Lanthanum doping and surface Li3BO3 passivating layer enabling 4.8 V nickel-rich layered oxide cathodes toward high energy lithium-ion batteries.

Single crystalline Ni-rich layered oxide cathodes show high energy density and low cost, have been regarded as one of the most promising candidates for next generation lithium-ion batteries (LIBs). Extending the cycling voltage window will significantly improve the energy density, however, suffers from bulk structural and interfacial chemistry degradation, leading to rapidly cycle performance deterioration. Here, we propose a dual-modification strategy to synthesize La doping and Li3BO3 (LBO) coating layers modified LiNi0.8Co0.1Mn0.1O2 (NCM811) by a facile one-step heating treatment processing. In-situ EIS and XRD, ex-situ XPS techniques are applied to demonstrate that the La diffused amorphous domains and Li3BO3 passivating layers dampen the lattice distortion, enhance the interfacial chemistry behavior as well as lithium ion transportation kinetics. Specifically, surface La doping amorphous domains successfully suppress the intense lattice stress and volume changes induced by the phase transitions during lithiation/delithiation, thus avoiding the intergranular crack and enhancing the mechanical stability of the material. Moreover, the LBO layer formed by the consumption of residual lithium prevents successive parasitic reactions at the interface as well as provides rapid Li-ion diffusion channels. Furthermore, the coating layer also diminishes the residual lithium compounds, increasing the atmosphere stability and safety of LIBs. Consequently, the La doping and LBO coating NCM811 exhibits an exceptional initial specific capacity (230.6 mAh/g) at 0.5C under a high cutoff voltage of 4.8 V, and a 73.8 % capacity retention following 100 cycles. In addition, a superior specific capacity of 133.8 mAh/g is provided even at a high current density (4C). Our work paves a promising road to tackle the integral structure deterioration and interfacial instability of Ni-rich cathodes.

Mitotic Functions and Characters of KIF11 in Cancers.

Mitosis mediates the accurate separation of daughter cells, and abnormalities are closely related to cancer progression. KIF11, a member of the kinesin family, plays a vital role in the formation and maintenance of the mitotic spindle. Recently, an increasing quantity of data have demonstrated the upregulated expression of KIF11 in various cancers, promoting the emergence and progression of cancers. This suggests the great potential of KIF11 as a prognostic biomarker and therapeutic target. However, the molecular mechanisms of KIF11 in cancers have not been systematically summarized. Therefore, we first discuss the functions of the protein encoded by KIF11 during mitosis and connect the abnormal expression of KIF11 with its clinical significance. Then, we elucidate the mechanism of KIF11 to promote various hallmarks of cancers. Finally, we provide an overview of KIF11 inhibitors and outline areas for future work.

Squamous cell carcinoma of the cystic duct: A case report and literature review.

RATIONALE: Pure squamous cell carcinoma (SCC) of the gallbladder is a rare malignant biliary tract tumor predominantly found in the body and neck of the gallbladder. However, its occurrence in the cystic duct is even rarer. Given its rarity, no established guidelines or consensus currently exist regarding the treatment of pure SCC of the gallbladder. We report an unusual case of SCC originating from the cystic duct with the intent of providing insights into the therapeutic approach for this type of malignancy. PATIENT CONCERNS: A male patient presented to our hospital with acute cholecystitis. Unexpectedly, imaging revealed gallbladder malignancy. DIAGNOSES: Pathologic examination after surgery confirmed SCC of the cystic duct. INTERVENTIONS: Despite elevated bilirubin levels, we were able to exclude hilar involvement, enabling radical tumor resection. Intraoperatively, we discovered that the tumor was located in the cystic duct, a site associated with a high likelihood of invasion into neighboring organs. The tumor demonstrated a predominantly exophytic growth pattern, which prompted us to refrain from extending the resection range, thereby striking a balance between complete tumor removal and surgical trauma. We performed liver wedge resection only to ensure a negative resection margin while preserving the anatomical structure to the greatest extent possible. Postoperative recovery was rapid and uncomplicated. Pathological examination confirmed pure SCC, which led us to initiate a regimen of nab-paclitaxel and cisplatin, which is known to be effective in other organ SCCs. Remarkably, the patient experienced a rare and severe posttreatment cardiovascular event. Consequently, we switched the patient to a chemotherapy regimen of gemcitabine and cisplatin, which ultimately yielded positive clinical outcomes. OUTCOMES: no evidence of tumor recurrence was observed within 1 year after surgery. LESSONS: The diagnosis and therapeutic strategy for rare tumors such as gallbladder SCC should be meticulously tailored based on their unique characteristics to optimize postoperative patient outcomes.

A marginal structural model analysis for the effect modification by education on the association between cancer diagnosis history and major depressive symptoms: Findings from Midlife Development in the U.S. (MIDUS).

BACKGROUND: Limited research has employed a longitudinal approach to investigate the role of education level as an effect modifier on the relationship between cancer diagnosis history and the experience of major depressive disorder (MDD) with a nationally representative sample. METHODS: We harnessed data from three installments of the MIDUS Longitudinal study (n = 7108). A Marginal Structural Model facilitated the investigation of associations between a history of cancer diagnosis, MDD, and potential modifying effects of education level. Inverse probability weighting helped manage confounding factors. RESULTS: Findings indicated that a cancer diagnosis made one year prior was linked with 3.741 times greater odds of experiencing MDD (95 % CI: 1.411-9.918, p < 0.01). This connection was absent for diagnoses made two years earlier. Among individuals with education up to high school, a recent cancer diagnosis significantly increased the likelihood of MDD in the subsequent wave by 3.45 times (95 % CI: 1.31-9.08, p < 0.05). This pattern was not apparent among better-educated individuals. LIMITATIONS: As the exposure variable was dependent on self-reported questionnaires, recall bias could be a potential limitation. Moreover, unaccounted variables like genetic factors could introduce confounding. CONCLUSIONS: A recent cancer diagnosis, particularly among less educated individuals, correlated with an increased probability of MDD, while the impact was not observed for older diagnoses. These findings emphasize that the timing of a cancer diagnosis and education level need consideration in the mental health assessment of cancer survivors.

An overview of meta-analyses on radiomics: more evidence is needed to support clinical translation.

OBJECTIVE: To conduct an overview of meta-analyses of radiomics studies assessing their study quality and evidence level. METHODS: A systematical search was updated via peer-reviewed electronic databases, preprint servers, and systematic review protocol registers until 15 November 2022. Systematic reviews with meta-analysis of primary radiomics studies were included. Their reporting transparency, methodological quality, and risk of bias were assessed by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 checklist, AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews, version 2) tool, and ROBIS (Risk Of Bias In Systematic reviews) tool, respectively. The evidence level supporting the radiomics for clinical use was rated. RESULTS: We identified 44 systematic reviews with meta-analyses on radiomics research. The mean ± standard deviation of PRISMA adherence rate was 65 ± 9%. The AMSTAR-2 tool rated 5 and 39 systematic reviews as low and critically low confidence, respectively. The ROBIS assessment resulted low, unclear and high risk in 5, 11, and 28 systematic reviews, respectively. We reperformed 53 meta-analyses in 38 included systematic reviews. There were 3, 7, and 43 meta-analyses rated as convincing, highly suggestive, and weak levels of evidence, respectively. The convincing level of evidence was rated in (1) T2-FLAIR radiomics for IDH-mutant vs IDH-wide type differentiation in low-grade glioma, (2) CT radiomics for COVID-19 vs other viral pneumonia differentiation, and (3) MRI radiomics for high-grade glioma vs brain metastasis differentiation. CONCLUSIONS: The systematic reviews on radiomics were with suboptimal quality. A limited number of radiomics approaches were supported by convincing level of evidence. CLINICAL RELEVANCE STATEMENT: The evidence supporting the clinical application of radiomics are insufficient, calling for researches translating radiomics from an academic tool to a practicable adjunct towards clinical deployment.

Trends in estrogen and progesterone receptors in prostate cancer: a bibliometric analysis.

Introduction: The bibliometric analysis aims to identify research trends in estrogen receptor (ERs) and progesterone receptor (PRs) in prostate cancer (PCa), and also discuss the hotspots and directions of this field. Methods: 835 publications were sourced from the Web of Science database (WOS) from 2003 to 2022. Citespace, VOSviewer, and Bibliometrix were used for the bibliometric analysis. Results: The number of published publications increased in early years, but declined in the last 5 years. The United States was the leading country in citations, publications, and top institutions. Prostate and Karolinska Institutet were the most publications of journal and institution, respectively. Jan-Ake Gustafsson was the most influential author based on the number of citations/publications. The most cited paper was "Estrogen receptors and human disease" by Deroo BJ, published in the Journal of Clinical Investigation. The most frequently used keywords were PCa (n = 499), gene-expression (n = 291), androgen receptor (AR) (n = 263), and ER (n = 341), while ERb (n = 219) and ERa (n = 215) further emphasized the importance of ER. Conclusions: This study provides useful guidance that ERa antagonists, ERb agonists, and the combination of estrogen with androgen deprivation therapy (ADT) will potentially serve as a new treatment strategy for PCa. Another interesting topic is relationships between PCa and the function and mechanism of action of PRs subtypes. The outcome will assist scholars in gaining a comprehensive understanding of the current status and trends in the field, and provide inspiration for future research.

Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation.

Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and in vitro ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.

Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials.

Denosumab, a fully humanized monoclonal neutralizing antibody, inhibits activation of the RANK/RANKL/OPG signaling pathway through competitive binding with RANKL, thereby inhibiting osteoclast-mediated bone resorption. Denosumab inhibits bone loss; therefore, it is used to treat metabolic bone diseases (including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis), in clinical practice. Since then, multiple effects of denosumab have been discovered. A growing body of evidence suggests that denosumab has a variety of pharmacological activities and broad potential in clinical diseases such as osteoarthritis, bone tumors, and other autoimmune diseases. Currently, Denosumab is emerging as a treatment for patients with malignancy bone metastases, and it also shows direct or indirect anti-tumor effects in preclinical models and clinical applications. However, as an innovative drug, its clinical use for bone metastasis of malignant tumors is still insufficient, and its mechanism of action needs to be further investigated. This review systematically summarizes the pharmacological mechanism of action of denosumab and the current understanding and clinical practice of the use of denosumab for bone metastasis of malignant tumors to help clinicians and researchers deepen their understanding of denosumab.

Survey on human milk feeding and enteral feeding practices for very-low-birth-weight infants in NICUs in China Neonatal Network.

BACKGROUND: The breastfeeding rate in China is lower than that in many other countries and the extent of adoption of the "Feeding Recommendations for Preterm Infants and Low Birth Weight Infants" guideline in NICUs remains unclear. METHOD: A web-based survey about the current status of human milk feeding and enteral feeding practices at NICUs was sent to all China Neonatal Network's cooperation units on September 7, 2021, and the respondents were given a month to send their responses. RESULTS: All sixty NICUs responded to the survey, the reply rate was 100%. All units encouraged breastfeeding and provided regular breastfeeding education. Thirty-six units (60.0%) had a dedicated breastfeeding/pumping room, 55 (91.7%) provided kangaroo care, 20 (33.3%) had family rooms, and 33 (55.0%) routinely provided family integrated care. Twenty hospitals (33.3%) had their own human milk banks, and only 13 (21.7%) used donor human milk. Eight units (13.3%) did not have written standard nutrition management guidelines for infants with body weight < 1500 g. Most units initiated minimal enteral nutrition with mother's milk for infants with birth weight ˂1500 g within 24 h after birth. Fifty NICUs (83.3%) increased the volume of enteral feeding at 10-20 ml/kg daily. Thirty-one NICUs (51.7%) assessed gastric residual content before every feeding session. Forty-one NICUs (68.3%) did not change the course of enteral nutrition management during drug treatment for patent ductus arteriosus, and 29 NICUs (48.3%) instated NPO for 1 or 2 feeds during blood transfusion. CONCLUSION: There were significant differences in human milk feeding and enteral feeding strategies between the NICUs in CHNN, but also similarities. The data obtained would be useful in the establishment of national enteral feeding guidelines for preterm infants and quality improvement of cooperation at the national level.

Taraxasterol Inhibits Tumor Growth by Inducing Apoptosis and Modulating the Tumor Microenvironment in Non-Small Cell Lung Cancer.

Taraxasterol (TAX), one of the active components in Dandelion, demonstrated strong antitumor properties in several cancers. However, the effect and underlying mechanism of TAX in non-small cell lung cancer (NSCLC) is unclear. In this study, we showed that TAX inhibited the proliferation of cells by inducing S-phase cell cycle arrest and prevented cell migration by interfering epithelial-mesenchymal transition (EMT) in Lewis lung cancer (LLC) cells and lung carcinoma SPC-A1 cells. The pharmacological network analysis predicted that induction of apoptosis might be the potential mechanism of TAX-mediated cell deaths. Further in vitro experiments showed that TAX could significantly induce cancer cell apoptosis as verified by increased pro-apoptotic molecules including Bax, caspase-9, and PARP1 downregulated anti-apoptotic protein Bcl-2; and decreased mitochondrial potential. The LLC subcutaneous tumor model demonstrated that TAX inhibited tumor growth by induction of apoptosis and inhibition of proliferation in vivo, which is consistent with the in vitro data. Importantly, TAX administration downregulated the proportion of Treg cells and upregulated CD107a+ NK cells in the tumor microenvironment in the tumor model. Together, these data reveal that TAX performs its antitumor effect by inducing apoptosis and modulating the tumor microenvironment, providing evidence that TAX could serve as a potential natural drug for lung cancer therapy.

Modified Qing' e Pills exerts anti-osteoporosis effects and prevents bone loss by enhancing type H blood vessel formation.

Objective: To explore whether the modified Qing' e Pills (MQEP) exerts anti-osteoporotic effects and prevents bone loss by enhancing angiogenesis. Methods: Network pharmacology was used to assess whether MQEP has a pro-angiogenic capacity and to predict its potential targets. Human umbilical vein endothelial cells were treated with glucocorticoids and MQEP to assess cell viability. The expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor, and angiotensin converting enzyme, which are associated with the activation of the renin-angiotensin-aldosterone system, and the expression of vascular endothelial growth factor and hypoxia-inducible factor 1 alpha, which are associated with the formation of type H blood vessels, were examined by western blot and RT-qPCR. Thereafter, the glucocorticoid-induced osteoporosis model was established and intervened with MQEP. Femur scanning was performed with micro-computed tomography; trabecular spacing, trabecular thickness, and trabecular number were observed and calculated; the expression of nuclear factor-kappa B ligand and osteoprotegerin was detected by ELISA, and the ratio was calculated to evaluate the degree of bone resorption. Finally, type H blood vessels that were highly coupled to osteogenic cells were identified by immunohistochemistry staining and flow cytometry. Results: This is the first study to reveal and confirm that MQEP could prevent bone loss in glucocorticoid-induced osteoporosis by promoting the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, which are highly associated with type H blood vessel formation. In vitro experiments confirmed that MQEP could effectively promote the proliferation of vascular endothelial cells and alleviate glucocorticoids-induced activation of the renin-angiotensin-aldosterone system, thereby reducing vascular injury. Conclusion: MQEP exerts anti-osteoporosis effects and prevents bone loss by alleviating vascular injury caused by renin-angiotensin-aldosterone system activation and promoting type H blood vessel formation.

The analysis of Modified Qing' E Formula on the differential expression of exosomal miRNAs in the femoral head bone tissue of mice with steroid-induced ischemic necrosis of femoral head.

Objective: To investigate the differential expression of exosomal miRNAs in the bone marrow tissue of Modified Qing' E Formula (MQEF) on steroid-induced ischemic necrosis of the femoral head (INFH) model. Methods: Steroid hormones were used to establish the INFH model and treated with MQEF. After successful modeling, femoral tissue exosomes were isolated for miRNA sequencing to obtain femoral tissue exosomal differential miRNAs. By GO analysis and KEGG analysis of the differential genes in both groups, the major exosomal miRNAs of MQEF exerting anti-INFH as well as the major signaling pathways were identified. Next, a quantitative metabolomic validation of MQEF with broad targeting was performed to obtain the main active components of MQEF and to perform biological analysis and signaling pathway prediction of the active components by network pharmacology. Finally, the sequencing results were validated by using RT-qPCR. The results of miRNA sequencing were verified by double examination of network pharmacology and RT-qPCR, and the exosomal miRNAs regulated by the anti-INFH effect of MQEF and the specific signaling pathway of the effect were clarified. Results: A total of 65,389 target genes were predicted in the exosomes of two groups of mice, and 18 significant differentially expressed miRNAs were obtained, of which 14 were up-regulated and 4 down-regulated. GO enrichment analysis showed that these predicted target genes were enriched in 12371 biological processes, 1727 cell components, and 4112 molecular functions. KEGG analysis showed that the predicted miRNA target genes were annotated to 342 signal pathways, in which the highly enriched pathways closely related to bone metabolism were PI3K-Akt signal pathway, MAPK signal pathway, and Wnt signal pathway. The most significantly up-regulated miRNAs were miR-185-3p and miR-1b-5p and the most significantly down-regulated miRNAs were miR-129b-5p and miR-223-5p, of which the targeted genes were closely related to the PI3K-Akt signal pathway. MQEF aqueous decoction extract targeted metabolomics quantitatively combined with network pharmacology predicted targets also closely related to PI3K-Akt signaling pathway. Real-time quantitative PCR validation showed that miR-185-3p was up-regulated 7.2-fold and miR-129b-5p was down-regulated 2.2-fold in the treatment group, and the difference was significant (P < 0.05). Conclusions: MQEF can regulate exosomal miRNA expression in steroid-induced INFH models, miR-185-3p or miR-129b-5p/PI3K-Akt signal axis may be part of the mechanism of MQEF against steroid-induced INFH.

A multimodal iPSC platform for cystic fibrosis drug testing.

Cystic fibrosis is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of CFTR using established animal and cell-based models led to the recent discovery of effective modulators for most individuals with CF. However, a subset of individuals with CF do not respond to these modulators and there is an urgent need to develop novel therapeutic strategies. In this study, we generate a panel of airway epithelial cells using induced pluripotent stem cells from individuals with common or rare CFTR variants representative of three distinct classes of CFTR dysfunction. To measure CFTR function we adapt two established in vitro assays for use in induced pluripotent stem cell-derived airway cells. In both a 3-D spheroid assay using forskolin-induced swelling as well as planar cultures composed of polarized mucociliary airway epithelial cells, we detect genotype-specific differences in CFTR baseline function and response to CFTR modulators. These results demonstrate the potential of the human induced pluripotent stem cell platform as a research tool to study CF and in particular accelerate therapeutic development for CF caused by rare variants.

Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy.

On the basis of the synergism of topoisomerase (Top) and histone deacetylase (HDAC) inhibitors in antitumor therapy, a series of novel Top/HDAC dual inhibitors were designed and synthesized by the pharmacophore fusion strategy. After systematic structure-activity relationship studies, lead compound 16j was identified to simultaneously inhibit both Top and HDAC with good potency, which showed potent antiproliferative activities with a broad spectrum. Mechanistic studies indicated that compound 16j efficiently induced apoptosis with S cell-cycle arrest in HEL cancer cells. It was orally active in HEL xenograft models and exhibited excellent in vivo antitumor efficacy (TGI = 68.5%; 10 mg/kg). Altogether, this work highlights the therapeutic potential of evodiamine-inspired Top/HDAC dual inhibitors and provides a valuable lead compound for the development of novel antitumor agents for leukemia therapy.

A new biomechanical classification system for split fractures of the humeral greater tuberosity: guidelines for surgical treatment.

BACKGROUND: Split fractures of the humeral greater tuberosity (HGT) are common injuries. Although there are numerous surgical treatments for these fractures, no classification system combining clinical and biomechanical characteristics has been presented to guide the choice of fixation method. METHODS: We created a standardised fracture of the HGT in 24 formalin-fixed cadavers. Six were left as single-fragment fractures (Group A), six were further prepared to create single-fragment with medium size full-thickness rotator cuff tear (FT-RCT) fractures (Group B), six were cut to create multi-fragment fractures (Group C), and six were cut to create multi-fragment with FT-RCT fractures (Group D). Each specimen was fixed with a shortened proximal humeral internal locking system (PHILOS) plate. The fixed fractures were subjected to load and load-to-failure tests and the differences between groups analysed. RESULTS: The mean load-to-failure values were significantly different between groups (Group A, 446.83 ± 38.98 N; Group B, 384.17 ± 36.15 N; Group C, 317.17 ± 23.32 N and Group D, 266.83 ± 37.65 N, P < 0.05). The load-to-failure values for fractures with a greater tuberosity displacement of 10 mm were significantly different between each group (Group A, 194.00 ± 29.23 N; Group B, 157.00 ± 29.97 N; Group C, 109.00 ± 17.64 N and Group D, 79.67.83 ± 15.50 N; P < 0.05). These findings indicate that fractures with a displacement of 10 mm have different characteristics and should be considered separately from other HGT fractures when deciding surgical treatment. CONCLUSIONS: Biomechanical classification of split fractures of the HGT is a reliable method of categorising these fractures in order to decide surgical treatment. Our findings and proposed system will be a useful to guide the choice of surgical technique for the treatment of fractures of the HGT.

Magnetothermal regulation of in vivo protein corona formation on magnetic nanoparticles for improved cancer nanotherapy.

Engineering the protein corona (PC) on nanodrugs is emerging as an effective approach to improve their pharmacokinetics and therapeutic efficacy, but conventional in vitro pre-programmed methods have shown great limitation for regulation of the PC in the complex and dynamic in vivo physiological environment. Here, we demonstrate an magnetothermal regulation approach that allows us to in situ modulate the in vivo PC composition on iron oxide nanoparticles for improved cancer nanotherapy. Experimental results revealed that the relative levels of major opsonins and dysopsonins in the PC can be tuned quantitatively by means of heat induction mediated by the nanoparticles under an alternating magnetic field. When the PC was magnetically optimized in vivo, the nanoparticles exhibited prolonged circulation and enhanced tumor delivery efficiency in mice, 2.53-fold and 2.02-fold higher respectively than the control. This led to a superior thermotherapeutic efficacy of systemically delivered nanoparticles. In vivo magnetothermal regulation of the PC on nanodrugs will find wide applications in biomedicine.

Expression of long non-coding RNA LUCAT1 in patients with chronic obstructive pulmonary disease and its potential functions in regulating cigarette smoke extract-induced 16HBE cell proliferation and apoptosis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), characterized by persistent airflow limitation, was a disease mediated by a combination of inflammatory factors, immune cells, and immune mediators. COPD was an inflammatory and autoimmune disease involving T-lymphocytes triggered by cigarette smoke and other factors that progressively affected the bronchi, lung parenchyma, and pulmonary blood vessels. LncRNAs were reported to be implicated in COPD pathogenesis and development. METHODS: Non-smokers, smokers (non-COPD), and COPD patients were randomly selected in an established COPD surveillance cohort. Demographic and clinical information of all subjects were collected. Pulmonary function was measured by post-bronchodilator testing. qRT-PCR and ELISA assays were performed to detect the expression levels of lncRNA LUCAT1, miR-181a-5p, and inflammatory cytokines. An in vitro exposure model was constructed using cigarette smoke extract (CSE)-induced human bronchial epithelial (16HBE) cells. The dual-luciferase reporter and RNA pull-down assays were used to detect the binding relationship between lncRNA LUCAT1 and miR-181a-5p; meanwhile, Spearman's correlation assay was used to verify the correlation between lncRNA LUCAT1 and miR-181a-5p. Afterward, the lncRNA LUCAT1 silencing plasmid was constructed and co-transfected with a miR-181a-5p inhibitor to evaluate the effects on CSE-induced 16HBE cell proliferation and apoptosis. Finally, a Western blot assay was utilized to determine the mechanism of lncRNA LUCAT1/miR-181a-5p/Wnt/ß-catenin axis in COPD. RESULTS: LncRNA LUCAT1 was upregulated in the serums of COPD patients. Correlation analysis further confirmed the strong correlation between LUCAT1 expression and inflammatory cytokines IL-1ß, IL-6, and TNF-α. Receiver operating characteristic (ROC) analysis verified the potential of LUCAT1 in COPD diagnosis. After treatment with CSE, LUCAT1 was significantly increased while its target miR-181a-5p was decreased in 16HBE cells. Cell proliferation and apoptosis assays showed that LUCAT1 silencing alleviated CSE's effects on 16HBE cell proliferation and apoptosis. Mechanically, rescue assays demonstrated that miR-181a-5p inhibition could partially counteract the impact of LUCAT1 on COPD progression through the Wnt/ß-catenin pathway. CONCLUSIONS: LncRNA LUCAT1 may be a valuable indicator for differentiating COPD. Moreover, LncRNA LUCAT1/miR-181-5p/Wnt/ß-catenin axis behaved as a critical role in COPD development, shedding new sights for clinical treatment.

Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition.

Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts more than 70,000 people. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most important determinant of morbidity and mortality. Here we report results from a multi-institute consortium in which single-cell transcriptomics were applied to define disease-related changes by comparing the proximal airway of CF donors (n = 19) undergoing transplantation for end-stage lung disease with that of previously healthy lung donors (n = 19). Disease-dependent differences observed include an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subsets coupled with an unexpected decrease in cycling basal cells. Our study yields a molecular atlas of the proximal airway epithelium that will provide insights for the development of new targeted therapies for CF airway disease.