Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging.

Multivalent glycosidase inhibitors based on 1-deoxynojirimycin derivatives against α-glucosidases have been rapidly developed. Nonetheless, the mechanism based on self-assembled multivalent glucosidase inhibitors in living systems needs to be further studied. It remains to be determined whether the self-assembly possesses sufficient stability to endure transit through the small intestine and subsequently bind to the glycosidases located therein. In this paper, two amphiphilic compounds, 1-deoxynojirimycin and α-peptoid conjugates (LP-4DNJ-3C and LP-4DNJ-6C), were designed. Their self-assembling behaviors, multivalent α-glucosidase inhibition effect, and fluorescence imaging on living organs were studied. LP-4DNJ-6C exhibited better multivalent α-glucosidase inhibition activities in vitro. Moreover, the self-assembly of LP-4DNJ-6C could effectively form a complex with Nile red. The complex showed fluorescence quenching effect upon binding with α-glucosidases and exhibited potent fluorescence imaging in the small intestine. This result suggests that a multivalent hypoglycemic effect achieved through self-assembly in the intestine is a viable approach, enabling the rational design of multivalent hypoglycemic drugs.

Induction of apoptosis in triple-negative breast cancer cells by petroleum ether extract of Sageretia thea / 药学实践与服务

Objective To investigate the effect of the petroleum ether extract of Sageretia thea on the proliferation and apoptosis of breast cancer cells. Methods After breast cancer cells were incubated with the petroleum ether extract for different times, cell viability was analyzed by CCK8 assay, cell proliferation was detected by plate cloning test, nuclear morphology was observed by DAPI staining, mitochondrial membrane potential（MMP）and reactive oxygen species（ROS）were determined by immunofluorescence, and the cell cycle and apoptosis were detected by flow cytometry. After incubating with the extract for 24 h, the CCK8 assay was used to observe the toxicity to normal human vascular endothelial cells. Results The IC50 of BT549 and MDA-MB-231 breast cancer cell lines treated with the petroleum ether extract for 24 h were 45.40 μg/ml and 12.23 μg/ml, respectively. The extract time and dose dependently inhibited breast cancer cell viability and clonal formation, induced cell apoptosis and cycle arrest in G1/S phase, decreased MMP and increased ROS levels. There was no toxic effect on normal endothelial cells. Conclusion The petroleum ether extract of Sageretia thea may induce apoptosis by increasing ROS to cause MMP collapse, followed by activating mitochondrial pathway, thereby hindering the growth of breast cancer cells. These results could support the application of Sageretia thea to anti-breast tumor in the folk.

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The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent Mpro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent Mpro inhibitors with desirable properties have been developed based on available crystal structures of Mpro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent Mpro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent Mpro inhibitors are also discussed.

Nucleolus imaging based on naphthalimide derivatives.

Nucleolus was an important cellular organelle. The abnormal morphology and number of the nucleolus have been considered as diagnostic biomarkers for some human diseases. However, the imaging agent based on nucleolus was limited. In this manuscript, a series of nucleolar fluorescent probes based on naphthalimide derivatives (NI-1 âˆ¼ NI-5) had been designed and synthesized. NI-1 âˆ¼ NI-5 could penetrate cell membranes and nuclear membranes, achieve clear nucleolar staining in living cells. These results suggested that the presence of amino groups on the side chains of naphthalimide backbone could enhance the targeting to the cell nucleolus. In addition, the molecular docking results showed that NI-1 âˆ¼ NI-5 formed hydrogen bonds and hydrophobic interactions with RNA, and exhibited enhanced fluorescence upon binding with RNA. These results will provide favorable support for the diagnosis and treatment of nucleolus-related diseases in the future.

Endovascular Treatment of Ruptured or Symptomatic Thoracoabdominal and Pararenal Aortic Aneurysms Using Octopus Endograft Technique: Mid-Term Clinical Outcomes.

OBJECTIVE: To evaluate the effectiveness and safety of using off-the-shelf "Octopus" technique to treat ruptured or symptomatic thoracoabdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PRAAA). METHODS AND RESULTS: All cases who underwent "Octopus" technique from May 2016 to May 2019 at our center were retrospectively analyzed. A total of 10 cases (8 males) were included. The mean age was 54.5±14.2 years (range: 31-80 years). Eight cases presented as aneurysm rupture or impending rupture accepted emergency repair. Technical success, defined by placement of all endografts as planned, was achieved in all cases. A total of 30 target visceral branches were successfully cannulated, 9 celiac arteries were covered intentionally. Intraoperative endoleak was observed in 6 patients, all of them were gutter leak. During hospital stay, there was no death, no side branch occlusion or spinal cord ischemia. Median follow-up was 30 months (range: 12-50 months). One patient died of lung cancer at 14-month follow-up. There was no secondary endoleak. The primary endoleak were found spontaneously resolved in 3 cases at 7 days, 3-month, and 1-year imaging. One persistent endoleak totally resolved after sealing of gutter spaces at 4-month follow-up. The other 2 persistent endoleak decreased during follow-up, which are still under observation. The branch patency rate was 90.3% (28/31). All the 3 occluded branches were renal arteries. Branch occlusion occurred in 2 cases at 1-month follow-up and 1 case at 2-year follow-up, but renal insufficiency was not observed in these cases. Obvious aneurysm sac shrinkage (≥5 mm) was observed in all cases. The aneurysm size shrunk from 7.6±1.9 to 5.5±1.4 cm. No spinal cord ischemia occurred during follow-up. CONCLUSION: Treatment of ruptured TAAA and PRAAA with "Octopus" technique is feasible and safe for high surgical risk patients in the absence of fenestrated and branched devices. The long-term clinical outcomes needed to be investigated.

Screening methods of SARS-CoV-2 main protease inhibitors and current applications / 药学学报

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.

Clinicopathological and molecular features of metaplastic thymoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.

Research progress of SARS-CoV-2 main protease inhibitors / 药学学报

As a common protease with high similarity among coronavirus species, the main protease (Mpro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

Discovery of novel sulfonamide substituted indolylarylsulfones as potent HIV-1 inhibitors with better safety profiles

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R10L4 was endowed with significant inhibitory activity towards wild-type HIV-1 (EC50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC50 = 0.017 μmol/L, SI = 13,055), E138K (EC50 = 0.017 μmol/L, SI = 13,123) and Y181C (EC50 = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R10L4 was characterized with significantly reduced cytotoxicity (CC50 = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R10L4 and HIV-1 RT. Additionally, R10L4 presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

[Inhibition of the Wnt signaling pathway contributes to the cardiac protection of exercise training in spontaneously hypertensive rats].

The objective of this study was to investigate the cardiac protective effect of low-to-moderate intensity exercise training and the role of the Wnt signaling pathway in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto (WKY) rats were randomly divided into 5 groups, namely hypertensive control (SHR-S), hypertensive plus exercise training (SHR-E), normal blood pressure control (WKY-S), normal blood pressure plus exercise training (WKY-E) and SHR-E plus Wnt agonist (SHR-E-Wnt). The rats in SHR-E and WKY-E groups underwent low-to-moderate intensity swimming for 16 weeks, and the rats in SHR-E-Wnt group were injected with Wnt agonist 1 through tail vein 4 weeks before the end of swimming. The blood pressure of rats was measured every week. After exercise training, the left ventricular wall thickness and ejection function were measured by ultrasound cardiogram, myocardial structure and collagen fiber changes were observed by HE staining and Masson staining, and the expression levels of ß-catenin and Dishevelled-1 (DVL-1) mRNA and protein in left ventricular myocardium were detected by real-time fluorescence quantitative PCR and Western blot, respectively. The results showed that the body weight was decreased (P < 0.05), blood pressure was increased (P < 0.01), heart weight and ventricular wall thickness were increased (P < 0.01), and the left ventricular ejection function was decreased (P < 0.05) in SHR-S group compared with those in WKY-S group. In addition, the heart structure was damaged, collagen fibers were significantly increased, and the mRNA and protein expressions of ß-catenin and DVL-1 in the left ventricle were significantly up-regulated in SHR-S group compared with those in WKY-S group (P < 0.01). Compared with those in SHR-S group, the body weight of SHR-E group did not change significantly (P > 0.05), but the blood pressure was decreased (P < 0.01), heart weight and ventricular wall thickness were diminished, ejection function was increased (P < 0.01), myocardial structure injury was significantly improved, collagen fibers were significantly reduced, and mRNA and protein expression levels of ß-catenin and DVL-1 in the left ventricle were significantly down-regulated (P < 0.01) in SHR-E group. Importantly, exercise-induced antihypertensive and cardioprotective effects in SHR were blunted by Wnt agonist. These results suggest that low-to-moderate intensity exercise training exerts cardioprotective effects in SHR, possibly through inhibiting the Wnt signaling pathway.

Papillary renal neoplasm with reverse polarity: a clinicopathological analysis / 中华病理学杂志

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.

Ionic indium(III) chloride hybrids incorporating a 2,2'-bipyrimidine ligand: studies on photoluminescence and structural transformation.

Although luminescent indium(III) based halide perovskites have been widely investigated, the study of emissive indium(III) halide hybrids is limited. Three indium(III) chloride hybrids based on a bpym ligand were synthesized, namely [EPy]2[InCl4(bpym)InCl4]·DMF (1), [EPy]2[InCl4(bpym)InCl4] (2), and [BPy]2[InCl4(bpym)InCl4] (3) (EPy = N-ethylpyridinium; BPy = N-butylpyridinium; bpym = 2,2'-bipyrimidine). They all exhibit a zero-dimensional structure, in which the ligand bpym interconnects two [InCl4]- to form a [InCl4(bpym)InCl4]2- anion that is further charge-compensated by the corresponding pyridinium cations. This is the first time using bpym to coordinate with an In atom. At 298 K, 1 exhibits a weak emission at 600 nm while 2 and 3 exhibit emissions peaking at 500 nm and 540 nm, respectively. Interestingly, the DMF solvent molecule in 1 can be removed by heating, thus resulting in the structural transformation of 1 into 2 together with a photoluminescence (PL) change. Density functional theory (DFT) calculations confirm that halogen-to-ligand charge-transfer (HLCT) occurs in the emission process. To the best of our knowledge, this is the first report on PL of ionic indium(III) halide hybrids incorporating organic ligands.

Critical Role of Simultaneous Reduction of Atmospheric Odd Oxygen for Winter Haze Mitigation.

The lockdown due to COVID-19 created a rare opportunity to examine the nonlinear responses of secondary aerosols, which are formed through atmospheric oxidation of gaseous precursors, to intensive precursor emission reductions. Based on unique observational data sets from six supersites in eastern China during 2019-2021, we found that the lockdown caused considerable decreases (32-61%) in different secondary aerosol components in the study region because of similar-degree precursor reductions. However, due to insufficient combustion-related volatile organic compound (VOC) reduction, odd oxygen (Ox = O3 + NO2) concentration, an indicator of the extent of photochemical processing, showed little change and did not promote more decreases in secondary aerosols. We also found that the Chinese provinces and international cities that experienced reduced Ox during the lockdown usually gained a greater simultaneous PM2.5 decrease than other provinces and cities with an increased Ox. Therefore, we argue that strict VOC control in winter, which has been largely ignored so far, is critical in future policies to mitigate winter haze more efficiently by reducing Ox simultaneously.

Divergent Alterations of Structural-Functional Connectivity Couplings in First-episode and Chronic Schizophrenia Patients.

Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. Positive and negative syndrome scale (PANSS) scores were assessed for all patients. Structural and functional brain networks were constructed using gray matter volume (GMV) and resting-state magnetic resonance imaging (rs-fMRI) time series measurements. At the connectivity level, the CSZ patients showed significantly increased SC-FC coupling strength compared with the FeSZ patients. At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.

Cytotoxic jatrophane diterpenoids from the aerial parts of Euphorbia helioscopia.

A phytochemical study of 80% ethanol extract from the aerial parts of Euphorbia helioscopia led to the isolation of three new jatrophane diterpenoids, euphoheliphanes A-C (1-3). Their structures were established on the basis of spectroscopic data (NMR, IR, UV, and MS). The isolated diterpenoids were tested in vitro for cytotoxic potentials against 6 renal cancer cell lines. As a result, compounds 1-3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 50 µM.[Formula: see text].

Optimization of Sulfurization Process of Cobalt Sulfide and Nitrogen Doped Carbon Material for Boosting the Oxygen Reduction Reaction Catalytic Activity in Alkaline Medium.

In order to reduce fuel cell material cost and promote its application, it is urgent to develop non-noble metal materials to replace platinum as the cathode catalysts in fuel cells. The cobalt sulfide and nitrogen co-doped carbon (S-Co-N/C) materials with metal-organic frameworks as precursors have shown good oxygen reduction reaction (ORR) catalytic activity. Benefiting from the protection of catalytic active sites by sulfur atoms, the stability and alcohol-tolerance of the S-Co-N/C catalyst can be significantly improved. In order to fully understand the effect of the sulfurization process on the properties of the material, zeolite imidazole frameworks (ZIF)-8, and ZIF-67 are used as precursors to prepare a novel material of S-Co-N/C by using a sulfurization-pyrolysis method. Another S-Co-N/C material by using a pyrolysis- sulfurization method is prepared for comparison. The effects of the sulfurization process in the preparation on the morphology, chemical structure, specific surface area, and ORR catalytic activity of the final material are investigated. The experimental results show that the surface of the S-Co-N/C material tends to be rough due to the sulfurization reaction of the metal elements. The porosity of the material is reduced to some extent due to the remaining Zn elements in the final product. Interestingly, some carbon nanotubes are found to be generated on the surface of the S-Co-N/C material because of the synergistic effect of Zn and Co on the carbon material during the pyrolysis process, which is beneficial to accelerate the adsorption of oxygen on the S-Co-N/C surface and the electron transportation during the oxygen reduction reaction. In addition, the generated CoS during the sulfurization process can further protect the Co elements from agglomeration, which can effectively increase the ORR catalytic active sites in the final material. The S-Co-N/C material prepared by the sulfurization-pyrolysis method performs a superior ORR catalytic activity to the one synthesized by the pyrolysis-sulfurization method.

Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics.@*METHODS@#Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve.@*RESULTS@#The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis.@*CONCLUSION@#High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

Comparative Transcriptome Analysis Reveals the Biocontrol Mechanism of Bacillus velezensis F21 Against Fusarium Wilt on Watermelon.

The watermelon (Citrullus lanatus) is one of the most important horticultural crops for fruit production worldwide. However, the production of watermelon is seriously restricted by one kind of soilborne disease, Fusarium wilt, which is caused by Fusarium oxysporum f. sp. niveum (Fon). In this study, we identified an efficient PGPR strain B. velezensis F21, which could be used in watermelon production for Fon control. The results of biocontrol mechanisms showed that B. velezensis F21 could suppress the growth and spore germination of Fon in vitro. Moreover, B. velezensis F21 could also enhance plant basal immunity to Fon by increasing the expression of plant defense related genes and activities of some defense enzymes, such as CAT, POD, and SOD. To elucidate the detailed mechanisms regulating B. velezensis F21 biocontrol of Fusarium wilt in watermelon, a comparative transcriptome analysis using watermelon plant roots treated with B. velezensis F21 or sterile water alone and in combination with Fon inoculation was conducted. The transcriptome sequencing results revealed almost one thousand ripening-related differentially expressed genes (DEGs) in the process of B. velezensis F21 triggering ISR (induced systemic resistance) to Fon. In addition, the Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that numerous of transcription factors (TFs) and plant disease resistance genes were activated and validated by using quantitative real-time PCR (qRT-PCR), which showed significant differences in expression levels in the roots of watermelon with different treatments. In addition, genes involved in the MAPK signaling pathway and phytohormone signaling pathway were analyzed, and the results indicated that B. velezensis F21 could enhance plant disease resistance to Fon through the above related genes and phytohormone signal factors. Taken together, this study substantially expands transcriptome data resources and suggests a molecular framework for B. velezensis F21 inducing systemic resistance to Fon in watermelon. In addition, it also provides an effective strategy for the control of Fusarium wilt in watermelon.

Association Between Organic Dust Exposure and Adult-Asthma: A Systematic Review and Meta-Analysis of Case-Control Studies

BACKGROUND: Exposure to organic dust has been widely investigated as a potential risk factor for asthma with different results. To clarify a potential relationship, we performed the present meta-analysis to integrate the results of studies examining the association of organic dust exposure with asthma. METHODS: A comprehensive literature search in the electronic databases including EMBASE, PubMed and Cochrane Library databases (up to August 2018) was conducted. The adjusted odds ratios (ORs) with corresponding 95% confidence interval (CI) for organic dust exposure and asthma were retrieved and pooled to generate summary effect estimates in Revman 5.2. RESULTS: Database searches retrieved 1,016 records. A total of 17 studies containing 3,619 cases and 6,585 controls were finally included in our meta-analysis. The summary estimates suggested that organic dust exposure was positively associated with asthma (OR, 1.48; 95% CI, 1.26–1.75; P < 0.00001), whether among population-based case-control studies (OR, 1.24; 95% CI, 1.13–1.35; P < 0.00001) or hospital-based case-control studies (OR, 2.79; 95% CI, 1.27–6.12; P = 0.01). Subgroup analysis showed that paper/wood (OR, 1.62; 95% CI, 1.38–1.90; P < 0.00001), flour/grain (OR, 1.48; 95% CI, 1.11–1.97; P = 0.008), and textile dust (OR, 1.50; 95% CI, 1.08–2.09; P = 0.02) exposure were significantly associated with asthma. CONCLUSIONS: Based on the studies evaluated, our meta-analysis results prompt that organic dust exposure is a risk factor inducing asthma, although precise analysis focus on specific organic dust materials is still warranted.

Primary testicular diffuse large B-cell lymphoma: A clinicopathological analysis / 中华男科学杂志

Objective@#To investigate the clinicopathological features, immunophenotype and treatment of primary testicular diffuse large B-cell lymphoma (DLBCL).@*METHODS@#We retrospectively analyzed the pathomorphological characteristics and immunohistochemical markers of 23 cases of primary testicular DLBCL as well as their clinicopathological features with a review of the relevant literature. The patients were aged 48－76 (mean 61.4) years, 82.6% over 50 years, and all clinically presented with painless progressive unilateral testicular swelling, 9 cases in the left and the other 14 in the right testis.@*RESULTS@#Histologically, the lymphomas were composed of large atypical cells with prominent karyokinesis and diffusely infiltrated the testicular parenchyma. The neoplastic cells were positive for B-cell markers. Five of the patients were followed up for 2 to 32 months, of whom 4 survived and 1 died at 9 months.@*CONCLUSIONS@#Primary testicular DLBCL is a rare tumor with an invasive biological behavior, mostly found in elderly males and easily misdiagnosed or missed in diagnosis. Histopathology plays a key role and immunohistochemical markers are of high value in the definite diagnosis and differential diagnosis of the tumor.