Schistosoma japonicum MiRNA-7-5p Inhibits the Growth and Migration of Hepatoma Cells via Cross-Species Regulation of S-Phase Kinase-Associated Protein 2

MicroRNAs (miRNAs) play important roles in human diseases, such as cancer. Human miRNA-7-5p is a tumor suppressor miRNA that inhibits tumor growth by regulating multiple oncogenic signal pathways. Recently, studies revealed that plant miRNAs could regulate mammalian gene expression in a cross-kingdom manner. Schistosoma japonicum miRNA-7-5p (designated as sja-miR-7-5p) is conserved between the parasites and mammals. Thus, we investigated whether sja-miR-7-5p has similar antitumor activity to its mammalian counterpart. We first showed that sja-miR-7-5p was detected in host hepatocytes during S. japonicum infection. The sja-miR-7-5p mimics significantly inhibited the growth, migration, and colony formation of mouse and human hepatoma cell lines in vitro, and induced G1/G0 cell cycle arrest. In a xenograft animal model, the tumor volume and weight were significantly reduced in mice inoculated with hepatoma cells transfected with sja-miR-7-5p mimics compared with those transfected with NC miRNAs. Furthermore, the antitumor activity of sja-miR-7-5p was suggested by cross-species downregulation of the S-phase kinase-associated protein 2 gene in the host. Thus, sja-miR-7-5p is translocated into hepatocytes and exerts its anti-cancer activities in mammals, implying that sja-miR-7-5p might strengthen host resistance to hepatocellular carcinoma during schistosome infection

Effects of Polymorphisms in the SjSP-13 Gene of Schistosoma japonicum on Its Diagnostic Efficacy and Immunogenicity

Schistosomiasis japonica is one of the most prevalent parasitic diseases in China. The scarcity of effective diagnostic tools is a major factor that contributes to the high prevalence of schistosomiasis japonica. SjSP-13 is a promising serological diagnostic biomarker of the disease. However, it is unclear whether polymorphisms in SjSP-13 affect its diagnostic efficacy and immunogenicity. Here, we found the SjSP-13 gene was highly polymorphic, and all the alleles of the gene were clustered into two clades, clade A and B. SjSP-13.6 and SjSP-13.25, the representative alleles of clade A and B, were produced in Escherichia coli. The diagnostic value of SjSP-13.6 (AUC = 0.983 ± 0.006), was found to be similar to the SjSP-13.25 (AUC = 0.973 ± 0.009) by receiver operating characteristic (ROC) analysis. SjSP-13.6 and SjSP-13.25 have the same specificity (96.7%), while the sensitivity of SjSP-13.6 (90.4%) is slightly but not significantly higher than SjSP-13.25 (85.2%). The combination use of the two alleles (SjSP-13.6/25) didn’t increase the diagnostic performance of SjSP-13 as the AUC value of SjSP-13.6/25 is 0.977 ± 0.009, lower than individual SjSP-13.6 (AUC = 0.983 ± 0.006). In addition, we found the immunogenicity of clade A alleles is significantly higher than clade B in Schistosoma japonicum naturally infected animals and patients, as the mean antibody levels of SjSP-13.6 was significantly higher than SjSP-13.25. We conclude that polymorphisms of the SjSP-13 gene should not affect its diagnostic efficacy, and it is not necessary to combine the alleles of the two clades for diagnosis of schistosomiasis

Adverse childhood experiences in patients with schizophrenia: related factors and clinical implications

The relationship between adverse childhood experiences (ACEs) and the development of psychotic symptoms is not well understood. Therefore, this study aimed to investigate the frequency and distribution of ACEs among patients with schizophrenia and their potential correlation with symptomatology and personality pathology. We conducted a cross-sectional study involving 571 patients with schizophrenia in Shanghai, China. Symptomatology was assessed using the Positive and Negative Symptoms Scale (PANSS) and personality pathology was assessed using the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+). ACEs were assessed using the Child Trauma Questionnaire-Short Form (CTQ-SF). ACEs were highly prevalent, with 80.8% of the patients with schizophrenia reporting at least one ACE. The three most common types of ACE were physical neglect (69.8%), emotional neglect (28.2%), and emotional abuse (22.9%). For specific ACE, emotional abuse was significantly associated with PD traits, whereas emotional and physical neglect types of ACE was significantly associated with negative symptoms. A higher level of physical abuse was more commonly reported by men, younger individuals, and those with a higher level of antisocial PD traits. Higher levels of physical neglect were associated with more severe negative symptoms. ACEs are commonly observed in patients with schizophrenia. Therefore, it is strongly recommended that this clinical population be provided with a comprehensive assessment and individualized intervention for those exposed to specific ACEs

Biomechanical evaluation of different posterior fixation techniques for treating thoracolumbar burst fractures of osteoporosis old patients: a finite element analysis

Objective: To investigate the biomechanical characteristics of different posterior fixation techniques in treatment of osteoporotic thoracolumbar burst fractures by finite element analysis.Methods: The Dicom format images of T10-L5 segments were obtained from CT scanning of a volunteer, and transferred to the Geomagic Studio software, which was used to build digital models. L1 osteoporotic burst fracture and different posterior fixation techniques were simulated by SolidWorks software. The data of ROM, the maximum displacement of fixed segment, ROM of fractured L1 vertebrae, the stress on the screws and rods as well as on fractured L1 vertebrae under different movement conditions were collected and analysed by finite element analysis.Results: Among the four groups, the largest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae occurred in CBT, and the corresponding data was 1.3°, 2.57 mm and 1.37°, respectively. While the smallest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae was found in LSPS, and the corresponding data was 0.92°, 2.46 mm and 0.89°, respectively. The largest stress of screws was 390.97 Mpa, appeared in CBT, and the largest stress of rods was 84.68 MPa, appeared in LSPS. The stress concentrated at the junction area between the root screws and rods. The maximum stress on fractured vertebrae was 93.25 MPa, appeared in CBT and the minimum stress was 56.68 MPa, appeared in CAPS. And the stress of fractured vertebrae concentrated in the middle and posterior column of the fixed segment, especially in the posterior edge of the superior endplate.Conclusion: In this study, long-segment posterior fixation (LSPF) provided with the greatest stability of fixed segment after fixation, while cortical bone screw fixation (CBT) provided with the smallest stability. Cement-augmented pedicle screw-rod fixation (CAPS) and combined using cortical bone screw and pedicle screw fixation (CBT-PS) provided with the moderate stability. CBT-PS exhibited superiority in resistance of rotational torsion for using multiple connecting rods. CAPS and CBT-PS maybe biomechanically superior options for the surgical treatment of burst TL fractures in osteoporotic patients

Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases

The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases

Genome sequence of the cultivated cotton <i>Gossypium arboreum</i>

The complex allotetraploid nature of the cotton genome (AADD; 2n = 52) makes genetic, genomic and functional analyses extremely challenging. Here we sequenced and assembled the Gossypium arboreum (AA; 2n = 26) genome, a putative contributor of the A subgenome. A total of 193.6 Gb of clean sequence covering the genome by 112.6-fold was obtained by paired-end sequencing. We further anchored and oriented 90.4% of the assembly on 13 pseudochromosomes and found that 68.5% of the genome is occupied by repetitive DNA sequences. We predicted 41,330 protein-coding genes in G. arboreum. Two whole-genome duplications were shared by G. arboreum and Gossypium raimondii before speciation. Insertions of long terminal repeats in the past 5 million years are responsible for the twofold difference in the sizes of these genomes. Comparative transcriptome studies showed the key role of the nucleotide binding site (NBS)-encoding gene family in resistance to Verticillium dahliae and the involvement of ethylene in the development of cotton fiber cells.Genetics &amp; HereditySCI(E)[email protected]; [email protected]; [email protected]

Baiji genomes reveal low genetic variability and new insights into secondary aquatic adaptations

The baiji, or Yangtze River dolphin (Lipotes vexillifer), is a flagship species for the conservation of aquatic animals and ecosystems in the Yangtze River of China; however, this species has now been recognized as functionally extinct. Here we report a high-quality draft genome and three re-sequenced genomes of L. vexillifer using Illumina short-read sequencing technology. Comparative genomic analyses reveal that cetaceans have a slow molecular clock and molecular adaptations to their aquatic lifestyle. We also find a significantly lower number of heterozygous single nucleotide polymorphisms in the baiji compared to all other mammalian genomes reported thus far. A reconstruction of the demographic history of the baiji indicates that a bottleneck occurred near the end of the last deglaciation, a time coinciding with a rapid decrease in temperature and the rise of eustatic sea level

Safety and Immunogenicity of a Malaria Vaccine, Plasmodium falciparum AMA-1/MSP-1 Chimeric Protein Formulated in Montanide ISA 720 in Healthy Adults

The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 µg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1∶10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.