Site-specific allylic C-H bond functionalization with a copper-bound N-centred radical.

Methods for selective C-H bond functionalization have provided chemists with versatile and powerful toolboxes for synthesis, such as the late-stage modification of a lead compound without the need for lengthy de novo synthesis1-5. Cleavage of an sp3 C-H bond via hydrogen atom transfer (HAT) is particularly useful, given the large number of available HAT acceptors and the diversity of reaction pathways available to the resulting radical intermediate6-17. Site-selectivity, however, remains a formidable challenge, especially among sp3 C-H bonds with comparable properties. If the intermediate radical could be further trapped enantioselectively, this should enable highly site- and enantioselective functionalization of C-H bonds. Here we report a copper (Cu)-catalysed site- and enantioselective allylic C-H cyanation of complex alkenes, in which a Cu(II)-bound nitrogen (N)-centred radical plays the key role in achieving precise site-specific HAT. This method is shown to be effective for a diverse collection of alkene-containing molecules, including sterically demanding structures and complex natural products and pharmaceuticals.

Decoding the complete organelle genomic architecture of Stewartia gemmata: an early-diverging species in Theaceae.

BACKGROUND: Theaceae, comprising 300 + species, holds significance in biodiversity, economics, and culture, notably including the globally consumed tea plant. Stewartia gemmata, a species of the earliest diverging tribe Stewartieae, is critical to offer insights into Theaceae's origin and evolutionary history. RESULT: We sequenced the complete organelle genomes of Stewartia gemmata using short/long reads sequencing technologies. The chloroplast genome (158,406 bp) exhibited a quadripartite structure including the large single-copy region (LSC), a small single-copy region (SSC), and a pair of inverted repeat regions (IRs); 114 genes encoded 80 proteins, 30 tRNAs, and four rRNAs. The mitochondrial genome (681,203 bp) exhibited alternative conformations alongside a monocyclic structure: 61 genes encoding 38 proteins, 20 tRNAs, three rRNAs, and RNA editing-impacting genes, including ATP6, RPL16, COX2, NAD4L, NAD5, NAD7, and RPS1. Comparative analyses revealed frequent recombination events and apparent rRNA gene gains and losses in the mitochondrial genome of Theaceae. In organelle genomes, the protein-coding genes exhibited a strong A/U bias at codon endings; ENC-GC3 analysis implies selection-driven codon bias. Transposable elements might facilitate interorganelle sequence transfer. Phylogenetic analysis confirmed Stewartieae's early divergence within Theaceae, shedding light on organelle genome characteristics and evolution in Theaceae. CONCLUSIONS: We studied the detailed characterization of organelle genomes, including genome structure, composition, and repeated sequences, along with the identification of lateral gene transfer (LGT) events and complexities. The discovery of a large number of repetitive sequences and simple sequence repeats (SSRs) has led to new insights into molecular phylogenetic markers. Decoding the Stewartia gemmata organellar genome provides valuable genomic resources for further studies in tea plant phylogenomics and evolutionary biology.

Advancing Meta-Selective C-H Amination through Non-Covalent Interactions.

Regioselective C-H amination of simple arenes is highly desirable, but accessing meta-sites of ubiquitous arenes has proven challenging due to the lack of both electronic and spatial preference. This study demonstrates the successful use of various privileged nitrogen-containing functionalities found in pharmaceutical compounds to direct meta-C-H amination of arenes, overcoming the long-standing requirement for a redundant directing group. The remarkable advancements in functional group accommodation for precise regiochemical control were achieved through the discovery of an unprecedented organo-initiator and the strategic utilization of non-covalent interactions. This protocol has been successfully applied in the concise synthesis and late-stage derivatization of drug molecules, which would have been otherwise challenging to achieve.

Enantioselective Cyanofunctionalization of Aromatic Alkenes via Radical Anions.

Alkene radical ions constitute an integral and unique class of reactive intermediates for the synthesis of valuable compounds because they have both unpaired spins and charge. However, relatively few synthetic applications of alkene radical anions have emerged due to a dearth of generally applicable and mild radical anion generation approaches. Precise control over the chemo- and stereoselectivity in alkene radical anion-mediated processes represents another long-standing challenge due to their high reactivity. To overcome these issues, here, we develop a new redox-neutral strategy that seamlessly merges photoredox and copper catalysis to enable the controlled generation of alkene radical anions and their orthogonal enantioselective cyanofunctionalization via distonic-like species. This new strategy enables highly regio-, chemo-, and enantioselective hydrocyanation, deuterocyanation, and cyanocarboxylation of alkenes without stoichiometric reductants or oxidants under visible light irradiation. This protocol provides a new blueprint for the exploration of the transformation potential of alkene radical anions.

Deciphering the pancreatic cancer microbiome in Mainland China: Impact of Exiguobacterium/Bacillus ratio on tumor progression and prognostic significance.

The existing body of research underscores the critical impact of intratumoral microbiomes on the progression of pancreatic ductal adenocarcinoma (PDAC), particularly in reshaping the tumor microenvironment and influencing gemcitabine resistance. However, peritumoral tissues' microbiome, distinct from PDAC tumors, remain understudied, and Western-centric analyses overlooking potential variations in dietary-influenced microbiomes. Our study addresses this gap by 16 S rRNA sequencing of PDAC tumors and matched peritumoral tissues from Chinese Mainland patients. Our research has uncovered that the microbiome composition within tumors and paired peritumoral tissues exhibits a high degree of similarity, albeit with certain discrepancies. Notably, Exiguobacterium is found to be more abundant within the tumor tissues. Further investigations have revealed that a lower Exiguobacterium/Bacillus ratio in both the tumor and peritumoral tissues of PDAC patients is indicative of a more favorable prognosis. Further exploration utilizing an orthotopic tumor model demonstrates that the probiotic Bacillus Coagulans impedes PDAC progression, accompanied by an increased infiltration of inflammatory neutrophils in tumors. Additionally, in the subgroup with a low Exiguobacterium/Bacillus ratio, whole-exome sequencing reveals elevated missense mutations in ABL2 and MSH2. The elevated expression of ABL2 and MSH2 has been correlated with poorer prognostic outcomes in PDAC patients. Together, these insights shed light on risk factors influencing PDAC progression and unveil potential therapeutic targets, alongside probiotic intervention strategies.

FragGrow: A Web Server for Structure-Based Drug Design by Fragment Growing within Constraints.

Fragment growing is an important ligand design strategy in drug discovery. In this study, we present FragGrow, a web server that facilitates structure-based drug design by fragment growing. FragGrow offers two working modes: one for growing molecules through the direct replacement of hydrogen atoms or substructures and the other for growing via virtual synthesis. FragGrow works by searching for suitable fragments that meet a set of constraints from an indexed 3D fragment database and using them to create new compounds in 3D space. The users can set a range of constraints when searching for their desired fragment, including the fragment's ability to interact with specific protein sites; its size, topology, and physicochemical properties; and the presence of particular heteroatoms and functional groups within the fragment. We hope that FragGrow will serve as a useful tool for medicinal chemists in ligand design. The FragGrow server is freely available to researchers and can be accessed at https://fraggrow.xundrug.cn.

The multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy lesion with multiple evanescent white dot syndrome-like features: a retrospective study.

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS)-like features is a rare condition triggered by a macular disease or iatrogenic injury, exhibiting MEWDS changes in the fundus. This study aims to describe the multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) lesions with MEWDS-like features. METHODS: Six cases were studied retrospectively. All cases were given regional and oral corticosteroids. RESULTS: All cases showed an isolated juxtafoveal yellowish-white MFC/PIC lesion with disruption of RPE-Bruch's membrane-choriocapillaris complex (RPE-BM-CC), subretinal hyperreflective materials and choroidal thickening on optical coherence tomography. Two weeks after presentation, the grayish-white dots disappeared spontaneously and the corticosteroids were given. After four weeks, the ellipsoid zone (EZ) around the lesion and hyper-autofluorescence resolved. After 13 weeks, five cases showed shrinkage of the juxtafoveal lesion and restoration of foveal EZ. After six months, the juxtafoveal lesion became pigmented. Only one case developed type 2 choroidal neovascularization. CONCLUSIONS: The clinical course of MEWDS-like manifestations is still evanescent in our cases. The yellowish-white juxtafoveal MFC/PIC lesions with disruption of RPE-BM-CC and choroidal thickening showed a well-controlled prognosis after corticosteroid treatment.

Cobalt-Catalyzed Enantioselective Alkenylation of Aldehydes.

Catalytic enantioselective alkenylation of aldehydes with easily accessible alkenyl halides promoted by a chiral cobalt complex derived from a newly developed tridentate bisoxazolinephosphine is presented. Such processes represent an unprecedented reaction pathway for cobalt catalysis and a general approach that enable rapid construction of highly diversified enantioenriched allylic alcohols containing a 1,1-, 1,2-disubstituted and trisubstituted alkene as well as axial stereogenicity in up to 99% yield and 99:1 er without the need of preformation of alkenyl-metal reagents. DFT calculations revealed the origin of enantioselectivity.

Photoinduced Copper-Catalyzed Asymmetric Three-Component Radical 1,2-Azidooxygenation of 1,3-Dienes.

Radical-involved multicomponent difunctionalization of 1,3-dienes has recently emerged as a promising strategy for rapid synthesis of valuable allylic compounds in one-pot operation. However, the expansion of radical scope and enantiocontrol remain two major challenges. Herein, we describe an unprecedented photoinduced copper-catalyzed highly enantioselective three-component radical 1,2-azidooxygenation of 1,3-dienes with readily available azidobenziodazolone reagent and carboxylic acids. This mild protocol exhibits a broad substrate scope, high functional group tolerance, and exceptional control over chemo-, regio- and enantioselectivity, providing practical access to diverse valuable azidated chiral allylic esters. Mechanistic studies imply that the chiral copper complex is implicated as a bifunctional catalyst in both the photoredox catalyzed azidyl radical generation and enantioselective radical C-O cross-coupling.

Asymmetric [3 + 2] Photocycloaddition of ß-Keto Esters and Vinyl Azides by Dual Photoredox/Nickel Catalysis.

Photocatalytic [3 + 2] cycloadditions and control of stereochemistry have remained a substantial challenge, particularly in the context of heterocycle synthesis; sporadic successful examples have involved enantioselective [3 + 2] photocycloaddition between redox-active direct group-containing cyclopropanes and alkenes for creation of cyclopentanes. Herein, we report a cooperative catalytic system comprising a chiral nickel Lewis acid catalyst and an organic photocatalyst fueled by visible-light irradiation that allows for the hitherto elusive asymmetric [3 + 2] photocycloaddition of ß-keto esters with vinyl azides under redox-neutral conditions. This protocol enables highly enantioselective construction of polycyclic densely substituted 3,4-dihydro-2H-pyrrole heterocycles featuring two contiguous tetrasubstituted carbon stereocenters, including a useful chiral N,O-ketal motif that is not easily accessible with other catalytic methods. Mechanistic studies revealed that the overall reactivity relies on the seamless integration of dual roles of nickel catalysts by the catalytic formation of the substrate/Ni complex, assisting both photoredox event and enantioselective radical addition.

New biomarkers exploration and nomogram construction of prognostic and immune-related adverse events of advanced non-small cell lung cancer patients receiving immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are regarded as the most promising treatment for advanced-stage non-small cell lung cancer (aNSCLC). Unfortunately, there has been no unified accuracy biomarkers and systematic model specifically identified for prognostic and severe immune-related adverse events (irAEs). Our goal was to discover new biomarkers and develop a publicly accessible method of identifying patients who may maximize benefit from ICIs. METHODS: This retrospective study enrolled 138 aNSCLC patients receiving ICIs treatment. Progression-free survival (PFS) and severe irAEs were end-points. Data of demographic features, severe irAEs, and peripheral blood inflammatory-nutritional and immune indices before and after 1 or 2 cycles of ICIs were collected. Independent factors were selected by least absolute shrinkage and selection operator (LASSO) combined with multivariate analysis, and incorporated into nomogram construction. Internal validation was performed by applying area under curve (AUC), calibration plots, and decision curve. RESULTS: Three nomograms with great predictive accuracy and discriminatory power were constructed in this study. Among them, two nomograms based on combined inflammatory-nutritional biomarkers were constructed for PFS (1 year-PFS and 2 year-PFS) and severe irAEs respectively, and one nomogram was constructed for 1 year-PFS based on immune indices. ESCLL nomogram (based on ECOG PS, preSII, changeCAR, changeLYM and postLDH) was constructed to assess PFS (1-, 2-year-AUC = 0.893 [95% CI 0.837-0.950], 0.828 [95% CI 0.721-0.935]). AdNLA nomogram (based on age, change-dNLR, changeLMR and postALI) was constructed to predict the risk of severe irAEs (AUC = 0.762 [95% CI 0.670-0.854]). NKT-B nomogram (based on change-CD3+CD56+CD16+NKT-like cells and change-B cells) was constructed to assess PFS (1-year-AUC = 0.872 [95% CI 0.764-0.965]). Although immune indices could not be modeled for severe irAEs prediction due to limited data, we were the first to find CD3+CD56+CD16+NKT-like cells were not only correlated with PFS but also associated with severe irAEs, which have not been reported in the study of aNSCLC-ICIs. Furthermore, our study also discovered higher change-CD4+/CD8+ ratio was significantly associated with severe irAEs. CONCLUSIONS: These three new nomograms proceeded from non-invasive and straightforward peripheral blood data may be useful for decisions-making. CD3+CD56+CD16+NKT-like cells were first discovered to be an important biomarker for treatment and severe irAEs, and play a vital role in distinguishing the therapy response and serious toxicity of ICIs.

Angiotensin-converting enzyme 2 in human plasma and lung tissue.

PURPOSE: We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery. MATERIALS AND METHODS: The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (n = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women). RESULTS: In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 vs. 0.98 ng/mL, p = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 vs. 53.9 a.u., p = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (p = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (p = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 vs. 0.98 ng/mL, p = 0.029 vs. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (p = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (p = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (p ≥ 0.20). CONCLUSION: ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.Plain language summary What is the context? • The primary physiological function of ACE2 is the degradation of angiotensin I and II to angiotensin 1-9 and 1-7, respectively. • ACE2 was found to behave as a mediator of the severe acute respiratory syndrome coronavirus (SARS) infection. • There is little research on ACE2 in humans, especially in the lung tissue. • In the present report, we investigated plasma ACE2 concentration and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue respectively in two study populations. What is new? • Our study investigated both circulating and tissue ACE2 in human subjects. The main findings were: • In men as well as women, plasma ACE2 concentration was higher in younger than older participants, whereas the mean intensity of ACE2 in the lung tissue increase with age increasing. • Compared with normotension, hypertensive patients had higher plasma ACE2 concentration but similar mean intensity of ACE2 in the lung tissue. • Neither plasma ACE2 concentration nor lung tissue ACE2 expression significantly differed between users of RAS inhibitors and other classes of antihypertensive drugs. What is the impact? • ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics, such as sex, age, and treated and untreated hypertension. • A major implication is that plasma ACE2 concentration might not be an appropriate surrogate for the ACE2 expression in the lung tissue, and hence not a good predictor of SARS-COV-2 infection or fatality.

Integrative Bioinformatics Analysis of mRNA Expression Profiles of Mice to Explore the Key Genes Involved in Crim1 Mutation-Induced Congenital Cataracts.

Crim1 has been implicated in cataracts in mice and is of great importance in the development of the eye in both humans and mice. Therefore, we aimed to clarify how Crim1 mutations affect lens development and the molecular mechanism of cataracts in mice through comprehensive bioinformatics analysis. The microarray chip was downloaded from the GEO database to obtain the gene expression profile data set. Differentially expressed genes (DEGs) were screened using the limma package. GO and KEGG analyses of DEGs were performed using the DAVID database. Then, we established the protein-protein interaction (PPI) network in Cytoscape. Next, we used MCODE to analyze the data. We obtained 750 DEGs in total, including 407 upregulated DEGs and 343 downregulated DEGs. GO analysis showed that the DEGs were mainly related to biological processes, such as apoptosis, cell translation and the immune system. KEGG analysis showed that the enriched functions and pathways were related to the processing and presentation of ribosomes, lysosomes, and antigens. We identified 18 HUB genes, among which four core genes, C1qa, C1qb, C1qc, and Cd74, were closely related to congenital cataracts induced by Crim1 mutation. This study reveals the molecular pathogenesis of congenital cataracts induced by Crim1, and this information is expected to facilitate clinical genetic testing, molecular diagnosis, prognosis, and individualized chemotherapy for congenital cataracts (CC).

YY1 (Yin-Yang 1), a transcription factor regulating systemic inflammation, is involved in cognitive impairment of depression.

AIM: Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation. METHODS: Plasma levels of YY1, interleukin (IL) 6, and IL-1ß in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1ß inflammatory pathway were measured in related brain regions. RESULTS: Plasma levels of YY1 and IL-1ß were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1ß in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1ß inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine. CONCLUSION: The current study suggests that the YY1-NF-κB-IL-1ß inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.

[Latest Findings on the Interaction Mechanism Between Depressive Disorder and Intestinal Permeability].

The intestinal barrier, a complex structure consisting of multiple layers of defense barriers, blocks the transfer of intestinal and foreign bacteria and their metabolites into the internal environment of the human body. Intestinal permeability can be used to evaluate the integrity of the intestinal barrier. Increased intestinal permeability has been observed in patients with depressive disorder. Some studies have reported an interaction between depressive disorder and intestinal barrier. Herein, we reviewed reported findings on the mechanisms of how systematic low-grade inflammation, vagal nerve dysfunction, and hypothalamic-pituitary-adrenal axis dysfunction cause changes in intestinal permeability in patients with depressive disorder and the pathogenic mechanism of how bacterial translocation caused by damaged intestinal barrier leads to depressive disorder. In addition, the potential mechanisms of how antidepressants improve intestinal permeability and how probiotics improve depressive disorder have been discussed.

Visible Light Induced Copper-Catalyzed Enantioselective Deaminative Arylation of Amino Acid Derivatives Assisted by Phenol.

The exploration of value-added conversions of naturally abundant amino acids has received considerable attention from the synthetic community. Compared with the well-established asymmetric decarboxylative transformation, the asymmetric deaminative transformation of amino acids still remains a formidable challenge, mainly due to the lack of effective strategies for the C-N bond activation and the potential incompatibility with chiral catalysts. Here, we disclose a photoinduced Cu-catalyzed asymmetric deaminative coupling reaction of amino acids with arylboronic acids. This new protocol provides a series of significant chiral phenylacetamides in generally good yields and excellent stereoselectivity under mild and green conditions (42-85 % yields, up to 97 % ee). Experimental investigations and theoretical calculations were performed to reveal the crucial role of additional phenols in improving catalytic efficiency and enantiocontrol.

Photoinduced Five-Component Radical Relay Aminocarbonylation of Alkenes.

Radical single carbonylation reactions with CO constitute a direct and robust strategy toward various carbonyl compounds from readily available chemicals, and have been extensively studied over the past decades. However, realizing highly selective catalytic systems for controlled radical double carbonylation reactions has remained a substantial challenge, particularly for the more advanced multicomponent variants, despite their great potential value. Herein, we report a visible-light-driven radical relay five-component radical double aminocarbonylation reaction of unactivated alkenes using CO under metal-free conditions. This protocol provides direct access to valuable γ-trifluoromethyl α-ketoamides with good yields and high chemoselectivity. Crucial was the identification of distinct dual roles of amine coupling partners, sequentially acting as electron donors for the formation of photoactive electron donor-acceptor (EDA) complexes with radical precursors and then as a CO acceptor via nitrogen radical cations to form carbamoyl radicals. Cross-coupling of carbamoyl radicals with the acyl radicals that are formed in an alkene-based relay process affords double aminocarbonylation products.

Direct Catalytic Asymmetric and Regiodivergent N1- and C3-Allenylic Alkylation of Indoles.

Herein we report a Pd-catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H-indoles by employing P-chiral BIBOP-type ligands. The regioselectivity (N1/C3) of this process can be switched efficiently. Using Cs2 CO3 at elevated temperatures in MeCN, N1-alkylated indoles bearing axial chirality with a stereocenter non-adjacent (ß) to the nitrogen are produced in good yields with high enantioselectivity and complete N1-regioselectivity regardless of the electronic properties and substitution patterns of diverse indoles. Using K2 CO3 at room temperature in CH2 Cl2 , chiral C3-alkylated indoles can also be obtained. Notably, we introduce a new class of tri-substituted allenylic electrophiles that proceeded through different pathways from di-substituted allenylic electrophiles.

Concise Total Synthesis of Salimabromide.

We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule's structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.

Clinical significance of MYD88 non-L265P mutations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a group of heterogeneous tumors with different molecular traits and clinical features. MYD88 is an oncogene that activates the nuclear factor κB pathway in DLBCL. MYD88 L265P mutation frequently occurs in DLBCL with poor prognosis, while the clinical significance of non-L265P mutations needs to be clarified. Next-generation sequencing was performed on a cohort of 356 patients with DLBCL to investigate the impact of MYD88 mutation. Ten MYD88 mutated variants were detected in 32% (114/356) of the cases. V217F, S219C, S222R, M232T, S243N, and T294P were identified as pathogenic variants. MYD88 non-L265P mutations occurred less than L265P mutation in DLBCL of the central nervous system and breast tissue. The coexistence of MYD88 non-L265P mutations with PIM1 mutation was also less than that of L265P mutation. The progression-free survival in patients with DLBCL with MYD88 non-L265P mutation was statistically better than in patients with MYD88 L265P mutation. The interpretation of variants of MYD88 mutation offers a precise guide for the management of DLBCL.