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| Open AccessDiet-omics in the
S tudy ofU rban andR uralC rohn diseaseE volution (SOURCE) cohortExposures rather than genetics likely contribute to the worldwide increased prevalence of Crohn Disease (CD). Here, the authors constructed the Study Of Urban and Rural Crohn disease Evolution (SOURCE), a multicenter and multi-omics cross-sectional study, to identify that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirrored those seen in CD. Reviewer recognition:
- Tzipi Braun
- , Rui Feng
- & Yael Haberman
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Article
| Open AccessGenetic association of inflammatory marker GlycA with lung function and respiratory diseases
Here, the authors observed significant genetic correlation of GlycA with lung function, asthma and COPD and identified ten shared loci revealing potential shared biological mechanisms involving ubiquitination and Wnt/β-catenin signaling.
- Yanjun Guo
- , Quanhong Liu
- & Weihong Chen
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Article
| Open AccessTargeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow
Excessive bone marrow adipocytes accumulation is involved in bone deterioration. Here, the authors show that adipocyte ESRRA abrogation promotes osteogenesis and vascular formation in adipocyte-rich bone marrow via oppositely regulating the expression and secretion of leptin and SPP1.
- Tongling Huang
- , Zhaocheng Lu
- & Min Guan
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Article
| Open AccessOzone as an environmental driver of influenza
Temperature and absolute humidity are associated with influenza activity, and recent data from Hong Kong have suggested ozone as an additional environmental driver. Here, the authors investigate the relationship between ozone and influenza transmission using surveillance data from the USA and find evidence for an inhibitory effect.
- Fang Guo
- , Pei Zhang
- & Linwei Tian
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Article
| Open AccessA multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma
Correct diagnosis of primary central nervous system lymphoma is key in determining treatment, however, this depends on pathology analysis. Here, the authors develop a deep learning method to diagnose primary nervous system lymphoma from stained whole-slide images.
- Xinke Zhang
- , Zihan Zhao
- & Muyan Cai
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Article
| Open AccessIL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube
In pelvic inflammatory disease, host immune responses to Neisseria gonorrhoeae damage Fallopian tube tissue and cause infertility. Here, Garcia et al. show that the cytokine IL-17C induces inflammatory responses, and peptidoglycan fragments reduce transcripts related to tissue integrity.
- Erin M. Garcia
- , Jonathan D. Lenz
- & Joseph P. Dillard
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Article
| Open AccessLncRNA-LncDACH1 mediated phenotypic switching of smooth muscle cells during neointimal hyperplasia in male arteriovenous fistulas
Arteriovenous fistulas are the most common vascular access points for hemodialysis, but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia. Here, the author shows that LncDACH1 regulates NIH through the HSP90/ SRPK1/ AKT signaling axis.
- Zhaozheng Li
- , Yao Zhao
- & Jundong Jiao
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Article
| Open AccessCD74 supports accumulation and function of regulatory T cells in tumors
CD74, the MHC class II invariant chain, was thought to be mainly expressed by antigen presenting cells. Here the authors report that CD74 is overexpressed by human tumor infiltrating regulatory T cells (Tregs) and that its loss affects Treg accumulation and function in tumors.
- Elisa Bonnin
- , Maria Rodrigo Riestra
- & Eliane Piaggio
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Article
| Open AccessCirculating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank
Different fatty acids have been associated to liver diseases. Here, the authors show that plasma levels of different circulating fatty acids are either negatively or positively associated with the risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank cohort.
- Zhening Liu
- , Hangkai Huang
- & Chengfu Xu
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Article
| Open AccessResponse of treatment-naive brain metastases to stereotactic radiosurgery
Current guidelines recommend stereotactic radiosurgery for brain metastasis measuring less than 3 cm but there is significant variability in outcomes following treatment. This study shows that in treatment naïve brain metastasis less than 3 cm, intrinsic biological differences across multiple histologies may influence response to stereotactic radiosurgery.
- Chibawanye I. Ene
- , Christina Abi Faraj
- & Raymond E. Sawaya
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Article
| Open AccessMultimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions
Please let us know if there are any inaccuracies: ‘Esophageal squamous cell carcinoma is most commonly detected at a late stage, which limits survival and treatment options. Here, the authors utilise whole genome bisulfite sequencing to create a cfDNA framework to detect cfDNA methylation, copy number variants and fragmentation.
- Jiaqi Liu
- , Lijun Dai
- & Zhihua Liu
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Article
| Open AccessUsing genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes
Here, the authors integrate genomic and transcriptomic data obtained from African-ancestry female participants and identify six genes associated with breast cancer risk which provides biological insights into this common cancer in an underrepresented population.
- Jie Ping
- , Guochong Jia
- & Wei Zheng
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Article
| Open AccessA patient-based iPSC-derived hepatocyte model of alcohol-associated cirrhosis reveals bioenergetic insights into disease pathogenesis
Most people affected by Alcohol Use Disorder do not develop cirrhosis. Here, the authors show that induced pluripotent stem cell-derived hepatocytes from patients with Alcohol Cirrhosis, have impaired cell energy production and were more susceptible to oxidative stress, which is partially reversed by treatment with Aramchol.
- Bani Mukhopadhyay
- , Cheryl Marietta
- & David Goldman
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Article
| Open AccessModelling the transmission dynamics of H9N2 avian influenza viruses in a live bird market
H9N2 avian influenza is a virus with zoonotic potential that is common in poultry in live bird markets in Asia. In this study, the authors use mathematical modelling to characterise transmission of H9N2 in live bird markets in Bangladesh and assess the effectiveness of potential interventions to reduce its circulation.
- Francesco Pinotti
- , Lisa Kohnle
- & Guillaume Fournié
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| Open AccessConcomitant human papillomavirus (HPV) vaccination and screening for elimination of HPV and cervical cancer
Here the authors report baseline results of a population-based trial testing concomitant human papillomavirus (HPV) vaccination and HPV-based screening of young women in Sweden and, using a transmission model, suggest that this approach may reduce high-risk HPV infections.
- Laila Sara Arroyo Mühr
- , Andrea Gini
- & Joakim Dillner
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Article
| Open AccessGalectin-3 impairs calcium transients and β-cell function
Galectin-3, mainly produced and secreted by macrophages, is elevated in diabetes. Here, the authors show that galectin-3 directly interacts with voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and blocks calcium transients and subsequent insulin secretion.
- Qian Jiang
- , Qijin Zhao
- & Pingping Li
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Article
| Open AccessCerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases
CSF biomarker concentrations may be influenced by non-disease related interindividual variability. Here, the authors show that reference proteins can capture this variability and enhance the accuracy of Alzheimer’s disease biomarkers.
- Linda Karlsson
- , Jacob Vogel
- & Oskar Hansson
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Article
| Open AccessDevelopment of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy
The development of metal-nucleic acid nanocomposites for therapeutic is limited by poor stability and synthesis efficiency. Here, the authors develop a multi-fragmented aptamer DNAzyme metal-nucleic acid frameworks (MNFs) under milder conditions and demonstrate its preclinical efficacy in gastric cancer.
- Jiaqi Yan
- , Rajendra Bhadane
- & Hongbo Zhang
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Article
| Open AccessGlis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease
Cyst growth in autosomal dominant polycystic kidney disease (ADPKD) is driven by unknown molecular signals that require the presence of intact primary cilia in the absence of the PKD gene products. Here, the authors show that the transcription factor Glis2 is a key effector of this cilia dependent cyst growth pathway and a potential target for therapy in ADPKD
- Chao Zhang
- , Michael Rehman
- & Stefan Somlo
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| Open AccessCost-effectiveness and cost-utility of a digital technology-driven hierarchical healthcare screening pattern in China
Economic evaluation of utilization of digital technologies for cataract screening remains unknown. Here the authors show that digital hierarchical screening is cost-effective in China and annual screening proved to be the most cost-effective option.
- Xiaohang Wu
- , Yuxuan Wu
- & Haotian Lin
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Article
| Open AccessFn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity
The potential of oncolytic virus (OV) for cancer therapy is limited by the efficiency of immune response induced. Here the authors show that HSV-1-based OV is capable of triggering ZBP1-mediated PANoptosis resulting in effective tumor growth inhibition.
- Shuo Wang
- , An Song
- & Zhi-Jun Sun
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Article
| Open AccessPrimary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma
Cutaneous squamous cell carcinoma is more frequent and more aggressive in the organ transplanted and represent a therapeutic challenge due to the ongoing transplantrelated immune suppression. Here, the authors present a case report of a patient whose T cell responses were successfully strengthened via primary prophylactic therapy with mammalian target of rapamycin inhibition and intra-lesion injection of the oncolytic herpesvirus T-VEC.
- Victor Joo
- , Karim Abdelhamid
- & Michel Obeid
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Article
| Open AccessDopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo
Here, the authors report that schizophrenia risk variants mapping to a striatal dopamine-related gene set are associated with increased striatal dopamine synthesis capacity and increased striatal activity during reward anticipation in humans.
- Leonardo Sportelli
- , Daniel P. Eisenberg
- & Giulio Pergola
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Article
| Open AccessProtein mimetic 2D FAST rescues alpha synuclein aggregation mediated early and post disease Parkinson’s phenotypes
The aggregation of the neuronal protein α-Synuclein is associated with the onset of Parkinson’s disease. Here the authors report a two-dimensional Fragment Assisted Structure-based technique to find antagonists of α-Synuclein aggregation and show its promise for identifying lead therapeutics for Parkinson’s disease.
- Nicholas H. Stillman
- , Johnson A. Joseph
- & Sunil Kumar
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Article
| Open AccessDynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19
In this study, the authors report the case of a patient who underwent lung transplantation and subsequently developed COVID-19 that resulted in persistent infection. Following antiviral treatment, SARS-CoV-2 (BA.5) showed dynamic genetic diversity with remdesivir resistant mutations leading to enhanced fusogenicity.
- Hidetoshi Igari
- , Seiichiro Sakao
- & Eiji Ido
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Article
| Open AccessA secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1
Triazole antifungals are widely used and exert their action by inhibiting ergosterol biosynthesis. Here, Rybak et al show that these drugs both inhibit ergosterol biosynthesis and induce accumulation of pathway intermediates that directly induce inhibition of sterol synthesis.
- Jeffrey M. Rybak
- , Jinhong Xie
- & Jarrod R. Fortwendel
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Article
| Open AccessGut microbiome composition and metabolic activity in women with diverticulitis
Here, the authors present a multi-omics examination of stool samples obtained from individuals with diverticulitis and controls, uncovering disruptions in the balance of microbial composition and metabolites, as well as co-occurring microbe-metabolite associations relevant to the disease.
- Wenjie Ma
- , Yiqing Wang
- & Andrew T. Chan
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Article
| Open AccessIdentifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
Circulating proteins are a potential source of cancer biomarkers. Here, the authors assessed 2,074 circulating proteins and used Mendelian randomisation to compare with the risk of 9 common cancer types across multiple GWAS cohorts and identified key considerations with respect to the potential for adverse effects of altering cancer-risk proteins that inform their utility in cancer prevention.
- Karl Smith-Byrne
- , Åsa Hedman
- & Anders Mälarstig
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Article
| Open AccessMitochondrial complex I deficiency stratifies idiopathic Parkinson’s disease
Idiopathic Parkinson’s disease can be stratified according to the severity of neuronal respiratory complex I deficiency. The emerging disease subtypes show distinct molecular and clinical profiles.
- Irene H. Flønes
- , Lilah Toker
- & Charalampos Tzoulis
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Article
| Open AccessIndividualized prevention of proton pump inhibitor related adverse events by risk stratification
The safety profile of proton pump inhibitor (PPI) use remains controversial. Here, the authors show that PPI use is associated with an increased risk of 15 leading global diseases, with absolute risks increasing with baseline risks, highlighting the need for personalized PPI use strategies.
- Bin Xia
- , Qiangsheng He
- & Jinqiu Yuan
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Article
| Open AccessReservoir displacement by an invasive rodent reduces Lassa virus zoonotic spillover risk
Mastomys natalensis is a rodent species native to West Africa that is the primary reservoir host for Lassa virus. Here, the authors investigate whether the invasive rodent Rattus rattus decreases M. natalensis density and could therefore indirectly decrease zoonotic transmission of Lassa virus to humans.
- Evan A. Eskew
- , Brian H. Bird
- & Scott L. Nuismer
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Article
| Open AccessMacrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer
An inflammatory-fibrotic tumor microenvironment supports metastatic disease progression in pancreatic ductal adenocarcinoma (PDAC). Here the authors show that metastasis-infiltrating macrophages influence metastasis-associated fibroblast (MAF) heterogeneity in liver metastatic PDAC, by promoting JAK/STAT signalling pathway activation in MAFs.
- Meirion Raymant
- , Yuliana Astuti
- & Michael C. Schmid
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Article
| Open AccessA cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming
A regulated stress response is essential for healthy child growth and development. Here, the authors show that a nutrition, water, sanitation, and hygiene intervention enhanced adaptive responses of the physiological stress system in early childhood.
- Audrie Lin
- , Andrew N. Mertens
- & Douglas A. Granger
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Article
| Open AccessAn individualized protein-based prognostic model to stratify pediatric patients with papillary thyroid carcinoma
Papillary thyroid carcinoma has a heterogenous outcome, particularly in paediatric patients. Here, the authors utilise machine learning to create a protein-based prognostic model to predict recurrence risk.
- Zhihong Wang
- , He Wang
- & Yaoting Sun
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Article
| Open AccessLSD1 inhibition circumvents glucocorticoid-induced muscle wasting of male mice
Even though glucocorticoids are potent anti-inflammatory agents, they can cause muscle wasting. Here, the authors show that targeting the glucocorticoid receptor coactivator LSD1 limits muscle loss without reducing the drugs’ efficiency on the immune system.
- Qingshuang Cai
- , Rajesh Sahu
- & Delphine Duteil
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Article
| Open AccessFine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.
- Zhishan Chen
- , Xingyi Guo
- & Wei Zheng
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Article
| Open AccessMetabolomics facilitates differential diagnosis in common inherited retinal degenerations by exploring their profiles of serum metabolites
Diagnosing inherited retinal degeneration is challenging. This exploratory study showed that metabolomic profiles differ among different subtypes of IRD, and potential biomarkers could be identified to facilitate diagnosis workflow in the near future.
- Wei-Chieh Wang
- , Chu-Hsuan Huang
- & Ta-Ching Chen
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Article
| Open AccessMucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques
Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.
- Jaclyn A. Kaiser
- , Christine E. Nelson
- & Cyril Le Nouën
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Article
| Open AccessDiphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects
Rare disease DEDSSH1-associated DPH1 mutations impair eEF2 diphthamide modification that leads to eEF2 as a transcriptional coactivator for p53 to enhance expression of the cell proliferation inhibitor p21, resulting in birth defects.
- Yu Shi
- , Daochao Huang
- & Weihong Song
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Article
| Open AccessThe airborne transmission of viruses causes tight transmission bottlenecks
Genomic analyses have indicated that a small number of virus particles usually found new infections. Here, the authors use a mathematical model to show that this small transmission bottleneck is a result of the physical processes of airborne virus emission, diffusion, and inhalation.
- Patrick Sinclair
- , Lei Zhao
- & Christopher J. R. Illingworth
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Article
| Open AccessCAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition
It has been suggested that targeting the PD-1/PD-L1 axis can increase the anti-tumor properties of chimeric antigen receptor (CAR)-T cells. Here the authors report that CAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition.
- Irene Andreu-Saumell
- , Alba Rodriguez-Garcia
- & Sonia Guedan
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Article
| Open AccessSingle-cell analyses reveal transient retinal progenitor cells in the ciliary margin of developing human retina
Formation of the retina during development involves the coordinated action of retinal progenitor cells and their differentiated cell types, which is key for producing a functioning eye. Here the authors provide a detailed atlas of human retinal development, combining scRNA-seq and spatial transcriptomics, and identify key genetic factors that mediate retinal progenitor cell proliferation and differentiation.
- Birthe Dorgau
- , Joseph Collin
- & Majlinda Lako
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Article
| Open AccessLoss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice
Knowledge of pathogenesis mechanisms and effective treatments for viral myocarditis is lacking. Here, Wang et al show that loss of TRIM29 and PERK inhibitor mitigate viral myocarditis by attenuating PERK-driven ER stress and ROS responses in male mice.
- Junying Wang
- , Wenting Lu
- & Junji Xing
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Article
| Open AccessThe gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids
Here, the authors show that elevating fiber intake in humans alters their gut microbiota, which, upon transplantation into mice, enhances intestinal mucus function, and identify a crucial role played by the commensal bacterium Blautia and its fermentation products.
- Sandra M. Holmberg
- , Rachel H. Feeney
- & Bjoern O. Schroeder
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Article
| Open AccessBat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets
In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.
- Nico Joel Halwe
- , Lea Hamberger
- & Martin Beer
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Article
| Open AccessBIN1 knockdown rescues systolic dysfunction in aging male mouse hearts
Cardiac dysfunction is a hallmark of aging in humans and mice. Here, the authors show that by restoring youthful Bridging Integrator 1 (BIN1) protein levels in the hearts of 24-month-old mice in vivo cardiac systolic function is rejuvenated, and the aging phenotype partially reversed within two weeks.
- Maartje Westhoff
- , Silvia G. del Villar
- & Rose E. Dixon
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Article
| Open AccessTravel surveillance uncovers dengue virus dynamics and introductions in the Caribbean
Dengue is a major public health concern in the Americas, and the Caribbean can be a source for reintroduction and spread. Here, the authors use travel surveillance data and genomic epidemiology to reconstruct Dengue epidemic dynamics in the Caribbean from 2009-2022.
- Emma Taylor-Salmon
- , Verity Hill
- & Nathan D. Grubaugh
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Article
| Open AccessAmbient carbon dioxide concentration correlates with SARS-CoV-2 aerostability and infection risk
Carbon dioxide concentration has previously been used as a proxy for overall ventilation efficiency to indirectly estimate the risk of indoor SARS-CoV-2 transmission. Here, authors investigate whether the concentration of carbon dioxide also has a direct mechanistic role in improving transmission efficiency.
- Allen Haddrell
- , Henry Oswin
- & Jonathan P. Reid
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Article
| Open AccessOverlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange
Streptococcus dysgalactiae subsp. equisimilis is closely related to Streptococcus pyogenes and colonises the same sites in humans. This study examines cross-species transmission interactions and genetic exchange in a high disease burden setting.
- Ouli Xie
- , Cameron Zachreson
- & Steven Y. C. Tong