Biology subjects

Zeng, W.

Publications and source records attributed to Zeng, W..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Towards Optimizing Target Engagement in Non-Invasive Trigeminal Nerve Stimulation: Anatomical Characterization and Computational Modeling of the Human Trigeminal Nerve

ObjectiveCranial nerve stimulation (CNS) uses electric current to modulate higher-order brain activity and organ function via nerves, including the vagus and trigeminal, with applications in migraine, epilepsy, and pediatric ADHD. The trigeminal nerve is an emerging target for non-invasive neuromodulation due to the superficial trajectory of its branches, the supraorbital (SON), infraorbital (ION), and mental nerves (MN), and the predominantly sensory composition of the SON and ION. However, the parameters and outcomes of trigeminal nerve stimulation (TNS) remain varied. ApproachThis study characterizes the anatomical course, tissue composition, and activation profiles of the SON, ION, and MN using five human donors. CT imaging was utilized to localize each nerves exit foramen and distance to midline. Microdissections quantified nerve circumference and depth relative to the skin surface. Histological analysis described the number of fascicles and fascicular tissue area. Nerve depths were incorporated into computational models to illustrate the activation function across tissue layers, comparing expected nociceptor and nerve trunk activation functions as a measure of neural engagement. Main ResultsThe SON was found to be significantly more superficial than the ION and MN and had a higher nerve-to-connective tissue ratio relative to the MN. Computational modeling demonstrated that the activation function at the depths of nociceptors was orders of magnitude greater than within the main nerve trunks, suggesting preferential recruitment of cutaneous nociceptors, dependent on nociceptor density. SignificanceThe SON presents the most accessible and anatomically favorable target for transcutaneous trigeminal nerve stimulation among the branches examined due to its superficial location. However, preferential activation of low-threshold nociceptors compared to nerve trunks may lead to treatment-limiting off-target side effects, favoring strategies that target fibers of interest within the skin. These findings offer an anatomically informed framework to guide further computational modeling and electrode design for targeted trigeminal neuromodulation.

neuroscience↗

bioRxiv2025

Complex I Governs Iron Levels in Bat Mitochondria to Couple Respiration with Lipid Metabolism

The evolution of mitochondrial respiration has been implicated in the remarkable adaptations of bats, including powered flight, longevity and viral tolerance. However, the mechanisms coordinating mitochondrial respiration with lipid metabolism--a critical energy source for flight--remain poorly understood. Here, we discovered that complex I inhibition triggered iron overload into bat mitochondria, inducing a burst of reactive oxygen species (ROS). This iron translocation relied on the VDAC-MCU axis and mitochondrial membrane potential. Intriguingly, disrupting VDAC oligomerization enhanced iron uptake in a complex I-dependent manner. Mitochondrial iron translocation perturbed fatty acid oxidation and upregulated linoleic acid species, which promoted the reversible accumulation of lipid droplets, suggesting metabolic plasticity crucial for bat energetics. Our findings establish complex I as a pivotal regulatory hub that directly couples respiratory efficiency to lipid metabolism by governing mitochondrial iron levels. This mechanism may represent a key evolutionary adaptation supporting the unique metabolic demands of bat physiology. HIGHLIGHTSComplex I inhibition induces unique mitochondrial ROS burst in bat cells. Mitochondrial iron overload is the primary trigger of complex I-linked ROS burst. VDAC-MCU axis couples membrane potential to drive mitochondrial iron influx. Mitochondrial iron translocation remodels lipid metabolism in bat cells.

cell biology↗

bioRxiv2025

Spatial transcriptomics reveals heterogeneous cell-cell interactions among brain regions in a cuprizone model consistent with multiple sclerosis lesions

The cuprizone (CPZ) model is widely used for modeling demyelination in multiple sclerosis (MS) and for testing potential remyelination therapies. We integrated single-cell and spatial transcriptomics (ST) to fine map the spatial cellular and molecular responses during de and remyelination. ST revealed global demyelination and neuroinflammation in the brain beyond the corpus callosum, with region-specific differences. We identified oligodendroglia and microglia as two major cell types with significant transcriptomic changes in the model. Ligand receptor pairing analyses predicted growth factor and phagocytic pathway enrichment during demyelination, which is consistent with changes in MS lesions. During remyelination, while mature oligodendrocytes nearly reversed their phenotype back to the control state, microglia remained associated with the demyelination phenotype. Finally, astrocytes in the CPZ model had the greatest preservation of disease-associated modules to MS lesions, while the MOL, OPC, and microglia showed moderate to low preservation, which overall suggested that the CPZ model had moderate translatability to chronically active MS lesions.

neuroscience↗

bioRxiv2025

Combined Central and Peripheral Nerve Stimulation Improves Functional Recovery of Mixed Peripheral Nerve Injury in a Rat Forelimb Model

IntroductionPeripheral nerve reinnervation following nerve injury is often a slow and incomplete process, resulting in significant morbidity and permanent loss of function of the injured extremity in many patients. Prior studies have shown the efficacy of electrical stimulation to synchronize the axonal regeneration of both motor and sensory neurons in peripheral nerve injury models. Moreover, separate investigations have also shown the use of cranial nerve stimulation, principally the vagus nerve, to improve functional outcomes. However, no study has investigated the synergistic effects of both intraoperative electrical stimulation and cranial nerve stimulation for functional improvement within a peripheral nerve injury model. This investigation quantifies the efficacy of combined intraoperative electrical stimulation and trigeminal nerve stimulation on motor and sensory functional recovery in a rat peripheral nerve injury model. MethodsTwelve adult male Lewis rats were trained in a reach and pull task for a food reward using their right forelimb with baseline force thresholds and percent success of the pull task recorded. Baseline sensory data was retrieved using an automated von Frey monofilament test. All rats underwent surgical transection and 2mm gap repair of their median and ulnar nerve of their right forelimb followed by 1 hour of intraoperative electrical stimulation. Trigeminal nerve stimulation throughout the rehabilitation period was completed via supraorbital nerve headcap electrodes. Motor and sensory data were compared to historic cohorts comprised of sham surgery (no nerve injury), brief intraoperative electrical stimulation, trigeminal nerve stimulation, and a sham peripheral and trigeminal nerve stimulation group. Polarization sensitive optical computed tomography (PS-OCT) was used to assess nerve regeneration in fixed tissue samples. ResultsThe combined cohort of rodents were able to recover to their pre-injury motor function by the third week of rehabilitation, faster than either of the singular electrical stimulation cohorts assessed previously. Moreover, functional sensory data of the combined stim cohort demonstrated no change when compared to their pre-injury baseline. ConclusionsPeripheral nerve electrical stimulation and trigeminal nerve stimulation are two separately acting mechanisms of therapy that employ electric waveforms to improve the functional recovery of injured peripheral nerves. The former acts within the periphery to synchronize axonal growth and regeneration of the injured neurons, while the latter acts centrally to augment neuroplasticity. When used simultaneously in a rodent peripheral nerve injury model, these modalities have shown to build upon each other to deliver a faster functional motor recovery, while sensory recovery outcomes remain to be demonstrated.

neuroscience↗

bioRxiv2024

Accurate nucleic acid-binding residue identification based on domain-adaptive protein language model and explainable geometric deep learning

Protein-nucleic acid interactions play a fundamental and critical role in a wide range of life activities. Accurate identification of nucleic acid-binding residues helps to understand the intrinsic mechanisms of the interactions. However, the accuracy and interpretability of existing computational methods for recognizing nucleic acid-binding residues need to be further improved. Here, we propose a novel method called GeSite based the domain adaptive protein language model and explainable E(3)-equivariant graph convolution neural network. Prediction results across multiple benchmark test sets demonstrate that GeSite is superior or comparable to state-of-the-art prediction methods. The performance comparison on low structure similarity and newly released test proteins demonstrates the robustness and generalization of the method. Detailed experimental results suggest that the advanced performance of GeSite lies in the well-designed nucleic acid-binding protein adaptive language model. Meanwhile, interpretability analysis exposes the perception of the prediction model on various remote and close functional domains, which is the source of its discernment. The data and source code of GeSite are freely accessible at https://github.com/pengsl-lab/GeSite.

bioinformatics↗

bioRxiv2024

Optimization of metagenomic detection method for human breast milk microbiome

This study aims to optimize the metagenomic detection methodology of the human breast milk microbiome and analyze its composition. Twenty-two milk samples were collected from the left and right sides of lactating women during re-examinations at the Haidian Maternal and Child Health Hospital, Beijing. Microbial cell wall disruption parameters were optimized, and a nucleic acid extraction method was developed to construct a microbial DNA/RNA library. Metagenomic next-generation sequencing (mNGS) sequencing was performed, and microbial composition was analyzed using the k- mer Lowest Common Ancestor (LCA) method with a self-generated database constructed via Kraken2 software. Data showed Q20 > 95% and Q30 > 90%, with an average total data volume of 5,567 {+/-} 376.6 Mb and non-human sequence data of 445.1 {+/-} 63.75 Mb, significantly enhancing sequencing efficiency. The microbiome included 21 phyla, 234 genera, and 487 species, with Firmicutes and Proteobacteria as dominant phyla. Predominant genera included Staphylococcus and Streptococcus, and major species were Staphylococcus aureus, Streptococcus bradystis, and Staphylococcus epidermidis. Species levels exhibited significant variations among different individuals. Microbial profiles of left- and right-sided milk samples were consistent at the phylum, genus, and species levels. In addition to common bacteria, diverse viral, eukaryotic, and archaeal sequences were detected. This study refined metagenomic detection methods for human breast milk microbiota. Specific flora colonization occurred in healthy breast milk, with the left and right sides exhibiting both correlations and distinct flora environments. ImportanceBreast milk is a vital source of nutrition and immunity for infants, with its microbial composition playing a critical role in shaping the neonatal gut microbiome and supporting early development. However, technical challenges in detecting microorganisms in milks complex, lipid-rich environment have limited understanding of the diversity and function of these microbial communities. This study developed an optimized metagenomic sequencing method to analyze the microbial communities in breast milk from healthy mothers, identifying a wide array of bacteria, viruses, eukaryotes, and archaea. Key bacterial genera such as Staphylococcus and Streptococcus were predominant, with specific flora exhibiting inter-individual variability. Additionally, the study revealed distinct yet correlated microbial environments in the milk from the left and right breasts. These findings advance the understanding of breast milk microbiota and provide a foundation for exploring its implications for maternal and infant health.

microbiology↗

bioRxiv2024

Structural mechanisms of PIP2 activation and SEA0400 inhibition in human cardiac sodium-calcium exchanger NCX1

Na+/Ca2+ exchangers (NCXs) transport Ca2+ across the plasma membrane in exchange for Na+ and play a vital role in maintaining cellular Ca2+ homeostasis. Our previous structural study of human cardiac NCX1 (HsNCX1) reveals the overall architecture of the eukaryotic exchanger and the formation of the inactivation assembly by the intracellular regulatory domain that underlies the cytosolic Na+-dependent inactivation and Ca2+ activation of NCX1. Here we present the cryo-EM structures of HsNCX1 in complex with a physiological activator phosphatidylinositol 4,5-bisphosphate (PIP2), or pharmacological inhibitor SEA0400 that enhances the inactivation of the exchanger. We demonstrate that PIP2 binding stimulates NCX1 activity by inducing a conformational change at the interface between the TM and cytosolic domains that destabilizes the inactivation assembly. In contrast, SEA0400 binding in the TM domain of NCX1 stabilizes the exchanger in an inward-facing conformation that facilitates the formation of the inactivation assembly, thereby promoting the Na+-dependent inactivation of NCX1. Thus, this study reveals the structural basis of PIP2 activation and SEA0400 inhibition of NCX1 and provides some mechanistic understandings of cellular regulation and pharmacology of NCX family proteins.

biophysics↗

bioRxiv2024

High-resolution imaging atlas reveals context-dependent role of pancreatic sympathetic innervation in diabetic mice

Gaining a better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in islets of adult WT and diabetic mice. Our data shows that more than [~]30% /{beta}-cells are innervated by sympathetic nerves in both WT and diabetic mice. Also, sympathetic innervated /{beta}-cells are reduced in DIO mice, whereas sympathetic innervated {beta}-cells are increased in db/db mice. Besides, in situ chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in WT and db/db mice, but decreases in DIO mice. In situ cPSD also enhances insulin sensitivity in diabetic mice without affecting WT mice. Overall, our findings advance our comprehension of diabetes by highlighting the distinctive impact of pancreatic sympathetic innervation on glucose regulation. HighlightsPancreatic sympathetic innervation plays an important role in glucose homeostasis. In our study, we systematically investigate sympathetic innervation in the islets of WT and diabetic mice. O_LI45.9% -cells and 31.8% {beta}-cells are innervated by sympathetic nerves in 10-week-old WT mice. C_LIO_LISympathetic innervated /{beta}-cells are reduced in DIO mice, whereas sympathetic innervated {beta}-cells are increased in db/db mice. C_LIO_LIUnlike the core-mantle structure observed in WT and DIO mice, -cells and {beta}-cells are intermixed in db/db mice. C_LIO_LIPancreatic sympathetic denervation elicits varied responses across diabetic models, where it improves glucose tolerance and insulin sensitivity in db/db mice, yet it increases insulin sensitivity but reduces glucose tolerance in DIO mice. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/623708v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@183be78org.highwire.dtl.DTLVardef@4dc76borg.highwire.dtl.DTLVardef@5f5ca0org.highwire.dtl.DTLVardef@ba3cc7_HPS_FORMAT_FIGEXP M_FIG Summary of morphological and physiological phenotypes in diabetic mice. All data are normalized to that of WT-10 mice. The numbers of "+" refer to their relative numbers. {uparrow} or {downarrow} refers to increase or decrease, ns refers to "not significant". "-" refers to the experiment has not been carried out. C_FIG

neuroscience↗

bioRxiv2024

DEMINERS enables clinical metagenomics and comparative transcriptomic analysis by increasing throughput and accuracy of nanopore direct RNA sequencing

Nanopore direct RNA sequencing (DRS) advances RNA biology but is limited by relatively low basecalling accuracy, low throughput, yet high RNA input and costs. Here we introduce a novel DRS toolkit, DEMINERS, which integrates an RNA multiplexing experimental workflow, a machine-learning barcode classifier based on Random Forest and a novel basecaller built on an optimized convolutional neural network providing an additional species-specific training module. With the increased accuracy in barcode classification and basecalling, DEMINERS can demultiplex up to 24 samples and the required RNA input and running time are both substantially reduced. We demonstrated the applications of DEMINERS in clinical metagenomics, cancer transcriptomics and parallel comparison of transcriptomic features in different biological conditions, revealing altered airway microbial diversity in COVID-19 and a potential role of m6A in increasing transcriptomic diversity in glioma and the mature blood-stage of malaria parasites. Overall, DEMINERS is a simple, robust, high-throughput DRS method for accurately estimating transcript levels, poly(A) lengths, and mutation and RNA modification heterogeneity at single-read level, with minimal sequencing biases.

bioinformatics↗

bioRxiv2024

Inferring Gene Regulatory Network Based on scATAC-seq Data with Gene Perturbation

Gene regulatory networks (GRNs) are critical blueprints for understanding gene regulation and the intricate interactions that drive biological processes. Recent advances have highlighted the potential of single-cell ATAC-seq (scATAC-seq) data in GRN inference, offering unprecedented insights into how chromatin accessibility plays an important part in gene regulation. However, existing methods often fall short in providing a quantitative and holistic depiction of regulatory relationships, particularly in capturing the strength, direction, and type of gene regulation simultaneously. In this paper, we present a novel approach that addresses these limitations by leveraging genetically perturbed scATAC-seq data to infer more comprehensive and accurate GRNs. Our method advances the field by integrating pre- and post-perturbation chromatin accessibility data, enabling the construction of GRNs that more accurately reflect the dynamic regulatory landscape. Through rigorous evaluation on seven real datasets, we demonstrate the methods superior performance in reconstructing GRNs with enhanced precision and interpretability. This work significantly contributes to the field by providing a robust framework for GRN inference, with broad implications for understanding gene regulation in complex biological systems.

bioinformatics↗

bioRxiv2024

CREATE: cell-type-specific cis-regulatory elements identification via discrete embedding

Identifying cis-regulatory elements (CREs) within non-coding genomic regions--such as enhancers, silencers, promoters, and insulators--is pivotal for elucidating the intricate gene regulatory mechanisms underlying complex biological traits. The current prevalent sequence-based methods often focus on singular CRE types, limiting insights into cell-type-specific biological implications. Here, we introduce CREATE, a multimodal deep learning model based on the Vector Quantized Variational AutoEncoder framework, designed to extract discrete CRE embeddings and classify multiple CRE classes using genomic sequences, chromatin accessibility, and chromatin interaction data. CREATE excels in accurate CRE identification and exhibits strong effectiveness and robustness. We showcase CREATEs capability in generating comprehensive CRE-specific feature spectrum, offering quantitative and interpretable insights into CRE specificity. By enabling large-scale prediction of CREs in specific cell types, CREATE facilitates the recognition of disease- or phenotype-related biological variabilities of CREs, thereby expanding our understanding of gene regulation landscapes.

bioinformatics↗

bioRxiv2024

Circulatory proteins shape microglia state and boost phagocytosis

Microglia, the brains immune cells, are highly responsive to their local environment. Given that circulatory proteins can enter the brain, we asked whether microglia are responsive to such proteins. Here, we identify a stable population of microglia specialized to take up circulatory proteins in a region-specific manner under physiological conditions; human hematopoietic stem cell-derived microglia replacing endogenous microglia in chimeric mice show similar regional specialization. Plasma-positive microglia are characterized by prominent expression of genes related to innate immunity and antigen presentation and exhibit high metabolic and phagocytic activity. This activity is dependent, in part, on microglial uptake and accumulation of circulatory Apolipoprotein AI (ApoA-I). Our findings thus identify a new model of communication between brain and periphery through specialized microglia.

neuroscience↗

bioRxiv2024

Lymphatic dynamics visualized by native transient hypoxia imaging in areas of tissue damage, edema and in sentinel lymph nodes.

Imaging lymphatic compartments and their function has always been challenging, yet this capability is key to understanding the dynamics of immune response and lymph dysfunction in disease states. This study reports the first ever visualization of murine lymphatic pumping and function imaged from the inherent transient hypoxia that occurs within the lymph ducts and nodes. The lymphatic system appears as one of the few naturally hypoxic areas in vivo. Hypoxia in lymphatics is detected via delayed fluorescence (DF) of endogenous protoporphyrin IX (PpIX), enabling real-time imaging. Lymph nodes and their function were localized by hypoxia transcutaneous imaging and in surgically exposed nodes, followed by correlation of localization to indocyanine green (ICG) local injection. The lymphatic pumping frequency was altered through progressive damage from mild, moderate, and severe wound injuries, and hypoxia appeared readily in the sentinel lymph nodes near tumor regions. Cyclical pumping was observed at sites of edema and in nodes near tumors. Control data from uninjured anesthetized mice showed little lymphatic contrast, whereas awake mice exhibited hypoxia localized to lymph nodes. Unlike contrast injection-based regional lymph node imaging by ICG or MRI, DF hypoxia imaging appears to provide a natural whole-body contrast mechanism, highlighting its potential for visualizing lymphatic function and associated hypoxia dynamics. The value for localization of sentinel lymph nodes and for allowing for visualization of damaged lymph has very practical potential applications.

bioengineering↗

bioRxiv2024

Interpretable improving prediction performance of general protein language model by domain-adaptive pretraining on DNA-binding protein

DNA-protein interactions exert the fundamental structure of many pivotal biological processes, such as DNA replication, transcription, and gene regulation. However, accurate and efficient computational methods for identifying these interactions are still lacking. In this study, we propose a novel method ESM-DBP through refining the DNA-binding protein (DBP) sequence repertory and domain-adaptive pretraining based the protein language model (PLM). Our method considers the lack of exploration of general PLM for DBP domain-specific knowledge, so we screened out 170,264 DBPs from the UniProtKB database to construct the model that more suitable for learning crucial characteristics of DBP. The evaluation of ESM-DBP is systematically performed in four different DBP-related downstream prediction tasks, i.e., DNA-binding protein, DNA-binding residue, transcription factor, and DNA-binding Cys2His2 zinc-finger predictions. Experimental results show that ESM-DBP provides a better feature representation of DBP compared to the original PLM, resulting in improved prediction performance and outperforming other state-of-the-art prediction methods. In addition, ESM-DBP incorporates the integrated gradient algorithm for interpretable analysis, which usually ignored in the previous methods. It reveals that ESM-DBP possesses high sensitivity to the key decisive DNA-binding domains. Moreover, we find that ESM-DBP can still perform well even for those DBPs with only a few similar homologous sequences, and this generalization performs better than the original PLM. The data and standalone program of ESM-DBP are freely accessible at https://github.com/pengsl-lab/ESM-DBP.

bioinformatics↗

bioRxiv2024

Dual-Targeted Microbubbles Promote Apoptosis of M1 Macrophages by Inhibiting Telomerase Activity for Atherosclerosis Therapy

It is known that M1 macrophages are the dominant phenotype in progressive atherosclerosis (AS). Studies have shown that telomerase in macrophages can be activated during the atherosclerosis formation, but how to regulate the telomerase activity of M1 macrophages is the focus of treatment of AS. Herein, we report a dual-targeted microbubbles delivery system encapsulating the telomerase inhibitor BIBR1532 (Ab-MMB1532), designed for precise targeted therapy of AS. The Ab-MMB1532 exhibits excellent biocompatibility and remarkable targeting capability towards M1 macrophages with its targeting advantage notably accentuated under high shear forces. Furthermore, it significantly downregulates telomerase activity. Metabolomics analysis indicates that the decrease in telomerase activity upregulates the expression of aspartic acid, a key protein in the Caspase pathway of apotosis. In vivo, Ab-MMB1532 efficiently targeted and accumulated within AS lesions, leading to significantly delay of the AS progression by inhibiting telomerase activity and promoting apoptosis of M1 macrophages after 4-week treatment. In summary, Ab-MMB1532 provides a new approach for potentially safer and more effective treatment of AS in the future.

bioengineering↗

bioRxiv2024

Association study of Plasmodium falciparum Acetyl-CoA Synthetase Mutations S868G and V949I with antimalarial drugs

Plasmodium falciparum acetyl-CoA synthetase (PfACAS) protein is an important source of acetyl-CoA. We detected the mutations S868G and V949I in PfACAS by whole-genome sequencing analysis in some recrudescent parasites after antimalarial treatment with artesunate and dihydroartemisinin-piperaquine, suggesting that they may confer drug resistance. Using CRISPR/Cas9 technology, we engineered parasite lines carrying the PfACAS S868G and V949I mutations in two genetic backgrounds and evaluated their susceptibility to antimalarial drugs in vitro. The results demonstrated that PfACAS S868G and V949I mutations alone or in combination were not enough to provide resistance to antimalarial drugs.

microbiology↗

bioRxiv2024

TRPML1 gating modulation by allosteric mutations and lipids

Transient Receptor Potential Mucolipin 1 (TRPML1) is a lysosomal cation channel whose loss-of-function mutations directly cause the lysosomal storage disorder mucolipidosis type IV (MLIV). TRPML1 can be allosterically regulated by various ligands including natural lipids and small synthetic molecules and the channel undergoes a global movement propagated from ligand-induced local conformational changes upon activation. In this study, we identified a functionally critical residue, Tyr404, at the C-terminus of the S4 helix, whose mutations to tryptophan and alanine yield gain- and loss-of-function channels, respectively. These allosteric mutations mimic the ligand activation or inhibition of the TRPML1 channel without interfering with ligand binding and both mutant channels are susceptible to agonist or antagonist modulation, making them better targets for screening potent TRPML1 activators and inhibitors. We also determined the high-resolution structure of TRPML1 in complex with the PI(4,5)P2 inhibitor, revealing the structural basis underlying this lipid inhibition. In addition, an endogenous phospholipid likely from sphingomyelin is identified in the PI(4,5)P2-bound TRPML1 structure at the same hotspot for agonists and antagonists, providing a plausible structural explanation for the inhibitory effect of sphingomyelin on agonist activation.

biophysics↗

bioRxiv2024

Acetyl-CoA Synthetase Mutations S868G and V949I Do Not Confer Resistance to Antimalarial Drugs in vitro in Plasmodium falciparum.

microbiology↗