Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity.

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Phosphocreatine promotes epigenetic reprogramming to facilitate glioblastoma growth through stabilizing BRD2.

Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells (GSCs) reprogram the epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to the elevated transcription of brain-type creatine kinase (CKB), mediated by Zinc finger E-box binding homeobox 1 (ZEB1). PCr inhibits the poly-ubiquitination of the chromatin regulator bromodomain containing protein 2 (BRD2) by outcompeting the E3 ubiquitin ligase SPOP for BRD2 binding. Pharmacological disruption of PCr biosynthesis by cyclocreatine leads to BRD2 degradation and a decrease in its targets' transcription, which inhibits chromosome segregation and cell proliferation. Notably, cyclocreatine treatment significantly impedes tumor growth and sensitizes tumors to a BRD2 inhibitor in mouse GBM models without detectable side effects. These findings highlight that high production of PCr is a druggable metabolic feature of GBM and a promising therapeutic target for GBM treatment.

Tiny clue reveals the general trend: a bibliometric and visualized analysis of renal microcirculation.

BACKGROUND: Renal microcirculation plays a pivotal role in kidney function by maintaining structural and functional integrity, facilitating oxygen and nutrient delivery, and waste removal. However, a thorough bibliometric analysis in this area remains lacking. Therefore, we aim to provide valuable insights through a bibliometric analysis of renal microcirculation literature using the Web of Science database. METHODS: We collected renal microcirculation-related publications from the Web of Science database from January 01, 1990, to December 31, 2022. The co-authorship of authors, organizations, and countries/regions was analyzed with VOSviewer1.6.18. The co-occurrence of keywords and co-cited references were analyzed using CiteSpace6.1.R6 software to generate visualization maps. Additionally, burst detection was applied to keywords and cited references to forecast research hotspots and future trends. RESULTS: Our search yielded 7462 publications, with the American Journal of Physiology-Renal Physiology contributing the most articles. The United States, Mayo Clinic, and Lerman Lilach O emerged with the highest publication count, indicating their active collaborations. 'Type 2 diabetes' was the most significant keyword cluster, and 'diabetic kidney disease' was the largest cluster of cited references. 'Cardiovascular outcome' and 'diabetic kidney diseases' were identified as keywords in their burst period over the past three years. CONCLUSION: Our bibliometric analysis illuminates the contours of nephrology and microcirculation research, revealing a landscape ripe for challenges and the seeds of future scientific innovation. While the trends discerned from the literature emerging opportunities in diagnostic innovation, renal microcirculation research, and precision medicine interventions, their translation to clinical practice is anticipated to be a deliberate process.

Promoting bond durability by a novel fabricated bioactive dentin adhesive.

OBJECTIVE: To prepare a bioactive dentin adhesive and investigate its effect on promoting bonding durability of dentin. METHODS: The mineralization of the bioactive glass with high phosphorus (10.8 mol% P2O5-54.2 mol% SiO2-35 mol% CaO, named PSC) and its ability to induce type I collagen mineralization were observed by SEM and TEM. The Control-Bond and the bioactive dentin adhesive containing 20 wt% PSC particles (PSC-Bond) were prepared, and their degree of conversion (DC), microtensile bond strength (µTBS), film thickness and mineralization performance were evaluated. To evaluate the bonding durability, dentin bonding samples were prepared by Control-Bond and PSC-Bond, and mineralizated in simulated body fluid for 24 h, 3 months, and 6 months. Then, the long-term bond strength and microleakage at the adhesive interface of dentin bonding samples were evaluated by microtensile testing and semiquantitative ELIASA respectively. RESULTS: The PSC showed superior mineralization at 24 h and induced type I collagen mineralization to some extent under weakly alkaline conditions. For PSC-Bond, DC was 62.65 ± 1.20%, µTBS was 39.25 ± 4.24 MPa and film thickness was 17.00 ± 2.61 µm. PSC-Bond also formed hydroxyapatite and maintained good mineralization at the bonding interface. At 24 h, no significant differences in µTBS and interface microleakage were observed between the Control-Bond and PSC-Bond groups. After 6 months of aging, the µTBS was significantly higher and the interface microleakage was significantly lower of PSC-Bond group than those of Control-Bond group. SIGNIFICANCE: PSC-Bond maintained bond strength stability and reduced interface microleakage to some extent, possibly reducing the occurrence of secondary caries, while maintaining long-term effectiveness of adhesive restorations.

Ranolazine for improving coronary microvascular function in patients with nonobstructive coronary artery disease: a systematic review and meta-analysis with a trial sequential analysis of randomized controlled trials.

Background: Microvascular dysfunction in patients with nonobstructive coronary artery disease is increasingly being recognized as an important health issue. This systematic review and meta-analysis evaluated the effectiveness of ranolazine, an antianginal agent, in improving coronary microvascular function. Methods: We conducted a comprehensive literature search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, the Chinese BioMedical Literature Database, and gray literature databases until September 30, 2023. The included studies were randomized controlled trials (RCTs) published in the English or Chinese languages that screened for eligibility using two independent investigators. Risk of bias was evaluated with the Cochrane Collaboration tool. Subgroup and sensitivity analyses were used to identify sources of heterogeneity. Meta-analysis was performed using RevMan version 5.4 (Cochrane) and Stata version 16.0 (StataCorp). Results: From 1,470 citations, 8 RCTs involving 379 participants were included in this analysis. Our findings showed that ranolazine increased coronary flow reserve (CFR) over an 8 to 12-week follow-up period [standardized mean difference =1.16; 95% confidence interval (CI): 0.4-1.89; P=0.002]. Ranolazine increased the global myocardial perfusion reserve index (MPRI) [weighted mean difference (WMD) =0.18; 95% CI: 0.07-0.29; P=0.002] and the midsubendocardial MPRI (WMD =0.10; 95% CI: 0.02-0.19; P=0.02). Moreover, ranolazine improved 3 of the 5 Seattle Angina Questionnaire scores, namely, physical functioning (WMD =4.89; 95% CI: 0.14 to 9.64; P=0.04), angina stability (WMD =17.31; 95% CI: 7.13-27.49; P=0.0009), and quality of life (WMD =10.11; 95% CI: 3.57-16.65; P=0.0003). Trial sequential analysis showed that the meta-analysis of angina stability and quality of life scores had a sufficient sample size and statistical power. Conclusions: Our analysis suggests that ranolazine is associated with improvements in CFR, myocardial perfusion, and the Seattle Angina Questionnaire scores in patients with nonobstructive coronary artery disease. However, further large-scale RCTs with long-term follow-up are recommended to validate these findings and provide a more comprehensive understanding of the effects of ranolazine on coronary microvascular function.

3D bioprinting bioglass to construct vascularized full-thickness skin substitutes for wound healing.

Constructing three-dimensional (3D) bioprinted skin tissues that accurately replicate the mechanical properties of native skin and provide adequate oxygen and nutrient support remains a formidable challenge. In this study, we incorporated phosphosilicate calcium bioglasses (PSCs), a type of bioactive glass (BG), into the bioinks used for 3D bioprinting. The resulting bioink exhibited mechanical properties and biocompatibility that closely resembled those of natural skin. Utilizing 3D bioprinting technology, we successfully fabricated full-thickness skin substitutes, which underwent comprehensive evaluation to assess their regenerative potential in treating full-thickness skin injuries in rats. Remarkably, the skin substitutes loaded with PSCs exhibited exceptional angiogenic activity, as evidenced by the upregulation of angiogenesis-related genes in vitro and the observation of enhanced vascularization in wound tissue sections in vivo. These findings conclusively demonstrated the outstanding efficacy of PSCs in promoting angiogenesis and facilitating the repair of full-thickness skin wounds. The insights garnered from this study provide a valuable reference strategy for the development of skin tissue grafts with potent angiogenesis-inducing capabilities.

The morphology of occlusion stump for endovascular recanalization in non-acute vertebral ostial occlusion.

PURPOSE: Non-acute vertebral ostial occlusion (VOO) is a debilitating condition with significant mortality and morbidity rates. However, currently, there is no consensus on the optimal treatment strategy for VOO. This study aims to examine the feasibility, effectiveness, and safety of endovascular recanalization in patients with VOO. METHODS: We conducted a retrospective review of data from 21 consecutive patients with VOO who underwent endovascular recanalization between May 2018 and August 2023. The patients were divided into two groups based on a new angiographic classification proposed by Gao et al. Type I (tapered stump group) included patients with non-acute extracranial vertebral artery ostial occlusion presenting a tapered occlusion stump. Type II (nontapered stump group) consisted of patients with a nontapered occlusion stump. We collected data on recanalization rates, perioperative complications, and follow-up outcomes. RESULTS: Our analysis included data from a total of 21 patients (22 lesions) with a mean age of 64.6 ± 10.6 years. The technical success rate was 66.7 % (14/21), and the rate of periprocedural complications was 14.3 % (3/21). The success rate of transitioning from the tapered stump group to the nontapered stump group was 90.9 % (10/11) and 40 % (4/10), respectively (P = 0.024). The perioperative complication rate for type I and type II patients was 18.2 % (2/11) and 10 % (1/10), respectively. Among these patients, 18 cases underwent endovascular recanalization using transfemoral access, while 3 patients underwent transradial access after failed transfemoral access, with successful outcomes for two patients. CONCLUSIONS: This study suggests that endovascular recanalization may offer a safe, effective, and feasible treatment option for VOO patients. Additionally, the proposed angiographic classification may serve as a useful guide in selecting suitable candidates for surgery.

The structural transformation reversibility of biogas slurry derived dissolved organic matter and its binding properties with norfloxacin under temperature fluctuation.

The widespread use of biogas slurry could potentially raise the environmental risk of antibiotics. Dissolved organic matter (DOM), as the most active part of biogas slurry, was able to interact with antibiotics and play a crucial role in the structure and function of soil and aquatic ecosystems. The recent shifts in global climate patterns have garnered significant attention due to their substantial impact on temperature, thereby exerting a direct influence on the characteristics of DOM and subsequently on the environmental behavior of antibiotics. However, there is limited research concerning the impact of temperature on the binding of DOM and antibiotics. Thus, this study aimed to explore the temperature-dependent structural transformation and driving factors of biogas slurry-derived DOM (BSDOM). Additionally, the binding characteristics between BSDOM and the commonly used antibiotic norfloxacin (NOR) at different temperatures were studied by using multi spectroscopic methods and two-dimensional correlation spectroscopy (2D-COS) analysis. The results suggested that the temperature-dependent structural transformation of BSDOM was reversible, with a slight lag in the transition temperature under cooling (13 °C for heating and 17 °C for cooling). Heating promoted the conversion of protein-like to humic-like substances while cooling favored the decomposition of humic-like substances. BSDOM and NOR were static quenching, with oxygen-containing functional groups such as C-O and -OH playing an important role. Temperature influenced the order of binding, the activity of the protein fraction, and its associated functional groups. At temperatures of 25 °C and 40 °C, the fluorescent components were observed to exhibit consistent binding preferences, whereby the humic-like component demonstrated a greater affinity for NOR compared to the protein-like component. However, the functional group binding order exhibited an opposite trend. At 10 °C, a new protein-like component appeared and bound preferentially to NOR, when no C-O stretch corresponding to the amide was observed. The finding will contribute to a comprehensive understanding of the interaction mechanisms between DOM and antibiotics under climate change, as well as providing a theoretical basis to reduce the environmental risks of biogas slurry and antibiotics.

Mutator-like transposable element 9A interacts with metacaspase 1 and modulates the incidence of Al-induced programmed cell death in peanut.

The toxicity of aluminum (Al) in acidic soil inhibits plant root development and reduces crop yields. In the plant response to Al toxicity, the initiation of programmed cell death (PCD) appears to be an important mechanism for the elimination of Al-damaged cells to ensure plant survival. In a previous study, the type I metacaspase AhMC1 was found to regulate the Al stress response and to be essential for Al-induced PCD. However, the mechanism by which AhMC1 is altered in the peanut response to Al stress remained unclear. Here, we show that a nuclear protein, mutator-like transposable element 9A (AhMULE9A), directly interacts with AhMC1 in vitro and in vivo. This interaction occurs in the nucleus in peanut and is weakened during Al stress. Furthermore, a conserved C2HC zinc finger domain of AhMULE9A (residues 735-751) was shown to be required for its interaction with AhMC1. Overexpression of AhMULE9A in Arabidopsis and peanut strongly inhibited root growth with a loss of root cell viability under Al treatment. Conversely, knock down of AhMULE9A in peanut significantly reduced Al uptake and Al inhibition of root growth, and alleviated the occurrence of typical hallmarks of Al-induced PCD. These findings provide novel insight into the regulation of Al-induced PCD.

Harnessing the benefits of glycine supplementation for improved pancreatic microcirculation in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM.

Characterization of the FLA Gene Family in Tomato (Solanum lycopersicum L.) and the Expression Analysis of SlFLAs in Response to Hormone and Abiotic Stresses.

Fasciclin-like arabinogalactan proteins (FLAs), a subclass of arabinogalactan proteins (AGPs), participate in mediating plant growth, development, and response to abiotic stress. However, the characterization and function of FLAs in tomato are currently unknown. In this study, members of the tomato FLA family are characterized and analyzed in relation to their response to phytohormonal and abiotic stresses. The results show that a total of 24 FLA members were characterized in tomato. The structural domain analysis showed that these members have a high protein similarity. The expression profiles of different tissues indicated that the genes of most members of the tomato FLA gene family are highly expressed in roots, but to a lower extent in fruits. qRT-PCR analysis revealed that all 24 tomato FLA genes are responsive to ABA and MeJA. SlFLAs showed a positive response to salt and cold stress. SlFLA1, SlFLA12, and SlFLA14 are significantly induced under darkness. SlFLA1 and SlFLA3 are significantly induced under drought stress. This study provides a basis for a further understanding of the role of tomato FLA homologous genes in plant response to abiotic stress and lays the foundation for further research on the function of FLAs in tomato.

Identification and functional characterization of REGULATORY PARTICLE NON-ATPASE 1a-like (AhRPN1a-like) in peanuts during aluminum-induced programmed cell death.

The toxicity of aluminum (Al) in acidic soil is a prevalent problem and causes reduced crop yields. In the plant response to Al toxicity, programmed cell death (PCD) appears to be one of the important mechanisms. However, the regulation of Al-induced PCD remains poorly understood. Here, we found that an uncharacterized protein REGULATORY PARTICLE NON-ATPASE 1a-like in peanut (AhRPN1a-like), located in the nucleus and cytoplasm, directly interacted with type I metacaspase in peanut (AhMC1). The overexpression of AhRPN1a-like in Arabidopsis strongly enhanced Al inhibition of root growth with a loss of root tip cell viability. Furthermore, in response to Al treatment, the VIGS knockdown line of AhRPN1a-like in peanut displayed decreased transcription of AhMC1, increased root growth, reduced Al-induced PCD and decreased 26S proteasomal activity. Taken together, these findings demonstrated that AhRPN1a-like interacted directly with AhMC1, and promotes the occurrence of Al-induced PCD via the 26S proteasome pathway, thereby reducing Al-resistance.

LEF1 enhances ß-catenin transactivation through IDR-dependent liquid-liquid phase separation.

Wnt/ß-catenin signaling plays a crucial role in cancer development, primarily activated by ß-catenin forming a transcription complex with LEF/TCF in the nucleus and initiating the transcription of Wnt target genes. Here, we report that LEF1, a member of the LEF/TCF family, can form intrinsically disordered region (IDR)-dependent condensates with ß-catenin both in vivo and in vitro, which is required for ß-catenin-dependent transcription. Notably, LEF1 with disrupted IDR lost its promoting activity on tumor proliferation and metastasis, which can be restored by substituting with FUS IDR. Our findings provide new insight into the essential role of liquid-liquid phase separation in Wnt/ß-catenin signaling and present a potential new target for cancer therapy.

A colorimetric and fluorometric dual-mode probe for Cu2+detection based on functionalized silver nanoparticles.

A novel colorimetric/fluorescent probe (AgNPs-GSH-Rh6G2) was prepared by linking silver nanoparticles (AgNPs) with rhodamine 6G derivative (Rh6G2) using glutathione (GSH) as a linker molecule. The prepared probe showed obvious fluorescence change and colorimetric response after adding copper ions. Based on this phenomenon, a colorimetric/fluorescence dual-mode detection method was constructed to recognize copper ions. The linear ranges of fluorescence detection and colorimetric detection were 0.10 to 0.45 mM and 0.15 to 0.65 mM, respectively, and the limit of detection were 0.18 µM and 24.90 µΜ. In addition, the dual-mode probe has achieved satisfactory results in the detection of copper ions in sediment samples. The successful construction of AgNPs-GSH-Rh6G2 not only provide a reliable tool for the detection of copper ions, but also shed light on a new idea for the multi-mode development of the detection platform.

Increased plasma expression of a disintegrin and metalloproteinase with thrombospondin motifs like 4 in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can result in right heart failure. We aimed to evaluate the plasma protein levels of a disintegrin and metalloproteinase with thrombospondin motifs like 4 (ADAMTSL4) and its relationship with IPAH and CTEPH. Plasma ADAMTSL4 protein levels were measured using proteomics analysis in eight patients with IPAH and nine healthy controls. ADAMTSL4 levels in pulmonary tissues were assessed using bioinformatics tools. Protein expression of ADAMTSL4 in platelet-derived growth factor (PDGF)-BB-treated primary rat pulmonary arterial smooth muscle cells (PASMCs) was detected by Western blot. Plasma ADAMTSL4 concentrations were measured in 45 patients (15 with IPAH and 30 with CTEPH) using enzyme-linked immunosorbent assay (ELISA). Correlation between ADAMTSL4 levels and clinical parameters was evaluated. In patients with IPAH, the plasma levels of ADAMTSL4 protein were significantly higher than those in healthy controls (flod change [FC] 1.85, p < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, p < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup (p < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 ± 0.73 ng/mL, p < 0.01) and CTEPH (4.22 ± 0.66 ng/mL, p < 0.01) were higher than in healthy controls (3.01 ± 0.46 ng/mL). Plasma ADAMATL4 protein levels had a cutoff value of 3.55 ng/mL based on the receiver operator characteristic curve and were positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.305, p < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP.

Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.

Nitrogen-Rich Porous Organic Polymers from an Irreversible Amine-Epoxy Reaction for Pd Nanocatalyst Carrier.

Nitrogen-rich porous organic polymers were fabricated through a nonreversible ring-opening reaction from polyamines and polyepoxides (PAEs). The epoxide groups reacted with both primary and secondary amines provided by the polyamines at different epoxide/amine ratios with polyethylene glycol as the solvent to form the porous materials. Fourier-transform infrared spectroscopy confirmed the occurrence of ring opening between the polyamines and polyepoxides. The porous structure of the materials was confirmed through N2 adsorption-desorption data and scanning electron microscopy images. The polymers were found to possess both crystalline and noncrystalline structures, as evidenced by X-ray diffraction and high-resolution transmission electron microscopy (HR-TEM) results. The HR-TEM images revealed a thin, sheet-like layered structure with ordered orientations, and the lattice fringe spacing measured from these images was consistent with the interlayer of the PAEs. Additionally, the selected area electron diffraction pattern indicated that the PAEs contained a hexagonal crystal structure. The Pd catalyst was fabricated in situ onto the PAEs support by the NaBH4 reduction of the Au precursor, and the size of the nano-Pd was about 6.9 nm. The high nitrogen content of the polymer backbone combined with Pd noble nanometals resulted in excellent catalytic performance in the reduction of 4-nitrophenol to 4-aminophenol.

Identification of ABF/AREB gene family in tomato (Solanum lycopersicum L.) and functional analysis of ABF/AREB in response to ABA and abiotic stresses.

Abscisic acid (ABA) is a plant hormone that plays an important regulatory role in plant growth and stress response. The AREB (ABA-responsive element binding protein)/ABF (ABRE-binding factor) are important ABA-signaling components that participate in abiotic stress response. However, genome-scale analysis of ABF/AREB has not been systemically investigated in tomato. This study was conducted to identify tomato ABF/AREB family members and analyze their response to ABA and abiotic stresses. The results show that a total of 10 ABF/AREB members were identified in tomato, which are randomly distributed on five chromosomes. Domain analysis showed that these members exhibit high protein similarity, especially in the basic leucine zipper (bZIP) domain region. Subcellular localization analysis indicated that all 10 ABF/AREB members are localized in the nucleus. Phylogenetic tree analysis showed that tomato ABF/AREB genes are divided into two groups, and they are similar with the orthologs of other plants. The analysis of cis-acting elements showed that most tomato ABF/AREB genes contain a variety of hormones and stress-related elements. Expression profiles of different tissues indicated that SlABF2 and SlABF10 play an important role in fruit ripening. Finally, qRT-PCR analysis revealed that 10 tomato ABF/AREB genes respond to ABA, with SlABF3 being the most sensitive. SlABF3, SlABF5 and SlABF10 positively respond to salt and cold stresses. SlABF1, SlABF3 and SlABF10 are significantly induced under UV radiation treatment. SlABF3 and SlABF5 are significantly induced in osmotic stress. Overall, this study may provide insight into the role of tomato ABF/AREB homologues in plant response to abiotic stresses, which laid a foundation for future functional study of ABF/AREB in tomato.

3D bioprinting microgels to construct implantable vascular tissue.

Engineered implantable functional thick tissues require hierarchical vasculatures within cell-laden hydrogel that can mechanically withstand the shear stress from perfusion and facilitate angiogenesis for nutrient transfer. Yet current extrusion-based 3D printing strategies are unable to recapitulate hierarchical networks, highlighting the need for bioinks with tunable properties. Here, we introduce an approach whereby crosslinkable microgels enhance mechanical stability and induce spontaneous microvascular networks comprised of human umbilical cord vein endothelial cells (HUVECs) in a soft gelatin methacryoyl (GelMA)-based bioink. Furthermore, we successfully implanted the 3D printed multi-branched tissue, being connected from the rat carotid artery to the jugular vein direct surgical anastomosis. The work represents a significant step toward in the field of large vascularized tissue fabrication and may have implications for the treatment of organ failure in the future.

Protective effect of Nrf2 in periodontitis - A preclinical systematic review and meta-analysis.

OBJECTIVE: Periodontitis is an inflammatory disease, while Nuclear factor erythroid-2 related factor 2 (Nrf2) acts a significant part in antioxidant, anti-inflammatory and immune response. However, the evidence in preclinical studies to certify Nrf2 can slow down the progression of periodontitis or facilitate its recovery is not enough. The present report aims to investigate the functional implications of Nrf2 in animal periodontitis models by evaluating the changes of Nrf2 levels and analyzing the clinical benefits of Nrf2 activation in the same models. DESIGN: We searched PubMed, Web of Science, EBSCO, CNKI, VIP, Wan Fang databases. The random-effects model was used to evaluate the mean differences (MD) and 95 % confidence intervals (95%CI) when the units of measurements of outcome indicators were the same, in contrast, the standardized mean differences (SMD) and 95%CI were evaluated while the units were different. RESULTS: 8 studies were included for quantitative synthesis. Compared with healthy groups, the expression of Nrf2 was markedly lower in periodontitis groups (SMD: -3.69; 95%CI: -6.25, -1.12). After administration of kinds of Nrf2-activators, a significant increase in Nrf2 levels (SMD: 2.01; 95%CI: 1.27, 2.76) was accompanied by a decrease in distance between cementoenamel junction and alveolar bone crest (CEJ-ABC) (SMD: -2.14; 95%CI: -3.29, -0.99) and an improvement of bone volume/tissue volume (BV/TV) (SMD:17.51; 95%CI: 16.24, 18.77) was evaluated compared with periodontitis groups. CONCLUSIONS: Nrf2 has a certain protective effect on periodontitis, however, the specific role Nrf2 plays in the development and severity of periodontitis remains to be demonstrated. PROSPERO registration number: CRD42022328008.