Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade.

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.

Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.

Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.

Salience Interest Option: Temporal abstraction with salience interest functions.

Reinforcement Learning (RL) is a significant machine learning subfield that emphasizes learning actions based on environment to obtain optimal behavior policy. RL agents can make decisions at variable time scales in the form of temporal abstractions, also known as options. The issue of discovering options has seen a considerable research effort. Most notably, the Interest Option Critic (IOC) algorithm first extends the initial set to the interest function, providing a method for learning options specialized to certain state space regions. This approach offers a specific attention mechanism for action selection. Unfortunately, this method still suffers from the classic issues of poor data efficiency and lack of flexibility in RL when learning options end-to-end through backpropagation. This paper proposes a new approach called Salience Interest Option Critic (SIOC), which chooses subsets of existing initiation sets for RL. Specifically, these subsets are not learned by backpropagation, which is slow and tends to overfit, but through particle filters. This approach enables the rapid and flexible identification of critical subsets using only reward feedback. We conducted experiments in discrete and continuous domains, and our proposed method demonstrate higher efficiency and flexibility than other methods. The generated options are more valuable within a single task and exhibited greater interpretability and reusability in multi-task learning scenarios.

The Real-World Data on Patients With Cardiac Stage IIIb AL Amyloidosis.

BACKGROUND: Morbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in patients with cardiac stage IIIb, but the real-world data on these patients is still limited. PATIENTS AND METHODS: A retrospective analysis was conducted on 77 patients diagnosed with cardiac stage IIIb AL amyloidosis at our center. We analyzed the clinical characteristics, treatment and outcome of the patients. RESULTS: The median age of patients was 57 years and 49.4% were male. Median serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were 13,384 ng/L and 0.166 ug/L, and 42 (54.5%) patients had heart failure at diagnosis. Fifty-seven (74.0%) patients received antiplasma cell treatment, and the main treatment options include bortezomib or thalidomide combined with dexamethasone. The hematologic overall response rate was 70% (28/40), and at 6-month landmark analysis, patients with hematologic responses had a higher survival rate. Cardiac and renal responses were achieved in 14 (37.8%) and 13 (32.5%) patients, respectively. After a median follow-up of 10 months (range 1-115 months), median overall survival (OS) was 18 months, and the estimated survival rates at 3, 6, and 12 months were 79.9%, 75.6%, and 54.5%, respectively. In Cox regression models, age, hypotension and cTnT were independently predictive of mortality after adjusting for heart failure. CONCLUSION: The hematologic, cardiac and renal responses were relative lower in patients with cardiac stage IIIb AL amyloidosis. The overall prognosis of patients was poor, and age, hypotension, and cTnT can be used to predict mortality.

Metabolic reprogramming of tumor-associated macrophages using glutamine antagonist JHU083 drives tumor immunity in myeloid-rich prostate and bladder cancer tumors.

Glutamine metabolism in tumor microenvironments critically regulates anti-tumor immunity. Using glutamine-antagonist prodrug JHU083, we report potent tumor growth inhibition in urologic tumors by JHU083-reprogrammed tumor-associated macrophages (TAMs) and tumor-infiltrating monocytes (TIMs). We show JHU083-mediated glutamine antagonism in tumor microenvironments induces TNF, pro-inflammatory, and mTORC1 signaling in intratumoral TAM clusters. JHU083-reprogrammed TAMs also exhibit increased tumor cell phagocytosis and diminished pro-angiogenic capacities. In vivo inhibition of TAM glutamine consumption resulted in increased glycolysis, a broken TCA cycle, and purine metabolism disruption. Although the anti-tumor effect of glutamine antagonism on tumor-infiltrating T cells was moderate, JHU083 promoted a stem cell-like phenotype in CD8+ T cells and decreased Treg abundance. Finally, JHU083 caused a ubiquitous shutdown in glutamine utilizing metabolic pathways in tumor cells, leading to reduced HIF-1alpha, c-MYC phosphorylation, and induction of tumor cell apoptosis, all key anti-tumor features.

Accountability analysis of health benefits related to National Action Plan on Air Pollution Prevention and Control in China.

China is one of the largest producers and consumers of coal in the world. The National Action Plan on Air Pollution Prevention and Control in China (2013-2017) particularly aimed to reduce emissions from coal combustion. Here, we show whether the acute health effects of PM2.5 changed from 2013 to 2018 and factors that might account for any observed changes in the Beijing-Tianjin-Hebei (BTH) and the surrounding areas where there were major reductions in PM2.5 concentrations. We used a two-stage analysis strategy, with a quasi-Poisson regression model and a random effects meta-analysis, to assess the effects of PM2.5 on mortality in the 47 counties of BTH. We found that the mean daily PM2.5 levels and the SO42- component ratio dramatically decreased in the study period, which was likely related to the control of coal emissions. Subsequently, the acute effects of PM2.5 were significantly decreased for total and circulatory mortality. A 10 µg/m3 increase in PM2.5 concentrations was associated with a 0.16% (95% CI: 0.08, 0.24%) and 0.02% (95% CI: -0.09, 0.13%) increase in mortality from 2013 to 2015 and from 2016 to 2018, respectively. The changes in air pollution sources or PM2.5 components appeared to have played a core role in reducing the health effects. The air pollution control measures implemented recently targeting coal emissions taken in China may have resulted in significant health benefits.

Severe flood modulates the sources and age of dissolved organic carbon in the Yangtze River Estuary.

Floods in global large rivers modulate the transport of dissolved organic carbon (DOC) and estuarine hydrological characteristics significantly. This study investigated the impact of a severe flood on the sources and age of DOC in the Yangtze River Estuary (YRE) in 2020. Comparing the flood period in 2020 to the non-flood period in 2017, we found that the flood enhanced the transport of young DOC to the East China Sea (ECS), resulting in significantly enriched Δ14C-DOC values. During the flood period, the proportion of modern terrestrial organic carbon (OC) was significantly higher compared to the non-flood period. Conversely, the proportion of pre-aged sediment OC was significantly lower during the flood period. The high turbidity associated with the flood facilitated rapid transformation and mineralization of sedimentary and fresh terrestrial OC, modifying the sources of DOC. The flux of modern terrestrial OC transported to the ECS during the flood period was 1.58 times higher than that of the non-flood period. These findings suggest that floods can modulate the sources and decrease the age of DOC, potentially leading to increased greenhouse gas emissions. Further research is needed to understand the long-term impacts of floods on DOC dynamics in global estuaries.

Multi-omics reveal the gut microbiota-mediated severe foraging environment adaption of small wild ruminants in the Three-River-Source National Park, China.

The Tibetan antelope (Pantholops hodgsonii), blue sheep (Pseudois nayaur), and Tibetan sheep (Ovis aries) are the dominant small ruminants in the Three-River-Source National Park (TRSNP). However, knowledge about the association between gut microbiota and host adaptability remains poorly understood. Herein, multi-omics sequencing approaches were employed to investigate the gut microbiota-mediated forage adaption in these ruminants. The results revealed that although wild ruminants (WR) of P. hodgsoni and P. nayaur were faced with severe foraging environments with significantly low vegetation coverage and nutrition, the apparent forage digestibility of dry matter, crude protein, and acid detergent fiber was significantly higher than that of O. aries. The 16s rRNA sequencing showed that the gut microbiota in WR underwent convergent evolution, and alpha diversity in these two groups was significantly higher than that in O. aries. Moreover, indicator species, including Bacteroidetes and Firmicutes, exhibited positive relationships with apparent forage digestibility, and their relative abundances were enriched in the gut of WR. Enterotype analysis further revealed that enterotype 1 belonged to WR, and the abundance of fatty acid synthesis metabolic pathway-related enzyme genes was significantly higher than enterotype 2, represented by O. aries. Besides, the metagenomic analysis identified 14 pathogenic bacterial species, among which 10 potentially pathogenic bacteria were significantly enriched in the gut microbiota of O. aries. Furthermore, the cellulolytic strains and genes encoding cellulase and hemicellulase were significantly enriched in WR. In conclusion, our results provide new evidence of gut microbiota to facilitate wildlife adaption in severe foraging environments of the TRSNP, China.

Discovery of Potent, Selective, and Orally Available IRE1α Inhibitors Demonstrating Comparable PD Modulation to IRE1 Knockdown in a Multiple Myeloma Model.

The lack of selective and safe in vivo IRE1α tool molecules has limited the evaluation of IRE1α as a viable target to treat multiple myeloma. Focus on improving the physicochemical properties of a literature compound by decreasing lipophilicity, molecular weight, and basicity allowed the discovery of a novel series with a favorable in vitro safety profile and good oral exposure. These efforts culminated in the identification of a potent and selective in vivo tool compound, G-5758, that was well tolerated following multiday oral administration of doses up to 500 mg/kg. G-5758 demonstrated comparable pharmacodynamic effects to induced IRE1 knockdown as measured by XBP1s levels in a multiple myeloma model (KMS-11).

Socioeconomic characteristics, cancer mortality, and universal health coverage: A global analysis.

BACKGROUND: Achieving universal health coverage (UHC) involves all individuals attaining accessible health interventions at an affordable cost. We examined current patterns and temporal trends of cancer mortality and UHC across sociodemographic index (SDI) settings, and quantified these association. METHODS: We used data from the Global Burden of Disease Study 2019 and Our World in Data. The UHC effective coverage index was obtained to assess the potential population health gains delivered by health systems. The estimated annual percentage change (EAPC) with a 95% confidence interval (CI) was calculated to quantify the trend of cancer age-standardized mortality rate (ASMR). A generalized linear model was applied to estimate the association between ASMR and UHC. FINDINGS: The high (EAPC = -0.9% [95% CI, -1.0%, -0.9%]) and high-middle (-0.9% [-1.0%, -0.8%]) SDI regions had the fastest decline in ASMR (per 100,000) for total cancers from 1990 to 2019. The overall UHC effective coverage index increased by 27.9% in the high-SDI quintile to 62.2% in the low-SDI quintile. A negative association was observed between ASMR for all-cancer (adjusted odds ratio [OR] = 0.87 [0.76, 0.99]), stomach (0.73 [0.56, 0.95]), breast (0.64 [0.52, 0.79]), cervical (0.42 [0.30, 0.60]), lip and oral cavity (0.55 [0.40, 0.75]), and nasopharynx (0.42 [0.26, 0.68]) cancers and high UHC level (the lowest as the reference). CONCLUSIONS: Our findings strengthen the evidence base for achieving UHC to improve cancer outcomes. FUNDING: This work is funded by the China National Natural Science Foundation and Chinese Academy of Medical Sciences Innovation Fund for Medical Science.

Subtype-WGME enables whole-genome-wide multi-omics cancer subtyping.

We present an innovative strategy for integrating whole-genome-wide multi-omics data, which facilitates adaptive amalgamation by leveraging hidden layer features derived from high-dimensional omics data through a multi-task encoder. Empirical evaluations on eight benchmark cancer datasets substantiated that our proposed framework outstripped the comparative algorithms in cancer subtyping, delivering superior subtyping outcomes. Building upon these subtyping results, we establish a robust pipeline for identifying whole-genome-wide biomarkers, unearthing 195 significant biomarkers. Furthermore, we conduct an exhaustive analysis to assess the importance of each omic and non-coding region features at the whole-genome-wide level during cancer subtyping. Our investigation shows that both omics and non-coding region features substantially impact cancer development and survival prognosis. This study emphasizes the potential and practical implications of integrating genome-wide data in cancer research, demonstrating the potency of comprehensive genomic characterization. Additionally, our findings offer insightful perspectives for multi-omics analysis employing deep learning methodologies.

Predicting the association of different levels of physical activity on postoperative pulmonary complications using the international physical activity questionnaire in patients undergoing thoracoscopic lung surgery under general anaesthesia: protocol for a prospective cohort study.

INTRODUCTION: Postoperative pulmonary complications (PPCs) occur frequently in patients undergoing lung surgery under general anaesthesia and are strongly associated with longer postoperative hospital stays and increased mortality. The existing literature has shown that a higher level of preoperative physical activity (PA) plays a positive role in the low incidence of postoperative complications and the quality of life in patients undergoing lung surgery. However, the association between preoperative PA levels and the incidence of PPCs has rarely been studied, particularly in thoracoscopic lung surgery. This study aims to evaluate PA levels in patients undergoing thoracoscopic lung surgery using the International Physical Activity Questionnaire and to investigate the association between PA levels and the incidence of PPCs. METHODS AND ANALYSIS: A total of 204 participants aged 18-80 years undergoing thoracoscopic lung surgery (thoracoscopic wedge resection, thoracoscopic segmentectomy and thoracoscopic lobectomy) will be included in the study. The primary outcome is the incidence of PPCs within the first 5 postoperative days. The secondary outcomes include the number of PPCs, the incidence of PPCs 1 month postoperatively, the arterial blood levels of inflammatory markers, the incidence of postoperative adverse events within the first 5 postoperative days, extubation time, unplanned admission to the intensive care unit, postoperative length of stay and mortality 1 month postoperatively. ETHICS AND DISSEMINATION: The study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Shandong First Medical University on 31 March 2022 (YXLL-KY-2022(014)) and is registered at ClinicalTrials.gov. We plan to disseminate the data and findings of this study in international and peer-reviewed journals. TRIAL REGISTRATION NUMBER: The trial has been prospectively registered at the clinicaltrials.gov registry (NCT05401253).

Effect of Antioxidants in Medicinal Products on Intestinal Drug Transporters.

The presence of mutagenic and carcinogenic N-nitrosamine impurities in medicinal products poses a safety risk. While incorporating antioxidants in formulations is a potential mitigation strategy, concerns arise regarding their interference with drug absorption by inhibiting intestinal drug transporters. Our study screened thirty antioxidants for inhibitory effects on key intestinal transporters-OATP2B1, P-gp, and BCRP in HEK-293 cells (OATP2B1) or membrane vesicles (P-gp, BCRP) using 3H-estrone sulfate, 3H-N-methyl quinidine, and 3H-CCK8 as substrates, respectively. The screen identified that butylated hydroxyanisole (BHA) and carnosic acid inhibited all three transporters (OATP2B1, P-gp, and BCRP), while ascorbyl palmitate (AP) inhibited OATP2B1 by more than 50%. BHA had IC50 values of 71 ± 20 µM, 206 ± 14 µM, and 182 ± 49 µM for OATP2B1, BCRP, and P-gp, respectively. AP exhibited IC50 values of 23 ± 10 µM for OATP2B1. The potency of AP and BHA was tested with valsartan, an OATP2B1 substrate, and revealed IC50 values of 26 ± 17 µM and 19 ± 11 µM, respectively, in HEK-293-OATP2B1 cells. Comparing IC50 values of AP and BHA with estimated intestinal concentrations suggests an unlikely inhibition of intestinal transporters at clinical concentrations of drugs formulated with antioxidants.

Molecular Design Based on Integer Programming and Splitting Data Sets by Hyperplanes.

A novel framework for designing the molecular structure of chemical compounds with a desired chemical property has recently been proposed. The framework infers a desired chemical graph by solving a mixed integer linear program (MILP) that simulates the computation process of two functions: a feature function defined by a two-layered model on chemical graphs and a prediction function constructed by a machine learning method. To improve the learning performance of prediction functions in the framework, we design a method that splits a given data set C into two subsets C(i),i=1,2 by a hyperplane in a chemical space so that most compounds in the first (resp., second) subset have observed values lower (resp., higher) than a threshold θ. We construct a prediction function ψ to the data set C by combining prediction functions ψi,i=1,2 each of which is constructed on C(i) independently. The results of our computational experiments suggest that the proposed method improved the learning performance for several chemical properties to which a good prediction function has been difficult to construct.

Correlations of FCGR2A 131R/H and FCGR3A 158V/F Polymorphisms with the Susceptibility of Peri-implantitis in Chinese Han Population.

The purpose of the study is to investigate the relationship of peri-implantitis (PI) with FCGR2A and FCGR3A gene polymorphisms. One hundred and forty-four patients with PI and 136 patients without PI infection were selected. Gingival crevicular fluid samples were collected from the two groups. The FCGR2A and FCGR3A polymorphism in the two groups were measured. All volunteers were evaluated for periodontal status. The effect of polymorphisms on PI susceptibility was investigated by chi-square analysis and logistic regression. The frequency of FCGR2A rs1801274 GG genotype of PI group was higher than that of the control group, while the GA and AA genotype carriers were less in PI group. After adjusting for other clinical indicators, rs1801274 GA genotype, AA genotype, and the A allele were still negatively correlated with the onset of PI. FCGR3A rs396991 polymorphism was not associated with PI. FCGR2A rs1801274 polymorphism was significantly associated with PI in the Chinese Han population, and GG genotype might be a genetic risk factor for PI.

Transcriptomic analysis of epicardial adipose tissue reveals the potential crosstalk genes and immune relationship between type 2 diabetes mellitus and atrial fibrillation.

BACKGROUND: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. METHOD: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. RESULTS: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. CONCLUSION: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes.

Multi-resource dynamic coordinated planning of flexible distribution network.

The flexible distribution network presents a promising architecture to accommodate highly integrated distributed generators and increasing loads in an efficient and cost-effective way. The distribution network is characterised by flexible interconnections and expansions based on soft open points, which enables it to dispatch power flow over the entire system with enhanced controllability and compatibility. Herein, we propose a multi-resource dynamic coordinated planning method of flexible distribution network that allows allocation strategies to be determined over a long-term planning period. Additionally, we establish a probabilistic framework to address source-load uncertainties, which mitigates the security risks of voltage violations and line overloads. A practical distribution network is adopted for flexible upgrading based on soft open points, and its cost benefits are evaluated and compared with that of traditional planning approaches. By adjusting the acceptable violation probability in chance constraints, a trade-off between investment efficiency and operational security can be realised.

Compensation of small data with large filters for accurate liver vessel segmentation from contrast-enhanced CT images.

BACKGROUND: Segmenting liver vessels from contrast-enhanced computed tomography images is essential for diagnosing liver diseases, planning surgeries and delivering radiotherapy. Nevertheless, identifying vessels is a challenging task due to the tiny cross-sectional areas occupied by vessels, which has posed great challenges for vessel segmentation, such as limited features to be learned and difficult to construct high-quality as well as large-volume data. METHODS: We present an approach that only requires a few labeled vessels but delivers significantly improved results. Our model starts with vessel enhancement by fading out liver intensity and generates candidate vessels by a classifier fed with a large number of image filters. Afterwards, the initial segmentation is refined using Markov random fields. RESULTS: In experiments on the well-known dataset 3D-IRCADb, the averaged Dice coefficient is lifted to 0.63, and the mean sensitivity is increased to 0.71. These results are significantly better than those obtained from existing machine-learning approaches and comparable to those generated from deep-learning models. CONCLUSION: Sophisticated integration of a large number of filters is able to pinpoint effective features from liver images that are sufficient to distinguish vessels from other liver tissues under a scarcity of large-volume labeled data. The study can shed light on medical image segmentation, especially for those without sufficient data.

Carboxypeptidase M modulates BMSCs osteogenesis-adipogenesis via the MAPK/ERK pathway: An integrated single-cell and bulk transcriptomic study.

The pathogenesis of osteoporosis (OP) is closely associated with the disrupted balance between osteogenesis and adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). We analyzed published single-cell RNA sequencing (scRNA-seq) data to dissect the transcriptomic profiles of bone marrow-derived cells in OP, reviewing 56 377 cells across eight scRNA-seq datasets from femoral heads (osteoporosis or osteopenia n = 5, osteoarthritis n = 3). Seventeen genes, including carboxypeptidase M (CPM), were identified as key osteogenesis-adipogenesis regulators through comprehensive gene set enrichment, differential expression, regulon activity, and pseudotime analyses. In vitro, CPM knockdown reduced osteogenesis and promoted adipogenesis in BMSCs, while adenovirus-mediated CPM overexpression had the reverse effects. In vivo, intraosseous injection of CPM-overexpressing BMSCs mitigated bone loss in ovariectomized mice. Integrated scRNA-seq and bulk RNA sequencing analyses provided insight into the MAPK/ERK pathway's role in the CPM-mediated regulation of BMSC osteogenesis and adipogenesis; specifically, CPM overexpression enhanced MAPK/ERK signaling and osteogenesis. In contrast, the ERK1/2 inhibitor binimetinib negated the effects of CPM overexpression. Overall, our findings identify CPM as a pivotal regulator of BMSC differentiation, which provides new clues for the mechanistic study of OP.

A Critical Review on Recent Progress of Solution-Processed Monolayer Assembly of Nanomaterials and Applications.

The rapid development in nanotechnology has necessitated accurate and efficient assembly strategies for nanomaterials. Monolayer assembly of nanomaterials (MAN) represents a challenging and important architecture to manufacture and is critical in understanding interactions among nanomaterials, solvents, and substrates. MAN enables highly tunable performance in electronic and photonic devices. This review summarizes the recent progress on the methods to achieve MAN and discusses important control factors. Moreover, the importance of MAN is elaborated by a broad range of applications in electronics and photonics. In the end, the opportunities as well as challenges in manufacturing and new applications are outlooked.