Life Sciences Research Articles

Fourteen years of cellular deconvolution: methodology, applications, technical evaluationand outstanding challenges.

Single-cell RNA sequencing (scRNA-Seq) is a recent technology that allows for the measurement of the expression of all genes in each individual cell contained in a sample. Information at the single-cell level has been shown to be extremely useful in many areas. However, performing single-cell experiments is expensive. Although cellular deconvolution cannot provide the same comprehensive information as single-cell experiments, it can extract cell-type information from bulk RNA data, and therefore it allows researchers to conduct studies at cell-type resolution from existing bulk datasets. For these reasons, a great effort has been made to develop such methods for cellular deconvolution. The large number of methods available, the requirement of coding skills, inadequate documentation, and lack of performance assessment all make it extremely difficult for life scientists to choose a suitable method for their experiment. This paper aims to fill this gap by providing a comprehensive review of 53 deconvolution methods regarding their methodology, applications, performance, and outstanding challenges. More importantly, the article presents a benchmarking of all these 53 methods using 283 cell types from 30 tissues of 63 individuals. We also provide an R package named DeconBenchmark that allows readers to execute and benchmark the reviewed methods (https://github.com/tinnlab/DeconBenchmark).

First report of sweepoviruses infecting Ipomeas batatas L. cultivars and landraces in Trinidad.

Root crops, referred to as ground provisions in the Caribbean, are traditional staples in Trinidad. One widely consumed example is sweet potato (Ipomeas batatas L.). The crop is mainly produced by subsistence farming which together with imports from neighboring Caribbean countries meet domestic demand (Singh et al. 2008). The Central Experiment Station, situated in the eastern part of Trinidad, maintains a sweet potato germplasm collection comprising both imported and locally-sourced landraces for cultivar development and distribution of propagules. In May 2017 chlorosis and leaf curling symptoms, typically associated with sweepoviruses, were observed on imported cultivars, Centennial, Jewel, 86 BM 31, TIB 313, TIB 8 21 1, and S128, and the landraces, Kick Up Jenny, John, and Carrot. Leaf samples from these nine symptomatic plants were collected for analysis, along with samples from the asymptomatic landrace, Chickenfoot. Total nucleic acids were extracted (Sharma et al. 2008) and the samples were assayed by PCR using degenerate primers SPG1 and SPG2 (Li et al. 2004) that target the replication associated protein gene (ORF C1), a highly conserved region of sweepoviruses. Amplicons of 912-bp were obtained from two of the nine symptomatic plants (TIB 8 21 1, Kick Up Jenny), but not from the asymptomatic Chickenfoot. The same samples were assayed by PCR amplification using primers SpvF and SpvR (Avelar 2015) which are specific to a highly conserved 632-bp region of the coat protein gene (ORF V1) of sweet potato leaf curl virus (SPLCV). All 10 samples tested positive for SPLCV, including the asymptomatic landrace, Chickenfoot. The ORF V1 PCR products from three of the 10 samples, namely Chickenfoot, TIB 8 21 1, and Kick Up Jenny, were cloned and sequenced (two clones per sample). Comparison of the sequences (GenBank accession nos. OR882007 [Chickenfoot], OR913125 [TIB 8 21 1] and OR913126 [Kick Up Jenny]) identified up to 4% nt sequence variability between samples. In BLASTn analysis, they were most closely related to the SPLCV isolate China:Sichuan (GenBank accession no. KJ013557), sharing 94 to 98% nt identity. Total nucleic extracts from one representative sample (TIB 8 21 1) was used as template for rolling circle amplification (RCA, TempliPhi Amplification Kit, GE Healthcare Life Sciences, Piscataway, NJ, USA). Digestion of the RCA product with StuI (Thermo Scientific, MA, USA) yielded ~2.8 kb DNA fragments indicative of monomeric full length genomes. Digested fragments were cloned, completely sequenced and deposited in GenBank under the accession nos. OR866202 (2,821 nts) and OR866203 (2,828 nts). Two species of sweepoviruses were detected. In BLASTn analysis, OR866202 showed 95% nt identity with sweet potato golden vein associated virus (SPGVaV) US:MS:1B-3 (GenBank accession no. HQ333143.1) which is a recombinant virus comprised of SPLCV and sweet potato leaf curl Georgia virus (SPLCGV) (Zhang and Ling 2011) and in BLASTx analysis OR866202 was most similar (92-99%) to SPLCV isolates from Brazil (GenBank accession nos. ACI23475.1, AGW16179.1, ACY79479.1), Peru (GenBank accession no. ACY79466.1) and China (GenBank accession nos. ACY79439.1). OR866203 shared 96% nt identity with SPLCV China:Henan25(8):2012 (GenBank accession no. KF040465.1) in BLASTn analysis and BLASTx analysis revealed ≥ 94% aa sequence identity with SPLCV from Brazil (GenBank accession nos. ACI23475.1, AGW16179.1, ADZ96559.1), Peru (GenBank accession no. ACY79479.1), China (GenBank accession no. ACY79466.1). and Spain (GenBank accession no. QWQ56365.1). Both Trinidad isolates also showed 90-96% nt identity with SPLCV from Korea (GenBank accession no.s KT992061.1, KT992064.1, unpublished). This is the first detection of sweepoviruses in Trinidad. SPGVaV has been reported in Brazil, the United States and Korea (Kil et al. 2014), while SPLCV has been described in other Caribbean islands, including Cuba, Jamaica, Puerto Rico, St. Vincent (Cuellar et al. 2015), and Barbados (Alleyne et al. 2019), as well as several countries in South America. Although Koch's postulates were not completed, our findings suggest that sweet potato crops in Trinidad harbor sweepoviruses, notwithstanding efforts to distribute pathogen-free materials and, in some instances, the apparent absence of visible symptoms on infected plants. Further studies on the management and impact of these viruses are necessary, including their prevalence in the sweet potato production regions of Trinidad.

The mechanical effects of chemical stimuli on neurospheres.

The formulation of more accurate models to describe tissue mechanics necessitates the availability of tools and instruments that can precisely measure the mechanical response of tissues to physical loads and other stimuli. In this regard, neuroscience has trailed other life sciences owing to the unavailability of representative live tissue models and deficiency of experimentation tools. We previously addressed both challenges by employing a novel instrument called the cantilevered-capillary force apparatus (CCFA) to elucidate the mechanical properties of mouse neurospheres under compressive forces. The neurospheres were derived from murine stem cells, and our study was the first of its kind to investigate the viscoelasticity of living neural tissues in vitro. In the current study, we demonstrate the utility of theCCFA as a broadly applicable tool to evaluate tissue mechanics by quantifying the effect that oxidative stress has on the mechanical properties of neurospheres. We treated mouse neurospheres with non-cytotoxic levels of hydrogen peroxide and subsequently evaluated the storage and loss moduli of the tissues under compression and tension. We observed that the neurospheres exhibit viscoelasticity consistent with neural tissue and show that elastic modulus decreases with increasing size of the neurosphere. Our study yields insights for establishing rheological measurements as biomarkers by laying the groundwork for measurement techniques and showing that the influence of a particular treatment may be misinterpreted if the size dependence is ignored.

Pretraining a foundation model for generalizable fluorescence microscopy-based image restoration.

Fluorescence microscopy-based image restoration has received widespread attention in the life sciences and has led to significant progress, benefiting from deep learning technology. However, most current task-specific methods have limited generalizability to different fluorescence microscopy-based image restoration problems. Here, we seek to improve generalizability and explore the potential of applying a pretrained foundation model to fluorescence microscopy-based image restoration. We provide a universal fluorescence microscopy-based image restoration (UniFMIR) model to address different restoration problems, and show that UniFMIR offers higher image restoration precision, better generalization and increased versatility. Demonstrations on five tasks and 14 datasets covering a wide range of microscopy imaging modalities and biological samples demonstrate that the pretrained UniFMIR can effectively transfer knowledge to a specific situation via fine-tuning, uncover clear nanoscale biomolecular structures and facilitate high-quality imaging. This work has the potential to inspire and trigger new research highlights for fluorescence microscopy-based image restoration.

Continuous Synthesis of a Macrocyclic Sulfite of Polyethylene Glycol by Cascaded Continuous Stirred Tank Reactors (CSTRs).

Invited for the cover of this issue is the group of Long Pan and co-workers at Asymchem Life Sciences (Tianjin) Co. Ltd. The image depicts a novel continuous process for the synthesis of a macrocyclic poly(ethylene glycol) (PEG) sulfite, the precursor to PEG macrocyclic sulfate, a useful building block in PEG chemistry. Read the full text of the article at 10.1002/chem.202304319.

Public research funding and science-based innovation: An analysis of ERC research grants, publications and patents

Abstract This study aims to advance the discussion around the linkages between public funding for scientific research and new technology development. We develop and test a methodology that matches patents to scientific publications, the latter of which stemming from publicly funded research. We specifically focus on projects that were funded by the European Research Council (ERC) in the Life Sciences and Physical Science and Engineering sectors during the FP7 Programme. We also compare this method’s results with the patents directly reported by the PIs of ERC-funded projects at the end of their grants, finding that the two methods are complementary. In addition to documenting important technological diffusion effects generated by ERC-funded research, our results highlight some factors that shape the relationships between patents, publications, and grants, such as project type, age, duration, scientific domain and number and quality of associated publications. Therefore, our findings present significant policy implications for funding agencies, universities, TTOs, and policymakers who want to monitor the technological outcomes of public research investments.

High‐Resolution 3D Printing of Dual‐Curing Thiol‐Ene/Epoxy System for Fabrication of Microfluidic Devices for Bioassays

AbstractThe customized processing of polymer materials in the microscale by high‐resolution 3D printing provides an easy access to advanced applications in the fields of optics, microfluidics, tissue engineering, and life science. However, the 3D printing of enclosed structures in the scale of tens of microns such as closed microfluidic channels remains a challenge as channel structures often are clogged by residual cured resin. Dual‐curing systems based on off‐stoichiometric thiol‐ene and thiol‐ene/epoxy chemistry are well‐known for adhesive‐free bonding in the fabrication of cast or injection molded microfluidic devices. Herein, the first high‐resolution stereolithography 3D printing of a dual‐curing thiol‐ene/epoxy system in the microscale for the fabrication of customized microfluidic devices is presented. In the first curing step, by high‐resolution 3D printing open microfluidic structures are produced. Consecutively, the microchannels are sealed by adhesive‐free dry bonding upon thermal initiation, producing well‐controlled structures with channel sizes down to 80 µm. Before bonding, the intermediate material allows for tailored surface modification with biotin, which allows for consecutive immobilization of various biomolecules. A DNA‐bioassay with specific patterning is shown in the sealed chip. The presented work paves the way toward the fabrication of customized microfluidic devices for a large range of specific bioassays.

Application and perspective of CRISPR/Cas9 genome editing technology in human diseases modeling and gene therapy

The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) mediated Cas9 nuclease system has been extensively used for genome editing and gene modification in eukaryotic cells. CRISPR/Cas9 technology holds great potential for various applications, including the correction of genetic defects or mutations within the human genome. The application of CRISPR/Cas9 genome editing system in human disease research is anticipated to solve a multitude of intricate molecular biology challenges encountered in life science research. Here, we review the fundamental principles underlying CRISPR/Cas9 technology and its recent application in neurodegenerative diseases, cardiovascular diseases, autoimmune related diseases, and cancer, focusing on the disease modeling and gene therapy potential of CRISPR/Cas9 in these diseases. Finally, we provide an overview of the limitations and future prospects associated with employing CRISPR/Cas9 technology for diseases study and treatment.

Infections Associated with Medtronic Duet External Ventricular Drains - Rhode Island Hospital, Providence, Rhode Island, January 2023-January 2024.

External ventricular drains (EVDs) are medical devices that are inserted into the ventricles of the brain to drain excess fluid, manage intracranial hypertension, monitor intracranial pressure, and administer medications. Unintentional disconnections and breaks or fractures (breaks) of EVDs or associated drainage system components can result in cerebrospinal fluid (CSF) leakage and increased risk for EVD-associated infections. After replacement of Integra Life Sciences EVD systems with Medtronic Duet EVD systems at Rhode Island Hospital in mid-September 2023, a threefold increase was observed in the prevalence of positive CSF cultures, from 2.8 per 1,000 days with an EVD in place (EVD days) during January-September 2023 to 11.4 per 1,000 EVD days during October 2023-January 2024 (rate ratio [RR] = 5.7; 95% CI = 1.5-22.0; p = 0.01) and an eightfold increase in the prevalence of infections, from 0.7 to 6.5 per 1,000 EVD days (RR = 9.8; 95% CI = 1.1-87.3; p = 0.04). An investigation by Rhode Island Hospital Infection Control during December 2023-January 2024 identified frequent reports of disconnections and breaks of the Medtronic Duet EVD system. A search of the Food and Drug Administration Manufacturer and User Facility Device Experience database identified 326 reports nationwide of disconnection and breaks of components of the Duet EVD system, including 175 during 2023. A Medical Product Safety Network report was filed. The Duet EVD product was ultimately recalled in January 2024, citing disconnections of the EVD system and reports of CSF leakage and infection. Given the widespread use of EVD systems by neurosurgery centers and the risk for EVD-associated infections, a strategy for future consideration by hospital infection prevention and control programs might be inclusion of EVD-associated infections in hospital surveillance programs to rapidly identify increases in these events and determine factors related to such infections to prevent additional infections.

Utility of Parinama Vada in Ayurveda

Ayurveda is a science of life which is greatly influenced by all Bharatiya Darshana. Sankhya Darshana is one of Aastik Darshana knowledge for permanent and sure relief from miseries is obtained through Darshanas. In Ayurveda Roga is considered as unhappiness Different theories were postulated by different Darshanas. Parinama Vada and Satkarya Vada have been explained by Sankhya Darshana. As per Satkaryavada every Karya (effect) is originated by specific Karana (cause) Parinama Vada tells that due to Parinama Karya and Karana are seems different. Parinama means change or transformation. As per Sanskhya Darshana universe is originated from Avyakta to Ekadash Indriya and Panchamahbhuta is due to Parinama only. Parinamavada is applied in Ayurveda to understand basic concepts of Ayurveda like Ahara Parinama, Dhatu Nirmana, Dhatu Poshana, Vyadhi Sama Nirama Avastha, Aoushadhi Nirmana etc.

Immune Response to an Inactivated Vaccine of SARS-CoV-2 (CoronaVac) in an Indigenous Brazilian Population: A Cohort Study

Introduction: Although the adaptive immune responses to the CoronaVac vaccine are known, their dynamics in indigenous communities remain unclear. In this study, we assessed the humoral and cellular immune responses to CoronaVac (Sinovac Biotech Life Sciences, 2021 NCT05225285, Beijing, China), in immunized Brazilian indigenous individuals. Methods: We conducted a prospective cohort study on indigenous Brazilian people between February 2021 and June 2021. Analyses of immune responses were carried out before (T1) and after a vaccination schedule was completed (T2). Demographic data were collected using a questionnaire. Results: We initially included 328 patients; among them, 120 (36.6%) had no SARS-CoV-2 antibodies. Peripheral blood mononuclear cells (PBMCs) were collected from 106 patients during follow-up visits, of which 91 samples were analyzed by immunophenotyping assay to detect SARS-CoV-2-specific memory T-cell response. Post-vaccination, the levels of memory B-cells and Natural Killer T-lymphocytes increased. Bororó village residents, females, and Terena ethnic group members had higher levels of anti-spike IgG antibodies post-vaccination, whereas alcohol and tobacco users had lower concentrations. Conclusions: To our best knowledge, this was the first comprehensive assessment of antibody and T-cell responses against CoronaVac vaccination in indigenous patients. Our findings showed that antibody response and T-cell immunity against SARS-CoV-2 were present in most patients following the vaccination schedule.

Facile and Rapid Microcontact Printing of Additive-Free Polydimethylsiloxane for Biological Patterning Diversity.

The development and application of micropatterning technology play a promising role in the manipulation of biological substances and the exploration of life sciences at the microscale. However, the universally adaptable micropatterning method with user-friendly properties for acceptance in routine laboratories remains scarce. Herein, a green, facile, and rapid microcontact printing method is reported for upgrading popularization and diversification of biological patterning. The three-step printing can achieve high simplicity and fidelity of additive-free polydimethylsiloxane (PDMS) micropatterning and chip fabrication within 8 min as well as keep their high stability and diversity. A detailed experimental report is provided to support the advanced microcontact printing method. Furthermore, the applications of easy-to-operate PDMS-patterned chips are extensively validated to complete microdroplet array assembly with spatial control, cell pattern formation with high efficiency and geometry customization, and microtissue assembly and biomimetic tumor construction on a large scale. This straightforward method promotes diverse micropatternings with minimal time, effort, and expertise and maximal biocompatibility, which might broaden its applications in interdisciplinary scientific communities. This work also offers an insight into the establishment of popularized and market-oriented microtools for biomedical purposes such as biosensing, organs on a chip, cancer research, and bioscreening.

Advice to a Young Mathematical Biologist

This paper offers advice to early-mid career researchers in Mathematical Biology from ten past and current Presidents of the Society for Mathematical Biology. The topics covered include deciding if a career in academia is right for you; finding and working with a mentor; building collaborations and working with those from other disciplines; formulating a research question; writing a paper; reviewing papers; networking; writing fellowship or grant proposals; applying for faculty positions; and preparing and giving lectures. While written with mathematical biologists in mind, it is hoped that this paper will be of use to early and mid career researchers across the mathematical, physical and life sciences, as they embark on careers in these disciplines.

The Evaluation of Sweetcorn (Zea mays saccharata Sturt.) Infestation of Barnyardgrass (Echinochloa crus-galli) Depending on Weather Conditions and Crop Rotation

This paper focuses on the weed species Echinochloa crus-galli, commonly known as barnyardgrass, which is a persistent threat to crop yield and quality, especially in maize (Zea mays) cultivation. It is one of the most problematic weeds in agricultural fields due to its aggressive growth, adaptability to different environmental conditions and prolific seed production. The incidence of Echinochloa crus-galli in maize fields has increased in recent years. This study aims to provide a comprehensive understanding of the characteristics and behavior of Echinochloa crus-galli, and to suggest effective measures to control it. This research on sweetcorn was conducted from 1992 to 2019 at the Research and Education Center Gorzyń, Złotniki branch, which belongs to the Poznań University of Life Sciences. The evaluation of weed infestation was carried out in experiments focusing on chemical weed control in maize. The experiments were designed as a one-factor randomised block design with four field replications. The condition and the degree of weed infestation (number of weeds and fresh weight of weeds) in the control plots was assessed on an annual basis at the end of June and in July. The aim of the study was to evaluate the dynamic changes in the status and extent of barnyardgrass (Echinochloa crus-galli) infestation in maize grown after various other crops in the Wielkopolska region, with a focus on the weather conditions. The study found that barnyardgrass was most likely to occur when maize was sown after winter wheat in a dry and warm year, and least likely when maize was grown in rotation after winter wheat in a cold year with average rainfall. The proportion of barnyardgrass weed mass in the total weed mass was significantly lower after winter rye than after winter wheat, winter oilseed rape and winter triticale. Further research into the biology and ecology of barnyardgrass is key to effectively controlling this weed and safeguarding sweetcorn yields.

What do early-career life scientists in India want?

What do early-career life scientists in India want?

G. G. Avtandilov and A. P. Avtsyn: Two Outstanding Pathologists, Two Unique Lives

Academician A.P. Avtsyn and Professor G.G. Avtandilov are generally recognized world authorities in pathological anatomy. Alexander Pavlovich Avtsyn is known as an outstanding scientist, a famous community health administrator, an active public personality, a wonderful teacher, a corresponding member of the USSR Academy of Medical Sciences and a laureate of the USSR State Prize, the founder of the Research Institute of Human Morphology, which was later given his name. Georgy Gerasimovich Avtandilov is an outstanding scientist and educator, a prominent specialist, professor, Doctor of Medical Sciences, Honored Doctor of Kabardino-Balkaria and Honored Scientist of the RSFSR and the Republic of North Ossetia – Alania, as well as an academician of the Russian Academy of Natural Sciences. G.G. Avtandilov specialised in the field of pathological anatomy, mainly in morphometry. The paper describes details of their contribution to the development of pathological anatomy, from both a fundamental and practical point of view. Unique methodological approaches developed by G.G. Avtandilov and A.P. Avtsyn, which are used today by numerous scientists, are presented by the authors. In addition to the scientific life of two outstanding researchers, the article highlights important events from their biographies.

How do life sciences cite social sciences? Characterizing the volume and trajectory of citations

AbstractSocial sciences are increasingly recognized as significant for building a sustainable world since the social perspective can assist researchers in other fields in navigating public controversy and designing more responsible interaction mechanisms between the natural and social systems. However, the question arises: to what extent do natural sciences rely on social science research in their studies? Examining life science publications from seven PLoS journals, this paper attempts to characterize the volume and trajectory of citations from life sciences to social sciences. We explore three core questions: To what extent do life sciences cite social sciences? What actors in the life sciences are citing social sciences? Which actors in the social sciences are being cited? Our analysis estimates social sciences influence 15%–19% of life science publications, contributing to 1.1%–1.5% of references in 2018. Social science citers are found across peripheral and central topics of life science disciplines. Cited social science publications exhibit various levels of interdisciplinarity and achieve the greatest citation impact among peers. Citations to social sciences are prevalent in both theoretically and methodologically oriented sections. We show empirically the increasing impact of social sciences on the development of the life sciences.

Life scientists’ experience with posting preprints during the COVID-19 pandemic

AbstractIn the COVID-19 pandemic, it was much more critical for many life science researchers to rapidly disseminate research results—so they used preprints as upstream publication opportunities. This was rather new to the life sciences where preprint servers had only appeared as early as 2013. With a mixed-methods-study we examined this development and investigated whether preprint posting is a temporary phenomenon or the beginning of a cultural shift in publishing behavior in the life sciences. First, we conducted a survey of researchers who have posted COVID-19 related preprints. We investigated experiences with posting preprints during the COVID-19 pandemic, motivations for and concerns about posting preprints, the role of research institutions or funders, and the future of preprint publishing. Answers were grouped to compare differences between respondents’ gender, career stage, region of origin (global south or global north) and experience with posting preprints before and during the COVID-19 pandemic. We further analyzed eight popular preprint repositories regarding the number of posted preprints and preprint characteristics, such as the number of authors and citations. Interestingly, survey and preprint server analysis have presented different, if not contradicting results: While the majority of surveyed researchers was willing to continue posting preprints, the numbers of preprints published, especially on servers for the life sciences, have stagnated or declined. Also, while certain preprints garnered substantial citations during the COVID-19 pandemic, this has not resulted in a significant shift in researchers’ publishing behavior, and the posting of preprints has not become a routine. We concluded that the sustainability of preprint publishing practices is more strongly influenced by disciplinary norms and practices than by external shocks as the COVID-19 pandemic.

Experiences of Using a Real Compound Microscope and a Virtual Compound Microscope in Understanding Plant Tissues by First-year Life Science Students at a Tertiary Institution in South Africa

During the COVID-19 outbreak, the majority of tertiary institutions preferred virtual laboratories to face-to-face laboratories which posed a challenge to many students. The objective of the study was to examine students’ experiences at a higher institution using both a physical and virtual microscope. This qualitative study involved ten randomly chosen first-year Life Science students. They had to prepare and view onion cells under a real microscope, while the second assignment required them to observe onion cell preparation in a virtual laboratory. Students completed a questionnaire containing open-ended questions. The results were analyzed using themes, and the study found that pupils prefer physical microscopes to virtual microscopes. This is because students interact with the equipment in the laboratory, which encourages intellectual interests, knowledge sharing, and the development of social connections. Students can manipulate actual objects, manually focus microscopes, and interact in real time with microscopic worlds. This hands-on expertise is critical for instructing students and researchers on laboratory practices. Real microscopes are versatile pieces of equipment that can be utilized for a wide range of applications, from basic instruction to advanced research. Although virtual microscopes have advanced in terms of image quality, real microscopes provide better resolution and clarity. The study will make a substantial addition to university laboratory pedagogies and expose students to scientific investigations, given the majority of students come from rural schools with limited laboratory equipment such as microscopes. Keywords: Physical Microscope, Virtual Microscope, Experiences, Intellectual Interest, Social Interactions

Abstract LB236: Metabolically armed CD19 CAR-T cells for safe and effective treatment of relapsed or refractory CD19+ B cell hematological malignancies at extremely low doses

Abstract Background: The undeniable success of CD19 CAR-T cell therapy in managing relapsed or refractory (r/r) B-cell hematological malignancies, such as diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL), underscores its significance. Despite the favorable complete remission (CR) rates of around 50% for r/r DLBCL and up to 90% for r/r B-ALL, a notable challenge persists as more than half of patients experiencing CR after CD19 CAR-T cells treatment encounter relapse within a year, attributed to inadequate CAR-T persistence in both indications. Urgent attention is required to devise innovative strategies to overcome these challenges. Recently, we developed metabolically armed CD19 CAR-T cells expressing IL-10 can enhance OXPHOS metabolism, proliferation, and persistence of CAR-T cells in vivo. Significantly, these IL-10-expressing CAR-T cells trigger stem-like memory responses in various lymphoid organs, leading to robust tumor eradication and durable protection. Motivated by these promising findings, an open-label, single arm, investigator-initiated trial (IIT, ClinicalTrials.gov identifier: NCT05715606, NCT05747157) was conducted to assess the safety and efficacy of newly developed metabolically armed IL-10-expressing CD19 CAR-T (product name: Meta10-19 infusion) for treating patients with r/r DLBCL or r/r B-ALL. Method: From Feb 2023 to Dec 2023, this IIT clinical trial evaluated Meta10-19 infusion in adult patients with r/r DLBCL or r/r B-ALL. The patients were recruited and treated at the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China. Patients in 3 dose cohorts (2.0 × 104, 5.0 × 104, or 1.0 × 105 CAR-T cells/kg, corresponding to 1%, 2.5%, or 5% doses of commercialized CAR-T infusion) underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine before Meta10-19 infusion. The primary endpoint was the incidence of dose-limiting toxicities. The secondary endpoint was the response and survival. Results: The treatment with Meta10-19 infusion has successfully induced CR in all 12 cases of r/r DLBCL (n=6) or r/r B-ALL (n=6), as evaluated by PET-CT scan, NMR spectroscopy or minimal residual disease assessment of bone marrow. No server cytokine storm syndrome or neurotoxicity was observed. All treated patients achieved CR at 3 months post treatment, with the first patient maintaining continuous remission up to 9 months until now. Notably, these metabolically armed CD19 CAR-T cells demonstrated efficacy even for patients with bulky mass (≥7.5 cm) of DLBCL at extremely low infusion dose (1~5% doses of commercialized CAR-T). Conclusion: Preliminary findings suggest that Meta10-19 infusion exhibits promising breakthrough efficacy and safety profile, and active enrollment is ongoing to validate the initial results. Citation Format: Yugang Guo, Qianwen Xu, Lei Xue, Erling Chen, Chonglin Liu, Min Gao, Youjia Li, Jingjing Ren, Jinping Li, Li Tang, Xingbing Wang. Metabolically armed CD19 CAR-T cells for safe and effective treatment of relapsed or refractory CD19+ B cell hematological malignancies at extremely low doses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB236.