Outcomes of COVID-19 in patients with obinutuzumab compared with patients with rituximab: a retrospective cohort study.

BACKGROUND: Patients treated with anti-CD20 monoclonal antibodies could have a higher risk of adverse outcomes of coronavirus disease 2019 (COVID-19). The novel anti-CD20 monoclonal antibody obinutuzumab has shown greater B-cell depletion and superior in vitro efficacy than rituximab. We aimed to assess whether obinutuzumab would result in worse COVID-19 outcomes than rituximab. METHODS: We retrospectively reviewed 124 patients with B-cell lymphoma, 106 of whom received rituximab treatment and 18 of whom received obinutuzumab treatment. The adverse outcomes of COVID-19 were compared between patients in the two cohorts. RESULTS: The proportions of patients who were hospitalized (55.6% vs. 20.8%, p = 0.005), experienced prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (38.9% vs. 2.9%, p < 0.001), and developed severe COVID-19 (33.3% vs. 4.7%, p < 0.001) were higher in patients with obinutuzumab than in those with rituximab. Multivariate analyses showed that obinuzumab treatment was associated with higher incidences of prolonged SARS-CoV-2 infection (OR 27.05, 95% CI 3.75-195.22, p = 0.001) and severe COVID-19(OR 15.07, 95% CI 2.58-91.72, p = 0.003). CONCLUSIONS: Our study suggested that patients treated with obinutuzumab had a higher risk of prolonged SARS-CoV-2 infection and severe COVID-19 than those treated with rituximab.

Triple quenching effect of nanozyme catalyzed precipitation combined with enzyme-free amplification for photoelectrochemical biosensing of circulating tumor DNA.

In this work, a new photoelectrochemical (PEC) biosensor based on triple quenching effect of nanozyme catalyzed precipitation to PEC signal of MgIn2S4 was constructed for ultrasensitive detection of circulating tumor DNA (ctDNA). Enzyme-free amplification technology was used to convert target ctDNA into a large number of product chains (PC) to improve the detection sensitivity. Co3O4 nanozyme with excellent peroxidase (POD)-like activity was introduced to the surface of MgIn2S4 by PC. Co3O4 could oxidize chromogenic agent 3-Amino-9-ethylcarbazole (AEC) to produce red insoluble precipitation in the presence of H2O2, resulting in the PEC signal "off" of MgIn2S4 to achieve ultrasensitive detection of ctDNA. In particular, Co3O4 nanozyme showed three synergistic quenching effects on PEC signal of MgIn2S4, which contributed greatly to improving the detection sensitivity. Firstly, the light absorption range of Co3O4 could reach 1000 nm, and compete with MgIn2S4 for light absorption. Secondly, the produced red precipitation belonged to the insulating material and had large electrochemical impedance, which hindered the transmission of photogenerated carriers. Thirdly, the precipitation also prevented the electron donor ascorbic acid (AA) from transferring electrons to MgIn2S4. This biosensor provided a promising sensitive PEC detection technology for ctDNA, and further broadened the application of nanozymes in the field of PEC analysis.

"Two in one": A novel DNA cascade amplification strategy for trace detection of dual targets.

According to the characteristics of DNA programming, the cascaded nucleic acid amplification technology with larger output can overcome the problem of insufficient sensitivity of single nucleic acid amplification technology, and it combines the advantages of two or even multiple nucleic acid amplification technologies at the same time. In this work, a novel cascade signal amplification strategy with strand displacement amplification (SDA) and cascade hybridization chain reaction (HCR) was proposed for trace detection of hAAG and VEGF165. HAAG-induced SDA produced a large amount of S2 to open H2 on Polystyrene (PS) nanospheres, thereby triggering cascade HCR to form DNA dendritic nanostructures with rich fluorescence (FL) signal probes (565 nm). It could realize the amplification of FL signals for the detection of hAAG. Moreover, many doxorubicin (Dox) were loaded into the GC bases of DNA dendritic nanostructures, and its FL signal was effectively shielded. VEGF165 specifically bound to its aptamer to form G-quadruplex structures, which released Dox to produce a high FL signal (590 nm) for detection of VEGF165. This work developed a unique multifunctional DNA dendritic nanostructure fluorescence probe, and cleverly designed a new "On-off" switch strategy for sensitive trace detection of cancer markers.

A spatial-potential resolved bipolar electrode electrochemiluminescence biosensor based on polarity conversion for dual-mode detection of miRNA-122 and CEA.

In this work, a spatial-potential resolved bipolar electrode electrochemiluminescence (BPE-ECL) biosensor based on polarity conversion strategy and CuHCF electrocatalyst was constructed for dual-mode detection of miRNA-122 and carcinoembryonic antigen (CEA). ECL technology was firstly used to systematically study the polarity conversion of BPE. It was found that changing the polarity of the driving voltage would cause the polarity change of BPE, and led to the change of the luminescent position of Ru(bpy)32+. As a "proof-of-concept application", we developed a shielded dual-channel BPE-ECL biosensor for dual-mode detection of miRNA-122 and CEA. In order to further improve the detection sensitivity, a non-precious metal electrocatalyst CuHCF with outstanding electrocatalytic reduction activity of H2O2 was firstly introduced to the BPE-ECL biosensor for signal amplification, which could generate high faradaic current under the excitation of negative potential. Based on the charge neutrality principle of BPE, the enhancement of the faradaic current resulted in the ECL signal amplification of Ru(bpy)32+. The targets in the sensing grooves caused the introduction or fall off of CuHCF, which led to the ECL signal change of Ru(bpy)32+ in the signal grooves, and realized the dual-mode detection of miRNA-122 and CEA. This work provided a deeper understanding of the polarity change of BPE. Furthermore, the introduction of non-precious metal electrocatalyst had broadened the application range of BPE-ECL sensors.

Brain-Type Glycogen Phosphorylase (PYGB) in the Pathologies of Diseases: A Systematic Review.

Glycogen metabolism is a form of crucial metabolic reprogramming in cells. PYGB, the brain-type glycogen phosphorylase (GP), serves as the rate-limiting enzyme of glycogen catabolism. Evidence is mounting for the association of PYGB with diverse human diseases. This review covers the advancements in PYGB research across a range of diseases, including cancer, cardiovascular diseases, metabolic diseases, nervous system diseases, and other diseases, providing a succinct overview of how PYGB functions as a critical factor in both physiological and pathological processes. We present the latest progress in PYGB in the diagnosis and treatment of various diseases and discuss the current limitations and future prospects of this novel and promising target.

Pneumocystis jirovecii with high probability detected in bronchoalveolar lavage fluid of chemotherapy-related interstitial pneumonia in patients with lymphoma using metagenomic next-generation sequencing technology.

BACKGROUND: Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). METHODS: Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. RESULTS: Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. CONCLUSION: Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

Comprehensive analysis of mitophagy-related genes in NSCLC diagnosis and immune scenery: based on bulk and single-cell RNA sequencing data.

Lung cancer is the main cause of cancer-related deaths, and non-small cell lung cancer (NSCLC) is the most common type. Understanding the potential mechanisms, prognosis, and treatment aspects of NSCLC is essential. This study systematically analyzed the correlation between mitophagy and NSCLC. Six mitophagy-related feature genes (SRC, UBB, PINK1, FUNDC1, MAP1LC3B, and CSNK2A1) were selected through machine learning and used to construct a diagnostic model for NSCLC. These feature genes are closely associated with the occurrence and development of NSCLC. Additionally, NSCLC was divided into two subtypes using unsupervised consensus clustering, and their differences in clinical characteristics, immune infiltration, and immunotherapy were systematically analyzed. Furthermore, the interaction between mitophagy-related genes (MRGs) and immune cells was analyzed using single-cell sequencing data. The findings of this study will contribute to the development of potential diagnostic biomarkers for NSCLC and the advancement of personalized treatment strategies.

A bibliometric study and visualization analysis of ferroptosis-inducing cancer therapy.

Ferroptosis is a form of regulated cell death that was first formally proposed a decade ago. While its role in cancer cell death was initially understudied, it has recently gained considerable interest from researchers. In recent years, a growing number of studies have focused on the role of ferroptosis in cancer progression, with the goal of developing novel ferroptosis-inducing cancer therapies. This study aims to present the developmental trend and hotspots of research on ferroptosis-inducing cancer therapy using bibliometric analysis. A literature search was conducted using the Web of Science Core Collection on October 1st, 2022, to retrieve articles and reviews pertaining to ferroptosis and cancer published from 2012 to 2022. Microsoft Excel 2016, VOSviewer 1.6.18 and CiteSpace (version 6.1. R6) were utilized to conduct the bibliometric analysis of publication trends, authorship, and citation networks, with a focus on identifying countries, institutions, journals, and authors contributing to the field. These analyses were used to predict future trends in this area. A total of 2839 articles were identified and extracted for analysis. The number of publications has increased almost every year, with a sharp increase after 2018. China produced the most publications in this area, followed by the United States. Central South University was the institution that published the most papers. Frontiers in Oncology was the journal with the highest number of publications, while Cell had the greatest impact factor. Daolin Tang was the most productive author and Dixon SJ was the most influential author. Co-occurrence and burst analyses of keywords and references were conducted to identify the developmental trends and hotspots in ferroptosis-inducing cancer therapy research. Main research directions have shifted from investigating the mechanism of ferroptosis to developing novel ferroptosis-targeting cancer therapies. Emerging topicsfocus on the role of ferroptosis in solid tumor therapy. Based on our bibliometric analysis, we predict that research on ferroptosis in cancer therapy will continue to be a hot topic in the future, with a growing number of treatment modalities related to ferroptosis being developed. Our study provides valuable insights into the current state and future trends of research in this field, serving as a useful guide for researchers seeking to make important contributions in this area.

Single-cell transcriptome analysis reveals dynamic changes of the preclinical A549 cancer models, and the mechanism of dacomitinib.

The in vitro A549 cells, and A549 xenografts in nude mouse, were two commonly used models for anti-cancer drug discovery. However, the biological and molecular characteristics of these two classic models, and also the dynamic transcriptome changes after dacomitinib exposure remains elusive. We performed single-cell RNA sequencing to define the transcriptome profile at single-cell resolution, and processed tumor samples for bulk RNA and protein analysis to validate the differently expressed genes. Transcriptome profiling revealed that the in vitro A549 cells are heterogeneous. The minimal subpopulation of the in vitro A549 cells, which were characterized by the signature of response to unfolded protein, became the overriding subpopulation of the xenografts. The EGFR non-activating A549 cells were resistant to dacomitinib in vitro, while A549 xenografts were comparatively sensitive as EGFR-activating HCC827 xenografts. Dacomitinib inhibited MAPK signaling pathway, and increased the immune response in the A549 xenografts. A phagocytosis checkpoint stanniocalcin-1 (STC1) was significantly inhibited in dacomitinib-treated xenografts. So here our study gives the first insight of the heterogeneity of the two classic models, and the translational potential of dacomitinib being used into a broader patient population rather than EGFR common activating mutation.

Versatile photoelectrochemical biosensor based on AIS/ZnS QDs sensitized-WSe2 nanoflowers coupled with DNA nanostructure probe for"On-Off"assays of TNF-α and MTase.

Herein, a novel multifunctional photoelectrochemical (PEC) biosensor based on AgInS2 (AIS)/ZnS quantum dots (QDs) sensitized-WSe2 nanoflowers and DNA nanostructure signal probe was designed to achieve ultra-sensitive "On-Off" detection of human tumor necrosis factor α (TNF-α) and methylase Dam MTase (MTase). AIS/ZnS QDs as an excellent photosensitive material was found to match WSe2 in energy level for the first time, and the photocurrent signal after sensitization was 65 times that of WSe2 nanoflowers and 17.9 times that of AIS/ZnS QDs. Moreover, abundant AIS/ZnS QDs were loaded on the TiO2 nanoparticles with good conductivity by DNA to fabricate a multifunctional probe, which can not only amplify signal but also specifically recognize target. When target TNF-α was present, the AIS/ZnS QDs signal probe was attached to the WSe2 nanoflowers-modified electrode through binding to aptamer, and the amplified PEC signal was generated for "on" assay of TNF-α. Furthermore, Dam MTase as second target induced methylation of hairpin HDam, so it is cleaved by the endonuclease DpnI, resulting in the shedding of AIS/ZnS QDs signal probe for signal "off" detection of MTase. This work opened a new photosensitized probe and developed a promising PEC biosensor for dual-targets assay. By programming the DNA nanostructure, the biosensor can detect versatile targets in a simple and sensitive method, which has good practical application value in human serum.

Development and validation of a nomogram model for lung cancer based on radiomics artificial intelligence score and clinical blood test data.

Background: Artificial intelligence (AI) discrimination models using single radioactive variables in recognition algorithms of lung nodules cannot predict lung cancer accurately. Hence, we developed a clinical model that combines AI with blood test variables to predict lung cancer. Methods: Between 2018 and 2021, 584 individuals (358 patients with lung cancer and 226 individuals with lung nodules other than cancer as control) were enrolled prospectively. Machine learning algorithms including lasso regression and random forest (RF) were used to select variables from blood test data, Logistic regression analysis was used to reconfirm the features to build the nomogram model. The predictive performance was assessed by performing the receiver operating characteristic (ROC) curve analysis as well as calibration, clinical decision and impact curves. A cohort of 48 patients was used to independently validate the model. The subgroup application was analyzed by pathological diagnosis. Findings: A total of 584 patients were enrolled (358 lung cancers, 61.30%,226 patients for the control group) to establish the model. The integrated model identified eight potential factors including carcinoembryonic antigen (CEA), AI score, Pro-Gastrin Releasing Peptide (ProGRP), cytokeratin 19 fragment antigen21-1(CYFRA211), squamous cell carcinoma antigen(SCC), indirect bilirubin(IBIL), activated partial thromboplastin time(APTT) and age. The area under the curve (AUC) of the nomogram was 0.907 (95% CI, 0.881-0.929). The decision and clinical impact curves showed good predictive accuracy of the model. An AUC of 0.844 (95% CI, 0.710 - 0.932) was obtained for the external validation group. Conclusion: The nomogram model integrating AI and clinical data can accurately predict lung cancer, especially for the squamous cell carcinoma subtype.

Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion.

Septins as GTPases in the cytoskeleton, are linked to a broad spectrum of cellular functions, including cell migration and the progression of hepatocellular carcinoma (HCC). However, roles of SEPT11, the new member of septin, have been hardly understood in HCC. In the study, the clinical significance and biological function of SEPT11 in HCC was explored. SEPT11 was screened out by combining ATAC-seq with mRNA-seq. Role of SEPT11 in HCC was further investigated by using overexpression, shRNA and CRISPR/Cas9-mediated SEPT11-knockout cells or in vivo models. We found RNA-seq and ATAC-seq highlights LncRNA AY927503 (AY) induced SEPT11 transcription, resulting in Rho GTPase activation and cytoskeleton actin aggregation. The GTP-binding protein SEPT11 is thus considered, as a downstream factor of AY, highly expressed in various tumors, including HCC, and associated with poor prognosis of the patients. In vitro, SEPT11 overexpression promotes the migration and invasion of HCC cells, while SEPT11-knockout inhibits migration and invasion. In vivo, SEPT11-overexpressed HCC cells show high metastasis incidents but don't significantly affect proliferation. Meanwhile, we found SEPT11 targets RhoA, thereby regulating cytoskeleton rearrangement and abnormal cell adhesion through ROCK1/cofilin and FAK/paxillin signaling pathways, promoting invasion and migration of HCC. Further, we found SEPT11 facilitates the binding of GEF-H1 to RhoA, which enhances the activity of RhoA. Overall, our study confirmed function of SEPT11 in promoting metastasis in HCC, and preliminarily explored its related molecular mechanism. SEPT11 acts as an oncogene in HCC, also draws further interest regarding its clinical application as a potential therapeutic target.

Versatile FeMoOv nanozyme bipolar electrode electrochemiluminescence biosensing and imaging platform for detection of H2O2 and PSA.

In this work, a unique FeMoOv nanozyme-bipolar electrode (NM-BPE) electrochemiluminescence (ECL) biosensing and imaging platform was proposed for the first time to realize sensitive detection of target hydrogen peroxide (H2O2) and prostate specific antigen (PSA). Considering the advantage that the cathode and anode poles of the bipolar electrode (BPE) can be modified respectively, this work was carried out using anode equipped with ECL reagent bipyridine ruthenium (Ru(bpy)32+), and cathode equipped with the Fe-doped molybdenum oxide/Au nanoparticles (FeMoOv/AuNPs) with excellent peroxidase (POD) and catalase (CAT)-like activity. Because FeMoOv/AuNPs show efficient enzyme catalysis effect and can greatly promote the decomposition of H2O2, thus the electron transfer rate in the NM-BPE system would be much accelerated to enhance the ECL signal of Ru(bpy)32+. Based on this principle, this work not only realized sensitive detection of H2O2, but also ingeniously designed an sandwich immunosensor using FeMoOv/AuNPs as recognition probe to mediate the ECL response on the anode, achieving highly sensitive detection of PSA. Furthermore, a unique mobile phone ECL imaging system was developed for assay of PSA at different concentrations, which opened a new portable imaging sensing device for bioassays. This work was the first time to combine nanozymes with bipolar electrodes for ECL analysis and imaging, which not only broadened the applications of nanozymes, but also pioneered the new joint ECL research technique of bipolar electrode and ECL imaging in bioassays, showing great application prospect for multiple detection of proteins, nucleic acids and cancer cells.

Versatile fluorescence detection of T4 PNK and mRNA based on unique DNA nanomachine amplification.

The development of DNA nanomachines provides a new strategy for the detection of tumor markers. In this work, an intelligent three-dimensional (3D) DNA walking machine with polynucleotide kinase (PNK) activator was designed, which was coupled with unique nanomachine formed by DNA nanowire cascade amplification reaction for versatile fluorescence detection of T4 PNK activity and messenger RNA (mRNA). When PNK exists, the free DNA walker was formed by hydrolysis cleavage of exonuclease, then the fluorophore-labeled report probe on the Au nanoparticles (NPs) was sheared during cycling cleavage reaction, thus the fluorescence signal was recovered for detection of PNK. Moreover, the DNA nanowires were produced by rolling ring amplification, then target mRNA sequentially initiated interval hybridization of hairpin probes through DNA nanowire, thus realizing DNA cascade reaction (DCR) with high "on" signal of DNA nanomachine for mRNA assay. This developed novel fluorescence nanomachine reported a new assay method with promising application for versatile targets and showed great potential for molecular-target therapies, and clinic diagnostics.

Effect of comprehensive nursing intervention on perioperative anxiety and sleep quality in elderly patients with digestive tract malignancies.

OBJECTIVE: To analyze the effect of comprehensive nursing intervention on perioperative anxiety and sleep quality in elderly patients with digestive tract malignancies. METHODS: In this retrospective study, a total of 96 elderly patients with digestive tract malignancies treated in The First People's Hospital of Wenling from January 2020 to July 2021 were included into a comprehensive group (n=49, comprehensive nursing) and a conventional group (n=47, conventional nursing) according to different intervention methods. Anxiety was assessed using Self-rating Anxiety Scale (SAS) and Hamilton Anxiety Scale (HAMA), and sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). RESULTS: The scores of SAS and HAMA of the comprehensive group on day 1 before surgery and day 7 after surgery were lower than those of the conventional group (P<0.05). After intervention, PSQI score of the comprehensive group was lower than that of the conventional group (P<0.05). The comprehensive group had a higher percentage of rapid eye movement sleep, sleep efficiency, and subjective sleep quality scores, and had lower arousal index on the 1st night after surgery than the conventional group (P<0.05). The comprehensive group had a lower incidence of complications and mortality than the conventional group (P<0.05). Univariate analysis showed that the mortality of elderly patients with digestive tract malignancies was significantly higher in patients with age over 70 years old, negative emotions, low degree of tumor differentiation, tumor stage III-IV, history of surgery, no preoperative chemoradiotherapy and conventional nursing. Poorly differentiated tumor, stage III-IV, history of surgery, and conventional nursing were independent risk factors (P<0.05). CONCLUSION: Comprehensive nursing intervention could effectively improve the perioperative anxiety and sleep quality as well as reduce the incidence of complications in elderly patients with digestive tract malignancies. Attention should be paid to the degree of tumor differentiation, tumor stage, and surgical history in the perioperative period.

Circular RNA circ_0008365 regulates SOX9 by targeting miR-338-3p to inhibit IL-1ß-induced chondrocyte apoptosis and extracellular matrix degradation.

BACKGROUND: Osteoarthritis (OA) is a chronic disease that involves chondrocyte injury and dysfunction. CircRNAs participate in OA progression, but the roles of circRNAs in the occurrence of OA are unclear. In this study, we explore the role of circ_0008365 in OA. METHODS: CHON-001 cells were treated with interleukin-1ß (IL-1ß) to construct an in vitro OA cell model. The levels of circ_0008365, SRY-related high mobility group-box gene9 (SOX9) mRNA, and microRNA-338-3p (miR-338-3p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Western blot (WB) assay was used to measure protein levels. Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, and flow cytometry analysis were used to detect cell viability, proliferation, and apoptosis, respectively. Dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between miR-338-3p with circ_0008365 or SOX9. RESULTS: Circ_0008365 expression was reduced in OA tissues and IL-1ß-induced CHON-001 cells. Functionally, circ_0008365 inhibited viability, proliferation, and ECM degradation and promoted apoptosis of IL-1ß-induced CHON-001 cells. Mechanistically, circ_0008365 acted as a sponge of miR-338-3p to regulate SOX9 expression, thus exerting its functions in IL-1ß-induced CHON-001 cells. Moreover, exosomal circ_0008365 had great value in diagnosing OA. CONCLUSION: Circ_0008365 alleviates IL-1ß-induced CHON-001 cell damage through the miR-338-3p/SOX9 axis, which suggested that circ_0008365 might be a new therapeutic target for OA.

Laser-Induced Slippery Liquid-Infused Surfaces with Anticorrosion and Wear Resistance Properties on Aluminum Alloy Substrates.

Slippery liquid-infused surfaces (SLISs) are developed as a potential alternative to superhydrophobic surfaces (SHSs) to resolve the issues of poor durability in corrosion protection and wear resistance. In this work, we used a simple laser processing technology to prepare a SLIS on the aluminum alloy (7075) surface. The superhydrophobicities of the modified surface and the oil film formed by liquid injection make the corrosive medium difficult to directly contact the surface and thus have a significant effect on corrosion resistance. The water and oil repellent SLIS exhibits durable corrosion resistance and excellent tribological properties compared with the SHS. The anticorrosion and wear resistance performances provided by the composite film have been assessed by multiple methods including the electrochemical test, immersion test, and friction wear test. The results indicate that compared to the bare surface, laser-ablated surface (LAS), and fluoroalkyl silane-modified SHS, the SLIS composite coating has better corrosion resistance and wear resistance, which is of great significance to expand the potential applications of 7075 aluminum alloys. The work provides a research basis for expanding the practical application of SLISs in complex environments.

Study of the G Protein Nucleolar 2 Value in Liver Hepatocellular Carcinoma Treatment and Prognosis.

LIHC (liver hepatocellular carcinoma) mostly occurs in patients with chronic liver disease. It is primarily induced by a vicious cycle of liver injury, inflammation, and regeneration that usually last for decades. The G protein nucleolar 2 (GNL2), as a protein-encoding gene, is also known as NGP1, Nog2, Nug2, Ngp-1, and HUMAUANTIG. Few reports are shown towards the specific biological function of GNL2. Meanwhile, it is still unclear whether it is related to the pathogenesis of carcinoma up to date. Here, our study attempts to validate the role and function of GNL2 in LIHC via multiple databases and functional assays. After analysis of gene expression profile from The Cancer Genome Atlas (TCGA) database, GNL2 was largely heightened in LIHC, and its overexpression displayed a close relationship with different stages and poor prognosis of carcinoma. After enrichment analysis, the data revealed that the genes coexpressed with GNL2 probably participated in ribosome biosynthesis which was essential for unrestricted growth of carcinoma. Cell functional assays presented that GNL2 knockdown by siRNA in LIHC cells MHCC97-H and SMCC-7721 greatly reduced cell proliferation, migration, and invasion ability. All in all, these findings capitulated that GNL2 could be a promising treatment target and prognosis biomarker for LIHC.

Cereblon expression is a prognostic marker in newly diagnosed POEMS syndrome treated with lenalidomide plus dexamethasone.

POEMS syndrome is a rare plasma cell disorder. Lenalidomide has recently emerged as a therapeutic option for POEMS syndrome. Cereblon has been identified as the direct target of lenalidomide, and high cereblon expression is associated with better response and outcome to lenalidomide therapy in multiple myeloma patients. Here, we analyzed the predictive value of cereblon, IKZF1, and IKZF3 in CD138+ selected plasma cells from forty-one newly diagnosed POEMS syndrome patients treated with lenalidomide in combination with dexamethasone at both gene and protein levels. We found that patients with high cereblon expression tended to achieve better hematologic response compared to those with low expression (p = 0.024 for gene expression; p = 0.01 for protein expression). Multivariate Cox regression analysis revealed high cereblon mRNA expression as an independent prognostic marker for longer progression-free survival (hazard ratio 0.542; 95% CI 0.337-0.871; p = 0.011). In conclusion, our results emphasized the role of cereblon mRNA expression as a unique biomarker for predicting the clinical response and outcome of lenalidomide-based therapy in newly diagnosed POEMS syndrome patients.

Ganoderic acid A attenuates high-fat-diet-induced liver injury in rats by regulating the lipid oxidation and liver inflammation.

Ganoderic Acid A (GA) has many pharmacological effects such as anti-tumor, antibacterial, anti-inflammatory, and immunosuppressive effects. However, the protective effect of GA on liver injury has not been reported. This study aimed to investigate the action of GA on insufficient methionine and choline combined with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats. NAFLD model was established by insufficient methionine and choline combined with high fat feeding to rats. The levels of Acetyl-CoA carboxylase, fatty acid synthase, sterol regulatory element binding protein, liver X receptors, AMP-activated protein kinase, peroxisome proliferator-activated receptor α, PPARg coactivator 1α and NF-κB pathway in the liver were detected by western blot. The results of this study demonstrated that the expression of GA can not only significantly decrease the live weight and liver weight per body weight of HFD mice, but also restore the alanine aminotransferase, aspartate aminotransferase, total bilirubin levels, triglyceride and cholesterol in serum. In addition, the expression of GA increased the levels of high-density lipoprotein cholesterol in serum, ameliorated pathological changes and decreased NAS score of mice's liver. In conclusion, the treatment with GA could improve NAFLD in rats by regulating the levels of signaling events involved in free fatty acid production, lipid oxidation and liver inflammation.