Unravelling the metabolic landscape of cutaneous melanoma: Insights from single-cell sequencing analysis and machine learning for prognostic assessment of lactate metabolism.

This manuscript presents a comprehensive investigation into the role of lactate metabolism-related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk-transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the 'AUCell' package. Weighted Co-expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high-risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high-risk SKCM patients. NDUFS7 was found to be a hub gene in the protein-protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK-8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism-related genes in SKCM.

Peripheral blood eosinophils: an important reference for radiologists to distinguish between pulmonary paragonimiasis and tuberculous pleurisy in children.

OBJECTIVE: In this study, we examined the value of chest CT signs combined with peripheral blood eosinophil percentage in differentiating between pulmonary paragonimiasis and tuberculous pleurisy in children. METHODS: Patients with pulmonary paragonimiasis and tuberculous pleurisy were retrospectively enrolled from January 2019 to April 2023 at the Kunming Third People's Hospital and Lincang People's Hospital. There were 69 patients with pulmonary paragonimiasis (paragonimiasis group) and 89 patients with tuberculous pleurisy (tuberculosis group). Clinical symptoms, chest CT imaging findings, and laboratory test results were analyzed. Using binary logistic regression, an imaging model of CT signs and a combined model of CT signs and eosinophils were developed to calculate and compare the differential diagnostic performance of the two models. RESULTS: CT signs were used to establish the imaging model, and the receiver operating characteristic (ROC) curve was plotted. The area under the curve (AUC) was 0.856 (95% CI: 0.799-0.913), the sensitivity was 66.7%, and the specificity was 88.9%. The combined model was established using the CT signs and eosinophil percentage, and the ROC was plotted. The AUC curve was 0.950 (95% CI: 0.919-0.980), the sensitivity was 89.9%, and the specificity was 90.1%. The differential diagnostic efficiency of the combined model was higher than that of the imaging model, and the difference in AUC was statistically significant. CONCLUSION: The combined model has a higher differential diagnosis efficiency than the imaging model in the differentiation of pulmonary paragonimiasis and tuberculous pleurisy in children. The presence of a tunnel sign on chest CT, the absence of pulmonary nodules, and an elevated percentage of peripheral blood eosinophils are indicative of pulmonary paragonimiasis in children.

Critical Secondary Metabolites Confer the Broad-Spectrum Pathogenic Fungi Resistance Property of a Marine-Originating Streptomyces sp. HNBCa1.

Obtaining a microorganism strain with a broad-spectrum resistance property and highly efficient antifungal activity is important to the biocontrol strategy. Herein, a marine Streptomyces sp. HNBCa1 demonstrated a broad-spectrum resistance to 17 tested crop pathogenic fungi and exhibited a high biocontrol efficiency against mango anthracnose and banana fusarium wilt. To uncover the critical bioactive secondary metabolites basis, genome assembly and annotation, metabolomic analysis, and a semipreparative HPLC-based activity-guide method were employed. Finally, geldanamycin and ectoine involved in codifferential secondary metabolites were also found to be related to biosynthetic gene clusters in the genome of HNBCa1. Reblastatin and geldanamycin were uncovered in response to broad-spectrum resistance to the 17 crop pathogenic fungi. Our results suggested that reblastatin and geldanamycin were critical to maintaining the broad-spectrum resistance property and highly efficient antifungal activity of HNBCa1, which could be further developed as a biological control agent to control crop fungal diseases.

Finely manipulating room temperature phosphorescence by dynamic lanthanide coordination toward multi-level information security.

Room temperature phosphorescence materials have garnered significant attention due to their unique optical properties and promising applications. However, it remains a great challenge to finely manipulate phosphorescent properties to achieve desirable phosphorescent performance on demand. Here, we show a feasible strategy to finely manipulate organic phosphorescent performance by introducing dynamic lanthanide coordination. The organic phosphors of terpyridine phenylboronic acids possessing excellent coordination ability are covalently embedded into a polyvinyl alcohol matrix, leading to ultralong organic room temperature phosphorescence with a lifetime of up to 0.629 s. Notably, such phosphorescent performance, including intensity and lifetime, can be well controlled by varying the lanthanide dopant. Relying on the excellent modulable performance of these lanthanide-manipulated phosphorescence films, multi-level information encryption including attacker-misleading and spatial-time-resolved applications is successfully demonstrated with greatly improved security level. This work opens an avenue for finely manipulating phosphorescent properties to meet versatile uses in optical applications.

Deciphering cutaneous melanoma prognosis through LDL metabolism: Single-cell transcriptomics analysis via 101 machine learning algorithms.

Cutaneous melanoma poses a formidable challenge within the field of oncology, marked by its aggressive nature and capacity for metastasis. Despite extensive research uncovering numerous genetic and molecular contributors to cutaneous melanoma development, there remains a critical knowledge gap concerning the role of lipids, notably low-density lipoprotein (LDL), in this lethal skin cancer. This article endeavours to bridge this knowledge gap by delving into the intricate interplay between LDL metabolism and cutaneous melanoma, shedding light on how lipids influence tumour progression, immune responses and potential therapeutic avenues. Genes associated with LDL metabolism were extracted from the GSEA database. We acquired and analysed single-cell sequencing data (GSE215120) and bulk-RNA sequencing data, including the TCGA data set, GSE19234, GSE22153 and GSE65904. Our analysis unveiled the heterogeneity of LDL across various cell types at the single-cell sequencing level. Additionally, we constructed an LDL-related signature (LRS) using machine learning algorithms, incorporating differentially expressed genes and highly correlated genes. The LRS serves as a valuable tool for assessing the prognosis, immunity and mutation status of patients with cutaneous melanoma. Furthermore, we conducted experiments on A375 and WM-115 cells to validate the function of PPP2R1A, a pivotal gene within the LRS. Our comprehensive approach, combining advanced bioinformatics analyses with an extensive review of current literature, presents compelling evidence regarding the significance of LDL within the cutaneous melanoma microenvironment.

Dietary tryptophan improves growth and intestinal health by promoting the secretion of intestinal ß-defensins against enterotoxigenic Escherichia coli F4 in weaned piglets.

Adequate dietary L-tryptophan (Trp) governs intestinal homeostasis in piglets. However, the defensive role of Trp in the diet against enterotoxigenic Escherichia coli F4 (K88) in pigs is still poorly understood. Here, sixty (6.15 ± 1.52 kg, 24-day-old, Duroc × Landrace × Yorkshire) weaned piglets were used for an E. coli F4 attack test in a 2 × 2 factorial design. The growth (ADG, ADFI, GH), immune factors (IL-10, IgA, IgG, IgM), Trp metabolite 5-HT, intestinal morphology (jejunal and colonic VH), mRNA expression of ß-defensins (jejunal BD-127, BD-119, ileal BD-1, BD-127), and abundance of beneficial microorganisms in the colon (Prevotella 9, Lactobacillus, Phascolarctobacterium, Faecalibacterium) were higher in the piglets in the HT (High Trp) and HTK (High Trp, K88) groups than in the LT (Low Trp) and LTK (Low Trp, K88) groups (P<.05), while FCR, diarrhea rate, diarrhea index, serum Trp, Kyn, IDO, D-LA, ET, and abundance of harmful microorganisms in the colon (Spirochaetes, Fusobacteria, Prevotella, Christensenellaceae R7) were lower in the HT and HTK groups than in the LT and LTK groups (P<.05). High Trp reduced the expression of virulence genes (K88 and LT) after E. coli F4 attack (P<.05). The IL-6, TNF-α was lower in the HTK group than in the LT, LTK group (P<.05). In short, a diet containing 0.35% Trp protected piglets from enterotoxigenic E. coli F4 (K88) via Trp metabolism promoting BD expression in the intestinal mucosa, which improved growth and intestinal health.

The Impact of Sleep Quality on Cognitive Function in Patients with Chronic Subjective Tinnitus.

BACKGROUND: The aim of this study was to explore the impact of sleep quality on cognitive function in patients with chronic subjective tinnitus. METHODS: The Pittsburgh Sleep Quality Index (PSQI) and the Montreal Cognitive Assessment Scale (MoCA) were used to assess sleep quality and cognitive function in patients with chronic subjective tinnitus, sleep disorder patients (SD), and normal controls (NC). The tinnitus evaluation questionnaire (TEQ) and tinnitus loudness were used to assess the severity in patients with chronic subjective tinnitus. Tinnitus patients were divided into two groups based on PSQI results: "tinnitus with sleep disorder (TwSD)" and "tinnitus without sleep disorder (TnSD)." The MoCA scores in TwSD and TnSD groups were compared with those in SD and NC groups, and the correlation between PSQI, TEQ, tinnitus loudness, and MoCA scores in subjective tinnitus patients were analyzed. RESULTS: Whether TwSD group or TnSD group, the MoCA score was significantly lower than those in the NC group and SD group. Meanwhile, there was no significant difference between TwSD and TnSD groups in MoCA score, and PSQI, TEQ, and tinnitus loudness were not significantly correlated with MoCA. CONCLUSION: Subjective tinnitus may be an independent risk factor for cognitive impairment. The underlying neural mechanisms between subjective tinnitus, sleep disorders, and cognitive impairment need to be further explored and clarified.

Cation/Anion-Dual regulation in Na3MnTi(PO4)3 cathode achieves the enhanced electrochemical properties of Sodium-Ion batteries.

Na3MnTi(PO4)3 (NMTP) emerges as a promising cathode material with high-performance for sodium-ion batteries (SIBs). Nevertheless, its development has been limited by several challenges, including poor electronic conductivity, the Mn3+ Jahn-Teller effect, and the presence of a Na+/Mn2+ cation mixture. To address these issues, we have developed a cation/anion-dual regulation strategy to activate the redox reactions involving manganese, thereby significantly enhancing the performance of NMTP. This strategy simultaneously enhances the structural dynamics and facilitates rapid ion transport at high rates by inducing the formation of sodium vacancy. The combined effects of these modifications lead to a substantial improvement in specific capacity (79.1 mAh/g), outstanding high-rate capabilities (35.9 mAh/g at 10C), and an ultralong cycle life (only 0.040 % capacity attenuation per cycle over 250 cycles at 1C for Na3.34Mn1.2Ti0.8(PO3.98F0.02)3) when used as a cathode material in SIBs. Furthermore, its performance in full cell demonstrates impressive rate capability (44.4 mAh/g at 5C) and exceptional cycling stability (with only 0.116 % capacity decay per cycle after 150 cycles at 1C), suggesting its potential for practical applications. This work presents a dual regulation strategy targeting different sites, offering a significant advancement in the development of NASICON phosphate cathodes for SIBs.

Roles of mechanosensitive ion channel PIEZO1 in the pathogenesis of brain injury after experimental intracerebral hemorrhage.

Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but the underlying mechanisms remain less known. The involvement of Piezo1 in brain injury after ICH was studied in a mouse model of ICH. ICH was established by injecting autologous arterial blood into the basal ganglia in mice. After vehicle, Piezo1 blocker, GsMTx4, Piezo1 activator, Yoda-1, or together with mannitol (tail vein injection) was injected into the left lateral ventricle of mouse brain, Piezo1 level and the roles of Piezo1 in neuronal injury, brain edema, and neurological dysfunctions after ICH were determined by the various indicated methods. Piezo1 protein level in neurons was significantly upregulated 24 h after ICH in vivo (human and mice). Piezo1 protein level was also dramatically upregulated in HT22 cells (a murine neuron cell line) cultured in vitro 24 h after hemin treatment as an in vitro ICH model. GsMTx4 treatment or together with mannitol significantly downregulated Piezo1 and AQP4 levels, markedly increased Bcl2 level, maintained more neurons alive, considerably restored brain blood flow, remarkably relieved brain edema, substantially decreased serum IL-6 level, and almost fully reversed the neurological dysfunctions at ICH 24 h group mice. In contrast, Yoda-1 treatment achieved the opposite effects. In conclusion, Piezo1 plays a crucial role in the pathogenesis of brain injury after ICH and may be a target for clinical treatment of ICH.

Reversibly Cross-Linked Isoporous Membranes Fabricated by the Recyclable Block Copolymer with Pendent Dithiolane Groups.

The reversible formation and cleavage of disulfide bonds under physical/chemical stimuli make it a valuable motif in constructing dynamically cross-linked materials. In the present work, the block copolymer bearing pendent dithiolanes was synthesized and fabricated into isoporous membranes by the combination of self-assembly and nonsolvent-induced phase separation strategy. The cross-linking within the membrane was realized by the thiol-initiated ring-opening cascades of cyclic disulfides. Successful formation of disulfide bond networks within the isoporous membranes was proved by the Raman spectra, UV-vis diffuse reflectance spectroscopy, differential scanning calorimetry, and rheological analysis. The cross-linking in membranes was further demonstrated by the notably improved toughness and obviously enhanced swelling resistance to acid/alkaline solution as well as organic solvents. Importantly, the cross-linked isoporous membranes were fully dissolvable in solution containing dithiothreitol, which enabled the complete cleavage of disulfide bonds and successful recovery of the block copolymer that was able to be repeatedly fabricated into isoporous membranes with pore sizes identical to membranes prepared from the freshly synthesized copolymer. Our results indicate that dynamically cross-linked isoporous membranes with improved durability and good recyclability can be custom-made by simply incorporating active dithiolane moieties into self-assembling block copolymers.

Predictive value of placental real-time shear wave elastography combined with 3-dimensional power Doppler index for preeclampsia.

This study aimed to investigate the value of placental real-time shear wave elastography combined with three-dimensional power Doppler index (3D-PDI) in the prediction of preeclampsia. We conducted a retrospective study selecting 60 pregnant women diagnosed with preeclampsia as the experimental group and 60 normal pregnant women as the control group from January 2021 to December 2022. The elastic modulus values of different regions of the placenta and placental 3D-PDI were detected and compared between the two groups. The ROC curve was used to evaluate the diagnostic value of each parameter, alone or in combination, for preeclampsia. The study findings demonstrated that the elastic modulus values of different regions of the placenta and 3D-PDI of the two groups have statistical significance. The values of SWE, VI, FI, and VFI are different in prediction of preeclampsia, and the combination of various parameters can improve the prediction value. Overall, our study provides a valuable method for the prediction of preeclampsia with the advantages of non-invasiveness, efficiency, and simplicity.

TREM2 Alleviates Subarachnoid Hemorrhage-Induced Brain Injury through Attenuating Neuroinflammation and Programmed Cell Death in Vivo and in Vitro.

BACKGROUND: Apoptosis and pyroptosis are two types of programmed cell death related to the neuroinflammatory reaction after subarachnoid hemorrhage (SAH). Research indicates that triggering receptor expressed on myeloid cells 2 (TREM2) can regulate the SAH-induced inflammatory response. However, whether TREM2 regulates programmed cell death (apoptosis and pyroptosis) remains to be clarified. The purpose of the present study was to investigate the effects of TREM2 on cell death in SAH. METHODS: SAH was induced in adult male C57BL/6J mice by endovascular perforation. An in-vitro cellular model of SAH was established by treating cocultured BV2 microglia and HT22 neuronal cells with oxyhemoglobin. TREM2 overexpression or knockdown was carried out by intraventricular lentivirus injection at 7 d before SAH induction in mice or lentiviral transfection, respectively. Neurobehavioral tests as well as western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, Evans blue (EB) staining, Nissl staining, and flow cytometry assays were performed to investigate the neuroprotective role of TREM2 after SAH. RESULTS: After SAH, the TREM2 mRNA and protein levels were elevated in SAH mice, exhibiting a peak at 72 h. TREM2 overexpression improved the SAH-induced neurological deficits in mice, while TREM2 knockdown worsened them. In the brains of mice with TREM2 overexpression, less neuronal death and more neuronal survival were detected at 72 h post SAH. Meanwhile, TREM2 overexpression showed an inhibitory effect on microglial activation, neutrophil infiltration, and the expression of cell death marker proteins. Consistent results were obtained in vitro. CONCLUSIONS: Our research indicates the important role of TREM2 on cell death after SAH, suggesting that targeting TREM2 might be an effective approach for treating SAH.

Targeting Compact and Ordered Emitters by Supramolecular Dynamic Interactions for High-performance Organic Ambient Phosphorescence.

Purely organic room-temperature phosphorescence (RTP) materials have received intense attention due to their fascinating optical properties and advanced optoelectronic applications. The promotion of intersystem crossing (ISC) and minimalization of nonradiative dissipation under ambient conditions are key prerequisites for realizing high-performance organic RTP; However, the ISC process is generally inefficient for organic fluorogens and the populated triplet excitons are always too susceptible to be well stabilized by conventional means. Particularly, organizing organic fluorophores into compact and ordered entities by supramolecular dynamic interactions has proven to be a newly-emerged strategy to boost the ISC process greatly and suppress the non-radiative relaxations immensely, facilitating the population and stabilization of triplet excitons to access high-performance organic RTP. Consequently, well-defined organic emitters enable robust RTP emission even in the solution state, thus greatly extending the applications. Here, this review is focused on a timely and brief introduction to recent progress in tailoring ordered high-performance RTP emitters by supramolecular dynamic interactions. Their typical preparation strategies, optoelectronic properties, and applications are thoroughly summarized. In the summary section, key challenges and perspectives of this field are highlighted to suggest potential directions for future study.

Species identification through deep learning and geometrical morphology in oaks (Quercus spp.): Pros and cons.

Plant phenotypic characteristics, especially leaf morphology of leaves, are an important indicator for species identification. However, leaf shape can be extraordinarily complex in some species, such as oaks. The great variation in leaf morphology and difficulty of species identification in oaks have attracted the attention of scientists since Charles Darwin. Recent advances in discrimination technology have provided opportunities to understand leaf morphology variation in oaks. Here, we aimed to compare the accuracy and efficiency of species identification in two closely related deciduous oaks by geometric morphometric method (GMM) and deep learning using preliminary identification of simple sequence repeats (nSSRs) as a prior. A total of 538 Asian deciduous oak trees, 16 Q. aliena and 23 Q. dentata populations, were firstly assigned by nSSRs Bayesian clustering analysis to one of the two species or admixture and this grouping served as a priori identification of these trees. Then we analyzed the shapes of 2328 leaves from the 538 trees in terms of 13 characters (landmarks) by GMM. Finally, we trained and classified 2221 leaf-scanned images with Xception architecture using deep learning. The two species can be identified by GMM and deep learning using genetic analysis as a priori. Deep learning is the most cost-efficient method in terms of time-consuming, while GMM can confirm the admixture individuals' leaf shape. These various methods provide high classification accuracy, highlight the application in plant classification research, and are ready to be applied to other morphology analysis.

SECTM1 promotes the development of glioblastoma and mesenchymal transition by regulating the TGFß1/Smad signaling pathway.

Objective: Secreted and transmembrane protein 1 (SECTM1) is a gene encoding a transmembrane protein. The role of SECTM1 in glioblastoma (GBM) is unclear. Here, we reported the abnormal expression of SECTM1 in GBM for the first time and studied the role and mechanism of SECTM1 in GBM. Methods: qRT-PCR, Western blotting and immunofluorescence were used to detect the expression of SECTM1 in gliomas of different grades and GBM cell lines. After the knockdown of SECTM1 expression in cell lines by shRNA, the effect of SECTM1 in GBM cell lines was verified by CCK-8, Transwell, EdU and wound healing experiments. We further investigated the effect and mechanism of SECTM1 on GBM in vitro and in vivo. The effect of SECTM1 on glioma growth was detected by subcutaneous tumor xenografts in nude mice in vivo. Results: The results showed that the knockdown of SECTM1 expression in cell lines significantly inhibited the proliferation, migration and invasion of GBM cells while inhibiting the progression of subcutaneous xenograft tumors in nude mice. However, the role and molecular mechanism of SECTM1 in GBM remain unclear. SECTM1 was found to promote GBM epithelial-mesenchymal transition (EMT) like processes. Bioinformatics analysis and Western blotting showed that SECTM1 regulates glioblastoma invasion and EMT-like processes mainly through the TGFß1/Smad signaling pathway. Conclusion: The low expression of SECTM1 has an inhibitory effect on GBM and is a potential target for GBM treatment. SECTM1 may also be a promising biomarker for the diagnosis and prognosis of GBM.

PANoptosis-related signature in melanoma: Transcriptomic mapping and clinical prognostication.

Programmed cell death plays a pivotal role in maintaining tissue homeostasis, and recent advancements in cell biology have uncovered PANoptosis-a novel paradigm integrating pyroptosis, apoptosis, and necroptosis. This study investigates the implications of PANoptosis in melanoma, a formidable skin cancer known for its metastatic potential and resistance to conventional therapies. Leveraging bulk and single-cell transcriptome analyses, machine learning modeling, and immune correlation assessments, we unveil the molecular intricacies of PANoptosis in melanoma. Single-cell sequencing identifies diverse cell types involved in PANoptosis, while bulk transcriptome analysis reveals key gene sets correlated with PANoptosis. Machine learning algorithms construct a robust prognostic model, demonstrating consistent predictive power across diverse cohorts. Patients with different cohorts can be divided into high-risk and low-risk groups according to this PANoptosis score, with the high-risk group having a significantly worse prognosis. Immune correlation analyses unveil a link between PANoptosis and immunotherapy response, with potential therapeutic implications. Mutation analysis and enrichment studies provide insights into the mutational landscape associated with PANoptosis. Finally, we used cell experiments to verify the expression and function of key gene PARVA, showing that PARVA was highly expressed in melanoma cell lines, and after PARVA is knocked down, cell invasion, migration, and colony formation ability were significantly decreased. This study advances our understanding of PANoptosis in melanoma, offering a comprehensive framework for targeted therapeutic interventions and personalized medicine strategies in combating this aggressive malignancy.

Detection of botulinum neurotoxin A (BoNT/A) enzymatic activity by pregnancy test strips based on hCG-modified magnetic nanoparticles.

The detection of botulinum neurotoxin A (BoNT/A) endopeptidase activity by pregnancy test paper based on human chorionic gonadotropin (hCG)-functionalized peptide-modified magnetic nanoparticles (MNs) is described for the first time. HCG-functionalized SNAP-25 peptide substrate with hydrolysis recognition sites was optimally designed. HCG can be recognized by pregnancy test strips. BoNT/A light chain (BoNT-LcA) is the central part of the endopeptidase function in holotoxin, which can specifically hydrolyze SNAP-25 peptide to release the hCG-peptide probe, and the hCG-peptide probe released can be quantitatively detected by pregnancy test strips, achieving indirect determination of BoNT/A. By quantifying the T-line color intensity of test strips, the visual detection limit for BoNT-LcA is 12.5 pg/mL, and the linear range of detection for BoNT-LcA and BoNT/A holotoxin was 100 pg/mL to 1 ng/mL and 25 to 250 ng/mL. The ability of the method to quantify BoNT/A was validated in human serum samples. This method shows the potential for sensitive detecting BoNT/A and has prospects for the diagnosis and prognosis of clinical botulism.

Case-controlled study of tuberculosis in in-vitro fertilisation-embryo transfer and natural pregnancy.

OBJECTIVE: To improve the understanding of the clinical features and imaging characteristics of pregnant women with and without in-vitro fertilisation-embryo transfer combined with pulmonary tuberculosis (TB). METHODS: A retrospective analysis was conducted involving 50 patients with pregnancy who had pulmonary TB and were admitted to the Third People's Hospital of Kunming (China) between 1 January 2017 and 31 December 2021. These patients were divided into an in-vitro fertilisation and embryo transfer (IVF-ET) conception group and a natural conception group according to the conception method. The clinical and imaging data were then collected and compared. RESULTS: The mean age of the IVF-ET group (n = 13, 31.85 ± 5.84 years) was higher than in the natural conception group (n = 37, 27.05 ± 5.5 years). The proportions of fever, haematogenous TB and extrapulmonary TB in the IVF-ET group (92.31%, 84.62% and 76.92%, respectively) were higher than those in the natural conception group (40.54%,16.22%,27.03%,respectively). The percentage of patients with pregnancy who had intracranial TB (76.9%) in the IVF-ET group was higher than in the natural conception group (10.8%). The percentage of pregnancy terminations in the IVF-ET conception group (84.62%) was higher than in the natural conception group (48.65%). All the above results had statistically significant differences (p < 0.05). CONCLUSION: Overall, IVF-ET conception combined with extensive pulmonary TB lesions lead to heavy systemic toxic symptoms, severe disease and poor pregnancy outcomes. Therefore, screening for TB prior to performing IVF-ET is recommended.

3D-printing of biomass furan-based polyesters with robust mechanical performance and shape memory property.

3D-printing provides a feasible technique for realizing new materials into structural and intelligent parts. In this work, biomass furan-based polyesters poly (ethylene furanoate) (PEF), poly (trimethylene furanoate) (PTF), and poly (butylene furanoate) (PBF) were successfully synthesized in a 5 L reactor through the melt polycondensation process and fabricated into 3D-printing feedstocks. It was demonstrated that the three furan-based polyesters were additively-manufactured into complicated structures. Besides, the mechanical and thermal properties of furan-based polyesters could be tailored by the chain length of diol monomer. The mechanical performance of 3D-printed PEF, PTF and PBF were characterized and compared with commercial filaments. The tensile strength of PEF and PTF could reach 74.6 and 63.8 MPa respectively, which exhibited superior tensile property to poly(ether-ether-ketone) (PEEK), polyamide (PA) and polylactic acid (PLA). Meanwhile, the compression results demonstrated that the PEF and PTF possessed comparable energy absorption capacity with PEEK and PLA respectively, which indicated excellent mechanical properties of furan-based polyesters. It was interesting to find that the 3D-printed structures including solid cube, bionic flower and lattice structures were employed to prove that the PTF possessed excellent shape memory properties. Therefore, the proposed biomass furan-based polymers would offer more freedom in the field of 3D-printing.

Hollow Cu2MoS4 nanoparticles loaded with immune checkpoint inhibitors reshape the tumor microenvironment to enhance immunotherapy for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to single-drug immunotherapy with PD-L1 (CD274) inhibitors. Here, we prepared mesoporous nanomaterials Cu2MoS4 (CMS)/PEG loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. In vitro experiments, CMS/PEG-B-P have a more substantial inhibitory effect on the expression of PD-L1 and CXCR4 as well as to promote the apoptosis of pancreatic cancer cells KPC and suppressed KPC cell proliferation were detected by flow cytometry, qPCR and Western blotting (WB). Promotes the release of the cytotoxic substance reactive oxygen species (ROS) and the production of the immunogenic cell death (ICD) marker calreticulin (CRT) in KPC cells. CMS/PEG-B-P was also detected to have a certain activating effect on mouse immune cells, dendritic cells (mDC) and macrophage RAW264.7. Subcutaneous tumorigenicity experiments in C57BL/6 mice verified that CMS/PEG-B-P had an inhibitory effect on the growth of tumors and remodeling of the tumor immune microenvironment, including infiltration of CD4+ and CD8+ T cells and polarization of macrophages, as well as reduction of immunosuppressive cells. Meanwhile, CMS/PEG-B-P was found to have different effects on the release of cytokines in the tumor immune microenvironment, including The levels of immunostimulatory cytokines INF-γ and IL-12 are increased and the levels of immunosuppressive cytokines IL-6, IL-10 and IFN-α are decreased. In conclusion, nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach. STATEMENT OF SIGNIFICANCE: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that has a low response to single-drug immunotherapy with PD-L1 (CD274) inhibitors. We preared PEG-modified mesoporous nanomaterials Cu2MoS4 (CMS) loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. Our study demonstrated that Nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach.