Sesquiterpenoids and steroids from Eupatorium fortunei and their inhibitory effects on NO production.

Two heterodimers including a clovane-phenylpropanoid hybrid (1) and a clovane-menthane hybrid (2), five linear sesquiterpenoids incorporating a tetrahydrofuran ring (3-6 & 8), and four steroids (7 & 9-11), were separated from the ethanolic extract of a well-known aromatic and medicinal herb Eupatorium fortunei. Their structures were characterised by detailed analyses of spectroscopic data and comparison with known analogues, with seven (1-7) of them being described for the first time. The hybrids 1 and 2 represent the first examples of clovane type sesquiterpenoids hybridising with other class of natural products, and compounds 3-6 and 8 are first linear sesquiterpenyl constituents reported from the title species. All the isolates were evaluated for their inhibitory effect on the NO production induced by LPS in murine RAW264.7 macrophage cells, and 1, 7, 10 and 11 exhibited moderate activity with IC50 values in the range of 24.4-43.5 µM.

Bilateral synchronous double primary lung cancer: A case report.

Key Clinical Message: Bilateral synchronous double primary lung cancer (sDPLC) is a rare disease in clinics. This study analyzed the clinical data of a patient with bilateral sDPLC, aiming to improve medical workers' understanding of the disease and avoid missed diagnosis and misdiagnosis. Abstract: A 68-year-old male was admitted to the hospital with "intermittent cough and expectoration for two months." Enhanced chest computed tomography (CT) showed that the upper lobe of the left lung had a mass of high-density shadow, bronchial opening of the left lobe was thickened, lumen was narrow, and middle lobe of the right lung had a mass of high-density shadow. Bronchoscopy was performed to observe the microscopic characteristics of the lesions in the upper lobe of the left lung, and abnormal mucosa was biopsied. The pathological and immunohistochemical results confirmed that it was small cell lung cancer (SCLC) in the upper lobe of the left lung. Considering the occupation of the middle lobe of the right lung, CT-guided lung biopsy was performed, and the pathological and immunohistochemical results confirmed that it was moderately differentiated squamous cell carcinoma (SCC) in the middle lobe of the right lung. Clinicians should strengthen their understanding of sDPLC and focus on the imaging characteristics of chest CT and performance under bronchoscopy. Additionally, it is necessary to perform both CT-guided lung biopsy and bronchoscopy to obtain histopathological findings for the diagnosis.

Hierarchical and reconfigurable interfibrous interface of bioinspired Bouligand structure enabled by moderate orderliness.

Introducing natural Bouligand structure into synthetics is expected to develop high-performance structural materials. Interfibrous interface is critical to load transfer, and mechanical functionality of bioinspired Bouligand structure yet receives little attention. Here, we propose one kind of hierarchical and reconfigurable interfibrous interface based on moderate orderliness to mechanically reinforce bioinspired Bouligand structure. The interface imparted by moderate alignment of adaptable networked nanofibers hierarchically includes nanofiber interlocking and hydrogen-bonding (HB) network bridging, being expected to facilitate load transfer and structural stability through dynamic adjustment in terms of nanofiber sliding and HB breaking-reforming. As one demonstration, the hierarchical and reconfigurable interfibrous interface is constructed based on moderate alignment of networked bacterial cellulose nanofibers. We show that the resultant bioinspired Bouligand structural material exhibits unusual strengthening and toughening mechanisms dominated by interface-microstructure multiscale coupling. The proposed interfibrous interface enabled by moderate orderliness would provide mechanical insight into the assembly of widely existing networked nanofiber building blocks toward high-performance macroscopic bioinspired structural assemblies.

Alveoli-Inspired Carbon Cathodes with Interconnected Porous Structure and Asymmetric Coordinated Vanadium Sites for Superior Li-S Batteries.

Accelerating sulfur conversion catalysis to alleviate the shuttle effect has become a novel paradigm for effective Li-S batteries. Although nitrogen-coordinated metal single-atom (M-N4) catalysts have been investigated, further optimizing its utilization rate and catalytic activities is urgently needed for practical applications. Inspired by the natural alveoli tissue with interconnected structure and well-distributed enzyme catalytic sites on the wall for the simultaneously fast diffusion and in-situ catalytic conversion of substrates, here, we proposed the controllable synthesis of bioinspired carbon cathode with interconnected porous structure and asymmetric coordinated V-S1N3 sites for efficient and stable Li-S batteries. The enzyme-mimetic V-S1N3 shows asymmetric electronic distribution and high tunability, therefore enhancing in-situ polysulfide conversion activities. Experimental and theoretical results reveal that the high charge asymmetry degree and large atom radius of S in V-S1N3 result in sloping adsorption for polysulfide, thereby exhibiting low thermodynamic energy barriers and long-range stability (0.076% decay over 600 cycles).

[Establishment and Evaluation Strategy of an in vitro Cell Model of Bone Marrow Microenvironment Injury in Mouse Acute Graft-Versus-Host Disease].

OBJECTIVE: To establish a mesenchymal stem cell（MSC）-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease (aGVHD). METHODS: Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors, and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients. The recipient mouse received a lethal dose (8.0 Gy,72.76 cGy/min) of total body γ irradiation, and injected with donor mouse derived bone marrow cells (1×107/mouse) in 6-8 hours post irradiation to establish a bone marrow transplantation (BMT) mouse model (n=20). In addition, the recipient mice received a lethal dose (8.0 Gy,72.76 cGy/min) of total body γ irradiation, and injected with donor mouse derived bone marrow cells (1×107/mouse) and spleen lymphocytes (2×106/mouse) in 6-8 hours post irradiation to establish a mouse aGVHD model (n=20). On the day 7 after modeling, the recipient mice were anesthetized and the blood was harvested post eyeball enucleation. The serum was collected by centrifugation. Mouse MSCs were isolated and cultured with the addition of 2%, 5%, and 10% recipient serum from BMT group or aGVHD group respectively. The colony-forming unit-fibroblast（CFU-F) experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC. The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining. In addition, the expression of self-renewal-related genes including Oct-4, Sox-2, and Nanog in MSC was detected by real-time fluorescence quantitative PCR（RT-qPCR). RESULTS: We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD. CFU-F assay showed that, on day 7 after the culture, compared with the BMT group, MSC colony formation ability of aGVHD serum concentrations groups of 2% and 5% was significantly reduced （P < 0．05）; after the culture, at day 14, compared with the BMT group, MSC colony formation ability in different aGVHD serum concentration was significantly reduced （P < 0．05）. The immunofluorescence staining showed that, compared with the BMT group, the proportion of MSC surface molecules CD29+ and CD105+ cells was significantly dereased in the aGVHD serum concentration group (P < 0.05), the most significant difference was at a serum concentration of 10% （P < 0．001, P < 0.01）. The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4, Sox-2, and Nanog was decreased, the most significant difference was observed at an aGVHD serum concentration of 10% （P < 0.01,P < 0．001,P < 0．001）. CONCLUSION: By co-culturing different concentrations of mouse aGVHD serum and mouse MSC, we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability, which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Super-Stretchable and High-Energy Micro-Pseudocapacitors Based on MXene Embedded Ag Nanoparticles.

The advancement of aqueous micro-supercapacitors offers an enticing prospect for a broad spectrum of applications, spanning from wearable electronics to micro-robotics and sensors. Unfortunately, conventional micro-supercapacitors are characterized by low capacity and slopy voltage profiles, limiting their energy density capabilities. To enhance the performance of these devices, the use of 2D MXene-based compounds has recently been proposed. Apart from their capacitive contributions, these structures can be loaded with redox-active nanowires which increase their energy density and stabilize their operation voltage. However, introducing rigid nanowires into MXene films typically leads to a significant decline in their mechanical properties, particularly in terms of flexibility. To overcome this issue, super stretchable micro-pseudocapacitor electrodes composed of MXene nanosheets and in situ reconstructed Ag nanoparticles (Ag-NP-MXene) are herein demonstrated, delivering high energy density, stable operation voltage of ≈1 V, and fast charging capabilities. Careful experimental analysis and theoretical simulations of the charging mechanism of the Ag-NP-MXene electrodes reveal a dual nature charge storage mechanism involving ad(de)sorption of ions and conversion reaction of Ag nanoparticles. The superior mechanical properties of synthesized films obtained through in situ construction of Ag-NP-MXene structure show an ultra stretchability, allowing the devices to provide stable voltage and energy output even at 100% elongation.

Effect of extreme high temperature on cognitive function at different time scales: A national difference-in-differences analysis.

BACKGROUND: Mounting evidence has demonstrated that high temperature was associated with adverse health outcomes, especially morbidity and mortality. Nonetheless, the impact of extreme high temperature on cognitive performance, which is the fundamental capacity for interpreting one's surroundings, decision-making, and acquiring new abilities, has not been thoroughly investigated. METHODS: We aimed to assess associations between extreme high temperature at different time scales and poor cognitive function. We used longitudinal survey data from the three waves of data from China Family Panel Study, providing an 8-year follow-up of 53,008 participants from China. We assessed temperature and extreme high temperature exposure for each participant based on the residential area and date of cognitive test. We defined the proportion of days/hours above 32 °C as the metric of the exposure to extreme high temperature. Then we used generalized additive model and difference-in-differences approach to explore the associations between extreme high temperature and cognitive function. RESULTS: Our results demonstrated that either acute exposure or long-term exposure to extreme high temperature was associated with cognitive decline. At hourly level, 0-1 hour acute exposure to extreme high temperature would induce -0.93 % (95 % CI: -1.46 %, -0.39 %) cognitive change. At annual level, 10 percentage point increase in the hours proportion exceeding 32 °C in the past two years induced -9.87 % (95 % CI: -13.99 %, -5.75 %) cognitive change. Furthermore, subgroup analyses indicated adaptation effect: for the same 10 percentage increase in hours proportion exceeding 32 °C, people in warmer areas had cognitive change of -6.41 % (-11.22 %, -1.61 %), compared with -15.30 % (-21.07 %, -9.53 %) for people in cool areas. CONCLUSION: Our results demonstrated that extreme high temperature was associated with reduced cognitive function at hourly, daily and annual levels, warning that people should take better measures to protect the cognitive function in the context of climate change.

Constructing the metabolic network of wheat kernels based on structure-guided chemical modification and multi-omics data.

Metabolic network construction plays a pivotal role in unraveling the regulatory mechanism of biological activities, although it often proves to be challenging and labor-intensive, particularly with non-model organisms. In this study, we develop a computational approach that employs reaction models based on structure-guided chemical modification and related compounds to construct a metabolic network in wheat. This construction results in a comprehensive structure-guided network, including 625 identified metabolites and additional 333 putative reactions compared with the Kyoto Encyclopedia of Genes and Genomes database. Using a combination of gene annotation, reaction classification, structure similarity, and transcriptome and metabolome analysis correlations, a total of 229 potential genes related to these reactions are identified within this network. To validate the network, the functionality of a hydroxycinnamoyltransferase (TraesCS3D01G314900) for the synthesis of polyphenols and a rhamnosyltransferase (TraesCS2D01G078700) for the modification of flavonoids are verified through in vitro enzymatic studies and wheat mutant tests, respectively. Our research thus supports the utility of structure-guided chemical modification as an effective tool in identifying causal candidate genes for constructing metabolic networks and further in metabolomic genetic studies.

Heat stroke-induced cerebral cortex nerve injury by mitochondrial dysfunction: A comprehensive multi-omics profiling analysis.

In recent years, global warming has led to frequent instances of extremely high temperatures during summer, arousing significant concern about the adverse effects of high temperature. Among these, heat stroke is the most serious, which has detrimental effects on the all organs of human body, especially on brain. However, the comprehensive pathogenesis leading to brain damage remains unclear. In this study, we constructed a mouse model of heat stroke and conducted multi-omics profiling to identify relevant pathogenesis induced by heat stroke. The mice were placed in a constant temperature chamber at 42 °C with a humidity of 50 %, and the criteria for success in modeling were that the rectal temperature reached 42 °C and that the mice were trembling. Then the mice were immediately taken out for further experiments. Firstly, we conducted cFos protein localization and identified the cerebral cortex, especially the anterior cingulate cortex as the region exhibiting the most pronounced damage. Secondly, we performed metabolomics, transcriptomics, and proteomics analysis on cerebral cortex. This multi-omics investigation unveiled noteworthy alterations in proteins and metabolites within pathways associated with neurotransmitter systems, heatstroke-induced mitochondrial dysfunction, encompassing histidine and pentose phosphate metabolic pathways, as well as oxidative stress. In addition, the cerebral cortex exhibited pronounced Reactive Oxygen Species (ROS) production, alongside significant downregulation of the mitochondrial outer membrane protein Tomm40 and mitochondrial permeability transition pore, implicating cerebral cortex mitochondrial dysfunction as the primary instigator of neural impairment. This study marks a significant milestone as the first to employ multi-omics analysis in exploring the molecular mechanisms underlying heat stroke-induced damage in cerebral cortex neurons. It comprehensively identifies all potentially impacted pathways by heat stroke, laying a solid foundation for ensuing research endeavors. Consequently, this study introduces a fresh angle to clinical approaches in heatstroke prevention and treatment, as well as establishes an innovative groundwork for shaping future-forward environmental policies.

Anti-inflammatory Polyketides from an Endophytic Fungus Chaetomium sp. UJN-EF006 of Vaccinium bracteatum.

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.

Non-invasive load monitoring based on deep learning to identify unknown loads.

With the rapid development of smart grids, society has become increasingly urgent to solve the problems of low energy utilization efficiency and high energy consumption. In this context, load identification has become a key element in formulating scientific and effective energy consumption plans and reducing unnecessary energy waste. However, traditional load identification methods mainly focus on known electrical equipment, and accurate identification of unknown electrical equipment still faces significant challenges. A new encoding feature space based on Triplet neural networks is proposed in this paper to detect unknown electrical appliances using convex hull coincidence degree. Additionally, transfer learning is introduced for the rapid updating of the pre-classification model's self-incrementing class with the unknown load. In experiments, the effectiveness of our method is successfully tested on the PLAID dataset. The accuracy of unknown load identification reached 99.23%. Through this research, we expect to bring a new idea to the field of load identification to meet the urgent need for the identification of unknown electrical appliances in the development of smart grids.

Research on Time Series Monitoring of Surface Deformation in Tongliao Urban Area Based on SBAS-PS-DS-InSAR.

As urban economies flourish and populations become increasingly concentrated, urban surface deformation has emerged as a critical factor in city planning that cannot be overlooked. Surface deformation in urban areas can lead to deformations in structural supports of infrastructure such as road bases and bridges, thereby posing a serious threat to public safety and creating significant safety hazards. Consequently, research focusing on the monitoring of urban surface deformation holds paramount importance. Interferometric synthetic aperture radar (InSAR), as an important means of earth observation, has all-day, wide-range, high-precision, etc., characteristics and is widely used in the field of surface deformation monitoring. However, traditional solitary InSAR techniques are limited in their application scenarios and computational characteristics. Additionally, the manual selection of ground control points (GCPs) is fraught with errors and uncertainties. Permanent scatterers (PS) can maintain high interferometric coherence in man-made building areas, and distributed scatterers (DS) usually show moderate coherence in areas with short vegetation; the combination of DS and PS solves the problem of manually selecting GCPs during track re-flattening and regrading, which affects the monitoring results. In this paper, 45 Sentinel-1B data from 16 February 2019 to 14 December 2021 are used as the data source in the urban area of Horqin District, Tongliao City, Inner Mongolia Autonomous Region, for example. A four-threshold (coherence coefficient threshold, FaSHPS adaptive threshold, amplitude divergence index threshold, and deformation velocity interval) GCPs point screening method for PS-DS, as well as a Small Baseline Subset-Permanent Scatterers-Distributed Scatterers-Interferometric Synthetic Aperture Radar (SBAS-PS-DS-InSAR) method for selecting PS and DS points as ground control points for orbit refinement and re-flattening, are proposed. The surface deformation results obtained using the Small Baseline Subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) and the SBAS-PS-DS-InSAR proposed in this paper were comparatively analysed and verified. The maximum cumulative line-of-sight settlements were -90.78 mm and -83.68 mm, and the maximum cumulative uplifts are 74.94 mm and 97.56 mm, respectively; the maximum annual average line-of-sight settlements are -35.38 mm/y and -30.38 mm/y, and the maximum annual average uplifts are 25.27 mm/y and 27.92 mm/y. The results were evaluated and analysed in terms of correlation, mean absolute error (MAE), and root mean square error (RMSE). The deformation results of the two InSAR methods were evaluated and analysed in terms of correlation, MAE, and RMSE. The errors show that the Pearson correlation coefficients between the vertical settlement results obtained using the SBAS-PS-DS-InSAR method and the GPS monitoring results were closer to 1. The maximum MAE and RMSE were 13.7625 mm and 14.8004 mm, respectively, which are within the acceptable range; this confirms that the monitoring results of the SBAS-PS-DS-InSAR method were better than those of the original SBAS-InSAR method. SBAS-InSAR method, which is valid and reliable. The results show that the surface deformation results obtained using the SBAS-InSAR, SBAS-PS-DS-InSAR, and GPS methods have basically the same settlement locations, extents, distributions, and temporal and spatial settlement patterns. The deformation results obtained using these two InSAR methods correlate well with the GPS monitoring results, and the MAE and RMSE are within acceptable limits. By comparing the deformation information obtained using multiple methods, the surface deformation in urban areas can be better monitored and analysed, and it can also provide scientific references for urban municipal planning and disaster warning.

Imbalance Between Angiotensin II and Kallikrein in Patients With ST-Segment Elevation Myocardial Infarction: A Case-Control Emergency Room Study.

The present study aimed to investigate the balance between angiotensin II (Ang-II) and kallikrein (KLK1) in the pathogenesis of ST-segment elevation acute myocardial infarction (STEMI). The study included a total of 261 participants: 151 STEMI patients and 110 individuals with normal coronary arteries. The plasma levels of Ang-II and KLK1 were measured using enzyme-linked immunosorbent assays (ELISA). Multivariate logistic regression analysis indicated that the plasma levels of Ang-II, KLK1 and the ratio of Ang-II and KLK1 (Ang-II/KLK1) independently correlated with the presence of STEMI. Furthermore, we found independent associations between STEMI and smoking, cholesterol (CHO), high-density lipoprotein cholesterol (HDL-c), as well as age. The ratio of Ang-II/KLK1 correlated with the plasma level of the inflammatory cytokine, interleukin-6 (IL-6). Both Ang-II and KLK1 levels are significantly elevated in patients with STEMI. An increased Ang-II/KLK1 ratio may result in the over-activation of Ang-II and exacerbate the progression of STEMI(P = .046). In conclusion, we have demonstrated, for the first time, an Ang-II and KLK1 imbalance in patients with STEMI.

Case report: enzyme replacement therapy for Fabry disease presenting with proteinuria and ventricular septal thickening.

Fabry disease (FD) is an uncommon, X-linked, lysosomal storage disease that causes defects in the glycosphingolipid metabolic pathway due to deficient or absent lysosomal α-galactosidase (α-Gal A) activity. This leads to the accumulation of globotriaosylceramide (GL-3) within lysosomes in a wide range of cells, including endothelial, cardiac, renal, and corneal cells, and consequently, the progressive appearance of clinical symptoms in target organs. Enzyme replacement therapy (ERT), which involves the exogenous supplementation of α-Gal A enzyme and has been successfully administered for treating FD.Here, we report a case of a 37-year-old male with complaints of recurrent proteinuria and ventricular septal thickening. A renal biopsy revealed vacuolization and foamy changes in podocytes, and the presence of myelin-like bodies and zebra bodies. The white blood cell α-Gal A activity was very low, while the Lyso-GL-3 level was high. Additionally, genetic analysis revealed a gene variant c.902G > A p. Arg301Gln. The patient was diagnosed with FD, and subsequently received intravenous ERT with a dose of Agalsidase α (0.2 mg/kg, 17.5 mg every 2 weeks). Currently, the values of proteinuria and ventricular septum thickness remain stable during the 6-month follow-up. Initiating ERT at an early age can effectively decrease the deposition of GL-3, attenuate the progressive clinical manifestations of FD, and provide greater long-term benefits.

Biomimetic Multimodal Receptors for Comprehensive Artificial Human Somatosensory System.

Electronic skin (e-skin) capable of acquiring environmental and physiological information has attracted interest for healthcare, robotics, and human-machine interaction. However, traditional 2D e-skin only allows for in-plane force sensing, which limits access to comprehensive stimulus feedback due to the lack of out-of-plane signal detection caused by its 3D structure. Here, a dimension-switchable bioinspired receptor is reported to achieve multimodal perception by exploiting film kirigami. It offers the detection of in-plane (pressure and bending) and out-of-plane (force and airflow) signals by dynamically inducing the opening and reclosing of sensing unit. The receptor's hygroscopic and thermoelectric properties enable the sensing of humidity and temperature. Meanwhile, the thermoelectric receptor can differentiate mechanical stimuli from temperature by the voltage. The development enables a wide range of sensory capabilities of traditional e-skin and expands the applications in real life.

Preparation of a New Type of Iron-Based Polymer Hydrogel for Mining and Its Firefighting Performance.

To address the issue of coal self-ignition in mining areas, a water-based gel was developed using carboxymethyl cellulose sodium (CMC), ferric citrate, and glucono-delta-lactone as raw materials. The gel's gelation time was found to be controllable, and the system viscosity exhibited a threshold between 2.5 and 3% CMC content. Compared to water, the gel showed improved thermal stability by 26-31% for different formulations. The addition of the gel reduced CO emissions from coal by 31.3% within the temperature range of 80-220 °C, and it also decreased the reactivity of functional groups in coal molecules, resulting in a 1.7-37.7% increase in coal's activation energy. In simulated fire extinguishing experiments, the gel effectively adhered to the surface of the coal seam, forming an oxygen isolation film, and significantly enhanced the cooling and extinguishing effect compared to water.

Polyoxometalate-Structured Materials: Molecular Fundamentals and Electrocatalytic Roles in Energy Conversion.

Polyoxometalates (POMs), a kind of molecular metal oxide cluster with unique physical-chemical properties, have made essential contributions to creating efficient and robust electrocatalysts in renewable energy systems. Due to the fundamental advantages of POMs, such as the diversity of molecular structures and large numbers of redox active sites, numerous efforts have been devoted to extending their application areas. Up to now, various strategies of assembling POM molecules into superstructures, supporting POMs on heterogeneous substrates, and POMs-derived metal compounds have been developed for synthesizing electrocatalysts. From a multidisciplinary perspective, the latest advances in creating POM-structured materials with a unique focus on their molecular fundamentals, electrocatalytic roles, and the recent breakthroughs of POMs and POM-derived electrocatalysts, are systematically summarized. Notably, this paper focuses on exposing the current states, essences, and mechanisms of how POM-structured materials influence their electrocatalytic activities and discloses the critical requirements for future developments. The future challenges, objectives, comparisons, and perspectives for creating POM-structured materials are also systematically discussed. It is anticipated that this review will offer a substantial impact on stimulating interdisciplinary efforts for the prosperities and widespread utilizations of POM-structured materials in electrocatalysis.

Macrophage barrier in the tumor microenvironment and potential clinical applications.

The tumor microenvironment (TME) constitutes a complex microenvironment comprising a diverse array of immune cells and stromal components. Within this intricate context, tumor-associated macrophages (TAMs) exhibit notable spatial heterogeneity. This heterogeneity contributes to various facets of tumor behavior, including immune response modulation, angiogenesis, tissue remodeling, and metastatic potential. This review summarizes the spatial distribution of macrophages in both the physiological environment and the TME. Moreover, this paper explores the intricate interactions between TAMs and diverse immune cell populations (T cells, dendritic cells, neutrophils, natural killer cells, and other immune cells) within the TME. These bidirectional exchanges form a complex network of immune interactions that influence tumor immune surveillance and evasion strategies. Investigating TAM heterogeneity and its intricate interactions with different immune cell populations offers potential avenues for therapeutic interventions. Additionally, this paper discusses therapeutic strategies targeting macrophages, aiming to uncover novel approaches for immunotherapy. Video Abstract.

Comparative Efficacy of Augmenting Escitalopram with Modified Electroconvulsive Therapy or High-Frequency Repetitive Transcranial Magnetic Stimulation on Depressive Symptoms, Quality of Life, and Cognitive Function in Treatment-Resistant Depression.

Treatment-resistant depression (TRD) poses significant therapeutic challenges despite available interventions. Escitalopram (ESC) is a highly selective antidepressant. This study aimed to compare ESC alone and ESC combined with modified electroconvulsive therapy (MECT) or high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in TRD patients. Ninety participants were randomized into ESC alone, ESC + MECT, and ESC + HF-rTMS groups. Notable differences were observed in Hamilton Depression Rating Scale (HDRS-17) scores at 12 weeks among ESC (14.37), ESC + MECT (10.27), and ESC + HF-rTMS (10.77) groups (P = 0.006). In terms of overall quality of life (QoL) evaluated using the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) at 12 weeks, the ESC, ESC + MECT, and ESC + HF-rTMS groups scored 2, 3, and 3.5, respectively. ESC + MECT/HF-rTMS groups showed reduced depressive symptoms compared to the ESC group, accompanied by higher overall QoL scores and increased satisfaction with health. Patients receiving ESC + MECT demonstrated no significant alterations in short-term memory and orientation, as measured by the Montreal Cognitive Assessment (MoCA), before and after treatment. Moreover, a decline in language was observed compared to baseline (12 weeks: median 2, IQR 2-3; baseline: median 1, IQR 1-3; P = 0.022). The positive impact of ESC with HF-rTMS on cognitive function was evidenced by improvements in all domines MoCA.Combining ESC with MECT or HF-rTMS exhibited enhanced effectiveness in alleviating depressive symptoms and enhancing QoL compared to ESC monotherapy. Specifically, the ESC + HF-rTMS combination displayed potential as a comprehensive treatment strategy for TRD, addressing both emotional and cognitive aspects.

Microgel-based carriers enhance skeletal stem cell reprogramming towards immunomodulatory phenotype in osteoarthritic therapy.

Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+ and Grem1+ SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+ SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC, which further suppressed the expression of TNF-ɑ, IL-1ß and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.