Bone Marrow Mesenchymal Stem Cells-Derived miR-21-5p Protects Grafted Islets Against Apoptosis by Targeting PDCD4.

The apoptosis of grafted islets is an urgent problem due to the high rate of islet loss soon after transplantation. MicroRNA-21-5p (miR-21-5p) is an essential mediator of bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exo) during anti-apoptosis, but its effect and the underlying molecular mechanism in islet transplantation remain partially understood. Here, we found that miR-21-5p could be delivered to islet cells via BMSCs-Exo. Subsequently, we demonstrated that miR-21-5p overexpression reduced apoptosis in islets and INS-1 cells, whereas miR-21-5p inhibition enhanced apoptosis. A mechanistic analysis involving RNA sequencing and bioinformatic analysis was performed to determine the interaction between miR-21-5p and its target gene programmed cell death 4 (PDCD4), which was further verified by a dual luciferase assay. In vivo, the grafted islets overexpressing miR-21-5p showed a higher survival rate, better insulin secretion function, and a lower apoptosis rate. In conclusion, these results demonstrated that miR­21­5p from BMSCs-Exo protects against the apoptosis of grafted islets by inhibiting PDCD4 expression. Hence, miR-21-5p can be used as a cell-free therapeutic agent to minimize ß-cell apoptosis at the early stage of islet transplantation.

Low concentrations of saracatinib promote definitive endoderm differentiation through inhibition of FAK-YAP signaling axis.

Optimizing the efficiency of definitive endoderm (DE) differentiation is necessary for the generation of diverse organ-like structures. In this study, we used the small molecule inhibitor saracatinib (SAR) to enhance DE differentiation of human embryonic stem cells and induced pluripotent stem cells. SAR significantly improved DE differentiation efficiency at low concentrations. The interaction between SAR and Focal Adhesion Kinase (FAK) was explored through RNA-seq and molecular docking simulations, which further supported the inhibition of DE differentiation by p-FAK overexpression in SAR-treated cells. In addition, we found that SAR inhibited the nuclear translocation of Yes-associated protein (YAP), a downstream effector of FAK, which promoted DE differentiation. Moreover, the addition of SAR enabled a significant reduction in activin A (AA) from 50 to 10 ng/mL without compromising DE differentiation efficiency. For induction of the pancreatic lineage, 10 ng/ml AA combined with SAR at the DE differentiation stage yielded a comparative number of PDX1+/NKX6.1+ pancreatic progenitor cells to those obtained by 50 ng/ml AA treatment. Our study highlights SAR as a potential modulator that facilitates the cost-effective generation of DE cells and provides insight into the orchestration of cell fate determination.

Promoter replication of grape MYB transcription factor is associated with a new red flesh phenotype.

KEY MESSAGE: In our study, we discovered a fragment duplication autoregulation mechanism in 'ZS-HY', which may be the reason for the phenotype of red foliage and red flesh in grapes. In grapes, MYBA1 and MYBA2 are the main genetic factors responsible for skin coloration which are located at the color loci on chromosome 2, but the exact genes responsible for color have not been identified in the flesh. We used a new teinturier grape germplasm 'ZhongShan-HongYu' (ZS-HY) which accumulate anthocyanin both in skin and flesh as experimental materials. All tissues of 'ZS-HY' contained cyanidin 3-O-(6″-p-coumaroyl glucoside), and pelargonidins were detected in skin, flesh, and tendril. Through gene expression analysis at different stage of flesh, significant differences in the expression levels of VvMYBA1 were found. Gene amplification analysis showed that the VvMYBA1 promoter is composed of two alleles, VvMYBA1a and 'VvMYBA1c-like'. An insertion of a 408 bp repetitive fragment was detected in the allele 'VvMYBA1c-like'. In this process, we found the 408 bp repetitive fragment was co-segregated with red flesh and foliage phenotype. Our results revealed that the 408 bp fragment replication insertion in promoter of 'VvMYBA1c-like' was the target of its protein, and the number of repeat fragments was related to the increase of trans-activation of VvMYBA1 protein. The activation of promoter by VvMYBA1 was enhanced by the addition of VvMYC1. In addition, VvMYBA1 interacted with VvMYC1 to promote the expression of VvGT1 and VvGST4 genes in 'ZS-HY'. The discovery of this mutation event provides new insights into the regulation of VvMYBA1 on anthocyanin accumulation in red-fleshed grape, which is of great significance for molecular breeding of red-fleshed table grapes.

Internet development, information availability, and Chinese enterprises' cooperative green technology innovation.

Cooperative green technology innovation is potentially the answer to the lack of motivation for independent green innovation, which can effectively alleviate many difficulties faced by enterprises engaging in independent green innovation. Internet development provides new opportunities to stimulate innovative cooperation of enterprises. However, little literature has studied the impact of Internet development on enterprises' cooperative green technology innovation. Based on the data of Chinese A-share 3284 listed companies from 2010 to 2019, this paper uses a panel two-way fixed effects model to assess the effect of Internet development on enterprises' cooperative green innovation. The findings are: (1) Internet development significantly drives firms' collaborative green innovation behavior. The result remains robust even after performing a series of robust tests. (2) The Internet empowers green innovation cooperation among firms by improving information availability, including market information availability and technical information availability. (3) The heterogeneous results show enterprises use the Internet to accomplish high-quality collaborative green innovation. Internet development is more helpful in encouraging the cooperative green innovation of enterprises located in central cities and state-owned enterprises. This study provides novel and targeted policy implications to empower enterprises' green innovation cooperation and drive sustainable economic development through Internet development.

Gold nanoparticles and gold nanorods in the landscape of cancer therapy.

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

DBU-Mediated Isomerization/6-π Electro-Cyclization/Oxidation Cascade of Sulfonyl-Substituted Allenyl Ketones for the Construction of Hetero-1,3,5-Trisubstituted Benzene.

1,3,5-tri-substituted benzene rings emerged with unique properties has widespread applications in materials, boosting the rapid development of their synthesis. Despite the significance, the direct construction of hetero-1,3,5-trisubstituted benzene core was far less-developed. Herein, we realized a DBU-mediated isomerization/6-π electro-cyclization/oxidative aromatization cascade of sulfonyl-substituted allenyl ketones under an air atmosphere (DBU=1,8-diazabicyclo[5.4.0]undec-7-ene). This versatile protocol featured metal-free conditions, easy operation, and broad functional group tolerance provides a new avenue for the construction of hetero-1,3,5-tri-substituted benzene.

Phenolic metabolites as therapeutic in inflammation and neoplasms: Molecular pathways explaining their efficacy.

Polyphenols, also known as phenolic compounds, are chemical substances containing aromatic rings as well as at least two hydroxyl groups. Natural phenolic compounds exist widely in plants, which protect plants from ultraviolet radiation and other insults. Phenolic compounds have superior pharmacological and nutritional properties (antimicrobial, antibacterial, antiviral, anti-sclerosis, antioxidant, and anti-inflammatory activities), which have been paid more and more attention by the scientific community. Phenols can protect key cellular components from reactive free radical damage, which is mainly due to their property to activate antioxidant enzymes and alleviate oxidative stress and inflammation. It can also inhibit or isolate reactive oxygen species and transfer electrons to free radicals, thereby avoiding cell damage. It has a regulatory role in glucose metabolism, which has a promising prospect in the prevention and intervention of diabetes. It also prevents cardiovascular disease by regulating blood pressure and blood lipids. Polyphenols can inhibit cell proliferation by affecting Erk1/2, CDK, and PI3K/Akt signaling pathways. Polyphenols can function as enhancers of intrinsic defense systems, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Simultaneously, they can modulate multiple proteins and transcription factors, making them promising candidates in the investigation of anti-cancer medications. This review focuses on multiple aspects of phenolic substances, including their natural origins, production process, disinfection activity, oxidative and anti-inflammatory functions, and the effects of different phenolic substances on tumors.

BMSCs overexpressed ISL1 reduces the apoptosis of islet cells through ANLN carrying exosome, INHBA, and caffeine.

Early apoptosis of grafted islets is one of the main factors affecting the efficacy of islet transplantation. The combined transplantation of islet cells and bone marrow mesenchymal stem cells (BMSCs) can significantly improve the survival rate of grafted islets. Transcription factor insulin gene enhancer binding protein 1 (ISL1) is shown to promote the angiogenesis of grafted islets and the paracrine function of mesenchymal stem cells during the co-transplantation, yet the regulatory mechanism remains unclear. By using ISL1-overexpressing BMSCs and the subtherapeutic doses of islets for co-transplantation, we managed to reduce the apoptosis and improve the survival rate of the grafts. Our metabolomics and proteomics data suggested that ISL1 upregulates aniline (ANLN) and Inhibin beta A chain (INHBA), and stimulated the release of caffeine in the BMSCs. We then demonstrated that the upregulation of ANLN and INHBA was achieved by the binding of ISL1 to the promoter regions of the two genes. In addition, ISL1 could also promote BMSCs to release exosomes with high expression of ANLN, secrete INHBA and caffeine, and reduce streptozocin (STZ)-induced islets apoptosis. Thus, our study provides mechanical insight into the islet/BMSCs co-transplantation and paves the foundation for using conditioned medium to mimic the ISL1-overexpressing BMSCs co-transplantation.

Mechanical stability of angulated zirconia abutments supporting maxillary anterior single crowns on narrow-diameter implants.

OBJECTIVES: To investigate the fracture strength of angulated hybrid abutments supporting anterior single crowns on narrow-diameter implants (NDIs). MATERIAL AND METHODS: Zirconia abutment with angulations of labial inclination 0° (TZ0Z), 15° (TZ15Z), 30° (TZ30Z) and palatal inclination 15° (TZ - 15Z) was designed on 3.3-mm titanium-zirconium (Ti-Zr) NDIs. Titanium abutment connected with Ti-Zr implant (TZ0T) and 0° zirconia abutment connected with pure titanium (Ti) implant (T0Z) were control groups. Thirty-six un-restored abutments and 36 abutments restored with highly translucent zirconia (HTZ) crowns were tested. Failure loads were compared among 6 groups, and bending moments were calculated for comparison between un-restored and restored abutments. RESULTS: Failure loads of un-restored abutments were affected by the abutment angle. Sixty-seven percent samples in TZ30Z and 83% samples in TZ - 15Z group fractured at the thinnest part of the zirconia abutment and exhibited lower failure load (p < .05). Failure loads of restored abutments were close to or exceeded the maximum bite force of anterior teeth, and no differences were found among six groups (p > .05). Except TZ15Z and TZ0T group, the bending moment increased with the crown construction, especially for TZ30Z and TZ - 15Z groups (p < .001). CONCLUSIONS: The fracture strength of hybrid abutments restored with HTZ crown on Ti-Zr NDIs exceeded the bite forces of anterior teeth for all the groups and were not affected by the abutment angle. CLINICAL RELEVANCE: In terms of fracture strength, Ti-Zr NDIs combined with angulated hybrid abutments and HTZ crowns can be used in the anterior region.

Evaluating the synergistic effect of digitalization and industrialization on total factor carbon emission performance.

Combating climate change and reducing carbon dioxide emissions are serious challenges shared by countries around the world. In the current era, digitalization has a significant impact on CO2 emissions. However, prior studies have not assessed the synergy between digitalization and industrialization on carbon emission performance. The principal component analysis and non-radial directional distance function (NDDF) are used to measure the digitalization and total factor carbon emission performance of Chinese 245 prefecture-level cities from 2003 to 2019. This study establishes a fixed effects model to study the panel data. The findings are as follows: (1) Digitalization can significantly promote Chinese cities' CO2 emission reduction. This result still holds after several robustness checks. (2) The heterogeneity results indicate that digitalization mainly improves central cities' carbon emission performance. Meanwhile, the impact of digitalization is more obvious after 2011. (3) Digitalization improves urban carbon emission performance through energy efficiency, industrial transformation, and technological innovation. (4) It is worth noting that digitalization synergizes with industrialization to improve carbon emission performance in Chinese cities. This study provides empirical evidence and some constructive policy recommendations for the government to push the collaborative development of the digitalization and low-carbon economy.

The Mechanism of Action of Nanomaterials Loaded with Clarithromycin after Sinusitis Surgery under the Guidance of Dynamic Enhanced Scanning.

This study was to explore the mechanism of action of nanomaterial-loaded clarithromycin (CLA) after sinusitis surgery. Under the guidance of dynamic enhanced scanning (DES). 120 patients with sinusitis admitted to the First Affiliated Hospital of China Medical University from July 2019 to March 2020 were selected and divided into a control group and an observation group according to the random number table method, with 60 cases in each group. Then, the CLA-containing nano-polylactic acid material was prepared, observed with the scanning electron microscope (SEM), and its drug release ability was tested. All patients underwent endoscopic sinus surgery under general anesthesia. After the surgery was completed, patients in the control group were given only CLA capsules, and patients in the observation group were given freshly prepared nanomaterial-loaded CLA, and both groups of patients were continuously observed for two weeks. After that, the patients were examined using the dynamic enhancement computed tomography (CT). The clinical efficacy, serum interleukin-4 (IL-4), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α) levels of the two groups of patients were observed. The secretions of the patients' sinuses were performed with microbial bacterial culture, and the results were observed and recorded. Results showed that the characterization and analysis of the nano drug-carrying preparation suggested that the polylactic acid nanomembrane showed linear fiber morphology, relatively dense distribution, not greatly different fiber diameter, and small porosity. Characterization under a field of view (FOV) of 500 um showed that the fiber surface was smooth and rich in content. The release of CLA showed a gradual and steady upward trend. On the 25th day, nearly 50% of the dose had been released, and it had reached more than 90% of the total release on the 55th day. According to the statistics on the clinical efficacy of patients, it was found that the number of cured and effective patients in the observation group was higher than that of the control group, while the number of ineffective cases was much lower than that of the control group. The dynamic enhanced CT examination results of the patients in the control group after treatment showed that the soft tissue mass on the posterior right side of the nasopharynx was reduced, but the pharyngeal suture still existed; while those in the observation group showed that the plain scan density was uniform, and the mastoid air cells were clear on both sides. The number of cases with Staphylococcus aureus (S. aureus), Staphylococcus saprophyticus (S. saprophyticus), and Pasteurella multocida infections in the observation group were observably lower than those of the control group (P< 0.05), and it was the same case for the levels of serum IL-4, IL-8, and TNF-α. Conclusion: after dynamic enhanced CT scanning, it can be found that the nanomaterial-loaded CLA increased the utilization rate of the drug, showing good clinical efficacy, and effectively improved the clinical symptoms of patients, achieving the therapeutic effect.

How does digital finance influence green technology innovation in China? Evidence from the financing constraints perspective.

Green innovation activities of enterprises often fall into the dilemma of financing constraints. Hence, it is urgent that the financial system develops and becomes innovative, especially for a developing country like China. Existing literature mainly explores the influencing factors of green innovation from the environmental regulation, economic growth and government subsidies perspective. However, few papers critically study how digital finance influences green innovations. To explore the internal influencing mechanism of digital finance on the quantity and quality of green technology innovation, panel data of 271 prefecture-level cities from 2011 to 2019 in China is used. Based on theoretical analysis and empirical research, we get the following conclusions. First, digital finance can improve the quantity and quality of green technological innovation, which has become a significant driving force for green innovations in China. The results are still robust after the endogeneity tests. Second, the results of heterogeneous analysis indicate that the different dimensions of digital finance can improve green innovations. They include breadth of coverage, depth of use, and degree of digitization. The positive effect of digital finance is most substantial in eastern cities, followed by central cities, and weakest in western cities. Third, digital finance indirectly improves green innovation mainly by alleviating financing constraints. Our empirical results provide policy enlightenment for realizing the coordination of China's urban digital transformation and green economic development.

ß-Cyclodextrin polymer@Fe3 O4 based magnetic solid-phase extraction coupled with HPLC for the determination of benzoylurea insecticides from honey, tomato, and environmental water samples.

In this work, a magnetic ß-cyclodextrin polymer was successfully prepared and used as an adsorbent for the magnetic solid-phase extraction of six benzoylurea insecticides (diflubenzuron, triflumuron, hexaflumuron, teflubenzuron, flufenoxuron, and chlorfluazuron) from honey, tomato, and environmental water samples. The influence of the main experimental conditions on the extraction was studied. Under the optimized conditions, the ß-cyclodextrin polymer@Fe3 O4 showed an excellent extraction performance for the benzoylurea insecticides. A good linearity was obtained for the analytes in the range of 3.0-800 ng/g for honey samples, 0.3-160 ng/g for tomato samples, and 0.1-80.0 ng/mL for water samples, with the correlation coefficients above 0.9998. Satisfactory repeatabilities were achieved, with the relative standard deviations less than 5.7%. The limits of detection (S/N = 3) of the method for the benzoylurea insecticides were 0.2-0.8 ng/g for honey samples, 0.04-0.10 ng/g for tomato samples, and 0.02-0.05 ng /mL for water samples. The method was successfully used for the determination of the six benzoylurea insecticides residues in honey, tomato, and environmental water samples with a satisfactory result.

A hyper-cross linked polymer as an adsorbent for the extraction of chlorophenols.

A porous material (polytriphenylamine; PTPA) was synthesized by using triphenylamine as the monomer and dimethoxymethane as the cross-linker. PTPA was characterized by Fourier infrared spectrometry, X-ray diffraction measurements, scanning electron microscopy and N2 adsorption-desorption isotherms. The PTPA has a spherical-shape morphology and relatively high specific surface area. It is shown to be a viable adsorbent for solid phase extraction of 3-chlorophenol, 2,3-dichlorophenol, 2,4-dichlorophenol and 2,4.6-trichlorophenol prior to their determination by high performance liquid chromatography-mass spectrometry. Under the optimized conditions, recoveries from spiked samples are in the range from 92.5% to 106.3%. The limits of detection range from 0.03 to 0.3 ng mL-1 (at an S/N ratio of 3) in case of bottled juice, and from 0.03 to 0.1 ng g-1 in case of tomato samples. The enrichment factors for the four analytes are in the range of 127-183 for bottle juice, and from 110-150 for tomatos. Response is linear in the range of 1.0 to 40.0 ng mL-1 for juice, and 0.3-40.0 ng g-1 for tomatos. The relative standard deviations for the determination of the chlorophenols at 20 ng mL-1 in bottled beverage, and 20 ng g-1 in tomatos are lower than 5.7%. Graphical abstract A polytriphenylamine polymer (PTPA) was prepared by using an external cross-linker method with triphenylamine as monomer and dimethoxymethane as cross-linker, and it was used as an adsorbent to extract chlorophenols from juice and vegetable samples.

Preparation of a magnetic porous carbon with hierarchical structures from waste biomass for the extraction of some carbamates.

In this study, corn stalk was used to synthesize a magnetic adsorbent by pyrolysis together with KHCO3 as the chemical activator and iron(III) salt as the magnetic reagent. The characterization by scanning electron microscopy, transmission electron microscopy and N2 adsorption-desorption analysis showed that the magnetic carbon adsorbent had a structure of hierarchical pores with a high specific surface area. To evaluate its adsorption performance, the adsorbent was used for the extraction of carbamates pesticides (propoxur, isoprocarb and fenobucarb) from water and zucchini samples before high-performance liquid chromatography analysis. The result showed that the adsorbent had a good adsorption capability for the analytes. Under the optimized conditions, a good linearity for the analytes existed in the range of 0.1-100.0 ng/mL for water samples and 0.5-100.0 ng/g for zucchini samples with the correlation coefficients of 0.9992-0.9998. The limits of detection for the analytes at a signal to noise ratio of 3 were 0.03 ng/mL for water samples and 0.20-0.50 ng/g for zucchini samples.

Magnetic mesoporous polymelamine-formaldehyde resin as an adsorbent for endocrine disrupting chemicals.

A magnetic mesoporous poly(melamine-formaldehyde) composite (Fe3O4-mPMF) was prepared via grafting poly(melamine-formaldehyde) onto the surface of amino-functionalized magnetite (Fe3O4) nanoparticles. The material was characterized by scanning electron micrography, transmission electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, nitrogen adsorption-desorption isotherms, and thermogravimetric analysis. It has a large surface area, a typical mesoporous structure, and a high thermal stability. It was employed as a magnetic sorbent for the solid phase extraction of the following endocrine disrupting chemicals (EDCs): Bisphenol A, 4-tert-butylphenol, 4-tert-octylphenol and nonylphenol. The EDCs were then quantified by HPLC. Under the optimized conditions, the response to the EDCs is linear in the range of 0.5-100 ng·mL-1, and the limits of detection are 0.02-0.1 ng·mL-1. The high adsorption capability of the Fe3O4-mPMF is mainly attributed to multiple interactions including π-stacking, hydrogen bonding, and hydrophobic interactions. The method was applied to the extraction of EDCs from spiked river water and bottled juice samples. The results demonstrated that the Fe3O4-mPMF is an efficient adsorbent for the extraction of organic compounds with large conjugated π-system, plenty of hydrogen-bonding sites, and strong hydrophobicity. Graphical abstract A magnetic mesoporous polymelamine-formaldehyde composite (Fe3O4-mPMF) was prepared and employed as a magnetic sorbent for the solid phase extraction of endocrine disrupting chemicals from river water and bottled juice samples prior to high-performance liquid chromatographic analysis.

Magnetic porous carbon derived from a metal-organic framework as a magnetic solid-phase extraction adsorbent for the extraction of sex hormones from water and human urine.

An iron-embedded porous carbon material (MIL-53-C) was fabricated by the direct carbonization of MIL-53. The MIL-53-C possesses a high surface area and good magnetic behavior. The structure, morphology, magnetic property, and porosity of the MIL-53-C were studied by scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, and N2 adsorption. With the use of MIL-53-C as the magnetic solid-phase extraction adsorbent, a simple and efficient method was developed for the magnetic solid-phase extraction of three hormones from water and human urine samples before high-performance liquid chromatography with UV detection. The developed method exhibits a good linear response in the range of 0.02-100 ng/mL for water and 0.5-100 ng/mL for human urine samples, respectively. The limit of detection (S/N = 3) for the analytes was 0.005-0.01 ng/mL for water sample and 0.1-0.3 ng/mL for human urine sample. The limit of quantification (S/N = 10) of the analytes were in the range of 0.015-0.030 and 0.3-0.9 ng/mL, respectively.

Application of a solid-phase microextraction fiber coated with a graphene oxide-poly(dimethylsiloxane) composite for the extraction of triazoles from water.

A solid-phase microextraction fiber was prepared by mixing graphene oxide and hydroxyl-terminated polydimethylsiloxane together and then coating the mixture on the surface of etched stainless-steel wire by sol-gel technology. After aging by heating, the graphene oxide-polydimethylsiloxane composite coated fiber was used for the direct solid phase microextraction of triazole fungicides from water samples. The properties of the graphene oxide-polydimethylsiloxane coating were characterized by transmission electron microscopy and thermogravimetric analysis. And the chemical stability of the coating was tested as well. Several important experimental parameters that could influence the extraction efficiency such as desorption temperature and time, extraction temperature and time, sample pH and stirring rate, were investigated and optimized. Under the optimized conditions, the limits of detection were in the range from 0.01 to 0.03 µg/L. The results indicated that the homemade fiber had the advantages of good thermal and chemical stability and high extraction efficiency, which was successfully applied to the analysis of triazoles in water samples.

Influence of Abutment Screw-Tightening Methods on the Screw Joint: Immediate and Long-Term Stability.

Objective: To evaluate the influence of screw-tightening methods on the immediate and long-term stability of dental implant screw joints. Methodology. A total of 150 implants of three different implant systems with different diameters were used in this study. Each group was divided into three subgroups (n = 5), according to the tightening methods (A-tightening with recommended torque and retorque after 10 min; B-tightening with recommended torque, then loosening and immediate retorque; C-tightening with recommended torque only once). The operating time of tightening the assemblies was recorded. Ten minutes later, the immediate removal torque (IRT) (Ncm) was measured. After retightening the assemblies, a dynamic load between 20 and 200 N was applied for 105 cycles, and the postloading removal torque (PRT) (Ncm) was measured. Scanning electron microscopy (SEM) was used to observe the surface topography of the screws. Results: For different types of implants, the IRTs were 11.92 ± 1.04-34.12 ± 0.36 Ncm for method A, 11.64 ± 0.57-33.96 ± 0.29 Ncm for method B, and 10.30 ± 0.41-31.62 ± 0.52 Ncm for method C, and the IRTs of methods A and B were 6.28%-21.58% higher than that of method C (P ≤ 0.046). The PRTs were 4.08 ± 0.77-29.86 ± 0.65 Ncm for method A, 4.04 ± 0.40-29.60 ± 0.36 Ncm for method B, and 2.98 ± 0.26-26.38 ± 0.59 Ncm for method C, and the PRTs of methods A and B were 11.77%-44.87% higher than that of method C (P ≤ 0.016). The removal torque loss rates of methods A (12.49% ± 0.99%-65.88% ± 4.83%) and B (12.84% ± 0.96%-65.35% ± 1.95%) were 3.04%-7.74% lower than that of method C (16.58% ± 0.56%-71.10% ± 1.58%) (P ≤ 0.017). The operating time of method A was much longer than those of methods B and C (P < 0.001). The structural integrity disruption of the screw thread was observed according to the SEM results in all postloading groups. Conclusions: Method B (torquing and then loosening and immediate retorquing) increases the screw joint immediate stability by 6.28%-21.58% and the long-term stability by 11.77%-44.87% compared with method C (torquing only once), has comparable screw joint stability compared with method A (retorquing after 10 min), saves time and is recommended in clinical settings.

Fundamental insights and molecular interactions in pancreatic cancer: Pathways to therapeutic approaches.

The gastrointestinal tract can be affected by a number of diseases that pancreatic cancer (PC) is a malignant manifestation of them. The prognosis of PC patients is unfavorable and because of their diagnosis at advanced stage, the treatment of this tumor is problematic. Owing to low survival rate, there is much interest towards understanding the molecular profile of PC in an attempt in developing more effective therapeutics. The conventional therapeutics for PC include surgery, chemotherapy and radiotherapy as well as emerging immunotherapy. However, PC is still incurable and more effort should be performed. The molecular landscape of PC is an underlying factor involved in increase in progression of tumor cells. In the presence review, the newest advances in understanding the molecular and biological events in PC are discussed. The dysregulation of molecular pathways including AMPK, MAPK, STAT3, Wnt/ß-catenin and non-coding RNA transcripts has been suggested as a factor in development of tumorigenesis in PC. Moreover, cell death mechanisms such as apoptosis, autophagy, ferroptosis and necroptosis demonstrate abnormal levels. The EMT and glycolysis in PC cells enhance to ensure their metastasis and proliferation. Furthermore, such abnormal changes have been used to develop corresponding pharmacological and nanotechnological therapeutics for PC.