PD-1/PD-L1 Inhibitor Plus Chemotherapy Versus PD-1/PD-L1 Inhibitor in Microsatellite Instability Gastrointestinal Cancers: A Multicenter Retrospective Study.

PURPOSE: To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti-PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS: We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti-PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti-PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti-PD-1/PD-L1 group). Propensity score-based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS: A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti-PD-1/PD-L1 and anti-PD-1/PD-L1, respectively. The chemo-anti-PD-1/PD-L1 group showed significant improvements versus the anti-PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti-PD-1/PD-L1 versus anti-PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION: Chemo-anti-PD-1/PD-L1 is superior to anti-PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.

Andrographolide Promotes Uptake of Glucose and GLUT4 Transport through the PKC Pathway in L6 Cells.

Glucose transporter 4 (GLUT4) is a membrane protein that regulates blood glucose balance and is closely related to type 2 diabetes. Andrographolide (AND) is a diterpene lactone extracted from herbal medicine Andrographis paniculata, which has a variety of biological activities. In this study, the antidiabetic effect of AND in L6 cells and its mechanism were investigated. The uptake of glucose of L6 cells was detected by a glucose assay kit. The expression of GLUT4 and phosphorylation of protein kinase B (PKB/Akt), AMP-dependent protein kinase (AMPK), and protein kinase C (PKC) were detected by Western blot. At the same time, the intracellular Ca2+ levels and GLUT4 translocation in myc-GLUT4-mOrange-L6 cells were detected by confocal laser scanning microscopy. The results showed that AND enhanced the uptake of glucose, GLUT4 expression and fusion with plasma membrane in L6 cells. Meanwhile, AND also significantly activated the phosphorylation of AMPK and PKC and increased the concentration of intracellular Ca2+. AND-induced GLUT4 expression was significantly inhibited by a PKC inhibitor (Gö6983). In addition, in the case of 0 mM extracellular Ca2+ and 0 mM extracellular Ca2+ + 10 µM BAPTA-AM (intracellular Ca2+ chelator), AND induced the translocation of GLUT4, and the uptake of glucose was significantly inhibited. Therefore, we concluded that AND promoted the expression of GLUT4 and its fusion with plasma membrane in L6 cells through PKC pathways in a Ca2+-dependent manner, thereby increasing the uptake of glucose.

Discovery of bicyclic polyprenylated acylphloroglucinols from Hypericum himalaicum with glucose transporter 4 translocation activity.

Hyperhimatins A-P (1-16), sixteen new bicyclic polyprenylated acylphloroglucinols (BPAPs), were isolated and identified from Hypericum himalaicum. The planner structures of hyperhimatins A-P were confirmed via extensive NMR and careful HRESIMS data analysis. The absolute configurations of the new compounds were mainly determined by electronic circular dichroism (ECD) calculation, NMR calculation, and the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complexes. All compounds were assessed for the glucose transporter 4 (GLUT-4) translocation and expression enhancing effects in L6 myotubes. Compounds 1-16 could promote the GLUT-4 expression by the range of 1.95-6.04 folds, and accelerate the GLUT-4 fusion with the plasma membrane ranged from 53.56% to 76.97% at a consistence of 30 µg/mL, among compound 10 displayed the strongest GLUT-4 translocation effect.

Metagenomics Reveal Microbial Effects of Lotus Root-Fish Co-Culture on Nitrogen Cycling in Aquaculture Pond Sediments.

Feed input leads to a large amount of nitrogen-containing sediment accumulating in the substrate in the pond culture process, threatening the safety of aquaculture production. Planting lotus roots (Nelumbo nucifera Gaertn.) in ponds can accelerate the removal of bottom nitrogen, while the role of nitrogen cycle-related microorganisms in the removal is still unclear. In this study, eight yellow catfish (Pelteobagrus fulvidraco) culture ponds with the same basic situation were divided into fishponds with planted lotus roots and ponds with only fish farming. Sediment samples were taken from the fishponds with planted lotus roots and the ponds with only fish farming before and after fish farming, marked as FPB, FPA, FOB, and FOA, respectively, and subjected to physicochemical and metagenomic sequencing analyses. The results show that the contents of NH4+, NO2−, TN, TP, and OM were significantly lower (p < 0.05) in FPA than in FOA. The abundance of metabolic pathways for inorganic nitrogen transformation and ammonia assimilation increased considerably after culture compared to the sediments before culture. A total of eight ammonia production pathways and two ammonia utilization pathways were annotated in the sediments of the experimental ponds, with a very high abundance of ammonia assimilation. Acinetobacter and Pseudomonas (34.67%, 18.02%) were the dominant bacteria in the pond sediments before culture, which changed to Thiobacillus (12.16%) after culture. The FPA had significantly higher relative abundances of Thiobacillus denitrificans and Sulfuricella denitrificans, and the FOA had significantly a higher abundance of Microcystis aeruginosa compared to other samples. The massive growth of Microcystis aeruginosa provided two new inorganic nitrogen metabolic pathways and one organic nitrogen metabolic pathway for FOA. The relative abundances of these three microorganisms were negatively correlated with NH4+ content (p < 0.01) and significantly positively correlated with AP, OM content, and pH value. Compared with ponds with only fish farming, lotus root−fish co-culture can significantly reduce the nitrogen content in sediment, increase the abundance of denitrifying bacteria, and inhibit algae growth. Still, it has little effect on the abundance of nitrogen cycle-related enzymes and genes. In summary, it is shown that, although lotus roots promote the growth of denitrifying microorganisms in the sediment, nitrogen removal relies mainly on nutrient uptake by lotus roots.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor.

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS: In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.

[Clinical Characteristics and Prognosis of 76 Lung Adenocarcinoma Patients 
Harboring EGFR Mutations with Pleural Effusion at Initial Diagnosis: 
A Single-center Retrospective Study].

BACKGROUND: Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them. METHODS: A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis. RESULTS: 76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05). CONCLUSIONS: PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.

A glycolysis-related two-gene risk model that can effectively predict the prognosis of patients with rectal cancer.

BACKGROUND: Aerobic glycolysis is an emerging hallmark of cancer. Although some studies have constructed glycolysis-related prognostic models of colon adenocarcinoma (COAD) based on The Cancer Genome Atlas (TCGA) database, whether the COAD glycolysis-related prognostic model is appropriate for distinguishing the prognosis of rectal adenocarcinoma (READ) patients remains unknown. Exploring critical and specific glycolytic genes related to READ prognosis may help us discover new potential therapeutic targets for READ patients. RESULTS: Three gene sets, HALLMARK_GLYCOLYSIS, REACTOME_GLYCOLYSIS and REACTOME_REGULATION_OF_GLYCOLYSIS_BY_FRUCTOSE_2_6_BISPHOSPHATE_METABOLISM, were both significantly enriched in both COAD and READ through glycolysis-related gene set enrichment analysis (GSEA). We found that six genes (ANKZF1, STC2, SUCLG2P2, P4HA1, GPC1 and PCK1) were independent prognostic genes in COAD, while TSTA3 and PKP2 were independent prognostic genes in READ. Glycolysis-related prognostic model of COAD and READ was, respectively, constructed and assessed in COAD and READ. We found that the glycolysis-related prognostic model of COAD was not appropriate for READ, while glycolysis-related prognostic model of READ was more appropriate for READ than for COAD. PCA and t-SNE analysis confirmed that READ patients in two groups (high and low risk score groups) were distributed in discrete directions based on the glycolysis-related prognostic model of READ. We found that this model was an independent prognostic indicator through multivariate Cox analysis, and it still showed robust effectiveness in different age, gender, M stage, and TNM stage. A nomogram combining the risk model of READ with clinicopathological characteristics was established to provide oncologists with a practical tool to evaluate the rectal cancer outcomes. GO enrichment and KEGG analyses confirmed that differentially expressed genes (DEGs) were enriched in several glycolysis-related molecular functions or pathways based on glycolysis-related prognostic model of READ. CONCLUSIONS: We found that a glycolysis-related prognostic model of COAD was not appropriate for READ, and we established a novel glycolysis-related two-gene risk model to effectively predict the prognosis of rectal cancer patients.

Successful immune checkpoint inhibitor-based rechallenge in a patient with advanced esophageal squamous cell cancer: A case report.

Immune checkpoint inhibitors (ICIs) have been shown to improve survival in patients with advanced or metastatic esophageal cancer. However, ICI-based rechallenges after recovery from fatal adverse events (AEs) are equivocal, especially in patients who have already undergone treatment-related AEs. In this study, we report the case of a patient with advanced esophageal squamous cell cancer (ESCC) who developed a treatment-related tracheoesophageal fistula (TEF) after two cycles of ICI administration, provided in combination with traditional chemotherapeutics. After spontaneous healing of the TEF, the patient was again treated with ICIs and achieved a durable clinical response without any signs of fistula recurrence. Successful ICI-based rechallenges after fistula healing have rarely been reported. Therefore, ICI-based rechallenge in patients with esophageal cancer having an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 after serious AEs may serve as a clinically viable treatment strategy that should be administered under close monitoring.

Dilemma and solutions of treatment delay in cancer patients during the COVID-19 pandemic: A single-center, prospective survey.

INTRODUCTION: During the COVID-19 pandemic, the protective and medical resources were limited, while a limited number of studies have concentrated on the influences of COVID-19 on the treatment of cancer patients. This survey aimed to explore the protective awareness about COVID-19, the incidence and factors influencing treatment delay, and expected treatment modality of cancer patients, so as to assist cancer patients. METHODS: A current prospective, online survey was conducted through the WeChat platform on cancer outpatients at the Department of Peking University Third Hospital in China from March 4 to April 4, 2020. RESULTS: A total of 141 patients completed the survey after excluding 35 patients with an incomplete questionnaire. Note that 100% of the patients wore masks and paid attention to hand hygiene during the hospital visits, 73.0% of the patients had a strong desire to treat cancer, and 41.8% experienced treatment delay. The rate of treatment delay among the patients treated in other departments was markedly higher than that in our department (64.7% vs. 38.7%, p = .042). The results of logistic regression analysis showed that the previous treatment department was independently correlated with treatment delay. Moreover, 51.8% of the patients preferred to receive chemotherapy in the day ward, 54.6% hoped to receive a strong contact with doctors, and 83.7% would like to receive online therapeutic consultation. CONCLUSION: The rate of treatment delay was remarkable, which may be related to previous treatment departments. Promotion of "active management of attending physician" and "telemedicine" may be highly advantageous for cancer patients during the COVID-19 pandemic.

Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells.

GLUT4 is an important glucose transporter, which is closely related to insulin resistance and type 2 diabetes. In this study, we investigated the mechanism of Estradiol Dipropionate (EDP) on uptake of glucose in L6 skeletal muscle cells. In our study, we confirmed that EDP promoted uptake of glucose in L6 skeletal muscle cells in both normal and insulin resistant models. Western blot indicated that EDP accelerated GLUT4 expression and significantly activated AMPK and PKC phosphorylation; the expression of GLUT4 was significantly inhibited by AMPK inhibitor compound C and PKC inhibitor Gö6983, but not by Wortmannin (Akt inhibitor). Meanwhile, EDP boosted GLUT4 expression, and also increased intracellular Ca2+ levels. In the presence of 2 mM, 0 mM extracellular Ca2+ and 0 mM extracellular Ca2+ + BAPTA-AM, the involvement of intracellular Ca2+ levels contribute to EDP-induced GLUT4 expression and fusion with plasma membrane. Therefore, this study investigated whether EDP promoted GLUT4 expression through AMPK and PKC signaling pathways, thereby enhancing GLUT4 uptake of glucose and fusion into plasma membrane in L6 skeletal muscle cells. In addition, both EDP induced GLUT4 translocation and uptake of glucose were Ca2+ dependent. These findings suggested that EDP may be potential drug for the treatment of type 2 diabetes.

Serious Adverse Events Reporting in Phase III Randomized Clinical Trials of Colorectal Cancer Treatments: A Systematic Analysis.

Objective: The occurrence, development, and prognosis of serious adverse events (SAEs) associated with anticancer drugs in clinical trials have important guiding significance for real-world clinical applications. However, to date, there have been no studies investigating SAEs reporting in randomized clinical trials of colorectal cancer treatments. This article systematically reviewed the SAEs reporting of phase III randomized clinical trials of colorectal cancer treatments and analyzed the influencing factors. Methods: We reviewed all articles about phase III randomized clinical trials of colorectal cancer treatments published in the PubMed, Embase, Medline, and New England Journal of Medicine databases from January 1, 1993, to December 31, 2018, and searched the registration information of clinical trials via the internet sites such as "clinicaltrials.gov". We analyzed the correlation between the reported proportion (RP) of SAEs in the literature and nine elements, including the clinical trial sponsor and the publication time. Chi-square tests and binary logistic regression were used to identify the factors associated with improved SAEs reports. This study was registered on PROSPERO. Results: Of 1560 articles identified, 160 were eligible, with an RP of SAEs of 25.5% (41/160). In forty-one publications reporting SAEs, only 14.6% (6/41) described the pattern of SAEs in detail. In clinical trials sponsored by pharmaceutical companies, the RP of SAEs was significantly higher than that in those sponsored by investigators (57.6 versus 20.7%, p < 0.001). From 1993 to 2018, the RP of SAEs gradually increased (none (0/6) before 2000, 17.1% (12/70) from 2000 to 2009, and 34.5% (29/84) after 2009). The average RP of SAEs published in the New England Journal of Medicine (N Engl J Med), the Lancet, the Journal of the American Medical Association (JAMA), the Lancet Oncology (Lancet Oncol), and the Journal of Clinical Oncology (J Clin Oncol) was significantly higher than that published in other journals (31.9 versus 16.7%, p = 0.030). In the clinical trials referenced by clinical guidelines, the RP of SAEs was higher than that in non-referenced clinical trials (32.0 versus 15.9%, p = 0.023). Binary logistic regression analysis showed that pharmaceutical company sponsorship, new drug research, and sample size greater than 1000 were positive influencing factors for SAEs reporting. Conclusion: Although the RP of SAEs increased over time, SAEs reporting in clinical trials needs to be further improved. The performance, outcomes and prognosis of SAEs should be reported in detail to guide clinical practice in the real world.

Elevations of monocyte and neutrophils, and higher levels of granulocyte colony-stimulating factor in peripheral blood in lung cancer patients.

INTRODUCTION: Immune cells and molecules are considered as clinical biomarkers and potential targets for immunotherapy. Analyses of the composition of peripheral blood cells hold promise for providing a basis for diagnosing and prognosis lung cancer. In this study, we assessed correlations between immune cell subset profiles in peripheral blood and disease prognosis in patients with lung cancer. METHODS: One hundred and thirteen patients with lung cancer and 99 age-matched healthy people were enrolled in this study. The percentage and cell count of monocytes, neutrophils, T cells, B cells, natural killer (NK), and NKT cells in peripheral blood were analyzed by flow cytometry or peripheral blood analyzer. Serum cytokines and colony-stimulating factors were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: A reduction in antitumor NK cells (p < 0.0001) and an increase in the protumor MDSCs (p < 0.0001) were observed in the lung cancer patients compared with the controls. Monocyte counts were significantly higher in lung cancer patients with histories of smoking (p < 0.05) or drinking (p < 0.01) than in patients with no relevant history or healthy controls. The number of neutrophils and the neutrophil-to-lymphocyte ratio (NLR) were particularly higher in patients with liver metastasis (p < 0.01) compared with no metastasis patients or healthy controls. Levels of the monocyte-derived cytokine interleukin-6 (p < 0.05), granulocyte colony-stimulating factor (G-CSF) (p < 0.0001), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.0001) were higher in patients than in controls. G-CSF levels decreased during the remission phase (p < 0.05), and positively correlated with carbohydrate antigen 19-9 (p < 0.05) and gene mutation (p < 0.05). CONCLUSION: Monocyte and neutrophil counts were higher in peripheral blood in lung cancer patients than in controls, especially when patients had histories of smoking, drinking, and liver metastasis. Serum levels of G-CSF and GM-CSF were higher in lung cancer patients, and G-CSF levels positively correlated with disease severity.

Integrated analysis of miRNA-mRNA regulatory networks of potato (Solanum tuberosum L.) in response to cadmium stress.

Cadmium (Cd) stress is a ubiquitous abiotic stress affecting plant growth worldwide and negatively impacting crop yield and food safety. Potato is the most important non-grain crop globally, but there is limited research available on the response of this crop to Cd stress. This study explored the coping mechanism for Cd stress in potato through analyses of miRNA and mRNA. Tissue culture seedlings (20-day-old) of potato variety 'Atlantic' were cultured for up to 48 h in liquid medium containing 5 mmol/L CdCl2, and phenotypic, physiological, and transcriptomic changes were observed at specific times. With the extension of Cd stress time, the potato leaves gradually wilted and curled, and root salicylic acid (SA), glutathione (GSH), and lignin contents and peroxidase (POD) activity increased, while indole-3-acetic acid (IAA) and zeatin (ZT) contents decreased. Using miRNA-seq, 161 existing miRNAs, 383 known miRNAs, and 7361 novel miRNAs were identified, and, 18 miRNAs were differentially expressed in response to Cd stress. Based on mRNA-seq, 7340 differentially expressed mRNAs (DEGs) were found. Through mRNA-miRNA integrated analysis, miRNA-target gene pairs consisting of 23 DEGs and 33 miRNAs were identified. Furthermore, "glutathione metabolism" "plant hormone signal transduction" and "phenylpropanoid biosynthesis" were established as crucial pathways in the Cd stress response of potato. Novel miRNAs novel-m3483-5p and novel-m2893-5p participate in these pathways through targeted regulation of cinnamic alcohol dehydrogenase (CAD; PG0005359) and alanine aminotransferase (POP; PG0024281), respectively. This study provides information that will help elucidate the complex mechanism of the Cd stress response in potato. Moreover, candidate miRNAs and mRNAs could yield new strategies for the development of Cd-tolerant potato breeding.

Integration of mRNA and miRNA analysis reveals the molecular mechanism of potato (Solanum tuberosum L.) response to alkali stress.

The continuing increase in the global saline-alkali land area has made saline-alkali stress the principal abiotic stress limiting plant growth. Potato is the most important non-grain crop, and its production is also severely limited by saline-alkali stress. However, few studies have addressed the mechanism of saline-alkali tolerance of potato with a focus on its response to neutral salt NaCl stress, or its response to alkali stress. Recently, miRNA-mRNA analyses have helped advance our understanding of how plants respond to stress. Here, we have characterized the morphological, physiological, and transcriptome changes of tissue culture seedlings of potato variety "Qingshu No. 9" treated with NaHCO3 (for 0, 2, 6, and 24 h). We found that the leaves of tissue culture seedlings wilted and withered under alkali stress, and the contents of ABA, BRs, trehalose, and lignin in roots increased significantly. The contents of GAs decreased significantly. Subsequently, miRNA-seq analysis results identified 168 differentially expressed miRNAs (DEMIs) under alkali stress, including 21 exist miRNAs and 37 known miRNAs from 47 families and 110 novel miRNAs. The mRNA-seq results identified 5731 differentially expressed mRNAs (DEMs) under alkali stress. By miRNA-mRNA integrated analysis, were obtained 33 miRNA-target gene pairs composed of 20 DEMIs and 33 DEMs. Next, we identified the "phenylpropanoid biosynthesis", "plant hormone signal transduction", and "starch and sucrose metabolism" pathways as necessary for potato to respond to alkali stress. miR4243-x and novel-m064-5p were involved in the response of potato to alkali stress by their negative regulatory effects on shikimate O-hydroxycinnamoyltransferase (HCT) and sucrose-phosphate synthase (SPS) genes, respectively. The expression results of miRNA and mRNA were verified by quantitative real-time PCR (qRT-PCR). Our results clarify the mechanism of potato response to alkali stress at the miRNA level, providing new insights into the molecular mechanisms of potato's response to alkali stress. We report many candidate miRNAs and mRNAs for molecular-assisted screening and salt-alkali resistance breeding.

[The Effects and Management of Viral Pneumonia on Lung Cancer Patients].

The worldwide epidemic of three coronaviruses and one influenza virus in 21st century have seriously threatened human health. Infection with these viruses can cause respiratory symptoms. The patients with lung cancer are more susceptible to viral infection and have a worse prognosis due to the advanced age and the systemic immunosuppressive state caused by malignancy itself and the anticancer treatments. In addition, without sufficient clinical awareness, a missed diagnosis of viral pneumonia may occur due to the fever and respiratory symptoms caused by lung cancer and its secondary diseases. Furthermore, control measures against viral outbreaks may interfere with routine diagnosis and treatment of lung cancer patients. Therefore, scientific protection and individualized management of lung cancer patients are particularly important during virus epidemic prevention and control. Here, we systematically reviewed the epidemiological and clinical characteristics of viral pneumonia, its impact on patients with lung cancer and the differential diagnosis of lung cancer-related respiratory manifestations, aiming to provide guidance for the individual management of lung cancer patients during the prevention and control of viral pneumonia epidemic.

[Effect of Nitrate Amendment on Soil Denitrification Activity and Anthracene Anaerobic Degradation].

The degradation of soil polycyclic aromatic hydrocarbons (PAHs) under denitrification is one of the most important pathways for anaerobic PAH elimination, but little is known about the effect of nitrate (the terminal electron acceptor for denitrification) on soil denitrification activity and PAH degradation under anaerobic conditions. In this study, the effect of nitrate on soil anthracene anaerobic degradation and denitrification activity was investigated through an anaerobic microcosm experiment. Two groups of treatments without (N0) and with (N30) nitrate (30 mg·kg-1) amendment were conducted. Each group contained three treatments with different anthracene concentrations (0, 15, and 30 mg·kg-1, denoted as A0, A15, and A30, respectively). Therefore, a total of six treatments (N0A0, N0A15, N0A30, N30A0, N30A15, and N30A30) were incubated in darkness at 25℃ for 45 days, and the production rates of N2O and CO2, abundances of denitrification related genes (narG:periplasmic nitrate reductase gene; nirK:copper-containing nitrite reductase gene; and nirS:cd1-nitrite reductase gene), and soil anthracene content were measured at 3, 7, 14, and 45 days. The results indicated that the intensive denitrification enzyme activity in each treatment was only detected at day 3, which could be significantly enhanced by both nitrate and anthracene amendments. Subsequently, a sharp decline of denitrification enzyme activity was observed in each treatment, while anthracene showed an obvious inhibition of soil denitrification enzyme activity. The result of a two-way ANOVA also indicated that nitrate, anthracene, and their interactions had significant effects on soil denitrification enzyme activity. The result of a quantitative-PCR indicated that, during the incubation, the abundances of narG and nirS exhibited an increasing tendency, but the abundance of nirK was relatively constant compared with its former counterparts. The final removal rate of anthracene under anaerobic soil environment was in the range of 33.83%-55.01%, and neither the final removal rate nor the degradation rate of anthracene could be significantly affected by nitrate amendment during incubation. The anthracene degradation rates in the higher anthracene containing treatments (N0A30 and N30A30) were significantly higher than those in the lower anthracene containing treatments (N0A15 and N30A15). In summary, nitrate amendments had no effect on soil anthracene anaerobic degradation but could significantly affect soil denitrification enzyme activity and the abundance of denitrification related narG and nirS genes.

A Robust Inner and Outer Loop Control Method for Trajectory Tracking of a Quadrotor.

In order to achieve the complicated trajectory tracking of quadrotor, a geometric inner and outer loop control scheme is presented. The outer loop generates the desired rotation matrix for the inner loop. To improve the response speed and robustness, a geometric SMC controller is designed for the inner loop. The outer loop is also designed via sliding mode control (SMC). By Lyapunov theory and cascade theory, the closed-loop system stability is guaranteed. Next, the tracking performance is validated by tracking three representative trajectories. Then, the robustness of the proposed control method is illustrated by trajectory tracking in presence of model uncertainty and disturbances. Subsequently, experiments are carried out to verify the method. In the experiment, ultra wideband (UWB) is used for indoor positioning. Extended Kalman Filter (EKF) is used for fusing inertial measurement unit (IMU) and UWB measurements. The experimental results show the feasibility of the designed controller in practice. The comparative experiments with PD and PD loop demonstrate the robustness of the proposed control method.

Indoor Autonomous Control of a Two-Wheeled Inverted Pendulum Vehicle Using Ultra Wide Band Technology.

In this paper, we aimed to achieve the indoor tracking control of a two-wheeled inverted pendulum (TWIP) vehicle. The attitude data are acquired from a low cost micro inertial measurement unit (IMU), and the ultra-wideband (UWB) technology is utilized to obtain an accurate estimation of the TWIP's position. We propose a dual-loop control method to realize the simultaneous balance and trajectory tracking control for the TWIP vehicle. A robust adaptive second-order sliding mode control (2-RASMC) method based on an improved super-twisting (STW) algorithm is investigated to obtain the control laws, followed by several simulations to verify its robustness. The outer loop controller is designed using the idea of backstepping. Moreover, three typical trajectories, including a circle, a trifolium and a hexagon, have been designed to prove the adaptability of the control combinations. Six different combinations of inner and outer loop control algorithms have been compared, and the characteristics of inner and outer loop algorithm combinations have been analyzed. Simulation results demonstrate its tracking performance and thus verify the validity of the proposed control methods. Trajectory tracking experiments in a real indoor environment have been performed using our experimental vehicle to further validate the feasibility of the proposed algorithm in practice.

Co-effects of pyrene and nitrate on the activity and abundance of soil denitrifiers under anaerobic condition.

It has previously been confirmed that polycyclic aromatic hydrocarbons (PAHs) could be degraded by soil microbes coupling with denitrification, but the relationships among soil denitrifiers, PAHs, and nitrate under obligate anaerobic condition are still unclear. Here, co-effects of pyrene and nitrate on the activity and abundance of soil denitrifiers were investigated through a 45-day incubation experiment. Two groups of soil treatments with (N30) and without (N0) nitrate (30 mg kg-1 dry soil) amendment were conducted, and each group contained three treatments with different pyrene concentrations (0, 30, and 60 mg kg-1 dry soil denoted as P0, P30, and P60, respectively). The pyrene content, abundances of denitrification concerning genes (narG, periplasmic nitrate reductase gene; nirS, cd 1-nitrite reductase gene; nirK, copper-containing nitrite reductase gene), and productions of N2O and CO2 were measured at day 3, 14, 28, and 45, and the bacterial community structures in four represented treatments (N0P0, N0P60, N30P0, and N30P60) were analyzed at day 45. The results indicated that the treatments with higher pyrene concentration had higher final pyrene removal rates than the treatments with lower pyrene concentration. Additionally, intensive emission of N2O was detected in all treatments only at day 3, but a continuous production of CO2 was measured in each treatment during the incubation. Nitrate amendment could enhance the activity of soil denitrifiers, and be helpful for soil microbes to sustain their activity. While pyrene seemed had no influence on the productions of N2O and CO2, and amendment with pyrene or nitrate both had no obvious effect on abundances of denitrification concerning genes. Furthermore, it was nitrate but not pyrene had an obvious influence on the community structure of soil bacteria. These results revealed that, under anaerobic condition, the activity and abundance of soil denitrifiers both were insensitive to pyrene, but nitrate could improve the activity of soil denitrfiers and induce the shifts in soil bacterial community structure.

Comparative Investigation of Bacterial, Fungal, and Archaeal Community Structures in Soils in a Typical Oilfield in Jianghan, China.

Agricultural soils in oilfields have high risk for polycyclic aromatic hydrocarbon (PAH) pollution. In this study, from the Jianghan Oilfield (Hubei Province, China) with a history of >50 years, 7 soil samples (OS-1 to OS-7) were collected. Subsequently, the bacterial, archaeal, and fungal community structures were investigated by Illumina MiSeq sequencing, and the relationship between microbial community structure and soil PAH content was analyzed. The results indicated that bacterial and archaeal Chao 1 indices showed a significantly negative relationship with soil PAH content, and only the bacterial Shannon index had a significantly negative relationship with soil PAH content. Moreover, the community structure of bacteria (r 2 = 0.9001, p = 0.013) showed a stronger correlation with PAH content than that of fungi (r 2 = 0.7357, p = 0.045), and no significant relationship was found between archaeal community structure (r 2 = 0.4553, p = 0.262) and soil PAH content. In addition, the relative greater abundances of some bacterial genus belonging to Actinobacteria (Mycobacterium and Micromonospora) and Proteobacteria (Pseudomonas, Lysobacter, Idiomarina, Oxalobacteraceae, and Massilia), fungal genus belonging to Ascomycota (Sordariales and Pleosporales), and archaeal phylum (Euryarchaeota) were detected in the soil samples (OS-3 and OS-5) with greater PAH content. In summary, soil PAHs showed an obvious influence and selectivity on the soil microbiota. Furthermore, compared with fungi and archaea, bacteria was more sensitive to soil PAH pollution, and the diversity indices and community structure of bacteria both might be suitable indicators for assessment of soil PAH stress on the soil ecosystem.