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1.
Article in English | MEDLINE | ID: mdl-38959139

ABSTRACT

We present the first real-time method for inserting a rigid virtual object into a neural radiance field (NeRF), which produces realistic lighting and shadowing effects, as well as allows interactive manipulation of the object. By exploiting the rich information about lighting and geometry in a NeRF, our method overcomes several challenges of object insertion in augmented reality. For lighting estimation, we produce accurate and robust incident lighting that combines the 3D spatially-varying lighting from NeRF and an environment lighting to account for sources not covered by the NeRF. For occlusion, we blend the rendered virtual object with the background scene using an opacity map integrated from the NeRF. For shadows, with a precomputed field of spherical signed distance fields, we query the visibility term for any point around the virtual object, and cast soft, detailed shadows onto 3D surfaces. Compared with state-of-the-art techniques, our approach can insert virtual objects into scenes with superior fidelity, and has great potential to be further applied to augmented reality systems.

2.
Eur J Immunol ; : e2350655, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38973083

ABSTRACT

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

3.
Cell Death Dis ; 15(7): 516, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39025830

ABSTRACT

Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.


Subject(s)
Cell Proliferation , Glucose , Glucosephosphate Dehydrogenase , Triple Negative Breast Neoplasms , Up-Regulation , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/genetics , Humans , Female , Glucosephosphate Dehydrogenase/metabolism , Glucosephosphate Dehydrogenase/genetics , Animals , Cell Line, Tumor , Mice , Glucose/metabolism , Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic , Mice, Nude
4.
J Environ Manage ; 366: 121696, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39013313

ABSTRACT

The dune ecosystem plays a significant role in the global carbon cycle. The Horqin Sandy Land is a typical semi-arid fragile ecosystem in northern China. Understanding the magnitudes and dynamics of carbon dioxide fluxes within this region is essential for understanding the carbon balance. Used 6 years (2013-2018) measurements from an eddy-covariance system, we analyzed the dynamic patterns of net ecosystem carbon exchange (NEE), gross primary production (GPP), and ecosystem respiration (Reco) of the dune ecosystem in Horqin Sandy Land and examined their responses to climate factors with a focus on the precipitation. The results showed that the NEE of the dune ecosystem fluctuated from -166 to 100 gCO2·m-2·year-1 across the 6 growing seasons, with an average of -56 gCO2·m-2·year-1. The precipitation was not a key factor influencing the carbon flux variability. During the mid-growth stage, GPP was primarily affected by the effective precipitation frequency (R2 ranging from 0.65 to 0.85, P < 0.05), followed by fractional vegetation cover (R2 ranging from 0.65 to 0.68, P < 0.05). However, in the early and late growth stages, temperature predominantly drove the carbon flux (R2 = 0.75, P < 0.01). The interannual variability of carbon flux can be predominantly elucidated by phenological indicators such as CO2 uptake (CUstart), end of CO2 uptake (CUend), CO2 uptake period (CUP), and Spring lag. The results demonstrated the dune ecosystem is a weak carbon sink in semi-arid ecosystems. Furthermore, we emphasized the significance of effective precipitation frequency in regulating carbon fluxes. Our results provide a foundational understanding of the carbon balance in semi-arid ecosystems.

5.
Diabetes ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39058602

ABSTRACT

A hallmark of type 2 diabetes (T2D) is endocrine islet ß-cell failure, which can occur via cell dysfunction, loss-of-identity, and/or death. How each is induced remains largely unknown. Here, we use mouse ß-cells that are deficient for Myelin transcription factors (Myt TFs, including Myt1, 2, and 3) to address this question. We have reported that inactivating all three Myt genes in pancreatic progenitor cells (MytPancΔ) causes ß-cell failure and late onset diabetes in mice. Their lower expression in human ß-cells is correlated with ß-cell dysfunction and SNPs in MYT2 and MYT3 are associated in higher risk of T2D. We now show that these Myt TF-deficient postnatal ß-cells also de-differentiate by reactivating several progenitor markers. Intriguingly, mosaic Myt TF inactivation in only a portion of islet ß-cells does not results in overt diabetes, but this creates a condition where Myt TF-deficient ß-cells stay alive while activating several markers of Ppy-expressing islet cells. By transplanting MytPancΔ islets into the anterior eye chambers of immune-compromised mice, we directly show that glycemic and obesity-related conditions influence cell fate, with euglycemia inducing several Ppy+ cell markers while hyperglycemia and insulin resistance inducing additional cell death. These findings suggest that the observed ß-cell defects in T2D depend on not only their inherent genetic/epigenetic defects, but also the metabolic load.

6.
Cell Death Dis ; 15(7): 525, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043653

ABSTRACT

BUB1 mitotic checkpoint serine/threonine kinase B (BUB1b) has been unequivocally identified as an oncogene in various cancers. However, the potential mechanism by which BUB1b orchestrates the progression of lung adenocarcinoma (LUAD) remains unclear. Here we found that both the transcript and protein levels of BUB1b were dramatically upregulated in tumor tissues and contributed to the dismal prognosis of LUAD patients. Moreover, gain- and loss-of-function assays, conducted both in vitro and in vivo, confirmed that BUB1b enhanced the viability of LUAD cells. Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy. In BALB/c nude mice bearing subcutaneous tumors that overexpress BUB1b, a combined strategy of ML385 targeting and chemotherapy achieved synergistic effects, inhibiting tumor growth and obviously improving survival. Taken together our study uncovered the underlying mechanism by which BUB1b promotes the progression of LUAD and proposed a novel strategy to enhance the efficacy of chemotherapy.


Subject(s)
Adenocarcinoma of Lung , Drug Resistance, Neoplasm , Ferroptosis , Lung Neoplasms , Mice, Inbred BALB C , Mice, Nude , Protein Serine-Threonine Kinases , Humans , Ferroptosis/drug effects , Ferroptosis/genetics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Animals , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mice , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Cell Line, Tumor , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Female , Male , Signal Transduction/drug effects , Gene Expression Regulation, Neoplastic/drug effects
7.
J Nanobiotechnology ; 22(1): 426, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030593

ABSTRACT

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. MATERIALS AND METHODS: SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. RESULTS: The expressions of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3'-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. CONCLUSIONS: DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH.


Subject(s)
Dental Pulp , Exosomes , Forkhead Box Protein O3 , Mesenchymal Stem Cells , MicroRNAs , Microglia , Neuroinflammatory Diseases , Pyroptosis , Rats, Sprague-Dawley , Subarachnoid Hemorrhage , Animals , Exosomes/metabolism , MicroRNAs/metabolism , MicroRNAs/genetics , Forkhead Box Protein O3/metabolism , Male , Mesenchymal Stem Cells/metabolism , Rats , Dental Pulp/cytology , Dental Pulp/metabolism , Subarachnoid Hemorrhage/metabolism , Subarachnoid Hemorrhage/therapy , Humans , Neuroinflammatory Diseases/metabolism , Microglia/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Mice , Disease Models, Animal
8.
Environ Sci Technol ; 58(29): 13110-13119, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38989600

ABSTRACT

Transition-metal dichalcogenides (TMDs) have shown great promise as selective and high-capacity sorbents for Hg(II) removal from water. Yet, their design should consider safe disposal of spent materials, particularly the subsequent formation of methylmercury (MeHg), a highly potent and bioaccumulative neurotoxin. Here, we show that microbial methylation of mercury bound to MoS2 nanosheets (a representative TMD material) is significant under anoxic conditions commonly encountered in landfills. Notably, the methylation potential is highly dependent on the phase compositions of MoS2. MeHg production was higher for 1T MoS2, as mercury bound to this phase primarily exists as surface complexes that are available for ligand exchange. In comparison, mercury on 2H MoS2 occurs largely in the form of precipitates, particularly monovalent mercury minerals (e.g., Hg2MoO4 and Hg2SO4) that are minimally bioavailable. Thus, even though 1T MoS2 is more effective in Hg(II) removal from aqueous solution due to its higher adsorption affinity and reductive ability, it poses a higher risk of MeHg formation after landfill disposal. These findings highlight the critical role of nanoscale surfaces in enriching heavy metals and subsequently regulating their bioavailability and risks and shed light on the safe design of heavy metal sorbent materials through surface structural modulation.


Subject(s)
Mercury , Methylation , Adsorption , Nanostructures/chemistry , Water Pollutants, Chemical/chemistry , Methylmercury Compounds , Molybdenum/chemistry
9.
Arch Physiol Biochem ; : 1-7, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39084250

ABSTRACT

CONTEXT: Polycystic ovary syndrome (PCOS) is an endocrine gynaecological disorder that affects many women of childbearing age. OBJECTIVE: To evaluate the efficacy and safety of glucose-like peptide-1 receptor agonists for obese women with PCOS. METHODS: We searched the PubMed, Embase, WOS, and Cochrane Libarary databases up to June 2023. Studies were eligible if they were randomised controlled trials (RCTs) comparing GLP-1RAs against any other treatments for patients with PCOS. RESULTS: Overall, a total of 8 RCTs were included in this review, 7 of the RCTs compared GLP-1RAs with metformin, and 1 RCT compared GLP-1Ras with dapagliflozin. Compared with control group, GLP-1RAs were more effective at improving insulin sensitivity, reducing BMI, and resulting in a smaller waist circumference. CONCLUSIONS: GLP-1RAs may be a good option for obese women with PCOS, especially those with insulin resistance. However, high-quality studies are also needed in the future to assess the efficacy of GLP-1RAs in women with PCOS.

10.
Neurosurg Rev ; 47(1): 330, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007950

ABSTRACT

Despite advancements in treatment modalities such as flow diverters, the optimal management of posterior communicating artery (PComA) aneurysms remains uncertain. While PComA aneurysms treated with the Pipeline Embolization Device (PED) has been reported, the characteristics and progression of incomplete occluded aneurysms remain unclear. Therefore, our study aims to investigate the occlusion status and recurrence rates of PComA aneurysms treated with PED. A retrospective review of consecutive PComA aneurysm patients treated with PED was conducted between January 2015 and December 2020. Only patients with radiological follow-up were included. PComA aneurysms were categorized into incomplete occlusion and complete occlusion group. The primary outcomes included the characteristics of incomplete occlusion at the follow-up angiography. Among 121 PComA aneurysms treated with PED at our institution, 80 aneurysms were eligible in our study. During the follow-up period, 19 (23.8%) aneurysms demonstrated incomplete occlusion. Notably, there were no instances of recurrence among the 80 followed-up cases. Baseline characteristics of patients and aneurysms were comparable between the groups with complete and incomplete occlusion. However, the incomplete occlusion group showed a lower rate of assisted coils embolization (21.2% vs. 55.7%, P = 0.017) and shorter median operative time (91.0 vs. 145.5 min, P = 0.039). Differences in functional outcomes, complications, and PComA occlusion status between the groups were not significant. Multivariate analysis revealed the use of coils was associated with lower odds of incomplete PComA aneurysm occlusion (OR 0.01, 95% CI 0.001-0.12; P = 0.001), while aneurysm size was associated with higher odds of incomplete occlusion (OR 1.25, 95% CI 1.10-1.46; P = 0.002). The treatment of PED for PComA aneurysm demonstrated favorable outcomes, with an acceptable rate of incomplete occlusion and no instances of recurrence observed. However, further research is needed to explore the optimal procedural strategy for large-sized PComA aneurysms.


Subject(s)
Embolization, Therapeutic , Intracranial Aneurysm , Recurrence , Humans , Intracranial Aneurysm/therapy , Male , Embolization, Therapeutic/methods , Embolization, Therapeutic/instrumentation , Female , Middle Aged , Aged , Retrospective Studies , Treatment Outcome , Adult , Cerebral Angiography
11.
J Consult Clin Psychol ; 92(6): 367-384, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39023984

ABSTRACT

OBJECTIVE: Web-based cognitive bias modification for interpretation (CBM-I) can improve interpretation biases and anxiety symptoms but faces high rates of dropout. This study tested the effectiveness of web-based CBM-I relative to an active psychoeducation condition and the addition of low-intensity telecoaching for a subset of CBM-I participants. METHOD: 1,234 anxious community adults (Mage = 35.09 years, 81.2% female, 72.1% white, 82.6% not Hispanic) were randomly assigned at Stage 1 of a sequential, multiple-assignment randomized trial to complete five weekly sessions of CBM-I or psychoeducation on our team's public research website. After the first session, for Stage 2, an algorithm attempted to classify CBM-I participants as higher (vs. lower) risk for dropping out; those classified as higher risk were then randomly assigned to complete four brief weekly telecoaching check-ins (vs. no coaching). RESULTS: As hypothesized (https://doi.org/j2xr; Daniel, Eberle, & Teachman, 2020), CBM-I significantly outperformed psychoeducation at improving positive and negative interpretation biases (Recognition Ratings, Brief Body Sensations Interpretation Questionnaire) and anxiety symptoms (Overall Anxiety Severity and Impairment Scale, Anxiety Scale from Depression Anxiety Stress Scales-Short Form), with smaller treatment gains remaining significant at 2-month follow-up. Unexpectedly, CBM-I had significantly worse treatment dropout outcomes than psychoeducation, and adding coaching (vs. no coaching) did not significantly improve efficacy or dropout outcomes (notably, many participants chose not to interact with their coach). CONCLUSIONS: Web-based CBM-I appears effective, but supplemental coaching may not mitigate the challenge of dropout. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Anxiety , Cognitive Behavioral Therapy , Humans , Female , Male , Adult , Cognitive Behavioral Therapy/methods , Anxiety/therapy , Internet-Based Intervention , Middle Aged , Internet , Anxiety Disorders/therapy , Patient Dropouts/psychology
12.
Pharmaceutics ; 16(7)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39065572

ABSTRACT

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies.

13.
Sensors (Basel) ; 24(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39065987

ABSTRACT

Protection suits are vital for firefighters' safety. Traditional protection suits physically protect firemen from burns, but cannot locate the position of bodily injuries caused by impact debris. Herein, we present a wearable impact debris positioning system for firefighter protection suits based on an accelerometer array. Wearable piezoelectric accelerometers are distributed regularly on the suit to detect the vibration on different body parts, which is conducive to determining the position of injured body parts. In addition, the injured parts can be displayed on a dummy body model on the upper computer with a higher localization accuracy of 4 cm. The positioning alarm system has a rapid response time of 0.11 ms, attributed to the smart signal processing method. This work provides a reliable and smart method for locating and assessing the position of bodily injuries caused by impact debris, which is significant because it enables fire commanders to rescue injured firefighters in time.


Subject(s)
Accelerometry , Firefighters , Accelerometry/instrumentation , Humans , Protective Clothing , Wearable Electronic Devices , Vibration
14.
J Nanobiotechnology ; 22(1): 409, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992688

ABSTRACT

OBJECTIVE: This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination. METHODS: Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses. RESULTS: CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors. CONCLUSION: CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.


Subject(s)
Colorectal Neoplasms , Myeloid-Derived Suppressor Cells , RNA, Small Interfering , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor , STAT3 Transcription Factor , Animals , Myeloid-Derived Suppressor Cells/metabolism , Mice , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/immunology , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , STAT3 Transcription Factor/metabolism , Cell Line, Tumor , Humans , Signal Transduction/drug effects , Programmed Cell Death 1 Receptor/metabolism , Female , Mice, Inbred BALB C , Janus Kinases/metabolism , Immunomodulation/drug effects , Receptor, Macrophage Colony-Stimulating Factor
15.
Article in English | MEDLINE | ID: mdl-39066693

ABSTRACT

Atomic engineering of the basal plane active sites in MoS2 holds great promise to boost the electrocatalytic activity for hydrogen evolution reactions (HER), yet the performance optimization and mechanism exploration are still not satisfactory. Herein, we proposed a dual-plasma engineering strategy to implant Ti and N heteroatoms into the basal plane of MoS2 supported by Ni3S2 nanorods on nickel foam (MSNF) for efficient electrocatalysis of HER. Owing to the low formation energy of Ti dopants in MoS2 and the extra charge carriers introduced by N dopants, the optimally codoped samples N1.0@Ti500-MSNF demonstrate significant morphology changes from nanorods to urchin-like nanospheres with the surface active areas increased by seven-fold, as well as enhanced electrical conductivity in comparison with the nondoped counterparts. The HER performance of N1.0@Ti500-MSNF is comparable with the Pt-based catalyst: overpotential of 26 mV at 20 mA cm-2, Tafel slope of 35.6 mV dec-1, and long-term stability over 50 h. First-principles calculation reveals that N doping accelerates the dissociation of water molecules while Ti doping activates the adjacent S sites for hydrogen adsorption by lowering the Gibbs free energy, resulting in excellent HER activity. This work thus provides an effective strategy for basal plane engineering of MoS2 heterostructures toward high-performance HER and sustainable energy supply at reasonable costs.

16.
Virol J ; 21(1): 127, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38835029

ABSTRACT

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.


Subject(s)
Alanine Transaminase , DNA, Viral , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , Liver Cirrhosis , Humans , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/blood , Male , Female , Adult , Liver Cirrhosis/virology , Liver Cirrhosis/blood , Liver Cirrhosis/pathology , DNA, Viral/blood , Alanine Transaminase/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Middle Aged , Viral Load , Young Adult , Liver/pathology , Liver/virology , Biopsy
17.
Neurosurg Rev ; 47(1): 256, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38834876

ABSTRACT

OBJECTIVE: White blood cells (WBC) play an important role in the inflammatory response of the body. Elevated WBC counts on admission in patients with subarachnoid hemorrhage (SAH) correlate with a poor prognosis. However, the role of longitudinal WBC trajectories based on repeated WBC measurements during hospitalization remains unclear. We explored the association between different WBC trajectory patterns and in-hospital mortality. METHODS: We analyzed a cohort of consecutive patients with SAH between 2012 and 2020. Group-based trajectory modeling (GBTM) was used to group the patients according to their white blood cell patterns over the first 4 days. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. We analyzed the association between the WBC trajectory groups and in-hospital mortality using a Cox proportional hazards model. RESULTS: In total, 506 patients with SAH were included in this retrospective cohort. The final model identified two distinct longitudinal WBC trajectories. After adjusting for confounding factors, multivariate regression analysis suggested that an elevated longitudinal WBC trajectory increased the risk of in-hospital mortality (hazard ratio [HR], 2.476; 95% confidence interval [CI] 1.081-5.227; P = 0.024) before sIPTW, and (HR, 2.472; 95%CI 1.489-4.977; P = 0.018) after sIPTW. CONCLUSION: In patients with SAH, different clinically relevant groups could be identified using WBC trajectory analysis. The WBC count trajectory-initially elevated and then decreased- may lead to an increased risk of in-hospital mortality following SAH.


Subject(s)
Hospital Mortality , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/mortality , Subarachnoid Hemorrhage/blood , Male , Female , Middle Aged , Aged , Leukocyte Count , Retrospective Studies , Inflammation , Adult , Prognosis , Cohort Studies
18.
Adv Mater ; : e2402912, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38923167

ABSTRACT

Colloidal quantum dots (QDs) hold great promise as building blocks in solar technologies owing to their remarkable photostability and adjustable properties through the rationale involving size, atomic composition of core and shell, shapes, and surface states. However, most high-performing QDs in solar conversion contain hazardous metal elements, including Cd and Pb, posing significant environmental risks. Here, a comprehensive review of heavy-metal-free colloidal QDs for solar technologies, including photovoltaic (PV) devices, solar-to-chemical fuel conversion, and luminescent solar concentrators (LSCs), is presented. Emerging synthetic strategies to optimize the optical properties by tuning the energy band structure and manipulating charge dynamics within the QDs and at the QDs/charge acceptors interfaces, are analyzed. A comparative analysis of different synthetic methods is provided, structure-property relationships in these materials are discussed, and they are correlated with the performance of solar devices. This work is concluded with an outlook on challenges and opportunities for future work, including machine learning-based design, sustainable synthesis, and new surface/interface engineering.

19.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38931471

ABSTRACT

Purpose: Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored. Methods: The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell-crystal adhesion were examined in the presence of Laminarin polysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions. Results: Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP. Conclusions: SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal-cell adhesion interactions and the risks of kidney stone formation.

20.
J Stroke Cerebrovasc Dis ; 33(8): 107833, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38925449

ABSTRACT

BACKGROUND AND PURPOSE: Flow-diversion treatment for intracranial aneurysms has been associated with the development of in-stent stenosis (ISS) for unclear reasons. We assess whether the size of the stent relative to that of the vessel (the stent-to-vessel diameter ratio, or SVR) may be predictive of the development of ISS after treatment with flow diverters. METHODS: We retrospectively reviewed patients with unruptured intracranial aneurysms who underwent flow-diversion treatment using either the Pipeline or Tubridge embolization device from September 2018 to September 2022. The relationship between SVR and ISS was analyzed. Multiple logistic regression models were used to determine the significant predictors. RESULTS: A total of 458 patients with 481 aneurysms were included. In a mean angiographic follow-up of 10.73 ± 3.97 months, ISS was detected in 68 cases (14.1 %). After adjusting for candidate variables, a higher distal SVR (DSVR) was associated with an increased risk of ISS (adjusted odds ratio [aOR] = 3.420, 95 % confidence interval [CI] = 1.182 - 9.889, p = 0.023). We conducted a subgroup analysis of the two different flow diverters to assess the effects of their individual characteristics. Our results showed a significant association between the DSVR and the incidence of ISS in both the Pipeline (aOR = 4.033, 95 % CI = 1.156-14.072, p = 0.029) and Tubridge groups (aOR = 11.981, 95 % CI=1.005-142.774, p = 0.049). CONCLUSION: A higher DSVR was associated with an increased risk of ISS. This may help neurointerventionalists select an appropriate stent size when conducting flow-diversion treatment for intracranial aneurysms.


Subject(s)
Endovascular Procedures , Intracranial Aneurysm , Prosthesis Design , Stents , Humans , Intracranial Aneurysm/therapy , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/physiopathology , Male , Female , Retrospective Studies , Middle Aged , Risk Factors , Aged , Treatment Outcome , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Risk Assessment , Time Factors , Embolization, Therapeutic/instrumentation , Embolization, Therapeutic/adverse effects , Adult , Cerebral Angiography , Cerebrovascular Circulation , Vascular Patency
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