BLVRA exerts its biological effects to induce malignant properties of hepatocellular carcinoma cells via Wnt/ß-catenin pathway.

The function of Biliverdin Reductase A (BLVRA) in hepatocellular carcinoma (HCC) cells proliferation, invasion and migration remains unclear. Therefore, this research intends to explore the effect of BLVRA on HCC cells growth and metastasis. BLVRA expression was analyzed in public dataset and examined by using western blot. The malignant function of BLVRA in HCC cell lines and its effect on Wnt/ß-catenin pathway were measured. Analysis from GEPIA website showed that BLVRA expression was significantly increased in HCC tissues, and high expression of BLVRA resulted in worse prognosis of HCC patients. Results from western blot showed that BLVRA expression was obviously increased in HCC cell lines. Moreover, HepG2 and Hep3B cells in si-BLVRA-1 or si-BLVRA-2 group displayed an obvious reduction in its proliferation, cell cycle, invasion and migration compared to those in the si-control group. Additionally, si-BLVRA-1 or si-BLVRA-2 transfection significantly reduced the protein levels of Vimentin, Snail1 and Snail2, as well as decreased Bcl-2 expression and increased Bax and cleaved-caspase 3 expression. Furthermore, si-BLVRA treatment inhibited the protein levels of c-MYC, ß-catenin, and Cyclin D1. After IWP-4 (Wnt/ß-catenin inhibitor) treatment, the proliferation ability of HCC cells was significantly reduced. BLVRA expression was significantly increased in HCC tissues and cell lines, and knocked down of BLVRA could suppress the proliferation, invasion and migration in HCC cell lines, as well as induce cell apoptosis. Moreover, si-BLVRA transfection blocked the activation of Wnt/ß-catenin pathway.

Preparation and investigation of a novel antibacterial collagen-based material loaded with gentamicin following surface modification with citric acid for corneal tissue engineering.

Corneal disease is an important clinical problem that affects millions of blind people and keratoplasty is currently the most successful treatment for corneal blindness. Unfortunately, there is a very high risk of bacterial infection during corneal transplantation. In this study, we proposed a novel synthetic collagen-based film for corneal therapy, and we effectively incorporated aminoglycoside gentamicin molecules onto the surface of the collagen film. We anticipate that this collagen-based substance will be antimicrobial and repair corneal tissue damage. Three steps were used to create this gentamicin-modified carboxylated collagen film, including: (i) Cross-link the collagen molecules with 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and n-hydroxysuccinimide to create a collagen (Col) film. (ii) Citric acid was used to modify the Col film's surface in order to increase the number of carboxyl groups there (ColCA). (iii) Gentamicin molecules were grafted onto the surface of ColCA film by forming amide bonds (ColCA-GM). We discovered that this ColCA-GM film has good physicochemical properties and excellent biocompatibility. Furthermore, it was demonstrated that treating collagen films with citric acid significantly improved the antibacterial properties of ColCA-GM film. The outcomes point to a variety of potential applications for this novel film in corneal tissue engineering.

A solvent-responsive terbium-organic framework for photocatalytic CO2 reduction.

A Tb-MOF with a 5,5,6-c 3-nodal net, {[Tb(DTDA)1.5·2H2O]·DMF·8H2O}n (AQNU-4), has been synthesized (DTDA = 2',5'-diethoxy-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid). AQNU-4 contains a 1-periodic secondary building unit (rod SBU) and has an unusual topological type with the point symbol {32·44·62·7·8}{32·46·5·6}{32·46·52·65}. Efficient light harvesting and electron-hole separation make AQNU-4 an effective photocatalyst for use in the CO2 reduction reaction (CO2RR). Interestingly, as a photocatalyst, AQNU-4 shows an obvious solvent dependence during the catalytic process. In cyclohexanone in particular, it shows the highest CO2 to CO conversion, reaching 138.65 µmol g-1 h-1, making AQNU-4 a good solvent-responsive MOF material.

Preparation and Characterization of a Photo-Crosslinked Methacryloyl-Collagen Composite Film to Promote Corneal Nerve Regeneration via Surface Grafting of Taurine Molecules.

Blindness is frequently caused by corneal abnormalities, and corneal transplantation is the most effective treatment method. It is extremely important to develop high-quality artificial corneas because there are not enough donor corneas accessible for cornea transplantation. One of the most-often utilized materials is collagen, which is the primary component of natural cornea. Collagen-based corneal repair materials have good physicochemical properties and excellent biocompatibility, but how to promote the regeneration of the corneal nerve after keratoplasty is still a big challenge. In this research, in order to promote the growth of nerve cells on a collagen (Col) substrate, a novel collagen-based material was synthesized starting from the functionalization of collagen with unsaturated methacryloyl groups that three-dimensionally photopolymerize to a 3D network of chemically crosslinked collagen (ColMA), onto which taurine molecules were eventually grafted (ColMA-Tr). The physicochemical properties and biocompatibility of the Col, ColMA and ColMA-Tr films were evaluated. By analyzing the results, we found that all the three samples had good moisture retention and aq high covalent attachment of methacryloyl groups followed by their photopolymerization improved the mechanical properties of the ColMA and ColMA-Tr. Most importantly, compared with ColMA, the taurine-modified collagen-MA film significantly promoted the growth of nerve cells and corneal epithelial cells on its surface. Our preliminary results suggest that this novel ColMA-Tr film may have potential use in cornea tissue engineering in the future.

Microenvironment Modulation of Metal-Organic Frameworks (MOFs) for Coordination Olefin Oligomerization and (co)Polymerization.

The majority of commercial polyolefins are produced by coordination polymerization using early or late transition metal catalysts. Molecular catalysts containing these transition metals (Ti, Zr, Cr, Ni, and Fe, etc.) are loaded on supports for controlled polymerization behavior and polymer morphology in slurry or gas phase processes. Within the last few years, metal-organic frameworks (MOFs), a class of unique porous crystalline materials constructed from metal ions/clusters and organic ligands, have been designed and utilized as excellent supports for heterogeneous polymerization catalysis whose high density and uniform distribution of active sites would benefit the modulations of molecular weight distributions of high-performance olefin oligomers and (co)polymers. Impressive efforts have been made to modulate the microenvironment surrounding the active centers at the atomic level for improved activities of MOFs-based catalysts and controlled selectivity of olefin insertion. This review aims to draw a comprehensive picture of MOFs for coordination olefin oligomerization and (co)polymerization in the past decades with respect to different transition metal active centers, various incorporation sites, and finally microenvironment modulation. In consideration of more efforts are needed to overcome challenges for further industrial and commercial application, a brief outlook is provided.

One case of iodine-125 therapy - A new minimally invasive treatment of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer associated with a poor prognosis. ICC accounts for about 10% of primary liver malignancies but with increasing incidence in recent years. Recently, some studies suggested that minimally interventional therapy can be used in the treatment of ICC. However, there are few references on interventional therapy for the clinical treatment of ICC. Herein we reported a case of a 48-year-old man who suffered from ICC. The patient was diagnosed with ICC by computerized tomography scan and pathological biopsy. The patient was completely cured by minimally interventional therapy with iodine-125 seed implantation. These results provide an important reference for the treatment option of ICC.

Modification of Collagen Film via Surface Grafting of Taurine Molecular to Promote Corneal Nerve Repair and Epithelization Process.

Corneal defects can seriously affect human vision, and keratoplasty is the most widely accepted therapy method for visual rehabilitation. Currently, effective treatment for clinical patients has been restricted due to a serious shortage of donated cornea tissue and high-quality artificial repair materials. As the predominant component of cornea tissue, collagen-based materials have promising applications for corneal repair. However, the corneal nerve repair and epithelization process after corneal transplantation must be improved. This research proposes a new collagen-based scaffold with good biocompatibility and biological functionality enhanced by surface chemical grafting of natural taurine molecular. The chemical composition of collagen-taurine (Col-Tau) material is evaluated by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, and its hydrophilic properties, light transmittance, swelling performance and mechanical tensile properties have been measured. The research results indicate that the Col-Tau sample has high transmittance and good mechanical properties, and exhibits excellent capacity to promote corneal nerve cell growth and the epithelization process of corneal epithelial cells. This novel Col-Tau material, which can be easily prepared at a low cost, should have significant application potential for the treating corneal disease in the future.

Collagen Film with Bionic Layered Structure and High Light Transmittance for Personalized Corneal Repair Fabricated by Controlled Solvent Evaporation Technique.

Corneal blindness is a common phenomenon, and corneal transplantation is an effective treatment for corneal defects. However, there is usually a mismatch between the corneal repair material and the degree of the patient's corneal defect. Therefore, patients with different corneal defects need suitable corneal repair materials with a specific microstructure for personalized treatment. In this research, collagen films with bionic structures were fabricated through ethanol evaporation technique by regulating the volume ratios of collagen solution: ethanol = 10:0(Col)/9:1(CC91)/8:2(CC82)/CC73(CC73). Under various preparation conditions, the obtained collagen films contain layered structures of different density. SEM photos show that the CC73 film with a dense layer arrangement has a microstructure similar to that of the corneal epithelial layer, whereas the Col film has a loose layered structure similar to that of the corneal stroma layer. Four kinds of collagen films showed different optical properties and water absorption ability. A more ordered arrangement of internal layer structure leads to better mechanical properties of the collagen film. In view of this, we think that these collagen films with different microstructures and different interlayer spacing may have huge potential applications for personalized corneal repair.

Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China.

Purpose: Anlotinib, a novel multi-target tyrosine kinase inhibitor, has shown encouraging antitumor effects in advanced hepatocellular carcinoma (HCC). This study evaluated the effectiveness and safety of anlotinib with or without programmed death-1 (PD-1) blockades for patients with advanced primary HCC in a real-world setting in China. Patients and Methods: Between July 2019 and May 2021, 27 patients with advanced primary HCC who received at least 2 cycles of anlotinib were included in this retrospective study. Primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Of the 27 patients, ORR and DCR were 25.93% and 74.07%, respectively. The median follow-up time was 6.27 months (range: 1.30-17.40) with a median PFS and OS of 3.29 months (95% CI: 1.31-15.47) and 6.21 months (95% CI: 2.23-15.87), respectively. A total of 14 patients received anlotinib and PD-1 blockade combination therapy, and 13 received anlotinib monotherapy. No significant differences were observed in ORR (28.57 vs 23.08%), DCR (71.43 vs 76.92%), PFS (3.38 [95% CI: 2.66-13.14] vs 11.86 months [95% CI: 4.27-15.93]) and OS (4.90 [95% CI: 2.56-13.60] vs 11.04 months [95% CI: 1.31-17.18]) between the two groups (all p>0.05). Treatment-related AEs were reported in 88.89% of patients. Grade 3 AE was bleeding, which occurred in 3 patients (11.11%). Conclusion: Anlotinib yielded a promising efficacy and manageable safety in patients with advanced primary HCC irrespective of whether patients received PD-1 blockades, indicating that anlotinib might be a promising treatment option for this patient population.

Response to the Temperature and Solvent Stimulation of MOF Material in a Single-Crystal to Single-Crystal Manner.

Under solvothermal conditions, a three-dimensional mononuclear crystal AQNU-1, {[Co(H2L)(DPD)(H2O)2]·2DMA}n (H2L = 5-(bis(4-carboxybenzyl)amino)isophthalic acid, DPD = 4,4'-(2,5-diethoxy-1,4-phenylene)dipyridine) has been synthesized. The transformations of AQNU-1 to binuclear {[Co2(L)(DPD)1.5(H2O)3]·DMA·H2O}n (AQNU-2) and pentanuclear {[Co5(L)2(DPD)2(OH)2]·2H2O}n (AQNU-3) were realized by double stimulation of temperature and solvent, which were accomplished by single-crystal to single-crystal (SC-SC) reaction.

Multiscale Convolutional Neural Networks with Attention for Plant Species Recognition.

Plant species recognition is a critical step in protecting plant diversity. Leaf-based plant species recognition research is important and challenging due to the large within-class difference and between-class similarity of leaves and the rich inconsistent leaves with different sizes, colors, shapes, textures, and venations. Most existing plant leaf recognition methods typically normalize all leaf images to the same size and then recognize them at one scale, which results in unsatisfactory performances. A novel multiscale convolutional neural network with attention (AMSCNN) model is constructed for plant species recognition. In AMSCNN, multiscale convolution is used to learn the low-frequency and high-frequency features of the input images, and an attention mechanism is utilized to capture rich contextual relationships for better feature extraction and improving network training. Extensive experiments on the plant leaf dataset demonstrate the remarkable performance of AMSCNN compared with the hand-crafted feature-based methods and deep-neural network-based methods. The maximum accuracy attained along with AMSCNN is 95.28%.

Circular RNA circNTRK2 facilitates the progression of esophageal squamous cell carcinoma through up-regulating NRIP1 expression via miR-140-3p.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality. Circular RNAs (CircRNAs) have become a research hotspot in recent years for their vital roles in cancer development and progression. This study aims to clarify the roles of circNTRK2 and its underlying molecular mechanisms in ESCC. METHODS: The levels of circNTRK2, miR-140-3p, and nuclear receptor-interacting protein 1 (NRIP1) mRNA were examined by qRT-PCR. The cell proliferation ability was detected via CCK-8, EdU and colony formation assays. The invasion capacity was tested by using transwell assay. The apoptotic rate was evaluated through flow cytometry. The protein levels of cleaved PARP, cleaved caspase-3, E-cadherin, vimentin, and NRIP1 were measured by western blot assay. The validation of circular structure was performed by Sanger sequencing, divergent primer PCR, and RNase R treatments. The ceRNA regulatory mechanism of circNTRK2 was observed via dual-luciferase reporter, RIP and RNA pull-down assays. The mice xenograft models were constructed to confirm the oncogenicity of circNTRK2 in ESCC in vivo. RESULTS: CircNTRK2 was highly expressed in ESCC tissues and cells. High expression of circNTRK2 was correlated with advanced TNM stage, lymph node metastasis and short survival. Knockdown of circNTRK2 inhibited ESCC cell proliferation, invasion and epithelial-mesenchymal transition (EMT), and accelerated apoptosis in vitro. Mechanistic assays disclosed that circNTRK2 could act as a sponge for miR-140-3p to abate its suppression on target NRIP1 expression. Moreover, miR-140-3p-induced inhibitory effects on ESCC cell malignant phenotypes were attenuated by the overexpression of circNTRK2. In addition, depletion of NRIP1 impeded cell proliferation, invasion and EMT, while enhanced apoptosis. Furthermore, silencing of circNTRK2 suppressed cell proliferation and invasion through regulating NRIP1 expression. Also, knockdown of circNTRK2 slowed ESCC tumor growth in vivo. CONCLUSION: CircNTRK2 promoted ESCC progression by regulating miR-140-3p/NRIP1 pathway. Our findings contribute to a better understanding of circRNAs as miRNA sponges and highlight a promising therapy target in ESCC.

Light- and temperature-assisted spin state annealing: accessing the hidden multistability.

Among responsive multistable materials, spin crossover (SCO) systems are of particular interest for stabilizing multiple spin states with various stimulus inputs and physical outputs. Here, in a 2D Hofmann-type coordination polymer, [Fe(isoq)2{Au(CN)2}2] (isoq = isoquinoline), a medium-temperature annealing process is introduced after light/temperature stimulation, which accesses the hidden multistability of the spin state. With the combined effort of magnetic, crystallographic and Mössbauer spectral investigation, these distinct spin states are identified and the light- and temperature-assisted transition pathways are clarified. Such excitation-relaxation and trapping-relaxation joint mechanisms, as ingenious interplays between the kinetic and thermodynamic effects, uncover hidden possibilities for the discovery of multistable materials and the development of multistate intelligent devices.

Retracted Article: Panax notoginseng saponins regulate VEGF to suppress esophageal squamous cell carcinoma progression via DVL3-mediated Wnt/ß-catenin signaling.

Panax notoginseng saponins (PNS) have recently attracted increasing attention for their anti-tumor activities. The aim of this study was to explore the functional role and underlying mechanisms of PNS on the progression of esophageal squamous cell carcinoma (ESCC). The mRNA levels of vascular endothelial growth factor (VEGF), ß-catenin and dishevelled-3 (DVL3) were assessed using qRT-PCR. Western blot was performed to detect the expression levels of VEGF, ß-catenin and DVL3. Cell viability and proliferation abilities were determined using MTT assay. Transwell assays were used to evaluate cell migration and invasion capacities. Our data revealed that PNS hampered the viability of ESCC cells. VEGF silencing weakened proliferation, migration and invasion in ESCC cells. Mechanistically, PNS time-dependently reduced VEGF expression and PNS hampered ESCC cell proliferation, migration and invasion through VEGF. Moreover, ß-catenin and DVL3 were upregulated in ESCC tissues and cells and positively correlated with VEGF level in ESCC tissues. VEGF regulated DVL3 via the Wnt/ß-catenin signaling pathway in ESCC cells. Furthermore, PNS repressed DVL3 expression through VEGF in ESCC cells. Our study suggested that PNS suppressed ESCC progression at least partly through repressing VEGF via the DVL3-mediated Wnt/ß-catenin signaling pathway, indicating that PNS might be promising anti-tumor agents for ESCC treatment.

Oral Lactobacillus reuteri LR06 or Bifidobacterium BL5b supplement do not produce analgesic effects on neuropathic and inflammatory pain in rats.

BACKGROUND: Previous studies have reported that certain bacteria exert visceral antinociceptive activity in visceral pain and may also help to relieve neuropathic and inflammatory pain. OBJECTIVE: The aim of this study was to explore the analgesic effect of Lactobacillus reuteri LR06 (LR06) or Bifidobacterium BL5b (BL5b) in chronic pain in vivo. DESIGN: Rats were randomly assigned into four groups: sham, Chronic Constriction Injury (CCI)/Complete Freund's Adjuvant (CFA) + control, CCI/CFA + LR06, and CCI/CFA + BL5b. Rats from the probiotic groups were treated with 1 x 109 cfu (LR06 or BL5b) daily through gavage for 14 days after a pain model was successfully established. Mechanical and thermal hyperalgesia were used to assess the analgesic effect of the probiotics. Iba1 was used to verify the microglial inflammatory reaction in the different groups. RESULTS: The results showed that probiotics L. reuteri LR06 or Bifidobacterium BL5b had no significant antinociception effects in chronic pain rats. The chronic pain-induced activation of microglia (Iba1) was not relieved by probiotics in CCI/CFA-induced neuropathic or inflammatory pain rats. CONCLUSION: Our results suggested that L. reuteri LR06 or Bifidobacterium BL5b had no antinociceptive effects on CCI-induced neuropathic pain and CFA-induced inflammatory pain in rats.

An excellent example illustrating the fluorescence sensing property of cobalt-organic frameworks.

A novel luminescent cobalt-organic framework was assembled and employed as a chemosensor for the detection of metal ions via fluorescence enhancement and quenching. The sensing mechanism was based on the exposed pyridyl and carboxyl functional sites in the MOF structure, which interacted with metal ions via Lewis acid-base interactions and electrostatic interactions.

The Mutation in the Single-Crystal Structural Transformation Process, Induced by the Combined Stimuli of Temperature and Solvent.

A 2D coordination polymer containing a free ligand (Lf ), fixed by hydrogen bonds, transformed into a 3D metal-organic framework (MOF) in a single-crystal to single-crystal fashion. This transformation occurs through the combined stimuli of temperature and solvent. From 50 to 90 °C, a series of changes take place in a gradual form: the Lf is slowly moved to the cobalt center, which is accompanied by a contraction of unit cell and hydrogen bond. When the temperature rises to 95 °C, the hydrogen bond is destroyed, and Lf is suddenly combined with the cobalt ion to form an intricate 3D structure. This mutation process is irreversible and cannot occur just with the stimulus of either temperature or solvent. Notably, even under the combined stimuli, this mutation phenomena is difficult to reproduce when the solvent species and proportions change. DFT calculations were used to try to explain the nature of the phenomenon.

Proteomic Identification of an Upregulated Isoform of Annexin A3 in the Spinal Cords of Rats in a Neuropathic Pain Model.

Neuropathic pain (NP) is induced by nerve damage or a disturbance in the peripheral or central nervous systems. Nerve damage causes the activation of sensitizing mechanisms in the peripheral and central nervous systems, which induces transcriptional and post-transcriptional alterations in sensory nerves. However, the underlying mechanisms of NP remain elusive. In the study, Two-dimensional gel electrophoresis (2DGE)-based comparative proteomics identified 38 differential gel spots, and 15 differentially expressed proteins (DEPs) between the sham and the chronic constriction injury (CCI)-induced neuropathic pain rats. Of them, Annexin A3 (ANXA3) was significantly increased after CCI with Western blot analysis and immunofluorescence imaging. A lentivirus delivering ANXA3 shRNA (LV-shANXA3) was administered intrathecally to determine the analgesic effects of ANXA3 on allodynia and hyperalgesia in a CCI-induced neuropathic pain model in rats. Further study showed that LV-shANXA3 reversed the upregulation of ANXA3, alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. The study indicated that ANXA3 may play an important role in neuropathic pain.