CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.

Exosomes from human urine-derived stem cells carry NRF1 to alleviate bladder fibrosis via regulating miR-301b-3p/TGFßR1 pathway.

Bladder outlet obstruction (BOO) is a common disease that always make the bladder develops from inflammation to fibrosis. This study was to investigate the effect of exosomes from human urine-derived stem cells (hUSCs) on bladder fibrosis after BOO and the underlying mechanism. The BOO mouse model was established by inserting a transurethral catheter, ligation of periurethral wire, and removal of the catheter. Mouse primary bladder smooth muscle cells (BSMCs) were isolated and treated with TGFß1 to mimic the bladder fibrosis model in vitro. Exosomes from hUSCs (hUSC-Exos) were injected into the bladder of BOO mice and added into the culture of TGFß1-induced BSMCs. The associated factors in mouse bladder tissues and BSMCs were detected. It was confirmed that the treatment of hUSC-Exos alleviated mouse bladder fibrosis and down-regulated fibrotic markers (a-SMA and collagen III) in bladder tissues and TGFß1-induced BSMCs. Overexpression of NRF1 in hUSC-Exos further improved the effects of hUSC-Exos on bladder fibrosis both in vivo and in vitro. TGFßR1 was a target of NRF1 and miR-301b-3p, and miR-301b-3p was a target of NRF1. It was next characterized that hUSC-Exos carried NRF1 to up-regulate miR-301B-3p, thereby reducing TGFßR1level. Our results illustrated that hUSC-Exos carried NRF1 to alleviate bladder fibrosis through regulating miR-301b-3p/TGFßR1 pathway.

Robust Superhydrophobic PDMS@SiO2@UiO66-OSiR Sponge for Efficient Water-in-Oil Emulsion Separation.

A major challenge in oil/water separation is the processing of surfactant-stabilized emulsions from the water medium. One of the feasible schemes of emulsion separation is the porous melamine sponge coupled with functional particles. Here, we proposed a novel superhydrophobic metal-organic framework (MOF)-based sponge for water-in-oil emulsion separation. The porous melamine sponge was combined with poly(dimethylsiloxane) (PDMS)-coated hydrophobic SiO2 and UiO66-OSiR particles were prepared for demulsification via the one-step dipping method for the first time. The PDMS@SiO2@UiO66-OSiR sponge revealed excellent superhydrophobicity at a water contact angle of 160.7° and superlipophilicity at an oil contact angle of 0°. Compared with the pristine melamine sponge, the size-controllable PDMS@SiO2@UiO66-OSiR sponge could separate stabilized water-in-oil emulsions with ultrahigh separation efficiency (>98.64%) and high flux (e.g., 970 L·m-2·h-1). Meanwhile, the PDMS@SiO2@UiO66-OSiR sponge exhibited superior durability and mechanical reusability. Under harsh conditions such as strong acid and alkali, organic solvent corrosion, etc., all water contact angles of the PDMS@SiO2@UiO66-OSiR sponge were over 152°. Furthermore, the stress decreased by 5% when the sponge was subjected to 10 loading/unloading compression cycles at a constant strain of 60%. These results demonstrate that the PDMS@SiO2@UiO66-OSiR sponge can efficiently separate water-in-oil emulsions through its adjustable porous structure coupled with demulsification and hydrophobic particles. This study provides a step forward in developing a feasible strategy for the MOF-based sponge for emulsion separation.

ABT-263 exerts a protective effect on upper urinary tract damage by alleviating neurogenic bladder fibrosis.

This study investigated the mechanism of action of ABT-263 in the treatment of neurogenic bladder fibrosis (NBF)and its protective effects against upper urinary tract damage (UUTD). Sixty 12-week-old Sprague-Dawley (SD) rats were randomly divided into sham, sham + ABT-263 (50 mg/kg), NBF, NBF + ABT-263 (25 mg/kg, oral gavage), and NBF + ABT-263 (50 mg/kg, oral gavage) groups. After cystometry, bladder and kidney tissue samples were collected for hematoxylin and eosin (HE), Masson, and Sirius red staining, and Western Blotting (WB) and qPCR detection. Primary rat bladder fibroblasts were isolated, extracted, and cultured. After co-stimulation with TGF-ß1 (10 ng/mL) and ABT-263 (concentrations of 0, 0.1, 1, 10, and 100 µmol/L) for 24 h, cells were collected. Cell apoptosis was detected using CCK8, WB, immunofluorescence, and annexin/PI assays. Compared with the sham group, there was no significant difference in any physical parameters in the sham + ABT-263 (50 mg/kg) group. Compared with the NBF group, most of the markers involved in fibrosis were improved in the NBF + ABT-263 (25 mg/kg) and NBF + ABT-263 (50 mg/kg) groups, while the NBF + ABT-263 (50 mg/kg) group showed a significant improvement. When the concentration of ABT-263 was increased to 10 µmol/L, the apoptosis rate of primary bladder fibroblasts increased, and the expression of the anti-apoptotic protein BCL-xL began to decrease.ABT-263 plays an important role in relieving NBF and protecting against UUTD, which may be due to the promotion of myofibroblast apoptosis through the mitochondrial apoptosis pathway.

Anti-Spoofing Method for Improving GNSS Security by Jointly Monitoring Pseudo-Range Difference and Pseudo-Range Sum Sequence Linearity.

Spoofing interference is one of the most emerging threats to the Global Navigation Satellite System (GNSS); therefore, the research on anti-spoofing technology is of great significance to improving the security of GNSS. For single spoofing source interference, all the spoofing signals are broadcast from the same antenna. When the receiver is in motion, the pseudo-range of spoofing signals changes nonlinearly, while the difference between any two pseudo-ranges changes linearly. Authentic signals do not have this characteristic. On this basis, an anti-spoofing method is proposed by jointly monitoring the linearity of the pseudo-range difference (PRD) sequence and pseudo-range sum (PRS) sequence, which transforms the spoofing detection problem into the sequence linearity detection problem. In this paper, the model of PRD and PRS is derived, the hypothesis based on the linearity of PRD sequence and PRS sequence is given, and the detection performance of the method is evaluated. This method uses the sum of squares of errors (SSE) of linear fitting of the PRD sequence and PRS sequence to construct detection statistics, and has low computational complexity. Simulation results show that this method can effectively detect spoofing interference and distinguish spoofing signals from authentic signals.

Bone marrow mesenchymal stem cell-derived extracellular vesicles facilitate endometrial injury repair by carrying the E3 ubiquitin ligase WWP1.

Bone marrow mesenchymal stem cells-derived extracellular vesicles (BMSC-EVs) relieve endometrial injury. This study aimed to elucidate the BMSC-EV mechanism in alleviating endometrial injury. Endometrial injury model in vivo was induced using 95% ethanol, and endometrial epithelial cells (EECs) treated with mifepristone were applied as an endometrial injury model in vitro. After BMSCs and BMSC-EVs were isolated and identified, the BMSC-EV function was evaluated by hematoxylin-eosin and Masson staining, immunohistochemistry, quantitative real-time PCR, Cell Counting Kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and Transwell and tubule formation assays. The BMSC-EV mechanism was assessed using Western blot, ubiquitination, and cycloheximide-chase assays. After isolation and identification, BMSC-EVs were effective in endometrial injury repair in vivo and facilitated EEC proliferation and repressed cell apoptosis in vitro; the EEC supernatants accelerated human umbilical vein endothelial cell proliferation, migration, and invasion and facilitated angiogenesis after endometrial injury in vitro. For the BMSC-EV mechanism, E3 ubiquitin ligase WWP1 in BMSC-EVs mediated the ubiquitination of peroxisome proliferator-activated receptor gamma (PPARγ), thus relieving the PPARγ inhibition on vascular endothelial growth factor expression. Furthermore, the WWP1 in BMSC-EVs alleviated endometrial injury in vitro and in vivo. BMSC-EVs facilitated endometrial injury repair by carrying WWP1.

Molecular evolutionary process of advanced gastric cancer during sequential chemotherapy detected by circulating tumor DNA.

BACKGROUND: Efficacy of conventional sequential chemotherapy paradigm for advanced gastric cancer (AGC) patients has largely plateaued. Dynamic molecular changes during and after sequential chemotherapy have not been fully delineated. We aimed to profile the molecular evolutionary process of AGC patients during sequential chemotherapy by next generation sequencing (NGS) of plasma circulating tumor DNA (ctDNA). METHODS: A total of 30 chemo-naïve patients who were diagnosed with unresectable advanced or metastatic stomach adenocarcinoma were enrolled. All patients received sequential chemotherapy regimens following the clinical guideline. One hundred and eight serial peripheral blood samples were collected at baseline, radiographical assessment and disease progression. Plasma ctDNA was isolated and a customized NGS panel was used to detect the genomic features of ctDNA including single nucleotide variants (SNVs) and gene-level copy number variations (CNVs). KEGG pathway enrichment analysis was performed. RESULTS: Platinum-based combination chemotherapy was administrated as first-line regimen. Objective response rate was 50% (15/30). Patients with higher baseline values of copy number instability (CNI), CNVs and variant allel frequency (VAF) were more sensitive to platinum-based first-line regimens. Tumor mutation burden (TMB), CNI and CNV burden at partial response and stable disease were significantly lower than those at baseline, where at progressive disease they recovered to baseline levels. Dynamic change of TMB (ΔTMB) was correlated with progression-free survival of first-line treatment. Fluctuating changes of SNVs and gene-level CNVs could be observed during sequential chemotherapy. Under the pressure of conventional chemotherapy, the number of novel gene-level CNVs were found to be higher than that of novel SNVs. Such novel molecular alterations could be enriched into multiple common oncologic signaling pathways, including EGFR tyrosine kinase inhibitor resistance and platinum drug resistance pathways, where their distributions were found to be highly heterogenous among patients. The impact of subsequent regimens, including paclitaxel-based and irinotecan-based regimens, on the molecular changes driven by first-line therapy was subtle. CONCLUSION: Baseline and dynamic changes of genomic features of ctDNA could be biomarkers for predicting response of platinum-based first-line chemotherapy in AGC patients. After treatment with standard chemotherapy regimens, convergent oncologic pathway enrichment was identified, which is yet characterized by inter-patient heterogenous gene-level CNVs.

Camrelizumab and metronomic capecitabine for patients with treatment-refractory solid tumors (McCREST trial).

This is an open-label, single-center, multi-cohort phase Ib trial, which consists of three cohorts, including cohort 1 (HER2 negative gastric or gastric esophageal junction adenocarcinoma), cohort 2 (esophageal squamous cell carcinoma and head and neck squamous cell carcinoma) and cohort 3 (hepato-biliary-pancreatic and non-stomach non-esophagi gastrointestinal carcinoma). All eligible patients will be treated by camrelizumab (200 mg, every 2 weeks) and capecitabine (500 mg, twice a day, per os). The primary end point is the safety profiles of camrelizumab plus metronomic capecitabine according to CTCAE v5.0. The secondary end points are progression free survival, overall survival, objective response rate, disease control rate and duration of response. Planned enrollment is 20 subjects for each cohort. Total duration of this trial is expected to be 2 years.

Immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors have been used to treat gastrointestinal cancer patients in clinical practices. Combination with other drugs can improve the efficacy of ICIs. Metronomic chemotherapy using low dose and high frequency of cytotoxic drugs has multi-targeted anti-tumor effects and can be a potential partner of ICIs. In this study, the authors assess the safety and efficacy of a combination of a PD-1 inhibitor (camrelizumab) and an oral chemotherapy drug (capecitabine with metronomic dose) in patients with metastatic treatment-refractory solid tumors.

Biocompatible curcumin coupled nanofibrous membrane for pathogens sterilization and isolation.

Airborne transmission of pathogens is the most probable cause for the spread of respiratory diseases, which can be intercepted by personal protective equipment such as masks. In this study, an efficient antiviral personal protective filter was fabricated by coupling the biocompatible curcumin (CCM) with nanofibrous polytetrafluoroethylene (PTFE) membrane. The CCM extracted from plants was first dissolved in acidified ethanol at a certain pH and temperature to optimize its loading concentration, antiviral activation, and binding forces on the polyethylene terephthalate (PET) support to form a pre-filtration layer at the front section of the filter. Ultrathin PTFE membrane was then fabricated on the antibacterial-antiviral PET support (A-A PET) by controllable heating lamination. This functional layer of the filter exhibits good gas permeance (3423.6 m3/(m2·h·kPa)) and ultrafine particles rejection rate (>98.79%). Moreover, the obtained A-A filter exhibit a high antibacterial rate against a variety of bacteria (E. coli, B. subtilis, A. niger, and Penicillium were 99.84%, 99.02%, 93.60%, 95.23%, respectively). Forthwith virucidal (SARS-CoV-2) efficiency of the A-A filter can reach 99.90% for 5 min. The filter shows good stability after 10 heating cycles, demonstrating its reusability.

Early prediction of moderate-to-severe condition of inhalation-induced acute respiratory distress syndrome via interpretable machine learning.

BACKGROUND: Several studies have investigated the correlation between physiological parameters and the risk of acute respiratory distress syndrome (ARDS), in addition, etiology-associated heterogeneity in ARDS has become an emerging topic quite recently; however, the intersection between the two, which is early prediction of target conditions in etiology-specific ARDS, has not been well-studied. We aimed to develop and validate a machine-learning model for the early prediction of moderate-to-severe condition of inhalation-induced ARDS. METHODS: Clinical expertise was applied with data-driven analysis. Using data from electronic intensive care units (retrospective derivation cohort) and the three most accessible vital signs (i.e. heart rate, temperature, and respiratory rate) together with feature engineering, we applied a random forest approach during the time window of 90 h that ended 6 h prior to the onset of moderate-to-severe respiratory failure (the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤ 200 mmHg). RESULTS: The trained random forest classifier was validated using two independent validation cohorts, with an area under the curve of 0.9127 (95% confidence interval 0.8713-0.9542) and 0.9026 (95% confidence interval 0.8075-1), respectively. A Stable and Interpretable RUle Set (SIRUS) was used to extract rules from the RF to provide guidelines for clinicians. We identified several predictive factors, including resp_96h_6h_min < 9, resp_96h_6h_mean ≥ 16.1, HR_96h_6h_mean ≥ 102, and temp_96h_6h_max > 100, that could be used for predicting inhalation-induced ARDS (moderate-to-severe condition) 6 h prior to onset in critical care units. ('xxx_96h_6h_min/mean/max': the minimum/mean/maximum values of the xxx vital sign collected during a 90 h time window beginning 96 h prior to the onset of ARDS and ending 6 h prior to the onset from every recorded blood gas test). CONCLUSIONS: This newly established random forest­based interpretable model shows good predictive ability for moderate-to-severe inhalation-induced ARDS and may assist clinicians in decision-making, as well as facilitate the enrolment of patients in prevention programmes to improve their outcomes.

Effect of sidedness on survival among patients with early-stage colon cancer: a SEER-based propensity score matching analysis.

BACKGROUND: Most previous studies compared survival between left-sided and right-sided colon cancer without adjustment for clinicopathological parameters. We investigated the effect of sidedness on survival among patients with early-stage colon cancer, using a propensity score matching method. METHODS: The 18 registry custom data within the SEER database were used to identify patients who were diagnosed with colon cancer between 2010 and 2014. A propensity score matching analysis was performed using the nearest neighbor method. Survival was estimated using the Kaplan-Meier method. A Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: In the unmatched cohort, 25,094 (35.72%) patients were diagnosed with left-sided colon cancer and 45,156 (64.28%) with right-sided colon cancer. After propensity score matching, each cohort included 5118 patients, and the clinicopathological characteristics were well balanced. In the unmatched cohort, left-sided colon cancer had superior all-cause (χ2=315, P<0.01) and cancer-specific (χ2=43, P<0.01) survival than right-sided tumors. However, in the matched cohort, no difference was observed for all-cause (χ2=0.7, P=0.4) and cancer-specific (χ2=0, P=0.96) survival between left and right colon cancer. The Cox model did not indicate sidedness as a prognostic factor. In the subgroup analysis, stage II right-sided colon cancer had a better survival outcome, while stage III left-sided tumors had a better survival outcome. CONCLUSIONS: After adjusting for clinicopathological characteristics in this study, sidedness showed no impact on survival in early-stage colon cancer. However, sidedness was associated with prognostic differences in stages II and III early-stage colon cancer.

Identification, Characterization and Expression Analysis of Anthocyanin Biosynthesis-related bHLH Genes in Blueberry (Vaccinium corymbosum L.).

Basic helix-loop-helix proteins (bHLHs) play very important roles in the anthocyanin biosynthesis of many plant species. However, the reports on blueberry anthocyanin biosynthesis-related bHLHs were very limited. In this study, six anthocyanin biosynthesis-related bHLHs were identified from blueberry genome data through homologous protein sequence alignment. Among these blueberry bHLHs, VcAN1, VcbHLH42-1, VcbHLH42-2 and VcbHLH42-3 were clustered into one group, while VcbHLH1-1 and VcbHLH1-2 were clustered into the other group. All these bHLHs were of the bHLH-MYC_N domain, had DNA binding sites and reported conserved amino acids in the bHLH domain, indicating that they were all G-box binding proteins. Protein subcellular location prediction result revealed that all these bHLHs were nucleus-located. Gene structure analysis showed that VcAN1 gDNA contained eight introns, while all the others contained seven introns. Many light-, phytohormone-, stress- and plant growth and development-related cis-acting elements and transcription factor binding sites (TFBSs) were identified in their promoters, but the types and numbers of cis-elements and TFBSs varied greatly between the two bHLH groups. Quantitative real-time PCR results showed that VcAN1 expressed highly in old leaf, stem and blue fruit, and its expression increased as the blueberry fruit ripened. Its expression in purple podetium and old leaf was respectively significantly higher than in green podetium and young leaf, indicating that VcAN1 plays roles in anthocyanin biosynthesis regulation not only in fruit but also in podetium and leaf. VcbHLH1-1 expressed the highest in young leaf and stem, and the lowest in green fruit. The expression of VcbHLH1-1 also increased as the fruit ripened, and its expression in blue fruit was significantly higher than in green fruit. VcbHLH1-2 showed high expression in stem but low expression in fruit, especially in red fruit. Our study indicated that the anthocyanin biosynthesis regulatory functions of these bHLHs showed certain spatiotemporal specificity. Additionally, VcAN1 might be a key gene controlling the anthocyanin biosynthesis in blueberry, whose function is worth exploring further for its potential applications in plant high anthocyanin breeding.

Meltblown fabric vs nanofiber membrane, which is better for fabricating personal protective equipments.

The coronavirus disease 2019 (COVID-19) pandemic has led to a great demand on the personal protection products such as reusable masks. As a key raw material for masks, meltblown fabrics play an important role in rejection of aerosols. However, the electrostatic dominated aerosol rejection mechanism of meltblown fabrics prevents the mask from maintaining the desired protective effect after the static charge degradation. Herein, novel reusable masks with high aerosols rejection efficiency were fabricated by the introduction of spider-web bionic nanofiber membrane (nano cobweb-biomimetic membrane). The reuse stability of meltblown and nanofiber membrane mask was separately evaluated by infiltrating water, 75% alcohol solution, and exposing under ultraviolet (UV) light. After the water immersion test, the filtration efficiency of meltblown mask was decreased to about 79%, while the nanofiber membrane was maintained at 99%. The same phenomenon could be observed after the 75% alcohol treatment, a high filtration efficiency of 99% was maintained in nanofiber membrane, but obvious negative effect was observed in meltblown mask, which decreased to about 50%. In addition, after long-term expose under UV light, no filtration efficiency decrease was observed in nanofiber membrane, which provide a suitable way to disinfect the potential carried virus. This work successfully achieved the daily disinfection and reuse of masks, which effectively alleviate the shortage of masks during this special period.

Postoperative BMI Loss at One Year Correlated with Poor Outcomes in Chinese Gastric Cancer Patients.

Purpose: The present study focused on the long-term prognostic value of dynamic body mass index (BMI) change in gastric cancer patients who underwent gastrectomy. Methods: Clinical data from a total of 576 gastric cancer patients who underwent radical gastrectomy were collected. Univariate and multivariate analyses were performed to demonstrate the association between dynamic BMI variables (BMI before surgery, 1 month, 6 months or 12 months after surgery) and prognosis (DFS and OS). The correlation between BMI loss after surgery and survival outcomes was also evaluated. Results: Post-operative BMI, especially BMI at one year after surgery (p<0.001), was an independent risk factor of recurrence and mortality, wherein patients with high-BMI (≥23) showed significantly better outcomes than patients with normal-BMI (18.5-23) (DFS, HR:0.49; 95% CI:0.31-0.78; OS, HR:0.30; 95% CI: 0.15-0.59). On the contrary, low-BMI (<18.5) patients presented with worse outcomes (DFS, HR: 1.34; 95% CI: 1.00-1.80; OS, HR: 1.68; 95% CI: 1.20-2.34). In addition, compared with moderate BMI loss (≤10%), severe postoperative BMI loss (>10%) at one year was independently associated with substantially worse prognosis for DFS (HR: 1.54; 95% CI: 1.15-2.08) and OS (HR: 1.45; 95% CI: 1.02-2.06). Subgroup analysis indicated that gender (p=0.03), extent of resection (p<0.001), tumor site (p=0.001) and perineural invasion (p=0.007) were associated with postoperative BMI loss at one year. The prognostic value of postoperative BMI loss at one year was consistent among most clinicopathological subgroups, except for tumor site (interaction p=0.025 for OS). Conclusion: In Chinese gastric cancer patients who underwent gastrectomy, higher postoperative BMI (≥ 23) was significantly associated with longer survival time, whereas severe BMI loss (>10%) at one year after surgery was associated with worse outcomes. Thus, body weight maintenance after treatment is important, and dynamic monitoring of body weight and nutritional status should be emphasized in clinical practice.

Genome-Wide Identification and Characterization of UTR-Introns of Citrus sinensis.

Introns exist not only in coding sequences (CDSs) but also in untranslated regions (UTRs) of a gene. Recent studies in animals and model plants such as Arabidopsis have revealed that the UTR-introns (UIs) are widely presented in most genomes and involved in regulation of gene expression or RNA stability. In the present study, we identified introns at both 5'UTRs (5UIs) and 3'UTRs (3UIs) of sweet orange genes, investigated their size and nucleotide distribution characteristics, and explored the distribution of cis-elements in the UI sequences. Functional category of genes with predicted UIs were further analyzed using GO, KEGG, and PageMan enrichment. In addition, the organ-dependent splicing and abundance of selected UI-containing genes in root, leaf, and stem were experimentally determined. Totally, we identified 825 UI- and 570 3UI-containing transcripts, corresponding to 617 and 469 genes, respectively. Among them, 74 genes contain both 5UI and 3UI. Nucleotide distribution analysis showed that 5UI distribution is biased at both ends of 5'UTR whiles 3UI distribution is biased close to the start site of 3'UTR. Cis- elements analysis revealed that 5UI and 3UI sequences were rich of promoter-enhancing related elements, indicating that they might function in regulating the expression through them. Function enrichment analysis revealed that genes containing 5UI are significantly enriched in the RNA transport pathway. While, genes containing 3UI are significantly enriched in splicesome. Notably, many pentatricopeptide repeat-containing protein genes and the disease resistance genes were identified to be 3UI-containing. RT-PCR result confirmed the existence of UIs in the eight selected gene transcripts whereas alternative splicing events were found in some of them. Meanwhile, qRT-PCR result showed that UIs were differentially expressed among organs, and significant correlation was found between some genes and their UIs, for example: The expression of VPS28 and its 3UI was significantly negative correlated. This is the first report about the UIs in sweet orange from genome-wide level, which could provide evidence for further understanding of the role of UIs in gene expression regulation.

An Interface-Bridged Organic-Inorganic Layer that Suppresses Dendrite Formation and Side Reactions for Ultra-Long-Life Aqueous Zinc Metal Anodes.

Aqueous zinc (Zn) batteries (AZBs) are widely considered as a promising candidate for next-generation energy storage owing to their excellent safety features. However, the application of a Zn anode is hindered by severe dendrite formation and side reactions. Herein, an interfacial bridged organic-inorganic hybrid protection layer (Nafion-Zn-X) is developed by complexing inorganic Zn-X zeolite nanoparticles with Nafion, which shifts ion transport from channel transport in Nafion to a hopping mechanism in the organic-inorganic interface. This unique organic-inorganic structure is found to effectively suppress dendrite growth and side reactions of the Zn anode. Consequently, the Zn@Nafion-Zn-X composite anode delivers high coulombic efficiency (ca. 97 %), deep Zn plating/stripping (10 mAh cm-2 ), and long cycle life (over 10 000 cycles). By tackling the intrinsic chemical/electrochemical issues, the proposed strategy provides a versatile remedy for the limited cycle life of the Zn anode.

Droplet-based microfluidics systems in biomedical applications.

Microfluidics has made a very impressive progress in the past decades due to its unique and instinctive advantages. Droplet-based microfluidic systems show excellent compatibility with many chemical and biological reagents and are capable of performing variety of operations that can implement microreactor, complex multiple core-shell structure, and many applications in biomedical research such as drug encapsulation, targeted drug delivery systems, and multifunctionalization on carriers. Droplet-based systems have been directly used to synthesize particles and encapsulate many biological entities for biomedicine applications due to their powerful encapsulation capability and facile versatility. In this paper, we review its origin, deviation, and evolution to draw a clear future, especially for droplet-based biomedical applications. This paper will focus on droplet generation, variations and complication as starter, and logistically lead to the numerous typical applications in biomedical research. Finally, we will summarize both its challenge and future prospects relevant to its droplet-based biomedical applications.

Aquaporin1-3 expression in normal and hydronephrotic kidneys in the human fetus.

BACKGROUND: Decreased expression of the renal aquaporin (AQP) protein family is associated with hydronephrosis in adult humans and animals. However, the expression of AQPs, especially subtypes AQP1-3, which play a core role in the urinary concentration function, in hydronephrotic human fetuses is not clear. The aim of this study is to investigate the expression of the AQP1-3 in normal and hydronephrotic human fetal kidneys. METHODS: Twenty-one normal and six hydronephrotic kidney (HK) samples were harvested from abortive fetuses. Meanwhile, seven normal adult human kidney samples were collected as positive controls. Quantitative real-time PCR, western blotting, and immunohistochemistry were used to analyze the expression of AQP1-3. RESULTS: Both the protein and messenger mRNA expression levels of AQP1-3 increased with gestational age in the normal fetuses, but the levels were significantly lower than those in the adult tissues and significantly higher than those in the hydronephrotic fetuses at the same gestational age. CONCLUSIONS: The increased expression of AQP1-3 with gestational age in the fetal kidney may indicate maturation of the urinary concentrating ability. The lower expression of AQP1-3 in HKs may reflect a maturation obstacle with regard to urinary concentration in human hydronephrotic fetuses.

Expression pattern of CDK12 protein in gastric cancer and its positive correlation with CD8+ cell density and CCL12 expression.

Background: The aims of this study were to investigate the expression pattern of CDK12 protein in gastric cancer, and to analyze the correlations of CDK12 expression between CD8+ cell density and CCL12 expression. Methods: Eighty-six paired tumor and non-tumor samples were collected from patients who underwent radical surgery and had pathological confirmed gastric adenocarcinoma. Immunohistochemistry was used to assess CDK12 expression and CD8+ cell density. Expression of CDK12 and CCL21 mRNA was detected by quantitative reverse transcription-polymerase chain reaction. Results: CDK12 expression in gastric tumor tissues was significantly higher than it in paired non-tumor tissues (P<0.001). High expression of CDK12 was identified in 43 cases (50%), and it was significantly correlated with Lauren's classification (diffuse type) and number of metastatic lymph nodes (≥15). High CDK12 protein level indicated a relative poorer overall survival than patients with CKD12 low expression, while it was not identified as an independent prognostic factor. Median number of CD8+ cells in tumor tissues was 51 (range: 0-292). Number of CD8+ cells was positively correlated with CDK12 expression score in tumor tissues (r=0.243, P=0.024). Positive correlation was also found between CDK12 and CCL21 mRNA expression (r=0.419, P=0.017). Conclusion: High CDK12 expression was detected in gastric cancer which was correlated with malignant phenotypes and worse outcome. Positive correlations of CD8+ cell number and CCL21 mRNA expression with CDK12 level were identified.

Prognosis and risk factors of patients with upper urinary tract urothelial carcinoma and postoperative recurrence of bladder cancer in central China.

BACKGROUND: To investigate the prognostic risk factors and postoperative recurrence of bladder cancer in patients with upper urinary tract urothelial carcinomas (UTUCs). METHODS: Data of 439 UTUC patients were retrospectively analyzed. Follow-up and analysis of smoking effects, consumption of traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, sex, presence or absence of diabetes mellitus (DM), metformin use, tumor characteristics (number, location, stage, grade), and open or laparoscopic surgery on the prognosis of UTUCs were performed. Cox proportional hazard regression analysis was performed to analyze the relationship between various factors and the postoperative survival rate. The survival rate was analyzed using the Kaplan-Meier method. Moreover, logistic regression analysis was performed to analyze the relationship between the above mentioned factors and postoperative recurrence of bladder cancer. RESULTS: Overall, 439 patients met, including 236 males (53.7%) and 203 females (46.3%), the criteria for the final statistical analysis, and the average age was 66.7 years. The 1-, 3-, and 5-year overall survival rates of 439 UTUC patients were 90.0, 76.4, and 67.7%, respectively. The 5-year survival rates of T1, T2, T3, and T4 patients were 90.2%, 78%, 43.8%, and 18.5%, respectively. Factors influencing the long-term survival rate of UTUC patients were smoking, taking traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, tumor size, tumor stage, tumor grade, and lymph node metastasis. The risk factors related to postoperative bladder cancer recurrence were advanced tumor stage, high grade tumor, preoperative ureteroscopy, ureteral urothelial carcinoma, no postoperative bladder perfusion chemotherapy and DM without metformin use. CONCLUSIONS: Advanced tumor stage and presence of a high-grade tumor were risk factors for not only poor UTUC prognosis but also BC recurrence. In addition, preoperative ureteroscopy, ureteral urothelial carcinoma and DM without metformin use were high risk factors for BC recurrence, whereas regular postoperative bladder perfusion chemotherapy was a protective factor.