tbuckley/cabot-search huggingface dataset:
Pathogenesis and therapeutic opportunities of gut microbiome dysbiosis in critical illness
Authors: Nicole A Cho, Kathryn Strayer, Breenna Dobson, Braedon McDonald
Journal: Gut Microbes (2024)

For many years, it has been hypothesized that pathological changes to the gut microbiome in critical illness is a driver of infections, organ dysfunction, and other adverse outcomes in the intensive care unit (ICU). The advent of contemporary microbiome methodologies and multi-omics tools have allowed researchers to test this hypothesis by dissecting host-microbe interactions in the gut to better define its contribution to critical illness pathogenesis. Observational studies of patients in ICUs have revealed that gut microbial communities are profoundly altered in critical illness, characterized by markedly reduced alpha diversity, loss of commensal taxa, and expansion of potential pathogens. These key features of ICU gut dysbiosis have been associated with adverse outcomes including life-threatening hospital-acquired (nosocomial) infections. Current research strives to define cellular and molecular mechanisms connecting gut dysbiosis with infections and other outcomes, and to identify opportunities for therapeutic modulation of host-microbe interactions. This review synthesizes evidence from studies of critically ill patients that have informed our understanding of intestinal dysbiosis in the ICU, mechanisms linking dysbiosis to infections and other adverse outcomes, as well as clinical trials of microbiota-modifying therapies. Additionally, we discuss novel avenues for precision microbial therapeutics to combat nosocomial infections and other life-threatening complications of critical illness.
Ultra‐Hydrophobic Gauze Driving Super‐Haemostasis
Authors: Ying Chen, Jinrui Yang, Yuqing Liu, Xiaoqiang Liu, Kexin Deng, Kaige Xu, Hongling Zhou, Xupin Jiang, Malcolm Xing, Jiaping Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Controlling bleeding by applying pressing cotton gauze is the most facile treatment in prehospital emergencies. However, the wettable nature of cotton fibers leads to unnecessary blood loss due to excessive blood absorption, inseparable adhesion‐induced pain, and pliable to infection. Here, a kind of ultra‐hydrophobic haemostatic anti‐adhesive gauze whose surface is loaded with polydimethylsiloxane (PDMS) and hydrophobic‐modified cellulose nanocrystals (CNCs), achieving a water contact angle of ≈160° is developed. It is demonstrated that the mechanism by which hydrophobic CNCs promote blood clotting is associated with their ability to activate coagulation factors, contributing to fibrin formation, and promoting platelet activation. The blood‐restricting effect results from the low surface energy layer formed by PDMS and then the alkyl chains of hydrophobic CNCs are combined. The produced ultra‐hydrophobic gauze resists blood flow and diffusion, decreases blood loss, is effortlessly peelable, and minimizes pathogen adhesion. Compared to the commercial cotton gauze, this gauze achieved effective haemostasis and antiadhesion by reducing blood loss by more than 90%, shortening haemostasis time by more than 75%, lowering peeling force by more than 90% and minifying bacterium attachment by more than 95%. This work presents promising applications in terms of prehospital first aid.
Dietary restriction rescues 5-fluorouracil-induced lethal intestinal toxicity in old mice by blocking translocation of opportunistic pathogens
Authors: Duozhuang Tang, Rongrong Qiu, Xingxing Qiu, Man Sun, Mingyue Su, Zhendong Tao, Liu Zhang, Si Tao
Journal: Gut Microbes (2024)

Chemotherapy remains a major treatment for malignant tumors, yet the application of standard dose intensity chemotherapy is limited due to the side effects of cytotoxic drugs, especially in old populations. The underlying mechanisms of cytotoxicity and strategies to increase the safety and tolerance of chemotherapy remain to be explored. Using 5-fluorouracil (5-FU), a cornerstone chemotherapeutic drug, we demonstrate that the main cause of death in ad libitum (AL) fed mice after 5-FU chemotherapy was infection caused by translocation of intestinal opportunistic pathogens. We show that these opportunistic pathogens greatly increase in the intestine after chemotherapy, which was closely related to loss of intestinal lysozyme. Of note, two weeks of dietary restriction (DR) prior to chemotherapy significantly protected the loss of lysozyme and increased the content of the beneficial Lactobacillus genera, resulting in a substantial inhibition of intestinal opportunistic pathogens and their translocation. The rescue effect of DR could be mimicked by Lysozyme or Lactobacillus gavage. Our study provides the first evidence that DR achieved a comprehensive protection of the intestinal physical, biological and chemical barriers, which significantly improved the overall survival of 5-FU-treated mice. Importantly, the above findings were more prominent in old mice. Furthermore, we show that patients over 65 years old have enriched opportunistic pathogens in their gut microbiota, especially after 5-FU based chemotherapy. Our study reveals important mechanisms for the poor chemotherapy tolerance of the elderly population, which can be significantly improved by short-term DR. This study generates new insights into methods for improving the chemotherapeutic prognosis by increasing the chemotherapy tolerance and safety of patients with malignant tumors.
Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants
Authors: Danielle E. McBride, Amit Bhattacharya, Heidi Sucharew, Kelly J. Brunst, Mary Barnas, Cyndy Cox, Lorenna Altman, Timothy J. Hilbert, Jeff Burkle, Susan Westneat, Kaitlin Vollet Martin, Patrick J. Parsons, Meredith L. Praamsma, Christopher D. Palmer, Kurunthachalam Kannan, Donald R. Smith, Robert Wright, Chitra Amarasiriwardena, Kim N. Dietrich, Kim M. Cecil, Erin N. Haynes
Journal: Environmental Health Perspectives (2024)

Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance.
Tuning Recombinant Perlecan Domain V to Regulate Angiogenic Growth Factors and Enhance Endothelialisation of Electrospun Silk Vascular Grafts
Authors: Shouyuan Jiang, Nanji Yang, Richard P. Tan, Edward S. X. Moh, Lu Fu, Nicolle H. Packer, John M. Whitelock, Steven G. Wise, Jelena Rnjak‐Kovacina, Megan S. Lord
Journal: Advanced Healthcare Materials (2024)

Abstract Synthetic vascular grafts are used to bypass significant arterial blockage when native blood vessels are unsuitable, yet their propensity to fail due to poor blood compatibility and progressive graft stenosis remains an intractable challenge. Perlecan is the major heparan sulfate (HS) proteoglycan in the blood vessel wall with an inherent ability to regulate vascular cell activities associated with these major graft failure modes. Here the ability of the engineered form of perlecan domain V (rDV) to bind angiogenic growth factors is tuned and endothelial cell proliferation via the composition of its glycosaminoglycan (GAG) chain is supported. It is shown that the HS on rDV supports angiogenic growth factor signaling, including fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF)165, while both HS and chondroitin sulfate on rDV are involved in VEGF189 signaling. It is also shown that physisorption of rDV on emerging electrospun silk fibroin vascular grafts promotes endothelialization and patency in a murine arterial interposition model, compared to the silk grafts alone. Together, this study demonstrates the potential of rDV as a tunable, angiogenic biomaterial coating that both potentiates growth factors and regulates endothelial cells.
A Cyanine with 83.2% Photothermal Conversion Efficiency and Absorption Wavelengths over 1200 nm for Photothermal Therapy
Authors: Liang Zhao, Han Zhu, You‐Yang Duo, Zhi‐Gang Wang, Dai‐Wen Pang, Shu‐Lin Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Developing small‐molecule photothermal agents (PTAs) with good near‐infrared‐II (NIR‐II) response for deeper tissue penetration and minimizing damage to healthy tissues has attracted much attention in photothermal therapy (PTT). However, concentrating ultra‐long excitation wavelengths and high photothermal conversion efficiencies (PCEs) into a single organic small molecule is still challenging due to the lack of suitable molecular structures. Here, six polymethine cyanine molecules based on the structure of indocyanine green are synthesized by increasing the conjugated structure of the two‐terminal indole salts and the number of rigid methine units, and incorporating longer alkyl side chains into the indole salts. Ultimately, IC‐1224 is obtained with an absorption wavelength of more than 1200 nm, which has a high PCE up to 83.2% in the NIR‐II window and exhibits excellent PTT tumor ablation performance. This provides a high‐performance NIR‐II‐responsive PTA, and offers further possibilities for the application of PTT in biomedical fields.
Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis
Authors: Xiaobo Zhu, Mingde Cao, Kejia Li, Yau-Tsz Chan, Hon-Fai Chan, Yi-Wah Mak, Hao Yao, Jing Sun, Michael Tim-Yun Ong, Kevin Ki-Wai Ho, Chien-Wei Lee, Oscar Kuang-Sheng Lee, Patrick Shu-Hang Yung, Yangzi Jiang
Journal: Bioactive Materials (2024)

Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor β (TGFβ) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFβ inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1 (as those levels found in patients' synovial fluid). A monthly injection strategy was then designed of using poly lactic-
Author Correction: Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis
Authors: Sneha Mitra, Rohan Malik, Wilfred Wong, Afsana Rahman, Alexander J. Hartemink, Yuri Pritykin, Kushal K. Dey, Christina S. Leslie
Journal: Nature Genetics (2024)

to 0.25 (one-quarter) rather than 0.2 (one-fifth) in the sentence "We left out one-fourth of the data for testing.The regularization parameter was selected using fourfold cross-validation on the remaining three-quarters of the cells."These corrections have been made to the HTML and PDF versions of the article and do not change the results reported in the paper.
Author Correction: c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis
Authors: Christian Neumann, Jonas Blume, Urmi Roy, Peggy P. Teh, Ajithkumar Vasanthakumar, Alexander Beller, Yang Liao, Frederik Heinrich, Teresita L. Arenzana, Jason A. Hackney, Celine Eidenschenk, Eric J. C. Gálvez, Christina Stehle, Gitta A. Heinz, Patrick Maschmeyer, Tom Sidwell, Yifang Hu, Derk Amsen, Chiara Romagnani, Hyun-Dong Chang, Andrey Kruglov, Mir-Farzin Mashreghi, Wei Shi, Till Strowig, Sascha Rutz, Axel Kallies, Alexander Scheffold
Journal: Nature Immunology (2024)
MNMST: topology of cell networks leverages identification of spatial domains from spatial transcriptomics data
Authors: Yu Wang, Zaiyi Liu, Xiaoke Ma
Journal: Genome biology (2024)

Abstract Advances in spatial transcriptomics provide an unprecedented opportunity to reveal the structure and function of biology systems. However, current algorithms fail to address the heterogeneity and interpretability of spatial transcriptomics data. Here, we present a multi-layer network model for identifying spatial domains in spatial transcriptomics data with joint learning. We demonstrate that spatial domains can be precisely characterized and discriminated by the topological structure of cell networks, facilitating identification and interpretability of spatial domains, which outperforms state-of-the-art baselines. Furthermore, we prove that network model offers an effective and efficient strategy for integrative analysis of spatial transcriptomics data from various platforms.
Identification of the RSX interactome in a marsupial shows functional coherence with the Xist interactome during X inactivation
Authors: Kim L. McIntyre, Shafagh A. Waters, Ling Zhong, Gene Hart-Smith, Mark Raftery, Zahra A. Chew, Hardip R. Patel, Jennifer A. Marshall Graves, Paul D. Waters
Journal: Genome biology (2024)

Abstract The marsupial specific RSX lncRNA is the functional analogue of the eutherian specific XIST , which coordinates X chromosome inactivation. We characterized the RSX interactome in a marsupial representative (the opossum Monodelphis domestica ), identifying 135 proteins, of which 54 had orthologues in the XIST interactome. Both interactomes were enriched for biological pathways related to RNA processing, regulation of translation, and epigenetic transcriptional silencing. This represents a remarkable example showcasing the functional coherence of independently evolved lncRNAs in distantly related mammalian lineages.
scCDC: a computational method for gene-specific contamination detection and correction in single-cell and single-nucleus RNA-seq data
Authors: Weijian Wang, Yihui Cen, Zezhen Lu, Yueqing Xu, Tianyi Sun, Ying Xiao, Wanlu Liu, Jingyi Jessica Li, Chaochen Wang
Journal: Genome biology (2024)

Abstract In droplet-based single-cell and single-nucleus RNA-seq assays, systematic contamination of ambient RNA molecules biases the quantification of gene expression levels. Existing methods correct the contamination for all genes globally. However, there lacks specific evaluation of correction efficacy for varying contamination levels. Here, we show that DecontX and CellBender under-correct highly contaminating genes, while SoupX and scAR over-correct lowly/non-contaminating genes. Here, we develop scCDC as the first method to detect the contamination-causing genes and only correct expression levels of these genes, some of which are cell-type markers. Compared with existing decontamination methods, scCDC excels in decontaminating highly contaminating genes while avoiding over-correction of other genes.
Platelet-mediated circulating tumor cell evasion from natural killer cell killing through immune checkpoint CD155-TIGIT
Authors: Yunfan Sun, Tong Li, Lin Ding, Jiyan Wang, Chen Chen, Te Liu, Yu Liu, Qian Li, Chuyu Wang, Ran Huo, Hao Wang, Tongtong Tian, Chunyan Zhang, Baishen Pan, Jian Zhou, Jia Fan, Xinrong Yang, Wenjing Yang, Beili Wang, Wei Guo
Journal: Hepatology (2024)

Background and Aims: Circulating tumor cells (CTCs) are precursors of cancer metastasis. However, how CTCs evade immunosurveillance during hematogenous dissemination remains unclear. Approach and Results: We identified CTC-platelet adhesions by single-cell RNA sequencing and multiplex immunofluorescence of blood samples from multiple cancer types. Clinically, CTC-platelet aggregates were associated with significantly shorter progression-free survival and overall survival in patients with HCC. In vitro, ex vivo, and in vivo assays demonstrated direct platelet adhesions gifted cancer cells with an evasive ability from NK cell killing by upregulating inhibitory checkpoint CD155 (PVR cell adhesion molecule), therefore facilitating distant metastasis. Mechanistically, CD155 was transcriptionally regulated by the FAK/JNK/c-Jun cascade in a platelet contact–dependent manner. Further competition assays and cytotoxicity experiments revealed that CD155 on CTCs inhibited NK-cell cytotoxicity only by engaging with immune receptor TIGIT, but not CD96 and DNAM1, another 2 receptors for CD155. Interrupting the CD155-TIGIT interactions with a TIGIT antibody restored NK-cell immunosurveillance on CTCs and markedly attenuated tumor metastasis. Conclusions: Our results demonstrated CTC evasion from NK-cell–mediated innate immunosurveillance mainly through immune checkpoint CD155-TIGIT, potentially offering an immunotherapeutic strategy for eradicating CTCs.
Microbiome research in Africa must be based on equitable partnerships
Authors: Ovokeraye H. Oduaran, Moréniké Oluwátóyìn Foláyan, Arox W. Kamng’ona, Annettee Nakimuli, Lamech M. Mwapagha, Mathabatha E. Setati, Michael Owusu, Nicola Mulder, Thulani P. Makhalanyane, Soumaya Kouidhi
Journal: Nature Medicine (2024)
Cicer super-pangenome provides insights into species evolution and agronomic trait loci for crop improvement in chickpea
Authors: Aamir W. Khan, Vanika Garg, Shuai Sun, Saurabh Gupta, Olga Dudchenko, Manish Roorkiwal, Annapurna Chitikineni, Philipp E. Bayer, Chengcheng Shi, Hari D. Upadhyaya, Abhishek Bohra, Chellapilla Bharadwaj, Reyazul Rouf Mir, Kobi Baruch, Bicheng Yang, Clarice J. Coyne, Kailash C. Bansal, Henry T. Nguyen, Gil Ronen, Erez Lieberman Aiden, Erik Veneklaas, Kadambot H. M. Siddique, Xin Liu, David Edwards, Rajeev K. Varshney
Journal: Nature Genetics (2024)
In vivo rescue of genetic dilated cardiomyopathy by systemic delivery of nexilin
Authors: Yanjiao Shao, Canzhao Liu, Hsin-Kai Liao, Ran Zhang, Baolei Yuan, Hanyan Yang, Ronghui Li, Siting Zhu, Xi Fang, Concepcion Rodriguez Esteban, Ju Chen, Juan Carlos Izpisua Belmonte
Journal: Genome biology (2024)

Abstract Background Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Multiple identified mutations in nexilin (NEXN) have been suggested to be linked with severe DCM. However, the exact association between multiple mutations of Nexn and DCM remains unclear. Moreover, it is critical for the development of precise and effective therapeutics in treatments of DCM. Results In our study, Nexn global knockout mice and mice carrying human equivalent G645del mutation are studied using functional gene rescue assays. AAV-mediated gene delivery is conducted through systemic intravenous injections at the neonatal stage. Heart tissues are analyzed by immunoblots, and functions are assessed by echocardiography. Here, we identify functional components of Nexilin and demonstrate that exogenous introduction could rescue the cardiac function and extend the lifespan of Nexn knockout mouse models. Similar therapeutic effects are also obtained in G645del mice, providing a promising intervention for future clinical therapeutics. Conclusions In summary, we demonstrated that a single injection of AAV-Nexn was capable to restore the functions of cardiomyocytes and extended the lifespan of Nexn knockout and G645del mice. Our study represented a long-term gene replacement therapy for DCM that potentially covers all forms of loss-of-function mutations in NEXN.
Adult-onset hearing loss and incident cognitive impairment and dementia – A systematic review and meta-analysis of cohort studies
Authors: Ruan-Ching Yu, Danielle Proctor, Janvi Soni, Liam Pikett, Gill Livingston, Glyn Lewis, Anne Schilder, Doris Bamiou, Rishi Mandavia, Rumana Omar, Menelaos Pavlou, Frank Lin, Adele M. Goman, Sergi Costafreda Gonzalez
Journal: Ageing Research Reviews (2024)

We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive. We included cohort studies with participants without dementia and with hearing assessments at baseline, minimum 2 years follow-up and incident cognitive outcomes. We used random-effect models and subgroup and meta-regression on moderator analyses. We identified fifty studies (N=1,548,754). Hearing loss (yes/no) was associated with incident dementia risk (HR=1.35 [95% CI = 1.26 – 1.45), mild cognitive impairment (MCI HR=1.29 [95% CI = 1.11 – 1.50]), cognitive decline not specified as MCI or dementia (HR=1.29 [95% CI = 1.17 – 1.42]), and Alzheimer's disease dementia (ADD, HR=1.56 [95% CI = 1.30 – 1.87]), but not with vascular dementia (HR, 1.30 [95% CI = 0.83 – 2.05]). Each 10-decibel worsening of hearing was associated with a 16% increase in dementia risk (95% CI = 1.07 – 1.27). The effect of hearing loss did not vary across potential moderators. Cohort studies consistently support that adult-onset hearing loss increases the risk of incident cognitive decline, dementia, MCI, and ADD.
METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs
Authors: Yizhou Jin, Xiao Han, Yuejun Wang, Zhipeng Fan
Journal: International Journal of Oral Science (2024)

Abstract Bisphosphonate-related osteonecrosis of jaw (BRONJ) is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells (BMSCs). Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders. However, the role of corin in BRONJ-related BMSCs dysfunction remains unclarified. A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation. Corin knockdown inhibits BMSCs osteogenic differentiation, whereas corin overexpression or soluble corin (sCorin) exerts a promotion effect. Furthermore, corin expression is negatively regulated by bisphosphonates (BPs). Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability. Mechanistically, we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation. PD98059 (a selective ERK inhibitor) blocks the corin-mediated promotion effect. With regard to the high methylation level of corin during osteogenic differentiation, we apply a non-selective m6A methylase inhibitor, Cycloleucine, which also blocks the corin-mediated promotion effect. Furthermore, we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function, indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability. To conclude, our study reveals that corin reverses BPs-induced BMSCs dysfunction, and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway. We hope this brings new insights into future clinical treatments for BRONJ.
CD44 and its implication in neoplastic diseases
Authors: Yiming Xu, Ziyi Bai, Tianxia Lan, Chenying Fu, Ping Cheng
Journal: MedComm (2024)

CD44, a nonkinase single span transmembrane glycoprotein, is a major cell surface receptor for many other extracellular matrix components as well as classic markers of cancer stem cells and immune cells. Through alternative splicing of