Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease.

A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion.

Vertebrate cells have evolved elaborate cell-autonomous defense programs to monitor subcellular compartments for infection and to evoke counter-responses. These programs are activated by pathogen-associated pattern molecules and by various strategies intracellular pathogens employ to alter cellular microenvironments. Here, we show that, when uropathogenic E. coli (UPEC) infect bladder epithelial cells (BECs), they are targeted by autophagy but avoid degradation because of their capacity to neutralize lysosomal pH. This change is detected by mucolipin TRP channel 3 (TRPML3), a transient receptor potential cation channel localized to lysosomes. TRPML3 activation then spontaneously initiates lysosome exocytosis, resulting in expulsion of exosome-encased bacteria. These studies reveal a cellular default system for lysosome homeostasis that has been co-opted by the autonomous defense program to clear recalcitrant pathogens.

Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.

The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.

Intention affects fairness processing: Evidence from behavior and representational similarity analysis of event-related potential signals.

In an ultimatum game, the responder must decide between pursuing self-interest and insisting on fairness, and these choices are affected by the intentions of the proposer. However, the time course of this social decision-making process is unclear. Representational similarity analysis (RSA) is a useful technique for linking brain activity with rich behavioral data sets. In this study, electroencephalography (EEG) was used to measure the time course of neural responses to proposed allocation schemes with different intentions. Twenty-eight participants played an ultimatum game as responders. They had to choose between accepting and rejecting the fair or unfair money allocation schemes of proposers. The schemes were offered based on the proposer's selfish intention (monetary gain), altruistic intention (donation to charity), or ambiguous intention (unknown to the responder). We used a spatiotemporal RSA and inter-subject RSA (IS-RSA) to explore the connections between event-related potentials (ERPs) after offer presentation and intention presentation with four types of behavioral data (acceptance, response time, fairness ratings, and pleasantness ratings). The spatiotemporal RSA results revealed that only response time variation was linked with the difference in ERPs at 432-592 ms after offer presentation on the posterior parietal and prefrontal regions. Meanwhile, the IS-RSA results found a significant association between inter-individual differences in response time and differences in ERP activity at 596-812 ms after the presentation of ambiguous intention, particularly in the prefrontal region. This study expands the intention-based reciprocal model to the third-party context and demonstrates that brain activity can represent response time differences in social decision-making.

Plasma exosomal microRNA expression profiles in patients with high-altitude polycythemia.

High-altitude polycythemia (HAPC) is a chronic mountain sickness characterized by multiple severe ill-effects. Its pathogenesis is still unclear, and till date, no study has been conducted to investigate the plasma exome profile of Tibetan patients with HAPC. In this study, we aimed to elucidate the pathogenesis of HAPC by determining the microRNA (miRNA) signatures. We compared the plasma exosome miRNA expression profiles of eight patients with HAPC and eight healthy controls using next-generation miRNA sequencing. Further, we extracted and identified plasma exosomes using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to validate differentially expressed plasma exosomal miRNAs. Finally, we analyzed the diagnostic values of the differentially expressed miRNAs for HAPC using receiver operating characteristic (ROC) curves. We detected 2007 miRNAs from confirmed plasma exosomes, including 1342 known miRNAs and 665 newly predicted miRNAs. We verified the expression of the top 10 differentially expressed miRNAs via qRT-PCR. Patients with HAPC showed significantly upregulated hsa-miR-122-5p, hsa-miR-423-5p, hsa-miR-4433b-3p, hsa-miR-1291, and hsa-miR-106b-5p expression levels, while hsa-miR-200c-3p expression was downregulated. This study may provide background knowledge for future studies on HAPC studies, which may further facilitate the development of novel therapies against this common disease.

Stereochemical Properties of Two Schiff-Base Transition Metal Complexes and Their Ligand by Using Multiple Chiroptical Spectroscopic Tools and DFT Calculations.

Two transition metal complexes were synthesized with Ni(II) and Cu(II) using a tetradentate Schiff-base ligand, (R,R) and (S,S)-N,N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine. The stereochemical properties of the ligand and the metal complexes were investigated using a combined experimental and theoretical approach. Multiple spectroscopic techniques, which include IR, vibrational circular dichroism (VCD), UV-Vis and electronic circular dichroism (ECD), as well as Raman and the newly discovered ECD-circularly polarized Raman (i.e., eCP-Raman) spectroscopies were utilized. The good agreement achieved between the experimental and simulated IR, VCD, UV-Vis and ECD spectra of the ligand allowed one to identify the presence of three main ligand conformers in solution, thanks, especially to the high VCD sensitivity to the conformations associated with the tertbutyl groups. The helicity of the metal complexes was identified to be M and P for those with the (R,R) and (S,S) ligands, respectively. Furthermore, eCP-Raman measurements were carried out for the two metal complexes under (near) resonance. Their induced solvent chiral Raman features were explained, and the potential application of eCP-Raman was discussed.

Electronic Circular Dichroism-Circularly Polarized Raman (eCP-Raman): A New Form of Chiral Raman Spectroscopy.

This Concept article summarizes recent work on the development of a new form of chiral Raman spectroscopy, eCP-Raman, which combines two spectroscopies: electronic circular dichroism (ECD) and circularly polarized Raman (CP-Raman). First, some puzzling observations while carrying out Raman optical activity (ROA) measurements of several transition metal complexes under resonance are described, as well as the search for the mechanisms responsible. Then an equation for quantifying the eCP-Raman contribution is presented, followed by several examples of how eCP-Raman influences the IR -IL spectra of achiral and chiral solvent molecules and of a number of chiral solutes under resonance. The conditions to extract resonance ROA, when the eCP-Raman contribution is minimized, are also discussed. Finally, we comment on the potential applications of eCP-Raman.

The whole-genome landscape of Burkitt lymphoma subtypes.

Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.

Fungal diversity notes 1387-1511: taxonomic and phylogenetic contributions on genera and species of fungal taxa.

This article is the 13th contribution in the Fungal Diversity Notes series, wherein 125 taxa from four phyla, ten classes, 31 orders, 69 families, 92 genera and three genera incertae sedis are treated, demonstrating worldwide and geographic distribution. Fungal taxa described and illustrated in the present study include three new genera, 69 new species, one new combination, one reference specimen and 51 new records on new hosts and new geographical distributions. Three new genera, Cylindrotorula (Torulaceae), Scolecoleotia (Leotiales genus incertae sedis) and Xenovaginatispora (Lindomycetaceae) are introduced based on distinct phylogenetic lineages and unique morphologies. Newly described species are Aspergillus lannaensis, Cercophora dulciaquae, Cladophialophora aquatica, Coprinellus punjabensis, Cortinarius alutarius, C. mammillatus, C. quercoflocculosus, Coryneum fagi, Cruentomycena uttarakhandina, Cryptocoryneum rosae, Cyathus uniperidiolus, Cylindrotorula indica, Diaporthe chamaeropicola, Didymella azollae, Diplodia alanphillipsii, Dothiora coronicola, Efibula rodriguezarmasiae, Erysiphe salicicola, Fusarium queenslandicum, Geastrum gorgonicum, G. hansagiense, Helicosporium sexualis, Helminthosporium chiangraiensis, Hongkongmyces kokensis, Hydrophilomyces hydraenae, Hygrocybe boertmannii, Hyphoderma australosetigerum, Hyphodontia yunnanensis, Khaleijomyces umikazeana, Laboulbenia divisa, Laboulbenia triarthronis, Laccaria populina, Lactarius pallidozonarius, Lepidosphaeria strobelii, Longipedicellata megafusiformis, Lophiotrema lincangensis, Marasmius benghalensis, M. jinfoshanensis, M. subtropicus, Mariannaea camelliae, Melanographium smilaxii, Microbotryum polycnemoides, Mimeomyces digitatus, Minutisphaera thailandensis, Mortierella solitaria, Mucor harpali, Nigrograna jinghongensis, Odontia huanrenensis, O. parvispina, Paraconiothyrium ajrekarii, Parafuscosporella niloticus, Phaeocytostroma yomensis, Phaeoisaria synnematicus, Phanerochaete hainanensis, Pleopunctum thailandicum, Pleurotheciella dimorphospora, Pseudochaetosphaeronema chiangraiense, Pseudodactylaria albicolonia, Rhexoacrodictys nigrospora, Russula paravioleipes, Scolecoleotia eriocamporesi, Seriascoma honghense, Synandromyces makranczyi, Thyridaria aureobrunnea, Torula lancangjiangensis, Tubeufia longihelicospora, Wicklowia fusiformispora, Xenovaginatispora phichaiensis and Xylaria apiospora. One new combination, Pseudobactrodesmium stilboideus is proposed. A reference specimen of Comoclathris permunda is designated. New host or distribution records are provided for Acrocalymma fici, Aliquandostipite khaoyaiensis, Camarosporidiella laburni, Canalisporium caribense, Chaetoscutula juniperi, Chlorophyllum demangei, C. globosum, C. hortense, Cladophialophora abundans, Dendryphion hydei, Diaporthe foeniculina, D. pseudophoenicicola, D. pyracanthae, Dictyosporium pandanicola, Dyfrolomyces distoseptatus, Ernakulamia tanakae, Eutypa flavovirens, E. lata, Favolus septatus, Fusarium atrovinosum, F. clavum, Helicosporium luteosporum, Hermatomyces nabanheensis, Hermatomyces sphaericoides, Longipedicellata aquatica, Lophiostoma caudata, L. clematidis-vitalbae, Lophiotrema hydei, L. neoarundinaria, Marasmiellus palmivorus, Megacapitula villosa, Micropsalliota globocystis, M. gracilis, Montagnula thailandica, Neohelicosporium irregulare, N. parisporum, Paradictyoarthrinium diffractum, Phaeoisaria aquatica, Poaceascoma taiwanense, Saproamanita manicata, Spegazzinia camelliae, Submersispora variabilis, Thyronectria caudata, T. mackenziei, Tubeufia chiangmaiensis, T. roseohelicospora, Vaginatispora nypae, Wicklowia submersa, Xanthagaricus necopinatus and Xylaria haemorrhoidalis. The data presented herein are based on morphological examination of fresh specimens, coupled with analysis of phylogenetic sequence data to better integrate taxa into appropriate taxonomic ranks and infer their evolutionary relationships.

Can One Measure Resonance Raman Optical Activity?

Resonance Raman optical activity (RROA) is commonly measured as the difference in intensity of Raman scattered right and left circularly polarized light, IR -IL , when a randomly polarized light is in resonance with a chiral molecule. Strong and sometimes mono-signate experimental RROA spectra of several chiral solutes were reported previously, although their signs and relative intensities could not be reproduced theoretically. By examining multiple light-matter interaction events which can occur simultaneously under resonance, we show that a new form of chiral Raman spectroscopy, eCP-Raman, a combination of electronic circular dichroism and circularly polarized Raman, prevails. By incorporating the finite-lifetime approach for resonance, the experimental patterns of the model chiral solutes are captured theoretically by eCP-Raman, without any RROA contribution. The results open opportunity for applications of eCP-Raman spectroscopy and for extracting true RROA experimentally.

Two Spectroscopies in One: Interference of Circular Dichroism and Raman Optical Activity.

Previously, we and other laboratories have reported an unusual and strong Raman optical activity (ROA) induced in solvents by chiral dyes. Various theories of the phenomenon appeared, but they were not capable of explaining fully the observed ROA band signs and intensities. In this work, an analysis based both on the light scattering theory and dedicated experiments provides a more complete understanding. For example, double-cell magnetic circular dichroism and magnetic ROA experiments with copper-porphyrin complex show that the induced chirality is observed without any contact of the solvents with the complex. The results thus indicate that a combination of electronic circular dichroism (ECD) with the polarized Raman scattering is responsible for the effect. The degree of circularity of solvent vibrational bands is a principal molecular property participating in the event. The insight and the possibility to predict the chirality transfer promise future applications in spectroscopy, chemical analysis and polarized imaging.

Long-noncoding RNA HOTAIR inhibits immunologic rejection of mouse leukemia cells through activating the Wnt/ß-catenin signaling pathway in a mouse model of leukemia.

Long-noncoding RNAs (lncRNAs) is involved in the development of diverse diseases, including leukemia, while the role lncRNA HOX transcript antisense RNA (HOTAIR) played in leukemia remains unclear and in need of further investigation. Therefore, this study was conducted to explore the effects of lncRNA HOTAIR on the immunologic rejection of leukemia cells through the Wnt/ß-catenin in mice. Mice were administrated with HOTAIR mimics as well as small interfering RNA HOTAIR to explore the regulatory role of HOTAIR. The numbers of white blood cell (WBC) and platelet (PLT) and the content of hemoglobin in peripheral blood (PB) were determined. The cytokine level in PB was measured. T-lymphocyte proliferation activity, Ig production by B cells, natural killer (NK) cell activity, and the proportion of cluster of differentiation 4 (CD4)/CD8 T cell subsets were detected. Expression of HOTAIR, ß-catenin, cyclinD1, GSK-3ß, and c-Myc in bone marrow was determined. It was revealed that the WBC number increased, while the PLT number along with the hemoglobin content in PB decreased with the upregulated HOTAIR. Additionally, elevated HOTAIR led to decreased levels of transforming growth factor-ß, interferon-γ, interleukin-10, and tumor necrosis factor-α in PB, proliferation activity in T-lymphocyte, and inhibited Ig production, NK cell activity, and the ratio of CD4/CD8 T cell subsets in B-lymphocyte. Furthermore, Wnt/ß-catenin was activated by overexpressing HOTAIR. Enhanced survival and proliferation were shown with increased expression of cyclinD1, GSK-3ß, and c-Myc in the bone marrow of mice induced by overexpressing HOTAIR. These results indicate that restored HOTAIR reduces the immunologic rejection of leukemia cells in mice by activating Wnt/ß-catenin pathway.

Transfer and Amplification of Chirality Within the "Ring of Fire" Observed in Resonance Raman Optical Activity Experiments.

We report extremely strong chirality transfer from a chiral nickel complex to solvent molecules detected as Raman optical activity (ROA). Electronic energies of the complex were in resonance with the excitation-laser light. The phenomenon was observed for a wide range of achiral and chiral solvents. For chiral 2-butanol, the induced ROA was even stronger than the natural one. The observations were related to so-called quantum (molecular) plasmons that enable a strong chiral Rayleigh scattering of the resonating complex. According to a model presented here, the maximal induced ROA intensity occurs at a certain distance from the solute, in a three-dimensional "ring of fire", even after rotational averaging. Most experimental ROA signs and relative intensities could be reproduced. The effect might significantly increase the potential of ROA spectroscopy in bioimaging and sensitive detection of chiral molecules.

Controlling Nucleation in Lithium Metal Anodes.

Rechargeable batteries are regarded as the most promising candidates for practical applications in portable electronic devices and electric vehicles. In recent decades, lithium metal batteries (LMBs) have been extensively studied due to their ultrahigh energy densities. However, short lifespan and poor safety caused by uncontrollable dendrite growth hinder their commercial applications. Besides, a clear understanding of Li nucleation and growth has not yet been obtained. In this Review, the failure mechanisms of Li metal anodes are ascribed to high reactivity of lithium, virtually infinite volume changes, and notorious dendrite growth. The principles of Li deposition nucleation and early dendrite growth are discussed and summarized. Correspondingly, four rational strategies of controlling nucleation are proposed to guide Li nucleation and growth. Finally, perspectives for understanding the Li metal deposition process and realizing safe and high-energy rechargeable LMBs are given.

A Case Report of Double-Chambered Right Ventricle Associated with Subaterial Ventricular Septal Defect and Rupture of Right Coronary Sinus Aneurysm.

Double-chambered right ventricle (DCRV) is a rare congenital heart disease in which the right ventricle (RV) is divided into two chambers by anomalous muscle bundles. Here, we report a case of DCRV associated with subarterial ventricular septal defect (VSD) and rupture of right coronary sinus aneurysm (RCSA); the patient was diagnosed by echocardiography and later confirmed by surgical operation.

Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells.

The superficial bladder epithelium is a powerful barrier to urine and also serves as a regulator of bladder volume, which is achieved by apical exocytosis of specialized fusiform vesicles during distension of the bladder. We report that type 1 fimbriated uropathogenic Escherichia coli (UPEC) circumvents the bladder barrier by harboring in these Rab27b/CD63-positive and cAMP-regulatable fusiform vesicles within bladder epithelial cells (BECs). Incorporation of UPEC into BEC fusiform compartments enabled bacteria to escape elimination during voiding and to re-emerge in the urine as the bladder distended. Notably, treatment of UPEC-infected mice with a drug that increases intracellular cAMP and induces exocytosis of fusiform vesicles reduced the number of intracellular E. coli.

Application of multi-planar reconstruction technique in endovascular repair of aortic dissection.

BACKGROUND: Endovascular repair of aortic dissection is an effective method commonly used in the treatment of Stanford type B aortic dissection. Stent placement during the operation was one-time and could not be repeatedly adjusted during the operation. Therefore, it is of great significance for cardiovascular physicians to fully understand the branch status, position, angle, and other information regarding aortic arch dissection before surgery. AIM: To provide more references for clinical cardiovascular physicians to develop treatment plans. METHODS: Data from 153 patients who underwent endovascular repair of aortic dissection at our hospital between January 2021 and December 2022 were retrospectively collected. All patients underwent multi-slice spiral computed tomography angiography. Based on distinct post-image processing techniques, the patients were categorized into three groups: Multiplanar reconstruction (MPR) (n = 55), volume reconstruction (VR) (n = 46), and maximum intensity projection (MIP) (n = 52). The detection rate of aortic rupture, accuracy of the DeBakey classification, rotation, and tilt angles of the C-arm during the procedure, dispersion after stent release, and the incidence of late complications were recorded and compared. RESULTS: The detection rates of interlayer rupture in the MPR and VR groups were significantly higher than that in the MIP group (P < 0.05). The detection rates of DeBakey subtypes I, II, and III in the MPR group were higher than those in the MIP group, and the detection rate of type III in the MPR group was significantly higher than that in the VR group (P < 0.05). There was no statistically significant difference in the detection rates of types I and II compared to the VR group (P > 0.05). The scatter rate of markers and the incidence of complications in the MPR group were significantly lower than those in the VR and MIP groups (P < 0.05). CONCLUSION: The application of MPR in the endovascular repair of aortic dissection has improved the detection rate of dissection rupture, the accuracy of anatomical classification, and safety.

Four new species of Russula from the Xizang Autonomous Region and other provinces of China.

Russula is the largest genus in the Russulales and is widespread throughout the world. Almost all Russula species are known to be ectomycorrhizal with high ecological and edible values, and some are lethal poisonous. In this study, four new species belonging to the subgenus Russula crown clade are identified based on morphological and phylogenetic evidence from the Xizang Autonomous Region and other provinces of China. Morphologically, Russula paragraveolens (sect. Polychromae, subsect. Xerampelinae) is mainly characterised by a cherry red to blood red pileus centre, a reddish orange pileus margin; R. pseudograveolens (sect. Polychromae, subsect. Xerampelinae) is characterised by a violet brown to brownish red pileus centre, a pale red to pastel red pileus margin and short basidia; R. shigatseensis (sect. Flavisiccantes, subsect. Lepidinae) is characterised by a brownish orange to madder red pileus centre, pinkish red pileus margin, and having lateral branches or branches of hyphal terminations in pileipellis; R. yadongensis (sect. Tenellae, subsect. Laricinae) is characterised by a dark purplish red pileus centre with brownish purple tints and having isolated to clustered spines of spore ornamentations. Their distinct taxonomic status is confirmed by the positions of the four new species in both the ITS and 4-locus (nucLSU, mtSSU, rpb2, tef1) phylogenetic trees.

APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease.

Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and G2 cause kidney disease is poorly understood. Here, we leveraged 3 experimental models and a recently reported small molecule blocker of APOL1 protein, VX-147, to identify the upstream mechanism of G1-induced cytotoxicity. In HEK293 cells, we demonstrated that G1-mediated Na+ import/K+ efflux triggered activation of GPCR/IP3-mediated calcium release from the ER, impaired mitochondrial ATP production, and impaired translation, which were all reversed by VX-147. In human urine-derived podocyte-like epithelial cells (HUPECs), we demonstrated that G1 caused cytotoxicity that was again reversible by VX-147. Finally, in podocytes isolated from APOL1 G1 transgenic mice, we showed that IFN-γ-mediated induction of G1 caused K+ efflux, activation of GPCR/IP3 signaling, and inhibition of translation, podocyte injury, and proteinuria, all reversed by VX-147. Together, these results establish APOL1-mediated Na+/K+ transport as the proximal driver of APOL1-mediated kidney disease.

Numerical investigation on red blood cell flow based on unstructured grid.

Prediction of blood cell flow is known as the difficult research by reason of the complexity of blood vessel. In this study, considering the complex structure of blood vessels, a mechanical model for red blood cell (RBC) based on unstructured grid has been established to study the flow characteristics of RBCs in complex blood vessels. In the model, the strain-energy function by Skalak is employed to model the shear elasticity and surface-area conservation of the membrane, and the hinge spring is used to describe the forces originating from local bending of the membrane. The immersed boundary method is utilized to couple the interphase force. Using the model, the stretching test of RBC is compared with the experiment data, and the good agreement verified the validation of the present model. The morphology of red blood cell and the blood viscosity in micro-vessel are studied. RBCs move with a symmetric shape (parachute shape) in small blood vessels, and the buckling instability is observed when the RBC flow slowly through a micro-vessel or a converging-diverging capillary. When the vessel diameter is around 10 µm, the reverse Fahraeus-Lindqvist effect is presented. The blood apparent viscosity shows linear increase with the blood hematocrit. In addition, Malaria infection can make the RBC deformability decreased and the blood apparent viscosity increased.