Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin - 801 Cases from a Single Institution in China

Aim: As more and more centers has published their treatment results ofpseudomyxoma peritonei (PMP) with cytoreductive surgery (CRS) andhyperthermic intraperitoneal chemotherapy (HIPEC), the data from Chinais missing. Myxoma Department of Aerospace Hospital is the biggestcenter treating PMP in China. The purpose of this study is to report theearly and long-term outcomes for PMP from this single center. Methods:801 appendix-derived PMP out of 1008 consecutive patients treated inMyxoma Department of Aerospace Hospital between 2008 and 2019 wereretrospectively analyzed. Results: Complete cytoreductive surgery (CCRS)was achieved in 240 (30%) patients with median PCI of 14(1~39), andthe rest had maximal tumor debulking (MTD), HIPEC was implementedin 96.3% of CCRS and 78.6% of MTD. The major morbidity (gradeIII/IV) was 11.4% and the 30-day operative mortality is 0.7%. The 5-and 10-year OS of CCRS was 76.9% and 64.1%, which is significantlyhigher than MTD (5-, 10-year OS as 36.1%, 27.1%; p20, MTD, high pathologic grade and without HIPECwere independent factors predicting poorer prognosis. Conclusions: CCRS+HIPEC can benefit PMP well with controllable risks. MTD+HIPEC maybenefit PMP as well when CCRS cannot be achieved after fully asscessmentby an experienced peritoneal maglignacy center, but the surgery should beperformed as limited as possible

Impact of intestinal microbiota on metabolic toxicity and potential detoxification of amygdalin

Amygdalin (Amy) is metabolized into cyanide in vivo, which may lead to fatal poisoning after oral administration. The defense mechanisms against toxic cyanide have not yet been adequately studied. In this study, comparative toxicokinetics study of Amy was performed in normal and pseudo germ-free rats. The efficiency of cyanide release was significant higher in normal group when given a single oral dose of 440 mg/kg (50% median lethal dose). Thiocyanate, the detoxification metabolite, was firstly detected in feces, caecum, and intestinal microbiota incubation enzymic system. The results suggest intestinal microbiota is involved in bidirectional regulation of toxicity and detoxification of Amy. We further identified the species related to cyanogenesis of Amy with metagenomic sequencing, such as Bifidobacterium pseudolongum, Marvinbryantia formatexigens, and Bacteroides fragilis. Functional analysis of microbiota reveals the detoxification potential of intestinal microbiota for cyanide. Sulfurtransferase superfamily, such as rhodanese, considered as main detoxification enzymes for cyanide, are largely found in Coriobacteriaceae bacterium, Butyricicoccus porcorum, Akkermansia muciniphila, etc. Besides, cyanoamino acid metabolism pathway dominated by Escherichia coli may contribute to the detoxification metabolism of cyanide. In summary, intestinal microbiota may be the first line of defense against the toxicity induced by Amy

Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia.

Bypassing tyrosine kinases responsible for Stat5a/b phosphorylation would be advantageous for therapy development for Stat5a/b-regulated cancers. Here, we sought to identify small molecule inhibitors of Stat5a/b for lead optimization and therapy development for prostate cancer and Bcr-Abl-driven leukemias. In silico screening of chemical structure databases combined with medicinal chemistry was used for identification of a panel of small molecule inhibitors to block SH2 domain-mediated docking of Stat5a/b to the receptor-kinase complex and subsequent phosphorylation and dimerization. We tested the efficacy of the lead compound IST5-002 in experimental models and patient samples of two known Stat5a/b-driven cancers, prostate cancer and chronic myeloid leukemia (CML). The lead compound inhibitor of Stat5-002 (IST5-002) prevented both Jak2 and Bcr-Abl-mediated phosphorylation and dimerization of Stat5a/b, and selectively inhibited transcriptional activity of Stat5a (IC50 = 1.5μmol/L) and Stat5b (IC50 = 3.5 μmol/L). IST5-002 suppressed nuclear translocation of Stat5a/b, binding to DNA and Stat5a/b target gene expression. IST5-002 induced extensive apoptosis of prostate cancer cells, impaired growth of prostate cancer xenograft tumors, and induced cell death in patient-derived prostate cancers when tested ex vivo in explant organ cultures. Importantly, IST5-002 induced robust apoptotic death not only of imatinib-sensitive but also of imatinib-resistant CML cell lines and primary CML cells from patients. IST5-002 provides a lead structure for further chemical modifications for clinical development for Stat5a/b-driven solid tumors and hematologic malignancies

The Relationship between Team Hometown Diversity and Team Creativity: From the Chinese Perspective

Since no specialized work has researched the relationship between team members’ hometown diversity (team hometown diversity) and team creativity, we investigated their underlying relationship by conducting a two-wave survey from 304 employees in 54 teams and 54 team leaders from 17 companies. The results proved that team hometown diversity was negatively related to both team information exchange and team creativity, while team information exchange was significantly positively associated with team creativity and the mediation effect of team information exchange between team hometown diversity and team creativity was verified. The moderation role of team identification in the relationship between team hometown diversity and team information exchange as well as the moderation function of team conformity on the relationship between team information exchange and team creativity were both verified. This work made at least four contributions. Firstly, it was among the first to research the impact of team hometown diversity on team creativity, which supplemented the gap and provided a new perspective for exploration of team creativity in future. Secondly, we adopted a two-wave design to check the dynamic impact of earlier team information exchange and team conformity on team creativity afterwards, which can be replicated for future studies. Thirdly, by using supervisor and subordinate ratings together and conducting electronic and paper surveys together, the results were more persuasive. Finally, we included a large dataset from a broad range of companies, which maximized the variables and generated our results. The implications and limitations were also illustrated

A Putative Type II Secretion System Is Involved in Cellulose Utilization in Cytophaga hutchisonii

Cytophaga hutchinsonii is a gliding cellulolytic bacterium that degrades cellulose in a substrate contact-dependent manner. Specific proteins are speculated to be translocated to its extracellular milieu or outer membrane surface to participate in adhesion to cellulose and further digestion. In this study, we show that three orthologous genes encoding the major components (T2S-D, -F, and -G) of type II secretion system (T2SS) are involved in cellulose degradation but not in cell motility. The individual disruption of the three t2s genes results in a significantly retarded growth on cellobiose, regenerated amorphous cellulose, and Avicel cellulose. Enzymatic analyses demonstrate that, whereas the endoglucanase activity of the t2s mutant cells is increased, the β-glucosidase activity is remarkably reduced compared to that of WT cells. Further analyses reveal that the t2s mutant cells not only exhibit a different profile of cellulose-bound outer membrane proteins from that of wild-type cells, but also display a significant decrease in their capability to adhere to cellulose. These results indicate that a functional link exits between the putative T2SS and cellulose utilization in C. hutchinsonii, and thus provide a conceptual framework to understand the unique strategy deployed by C. hutchinsonii to assimilate cellulose

Colonization of Bacteria on the Surfaces of Cold-Sprayed Copper Coatings Alters Their Electrochemical Behaviors

Copper coatings were fabricated on stainless steel plates by cold spraying. Attachment and colonization of Bacillus sp. on their surfaces in artificial seawater were characterized, and their effects on anticorrosion performances of the coatings were examined. Attached bacteria were observed using field emission scanning electron microscopy. Electrochemical behaviors including potentiodynamic polarization and electrochemical impedance spectroscopy with/without bacterial attachment were evaluated using commercial electrochemical analysis station Modulab. Results show that Bacillus sp. opt to settle on low-lying spots of the coating surfaces in early stage, followed by recruitment and attachment of extracellular polymeric substances (EPS) secreted through metabolism of Bacillus sp. The bacteria survive with the protection of EPS. An attachment model is proposed to illustrate the bacterial behaviors on the surfaces of the coatings. Electrochemical data show that current density under Bacillus sp. environment decreases compared to that without the bacteria. Charge-transfer resistance increases markedly in bacteria-containing seawater, suggesting that corrosion resistance increases and corrosion rate decreases. The influencing mechanism of bacteria settlement on corrosion resistance of the cold-sprayed copper coatings was discussed and elucidated

Mapping and verification of grain shape QTLs based on an advanced backcross population in rice.

Grain shape is a key factor that influences both the appearance quality and grain yield of rice. To clarify the genetic basis of grain shape, an advanced backcross population was developed from the cross of a slender indica variety Jin23B and a round japonica variety QingGuAi, and a total of 10 quantitative trait loci (QTLs) for grain shape were detected over 2 years. Three QTLs, qGW1, qGS3 and qGS7 have large effects on grain shape and were detected in both years. To further validate their effects, the BC4F2 populations of the three QTLs were constructed. The alleles from QingGuAi of qGW1 and qGS7 both greatly increase grain width and the alleles from Jin23B of qGS3 greatly increase grain length. The allele variations of the three QTLs lead to the totally different grain shape of the two rice varieties. Our study provides insights into the genetic bases of grain shape and will promote the improvements of grain quality and yield in rice

Asymmetry of Hippocampus and Amygdala Defect in Subjective Cognitive Decline Among the Community Dwelling Chinese

Background: Subjective cognitive decline (SCD) may be the first clinical sign of Alzheimer's disease (AD). SCD individuals with normal cognition may already have significant medial temporal lobe atrophy. However, few studies have been devoted to exploring the alteration of left-right asymmetry with hippocampus and amygdala in SCD. The aim of this study was to compare SCD individuals with amnestic mild cognitive impairment (MCI) patients and the normal population for volume and asymmetry of hippocampus, amygdala and temporal horn, and to assess their relationship with cognitive function in elderly population living in China.Methods: 111 SCD, 30 MCI, and 67 healthy controls (HC) underwent a standard T1-weighted MRI, from which the volumes of the hippocampus and amygdala were calculated and compared. Then we evaluated the pattern and extent of asymmetry in hippocampus and amygdala of these samples. Furthermore, we also investigated the relationship between the altered brain regions and cognitive function.Results: Among the three groups, SCD showed more depressive symptoms (p < 0.001) and higher percentage of heart disease (16.4% vs. 35.1%, p = 0.007) than controls. In terms of brain data, significant differences were found in the volume and asymmetry of both hippocampus and amygdala among the three groups (P < 0.05). In logistic analysis controlled by age, gender, education level, depression symptoms, anxiety symptom, somatic disease and lifestyle in terms of smoking, both SCD and MCI individuals showed significant decreased right hippocampal and amygdala volume than controls. For asymmetry pattern, a ladder-shaped difference of left-larger-than-right asymmetry was found in amygdala with MCI>SCD>HC, and an opposite asymmetry of left-less-than-right pattern was found with HC>SCD>MCI in hippocampus. Furthermore, correlation was shown between the volume of right hippocampus and right amygdala with MMSE and MoCA in SCD group.Conclusion: Our results supported that SCD individuals are biologically distinguishable from HC, and this may relate to cognitive impairment, although more longitudinal studies are need to investigate this further.Moreover, different levels of asymmetry in hippocampus and amygdala might be a potential dividing factor to differentiate clinical diagnosis

A novel transcriptional repressor specifically regulates xylanase gene 1 in Trichoderma reesei

Abstract Background The well-known industrial fungus Trichoderma reesei has an excellent capability of secreting a large amount of cellulases and xylanases. The induced expression of cellulase and xylanase genes is tightly controlled at the transcriptional level. However, compared to the intensive studies on the intricate regulatory mechanism of cellulase genes, efforts to understand how xylanase genes are regulated are relatively limited, which impedes the further improvement of xylanase production by T. reesei via rational strain engineering. Results To identify transcription factors involved in regulating xylanase gene expression in T. reesei, yeast one-hybrid screen was performed based on the promoters of two major extracellular xylanase genes xyn1 and xyn2. A putative transcription factor named XTR1 showing significant binding capability to the xyn1 promoter but not that of xyn2, was successfully isolated. Deletion of xtr1 significantly increased the transcriptional level of xyn1, but only exerted a minor promoting effect on that of xyn2. The xylanase activity was increased by ~ 50% with XTR1 elimination but the cellulase activity was hardly affected. Subcellular localization analysis of XTR1 fused to a green fluorescence protein demonstrated that XTR1 is a nuclear protein. Further analyses revealed the precise binding site of XTR1 and nucleotides critical for the binding within the xyn1 promoter. Moreover, competitive EMSAs indicated that XTR1 competes with the essential transactivator XYR1 for binding to the xyn1 promoter. Conclusions XTR1 represents a new transcriptional repressor specific for controlling xylanase gene expression. Isolation and functional characterization of this new factor not only contribute to further understanding the stringent regulatory network of xylanase genes, but also provide important clues for boosting xylanase biosynthesis in T. reesei