The association between dietary patterns before pregnancy and gestational diabetes mellitus: a matched case-control study in China.

BACKGROUND AND OBJECTIVES: We aimed to explore the relationship between dietary patterns and gestational diabetes mellitus (GDM) during pre-pregnancy six months using principal component analysis (PCA) and the geometric framework for nutrition (GFN). METHODS AND STUDY DESIGN: We conducted a case-control study that included 210 GDM pregnant women and 210 controls. The dietary intake of all participants was assessed by a validated semi-quantitative food frequency questionnaire (FFQ). Major dietary patterns were extracted by PCA. A conditional logistic regression model was used to determine whether specific dietary patterns are associated with the risk of GDM. Meanwhile, the relationship between dietary patterns and GDM was visualized using GFN. RESULTS: Four major dietary patterns were identified: "protein-rich pattern," "plant-based pattern," "oil-pickles-desserts pattern," and "cereals-nuts pattern." After adjustment for confounders, the "plant-based pattern" was associated with decreased risk of GDM (Q4 vs. Q1: OR = 0.01, 95% CI: 0.00-0.08), whereas no significant association was found in other dietary patterns. Moreover, there was no dietary intake of ice cream cones and deep-fried dough sticks for the population, which would produce fewer patients with GDM. Deep-fried dough sticks had statistically significant differences in the case and control groups (p < 0.001), while ice cream cones had the opposite result. CONCLUSIONS: The "plant-based pattern" may reduce the risk of GDM. Besides, although the "cereals-nuts pattern" had no association with GDM risk, avoiding the intake of deep-fried dough sticks could decrease GDM risk.

A strategy to distinguish similar traditional Chinese medicines by liquid chromatography-mass spectrometry, electronic senses, and gas chromatography-ion mobility spectrometry: Marsdeniae tenacissimae Caulis and Paederiae scandens Caulis as examples.

INTRODUCTION: Marsdeniae tenacissimae Caulis (MTC), a popular traditional Chinese medicine, has been widely used in the treatment of tumor diseases. Paederiae scandens Caulis (PSC), which is similar in appearance to MTC, is a common counterfeit product. It is difficult for traditional methods to effectively distinguish between MTC and PSC. Therefore, there is an urgent need for a rapid and accurate method to identify MTC and PSC. OBJECTIVES: The aim is to distinguish between MTC and PSC by analyzing the differences in nonvolatile organic compounds (NVOCs), taste, odor, and volatile organic compounds (VOCs). METHODS: Liquid chromatography-mass spectrometry (LC-MS) was utilized to analyze the NVOCs of MTC and PSC. Electronic tongue (E-tongue) and electronic nose (E-nose) were used to analyze their taste and odor respectively. Gas chromatography-ion mobility spectrometry (GC-IMS) was applied to analyze VOCs. Finally, multivariate statistical analyses were conducted to further investigate the differences between MTC and PSC, including principal component analysis, orthogonal partial least squares discriminant analysis, discriminant factor analysis, and soft independent modeling of class analysis. RESULTS: The results of this study indicate that the integrated strategy of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis can be effectively applied to distinguish between MTC and PSC. Using LC-MS, 25 NVOCs were identified in MTC, while 18 NVOCs were identified in PSC. The major compounds in MTC are steroids, while the major compounds in PSC are iridoid glycosides. Similarly, the distinct taste difference between MTC and PSC was precisely revealed by the E-tongue. Specifically, the pronounced bitterness in PSC was proven to stem from iridoid glycosides, whereas the bitterness evident in MTC was intimately tied to steroids. The E-nose detected eight odor components in MTC and six in PSC, respectively. The subsequent statistical analysis uncovered notable differences in their odor profiles. GC-IMS provided a visual representation of the differences in VOCs between MTC and PSC. The results indicated a relatively high relative content of 82 VOCs in MTC, contrasted with 32 VOCs exhibiting a similarly high relative content in PSC. CONCLUSION: In this study, for the first time, the combined use of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis has proven to be an effective method for distinguishing between MTC and PSC from multiple perspectives. This approach provides a valuable reference for the identification of other visually similar traditional Chinese medicines.

The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis.

BACKGROUND: Renal interstitial fibrosis (RIF) is a progressive, irreversible terminal kidney disease with a poor prognosis and high mortality. Angiopoietin-like 4 (ANGPTL4) is known to be associated with fibrosis in various organs, but its impact on the RIF process remains unclear. This study aimed to elucidate the role and underlying mechanisms of ANGPTL4 in the progression of RIF. METHODS: In vivo, a chronic kidney disease (CKD) rat model of renal interstitial fibrosis was established via intragastric administration of adenine at different time points (4 and 6 weeks). Blood and urine samples were collected to assess renal function and 24-h urinary protein levels. Kidney tissues were subjected to HE and Masson staining for pathological observation. Immunohistochemistry and real-time quantitative PCR (qRT‒PCR) were performed to evaluate the expression of ANGPTL4 and hypoxia-inducible factor-1α (HIF-1α), followed by Pearson correlation analysis. Subsequently, kidney biopsy tissues from 11 CKD patients (6 with RIF and 5 without RIF) were subjected to immunohistochemical staining to validate the expression of ANGPTL4. In vitro, a fibrosis model of human renal tubular epithelial cells (HK2) was established through hypoxic stimulation. Subsequently, an HIF-1α inhibitor (2-MeOE2) was used, and ANGPTL4 was manipulated using siRNA or plasmid overexpression. Changes in ANGPTL4 and fibrosis markers were analyzed through Western blotting, qRT‒PCR, and immunofluorescence. RESULTS: ANGPTL4 was significantly upregulated in the CKD rat model and was significantly positively correlated with renal injury markers, the fibrotic area, and HIF-1α. These results were confirmed by clinical samples, which showed a significant increase in the expression level of ANGPTL4 in CKD patients with RIF, which was positively correlated with HIF-1α. Further in vitro studies indicated that the expression of ANGPTL4 is regulated by HIF-1α, which in turn is subject to negative feedback regulation by ANGPTL4. Moreover, modulation of ANGPTL4 expression influences the progression of fibrosis in HK2 cells. CONCLUSION: Our findings indicate that ANGPTL4 is a key regulatory factor in renal fibrosis, forming a loop with HIF-1α, potentially serving as a novel therapeutic target for RIF.

Association between fluoride exposure and psychiatric disorders in adults.

To explore the association between fluoride exposure and depression / anxiety in adults, the 1,169 participants were recruited. The demographic information of participants was obtained through questionnaire survey and physical measurements. Morning urine samples were collected, and urinary fluoride (UF) level was determined. Changes in depression and anxiety levels were evaluated using the Patient Health Questionnaire-2 and General Anxiety Disorder-2 scales. The association between psychiatric disorders and UF levels was analyzed. In the total population, the prevalence of depression and anxiety were 3.17% and 4.19%, respectively. These results showed no significant association between depression / anxiety scale scores and UF levels. Logistic regression suggested no significant association between depression / anxiety levels, and UF levels, but there was an interaction between UF and income on depression. Our findings highlighted the interaction between fluoride exposure and monthly income, which may affect depression in adults.

Integrated Pristine van der Waals Homojunctions for Self-Powered Image Sensors.

Van der Waals junctions hold significant potentials for various applications in multifunctional and low-power electronics and optoelectronics. The multistep device fabrication process usually introduces lattice mismatch and defects at the junction interfaces, which deteriorate device performance. Here the layer engineering synthesis of van der Waals homojunctions consisting of 2H-MoTe2 with asymmetric thickness to eliminate heterogenous interfaces and thus obtain clean interfaces is reported. Experimental results confirm that the homostructure nature gives rise to the formation of pristine van der Waals junctions, avoiding chemical disorders and defects. The ability to tune the energy bands of 2H-MoTe2 continuously through layer engineering enables the creation of adjustable built-in electric field at the homojunction boundaries, which leads to the achievement of self-powered photodetection based on the obtained 2H-MoTe2 films. Furthermore, the successful integration of 2H-MoTe2 homojunctions into an image sensor with 10 × 10 pixels, brings about zero-power consumption and near-infrared imaging functions. The pristine van der Waals homojunctions and effective integration strategies shed new insights into the development of large-scale application for two-dimensional materials in advanced electronics and optoelectronics.

Boosting Monolayer Transition Metal Dichalcogenides Growth by Hydrogen-Free Ramping during Chemical Vapor Deposition.

The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H2) in their synthesis. Using CVD growth of MoSe2 as an example, this study illustrates the role of a H2-free environment during temperature ramping in suppressing the reduction of MoO3, which promotes effective vaporization and selenization of the Mo precursor to form MoSe2 monolayers with excellent crystal quality. As-synthesized MoSe2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm2/(V·s) with an on-off ratio of 7 × 107. This approach can be extended to other TMDs, such as WSe2, MoTe2, and MoSe2/WSe2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.

Molecular Transformers: Adaptive Multitarget Ligands for Esterase-Induced Transition from Analgesics to Anesthetics.

Multitarget strategies are essential in addressing complex diseases, yet developing multitarget-directed ligands (MTDLs) is particularly challenging when aiming to engage multiple therapeutic targets across different tissues. Here, we present a molecular transformer strategy, enhancing traditional MTDLs. By utilizing esterase-driven hydrolysis, this approach mimics the adaptive nature of transformers for enabling molecules to modify their pharmacological effects in response to the biological milieu. By virtual screening and biological evaluation, we identified KGP-25, a novel compound initially targeting the voltage-gated sodium channel 1.8 (Nav1.8) in the peripheral nervous system (PNS) for analgesia, and later the γ-aminobutyric acid subtype A receptor (GABAA) in the central nervous system (CNS) for general anesthesia. Our findings confirm KGP-25's dual efficacy in cellular and animal models, effectively reducing opioid-related side effects. This study validates the molecular transformer approach in drug design and highlights its potential to overcome the limitations of conventional MTDLs, paving new avenues in innovative therapeutic strategies.

Sodium bicarbonate treatment and clinical outcomes in chronic kidney disease with metabolic acidosis: a meta-analysis.

BACKGROUND: In patients with chronic kidney disease (CKD), impaired kidney acid excretion leads to the onset of metabolic acidosis (MA). However, the evidence is not yet conclusive regarding the effects of sodium bicarbonate in treating CKD with MA. METHODS: Databases with PubMed, Embase, and the Cochrane Library were used to search for randomized controlled trials from the inception until November 11, 2023 to identify randomized controlled trials investigating the effect of sodium bicarbonate in participants with CKD and MA. The primary outcome was the change in estimated glomerular filtration rate (eGFR). Secondary outcomes included hospitalization rates, change in systolic blood pressure (SBP), all-cause mortality, and mid-arm muscle circumference (MAMC). A random-effects model was applied for analysis, and subgroup, sensitivity analyses were also performed. RESULTS: Fourteen RCTs comprising 2,037 patients demonstrated that sodium bicarbonate supplementation significantly improved eGFR (standardized mean difference [SMD]: 0.33, 95% CI: 0.03 to 0.63, P = 0.03). The group receiving sodium bicarbonate had a lower hospitalization rate (odds ratio: 0.37, 95% CI: 0.25 to 0.55, P < 0.001). Higher MAMC was observed with sodium bicarbonate treatment compared with those without (SMD:0.23, 95% CI: 0.08 to 0.38, P = 0.003, I2 < 0.001). However, higher risk of elevated SBP was found with sodium bicarbonate treatment (SMD:0.10, 95% CI: 0.01 to 0.20, P = 0.03). No significant difference in all-cause mortality was noted. CONCLUSION: In patients with CKD and MA, sodium bicarbonate supplementation may provide potential benefits in preventing the deterioration of kidney function and increasing muscle mass. However, treatment may be associated with higher blood pressure. Due to the risk of bias stemming from the absence of double-blinded designs and inconsistencies in control group definitions across the studies, further research is crucial to verify these findings.

The effect of biofeedback on nonneurological dysfunctional voiding in children: A meta-analysis and systematic review.

OBJECTIVE: This study was conducted to investigate the effect of biofeedback (BF) on the rehabilitation of children with nonneurological dysfunctional voiding (NDV). METHODS: RCTs were retrieved from various databases (published from inception to February 29, 2024). The effects of the BF and non-BF treatments were compared. A random-effects model was used to evaluate the combined data. RESULTS: Meta-analysis revealed that BF increased the maximum urinary flow rate (SMD = 3.78, 95% CI 1.33∼6.22), improved urination time (SMD = 5.88, 95% CI 3.75∼8.01), and reduced the postvoid residual (SMD = -19.18, 95% CI -27.03∼-11.33) and urinary tract infection incidence (RR = 0.43, 95% CI 0.21∼0.87). Electromyogram activity (RR = 0.46, 95% CI 0.25∼0.84) and abnormal urination patterns (RR = 0.51, 95% CI 0.35∼0.74) improved, with effects persisting for more than 1 year. However, the effect of BF on the mean urinary flow rate in children with NDV was significant only after 1 year of follow-up (SMD = 1.90, 95% CI 0.87∼2.92). CONCLUSION: Existing evidence indicates that BF can enhance urinary parameters and patterns in children with NDV. However, its effectiveness in addressing constipation, daytime urinary incontinence, and nocturnal urinary incontinence is not substantial. High-quality randomized controlled trials can offer additional insights.

Arsenic Sulfide Enhances Radiosensitivity in Rhabdomyosarcoma via Activating NFATc3-RAG1 Mediated DNA Double Strand Break (DSB).

Rhabdomyosarcoma (RMS) represents one of the most lethal soft-tissue sarcomas in children. The toxic trace element arsenic has been reported to function as a radiosensitizer in sarcomas. To investigate the role of arsenic sulfide (As4S4) in enhancing radiation sensitization in RMS, this study was conducted to elucidate its underlying mechanism in radiotherapy. The combination of As4S4 and radiotherapy showed significant inhibition in RMS cells, as demonstrated by the cell counting kit-8 (CCK-8) assay and flow cytometry. Subsequently, we demonstrated for the first time that As4S4, as well as the knockdown of NFATc3 led to double-strand break (DSB) through increased expression of RAG1. In vivo experiment confirmed that co-treatment efficiently inhibited RMS growth. Furthermore, survival analysis of a clinical cohort consisting of 59 patients revealed a correlation between NFATc3 and RAG1 expression and overall survival (OS). Cox regression analysis also confirmed the independent prognostic significance of NFATc3 and RAG1.Taken together, As4S4 enhances radiosensitivity in RMS via activating NFATc3-RAG1 mediated DSB. NFATc3 and RAG1 are potential therapeutic targets. As4S4 will hopefully serve as a prospective radio-sensitizing agent for RMS.

Deep simulated annealing for the discovery of novel dental anesthetics with local anesthesia and anti-inflammatory properties.

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects. The primary challenge is to integrate diverse pharmacophores within a single-molecule framework. To address this, we introduced DeepSA, a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine, a well-known local anesthetic. DeepSA integrates deep neural networks into metaheuristics, effectively constraining molecular space during compound generation. This framework employs a sophisticated objective function that accounts for scaffold preservation, anti-inflammatory properties, and covalent constraints. Through a sequence of local editing to navigate the molecular space, DeepSA successfully identified AT-17, a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models. Mechanistic insights into AT-17 revealed its dual mode of action: selective inhibition of NaV1.7 and 1.8 channels, contributing to its prolonged local anesthetic effects, and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway. These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery, particularly within stringent chemical constraints.

Implementation of a novel computer assisted telephone follow-up model for older patients after emergency department discharge in an Asian population.

BACKGROUND: While the impact of telephone follow-up (TFU) for older emergency department (ED) patients is controversial, its effects on the Asian population remain uncertain. In this study, we evaluated the effectiveness of a novel computer assisted TFU model specifically for this demographic. METHODS: At a Taiwanese tertiary medical center, we developed a TFU protocol that included a referral and case management system within the ED hospital information system. We provided TFU to older discharged patients between April 1, 2021, and May 31, 2021. We compared this cohort with a non-TFU cohort of older ED patients and analyzed demographic characteristics and post-ED discharge outcomes. RESULTS: The TFU model was successfully implemented, with 395 patients receiving TFU and 191 without TFU. TFU patients (median age: 76 years, male proportion: 48.9%) differed from non-TFU patients (median age: 74 years, male proportion: 43.5%). Compared with the non-TFU cohort, the multivariate logistic regression analysis revealed that the TFU cohort had a lower total medical expenditure < 1 month (adjusted odds ratio [AOR]: 0.32; 95% CI: 0.21 - 0.47 for amounts exceeding 5,000 New Taiwan Dollars), and higher satisfaction (AOR: 2.80; 95% CI: 1.46 - 5.36 for scores > 3 on a five-point Likert Scale). However, the TFU cohort also had a higher risk of hospitalization < 1 month (AOR: 2.50; 95% CI: 1.31 - 4.77) compared to the non-TFU cohort. CONCLUSION: Computer-assisted TFU appears promising. Further research involving a larger number of patients and validation in other hospitals is necessary to bolster the evidence and extend the findings to a broader context.

Integration of High-Resolution LC-Q-TOF Mass Spectrometry and Multidimensional Chemical-Biological Analysis to Detect Nanomolar-Level Acetylcholinesterase Inhibitors from Different Parts of Zanthoxylum nitidum.

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 µM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.

Rationale Design for Anchoring Pendant Groups of Zwitterionic Polymeric Medical Coatings.

A biocompatible and antifouling polymeric medical coating was developed through rational design for anchoring pendant groups for the modification of stainless steel. Zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was copolymerized individually with three anchoring monomers of carboxyl acrylamides with different alkyl spacers, including acryloylglycine (2-AE), 6-acrylamidohexanoic acid (6-AH), and 11-acrylamidoundecanoic acid (11-AU). The carboxylic acid groups are responsible for the stable grafting of copolymers onto stainless steel via a coordinative interaction with metal oxides. Due to hydrophobic interaction and hydrogen bonding, the anchoring monomers enable the formation of self-assembling structures in solution and at a metallic interface, which can play an important role in the thin film formation and functionality of the coatings. Therefore, surface characterizations of anchoring monomers on stainless steel were conducted to analyze the packing density and strength of the intermolecular hydrogen bonds. The corresponding copolymers were synthesized, and their aggregate structures were assessed, showing micelle aggregation for copolymers with higher hydrophobic compositions. The synergistic effects of inter/intramolecular interactions and hydrophobicity of the anchoring monomers result in the diversity of the thickness, surface coverage, wettability, and friction of the polymeric coatings on stainless steel. More importantly, the antifouling properties of the coatings against bacteria and proteins were strongly correlated to thin film formation. Ultimately, the key lies in deciphering the molecular structure of the anchoring pendants in thin film formation and assessing the effectiveness of the coatings, which led to the development of medical coatings through the graft-onto approach.

Amelioration of walnut, peony seed and camellia seed oils against D-galactose-induced cognitive impairment in mice by regulating gut microbiota.

Diet adjustment will affect the health of gut microbiota, which in turn influences the development and function of the organism's brain through the gut-brain axis. Walnut oil (WO), peony seed oil (PSO) and camellia seed oil (CSO), as typical representatives of woody plant oils, have been shown to have the potential to improve cognitive impairment in mice, but the function mechanisms are not clear. In this study, we comparatively investigated the neuroprotective effects of these three oils on D-galactose (D-gal)-induced cognitive impairment in mice, and found that the ameliorative effect of WO was more prominent. During the behavioral experiments, supplementation with all three oils would improve spatial learning and memory functions in D-gal mice, with a significant reduction in the error times (p < 0.001) and a significant increase in step-down latency (p < 0.001); walnut oil supplementation also significantly increased the number of hidden platform traversals, the target quadrant spent times and percentage of distance (p < 0.05). The results of biomarker analysis showed that WO, in addition to significantly inhibiting D-gal-induced oxidative stress and neuroinflammation as did PSO, significantly increased the ACh content in the mouse brain (p < 0.05) and modulated neurotransmitter levels. The results of further microbiota diversity sequencing experiments also confirmed that dietary supplementation with all three oils affected the diversity and composition of the gut microbiota in mice. Among them, WO significantly restored the balance of the mouse gut microbiota by increasing the abundance of beneficial bacteria (Bacteroidetes, Actinobacteria, Firmicutes) and decreasing the abundance of harmful bacteria (Clostridium, Shigella, Serratia), which was consistent with the results of behavioral experiments and biomarker analyses. Based on the analysis of the fatty acid composition of the three oils and changes in the gut microbiota, it is hypothesized that there is a correlation between the fatty acid composition of the dietary supplement oils and neuroprotective effects. The superiority of WO over PSO and CSO in improving cognitive impairment is mainly attributed to its balanced composition of omega-6 and omega-3 fatty acids.

Epitaxial Growth of Two-Dimensional MoO2-MoSe2 Metal-Semiconductor Heterostructures for Schottky Diodes.

The metal-semiconductor interface fabricated by conventional methods often suffers from contamination, degrading transport performance. Herein, we propose a one-pot chemical vapor deposition (CVD) process to create a two-dimensional (2D) MoO2-MoSe2 heterostructure by growing MoO2 seeds under a hydrogen environment, followed by depositing MoSe2 on the surface and periphery. The ultraclean interface is verified by cross-sectional scanning transmission electron microscopy and photoluminescence. Along with the high work function of semimetallic MoO2 (Ef = -5.6 eV), a high-rectification Schottky diode is fabricated based on this heterostructure. Furthermore, the Schottky diode exhibits an excellent photovoltaic effect with a high open-circuit voltage of 0.26 eV and ultrafast photoresponse, owing to the naturally formed metal-semiconductor contact with suppressed pinning effect. Our method paves the way for the fabrication of an ultraclean 2D metal-semiconductor interface, without defects or contamination, offering promising prospects for future nanoelectronics.

Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy.

Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox-induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin-induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h in vitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real-time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. In vitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox-induced cardiotoxicity. In addition, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

The role of tumor-associated macrophages in tumor immune evasion.

BACKGROUND: Tumor growth is closely linked to the activities of various cells in the tumor microenvironment (TME), particularly immune cells. During tumor progression, circulating monocytes and macrophages are recruited, altering the TME and accelerating growth. These macrophages adjust their functions in response to signals from tumor and stromal cells. Tumor-associated macrophages (TAMs), similar to M2 macrophages, are key regulators in the TME. METHODS: We review the origins, characteristics, and functions of TAMs within the TME. This analysis includes the mechanisms through which TAMs facilitate immune evasion and promote tumor metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. RESULTS: TAMs are instrumental in mediating tumor immune evasion and malignant behaviors. They release cytokines that inhibit effector immune cells and attract additional immunosuppressive cells to the TME. TAMs primarily target effector T cells, inducing exhaustion directly, influencing activity indirectly through cellular interactions, or suppressing through immune checkpoints. Additionally, TAMs are directly involved in tumor proliferation, angiogenesis, invasion, and metastasis. Developing innovative tumor-targeted therapies and immunotherapeutic strategies is currently a promising focus in oncology. Given the pivotal role of TAMs in immune evasion, several therapeutic approaches have been devised to target them. These include leveraging epigenetics, metabolic reprogramming, and cellular engineering to repolarize TAMs, inhibiting their recruitment and activity, and using TAMs as drug delivery vehicles. Although some of these strategies remain distant from clinical application, we believe that future therapies targeting TAMs will offer significant benefits to cancer patients.

The Impact of NLRP3 Inflammasome on Osteoblasts and Osteogenic Differentiation: A Literature Review.

Osteoblasts (OBs), which are a crucial type of bone cells, derive from bone marrow mesenchymal stem cells (MSCs). Accumulating evidence suggests inflammatory cytokines can inhibit the differentiation and proliferation of OBs, as well as interfere with their ability to synthesize bone matrix, under inflammatory conditions. NLRP3 inflammasome is closely associated with cellular pyroptosis, which can lead to excessive release of pro-inflammatory cytokines, causing tissue damage and inflammatory responses, however, the comprehensive roles of NLRP3 inflammasome in OBs and their differentiation have not been fully elucidated, making targeting NLRP3 inflammasome approaches to treat diseases related to OBs uncertain. In this review, we provide a summary of NLRP3 inflammasome activation and its impact on OBs. We highlight the significant roles of NLRP3 inflammasome in regulating OBs differentiation and function. Furthermore, current available strategies to affect OBs function and osteogenic differentiation targeting NLRP3 inflammasome are listed and analyzed. Finally, through the prospective discussion, we seek to provide novel insights into the crucial role of NLRP3 inflammasome in diseases related to OBs and offer valuable information for devising treatment strategies.

The complete chloroplast genome of Lagochilus ilicifolius Bunge ex Bentham, Labiat. Gen. 1834 (Lamiaceae) and its phylogenetic analysis.

Lagochilus ilicifolius Bunge ex Bentham, Labiat. Gen is a perennial herb with much-branched stems native to Nei Mongol, Ningxia, Gansu, N Shaanxi. It can be used clinically as a hemostatic agent. The chloroplast genome length is 151,466 bp. It contained two inverted repeat regions of 25,660 bp each, a large single-copy region of length 82,504 bp, and a small single-copy region of length 17,642 bp. Also, the GC content is 38.6%. There were 133 genes annotated, including 88 known protein-coding genes, 37 tRNAs, and eight rRNAs. The phylogenetic tree was constructed using Bayesian method for plastome data of 29 species. The entire chloroplast genome of L. ilicifolius within the Lamiaceae is the first to reveal genetic taxonomy at the molecular level, and the new phylogenetic tree data can be used for future evolutionary studies.