Genome-scale CRISPR-Cas9 screen identifies PAICS as a therapeutic target for EGFR wild-type non-small cell lung cancer.

Epidermal growth factor receptor-targeted (EGFR-targeted) therapies show promise for non-small cell lung cancer (NSCLC), but they are ineffective in a third of patients who lack EGFR mutations. This underlines the need for personalized treatments for patients with EGFR wild-type NSCLC. A genome-wide CRISPR/Cas9 screen has identified the enzyme phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), which is vital in de novo purine biosynthesis and tumor development, as a potential drug target for EGFR wild-type NSCLC. We have further confirmed that PAICS expression is significantly increased in NSCLC tissues and correlates with poor patient prognosis. Knockdown of PAICS resulted in a marked reduction in both in vitro and in vivo proliferation of EGFR wild-type NSCLC cells. Additionally, PAICS silencing led to cell-cycle arrest in these cells, with genes involved in the cell cycle pathway being differentially expressed. Consistently, an increase in cell proliferation ability and colony number was observed in cells with upregulated PAICS in EGFR wild-type NSCLC. PAICS silencing also caused DNA damage and cell-cycle arrest by interacting with DNA repair genes. Moreover, decreased IMPDH2 activity and activated PI3K-AKT signaling were observed in NSCLC cells with EGFR mutations, which may compromise the effectiveness of PAICS knockdown. Therefore, PAICS plays an oncogenic role in EGFR wild-type NSCLC and represents a potential therapeutic target for this disease.

Interfacial Electron Transfer in PbI2@Single-Walled Carbon Nanotube van der Waals Heterostructures for High-Stability Self-Powered Photodetectors.

Acquiring a deep insight into the electron transfer mechanism and applications of one-dimensional (1D) van der Waals heterostructures (vdWHs) has always been a significant challenge. Herein, through direct observation using aberration-corrected transmission electron microscopy (AC-TEM), we verify the stable formation of a high-quality 1D heterostructure composed of PbI2@single-walled carbon nanotubes (SWCNTs). The phenomenon of electron transfer between PbI2 and SWCNT is elucidated through spectroscopic investigations, including Raman and X-ray photoelectron spectroscopy (XPS). Electrochemical testing indicates the electron transfer and enduring stability of 1D PbI2 within SWCNTs. Moreover, leveraging the aforementioned electron transfer mechanism, we engineer self-powered photodetectors that exhibit exceptional photocurrent and a 3-order-of-magnitude switching ratio. Subsequently, we reveal its unique electron transfer behavior using Kelvin probe force microscopic (KPFM) tests. According to KPFM, the average surface potential of SWCNTs decreases by 80.6 mV after filling. Theoretical calculations illustrate a charge transfer of 0.02 e per unit cell. This work provides an effective strategy for the in-depth investigation and application of electron transfer in 1D vdWHs.

Multiple geriatric syndromes in community-dwelling older adults in China.

This study aims to assess the prevalence of geriatric syndromes and identify factors associated with multiple geriatric syndromes in community-dwelling older adults in China. We utilized a convenience sampling method to recruit older adults and from one rural and one urban community in Chengdu, China, from October 2022 to March 2023. A total of 706 older adults aged 60 years or older were included. Ten geriatric syndromes were investigated including two mental disorders: depressive symptoms, cognitive impairment; and eight somatic disorders: pain, falls, sleep disturbance, constipation, polypharmacy, multimorbidity, malnutrition and frailty. Multiple geriatric syndromes were defined as an individual having two or more geriatric syndromes. The data obtained were analysed using descriptive statistics. The independent risk factors for multiple geriatric syndromes were assessed using a logistic regression model. This study found that 90.5% of the participants had at least one geriatric syndrome, with 72.8% experiencing multiple geriatric syndromes. The top four geriatric syndromes in our study were polypharmacy (58.5%), malnutrition/at risk of malnutrition (43.1%), multimorbidity (42.1%), and frailty/prefrailty (34.3%). Of the older adults, 368(52.1%) had only somatic disorders, 18(2.5%) had only mental disorders and 253 (35.8%) had somatic-mental disorders. According to the logistic regression analysis, residence, age, marriage, BMI, and self-related health were significantly associated with multiple geriatric syndromes among older adults. This study highlights that multiple geriatric syndromes are prevalent among community-dwelling older adults in China, and underscores the significance of certain demographic factors in their occurrence. Future longitudinal studies are needed to establish the temporal relationship between multiple geriatric syndromes and these demographic factors, as well as to explore causal relationships and effective prevention strategies for geriatric syndrome.

Caffeine intake and anxiety: a meta-analysis.

The results from studies on relationship between caffeine intake and risk of anxiety remains controversial, so we conducted a meta-analysis to summarize the evidence about the association between caffeine intake and risk of anxiety. Relevant articles were identified by researching PubMed, Web of Science, Cochrane library, Embase, CNKI, WANFANG DATA, SinoMed and VIP from the inception to December, 2022. Three investigators independently sifted through the literature, extracted the data, and evaluated the quality of the included studies based on predetermined selection criteria and assessed articles with Risk of bias assessment tool for Cochrane systematic reviews and analytical cross-sectional study quality assessment tool from JBI PACES. After assessing the quality of the literature, meta-analysis was performed using Revman 5.4 and Stata 12.0. Data were obtained from eight articles, and 546 participants from 14 studies in eight articles from healthy populations were included in the caffeine-anxiety analyses. As the scales used to assess anxiety vary in the literature, we chose standardized mean difference as the outcome indicator. In terms of overall effect, the results of the meta-analysis showed that caffeine intake increased the risk of anxiety [SMD = 0.94, 95% Cl = (0.28, 1.60), p < 0.05]. After suspecting that dose size might be responsible for the heterogeneity by sensitivity analysis, we performed subgroup analysis according to dose size and found that low-dose caffeine intake moderately increased the risk of anxiety [SMD = 0.61, 95%Cl = (0.42, 0.79), p < 0.05], whereas high-dose caffeine intake had a highly significant increase in the risk of anxiety [SMD = 2.86, 95%Cl = (2.50, 3.22), p < 0.05]. The results confirm that caffeine intake is associated with an elevated risk of anxiety in healthy individuals without psychiatric disorders, especially when the intake dose is greater than 400 mg.

Vitamin D levels in idiopathic inflammatory myopathy patients: a meta-analysis.

PURPOSE: This meta-analysis aimed to explore correlations between vitamin D and idiopathic inflammatory myopathy (IIM). METHODS: A comprehensive database search was conducted on 13 October 2020. Mean differences (MDs) and aggregated risk ratios (RR) with 95% confidence intervals (CIs) were used to determine the correlation between vitamin D deficiency (VDD) and IIM. Statistical analysis was performed with RevMan 5.4 and Stata15, statistical significance was set at p < 0.05. RESULTS: Search revealed five studies with 286 IIM patients and 480 healthy controls. Results with random-effects modeling indicated that serum vitamin D levels were significantly lower in IIM patients than in healthy controls (MD = -13.10 ng/mL; 95% CI: -16.51 to -9.68; p < 0.00001). No differences were found between patients with IIM and other autoimmune diseases on vitamin D levels (MD =-2.65 ng/mL; 95% CI: -11.31-6.01; p = 0.55). In two studies with 185 IIM patients, those with low vitamin D levels exhibited higher creatine kinase levels (MD = 85.20 IU/L; 95% CI: 72.67-97.73; p < 0.00001) than those with normal vitamin D levels. VDD was correlated with an increased risk of IIM (RR = 3.24, 95% CI: 1.81-5.79; p < 0.0001). CONCLUSION: This meta-analysis showed correlations between vitamin D level and IIM. The results indicated, VDD may be a risk factor for IIM, a determinant of immune dysregulation in IIM, or a consequence of IIM. Also, it implied further research to determine whether vitamin D supplementation is beneficial for patients with IIM.

Interlayer Charge Transfer Induced Electrical Behavior Transition in 1D AgI@sSWCNT van der Waals Heterostructures.

The emergence of one-dimensional van der Waals heterostructures (1D vdWHs) opens up potential fields with unique properties, but precise synthesis remains a challenge. The utilization of mixed conductive types of carbon nanotubes as templates has imposed restrictions on the investigation of the electrical behavior and interlayer interaction of 1D vdWHs. In this study, we efficiently encapsulated silver iodide in high-purity semiconducting single-walled carbon nanotubes (sSWCNTs), forming 1D AgI@sSWCNT vdWHs. We characterized the semiconductor-metal transition and increased the carrier concentration of individual AgI@sSWCNTs via sensitive dielectric force microscopy and confirmed the results through electrical device tests. The electrical behavior transition was attributed to an interlayer charge transfer, as demonstrated by Kelvin probe force microscopy. Furthermore, we showed that this method of synthesizing 1D heterostructures can be extended to other metal halides. This work opens the door for the further exploration of the electrical properties of 1D vdWHs.

Energy-efficient extraction of linear alkanes from various isomers using structured metal-organic framework membrane.

Extraction of low concentration linear alkanes (C5-C7) from various isomers is critical for the petrochemical industry. At present, the separation of alkane isomers is mainly accomplished by distillation, which results in substantial energy expenditure. Metal-organic frameworks (MOFs) with well-tailored nanopores have been demonstrated to be capable of realizing molecule-level separation. In this study, oriented HKUST-1 membranes are formulated according to the morphology-biased principle and finally realized with a low dose synthesis method for terminating undesired crystal nucleation and growth. The fully exposed triangular sieving pore array of the membrane induces configuration entropic diffusion to split linear alkanes from mono-branched and di-branched isomers as well as their cyclical counterparts. Typically, the current separation technique consumes 91% less energy than vacuum distillation. Furthermore, our membranes can realize one-step extraction of normal-pentane, normal-hexane and normal-heptane from a ten-component alkane isomer solution that mimics light naphtha.

Abnormal dynamic functional network connectivity in patients with early-onset bipolar disorder.

Objective: To explore the changes in dynamic functional brain network connectivity (dFNC) in patients with early-onset bipolar disorder (BD). Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 39 patients with early-onset BD and 22 healthy controls (HCs). Four repeated and stable dFNC states were characterised by independent component analysis (ICA), sliding time windows and k-means clustering, and three dFNC temporal metrics (fraction of time, mean dwell time and number of transitions) were obtained. The dFNC temporal metrics and the differences in dFNC between the two groups in different states were evaluated, and the correlations between the differential dFNC metrics and neuropsychological scores were analysed. Results: The dFNC analysis showed four connected patterns in all subjects. Compared with the HCs, the dFNC patterns of early-onset BD were significantly altered in all four states, mainly involving impaired cognitive and perceptual networks. In addition, early-onset BD patients had a decreased fraction of time and mean dwell time in state 2 and an increased mean dwell time in state 3 (p < 0.05). The mean dwell time in state 3 of BD showed a positive correlation trend with the HAMA score (r = 0.4049, p = 0.0237 × 3 > 0.05 after Bonferroni correction). Conclusion: Patients with early-onset BD had abnormal dynamic properties of brain functional network connectivity, suggesting that their dFNC was unstable, mainly manifesting as impaired coordination between cognitive and perceptual networks. This study provided a new imaging basis for the neuropathological study of emotional and cognitive deficits in early-onset BD.

Targeting CDK4/6 in glioblastoma via in situ injection of a cellulose-based hydrogel.

Despite aggressive treatments, including surgery, chemotherapy and radiotherapy, the prognosis of glioblastoma (GBM) remains poor, and tumor recurrence is inevitable. The FDA-approved CDK4/6 inhibitor palbociclib (PB) showed interesting anti-GBM effects, but its brain penetration is limited by the blood-brain barrier. The aim of this project is to find whether the cellulose-based hydrogel via in situ injection could provide an alternative route to PB brain delivery and generate sufficient drug exposure in orthotopic GBM. In brief, PB was encapsulated in a cellulose nanocrystal network structure crosslinked by polydopamine via divalent Cu2+ and hexadecylamine. The formed hydrogel (PB@PH/Cu-CNCs) exhibited sustained drug retention and acid-responsive network de-polymerization for controlled release in vivo. Specifically, the released Cu2+ catalyzed a Fenton-like reaction to generate reactive oxygen species (ROS), which was further enhanced by PB, and consequently, irreversible senescence and apoptosis were induced in GBM cells. Finally, PB@PH/Cu-CNCs demonstrated a more potent anti-GBM effect than those treated with free PB or PH/Cu-CNCs (drug-free hydrogel) in cultured cells or in an orthotopic glioma model. These results prove that the injection of the PB-loaded hydrogel in situ is an effective strategy to deliver the CDK4/6 inhibitor into the brain and its anti-GBM effect can be further enhanced by combining Cu2+-mediated Fenton-like reaction.

Heat-driven molecule gatekeepers in MOF membrane for record-high H2 selectivity.

Hydrogen/carbon dioxide (H2/CO2) separation for sustainable energy is in desperate need of reliable membranes at high temperatures. Molecular sieve membranes take their nanopores to differentiate sizes between H2 and CO2 but have compromised at a marked loss of selectivity at high temperatures owing to diffusion activation of CO2. We used molecule gatekeepers that were locked in the cavities of the metal-organic framework membrane to meet this challenge. Ab initio calculations and in situ characterizations demonstrate that the molecule gatekeepers make a notable move at high temperatures to dynamically reshape the sieving apertures as being extremely tight for CO2 and restitute with cool conditions. The H2/CO2 selectivity was improved by an order of magnitude at 513 kelvin (K) relative to that at the ambient temperature.

RcSPL1-RcTAF15b regulates the flowering time of rose (Rosa chinensis).

Rose (Rosa chinensis), which is an economically valuable floral species worldwide, has three types, namely once-flowering (OF), occasional or re-blooming (OR), and recurrent or continuous flowering (CF). However, the mechanism underlying the effect of the age pathway on the duration of the CF or OF juvenile phase is largely unknown. In this study, we observed that the RcSPL1 transcript levels were substantially upregulated during the floral development period in CF and OF plants. Additionally, accumulation of RcSPL1 protein was controlled by rch-miR156. The ectopic expression of RcSPL1 in Arabidopsis thaliana accelerated the vegetative phase transition and flowering. Furthermore, the transient overexpression of RcSPL1 in rose plants accelerated flowering, whereas silencing of RcSPL1 had the opposite phenotype. Accordingly, the transcription levels of floral meristem identity genes (APETALA1, FRUITFULL, and LEAFY) were significantly affected by the changes in RcSPL1 expression. RcTAF15b protein, which is an autonomous pathway protein, was revealed to interact with RcSPL1. The silencing and overexpression of RcTAF15b in rose plants led to delayed and accelerated flowering, respectively. Collectively, the study findings imply that RcSPL1-RcTAF15b modulates the flowering time of rose plants.

Inhibitory Effects and Related Molecular Mechanisms of Huanglian-Ganjiang Combination Against H1N1 Influenza Virus.

Influenza is an infectious acute respiratory disease with complications and a high mortality rate; the effective medicines for influenza therapy are limited. "Huanglian" or Coptidis Rhizoma, Coptis chinensis Franch., Ranunculaceae, and "ganjiang" or Zingiberis Rhizoma, Zingiber officinale Roscoe, Zingiberaceae, combination is clinically used for treating respiratory diseases. HPLC was applied for the quantification of berberine hydrochloride (1.101 mg/ml) and 6-gingerol (38.41 µg/ml) in the H2O-soluble extract of the herbal formulation. In this study, the effect of "huanglian"- "ganjiang" extract on influenza virus H1N1-induced acute pulmonary inflammation was evaluated, in addition to the investigation of its anti-influenza mechanism in a mouse model. The analyzed herbal combination inhibited the expression of cytokine IL-6 and stimulated the expression of IL-2 in the serum of influenza virus-infected mice. Meanwhile, the herbal combination downregulated the gene and protein expression levels of TLR3, TLR7, MyD88, RIG-I, MAVS, TRAF3, and NF-κB p65, which are key targets of toll-like and RIG-I-like receptor signaling pathways in mice. In addition, the herbal combination could also promote the combination of intracellular autophagosomes and lysosomes in autophagosome-lysosome formation and improve impaired fusion of autophagosomes and lysosomes by influenza virus. This study suggested that the "huanglian"- "ganjiang" extract may be a candidate therapeutic strategy for the treatment of H1N1 influenza. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00372-z.

Aberrant functional connectivity within and between brain networks in patients with early-onset bipolar disorder.

OBJECTIVE: This study used independent component analysis (ICA) to investigate the connectivity patterns of resting-state functional large-scale brain networks in patients with early-onset bipolar disorder (BD). METHODS: ICA was used to extract brain functional network components from 43 early-onset BD patients and 21 healthy controls (HCs). Then, the functional connectivity (FC) and functional network connectivity (FNC) within and between the independent brain networks was calculated, and the correlation between the connectivity changes and neuropsychological scale was evaluated. RESULTS: Compared with HCs, FC increased in the right hippocampus and inferior temporal gyrus, and left triangular inferior frontal gyrus of the anterior default mode network (aDMN); right median cingulate and paracingulate gyri, and inferior parietal lobule of the posterior DMN (pDMN); and right precentral and postcentral gyrus of the sensorimotor network (SMN) in early-onset BD patients. However, FC decreased in the left superior frontal gyrus of the aDMN, left paracentral lobule of the SMN, and left lingual gyrus and calcarine of the visual network in early-onset BD patients. There was no significant correlation between FC values of differential brain regions within resting-state networks (RSNs) and neuropsychological scores (uncorrected p > 0.05). In addition, the FNC among the pDMN-auditory network, pDMN-visual network, left frontoparietal network (lFPN)-visual network, lFPN-aDMN and dorsal attention network-ventral attention network (DAN-VAN) were increased in early-onset BD patients. The zFNC of the pDMN-visual network was positively correlated with the anxiety/somatization score (r = 0.5833, p < 0.0001) and sleep disorders (r = 0.6150, p < 0.0001). The zFNC of the lFPN-aDMN was positively correlated with despair (r = 0.4505, p = 0.004 × 10 < 0.05 after Bonferroni correction). The zFNC of the DAN-VAN was positively correlated with cognitive impairment (r = 0.4598, p = 0.0032 × 10 < 0.05 after Bonferroni correction). The zFNC of the DAN-VAN showed a positive correlation trend with the Hamilton Depression Scale (HAMD) total score (r = 0.4404, p = 0.005 × 10 = 0.05 after Bonferroni correction). CONCLUSIONS: Patients with early-onset BD showed changes in a wide range of neural functional networks, involving changes in executive control, attention, perceptual regulation, cognition and other neural networks, which may provide new imaging evidence for understanding the pathogenesis of early-onset BD and for therapeutic intervention targets.

Toward the next generation EGFR inhibitors: an overview of osimertinib resistance mediated by EGFR mutations in non-small cell lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is currently the standard first-line therapy for EGFR-mutated advanced non-small cell lung cancer (NSCLC). The life quality and survival of this subgroup of patients were constantly improving owing to the continuous iteration and optimization of EGFR-TKI. Osimertinib, an oral, third-generation, irreversible EGFR-TKI, was initially approved for the treatment of NSCLC patients carrying EGFR T790M mutations, and has currently become the dominant first-line targeted therapy for most EGFR mutant lung cancer. Unfortunately, resistance to osimertinib inevitably develops during the treatment and therefore limits its long-term effectiveness. For both fundamental and clinical researchers, it stands for a major challenge to reveal the mechanism, and a dire need to develop novel therapeutics to overcome the resistance. In this article, we focus on the acquired resistance to osimertinib caused by EGFR mutations which account for approximately 1/3 of all reported resistance mechanisms. We also review the proposed therapeutic strategies for each type of mutation conferring resistance to osimertinib and give an outlook to the development of the next generation EGFR inhibitors. Video Abstract.

Spectroscopic Insights into the Influence of Filling Carbon Nanotubes with Atomic Nanowires for Photophysical and Photochemical Applications.

Studying the optical performance of carbon nanotubes (CNTs) filled with guest materials can reveal the fundamental photochemical nature of ultrathin one-dimensional (1D) nanosystems, which are attractive for applications including photocatalysis. Here, we report comprehensive spectroscopic studies of how infiltrated HgTe nanowires (NWs) alter the optical properties of small-diameter (d t < 1 nm) single-walled carbon nanotubes (SWCNTs) in different environments: isolated in solution, suspended in a gelatin matrix, and heavily bundled in network-like thin films. Temperature-dependent Raman and photoluminescence measurements revealed that the HgTe NW filling can alter the stiffness of SWCNTs and therefore modify their vibrational and optical modes. Results from optical absorption and X-ray photoelectron spectroscopy demonstrated that the semiconducting HgTe NWs did not provide substantial charge transfer to or from the SWCNTs. Transient absorption spectroscopy further highlighted that the filling-induced nanotube distortion can alter the temporal evolution of excitons and their transient spectra. In contrast to previous studies on functionalized CNTs, where electronic or chemical doping often drove changes to the optical spectra, we highlight structural distortion as playing an important role.

A LDH Template Triggers the Formation of a Highly Compact MIL-53 Metal-Organic Framework Membrane for Acid Upgrading.

Highly compact metal-organic framework (MOF) membranes offer hope for the ambition to cope with challenging separation scenarios with industrial implications. A continuous layer of layered double hydroxide (LDH) nanoflakes on an alumina support as a template triggered a chemical self-conversion to a MIL-53 membrane, with approximately 8 hexagonal lattices (LDH) traded for 1 orthorhombic lattice (MIL-53). With the sacrifice of the template, the availability of Al nutrients from the alumina support was dynamically regulated, which resulted in synergy for producing membranes with highly compact architecture. The membrane can realize nearly complete dewatering from formic acid and acetic acid solutions, respectively, and maintain stability in a continuous pervaporation over 200 h. This is the first success in directly applying a pure MOF membrane to such a corrosive chemical environment (lowest pH value of 0.81). The energy consumption is saved by up to 77 % when compared with the traditional distillation.

Surface Engineering for Ultrathin Metal Anodes Enabling High-Performance Zn-Ion Batteries.

Zn-ion batteries with low cost and high safety have been regarded as a promising energy storage technology for grid storage. It is well-known that the metal anode surface orientation is vital to its reversibility. Herein, we demonstrate a facile route to control the Zn metal anode surface orientation through electrodeposition with electrolyte additives. An ultrathin (101)-inclined Zn metal anode (down to 2 µm) is obtained by adding a small amount of dimethyl sulfoxide (DMSO) in the ZnSO4 aqueous electrolyte. Scanning electron microscopy indicates the formation of flat terrace-like surfaces, while in situ optical observations demonstrate the reversible plating and stripping. DFT calculations reveal that the large reconstruction of the Zn-(101) surface with DMSO and H2O adsorption to lower the interface energy is the main driving force for surface preference. Raman, XPS, and ToF-SIMS characterizations are performed to unveil the surface SEI components. Exceptional electrochemical performance is demonstrated for the (101)-inclined Zn metal anode in a half cell, which could cycle for 200 h with a low overpotential (<50 mV). The Zn||V2O full cells are assembled, showing much better cycle performance for the 5 µm (101)-inclined Zn metal anode as compared to the commercialized 10 µm Zn metal foil, with a maximum specific capacity of 359 mAh/g and >170 mAh/g after over 300 cycles. We hope this study will spur further interest in the control of surface crystallographic orientation for a stable ultrathin Zn metal anode.

Multifunctional Protein Hybrid Nanoplatform for Synergetic Photodynamic-Chemotherapy of Malignant Carcinoma by Homologous Targeting Combined with Oxygen Transport.

Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti-tumor treatment. In addition, central nervous system neoplasm-targeted nanoplatforms are urgently required. To address these issues, a new multi-functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP-TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione-responsive disulfide bond. Mechanistically, ODP-TH crosses the blood-brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down-regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia-inducible factor-1-α (HIF-1α). The results reveal that ODP-TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP-TH achieves a more efficient tumor-inhibiting effect. This study not only overcomes the hypoxia-related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi-functional targeted and intensive anti-tumor nanoplatform.

The therapeutic efficacy and safety of intravenous immunoglobulin in dermatomyositis and polymyositis: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of dermatomyositis (DM) and polymyositis (PM). METHODS: We searched PubMed, Embase, and the China National Knowledge Infrastructure for relevant studies from July 1919 to May 2021. RESULTS: Seventeen papers pertinent to our questions were found: In a meta-analysis, we found that IVIG significantly improved the level of CK (SMD (STD. Mean Difference) = -0.69; 95%CI -0.93, -0.46; P < 0.0001), Manual Muscle Test (SMD = 1.12; 95%CI 0.77, 1.47; P < 0.00001), Medical Research Council (SMD = 1.59; 95%CI 0.86, 2.33; P < 0.00001), Activities of Daily Living (SMD = 1.07; 95%CI 0.59, 1.56; P < 0.0001). The CK levels in DM and PM were also significantly improved after IVIG (SMD = -0.73; 95%CI -1.12, -0.34; P = 0.0002 and SMD = -3.29; 95%CI -5.82, -0.76; P < 0.0001, respectively). The meta-analysis of three RCTs showed that there was a statistically significant improvement after IVIG (SMD = 0.63; 95%CI 0.22, 1.03; P = 0.002). In a random effects model, pooled muscle power improvement rate was 77% (95% CI: 66.0-87.0%). Meta-analyses of IVIG as first-line therapy showed a significant improvement of the CK level (SMD = -0.71; 95%CI -1.12, -0.30; P = 0.0007). The polled improvement rate of oesophageal disorders was 88% (95% CI: 80.0-95.0%). There was no statistically significant difference in the rate of improvement between the number of courses <2 and ≥2 (0.80% vs. 0.80%, P = 0.9). The proportion of corticosteroid-sparing success reached 81.8%. Adverse reactions following IVIG administration are usually mild and transient. Seven patients developed serious adverse events. CONCLUSION: IVIG seems to be an effective drug for DM/PM, improving muscle strength, CK levels, and oesophageal involvement, and it is well tolerated by patients.

A glycosylation-related gene signature predicts prognosis, immune microenvironment infiltration, and drug sensitivity in glioma.

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype-Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)-regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy.