Direct ink writing 3D-printed optical waveguides for multi-layer interconnect.

Low-cost, short-range optical interconnect technology plays an indispensable role in high-speed board-level data communications. In general, 3D printing technology can easily and quickly produce optical components with free-form shapes, while the traditional manufacturing process is complicated and time-consuming. Here, we present a direct ink writing 3D-printing technology to fabricate optical waveguides for optical interconnects. The waveguide core is 3D printed optical polymethylmethacrylate (PMMA) polymer, with propagation loss of 0.21 dB/cm at 980 nm, 0.42 dB/cm at 1310 nm, and 1.08 dB/cm at 1550 nm, respectively. Furthermore, a high-density multilayer waveguide arrays, including a four-layer waveguide arrays with a total of 144 waveguide channels, is demonstrated. Error-free data transmission at 30 Gb/s is achieved for each waveguide channel, indicating that the printing method can produce optical waveguides with excellent optical transmission performance. We believe this simple, low-cost, highly flexible, and environmentally friendly method has great potential for high-speed short-range optical interconnects.

Discovery of a Nur77-mediated cytoplasmic vacuolation and paraptosis inducer (4-PQBH) for the treatment of hepatocellular carcinoma.

Nur77, an orphan nuclear receptor, has antitumor activity in hepatocellular carcinoma (HCC). However, its antitumor mechanisms of action in HCC are complicated and rarely reported. Our recent work demonstrated that certain quinoline-Schiff-base derivatives were good Nur77 mediators that exerted excellent anti-HCC activities in vitro and in vivo. Interestingly, these compounds shared similar chemical structures, but they displayed different Nur77-targeted anticancer mechanisms of action. As a continuous work, we synthesized a series of 4-(quinoline-4-amino) benzoylhydrazide derivatives and evaluated their anti-HCC activity and binding affinity to Nur77 in vitro. Compound 4-PQBH emerged as the best Nur77 binder (KD = 1.17 µM) and has potentially selective cytotoxicity to HCC cells. Mechanistically, 4-PQBH extensively induced caspase-independent cytoplasmic vacuolization and paraptosis through Nur77-mediated ER stress and autophagy. Moreover, 4-PQBH exhibited an effective xenograft tumor inhibition by modulating Nur77-dependent cytoplasmic vacuolation and paraptosis. This paper is the first to disclose that chemotherapeutic agents targeting Nur77-mediated cytoplasmic vacuolization and paraptosis may provide a promising strategy to combat HCC that frequently evade the apoptosis program.

Dynamic variations of dissolved organic matter from treated wastewater effluent in the receiving water: Photo- and bio-degradation kinetics and its environmental implications.

Dissolved effluent organic matter (dEfOM) from wastewater treatment plants (WWTPs) is bound to encounter photo- and bio-degradation as discharged into the receiving water body. However, the comprehensive variations of dEfOM by photo- and bio-degradation are not well unveiled because of its compositional heterogeneity. In this work, dissolved organic carbon (DOC) concentrations, UV-Vis and fluorescent spectra combined with fluorescence regional integration (FRI) analysis were used to investigate the changes in bulk dEfOM and its fluorescent components during photo- and bio-degradation processes in the receiving water body. Results showed that 48.49%-69.62% of the discharged dEfOM was decomposed by ultra violet (UV)-irradiation and indigenous microbes, while the others (33%-45%) were recalcitrant and stable in the receiving water body. Specifically, the photo- and bio-degradation of chromophoric, fluorescent dEfOM and its components were found to follow the single or double exponential kinetic model, and the differences in photo- and bio-degradability of each components shifted its composition. Furthermore, results of bio-degradation after UV-irradiated dEfOM indicated that there was overlapping of photo- and bio-degradable fractions in dEfOM, and photoreactions could improve the self-production of natural organic matter in the receiving water body. These results could improve the understanding the fate of discharged dEfOM in the receiving water body, and we proposed some cost-effective strategies for discharging WWTPs effluent.

Citrus Naringenin Increases Neuron Survival in Optic Nerve Crush Injury Model by Inhibiting JNK-JUN Pathway.

Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.

[Formulation of technical guidelines in line with characteristics and principles of traditional Chinese medicine changes to improve quality of such preparations--interpretation of Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines].

In leading the high-quality development of Chinese medicine preparations, it is an important link to formulate the scientific, reasonable, and feasible guidelines for the change of Chinese medicines in accordance with the change characteristics and principles of the Chinese medicines is an important work to promote the Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines was formed by a broad consensus based on the characteristics and research results of the pharmaceutical changes in Traditional Chinese Medicines(TCM)with the principles of science and risk management. This guideline has clarified the basic principles and requirements for the evaluation of changes in TCM, specified the research and verification work of common change scenarios, defined the boundaries of changes in TCM, and proposed to encourage the use of new technologies, new methods, and new excipients that meet product characteristics. It will definitely promote the quality improvement and the secondary development of TCM. In this article, the revision background and main content of the guideline were introduced, and the main features of the Guideline were analyzed, in order to provide references for the industry.

Linkage between water soluble organic matter and bacterial community in sediment from a shallow, eutrophic lake, Lake Chaohu, China.

Lacustrine sediment played important roles in migration and transformation of its water soluble organic matter (WSOM), and the source and composition of WSOM would affect water trophic status and the fate of pollutants. However, we know little about the pathway of WSOM transformation and its driving bacterial communities in lacustrine sediment. In the present study, we investigated the spatial distribution patterns of sediment WSOM and its fluorescent fractions across Lake Chaohu using fluorescence spectroscopy, and explored WSOM compositional structure through our proposed calculated ratios. In addition, we also analyzed sediment bacterial community using Illumina sequencing technology, and probed the possible pathway of sediment WSOM transformation under the mediate of indigenous bacteria. Our results showed that the inflowing rivers affected the spatial distribution patterns of WSOM and its five fractions (including tyrosine-, tryptophan-, fulvic acid-, humic acid-like substances and soluble microbial productions), and sediment WSOM originated from fresh algae detritus or bacterial sources. In parallel, we also found that Proteobacteria (mainly γ-Proteobacteria and δ-Proteobacteria), Firmicutes (mainly Bacilli), Chloroflexi, Acidobacteria, Planctomycetes and Actinobacteria dominate sediment bacterial community. Furthermore, these dominant bacteria triggered sediment WSOM transformation, specifically, the humic acid-like substances could be converted into fulvic acid-like substances, and further degraded into aromatic protein-like and SMP substances. In addition, our proposed ratios (P-L:H-L, Ar-P:SMP and H-L ratio), as supplementary tool, were effective to reveal WSOM composition structure. These results figured out possible pathway of WSOM transformation, and revealed its microbial mechanism in lacustrine sediment.

ß-TrCP-mediated ubiquitination and degradation of Dlg5 regulates hepatocellular carcinoma cell proliferation.

BACKGROUND: Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase (MAGUK) adaptor family of proteins and its deregulation has been implicated in the malignancy of several cancer types. Dlg5 was down-regulated in hepatocellular carcinoma (HCC) and lower Dlg5 expression was associated with poor survival of HCC patients. However, how to regulate Dlg5 remains largely unknown. METHODS: The co-immunoprecipitation assay was used to determine the interaction between Dlg5 and ß-TrCP. The in vivo ubiquitination assay was performed to determine the regulation of Dlg5 by ß-TrCP. CCK-8 and colony formation assay were implemented to detect the biological effect of Dlg5 on the growth of HCC cells in vitro. The effect of Dlg5 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. RESULTS: Here we report that Dlg5 is regulated by the ubiquitin proteasome system and depletion of either Cullin 1 or ß-TrCP led to increased levels of Dlg5. ß-TrCP regulated Dlg5 protein stability by targeting it for ubiquitination and subsequent destruction in a phosphorylation-dependent manner. We further demonstrated a crucial role of Ser730 in the non-canonical phosphodegron of Dlg5 in governing ß-TrCP-mediated Dlg5 degradation. Importantly, failure to degrade Dlg5 significantly inhibited HCC cells proliferation both in vitro and in vivo. CONCLUSION: Collectively, our finding provides a novel molecular mechanism for the negative regulation of Dlg5 by ß-TRCP in HCC cells. It further suggests that preventing Dlg5 degradation could be a possible novel strategy for clinical treatment of HCC.

Molecular characterisation of oestrogen receptor ERα and the effects of bisphenol A on its expression during sexual development in the Chinese giant salamander (Andrias davidianus).

The aim of this study was to characterise the molecular structure of the oestrogen receptor ERα and to evaluate the effect of bisphenol A (BPA) on ERα expression during sexual development of the Chinese giant salamander (Andrias davidianus). The ERα cDNA of A. davidianus includes an open reading frame of 1755bp (encoding 584 amino acids), a 219-bp 5' untranslated region (UTR) and a 611-bp 3'UTR. A polyadenylation signal was not found in the 3'UTR. Amino acid sequence analysis showed high homology between ERα of A. davidianus and that of other amphibians, such as Andrias japonicas (99.66% identity) and Rana rugose (81.06% identity). In 3-year-old A. davidianus, highest ERα expression was observed in the liver and gonads. During different developmental stages in A. davidianus (from 1 to 3 years of age), ERα expression in the testes increased gradually. ERα was localised in the epithelial cells of seminiferous lobules and in interstitial cells. ERα-positive cells were more abundant in the interstitial tissue during testicular development. ERα was located in the nucleus of oocytes during ovary development. We found that the sex of 6-month-old A. davidianus larvae could not be distinguished anatomically. The sex ratio did not change after larvae were treated with 10µM BPA for 1 month. However, BPA treatment reduced bodyweight and ERα expression in the gonads in male larvae.

Effect of manganese oxide-modified biochar addition on methane production and heavy metal speciation during the anaerobic digestion of sewage sludge.

Low organic matter content and high heavy metal levels severely inhibit the anaerobic digestion (AD) of sewage sludge. In this study, the effect of added manganese oxide-modified biochar composite (MBC) on methane production and heavy metal fractionation during sewage sludge AD was examined. The MBC could increase the buffering capacity, enhance the methane production and degradation of intermediate acids, buffer the pH of the culture, and stabilize the sewage sludge AD process. The application of MBC positively impacted methane production and the cumulative methane yield increased up to 121.97%, as compared with the control. The MBC addition can improve metal stabilization in the digestate. An optimum MBC dose of 2.36 g was recommended, which would produce up to 121.1 L/kg volatile solids of methane. After the AD process, even though most of the metals accumulated in the residual solids, they could be transformation from the bio-available fractions to a more stable fraction. The total organic- and sulfide-bound and residual fraction content at a 3 g dose of MBC that is 0.12 g/g dry matter were 51.06% and 35.11% higher than the control, respectively. The results indicated that the application of MBC could improve the performance of AD and promote stabilization of heavy metals in sewage sludge post the AD process.

Bacteria in Abnormal Eggs of Chinese Giant Salamanders (Andrias davidianus) May Derive from Gut.

Abnormal embryos of Chinese giant salamander (Andrias davidianus, CGS) were observed in an imitating ecologic breeding system at 20°C. The aim of the present study was to investigate the relationship of bacterial infection on the early embryonic development of CGS. The ratio of abnormal embryos at 10 days after embryos incubated was 35.0% ± 2.1%, 35.6% ± 2.3% and 34.7% ± 3.4% in six breeding system farms of Hanzhong city in the years 2014, 2015, and 2016, respectively. However, in the standard imitating ecology breeding mesocosm, the proportion of abnormal embryos was about 5%. Six bacteria species in the egg water of the early-dead embryos and eight bacteria species in the gut of healthy CGSs were detected and identified by PCR and 16S rRNA gene sequence homology analysis. All bacteria species in the egg water were also found in the cloaca contents. Cetobacterium somerae and Hafnia alvei, which individually can cause embryo death, were first isolated from egg water and gut of CGSs. Further, the egg jelly membrane and the egg water of embryos did not inhibit bacteria survival and the bacteria could individually lead to CGS larva death. These results suggest that bacteria in the eggs of CGS may derive from the gut and that high-velocity flow of water through nest may decrease bacterial infection of egg in the imitating ecologic culture system.

Comparative microRNAome analysis of the testis and ovary of the Chinese giant salamander.

MicroRNAs (miRNAs) are 18-24 nucleotides non-coding RNAs that regulate gene expression by post-transcriptional suppression of mRNA. The Chinese giant salamander (CGS, Andrias davidianus), which is an endangered species, has become one of the important models of animal evolution; however, no miRNA studies on this species have been conducted. In this study, two small RNA libraries of CGS ovary and testis were constructed using deep sequencing technology. A bioinformatics pipeline was developed to distinguish miRNA sequences from other classes of small RNAs represented in the sequencing data. We found that many miRNAs and other small RNAs such as piRNA and tsRNA were abundant in CGS tissue. A total of 757 and 756 unique miRNAs were annotated as miRNA candidates in the ovary and testis respectively. We identified 145 miRNAs in CGS ovary and 155 miRNAs in CGS testis that were homologous to those in Xenopus laevis ovary and testis respectively. Forty-five miRNAs were more highly expressed in ovary than in testis and 21 miRNAs were more highly expressed in testis than in ovary. The expression profiles of the selected miRNAs (miR-451, miR-10c, miR-101, miR-202, miR-7a and miR-499) had their own different roles in other eight tissues and different development stages of testis and ovary, suggesting that these miRNAs play vital regulatory roles in sexual differentiation, gametogenesis and development in CGS. To our knowledge, this is the first study to reveal miRNA profiles that are related to male and female CGS gonads and provide insights into sex differences in miRNA expression in CGS.

[Common questions and suggestions of evaluation for NDA of TCM].

According to the existing Provisions for Drug Registration (SFDA Order No. 28), applications for new drugs of traditional Chinese medicine are divided into two parts: the applications for drug clinical trial and for drug production (including new drug certificate). It will last for about 10 years from the application for drug clinical trial to get approving, and it also remains many problems and the low probability to succeed. From the sight of pharmaceutical review, there are mainly two aspects of regulatory compliance and technical issues, mainly for changes without approval of the competent authorities of the country. For example, sample preparation and approval of clinical trial process are significant changes. Technical problems are reporting incomplete data or information submitted does not comply with the technical requirements for review, such as: production process validation does not provide information, the preparation of samples for clinical trials and field inspection, production information, or the information provided does not meet the technical requirements. This paper summarizes the frequently asked questions and to make recommendations to advise applicants concerned, timely detection of problems, avoid risk, improving the quality and efficiency of the application for registration.

Mild salinization stimulated glyphosate degradation and microbial activities in a riparian soil from Chongming Island, China.

An incubation experiment was conducted to investigate the effects of simulated saltwater treatment with different percentages of artificial seawater on degradation dynamics of herbicide glyphosate and microbial activities in a riparian soil in Chongming Island, China. The results showed that 10% seawater treatment showed significantly enhancing effects on degradation efficiency of glyphosate with the lowest residual concentration among all the treatments. However, glyphosate degradation was markedly decreased in the riparian soil with 20% and 50% seawater treatments. The half-lives for 20% and 50% seawater treatments were prolonged by 12.1 and 39.0%, respectively, as compared to control. Microbial investigation indicated that 10% seawater treatment significantly stimulated microbial activities in the glyphosate-spiked riparian soil throughout the incubation period. At 42 day of incubation experiment, flourescein diacetate (FDA) hydrolysis rate, microbial adenosine triphosphate (ATP), and basal soil respiration (BSR) in the glyphosate-spiked riparian soil with 10% seawater were 59.2, 42.5 and 31.8% higher than those with no saltwater treatment, respectively. In contrast, saltwater treatment with 50% seawater significantly inhibited microbial activities. Especially, FDA hydrolysis rate, microbial ATP and BSR were decreased by 66.4, 58.6 and 66.8%, respectively, as compared to control. The results indicate that levels of simulated saltwater can exert variable effects on herbicide degradation dynamics and microbial parameters in the riparian soil.

Antimony and naphthalene can be simultaneously leached from a combined contaminated soil using carboxymethyl-ß-cyclodextrin as a biodegradable eluant.

In this study, we have investigated the removal efficiency of antimony (Sb) and naphthalene (Nap) from a combined contaminated soil by carboxymethyl-ß-cyclodextrin (CMCD) leaching and reveal its remediation mechanisms by FTIR and 1H NMR analyses. The results show that the highest removal efficiencies of Sb and Nap were 94.82% and 93.59%, respectively, with a CMCD concentration of 15 g L-1 at a pH of 4 and a leaching rate of 2.00 mL min-1 over an interval-time of 12 h. The breakthrough curves show that CMCD had a stronger inclusion capacity of Nap than Sb, and Sb could enhance the adsorption capacity of Nap, while Nap weakened the adsorption of Sb during CMCD leaching. Furthermore, the FTIR analysis suggests that the removal of Sb from combined contaminated soil involved complexation with the carboxyl and hydroxyl groups on CMCD, and the NMR analysis suggests that the inclusion of Nap occurred. These results indicate that CMCD is a good eluant for remediating soil contaminated by a combination of heavy metals and polycyclic aromatic hydrocarbons (PAHs), and its remediation mechanisms depend on the complexation reactions between the surface functional groups and inclusion reactions in the internal cavities.

Combined impacts of algae-induced variations in water soluble organic matter and heavy metals on bacterial community structure in sediment from Chaohu Lake, a eutrophic shallow lake.

Many lakes are suffering from eutrophication and heavy metals-contamination. However, the combined impacts of algae bloom and its induced variations in heavy metals on microbial community in sediment from eutrophic lakes remain unclear. In this study, we performed field experiments to investigate how algae bloom impacted water soluble organic matter (WSOM) and heavy metals in sediment from Chaohu Lake, a eutrophic shallow lake, and probed their combined impacts on sediment bacterial community structure. The results showed that algae bloom increased WSOM quantity, in particular, the soluble microbial by-product-like (SMP) and fulvic acid-like (Fa-L) components markedly enhanced by 203.70 % and 70.17 %, respectively. We also found that algae bloom redistributed the spatial patterns of heavy metals and altered their chemical species in sediment, then promoted contamination degree and potential ecological risk of heavy metals in sediment. Moreover, sediment bacterial community richness and diversity obviously decreased after algae bloom, and the variance partitioning analysis (VPA) results showed that combined impacts of algae-induced changes in WSOM and heavy metals explained 66.56 % of the variations in bacterial community structure. These findings depicted how algae bloom influence sediment WSOM and heavy metals, and revealed the combined impacts of algae-induced variations on microbial community structure in shallow eutrophic lake.

Hypoxia-inducible factor 1 regulated ARC expression mediated hypoxia induced inactivation of the intrinsic death pathway in p53 deficient human colon cancer cells.

Apoptosis repressor with caspase recruitment domain (ARC), an anti-apoptotic protein, plays an important role in the regulation of apoptosis by blocking both the extrinsic and intrinsic death pathways. However, its regulatory mechanism remains largely undefined. Here, we reported that hypoxia up-regulated the expression of ARC in p53 deficient human colon cancer cells. Moreover, ARC is a direct target of the hypoxia-inducible factor 1 (HIF-1), a key transcriptional factor for the cellular response to hypoxia. Silencing the expression of HIF-1α in SW480 colon cancer cells by RNA interference abolished hypoxia induced ARC expression. Using luciferase reporter and ChIP assay, we showed that HIF-1α directly bound to hypoxia-responsive element located at -419 to -414 of ARC gene, which is essential for HIF-1-induced expression. As a result of the increased ARC expression, TRAIL-induced apoptosis was reduced by hypoxia. These discoveries would shed novel insights on the mechanisms for ARC expression regulation and hypoxia induced inactivation of the intrinsic death pathway.

Influence of rhizosphere microbial ecophysiological parameters from different plant species on butachlor degradation in a riparian soil.

Biogeochemical processes in riparian zones regulate contaminant movement to receiving waters and often mitigate the impact of upland sources of contaminants on water quality. However, little research has been reported on the microbial process and degradation potential of herbicide in a riparian soil. Field sampling and incubation experiments were conducted to investigate differences in microbial parameters and butachlor degradation in the riparian soil from four plant communities in Chongming Island, China. The results suggested that the rhizosphere soil had significantly higher total organic C and water-soluble organic C relative to the nonrhizosphere soil. Differences in rhizosphere microbial community size and physiological parameters among vegetation types were significant. The rhizosphere soil from the mixed community of Phragmites australis and Acorus calamus had the highest microbial biomass and biochemical activity, followed by A. calamus, P. australis and Zizania aquatica. Microbial ATP, dehydrogenase activity (DHA), and basal soil respiration (BSR) in the rhizosphere of the mixed community of P. australis and A. calamus were 58, 72, and 62% higher, respectively, than in the pure P. australis community. Compared with the rhizosphere soil of the pure plant communities, the mixed community of P. australis and A. calamus displayed a significantly greater degradation rate of butachlor in the rhizosphere soil. Residual butachlor concentrations in rhizosphere soil of the mixed community of P. australis and A. calamus and were 48, 63, and 68% lower than three pure plant communities, respectively. Butachlor degradation rates were positively correlated to microbial ATP, DHA, and BSR, indicating that these microbial parameters may be useful in assessing butachlor degradation potential in the riparian soil.

[Excitation-emission matrix fluorescence spectra characteristics of DOM in a subsurface constructed wetland for advanced treatment of municipal sewage plant effluent].

Composition and dynamics of dissolved organic matter (DOM) were analyzed in a horizontal subsurface constructed wetland for advanced treatment of municipal sewage plant effluent using three-dimensional excitation emission matrix fluores cence spectroscopy (3D-EEM). The results indicate that the two subsurface constructed wetlands performed excellent purification of organic substances, and the removal rates of COD(cr), and DOC were 61.6% and 70.1%, respectively. The constructed wetland system filled with ceramsite showed slightly greater removal efficiency of organic substance than that with zeolite substrate. Four different types of peaks such as aromatic protein-like compounds (S), soluble microbial byproducts (T), fulvic acid-like compounds, visible fulvic-like (M) and UV fulvic-like compounds (A) were found in DOM from inflow and outflow of the subsurface wetlands based on the three-dimensional fluorescence spectroscopy analysis. The fluorescence intensity of the four peaks was significantly decreased in the effluent after purification by the subsurface constructed wetlands. Especially, the visible fulvic-like compounds and soluble microbial byproducts were effectively removed from the sewage plant effluent by the subsurface constructed wetland with fluorescence intensity reduction percentages of 16.4% and 11.7%. Aromatic structures of humic-like compounds were weakened and organic compounds with benzene rings were decreased in the outflow of the subsurface constructed wetland. This indicates that the subsurface constructed wetlands can decompose the chemically stable and biorefractory humic-like compounds. The fluorescence intensity of M and T peaks decreased along distance, while the fluorescence intensity of S peaks firstly increased, then decreased along the distance of the subsurface constructed wetlands. As compared to zeolite substrate constructed wetland system, the constructed wetland system filled with ceramsite was more effective to reduce the fluorescence intensity of characterized peaks of DOM from the sewage plant effluent.

SOX11-dependent CATSPER1 expression controls colon cancer cell growth through regulation the PI3K/AKT signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors and the fourth leading cause of cancer death worldwide. Constitutive activation of the PI3K/AKT signaling pathway is a hallmark of colon tumor growth. CATSPER1 gene encodes a pore-forming and pH-sensing subunit of the CatSper Ca2+-permeable channel, a sperm-specific calcium channel essential for hyperactivated motility and male fertility. However, the function of CATSPER1 outside the male reproductive system is unclear. OBJECTIVE: This study was designed to explore whether CatSper exerted its functional role in the progress of CRC, and investigate the possible mechanisms. METHODS: Microarray data (GSE146587) from 6 patients diagnosed with stage III CRC post-surgery was analyzed by Limma R package. The Kaplan Meier plotter (KM plotter) database was used to assess the relevance of CATSPER1 mRNA expression to the overall survival (OS) rates in CRC. Western blot, real-time PCR and luciferase reporter assays were used to determine the SOX11-CATSPER1 axis in CRC cells. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate CATSPER1 knockout (KO) CRC cells. The proliferation of CRC cells was determined by BrdU incorporation and colony formation assays. The effect of CATSPER1 on CRC tumor growth in vivo was investigated in a mice tumor xenograft model. RESULTS: Here, we show that CATSPER1 expression was significantly up-regulated in CRC and elevated CATSPER1 was associated with poor overall survival (OS). Moreover, the transcription factor SOX11 (SRY-related high-mobility-group (HMG) box 11) activated CATSPER1 transcription in CRC cells. Functionally, we showed that CATSPER1 promoted CRC cells proliferation both in vitro and in vivo. At the molecular level, we demonstrated that CATSPER1 might maintain CRC malignant process partly through the activation of the PI3K/AKT signaling pathway. CONCLUSION: Increased CATSPER1 expression facilitates CRC cells proliferation, suggesting that targeting CATSPER1 might represent a promising strategy for colon cancer treatment.

Cinnamaldehyde microcapsules enhance bioavailability and regulate intestinal flora in mice.

The effects of cinnamaldehyde microcapsules on the concentration of cinnamaldehyde and its metabolites in plasma, urine, and feces, the antioxidant capacity, and the intestinal flora in male C57/BL6 mice were evaluated by oral administration for 7 weeks. Microencapsulation significantly increased the contents of cinnamaldehyde, cinnamyl alcohol, and methyl cinnamate in plasma and decreased those in urine and feces excretion (p < 0.05). In addition, microencapsulated cinnamaldehyde improved antioxidant capacity in liver, duodenum, and colon. Furthermore, 16S rRNA gene sequencing data suggested that microencapsulated cinnamaldehyde significantly improved the gut microbial richness and diversity, increased  the abundance of Bacteroides, Bacteroidetes/Firmicutes, unclassified_f_Lachnospiraceae, Lactobacillus, and Blautia genera, and decreased in Ruminococcaceae_UCG-014, Faecalibaculum, norank_f_Muribaculaceae, and Gordonibacter genera, which was accompanied by the increased contents of butyric acid in feces. Therefore, microencapsulated cinnamaldehyde may increase its bioavailability and regulate the balance of intestinal flora.