Serial platelet count as a dynamic prediction marker of hospital mortality among septic patients.

Background: Platelets play a critical role in hemostasis and inflammatory diseases. Low platelet count and activity have been reported to be associated with unfavorable prognosis. This study aims to explore the relationship between dynamics in platelet count and in-hospital morality among septic patients and to provide real-time updates on mortality risk to achieve dynamic prediction. Methods: We conducted a multi-cohort, retrospective, observational study that encompasses data on septic patients in the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The joint latent class model (JLCM) was utilized to identify heterogenous platelet count trajectories over time among septic patients. We assessed the association between different trajectory patterns and 28-day in-hospital mortality using a piecewise Cox hazard model within each trajectory. We evaluated the performance of our dynamic prediction model through area under the receiver operating characteristic curve, concordance index (C-index), accuracy, sensitivity, and specificity calculated at predefined time points. Results: Four subgroups of platelet count trajectories were identified that correspond to distinct in-hospital mortality risk. Including platelet count did not significantly enhance prediction accuracy at early stages (day 1 C-indexDynamic  vs C-indexWeibull: 0.713 vs 0.714). However, our model showed superior performance to the static survival model over time (day 14 C-indexDynamic  vs C-indexWeibull: 0.644 vs 0.617). Conclusions: For septic patients in an intensive care unit, the rapid decline in platelet counts is a critical prognostic factor, and serial platelet measures are associated with prognosis.

Discovery of potent small molecule inhibitors of histone lysine methyltransferase NSDs.

Nuclear receptor binding SET domain (NSD) proteins are a class of histone lysine methyltransferases and implicated in multiple cancer types with aberrant expression and involvement of cancer related signaling pathways. In this study, a series of small-molecule compounds including compound 2 and 3 are identified against the SET domain of NSDs through structure-based virtual screening. Our lead compound 3 exhibits potent inhibitory activities in vitro towards the NSD2-SET and NSD3-SET with an IC50 of 0.81 µM and 0.84 µM, respectively, and efficiently inhibits histone H3 lysine 36 dimethylation and decreases the expression of NSDs-targeted genes in non-small cell lung cancer cells at 100 nM. Compound 3 suppresses cell proliferation and reduces the clonogenicity in H460 and H1299 non-small cell lung cancer cells, and induces s-phase cell cycle arrest and apoptosis. These data establish our compounds as a valuable tool-kit for the study of the biological roles of NSDs in cancer.

Modulation of HIV-1 capsid multimerization by sennoside A and sennoside B via interaction with the NTD/CTD interface in capsid hexamer.

Small molecules that bind to the pocket targeted by a peptide, termed capsid assembly inhibitor (CAI), have shown antiviral effects with unique mechanisms of action. We report the discovery of two natural compounds, sennoside A (SA) and sennoside B (SB), derived from medicinal plants that bind to this pocket in the C-terminal domain of capsid (CA CTD). Both SA and SB were identified via a drug-screening campaign that utilized a time-resolved fluorescence resonance energy transfer assay. They inhibited the HIV-1 CA CTD/CAI interaction at sub-micromolar concentrations of 0.18 µM and 0.08 µM, respectively. Mutation of key residues (including Tyr 169, Leu 211, Asn 183, and Glu 187) in the CA CTD decreased their binding affinity to the CA monomer, from 1.35-fold to 4.17-fold. Furthermore, both compounds induced CA assembly in vitro and bound directly to the CA hexamer, suggesting that they interact with CA beyond the CA CTD. Molecular docking showed that both compounds were bound to the N-terminal domain (NTD)/CTD interface between adjacent protomers within the CA hexamer. SA established a hydrogen-bonding network with residues N57, V59, Q63, K70, and N74 of CA1-NTD and Q179 of CA2-CTD. SB formed hydrogen bonds with the N53, N70, and N74 residues of CA1-NTD, and the A177and Q179 residues of CA2-CTD. Both compounds, acting as glue, can bring αH4 in the NTD and αH9 in the CTD of the NTD/CTD interface close to each other. Collectively, our research indicates that SA and SB, which enhance CA assembly, could serve as novel chemical tools to identify agents that modulate HIV-1 CA assembly. These natural compounds may potentially lead to the development of new antiviral therapies with unique mechanisms of action.

Central nervous system complications in SARS-CoV-2-infected patients.

OBJECTIVE: To investigate the clinical manifestations, treatment and prognosis of COVID-19-associated central nervous system (CNS) complications. METHODS: In this single-centre observation study, we recruited patients with COVID-19-associated CNS complications at the neurology inpatient department of the Eighth Affiliated Hospital, Sun Yat-Sen University (Futian, Shenzhen) from Dec 2022 to Feb 2023. Patients were analysed for demographics, clinical manifestations, cerebrospinal fluid properties, electroencephalographic features, neuroimaging characteristics, and treatment outcome. All patients were followed-up at 1 and 2 months after discharge until Apr 2023. RESULTS: Of the 12 patients with COVID-19-associated CNS complications, the CNS symptoms occur between 0 days and 4 weeks after SARS-CoV-2 infection. The most common CNS symptoms were memory deficits (4/12, 33%), Unresponsiveness (4/12, 33%), mental and behavioural disorders (4/12, 33%). Seven of 12 cases can be categorized as probable SARS-CoV-2 encephalitis, and 5 cases can be described as brainstem encephalitis, acute disseminated encephalomyelitis, optic neuritis, multiple sclerosis or tremor probably associated with SARS-CoV-2 infection. Six patients received antiviral therapy, and 11 patients received glucocorticoid therapy, of which 3 patients received human immunoglobulin synchronously. Nine patients recovered well, two patients had residual neurological dysfunction, and one patient passed away from complications associated with tumor. CONCLUSION: In this observational study, we found that the inflammatory or immune-related complications were relatively common manifestations of COVID-19-associated CNS complications, including different phenotypes of encephalitis and CNS inflammatory demyelinating diseases. Most patients recovered well, but a few patients had significant neurological dysfunctions remaining.

A Broad-Spectrum Antiviral Molecule, Protoporphyrin IX, Acts as a Moderator of HIV-1 Capsid Assembly by Targeting the Capsid Hexamer.

The capsid protein (CA), an essential component of human immunodeficiency virus type 1 (HIV-1), represents an appealing target for antivirals. Small molecules targeting the CAI-binding cavity in the C-terminal domain of HIV-1 CA (CA CTD) confer potent antiviral activities. In this study, we report that a small molecule, protoporphyrin IX (PPIX), targets the HIV-1 CA by binding to this pocket. PPIX was identified via in vitro drug screening, using a homogeneous and time-resolved fluorescence-based assay. CA multimerization and a biolayer interferometry (BLI) assay showed that PPIX promoted CA multimerization and bound directly to CA. The binding model of PPIX to CA CTD revealed that PPIX forms hydrogen bonds with the L211and E212 residues in the CA CTD. Moreover, the BLI assay demonstrated that this compound preferentially binds to the CA hexamer versus the monomer. The superposition of the CAI CTD-PPIX complex and the hexameric CA structure suggests that PPIX binds to the interface formed by the NTD and the CTD between adjacent protomers in the CA hexamer via the T72 and E212 residues, serving as a glue to enhance the multimerization of CA. Taken together, our studies demonstrate that PPIX, a hexamer-targeted CA assembly enhancer, should be a new chemical probe for the discovery of modulators of the HIV-1 capsid assembly. IMPORTANCE CA and its assembled viral core play essential roles in distinct steps during HIV-1 replication, including reverse transcription, integration, nuclear entry, virus assembly, and maturation through CA-CA or CA-host factor interactions. These functions of CA are fundamental for HIV-1 pathogenesis, making it an appealing target for antiviral therapy. In the present study, we identified protoporphyrin IX (PPIX) as a candidate CA modulator that can promote CA assembly and prefers binding the CA hexamer versus the monomer. PPIX, like a glue, bound at the interfaces between CA subunits to accelerate CA multimerization. Therefore, PPIX could be used as a new lead for a CA modulator, and it holds potential research applications.

Carboxypeptidase Vitellogenic-Like Promotes the Proliferation and Metastasis of Osteosarcoma through the TGF-ß/Smad Signaling Pathway.

OBJECTIVE: This research explored the biological role and underlying mechanisms of carboxypeptidase vitellogenic-like (CPVL) in the progression of osteosarcoma. METHODS: Through mining of microarray data from the GEO database and utilization of qRT-PCR and Western blot analyses, CPVL expression in osteosarcoma tissues and cells was evaluated. RNA interference and lentiviral transduction techniques were applied to edit the CPVL gene. RNA-seq was used to screen for the downstream target genes of CPVL. RESULTS: In both osteosarcoma biopsy samples and cell lines, the expression of CPVL was abnormally higher than that in normal cells or osteoblasts. CPVL silencing notably inhibited the proliferative activity of osteosarcoma cells, whereas CPVL overexpression had the opposite effect. CPVL silencing had potent tumor-suppressive ability in a xenograft osteosarcoma model in nude mice. CPVL silencing significantly suppressed osteosarcoma cell migration, invasion and EMT, whereas CPVL overexpression accelerated these events. Downstream genes related to the occurrence and development of osteosarcoma, including TGF-ß/Smad signaling pathway molecules (TGF-ß2, TGF-ßR1, Smad2/3, and Smad5), were suppressed by CPVL silencing. CONCLUSIONS: High CPVL expression in osteosarcoma not only promoted tumor growth but also induced the EMT process through the TGF-ß/Smad signaling pathway. CPVL may be a new antitumor therapeutic target for osteosarcoma.

A two-phase comprehensive NSCLC prognostic study identifies lncRNAs with significant main effect and interaction.

Long noncoding RNA (lncRNA) are involved in regulating physiological behaviors for various malignant tumors, including non-small-cell lung cancer (NSCLC). However, few studies comprehensively evaluated both lncRNA-lncRNA interaction effects and main effects of lncRNA on overall survival of NSCLC. Hence, we performed a two-phase designed study of lncRNA expression in tumor tissues using 604 NSCLC patients from The Cancer Genome Atlas as the discovery phase and 839 patients from Gene Expression Omnibus as the validation phase. In the discovery phase, we adopted a two-step strategy, Screening before Testing, for dimension reduction and signal detection. These candidate lncRNAs first screened out by the weighted random forest (Ranger), were then tested through the Cox proportional hazards model adjusted for covariates. Significant lncRNAs with either type of effects aforementioned were carried forward into the validation phase to confirm their significances again. As a result, in the discovery phase, 19 lncRNAs were identified by Ranger, among which five lncRNAs and one pair of lncRNA-lncRNA interaction exhibited significant effects (FDR-q ≤ 0.05) main and interaction effects on NSCLC survival, respectively, through Cox model. After the independent validation, we finally observed that one lncRNA (ENSG00000227403.1) with main effect was robustly associated with NSCLC prognosis (HRdiscovery = 0.90, P = 1.20 × 10-3; HRvalidation = 0.94, P = 4.11 × 10-3) and one pair of lncRNAs (ENSG00000267121.4 and ENSG00000272369.1) had significant interaction effect on NSCLC survival (HRdiscovery = 1.12, P = 3.07 × 10-4; HRvalidation = 1.11, P = 0.0397). Our comprehensive NSCLC prognostic study of lncRNA provided population-level evidence for further functional study.

Erythrocyte membrane protein band 4.1-like 3 inhibits osteosarcoma cell invasion through regulation of Snai1-induced epithelial-to-mesenchymal transition.

Erythrocyte membrane protein band 4.1-like 3 (EPB41L3) is an important membrane skeletal protein that may interact with numerous membrane proteins. Loss of EPB41L3 is reported in multiple cancer types, and it is originally identified as a tumor suppressor. In this study, through analyzing expression profiling retrieved from the Gene Expression Omnibus (GEO) dataset, we find that EPB41L3 is upregulated in primary osteosarcoma (OS) and osteosarcoma cell lines. Importantly, EPB41L3 may promote osteosarcoma cell proliferation and suppress osteosarcoma cell migration and invasion. Reduced EPB41L3 leads to a decrease of E-cadherin as well as an increase of N-cadherin and Vimentin, implying a prominent epithelial-to-mesenchymal transition. Furthermore, we demonstrate that EPB41L3 inhibits the epithelial-to-mesenchymal transition through destabilizing the Snai1 protein, one of the most important transcription factors of the epithelial-to-mesenchymal transition process. Collectively, our study has first established the complex and vital roles of EPB41L3 and implicated EPB41L3 as a potential biomarker in osteosarcoma.

Loss of histone H4 lysine 20 trimethylation in osteosarcoma is associated with aberrant expression ofhistone methyltransferase SUV420H2.

Epigenetic modifications of histones have crucial roles in various types of cancers. The aberrant trimethylation of histone H4 at lysine 20 (H4K20) has been implicated in carcinogenesis. At present, the status of trimethylation at H4k20 (H4K20me3) in osteosarcoma (OS), the predominant bone cancer in humans, is unknown. In the present study, a genome-wide decrease was observed in H4K20me3 levels in OS tissues and cell lines. Reduced levels of lysine methyltransferase 5C (SUV420H2), the histone methyltranferase responsible for modification of H4K20me3, was also observed in OS cells with the associated loss of H4K20me3. Furthermore, a total of 507 SUV420H2-regulated genes were identified through RNA-seq and a number of candidate genes were further validated. Bioinformatic analysis revealed an association between SUV420H2 and multiple signaling pathway, including the mitogen-activated protein kinase, P53, transforming growth factor and the ErbB pathways. These results demonstrated that there are aberrant levels of H4K20me3 and SUV420H2 in OS, and highlighted H4K20me3 as a candidate biomarker for the early detection of OS.

The selenium-containing drug ebselen potently disrupts LEDGF/p75-HIV-1 integrase interaction by targeting LEDGF/p75.

Lens-epithelium-derived growth-factor (LEDGF/p75)-binding site on HIV-1 integrase (IN), is an attractive target for antiviral chemotherapy. Small-molecule compounds binding to this site are referred as LEDGF-IN inhibitors (LEDGINs). In this study, compound libraries were screened to identify new inhibitors of LEDGF/p75-IN interaction. Ebselen (2-phenyl-1,2-benzisoselenazol-3-one), a reported anti-HIV-1 agent, was identified as a moderate micromolar inhibitor of LEDGF/p75-IN interaction. Ebselen inhibited the interaction by binding to LEDGF/p75 and the ability of ebselen to inhibit the interaction could be reversed by dithiothreitol (DTT). BLI experiment showed that ebselen probably formed selenium-sulphur bonds with reduced thiols in LEDGF/p75. To the best of our knowledge, we showed for the first time that small-molecule compound, ebselen inhibited LEDGF/p75-IN interaction by directly binding to LEDGF/p75. The compound discovered here could be used as probe compounds to design and develop new disrupter of LEDGF/p75-IN interaction.

Template-based modeling and ab-initio docking using CoDock in CAPRI.

Integration of template-based modeling, global sampling and precise scoring is crucial for the development of molecular docking programs with improved accuracy. We combined template-based modeling and ab-initio docking protocol as hybrid docking strategy called CoDock for the docking and scoring experiments of the seventh CAPRI edition. For CAPRI rounds 38-45, we obtained acceptable or better models in the top 10 submissions for eight out of the 16 evaluated targets as predictors, nine out of the 16 targets as scorers. Especially, we submitted acceptable models for all of the evaluated protein-oligosaccharide targets. For the CASP13-CAPRI experiment (round 46), we obtained acceptable or better models in the top 5 submissions for 10 out of the 20 evaluated targets as predictors, 11 out of the 20 targets as scorers. The failed cases for our group were mainly the difficult targets and the protein-peptide systems in CAPRI and CASP13-CAPRI experiments. In summary, this CAPRI edition showed that our hybrid docking strategy can be efficiently adapted to the increasing variety of challenges in the field of molecular interactions.

Natural-product-library-based screening for discovery of capsid C-terminal domain targeted HIV-1 inhibitors.

Antiretroviral therapy (ART) can effectively suppress replication of human immunodeficiency virus type 1 (HIV-1) and limit disease progression. However, ART is unable to eradicate the virus, and the requirement for lifelong treatment may have side effects and may lead to the development of resistance. New approaches to prevent and treat HIV-1 infection should therefore be developed. HIV-1 capsid (CA) protein is an unexploited but attractive target for antiviral drug development. The hydrophobic cavity of the C-terminal domain of CA (CA CTD) has been validated as a potential target for antiviral drugs. Binding of compounds to this conserved non-polar groove in CA CTD allosterically disrupts the CA assembly. This study screened 2080 natural products to identify potential antiviral agents for further development to combat HIV-1 infection. From the primary screen at a fixed concentration of 50 µM, 16 compounds were found to be effective against this target. Six compounds observed in the primary screen were confirmed in dose-response experiments, and were tested against HIV-1-induced cytopathic effects. Two compounds were found to inhibit HIV-1 replication, and the most active compound - rubranol - inhibited viral replication at a moderate micromolar concentration (EC50 = 15.85 µM). The binding modes of rubranol and hirsutanonol to CA CTD were analysed by molecular docking, providing insight for the design of drugs targeting HIV-1 CA. This study reports, for the first time, identification of natural products that showed potential as anti-HIV-1 agents by targeting the conserved hydrophobic cavity of HIV-1 CA CTD.

NSD2 Promotes Renal Cancer Progression Through Stimulating Akt/Erk Signaling.

BACKGROUND: Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase). The aim of this study was to investigate the biological role of NSD2 in clear cell renal cell carcinoma (ccRCC). METHODS: GEO and OncoLnc databases were used to identify NSD2 expression and estimate its clinical value in ccRCC. Immunohistochemistry (IHC) was applied to further evaluate NSD2 protein level in ccRCC tissues. The expression of NSD2 in different cell lines and the transfection efficiency were determined by quantitative real-time PCR and Western blot analysis. The effect of NSD2 and the underlying mechanism in ccRCC progression were investigated via MTT, flow cytometry, Western blotting and xenograft tumor assays. RESULTS: NSD2 was over-expressed in both ccRCC tissues and cell lines. NSD2 expression could discriminate ccRCC samples from normal samples, and moreover, high NSD2 expression was characterized with a short overall survival (OS) time. Additionally, knockdown of NSD2 suppressed proliferation and induced apoptosis of cancer cells by inhibiting Akt/Erk signaling and regulating Bcl-2 and Bax expression. Meanwhile, up-regulation of NSD2 contributed to the opposite effects. Silencing of NSD2 reduced xenograft tumor growth in vivo. CONCLUSION: NSD2 serves as an oncogenic factor in the progression of ccRCC via activation of Akt/Erk signaling.

Identify old drugs as selective bacterial ß-GUS inhibitors by structural-based virtual screening and bio-evaluations.

Irinotecan (CPT-11) is a cytotoxic drug that has wide applicability and usage in cancer treatment. Despite its success, patients suffer dose-dependent diarrhea, limiting the drug's efficacy. No effective therapy is available for this unmet medical need. The bacterial ß-glucuronidase (ß-GUS) plays pivotal role in CPT-11-induced diarrhea (CID) via activating the non-toxic SN-38G to toxic SN-38 inside intestine. By using structural-based virtual screening, three old drugs (N-Desmethylclozapine, Aspartame, and Gemifloxacin) were firstly identified as selective bacterial ß-GUS inhibitors. The IC50 values of the compounds in the enzyme-based and cell-based assays range from 0.0389 to 3.6040 and 0.0105 to 5.3730 µM, respectively. The compounds also showed good selectivity against mammalian ß-GUS and no significant cytotoxicity in bacteria. Molecular docking and molecular dynamics simulations were performed to further investigate the binding modes of compounds with bacterial ß-GUS. Binding free energy decomposition revealed that the compounds formed strong interactions with E413 in catalytic trail from primary monomer and F365' on the bacterial loop from the other monomer of bacterial ß-GUS, explaining the selectivity against mammalian ß-GUS. The old drugs identified here may be used as bacterial ß-GUS inhibitors for CID or other bacterial ß-GUS-related disorders.

A HTRF based competitive binding assay for screening specific inhibitors of HIV-1 capsid assembly targeting the C-Terminal domain of capsid.

Due to its multifaceted essential roles in virus replication and extreme genetic fragility, the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein is a valued therapeutic target. However, CA is as yet unexploited clinically, as there are no antiviral agents that target it currently on the market. To facilitate the identification of potential HIV-1 CA inhibitors, we established a homogeneous time-resolved fluorescence (HTRF) assay to screen for small molecules that target a biologically active and specific binding pocket in the C-terminal domain of HIV-1 CA (CA CTD). The assay, which is based on competition of small molecules for the binding of a known CA inhibitor (CAI) to the CA CTD, exhibited a signal-to-background ratio (S/B) > 10 and a Z' value > 0.9. In a pilot screen of three kinase inhibitor libraries containing 464 compounds, we identified one compound, TX-1918, as a low micromolecular inhibitor of the HIV-1 CA CTD-CAI interaction (IC50 = 3.81 µM) that also inhibited viral replication at moderate micromolar concentration (EC50 = 15.16 µM) and inhibited CA assembly in vitro. Based on the structure of TX-1918, an additional compound with an antiviral EC50 of 6.57 µM and cellular cytotoxicity CC50 of 102.55 µM was obtained from a compound similarity search. Thus, the HTRF-based assay has properties that are suitable for screening large compound libraries to identify novel anti-HIV-1 inhibitors targeting the CA CTD.

Cerebral Perforating Artery Disease : Characteristics on High-Resolution Magnetic Resonance Imaging.

PURPOSE: Our aims were to evaluate the feasibility of high-resolution magnetic resonance imaging (HR-MRI) for displaying the cerebral perforating arteries in normal subjects and to discuss the value of HR-MRI for detecting the causes of infarctions in the territory of the lenticulostriate artery (LSA). METHODS: Included in this study were 31 healthy subjects and 28 patients who had infarctions in the territory supplied by the LSA. The T1-weighted imaging (T1WI), T2WI, diffusion-weighted imaging (DWI), and HR-MRI, including 3­dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and 3D fast spin-echo T1WI (namely CUBE T1 in GE Healthcare), were applied on a 3-Tesla scanner. The numbers and route of the perforating arteries on both sides were independently confirmed on HR-MRI by two physicians. The Wilcoxon test was used to compare the differences. RESULTS: The numbers of perforating arteries in healthy subjects observed on 3D-TOF-MRA were as follows: numbers of the bilateral recurrent artery of Heubner (RAH) ranged from 0-3 (median 1), numbers of the left LSA ranged from 0-7 (median 3), numbers of the right LSA ranged from 0-5 (median 3), numbers of the bilateral anterior choroidal artery ranged from 1-2 (median 1) and the numbers of the bilateral thalamoperforating artery ranged from 1-2 (median 1). In the patients with lenticulostriate infarctions, the numbers of LSAs on the affected side were lower than on the opposite and ipsilateral sides in the healthy subjects. The results were statistically significant. An abnormality of the RAH may lead to a centrum semiovale infarct pattern, whereas an abnormality of the LSA is associated with a corona radiata infarct pattern. CONCLUSION: The use of HR 3D-TOF-MRA and CUBE T1 had unique advantages in displaying the tiny perforating arteries in vivo. Moreover, effective recognition of the associated cerebral perforating artery and infarct patterns may enhance our understanding of the mechanism of stroke in patients with lenticulostriate infarctions.

Histone methyltransferase SUV39H2 serves oncogenic roles in osteosarcoma.

Suppressor of variegation 3­9 homologue 2 (SUV39H2), a SET domain­containing histone methyl-transferase, trimethylates histone H3 at lysine 9 and serves crucial roles in heterochromatin organization and genome stability. SUV39H2 is overexpressed in various types of human cancer, whereas it is almost undetectable in normal adult tissues, except testis. The aim of this study was to investigate a potential role of SUV39H2 in osteosarcoma. In the present study, increased SUV39H2 expression levels were observed in osteosarcoma, the most common primary bone cancer in children and adolescents, and the knockdown of SUV39H2 expression by specific small interfering RNAs in osteosarcoma cells markedly suppressed cancer cell growth and led to a notable reduction in cell viability. Furthermore, overexpression of SUV39H2 promoted cell proliferation, which indicated that SUV39H2 may possess oncogenic activity in human osteosarcoma. Notably, depletion of SUV39H2 expression caused an increase in the population of G1 phase and induced apoptosis, which implied that SUV39H2 may have biological significance in the process of cell cycle. These results indicated that SUV39H2 may be an ideal target for osteosarcoma therapeutics.

Silencing of histone methyltransferase NSD3 reduces cell viability in osteosarcoma with induction of apoptosis.

NSD3 is a histone lysine methyltransferase that methylates histone H3 at lysine 36. NSD3 is located at chromosome 8p11.23, the locus that exhibits strong cancer relevance. Thus, NSD3 is likely involved in multiple human cancers. Nevertheless, its roles in human carcinogenesis remain unknown. In the present study, we demonstrated that silencing of NSD3 in osteosarcoma, the most common primary bone cancer in children and adolescents, results in a marked decrease in the number of viable cancer cells, accompanied by increases in the cell population at the G2/M phase and the number of apoptotic cells. In addition, 549 NSD3­regulated genes were identified and a set of selected candidate genes were validated. Bioinformatic analysis revealed that NSD3 negatively regulates a number of genes that are involved in the process of negative regulation of signal transduction as well as negative regulation of signaling and cell communication. Our results indicate the oncogenic roles of NSD3 in the development and progression of human osteosarcoma, and implicate NSD3 as a potential molecular target for selective therapy for human osteosarcoma.

Utilization of UPLC/Q-TOF-MS-Based Metabolomics and AFLP-Based Marker-Assisted Selection to Facilitate/Assist Conventional Breeding of Polygala tenuifolia.

As one of the most important traditional Chinese medicine, the quality of Polygala tenuifolia is difficult to control and a new method must be established to facilitate/assist the breeding of P. tenuifolia. In this study, UPLC/Q-TOF-MS-based metabolomics analysis was performed to determine the chemical composition and screen metabolite biomarkers according to agronomic traits. A total of 29 compounds and 18 metabolite biomarkers were found. AFLP-based marker-assisted selection (MAS) was used to identify molecular marker bands and screen characteristic bands associated with specific agronomic traits. 184 bands and 76 characteristic AFLP bands were found. The correlation network between compounds and characteristic AFLP bands was built, so we may directly breed certain P. tenuifolia herbs with special agronomic traits (or characteristic AFLP bands), which exhibit specific pharmacological functions depending on the content of the active compounds. The proposed method of metabolomics coupled with MAS could facilitate/assist the breeding of P. tenuifolia.

Clinical study of phacoemulsification and intraocular lens implantation combined with goniosynechialysis in the treatment of primary chronic angle closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To evaluate the efficacy of phacoemulsification and intraocular lens ( IOL ) implantation combined with goniosynechialysis in the treatment of primary chronic angle closure glaucoma.·METHODS: Eighty patients ( 96 eyes ) with primary chronic angle closure glaucoma were divided into observation group (40 cases, 46 eyes) and control group (40 cases, 50 eyes). The treatment group was treated with phacoemulsification, intraocular lens implantation and goniosynechialysis, while the control group was treated with phacoemulsification and intraocular lens implantation. The best corrected visual acuity, intraocular pressure, visual field mean deviation (MD), mean sensitivity ( MS) and the central anterior chamber depth of the two groups before and after the surgery were compared, and the occurrence of complications in patients with postoperative were record.·RESULTS:The best corrected visual acuity, visual field, intraocular pressure and central anterior chamber depth of the two groups before operation showed no significant differences (P>0. 05). The best corrected visual acuity, visual field, intraocular pressure and central anterior chamber depth between the groups at 6mo postoperatively showed statistically significant (P<0. 05). There was no serious complications in the two groups, and the difference between the two groups showed no statistically significant (x2=0. 351, P=2. 095).· CONCLUSION: The application of the phacoemulsification and intraocular lens implantation combined with goniosynechialysis in the treatment of primary chronic angle closure glaucoma is more effective than the simple use of phacoemulsification and intraocular lens implantation.