Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma.

Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) patients receiving targeted therapy. However, the mechanism that causes cetuximab resistance, especially microRNA (miRNA) regulation, remains unclear. Growing evidence suggests that miRNAs may act as "nuclear activating miRNAs" for targeting promoter regions or enhancers related to target genes. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, quantitative real-time polymerase chain reaction (qRT‒PCR) and fluorescence in situ hybridization (FISH) results provided compelling evidence of miR-451a nuclear enrichment in response to cetuximab treatment. Chromatin isolation via RNA purification, microarray analysis, and bioinformatic analysis revealed that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It has also been demonstrated that the activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Logistic regression analyses of 87 HNSCC samples indicated the significance of miR-451a and KDM7A in the development of cetuximab resistance. These discoveries support the potential of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear-activating miRNAs.

Magnetic-Field Response and Giant Electric-Field Modulation of Cu2S.

Cu2S likely plays an important role in the sharp resistivity transition of LK-99. Nevertheless, this immediately arouses an intriguing question of whether the extraordinary room-temperature colossal magnetoresistance in the initial reports, which has been less focused, originates from Cu2S as well. To resolve this issue, we have systematically investigated the electrical transport and magnetotransport properties of near-stoichiometric Cu2S pellets and thin films. Neither Cu2S nor LK-99 containing Cu2S in this study was found to exhibit the remarkable magnetoresistance effect implied by Lee et al. This implies that Cu2S could not account for all of the intriguing transport properties of the initially reported LK-99, and the initially reported LK-99 samples might contain magnetic impurities. Moreover, based on the crystal-structure-sensitive electrical properties of Cu2S, we have constructed a piezoelectric-strain-controlled device and obtained a giant and reversible resistance modulation of 2 orders of magnitude at room temperature, yielding a huge gauge factor of 160,000.

Altered epitopes enhance macrophage-mediated anti-tumour immunity to low-immunogenic tumour mutations.

Personalized neoantigen therapy has shown long-term and stable efficacy in specific patient populations. However, not all patients have sufficient levels of neoantigens for treatment. Although somatic mutations are commonly found in tumours, a significant portion of these mutations do not trigger an immune response. Patients with low mutation burdens continue to exhibit unresponsiveness to this treatment. We propose a design paradigm for neoantigen vaccines by utilizing the highly immunogenic unnatural amino acid p-nitrophenylalanine (pNO2Phe) for sequence alteration of somatic mutations that failed to generate neoepitopes. This enhances the immunogenicity of the mutations and transforms it into a suitable candidate for immunotherapy. The nitrated altered epitope vaccines designed according to this paradigm is capable of activating circulating CD8+ T cells and inducing immune cross-reactivity against autologous mutated epitopes in different MHC backgrounds (H-2Kb, H-2Kd, and human HLA-A02:01), leading to the elimination of tumour cells carrying the mutation. After immunization with the altered epitopes, tumour growth was significantly inhibited. It is noteworthy that nitrated epitopes induce tumour-infiltrating macrophages to differentiate into the M1 phenotype, surprisingly enhancing the MHC II molecule presenting pathway of macrophages. Nitrated epitope-treated macrophages have the potential to cross-activate CD4+ and CD8+ T cells, which may explain why pNO2Phe can enhance the immunogenicity of epitopes. Meanwhile, the immunosuppressive microenvironment of the tumour is altered due to the activation of macrophages. The nitrated neoantigen vaccine strategy enables the design of vaccines targeting non-immunogenic tumour mutations, expanding the pool of potential peptides for personalized and shared novel antigen therapy. This approach provides treatment opportunities for patients previously ineligible for new antigen vaccine therapy.

A soybean bZIP transcription factor is involved in submergence resistance.

Although the functions of basic leucine zipper (bZIP) family transcription factors in the regulation of various abiotic stresses are beginning to be unveiled, the precise roles of bZIP proteins in plants coping with submergence stress remain unclear. Here we identified a bZIP gene GmbZIP71-4 from soybean, which localized in the nucleus. The GmbZIP71-4 over-expressed tabocco line showed reduced submergence resistance due to the decreased abscisic acid (ABA) content. GO and KEGG pathway analysis based on chromatin immunoprecipitation assay sequencing (ChIP-seq) indicated that the differences expressed genes between submergence treatment and control groups were specially enriched in plant hormone signal transduction items, especially those in response to ABA. Electrophoretic mobility shift assays (EMSA) demonstrated that GmbZIP71-4 bound to the promoter of GmABF2 gene, which is consistent with the ChIP-qPCR results. GmbZIP71-4 function as a negative regulator of soybean in responding to submergence stress through manipulating ABA signaling pathway. This findings will set a solid foundation for the understanding of submergence resistance in plants.

Deep Cracking of Bulky Hydrocarbons into Light Products via Tandem Catalysis over Uniform Interconnected ZSM-5@AlSBA-15 Composites.

Deep cracking of bulky hydrocarbons on zeolite-containing catalysts into light products with high activity, desired selectivity, and long-term stability is demanded but challenging. Herein, the efficient deep cracking of 1,3,5-triisopropylbenzene (TIPB) on intimate ZSM-5@AlSBA-15 composites via tandem catalysis is demonstrated. The rapid aerosol-confined assembly enables the synthesis of the composites composed of a continuous AlSBA-15 matrix decorated with isolated ZSM-5 nanoparticles. The two components at various ZSM-5/AlSBA-15 mass ratios are uniformly mixed with chemically bonded pore walls, interconnected pores, and eliminated external surfaces of nanosized ZSM-5. The typical composite with a ZSM-5/AlSBA-15 mass ratio of 0.25 shows superior performance in TIPB cracking with outstanding activity (≈100% conversion) and deep cracking selectivity (mass of propylene + benzene > 60%) maintained for a long time (> 6 h) under a high TIPB flux (2 mL h-1), far better (several to tens of times higher) than the single-component and physically mixed catalysts and superior to literature results. The high performance is attributed to the cooperative tandem catalytic process, that is, selective and timely pre-cracking of TIPB to isopropylbenzene (IPB) in AlSBA-15 and subsequently timely diffusion and deep cracking of IPB in nanosized ZSM-5.

A regimen based on the combination of trimethoprim/sulfamethoxazole with caspofungin and corticosteroids as a first-line therapy for patients with severe non-HIV-related pneumocystis jirovecii pneumonia: a retrospective study in a tertiary hospital.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of sulfamethoxazole-trimethoprim (SMX-TMP) with caspofungin and glucocorticosteroids (GCSs) may be a potential first-line therapy for PJP. Therefore, it is important to explore the efficacy and safety of this synergistic therapy for treating non-HIV-related PJP patients. METHODS: We retrospectively analysed the data of 38 patients with non-HIV-related PJP at the First Affiliated Hospital of Xi'an Jiaotong University. Patients were divided into two groups: the synergistic therapy group (ST group, n = 20) and the monotherapy group (MT group, n = 18). All patients were from the ICU and were diagnosed with severe PJP. In the ST group, all patients were treated with SMX-TMP (TMP 15-20 mg/kg per day) combined with caspofungin (70 mg as the loading dose and 50 mg/day as the maintenance dose) and a GCS (methylprednisolone 40-80 mg/day). Patients in the MT group were treated only with SMX-TMP (TMP 15-20 mg/kg per day). The clinical response, adverse events and mortality were compared between the two groups. RESULTS: The percentage of patients with a positive clinical response in the ST group was significantly greater than that in the MT group (100.00% vs. 66.70%, P = 0.005). The incidence of adverse events in the MT group was greater than that in the ST group (50.00% vs. 15.00%, P = 0.022). Furthermore, the dose of TMP and duration of fever in the ST group were markedly lower than those in the MT group (15.71 mg/kg/day vs. 18.35 mg/kg/day (P = 0.001) and 7.00 days vs. 11.50 days (P = 0.029), respectively). However, there were no significant differences in all-cause mortality or duration of hospital stay between the MT group and the ST group. CONCLUSIONS: Compared with SMZ/TMP monotherapy, synergistic therapy (SMZ-TMP combined with caspofungin and a GCS) for the treatment of non-HIV-related PJP can increase the clinical response rate, decrease the incidence of adverse events and shorten the duration of fever. These results indicate that synergistic therapy is effective and safe for treating severe non-HIV-related PJP.

Glutathione-depleting Liposome Adjuvant for Augmenting the Efficacy of a Glutathione Covalent Inhibitor Oridonin for Acute Myeloid Leukemia Therapy.

BACKGROUND: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. METHODS: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets. RESULTS: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. CONCLUSION: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.

Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908-0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics.

Letrozole cotreatment progestin-primed ovarian stimulation in women undergoing controlled ovarian stimulation for in vitro fertilization.

AIM: To investigate the impact of letrozole cotreatment progestin-primed ovarian stimulation (PPOS) (Le PPOS) in controlled ovarian stimulation (COS) and the pregnancy outcomes in frozen-thawed embryo transfer cycles. METHODS: This retrospective cohort study included women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). A total of 2575 cycles were included (1675 in the Le PPOS group and 900 in the PPOS group). The primary outcome was the clinical pregnancy rates. The secondary outcome was the live birth rates. RESULTS: In this study, propensity score matching (PSM) was performed to create a perfect match of 379 patients in each group. After matching, the numbers of oocytes retrieved, mature oocytes, fertilization, and clinical pregnancy rates were more favorable in the Le PPOS group than in the PPOS group (all p < 0.05). The multivariable analysis showed that the clinical pregnancy rate was higher in the Le PPOS than in the PPOS group (odds ratio = 1.46, 95% confidence interval: 1.05-2.04, p = 0.024) after adjusting for potentially confounding factors (age, anti-Müllerian hormone levels, antral follicular count, the type of embryo transferred, number of transferred embryos, body mass index, and follicular stimulating hormone and estradiol levels on starting day). CONCLUSIONS: This retrospective study with a limited sample size suggests that the Le PPOS protocol might be an alternative to the PPOS protocol in women undergoing COS and could lead to better pregnancy outcomes. The results should be confirmed using a formal randomized controlled trial.

Ratiometric electrochemical immunosensor for simultaneous detection of C-myc and Bcl-2 based on multi-role alloy composites.

A ratiometric electrochemical immunosensor is proposed for simultaneous detection of cellular-myelocytomatosis oncoprotein (C-myc) and B-cell lymphoma 2 (Bcl-2) via the potential-resolved strategy. It relied on multi-role co-loaded alloy composites (CLACs) and poly(3,4-ethylenedioxythiophene) (PEDOT)-graphene oxide (GO)-multiwalled carbon nanotubes (MWCNTs) (PGM) modified electrodes. CLACs with good catalytic and enzyme-like properties were synthesized in one step by loading tetramethylbenzidine (TMB) or methylene blue (MB) into Pt-Pd alloy and used as label materials. After immunological reactions, CLACs showed distinguishable dual differential pulse voltammetry signals at - 0.26 V and 0.38 V, corresponding to C-myc and Bcl-2, and the PGM had an electrochemical signal at 1.2 V, which could be used as a reference signal to construct a ratiometric sensor. CLACs had a satisfactory synergistic effect with the PGM, and eventually achieved quadruple signal amplification. Thus, benefiting from multiple magnification and ratiometric self-calibration functions, sensitive detections of C-myc and Bcl-2 were achieved, with detection limits as low as 0.5 and 2.5 pg mL-1, respectively. Additionally, when the designed method was applied to blood samples from lymphoma patients, results consistent with the ELISA kit were obtained. This will open avenues for constructing multiple protein detection sensors.

Association between ambient temperature and hospitalizations for urolithiasis in four counties of Ganzhou, China.

We collected meteorological and urolithiasis-related hospitalization data from four counties in Ganzhou City for 2018-2019 and used the DLNM method to assess the lagged and cumulative effects of temperature on urolithiasis hospitalizations and obtain the total effect after meta-combination. Based on the nonlinear association between temperature and urolithiasis hospitalizations, the relative risk of overall high temperature (30℃) was 2.10 (95% CI: 1.07-4.10). No statistically significant difference (p = 0.07) was observed between males (RR = 2.04, 95% CI: 1.42-2.94) and females (RR = 1.45, 95% CI: 1.09-1.92) for the heat effect, which was higher in the ≥ 60 years age group (RR = 3.18, 95% CI: 1.76-5.76) than in the < 60 years age group (p = 0.007). High temperatures increased the risk of hospitalization for urolithiasis in Ganzhou, China, and the risk was greatest for individuals aged 60 and above, with similar risks observed across counties and genders.

Caregiving information needs of family caregivers of adolescent patients with suicide attempts: a qualitative study in China.

BACKGROUND: In the cultural milieu of China, family caregivers assume a pivotal role in the post-adolescent suicide attempt recovery journey. Nevertheless, they frequently encounter a dearth of requisite knowledge and information pertaining to the appropriate caregiving protocols for these adolescents. Notwithstanding, scholarly investigation into the informational requisites of this demographic concerning caregiving remains significantly constrained. METHODS: Between September and December 2023, a phenomenological approach was applied in qualitative research. Semi-structured interviews were undertaken with 15 family caregivers of adolescents who had experienced suicide attempts. The amassed data underwent systematic organization and analysis through the utilization of the Colaizzi method. RESULTS: Four primary themes were identified: (1) negative emotional encounters; (2) requirements for addressing dilemmas; (3) addressing the needs of the unknown; and (4) insufficient access to support. CONCLUSIONS: Family caregivers experience complex negative emotions upon learning about a teenager's suicide attempt. Throughout the caregiving process, they face numerous challenges, with apparent lack of external support, leading to an increased urgent need for caregiving information. Healthcare professionals, especially nurses, should actively identify and respond to the informational needs of family caregivers when caring for adolescents who have attempted suicide. This includes providing education on various coping mechanisms and support strategies, as well as assisting them in better understanding how to effectively manage the stress and challenges of caregiving. By doing so, healthcare professionals can help alleviate the psychological and emotional burden on family caregivers, thereby enhancing their caregiving abilities and overall well-being.

Therapeutic roles of platelet-rich plasma to restore female reproductive and endocrine dysfunction.

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility.

iRGD mediated pH-responsive mesoporous silica enhances drug accumulation in tumors.

The limited penetration of nanocarriers into tumors and the slow release of drugs from these carriers to tumor cells are significant challenges in cancer therapy. In this study, we developed a novel drug delivery carrier derived from mesoporous silica, dually modified with the tumor-homing cyclic peptide iRGD (CRGDKGPDC) and the pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) for treating triple-negative breast cancer. The carrier selectively bound to the αvß3 integrin receptor, which is specifically expressed in MDA-MB-231 breast cancer cells and vessels. Subsequently, it penetrated deep into the tumor parenchyma through NRP-1 receptor-dependent internalization, with the drug-loaded particles releasing drugs rapidly in the acidic cytoplasmic environment. Results indicated that the drug release rate of PEOz-modified formulations was pH-dependent. Lysosomal escape experiments demonstrated that PEOz-modified particles efficiently escaped lysosomes to release drugs. In vitro cytotoxicity assays revealed that iRGD-functionalized particles were more cytotoxic to NRP-1-positive MDA-MB-231 cells compared to NRP-1-negative MCF-7 cells. Cellular uptake studies demonstrated that iRGD mediated enhanced endocytosis of nanoparticles into MDA-MB-231 cells. In vitro tumor cell spheroid penetration assays confirmed that the PEOz and iRGD dual-modified carrier facilitated deeper distribution of DOX in multicellular spheroids compared to free DOX. Moreover, in a nude mouse model of triple-negative breast cancer, the dual-modified drug-loaded carrier significantly inhibited tumor growth without inducing weight loss or liver and kidney damage. This dual-modified mesoporous silica presents a novel and promising delivery carrier for enhancing cancer treatment.

The novel HLA-C*14:02:01:33 allele identified by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*14:02:01:33 differs from HLA-C*14:02:01:01 by one nucleotide substitution in intron 2.

Characterization of the novel HLA-C*06:376N allele by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*06:376N differs from HLA-C*06:02:01:01 by seven nucleotide changes in exon 2, intron 2, and exon 3.

Heterostructure Nanozyme with Hyperthermia-Amplified Enzyme-Like Activity and Controlled Silver Release for Synergistic Antibacterial Therapy.

Heterostructure nanozymes as antibiotic-free antimicrobial agents exhibit great potential for multidrug-resistant (MDR) bacterial strains elimination. However, realization of heterostructure antimicrobials with enhanced interfacial interaction for synergistically amplified antibacterial therapy is still a great challenge. Herein, oxygen-vacancy-enriched glucose modified MoOx (G-MoOx) is exploited as a reducing agent to spontaneously reduce Ag (I) into Ag (0) that in situ grows onto the surface of G-MoOx. The resultant Ag doped G-MoOx (Ag/G-MoOx) heterostructure displays augmenting photothermal effect and NIR-enhanced oxidase-like activity after introducing Ag nanoparticles. What's more, NIR hyperthermia accelerate Ag+ ions release from Ag nanoparticles. Introduction of Ag greatly enhances antimicrobial activities of Ag/G-MoOx against MDR bacteria, especially the hybrid loading with 1 wt% Ag NPs exhibiting antibacterial efficacy up to 99.99% against Methicillin-resistant Staphylococcus aureus (MRSA, 1×106 CFU mL-1).

Potential toxic components in size-resolved particles and gas from residential combustion: Emission factor and health risk.

Particulate matter (PM) from residential combustion is an existential threat to human health. Emission factors (EFs) of multiple potential toxic components (PTCs) in size-resolved PM and gas from eight residential fuel combustion were measured, and size distribution, gas/particle partitioning and health risks of the PTCs were investigated. Average EFs from clean coal and anthracite coal were PTEs (sum of EFs of 11 Potential Toxic Elements, 6.62 mg/kg fuels) > PAHs (sum of 22 Polycyclic Aromatic Hydrocarbons, 1.12 mg/kg) > OPAHs (sum of 5 Oxygenated Polycyclic Aromatic Hydrocarbons, 0.45 mg/kg) > PAEs (sum of 6 Phthalate Esters, 0.11 mg/kg) > NPAHs (sum of 14 Nitropolycyclic Aromatic Hydrocarbons, 16.84 µg/kg) > OPEs (sum of 7 Organophosphate Esters, 7.57 µg/kg) > PCBs (sum of 6 Polychorinated Biphenyls, 0.07 µg/kg), which were 2-3 and 1-2 orders of magnitude lower than the EFs of PTCs (except PTEs) from bituminous coal and biomass. Most PAHs, OPAHs and NPAHs, which may mainly originate from chemical reactions, showed similar size distributions and averagely 85 % concentrated in PM1. PTEs, PAEs, OPEs and PCBs generated from the release from raw fuels may have a higher proportion, so their size distributions were more complex and varied with combustion temperature, volatility of compounds, binding mode of the raw fuels, and so on. In addition, clean coal and high-quality anthracite coal could reduce the health risks from the potential organic toxic components, but also reveal the stumbling block of PTEs in risk control.

Two rearranged acylphloroglucinols with moderate neuroprotective effects from Hypericum ascyron Linn.

Phytochemical studies on the leaves and twigs of Hypericum ascyron Linn. led to the isolation of two previously undescribed rearranged polycyclic polyprenylated acylphloroglucinols (PPAP) with a 4,5-seco-3(2H)-furanone skeleton, named hyperascone A and B (1-2). Additionally, a known PPAP tomoeone A (3) and two known xanthones 1,3,5 -trihydroxy-6-O-prenylxanthone (4) and 3,7-dihydroxy-1,6-dimethoxyxanthone (5) were also isolated. The structures of the compounds were determined by the analysis of their spectroscopic data including HRMS, NMR and ECD. All of the five isolated compounds exhibited neuroprotective effects against MPP+ and microglia activation induced damage of SH-SY5Y cells.

Exploring natural killer cell-related biomarkers in multiple myeloma: a novel nature killer cell-related model predicting prognosis and immunotherapy response using single-cell study.

BACKGROUND: Natural killer cells (NKs) may be involved in multiple myeloma (MM) progression. The present study elucidated the correlation between NKs and the progression of MM using single-cell binding transcriptome probes to identify NK cell-related biomarkers. METHODS: Single-cell analysis was performed including cell and subtype annotation, cell communication, and pseudotime analysis. Hallmark pathway enrichment analysis of NKs and NKs-related differentially expressed genes (DEGs) were conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction (PPI) networks. Then, a risk model was structured based on biomarkers identified through univariate Cox regression analysis and least absolute shrinkage and selection operator regression analysis and subsequently validated. Additionally, correlation of clinical characteristics, gene set enrichment analysis, immune analysis, regulatory network, and drug forecasting were explored. RESULTS: A total of 13 cell clusters were obtained and annotated, including 8 cell populations that consisted of NKs. Utilizing 123 PPI network node genes, 8 NK-related DEGs were selected to construct a prognostic model. Immune cell infiltration results suggested that 11 immune cells exhibited marked differences in the high and low-risk groups. Finally, the model was used to screen potential drug targets to enhance immunotherapy efficacy. CONCLUSION: A new prognostic model for MM associated with NKs was constructed and validated. This model provides a fresh perspective for predicting patient outcomes, immunotherapeutic response, and candidate drugs.