Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 174
Filter
1.
Cancers (Basel) ; 16(12)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38927890

ABSTRACT

Due to limited effective therapeutics for uterine leiomyosarcoma (uLMS), the impact of the gamma secretase inhibitor (GSI) MK-0752 with common chemotherapeutics was explored in uLMS. MTT assays were performed on two human uLMS cell lines, SK-UT-1B and SK-LMS-1, using MK-0752, docetaxel, doxorubicin, and gemcitabine, individually and in combination, to determine cell viability after treatment. Synergistic combinations were used in transwell invasion assays, cell cycle flow cytometry, proliferation assays, and RNA sequencing. In SK-UT-1B, MK-0752 was synergistic with doxorubicin and gemcitabine plus docetaxel. In SK-LMS-1, MK-0752 was synergistic with all individual agents and with the combination of gemcitabine plus docetaxel. MK-0752, gemcitabine, and docetaxel decreased invasion in SK-UT-1B 2.1-fold* and in SK-LMS-1 1.7-fold*. In SK-LMS-1, invasion decreased 1.2-fold* after treatment with MK-0752 and docetaxel and 2.2-fold* after treatment with MK-0752 and doxorubicin. Cell cycle analysis demonstrated increases in the apoptotic sub-G1 population with MK-0752 alone in SK-UT-1B (1.4-fold*) and SK-LMS-1 (2.7-fold**), along with increases with all combinations in both cell lines. The combination treatments had limited effects on proliferation, while MK-0752 alone decreased proliferation in SK-LMS-1 (0.63-fold**). Both MK-0752 alone and in combination altered gene expression and KEGG pathways. In conclusion, the combinations of MK-0752 with either doxorubicin, docetaxel, or gemcitabine plus docetaxel are potential novel therapeutic approaches for uLMS. (* p < 0.05, ** p < 0.01).

2.
Angew Chem Int Ed Engl ; : e202409435, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38945832

ABSTRACT

Visualizing lithium (Li) ions and understanding Li plating/stripping processes as well as evolution of solid electrolyte interface (SEI) are critical for optimizing all-solid-state Li metal batteries (ASSLMB). However, the buried solid-solid interfaces present a challenge for detection which preclude the employment of multiple analysis techniques. Herein, by employing complementary in situ characterizations, morphological/chemical evolution, Li plating/stripping dynamics and SEI dynamics were efficiently decoupled and Li ion behavior at interface between different solid-state electrolytes (SSE) was successfully detected. The innovative combining experiments of in situ atomic force microscopy and in situ X-ray photoelectron spectroscopy on Li metal anode revealed interfacial morphological/chemical evolution and decoupled Li plating/stripping process from SEI evolution. Though Li plating speed in Li10GeP2S12 (LGPS) was higher than Li3PS4 (LPS), speed of SSE decomposition was similar and ~85% interfacial SSE turned into SEI during plating and remained unchanged in stripping. To leverage strengths of different SSEs, an LPS-LGPS-LPS sandwich electrolyte was developed, demonstrating enhanced ionic conductivity and improved interfacial stability with less SSE decomposition (25%). Using in situ Kelvin Probe Force Microscopy, Li-ion behavior at interface between different SSEs was effectively visualized, uncovering distribution of Li ions at LGPS|LPS interface under different potentials.

3.
Nat Commun ; 15(1): 4792, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839760

ABSTRACT

Innate lymphoid cell precursors (ILCPs) develop into distinct subsets of innate lymphoid cells (ILCs) with specific functions. The epigenetic program underlying the differentiation of ILCPs into ILC subsets remains poorly understood. Here, we reveal the genome-wide distribution and dynamics of the DNA methylation and hydroxymethylation in ILC subsets and their respective precursors. Additionally, we find that the DNA hydroxymethyltransferase TET1 suppresses ILC1 but not ILC2 or ILC3 differentiation. TET1 deficiency promotes ILC1 differentiation by inhibiting TGF-ß signaling. Throughout ILCP differentiation at postnatal stage, gut microbiota contributes to the downregulation of TET1 level. Microbiota decreases the level of cholic acid in the gut, impairs TET1 expression and suppresses DNA hydroxymethylation, ultimately resulting in an expansion of ILC1s. In adult mice, TET1 suppresses the hyperactivation of ILC1s to maintain intestinal homeostasis. Our findings provide insights into the microbiota-mediated epigenetic programming of ILCs, which links microbiota-DNA methylation crosstalk to ILC differentiation.


Subject(s)
Cell Differentiation , DNA Methylation , DNA-Binding Proteins , Immunity, Innate , Lymphocytes , Proto-Oncogene Proteins , Animals , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Mice , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Lymphocytes/metabolism , Lymphocytes/immunology , Mice, Inbred C57BL , Gastrointestinal Microbiome , Epigenesis, Genetic , Mice, Knockout , Transforming Growth Factor beta/metabolism , Signal Transduction
4.
Article in English | MEDLINE | ID: mdl-38752961

ABSTRACT

BACKGROUND: The extravascular (EV) implantable cardioverter-defibrillator (ICD) includes features to address sensing and arrhythmia detection challenges presented by its substernal lead location. OBJECTIVES: In this study, the authors sought to evaluate sensing and detection performance in 299 patients discharged with an EV-ICD in the global pivotal study. METHODS: We reviewed and adjudicated all induced ventricular fibrillation (VF) episodes and spontaneous device-stored episodes that satisfied rate and duration criteria in a programmed ventricular tachycardia (VT)/VF therapy zone. RESULTS: At implantation, all EV-ICDs detected induced VF at the programmed sensitivity; 95.9% detected VF with a 3× safety margin. In follow-up, EV-ICDs detected all 59 VT/VF episodes that sustained until therapy. Of 1,034 non-VT/VF episodes, oversensing caused 87.9% and supraventricular tachycardia caused 12.1%. Therapy was withheld in 80.9%, aborted in 10.6%, and delivered in 8.5%. The most common causes of oversensing were myopotentials (61.2%) and P-wave oversensing (PWOS) (19.9%). Inappropriate shocks occurred in only 3.2% of myopotential episodes, but in 21.8% of PWOS episodes. Myopotential oversensing was more common with Ring-Can sensing (P < 0.0001) and correlated with low R-wave amplitude (P < 0.0001). PWOS occurred almost exclusively with Ring1-Ring2 sensing (P = 0.0001) and began with transient decrease in R-wave or increase in P-wave amplitude (P < 0.0001). In software emulation, a new PWOS discriminator significantly reduced total inappropriate detections. CONCLUSIONS: In a global population, EV-ICD detected induced and spontaneous VT/VF accurately. Although discriminators withheld detection from most non-VT/VF episodes, inappropriate shocks were common. The most common cause was PWOS, which may be reduced by optimizing sensing at implantation and incorporation of the PWOS discriminator, which is now in the current device. (Extravascular ICD Pivotal Study [EV ICD]; NCT04060680).

5.
J Cancer Res Ther ; 20(2): 540-546, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38687923

ABSTRACT

PURPOSE: To retrospectively study the therapeutic effect and safety performance of the combination strategies of the computed tomography (CT)-guided microwave ablation (MWA) and percutaneous vertebroplasty (PVP) as a treatment for painful non-small cell lung cancer (NSCLC) with spinal metastases. MATERIALS AND METHODS: A retrospective review included 71 patients with 109 vertebral metastases who underwent microwave ablation combined with percutaneous vertebroplasty by the image-guided and real-time temperature monitoring. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry Disability Index (ODI) scores before treatment and during the follow-up period. RESULTS: Technical success was achieved in all patients. The mean pre-procedure VAS score and morphine doses were 6.6 ± 1.8 (4-10) and 137.2 ± 38.7 (40-200) mg, respectively. The mean VAS scores and daily morphine doses at 24 h and 1, 4, 12, and 24 weeks postoperatively were 3.3 ± 1.9 and 73.5 ± 39.4 mg; 2.2 ± 1.5 and 40.2 ± 29.8 mg; 1.7 ± 1.2 and 31.3 ± 23.6 mg; 1.4 ± 1.1 and 27.3 ± 21.4 mg; and 1.3 ± 1.1 and 24.8 ± 21.0 mg, respectively (all P < 0.001). ODI scores significantly decreased (P < 0.05). Minor cement leakage occurred in 51 cases (46.8%), with one patient having a grade 3 neural injury. No local tumor progression was observed by follow-up imaging. CONCLUSIONS: MWA combined with PVP can significantly relieve pain and improve patients' quality of life, which implied this is an effective treatment option for painful NSCLC with spinal metastases. Additionally, its efficacy should be further verified through the mid- and long-term studies.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Microwaves , Spinal Neoplasms , Vertebroplasty , Humans , Male , Female , Vertebroplasty/methods , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/secondary , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Middle Aged , Microwaves/therapeutic use , Spinal Neoplasms/secondary , Spinal Neoplasms/therapy , Spinal Neoplasms/complications , Aged , Retrospective Studies , Treatment Outcome , Combined Modality Therapy/methods , Pain Measurement , Tomography, X-Ray Computed , Adult , Cancer Pain/etiology , Cancer Pain/therapy , Cancer Pain/diagnosis , Aged, 80 and over , Pain Management/methods , Follow-Up Studies
6.
Nature ; 628(8006): 145-153, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38538785

ABSTRACT

As hippocampal neurons respond to diverse types of information1, a subset assembles into microcircuits representing a memory2. Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage3-5. Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early events, some neurons acquired an inflammatory phenotype involving activation of TLR9 signalling and accumulation of centrosomal DNA damage repair complexes6. Neuron-specific knockdown of Tlr9 impaired memory while blunting contextual fear conditioning-induced changes of gene expression in specific clusters of excitatory CA1 neurons. Notably, TLR9 had an essential role in centrosome function, including DNA damage repair, ciliogenesis and build-up of perineuronal nets. We demonstrate a novel cascade of learning-induced molecular events in discrete neuronal clusters undergoing dsDNA damage and TLR9-mediated repair, resulting in their recruitment to memory circuits. With compromised TLR9 function, this fundamental memory mechanism becomes a gateway to genomic instability and cognitive impairments implicated in accelerated senescence, psychiatric disorders and neurodegenerative disorders. Maintaining the integrity of TLR9 inflammatory signalling thus emerges as a promising preventive strategy for neurocognitive deficits.


Subject(s)
CA1 Region, Hippocampal , DNA Breaks, Double-Stranded , DNA Repair , Inflammation , Memory , Toll-Like Receptor 9 , Animals , Female , Male , Mice , Aging/genetics , Aging/pathology , CA1 Region, Hippocampal/physiology , Centrosome/metabolism , Cognitive Dysfunction/genetics , Conditioning, Classical , Extracellular Matrix/metabolism , Fear , Genomic Instability/genetics , Histones/metabolism , Inflammation/genetics , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Memory/physiology , Mental Disorders/genetics , Neurodegenerative Diseases/genetics , Neuroinflammatory Diseases/genetics , Neurons/metabolism , Neurons/pathology , Nuclear Envelope/pathology , Toll-Like Receptor 9/deficiency , Toll-Like Receptor 9/genetics , Toll-Like Receptor 9/immunology , Toll-Like Receptor 9/metabolism
7.
Sci Adv ; 10(13): eadl4842, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38552028

ABSTRACT

The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi0.8Mn0.1Co0.1O2 with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).

8.
Front Pharmacol ; 15: 1329307, 2024.
Article in English | MEDLINE | ID: mdl-38318141

ABSTRACT

With the increasing prevalence of multidrug-resistant Gram-negative bacterial pathogens worldwide, antimicrobial resistance has become a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) exhibited excellent in vitro activity against many carbapenemase-producing pathogens, and was widely used for the treatment of various complicated infections. CAZ-AVI is well tolerated across all dosing regimens, and its associated acute kidney injury (AKI) in phase II/III clinical trials is rare. However, recent real-world studies have demonstrated that CAZ-AVI associated AKI was more frequent in real-world than in phase II and III clinical trials, particularly in patients receiving concomitant nephrotoxic agents, with critically ill patients being at a higher risk. Herein, we reviewed the safety data related to renal impairment of CAZ-AVI, and discussed its pharmacokinetic/pharmacodynamic targets and dosage adjustment in patients with impaired renal function. This review aimed to emphasize the importance for healthcare professionals to be aware of this adverse event of CAZ-AVI and provide practical insights into the dosage optimization in critically ill patients with renal dysfunction.

9.
Angew Chem Int Ed Engl ; 63(13): e202316837, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38315104

ABSTRACT

The interfacial processes, mainly the lithium (Li) plating/stripping and the evolution of the solid electrolyte interphase (SEI), are directly related to the performance of all-solid-state Li-metal batteries (ASSLBs). However, the complex processes at solid-solid interfaces are embedded under the solid-state electrolyte, making it challenging to analyze the dynamic processes in real time. Here, using in situ electrochemical atomic force microscopy and optical microscopy, we directly visualized the Li plating/stripping/replating behavior, and measured the morphological and mechanical properties of the on-site formed SEI at nanoscale. Li spheres plating/stripping/replating at the argyrodite solid electrolyte (Li6 PS5 Cl)/Li electrode interface is coupled with the formation/wrinkling/inflating of the SEI on its surface. Combined with in situ X-ray photoelectron spectroscopy, details of the stepwise formation and physicochemical properties of SEI on the Li spheres are obtained. It is shown that higher operation rates can decrease the uniformity of the Li+ -conducting networks in the SEI and worsen Li plating/stripping reversibility. By regulating the applied current rates, uniform nucleation and reversible plating/stripping processes can be achieved, leading to the extension of the cycling life. The in situ analysis of the on-site formed SEI at solid-solid interfaces provides the correlation between the interfacial evolution and the electrochemical performance in ASSLBs.

10.
BMC Psychol ; 12(1): 35, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38238861

ABSTRACT

BACKGROUND: One noteworthy concern within the realm of education is the level of engagement demonstrated by students. Among the factor that can have a crucial role in this domain is teacher support, especially emotional support which has an impact on several aspects of learners' education. Furthermore, various studies have investigated the relationship between Emotional Intelligence (EI) and learners' engagement. METHODS: Accordingly, this study investigated the possible role of trait EI and the emotional support of teachers and how these constructs may work to associate learners' engagement. For this objective, a total of 309 Chinese students across different colleges and universities in 5 provinces of Beijing, Shanghai, Jiangsu, Hubei, and Shaanxi were enrolled. They were 126 females and 183 males, with ages ranging from 18 to 30 years old (Mean = 24.6). RESULTS: The results of this research through running Structural Equation Modeling (SEM) demonstrated that teachers' emotional support and trait EI both can associate students' learning engagement. The final measurement model shows that about 73% of changes in learners' engagement can be associated by their trait EI and teachers' emotional support. CONCLUSIONS: This study underscores the importance of emotional support from teachers and the trait of EI in relation to students' engagement in learning. Both factors were shown to play a significant role in associating student engagement. Moreover, this study could potentially have wider impacts on members of academic teams.


Subject(s)
Counseling , Educational Personnel , Emotional Intelligence , Adolescent , Adult , Female , Humans , Male , Young Adult , China , East Asian People , Learning
11.
Lancet Infect Dis ; 24(1): 65-74, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37708908

ABSTRACT

BACKGROUND: The 2022 global outbreak of mpox (formerly known as monkeypox) spread primarily among gay, bisexual, and other men who have sex with men (GBMSM), with the initial cluster being identified in England in May, 2022. Understanding its epidemiological characteristics and the reasons for its downturn in July, 2022, will help to control future outbreaks. METHODS: We collated data for all diagnosed mpox cases (3621) from England from May 1, 2022, to Nov 16, 2022. Data from 75 individuals with mpox allowed estimation of the incubation period, while data from 121 case-contact pairs were used to estimate the serial interval. Six methods, including a structured dynamic compartmental transmission model, were used to estimate the basic reproduction number (R0). The structured model assumed all male individuals with mpox were GBMSM, who were then stratified into subgroups for those at low risk and high risk for mpox. This best fitting model was used to estimate the reduction in transmissibility, and the effective infectious period (before isolating), that resulted in the outbreak downturn, and the effect of vaccination initiated from June 27, 2022. Bayesian methods were used for parameter estimation and model calibration. FINDINGS: Most cases occurred in men (3544 of 3621, 97·9%). The median incubation period for mpox was 6·90 days (95% credible interval [CrI] 4·08-20·21), and the serial interval was 8·82 days (5·22-25·81). R0 estimates ranged from 1·41 to 2·17. The structured transmission model estimated that 83·8% of infections (95% CrI 83·5-85·3) resulted from sexual partnerships with GBMSM individuals at high risk of mpox. The outbreak downturn probably resulted from a 44·5% reduction in the sexual partner rate among all GBMSM (24·9-55·8) and 20·0% reduction in the effective infectious period (4·1-33·9), preventing 165 896 infections (115 584-217 730). Vaccination marginally increased the number of infections prevented (166 081, 115 745-217 947), but minimised a resurgence in cases from January, 2023, and could have averted four times more infections if initiated earlier. Our findings were sensitive to assumptions regarding the vaccine's effectiveness and the GBMSM subgroup at high risk of mpox. INTERPRETATION: The mpox outbreak in England probably resulted from high sexual partner rates among some GBMSM, with reductions in partner rates reversing the outbreak, and with vaccination minimising future outbreaks. FUNDING: National Institute for Health Research (UK).


Subject(s)
Mpox (monkeypox) , Sexual and Gender Minorities , Male , Humans , Bayes Theorem , Homosexuality, Male , Disease Outbreaks/prevention & control , England/epidemiology
12.
BMC Cancer ; 23(1): 1185, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38049741

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. METHODS: CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the 'least absolute shrinkage and selection operator' Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. RESULTS: Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. CONCLUSION: The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , T-Cell Exhaustion , Liver Neoplasms/genetics , Genes, cdc , Annexin A5 , CD8-Positive T-Lymphocytes , Prognosis , Mad2 Proteins
13.
Discov Oncol ; 14(1): 225, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38063927

ABSTRACT

OBJECTIVE: To investigate the effect of COVID-19 infection on pancreatic cancer. METHODS: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. RESULTS: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. CONCLUSION: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

14.
Nat Commun ; 14(1): 7247, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37945604

ABSTRACT

Micron-sized Si anode promises a much higher theoretical capacity than the traditional graphite anode and more attractive application prospect compared to its nanoscale counterpart. However, its severe volume expansion during lithiation requires solid electrolyte interphase (SEI) with reinforced mechanical stability. Here, we propose a solvent-induced selective dissolution strategy to in situ regulate the mechanical properties of SEI. By introducing a high-donor-number solvent, gamma-butyrolactone, into conventional electrolytes, low-modulus components of the SEI, such as Li alkyl carbonates, can be selectively dissolved upon cycling, leaving a robust SEI mainly consisting of lithium fluoride and polycarbonates. With this strategy, raw micron-sized Si anode retains 87.5% capacity after 100 cycles at 0.5 C (1500 mA g-1, 25°C), which can be improved to >300 cycles with carbon-coated micron-sized Si anode. Furthermore, the Si||LiNi0.8Co0.1Mn0.1O2 battery using the raw micron-sized Si anode with the selectively dissolved SEI retains 83.7% capacity after 150 cycles at 0.5 C (90 mA g-1). The selective dissolution effect for tailoring the SEI, as well as the corresponding cycling life of the Si anodes, is positively related to the donor number of the solvents, which highlights designing high-donor-number electrolytes as a guideline to tailor the SEI for stabilizing volume-changing alloying-type anodes in high-energy rechargeable batteries.

15.
Dev Cell ; 58(23): 2700-2717.e12, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-37963469

ABSTRACT

How dedifferentiated stem-like tumor cells evade immunosurveillance remains poorly understood. We show that the lineage-plasticity regulator SOX9, which is upregulated in dedifferentiated tumor cells, limits the number of infiltrating T lymphocytes in premalignant lesions of mouse basal-like breast cancer. SOX9-mediated immunosuppression is required for the progression of in situ tumors to invasive carcinoma. SOX9 induces the expression of immune checkpoint B7x/B7-H4 through STAT3 activation and direct transcriptional regulation. B7x is upregulated in dedifferentiated tumor cells and protects them from immunosurveillance. B7x also protects mammary gland regeneration in immunocompetent mice. In advanced tumors, B7x targeting inhibits tumor growth and overcomes resistance to anti-PD-L1 immunotherapy. In human breast cancer, SOX9 and B7x expression are correlated and associated with reduced CD8+ T cell infiltration. This study, using mouse models, cell lines, and patient samples, identifies a dedifferentiation-associated immunosuppression mechanism and demonstrates the therapeutic potential of targeting the SOX9-B7x pathway in basal-like breast cancer.


Subject(s)
Breast Neoplasms , Animals , Female , Humans , Mice , CD8-Positive T-Lymphocytes , Immunosuppression Therapy , SOX9 Transcription Factor , V-Set Domain-Containing T-Cell Activation Inhibitor 1/metabolism
16.
Article in English | MEDLINE | ID: mdl-37874752

ABSTRACT

Ionogels are increasingly used in flexible strain sensors, but it is still challenging to incorporate multifunctional properties such as flexibility, self-healing, adhesion, temperature resistance, and electrical conductivity. Herein, a facile and rapid one-step photoinitiated polymerization strategy is employed to prepare multifunctional ionogels by filling a hydrophobic and conductive ionic liquid into a flexible, hydrophobic fluoropolymer matrix. Thanks to the presence of abundant noncovalent interactions (hydrogen-bonding and ion-dipole interactions), the ionogels exhibit high transparency, excellent mechanical properties, self-healing ability, and adhesion. Moreover, rich C-F bonds in the fluoropolymer matrix can eliminate the interference of water molecules, resulting in excellent environmental tolerance such as high and low temperature resistance, waterproofness, and anticorrosion. Furthermore, the ionogel-based wearable strain sensor can sensitively detect and differentiate human movements and subtle muscle movements and serve as a Morse code signal transmitter for information transmission. The presented work provides an effective method to develop versatile flexible conductive ionogels for wearable devices and ionotronics.

17.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4237-4242, 2023 Aug.
Article in Chinese | MEDLINE | ID: mdl-37802792

ABSTRACT

This study aims to evaluate the effectiveness and economic efficiency of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of chronic rhinosinusitis(CRS). The randomized controlled trial(RCT) of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS was searched against EMbase, PubMed, Cochrane Library, CNKI, VIP, SinoMed, and Wanfang. The efficacy, nasal mucociliary transport time, and safety of the therapy above in the treatment of CRS were analyzed with single-group rate and Meta-analysis, and the economy and sensitivity were evaluated from the perspective of payer. A total of 9 RCTs were included, including 1 145 patients. Meta-analysis showed that compared with Triamcinolone Acetonide Nasal Spray alone, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS patients increased the effective rate(RR=1.17, 95%CI[1.11, 1.24], P<0.000 01) and shortened the nasal mucociliary transport time(MD=-3.32, 95%CI[-5.86,-0.78], P=0.01), there was no significant difference in the incidence of adverse reactions between the two groups. The incremental cost-effectiveness analysis showed that the treatment costs of the control group and the observation group were 44.15 yuan and 1 044.96 yuan, respectively. In the Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray treatment group, 75.48 yuan was spent to improve the effective rate of CRS by 1%. The one-way sensitivity analysis indicated the days of treatment, the RR of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray, the price of unit preparation of Biyuan Tongqiao Granules, and the effective rate of Triamcinolone Acetonide Nasal Spray alone had great influence on the incremental cost-effectiveness ratio. In conclusion, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray improves the therapeutic effect on CRS. The probabilistic sensitivity analysis showed that when the willingness to pay was greater than 7 920 yuan(less than 0.1 of GDP per capita 8 098 yuan), the combined therapy was economically superior to the control. Due to the limited number of articles published, it is necessary to carry out a real-world clinical trial of Biyuan Tongqiao Gra-nules and Triamcinolone Acetonide Nasal Spray in the treatment of CRS, so as to compare the cost-effectiveness of Biyuan Tongqiao Granules and Triamcinolone Acetonide Nasal Spray.


Subject(s)
Sinusitis , Triamcinolone Acetonide , Humans , Triamcinolone Acetonide/therapeutic use , Triamcinolone Acetonide/adverse effects , Nasal Sprays , Cost-Effectiveness Analysis , Sinusitis/drug therapy , Chronic Disease
18.
Funct Integr Genomics ; 23(4): 312, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37775648

ABSTRACT

Recent advances in immunotherapeutic approaches have the potential to bring new hope to the treatment of pancreatic cancer. The tumor microenvironment contributes significantly to tumor development and progression. In this study, miR-429 overexpression was found to inhibit proliferation, invasion, and clonogenicity while promoting apoptosis in HepG2 cells. Furthermore, co-culture of miR-429-overpressing or silenced HepG2 cells with PBMCs showed that miR-429 induced CD4+ and CD8+ T cell infiltration, decreased the numbers of Tregs, inhibited CD8+ T cell apoptosis and exhaustion, and enhanced CD8+ T cell functions in PBMCs. miR-429 was found to prevent an immunosuppressive HCC microenvironment by targeting and suppressing PD-L1. In a C57BL/6 mouse subcutaneous xenograft tumor model, overexpression of miR-429 reduced tumorigenesis and both tumor volumes and weights were decreased relative to controls. In addition, CD4+ and CD8+ T cells were increased, Tregs were reduced, and CD8+ T cell apoptosis and depletion were reduced in the tumor tissues induced by miR-429-overexpressing HepG2 cells.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Animals , Humans , Mice , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Liver Neoplasms/genetics , Liver Neoplasms/drug therapy , Mice, Inbred C57BL , MicroRNAs/genetics , Tumor Microenvironment
19.
Front Oncol ; 13: 1206043, 2023.
Article in English | MEDLINE | ID: mdl-37664040

ABSTRACT

Cancer secondary to dermatomyositis (DM) is defined as paraneoplastic dermatomyositis, which is one of the major subtypes of DM. However, cases of DM with intrahepatic cholangiocarcinoma (ICC) are rarely reported. In the course of our clinical work, we encountered a case of a middle-aged female patient who was diagnosed with DM for 7 years and then diagnosed with ICC, and we would like to share this case. In addition, in order to further investigate the deeper mechanism of ICC associated with DM, we also analyzed the dataset related to DM and ICC in the Gene Expression Omnibus (GEO) database based on the machine learning methods and found that poly(ADP-ribose) polymerase family member 12 (PARP12) and metallothionein 1M (MT1M) were closely associated with ICC secondary to DM. They are potentially important biomarkers for predicting the occurrence of ICC in patients with DM.

20.
Elife ; 122023 09 04.
Article in English | MEDLINE | ID: mdl-37665325

ABSTRACT

The telencephalon and eye in mammals are originated from adjacent fields at the anterior neural plate. Morphogenesis of these fields generates telencephalon, optic-stalk, optic-disc, and neuroretina along a spatial axis. How these telencephalic and ocular tissues are specified coordinately to ensure directional retinal ganglion cell (RGC) axon growth is unclear. Here, we report self-formation of human telencephalon-eye organoids comprising concentric zones of telencephalic, optic-stalk, optic-disc, and neuroretinal tissues along the center-periphery axis. Initially-differentiated RGCs grew axons towards and then along a path defined by adjacent PAX2+ VSX2+ optic-disc cells. Single-cell RNA sequencing of these organoids not only confirmed telencephalic and ocular identities but also identified expression signatures of early optic-disc, optic-stalk, and RGCs. These signatures were similar to those in human fetal retinas. Optic-disc cells in these organoids differentially expressed FGF8 and FGF9; FGFR inhibitions drastically decreased early RGC differentiation and directional axon growth. Through the RGC-specific cell-surface marker CNTN2 identified here, electrophysiologically excitable RGCs were isolated under a native condition. Our findings provide insight into the coordinated specification of early telencephalic and ocular tissues in humans and establish resources for studying RGC-related diseases such as glaucoma.


Subject(s)
Glaucoma , Retinal Ganglion Cells , Animals , Humans , Retina , Axons , Telencephalon , Mammals
SELECTION OF CITATIONS
SEARCH DETAIL
...