Genetically engineered CD276-anchoring biomimetic nanovesicles target senescent escaped tumor cells to overcome chemoresistant and immunosuppressive breast cancer.

Chemotherapy-induced cellular senescence leads to an increased proportion of cancer stem cells (CSCs) in breast cancer (BC), contributing to recurrence and metastasis, while effective means to clear them are currently lacking. Herein, we aim to develop new approaches for selectively killing senescent-escape CSCs. High CD276 (95.60%) expression in multidrug-resistant BC cells, facilitates immune evasion by low-immunogenic senescent escape CSCs. CALD1, upregulated in ADR-resistant BC, promoting senescent-escape of CSCs with an anti-apoptosis state and upregulating CD276, PD-L1 to promote chemoresistance and immune escape. We have developed a controlled-released thermosensitive hydrogel containing pH- responsive anti-CD276 scFV engineered biomimetic nanovesicles to overcome BC in primary, recurrent, metastatic and abscopal humanized mice models. Nanovesicles coated anti-CD276 scFV selectively fuses with cell membrane of senescent-escape CSCs, then sequentially delivers siCALD1 and ADR due to pH-responsive MnP shell. siCALD1 together with ADR effectively induce apoptosis of CSCs, decrease expression of CD276 and PD-L1, and upregulate MHC I combined with Mn2+ to overcome chemoresistance and promote CD8+T cells infiltration. This combined therapeutic approach reveals insights into immune surveillance evasion by senescent-escape CSCs, offering a promising strategy to immunotherapy effectiveness in cancer therapy.

Enhanced computed tomography radiomics predicts solute carrier family 7, member 11 in head and neck squamous cell carcinoma.

Introduction: Traditional prognostic indicators for head and neck squamous cell carcinoma (HNSCC), such as clinicopathological features, human papillomavirus status, and imaging examinations, often lack precision in guiding medical therapy. Therefore, discovering novel tumor biomarkers that can accurately assess prognosis and aid in personalized medical treatment for HNSCC is critical. Solute carrier family 7, member 11 (SLC7A11), is implicated in ferroptosis, and various malignant tumor therapies regulate its expression. However, the mechanisms regulating SLC7A11 expression, the transporter activity, and its specific role in controlling ferroptosis in cancer cells remain unknown. Thus, in this study, we aimed to develop an improved computed tomography (CT) radiomics model that could predict SLC7A11 expression in patients with HNSCC. Methods: We used patient genomic data and corresponding augmented CT images for prognostic analysis and building models. Further, we investigated the potential molecular mechanisms underlying SLC7A11 expression in the immune microenvironment. Our radiomics model successfully predicted SLC7A11 mRNA expression in HNSCC tissues and elucidated its association with relevant genes and prognostic outcomes. Results: SLC7A11 expression level was high within tumor tissues and was connected to the infiltration of eosinophil, CD8+ T-cell, and macrophages, which was associated with poor overall survival. Our models demonstrated robust predictive power. The distribution of radiomics scores (RAD scores) within the training and validation sets was markedly different between the high- and low-expression groups of SLC7A11. Conclusion: SLC7A11 is likely an important factor in the prognosis of HNSCC. SLC7A11 expression can be predicted effectively and reliably by radiomics models based on enhanced CT.

Lightweight medical image segmentation network with multi-scale feature-guided fusion.

In the field of computer-aided medical diagnosis, it is crucial to adapt medical image segmentation to limited computing resources. There is tremendous value in developing accurate, real-time vision processing models that require minimal computational resources. When building lightweight models, there is always a trade-off between computational cost and segmentation performance. Performance often suffers when applying models to meet resource-constrained scenarios characterized by computation, memory, or storage constraints. This remains an ongoing challenge. This paper proposes a lightweight network for medical image segmentation. It introduces a lightweight transformer, proposes a simplified core feature extraction network to capture more semantic information, and builds a multi-scale feature interaction guidance framework. The fusion module embedded in this framework is designed to address spatial and channel complexities. Through the multi-scale feature interaction guidance framework and fusion module, the proposed network achieves robust semantic information extraction from low-resolution feature maps and rich spatial information retrieval from high-resolution feature maps while ensuring segmentation performance. This significantly reduces the parameter requirements for maintaining deep features within the network, resulting in faster inference and reduced floating-point operations (FLOPs) and parameter counts. Experimental results on ISIC2017 and ISIC2018 datasets confirm the effectiveness of the proposed network in medical image segmentation tasks. For instance, on the ISIC2017 dataset, the proposed network achieved a segmentation accuracy of 82.33 % mIoU, and a speed of 71.26 FPS on 256 × 256 images using a GeForce GTX 3090 GPU. Furthermore, the proposed network is tremendously lightweight, containing only 0.524M parameters. The corresponding source codes are available at https://github.com/CurbUni/LMIS-lightweight-network.

Ultrasensitive lab-on-paper electrochemical device via heterostructure copper/cuprous sulfide@N-doped C@Au hollow nanoboxes as signal amplifier for alpha-fetoprotein detection.

Rapid and accurate detection of tumor markers at extremely low levels is crucial for the early diagnosis of cancers. In this work, we developed a portable label-free sliding electrochemical paper-based analytical device (ePAD) using copper/cuprous sulfide@N-doped C@Au nanoparticles (Cu/Cu2S@NC@Au) hollow nanoboxes as the signal amplifier for the ultrasensitive detection of alpha-fetoprotein (AFP). Cu/Cu2S@NC nanoboxes were synthesized by sacrificial template and interface reaction methods, on which Au nanoparticles were electrodeposited to construct unique heterostructure for effectively capturing anti-AFP and serving as signal amplifier. The designed ePAD incorporates sliding microfluidic paper chips to form a flexible three-electrode system, enabling highly sensitive detection of AFP with a wide linear range of 0.005-50 ng mL-1 and a low detection limit of 0.62 pg mL-1. The practicality of the prepared ePAD was validated through AFP detection in clinical human serum, which was consistent with chemiluminescence immunoassay. In addition, the developed immunosensor demonstrates excellent specificity, repeatability and stability. This novel platform exhibits significant potential for rapid on-site analysis and point-of-care diagnosis.

Bioactive modification of cyclic olefin copolymer (COC) film surfaces by hyaluronic acid and chitosan for enhanced cell adhesion.

Cyclic olefin copolymer (COC) has recently emerged as an attractive material in biomedical fields for its high purity, excellent stability and chemical resistance, particularly in applications of microfluidic chips, prefilled syringes and bone regeneration. However, the high hydrophobicity of COC has inhibited the adhesion of cells and biological macromolecules, such as proteins, etc., significantly limiting its broader applications. In this study, we propose a new method to modify COC surfaces by sequential coating with polydopamine (PDA) followed by hyaluronic acid (HA) or O-carboxymethyl chitosan (CMC), while comparing the impacts of the positively charged HA and negatively charged CMC on protein adsorption and cell adhesion. FTIR and XPS measurements confirmed the successful modification on COC films, resulting in surfaces with highly increased hydrophilicity, anti-oxidative properties, and improved protein adsorption. Moreover, negatively charged HA, with signal transduction capabilities showed a greater effect in promoting cell adhesion. Thus, we present a straightforward strategy for enhancing the hydrophilicity of COC surfaces, offering new insights into COC modification and potential biomedical applications.

Tuning metal-support interactions in nickel-zeolite catalysts leads to enhanced stability during dry reforming of methane.

Ni-based catalysts are highly reactive for dry reforming of methane (DRM) but they are prone to rapid deactivation due to sintering and/or coking. In this study, we present a straightforward approach for anchoring dispersed Ni sites with strengthened metal-support interactions, which leads to Ni active sites embedded in dealuminated Beta zeolite with superior stability and rates for DRM. The process involves solid-state grinding of dealuminated Beta zeolites and nickel nitrate, followed by calcination under finely controlled gas flow conditions. By combining in situ X-ray absorption spectroscopy and ab initio simulations, it is elucidated that the efficient removal of byproducts during catalyst synthesis is conducted to strengthen Ni-Si interactions that suppress coking and sintering after 100 h of time-on-stream. Transient isotopic kinetic experiments shed light on the differences in intrinsic turnover frequency of Ni species and explain performance trends. This work constructs a fundamental understanding regarding the implication of facile synthesis protocols on metal-support interaction in zeolite-supported Ni sites, and it lays the needed foundations on how these interactions can be tuned for outstanding DRM performance.

Adverse event profile differences between pralsetinib and selpercatinib: a real-world study based on the FDA adverse events reporting system.

Aims: The objective of this study is to compare the adverse events (AEs) associated with pralsetinib and selpercatinib. Methods: To evaluate the imbalance of AEs linked to pralsetinib and selpercatinib in real-world data, the reporting odds ratio (ROR) was utilized to detect potential signals of AEs. Stratified analysis was conducted to examine the differences in AEs occurring among different genders and age groups taking pralsetinib and selpercatinib. Results: FAERS received 891 reports for pralsetinib and 569 reports for selpercatinib. Our analysis confirmed expected AEs like hypertension, fatigue, and elevated transaminase levels. Unexpected AEs such as rhabdomyolysis, myocardial injury and cognitive disorder were associated with pralsetinib, while selpercatinib was linked with pulmonary embolism, deep vein thrombosis, and pericardial effusion. The risk of AEs such as decreased platelet count, anemia, decreased white blood cell count, pneumonitis, asthenia, and edema caused by pralsetinib is significantly higher than that of selpercatinib. In contrast, the risk of AEs such as ascites, elevated alanine aminotransferase, and elevated aspartate aminotransferase caused by selpercatinib is significantly higher than that of pralsetinib. Women treated with pralsetinib experience higher rates of hypertension, pulmonary embolism, and blurred vision than men, who are more susceptible to rhabdomyolysis. Adults between 18 and 65 years are more likely to experience taste disorder, edema, and pulmonary embolism than individuals older than 65, who are particularly vulnerable to hypertension. For patients treated with selpercatinib, males demonstrate a significantly higher incidence of QT prolongation, urinary tract infection, and dysphagia. Individuals aged 18 to 65 are more likely to experience pyrexia and pleural effusion than those older than 65, who are more prone to hypersensitivity. Conclusion: In the clinical administration of pralsetinib and selpercatinib, it is crucial to monitor the effects of gender and age on AEs and to be vigilant for unlisted AEs.

Loss of MMP9 disturbs cranial suture fusion via suppressing cell proliferation, chondrogenesis and osteogenesis in mice.

Cranial sutures function as growth centers for calvarial bones. Abnormal suture closure will cause permanent cranium deformities. MMP9 is a member of the gelatinases that degrades components of the extracellular matrix. MMP9 has been reported to regulate bone development and remodeling. However, the function of MMP9 in cranial suture development is still unknown. Here, we identified that the expression of Mmp9 was specifically elevated during fusion of posterior frontal (PF) suture compared with other patent sutures in mice. Interestingly, inhibition of MMP9 ex vivo or knockout of Mmp9 in mice (Mmp9-/-) disturbed the fusion of PF suture. Histological analysis showed that knockout of Mmp9 resulted in wider distance between osteogenic fronts, suppressed cell condensation and endocranial bone formation in PF suture. Proliferation, chondrogenesis and osteogenesis of suture cells were decreased in Mmp9-/- mice, leading to the PF suture defects. Moreover, transcriptome analysis of PF suture revealed upregulated ribosome biogenesis and downregulated IGF signaling associated with abnormal closure of PF suture in Mmp9-/- mice. Inhibition of the ribosome biogenesis partially rescued PF suture defects caused by Mmp9 knockout. Altogether, these results indicate that MMP9 is critical for the fusion of cranial sutures, thus suggesting MMP9 as a potential therapeutic target for cranial suture diseases.

Association Between Circulating Inflammatory Cytokines and Dentofacial Anomalies.

INTRODUCTION AND AIMS: Previous studies have shown that some inflammatory cytokines are associated with dentofacial anomalies (DA), but the causal relationship is unclear. Therefore, the present study aimed to elucidate the relationship between circulating inflammatory cytokines, and DA risk by Mendelian randomization analysis. METHODS: A two-way two-sample Mendelian randomization analysis was used in our study. Data on 91 inflammatory cytokines were sourced from genome-wide association studies encompassing 14,824 participants across 11 distinct cohorts and protein quantitative trait loci from deCODE (35,559 participants). Summary statistics for DA were acquired from the FinnGen consortium (9254 cases and 245,664 controls). The inverse variance weighting method was used as the primary analysis, supplemented by a series of sensitivity analyses to determine the robustness and reliability of our findings. RESULTS: The analysis identified five cytokines - chemokine ligand 25, interleukin (IL)-10 receptor beta, IL-20, and stem cell factor - as inversely related to DA prevalence. Additionally, DA was associated with decreased levels of fibroblast growth factor (FGF)-19 and IL-24, and increased levels of FGF-23 and urokinase-type plasminogen activator. These findings were validated using protein quantitative trait loci data. CONCLUSION: Our study substantiates an association between inflammatory cytokines and DA, emphasizing inflammation's pivotal role in the aetiology of DA. CLINICAL SIGNIFICANCE: The findings provide a plausible genetic underpinning for the role of inflammation in DA, offering novel avenues for the development of targeted diagnostic and therapeutic strategies.

Ultrasound-Responsive Nanocarriers Delivering siRNA and Fe3O4 Nanoparticles Reprogram Macrophages and Inhibit M2 Polarization for Enhanced NSCLC Immunotherapy.

Lung cancer has emerged as the second most common type of malignant tumor worldwide, and it has the highest mortality rate. The overall 5-year survival rate stands at less than 20%, which is primarily related to the limited therapeutic options and the complexity of the tumor immune microenvironment. In the tumor microenvironment, M1 macrophages are known for their tumor-killing capabilities. Although they are less numerous, they play an important role in tumor immunity. Therefore, increasing M1 macrophages' presence is considered a strategy to enhance targeted phagocytosis and antitumor efficacy in nonsmall cell lung cancer (NSCLC). This study introduces the development of folic acid (FA)-conjugated liposomal nanobubbles for precise delivery of PFH, STAT3 siRNA, and Fe3O4 to the tumor microenvironment. These encapsulated PFH liposomal nanobubbles exhibit significant visualization potential and underwent phase transition when exposed to low-intensity focused ultrasound (LIFU). The release of Fe3O4 activates the IRF5 signaling pathway, converting M2-like macrophages to M1. In addition, STAT3 siRNA effectively interrupts the JAK-STAT3 pathway, inhibiting the polarization of M2-like macrophages in tumor-associated macrophages (TAMs). This dual-action therapy facilitates T-cell activation and proliferation, thereby enhancing the immune response against NSCLC.

Clinical benefits of deep inspiration breath-hold in postoperative radiotherapy for right-sided breast cancer: a meta-analysis.

OBJECTIVES: The study aims to emphasize the clinical importance of the Deep Inspiration Breath Hold (DIBH) technique by quantifying its dosimetric advantages over Free Breathing (FB) in reducing radiation exposure to the heart, liver, and lungs for right-sided breast cancer patients. This evidence supports its potential for routine clinical use to mitigate radiation-induced toxicity. METHODS: A systematic retrieval of controlled trials comparing DIBH and FB techniques in postoperative radiotherapy for right-sided breast cancer was conducted utilizing the PubMed, Embase, Cochrane Library, and Web of Science databases. The primary outcomes assessed included the doses of adjacent normal tissues (heart, liver, and lungs). Summary standardized mean differences (SMD) along with 95% confidence intervals (CI) were computed, respectively. StataMP 17 software was selected to perform data analysis. RESULTS: The study encompassed an analysis of 313 patients derived from seven online studies, comprising 168 individuals in the DIBH group and 269 individuals in the FB group. The findings indicated that the DIBH group received significantly lower irradiation doses to the heart, liver, and lungs in comparison to the FB group, with statistical significance (heart dose: SMD = -0.63, 95% CI -0.85 to -0.41, P < 0.05; liver dose: SMD = -1.15, 95% CI -1.91 to -0.38, P < 0.05; lung dose: SMD = -0.79, 95% CI -1.23 to -0.35, P < 0.05). CONCLUSION: This meta-analysis indicated that the application of DIBH during postoperative radiotherapy for right-sided breast cancer markedly decreases radiation exposure to the heart, liver, and lungs, while maintaining consistent tumor dose coverage. CLINICAL TRIAL NUMBER: Not applicable.

The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood.

BACKGROUND: Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old. METHODS: This research involved 895 mother-child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath's epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones. RESULTS: The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), - 13.22 (- 23.21 to - 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), - 14.13 (- 21.59 to - 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than - 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than - 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than - 1.35, followed by a plateau between - 1.35 and - 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than - 0.67. CONCLUSIONS: In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.

Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization.

An accurate diagnosis of Parkinson's disease (PD) remains challenging and the exact cause of the disease is unclean. The aims are to identify hub genes associated with the complement system in PD and to explore their underlying molecular mechanisms. Initially, differentially expressed genes (DEGs) and key module genes related to PD were mined through differential expression analysis and WGCNA. Then, differentially expressed CSRGs (DE-CSRGs) were obtained by intersecting the DEGs, key module genes and CSRGs. Subsequently, MR analysis was executed to identify genes causally associated with PD. Based on genes with significant MR results, the expression level and diagnostic performance verification were achieved to yield hub genes. Functional enrichment and immune infiltration analyses were accomplished to insight into the pathogenesis of PD. qRT-PCR was employed to evaluate the expression levels of hub genes. After MR analysis and related verification, CD93, CTSS, PRKCD and TLR2 were finally identified as hub genes. Enrichment analysis indicated that the main enriched pathways for hub genes. Immune infiltration analysis found that the hub genes showed significant correlation with a variety of immune cells (such as myeloid-derived suppressor cell and macrophage). In the qRT-PCR results, the expression levels of CTSS, PRKCD and TLR2 were consistent with those we obtained from public databases. Hence, we mined four hub genes associated with complement system in PD which provided novel perspectives for the diagnosis and treatment of PD.

Ultrasound-responsive nanocarriers with siRNA and Fe3O4 regulate macrophage polarization and phagocytosis for augmented non-small cell lung cancer immunotherapy.

The immunosuppressive tumor microenvironment (TME) significantly inhibits the effective anti-tumor immune response, greatly affecting the efficacy of immunotherapy. Most tumor-associated macrophages (TAMs) belong to the M2 phenotype, which contributes significantly to the immunosuppressive effects in non-small cell lung cancer (NSCLC) TME. The interaction between signal regulatory protein α (SIRPα) expressed on macrophages and CD47, a transmembrane protein overexpressed on cancer cells, activates the "eat-me-not" signaling pathway, inhibiting phagocytosis. In this study, a folic acid (FA)-modified ultrasound responsive gene/drugs delivery system, named FA@ PFP @ Fe3O4 @LNB-SIRPα siRNA (FA-PFNB-SIRPα siRNA), was developed using 1,2-dioleoacyl-3-trimethylammonium-propane (DOTAP), FA-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino (polyethylene glycol)2000] (DSPE-PEG2000-FA), cholesterol, and perfluoropentane (PFP), for the delivery of siRNA encoding SIRPα mRNA and immune adjuvant Fe3O4 nanoparticles. Under ultrasound conditions, the nanobubbles effectively transfected macrophages, inhibiting SIRPα mRNA and protein expression, promoting the phagocytosis of TAMs, and synergistically reversing M2 polarization. This system promotes the infiltration of T cells, enhances the proliferation and activation of cytotoxic T cells, and inhibits the infiltration of immunosuppressive cells in tumor tissues. Administration of FA-PFNB-SIRPα siRNA combined with ultrasound significantly inhibits NSCLC progression. The study highlights the potential of ultrasound nanotechnology-enabled delivery of SIRPα siRNA and Fe3O4 as an effective strategy for macrophage-based immunotherapy to reshape the immunosuppressive TME for cancer therapy.

Novel nanocomposite and biochar insights to boost rice growth and alleviation of Cd toxicity.

Cadmium (Cd) is an unessential and pervasive contaminant in agricultural soil, eventually affecting the food and instigating health issues. The implication of nanocomposites in agriculture attained significant attention to drive food security. Nanocomposites possess exceptional characteristics to stun the challenges of chemical fertilizers that can enhance plant yield and better nutrient bioavailability. Similarly, biochar has the ability to immobilize Cd in soil by reducing mobility and bioavailability. Rice husk biochar is produced at high temperature pyrolysis under anoxic conditions and a stable carbon-rich material is formed. To strive against this issue, rice plants were subjected to Cd (15, 20 mg kg- 1) stress and treated with alone/combined Ca + Mg (25 mg L- 1) nanocomposite and rice husk biochar. In our study, growth and yield traits showed the nurturing influence of Ca + Mg nanocomposite and biochar to improve rice defence mechanism by reducing Cd stress. Growth parameters root length 28%, shoot length 34%, root fresh weight 19%, shoot fresh weight 16%, root dry weight 9%, shoot dry weight 8%, number of tillers 32%, number of grains 20%, and spike length 17% were improved with combined application of Ca + Mg and biochar, with Cd (20 mg kg- 1), rivalled to alone biochar. Combined Ca + Mg and biochar application increased the SPAD 23%, total chlorophyll 26%, a 19%, b 18%, and carotenoids 15%, with Cd (20 mg kg- 1), rivalled to alone biochar. MDA 15%, H2O2 13%, and EL 10% were significantly regulated in shoots with combined Ca + Mg and biochar application with Cd (20 mg kg- 1) compared to alone biochar. POD 22%, SOD 17%, APX 18%, and CAT 9% were increased in shoots with combined Ca + Mg and biochar application with Cd (20 mg kg- 1) compared to alone biochar. Cd uptake in roots 13%, shoots 14%, and grains 21% were minimized under Cd (20 mg kg- 1) with combined Ca + Mg and B. pumilus application, compared to alone biochar. Subsequently, combined Ca + Mg and biochar application is a sustainable solution to boost crop production under Cd stress.

Effects of the Fungicide Prothioconazole on Lipid Metabolism in Mice: Whitening Alterations of Brown Adipose Tissue.

With considerable concerns about the associations between metabolic disorders and agricultural biocides, there are scattered data suggesting that the triazole fungicide prothioconazole (PTC) at lower doses than the no observed adverse effect level of 5000 µg/kg/d possibly has the potential to disrupt glycolipid metabolism in mammals. Here, we investigated the effects of 50, 500, and 5000 µg/kg/d of PTC on glycolipid metabolism in mice following 8 weeks of administration via drinking water, with specific attention on brown adipose tissue (BAT) and white adipose tissue (WAT) in addition to the liver. We found that along with the increased serum triglyceride level in the 5000 µg/kg/d group, small fatty vacuoles occurred in livers in all treatment groups, indicating lipid accumulation. No change in WAT was observed, but PTC caused BAT whitening, characterized by adipocyte hypertrophy, more unilocular adipocytes with enlarged lipid droplets, reduced UCP1 levels, and down-regulated Doi2 expression, and even the dose of 50 µg/kg/d was effective. Transcriptomic analysis revealed immune inhibition and circadian rhythm disturbance in BAT from the 5000 µg/kg/d group, which are in agreement with BAT whitening and inactivation. On employing the C3H10T1/2 cells in vitro, we found that PTC treatment concentration-dependently promoted lipid accumulation in brown adipocytes, along with altered expression of thermogenesis-related and circadian genes. Taken together, our study shows that low doses of PTC caused BAT whitening, calling for much attention to the new target by pollutants.

CREB3L1 deficiency impairs odontoblastic differentiation and molar dentin deposition partially through the TMEM30B.

Odontoblasts are primarily responsible for synthesizing and secreting extracellular matrix proteins, which are crucial for dentinogenesis. Our previous single-cell profile and RNAscope for odontoblast lineage revealed that cyclic adenosine monophosphate responsive element-binding protein 3 like 1 (Creb3l1) was specifically enriched in the terminal differentiated odontoblasts. In this study, deletion of Creb3l1 in the Wnt1+ lineage led to insufficient root elongation and dentin deposition. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing were performed to revealed that in CREB3L1-deficient mouse dental papilla cells (mDPCs), the genes near the closed chromatin regions were mainly associated with mesenchymal development and the downregulated genes were primarily related to biological processes including cell differentiation, protein biosynthesis and transport, all of which were evidenced by a diminished ability of odontoblastic differentiation, a significant reduction in intracellular proteins, and an even greater decline in extracellular supernatant proteins. Dentin matrix protein 1 (Dmp1), dentin sialophosphoprotein (Dspp), and transmembrane protein 30B (Tmem30b) were identified as direct transcriptional regulatory targets. TMEM30B was intensively expressed in the differentiated odontoblasts, and exhibited a significant decline in both CREB3L1-deficient odontoblasts in vivo and in vitro. Deletion of Tmem30b impaired the ability of odontoblastic differentiation, protein synthesis, and protein secretion in mDPCs. Moreover, overexpressing TMEM30B in CREB3L1-deficient mDPCs partially rescued the extracellular proteins secretion. Collectively, our findings suggest that CREB3L1 participates in dentinogenesis and facilitates odontoblastic differentiation by directly enhancing the transcription of Dmp1, Dspp, and other differentiation-related genes and indirectly promoting protein secretion partially via TMEM30B.

Effectiveness of pulpotomy in managing carious exposure in mature permanent teeth: A systematic review and meta-analysis.

OBJECTIVES: This quantitative systematic review evaluated whether pulpotomy performed with hydraulic calcium silicate cements may be used as an alternative to root canal treatment (RCT) in mature permanent teeth with carious pulp exposure. DATA SOURCES: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library. No language restrictions were applied. The search included randomised controlled trials that compared pulpotomy to root canal treatment for managing carious exposure in mature permanent teeth. STUDY SELECTION: Studies were selected based on predetermined inclusion criteria: randomised controlled trials involving mature permanent teeth with carious pulp exposure, using hydraulic calcium silicate cements for pulpotomy. Non-comparative studies, case reports, and trials involving primary or immature permanent teeth were excluded. DATA: Data were extracted on success rates, clinical outcomes, follow-up periods, pain profiles, and potential complications. A meta-analysis was performed, revealing no statistically significant differences in success rates between pulpotomy and RCT. Both interventions demonstrated success rates exceeding 90 % at one-year and two-year follow-up periods. Pain profiles consistently showed lower post-operative pain intensity in the pulpotomy group compared to the RCT group during the first week. Potential complications, such as non-responsive pulp and difficulties in determining pulp vitality, were reported more frequently in the pulpotomy group. CONCLUSIONS: Pulpotomy with bioactive hydraulic calcium silicate cements shows comparable success rates to RCT in managing carious pulp exposure in mature permanent teeth. The results suggest pulpotomy as a viable, less invasive alternative to RCT, particularly in cases where preservation of pulp vitality is paramount. CLINICAL SIGNIFICANCE: This systematic review highlights pulpotomy as a less invasive and cost-effective alternative to root canal treatment in mature permanent teeth. With comparable success rates and lower post-operative pain, pulpotomy offers a promising approach to managing carious exposure and preserving tooth vitality.

Interaction between macrophages and ferroptosis: Metabolism, function, and diseases.

ABSTRACT: Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated by several metabolic processes, including iron metabolism, lipid metabolism, and redox system. Macrophages are a group of innate immune cells that are widely distributed throughout the body, and play pivotal roles in maintaining metabolic balance by its phagocytic and efferocytotic effects. There is a profound association between the biological functions of macrophage and ferroptosis. Therefore, this review aims to elucidate three key aspects of the unique relationship between macrophages and ferroptosis, including macrophage metabolism and their regulation of cellular ferroptosis; ferroptotic stress that modulates functions of macrophage and promotion of inflammation; and the effects of macrophage ferroptosis and its role in diseases. Finally, we also summarize the possible mechanisms of macrophages in regulating the ferroptosis process at the global and local levels, as well as the role of ferroptosis in the macrophage-mediated inflammatory process, to provide new therapeutic insights for a variety of diseases.

Association between mode of delivery and early neurodevelopment: A prospective birth cohort study.

Previous research has assessed the effects of caesarean delivery (CD) on child neurodevelopment; however, whether the effects stem from the surgical procedure itself or its related medical conditions has not been conclusively determined. This study aimed to evaluate the associations among delivery mode, CD-related medical conditions and early childhood neurodevelopment. A total of 3829 maternal-infant pairs from a longitudinal birth cohort in Wuhan City, China, were included in the primary analysis. The neurodevelopment of the children was assessed by the Bayley Scales of Infant Development (BSID), the Conners Comprehensive Behaviour Rating Scale and the Chinese version of the Autism Behavior Checklist. Data on delivery mode and medical conditions were collected via medical records from the study hospital. Among the 3829 children for whom the BSID test was completed at two years of age, 50%, 27%, and 23% were delivered vaginally, by necessary CD, and by elective CD, respectively. Compared with vaginally delivered children, Necessary CD was associated with a 16.67% decrease in Mental Development Index (MDI) scores and a 13.37% decrease in Psychomotor Development Index (PDI) scores, while elective CD showed a 20.63% and 20.99% decrease after FDR correction, respectively. Similarly, among the 2448 children for whom the CBRS was completed, necessary CD was found to be associated with conduct disorders (adjusted ß: 0.06; 95% CI: 0.02, 0.09), hyperactivity (adjusted ß: 0.06; 95% CI: 0.02, 0.11), and hyperactivity index (adjusted ß: 0.07; 95% CI: 0.03, 0.11), while elective CD was significantly associated with hyperactivity problem scores (adjusted ß: 0.08, 95% CI: 0.03, 0.13). However, no significant association was found between CD and symptoms of autism in children, as assessed by the Autism Behavior Checklist (ABC). CONCLUSION: This study suggested that the adverse impact of CD on child neurodevelopment stems from the procedure itself rather than CD-related medical conditions. It is important to minimize the use of CD when there is no medical necessity. WHAT IS KNOWN: • Caesarean delivery (CD) may influence child neurodevelopment and other long-term outcomes. • In China, approximately one-quarter of CD are performed due to maternal request without medical indications. WHAT IS NEW: • The negative impact of CD on the neurodevelopmental outcomes of children may be primarily attributed to the procedure itself, as opposed to related medical conditions. • In the absence of medical indications, unnecessary CD may have adverse impacts on children's neurodevelopment.