Research progress and application strategies of sugar transport mechanisms in rice.

In plants, carbohydrates are central products of photosynthesis. Rice is a staple that contributes to the daily calorie intake for over half of the world's population. Hence, the primary objective of rice cultivation is to maximize carbohydrate production. The "source-sink" theory is proposed as a valuable principle for guiding crop breeding. However, the "flow" research lag, especially in sugar transport, has hindered high-yield rice breeding progress. This review concentrates on the genetic and molecular foundations of sugar transport and its regulation, enhancing the fundamental understanding of sugar transport processes in plants. We illustrate that the apoplastic pathway is predominant over the symplastic pathway during phloem loading in rice. Sugar transport proteins, such as SUTs and SWEETs, are essential carriers for sugar transportation in the apoplastic pathway. Additionally, we have summarized a regulatory pathway for sugar transport genes in rice, highlighting the roles of transcription factors (OsDOF11, OsNF-YB1, OsNF-YC12, OsbZIP72, Nhd1), OsRRM (RNA Recognition Motif containing protein), and GFD1 (Grain Filling Duration 1). Recognizing that the research shortfall in this area stems from a lack of advanced research methods, we discuss cutting-edge analytical techniques such as Mass Spectrometry Imaging and single-cell RNA sequencing, which could provide profound insights into the dynamics of sugar distribution and the associated regulatory mechanisms. In summary, this comprehensive review serves as a valuable guide, directing researchers toward a deep understanding and future study of the intricate mechanisms governing sugar transport.

Harringtonine metabolites: 5'-de-O-methylharringtonine and cephalotaxine, targeting spike protein and TMPRSS2 to double block membrane fusion of SARS-CoV-2 and its variants.

Membrane fusion is the main pathway for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to invade host cells. Harringtonine (HT), derived from cephalotaxus fortunei Hook. f., has been recognized as an effective antagonist of SARS-CoV-2. It can directly block the active binding of spike (S) protein to host angiotensin converting enzyme 2 (ACE2), as well as hinder the enzymolysis of transmembrane serine proteases 2 (TMPRSS2). This study examined the potential of HT metabolites, 5'-de-O-methylharringtonine and cephalotaxine, as the membrane fusion inhibitors for SARS-CoV-2. 5'-De-O-methylharringtonine was synthesized and subsequently characterized by high resolution mass spectrometry and nuclear magnetic resonance to be structurally consistent, with a purity of 92.677% determined by reverse phase high performance liquid chromatography. Both 5'-de-O-methylharringtonine and cephalotaxine can specifically bind to SARS-CoV-2 S protein and TMPRSS2 using cell membrane chromatography. They can form hydrogen bonds with key sites that correlated highly with the enhanced binding affinity of SARS-CoV-2 and its variants to ACE2 or nafamostat to TMPRSS2. Moreover, 5'-de-O-methylharringtonine and cephalotaxine can inhibit pseudotyped virus entry and membrane fusion in a dose-dependent manner, with enhanced effectiveness upon elevated expression of TMPRSS2. Importantly, they displayed low cytotoxic effects on human normal cell lines. Our study suggested that 5'-de-O-methylharringtonine and cephalotaxine were of low toxicity and safety for humans as potential antagonists of SARS-CoV-2 and its variants, which deserve further validation in a biosafety level 3 facility.

ALK-positive large B-cell lymphoma: a clinicopathological and molecular characteristics analysis of seven cases.

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare and highly aggressive lymphoma with characteristic ALK rearrangements. Various fusion genes involving ALK have been demonstrated, but the influence of the ALK fusion partners on ALK protein expression and the genetic characteristics of ALK+ LBCL remain relatively unknown. In this study, we conducted an extensive clinicopathological and molecular analysis on seven cases of ALK+ LBCL to explore the correlation between ALK fusion genes and ALK protein expression, thereby enriching the genetic characteristics of this tumour. We integrated the findings from clinical, histopathological/immunophenotypic, and molecular studies, including three samples subjected to next-generation sequencing, and six cases underwent RNA-based ALK fusion gene detection. We identified five distinct types of ALK fusion genes, including CLTC, NPM1, PABPC1, SEC31A, and TFG. Notably, only the NPM1::ALK fusion showed nuclear and cytoplasmic ALK staining, and the remaining four fusion genes resulted in cytoplasmic ALK staining. Our analysis revealed that the CLTC::ALK fusion resulted in a unique cytoplasmic perinuclear Golgi zone focal granular heterogeneous staining pattern of ALK. Additionally, we identified six potentially clinically significant gene mutations, including TET2, CHD2, DTX1, KMT2D, LRP1B, and XPO1. Furthermore, in all cases, the absence of 5-hydroxymethylcytosine (5hmC) was observed. We present seven cases of ALK+ LBCL, discussing the correlation between fusion genes and ALK protein expression, and enhancing our understanding of the genetic attributes of this tumour. This study also shows the loss of 5hmC in nearly all seven ALK+ LBCL cases, independently of TET2 mutations.

Clinicopathological and Molecular Characteristics of Rare EBV-associated Diffuse Large B-cell Lymphoma With IRF4 Rearrangement.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare form of aggressive B-cell lymphoma with limited molecular information reported regarding interferon regulatory factor 4 (IRF4) status. Here, we presented 3 EBV-positive DLBCL cases with IRF4 rearrangement (EBV+DLBCL-IRF4-R) verified by fluorescence in situ hybridization (FISH). Three patients, including 1 male and 2 females (median age: 64 y; range: 45 to 68 y), had normal immune function. During a median follow-up of 12 months (range: 0 to 24 mo), 2 patients succumbed to the disease, and 1 patient achieved complete response. Three tumors were present in the mediastinum, stomach, and thalamus, respectively. All three tumors exhibited DLBCL morphology and were identified as the non-germinal center B-cell subtype, with EBV-encoded small RNA positivity ranging from 70% to 80%. RNA sequencing was able to identify RHOH and IGH as fusion partners of IRF4 in two cases. No MYC and BCL2 rearrangements were detected in 3 cases by FISH and RNA sequencing. Next-generation sequencing revealed a low mutation burden, and only IRF4 was recurrently mutated in two EBV+DLBCL-IRF4-R cases. Using the LymphGen 2.0 classifier, 1 case was classified as the MCD (including MYD88L265P and CD79B mutations) subtype. We report rare EBV+DLBCL-IRF4-R that may enhance our understanding of the diverse spectrum of large B-cell lymphoma.

Pseudolaric Acid B Inhibits FLT4-induced Proliferation and Migration in Non-small Cell Lung Cancer.

OBJECTIVES: Non-Small Cell Lung Cancer (NSCLC) has attracted much attention on account of the high incidence and mortality of cancers. Vascular Endothelial Growth Factor Receptor 3 (VEGFR3/FLT4), which is a highly expressed receptor in NSCLC, greatly regulates cancer proliferation and migration. Pseudolaric Acid B (PAB) is a diterpenoid acid with antitumor activity isolated from Pseudolarix kaempferi. This study aimed to explore the inhibitory effect of PAB targeting FLT4 in NSCLC. METHODS: Cell membrane chromatography was used to evaluate the affinity of PAB binding on FLT4. NCIH1299 cells were used in this study, and an MTT assay was performed to determine the anti-proliferation effect of PAB. Cell cycle analysis was conducted to study the cycle arrest of PAB. Wound healing and Transwell assays assessed the rate of cell migration. Western blot analysis evaluated the expression of related proteins. RESULTS: PAB showed strong affinity to FLT4 with a KD value of 3.01 × 10- 6 M. Targeting FLT4 by PAB inactivated downstream P38MAPK and PI3K/AKT pathways, which inhibited the proliferation of NCI-H1299 cells. Meanwhile, PAB promoted G2/M phase arrest by influencing CyclinB1 and CDK1 complex formation to inhibit NCI-H1299 cell growth, but the effect was attenuated by knocking down the FLT4. Besides, PAB regulated MMP9 secretion through the Wnt/ß-catenin signaling pathway to inhibit NCI-H1299 cell migration. However, the ability of PAB to inhibit migration was significantly weakened by FLT4 knockdown in NCI-H1299 cells. CONCLUSION: PAB can inhibit the proliferation and migration of NSCLC cells through targeting FLT4 and is expected to be a promising FLT4 inhibitor for NSCLC treatment.

Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

SiO 2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model.

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2-induced cardiac injury using a mouse model. Methods: Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed. Results: SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2-induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion: Iron overload-induced ferroptosis contributes to SiO 2-induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway.

Co-immobilization of crosslinked enzyme aggregates on lysozyme functionalized magnetic nanoparticles for enhancing stability and activity.

Surface chemistry of carriers plays a key role in enzyme loading capacity, structure rigidity, and thus catalyze activity of immobilized enzymes. In this work, the two model enzymes of horseradish peroxidase (HRP) and glucose oxidase (GOx) are co-immobilized on the lysozyme functionalized magnetic core-shell nanocomposites (LYZ@MCSNCs) to enhance their stability and activity. Briefly, the HRP and GOx aggregates are firstly formed under the crosslinker of trimesic acid, in which the loading amount and the rigidity of the enzyme can be further increased. Additionally, LYZ easily forms a robust anti-biofouling nanofilm on the surface of SiO2@Fe3O4 magnetic nanoparticles with abundant functional groups, which facilitate chemical crosslinking of HRP and GOx aggregates with minimized inactivation. The immobilized enzyme of HRP-GOx@LYZ@MCSNCs exhibited excellent recovery activity (95.6 %) higher than that of the free enzyme (HRP&GOx). Specifically, 85 % of relative activity was retained after seven cycles, while 73.5 % of initial activity was also remained after storage for 33 days at 4 °C. The thermal stability and pH adaptability of HRP-GOx@LYZ@MCSNCs were better than those of free enzyme of HRP&GOx. This study provides a mild and ecofriendly strategy for multienzyme co-immobilization based on LYZ functionalized magnetic nanoparticles using HRP and GOx as model enzymes.

In vitro pharmacokinetic behavior in lung of harringtonine, an antagonist of SARS-CoV-2 associated proteins: New insights of inhalation therapy for COVID-19.

BACKGROUND: Recent studies have shown that harringtonine (HT) could specifically bind with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and host cell transmembrane serine protease 2 (TMPRSS2) to block membrane fusion, which is an effective antagonist for SARS-CoV-2. PURPOSE: Our study focused on in-depth exploration of in vitro pharmacokinetic characteristics of HT in lung. METHODS: HPLC-fluorescence detection method was used to detect changes of HT content. Incubation systems of lung microsomes for phase I metabolism and UGT incubation systems for phase II metabolism were performed to elucidate metabolites and metabolic mechanisms of HT, and then the metabolic enzyme phenotypes for HT were clarified by chemical inhibition method and recombinant enzyme method. Through metabolomics, we comprehensively evaluated the physiological dynamic changes in SD rat and human lung microsomes, and revealed the relationship between metabolomics and pharmacological activity of HT. RESULTS: HPLC-fluorescence detection method showed strong specificity, high accuracy, and good stability for rapid quantification of HT. We confirmed that HT mainly underwent phase I metabolism, and the metabolites of HT in different species were all identified as 4'-demethyl HT, with metabolic pathway being hydrolysis reaction. CYP1A2 and CYP2E1 participated in HT metabolism, but as HT metabolism was not NADPH dependent, the esterase HCES1 in lung also played a role. The main KEGG pathways in SD rat and human lung microsomes were cortisol synthesis and secretion, steroid hormone biosynthesis and linoleic acid metabolism, respectively. The downregulated key biomarkers of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME suggested that HT could prevent immunosuppression and interfere with infection and replication of SARS-CoV-2. CONCLUSION: HT was mainly metabolized into 4'-demethyl HT through phase I reactions, which was mediated by CYP1A2, CYP2E1, and HCES1. The downregulation of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME were key ways of HT against SARS-CoV-2. Our study was of great significance for development and clinical application of HT in the treatment of COVID-19.

Artificial intelligence-based assessment of PD-L1 expression in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is an aggressive blood cancer known for its rapid progression and high incidence. The growing use of immunohistochemistry (IHC) has significantly contributed to the detailed cell characterization, thereby playing a crucial role in guiding treatment strategies for DLBCL. In this study, we developed an AI-based image analysis approach for assessing PD-L1 expression in DLBCL patients. PD-L1 expression represents as a major biomarker for screening patients who can benefit from targeted immunotherapy interventions. In particular, we performed large-scale cell annotations in IHC slides, encompassing over 5101 tissue regions and 146,439 live cells. Extensive experiments in primary and validation cohorts demonstrated the defined quantitative rule helped overcome the difficulty of identifying specific cell types. In assessing data obtained from fine needle biopsies, experiments revealed that there was a higher level of agreement in the quantitative results between Artificial Intelligence (AI) algorithms and pathologists, as well as among pathologists themselves, in comparison to the data obtained from surgical specimens. We highlight that the AI-enabled analytics enhance the objectivity and interpretability of PD-L1 quantification to improve the targeted immunotherapy development in DLBCL patients.

Bifunctional MNPs@UIO-66-Arg core-shell-satellite nanocomposites for enrichment of phosphopeptides.

A facile and mild method based on self-assembled lysozyme (LYZ) to fabricate bifunctional MNPs@UIO-66-Arg core-shell-satellite nanocomposites (CSSNCs) is reported for the high-efficiency enrichment of phosphopeptides. Under physiological conditions, LYZ rapidly self-assembled into a robust coating on Fe3O4@SiO2 magnetic nanoparticles (MNPs) with abundant surface functional groups, which effectively mediate heterogeneous nucleation and growth of UIO-66 nanocrystals. Well-defined MNPs@UIO-66 CSSNCs with stacked pores, showing high specific surface area (333.65 m2 g- 1) and low mass transfer resistance, were successfully fabricated by fine-tuning of the reaction conditions including reaction time and acetic acid content. Furthermore, the UIO-66 shells were further modified with arginine to obtain bifunctional MNPs@UIO-66-Arg CSSNCs. Thanks to the unique morphology and synergistic effect of Zr-O clusters and guanidine groups, the bifunctional MNPs@UIO-66-Arg CSSNCs exhibited outstanding enrichment performance for phosphopeptides, delivering a low limit of detection (0.1 fmol), high selectivity (ß-casein/BSA, mass ratio 1:2000), and good capture capacity (120 mg g- 1). The mechanism for phosphopeptides capture may attribute to the hydrogen bonds, electrostatic interactions, and Zr-O-P bonds between phosphate groups in peptides and guanidyl/Zr-O clusters on bifunctional MNPs@UIO-66-Arg CSSNCs. In addition, the small stacking pores on the core-shell-satellite architecture may selectively capture phosphopeptides with low molecular weight, eliminating interference of other large molecular proteins in complex biological samples.

Dauricine Inhibits Non-small Cell Lung Cancer Development by Regulating PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2 Pathways in a FLT4-dependent Manner.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is still a solid tumor with high malignancy and poor prognosis. Vascular endothelial growth factor receptor 3 (FLT4, VEGFR3) is overexpressed in NSCLC cells, making it a potential target for NSCLC treatment. In this study, we aimed to explore the anti-cancer effects of dauricine on NSCLC cells and its mechanism targeting FLT4. METHODS: We found that dauricine inhibited the growth of NCI-H1299 cells by blocking the cycle in the G2/M phase through flow cytometry analysis. In addition, dauricine also inhibited the migration of NCI-H1299 cells by wound healing assay and transwell migration assay. More importantly, our empirical analysis found the anti-cancer effect of dauricine on NCI-H1299 cells and the protein level of FLT4 had a distinctly positive correlation, and this effect was weakened after FLT4 knockdown. RESULTS: It is suggested that dauricine suppressed the growth and migration of NCI-H1299 cells by targeting FLT4. Furthermore, dauricine inhibited FLT4 downstream pathways, such as PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2, thereby regulating cell migration-related molecule MMP3 and cell cycle-related molecules (CDK1, pCDK1-T161, and cyclin B1). CONCLUSION: Dauricine may be a promising FLT4 inhibitor for the treatment of NSCLC.

Facile fabrication of Ti4+-immobilized magnetic nanoparticles by phase-transitioned lysozyme nanofilms for enrichment of phosphopeptides.

In this study, titanium (IV)-immobilized magnetic nanoparticles (Ti4+-PTL-MNPs) were firstly synthesized via a one-step aqueous self-assembly of lysozyme nanofilms for efficient phosphopeptide enrichment. Under physiological conditions, lysozymes readily self-organized into phase-transitioned lysozyme (PTL) nanofilms on Fe3O4@SiO2 and Fe3O4@C MNP surfaces with abundant functional groups, including -NH2, -COOH, -OH, and -SH, which can be used as multiple linkers to efficiently chelate Ti4+. The obtained Ti4+-PTL-MNPs possessed high sensitivity of 0.01 fmol µL-1 and remarkable selectivity even at a mass ratio of ß-casein to BSA as low as 1:400 for phosphopeptide enrichment. Furthermore, the synthesized Ti4+-PTL-MNPs can also selectively identify low-abundance phosphopeptides from extremely complicated human serum samples and their rapid separation, good reproducibility, and excellent recovery were also proven. This one-step self-assembly of PTL nanofilms facilitated the facile and efficient surface functionalization of various nanoparticles for proteomes/peptidomes.

EBV-Associated Smooth Muscle Tumors With Autoimmune Hemolytic Anemia and Hepatitis B Infection: Report of a Previously Undescribed Neoplasm With Review.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors.

Initial Upper Palaeolithic material culture by 45,000 years ago at Shiyu in northern China.

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka.

HPLC-fluorescence detection for stability of harringtonine, and identification of degradation products by UPLC-Q-TOF-MS.

Harringtonine (HT) is an anticancer alkaloid early extracted and isolated from cephalotaxus fortunei Hook. f., also has various pharmacological activities such as antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, herbicidal and insecticidal. However, the factors affecting the stability of HT, the main degradation sites and mechanisms involved in its disposal process in vivo have not yet been elucidated. This study utilized HPLC-fluorescence detection method to establish a simple quantitative detection method for HT with good accuracy, precision, and high sensitivity. Temperature and pH were the main factors affecting the stability of HT, which underwent significant degradation in high temperature and alkaline environments because of the occurrence of hydrolysis reactions. In isolated biological homogenates of SD rats, except gastrointestinal tract, HT was degraded in other sites, especially respiratory, mainly in airway and lungs, and systemic metabolism, mainly in livers, spleens, and kidneys. Through UPLC-Q-TOF-MS, three forced degradation products were identified as 4'-demethyl HT, cephalotaxine, and dehydrated HT, respectively. However, the degradation product in isolated biological homogenates of SD rats was only 4'-demethyl HT due to the relatively mild environment. Our findings contributed to a necessary study basis for HT in terms of structural optimization, dosage form selection, storage and transportation.

Identification of M5c regulator-medicated methylation modification patterns for prognosis and immune microenvironment in glioma.

Glioma is a common intracranial tumor and is generally associated with poor prognosis. Recently, numerous studies illustrated the importance of 5-methylcytosine (m5C) RNA modification to tumorigenesis. However, the prognostic value and immune correlation of m5C in glioma remain unclear. We obtained RNA expression and clinical information from The Cancer Genome Atlas (TCGA) and The Chinese Glioma Genome Atlas (CGGA) datasets to analyze. Nonnegative matrix factorization (NMF) was used to classify patients into two subgroups and compare these patients in survival and clinicopathological characteristics. CIBERSORT and single-sample gene-set algorithm (ssGSEA) methods were used to investigate the relationship between m5C and the immune environment. The Weighted correlation network analysis (WGCNA) and univariate Cox proportional hazard model (CoxPH) were used to construct a m5C-related signature. Most of m5C RNA methylation regulators presented differential expression and prognostic values. There were obvious relationships between immune infiltration cells and m5C regulators, especially NSUN7. In the m5C-related module from WGCNA, we found SEPT3, CHI3L1, PLBD1, PHYHIPL, SAMD8, RAP1B, B3GNT5, RER1, PTPN7, SLC39A1, and MXI1 were prognostic factors for glioma, and they were used to construct the signature. The great significance of m5C-related signature in predicting the survival of patients with glioma was confirmed in the validation sets and CGGA cohort.

Identification and control of gas-producing bacteria isolated from the swollen bagged soy sauce.

The swelling of soy sauce bags seriously affects product quality and causes food safety problems, which has become an urgent problem to solve in the condiment industry. Here, gas-producing bacteria in the swollen bagged soy sauce were isolated and identified to provide an effective control method for inhibiting their growth and solving the swelling of soy sauce bags. It was found that three gas-producing bacteria isolated from the swollen bagged soy sauce were confirmed as Bacillus amyloliquefaciens (G1), Bacillus sp. (G2) and Bacillus subtilis (P3) using 16S rDNA analysis. The strains' morphologies, growth rates, and physiological and biochemical characteristics were also compared. Further studies yielded the optimal growth time, temperature and pH for the three gas-producing bacteria (B. amyloliquefacien: 24 h, 37 °C, and pH 7; Bacillus sp.: 18 h, 30 °C, and pH 6.5-7.5; B. subtilis: 36 h, 30 °C, and pH 8). Bacillus sp. was more salt tolerant than the other two. Then the antibacterial effect of the combination was tested by the physicochemical index. The results showed that filtering through a 0.22 µm inorganic micro-filtration membrane, sterilizing at 121 °C for 2 min, and adding 1 g/kg potassium sorbate was effective methods to inhibit three gas-producing bacteria and control the swelling of soy sauce.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.