VBP1 promotes tumor proliferation as a part of the hypoxia-related signature in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in East Asia. Hypoxia, a hallmark of solid tumors, significantly alters redox homeostasis inside tumor microenvironment. This alteration drives tumor proliferation, invasion, and metastasis, leading to poor prognostic outcomes. However, the role of hypoxia-related genes in ESCC remains poorly understood. We employed RNA sequencing to identify differentially expressed genes in ESCC. Clinical data, transcriptome profiles, and a hypoxia-related gene set were extracted from open-source databases. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression, which was then validated through Cox regression analysis. Within this prognostic model, we pinpointed and investigated a key hypoxia-related gene affecting prognosis. The gene's expression was validated using real-time PCR and immunohistochemistry in both esophageal carcinoma and normal tissues. Tumor proliferation was examined through in vitro and in vivo assays, including the Cell Counting Kit-8, EdU, colony formation, and subcutaneous tumor models. A robust four-gene prognostic model (VBP1, BGN, CDKN1A, and PPFIA1) was successfully constructed and validated. Among these, VBP1 emerged as a key gene, exhibiting high expression levels that correlated with poor prognosis in ESCC. Functional experiments confirmed that VBP1 significantly accelerated tumor proliferation both in vitro and in vivo. VBP1 is identified as a pivotal gene within the hypoxia-related prognostic signature, and it significantly promotes tumor proliferation in ESCC.

Association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography.

OBJECTIVE: Many previous studies reported the relationship between lipoprotein(a) and cardiovascular disease, but the conclusions were controversial. The aim of our study was to retrospectively investigate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. METHODS: We collected and compared clinical information of patients hospitalized for coronary angiography. Multivariable hierarchical logistic regression was used to evaluate the association between lipoprotein(a) and cardiovascular disease in patients undergoing coronary angiography. RESULTS: There were no significant differences in gender, hypertension, APOA1, smoking, hyperuricemia, obesity, acute myocardial infarction (AMI), cardiac insufficiency, family history of diabetes, or family history of hyperlipidemia among the four groups of lipoprotein(a). Elevated lipoprotein(a) does not increase the risk of hypertriglyceridemia, while elevated lipoprotein(a) increases the risk of high total cholesterol and high low-density lipoprotein cholesterol (LDL-c). Elevated lipoprotein(a) increases the risk of diabetes and premature coronary artery disease (CAD). Elevated lipoprotein(a) increases the incidence of CAD, multivessel lesions, and percutaneous coronary intervention (PCI). Multivariate logistic regression analysis further showed that elevated lipoprotein(a) increases the incidence of high total cholesterol, high LDL­c, diabetes, CAD, premature CAD, multivessel lesions, and PCI. CONCLUSION: The findings indicated that elevated lipoprotein(a) had no obvious relationship with hypertension and obesity. Elevated lipoprotein(a) increases the risk of high total cholesterol, high LDL­c, and premature CAD, and increases the occurrence and severity of coronary heart disease.

LepR-expressing cells are a critical population in periodontal healing post periodontitis.

Identification of promising seed cells plays a pivotal role in achieving tissue regeneration. This study demonstrated that LepR-expressing cells (LepR+ cells) are required for maintaining periodontal homeostasis at the adult stage. We further investigated how LepR+ cells behave in periodontal healing using a ligature-induced periodontitis (PD) and a self-healing murine model with LepRCre/+; R26RtdTomato/+ mice. Lineage tracing experiments revealed that the largely suppressed osteogenic ability of LepR+ cells results from periodontal inflammation. Periodontal defects were partially recovered when the ligature was removed, in which the osteogenic differentiation of LepR+ cell lineage was promoted and contributed to the newly formed alveolar bone. A cell ablation model established with LepRCre/+; R26RtdTomato/+; R26RDTA/+ mice further proved that LepR+ cells are an important cell source of newly formed alveolar bone. Expressions of ß-catenin and LEF1 in LepR+ cells were upregulated when the inflammatory stimuli were removed, which are consistent with the functional changes observed during periodontal healing. Furthermore, the conditional upregulation of WNT signaling or the application of sclerostin neutralized antibody promoted the osteogenic function of LepR+ cells. In contrast, the specific knockdown of ß-catenin in LepR+ human periodontal ligament cells with small interfering RNA caused arrested osteogenic function. Our findings identified the LepR+ cell lineage as a critical cell population for endogenous periodontal healing post PD, which is regulated by the WNT signaling pathway, making it a promising seed cell population in periodontal tissue regeneration.

Heterosis of endophytic microbiomes in hybrid rice varieties improves seed germination.

Seed endophytic microbiomes are shaped by host and environmental factors and play a crucial role in their host growth and health. Studies have demonstrated that host genotype, including hybridization, affects seed microbiomes. Heterosis features are also observed in root-associated microbiomes. It remains unclear, however, whether heterosis exists in seed endophytic microbiomes and whether hybrid microbiota provide noticeable advantages to host plant growth, especially to seed germination. Here, we investigated the structure of seed endophytic bacterial and fungal communities from three hybrid rice varieties and their respective parents using amplicon sequencing targeting 16S rRNA and ITS2 genes. Heterosis was found in diversity and composition of seed endophytic microbiomes in hybrids, which hosted more diverse communities and significantly higher abundances of plant growth-promoting taxa, such as Pseudomonas and Rhizobium genera compared with their parental lines. Co-occurrence network analysis revealed that there are potentially tighter microbial interactions in the hybrid seeds compared with their parent seeds. Finally, inoculation of seed-cultivable endophytes, isolated from hybrids, resulted in a greater promotion of seed germination compared with those isolated from parent lines. These findings suggest that heterosis exists not only in plant traits but also in seed endophytic microbiota, the latter in turn promotes seed germination, which offers valuable guidance for microbiome-assisted rice breeding.IMPORTANCEGenetic and physiological changes associated with plant hybridization have been studied for many crop species. Still, little is known about the impact of hybridization on the seed microbiota. In this study, we indicate that hybridization has a significant impact on the endophytic bacterial and fungal communities in rice seeds. The seed endophytic microbiomes of hybrids displayed distinct characteristics from those of their parental lines and exhibited potential heterosis features. Furthermore, the inoculation of seed-cultivable endophytes isolated from hybrids exhibited a greater promotion effect on seed germination compared with those isolated from the parents. Our findings make a valuable contribution to the emerging field of microbiome-assisted plant breeding, highlighting the potential for a targeted approach that aims to achieve not only desired plant traits but also plant-beneficial microbial communities on the seeds.

Random forest model in tax risk identification of real estate enterprise income tax.

The text describes improvements made to the random forest model to enhance its distinctiveness in addressing tax risks within the real estate industry, thereby tackling issues related to tax losses. Firstly, the paper introduces the potential application of the random forest model in identifying tax risks. Subsequently, the experimental analysis focuses on the selection of indicators for tax risk. Finally, the paper develops and utilizes actual taxpayer data to test a risk identification model, confirming its effectiveness. The experimental results indicate that the model's output report includes basic taxpayer information, a summary of tax compliance risks, value-added tax refund situations, directions of suspicious items, and detailed information on common indicators. This paper comprehensively presents detailed taxpayer data, providing an intuitive understanding of tax-related risks. Additionally, the paper reveals the level of enterprise risk registration assessment, risk probability, risk value, and risk assessment ranking. Further analysis shows that enterprise risk points primarily exist in operating income, selling expenses, financial expenses, and total profit. Additionally, the results indicate significant differences between the model's judgment values and declared values, especially in the high-risk probability of total operating income and profit. This implies a significant underreporting issue concerning corporate income tax for real estate enterprises. Therefore, this paper contributes to enhancing the identification of tax risks for real estate enterprises. Using the optimized random forest model makes it possible to accurately assess enterprises' tax compliance risks and identify specific risk points.

The survival of periodontally treated molars in long-term maintenance: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis aimed to determine the survival of periodontally treated molars during maintenance care and identify the risk factors associated with molar loss among patients with periodontitis who received professional periodontal therapy and maintenance. MATERIALS AND METHODS: Longitudinal studies with a minimum follow-up duration of 5 years published until 28 August 2023 were retrieved from the following databases: the Cochrane Library, Embase, MEDLINE and Web of Science. All included studies reported data on molar retention. Meta-analysis was performed using Review Manager 5.4. A modified version of the Newcastle-Ottawa Scale was used to evaluate the study quality. Statistical results of analyses of the overall survival rate and molar loss are presented as estimated standardized mean differences, whereas the results of the analyses of risk factors are presented as risk ratios with 95% confidence intervals (95% CIs). RESULTS: From among the 1323 potentially eligible reports, 41 studies (5584 patients, 29,908 molars retained at the beginning of maintenance therapy, mean follow-up duration of 14.7 years) were included. The pooled survival rate of the molars during maintenance therapy was 82% (95% CI: 80%-84%). The average loss of molars was 0.05 per patient per year (95% CI: 0.04-0.06) among the patients receiving long-term periodontal maintenance (PM) therapy. Fifteen factors were examined in this meta-analysis. Six patient-related factors (older age, lack of compliance, smoking, bruxism, diabetes and lack of private insurance) and five tooth-related factors (maxillary location, high probing pocket depth, furcation involvement, higher mobility and lack of pulpal vitality) were identified as risk factors for molar loss during maintenance therapy. CONCLUSIONS: The findings of the present study suggest that the long-term retention of periodontally compromised molars can be achieved. The average number of molars lost per decade was <1 among the patients receiving long-term PM therapy. Older age, noncompliance, smoking, bruxism, diabetes, lack of private insurance coverage, maxillary location, furcation involvement, higher mobility, increase in the probing pocket depth and loss of pulpal vitality are strong risk factors for the long-term prognosis of molars.

Association between cardiometabolic index and depression: National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Emerging evidence suggests a common pathophysiological basis for metabolic disorders and mental diseases. Despite the existence of reports suggesting a strong connection between dyslipidemia and depression, a comprehensive and reliable indicator to identify depression is still lacking. Cardiometabolic index (CMI) is an integrated index calculated from three vital metabolic indicators, including triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and waist height ratio (WHtR). OBJECTIVE: This study aims to explore the association between CMI and depression. METHODS: Cross-sectional data of participants with complete information of CMI, depression, and other covariates were obtained from the National Health and Nutrition Examination Survey (NHANES). Weighted student's t-test and Chi-square test were used to identify the differences between two groups. Weighted multivariate logistic regression model, restricted cubic spline (RCS) regression analysis, subgroup analysis and interaction tests were conducted to explore the association between CMI and depression. Receiver operating curve (ROC) analysis and area under the curve (AUC) were also utilized to evaluate the performance of CMI in identifying depression. RESULTS: A positive correlation between CMI and depression was observed in 3794 participants included in the study, which was further confirmed to be non-linear via RCS regression analysis, with two significant inflection points being identified, including 0.9522 and 1.58. In the crude or adjusted models, individuals with a CMI level ≥ 0.9522 exhibited remarkably increased risk for developing depression. CMI got an AUC of 0.748 in identifying depression. Subgroup analyses and interaction tests indicate that the association between CMI and depression remained consistent across different subgroups and was not modified by other covariates except drinking. Those who are current drinkers and with a high CMI are more susceptible to suffer depression. CONCLUSIONS: An elevated CMI is linked to increased risk for depression. Addressing dyslipidemia and improving lipid levels may potentially lower the risk for depression.

The Clinical Characteristics of Heart Rate Variability After Stroke: A Systematic Review.

The autonomic nervous system dysfunction has been reported in up to 76% of stroke patients 7 days after an acute stroke. Heart rate variability (HRV) is one of the important indicators reflecting the balance of sympathetic and parasympathetic nerves. Therefore, we performed a systematic literature review of existing literature on the association between heart rate variability and the different types of stroke. We included studies published in the last 32 years (1990 to 2022). The electronic databases MEDLINE and PubMed were searched. We selected the research that met the inclusion or exclusion criteria. A narrative synthesis was performed. This review aimed to summarize evidence regarding the potential mechanism of heart rate variability among patients after stroke. In addition, the association of clinical characteristics of heart rate variability and stroke has been depicted. The review further discussed the relationship between post-stroke infection and heart rate variability, which could assist in curbing clinical infection in patients with stroke. HRVas a noninvasive clinical monitoring tool can quantitatively assess the changes in autonomic nervous system activity and further predict the outcome of stroke. HRV could play an important role in guiding the clinical practice for autonomic nervous system disorder after stroke.

[Effects of Aeration Methods on Microbial Diversity and Community Structure in Rice Rhizosphere].

To explore the effects of different aeration methods on the abundance of microorganisms and microorganism community structure in rice rhizosphere soil, two rice varieties, Miyang 46(MY) and Zhenshan 97B(ZS), were used with three aeration treatments:alternate wetting and drying(AWD), continuous flooding and aeration(CFA), and continuous flooding(CF). The diversity of bacterial and fungal communities in rice rhizosphere soil was analyzed using Illumina MiSeq high-throughput sequencing. Soil physical and chemical factors were also analyzed. The results showed that the dominant bacterial communities in rice rhizosphere soil were Chloroflexi, Actinobaciota, Acidobacteria, Proteobacteria, and Firmicutes, and the dominant fungal communities were Ascomycota and Basidiomycota in rice rhizosphere soil. At each growth stage, the relative abundance of Chloroflexi and Acidobacteria was higher in the AWD treatment than in the other treatments, and the relative abundance of Actinobaciota was higher in the CFA treatment than in the other treatments. The relative abundance of Firmicutes was lower in the AWD treatment than in the other treatments. Aeration methods affected the diversity and richness of rhizosphere microbial species. For example, the diversity of bacterial species was higher, and the richness of bacterial species was lower in the AWD treatment than that in the other treatments. The diversity and richness of fungal species were higher in the AWD and CFA treatments than those in the CF treatment. The physical and chemical properties of rhizosphere soil were also affected by aeration method. The soil redox potential(Eh) was the highest in AWD, followed by that in CFA and CF, and significant differences were observed among treatments. The NO3--N content was significantly higher, and the NH4+-N content was significantly lower in the AWD and CFA treatments than in the CF treatment in rhizosphere soil at all growth stages. Correlation analysis showed that the pH and Eh of rhizosphere soil were positively correlated with the diversity of bacterial species, negatively correlated with the richness of bacterial species, and positively correlated with the diversity and richness of fungal species. Redundancy analysis indicated that the relative abundance of Chloroflexi was positively correlated with the pH and NH4+-N content at each period, positively correlated with the Eh and NO3--N content at the tillering and heading stages, and negatively correlated with Eh and NO3--N content at the maturity stage. At each growth stage, the pH and Eh were positively correlated with the relative abundance of Acidobacteria, Proteobacteria, and Basidiomycota and negatively correlated with the relative abundance of Firmicutes and Ascomycota. During the entire growth period, the relative abundance of Ascomycota was negatively correlated with the NO3--N content and positively correlated with the NH4+-N content, and the opposite patterns were observed for the relative abundance of Basidiomycota. In summary, rhizosphere oxygenation enhanced the soil oxygen environment, altered soil physical and chemical properties, and affected microbial community diversity and richness to optimize microbial community structure.

Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Anthocyanin attenuates high salt-induced hypertension via inhibiting the hyperactivity of the sympathetic nervous system.

BACKGROUND: Anthocyanin plays a protective role in cardiovascular disease through antioxidant effect. Whether anthocyanin can reduce salt-induced hypertension and the related mechanisms remain unclear. METHODS: Chronic infusion of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 µL/h) or anthocyanin (10 mg/kg, 0.4 µL/h) into bilateral paraventricular nucleus (PVN) of Sprague-Dawley rats was performed. Then, the rats were fed a high salt diet (8% NaCl, HS) or normal salt diet (0.9%, NaCl, NS) for 4 weeks. RESULTS: High salt diet induced an increase in blood pressure and peripheral sympathetic nerve activity (increased LF/HF and decreased SDNN and RMSSD), which was accompanied by increased reactive oxygen species (ROS) production and angiotensin II type-1 receptor (AT1R) expression and function in the PVN. Moreover, the NOD-like receptor protein 3 (NLRP3) and related inflammatory proteins (caspase-1) expression, the pro-inflammatory cytokine levels including IL-1ß and TNF-α were higher in PVN of rats with a high salt diet. Bilateral PVN infusion of anthocyanin attenuated NLRP3-dependent inflammation (NLRP3, caspase-1, IL-1ß and TNF-α) and ROS production, reduced AT1R expression and function in PVN and lowered peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension. CONCLUSIONS: Excessive salt intake activates NLRP3-dependent inflammation and oxidative stress and increased AT1R expression and function in the PVN. Bilateral PVN infusion of anthocyanin lowers peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension by improvement of expression and function of AT1R in the PVN through inhibiting NLRP3 related inflammatory and oxidative stress.

Axin2-CreERT2 mediated knockout of bone morphogenetic protein receptor type 1A caused abnormal secondary dentine and altered cell fate of Axin2-expressing odontogenic cells.

AIM: Inducing odontogenic differentiation and tubular dentine formation is extremely important in dentine repair and tooth regeneration. Bone morphogenic proteins (BMPs) signalling plays a critical role in dentine development and tertiary dentine formation, whilst how BMPR1A-mediated signalling affects odontoblastic differentiation of Axin2-expressing (Axin2+ ) odontogenic cells and tubular dentine formation remains largely unknown. This study aims to reveal the cellular and molecular mechanisms involved in the formation of secondary dentine. METHODOLOGY: Axin2lacZ/+ mice harvested at post-natal 21 (P21) were used to map Axin2+ mesenchymal cells. Axin2CreERT2/+ ; R26RtdTomato/+ mice and Axin2CreERT2/+ ; R26RDTA/+ ; R26RtdTomato/+ mice were generated to observe the tempo-spatial distribution pattern of Axin2-lineage cells and the effect of ablation of Axin2+ cells on dentinogenesis, respectively. A loss-of-function model was established with Axin2CreERT2/+ ; Bmpr1afl/fl ; R26RtdTomato/+ (cKO) mice to study the role of BMP signalling in regulating Axin2+ cells. Micro-computed tomography, histologic and immunostainings, and other approaches were used to examine biological functions, including dentine formation, mineralization and cell differentiation in cKO mice. RESULTS: The results showed rich expression of Axin2 in odontoblasts at P21. Lineage tracing assay confirmed the wide distribution of Axin2 lineage cells in odontoblast layer and dental pulp during secondary dentine formation (P23 to P56), suggesting that Axin2+ cells are important cell source of primary odontoblasts. Ablation of Axin2+ cells (DTA mice) significantly impaired secondary dentine formation characterized with notably reduced dentine thickness (Mean of control: 54.11 µm, Mean of DTA: 27.79 µm, p = .0101). Furthermore, malformed osteo-dentine replaced the tubular secondary dentine in the absence of Bmpr1a with irregular cell morphology, abnormal cellular process formation and lack of cell-cell tight conjunction. Remarkably increased expression of osteogenic markers like Runx2 and DMP1 was detected, whilst DSP expression was observed in a dispersed manner, indicating an impaired odontogenic cell fate and failure in producing tubular dentine in cKO mice. CONCLUSIONS: Axin2+ cells are a critical population of primary odontoblasts which contribute to tubular secondary dentine formation, and BMP signalling pathway plays a vital role in maintaining the odontogenic fate of Axin2+ cells.

The BrAFP1 promoter drives gene-specific expression in leaves and stems of winter rapeseed (Brassica rapa L.) under cold induction.

BrAFP1(antifreeze protein in winter turnip rape) effectively limits recrystallization and growth of ice crystals. The BrAFP1 expression level determines whether the freezing-induced damage to winter turnip rape plants is avoided. This study analyzed the activity of the BrAFP1 promoters of several varieties at various cold tolerance levels. We cloned the BrAFP1 promoters from five winter rapeseed cultivars. The multiple sequence alignment revealed the presence of one inDel and eight single-nucleotide mutations (SNMs) in the promoters. One of these SNMs (base mutation from C to T) at the -836 site away from the transcription start site (TSS) enhanced the transcriptional activity of the promoter at low temperature. The promoter activity was specific in cotyledons and hypocotyls during the seedling stage and was referential in stems, leaves, and flowers but not the calyx. This consequently drove the downstream gene to be specifically expressed in leaves and stems, but not in roots at low temperature. The truncated fragment GUS staining assays revealed that the core region of the BrAFP1 promoter was included in the 98 bp fragment from the -933 to -836 site away from the TSS, which was necessary for transcriptional activity. The LTR element of the promoter significantly enhanced expression at low temperatures and suppressed expression at moderate temperatures. Moreover, the BrAFP1 5'-UTR intron bound the scarecrow-like transcription factor and enhanced expression at low temperature.

Carbon nanosphere synthesis and applications for rechargeable batteries.

Carbon nanospheres (CNSs) have attracted great interest in energy conversion and storage technologies due to their excellent chemical and thermal stability, high electrical conductivity and controllable size structure characteristics. In order to further improve the energy storage properties, many efforts have been made to design suitable nanocarbon spherical materials to improve electrochemical performance. In this overview, we summarize the recent research progress on CNSs, mainly focusing on the synthesis methods and their application as high-performance electrode materials in rechargeable batteries. As for the synthesis methods, hard template methods, soft template methods, the extension of the Stöber method, hydrothermal carbonization, aerosol-assisted synthesis are described in detail. In addition, the use of CNSs as electrodes in energy storage devices (mainly concentrated on lithium-ion batteries (LIBs)), sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) are also discussed in detail in this article. Finally, some perspectives on the future research and development of CNSs are provided.

Osteogenic mesenchymal stem cells/progenitors in the periodontium.

Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor populations of alveolar bone formation will provide valuable insights into regenerative approaches to clinical practice, such as endogenous regeneration and stem-cell-based tissue engineering therapies. Classically, MSCs residing in the bone marrow, periosteum, periodontal ligament (PDL), and even the gingiva are considered to be osteogenic progenitors. Furthermore, the contributions of MSCs expressing specific markers, including Gli1, Axin2, PTHrP, LepR, and α-SMA, to alveolar bone formation have been studied using cell lineage tracing and gene knockout models. In this review, we describe the MSCs/progenitors of alveolar bone and the biological properties of different subpopulations of MSCs involved in alveolar bone development, remodeling, injury repair, and regeneration.

Loss of ß-catenin causes cementum hypoplasia by hampering cementogenic differentiation of Axin2-expressing cells.

BACKGROUND AND OBJECTIVE: Although cementum plays an essential role in tooth attachment and adaptation to occlusal force, the regulatory mechanisms of cementogenesis remain largely unknown. We have previously reported that Axin2-expressing (Axin2+ ) mesenchymal cells in periodontal ligament (PDL) are the main cell source for cementum growth, and constitutive activation of Wnt/ß-catenin signaling in Axin2+ cells results in hypercementosis. Therefore, the aim of the present study was to further evaluate the effects of ß-catenin deletion in Axin2+ cells on cementogenesis. MATERIALS AND METHODS: We generated triple transgenic mice to conditionally delete ß-catenin in Axin2-lineage cells by crossing Axin2CreERT2/+ ; R26RtdTomato/+ mice with ß-cateninflox/flox mice. Multiple approaches, including X-ray analysis, micro-CT, histological stainings, and immunostaining assays, were used to analyze cementum phenotypes and molecular mechanisms. RESULTS: Our data revealed that loss of ß-catenin in Axin2+ cells led to a cementum hypoplasia phenotype characterized by a sharp reduction in the formation of both acellular and cellular cementum. Mechanistically, we found that conditional removal of ß-catenin in Axin2+ cells severely impaired the secretion of cementum matrix proteins, for example, bone sialoprotein (BSP), dentin matrix protein 1 (DMP1) and osteopontin (OPN), and markedly inhibited the differentiation of Axin2+ mesenchymal cells into osterix+ cementoblasts. CONCLUSIONS: Our findings confirm the vital role of Axin2+ mesenchymal PDL cells in cementum growth and demonstrate that Wnt/ß-catenin signaling shows a positive correlation with cementogenic differentiation of Axin2+ cells.

Tendon Cells Root Into (Instead of Attach to) Humeral Bone Head via Fibrocartilage-Enthesis.

Large joints are composed of two closely linked cartilages: articular cartilage (AC; rich in type II collagen, a well-studied tissue) and fibrocartilaginous enthesis (FE; rich in type I collagen, common disorder sites of enthesopathy and sporting injuries, although receiving little attention). For many years, both cartilages were thought to be formed by chondrocytes, whereas tendon, which attaches to the humeral bone head, is primarily considered as a completely different connective tissue. In this study, we raised an unconventional hypothesis: tendon cells directly form FE via cell transdifferentiation. To test this hypothesis, we first qualitatively and quantitatively demonstrated distinct differences between AC and FE in cell morphology and cell distribution, mineralization status, extracellular matrix (ECM) contents, and critical ECM protein expression profiles using comprehensive approaches. Next, we traced the cell fate of tendon cells using ScxLin (a tendon specific Cre ScxCreERT2; R26R-tdTomato line) with one-time tamoxifen induction at early (P3) or young adult (P28) stages and harvested mice at different development ages, respectively. Our early tracing data revealed different growth events in tendon and FE: an initial increase but gradual decrease in the ScxLin tendon cells and a continuous expansion in the ScxLin FE cells. The young adult tracing data demonstrated continuous recruitment of ScxLin cells into FE expansion during P28 and P56. A separate tracing line, 3.2 Col 1Lin (a so-called "bone-specific" line), further confirmed the direct contribution of tendon cells for FE cell formation, which occurred in days but FE ECM maturation (including high levels of SOST, a potent Wnt signaling inhibitor) took weeks. Finally, loss of function data using diphtheria toxin fragment A (DTA) in ScxLin cells demonstrated a significant reduction of ScxLin cells in both tendons and FE cells, whereas the gain of function study (by stabilizing ß-catenin in ScxLin tendon cells via one-time injection of tamoxifen at P3 and harvesting at P60) displayed great expansion of both ScxLin tendon and FE mass. Together, our studies demonstrated that fibrocartilage is an invaded enthesis likely originating from the tendon via a quick cell transdifferentiation mechanism with a lengthy ECM maturation process. The postnatally formed fibrocartilage roots into existing cartilage and firmly connects tendon and bone instead of acting as a simple attachment site as widely believed. We believe that this study will stimulate more intense exploring in this understudied area, especially for patients with enthesopathy and sporting injuries.

Role of renal tubular programed cell death in diabetic kidney disease.

The pathogenic mechanism of diabetic kidney disease (DKD) is involved in various functions; however, its inadequate characterisation limits the availability of effective treatments. Tubular damage is closely correlated with renal function and is thought to be the main contributor to the injury observed in early DKD. Programed cell death (PCD) occurs during the biological development of the living body. Accumulating evidence has clarified the fundamental role of abnormalities in tubular PCD during DKD pathogenesis. Among PCD types, classical apoptosis, autophagic cell death, and pyroptosis are the most studied and will be the focus of this review. Our review aims to elucidate the current knowledge of the mechanism of DKD and the potential therapeutic potential of drugs targeting tubular PCD pathways in DKD.

Activation of Wnt signaling in Axin2+ cells leads to osteodentin formation and cementum overgrowth.

OBJECTIVES: In this study, we used the mouse incisor model to investigate the regulatory mechanisms of Wnt/ß-catenin signaling on Axin2+ cells in tooth development. MATERIALS AND METHODS: Axin2lacZ/+ reporter mice were used to define the expression pattern of Axin2 in mouse incisors. We traced the fate of Axin2+ cells from postnatal Day 21 (P21) to P56 using Axin2CreERT2/+ and R26RtdTomato/+ reporter mice. For constitutive activation of Wnt signaling, Axin2CreERT2/+ , ß-cateninflox(Ex3)/+ , and R26RtdTomato/+ (CA-ß-cat) mice were generated to investigate the gain of function (GOF) of ß-catenin in mouse incisor growth. RESULTS: The X-gal staining of Axin2lacZ/+ reporter mice and lineage tracing showed that Axin2 was widely expressed in dental mesenchyme of mouse incisors, and Axin2+ cells were essential cell sources for odontoblasts, pulp cells, and periodontal ligament cells. The constitutive activation of Wnt signaling in Axin2+ cells resulted in the formation of osteodentin featured with increased DMP1 and dispersed DSP expression and overgrowth of cementum. CONCLUSION: Wnt signaling plays a key role in the differentiation and maturation of Axin2+ cells in mouse incisors.

Nitrogen fertilization modulates rice seed endophytic microbiomes and grain quality.

The intensive use of chemical fertilizer, particularly nitrogen (N) has resulted in not only markedly increased crop yields but also detrimental effects on ecosystems. Plant microbiomes represent an eco-friendly alternative for plant nutrition and productivity, and the effect of N fertilization on plant and soil microbes has been well studied. However, if and how N fertilization modulates seed endophytic microbiomes and grain quality remains largely unknown. Here, we investigated the effect of different N fertilization rates on rice seed endophytic bacterial and fungal communities as well as on grain quality. Higher bacterial and fungal community diversity and richness, but lower grain protein and amino acid contents were found in seeds of rice treated moderate N fertilization than those treated insufficient or excessive N input. There were also more complex co-occurrence networks, and an enrichment of putative beneficial bacterial taxa in seeds under moderate N application, while there was an opposite trend under the excessive N treatment. In addition, the grain amylose and amylopectin contents were positively correlated with the relative abundance of bacterial and fungal dominant genera, while the grain amino acid contents were negatively correlated with the bacterial dominant genera but positively associated with fungal dominant genera. Together, we demonstrate that moderate N fertilization can enhance bacterial and fungal community colonization in seeds and improve grain eating and cooking qualities. This study extends our knowledge regarding the significant role of rational fertilization on seed-microbe interactions in sustainable agriculture.