Raising the Asymmetric Catalytic Efficiency of Chiral Covalent Organic Frameworks by Tuning the Pore Environment.

Chiral covalent organic frameworks (COFs) hold considerable promise in the realm of heterogeneous asymmetric catalysis. However, fine-tuning the pore environment to enhance both the activity and stereoselectivity of chiral COFs in such applications remains a formidable challenge. In this study, we have successfully designed and synthesized a series of clover-shaped, hydrazone-linked chiral COFs, each with a varying number of accessible chiral pyrrolidine catalytic sites. Remarkably, the catalytic efficiencies of these COFs in the asymmetric aldol reaction between cyclohexanone and 4-nitrobenzaldehyde correlate well with the number of accessible pyrrolidine sites within the frameworks. The COF featuring nearly one pyrrolidine moiety at each nodal point demonstrated excellent reaction yields and enantiomeric excess (ee) values, reaching up to 97 and 83%, respectively. The findings not only underscore the profound impact of a deliberately controlled chiral pore environment on the catalytic efficiencies of COFs but also offer a new perspective for the design and synthesis of advanced chiral COFs for efficient asymmetric catalysis.

Case Report: Radiation necrosis mimicking tumor progression in a patient with extranodal natural killer/T-cell lymphoma.

Radiation-induced cerebral necrosis, also known as radiation encephalopathy, is a debilitating condition that significantly impacts the quality of life for affected patients. Secondary central nervous system lymphoma (SCNSL) typically arises from highly aggressive mature B-cell lymphoma, but rarely from extranodal natural killer T-cell lymphoma (ENKTL). Treatment will be guided by differentiation between lymphoma progression from brain necrosis, and is particularly important for critically ill patients in an acute setting. However, differential diagnosis remains challenging because they share similar clinical manifestations and have no specific imaging features. We present the case of a 52-year-old man with ENKTL who suffered an emergency brain herniation secondary to massive radiation necrosis. The diagnosis established by brain biopsy ultimately led to appropriate treatment. The importance of the diagnostic biopsy is highlighted in this case for distinguishing between radiation necrosis and SCNSL.

Improved whale swarm algorithm for solving material emergency dispatching problem with changing road conditions.

To overcome the problem of easily falling into local extreme values of the whale swarm algorithm to solve the material emergency dispatching problem with changing road conditions, an improved whale swarm algorithm is proposed. First, an improved scan and Clarke-Wright algorithm is used to obtain the optimal vehicle path at the initial time. Then, the group movement strategy is designed to generate offspring individuals with an improved quality for refining the updating ability of individuals in the population. Finally, in order to maintain population diversity, a different weights strategy is used to expand individual search spaces, which can prevent individuals from prematurely gathering in a certain area. The experimental results show that the performance of the improved whale swarm algorithm is better than that of the ant colony system and the adaptive chaotic genetic algorithm, which can minimize the cost of material distribution and effectively eliminate the adverse effects caused by the change of road conditions.

Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients.

Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.

Generation of 978†nm dispersion-managed solitons from a polarization-maintaining Yb-doped figure-of-9 fiber laser.

Restricted by the narrow gain bandwidth of Yb3+ near 980 nm, it is challenging to generate dispersion-managed (DM) solitons at this wavelength. In this work, we demonstrate the generation of DM solitons at 978 nm in a polarization-maintaining (PM) figure-of-9 fiber laser. Highly coherent pulses with 14.4 nm spectral bandwidth and 175 fs pulse duration are experimentally obtained. To the best of our knowledge, this is the shortest ∼980 nm pulse ever reported in an Yb-doped mode-locked fiber laser. Numerical simulations are performed to reveal the DM solitons' temporal and spectral evolution inside the figure-of-9 cavity under the condition of a narrow gain bandwidth. This robust and cost-effective 978 nm femtosecond laser is a promising light source for applications such as underwater communication and biophotonics.

Generation of 1.3†µm femtosecond pulses by cascaded nonlinear optical gain modulation in phosphosilicate fiber.

Nonlinear optical gain modulation (NOGM) is a simple and effective approach to generate highly coherent ultrafast pulses with a flexible wavelength. In this work, we demonstrate 34 nJ, 170 fs pulse generation at 1319 nm through a piece of phosphorus-doped fiber by two-stage cascaded NOGM with a 1064 nm pulsed pump. Beyond the experiment, numerical results show that 668 nJ, 391 fs pulses at 1.3 µm can be produced with up to 67% conversion efficiency by increasing the pump pulse energy and optimizing the pump pulse duration. This would offer an efficient method to obtain high-energy sub-picosecond laser sources for applications such as multiphoton microscopy.

miR-433 Inhibits Glioblastoma Progression by Suppressing the PI3K/Akt Signaling Pathway Through Direct Targeting of ERBB4.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor where new biomarkers and drug targets are much needed in the oncology clinic. miR-433 was identified as a tumor-suppressing miRNA in several different types of human cancer. However, the integrative biology of miR-433 in GBM is still largely unknown. By analyzing the expression profiles of miR-433 in 198 patients with glioma at The Cancer Genome Atlas, we found that the miR-433 expression was decreased in glioma whereas the low expression of miR-433 was significantly associated with shorter overall survival. We then conducted in vitro studies and demonstrated that increased expression of miR-433 suppressed the proliferation, migration, and invasion of LN229 and T98G cells, two representative glioma cell lines. Further, using in vivo mouse model, we found that upregulation of miR-433 inhibited the tumor growth of glioma cells. To situate the integrative biology understanding of the action of miR-433 in glioma, we identified ERBB4 as a gene targeted directly by miR-433 in LN229 and T98G cells. Overexpressed ERBB4 rescued the phenotype caused by overexpression of miR-433. Finally, we showed that miR-433 suppressed the PI3K/Akt pathway in glioma cells. In conclusion, our study demonstrated that miR-433 could potentially act as a tumor suppressor for GBM and may serve as a potential therapeutic target for GBM. Further integrative biology and clinical translational research are warranted to evaluate miR-433 in GBM.

Derivation and validation of a novel score for early prediction of severe CRS after CAR-T therapy in haematological malignancy patients: A multi-centre study.

Chimeric antigen receptor T (CAR-T) cell therapy is highly effective in inducing complete remission in haematological malignancies. Severe cytokine release syndrome (CRS) is the most significant and life-threatening adverse effect of this therapy. This multi-centre study was conducted at six hospitals in China. The training cohort included 87 patients with multiple myeloma (MM), an external validation cohort of 59 patients with MM and another external validation cohort of 68 patients with acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL). The levels of 45 cytokines on days 1-2 after CAR-T cell infusion and clinical characteristics of patients were used to develop the nomogram. A nomogram was developed, including CX3CL1, GZMB, IL4, IL6 and PDGFAA. Based on the training cohort, the nomogram had a bias-corrected AUC of 0.876 (95% CI = 0.871-0.882) for predicting severe CRS. The AUC was stable in both external validation cohorts (MM, AUC = 0.907, 95% CI = 0.899-0.916; ALL/NHL, AUC = 0.908, 95% CI = 0.903-0.913). The calibration plots (apparent and bias-corrected) overlapped with the ideal line in all cohorts. We developed a nomogram that can predict which patients are likely to develop severe CRS before they become critically ill, improving our understanding of CRS biology, and may guide future cytokine-directed therapies.

Efficient single-frequency 972†nm Yb-doped fiber amplifier with core pumping and elevated temperature.

In this work, we present a monolithic single-frequency, single-mode and polarization maintaining Yb-doped fiber (YDF) amplifier delivering up to 6.9 W at 972 nm with a high efficiency of 53.6%. Core pumping at 915 nm and elevated temperature of 300 °C were applied to suppress the unwanted 977 nm and 1030 nm ASE in YDF, so as to improve the 972 nm laser efficiency. In addition, the amplifier was further used to generate a single-frequency 486 nm blue laser with 590 mW of output power by single-pass frequency doubling.

Secondary Raman and Brillouin mode suppression in two- and three-mirror-cavity diamond Raman lasers.

We report an investigation into secondary mode suppression in single longitudinal mode (SLM) 1240 nm diamond Raman lasers. For a three-mirror V-shape standing-wave cavity incorporating an intra-cavity LBO crystal to suppress secondary modes, we achieved stable SLM output with a maximum output power of 11.7 W and a slope efficiency 34.9%. We quantify the level of χ(2) coupling necessary to suppress secondary modes including those generated by stimulated Brillouin scattering (SBS). It is found that SBS-generated modes often coincide with higher-order spatial modes in the beam profile and can be suppressed using an intracavity aperture. Using numerical calculations, it is shown that the probability for such higher-order spatial modes is higher for an apertureless V-cavity than in two-mirror cavities due its contrasting longitudinal mode-structure.

Self-Assembly of Helical Nanofibrous Chiral Covalent Organic Frameworks.

Despite significant progress on the design and synthesis of covalent organic frameworks (COFs), precise control over microstructures of such materials remains challenging. Herein, two chiral COFs with well-defined one-handed double-helical nanofibrous morphologies were constructed via an unprecedented template-free method, capitalizing on the diastereoselective formation of aminal linkages. Detailed time-dependent experiments reveal the spontaneous transformation of initial rod-like aggregates into the double-helical microstructures. We have further demonstrated that the helical chirality and circular dichroism signal can be facilely inversed by simply adjusting the amount of acetic acid during synthesis. Moreover, by transferring chirality to achiral fluorescent molecular adsorbents, the helical COF nanostructures can effectively induce circularly polarized luminescence with the highest luminescent asymmetric factor (glum ) up to ≈0.01.

Long-term survival in a patient with primary refractory AML after salvage allogeneic hematopoietic transplantation and post-transplant localized irradiation and venetoclax maintenance: a case report.

For patients with primary refractory AML, allogeneic hematopoietic cell transplantation (allo-HCT) is considered the only curative approach. However, the therapeutic efficacy of salvage transplantation in the non-remission (NR) state remains controversial. We present a patient with primary refractory AML and concomitant central nervous system (CNS) leukemia, who received salvage allo-HCT, localized radiotherapy and venetoclax maintenance. Although he experienced systemic chronic graft-versus-host disease (cGVHD), he remained disease-free for 2 years. We propose that salvage transplantation is a feasible for primary refractory AML and discuss strategies to prevent relapse after allo-HCT, including maintenance therapy and donor lymphocyte infusion (DLI). Finally, we highlight the importance of radiotherapy, which can exert immunomodulatory effects to enhance immune responses against leukemia.

Case report: Successful treatment of a patient with relapsed/refractory primary central nervous system lymphoma with thiotepa-based induction, autologous stem cell transplantation and maintenance.

Despite significant improvements in prognosis, a subset of patients with primary central nervous system lymphoma (PCNSL) remains at high risk for relapse. The treatment of relapsed and refractory (R/R) PCNSL remains a major clinical challenge. Herein, we present a 24-year-old patient with PCNSL who relapsed 4 years after initial diagnosis and subsequently became refractory to high-dose methotrexate (HD-MTX), temozolomide, whole brain radiation therapy (WBRT), ibrutinib, and lenalidomide. She received thiotepa with anti-programmed cell death protein 1 (PD-1) antibody and achieved partial remission and then underwent autologous stem cell transplantation (ASCT) with thiotepa-based conditioning. Post-transplant maintenance with thiotepa and anti-PD-1 at 3-month intervals resulted in a durable complete response (CR) in this case of R/R PCNSL. Our report highlights the important role of thiotepa in the treatment of patients with R/R PCNSL.

Rituximab with high-dose methotrexate is effective and cost-effective in newly diagnosed primary central nervous system lymphoma.

Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3-4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.

Case report: Hashimoto's thyroiditis after CD19 chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor (CAR)-T cell therapy is a novel cell therapeutic approach that is increasingly being used to treat patients with relapsed refractory B-cell lymphoma. Despite the efficacy of CAR T cell therapy, it has various adverse effects that can affect any organ in the body. The application of immune checkpoint inhibitors such as programmed death 1 (PD-1), programmed death ligand 1 (PDL-1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies has previously been reported to be associated with immune-related adverse events such as thyroid dysfunction and thyroiditis. Reports of immune-related adverse reactions after CAR T therapy are currently extremely rare, with only one case of a cytokine storm (CRS) combined with severe arthritis in a patient with ALL after treatment. Here, we describe two cases of Hashimoto's thyroiditis secondary to CAR T therapy. Two patients with relapsed refractory diffuse large B-cell lymphoma developed elevated peroxidase and globulin antibodies secondary to CAR-T cell therapy and developed Hashimoto's thyroiditis. Complete remission was achieved in two patients at 1 and 3 months after CAR-T cell therapy. The inflammation of the thyroid tissue may be directly or indirectly related to CAR T cell therapy, and the mechanisms needs to be further investigated.

Numerical simulation of nonlinear optical gain modulation in a Raman fiber amplifier.

Nonlinear optical gain modulation (NOGM) in a Raman fiber amplifier is numerically simulated with the generalized nonlinear Schrödinger equation. In the NOGM setup, a single frequency continuous wave seed laser is gain modulated into femtosecond pulses by an ultrafast pump, which can induce strong stimulated Raman scattering in a piece of single mode optical fiber. Different parameters regarding seed, pump and nonlinear gain medium (Raman fiber) are investigated in detail to find the best condition for higher Raman conversion efficiency. Simulated results reveal that the walk-off between pump and Raman pulses due to dispersion is one of the most important factors affecting the NOGM pulse's performance. Only when the speed of walk-off matches with the one of Raman conversion process can the conversion efficiency be optimized. This work offers a guild-line for the design of a fiber-based NOGM laser, which is able to produce wavelength-agile, femtosecond laser pulses with µJ-level pulse energy under more than 85% efficiency.

A novel nonsense variant (c.1499C>G) in CRB1 caused Leber congenital amaurosis-8 in a Chinese family and a literature review.

BACKGROUND: Leber's congenital amaurosis (LCA) is a severe hereditary retinopathy disease that is characterized by early and severe reduction of vision, nystagmus, and sluggish or absent pupillary responses. To date, the pathogenesis of LCA remains unclear, and the majority of cases are caused by autosomal recessive inheritance. In this study, we explored the variant in the Crumbs homologue 1 (CRB1) gene in a Chinese family with LCA. METHODS: We conducted comprehensive ocular examinations and collected 5 ml of blood samples from members of a Chinese family with LCA. A pathogenic variant was identified by capturing (the panel in NGS) and Sanger sequencing validation. RESULTS: A nonsense variant (c.1499C>G) in the 6th exon of CRB1 gene in a Chinese family with LCA was identified, which predicted a change in the protein p. S500*, may lead to loss of gene function. We summarized the 76 variants reported thus far in CRB1 that caused LCA8. CONCLUSIONS: This study reported a novel variant c.1499C>G (p. S500*) of the CRB1 gene occurred in a Chinese family with LCA, thus expanding the spectrum of CRB1 variants causing LCA.

Porphyrin nanotubes based on a hydrogen-bonded organic framework.

Tubular structures offer a wide variety of applications; therefore, designing such materials with distinct dimensions is highly desirable yet challenging. In the current report, we have demonstrated the synthesis of a one-dimensional (1D) tubular assembly comprising porphyrin nanoring subunits. The porphyrin nanoring (PNR) 2 bearing ester groups was synthesized via Pt-mediated cyclization and then hydrolyzed to obtain PNR 3 with carboxylic groups. Under optimized conditions, porphyrin nanotubes (PNTs) were formed through hydrogen bonding between the carboxylic groups of 3. The morphology investigated by both SEM and TEM displayed well-defined arrays of nanotube bundles up to several micrometers long. Small crystals of PNTs were obtained by heating a solution of 3 in DMSO. High-resolution transmission electron microscopy (HR-TEM) accompanied by selected-area electron diffraction (SAED) exhibited a line of diffractions with d-spacing values of 6.17, 3.08, 2.07, and 1.57 Å. The miller indices of these diffractions could be assigned as 300, 600, 900, and 1200, respectively, suggesting that an ordered structure of 1D PNTs has been formed.

Deep reinforcement learning algorithm for solving material emergency dispatching problem.

In order to solve the problem that the scheduling scheme cannot be updated in real time due to the dynamic change of node demand in material emergency dispatching, this article proposes a dynamic attention model based on improved gated recurrent unit. The dynamic codec framework is used to track the change of node demand to update the node information. The improved gated recurrent unit is embedded between codecs to improve the representation ability of the model. By weighted combination of the node information of the previous time, the current time and the initial time, a more representative node embedding is obtained. The results show that compared with the elitism-based immigrants ant colony optimization algorithm, the solution quality of the proposed model was improved by 27.89, 27.94, 28.09 and 28.12% when the problem scale is 10, 20, 50 and 100, respectively, which can effectively deal with the instability caused by the change of node demand, so as to minimize the cost of material distribution.

Cascaded nonlinear optical gain modulation for coherent femtosecond pulse generation.

Nonlinear optical gain modulation (NOGM) is a method to generate high performance ultrafast pulses with wavelength versatility. Here we demonstrate coherent femtosecond Raman pulse generation through cascaded NOGM process experimentally. Two single-frequency seed lasers (1121 and 1178 nm) are gain-modulated by 117 nJ 1064 nm picosecond pulses in a Raman fiber amplifier. Second-order (1178 nm) Stokes pulses are generated, which have a pulse energy of 76 nJ (corresponding to an optical conversion efficiency of 65%) with a pulse duration of 621 fs (after compression). Dynamic evolution of both pump and cascaded Stokes pulses within the Raman amplifier are investigated by numerical simulations. The influences of pump pulse duration and energy are studied in detail numerically. Moreover, the simulations reveal that NOGM pulses with higher energy and shorter pulse duration could be obtained by limiting the impact of walk-off effect between pump and Raman pulses. This approach can offer a high energy and wavelength-agile ultrafast source for various applications such as optical metrology and biomedical imagining.