Cell Taxonomy: a curated repository of cell types with multifaceted characterization.

Single-cell studies have delineated cellular diversity and uncovered increasing numbers of previously uncharacterized cell types in complex tissues. Thus, synthesizing growing knowledge of cellular characteristics is critical for dissecting cellular heterogeneity, developmental processes and tumorigenesis at single-cell resolution. Here, we present Cell Taxonomy (https://ngdc.cncb.ac.cn/celltaxonomy), a comprehensive and curated repository of cell types and associated cell markers encompassing a wide range of species, tissues and conditions. Combined with literature curation and data integration, the current version of Cell Taxonomy establishes a well-structured taxonomy for 3,143 cell types and houses a comprehensive collection of 26,613 associated cell markers in 257 conditions and 387 tissues across 34 species. Based on 4,299 publications and single-cell transcriptomic profiles of ∼3.5 million cells, Cell Taxonomy features multifaceted characterization for cell types and cell markers, involving quality assessment of cell markers and cell clusters, cross-species comparison, cell composition of tissues and cellular similarity based on markers. Taken together, Cell Taxonomy represents a fundamentally useful reference to systematically and accurately characterize cell types and thus lays an important foundation for deeply understanding and exploring cellular biology in diverse species.

BrainBase: a curated knowledgebase for brain diseases.

Brain is the central organ of the nervous system and any brain disease can seriously affect human health. Here we present BrainBase (https://ngdc.cncb.ac.cn/brainbase), a curated knowledgebase for brain diseases that aims to provide a whole picture of brain diseases and associated genes. Specifically, based on manual curation of 2768 published articles along with information retrieval from several public databases, BrainBase features comprehensive collection of 7175 disease-gene associations spanning a total of 123 brain diseases and linking with 5662 genes, 16 591 drug-target interactions covering 2118 drugs/chemicals and 623 genes, and five types of specific genes in light of expression specificity in brain tissue/regions/cerebrospinal fluid/cells. In addition, considering the severity of glioma among brain tumors, the current version of BrainBase incorporates 21 multi-omics datasets, presents molecular profiles across various samples/conditions and identifies four groups of glioma featured genes with potential clinical significance. Collectively, BrainBase integrates not only valuable curated disease-gene associations and drug-target interactions but also molecular profiles through multi-omics data analysis, accordingly bearing great promise to serve as a valuable knowledgebase for brain diseases.

Gene Expression Nebulas (GEN): a comprehensive data portal integrating transcriptomic profiles across multiple species at both bulk and single-cell levels.

Transcriptomic profiling is critical to uncovering functional elements from transcriptional and post-transcriptional aspects. Here, we present Gene Expression Nebulas (GEN, https://ngdc.cncb.ac.cn/gen/), an open-access data portal integrating transcriptomic profiles under various biological contexts. GEN features a curated collection of high-quality bulk and single-cell RNA sequencing datasets by using standardized data processing pipelines and a structured curation model. Currently, GEN houses a large number of gene expression profiles from 323 datasets (157 bulk and 166 single-cell), covering 50 500 samples and 15 540 169 cells across 30 species, which are further categorized into six biological contexts. Moreover, GEN integrates a full range of transcriptomic profiles on expression, RNA editing and alternative splicing for 10 bulk datasets, providing opportunities for users to conduct integrative analysis at both transcriptional and post-transcriptional levels. In addition, GEN provides abundant gene annotations based on value-added curation of transcriptomic profiles and delivers online services for data analysis and visualization. Collectively, GEN presents a comprehensive collection of transcriptomic profiles across multiple species, thus serving as a fundamental resource for better understanding genetic regulatory architecture and functional mechanisms from tissues to cells.

Effect of TEVAR Combined with Drugs and Drug Therapy Alone on the Efficacy and Safety of Stable Standford B Aortic Dissection.

Objective: Stanford type B aortic dissection is a condition in which the intima of the aorta tears, and TEVAR is an interventional treatment to manage this dissection through intimal repair. To evaluate the medium-term clinical efficacy of endovascular repair (TEVAR) for Aortic dissection and drug Conservative management for Stanford B Aortic dissection aneurysms and further explore whether the former is superior to drug Conservative management in the medium-term efficacy. Methods: The clinical data of 70 patients with stable Standford type B Aortic dissection admitted to our hospital from March 2016 to March 2020 were retrospectively analyzed. They were divided into the treatment group (n = 47) and the control group (n = 23). The control group patients were treated solely with medication, while the treatment group patients were treated with TEVAR on the basis of the control group patients. The treatment efficacy and safety of the two groups of patients were compared and analyzed. All patients will be followed up once a month for 12 months after discharge and every 2 months thereafter (for a total of 3 years). Results: The findings highlight the need to carefully weigh the benefits and harms in the treatment of Stanford type B aortic dissection, especially when considering TEVAR surgery. Future research should focus on reducing postoperative complications to optimize treatment strategies and improve overall patient outcomes.TEVAR surgery significantly reduces hospital mortality, but is also associated with significantly increased postoperative complications, emphasizing the complexity of treatment decisions. This finding provides critical information about weighing the risks and survival benefits of surgery, helping medical teams and patients make informed treatment choices. The hospital mortality rate of patients in the treatment group was 12.77%, while the hospital mortality rate of patients in the control group was 21.74%. The difference between the two groups was statistically significant (P < .05). The incidence of postoperative complications in the treatment group was 23.40%, while the control group did not experience any major complications. The difference between the two groups was statistically significant (P < .05). The mortality rate of patients in the treatment group within 30 days of discharge was 0%, while the mortality rate of patients in the control group within 30 days of discharge was 11.11%. The difference between the two groups was statistically significant (P < .05). The Kaplan Meier curve showed that the survival rates at 3 years of the control and treatment groups were 56.52% and 95.12%, respectively. The log-rank test showed a statistical difference between the two groups. Univariate and multivariate regression analysis showed that postoperative neurological complications (HR = 32.41; P = .00) and preoperative Aortic valve regurgitation (HR = 3.91; P = .00) were risk factors for medium-term death. Conclusion: The TEVAR combination drug is a safe and effective treatment for stable Stanford B Aortic dissection. It can reduce mortality. Compared with drug treatment, it has obvious advantages in medium-term treatment effects. Early rising for high-risk patients can make them have better long-term outcomes. Limitations of the study include its retrospective nature and the use of data from only a single medical center, which may limit the external generalizability of the results.

Cytokines as drivers: Unraveling the mechanisms of epithelial-mesenchymal transition in COVID-19 lung fibrosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like other viruses, can induce proliferation of myofibroblasts and even lead to fibrosis in the lung. Epithelial-mesenchymal transition (EMT) is thought to play an essential role in the pathogenesis of Coronavirus disease 19 (COVID-19). EMT is originally a critical process that regulates the development of different tissues in the embryo, but in inflammatory situations, EMT tries to be activated again to control inflammation or even heal inflammatory damage. However, in pathological situations, such as chronic viral infections (e.g., COVID-19) or pulmonary fibrosis initiation, this benign healing transforms into sinister nature, pushing the lung into the fibrotic process. Notably, the cytokines released by inflammatory cells and the chronic inflammatory microenvironment shared by fibrotic cells promote each other as critical factors in the induction of pathological EMT. In the induction of SARS-CoV-2 virus, cytokines are an essential mediator of EMT transformation, and a summary of whether COVID-19 patients, during the infection phase, have many persistent inflammatory mediators (cytokines) that are a causative factor of EMT has not yet appeared. The following common signaling drivers, including Transforming growth factor beta (TGF-ß), cytokines, Notch signaling pathway, Wnt and hypoxia signaling pathways, drive the regulation of EMT. In this review, we will focus on 3 key EMT signaling pathways: TGF-ß, Leucine zipper transcription factor like 1 (LZTFL1) and the common interleukin family expressed in the lung. TGF-ß-induced SNAIL and LZTFL1 were identified as regulatory EMT in COVID-19. For cytokines, the interleukin family is a common inducer of EMT and plays an essential role in the formation of the microenvironment of fibrosis. We sought to demonstrate that cytokines act as "communicators" and build the "microenvironment" of fibrosis together with EMT as a "bridge" to induce EMT in fibrosis. The mechanisms utilized by these two pathways could serve as templates for other mesenchymal transformations and provide new potential therapeutic targets.

Editome Disease Knowledgebase (EDK): a curated knowledgebase of editome-disease associations in human.

RNA editing, as an essential co-/post-transcriptional RNA modification type, plays critical roles in many biological processes and involves with a variety of human diseases. Although several databases have been developed to collect RNA editing data in both model and non-model animals, there still lacks a resource integrating associations between editome and human disease. In this study, we present Editome-Disease Knowledgebase (EDK; http://bigd.big.ac.cn/edk), an integrated knowledgebase of RNA editome-disease associations manually curated from published literatures. In the current version, EDK incorporates 61 diseases associated with 248 experimentally validated abnormal editing events located in 32 mRNAs, 16 miRNAs, 1 lncRNA and 11 viruses, and 44 aberrant activities involved with 6 editing enzymes, which together are curated from more than 200 publications. In addition, to facilitate standardization of editome-disease knowledge integration, we propose a data curation model in EDK, factoring an abundance of relevant information to fully capture the context of editome-disease associations. Taken together, EDK is a comprehensive collection of editome-disease associations and bears the great utility in aid of better understanding the RNA editing machinery and complex molecular mechanisms associated with human diseases.

Plant editosome database: a curated database of RNA editosome in plants.

RNA editing plays an important role in plant development and growth, enlisting a number of editing factors in the editing process and accordingly revealing the diversity of plant editosomes for RNA editing. However, there is no resource available thus far that integrates editosome data for a variety of plants. Here, we present Plant Editosome Database (PED; http://bigd.big.ac.cn/ped), a curated database of RNA editosome in plants that is dedicated to the curation, integration and standardization of plant editosome data. Unlike extant relevant databases, PED incorporates high-quality editosome data manually curated from related publications and organelle genome annotations. In the current version, PED integrates a complete collection of 98 RNA editing factors and 20 836 RNA editing events, covering 203 organelle genes and 1621 associated species. In addition, it contains functional effects of editing factors in regulating plant phenotypes and includes detailed experimental evidence. Together, PED serves as an important resource to help researchers investigate the RNA editing process across a wide range of plants and thus would be of broad utility for the global plant research community.

EWAS Atlas: a curated knowledgebase of epigenome-wide association studies.

Epigenome-Wide Association Study (EWAS) has become increasingly significant in identifying the associations between epigenetic variations and different biological traits. In this study, we develop EWAS Atlas (http://bigd.big.ac.cn/ewas), a curated knowledgebase of EWAS that provides a comprehensive collection of EWAS knowledge. Unlike extant data-oriented epigenetic resources, EWAS Atlas features manual curation of EWAS knowledge from extensive publications. In the current implementation, EWAS Atlas focuses on DNA methylation-one of the key epigenetic marks; it integrates a large number of 329 172 high-quality EWAS associations, involving 112 tissues/cell lines and covering 305 traits, 1830 cohorts and 390 ontology entities, which are completely based on manual curation from 649 studies reported in 401 publications. In addition, it is equipped with a powerful trait enrichment analysis tool, which is capable of profiling trait-trait and trait-epigenome relationships. Future developments include regular curation of recent EWAS publications, incorporation of more epigenetic marks and possible integration of EWAS with GWAS. Collectively, EWAS Atlas is dedicated to the curation, integration and standardization of EWAS knowledge and has the great potential to help researchers dissect molecular mechanisms of epigenetic modifications associated with biological traits.

The long noncoding RNA XIST protects cardiomyocyte hypertrophy by targeting miR-330-3p.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in numerous kinds of cardiovascular diseases, and their vital role in regulating cardiac hypertrophy still needs to be explored. In this study, we demonstrated that lncRNA X-inactive specific transcript (XIST) was upregulated in hypertrophic cardiac of mice and phenylephrine (PE)-treated cardiomyocytes. Next, we observed that inhibition of XIST induced hypertrophic response of cardiomyocyte and overexpression of XIST attenuated cardiomyocyte hypertrophy induced by PE. Furthermore, through online predictive tools and functional experiments, we demonstrated that XIST and S100B were targets of miR-330-3p. XIST and miR-330-3p suppressed each other in a reciprocal way in cardiomyocytes. Additionally, XIST promoted S100B expression through harboring the complementary binding sites with miR-330-3p, eventually prevented cardiac hypertrophy. In conclusion, our findings revealed a novel molecular mechanism that XIST/miR-330-3p/S100B pathway modulates the progression of cardiomyocyte hypertrophy.

Influence of Fatty Acid Modification on Uptake of Lovastatin-Loaded Reconstituted High Density Lipoprotein by Foam Cells.

PURPOSE: Spherical reconstituted high density lipoprotein (rHDL) can target atherosclerotic lesions by the very low density lipoprotein (VLDL) receptor, which is seldom expressed in liver. By promoting this pathway, the targeting efficiency was hyphothesized to be improved due to avoiding undesired uptake in liver mediated by the scavenger receptor class B type I (SR-BI). In this study, how fatty acid modification in spherical rHDL influenced the VLDL receptor-mediated endocytosis pathway was investigated. METHODS: Stearic acid (SA) and arachidonic acid (AA) with different saturation levels were utilized to modify the lovastatin-loaded rHDL (LS-rHDL). Phagocytosis test on foam cells with or without cholesteryl ester transfer protein (CETP) expression was conducted to observe the cellular uptake of the SA or AA modified rHDL and the non-modified one. Raman spectroscopy, guanidine hydrochloride (Gdn-HCl) denaturation experiment and in vitro evaluation of drug release were used to analyze the related mechanism. RESULTS: In comparison with the non-modified rHDL, AA modification could reduce the packing order of the rHDL phospholipid acyl chains, leading to the decreased apoA-I binding extent with lipid and the increased drug release, while the opposite was true for SA modification. The AA-modified rHDL exhibited a higher uptake of foam cells expressing CETP than the non-modified one, while the SA-modified one showed the lowest cellular uptake among the three rHDLs. CONCLUSIONS: Increased unsaturation level can facilitate lipid-interchange process where the cargo in rHDL core may transfer to VLDL more easily, and then promote the endocytosis mediated by the VLDL receptor.

Evaluation and optimization of sample preparation methods for metabolic profiling analysis of Escherichia coli.

In this study, exemplified by Escherichia coli, a sample preparation method was developed and evaluated with more concerns on cell pellets washing, disruption, and metabolite extraction for global metabolite profiling analysis using GC-MS. We found that loss of some intracellular metabolites occurred inevitably, no matter which washing strategy was used. But PBS washing resulted in the least leakage of intercellular metabolites among the six tested methods. In addition, bead-beating showed better repeatability and high throughput than sonication for cell pellet disruption. Total six extraction solvents, including chloroform/methanol/water (2:0.21:0.79, v/v/v), methyl tert-butyl ether/methanol/water (2:0.21:0.79), acetonitrile/methanol/water (2:2:1), water/isopropanol/methanol (3:2:5), pure methanol, and methanol/water (1:1), were evaluated for metabolite extraction efficiency. We demonstrated that the numbers of extracted metabolites were almost the same, but methyl tert-butyl ether/methanol/water and chloroform/methanol/water could achieve the best recoveries in view of MS intensities. This study implies the necessity to evaluate the potential effects of serial sample preparation procedures prior to metabolomic analysis.

Betulin ameliorates neuronal apoptosis and oxidative injury via DJ-1/Akt/Nrf2 signaling pathway after subarachnoid hemorrhage.

AIMS: We aimed to resolve the uncertainty as to whether betulin exerted neuroprotection on early brain injury (EBI) caused by subarachnoid hemorrhage (SAH), and to investigate the related molecular mechanisms. METHODS: Bioinformatic analysis was performed to pre-study the differently expressed genes (DEGs) and the possible signaling pathways. Rat and cellular model of SAH were introduced in this study, and betulin, an activator of DJ-1 protein, was administered to reveal the effect. Gross assessment regarding mortality, neurofunctions, SAH grade, brain water content (BWC) along with multiple cellular and molecular studies in vivo or/and in vitro such as immunofluorescence (IF) staining, western blot (WB), reactive oxygen species (ROS) assay, and flow cytometry (FCM) were all conducted after SAH induction to verify the protective effect and the relevant mechanisms of DJ-1 in diverse levels. In addition, MK2206 (selective inhibitor of Akt) and iRNADj-1 (interfering RNA to Dj-1) were utilized to confirm the mechanisms of the effect. RESULTS: The data from our study showed that DJ-1 protein was moderately expressed in neurons, microglia, and astrocytes; its level in brain tissue elevated and peaked at 24-72 h after SAH induction. Betulin could efficaciously induce the expression of DJ-1 which in turn activated Akt and Bcl-2, and anti-oxidative enzymes SOD2 and HO-1, functioning to reduce the activation of cleaved caspase-3 (c-Casp-3) and reactive oxygen species (ROS). The induced DJ-1 could upregulate the expression of Nrf2. However, Akt seemed no direct effect on elevating the expression of Nrf2. DJ-1 alone could as well activate Akt-independent antiapoptotic pathway via suppressing the activation of caspase-8 (Casp-8). CONCLUSIONS: Betulin which was a potent agonist of DJ-1 had the ability to induce its expression in brain tissue. DJ-1 had neuroprotective effect on EBI through comprehensive mechanisms, including facilitating intrinsic and extrinsic antiapoptotic pathway, and reducing oxidative injury by upregulating the expression of redox proteins. Betulin as an inexpensive drug showed the potential for SAH treatment.

Seeing the unseen in characterizing RNA editome during rice endosperm development.

Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery.

Thermal infrared anomalies of several strong earthquakes.

In the history of earthquake thermal infrared research, it is undeniable that before and after strong earthquakes there are significant thermal infrared anomalies which have been interpreted as preseismic precursor in earthquake prediction and forecasting. In this paper, we studied the characteristics of thermal radiation observed before and after the 8 great earthquakes with magnitude up to Ms7.0 by using the satellite infrared remote sensing information. We used new types of data and method to extract the useful anomaly information. Based on the analyses of 8 earthquakes, we got the results as follows. (1) There are significant thermal radiation anomalies before and after earthquakes for all cases. The overall performance of anomalies includes two main stages: expanding first and narrowing later. We easily extracted and identified such seismic anomalies by method of "time-frequency relative power spectrum." (2) There exist evident and different characteristic periods and magnitudes of thermal abnormal radiation for each case. (3) Thermal radiation anomalies are closely related to the geological structure. (4) Thermal radiation has obvious characteristics in abnormal duration, range, and morphology. In summary, we should be sure that earthquake thermal infrared anomalies as useful earthquake precursor can be used in earthquake prediction and forecasting.

Advances, challenge and prospects in cell-mediated nanodrug delivery for cancer therapy: a review.

Nanomedicine offers considerable opportunities to improve drugability and reduce toxicity for tumour therapy. However, the application of nanomedicine has achieved little success in clinical trials due to multiple physiological barriers to drug delivery. Circulating cells are expected to improve the physical distribution of drugs and enhance the therapeutic effect by overcoming various biological barriers in collaboration with nano-drug delivery systems owing to excellent biocompatibility, low immunogenicity and a long-circulation time and strong binding specificity. Nonetheless, we have noticed some limitations in implementing tthe strategy. In this article, we intend to introduce the latest progress in research and application of circulating cell-mediated nano-drug delivery systems, describe the main cell-related drug delivery modes, sum up the relevant points of the transport systems in the process of loading, transport and release, and lastly discuss the advantages, challenges and future development trends in cell-mediated nano-drug delivery.

GPNMB Ameliorates Neuroinflammation Via the Modulation of AMPK/NFκB Signaling Pathway After SAH in Mice.

Glycoprotein non-metastatic melanoma protein B (GPNMB) got its name from the first discovery in a cell line of non-metastatic melanoma. Later studies found that GPNMB is widely expressed in various tissues and cells of the human body, most abundant in neural tissue, epithelial tissue, bone tissue, and monocyte-macrophage system. GPNMB has been shown to have anti-inflammatory effects in a variety of neurological diseases, however, it has not been reported in subarachnoid hemorrhage (SAH). Male CD-1 mice were used and intra-arterial puncture method was applied to establish the SAH model. Exogenous recombinant GPNMB (rGPNMB) was injected intracerebroventricularly 1 h after SAH. SAH grading, brain edema and blood-brain barrier (BBB) integrity were quantified, and neurobehavioral tests were performed to evaluate the effect of GPNMB on the outcome. Dorsomorphin, the selective inhibitor on AMPK was introduced to study the downstream signaling through which the GPNMB works. Furthermore, western blot, immunofluorescence staining and ELISA were utilized to confirm the signaling. After SAH, GPNMB expression increased significantly as a result of the inflammatory response. GPNMB was expressed extensively in mouse microglia, astrocytes and neurons. The administration of rGPNMB could alleviate brain edema, restore BBB integrity and improve the neurological outcome of mice with SAH. GPNMB treatment significantly magnified the expression of p-AMPK while p-NFκB, IL-1ß, IL-6 and TNF-α were suppressed; in the meantime, the combined administration of GPNMB and AMPK inhibitor could decrease the intensity of p-AMPK and reverse the quantity of p-NFκB and the above inflammatory cytokines. GPNMB has the potential of ameliorating the brain edema and neuroinflammation, protecting the BBB and improving the neurological outcome, possibly via the AMPK/NFκB signaling pathway.

Flow diverters in the treatment of unruptured vertebral artery dissecting aneurysm: A single-center experience.

Objective: To evaluate the efficacy and safety of flow diverters (FD) in the treatment of vertebral artery dissecting aneurysm (VADA). Methods: A total of 16 patients with 17 unruptured VADAs treated with FD from January 2017 to May 2021 were included. Data of clinical outcomes and radiographic examination were collected and assessed by the modified Rankin Scale (mRS) and O'Kelly-Marotta (OKM) grading scale. Results: All patients were treated with a single FD. No perioperative complications occurred. The mean age was 55.1 years old. The mean size of the aneurysm was 10.4 mm. All patients had a favorable occlusion (OKM D + C3) result and the complete occlusion rate in the 6th month was 66.7% (OKM D). The mean clinical follow-up time was 7.8 months, and all patients had a good clinical outcome (mRS = 0). No procedure-related complication occurred at the last follow-up time. Conclusion: FD is an effective and safe tool for treating unruptured VADA. Long-term prospective studies with a large sample are still needed to confirm these findings in the future.

Host-mediated RNA editing in viruses.

Viruses rely on hosts for life and reproduction, cause a variety of symptoms from common cold to AIDS to COVID-19 and provoke public health threats claiming millions of lives around the globe. RNA editing, as a crucial co-/post-transcriptional modification inducing nucleotide alterations on both endogenous and exogenous RNA sequences, exerts significant influences on virus replication, protein synthesis, infectivity and toxicity. Hitherto, a number of host-mediated RNA editing sites have been identified in diverse viruses, yet lacking a full picture of RNA editing-associated mechanisms and effects in different classes of viruses. Here we synthesize the current knowledge of host-mediated RNA editing in a variety of viruses by considering two enzyme families, viz., ADARs and APOBECs, thereby presenting a landscape of diverse editing mechanisms and effects between viruses and hosts. In the ongoing pandemic, our study promises to provide potentially valuable insights for better understanding host-mediated RNA editing on ever-reported and newly-emerging viruses.

Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension.

Background: There is growing evidence that the lung is a target organ for injury in diabetes and hypertension. There are no studies on the status of the lungs, especially cellular subpopulations, and related functions in patients with diabetes, hypertension, and hypertension-diabetes after combined SARS-CoV-2 infection. Method: Using single-cell meta-analysis in combination with bulk-RNA analysis, we identified three drug targets and potential receptors for SARS-CoV-2 infection in lung tissues from patients with diabetes, hypertension, and hypertension-diabetes, referred to as "co-morbid" patients. Using single-cell meta-analysis analysis in combination with bulk-RNA, we identified drug targets and potential receptors for SARS-CoV-2 infection in the three co-morbidities. Results: The single-cell meta-analysis of lung samples from SARS-CoV-2-infected individuals with diabetes, hypertension, and hypertension-diabetes comorbidity revealed an upregulation of fibroblast subpopulations in these disease conditions associated with a predictive decrease in lung function. To further investigate the response of fibroblasts to therapeutic targets in hypertension and diabetes, we analyzed 35 upregulated targets in both diabetes and hypertension. Interestingly, among these targets, five specific genes were upregulated in fibroblasts, suggesting their potential association with enhanced activation of endothelial cells. Furthermore, our investigation into the underlying mechanisms driving fibroblast upregulation indicated that KREMEN1, rather than ACE2, could be the receptor responsible for fibroblast activation. This finding adds novel insights into the molecular processes involved in fibroblast modulation in the context of SARS-CoV-2 infection within these comorbid conditions. Lastly, we compared the efficacy of Pirfenidone and Nintedanib as therapeutic interventions targeting fibroblasts prone to pulmonary fibrosis. Our findings suggest that Nintedanib may be a more suitable treatment option for COVID-19 patients with diabetes and hypertension who exhibit fibrotic lung lesions. Conclusion: In the context of SARS-CoV-2 infections, diabetes, hypertension, and their coexistence predominantly lead to myofibroblast proliferation. This phenomenon could be attributed to the upregulation of activated endothelial cells. Moreover, it is noteworthy that therapeutic interventions targeting hypertension-diabetes demonstrate superior efficacy. Regarding treating fibrotic lung conditions, Nintedanib is a more compelling therapeutic option.

Recent advances in ferroptosis and therapeutic strategies for glioblastoma.

Ferroptosis is an emerging form of cell death characterized by the over-accumulation of iron-dependent lipid peroxidation. Ferroptosis directly or indirectly disturbs glutathione peroxidases cycle through diverse pathways, impacting the cellular antioxidant capacities, aggravating accumulation of reactive oxygen species in lipid, and it finally causes oxidative overload and cell death. Ferroptosis plays a significant role in the pathophysiological processes of many diseases. Glioblastoma is one of the most common primary malignant brain tumors in the central nervous system in adults. Although there are many treatment plans for it, such as surgical resection, radiotherapy, and chemotherapy, they are currently ineffective and the recurrent rate is almost up to 100%. The therapies abovementioned have a strong relationship with ferroptosis at the cellular and molecular level according to the results reported by numerous researchers. The regulation of ferroptosis can significantly determine the outcome of the cells of glioblastoma. Thus ferroptosis, as a regulated form of programed cell death, has the possibility for treating glioblastoma.