Relevance and regulation of alternative splicing in plant secondary metabolism: current understanding and future directions.

The secondary metabolism of plants is an essential life process enabling organisms to navigate various stages of plant development and cope with ever-changing environmental stresses. Secondary metabolites, abundantly found in nature, possess significant medicinal value. Among the regulatory mechanisms governing these metabolic processes, alternative splicing stands out as a widely observed post-transcriptional mechanism present in multicellular organisms. It facilitates the generation of multiple mRNA transcripts from a single gene by selecting different splicing sites. Selective splicing events in plants are widely induced by various signals, including external environmental stress and hormone signals. These events ultimately regulate the secondary metabolic processes and the accumulation of essential secondary metabolites in plants by influencing the synthesis of primary metabolites, hormone metabolism, biomass accumulation, and capillary density. Simultaneously, alternative splicing plays a crucial role in enhancing protein diversity and the abundance of the transcriptome. This paper provides a summary of the factors inducing alternative splicing events in plants and systematically describes the progress in regulating alternative splicing with respect to different secondary metabolites, including terpenoid, phenolic compounds, and nitrogen-containing compounds. Such elucidation offers critical foundational insights for understanding the role of alternative splicing in regulating plant metabolism and presents novel avenues and perspectives for bioengineering.

Determination of the rat estrous cycle vased on EfficientNet.

In the field of biomedical research, rats are widely used as experimental animals due to their short gestation period and strong reproductive ability. Accurate monitoring of the estrous cycle is crucial for the success of experiments. Traditional methods are time-consuming and rely on the subjective judgment of professionals, which limits the efficiency and accuracy of experiments. This study proposes an EfficientNet model to automate the recognition of the estrous cycle of female rats using deep learning techniques. The model optimizes performance through systematic scaling of the network depth, width, and image resolution. A large dataset of physiological data from female rats was used for training and validation. The improved EfficientNet model effectively recognized different stages of the estrous cycle. The model demonstrated high-precision feature capture and significantly improved recognition accuracy compared to conventional methods. The proposed technique enhances experimental efficiency and reduces human error in recognizing the estrous cycle. This study highlights the potential of deep learning to optimize data processing and achieve high-precision recognition in biomedical research. Future work should focus on further validation with larger datasets and integration into experimental workflows.

A lightweight grape detection model in natural environments based on an enhanced YOLOv8 framework.

Grapefruit and stem detection play a crucial role in automated grape harvesting. However, the dense arrangement of fruits in vineyards and the similarity in color between grape stems and branches pose challenges, often leading to missed or false detections in most existing models. Furthermore, these models' substantial parameters and computational demands result in slow detection speeds and difficulty deploying them on mobile devices. Therefore, we propose a lightweight TiGra-YOLOv8 model based on YOLOv8n. Initially, we integrated the Attentional Scale Fusion (ASF) module into the Neck, enhancing the network's ability to extract grape features in dense orchards. Subsequently, we employed Adaptive Training Sample Selection (ATSS) as the label-matching strategy to improve the quality of positive samples and address the challenge of detecting grape stems with similar colors. We then utilized the Weighted Interpolation of Sequential Evidence for Intersection over Union (Wise-IoU) loss function to overcome the limitations of CIoU, which does not consider the geometric attributes of targets, thereby enhancing detection efficiency. Finally, the model's size was reduced through channel pruning. The results indicate that the TiGra-YOLOv8 model's mAP(0.5) increased by 3.33% compared to YOLOv8n, with a 7.49% improvement in detection speed (FPS), a 52.19% reduction in parameter count, and a 51.72% decrease in computational demand, while also reducing the model size by 45.76%. The TiGra-YOLOv8 model not only improves the detection accuracy for dense and challenging targets but also reduces model parameters and speeds up detection, offering significant benefits for grape detection.

Optics-free Spatial Genomics for Mapping Mouse Brain Aging.

Spatial transcriptomics has revolutionized our understanding of cellular network dynamics in aging and disease by enabling the mapping of molecular and cellular organization across various anatomical locations. Despite these advances, current methods face significant challenges in throughput and cost, limiting their utility for comprehensive studies. To address these limitations, we introduce IRISeq (Imaging R econstruction using Indexed Seq uencing), a optics-free spatial transcriptomics platform that eliminates the need for predefined capture arrays or extensive imaging, allowing for the rapid and cost-effective processing of multiple tissue sections simultaneously. Its capacity to reconstruct images based solely on sequencing local DNA interactions allows for profiling of tissues without size constraints and across varied resolutions. Applying IRISeq , we examined gene expression and cellular dynamics in thirty brain regions of both adult and aged mice, uncovering region-specific changes in gene expression associated with aging. Further cell type-centric analysis further identified age-related cell subtypes and intricate changes in cell interactions that are distinct to certain spatial niches, emphasizing the unique aspects of aging in different brain regions. The affordability and simplicity of IRISeq position it as a versatile tool for mapping region-specific gene expression and cellular interactions across various biological systems. One Sentence Summary: IRISeq , an innovative optics-free spatial transcriptomics method, uncovers aging-related changes in spatial gene expression and focal cell interactions in brain aging.

Real­world evidence of advanced non­small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy.

Immunotherapy is an effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Although clinical trials on immunotherapy have provided promising results, real-world research in clinical practice is needed to assess the effectiveness and safety of immunotherapy. The present study aimed to characterize real-world outcomes in patients with advanced NSCLC treated with immune checkpoint inhibitor (ICI)-based regimens. The medical records of patients with advanced NSCLC, who were treated with programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitors, were reviewed for data collection. The primary objectives were to evaluate progression-free survival (PFS) and overall survival (OS). Therefore, multiple Cox regression models were used to investigate the predictive factors for survival outcomes. Furthermore, survival curves for PFS and OS were created using Kaplan-Meier estimates and compared using the log-rank test. The present study included a total of 133 patients with advanced NSCLC who received therapy with ICIs between January 1, 2019 and December 31, 2022. The final follow-up date was August 24, 2023. The median PFS and OS times were 9.8 and 27.2 months, respectively. Univariate Cox regression analysis demonstrated that sex, clinical stage, PD-L1 status, previous systemic therapy, and brain and liver metastases were associated with PFS, while Eastern Cooperative Oncology Group (ECOG) status, clinical stage, PD-L1 status and brain metastasis were associated with OS. Furthermore, multivariate Cox regression analysis demonstrated that a PD-L1 tumor proportion score (TPS) of ≥50% was an indicator of favorable PFS and OS. An ECOG performance status score of ≥1 was also associated with poor OS but not with PFS. Furthermore, brain metastasis was an indicator for poor PFS and OS, while liver metastasis was only associated with a poor PFS. Finally, the results of the present study demonstrated that PD-L1 status was an independent predictor for PFS and OS in patients with advanced NSCLC, especially adenocarcinoma, who were treated with ICIs plus chemotherapy. The results also suggested that patients with a PD-L1 TPS of ≥50% could benefit when the aforementioned regimens were administrated as a first-line or later-line therapy.

Prediction of immunotherapy response of bladder cancer with a pyroptosis-related signature indicating tumor immune microenvironment.

Background: Although prognostic models based on pyroptosis-related genes (PRGs) have been constructed in bladder cancer (BLCA), the comprehensive impact of these genes on tumor microenvironment (TME) and immunotherapeutic response has yet to be investigated. Methods: Based on expression profiles of 52 PRGs, we utilized the unsupervised clustering algorithm to identify PRGs subtypes and ssGSEA to quantify immune cells and hallmark pathways. Moreover, we screened feature genes of distinct PRGs subtypes and validated the associations with immune infiltrations in tissue using the multiplex immunofluorescence. Univariate, LASSO, and multivariate Cox regression analyses were employed to construct the scoring scheme. Results: Four PRGs clusters were identified, samples in cluster C1 were infiltrated with more immune cells than those in others, implying a favorable response to immunotherapy. While the cluster C2, which shows an extremely low level of most immune cells, do not respond to immunotherapy. CXCL9/CXCL10 and SPINK1/DHSR2 were identified as feature genes of cluster C1 and C2, and the specimen with high CXCL9/CXCL10 was characterized by more CD8 + T cells, macrophages and less Tregs. Based on differentially expressed genes (DEGs) among PRGs subtypes, a predictive model (termed as PRGs score) including five genes (CACNA1D, PTK2B, APOL6, CDK6, ANXA2) was built. Survival probability of patients with low-PRGs score was significantly higher than those with high-PRGs score. Moreover, patients with low-PRGs score were more likely to benefit from anti-PD1/PD-L1 regimens. Conclusion: PRGs are closely associated with TME and oncogenic pathways. PRGs score is a promising indicator for predicting clinical outcome and immunotherapy response.

Resveratrol Inhibits Nasopharyngeal Carcinoma (NPC) by Targeting the MAPK Signaling Pathway.

BACKGROUND: With conventional cancer treatments facing limitations, interest in plant-derived natural products as potential alternatives is increasing. Although resveratrol has demonstrated antitumor effects in various cancers, its impact and mechanism on nasopharyngeal carcinoma remain unclear. OBJECTIVE: This study aimed to systematically investigate the anti-cancer effects of resveratrol on nasopharyngeal carcinoma using a combination of experimental pharmacology, network pharmacology, and molecular docking approaches. METHODS: CCK-8, scratch wound, and transwell assays were employed to confirm the inhibitory effect of resveratrol on the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. H&E and TUNEL stainings were used to observe the morphological changes and apoptosis status of resveratrol-treated cells. The underlying mechanisms were elucidated using a network pharmacology approach. Immunohistochemistry and Western blotting were utilized to validate key signaling pathways. RESULTS: Resveratrol inhibited the proliferation, invasion, and migration of nasopharyngeal carcinoma cells, ultimately inducing apoptosis in a time- and dose-dependent manner. Network pharmacology analysis revealed that resveratrol may exert its anti-nasopharyngeal carcinoma effect mainly through the MAPK pathway. Immunohistochemistry results from clinical cases showed MAPK signaling activation in nasopharyngeal carcinoma tissues compared to adjacent tissues. Western blotting validated the targeting effect of resveratrol, demonstrating significant inhibition of the MAPK signaling pathway. Furthermore, molecular docking supported its multi-target role with MAPK, TP53, PIK3CA, SRC, etc. Conclusion: Resveratrol has shown promising potential in inhibiting human nasopharyngeal carcinoma cells by primarily targeting the MAPK pathway. These findings position resveratrol as a potential therapeutic agent for nasopharyngeal carcinoma.

Predicting postacute phase anaemia after aneurysmal subarachnoid haemorrhage: nomogram development and validation.

BACKGROUND: Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients' complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH. METHODS: We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People's Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence. RESULTS: Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability. CONCLUSIONS: The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH.

B. glomerulata promotes neuroprotection against ischemic stroke by inhibiting apoptosis through the activation of PI3K/AKT/mTOR pathway.

BACKGROUND: Brassaiopsis glomerulata (Blum) Regel (B.glomerulata) is recognized as a traditional Chinese medicine (TCM) primarily used for promoting blood circulation and removing stasis. It is frequently utilized in the treatment of injuries resulting from falls and bumps. PURPOSE: Despite its effective use in clinical treatment for ischemic stroke (IS), there are currently no reports on its composition and mechanism of action, which affects its promotion. The study investigated the chemical components and molecular mechanisms of B.glomerulata, with the following components: UPLC-Q-TOF-MS, network pharmacology Analysis and experimental verification in vivo and vitro. METHODS: The effect of B.glomerulata on interfering with ischemic stroke was assessed on MCAO/R rats and ORD cell model. Then the compositional analysis was conducted using UPLC-Q-TOF-MS. Furthermore, network pharmacology and molecular docking techniques were explored to identify potential targets and pathways. The predicted mechanisms of action were ultimately confirmed by immunohistochemistry and protein blotting. RESULTS: B. glomerulata exhibited neuroprotective effects in MCAO/R rats by reductions in hippocampal and cortical neuronal damage, brain infarction, and cerebral edema. Both in vivo and in vitro experiments demonstrated that it decreased ROS and MDA levels, increased SOD and GSH levels, thereby inhibiting oxidative stress. Moreover, the improvements in neuronal morphology and the modulation of Nissl bodies suggested a potential mechanism underlying its neuroprotective action. Additionally, B.glomerulata exhibited concentration-dependent reductions in Bax and Caspase-3 expressions, along with increases in GFAP, Bcl2/Bax ratio, p-PI3K, p-AKT, and p-mTOR levels. CONCLUSION: B.glomerulata exhibited neuroprotective effects against cerebral ischemia-reperfusion injury both in vivo and in vitro. It prevented oxidative stress damage and inhibited apoptosis of ischemic stroke through the PI3K/AKT/mTOR pathway.

Exposure of water purification deficit network in response to nitrogen application intensity.

Ecosystem services are strongly responsive to changes in land use intensity, especially for the service of water purification, which is highly sensitive to water pollutant emission. Increased nitrogen (N) application to cropland has potential impacts on the supply and demand for water purification through changes in land use intensity. However, there has been a lack of research focusing on the impacts of cropland N application on population exposure to water purification deficit and their cross-regional delivery network. Taking the Dongting Lake (DTL) Basin as an example, this study explored the spatial pattern of N exposure in the DTL Basin from 1990 to 2015 by integrating water purification deficit and population density. Changes in potential N exposure in 2050 were simulated based on population projection data from the Shared Socioeconomic Pathways (SSP1-5). N delivery pathways in the DTL Basin were clarified by constructing the N delivery network. The results showed that N exposure increased significantly with increasing N application in DTL Basin. The DTL surrounding area and lower reaches of the Xiangjiang River Basin had high increases of N exposure (50.2 % and 71.6 %) and high increases in N exposure due to increases in N application per unit (N influence coefficients exceeding 0.5). The lower reaches of the Xiangjiang River Basin with the highest population density had the smallest decrease in N exposure (1.4 %-11.1 %) in the SSP1-5 scenarios. During 1990-2015, the increase of N export to the DTL surrounding area was higher in the lower reach sub-basins of DTL Basin. N application had a stronger impact on N delivery processes in the lower reaches of DTL Basin. Managers should distribute N applications to basins with high N retention and low N export to the DTL surrounding area. This study confirmed the strong response of water purification deficit and its population exposure to N application, and provided decision-making guidelines for water quality enhancement in DTL Basin from a spatial planning perspective.

Bacillus amyloliquefaciens LM-1 Affects Multiple Cell Biological Processes in Magnaporthe oryzae to Suppress Rice Blast.

Magnaporthe oryzae, one of the most destructive rice pathogens, causes significant losses during the rice harvest every year. Bacillus amyloliquefaciens has been explored in many crops as a potential biocontrol agent. However, the mechanisms of B. amyloliquefaciens controled rice blast are not fully understood. Here, a biocontrol strain LM-1, isolated from a contaminated medium, was identified as B. amyloliquefaciens using morphological observation, physiological and biochemical tests, and 16S rDNA sequencing. LM-1 inhibited the growth and pathogenicity of M. oryzae and Bipolaris oryzae (Breda de Haan) Shoem. The mycelia of M. oryzae co-cultured with LM-1 were enlarged and broken by fluorescence microscopy using calcofluor white. LM-1 inhibited the mycelia of M. oryzae from producing conidia. Genes itu, srf, and fenB were detected in LM-1. Furthermore, the supernatant of LM-1 interfered with the appressorium formation of M. oryzae, blocked conidial cell death, and reduced autophagy degradation but did not affect the normal germination of rice seeds and seeding growth. Additionally, we observed hypersensitivity reactions, reactive oxygen species, and iron accumulation reduction in rice cells inoculated with supernatant. Our study reveals that LM-1 has a control effect on rice blast and affects cell wall integrity, sporulation, appressorium formation, cell death, and autophagy.

Ten key issues for ecological restoration of territorial space.

This study innovatively puts forward the three-stage restoration goals and cutting-edge key scientific issues of ecological restoration, as well as their relationships.

Identification of the cytoplasmic DNA-Sensing cGAS-STING pathway-mediated gene signatures and molecular subtypes in prostate cancer.

BACKGROUND: Considering the age relevance of prostate cancer (PCa) and the involvement of the cGAS-STING pathway in aging and cancer, we aim to classify PCa into distinct molecular subtypes and identify key genes from the novel perspective of the cGAS-STING pathway. It is of significance to guide personalized intervention of cancer-targeting therapy based on genetic evidence. METHODS: The 430 patients with PCa from the TCGA database were included. We integrated 29 key genes involved in cGAS-STING pathway and analyzed differentially expressed genes and biochemical recurrence (BCR)-free survival-related genes. The assessments of tumor stemness and heterogeneity and tumor microenvironment (TME) were conducted to reveal potential mechanisms. RESULTS: PCa patients were classified into two distinct subtypes using AURKB, TREX1, and STAT6, and subtype 1 had a worse prognosis than subtype 2 (HR: 21.19, p < 0.001). The findings were validated in the MSKCC2010 cohort. Among subtype 1 and subtype 2, the top ten mutation genes were MUC5B, DNAH9, SLC5A10, ZNF462, USP31, SIPA1L3, PLEC, HRAS, MYOM1, and ITGB6. Gene set variation analysis revealed a high enrichment of the E2F target in subtype 1, and gene set enrichment analysis showed significant enrichment of base excision repair, cell cycle, and DNA replication in subtype 1. TME evaluation indicated that subtype 1 had a significantly higher level of T cells follicular helper and a lower level of plasma cells than subtype 2. CONCLUSIONS: The molecular subtypes mediated by the cGAS-STING pathway and the genetic risk score may aid in identifying potentially high-risk PCa patients who may benefit from pharmacologic therapies targeting the cGAS-STING pathway.

Local restrictions, population movement, and spillovers during the pandemic: Evidence from Japan's restaurant restriction.

We investigate how a local restaurant restriction aimed at containing the COVID-19 pandemic influenced population movement and COVID-19 prevalence within and outside the restricted districts. Using data on restaurant location and hourly population at the 500-m-mesh level and on COVID-19 prevalence at both prefecture and municipality level in Japan, we employ a triple-difference approach and a difference-in-differences approach with fixed effects. While the policy decreased population movement to restaurant areas in the restricted districts, it caused spillovers of increasing population movement to restaurant areas in the neighboring nonrestricted districts. Consequently, COVID-19 prevalence worsened in the neighboring nonrestricted districts but improved in the restricted districts. Our findings suggest that imposing such local restrictions in the context of the pandemic may contain the pandemic only in the restricted districts while sacrificing economic activities within these districts and public health in neighboring nonrestricted districts.

Realizing the high loading amount of active Cu on Al2O3 to boost its CO catalytic oxidation.

Catalytic oxidation of carbon monoxide (CO) by Cu/Al2O3 has garnered increasing interest in recent years due to its promising application prospects. Numerous investigations conducted on the Cu/Al2O3 system, but its catalytic performance for CO oxidation is still not as promising as that of precious metal catalysts. Increasing the loading amount of the active Cu on Al2O3 surface is a feasible method for improving its activity. However, with the increase of Cu loading, the agglomeration and enlargement of Cu particles is inevitable, which reduces the active Cu amount. Therefore, the utilization rate of Cu atoms is not high and the catalytic performance often can not further rise. Enhancing active Cu loading amount as high as possible is a prerequisite to further enlarge the activity of Cu/Al2O3 catalyst. Herein, self-synthesized Al2O3 nanofibers (Al2O3-nf) with high specific surface area and abundant penta-coordinated aluminum (AlV) are used as the support to maximize the Cu loading amount by chemical vapor deposition (CVD). And commercially available α-Al2O3 is used for comparative experiment. The high specific surface area could make Cu high dispersion on Al2O3, even at 20 wt% Cu loads, which is beneficial to high concentration load of active Cu. The catalytic activity of Cu/Al2O3-nf-CVD gradually increases with the increase of Cu loading from 2 wt% to 20 wt%, exhibiting a clear linear correlation with the surface content of Cu0 on the catalyst. Meanwhile, this result confirms that Cu0 plays a crucial role in CO oxidation of Cu/Al2O3. However, commercial α-Al2O3 reaches its highest activity when the Cu load is 5%, and then its activity begins to decrease due to the agglomeration of particles. Moreover, Cu/Al2O3-nf-CVD also exhibits remarkable thermal stability for CO oxidation. This work highlights a new strategy to synthesis of high Cu loading amount, high activity and thermostable Cu/Al2O3 catalyst for low-temperature oxidation of CO.

SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer.

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

Polyelectrolyte-Mediated Modulation of Spatial Internal Stresses of Hydrogels for Complex 3D Actuators.

Hydrogel actuators with complex 3D initial shapes show numerous important applications, but it remains challenging to fabricate such actuators. This article describes a polyelectrolyte-based strategy for modulating small-scale internal stresses within hydrogels to construct complex actuators with tailored 3D initial shapes. Introducing polyelectrolytes into precursor solutions significantly enhances the volume shrinkage of hydrogel networks during polymerization, allowing us to modulate internal stresses. Photopolymerization of these polyelectrolyte-containing solutions through a mask produces mechanically strong hydrogel sheets with large patterned internal stresses. Consequently, these hydrogel sheets attain complex 3D initial shapes at equilibrium, in contrast to the planar initial configuration of 2D actuators. We demonstrate that these 3D actuators can reversibly transform into other 3D shapes (i.e., 3D-to-3D shape transformations) in response to external stimuli. Additionally, we develop a predictive model based on the Flory-Rehner theory to analyze the polyelectrolyte-mediated shrinking behaviors of hydrogel networks during polymerization, allowing precise modulation of shrinkage and internal stress. This polyelectrolyte-boosted shrinking mechanism paves a route to the fabrication of high-performance 3D hydrogel actuators.

Phosphatidylserine and/or Sialic Acid Modified Liposomes Increase Uptake by Tumor-associated Macrophages and Enhance the Anti-tumor Effect.

DOX liposomes have better therapeutic effects and lower toxic side effects. The targeting ability of liposomes is one of the key factors affecting the therapeutic effect of DOX liposomes. This study developed two types of targeted liposomes. Sialic acid (SA)-modified liposomes were designed to target the highly expressed Siglec-1 receptor on tumor-associated macrophages surface. Phosphatidylserine (PS)-modified liposomes were designed to promote phagocytosis by monocyte-derived macrophages through PS apoptotic signaling. In order to assess and compare the therapeutic potential of different targeted pathways in the context of anti-tumor treatment, we compared four phosphatidylserine membrane materials (DOPS, DSPS, DPPS and DMPS) and found that liposomes prepared using DOPS as material could significantly improve the uptake ability of RAW264.7 cells for DOX liposomes. On this basis, normal DOX liposomes (CL-DOX) and SA-modified DOX liposomes (SAL-DOX), PS-modified DOX liposomes (PS-CL-DOX), SA and PS co-modified DOX liposomes (PS-SAL-DOX) were prepared. The anti-tumor cells function of each liposome on S180 and RAW264.7 in vitro was investigated, and it was found that SA on the surface of liposomes can increase the inhibitory effect. In vivo efficacy results exhibited that SAL-DOX and PS-CL-DOX were superior to other groups in terms of ability to inhibit tumor growth and tumor inhibition index, among which SAL-DOX had the best anti-tumor effect. Moreover, SAL-DOX group mice had high expression of IFN-γ as well as IL-12 factors, which could significantly inhibit mice tumor growth, improve the immune microenvironment of the tumor site, and have excellent targeted delivery potential.

Transcriptomics and metabolomics reveal hypothalamic metabolic characteristics and key genes after subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) is a serious hemorrhagic event with high mortality and morbidity. Multiple injurious events produced by SAH can lead to a series of pathophysiologic processes in the hypothalamus that can severely impact patients' life. These pathophysiologic processes usually result in physiologic derangements and dysfunction of the brain and multiple organs. This dysfunction involved multiple dimensions of the genome and metabolome. In our study, we induced the SAH model in rats to obtain hypothalamic tissue and serum. The samples were subsequently analyzed by transcriptomics and metabolomics. Next, the functional enrichment analysis of the differentially expressed genes and metabolites were performed by GO and KEGG pathway analysis. Through transcriptomic analysis of hypothalamus samples, 263 up-regulated differential genes, and 207 down-regulated differential genes were identified in SAH groups compared to Sham groups. In the KEGG pathway analysis, a large number of differential genes were found to be enriched in IL-17 signaling pathway, PI3K-Akt signaling pathway, and bile secretion. Liquid chromatography-mass spectrometry metabolomics technology was conducted on the serum of SAH rats and identified 11 up-regulated and 26 down-regulated metabolites in positive ion model, and 1 up-regulated and 10 down-regulated metabolites in negative ion model. KEGG pathways analysis showed that differentially expressed metabolites were mainly enriched in pathways of bile secretion and primary bile acid biosynthesis. We systematically depicted the neuro- and metabolism-related biomolecular changes occurring in the hypothalamus after SAH by performing transcriptomics and metabolomics studies. These biomolecular changes may provide new insights into hypothalamus-induced metabolic changes and gene expression after SAH.

Expanding China's protected areas network to enhance resilience of climate connectivity.

Expanding the network of connected and resilient protected areas (PAs) for climate change adaptation can help species track suitable climate conditions and safeguard biodiversity. This is often overlooked when expanding PAs and quantifying their benefits, resulting in an underestimate of the benefits of expanding PAs. We expanded PAs through terrestrial mammalian species distribution hotspots, Key Biodiversity Areas (KBAs), and wilderness areas. Then, we constructed climate connectivity networks using a resistance-based approach and further quantified the network resilience to propose resilient climate response strategies in China. The results showed that existing PAs suffered from location biases with important biodiversity areas. The existing PAs represented about half of the KBAs and wilderness areas, yet only 12.08% of terrestrial mammalian species distribution hotspots were located within existing PAs. Compared with the existing PA network, the network efficiency and resilience of the expanded PAs' climate connectivity increased to 1.80 times and 1.78 times, respectively. With 56% of the nodes remaining, the network efficiency of the expanded PAs was equivalent to that of the existing PAs with all nodes. The network resilience of preferentially protecting and restoring low human footprint patches was approximately 1.5-2 times that of the random scenario. These findings highlighted that confronted with the unoptimistic situation of global warming, nature conservation based on existing PAs was no longer optimal. It was critical to construct a connected and resilient conservation network relying on both important biodiversity areas and low human footprint patches.