1 can prevent the ZFC3H1-mediated RNA degradation of CUL3 mRNA and transport it to the cytoplasm. This activates the downstream epithelial-to-mesenchymal transition signaling pathway, and promote tumor invasion and metastasis. Implications: This study indicates that lncRNA MSL3P1 regulates CUL3 mRNA stability and promotes the metastasis and holds potential as a prognostic biomarker and therapeutic target in LUAD.

Inverted device architecture for high efficiency single-layer organic light-emitting diodes with imbalanced charge transport.

Many wide-gap organic semiconductors exhibit imbalanced electron and hole transport, therefore efficient organic light-emitting diodes require a multilayer architecture of electron- and hole-transport materials to confine charge recombination to the emissive layer. Here, we show that even for emitters with imbalanced charge transport, it is possible to obtain highly efficient single-layer organic light emitting diodes (OLEDs), without the need for additional charge-transport and blocking layers. For hole-dominated emitters, an inverted single-layer device architecture with ohmic bottom-electron and top-hole contacts moves the emission zone away from the metal top electrode, thereby more than doubling the optical outcoupling efficiency. Finally, a blue-emitting inverted single-layer OLED based on thermally activated delayed fluorescence is achieved, exhibiting a high external quantum efficiency of 19% with little roll-off at high brightness, demonstrating that balanced charge transport is not a prerequisite for highly efficient single-layer OLEDs.

Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level.

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.

Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.

In brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.

Acetyl-CoA metabolic accumulation promotes hepatocellular carcinoma metastasis via enhancing CXCL1-dependent infiltration of tumor-associated neutrophils.

High levels of acetyl-CoA are considered a key metabolic feature of metastatic cancers. However, the impacts of acetyl-CoA metabolic accumulation on cancer microenvironment remodeling are poorly understood. In this study, using human hepatocellular carcinoma (HCC) tissues and orthotopic xenograft models, we found a close association between high acetyl-CoA levels in HCCs, increased infiltration of tumor-associated neutrophils (TANs) in the cancer microenvironment and HCC metastasis. Cytokine microarray and enzyme-linked immunosorbent assays (ELISA) revealed the crucial role of the chemokine (C-X-C motif) ligand 1(CXCL1). Mechanistically, acetyl-CoA accumulation induces H3 acetylation-dependent upregulation of CXCL1 gene expression. CXCL1 recruits TANs, leads to neutrophil extracellular traps (NETs) formation and promotes HCC metastasis. Collectively, our work linked the accumulation of acetyl-CoA in HCC cells and TANs infiltration, and revealed that the CXCL1-CXC receptor 2 (CXCR2)-TANs-NETs axis is a potential target for HCCs with high acetyl-CoA levels.

Telomerase-related advances in hepatocellular carcinoma: A bibliometric and visual analysis.

BACKGROUND: As a critical early event in hepatocellular carcinogenesis, telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma (HCC) patients, and its function in the genesis and treatment of HCC has gained much attention over the past two decades. AIM: To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase. METHODS: The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to "articles" and "reviews" published in English. A total of 873 relevant publications related to HCC and telomerase were identified. We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications, such as the trends in the publications, citation counts, most prolific or influential writers, and most popular journals; to screen for keywords occurring at high frequency; and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences. VOSviewer was utilized to compile and visualize the bibliometric data. RESULTS: A surge of 51 publications on HCC/telomerase research occurred in 2016, the most productive year from 1996 to 2023, accompanied by the peak citation count recorded in 2016. Up to December 2023, 35226 citations were made to all publications, an average of 46.6 citations to each paper. The United States received the most citations (n = 13531), followed by China (n = 7427) and Japan (n = 5754). In terms of national cooperation, China presented the highest centrality, its strongest bonds being to the United States and Japan. Among the 20 academic institutions with the most publications, ten came from China and the rest of Asia, though the University of Paris Cité, Public Assistance-Hospitals of Paris, and the National Institute of Health and Medical Research (INSERM) were the most prolific. As for individual contributions, Hisatomi H, Kaneko S, and Ide T were the three most prolific authors. Kaneko S ranked first by H-index, G-index, and overall publication count, while Zucman-Rossi J ranked first in citation count. The five most popular journals were the World Journal of Gastroenterology, Hepatology, Journal of Hepatology, Oncotarget, and Oncogene, while Nature Genetics, Hepatology, and Nature Reviews Disease Primers had the most citations. We extracted 2293 keywords from the publications, 120 of which appeared more than ten times. The most frequent were HCC, telomerase and human telomerase reverse transcriptase (hTERT). Keywords such as mutational landscape, TERT promoter mutations, landscape, risk, and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Choline Dehydrogenase Contributes to Salt Tolerance in Dunaliella through Betaine Synthesis.

In Dunaliella tertiolecta, a microalga renowned for its extraordinary tolerance to high salinity levels up to 4.5 M NaCl, the mechanisms underlying its stress response have largely remained a mystery. In a groundbreaking discovery, this study identifies a choline dehydrogenase enzyme, termed DtCHDH, capable of converting choline to betaine aldehyde. Remarkably, this is the first identification of such an enzyme not just in D. tertiolecta but across the entire Chlorophyta. A 3D model of DtCHDH was constructed, and molecular docking with choline was performed, revealing a potential binding site for the substrate. The enzyme was heterologously expressed in E. coli Rosetta (DE3) and subsequently purified, achieving enzyme activity of 672.2 U/mg. To elucidate the role of DtCHDH in the salt tolerance of D. tertiolecta, RNAi was employed to knock down DtCHDH gene expression. The results indicated that the Ri-12 strain exhibited compromised growth under both high and low salt conditions, along with consistent levels of DtCHDH gene expression and betaine content. Additionally, fatty acid analysis indicated that DtCHDH might also be a FAPs enzyme, catalyzing reactions with decarboxylase activity. This study not only illuminates the role of choline metabolism in D. tertiolecta's adaptation to high salinity but also identifies a novel target for enhancing the NaCl tolerance of microalgae in biotechnological applications.

Anaerolentibacter hominis gen. nov. sp. nov., Diplocloster hominis sp. nov. and Pilosibacter fragilis gen. nov. sp. nov., isolated from human faeces.

Three Gram-positive, obligately anaerobic bacterial strains, namely CSJ-1T, CSJ-3T, and CSJ-4T, were isolated from faeces of healthy persons. They were characterized through a combination of whole-genome sequencing, phenotypic traits, and metabolomic analysis. The genome sizes of CSJ-1T, CSJ-4T, and CSJ-3T were 3.3, 3.8, and 6.1 Mbp, with DNA G+C contents of 47.2, 48.3, and 48.8 mol%, respectively. Strain CSJ-3T was identified as representing a novel species, Diplocloster hominis (type strain CSJ-3T=CGMCC 1.18033T=JCM 36512T) of the genus Diplocloster. The 16S rRNA gene sequence similarity and whole genome average nucleotide identity (gANI) of CSJ-4T to its closest related species, Diplocloster modestus ASD 4241T, were 98.3 and 91.4 %, respectively. Comparative analysis of 16S rRNA gene sequences showed 91.6 % similarity between CSJ-1T and its closest phylogenetic neighbour, Catenibacillus scindens DSM 106146T, and 93.3 % similarity between CSJ-4T and its closest relative strain, Clostridium fessum SNUG30386T. Based on the polyphasic taxonomic results, we proposed two novel genera and three novel species. Strain CSJ-1T was identified as representing a novel species of novel genus, Anaerolentibacter hominis gen. nov. sp. nov. (type strain CSJ-1T=CGMCC 1.18046T=JCM 36511T) of the family Lachnospiraceae, and strain CSJ-4T was identified as representing a novel species of novel genus Pilosibacter fragilis gen. nov. sp. nov. (type strain CSJ-4T=CGMCC 1.18026T= JCM 36513T) of the family Clostridiaceae.