Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice.

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs.

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.

Comparative evaluation of amino acid profiles, fatty acid compositions, and nutritional value of two varieties of head water Porphyra yezoensis: "Jianghaida No. 1" and "Sutong No.1".

Comparative nutritional analysis of Porphyra yezoensis strains "Jianghai No. 1" and "Sutong No.1" revealed significant differences in crude protein, crude fat, crude fiber, crude ash, and total sugar. Both strains contained 16 amino acids, with alanine as the highest and histidine the lowest content. Methionine was determined to be the first limiting amino acid for both strains in both amino acid score and chemical score assessment. They also featured 24 fatty acids, differing notably in four saturated fatty acids and five unsaturated fatty acids. All 12 mineral elements were present, notably differing in sodium, magnesium, potassium, calcium, iron, and zinc. The "Jianghai No. 1" strain stands out with its nutrient-rich profile, featuring high protein content, low fat, and abundant minerals, which could potentially command higher market prices and generate greater economic benefits due to its superior nutritional, and set a strong foundation for its future large-scale promotion and cultivation.

Comprehensive investigation of differentially expressed ncRNAs, mRNAs, and their ceRNA networks in the regulation of shell color formation in clam, Cyclina sinensis.

Noncoding RNAs (ncRNAs) have gained significant attention in recent years due to their crucial roles in various biological processes. However, our understanding of the expression and functions of ncRNAs in Cyclina sinensis, an economically important marine bivalve, remains limited. This study aimed to address this knowledge gap by systematically identifying ncRNAs in the mantles of C. sinensis with purple and white shells. Through our analysis, we identified a differential expression of 1244 mRNAs, 196 lncRNAs, 49 circRNAs, and 23 miRNAs between purple- and white-shell clams. Functional enrichment analysis revealed the involvement of these differentially expressed ncRNAs in biomineralization and pigmentation processes. To gain further insights into the regulatory mechanisms underlying shell color formation, we established competitive endogenous RNA (ceRNA) networks. These networks allowed us to identify targeted differentially expressed miRNAs (DEMis) and genes associated with shell color formation. Based on the ceRNA networks, we obtained an up-down-up lncRNA-miRNA-mRNA network consisting of 13 upregulated lncRNAs and a circRNA-miRNA-mRNA network comprising three upregulated circRNAs (novel_circ_0004787, novel_circ_0001165, novel_circ_0000245). Through these networks, we identified and selected an upregulated novel gene (evm.TU.Hic_asm_7.988) and a downregulated sponge miRNA (hru-miR-1985) as potential contributors to shell color regulation. In summary, the present investigation offers a comprehensive analysis of ncRNA catalogs expressed in the clam mantle of C. sinensis. The findings enhance our comprehension of the molecular mechanisms governing shell coloration and offer new perspectives for selective breeding of C. sinensis in the future.

Impact of the COVID-19 pandemic on the prevalence of respiratory viral pathogens in patients with acute respiratory infection in Shanghai, China.

Objective: This study aimed to evaluate the impact of nonpharmaceutical interventions (NPIs) taken to combat COVID-19 on the prevalence of respiratory viruses (RVs) of acute respiratory infections (ARIs) in Shanghai. Methods: Samples from ARI patients were collected and screened for 17 respiratory viral pathogens using TagMan low density microfluidic chip technology in Shanghai from January 2019 to December 2020. Pathogen data were analyzed to assess changes in acute respiratory infections between 2019 and 2020. Results: A total of 2,744 patients were enrolled, including 1,710 and 1,034 in 2019 and 2020, respectively. The total detection rate of RVs decreased by 149.74% in 2020. However, detection rates for human respiratory syncytial virus B (RSVB), human coronavirus 229E (HCoV229E), human coronavirus NL63 (HCoVNL63), and human parainfluenza virus 3 (HPIV3) increased by 91.89, 58.33, 44.68 and 24.29%, in 2020. The increased positive rates of RSVB, HPIV3, resulted in more outpatients in 2020 than in 2019. IFV detection rates declined dramatically across gender, age groups, and seasons in 2020. Conclusion: NPIs taken to eliminate COVID-19 had an impact on the prevalence of respiratory viral pathogens, especially the IFVs in the early phases of the pandemic. Partial respiratory viruses resurged with the lifting of NPIs, leading to an increase in ARIs infection.

Calibration method of the right-angle error of a hollow corner-cube retroreflector based on an independent autocollimator.

Hollow corner-cube retroreflectors (HCCRs) are an essential reflection component of next-generation lunar laser-ranging technology. The verticality among the three reflectors, known as the right-angle error, is a critical parameter that affects the emission performance, and thus, should be correctly measured and calibrated. However, conventional methods measure the three right-angle errors separately, which can induce error superposition during the measurement process. A one-time measurement method was developed for the three right-angle errors of the HCCR using a single autocollimator (AC). The method establishes a mathematical relationship between the right-angle error of the HCCR and the angle offset of the reflected beam, and it considers the observation coordinates of the AC simultaneously to perform the coordinate transformation of the relationship parameters. The corresponding measurement equation was derived to extract the three-plane right-angle error of the HCCR using the measured readings of a single AC. In addition, a HCCR was designed to freely adjust the angle of the two reflective surfaces and used to simulate the different states of the three right-angle errors in practice. The measurement results show that the root-mean-square error of the proposed method in all right-angle error states is smaller than 16 ' ' .

The genetic landscape of histologically transformed marginal zone lymphomas.

BACKGROUND: Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. METHODS: Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. RESULTS: All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. CONCLUSIONS: The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.

iAMP-Attenpred: a novel antimicrobial peptide predictor based on BERT feature extraction method and CNN-BiLSTM-Attention combination model.

As a kind of small molecule protein that can fight against various microorganisms in nature, antimicrobial peptides (AMPs) play an indispensable role in maintaining the health of organisms and fortifying defenses against diseases. Nevertheless, experimental approaches for AMP identification still demand substantial allocation of human resources and material inputs. Alternatively, computing approaches can assist researchers effectively and promptly predict AMPs. In this study, we present a novel AMP predictor called iAMP-Attenpred. As far as we know, this is the first work that not only employs the popular BERT model in the field of natural language processing (NLP) for AMPs feature encoding, but also utilizes the idea of combining multiple models to discover AMPs. Firstly, we treat each amino acid from preprocessed AMPs and non-AMP sequences as a word, and then input it into BERT pre-training model for feature extraction. Moreover, the features obtained from BERT method are fed to a composite model composed of one-dimensional CNN, BiLSTM and attention mechanism for better discriminating features. Finally, a flatten layer and various fully connected layers are utilized for the final classification of AMPs. Experimental results reveal that, compared with the existing predictors, our iAMP-Attenpred predictor achieves better performance indicators, such as accuracy, precision and so on. This further demonstrates that using the BERT approach to capture effective feature information of peptide sequences and combining multiple deep learning models are effective and meaningful for predicting AMPs.

Circulating tumor DNA in NK/T and peripheral T cell lymphoma.

Natural killer (NK)/T-cell lymphomas (NK/TCL) and peripheral T-cell lymphomas (PTCL) are aggressive hematological malignancies. With the development of next-generation sequencing, circulating tumor DNA (ctDNA) can be detected by several techniques with clinical implications. So far, the effect of ctDNA in pretreatment prognosis prediction, longitudinal monitoring of treatment response and surveillance of long-term remission or relapse in NK/TCL and PTCL has been reported in several researches.

Case report: Curing a rare, unstable hemoglobin variant Hb Bristol-Alesha using haploidentical hematopoietic stem cell transplantation.

Unstable hemoglobinopathies are a rare, heterogeneous group of diseases that disrupt the stability of hemoglobin (Hb), leading to chronic hemolysis and anemia. Patients with severe phenotypes often require regular blood transfusions and iron chelation therapy. Although rare, studies have reported that hematopoietic stem cell transplantation (HSCT) seems to be an available curative approach in transfusion-dependent patients with unstable hemoglobinopathies. Here, we describe successful haploidentical HSCT for the treatment of an unstable Hb variant, Hb Bristol-Alesha, in a 6-year-old boy with severe anemia since early childhood. Two years after transplantation, he had a nearly normal hemoglobin level without evidence of hemolysis. DNA analysis showed complete chimerism of the donor cell origin, confirming full engraftment with normal erythropoiesis.

Toxicities associated with immune checkpoint inhibitors: a systematic study.

BACKGROUND: Available evidence shows that the incidence of toxicities associated with cancer immunotherapy, such as programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1)-related toxicities, is estimated to be between 0.3 and 1.3%. OBJECTIVE: This systematic review aimed to investigate cancer patients' susceptibility to toxicities associated with PD-1/PD-L1 inhibitors and establish a clinically relevant landscape of side effects of PD-1/PD-L1 inhibitors. DATA SOURCES: Relevant publications from PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) between 2014 and 2019. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We searched randomized controlled trials (RCTs) reporting treatment-related toxicities associated with PD-1 and PD-L1 inhibitors in the treatment of cancers. The primary endpoint was to assess the difference in the incidences of toxicities between cancer patients who did and did not receive PD-1/PD-L1 inhibitors. A total of 29 RCTs, incorporating 8576 patients, met the eligibility criteria. STUDY APPRAISAL AND SYNTHESIS METHODS: We calculated the pooled relative risks and corresponding 95% CIs using a random-effects model and assessed the heterogeneity between different groups. The subgroup analyses were conducted based on cancer type, toxicity grade (severity), system and organ, treatment regimens in the intervention arm and the control arm, PD-1/PD-L1 inhibitor drug type, and cancer type. RESULTS: A total of 11 categories (e.g. endocrine toxicity), and 39 toxicity types (e.g. hyperthyroidism) were identified. For toxicities at any grade, those treated with PD-1/PD-L1 inhibitors were at lower risks for gastrointestinal toxicity, hematologic toxicity, and treatment event leading to discontinuation; and were at higher risks for respiratory toxicity (all P <0.05). Those treated with PD-1/PD-L1 inhibitors were at lower risks for fatigue, asthenia, and peripheral edema and were at higher risks for pyrexia, cough, dyspnea, pneumonitis, and pruritus. LIMITATIONS: The present research is a meta-analysis at the study level rather than at the patient level; insights on risk factors associated with the development of toxicities cannot be found in our study. There was a possible overlap in Common Terminology Criteria for Adverse Events (CTCAE) definitions which prevents understanding the true rates of specific toxicities. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: For most toxicity types based on system and organ, the incidence proportions for patients in the intervention arm were lower than those in the control arm, which suggested the general safety of PD-1/PD-L1 inhibitors against conventional chemotherapy and cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) inhibitors. Future research should focus on taking effective targeted measures to decrease the risks of different toxicities for different patient populations. SYSTEMATIC REVIEW REGISTRATION NUMBER: We registered the research protocol with PROSPERO (registration number CRD42019135113).

Gastric cancer-derived exosomes facilitate pulmonary metastasis by activating ERK-mediated immunosuppressive macrophage polarization.

Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.

Experimental and Quantum Chemical Study on the Inhibition Characteristics of Glutathione to Coal Oxidation at Low Temperature.

In response to the frequent occurrence of coal spontaneous combustion accidents, this paper proposes to use glutathione (GSH) as an inhibitor to inhibit the coal oxidation at low temperature. Based on the gas production of oxidation, thermogravimetric analysis, electron spin resonance, and in situ Fourier infrared transform spectroscopy experiments, it is known that GSH has a good inhibiting effect on lignite, long-flame coal, and fatty coal. The optimal action temperature of GSH is 60-150 °C, which can effectively slow down the weight loss and exothermic process and reduce the gas production of CO and CO2. Compared with the raw coal, the GSH-treated coal samples possess higher crossing point temperature and lower reactive group content. Subsequently, quantum chemical calculations are performed using density functional theory. The results demonstrate that the inhibiting mechanism of GSH is inerting the reactive radicals in coal and converting them into more stable compounds. Meanwhile, the activation energy of the reaction between GSH and each reactive radical is small, and all of them can occur at room temperature and pressure. This study lays the groundwork for future development of inhibitors.

Grading detection of "Red Fuji" apple in Luochuan based on machine vision and near-infrared spectroscopy.

A quality detection system for the "Red Fuji" apple in Luochuan was designed for automatic grading. According to the Chinese national standard, the grading principles of apple appearance quality and Brix detection were determined. Based on machine vision and image processing, the classifier models of apple defect, contour, and size were constructed. And then, the grading thresholds were set to detect the defective pixel ratio t, aspect ratio λ, and the cross-sectional diameter Wp in the image of the apple. Spectral information of apples in the wavelength range of 400 nm~1000 nm was collected and the multiple scattering correction (MSC) and standard normal variable (SNV) transformation methods were used to preprocess spectral reflectance data. The competitive adaptive reweighted sampling (CARS) algorithm and the successive projections algorithm (SPA) were used to extract characteristic wavelength points containing Brix information, and the CARS-PLS (partial least squares) algorithm was used to establish a Brix prediction model. Apple defect, contour, size, and Brix were combined as grading indicators. The apple quality online grading detection platform was built, and apple's comprehensive grading detection algorithm and upper computer software were designed. The experiments showed that the average accuracy of apple defect, contour, and size grading detection was 96.67%, 95.00%, and 94.67% respectively, and the correlation coefficient Rp of the Brix prediction set was 0.9469. The total accuracy of apple defect, contour, size, and Brix grading was 96.67%, indicating that the detection system designed in this paper is feasible to classify "Red Fuji" apple in Luochuan.

Dynamic change of soluble interleukin-2 receptor distinguished molecular heterogeneity and microenvironment alterations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with variable clinical outcomes and prediction of prognosis remains important for long-term remission. We performed serial serum soluble interleukin-2 receptor (sIL-2R) measurement pretreatment and before each cycle of the treatment in 599 patients with de novo DLBCL. Genomic and transcriptomic features were analyzed by 223 DNA- and 227 RNA-sequencing, respectively. Applying the cut-off value to sIL-2R pretreatment and cycle 2 (C2) level, patients were classified into FINE subtype (pretreatment low level) with good prognosis, RES subtype (pretreatment high level and C2 low level) with intermediate prognosis, and RET subtype (pretreatment high level and C2 high level) with poor prognosis, independent of International Prognostic Index. In "others" genetic subtype, dynamic change of sIL-2R showed prognostic significance and genetic features. Compared with FINE subtype, RES subtype had increased ARID1A and MYD88 mutations, and RET subtype had increased KMT2D, LYN and SOCS1 mutations. RES and RET subtypes showed significant enrichment in oncogenic pathways, such as ERK, NF-κB, JAK-STAT, and immune-associated pathways. As for tumor microenvironment, RES subtype exhibited increased recruiting activity of CD8 + T, T helper 1, and natural killer cells, and RET subtype with increased recruiting activity of CD4 + T and regulatory T cells in silico. There was a positive correlation between transcripts of IL-2R and immune checkpoint expressions including PD-1 and CTLA-4. Our findings identified that dynamic change of sIL-2R, with this simple and easy detection method in peripheral blood, had long-term prognostic effect and specific relation to microenvironment alterations in DLBCL.

Study of Butylated Hydroxytoluene Inhibiting the Coal Oxidation at Low Temperature: Combining Experiments and Quantum Chemical Calculations.

In order to cut off the chain reaction in the process of coal oxidation at low temperature (COLT), butylated hydroxytoluene (BHT) was used as an inhibitor to explore its inhibition effect and mechanism. In this paper, in situ Fourier transform infrared spectroscopy, electron paramagnetic resonance, and gas production of COLT experiments were conducted to compare the inhibited coal sample (BHT-Coal) with the raw coal. The results showed that BHT can effectively inhibit the formation of active free radicals, reduce the content of active alkoxy, carbonyl, and hydroxyl groups, increase the production temperature of CO, CO2, and C2H4, and reduce the concentration. The crossing point temperature increased from 132.3 to 157.4 °C, indicating that BHT can reduce the spontaneous combustion tendency of the raw coal. To explore the inhibition mechanism of BHT on COLT, five typical active free-radical models were established, and their active sites, active bonds, and thermodynamic parameters were calculated according to the density functional theory. The results showed that the highly active H atoms of the phenolic hydroxyl group in BHT can combine with active free radicals to generate stable compounds, and the activation energy of each reaction is small, which can occur under normal temperature and pressure. The inhibition mechanism of BHT is to reduce the concentration of the free radicals, so as to weaken the chain reaction strength during the COLT. This study provides a reference for the development and utilization of inhibitors.

Mate Analysis of Hepatocellular Carcinoma Immune Subtypes and Their Functional Effects Based on Fuzzy Logic and Evolutionary Algorithms.

Functional analysis of immune subtypes in hepatocellular carcinoma has attracted much attention due to its advantages in solving some optimization problems. At present, the research on the immune subtype of hepatocellular carcinoma is still in its infancy, and the high stability of its system still has problems. Based on fuzzy logic and evolutionary algorithms, this paper constructs a Mate analysis of the optimization problem of immune subtypes and dynamic optimization problems of hepatocellular carcinoma. The model conducts in-depth analysis and research on the biological immune subtype system, solving the problems of reliable information processing and body defense. Tested with existing test functions, very competitive results were achieved. The simulation results show that the improved algorithm based on data statistics has global search ability, the solution accuracy reaches 0.931, and the stability reaches 88.1%.

Integrated Genomic and Transcriptomic Analyses of Diffuse Large B-Cell Lymphoma With Multiple Abnormal Immunologic Markers.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma and related to autoimmune diseases (AIDs). Primary B-cell receptor-mediated AIDs are associated with poor clinical outcome of DLBCL. To further determine the role of immunological alterations on disease progression, our study integrated genomic and transcriptomic analyses on DLBCL with multiple abnormal immunologic markers. METHODS: The clinical data of 1,792 patients with newly diagnosed DLBCL were collected, with DNA- and RNA-sequencing conducted for 164 and 127 patients, respectively. Frequent gene mutations and the involved dysregulated pathways, along with gene expression pattern and tumor microenvironment alternations, were analyzed and compared based on the immune status of the patients. RESULTS: DLBCL with multiple abnormal immunologic markers demonstrated a variety of characteristics including elevated serum lactic dehydrogenase level, inferior prognosis, and dysregulated cell cycle and immune response, as well as activated oxidative phosphorylation pathway and increased Th1/Th2 and Th17/Treg ratios, which were highly similar as those that occur in AIDs. CONCLUSIONS: We piloted the description of the clinical and genetic features of DLBCL with multiple abnormal immunologic markers, illustrated possible mechanisms of disease progression, and provided a clinical rationale of mechanism-based targeted therapy in this subset of DLBCL.

All roads lead to targeted diffuse large B-cell lymphoma approaches.

Two recent reports in the New England Journal of Medicine highlight the successful application of novel targeted therapies to improve the clinical outcomes of diffuse large B-cell lymphoma (DLBCL). These findings encourage us to pursue further mechanism-based therapeutic uses to make DLBCL curable in the era of precision medicine.