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Enhancing cellulase biosynthesis of Bacillus subtilis Z2 by regulating intracellular NADH level

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-03 DOI: 10.1016/j.isci.2025.112341

Shuai Liu , Yi Li , Lin Quan , Hai-Xia Liu , Yang Luo , Yong-Zhong Wang

{"title":"Enhancing cellulase biosynthesis of Bacillus subtilis Z2 by regulating intracellular NADH level","authors":"Shuai Liu , Yi Li , Lin Quan , Hai-Xia Liu , Yang Luo , Yong-Zhong Wang","doi":"10.1016/j.isci.2025.112341","DOIUrl":"10.1016/j.isci.2025.112341","url":null,"abstract":"<div><div>Optimizing cellulase biosynthesis in <em>Bacillus subtilis</em> is crucial for enhancing enzymatic yield in lignocellulosic biomass conversion. However, the regulatory mechanisms linking intracellular NAD(H/<sup>+</sup>) levels to cellulase production remain elusive. In this study, we systematically screened 13 genes associated with NAD<sup>+</sup> biosynthesis and NADH regeneration in <em>B. subtilis</em> Z2. Employing a modular engineering strategy with four distinct modules, we directed metabolic flux to enhance NAD<sup>+</sup> biosynthesis and NADH regeneration. Key genes (<em>ycel</em>, <em>nadV</em>, <em>nadM</em>, <em>mdh</em>, and <em>sucB</em>) were identified, and their co-expression in <em>B. subtilis</em> Z2 resulted in a 13.09-fold increase in intracellular NADH levels and a consequential 2.24- and 2.04-fold enhancement in the filter paper-hydrolyzing (FPase [representing total cellulase]) activity and carboxymethylcellulose (CMCase [representing endoglucanase]) activity, respectively. Experimental validations, including antagonist LaCl<sub>3</sub> treatment and <em>spcF</em> gene deletion, unequivocally established the calcium signaling pathway’s role in regulating cellulase gene overexpression in response to elevated intracellular NAD(H/<sup>+</sup>) levels.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112341"},"PeriodicalIF":4.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocytic FABP5 mediates retrograde endocannabinoid transport at central synapses

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-02 DOI: 10.1016/j.isci.2025.112342

Saida Oubraim , Mohammad Fauzan , Keith Studholme , Chris Gordon , Sherrye T. Glaser , Roh-Yu Shen , Iwao Ojima , Martin Kaczocha , Samir Haj-Dahmane

{"title":"Astrocytic FABP5 mediates retrograde endocannabinoid transport at central synapses","authors":"Saida Oubraim , Mohammad Fauzan , Keith Studholme , Chris Gordon , Sherrye T. Glaser , Roh-Yu Shen , Iwao Ojima , Martin Kaczocha , Samir Haj-Dahmane","doi":"10.1016/j.isci.2025.112342","DOIUrl":"10.1016/j.isci.2025.112342","url":null,"abstract":"<div><div>Endocannabinoids (eCBs) regulate synaptic function via cannabinoid receptors. While eCB signaling is well understood, the mechanisms underlying eCB synaptic transport are poorly characterized. Using 2-arachidonoylglycerol (2-AG)-mediated depolarization-induced suppression of inhibition (DSI) in the hippocampus as a readout of retrograde eCB signaling, we demonstrate that the deletion of fatty acid binding protein 5 (FABP5) impairs DSI. In FABP5 KO mice, DSI was rescued by re-expressing wild-type FABP5 but not an FABP5 mutant that does not bind 2-AG. Importantly, the deletion of astrocytic FABP5 blunted DSI, which was rescued by its re-expression in the astrocytes of FABP5 KO mice. Neuronal FABP5 was dispensable for 2-AG signaling. DSI was also rescued by expressing a secreted FABP5 variant but not by FABP7, an astrocytic FABP that does not undergo secretion. Our results demonstrate that extracellular FABP5 of astrocytic origin controls 2-AG transport and that FABP5 is adapted to coordinate intracellular and synaptic eCB transport.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112342"},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Competing signaling pathways controls electrotaxis

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-02 DOI: 10.1016/j.isci.2025.112329

S. Kulkarni , F. Tebar , C. Rentero , M. Zhao , P. Sáez

引用次数: 0

NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-02 DOI: 10.1016/j.isci.2025.112343

Shuqing Tang , Yusang Zhang , Peiyun Wang , Qiyu Tang , Yating Liu , Fan Lu , Mengting Han , Miaojin Zhou , Qian Hu , Mai Feng , Desheng Liang

{"title":"NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand","authors":"Shuqing Tang , Yusang Zhang , Peiyun Wang , Qiyu Tang , Yating Liu , Fan Lu , Mengting Han , Miaojin Zhou , Qian Hu , Mai Feng , Desheng Liang","doi":"10.1016/j.isci.2025.112343","DOIUrl":"10.1016/j.isci.2025.112343","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) hold potential in cancer therapy; however, insufficient tumor homing ability and heterogeneity limit their therapeutic benefits. Obviously, the homogeneous induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) with enhanced ability of tumor targeting could be the solution. In this study, a CAR containing the NKG2D extracellular domain was targeted at the <em>B2M</em> locus of iPSCs to generate NKG2D-CAR-iPSCs, which were subsequently differentiated into NKG2D-CAR-iMSCs. <em>In vitro</em>, NKG2D-CAR significantly enhanced migration and adhesion of iMSCs to a variety of solid tumor cells expressing NKG2D ligands. RNA sequencing (RNA-seq) revealed significant upregulation of genes related to cell adhesion, migration, and binding in NKG2D-CAR-iMSCs. In A549 xenograft model, NKG2D-CAR-iMSCs demonstrated a 57% improvement in tumor-homing ability compared with iMSCs. In conclusion, our findings demonstrate enhanced targeting specificity of NKG2D-CAR-iMSCs to tumor cells expressing NKG2D ligands <em>in vitro</em> and <em>in vivo</em>, facilitating future investigation of iMSCs as an off-the-shelf living carrier for targeted delivery of anti-tumor agents.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112343"},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-fibrotic, muscle-promoting antibody-drug conjugates for the improvement and treatment of DMD 用于改善和治疗 DMD 的抗纤维化、促进肌肉生长的抗体药物共轭物

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-02 DOI: 10.1016/j.isci.2025.112335

Anas Odeh , Mor Sela , Shelly Zaffryar-Eilot , Ariel Shemesh , Maher Abu Saleh , Ido Mizrahi , Lavi Coren , Avi Schroeder , Peleg Hasson

引用次数: 0

Origin and development of uniparental and polyploid blastomeres

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-02 DOI: 10.1016/j.isci.2025.112337

Yan Zhao , Andrea Fernández-Montoro , Greet Peeters , Tatjana Jatsenko , Tine De Coster , Daniel Angel-Velez , Thomas Lefevre , Thierry Voet , Olga Tšuiko , Ants Kurg , Katrien Smits , Ann Van Soom , Joris Robert Vermeesch

{"title":"Origin and development of uniparental and polyploid blastomeres","authors":"Yan Zhao , Andrea Fernández-Montoro , Greet Peeters , Tatjana Jatsenko , Tine De Coster , Daniel Angel-Velez , Thomas Lefevre , Thierry Voet , Olga Tšuiko , Ants Kurg , Katrien Smits , Ann Van Soom , Joris Robert Vermeesch","doi":"10.1016/j.isci.2025.112337","DOIUrl":"10.1016/j.isci.2025.112337","url":null,"abstract":"<div><div>Whole-genome (WG) abnormalities, such as uniparental diploidy and triploidy, cause fetal death. Occasionally, they coexist with biparental diploid cells in live births. Understanding the origin and early development of WG abnormal blastomeres is crucial for explaining the formation of androgenotes, gynogenotes, triploidy, chimerism, and mixoploidy. By haplotyping 118 bovine blastomeres from the first cleavages, we identified that heterogoneic division occurs in both multipolar and bipolar cleaving zygotes. During heterogoneic division, parental genomes segregate into distinct blastomeres, resulting in the coexistence of uniparental and biparental diploid or polyploid cells. After culturing the totipotent blastomeres to three preimplantation stages and exploring transcriptomes of 446 cells, we discovered that stress responses contribute to developmental impairment in WG abnormal cells, resulting in either cell arrest or blastocyst formation. Their dominance in preimplantation embryos represents an overlooked cause of abnormal development. Haplotype-based screening could improve <em>in vitro</em> fertilization outcomes.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112337"},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of rRNA synthesis by BCL-2 induces chemoresistance in diffuse large B cell lymphoma

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-02 DOI: 10.1016/j.isci.2025.112333

Alessandra Rossi , Saveria Mazzara , Dorotea Salemi , Simone Zanetti , Maria Rosaria Sapienza , Stefania Orecchioni , Giovanna Talarico , Paolo Falvo , Alessandro Davini , Claudio Ceccarelli , Giovanna Motta , Federica Melle , Valentina Tabanelli , Claudio Agostinelli , Davide Trerè , Marianna Penzo , Chiara Corsini , Elena Baiardi , Angelica Calleri , Umberto Vitolo , Enrico Derenzini

{"title":"Downregulation of rRNA synthesis by BCL-2 induces chemoresistance in diffuse large B cell lymphoma","authors":"Alessandra Rossi , Saveria Mazzara , Dorotea Salemi , Simone Zanetti , Maria Rosaria Sapienza , Stefania Orecchioni , Giovanna Talarico , Paolo Falvo , Alessandro Davini , Claudio Ceccarelli , Giovanna Motta , Federica Melle , Valentina Tabanelli , Claudio Agostinelli , Davide Trerè , Marianna Penzo , Chiara Corsini , Elena Baiardi , Angelica Calleri , Umberto Vitolo , Enrico Derenzini","doi":"10.1016/j.isci.2025.112333","DOIUrl":"10.1016/j.isci.2025.112333","url":null,"abstract":"<div><div>Overexpression of the antiapoptotic oncogene <em>BCL-2</em> predicts poor prognosis in diffuse large B cell lymphoma (DLBCL) treated with anthracycline-based chemoimmunotherapy. Anthracyclines exert antitumor effects by multiple mechanisms including inhibition of ribosome biogenesis (RiBi) through rRNA synthesis blockade. RiBi inhibitors induce p53 stabilization through the ribosomal proteins-MDM2-p53 pathway, with stabilized p53 levels depending on baseline rRNA synthesis rate. We found that the BH3-mimetic venetoclax could not fully reverse BCL-2-mediated resistance to RiBi inhibitors in DLBCL cells. BCL-2 overexpression was associated with decreased baseline rRNA synthesis rate, attenuating p53 stabilization by RiBi inhibitors. Drugs stabilizing p53 irrespective of RiBi inhibition reversed BCL-2-induced resistance <em>in vitro</em> and <em>in vivo</em>, restoring p53 activation and apoptosis. A small nucleolar size, indicative of low baseline rRNA synthesis, correlated with high BCL-2 levels and poor outcomes in DLBCL patients. These findings uncover alternative BCL-2-dependent chemoresistance mechanisms, providing a rationale for specific combination strategies in BCL-2 positive lymphomas.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112333"},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Facilitating circularity of end-of-life photovoltaic in China with environmental benefits and costs informed by a high-resolution waste map

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-04-02 DOI: 10.1016/j.isci.2025.112332

Chen Wang , Peipei Tian , Jian Zuo , Honglin Zhong , Xi Liu , Hailiang Liu , Longpeng Ma , Peng Wang , Kuishuang Feng , Jiashuo Li

{"title":"Facilitating circularity of end-of-life photovoltaic in China with environmental benefits and costs informed by a high-resolution waste map","authors":"Chen Wang , Peipei Tian , Jian Zuo , Honglin Zhong , Xi Liu , Hailiang Liu , Longpeng Ma , Peng Wang , Kuishuang Feng , Jiashuo Li","doi":"10.1016/j.isci.2025.112332","DOIUrl":"10.1016/j.isci.2025.112332","url":null,"abstract":"<div><div>The rapid growth of global photovoltaic (PV) installation will lead to the emergence of end-of-life (EoL) modules in the coming decades. It is essential to understand when, where, and how much PV waste will be generated and the benefits of recycling in order to promote a circular PV economy. In this study, we develop a multi-model, multi-scale assessment framework to forecast PV waste distribution and explore the resource, environmental, and economic benefits of various waste management strategies in China. Our findings show that PV waste will reach 26 million tons by 2050. Decommissioning hotspots will first emerge in the Northwest, then spread to the North and East. Compared to a single strategy, the combined strategy generates significant benefits, reducing emissions by 39 MtCO<sub>2</sub>eq and cutting costs by $2.3 billion. By providing a comprehensive picture of the dynamics of PV waste, our study enables policymakers to formulate region-specific recycling strategies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112332"},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-31 DOI: 10.1016/j.isci.2025.112324

Pauline Chenuet , Manon Mellier , Yasmine Messaoud-Nacer , Elodie Culerier , Quentin Marquant , Louis Fauconnier , Nathalie Rouxel , Aurélie Ledru , Stéphanie Rose , Bernhard Ryffel , Lionel Apetoh , Valérie F.J. Quesniaux , Dieudonnée Togbe

{"title":"Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice","authors":"Pauline Chenuet , Manon Mellier , Yasmine Messaoud-Nacer , Elodie Culerier , Quentin Marquant , Louis Fauconnier , Nathalie Rouxel , Aurélie Ledru , Stéphanie Rose , Bernhard Ryffel , Lionel Apetoh , Valérie F.J. Quesniaux , Dieudonnée Togbe","doi":"10.1016/j.isci.2025.112324","DOIUrl":"10.1016/j.isci.2025.112324","url":null,"abstract":"<div><div>Detecting cytoplasmic or extracellular DNA from host or pathogen origin by DNA sensor cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggers immune responses with secretion of type I interferons and inflammatory cytokines. However, STING agonists function as type-2 adjuvant promoting allergic asthma. Here, we asked how cGAS/STING signaling pathway influences allergen-induced type-2 immune responses in models of allergic airway diseases induced by birch pollen extract, house dust mite, or ovalbumin plus Alum. We report increased extracellular dsDNA in the airways, together with cGAS and STING gene expression, following allergen challenge in these models, correlating dsDNA and type-2 cytokine IL-4, IL-5, and IL-13 release. Allergen-induced type-2 immune responses were reduced in cGAS- or STING-deficient mice. Further, blocking cGAS function with the specific inhibitor RU.521 protected mice from birch pollen allergen-induced airway inflammation and type-2 immune responses. Thus, DNA sensing by cGAS contributes to type-2 immune responses and may represent a therapeutic target for allergic lung inflammation.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112324"},"PeriodicalIF":4.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing dichromate transport and reduction via electric fields induced by photocatalysis

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-31 DOI: 10.1016/j.isci.2025.112327

Chen Chen , Siyu Zhao , Bingming Zhou , Changqing Ye , Baojiang Jiang , Liping Zhang

{"title":"Enhancing dichromate transport and reduction via electric fields induced by photocatalysis","authors":"Chen Chen , Siyu Zhao , Bingming Zhou , Changqing Ye , Baojiang Jiang , Liping Zhang","doi":"10.1016/j.isci.2025.112327","DOIUrl":"10.1016/j.isci.2025.112327","url":null,"abstract":"<div><div>Mass transport is a fundamental yet often overlooked factor in influencing adsorption and photocatalytic reaction kinetics. This study examines the role of mass transport using the model system of monoclinic bismuth vanadate (BiVO<sub>4</sub>) films and potassium dichromate (K<sub>2</sub>Cr<sub>2</sub>O<sub>7</sub>) in a representative photocatalytic reaction. We show that diffusion-driven delivery of K<sub>2</sub>Cr<sub>2</sub>O<sub>7</sub> to the BiVO<sub>4</sub> surface increases adsorption capacity but decreases the adsorption rate constant. Notably, during the model photocatalytic reduction, long-range electric fields were observed around the illuminated BiVO<sub>4</sub> films, a phenomenon also confirmed in a separate reaction system using TiO<sub>2</sub> as the photocatalyst. These electric fields, distinct from the localized fields formed within heterojunctions, enhance dichromate transport by more than three orders of magnitude. This enhanced transport ensures a continuous supply of reactant to the photocatalyst, significantly improving reaction efficiency without additional energy input. These findings introduce a new strategy for optimizing photocatalytic processes, offering broad insights for advancing sustainable chemical engineering applications.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 5","pages":"Article 112327"},"PeriodicalIF":4.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0