USP18 promotes colon adenocarcinoma progression via targeting the ERK-MNK signaling pathway.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide and is one of the leading causes of cancer-related mortality. Ubiquitin-specific peptidase 18 (USP18) protein has been reported to exert different tumor-related effects in distinct tumor types. Here, we initially investigated the expression and signaling pathways of USP18 in colon adenocarcinoma (COAD). METHODS: A quantitative real-time PCR was conducted to evaluate the mRNA level of USP18 in cultured cells. Immunohistochemical staining was used to explore the protein expression of USP18 in clinical COAD samples. Specific knockdown was achieved by transient transfection of small interfering RNAs into SW480 and HT29 cells using Lipo3000. Cell conting kit-8 assay, transwell assay and matrigel-transwell assays were conducted to evaluate proliferation, migration and invasion capacities, respectively. Western blotting was performed to analyze downstream signaling pathways. A chi-squared test and univariate and multivariate analyses were used to evaluate the clinical data. Xenografts from mice model were assessed to validate the in vitro findings. RESULTS: Higher USP18 level was identified in COAD tissues and was positively correlated with advanced tumor stage. High USP18 protein expression indicated poorer prognosis of COAD patients. Silencing USP18 suppressed COAD cell proliferation and invasion via destabilizing extracellular signal-regulated kinase (ERK) protein and suppressing ERK downstream pathways. Simultaneously silencing interferon-stimulated gene 15 (ISG15) with USP18 can partially rescue the tumor cell viability, indicating its involvement in USP18 signaling. The oncogenic effects of USP18 were also confirmed in mice models. CONCLUSIONS: USP18 plays oncogenic effects in colon adenocarcinoma via ISG15-ERK pathways. High USP18 expression indicates poor clinical outcomes for colon adenocarcinoma patients.

Syntaxin5 is essential for survival by ensuring midgut epithelial homeostsis and regulating feeding in Locusta migratoria.

Syntaxin5 (Syx5) belongs to SNAREs family, which play important roles in fusion of vesicles to target membranes. Most of what we know about functions of Syx5 originates from studies in fungal or vertebrate cells, how Syx5 operates during the development of insects is poorly understood. In this study, we investigated the role of LmSyx5 in the gut development of the hemimetabolous insect Locusta migratoria. LmSyx5 was expressed in many tissues, with higher levels in the gut. Knockdown of LmSyx5 by RNA interference (RNAi) considerably suppressed feeding in both nymphs and adults. The dsLmSyx5-injected locusts lost body weight and finally died at a mortality of 100%. Furthermore, hematoxylin-eosin staining indicated that the midgut is deformed in dsLmSyx5-treated nymphs and the brush border in midgut epithelial cells is severely damaged, suggesting that LmSyx5 is involved in morphogenesis of the midgut. TEM further showed that the endoplasmic reticulum of midgut cells have a bloated appearance. Taken together, these results suggest that LmSyx5 is essential for midgut epithelial homeostsis that affects growth and development of L. migratoria. Thus, Syx5 is a promising RNAi target for controlling L. migratoria, and even other pests.

High-Entropy Configuration Strategy to Build High Performance Na-Ion Layered Oxide Cathodes Derived from Simple Techniques.

Layered transition metal oxides are commonly used as the cathode materials in sodium-ion batteries due to their low cost and easy manufacturing. However, the application is hindered by poor rate performance and complex phase transitions. To address these challenges, a new seven-component high-entropy layered oxide cathode material, O3-NaNi0.25Fe0.15Mn0.3Ti0.1Sn0.05Co0.05Li0.1O2 (HEO) has been developed. The entropy stabilization effect plays a crucial role in improving the performance of electrochemical systems and the stability of structures. The HEO exhibits a specific discharge capacity of 154.1 mA h g-1 at 0.1 C and 94.5 mA h g-1 at 7 C. In-situ and ex-situ XRD results demonstrate that the HEO effectively retards complex phase transitions. This work provides a high-entropy design for the storage materials with a high energy density. Meanwhile, it eliminates industry doubts about the performance of sodium ion layered oxide cathode materials.

MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A.

BACKGROUND: Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission. AIM: To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance. METHODS: To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis. RESULTS: We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298's direct target. CONCLUSION: Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC.

RNA interference-mediated silencing of coat protein II (COPII) genes affects the gut homeostasis and cuticle development in Locusta migratoria.

The coat protein II (COPII) complex consists of five primary soluble proteins, namely the small GTP-binding protein Sar1, the inner coat Sec23/Sec24 heterodimers, and the outer coat Sec13/Sec31 heterotetramers. COPII is essential for cellular protein and lipid trafficking through cargo sorting and vesicle formation at the endoplasmic reticulum. However, the roles of COPII assembly genes remain unknown in insects. In present study, we identified five COPII assembly genes (LmSar1, LmSec23, LmSec24, LmSec13 and LmSec31) in Locusta migratoria. RT-qPCR results revealed that these genes showed different expression patterns in multiple tissues and developmental days of fifth-instar nymphs. Injection of double-stranded RNA against each LmCOPII gene induced a high RNAi efficiency, and considerably suppressed feeding, and increased mortality to 100 %. Results from the micro-sectioning and hematoxylin-eosin staining of midguts showed that the brush border was severely damaged and the number of columnar cells was significantly reduced in dsLmCOPII-injected nymphs, as compared with the control. The dilated endoplasmic reticulum phenotype of columnar cells was observed by transmission electron microscopy. RT-qPCR results further indicated that silencing any of the five genes responsible for COPII complex assembly repressed the expression of genes involved in insulin/mTOR-associated nutritional pathway. Therefore, COPII assembly genes could be promising RNAi targets for insect pest management by disrupting gut and cuticle development.

Decoding protein binding landscape on circular RNAs with base-resolution transformer models.

Circular RNAs (circRNAs), a class of endogenous RNA with a covalent loop structure, can regulate gene expression by serving as sponges for microRNAs and RNA-binding proteins (RBPs). To date, most computational methods for predicting RBP binding sites on circRNAs focus on circRNA fragments instead of circRNAs. These methods detect whether a circRNA fragment contains binding sites, but cannot determine where are the binding sites and how many binding sites are on the circRNA transcript. We report a hybrid deep learning-based tool, CircSite, to predict RBP binding sites at single-nucleotide resolution and detect key contributed nucleotides on circRNA transcripts. CircSite takes advantage of convolutional neural networks (CNNs) and Transformer for learning local and global representations of circRNAs binding to RBPs, respectively. We construct 37 datasets of circRNAs interacting with proteins for benchmarking and the experimental results show that CircSite offers accurate predictions of RBP binding nucleotides and detects key subsequences aligning well with known binding motifs. CircSite is an easy-to-use online webserver for predicting RBP binding sites on circRNA transcripts and freely available at http://www.csbio.sjtu.edu.cn/bioinf/CircSite/.

Preferential and efficient extraction of lithium under the combined action of reduction of herb-medicine residue and leaching of oxalic acid.

With the increasing demand for lithium resources, the efficient recovery of lithium from spent lithium-ion batteries (LIBs) has become the focus of social attention. Herein, a combined process of reduction roasting of herb-medicine residue (HMR) and oxalic acid (OA) leaching is proposed to improve the recovery efficiency of lithium. Due to the large amount of reducing gas produced by the pyrolysis of herb-medicine residue, the layered structure of LiNixCoyMnzO2 cathode powder can be destroyed at 650℃ for 10 min, and the cathode powder is converted into Li2CO3, Ni, Co, MnO. Moreover, about 99.6 % of Li in the roasting residue can be selectively extracted by 0.5 mol L-1 oxalic acid for 20 min. Under the combined action of HMR and OA, the extraction efficiency and kinetics of lithium are improved simultaneously. This work achieves synergistic treatment of two types of waste from the perspective of waste management for waste. Meanwhile, it provides an alternative and innovative approach for the difficult problem of low efficiency of lithium recovery from spent LIBs.

Recovery of valuable metals from spent lithium-ion batteries via zinc powder reduction roasting and cysteine leaching.

With the annual increase in lithium-ion batteries (LIBs) disposal, valuable resources are being generated with worrying waste, so it is strategically important to recover the critical metals from them. Individual high temperature or leaching processes do not apparently achieve very satisfactory results. In the present work, the reduction with zinc powder was able to convert the lithium in LiNixCoyMnzO2 (NCM) to soluble LiOH, while the reduction and ammonia complexation environment generated by the decomposition of cysteine (Cys) achieved an efficient leaching of transition metals without additional additives. The leaching efficiency of Li can reach more than 92 %, while that of Ni/Co/Mn reaches more than 97 % through the regulation of the parameters of each process. In particular, an in-situ redox mechanism is proposed to explain the efficient leaching of transition metals, which further enriches the theory of spent LIBs recycling and provides a promising idea for various hydrometallurgical extraction systems.

Classification and Quantitative Characterization of Archean Metamorphic Buried Hill Reservoirs in the Bohai Sea.

Based on productivity test data and physical property test results from multiple wells, a classification scheme of Archean metamorphic buried hill reservoirs in the Bohai Sea is established by means of mathematical function fitting. By combining data from cores, casting thin sections, scanning electron microscopy, imaging logging, and high-pressure mercury injection and nitrogen adsorption tests, we clarified the reservoir composition and pore structure characteristics of different types of reservoirs are clarified. Furthermore, taking the BZ19-6 and 13-2 wells in the Archean metamorphic buried hills as an example, the development sites of different types of reservoirs are analyzed and the reservoir development model is established. The results show that the Archean metamorphic buried hill reservoirs in the Bohai Sea can be divided into three categories and six subcategories, including type I reservoirs with porosities greater than 8% or permeabilities greater than 1 × 10-3 µm2 and type II reservoirs with porosities of 5-8% or permeabilities in the range of 0.1-1 × 10-3 µm2. Reservoirs with porosities of 2-5% and permeabilities of 0.01-0.1 × 10-3 µm2 are type III reservoirs. Each type of reservoir can be further divided into a fracture-pore type and a fracture type according to the relative contribution of the porosity and permeability to the reservoir. From type I to type III, the dissolution degree and fracture development gradually weaken, the pore size gradually decreases, and the pore volume gradually decreases. The distribution of favorable reservoirs is comprehensively controlled by weathering and tectonic transformation. The presence of a weathered glutenite zone, weathered leaching zone, or weathered disintegration zone is favorable for the development of type I reservoirs in the weathering crust. In the inner part of the buried hill, the presence of a fracture zone with a thickness of more than 10 m or a dense fracture zone with a thickness of more than 40 m is favorable for the formation of type I reservoirs.

Inhibition of FNDC1 suppresses gastric cancer progression by interfering with Gßγ-VEGFR2 complex formation.

Gastric cancer (GC) is a prevalent digestive tract malignant tumor characterized by an insidious onset, ease of metastasis, rapid growth, and poor prognosis. Here, we report that fibronectin type III domain containing 1 (FNDC1) has high expression in GC and indicates poor outcomes in patients with GC. FNDC1 over-expression or knockdown promotes or inhibits tumorigenesis and metastasis, respectively. The expression of FNDC1 is upregulated by TWIST1, strengthening its interaction with Gßγ and VEGFR2. The formation of the trimers, TWIST1 plus Gßγ and VEGFR2, increases VEGFR2 phosphorylation and Gßγ trafficking, which activates RAS-MAPK and PI3K-AKT signaling, benefiting GC progression. In this study, we demonstrated that arsenite can efficiently suppress FNDC1 expression, attenuating the formation of the trimers and downstream pathways. Altogether, our results indicate that FNDC1 might be a promising target for clinical treatment and prognostic judgment, while FNDC1 inhibition by arsenite provides a new opportunity for overcoming this fatal disease.

Three alternative splicing variants of Loquacious play different roles in miRNA- and siRNA-mediated RNAi pathways in Locusta migratoria.

RNA interference (RNAi) is a specific post-transcriptional gene-silencing phenomenon, which plays an important role in the regulation of gene expression and the protection from transposable elements in eukaryotic organisms. In Drosophila melanogaster, RNAi can be induced by microRNA (miRNA), endogenous small interfering RNA (siRNA), or exogenous siRNA. However, the biogenesis of miRNA and siRNA in these RNAi pathways is aided by the double-stranded RNA binding proteins (dsRBPs) Loquacious (Loqs)-PB, Loqs-PD or R2D2. In this study, we identified three alternative splicing variants of Loqs, namely Loqs-PA, -PB, and -PC in the orthopteran Locusta migratoria. We performed in vitro and in vivo experiments to study the roles of the three Loqs variants in the miRNA- and siRNA-mediated RNAi pathways. Our results show that Loqs-PB assists the binding of pre-miRNA to Dicer-1 to lead to the cleavage of pre-miRNA to yield matured miRNA in the miRNA-mediated RNAi pathway. In contrast, different Loqs proteins participate in different siRNA-mediated RNAi pathways. In exogenous siRNA-mediated RNAi pathway, binding of Loqs-PA or LmLoqs-PB to exogenous dsRNA facilitates the cleavage of dsRNA by Dicer-2, whereas in endogenous siRNA-mediated RNAi pathway, binding of Loqs-PB or Loqs-PC to endogenous dsRNA facilitates the cleavage of dsRNA by Dicer-2. Our findings provide new insights into the functional importance of different Loqs proteins derived from alternative splicing variants of Loqs in achieving high RNAi efficiency in different RNAi pathways in insects.

lncRNA PITPNA-AS1 promotes cell proliferation and metastasis in hepatocellular carcinoma by upregulating PDGFD.

Hepatocellular carcinoma (HCC) ranks high in morbidity and mortality among notorious malignancies because of the lack of effective biomarkers and treatments. LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) plays an oncogenic role in HCC, yet the mechanistic basis remains unprobed. Here using Bioinformatics and PCR analyses, we validated that PITPNA-AS1 expression was significantly increased in HCC. The levels of PITPNA-AS1 in tumors were reversely correlated with the prognosis in HCC patients. Downregulation of PITPNA-AS1 inhibited malignant activities of HCC cells. Next, we elucidated that PITPNA-AS1 acts as a competing endogenous RNA (ceRNA) to sponge miR-363-5p, thereby regulating the expression of platelet-derived growth factor-D (PDGFD). Moreover, the suppression of HCC cell activities by PITPNA-AS1 downregulation can be removed by PDGFD overexpression or miR-363-5p inhibition. Collectively, our work reveals the involvement of the PITPNA-AS1/miR-363-5p/PDGFD regulatory axis in HCC progression.

Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study.

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologically confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1. Findings: Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade ≥3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported. Conclusion: In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167. Funding: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015).

Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice.

The early phase lipid accumulation is essential for liver regeneration. However, whether this acute lipid accumulation can serve as signals to direct liver regeneration rather than simply providing building blocks for cell proliferation remains unclear. Through in vivo CRISPR screening, we identify MIER1 (mesoderm induction early response 1) as a key epigenetic regulator that bridges the acute lipid accumulation and cell cycle gene expression during liver regeneration in male animals. Physiologically, liver acute lipid accumulation induces the phosphorylation of EIF2S1(eukaryotic translation initiation factor 2), which consequently attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and regeneration through chromatin remodeling. Importantly, the lipids-EIF2S1-MIER1 pathway is impaired in animals with chronic liver steatosis; whereas MIER1 depletion significantly improves regeneration in these animals. Taken together, our studies identify an epigenetic mechanism by which the early phase lipid redistribution from adipose tissue to liver during regeneration impacts hepatocyte proliferation, and suggest a potential strategy to boost liver regeneration.

Robustness optimization for rapid prototyping of functional artifacts based on visualized computing digital twins.

This study presents a robustness optimization method for rapid prototyping (RP) of functional artifacts based on visualized computing digital twins (VCDT). A generalized multiobjective robustness optimization model for RP of scheme design prototype was first built, where thermal, structural, and multidisciplinary knowledge could be integrated for visualization. To implement visualized computing, the membership function of fuzzy decision-making was optimized using a genetic algorithm. Transient thermodynamic, structural statics, and flow field analyses were conducted, especially for glass fiber composite materials, which have the characteristics of high strength, corrosion resistance, temperature resistance, dimensional stability, and electrical insulation. An electrothermal experiment was performed by measuring the temperature and changes in temperature during RP. Infrared thermographs were obtained using thermal field measurements to determine the temperature distribution. A numerical analysis of a lightweight ribbed ergonomic artifact is presented to illustrate the VCDT. Moreover, manufacturability was verified based on a thermal-solid coupled finite element analysis. The physical experiment and practice proved that the proposed VCDT provided a robust design paradigm for a layered RP between the steady balance of electrothermal regulation and manufacturing efficacy under hybrid uncertainties.

NADPH-cytochrome P450 reductase knockdown decreases the response to precocene I in the migratory locust Locusta migratoria.

Precocene I is a juvenile hormone antagonist that needs to be activated via oxidative biotransformation catalyzed by cytochrome P450 (CYP). NADPH-cytochrome P450 reductase (CPR) supplies CYP with electrons in the oxidation-reduction process; however, its functional role in the activation of precocene I remains unexplored. Here, the representative characteristics of CPRs were analyzed in the CPR gene of Locusta migratoria (LmCPR), the result of model docking indicated that the hydrogen bonds were formed between reduced nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and NADPH-, FAD-, FMN-domains of LmCPR, respectively. Treating the fourth-instar nymphs with precocene I decreased the juvenile hormone titers of nymphs to 0.55-fold of that in acetone-treated controls, and extended the interval time between fourth- and fifth-instar nymphs. 68.75% of the treated fourth-instar nymphs developed into precocious adults in the fifth-instar. LmCPR knockdown decreased the response to precocene I in the nymphs, the occurrence rate of precocious adults induced by precocene I treatment reduced by 23.11%. Therefore, LmCPR may be involved in the activation of precocene I in L. migratoria. In addition, we generated an active recombinant LmCPR protein using a prokaryotic expression system, its activity in reducing cytochrome c was 33.13 ± 11.50 nmol CytCred/min/µg protein. This study lays the foundation for further research on the role of LmCPR in precocene I activation.

DNA Methylation Data Analysis Using Msuite.

DNA methylation is a widespread epigenetic modification responsible for many biological regulation pathways. The development of various powerful biochemical assays, including conventional bisulfite treatment-based and emerging bisulfite-free techniques, has promised high-resolution DNA methylome profiling and significantly propelled the DNA methylation research field. However, the analysis of large-scale data generated from such assays is still complex and challenging. In this paper, we present a step-by-step protocol for using Msuite for whole-spectrum DNA methylation data analysis, from quality control, read alignment, to methylation call and data visualization. The Msuite package and a testing dataset are freely available at https://github.com/hellosunking/Msuite.

Recovery of valuable metals from spent lithium-ion batteries by complexation-assisted ammonia leaching from reductive roasting residue.

Recycling valuable metals in spent LIBs is not only in line with the purpose of resource recycling but also an important measure for environmental protection. In this article, a process using biomass reduction roasting followed by a unique complexation-assisted ammonia leaching is proposed. Using waste areca powder (WAP) as a biomass reducing agent, the roasted residue is leached in an aqueous solution for the carbonate. The leaching efficiencies of Ni, Co, and Mn reach over 99% under ammonia leaching conditions of 1.5 M ammonium citrate (AC), 3 M ethylenediamine (EDA). The kinetics of ammonia leaching indicates the activation energies of Ni, Co, and Mn are 51.8 kJ mol-1, 47.7 kJ mol-1, and 40.8 kJ mol-1, respectively, which shows the whole duration is controlled by chemical reactions. Most importantly, this study systematically explores the mechanism of ammonia leaching and provided a useful recommendation for selecting the right ammonium salt.

One-step selective separation and efficient recovery of valuable metals from mixed spent lithium batteries in the phosphoric acid system.

The recovery of valuable elements in spent lithium-ion batteries (LIBs) has attracted more and more attention. Efficient recovery of valuable elements from spent LIBs with lower consumption and shorter process is the target that people have been pursuing. In this study, the valuable metals (Ni, Co, Mn and Li) and FePO4 products are simultaneously recovered from mixed spent LiNixCoyMnzO2 and LiFePO4 in one step under the optimized condition of 0.88 M H3PO4, a mass ratio of LFP/NCM of 2:1, a L/S ratio of 33:1 and 80 ℃ for 120 min without additional auxiliary reagents. Over 60 % of acid consumption is reduced and the process of adjusting pH is avoidable. The leaching efficiencies of the valuable elements reach up to 99.1 % for Ni, 98.9 % for Co, 99.6 % for Li and 97.3 % for Mn. Almost all of Fe is precipitated as FePO4·2H2O. By means of the empirical model, the research on leaching kinetics demonstrates that the leaching reaction is internal diffusion-controlled with the apparent activation energy of valuable metals less than 30 kJ/mol. Furthermore, the redox reaction mechanism between spent LiBs has been explored. And the intrinsic driving force in the phosphoric acid system is found out. This finding may provide an innovative and selective recycling method for valuable elements from mixed spent LIBs with high economic benefit and fewer environmental footprints.

Clinical Characteristics and Prognostic Factors in Primary Breast Diffuse Large B-Cell Lymphoma.

Background: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on the clinical features and prognostic factors. Patients and Methods: A consecutive cohort of patients with PB-DLBCL was retrospectively analyzed in our hospital from February 1997 through July 2018. The primary endpoint is overall survival (OS) contributing to any cause. Results: A total of 76 patients were diagnosed with PB-DLBCL. The median age at diagnosis was 51 years (range: 25-80 years), with female prevalence (98.7%). Forty (52.6%) patients had right-sided breast involvement but no bilateral breast involvement at diagnosis. Overall, disease stages IE and IIE were seen in 55 (72.4%) and 21 (27.6%) patients, respectively. According to the stage-modified International Prognostic Index (IPI), 37 (48.7%) patients were classified in the very good risk group (IPI 0). Of the 72 patients available, the non-germinal center B-cell (non-GCB) subtype of DLBCL was observed in 66 (91.6%) patients. All patients received anthracycline-based chemotherapy, 56 (73.7%) with rituximab, 31 (40.8%) also with additional radiation therapy, and 14 (18.4%) patients received a prophylactic intrathecal injection. Seven (9.2%) patients had refractory disease. With a median follow-up of 6.8 years (range 0.4-25.0 years), 10 (13.2%) patients had a relapse in the central nervous system (CNS) site. The 5-year and 10-year OS of all the patients was 97.2% (95% CI: 99.3-89.5) and 84.8% (95% CI: 70.0-93.5), respectively. The median OS was not reached. The median progression-free survival (PFS) was 10.3 years for patients with PB-DLBCL. The 5-year PFS of all the patients was 76.3% (95% CI: 64.6-84.6). Univariate analysis revealed several prognostic factors, including stage-modified IPI, breast surgery, refractory disease, and CNS relapse. Multivariate analyses produced two independent prognostic factors for patients with PB-DLBCL, including stage-modified IPI score (2-3 versus 0) (hazard ratio: 19.114, 95% CI 1.841 to 198.451, p=0.013) and CNS relapse (hazard ratio: 5.522, 95% CI 1.059 to 28.788, p=0.043). Conclusion: In our cohort, PB-DLBCL clinical features are similar to prior literature reports. Stage-modified IPI score and CNS relapse were associated with overall survival.