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1.
Front Allergy ; 5: 1345929, 2024.
Article En | MEDLINE | ID: mdl-38774588

Background: Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites. Methods: A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT. The clinical efficacy and safety in both groups were evaluated. Results: After 1 year of treatment, both SCIT and OIT demonstrated significant therapeutic effects. OIT was found to be more effective than SCIT in reducing the total AR symptom score and improving the results of nasal provocation tests. Local and systemic adverse reactions were observed in the SCIT group, while none were reported in the OIT group. Conclusion: OIT is an effective and safe treatment for mite-induced AR.

2.
Small ; : e2311967, 2024 May 07.
Article En | MEDLINE | ID: mdl-38712482

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

3.
Biol Proced Online ; 26(1): 12, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714954

BACKGROUND: Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. METHODS: To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. RESULTS: We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. CONCLUSION: Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

4.
Am J Rhinol Allergy ; : 19458924241252456, 2024 May 07.
Article En | MEDLINE | ID: mdl-38715340

BACKGROUND: It is reported that CD123 + HLA-DR- cells in PBMC are basophils, and CD203c, CD63, and FcεRI molecules are activation markers of basophils. However, little is known of CD123 + HLA-DR-cells in blood granulocytes. OBJECTIVE: To investigate the presence of CD123 + HLA-DR- cells in the blood granulocytes and peripheral PBMC of patients with allergic rhinitis (AR), as well as the impact of allergens on the cell membrane markers of basophils. METHODS: Flow cytometry was used to detect the expression of the membrane molecules. RESULTS: While CD123 + HLA-DR- PBMCs are representative of basophils, their presence did not significantly change in patients with AR. In contrast, both the percentage and number of CD123 + HLA-DR- granulocytes, which make up only up to 50% of basophils, were significantly increased in patients with seasonal (sAR) and perennial AR (pAR). CD63+, CD203c+, and FcεRIα+ cells within CD123 + HLA-DR- granulocytes also showed enhanced activity in patients with AR. Allergen extracts from house dust mite allergen extract (HDME) and Artemisia sieversiana wild extract further increased the number of CD123 + HLA-DR- cells in granulocytes of sAR and pAR patients, as well as in PBMCs of pAR patients. CONCLUSIONS: The use of CD123 + HLA-DR- granulocytes and PBMC may not be sufficient for diagnosing AR. Allergens could potentially contribute to the development of AR by influencing the number of CD123 + HLA-DR- cells, as well as the expression of CD63, CD203c, and FcεRIαin these cells.

5.
J Phys Chem Lett ; 15(19): 5096-5102, 2024 May 16.
Article En | MEDLINE | ID: mdl-38709010

Multivalent-ion battery technologies are increasingly attractive options for meeting diverse energy storage needs. Calcium ion batteries (CIB) are particularly appealing candidates for their earthly abundance, high theoretical volumetric energy density, and relative safety advantages. At present, only a few Ca-ion electrolyte systems are reported to reversibly plate at room temperature: for example, aluminates and borates, including Ca[TPFA]2, where [TPFA]- = [Al(OC(CF3)3)4]- and Ca[B(hfip)4]2, [B(hfip)4]2- = [B(OCH(CF3)2)4]-. Analyzing the structure of these salts reveals a common theme: the prevalent use of a weakly coordinating anion (WCA) consisting of a tetracoordinate aluminum/boron (Al/B) center with fluorinated alkoxides. Leveraging the concept of theory-aided design, we report an innovative, one-pot synthesis of two new calcium-ion electrolyte salts (Ca[Al(tftb)4]2, Ca[Al(hftb)4]2) and two reported salts (Ca[Al(hfip)4]2 and Ca[TPFA]2) where hfip = (-OCH(CF3)2), tftb = (-OC(CF3)(Me)2), hftb = (-OC(CF3)2(Me)), [TPFA]- = [Al(OC(CF3)3)4]-. We also reveal the dependence of Coulombic efficiency on their inherent propensity for cation-anion coordination.

6.
Curr Probl Cancer ; 50: 101098, 2024 May 04.
Article En | MEDLINE | ID: mdl-38704949

OBJECTIVE: To investigate the relationship between clinical pathological characteristics, pretreatment CT radiomics, and major pathologic response (MPR) of non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy, and to establish a combined model to predict the major pathologic response of neoadjuvant chemoimmunotherapy. METHODS: A retrospective study of 211 patients with NSCLC who underwent neoadjuvant chemoimmunotherapy and surgical treatment from January 2019 to April 2021 was conducted. The patients were divided into two groups: the MPR group and the non-MPR group. Pre-treatment CT images were segmented using ITK SNAP software to extract radiomics features using Python software. Then a radiomics model, a clinical model, and a combined model were constructed and validated using a receiver operating characteristic (ROC) curve. Finally, Delong's test was used to compare the three models. RESULTS: The radiomics model achieved an AUC of 0.70 (95 % CI: 0.62-0.78) in the training group and 0.60 (95 % CI: 0.45-0.76) in the validation group. RECIST assessment results were screened from all clinical characteristics as independent factors for MPR with multivariate logistic regression analysis. The AUC of the clinical model for predicting MPR was 0.66 (95 % CI: 0.59-0.73) in the training group and 0.77 (95 % CI: 0.66-0.87) in the validation group. The combined model with combined radiomics and clinicopathological characteristics achieved an AUC was 0.76 (95 % CI: 0.68-0.84) in the training group, and 0.80 (95 % CI: 0.67-0.92) in the validation group. Delong's test showed that the AUC of the combined model was significantly higher than that of the radiomics model alone in both the training group (P = 0.0067) and the validation group (P = 0.0009).The calibration curve showed good agreement between predicted and actual MPR. Clinical decision curve analysis showed that the combined model was superior to radiomics alone. CONCLUSIONS: Radiomics model can predict MPR in NSCLC after neoadjuvant chemoimmunotherapy with similar accuracy to RECIST assessment criteria. The combined model based on pretreatment CT radiomics and clinicopathological features showed better predictive power than independent radiomics model or independent clinicopathological features, suggesting that it may be more useful for guiding personalized neoadjuvant chemoimmunotherapy treatment strategies.

7.
Foods ; 13(9)2024 May 01.
Article En | MEDLINE | ID: mdl-38731768

In this study, a novel magnetic molecularly imprinted polymeric material (Fe3O4@MOF@MIP-160) with a metal-organic backbone (Fe3O4@MOF) carrier was prepared using dibutyl phthalate (DBP) as a template. The material can be used for the efficient, rapid, and selective extraction of trace amounts of phthalic acid esters (PAEs) in food and can detect them via gas chromatography-mass spectrometry (GC-MS). The synthesis conditions of the materials were optimized to prepare the Fe3O4@MOF@MIP160 with the highest adsorption performance. Transmission electron microscopy (TEM), Fourier Transform Infrared Spectra (FT-IR), Vibration Sample Magnetic (VSM), and the Brunauer-Emmett-Teller (BET) method were used to characterize the materials. Compared with Fe3O4@MOF and the magnetic non-imprinted polymeric material (Fe3O4@MOF@NIP), Fe3O4@MOF@MIP-160 possesses the advantages of easy and rapid manipulation of magnetic materials, the advantages of high specific surface area and the stability of metal-organic frameworks, and the advantages of high selectivity of molecularly imprinted polymers. Fe3O4@MOF@MIP-160 has good recognition and adsorption capacity for di-butyl phthalate (DBP) and diethylhexyl phthalate (DEHP): the adsorption capacity for DBP and DEHP is 260 mg·g-1 and 240.2 mg·g-1, and the adsorption rate is fast (reaching equilibrium in about 20 min). Additionally, Fe3O4@MOF@MIP160 could be recycled six times, making it cost-effective, easy to operate, and time-saving as compared to traditional solid-phase extraction materials. The phthalate ester content in drinking water, fruit juice, and white wine was analyzed, with recoveries ranging from 70.3% to 100.7%. This proved that Fe3O4@MOF@MIP160 was suitable for detecting and removing PAEs from food matrices.

8.
J Acoust Soc Am ; 155(5): 3410-3425, 2024 May 01.
Article En | MEDLINE | ID: mdl-38780198

The probability distribution of three-dimensional sound speed fields (3D SSFs) in an ocean region encapsulates vital information about their variations, serving as valuable data-driven priors for SSF inversion tasks. However, learning such a distribution is challenging due to the high dimensionality and complexity of 3D SSFs. To tackle this challenge, we propose employing the diffusion model, a cutting-edge deep generative model that has showcased remarkable performance in diverse domains, including image and audio processing. Nonetheless, applying this approach to 3D ocean SSFs encounters two primary hurdles. First, the lack of publicly available well-crafted 3D SSF datasets impedes training and evaluation. Second, 3D SSF data consist of multiple 2D layers with varying variances, which can lead to uneven denoising during the reverse process. To surmount these obstacles, we introduce a novel 3D SSF dataset called 3DSSF, specifically designed for training and evaluating deep generative models. In addition, we devise a high-capacity neural architecture for the diffusion model to effectively handle variations in 3D sound speeds. Furthermore, we employ state-of-the-art continuous-time-based optimization method and predictor-corrector scheme for high-performance training and sampling. Notably, this paper presents the first evaluation of the diffusion model's effectiveness in generating 3D SSF data. Numerical experiments validate the proposed method's strong ability to learn the underlying data distribution of 3D SSFs, and highlight its effectiveness in assisting SSF inversion tasks and subsequently characterizing the transmission loss of underwater acoustics.

9.
Bioorg Chem ; 148: 107467, 2024 May 16.
Article En | MEDLINE | ID: mdl-38772290

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.

10.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167233, 2024 May 12.
Article En | MEDLINE | ID: mdl-38744342

Hepatocellular carcinoma (HCC) poses a significant threat due to its highly aggressive and high recurrence characteristics, necessitating urgent advances in diagnostic and therapeutic approaches. Long non-coding RNAs exert vital roles in HCC tumorigenesis, however the mechanisms of their expression regulation and functions are not fully elucidated yet. Herein, we identify that a novel tumor suppressor 'lnc-PIK3R1' was significantly downregulated in HCC tissues, which was correlated with poor prognosis. Functionally, lnc-PIK3R1 played tumor suppressor roles to inhibit the proliferation and mobility of HCC cells, and to impede the distant implantation of xenograft in mice. Mechanistic studies revealed that lnc-PIK3R1 interacted with miR-1286 and alleviated the repression on GSK3B by miR-1286. Notably, pharmacological inhibition of GSK3ß compromised the tumor suppression effect by lnc-PIK3R1, confirming their functional relevance. Moreover, we identified that oncogenic YY1 acts as a specific transcriptional repressor to downregulate the expression of lnc-PIK3R1 in HCC. In summary, this study highlights the tumor-suppressive effect of lnc-PIK3R1, and provides new insights into the regulation of GSK3ß expression in HCC, which would benefit the development of innovative intervention strategies for HCC.

11.
Chem Sci ; 15(20): 7742-7748, 2024 May 22.
Article En | MEDLINE | ID: mdl-38784746

Artificial metalloenzymes (ArMs) are constructed by anchoring organometallic catalysts to an evolvable protein scaffold. They present the advantages of both components and exhibit considerable potential for the in vivo catalysis of new-to-nature reactions. Herein, Escherichia coli surface-displayed Vitreoscilla hemoglobin (VHbSD-Co) that anchored the cobalt porphyrin cofactor instead of the original heme cofactor was used as an artificial thiourea oxidase (ATOase) to synthesize 5-imino-1,2,4-thiadiazoles. After two rounds of directed evolution using combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy, the evolved six-site mutation VHbSD-Co (6SM-VHbSD-Co) exhibited significant improvement in catalytic activity, with a broad substrate scope (31 examples) and high yields with whole cells. This study shows the potential of using VHb ArMs in new-to-nature reactions and demonstrates the applicability of E. coli surface-displayed methods to enhance catalytic properties through the substitution of porphyrin cofactors in hemoproteins in vivo.

12.
J Acoust Soc Am ; 155(5): 3475-3489, 2024 May 01.
Article En | MEDLINE | ID: mdl-38785598

Reconstructing a three-dimensional ocean sound speed field (SSF) from limited and noisy measurements presents an ill-posed and challenging inverse problem. Existing methods used a number of pre-specified priors (e.g., low-rank tensor and tensor neural network structures) to address this issue. However, the SSFs are often too complex to be accurately described by these pre-defined priors. While utilizing neural network-based priors trained on historical SSF data may be a viable workaround, acquiring SSF data remains a nontrivial task. This work starts with a key observation: Although natural images and SSFs admit fairly different characteristics, their denoising processes appear to share similar traits-as both remove random components from more structured signals. This observation allows us to incorporate deep denoisers trained using extensive natural images to realize zero-shot SSF reconstruction, without any extra training or network modifications. To implement this idea, an alternating direction method of multipliers (ADMM) algorithm using such a deep denoiser is proposed, which is reminiscent of the plug-and-play scheme from medical imaging. Our plug-and-play framework is tailored for SSF recovery such that the learned denoiser can be simultaneously used with other handcrafted SSF priors. Extensive numerical studies show that the new framework largely outperforms state-of-the-art baselines, especially under widely recognized challenging scenarios, e.g., when the SSF samples are taken as tensor fibers. The code is available at https://github.com/OceanSTARLab/DeepPnP.

13.
Cell Death Dis ; 15(4): 241, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38561375

Soft-tissue sarcomas (STS) emerges as formidable challenges in clinics due to the complex genetic heterogeneity, high rates of local recurrence and metastasis. Exploring specific targets and biomarkers would benefit the prognosis and treatment of STS. Here, we identified RCC1, a guanine-nucleotide exchange factor for Ran, as an oncogene and a potential intervention target in STS. Bioinformatics analysis indicated that RCC1 is highly expressed and correlated with poor prognosis in STS. Functional studies showed that RCC1 knockdown significantly inhibited the cell cycle transition, proliferation and migration of STS cells in vitro, and the growth of STS xenografts in mice. Mechanistically, we identified Skp2 as a downstream target of RCC1 in STS. Loss of RCC1 substantially diminished Skp2 abundance by compromising its protein stability, resulting in the upregulation of p27Kip1 and G1/S transition arrest. Specifically, RCC1 might facilitate the nucleo-cytoplasmic trafficking of Skp2 via direct interaction. As a result, the cytoplasmic retention of Skp2 would further protect it from ubiquitination and degradation. Notably, recovery of Skp2 expression largely reversed the phenotypes induced by RCC1 knockdown in STS cells. Collectively, this study unveils a novel RCC1-Skp2-p27Kip1 axis in STS oncogenesis, which holds promise for improving prognosis and treatment of this formidable malignancy.


Sarcoma , Animals , Humans , Mice , Cell Cycle , Cell Cycle Proteins/metabolism , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Nuclear Proteins/metabolism , S-Phase Kinase-Associated Proteins/genetics , S-Phase Kinase-Associated Proteins/metabolism , Sarcoma/genetics , Sarcoma/pathology , Ubiquitination , Up-Regulation
14.
Mol Med Rep ; 29(6)2024 Jun.
Article En | MEDLINE | ID: mdl-38577934

Hepatitis B X­interacting protein (HBXIP) is a membrane protein located on the lysosomal surface and encoded by the Lamtor gene. It is expressed by a wide range of tumor types, including breast cancer, esophageal squamous cell carcinoma and hepatocellular carcinoma, and its expression is associated with certain clinicopathological characteristics. In the past decade, research on the oncogenic mechanisms of HBXIP has increased and the function of HBXIP in normal cells has been gradually elucidated. In the present review, the following was discussed: The normal physiological role of the HBXIP carcinogenic mechanism; the clinical significance of high levels of HBXIP expression in different tumors; HBXIP regulation of transcription, post­transcription and post­translation processes in tumors; the role of HBXIP in improving the antioxidant capacity of tumor cells; the inhibition of ferroptosis of tumor cells and regulating the metabolic reprogramming of tumor cells; and the role of HBXIP in promoting the malignant progression of tumors. In conclusion, the present review summarized the existing knowledge of HBXIP, established its carcinogenic mechanism and discussed future related research on HBXIP.


Adaptor Proteins, Signal Transducing , Oncogene Proteins , Humans , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Liver Neoplasms/genetics , Oncogene Proteins/metabolism
15.
BMC Med ; 22(1): 174, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658988

BACKGROUND: Osimertinib has become standard care for epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients whereas drug resistance remains inevitable. Now we recognize that the interactions between the tumor and the tumor microenvironment (TME) also account for drug resistance. Therefore, we provide a new sight into post-osimertinib management, focusing on the alteration of TME. METHODS: We conducted a retrospective study on the prognosis of different treatments after osimertinib resistance. Next, we carried out in vivo experiment to validate our findings using a humanized mouse model. Furthermore, we performed single-cell transcriptome sequencing (scRNA-seq) of tumor tissue from the above treatment groups to explore the mechanisms of TME changes. RESULTS: Totally 111 advanced NSCLC patients have been enrolled in the retrospective study. The median PFS was 9.84 months (95% CI 7.0-12.6 months) in the osimertinib plus anti-angiogenesis group, significantly longer than chemotherapy (P = 0.012) and osimertinib (P = 0.003). The median OS was 16.79 months (95% CI 14.97-18.61 months) in the osimertinib plus anti-angiogenesis group, significantly better than chemotherapy (P = 0.026), the chemotherapy plus osimertinib (P = 0.021), and the chemotherapy plus immunotherapy (P = 0.006). The efficacy of osimertinib plus anlotinib in the osimertinib-resistant engraft tumors (R-O+A) group was significantly more potent than the osimertinib (R-O) group (P<0.05) in vitro. The combinational therapy could significantly increase the infiltration of CD4+ T cells (P<0.05), CD25+CD4+ T cells (P<0.001), and PD-1+CD8+ T cells (P<0.05) compared to osimertinib. ScRNA-seq demonstrated that the number of CD8+ T and proliferation T cells increased, and TAM.mo was downregulated in the R-O+A group compared to the R-O group. Subtype study of T cells explained that the changes caused by combination treatment were mainly related to cytotoxic T cells. Subtype study of macrophages showed that proportion and functional changes in IL-1ß.mo and CCL18.mo might be responsible for rescue osimertinib resistance by combination therapy. CONCLUSIONS: In conclusion, osimertinib plus anlotinib could improve the prognosis of patients with a progressed disease on second-line osimertinib treatment, which may ascribe to increased T cell infiltration and TAM remodeling via VEGF-VEGFR blockage.


Acrylamides , Angiogenesis Inhibitors , Aniline Compounds , Carcinoma, Non-Small-Cell Lung , Drug Resistance, Neoplasm , Lung Neoplasms , Pyrimidines , Carcinoma, Non-Small-Cell Lung/drug therapy , Aniline Compounds/therapeutic use , Aniline Compounds/pharmacology , Acrylamides/therapeutic use , Acrylamides/pharmacology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Retrospective Studies , Drug Resistance, Neoplasm/drug effects , Female , Male , Animals , Mice , Middle Aged , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Aged , Tumor Microenvironment/drug effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Adult , Indoles/therapeutic use , Indoles/administration & dosage
16.
Bone Res ; 12(1): 20, 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38553442

To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress. Moreover, conditional knockout of Piezo1 (Col2a1-CreERT Piezo1flox/flox) attenuated the mechanical injury-induced intervertebral disc degeneration (IVDD). Notably, the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout (cDKO) mice (Col2a1-CreERT Piezo1flox/flox/Gpx4flox/flox). These findings suggest that Piezo1 is a potential determinant of iron influx, indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.


Ferroptosis , Intervertebral Disc Degeneration , Nucleus Pulposus , Animals , Mice , Stress, Mechanical , Mitochondria , Iron , Mice, Knockout , Ion Channels/genetics
17.
PLoS One ; 19(3): e0296811, 2024.
Article En | MEDLINE | ID: mdl-38512912

BACKGROUND: To analyze vault effects of crystalline lens rise (CLR) and anterior chamber parameters (recorded by Pentacam) in highly myopic patients receiving implantable collamer lenses (ICLs), which may avoid subsequent complications such as glaucoma and cataract caused by the abnormal vault. METHODS: We collected clinical data of 137 patients with highly myopic vision, who were all subsequent recipients of V4c ICLs between June 2020 and January 2021. Horizontal ciliary sulcus-to-sulcus diameter (hSTS) and CLR were measured by ultrasonic biomicroscopy (UBM), and a Pentacam anterior segment analyzer was used to measure horizontal white-to-white diameter (hWTW), anterior chamber depth (ACD), anterior chamber angle (ACA), anterior chamber volume (ACV), CLR, and postoperative vault (Year 1 and Month 1). The lens thickness (LT) was determined by optical biometry (IOL Master instrument). The predictive model was generated through multiple linear regression analyses of influential factors, such as hSTS, CLR, hWTW, ACD, ACA, ACV, ICL size, and LT. The predictive performance of the multivariate model on vault after ICL was assessed using the receiver operating characteristic (ROC) curve with area under the curve (AUC) as well as the point of tangency. RESULTS: Average CLR assessed by UBM was lower than the average value obtained by Pentacam (0.561 vs. 0.683). Bland-Altman analysis showed a good consistency in the two measurement methods and substantial correlation (r = 0.316; P = 0.000). The ROC curve of Model 1 (postoperative Year 1) displayed an AUC of 0.847 (95% confidence interval [CI]: 74.19-95.27), with optimal threshold of 0.581 (sensitivity, 0.857; specificity, 0.724). In addition, respective values for Model 2 (postoperative Month 1) were 0.783 (95% CI: 64.94-91.64) and 0.522 (sensitivity, 0.917; specificity, 0.605). CONCLUSION: CLR and anterior chamber parameters are important determinants of postoperative vault after ICL placement. The multivariate regression model we constructed may serve in large part as a predictive gauge, effectively avoid postoperative complication.


Lens, Crystalline , Myopia , Phakic Intraocular Lenses , Humans , Lens Implantation, Intraocular/adverse effects , Visual Acuity , Lens, Crystalline/surgery , Anterior Chamber/diagnostic imaging , Myopia/surgery , Retrospective Studies
18.
Nat Commun ; 15(1): 2695, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38538640

Global potent greenhouse gas nitrous oxide (N2O) emissions from soil are accelerating, with increases in the proportion of reactive nitrogen emitted as N2O, i.e., N2O emission factor (EF). Yet, the primary controls and underlying mechanisms of EFs remain unresolved. Based on two independent but complementary global syntheses, and three field studies determining effects of acidity on N2O EFs and soil denitrifying microorganisms, we show that soil pH predominantly controls N2O EFs and emissions by affecting the denitrifier community composition. Analysis of 5438 paired data points of N2O emission fluxes revealed a hump-shaped relationship between soil pH and EFs, with the highest EFs occurring in moderately acidic soils that favored N2O-producing over N2O-consuming microorganisms, and induced high N2O emissions. Our results illustrate that soil pH has a unimodal relationship with soil denitrifiers and EFs, and the net N2O emission depends on both the N2O/(N2O + N2) ratio and overall denitrification rate. These findings can inform strategies to predict and mitigate soil N2O emissions under future nitrogen input scenarios.


Agriculture , Soil , Soil/chemistry , Nitrous Oxide/analysis , Fertilizers/analysis , Nitrogen , Hydrogen-Ion Concentration , Soil Microbiology , Denitrification
19.
Article En | MEDLINE | ID: mdl-38512751

A microaerophilic, Gram-negative, motile, and spiral-shaped bacterium, designated Y-M2T, was isolated from oil sludge of Shengli oil field. The optimal growth condition of strain Y-M2T was at 25 °C, pH 7.0, and in the absence of NaCl. The major polar lipid was phosphatidylethanolamine. The main cellular fatty acid was iso-C17  :  0 3-OH. It contained Q-9 and Q-10 as the predominant quinones. The DNA G+C content was 68.1 mol%. Strain Y-M2T showed the highest 16S rRNA gene sequence similarity to Telmatospirillum siberiense 26-4bT (91.1 %). Phylogenetic analyses based on 16S rRNA gene and genomes showed that strain Y-M2T formed a distinct cluster in the order Rhodospirillales. Genomic analysis showed that Y-M2T possesses a complete nitrogen-fixation cluster which is phylogenetically close to that of methanogene. The nif cluster, encompassing the nitrogenase genes, was found in every N2-fixing strain within the order Rhodospirillales. Phylogeny, phenotype, chemotaxonomy, and genomic results demonstrated that strain Y-M2T represents a novel species of a novel genus in a novel family Oleispirillaceae fam. nov. in the order Rhodospirillales, for which the name Oleispirillum naphthae gen. nov., sp. nov. was proposed. The type strain is Y-M2T (=CCAM 827T=JCM 34765T).


Fatty Acids , Phospholipids , Fatty Acids/chemistry , Phospholipids/chemistry , Sewage/microbiology , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , DNA, Bacterial/genetics , Base Composition , Bacterial Typing Techniques
20.
Br J Soc Psychol ; 2024 Mar 23.
Article En | MEDLINE | ID: mdl-38520243

Interpersonal objectification, treating people as tools and neglecting their essential humanness, is a pervasive and enduring phenomenon. Across five studies (N = 1183), we examined whether subjective economic inequality increases objectification through a calculative mindset. Study 1 revealed that the perceptions of economic inequality at the national level and in daily life were positively associated with objectification. Studies 2 and 3 demonstrated a causal relationship between subjective economic inequality and objectification in a fictitious organization and society, respectively. Moreover, the effect was mediated by a calculative mindset (Studies 3-4). In addition, lowering a calculative mindset weakened the effect of subjective inequality on objectification (Study 4). Finally, increased objectification due to subjective inequality further decreased prosociality and enhanced exploitative intentions (Study 5). Taken together, our findings suggest that subjective economic inequality increases objectification, which further causes adverse interpersonal interactions.

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