Organocatalyzed Asymmetric Michael Addition of 3-Fluorooxindole to Vinylidene Bisphosphonates.

Both the 3-fluorooxindole and germinal bisphosphonate structural motifs are prevalent in bioactive molecules because of their associated biological activities. We describe an approach to accessing 3,3-disubstituted 3-fluorooxindoles bearing a geminal bisphosphate fragment through a highly enantioselective Michael addition reaction between 3-fluorooxindoles and vinylidene bisphosphonates. These reactions are catalyzed by a commercially available cinchona alkaloid catalyst, have a broad substrate scope concerning 3-fluorooxindoles, and provide the corresponding addition products in a yield of up to 95% with an enantiomeric excess of up to 95%. A reasonable reaction pathway to explain the observed stereochemistry is also proposed.

Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells.

OBJECTIVE: This study aimed to assess the effect of the collagen/silk fibroin scaffolds seeded with human umbilical cord-mesenchymal stem cells on functional recovery after acute complete spinal cord injury. METHODS: The fibroin and collagen were mixed (mass ratio, 3:7), and the composite scaffolds were produced. Forty rats were randomly divided into the Sham group (without spinal cord injury), spinal cord injury group (spinal cord transection without any implantation), collagen/silk fibroin scaffolds group (spinal cord transection with implantation of the collagen/silk fibroin scaffolds), and collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (spinal cord transection with the implantation of the collagen/silk fibroin scaffolds co-cultured with human umbilical cord-mesenchymal stem cells). Motor evoked potential, Basso-Beattie-Bresnahan scale, modified Bielschowsky's silver staining, and immunofluorescence staining were performed. RESULTS: The BBB scores in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group were significantly higher than those in the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). The amplitude and latency were markedly improved in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). Meanwhile, compared to the spinal cord injury and collagen/silk fibroin scaffolds groups, more neurofilament positive nerve fiber ensheathed by myelin basic protein positive structure at the injury site were observed in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (p<0.01, p<0.05). The results of Bielschowsky's silver staining indicated more nerve fibers was observed at the lesion site in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.01, p< 0.05). CONCLUSION: The results demonstrated that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen/silk fibroin scaffolds could promote nerve regeneration, and recovery of neurological function after acute spinal cord injury.

China Public Psychology Analysis About COVID-19 Under Considering Sina Weibo Data.

COVID-19 not only poses a huge threat to public health, but also affects people's mental health. Take scientific and effective psychological crisis intervention to prevent large-scale negative emotional contagion is an important task for epidemic prevention and control. This paper established a sentiment classification model to make sentiment annotation (positive and negative) about the 105,536 epidemic comments in 86 days on the official Weibo of People's Daily, the test results showed that the accuracy of the model reached 88%, and the AUC value was greater than 0.9. Based on the marked data set, we explored the potential law between the changes in Internet public opinion and epidemic situation in China. First of all, we found that most of the Weibo users showed positive emotions, and the negative emotions were mainly caused by the fear and concern about the epidemic itself and the doubts about the work of the government. Secondly, there is a strong correlation between the changes of epidemic situation and people's emotion. Also, we divided the epidemic into three period. The proportion of people's negative emotions showed a similar trend with the number of newly confirmed cases in the growth and decay period, and the extinction period. In addition, we also found that women have more positive emotional performance than men, and the high-impact groups is also more positive than the low-impact groups. We hope that these conclusions can help China and other countries experiencing severe epidemics to guide publics respond.

Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells

SUMMARY OBJECTIVE: This study aimed to assess the effect of the collagen/silk fibroin scaffolds seeded with human umbilical cord-mesenchymal stem cells on functional recovery after acute complete spinal cord injury. METHODS: The fibroin and collagen were mixed (mass ratio, 3:7), and the composite scaffolds were produced. Forty rats were randomly divided into the Sham group (without spinal cord injury), spinal cord injury group (spinal cord transection without any implantation), collagen/silk fibroin scaffolds group (spinal cord transection with implantation of the collagen/silk fibroin scaffolds), and collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (spinal cord transection with the implantation of the collagen/silk fibroin scaffolds co-cultured with human umbilical cord-mesenchymal stem cells). Motor evoked potential, Basso-Beattie-Bresnahan scale, modified Bielschowsky's silver staining, and immunofluorescence staining were performed. RESULTS: The BBB scores in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group were significantly higher than those in the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). The amplitude and latency were markedly improved in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). Meanwhile, compared to the spinal cord injury and collagen/silk fibroin scaffolds groups, more neurofilament positive nerve fiber ensheathed by myelin basic protein positive structure at the injury site were observed in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (p<0.01, p<0.05). The results of Bielschowsky's silver staining indicated more nerve fibers was observed at the lesion site in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.01, p< 0.05). CONCLUSION: The results demonstrated that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen/silk fibroin scaffolds could promote nerve regeneration, and recovery of neurological function after acute spinal cord injury.

Collagen/heparan sulfate porous scaffolds loaded with neural stem cells improve neurological function in a rat model of traumatic brain injury.

One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site, resulting in poor adhesion and proliferation of neural stem cells at the injured area. To enhance the targeted delivery of exogenous stem cells to the injury site, cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain injury. Collagen/heparan sulfate porous scaffolds, prepared using a freeze-drying method, have stable physical and chemical properties. These scaffolds also have good cell biocompatibility because of their high porosity, which is suitable for the proliferation and migration of neural stem cells. In the present study, collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury, which was established using the controlled cortical impact method. At 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells, there was significantly improved regeneration of neurons, nerve fibers, synapses, and myelin sheaths in the injured brain tissue. Furthermore, brain edema and cell apoptosis were significantly reduced, and rat motor and cognitive functions were markedly recovered. These findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain injury. This study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People's Armed Police Force, China (approval No. 2017-0007.2) on February 10, 2019.

Preoperative CD4+CD25+/CD4+ and tumor diameter predict prognosis in male patients with bladder cancer.

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4+CD25+/CD4+ and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan-Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

Photosystem II of Ligustrum lucidum in response to different levels of manganese exposure.

The toxic effect of excessive manganese (Mn) on photosystem II (PSII) of woody species remains largely unexplored. In this study, five Mn concentrations (0, 12, 24, 36, and 48 mM) were used, and the toxicity of Mn on PSII behavior in leaves of Ligustrum lucidum was investigated using in vivo chlorophyll fluorescence transients. Results showed that excessive Mn levels induced positive L- and K- bands. Variable fluorescence at 2 ms (VJ) and 30 ms (VI), absorption flux (ABS/RC), trapped energy flux (TRo/RC), and dissipated energy flux (DIo/RC) increased in Mn-treated leaves, whereas the performance index (PIABS), electron transport flux (ETo/RC), maximum quantum yield (φPo), quantum yield of electron transport (φEo), and probability that an electron moves further than QA- (ψo) decreased. Also, excessive Mn significantly decreased the net photosynthesis rate and increased intercellular CO2 concentration. The results indicated that Mn blocked the electron transfer from the donor side to the acceptor side in PSII, which might be associated with the accumulation of QA-, hence limiting the net photosynthetic rate.

RS 504393 inhibits M-MDSCs recruiting in immune microenvironment of bladder cancer after gemcitabine treatment.

Bladder cancer (BC) is a malignant tumor of urinary epithelium. Gemcitabine is an introduced treatment for BC and also has immunomodulatory function, but the immunoregulation mechanism is not clear. In this study, we found that gemcitabine-treated BC cell recruited more monocyte-myeloid-derived suppressed cells (M-MDSCs), which played a significant role in immune suppression and contributed to cancer progression. We found that this phenomenon was induced by Chemokine (C-C motif) ligand 2 (CCL2), an M-MDSCs recruitment related monomeric polypeptide. Gemcitabine treatment promotes the generation of CCL2 and CCL2 could attach to C-C chemokine receptor type 2 (CCR2) to recruit M-MDSCs. We used RS 504393, a selective CCR2 antagonist, to inhibit the recruitment of M-MDSCs. RS 504393 improved the prognosis by blocking chemotaxis of M-MDSCs, and this finding sheds lights on how to prevent and alleviate the side effects occurred on the gemcitabine-treated BC patients.

miRNA­26a­5p and miR­26b­5p inhibit the proliferation of bladder cancer cells by regulating PDCD10.

MicroRNA (miR)­26a­5p and miR­26b­5p consistently play an antitumor role in many types of cancers, but the underlying mechanism remains unclear in bladder cancer (BC). In the present study, we found that, in BC tissues, the levels of miR­26a­5p and miR­26b­5p were lower than in paired normal tissues. The upregulation of miR­26­5p significantly inhibited the proliferation of BC cell lines (T24 and 5637). Bioinformatics analysis indicated that Programmed Cell Death 10 (PDCD10) was the downstream target gene of miR­26a­5p/miR­26b­5p, and this was ascertained by western blotting and quantitative real­time reverse transcription PCR (RT­qPCR). In addition, in the 3'­UTR of PDCD10, the binding site was identified using a luciferase reporter assay. We determined that clinical BC tissues presented higher PDCD10 levels than adjacent normal tissues and that PDCD10 promoted proliferation of BC cell lines. Overexpression of miR­26a­5p/miR­26b­5p inhibited the stimulatory effect on proliferation of BC cells induced by PDCD10. In addition, in vivo experiments and clinical data revealed that the prognosis of BC patients with high expression of miR­26a­5p/miR­26b­5p and low expression of PDCD10 was better than that of patients with low miR­26­5p and high PDCD10 expression. These data revealed that miR­26a­5p and miR­26b­5p were pivotal regulators in BC progression by targeting the proliferation­related protein, PDCD10. The miR­26­5p/PDCD10 interaction may provide important insight into the pathway of BC progression and present novel opportunities for future diagnosis and treatment strategies, especially for patients with high levels of PDCD10.

miRNA array analysis of plasma miRNA alterations in rats exposed to a high altitude hypoxic environment.

In the present study, the microRNA (miRNA) expression profiles of rats exposed to high altitude hypoxia and normal conditions were obtained from miRNA array analysis. Bioinformatics analyses, including the use of the Gene Oncology and Kyoto Encyclopedia of Genes and Genomes databases, were used to identify the genes and pathways, which were specifically associated with high altitude hypoxic environment­associated miRNAs. A total of 26 miRNAs were differentially expressed in the two groups, comprising six upregulated and 20 downregulated miRNAs. In the present study, a novel pattern of upregulated miRNAs and their associated pathways were constructed, including proteoglycans in cancer, spliceosome, gluamatergic synapse, glycolysis/gluconeogenesis, Foxo, cGMP­PKG and p53 signaling pathways, which may provide novel targets for diagnosing and understanding the mechanism of high altitude hypoxia­induced disease.

[Emission Characteristics of Vehicles from National Roads and Provincial Roads in China].

In recent years, with the rapid increase in automobile volume, vehicle emissions have become one of the major emission sources of urban air pollution in China. In China, most of the national and provincial roads have been the channels that connect different cities. Up until 2015, the length of national and provincial roads have reached 1.85×105 km and 3.29×105km, respectively, accounting for 13% of the mileage of all classified highways. Therefore, active research on vehicle emissions from national and provincial roads between cities in China is of great significance. Few studies have been conducted on air pollutant emissions from intercity vehicles. In this study, emission characteristics of intercity vehicles were investigated based on traffic monitoring data and the "calculation guide of air pollutant emission for road vehicles". The results showed that the CO, NOx, PM, and HC emissions accounted for 4.5%, 27.9%, 14.4%, and 7.7% of national vehicle emissions, respectively. There were significant differences in emission contributions among different types of intercity vehicles. Heavy trucks were major contributors to NOx, PM10, and PM2.5 emissions and motorcycles contributed most to CO and HC. Furthermore, there were significant differences in emission contributions of vehicle types on different road types; the major contributor of CO and HC emissions was small passenger cars on expressways. Motorcycles were the main contributors to CO and HC emissions on ordinary roads.

Core value of laparoscopic colorectal surgery.

Since laparoscopy was first used in cholecystectomy in 1987, it has developed quickly and has been used in most fields of traditional surgery. People have now accepted its advantages like small incision, quick recovery, light pain, beauty and short hospital stays. In early times, there are still controversies about the application of laparoscopy in malignant tumor treatments, especially about the problems of oncology efficacy, incision implantation and operation security. However, these concerns have been fully eliminated by evidences on the basis of evidence-basis medicine. In recent years, new minimally invasive technologies are appearing continually, but they still have challenges and may increase the difficulties of radical dissection and the risks of potential complications, so they are confined to benign or early malignant tumors. The core value of the laparoscopic technique is to ensure the high quality of tumor's radical resection and less complications. On the basis of this, it is allowed to pursue more minimally invasive techniques. Since the development of laparoscopic colorectal surgery is rapid and unceasing, we have reasons to believe that laparoscopic surgery will become gold standard for colorectal surgery in the near future.

The PTTG1-targeting miRNAs miR-329, miR-300, miR-381, and miR-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/PTTG1 regulation feedback loop.

Deregulation of the pituitary tumor transforming gene (PTTG1), a newly discovered oncogene, is a hallmark of various malignancies, including pituitary tumors. However, the mechanisms regulating PTTG1 expression are still needed to be explored. MicroRNAs (miRNAs) are a novel class of small RNA molecules that act as posttranscriptional regulators of gene expression and can play a significant role in tumor development. Here, we identified a series of miRNAs, namely, miR-329, miR-300, miR-381 and miR-655, which could target PTTG1 messenger RNA and inhibit its expression. Interestingly, all four miRNAs significantly that are downregulated in pituitary tumors were mapped to the 14q32.31 locus, which acts as a tumor suppressor in several cancers. Functional studies show that the PTTG1-targeting miRNAs inhibit proliferation, migration and invasion but induce apoptosis in GH3 and MMQ cells. Furthermore, overexpression of a PTTG1 expression vector lacking the 3'UTR partially reverses the tumor suppressive effects of these miRNAs. Next, we identified the promoter region of PTTG1-targeting miRNAs with binding sites for p53. In our hands, p53 transcriptionally activated the expression of these miRNAs in pituitary tumor cells. Finally, we found that PTTG1 could inhibit p53 transcriptional activity to the four miRNAs. These data indicate the existence of a feedback loop between PTTG1 targeting miRNAs, PTTG1 and p53 that promotes pituitary tumorigenesis. Together, these findings suggest that these PTTG1-targeting miRNAs are important players in the regulation of pituitary tumorigenesis and that these miRNAs may serve as valuable therapeutic targets for cancer treatment.

MicroRNA-873 (miRNA-873) inhibits glioblastoma tumorigenesis and metastasis by suppressing the expression of IGF2BP1.

Glioblastoma multiforme (GBM) is known as a highly malignant brain tumor with a poor prognosis, despite intensive research and clinical efforts. In this study, we observed that microRNA-873 (miR-873) was expressed at low levels in GBM and that the overexpression of miR-873 dramatically reduced the cell proliferation, migration, and invasion of GBM cells. Our further investigations of the inhibition mechanism indicated that miR-873 negatively affected the carcinogenesis and metastasis of GBM by down-regulating the expression of IGF2BP1, which stabilizes the mRNA transcripts of its target genes. These results demonstrate that miR-873 may constitute a potential target for GBM therapy.

[Effects of ginkgo diterpene lactones meglumine injection's activated carbon adsorption technology on officinal components].

With the diversion rate of ginkgolide A, B, K as comprehensive evaluation indexes, the amount of activated carbon, ad- sorption time, mix rate, and adsorption temperature were selected as factors, orthogonal design which based on the evaluation method of information entropy was used to optimize activated carbon adsorption technology of ginkgo diterpene lactones meglumine injection. Opti- mized adsorption conditions were as follows: adsorbed 30 min with 0.2% activated carbon in 25 °C, 40 r ·min⁻¹, validation test re- sult display. The optimum extraction condition was stable and feasible, it will provide a basis for ginkgo diterpene lactone meglumine injection' activated carbon adsorption process.

Down-regulated MYH11 expression correlates with poor prognosis in stage II and III colorectal cancer.

The MYH11 gene may be related to cell migration and adhesion, intracellular transport, and signal transduction. However, its relationship with prognosis is still uncertain. The aim of this study was to investigate correlations between MYH11 gene expression and prognosis in 58 patients with stage II and III colorectal cancer. Quantitative real-time polymerase chain reaction was performed in fresh CRC tissues to examine mRNA expression, and immunohistochemistry was performed with paraffin-embedded specimens for protein expression. On univariate analysis, MYH11 expression at both mRNA and protein levels, perineural invasion and lymphovascular invasion were related to disease-free survival (p<0.05; log-rank test). Cancers with lower MYH11 expression were more likely to have a poor prognosis. Otherwise, MYH11 expression was unrelated to patient clinicopathological features. On multivariate analysis, low MYH11 expression proved to be an independent adverse prognosticator (p<0.05). These findings show that MYH11 can contribute to predicting prognosis in stage II and III colorectal cancers.

Diagnostic value of thyroglobulin measurement with fine-needle aspiration biopsy for lymph node metastases in patients with a history of differentiated thyroid cancer.

PURPOSE: The aim of this study was to evaluate the diagnostic value of FNA-Tg for detecting lymph node metastases in patients with a history of differentiated thyroid cancer (DTC). MATERIALS AND METHODS: A total of 58 patients with DTC diagnosis and evidence of single or multiple suspicious cervical lymph nodes were assessed. All underwent total or near-total thyroidectomy with (35 cases) or without (23 cases) radioiodine (RAI) ablation, followed by thyroid stimulating hormone (TSH) suppression therapy. A total of 68 lymph nodes were examined by ultrasound-guided fine needle aspiration (US-FNA) for both cytological examination and FNA-Tg measurement. Serum Tg and anti-thyroglobulin antibody (TgAb) levels were also measured. Diagnostic performance including sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) of FNAC and FNA-Tg were calculated and compared. The Spearman's rank correlation coefficient was used to estimate the relationship between FNA-Tg and serum TgAb. RESULTS: The FNA-Tg levels were significantly higher with DTC metastatic lymph nodes (median 927.7 ng/mL, interquartile range 602.9 ng/mL) than non-metastatic lymph nodes (median 0.1 ng/mL, interquartile range 0.4 ng/mL) (p<0.01). Considering 1.0 ng/mL as a threshold value for FNA-Tg, the sensitivity, specificity, accuracy, PPV and NPV of FNA-Tg were 95.7%, 95.5%, 95.6%, 97.8% and 91.3%, respectively. The sensitivity and accuracy of the combination of FNAC and FNA-Tg were significantly higher than that of FNAC alone (p<0.05). The diagnostic performance of FNA-Tg was not significantly different between cases with or without RAI ablation, and the serum TgAb levels did not interfere with FNA-Tg measurements. CONCLUSIONS: Measurement of FNA-Tg is useful. The combination of FNAC and FNA-Tg is more sensitive and accurate for detecting lymph node metastases in patients with a history of DTC than FNAC alone. Serum TgAbs appear to be irrelevant for measurement of FNA-Tg.

Image-based color ink diffusion rendering.

This paper proposes an image-based painterly rendering algorithm for automatically synthesizing an image with color ink diffusion. We suggest a mathematical model with a physical base to simulate the phenomenon of color colloidal ink diffusing into absorbent paper. Our algorithm contains three main parts: a feature extraction phase, a Kubelka-Munk (KM) color mixing phase, and a color ink diffusion synthesis phase. In the feature extraction phase, the information of the reference image is simplified by luminance division and color segmentation. In the color mixing phase, the KM theory is employed to approximate the result when one pigment is painted upon another pigment layer. Then, in the color ink diffusion synthesis phase, the physically-based model that we propose is employed to simulate the result of color ink diffusion in absorbent paper using a texture synthesis technique. Our image-based ink diffusing rendering (IBCIDR) algorithm eliminates the drawback of conventional Chinese ink simulations, which are limited to the black ink domain, and our approach demonstrates that, without using any strokes, a color image can be automatically converted to the diffused ink style with a visually pleasing appearance.

[Advances in the study of epididymal protease inhibitor].

The epididymal protease inhibitor (Eppin) has recently been cloned in human and mice, which is specifically expressed in the epididymis and testis. Eppin is a cystine-rich secretory protein which contains signal peptide, WAP and BPTI motifs. Eppin is involved in sperm maturation and fertilization, and in the innate immune system of human epididymis. Immunocontraception with Eppin is effective and reliable, but its safety is to be further proved. This paper summarizes the effects of Eppin of fertilization and immunity, as well as its utilization in immunocontraception.