Regulating the Solvation Structure in Polymer Electrolytes for High-Voltage Lithium Metal Batteries.

Solid polymer electrolytes are promising electrolytes for safe and high-energy-density lithium metal batteries. However, traditional ether-based polymer electrolytes are limited by their low lithium-ion conductivity and narrow electrochemical window because of the well-defined and intimated Li+-oxygen binding topologies in the solvation structure. Herein, we proposed a new strategy to reduce the Li+-polymer interaction and strengthen the anion-polymer interaction by combining strong Li+-O (ether) interactions, weak Li+-O (ester) interactions with steric hindrance in polymer electrolytes. In this way, a polymer electrolyte with a high lithium ion transference number (0.80) and anion-rich solvation structure is obtained. This polymer electrolyte possesses a wide electrochemical window (5.5 V versus Li/Li+) and compatibility with both Li metal anode and high-voltage NCM cathode. Li||LiNi0.5Co0.2Mn0.3O2 full cells with middle-high active material areal loading (~7.5 mg cm-2) can stably cycle at 4.5 V. This work provides new insight into the design of polymer electrolytes for high-energy-density lithium metal batteries through the regulation of ion-dipole interactions.

A large-strain and ultrahigh energy density dielectric elastomer for fast moving soft robot.

Dielectric elastomer actuators (DEAs) with large actuation strain and high energy density are highly desirable for actuating soft robots. However, DEAs usually require high driving electric fields (>100 MV m-1) to achieve high performances due to the low dielectric constant and high stiffness of dielectric elastomers (DEs). Here, we introduce polar fluorinated groups and nanodomains aggregated by long alkyl side chains into DE design, simultaneously endowing DE with a high dielectric constant and desirable modulus. Our DE exhibits a maximum area strain of 253% at a low driving electric field of 46 MV m-1. Notably, it achieves an ultrahigh specific energy of 225 J kg-1 at only|| ||40|| MV m-1, around 6 times higher than natural muscle and twice higher than the state-of-the-art DE. Using our DE, soft robots reach an ultrafast running speed of 20.6 BL s-1, 60 times higher than that of commercial VHB 4910, representing the fastest DEA-driven soft robots ever reported.

Intrinsic Solubilization of Lithium Nitrate in Ester Electrolyte by Multivalent Low-Entropy-Penalty Design for Stable Lithium-Metal Batteries.

LiNO3 is a remarkable additive that can dramatically enhance the stability of ether-based electrolytes at lithium metal anodes. However, it has long been constrained by its incompatibility with commercially used ester electrolytes. Herein, we correlated the fundamental role of entropy with the limited LiNO3 solubility and proposed a new low-entropy-penalty design that achieves high intrinsic LiNO3 solubility in ester solvents by employing multivalent linear esters. This strategy is conceptually different from the conventional enthalpic methods that relies on extrinsic high-polarity carriers. In this way, LiNO3 can directly interact with the primary ester solvents and fundamentally alters the electrolyte properties, resulting in substantial improvements in lithium-metal batteries with high Coulombic efficiency and cycling stability. This work illustrates the significance of regulating the solvation entropy for high-performance electrolyte design.

Dynamic behaviors of a stochastic virus infection model with Beddington-DeAngelis incidence function, eclipse-stage and Ornstein-Uhlenbeck process.

In this paper, we present a virus infection model that incorporates eclipse-stage and Beddington-DeAngelis function, along with perturbation in infection rate using logarithmic Ornstein-Uhlenbeck process. Rigorous analysis demonstrates that the stochastic model has a unique global solution. Through construction of appropriate Lyapunov functions and a compact set, combined with the strong law of numbers and Fatou's lemma, we obtain the existence of the stationary distribution under a critical condition, which indicates the long-term persistence of T-cells and virions. Moreover, a precise probability density function is derived around the quasi-equilibrium of the model, and spectral radius analysis is employed to identify critical condition for elimination of the virus. Finally, numerical simulations are presented to validate theoretical results, and the impact of some key parameters such as the speed of reversion, volatility intensity and mean infection rate are investigated.

A Highly Robust Amphibious Soft Robot with Imperceptibility Based on a Water-Stable and Self-Healing Ionic Conductor.

Dielectric elastomer actuators (DEAs) are widely exploited for actuating soft machines and granting soft robots with capability to operate in both underwater and on-land environments is important to make them adapt to more complex situations. Here, a DEA-driven, highly robust, amphibious imperceptible soft robot (AISR) based on an all-environment stable ionic conductive material is presented. A soft, self-healable, all-environment stable ionic conductor is developed by introducing cooperative ion-dipole interactions to provide underwater stability as well as efficient suppression of ion penetration. By tuning molecular structures of the material, a 50-time device lifetime increase compared with unmodified [EMI][TFSI]-based devices and excellent underwater actuating performance is achieved. With the synthesized ionic electrode, the DEA-driven soft robot exhibits amphibious functionality to traverse hydro-terrestrial regions. When encountering damage, the robot shows good resilience and can self-heal underwater and it also exhibits imperceptibility to light, sound, and heat.

Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma.

BACKGROUND: In recent years, morbidity and mortality from colorectal cancer have increased. Colorectal adenoma is the main precancerous lesion. Understanding the pathogenesis of colorectal adenoma will help to improve the early diagnosis rate of colorectal cancer. METHODS: In this case-control study, we focused on three single nucleotide polymorphisms (SNPs) in genes SLC8A1 (rs4952490), KCNJ1 (rs2855798), and SLC12A1 (rs1531916). We analyzed 207 colorectal adenoma patients (112 high-risk cases and 95 low-risk cases) and 212 control subjects by Sanger sequencing. A food frequency questionnaire (FFQ) was used to survey demographic characteristics and dietary nutrition. RESULTS: In the overall analysis, the results suggested that the AA+AG and AG genotype carriers of rs4952490 had a 73.1% and 78% lower risk of colorectal adenoma compared to GG genotype carriers, respectively. However rs2855798 and rs1531916 were not associated with the incidence of colorectal adenoma. Additionally, stratified analysis showed that rs4952490 AA+AG and AG genotypes had a protective effect against low-risk colorectal adenoma in patients aged ≤ 60 years old who were non-smokers. We also observed that when calcium intake was higher than 616 mg/d and patients carried at least one gene with variant alleles there was a protective effect against low-risk colorectal adenoma. CONCLUSIONS: Interactions between dietary calcium intake and calcium reabsorption genes may affect the occurrence and development of colorectal adenoma.

Correlation between Metabolite of Prostaglandin E2 and the incidence of colorectal adenomas.

Colorectal cancer is a common malignancy, and the incidence and mortality rates continue to rise. An important factor in the emergence of inflammation-induced colorectal carcinogenesis is elevated cyclooxygenase-2. Prostaglandin E2 (PGE2) over-production is frequently equated with cyclooxygenase-2 gene over-expression. PGE2 can be assessed by measuring the level of prostaglandin's main metabolite, PGE-M, in urine. Colorectal adenoma is a precancerous lesion that can lead to colorectal cancer. We conducted research to evaluate the association between urinary levels of the PGE-M and the risk of colorectal adenomas. In a western Chinese population, we identified 152 cases of adenoma and 152 controls patients without polyps. Adenoma cases were categorized into control, low-risk and high-risk groups. There was no significant change in PGE-M levels, between the control group and the low-risk adenoma group. In the high-risk group, the PGE-M levels were 23% higher than the control group. When compared to people with the lowest urine PGE-M levels (first quartile), people with greater urinary PGE-M levels had a higher chance of developing high-risk colorectal adenomas, with an adjusted odds ratio (95% CI) of 1.65 (0.76-3.57) in the fourth quartile group, (p= 0.013). We conclude urinary PGE-M is associated with the risk of developing high-risk adenomas. Urinary PGE-M level may be used as a non-invasive indicator for estimating cancer risk.

Multivalent Design of Low-Entropy-Penalty Ion-Dipole Interactions for Dynamic Yet Thermostable Supramolecular Networks.

Dynamic supramolecular networks are constantly accompanied by thermal instability. The fundamental reason is most reversible noncovalent bonds quickly decay at elevated temperatures and dissociate below 100 °C. Here, in this paper, we realize a reversible ion-dipole interaction with high-temperature stability exceeding 150 °C. The resultant supramolecular network can simultaneously possess mechanical strength of 1.32 MPa (14.8 times that of pristine material), dynamic self-healing capability, and a stable working temperature of up to 200 °C. From the prolonged characteristic relaxation time of 600 s even at 100 °C, our material represents one of the most thermally stable dynamic supramolecular polymers. These remarkable performances are achieved by using a new multivalent yet low-entropy-penalty molecular design. In this way, the noncovalent bond can reach a high enthalpy while minimizing the entropy-dominated thermal dissociations.

Nomogram based on the systemic immune-inflammation index for predicting the prognosis of diffuse large B-cell lymphoma.

AIM: To investigate systemic immune-inflammation index (SII) as prognostic factors and establish a nomogram based on SII for the prediction of survival in diffuse large B-cell lymphoma (DLBCL). METHODS: One hundred and fifty-five DLBCL patients were randomized into primary (N = 100) and validation (N = 55) cohorts. Kaplan-Meier survival curves and Cox regression models were used to evaluate the impact of SII on survival. The nomogram based on SII was analyzed by using R software. RESULTS: Univariate and multivariate analyses revealed that high SII (>1684.), C-reactive protein-to-albumin ratio (CAR > 0.21), and age-adjusted International Prognostic Index (aaIPI) score were independent predictors of overall survival (OS). High SII and aaIPI were independent predictors of progression-free survival. The nomogram had better accuracy and discrimination than the International Prognostic Index, National Comprehensive Cancer Network-International Prognostic Index, and aaIPI systems. The concordance index values of the nomogram for OS were 0.885 in the primary cohort and 0.821 in the validation cohort. CONCLUSIONS: Our results suggested that SII, CAR, and aaIPI could be used to judge the prognosis of DLBCL patients. The nomogram was a reliable model for predicting the OS of DLBCL patients.

Clinical considerations of CDK4/6 inhibitors in HER2 positive breast cancer.

Deregulation of cell cycles can result in a variety of cancers, including breast cancer (BC). In fact, abnormal regulation of cell cycle pathways is often observed in breast cancer, leading to malignant cell proliferation. CDK4/6 inhibitors (CDK4/6i) can block the G1 cell cycle through the cyclin D-cyclin dependent kinase 4/6-inhibitor of CDK4-retinoblastoma (cyclinD-CDK4/6-INK4-RB) pathway, thus blocking the proliferation of invasive cells, showing great therapeutic potential to inhibit the spread of BC. So far, three FDA-approved drugs have been shown to be effective in the management of advanced hormone receptor positive (HR+) BC: palbociclib, abemaciclib, and ribociclib. The combination strategy of CDK4/6i and endocrine therapy (ET) has become the standard therapeutic regimen and is increasingly applied to advanced BC patients. The present study aims to clarify whether CDK4/6i can also achieve a certain therapeutic effect on Human epidermal growth factor receptor 2 positive (HER2+) BC. Studies of CDK4/6i are not limited to patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced BC, but have also expanded to other types of BC. Several pre-clinical and clinical trials have demonstrated the potential of CDK4/6i in treating HER2+ BC. Therefore, this review summarizes the current knowledge and recent findings on the use of CDK4/6i in this type of BC, and provides ideas for the discovery of new treatment modalities.

Salvage high intensity focused ultrasound for residual or recurrent cervical cancer after definitive chemoradiotherapy.

Objective: The treatment of residual/recurrent cervical cancer within a previously irradiated area is challenging and generally associated with a poor outcome. Local treatments such as salvage surgery and re-irradiation are usually traumatic and have limited efficacy. High intensity focused ultrasound (HIFU) treatment can directly ablate solid tumors without damaging neighboring healthy tissue. However, the HIFU studies for these patients are limited. Experience gained over the course of 10 years with the use of HIFU for the management of residual/recurrent cervical cancer after chemoradiotherapy is reported herein. Methods: 153 patients with residual/recurrent cervical cancer in a previously irradiated field who received HIFU treatment between 2010 and 2021 were retrospectively analyzed. Adverse effects, survival benefit and factors affecting prognosis were given particular attention. Results: A total of 36 patients (23.5%) achieved a partial response following HIFU treatment and 107 patients (69.9%) had stable disease. The objective response and disease control rates were 23.5% and 93.5%, respectively. The median progression-free survival (mPFS) and median overall survival (mOS) were 17.0 months and 24.5 months, respectively. Moreover, patients with lesions ≥1.40 cm before HIFU treatment and a shrinkage rate ≥ 30% after treatment had a higher mPFS and mOS, and patients with lesions ≤1.00 cm after HIFU treatment had a higher mPFS (P=<0.05). All the treatment-related adverse events were limited to minor complications, which included skin burns, abdominal pain and vaginal discharge. Conclusions: HIFU treatment is likely a preferred option for cervical cancer patients with residual disease or recurrence following CRT that can safely improve the local control rate and extend survival.

Stable High-Temperature Lithium-Metal Batteries Enabled by Strong Multiple Ion-Dipole Interactions.

Lithium-metal batteries (LMBs) capable of operating stably at high temperature application scenarios are highly desirable. Conventional lithium-ion batteries could only work stably under 60 °C because of the thermal instability of electrolyte at elevated temperature. Here we design and develop a thermal stable electrolyte based on stable solvation structure using multiple ion-dipole interactions. The strong coordination in solvated structure of electrolyte defines the Li deposition behaviour and the evolution of solid electrolyte interphase at high temperature, which is important to achieve high Li Coulombic efficiency and avoid Li dendritic growth. For high mass loading LiFePO4 -Li cells, the cells at 60 °C with conventional electrolyte easily run into failures, but the cells with our electrolyte at 90 °C and 100 °C could cycle more than 120 and 50 cycles respectively. This work provides new insight into electrolyte design and contributes to the development of high temperature LMBs.

Analysis of the Expression and Role of Keratin 17 in Human Tumors.

Objective: We aimed to explore the expression and carcinogenic effect of KRT17 in human tumors and provide useful information for the study of KRT17. Methods: We used databases including the Cancer Genome Atlas, Gene Expression Omnibus, GTEx, and GEPIA2 to analyze the expression, mutation, and prognosis of KRT17 in human tumors. Through webservers, including UALCAN, TIMER2.0, and STRING, we learned about the genetic variation, immune cell penetration, and enrichment analysis of KRT17-related genes. Results: KRT17 was highly expressed in most tumors (such as esophageal cancer, lung cancer, cervical cancer, etc.), and the high expression level correlated with tumor stage and prognosis. In addition, amplification was the main type of KRT17 tumor variation, with an amplification rate of about 9%, followed by mutation, with a mutation rate of 4%. Moreover, KRT17 was strongly associated with tumor-infiltrating immune cells (such as macrophages, CD8+T, Tregs, and cancer-associated fibroblasts). KEGG analysis suggested that KRT17 may play a role in tumor pathogenesis following human papillomavirus infection, and the gene ontology enrichment analysis indicated that the carcinogenicity of KRT17 can be attributed to cadherin binding, intermediate fibrocytoskeleton and epidermal development. Conclusion: KRT17 may play an important role in the occurrence, development, and prognosis of malignant tumors. We provided a relatively comprehensive description of the carcinogenic role of KRT17 in different tumors for the first time.

The Role of LncRNAs in the Regulation of Radiotherapy Sensitivity in Cervical Cancer.

Cervical cancer (CC) is one of the three majors gynecological malignancies, which seriously threatens women's health and life. Radiotherapy (RT) is one of the most common treatments for cervical cancer, which can reduce local recurrence and prolong survival in patients with cervical cancer. However, the resistance of cancer cells to Radiotherapy are the main cause of treatment failure in patients with cervical cancer. Long non-coding RNAs (LncRNAs) are a group of non-protein-coding RNAs with a length of more than 200 nucleotides, which play an important role in regulating the biological behavior of cervical cancer. Recent studies have shown that LncRNAs play a key role in regulating the sensitivity of radiotherapy for cervical cancer. In this review, we summarize the structure and function of LncRNAs and the molecular mechanism of radiosensitivity in cervical cancer, list the LncRNAs associated with radiosensitivity in cervical cancer, analyze their potential mechanisms, and discuss the potential clinical application of these LncRNAs in regulating radiosensitivity in cervical cancer.

PD-1/PD-L1 Correlates With the Efficacy of the Treatment of Concurrent Chemoradiotherapy in Cervical Cancer.

Background: Cervical cancer (CC) is the third most common cancer worldwide, with high mortality rates. The programmed cell death 1 (PD-1)/(PD-1 ligand) PD-L1 has been reported to be an effective indicator in cancer development. In this study, we aim to explore the role of PD-1/PD-L1 in the evaluation of concurrent chemoradiotherapy (CCRT) efficacy and prognosis in CC patients. Methods: We included 55 CC patients in this study. Immunohistochemistry and flow cytometry were employed to detect the expression of PD-1, Treg cells, CD8, and CD68 in tumor tissues, and the contents of PD-1+ CD8+ T cells, PD-1+ CD4+ T cells, and PD-1+ Treg cells in the peripheral blood. The relationships of these indexes with CCRT efficacy were measured by Spearman correlation analysis, overall survival (OS), and disease-free survival (DFS) of patients were analyzed by Kaplan-Meier estimator, and the diagnostic values of these indexes in CC were assessed by a receiver operating characteristic (ROC) curve. Results: The clinical effectivity rate of CCRT was 89.10%. The positive expressions of PD-L1, Treg cells, PD-1+ CD8+ T cells, PD-1+ CD4+ T cells, and PD-1+ Treg cells were reduced after CCRT, while the CD8 and CD68 increased. All 7 indexes had diagnostic values in evaluating CCRT efficacy and were considered the influencing factors of OS, DFS, and the prognosis of CC patients. Conclusion: These findings indicate that PD-1/PD-L1 may be a potential indicator for the efficacy evaluation of CCRT and the prognosis of CC. This study may offer potential targets for CC treatment.

The Role of Keratin17 in Human Tumours.

Keratins are a group of proteins that can constitute intermediate fibers. It is a component of the cytoskeleton and plays an important role in cell protection and structural support. Keratin 17, a Type I keratin, is a multifunctional protein that regulates a variety of biological processes, including cell growth, proliferation, migration, apoptosis and signal transduction. Abnormal expression of KRT17 is associated with a variety of diseases, such as skin diseases. In recent years, studies have shown that KRT17 is abnormally expressed in a variety of malignant tumours, such as lung cancer, cervical cancer, oral squamous cell carcinoma and sarcoma. These abnormal expressions are related to the occurrence, development and prognosis of malignant tumors. In this review, we summarized the expression patterns of KRT17 in a variety of malignant tumours, the role of KRT17 in the development and prognosis of different malignant tumors and its molecular mechanisms. We also discuss the potential clinical application of KRT17 as a valuable therapeutic target.

Tough, stable and self-healing luminescent perovskite-polymer matrix applicable to all harsh aquatic environments.

Gelatinous underwater invertebrates such as jellyfish have organs that are transparent, luminescent and self-healing, which allow the creatures to navigate, camouflage themselves and, indeed, survive in aquatic environments. Artificial luminescent materials that can mimic such functionality can be used to develop aquatic wearable/stretchable displays and water-resistant devices. Here, a luminescent composite that is simultaneously transparent, tough and can autonomously self-heal in both dry and wet conditions is reported. A tough, self-healable fluorine elastomer with dipole-dipole interactions is synthesized as the polymer matrix. It exhibits excellent compatibility with metal halide perovskite quantum dots. The composite possesses a toughness of 19 MJ m-3, maximum strain of 1300% and capability to autonomously self-heal underwater. Notably, the material can withstand extremely harsh aqueous conditions, such as highly salty, acidic (pH = 1) and basic (pH = 13) environment for more than several months with almost no decay in mechanical performance or optical properties.

The Dynamic Alternation of Local and Systemic Tumor Immune Microenvironment During Concurrent Chemoradiotherapy of Cervical Cancer: A Prospective Clinical Trial.

PURPOSE: This work assessed local and systemic alternations of the tumor immune microenvironment during concurrent chemoradiation therapy (CCRT) of local advanced cervical cancer to estimate the optimal timing for immune therapy in relation to CCRT. METHODS AND MATERIALS: In this single-center prospective clinical trial, 55 patients with stage IIA through IVA cervical cancer were enrolled between December 2016 and November 2017. The median follow-up was 32.1 months. All patients received cisplatin concurrently with external beam radiation therapy combined with high-dose-rate brachytherapy. Tumor tissues and peripheral blood mononuclear cells (PBMCs) were collected before, during and after CCRT. We analyzed the changes in lymphocyte subpopulations, programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, and the T cell receptor (TCR) repertoire that occurred throughout CCRT. RESULTS: The frequencies of CD4+ and PD-1+ T cells in PBMCs decreased after the start of CCRT, whereas that of inhibitory regulatory T cells increased. In the tumor tissues, CCRT decreased the numbers of CD4+ and CD8+ T cells and reduced the median percentage of positive cells expressing PD-L1 from 78.1% to 49.8%. As indicated by the numbers of unique clones, the TCRs of PBMCs exhibited greater diversity before CCRT than after CCRT. Greater TCR diversity in PBMCs before CCRT was associated with superior 30-month progression-free survival (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.04-0.39; P = .001) and overall survival (HR, 0.17; 95% CI, 0.04-0.68; P = .004). CONCLUSIONS: CCRT for cervical cancer altered the tumor immune microenvironment by reducing CD4+ and CD8+ T lymphocyte populations, PD-1/PD-L1 expression, and TCR diversity. Higher TCR diversity in PBMCs before CCRT resulted in better survival and prognosis, indicating that CCRT might inhibit immune activation. Our results suggest that it might be more effective to administer immune checkpoint inhibitors before CCRT of cervical cancer rather than during or after CCRT.

A thermal activated and differential self-calibrated flexible epidermal biomicrofluidic device for wearable accurate blood glucose monitoring.

This paper reports a flexible electronics-based epidermal biomicrofluidics technique for clinical continuous blood glucose monitoring, overcoming the drawback of the present wearables, unreliable measurements. A thermal activation method is proposed to improve the efficiency of transdermal interstitial fluid (ISF) extraction, enabling extraction with a low current density to notably reduce skin irritation. An Na+ sensor and a correction model are proposed to eliminate the effect of individual differences, which leads to fluctuations in the amount of ISF extraction. An electrochemical sensor with a 3D nanostructured working electrode surface is designed to enable precise in situ glucose measurement. A differential structure is proposed to eliminate the effect of passive perspiration, which leads to inaccurate blood glucose prediction. Fabrications of the epidermal biomicrofluidic device including formation of flexible electrodes, nanomaterial modification, and enzyme immobilization are fully realized by inkjet printing to enable facile manufacturing with low cost, which benefits practical production.

Long Non-Coding RNA A2M-AS1 Promotes Breast Cancer Progression by Sponging microRNA-146b to Upregulate MUC19.

BACKGROUND: Long non-coding RNA (lncRNA) A2M-AS1 has been indicated to be augmented in breast cancer (BC), with its specific function undetermined. Therefore, this study is designed to investigate the mechanism of lncRNA A2M-AS1 in BC. METHODS: The expression of A2M-AS1, microRNA (miR)-146b, and MUC19 in BC tissues and cells was measured. Then, the interaction among A2M-AS1, miR-146b, and MUC19 was detected. After A2M-AS1, miR-146b, and MUC19 expression were altered in BC cells, cell proliferation, invasion, and apoptosis were detected, and the protein levels of Hippo-related proteins (YAP and p-YAP) were evaluated. Tumor growth assay was also performed to validate the effects of A2M-AS1 and miR-146b in vivo. RESULTS: A2M-AS1 and MUC19 were highly expressed in BC, while miR-146b was poorly expressed. A2M-AS1 acts as a molecular sponge for miR-146b, which targeted and negatively modulated MUC19. A2M-AS1 accelerated BC cell proliferation, invasion, and colony formation and suppressed apoptosis via the miR-146b/MUC19/Hippo axis, which was confirmed in vivo. CONCLUSION: Taken above together, an oncogenic role for A2M-AS1 in BC was elicited by acting as a miR-146b sponge to promote MUC19 expression. The findings will present some cues for a further approach to BC.