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1.
Macromol Rapid Commun ; : e2400234, 2024 Jun 02.
Article En | MEDLINE | ID: mdl-38824415

Invisible aligners have been widely used in orthodontic treatment but still present issues with plaque formation and oral mucosa abrasion, which can lead to complicated oral diseases. To address these issues, hydrophilic poly(sulfobetaine methacrylate) (polySBMA) coatings with lubricating, antifouling, and anti-adhesive properties have been developed on the aligner materials (i.e., polyethylene terephthalate glycol, PETG) via a simple and feasible glycidyl methacrylate (GMA)-assisted coating strategy. Poly(GMA-co-SBMA) was grafted onto the aminated PETG surface via the ring-opening reaction of GMA (i.e., "grafting to" approach to obtain G-co-S coating), or a polySBMA layer was formed on the GMA-grafted PETG surface via free radical polymerization (i.e., "grafting from" approach to obtain G-g-S coating). The G-co-S and G-g-S coatings significantly reduced the friction coefficient of PETG surface. Protein adsorption, bacterial adhesion, and biofilm formation on the G-co-S- and G-g-S-coated surfaces were significantly inhibited. The performance of the coatings remained stable after storage in air or artificial saliva for 2 weeks. Both coatings demonstrated good biocompatibility in vitro and did not cause irritation to the oral mucosa of rats in vivo over 2 weeks. This study proposed a promising strategy for the development of invisible aligners with improved performance, which is beneficial for oral health treatment. This article is protected by copyright. All rights reserved.

2.
J Cereb Blood Flow Metab ; : 271678X241251976, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38833561

Carotid atherosclerosis is a major cause of stroke. Hemodynamic forces, such as shear stress and oscillatory shear, play an important role in the initiation and progression of atherosclerosis. The alteration of the immune microenvironment is the fundamental pathological mechanism by which diverse external environmental factors impact the formation and progression of plaques. However, Current research on the relationship between hemodynamics and immunity in atherosclerosis still lack of comprehensive understanding. In this study, we combined computational fluid dynamics (CFD) and Mass cytometry (CyTOF) technologies to explore the changes in the immune microenvironment within plaques under different hemodynamic conditions. Our results indicated that neutrophils were enriched in adverse flow environments. M2-like CD163+CD86+ macrophages were predominantly enriched in high WSS and low OSI environments, while CD163-CD14+ macrophages were enriched in low WSS and high OSI environments. Functional analysis further revealed T cell pro-inflammatory activation and dysregulation in modulation, along with an imbalance in M1-like/M2-like macrophages, suggesting their potential involvement in the progression of atherosclerotic lesions mediated by adverse flow patterns. Our study elucidated the potential mechanisms by which hemodynamics regulated the immune microenvironment within plaques, providing intervention targets for future precision therapies.

3.
Food Chem Toxicol ; 189: 114773, 2024 May 31.
Article En | MEDLINE | ID: mdl-38823497

Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and Western blot analyses confirmed the upregulation of both Grp78 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94, chop, Atf6, Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride.

4.
Article En | MEDLINE | ID: mdl-38836741

Objective: To investigate the influence of preoperative detrusor muscle activity on the short-term prognosis of elderly patients diagnosed with benign prostatic hyperplasia (BPH) undergoing 1470 nm semiconductor laser surgery. Methods: A retrospective study was conducted on clinical data from 165 elderly BPH patients who underwent 1470 nm semiconductor laser surgery between May 2019 and April 2023. Patients were stratified based on preoperative urodynamic study findings, specifically their bladder contractility index (BCI). Patients with a BCI ≤100 constituted the detrusor underactivity (DU) group (n=64), while those with a BCI >100 formed the non-DU group (n=101). Surgical parameters, including duration, intraoperative blood loss, postoperative hospital stay, bladder irrigation, and catheterization duration, were compared. Additionally, changes in International Prostate Symptom Score (IPSS), Quality of Life (QOL) score, residual urine volume, and peak urinary flow rate (Qmax) were assessed before and three months after surgery in both groups. Results: There were no statistically significant differences observed between the DU and non-DU groups concerning surgical duration, intraoperative blood loss, postoperative hospitalization duration, bladder irrigation duration, and postoperative catheterization duration (P > .05). Similarly, no significant disparities were noted in the IPSS and QOL scores preoperatively and at the three-month follow-up in both groups (P > .05). Both cohorts exhibited no significant differences in residual urine volume before surgery and at the three-month mark postoperatively (P > .05). However, the postoperative Qmax was significantly reduced in the DU group compared to the non-DU group (P < .05). Conclusions: Detrusor muscle activity does not exert a significant impact on clinical symptom improvement and quality of life in elderly BPH patients treated with 1470 nm semiconductor laser surgery. However, patients with DU exhibited inferior postoperative recovery in Qmax, underscoring the importance of preoperative urodynamic studies for early intervention and enhanced surgical outcomes in this patient population.

5.
Eur J Pharm Biopharm ; : 114348, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38844097

Nitric oxide (NO) / ß-Lapachone (Lap) combined therapy by causing oxidative stress is an effective tumor therapy strategy. Herein, a dual-responsive lipid nanoparticles (LNPs) LSNO for NO / Lap co-delivery were constructed from the zinc-coordinated lipid (DSNO(Zn)) and the hydrophobic drug Lap in the presence of helper lipids (DOPE and DSPE-PEG2000). The zinc-coordinated structure in LSNO might elevate the Zn2+ content in tumor cells, contributing to antioxidant imbalance. The fluorescent assays proved the light-triggered NO release and fluorescent self-reporting abilities of LSNO. In addition, the LNPs had good drug release behavior under high concentration of GSH, indicating the NO / drug co-delivery capacity. In vitro antitumor assays showed that the NO / Lap combination treatment group could induce more significant tumor cell growth inhibition and cell apoptosis than individual NO or Lap treatment. The following mechanism studies revealed that NO / Lap combination treatment led to distinct oxidative stress by producing reactive oxygen species (ROS) and peroxynitrite anion (ONOO-). On the other hand, the intracellular redox balance could be further disrupted by Lap-induced NADPH consumption and Zn2+ / NO-induced reductase activities downregulation, thus promoting the degree of cell damage. Besides, it was also found that NO and Lap could directly damage nuclear DNA and induce mitochondrial dysfunction, thereby leading to caspase-3 activation and tumor cell death. These results proved that LSNO could serve as a promising multifunctional tumor therapy platform.

6.
Cell Death Dis ; 15(6): 397, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844455

Integrin αvß6 holds promise as a therapeutic target for organ fibrosis, yet targeted therapies are hampered by concerns over inflammatory-related side effects. The role of αvß6 in renal inflammation remains unknown, and clarifying this issue is crucial for αvß6-targeted treatment of chronic kidney disease (CKD). Here, we revealed a remarkable positive correlation between overexpressed αvß6 in proximal tubule cells (PTCs) and renal inflammation in CKD patients and mouse models. Notably, knockout of αvß6 not only significantly alleviated renal fibrosis but also reduced inflammatory responses in mice, especially the infiltration of pro-inflammatory macrophages. Furthermore, conditional knockout of αvß6 in PTCs in vivo and co-culture of PTCs with macrophages in vitro showed that depleting αvß6 in PTCs suppressed the migration and pro-inflammatory differentiation of macrophages. Screening of macrophage activators showed that αvß6 in PTCs activates macrophages via secreting IL-34. IL-34 produced by PTCs was significantly diminished by αvß6 silencing, and reintroduction of IL-34 restored macrophage activities, while anti-IL-34 antibody restrained macrophage activities enhanced by αvß6 overexpression. Moreover, RNA-sequencing of PTCs and verification experiments demonstrated that silencing αvß6 in PTCs blocked hypoxia-stimulated IL-34 upregulation and secretion by inhibiting YAP expression, dephosphorylation, and nuclear translocation, which resulted in the activation of Hippo signaling. While application of a YAP agonist effectively recurred IL-34 production by PTCs, enhancing the subsequent macrophage migration and activation. Besides, reduced IL-34 expression and YAP activation were also observed in global or PTCs-specific αvß6-deficient injured kidneys. Collectively, our research elucidates the pro-inflammatory function and YAP/IL-34/macrophage axis-mediated mechanism of αvß6 in renal inflammation, providing a solid rationale for the use of αvß6 inhibition to treat kidney inflammation and fibrosis.


Integrins , Macrophages , Mice, Knockout , Renal Insufficiency, Chronic , Animals , Macrophages/metabolism , Mice , Humans , Integrins/metabolism , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/metabolism , Inflammation/pathology , Inflammation/metabolism , Male , Antigens, Neoplasm/metabolism , Mice, Inbred C57BL , Signal Transduction , Disease Models, Animal , YAP-Signaling Proteins/metabolism , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Fibrosis
7.
Autophagy ; : 1-20, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38836496

Abnormal expression of long non-coding RNAs (lncRNAs) is associated with the dysfunctions of human trophoblast cells and the occurrence of miscarriage (abnormal early embryo loss). BBC3/PUMA (BCL2 binding component 3) plays significant roles in regulation of cell apoptosis. However, whether specific lncRNAs might regulate BBC3 in trophoblast cells and further induce apoptosis and miscarriage remains completely unclear. Through screening, we identified a novel lnc-HZ12, which was significantly highly expressed in villous tissues of recurrent miscarriage (RM) patients relative to their healthy control (HC) group. Lnc-HZ12 suppressed chaperone-mediated autophagy (CMA) degradation of BBC3, promoted trophoblast cell apoptosis, and was associated with miscarriage. In mechanism, lnc-HZ12 downregulated the expression levels of chaperone molecules HSPA8 and LAMP2A in trophoblast cells. Meanwhile, lnc-HZ12 (mainly lnc-HZ12-SO2 region in F2 fragment) and HSPA8 competitively bound with the 169RVLYNL174 patch on BBC3, which prevented BBC3 from interactions with HSPA8 and impaired the formation of BBC3-HSPA8-LAMP2A complex for CMA degradation of BBC3. Thus, lnc-HZ12 upregulated the BBC3-CASP9-CASP3 pathway and induced trophoblast cell apoptosis. In villous tissues, lnc-HZ12 was highly expressed, CMA degradation of BBC3 was suppressed, and the apoptosis levels were higher in RM vs HC villous tissues, all of which were associated with miscarriage. Interestingly, knockdown of murine Bbc3 could efficiently suppress placental apoptosis and alleviate miscarriage in a mouse miscarriage model. Taken together, our results indicated that lnc-HZ12 and BBC3 played important roles in trophoblast cell apoptosis and miscarriage and might act as attractive targets for miscarriage treatment.Abbreviation: 7-AAD: 7-aminoactinomycin D; BaP: benzopyrene; BBC3/PUMA: BCL2 binding component 3; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; CMA: chaperone-mediated autophagy; CQ: chloroquine; DMSO: dimethyl sulfoxide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HC: healthy control; HSPA8: heat shock protein family A (Hsp70) member 8; IP: immunoprecipitation; LAMP2A: lysosomal associated membrane protein 2; LncRNA: long non-coding RNA; mRNA: messenger RNA; MT: mutant-type; NC: negative control; NSO: nonspecific oligonucleotide; PARP1: poly(ADP-ribose) polymerase 1; RIP: RNA immunoprecipitation; RM: recurrent miscarriage; TBP: TATA-box binding protein; WT: wild-type.

8.
Front Microbiol ; 15: 1379203, 2024.
Article En | MEDLINE | ID: mdl-38832117

Background: Pork processing plants in the United States (US) cease operations for 24-48 h every six or twelve months to perform intense sanitization (IS) using fogging, foaming, and further antimicrobial treatments to disrupt natural biofilms that may harbor pathogens and spoilage organisms. The impact such treatments have on short-term changes in environmental microorganisms is not well understood, nor is the rate at which bacterial communities return. Methods: Swab samples were collected from floor drains to provide representative environmental microorganisms at two US pork processing plants before, during, and after an IS procedure. Samples were collected from four coolers where finished carcasses were chilled and from four locations near cutting tables. Each sample was characterized by total mesophile count (TMC), total psychrophile count (TPC), and other indicator bacteria; their biofilm-forming ability, tolerance of the formed biofilm to a quaternary ammonium compound (300 ppm, QAC), and ability to protect co-inoculated Salmonella enterica. In addition, bacterial community composition was determined using shotgun metagenomic sequencing. Results: IS procedures disrupted bacteria present but to different extents depending on the plant and the area of the plant. IS reduced TPC and TMC, by up to 1.5 Log10 CFU only to return to pre-IS levels within 2-3 days. The impact of IS on microorganisms in coolers was varied, with reductions of 2-4 Log10, and required 2 to 4 weeks to return to pre-IS levels. The results near fabrication lines were mixed, with little to no significant changes at one plant, while at the other, two processing lines showed 4 to 6 Log10 reductions. Resistance to QAC and the protection of Salmonella by the biofilms varied between plants and between areas of the plants as well. Community profiling of bacteria at the genus level showed that IS reduced species diversity and the disruption led to new community compositions that in some cases did not return to the pre-IS state even after 15 to 16 weeks. Discussion: The results found here reveal the impact of using IS to disrupt the presence of pathogen or spoilage microorganisms in US pork processing facilities may not have the intended effect.

10.
Redox Rep ; 29(1): 2345455, 2024 Dec.
Article En | MEDLINE | ID: mdl-38723197

OBJECTIVES: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. METHODS: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. RESULTS: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. DISCUSSION: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.


Methylenetetrahydrofolate Dehydrogenase (NADP) , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species , Stomach Neoplasms , Humans , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Methylenetetrahydrofolate Dehydrogenase (NADP)/metabolism , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Animals , Mice , Reactive Oxygen Species/metabolism , Multifunctional Enzymes/metabolism , Multifunctional Enzymes/genetics , Cell Line, Tumor , Homeostasis , Aminohydrolases/metabolism , Aminohydrolases/genetics , Disease Progression , Xenograft Model Antitumor Assays
11.
J Headache Pain ; 25(1): 72, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714978

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.


Headache , Intracranial Arteriovenous Malformations , Humans , Female , Intracranial Arteriovenous Malformations/complications , Intracranial Arteriovenous Malformations/therapy , Male , Headache/etiology , Headache/therapy , Adult , Retrospective Studies , Risk Factors , Middle Aged , Young Adult , Conservative Treatment/methods , Treatment Outcome , Embolization, Therapeutic/methods , Adolescent
12.
J Eye Mov Res ; 17(1)2024.
Article En | MEDLINE | ID: mdl-38694262

Although Severe Acute Respiratory Syndrome Coronavirus 2 infection (SARS-CoV-2) is primarily recognized as a respiratory disease, mounting evidence suggests that it may lead to neurological and cognitive impairments. The current study used three eye-tracking tasks (free-viewing, fixation, and smooth pursuit) to assess the oculomotor functions of mild infected cases over six months with symptomatic SARS-CoV-2 infected volunteers. Fifty symptomatic SARS-CoV-2 infected, and 24 self-reported healthy controls completed the eye-tracking tasks in an initial assessment. Then, 45, and 40 symptomatic SARS-CoV-2 infected completed the tasks at 2- and 6-months post-infection, respectively. In the initial assessment, symptomatic SARS-CoV-2 infected exhibited impairments in diverse eye movement metrics. Over the six months following infection, the infected reported overall improvement in health condition, except for self-perceived mental health. The eye movement patterns in the free-viewing task shifted toward a more focal processing mode and there was no significant improvement in fixation stability among the infected. A linear discriminant analysis shows that eye movement metrics could differentiate the infected from healthy controls with an accuracy of approximately 62%, even 6 months post-infection. These findings suggest that symptomatic SARSCoV- 2 infection may result in persistent impairments in oculomotor functions, and the employment of eye-tracking technology can offer valuable insights into both the immediate and long-term effects of SARS-CoV-2 infections. Future studies should employ a more balanced research design and leverage advanced machine-learning methods to comprehensively investigate the impact of SARSCoV- 2 infection on oculomotor functions.

13.
Plant J ; 2024 May 04.
Article En | MEDLINE | ID: mdl-38703081

A fundamental question in developmental biology is how to regulate grain size to improve crop yields. Despite this, little is still known about the genetics and molecular mechanisms regulating grain size in crops. Here, we provide evidence that a putative protein kinase-like (OsLCD3) interacts with the S-adenosyl-L-methionine synthetase 1 (OsSAMS1) and determines the size and weight of grains. OsLCD3 mutation (lcd3) significantly increased grain size and weight by promoting cell expansion in spikelet hull, whereas its overexpression caused negative effects, suggesting that grain size was negatively regulated by OsLCD3. Importantly, lcd3 and OsSAMS1 overexpression (SAM1OE) led to large and heavy grains, with increased ethylene and decreased polyamines production. Based on genetic analyses, it appears that OsLCD3 and OsSAMS1 control rice grain size in part by ethylene/polyamine homeostasis. The results of this study provide a genetic and molecular understanding of how the OsLCD3-OsSAMS1 regulatory module regulates grain size, suggesting that ethylene/polyamine homeostasis is an appropriate target for improving grain size and weight.

14.
Medicine (Baltimore) ; 103(18): e38057, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701266

Patients with hypertension have a higher risk of having constipation and vice versa. The causal association between these 2 variables is not proven. We performed a retrospective Mendelian randomization analysis to determine the causal association between constipation and hypertension. Two-sample 2-way Mendelian randomization analysis was used. Genetic variants for constipation were derived from genome-wide association study data of European origin (15,902 cases and 395,721 controls). Corresponding genetic associations for hypertension were derived from European ancestry GWAS data (54,358 cases and 408,652 controls). Genetic susceptibility to hypertension was associated with an increased risk of constipation (OR: 3.459, 95% CI: 1.820-6.573, P < .001). In an inverse Mendelian randomization analysis, no causal effect of constipation on hypertension was found (OR: 0.999, 95% CI: 0.987-1.011, P = .834). In sensitivity analyses, these associations persisted and no multiple effects were found. This study suggests that there is a causal relationship between hypertension and constipation and that hypertension may increase the risk of developing constipation.


Constipation , Genome-Wide Association Study , Hypertension , Mendelian Randomization Analysis , Humans , Constipation/epidemiology , Constipation/genetics , Hypertension/genetics , Hypertension/epidemiology , Retrospective Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Risk Factors
15.
Article En | MEDLINE | ID: mdl-38717885

Feature selection plays an important role in data analysis, yet traditional graph-based methods often produce suboptimal results. These methods typically follow a two-stage process: constructing a graph with data-to-data affinities or a bipartite graph with data-to-anchor affinities and independently selecting features based on their scores. In this article, a large-scale feature selection approach based on structured bipartite graph and row-sparse projection (RS 2 BLFS) is proposed to overcome this limitation. RS 2 BLFS integrates the construction of a structured bipartite graph consisting of c connected components into row-sparse projection learning with k nonzero rows. This integration allows for the joint selection of an optimal feature subset in an unsupervised manner. Notably, the c connected components of the structured bipartite graph correspond to c clusters, each with multiple subcluster centers. This feature makes RS 2 BLFS particularly effective for feature selection and clustering on nonspherical large-scale data. An algorithm with theoretical analysis is developed to solve the optimization problem involved in RS 2 BLFS. Experimental results on synthetic and real-world datasets confirm its effectiveness in feature selection tasks.

16.
Nat Chem Biol ; 2024 May 08.
Article En | MEDLINE | ID: mdl-38720107

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

17.
Mol Carcinog ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38712797

Although aberrant methylation of PAX1 is closely associated with cervical cancer (CC), PAX1 methylation (PAX1m) and its role in CC remain to be elucidated. Here, we clarified the biological function of PAX1 in CC. First, PAX1m in ThinPrep cytologic test samples was measured via quantitative methylation-specific PCR. The results showed that PAX1 promoter methylation levels were significantly increased in CC patients (p < 0.001). We also found that PAX1 promoter methylation levels were positively correlated with tumor purity but negatively correlated with immune-infiltration via public databases. Then, CRISPR-based methylation perturbation tools (dCas9-Tet1) were constructed to further demonstrate that DNA methylation participates in the regulation of PAX1 expression directly. Gain- and loss-of-function experiments were used to show that PAX1 overexpression restrained proliferation, migration and improved cisplatin sensitivity by interfering with the WNT/TIMELESS axis in CC cells. Additionally, Co-immunoprecipitation assays further confirmed the interaction between PAX1 and TCF7L2. Taken together, our results suggested that a tumor suppressor role of PAX1 in CC and that CRISPR-based PAX1 demethylation editing might be a promising therapeutic strategy for CC.

19.
Sci Adv ; 10(20): eadl4387, 2024 May 17.
Article En | MEDLINE | ID: mdl-38748786

4D printing enables 3D printed structures to change shape over "time" in response to environmental stimulus. Because of relatively high modulus, shape memory polymers (SMPs) have been widely used for 4D printing. However, most SMPs for 4D printing are thermosets, which only have one permanent shape. Despite the efforts that implement covalent adaptable networks (CANs) into SMPs to achieve shape reconfigurability, weak thermomechanical properties of the current CAN-SMPs exclude them from practical applications. Here, we report reconfigurable 4D printing via mechanically robust CAN-SMPs (MRC-SMPs), which have high deformability at both programming and reconfiguration temperatures (>1400%), high Tg (75°C), and high room temperature modulus (1.06 GPa). The high printability for DLP high-resolution 3D printing allows MRC-SMPs to create highly complex SMP 3D structures that can be reconfigured multiple times under large deformation. The demonstrations show that the reconfigurable 4D printing allows one printed SMP structure to fulfill multiple tasks.

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