Deciphering infected cell types, hub gene networks and cell-cell communication in infectious bronchitis virus via single-cell RNA sequencing.

Infectious bronchitis virus (IBV) is a coronavirus that infects chickens, which exhibits a broad tropism for epithelial cells, infecting the tracheal mucosal epithelium, intestinal mucosal epithelium, and renal tubular epithelial cells. Utilizing single-cell RNA sequencing (scRNA-seq), we systematically examined cells in renal, bursal, and tracheal tissues following IBV infection and identified tissue-specific molecular markers expressed in distinct cell types. We evaluated the expression of viral RNA in diverse cellular populations and subsequently ascertained that distal tubules and collecting ducts within the kidney, bursal mucosal epithelial cells, and follicle-associated epithelial cells exhibit susceptibility to IBV infection through immunofluorescence. Furthermore, our findings revealed an upregulation in the transcription of proinflammatory cytokines IL18 and IL1B in renal macrophages as well as increased expression of apoptosis-related gene STAT in distal tubules and collecting duct cells upon IBV infection leading to renal damage. Cell-to-cell communication unveiled potential interactions between diverse cell types, as well as upregulated signaling pathways and key sender-receiver cell populations after IBV infection. Integrating single-cell data from all tissues, we applied weighted gene co-expression network analysis (WGCNA) to identify gene modules that are specifically expressed in different cell populations. Based on the WGCNA results, we identified seven immune-related gene modules and determined the differential expression pattern of module genes, as well as the hub genes within these modules. Our comprehensive data provides valuable insights into the pathogenesis of IBV as well as avian antiviral immunology.

Adaptive truncation of the S gene in IBV during chicken embryo passaging plays a crucial role in its attenuation.

Like all coronaviruses, infectious bronchitis virus, the causative agent of infectious bronchitis in chickens, exhibits a high mutation rate. Adaptive mutations that arise during the production of live attenuated vaccines against IBV often decrease virulence. The specific impact of these mutations on viral pathogenicity, however, has not been fully elucidated. In this study, we identified a mutation at the 3' end of the S gene in an IBV strain that was serially passaged in chicken embryos, and showed that this mutation resulted in a 9-aa truncation of the cytoplasmic tail (CT) of the S protein. This phenomenon of CT truncation has previously been observed in the production of attenuated vaccines against other coronaviruses such as the porcine epidemic diarrhea virus. We next discovered that the 9-aa truncation in the S protein CT resulted in the loss of the endoplasmic-reticulum-retention signal (KKSV). Rescue experiments with recombinant viruses confirmed that the deletion of the KKSV motif impaired the localization of the S protein to the endoplasmic-reticulum-Golgi intermediate compartment (ERGIC) and increased its expression on the cell surface. This significantly reduced the incorporation of the S protein into viral particles, impaired early subgenomic RNA and protein synthesis, and ultimately reduced viral invasion efficiency in CEK cells. In vivo experiments in chickens confirmed the reduced pathogenicity of the mutant IBV strains. Additionally, we showed that the adaptive mutation altered the TRS-B of ORF3 and impacted the transcriptional regulation of this gene. Our findings underscore the significance of this adaptive mutation in the attenuation of IBV infection and provide a novel strategy for the development of live attenuated IBV vaccines.

A predictive model for therapy failure in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy.

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

Bioinspired Framework Catalysts: From Enzyme Immobilization to Biomimetic Catalysis.

Enzymatic catalysis has fueled considerable interest from chemists due to its high efficiency and selectivity. However, the structural complexity and vulnerability hamper the application potentials of enzymes. Driven by the practical demand for chemical conversion, there is a long-sought quest for bioinspired catalysts reproducing and even surpassing the functions of natural enzymes. As nanoporous materials with high surface areas and crystallinity, metal-organic frameworks (MOFs) represent an exquisite case of how natural enzymes and their active sites are integrated into porous solids, affording bioinspired heterogeneous catalysts with superior stability and customizable structures. In this review, we comprehensively summarize the advances of bioinspired MOFs for catalysis, discuss the design principle of various MOF-based catalysts, such as MOF-enzyme composites and MOFs embedded with active sites, and explore the utility of these catalysts in different reactions. The advantages of MOFs as enzyme mimetics are also highlighted, including confinement, templating effects, and functionality, in comparison with homogeneous supramolecular catalysts. A perspective is provided to discuss potential solutions addressing current challenges in MOF catalysis.

Research progress of the netrins and their receptors in cancer.

Netrins, a family of secreted and membrane-associated proteins, can regulate axonal guidance, morphogenesis, angiogenesis, cell migration, cell survival, and tumorigenesis. Four secreted netrins (netrin 1, 3, 4 and 5) and two glycosylphosphatidylinositols-anchored membrane proteins, netrin-G1 and G2, have been identified in mammals. Netrins and their receptors can serve as a biomarker and molecular therapeutic target for pathological differentiation, diagnosis and prognosis of malignant cancers. We review here the potential roles of the netrins family and their receptors in cancer.

Exceptionally High Perfluorooctanoic Acid Uptake in Water by a Zirconium-Based Metal-Organic Framework through Synergistic Chemical and Physical Adsorption.

Perfluorooctanoic acid (PFOA) is an environmental contaminant ubiquitous in water resources, which as a xenobiotic and carcinogenic agent, severely endangers human health. The development of techniques for its efficient removal is therefore highly sought after. Herein, we demonstrate an unprecedented zirconium-based MOF (PCN-999) possessing Zr6 and biformate-bridged (Zr6)2 clusters simultaneously, which exhibits an exceptional PFOA uptake of 1089 mg/g (2.63 mmol/g), representing a ca. 50% increase over the previous record for MOFs. Single-crystal X-ray diffraction studies and computational analysis revealed that the (Zr6)2 clusters offer additional open coordination sites for hosting PFOA. The coordinated PFOAs further enhance the interaction between coordinated and free PFOAs for physical adsorption, boosting the adsorption capacity to an unparalleled high standard. Our findings represent a major step forward in the fundamental understanding of the MOF-based PFOA removal mechanism, paving the way toward the rational design of next-generation adsorbents for per- and polyfluoroalkyl substance (PFAS) removal.

A Robust Pyrazolate Metal-Organic Framework for Efficient Catalysis of Dehydrogenative C-O Cross Coupling Reaction.

Construction of robust heterogeneous catalysts with atomic precision is a long-sought pursuit in the catalysis field due to its fundamental significance in taming chemical transformations. Herein, we present the synthesis of a single-crystalline pyrazolate metal-organic framework (MOF) named PCN-300, bearing a lamellar structure with two distinct Cu centers and one-dimensional (1D) open channels when stacked. PCN-300 exhibits exceptional stability in aqueous solutions across a broad pH range from 1 to 14. In contrast, its monomeric counterpart assembled through hydrogen bonding displays limited stability, emphasizing the role of Cu-pyrazolate coordination bonds in framework robustness. Remarkably, the synergy of the 1D open channels, excellent stability, and the active Cu-porphyrin sites endows PCN-300 with outstanding catalytic activity in the cross dehydrogenative coupling reaction to form the C-O bond without the "compulsory" ortho-position directing groups (yields up to 96%), outperforming homogeneous Cu-porphyrin catalysts. Moreover, PCN-300 exhibits superior recyclability and compatibility with various phenol substrates. Control experiments reveal the synergy between the Cu-porphyrin center and framework in PCN-300 and computations unveil the free radical pathway of the reaction. This study highlights the power of robust pyrazolate MOFs in directly activating C-H bonds and catalyzing challenging chemical transformations in an environmentally friendly manner.

Chiral Linker Installation in a Metal-Organic Framework for Enantioselective Luminescent Sensing.

Linker installation is a potent strategy for integrating specific properties and functionalities into metal-organic frameworks (MOFs). This method enhances the structural diversity of frameworks and enables the precise construction of robust structures, complementing the conventional postsynthetic modification approaches, by fully leveraging open metal sites and active organic linkers at targeting locations. Herein, we demonstrated an insertion of a d-camphorate linker into a flexible Zr-based MOF, PCN-700, through linker installation. The resultant homochiral MOF not only exhibits remarkable stability but also functions as a highly efficient luminescent material for enantioselective sensing. Competitive absorption and energy/electron transfer processes contribute to the sensing performance, while the difference in binding affinities dominates the enantioselectivity. This work presents a straightforward route to crafting stable homochiral MOFs for enantioselective sensing.

Treatment patterns, clinical outcomes and gene mutation characteristics of hepatitis B virus-associated mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an uncommon and incurable B-cell lymphoma subtype that has an aggressive course. Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas, and is characterized by distinct clinical and genetic features. Here, we showed that 9.5% of MCL Chinese patients were hepatitis B surface antigen positive (HBsAg+). Compared to HBsAg-negative (HBsAg-) patients, HBsAg+ MCL patients had a greater incidence of elevated lactate dehydrogenase (LDH), but no difference was observed in the other clinical characteristics, including sex, age, ECOG ps, Ann Arbor stage, MIPI, extranodal involvement and Ki-67. The HD-AraC (high-dose cytarabine) regimen was the main first-line induction regimen for younger HBsAg+ patients, and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were used for elderly patients. HBsAg seropositivity was associated with a significantly shorter PFS than HBsAg seronegativity when patients were treated with rituximab or CHOP-based regimens. Compared with CHOP, the HD-AraC regimen was associated with longer PFS in HBsAg+ patients. Treatment with a Bruton tyrosine kinase inhibitor (BTKi) alone can also cause HBV reactivation. Among the 74 patients who underwent targeted deep sequencing (TDS), the nonsynonymous mutation load of HBsAg+ MCL patients was greater than that of HBsAg- MCL patients. HDAC1, TRAF5, FGFR4, SMAD2, JAK3, SMC1A, ZAP70, BLM, CDK12, PLCG2, SMO, TP63, NF1, PTPR, EPHA2, RPTOR and FIP1L1 were significantly enriched in HBsAg+ MCL patients.

Repetitive transcranial magnetic stimulation rescues simulated space complex environment-induced emotional and social impairments by enhancing neuronal excitability in the medial prefrontal cortex.

Studies have shown that spaceflight affects the emotional and social performance of astronauts. Identifying the neural mechanisms underlying the emotional and social effects of spacefaring-specific environments is essential to specify targeted treatment and prevention interventions. Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve the neuronal excitability and is used to treat psychiatric disorders such as depression. To study the changes of excitatory neuron activity in medial prefrontal cortex (mPFC) in simulated space complex environment (SSCE), and to explore the role of rTMS in behavioral disorders caused by SSCE and the neural mechanism. We found that rTMS effectively ameliorated the emotional and social impairments of mice in SSCE, and acute rTMS could instantaneously enhance the excitability of mPFC neurons. During depression-like and social novelty behaviors, chronic rTMS enhanced the mPFC excitatory neuronal activity that was inhibited by SSCE. Above results suggested that rTMS can completely reverse the SSCE-induced mood and social impairment by enhancing the suppressed mPFC excitatory neuronal activity. It was further found that rTMS suppressed the SSCE-induced excessive dopamine D2 receptor expression, which may be the cellular mechanism by which rTMS potentiates the SSCE-evoked hypoactive mPFC excitatory neurons. Our current results raise the possibility of rTMS being applied as a novel neuromodulation for mental health protection in spaceflight.

Optimal ICSI timing on immature oocytes for low prognosis patients under the POSEIDON classification.

BACKGROUND: The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients. METHODS: Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4-6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained. RESULTS: Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94-14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24-14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23-8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4-6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively. CONCLUSIONS: Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4-6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes' cytoplasm from P-ICSI varied that from R-ICSI.

Optimal design of a gravitational wave telescope system for the suppression of stray light.

For gravitational wave detection, the telescope is required to have an ultra-low wavefront error and ultra-high signal-to-noise ratio, where the power of the stray light should be controlled on the order of less than 10-10. In this work, we propose an alternative stray light suppression method for the optical design of an off-axis telescope with four mirrors by carefully considering the optimal optical paths. The method includes three steps. First, in the period of the optical design, the stray light caused by the tertiary mirror and the quaternary mirror is suppressed by increasing the angle formed by the optical axes of the tertiary mirror and the quaternary mirror and reducing the radius of curvature of the quaternary mirror as much as possible to make sure the optical system provides a beam quality with a wavefront error less than λ/80. Next, the stray light could satisfy the requirement of the order of 10-10 when the level of roughness reaches 0.2 nm, and the pollution of mirrors is controlled at the level of CL100. Finally, traditional stray light suppression methods should also be applied to mechanics, including the use of the optical barrier, baffle tube, and black paint. It can be seen that the field stop can efficiently reduce stray light caused by the secondary mirror by more than 55% in the full field of view. The baffle tube mounted on the position of the exit pupil can reduce the overall stray light energy by 5%, and the difference between the ideal absorber (absorption coefficient is 100%) and the actual black paint (absorption coefficient is 90%) is 3.2%. These simulation results are confirmed by the Monte Carlo method for a stray light analysis. Based on the above results, one can conclude that the geometry structure of the optical design, the quality of mirrors, and the light barrier can greatly improve the stray light suppression ability of the optical system, which is vital when developing a gravitational wave telescope with ultra-low stray light energy.

Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma.

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.

Ultrasound-based radiomics-clinical nomogram for noninvasive prediction of residual cancer burden grading in breast cancer.

PURPOSE: To assess the predictive value of an ultrasound-based radiomics-clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. METHODS: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. RESULTS: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound-based radiomics-clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. CONCLUSIONS: Ultrasound-based radiomics-clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.

Uncovering the Anti-Angiogenic Mechanisms of Centella asiatica via Network Pharmacology and Experimental Validation.

BACKGROUND: Centella asiatica (CA) has been used to address cancer for centuries in traditional Chinese medicine (TCM). Previous studies demonstrated its anti-angiogenesis efficacy, but the underlying mechanism of its action remains to be further clarified. This study aims to investigate the underlying mechanisms of CA and its triterpenes in anti-angiogenesis for cancer therapeutics through network pharmacology and experimental validation. METHODS: Cytoscape was used to construct a network of compound-disease targets and protein-protein interactions (PPIs) from which core targets were identified. GO and KEGG analyses were performed using Metascape, and the AutoDock-Vina program was used to realize molecular docking for further verification. Then, VEGF165 was employed to establish an induced angiogenesis model. The anti-angiogenic effects of CA were evaluated through assays measuring cell proliferation, migration, and tubular structure formation. RESULTS: Twenty-five active ingredients in CA had potential targets for anti-angiogenesis including madecassoside, asiaticoside, madecassic acid, asiatic acid, and asiaticoside B. In total, 138 potential targets for CA were identified, with 19 core targets, including STAT3, SRC, MAPK1, and AKT1. A KEGG analysis showed that CA is implicated in cancer-related pathways, specifically PD-1 and AGE-RAGE. Molecular docking verified that the active components of CA have good binding energy with the first four important targets of angiogenesis. In experimental validation, the extracts and triterpenes of CA improved VEGF165-induced angiogenesis by reducing the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: Our results initially demonstrate the effective components and great anti-angiogenic activity of CA. Evidence of the satisfactory anti-angiogenic action of the extracts and triterpenes from CA was verified, suggesting CA's significant potential as a prospective agent for the therapy of cancer.

Treatment patterns and clinical outcomes of mantle cell lymphoma: A retrospective cohort study by CHOICE.

Regimens based on Bruton's tyrosine kinase inhibitors (BTKi) have been increasingly used to treat mantle cell lymphoma (MCL). A real-world multicenter study was conducted to characterize treatment patterns and outcomes in patients with newly diagnosed MCL by Chinese Hematologist and Oncologist Innovation Cooperation of the Excellent (CHOICE). The final analysis included 1261 patients. Immunochemotherapy was the most common first-line treatment, including R-CHOP in 34%, cytarabine-containing regimens in 21% and BR in 3% of the patients. Eleven percent (n = 145) of the patients received BTKi-based frontline therapy. Seventeen percent of the patients received maintenance rituximab. Autologous hematopoietic stem cell transplantation (AHCT) was conducted in 12% of the younger (<65 years) patients. In younger patients, propensity score matching analysis did not show significant difference in 2-year progression-free survival and 5-year overall survival rate in patients receiving standard high-dose immunochemotherapy followed by AHCT than induction therapy with BTKi-based regimens without subsequent AHCT (72% vs 70%, P = .476 and 91% vs 84%, P = .255). In older patients, BTKi combined with bendamustine plus rituximab (BR) was associated with the lowest POD24 rate (17%) compared with BR and other BTKi-containing regimens. In patients with resolved hepatitis B at the baseline, HBV reactivation rate was 2.3% vs 5.3% in those receiving anti-HBV prophylaxis vs not; BTKi treatment was not associated with higher risk of HBV reactivation. In conclusion, non-HD-AraC chemotherapy combined with BTKi may be a viable therapeutic strategy for younger patients. Anti-HBV prophylaxis should be implemented in patients with resolved hepatitis B.

Malignant phyllodes tumors of the breast: the malignancy grading and associations with prognosis.

PURPOSE: This study aimed to correlate clinicopathological parameters with survival outcomes in a cohort of patients diagnosed with malignant phyllodes tumors (MPTs). We also analyzed the malignancy grade of MPTs and investigated the prognostic significance of the malignancy grading system. METHODS: Clinicopathological parameters, malignancy grades, and clinical follow-up data of 188 women diagnosed with MPTs in a single-institution were analyzed. MPTs of the breast were grouped according to stromal atypia, stromal overgrowth, mitotic count, tumor differentiation, and necrosis. A Fleiss' kappa statistic was calculated to test the agreement between the pathologists for the grading of MPTs. Disease-free survival (DFS), distant metastasis-free survival (DMFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Cox regression was carried out to identify factors predictive of locoregional recurrence (LRR), distant metastasis (DM) and death. RESULTS: A total of 188 MPTs were classified according to the malignancy grading system: 88 (46.8%) as low grade, 77 (41%) as an intermediate grade, and 23 (12.2%) as high grade. Excellent agreement between pathologists for the grading of MPTs (Fleiss' kappa 0.807). In our study population, the occurrence of DM and death were associated with the malignancy grade of MPTs (P < 0.001). Based on the DFS curves, the presence of heterologous elements (P = 0.025) and younger age (P = 0.014) were independent prognostic indicators. Additionally, the malignancy grade retained independent prognostic significance for predicting DMFS and OS (P < 0.001 and P = 0.009). CONCLUSIONS: Higher malignancy grade, presence of heterologous elements, younger age, larger tumor size, and recent rapid tumor growth are poor prognostic factors for MPTs of the breast. The malignancy grading system may be generalized in the future.

Homologous recombination repair gene mutations in colorectal cancer favors treatment of immune checkpoint inhibitors.

Immune checkpoint inhibitor (ICI) therapy is insensitive for Colorectal cancer (CRC) patients with microsatellite stable (MSS). Genomic data of three CRC cohort, n = 35), and the Cancer Genome Atlas (TCGA CRC cohort, n = 377), were analyzed. A cohort treated with ICIs from Memorial Sloan Kettering Cancer Center (MSKCC CRC cohort, n = 110) and two cases from the local hospital were characterized the impact of the HRR mutation on prognosis of CRC. Homologous recombination repair (HRR) gene mutations were more common in CN and HL cohorts (27.85%; 48.57%) than in TCGA CRC cohort (15.92%), especially in the MSS populations, the frequencies of HRR mutation were higher in CN and HL cohort (27.45%, 51.72%) than in TCGA cohort (6.85%). HRR mutations were associated with high tumor mutational burden (TMB-H). Although HRR mutation uncorrelated with an improved overall survival in the MSKCC CRC cohort (p = 0.97), HRR mutated patients had a significantly improved OS compared to the HRR wildtype population particularly in MSS subgroups (p = 0.0407) under ICI treatment. It probably contributed by a higher neoantigen and increased CD4+ T cell infiltration which found in the TCGA MSS HRR mutated CRC cohort. The similar phenomenon on cases was observed that MSS metastatic CRC patient with HRR mutation seemed more sensitive to ICI after multi-line chemotherapy in clinical practice than HRR wildtype. This finding suggests the feasibility of HRR mutation as an immunotherapy response predictor in MSS CRC, which highlights a potential therapeutic approach for these patients.

Boosting Hydrostability and Carbon Dioxide Capture of Boroxine-Linked Covalent Organic Frameworks by One-Pot Oligoamine Modification.

Boron-based covalent organic frameworks (COFs) are susceptible to nucleophilic attack by water at the electron-deficient boron sites and even slightly humid air could destroy the integrity of their porous frameworks within hours. Such instability is a major limitation to the practical applications of boron-based COFs. Herein we report a significant enhancement of hydrostability of boroxine-linked COFs (COF-1 as representative) by modification with an oligoamine (tetraethylenepentamine, TEPA), which leads to survival of the modified COF in water and long-time stability under humid atmosphere. Meanwhile, the TEPA modification also results in a considerable increase in CO2 adsorption capacity up to 13 times and a dramatic improvement in CO2 /N2 selectivity in low pressure region, which make the modified COF suitable for capturing CO2 from flue gas. This work provides a facile, efficient, and scalable method to greatly improve hydrostability of boroxine-linked COFs and reshape them into high-performance CO2 adsorbents.

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs). METHODS: The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort. RESULTS: A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7-51.2] in the MTX cohort and 24.3 months (95% CI: 16.6-32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8-35.2) in the MTX cohort and 32 months (95% CI: 27.6-36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts. CONCLUSIONS: This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate - based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.