Advanced Smart Biomaterials for Regenerative Medicine and Drug Delivery Based on Phosphoramidite Chemistry: From Oligonucleotides to Precision Polymers.

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.

Preservation of the left colic artery in modified laparoscopic anterior rectal resections without auxiliary abdominal incisions for transanal specimen retrieval.

BACKGROUND: Laparoscopic low anterior rectal resection is the most widely used surgical procedure for middle and low rectal cancer. The aim of this study was to investigate the feasibility and safety of the extracorporeal placement of the anvil in preserving the left colic artery in laparoscopic low anterior rectal resection without auxiliary incisions for transanal specimen retrieval in this research. METHODS: Clinical data and follow-up data of patients undergoing laparoscopic low anterior rectal resection from January 2017 to October 2020 were collected. The resections were modified such that the resisting nail holder was extracorporeally placed for the transanal exenteration of the specimen without using auxiliary abdominal incisions while preserving the left colic artery. By analyzing the data of anastomotic stenosis, anastomotic bleeding and anastomotic fistulas after surgery, the advantages and disadvantages of this surgical method for patients were clarified. RESULTS: A total of 22 patients were enrolled. Five of 22 patients simultaneously underwent double-barrel terminal ileostomy. The postoperative exhaust time was 2-7 (median, 3) days. Postoperative anastomotic bleeding occurred in one patient, postoperative anastomotic fistula occurred in four patients, and postoperative anastomotic stenosis occurred in six patients. There were four patients with postoperative distant metastasis, of which three had concomitant local recurrence. Seventeen patients had no obvious symptoms or signs of recurrent metastases during follow-up appointments, and one died of liver failure. CONCLUSIONS: Modified laparoscopic low anterior rectal resection, which resects the specimen through anus eversion by inserting the anvil extracorporeally while preserving the left colic artery, is safe and feasible for patients with low rectal cancer.

Interleukin-22 promotes PD-L1 expression via STAT3 in colon cancer cells.

Blocking the expression of programmed cell death ligand 1 (PD-L1) is a promising approach for the treatment of colon cancer. The binding of PD-L1 to its receptor programmed cell death 1 (PD-1) on immune cells leads to the apoptosis of activated T cells and causes immune escape. However, there is a limited number of patients with colon cancer that can benefit from the inhibition of PD-L1, and the regulation of PD-L1 expression is poorly understood in colon cancer. The present study demonstrated that interleukin-22 (IL-22) and PD-L1 were upregulated in colon cancer tissues and there was a positive correlation between IL-22 expression and PD-L1 expression. In the present study, exogenous IL-22 was found to upregulate PD-L1 expression via the signal transducer and activator of transcription 3 signaling pathway in human colon cancer cells (DLD-1 and primary colon cancer cells). The results of the present study revealed a novel regulatory mechanism of PD-L1 expression in colon cancer, which provides a theoretical basis for decreasing the immune tolerance of colon cancer via IL-22 overexpression.

Deciphering the Enigma of Li2CO3 Oxidation Using a Solid-State Li-Air Battery Configuration.

Li2CO3 is a ubiquitous byproduct in Li-air (O2) batteries, and its accumulation on the cathode could be detrimental to the devices. As a result, much efforts have been devoted to investigating its formation and decomposition, in particular, upon cycling of Li-O2 batteries. At high voltages, Li2CO3 is expected to decompose into CO2 and O2. However, as recognized from the work of many authors, only CO2, and no O2, has been identified, and the underlying mechanism remains uncertain so far. Herein, a solid-state Li-O2 battery (Li|Li6.4La3Zr1.4Ta0.6O12|Au) has been designed to interrogate the Li2CO3 oxidation without interferences from the decomposition of other battery components (organic electrolyte, binder, and carbon cathode) widely applied in conventional Li-O2 batteries. It is revealed that Li2CO3 can indeed be oxidized to CO2 and O2 in a more stable solid-state Li-O2 battery configuration, highlighting the feasibility of reversible operation of Li-O2 batteries with ambient air as the feeding gas.

Perfluorinated organics regulating Li2O2 formation and improving stability for Li-oxygen batteries.

Lithium-oxygen batteries have a high theoretical capacity, but they are still far from meeting the capacity required for practical applications. In this study, we systematically investigate the synergistic effect of perfluorotributylamine (PFTBA) as an additive in a TEGDME-based electrolyte to optimize the electrochemical performance of Li-O2 batteries. PFTBA promotes cyclic Li2O2 growth, and the discharge capacity is increased to 9548.7 mA h g-1. Moreover, the hydrophobicity of PFTBA can aid in the protection of the lithium anode against corrosion as it remains stable during cycling. The Li-O2 battery exhibited enhanced cycling stability (200 cycles) as a consequence. This study reveals that PFTBA increases the capacity and provides more possibilities for the application of perfluorinated chemicals in Li-O2 batteries.

Oncological Outcomes of Transanal Endoscopic Microsurgery Plus Adjuvant Chemoradiotherapy for Patients with High-Risk T1 and T2 Rectal Cancer.

Background: Radical surgery is recommended for high-risk pathological stage T1 (pT1) or pT2 rectal cancer after transanal endoscopic microsurgery (TEM). However, in clinical practice, many patients may unfit or decline radical surgery. In recent years, adjuvant chemoradiotherapy (CRT) after TEM was considered as an alternative to radical surgery for these patients. This study aimed to assess oncological outcomes of adjuvant CRT after TEM for high-risk early rectal cancer. Materials and Methods: We collected retrospectively data of 97 patients who underwent TEM with pT1 and pT2 between January 2008 and December 2018. Of these, 35 patients were excluded. Of the remaining 62 patients, 42 were managed by TEM alone and 20 by TEM plus adjuvant CRT. Demographics, recurrence, and survival were analyzed between the two groups. Results: At a median follow-up of 52.5 months, the 3-year local recurrence-free survival and disease-free survival (DFS) in TEM alone group were significantly lower than those in TEM+CRT group (66.6% versus 93.3%, P = .035; 63.7% versus 93.3%, P = .022). Although the 3-year overall survival in TEM+CRT group was higher than TEM alone group (100% versus 83.3%), the difference was not statistically significant (P = .13). The local recurrence rate in TEM alone was 31%, compared with 5% in TEM+CRT group (P = .025). Multivariate analysis showed that adjuvant CRT was an independent prognostic factor for DFS (hazard ratio: 0.094; 95% confidence interval: 0.001-0.764; P = .027). Conclusions: Our study suggests that adjuvant CRT after TEM may be an alternative for pT1 high-risk and T2 rectal cancer who are not suitable or unwilling to undergo salvage radical surgery.

Long non­coding RNA ZEB1­AS1 predicts a poor prognosis and promotes cancer progression through the miR­200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma.

Emerging evidence suggests that long non­coding RNAs (lncRNAs) play pivotal roles in cancer progression, including in intrahepatic cholangiocarcinoma (IHCC). The overexpression of lncRNA ZEB1 antisense 1 (ZEB1­AS1) has been discovered in several types of cancer; however, the clinical significance and functional role of ZEB1­AS1 in IHCC have not yet been determined. In the present study, ZEB1­AS1 was found to be upregulated in IHCC cell lines and tissues. A high ZEB1­AS1 expression was associated with clinical progression and a poor survival of patients with IHCC, and was identified as an independent risk factor for a poor prognosis. In addition, ZEB1­AS1 promoted the proliferation and metastasis of IHCC cells both in vitro and in vivo. ZEB1­AS1 was demonstrated to increase the expression of ZEB1 by sponging miR­200a and to thereby accelerate epithelial­mesenchymal transition (EMT). On the whole, the findings of the present study demonstrate that ZEB1­AS1 promotes proliferation and metastasis in IHCC, and induces EMT through the miR­200a/ZEB1 signaling pathway. ZEB1­AS1 may thus be a promising prognostic biomarker and essential therapeutic target for IHCC.

WITHDRAWN: Demethylation of Di-Methylation of Lysine 4 on Histone 3 Is Inhibited by General Control Nondepressible 5-Induced Acetylation of Lysine-Specific Demethylase 1.

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Conversion inorganic interlayer of a LiF/graphene composite in all-solid-state lithium batteries.

The issues at the interface between the solid-state electrolyte (SSE) and electrodes limit the development of all-solid-state lithium batteries (ASSLBs). Herein, we report a LiF/graphene inorganic composite interlayer (ICI) which is in situ constructed at the cathode/garnet interface by electrochemical pre-lithiation of fluorinated graphene (GF). The ICI with flexibility and ion-conductivity can improve the contact between the cathode and garnet electrolyte, and thus enables the ASSLB to stably operate for 60 cycles without any liquid conditions.

MicroRNA-204-3p represses colon cancer cells proliferation, migration, and invasion by targeting HMGA2.

Colon cancer is a detrimental neoplasm of the digestive tract. MicroRNAs (miRNAs) as central regulators have been discovered in colon cancer. Nonetheless, the impact of miR-204-3p on colon cancer remains indistinct. The research attempted to uncover the impacts of miR-204-3p on colon cancer cells growth, migration, and invasion. miR-204-3p expression level in colon cancer tissues and diverse colon cancer cell lines were testified by the quantitative real-time polymerase chain reaction. Exploration of the impacts of miR-204-3p on cell growth, migration, invasion, and their associated factors through assessment of CCK-8, flow cytometry, Transwell, and western blot, respectively. High mobility group AT-hook 2 (HMGA2) expression was then detected in Caco-2 cells after miR-204-3p mimic and inhibitor transfection, additionally dual-luciferase activity was implemented to further uncover the correlation between HMGA2 and miR-204-3p. The impact of HMGA2 on Caco-2 cell growth, migration, and invasion was finally assessed. We found that repression of miR-204-3p was discovered in colon cancer tissues and HCT116, SW480, Caco-2, HT29 and SW620 cell lines. MiR-204-3p overexpression mitigated Coca-2 cell viability, facilitated apoptosis, simultaneously adjusted CyclinD1 and cleaved caspase-3 expression. Cell migration, invasion, and the associated factors were all suppressed by miR-204-3p overexpression. Reduction of HMGA2 was presented in Caco-2 cells with miR-204-3p mimic transfection, and HMGA2 was predicated to be a target gene of miR-204-3p. Besides, HMGA2 silence showed the inhibitory effect on Caco-2 cells growth, migration, and invasion. In conclusion, miR-204-3p repressed colon cancer cell growth, migration, and invasion through targeting HMGA2.

Prognostic significance of mRNA expression of CASPs in gastric cancer.

Current studies suggest that the cysteinyl aspartate specific proteinase (caspase/CASP) family may be closely associated with apoptosis. Scientists have suggested that caspases may be a key to the development of more effective anti-cancer therapies. However, the prognostic value of CASP expression in gastric cancer (GC) remains unclear. Using a Kaplan-Meier plotter online database, the predictive prognostic significance of the expression of 12 CASPs genes (CASP1, CASP2, CASP3, CASP4, CASP5, CASP6, CASP7, CASP8, CASP9, CASP10, CASP12 and CASP14) to overall survival (OS) in different clinicopathological features, including Lauren classification, pathological stages, therapies employed and differentiation in gastric cancer patients was explored. The present study revealed that higher CASP1, 2, 3, 4, 5, 6, 7 and 8 mRNA expression was associated with better OS, whereas higher expression of CASP9, 10, 12 and 14 showed an unfavorable OS in all GC patients. Moreover, CASP1 to 8 were all associated with favorable OS in intestinal type and diffuse type classified by Lauren classification. Therefore, the results of the present study suggested that the CASP family may function as new prognostic indicators in GC and may be helpful in making treatment decisions.

Formation of Nanosized Defective Lithium Peroxides through Si-Coated Carbon Nanotube Cathodes for High Energy Efficiency Li-O2 Batteries.

The formation and decomposition of lithium peroxides (Li2O2) during cycling is the key process for the reversible operation of lithium-oxygen batteries. The manipulation of such products from the large toroidal particles about hundreds of nanometers to the ones in the scale of tens of nanometers can improve the energy efficiency and the cycle life of the batteries. In this work, we carry out an in situ morphology tuning of Li2O2 by virtue of the surface properties of the n-type Si-modified aligned carbon nanotube (CNT) cathodes. With the introduction of an n-type Si coating layer on the CNT surface, the morphology of Li2O2 formed by discharge changes from large toroidal particles (∼300 nm) deposited on the pristine CNT cathodes to nanoparticles (10-20 nm) with poor crystallinity and plenty of lithium vacancies. Beneficial from such changes, the charge overpotential dramatically decreases to 0.55 V, with the charge plateau lying at 3.5 V even in the case of a high discharge capacity (3450 mA h g-1) being delivered, resulting in the high electrical energy efficiency approaching 80%. Such an improvement is attributed to the fact that the introduction of the n-type Si coating layer changes the surface properties of CNTs and guides the formation of nanosized amorphous-like lithium peroxides with plenty of defects. These results demonstrate that the cathode surface properties play an important role in the formation of products formed during the cycle, providing inspiration to design superior cathodes for the Li-O2 cells.

Sustainable Interfaces between Si Anodes and Garnet Electrolytes for Room-Temperature Solid-State Batteries.

Solid-state batteries (SSBs) have seen a resurgence of research interests in recent years for their potential to offer high energy density and excellent safety far beyond current commercialized lithium-ion batteries. The compatibility of Si anodes and Ta-doped Li7La3Zr2O12 (Li6.4La3Zr1.4Ta0.6O12, LLZTO) solid electrolytes and the stability of the Si anode have been investigated. It is found that Si layer anodes thinner than 180 nm can maintain good contact with the LLZTO plate electrolytes, leading the Li/LLZTO/Si cells to exhibit excellent cycling performance with a capacity retention over 85% after 100 cycles. As the Si layer thickness is increased to larger than 300 nm, the capacity retention of Li/LLZTO/Si cells becomes 77% after 100 cycles. When the thickness is close to 900 nm, the cells can cycle only for a limited number of times because of the destructive volume change at the interfaces. Because of the sustainable Si/LLZTO interfaces with the Si layer anodes with a thickness of 180 nm, full cells with the LiFePO4 cathodes show discharge capacities of 120 mA h g-1 for LiFePO4 and 2200 mA h g-1 for the Si anodes at room temperature. They cycle 100 times with a capacity retention of 72%. These results indicate that the combination between the Si anodes and the garnet electrolytes is a promising strategy for constructing high-performance SSBs.

Monodispersed Carbon-Coated Cubic NiP2 Nanoparticles Anchored on Carbon Nanotubes as Ultra-Long-Life Anodes for Reversible Lithium Storage.

In search of new electrode materials for lithium-ion batteries, metal phosphides that exhibit desirable properties such as high theoretical capacity, moderate discharge plateau, and relatively low polarization recently have attracted a great deal of attention as anode materials. However, the large volume changes and thus resulting collapse of electrode structure during long-term cycling are still challenges for metal-phosphide-based anodes. Here we report an electrode design strategy to solve these problems. The key to this strategy is to confine the electroactive nanoparticles into flexible conductive hosts (like carbon materials) and meanwhile maintain a monodispersed nature of the electroactive particles within the hosts. Monodispersed carbon-coated cubic NiP2 nanoparticles anchored on carbon nanotubes (NiP2@C-CNTs) as a proof-of-concept were designed and synthesized. Excellent cyclability (more than 1000 cycles) and capacity retention (high capacities of 816 mAh g-1 after 1200 cycles at 1300 mA g-1 and 654.5 mAh g-1 after 1500 cycles at 5000 mA g-1) are characterized, which is among the best performance of the NiP2 anodes and even most of the phosphide-based anodes reported so far. The impressive performance is attributed to the superior structure stability and the enhanced reaction kinetics incurred by our design. Furthermore, a full cell consisting of a NiP2@C-CNTs anode and a LiFePO4 cathode is investigated. It delivers an average discharge capacity of 827 mAh g-1 based on the mass of the NiP2 anode and exhibits a capacity retention of 80.7% over 200 cycles, with an average output of ∼2.32 V. As a proof-of-concept, these results demonstrate the effectiveness of our strategy on improving the electrode performance. We believe that this strategy for construction of high-performance anodes can be extended to other phase-transformation-type materials, which suffer a large volume change upon lithium insertion/extraction.

In Situ Fabrication of CoS and NiS Nanomaterials Anchored on Reduced Graphene Oxide for Reversible Lithium Storage.

CoS and NiS nanomaterials anchored on reduced graphene oxide (rGO) sheets, synthesized via combination of hydrothermal with sulfidation process, are studied as high-capacity anode materials for the reversible lithium storage. The obtained CoS nanofibers and NiS nanoparticles are uniformly dispersed on rGO sheets without aggregation, forming the sheet-on-sheet composite structure. Such nanoarchitecture can not only facilitate ion/electron transport along the interfaces, but also effectively prevent metal-sulfide nanomaterials aggregation during the lithium reactions. Both the rGO-supported CoS nanofibers (NFs) and NiS nanoparticles (NPs) show superior lithium storage performance. In particular, the CoS NFs-rGO electrodes deliver the discharge capacity as high as 939 mA h g(-1) after the 100th cycle at 100 mA g(-1) with Coulombic efficiency above 98%. This strategy for construction of such composite structure can also synthesize other metal-sulfide-rGO nanomaterials for high-capacity lithium-ion batteries.

Effect of microRNA-1 on hepatocellular carcinoma tumor endothelial cells.

AIM: To investigate the effect of microRNA-1 (miR-1) on tumor endothelial cells (TECs) of human hepatocellular carcinoma (HCC). METHODS: MiR-1 specific short hairpin RNA (shRNA) was synthesized and cloned into a recombinant lentiviral vector. TECs were then infected by the miRNA-1-shRNA recombinant lentivirus. TECs were divided into three groups: a control (CON) group consisting of normal TECs without lentiviral infection, a negative control (NC) group consisting of normal TECs infected with a negative control virus, and a micro-down (MD) group consisting of normal TECs infected with the miR-1-inhibition virus containing the target gene. Silencing of miR-1 expression was quantified via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The proliferation of TECs was detected using MTT (Thiazolyl Blue Tetrazolium Bromide) assay; the observations were continued for 5 d, and the optical density value at 490 nm was detected every day. Apoptosis was detected via flow cytometry using Annexin V-APC single staining. The migration and invasion of TECs were detected using transwell assays. RESULTS: Lentiviral miR-1 shRNA was successfully transduced into TECs, and specifically silenced the expression of miR-1. The results of qRT-PCR showed that the expression of miR-1 was significantly decreased in the MD group (2(-ΔΔCt) = 0.57 ± 0.14) compared with the CON group (2(-ΔΔCt) = 1) and the NC group (2(-ΔΔCt) = 1.05 ± 0.13) (P < 0.01). The results of MTT assay showed that the cell proliferation was all significantly inhibited in the MD group in the 5 days compared with the CON and NC groups (P < 0.01). The results of flow cytometry showed that the apoptosis was significantly increased in the MD group (6.32% ± 0.33%) compared with the CON group (2.03% ± 0.30%) and the NC group (2.18% ± 0.15%) (P < 0.01). The ability of cell migration was significantly inhibited in the MD group (62.0 ± 5.48) compared with the CON group (99.8 ± 3.11) and the NC group (97.2 ± 3.70) (P < 0.01). The ability of invasion of TECs was also significantly inhibited in the MD group (29.8 ± 2.39) compared with the CON group (44.6 ± 3.36) and the NC group (44.4 ± 5.17) (P < 0.01). CONCLUSION: MiR-1 might be a potential tumor activator. Inhibiting its expression could decrease proliferation, induce apoptosis, and inhibit the migration and invasion of TECs of human HCC.

Growth inhibition of hepatocellular carcinoma tumor endothelial cells by miR-204-3p and underlying mechanism.

AIM: To investigate the mechanism by which miR-204-3p inhibits the growth of hepatocellular carcinoma (HCC) tumor endothelial cells (TECs). METHODS: Flow cytometry was used to identify HCCTECs and analyze their purity. Differentially expressed miRNAs in HCC TECs as compared to normal hepatic sinusoidal endothelial cells (HSECs) were examined using the HmiOA v4 Human miRNA OneArray microarray. miR-204-3p showed the most significant decrease in expression and was further studied. Over-expression of miR-204-3p was achieved using lentiviral transduction into TECs of HCC. The biological changes in HCC TECs before and after transduction were detected using MTT and apoptosis assays. The association between miR-204-3p and fibronectin 1 (FN1) was determined using the dual luciferase activity assay. Changes in FN1 protein expression before and after transduction were detected using Western blot analysis. RESULTS: Microarray results showed that compared to normal HSECs, 15 miRNAs were differentially expressed in HCC TECs, including 6 miRNAs with increased expression and 9 miRNAs with decreased expression. Among them, miR-204-3p showed the most significant decrease in expression (log2 = -1.233477, P = 0.000307). Over-expression of miR-204-3p in HCC TECs via lentiviral transduction significantly inhibited the proliferation of HCC TECs and promoted apoptosis. Results from the dual luciferase activity experiment showed that the luciferase intensity in the wild type FN1 group was significantly inhibited (P < 0.05), while that in the mutant FN1 group was not obviously affected. This observation indicated that FN1 was one of the potential targets of miR-204-3p. After over-expression of miR-204-3p in HCC TECs, Western blot analysis showed that the expression of FN1 protein was significantly inhibited. CONCLUSION: MiR-204-3p acts on its potential target gene, FN1, and inhibits its expression, thus blocking the adhesion function of FN1 in promoting the growth of TECs.

A novel type of Ge nanotube arrays for lithium storage material.

Amorphous Ge nanotubes, featured of a top-closed tubular structure, were synthesized directly on metallic current collector substrates via a template technique. Measurement of electrochemical cycling reveals that these nanotubes can deliver reversible capacities of -1300 mAh/g (81% of the theoretical capacity) at the current density of C/20 (1C = 1600 mAh/g) and retain -700 mAh/g at 2C with columbic efficiencies over 99%. Such performance is comparable to that of the recently reported Ge nanowire anodes grown directly on the metallic substrates by the chemical vapor deposition, indicating that the present Ge nanotubes are a type of anode materials with high capacity and good rate performance for lithium storage.