Highly deformable bi-continuous conducting polymer hydrogels for electrochemical energy storage.

Conducting polymer hydrogels with inherent flexibility, ionic conductivity and environment friendliness are promising materials in the fields of energy storage. However, a trade-off between mechanical and electrochemical properties has limited the development of flexible/stretchable conducting polymer hydrogel electrodes, owing to the intrinsic conflict among mechanical and electrical phases. Here, we report a reliable design to enable conducting polymer with both exceptional mechanical and electrical/electrochemical performance through the construction of bi-continuous conducting polymer crosslinked network. The resultant bi-continuous conducting polymer hydrogels (BCPH) demonstrate significantly improved mechanical and electrochemical properties compared to the conventional conducting polymer hydrogel (CPH) electrode. BCPH presents a high specific capacitance of 715 F g-1 at 0.5 A/g, a high mechanical strength (∼1 MPa) and a large stretchability (∼300%). Enabled by such intrinsically deformability and electrochemical properties, we further demonstrate its utility in flexible solid-state supercapacitor (FSSC), which exhibits an outstanding specific capacitance of 760 mF cm-2 at 2 mA cm-2, excellent electrochemical stability with 81% capacitance retention after 5000 charge/discharge cycles, and superior bending cycle stability. This simple and scalable strategy provides a platform for the fabrication of high-performance conducting hydrogel electrodes for various wearable electronic equipment.

Evaluate the clinical efficacy of traditional Chinese Medicine as the neoadjuvant treatment in reducing the incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis: A systematic review and meta-analysis.

Background: Traditional Chinese Medicine (TCM), has been used for hepatocellular carcinoma (HCC) at every therapeutic stage, even before tumor formation. However, the efficacy of TCM in reducing the incidence of HCC in patients with chronic hepatitis B-related cirrhosis remains unclear. This study aims to address this gap. Methods: Publications were collected from PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Sino Med, VIP, and Wan Fang Databases. Relative risk (RR) was calculated with a 95 % confidence interval (CI). Heterogeneity was assessed. The Cochrane Collaboration's tool was used to assess the risk of bias. Results: 10 studies with 2702 patients showed that the combination therapy significantly reduced the incidence of HCC in patients with post-hepatitis B cirrhosis at 1, 3, and 5 years. However, the preventive effects of TCM were in compensated cirrhosis, but not the decompensated cirrhosis. Furthermore, TCM correlated with improved liver function and enhanced virological response. Conclusion: Combination therapy with TCM demonstrated the certain potential in reducing the incidence of HCC in patients with hepatitis B cirrhosis. This is attrinuted to the improvement of liver function and enhancement of the viral response. However, the efficacy of TCM in the field still needs more high-quality RCTs to provide stronger evidence in the future.

General room-temperature Suzuki-Miyaura polymerization for organic electronics.

π-Conjugated polymers (CPs) have broad applications in high-performance optoelectronics, energy storage, sensors and biomedicine. However, developing green and efficient methods to precisely synthesize alternating CP structures on a large scale remains challenging and critical for their industrialization. Here a room-temperature, scalable and homogeneous Suzuki-Miyaura-type polymerization reaction is developed with broad generality validated for 24 CPs including donor-donor, donor-acceptor and acceptor-acceptor connectivities, yielding device-quality polymers with high molecular masses. Furthermore, the polymerization protocol significantly reduces homocoupling structural defects, yielding more structurally regular and higher-performance electronic materials and optoelectronic devices than conventional thermally activated polymerizations. Experimental and theoretical studies reveal that a borate transmetalation process plays a key role in suppressing protodeboronation, which is critical for large-scale structural regularity. Thus, these results provide a general polymerization tool for the scalable production of device-quality CPs with alternating structural regularity.

A Deep Neural Network for Predicting Synergistic Drug Combinations on Cancer.

The exploration of drug combinations presents an opportunity to amplify therapeutic effectiveness while alleviating undesirable side effects. Nevertheless, the extensive array of potential combinations poses challenges in terms of cost and time constraints for experimental screening. Thus, it is crucial to narrow down the search space. Deep learning approaches have gained widespread popularity in predicting synergistic drug combinations tailored for specific cell lines in vitro settings. In the present study, we introduce a novel method termed GTextSyn, which utilizes the integration of gene expression data and chemical structure information for the prediction of synergistic effects in drug combinations. GTextSyn employs a sentence classification model within the domain of Natural Language Processing (NLP), wherein drugs and cell lines are regarded as entities possessing biochemical relevance. Meanwhile, combinations of drug pairs and cell lines are construed as sentences with biochemical relational significance. To assess the efficacy of GTextSyn, we conduct a comparative analysis with alternative deep learning approaches using a standard benchmark dataset. The results from a five-fold cross-validation demonstrate a 49.5% reduction in Mean Square Error (MSE) achieved by GTextSyn, surpassing the performance of the next best method in the regression task. Furthermore, we conduct a comprehensive literature survey on the predicted novel drug combinations and find substantial support from prior experimental studies for many of the combinations identified by GTextSyn.

Integration of single-cell and bulk RNA-sequencing to analyze the heterogeneity of hepatocellular carcinoma and establish a prognostic model.

BACKGROUND: The highly heterogeneous nature of hepatocellular carcinoma (HCC) results in different responses and prognoses to the same treatment in patients with similar clinical stages. AIMS: Thus, it is imperative to investigate the association between HCC tumor heterogeneity and treatment response and prognosis. METHODS AND RESULTS: At first, we downloaded scRNA-seq, bulk RNA-seq, and clinical data from TCGA and GEO databases. We conducted quality control, normalization using SCTransform, dimensionality reduction using PCA, batch effect removal using Harmony, dimensionality reduction using UMAP, and cell annotation-based marker genes on the scRNA-seq data. We recognized tumor cells, identified tumor-related genes (TRGs), and performed cell communication analysis. Next, we developed a prognostic model using univariable Cox, LASSO, and multivariate Cox analyses. The signature was evaluated using survival analysis, ROC curves, C-index, and nomogram. Last, we studied the predictability of the signature in terms of prognosis and immunotherapeutic response for HCC, assessed a variety of drugs for clinical treatment, and used the qRT-PCR analysis to validate the mRNA expression levels of prognostic TRGs. CONCLUSION: To conclude, this study expounded upon the influence of tumor cell heterogeneity on the prediction of treatment outcomes and prognosis in HCC. This, in turn, enhances the predictive ability of the TNM staging system and furnishes novel perspectives on the prognostic assessment and therapy of HCC.

Temperature responses of leaf respiration in light and darkness are similar and modulated by leaf development.

Our ability to predict temperature responses of leaf respiration in light and darkness (RL and RDk ) is essential to models of global carbon dynamics. While many models rely on constant thermal sensitivity (characterized by Q10 ), uncertainty remains as to whether Q10 of RL and RDk are actually similar. We measured short-term temperature responses of RL and RDk in immature and mature leaves of two evergreen tree species, Castanopsis carlesii and Ormosia henry in an open field. RL was estimated by the Kok method, the Yin method and a newly developed Kok-iterCc method. When estimated by the Yin and Kok-iterCc methods, RL and RDk had similar Q10 (c. 2.5). The Kok method overestimated both Q10 and the light inhibition of respiration. RL /RDk was not affected by leaf temperature. Acclimation of respiration in summer was associated with a decline in basal respiration but not in Q10 in both species, which was related to changes in leaf nitrogen content between seasons. Q10 of RL and RDk in mature leaves were 40% higher than in immature leaves. Our results suggest similar Q10 values can be used to model RL and RDk while leaf development-associated changes in Q10 require special consideration in future respiration models.

Advances on cardiovascular effects of GLP-lRAs / 中国药理学通报

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

An Overview of Traditional Chinese Medicine in the Treatment After Radical Resection of Hepatocellular Carcinoma.

According to the Barcelona Clinic Liver Cancer (BCLC) system, radical resection of early stage primary hepatocellular carcinoma (HCC) mainly includes liver transplantation, surgical resection, and radiofrequency ablation (RFA), which yield 5-year survival rates of about 70-79%, 41.3-69.5%, and 40-70%, respectively. The tumor-free 5-year rate for HCC patients undergoing radical resection only reach up to 13.7 months, so the prevention of recurrence after radical resection of HCC is very important for the prognosis of patients. The traditional Chinese medicine (TCM) takes the approach of multitarget and overall-regulation to treat tumors, it can also independently present the "component-target-pathway" related to a particular disease, and its systematic and holistic characteristics can provide a personalized therapy based on symptoms of the patient by treating the patient as a whole. TCM as postoperative adjuvant therapy after radical resection of HCC in Barcelona Clinic liver cancer A or B stages, and the numerous clinical trials confirmed that the efficacy of TCM in the field of HCC has a significant effect, not only improving the prognosis and quality of life but also enhancing patient survival rate. However, with the characteristics of multi-target, multi-component, and multi-pathway, the specific mechanism of Chinese medicine in the treatment of diseases is still unclear. Because of the positive pharmacological activities of TCM in combating anti-tumors, the mechanism studies of TCM have demonstrated beneficial effects on the regulation of immune function, chronic inflammation, the proliferation and metastasis of liver cancer cells, autophagy, and cell signaling pathways related to liver cancer. Therefore, this article reviews the mechanism of traditional Chinese medicine in reducing the recurrence rate of HCC after radical resection.

DFT-Based Study of the Structure, Stability, and Spectral and Optical Properties of Gas-Phase NbMgn (n = 2-12) Clusters.

Gas-phase NbMgn (n = 2-12) clusters were fully searched by CALYPSO software, and then the low-energy isomers were further optimized and calculated under DFT. It is shown that the three lowest energy isomers of NbMgn (n = 3-12) at each size are grown from two seed structures, i.e., tetrahedral and pentahedral structures, and the transition size occurs at the NbMg8 cluster. Interestingly, the relative stability calculations of the NbMg8 cluster ground-state isomer stand out under the examination of several parameters' calculations. The charge-transfer properties of the clusters of the ground-state isomers of various sizes had been comprehensively investigated. In order to be able to provide data guidance for future experimental probing of these ground-state clusters, this work also predicted infrared and Raman spectra at the same level of theoretical calculations. The results show that the multipeak nature of the IR and Raman spectra predicts that it is difficult to distinguish them directly. Finally, the optical properties of these clusters were investigated by calculating the static linear, second-order nonlinear, and third-order nonlinear coefficients. Importantly and interestingly, the NbMg8 cluster was shown to have superior nonlinear optical characteristics to all other clusters; thus, it is a powerful candidate for a potentially ultrasensitive nonlinear optical response device for some special purpose.

Nickel-Doped Graphite and Fusible Alloy Bilayer Back Electrode for Vacuum-Free Perovskite Solar Cells.

With the rapid development of perovskite solar cells (PSCs), lowering fabrication costs for PSCs has become a prominent challenge for commercialization. At present, gold is commonly used as the back metal electrode in state-of-the-art n-i-p structured PSCs due to its compatible work function, chemical inertness, and high conductivity. However, the high cost of gold and the expensive and time-consuming vacuum-based thin-film coating facilities may impede large-scale industrialization of PSCs. Here, we report a bilayer back electrode configuration consisting of an Ni-doped natural graphite layer with a fusible Bi-In alloy. This back electrode can be deposited in a vacuum-free approach and enables PSCs with a power conversion efficiency of 21.0%. These inexpensive materials and facile ambient fabrication techniques provide an appealing disruptive solution to low-cost PSC industrialization.

Oxidative-Reductive Near-Infrared Electrochromic Switching Enabled by Porous Vertically Stacked Multilayer Devices.

Here, we demonstrate for the first time the ability of a porous π-conjugated semiconducting polymer film to enable facile electrolyte penetration through vertically stacked redox-active polymer layers, thereby enabling electrochromic switching between p-type and/or n-type polymers. The polymers P1 and P2, with structures diketopyrrolopyrrole (DPP)-πbridge-3,4,-ethylenedioxythiophene (EDOT)-πbridge [πbridge = 2,5-thienyl for P1 and πbridge = 2,5-thiazolyl for P2] are selected as the p-type polymers and N2200 (a known naphthalenediimide-dithiophene semiconductor) as the n-type polymer. Single-layer porous and dense (control) polymer films are fabricated and extensively characterized using optical microscopy, atomic force microscopy, scanning electron microscopy, and grazing incidence wide-angle X-ray scattering. The semiconducting films are then incorporated into single and multilayer electrochromic devices (ECDs). It is found that when a p-type (P2) porous top layer is used in a multilayer ECD, it enables electrolyte penetration to the bottom layer, enabling oxidative electrochromic switching of the P1 bottom layer at low potentials (+0.4 V versus +1.2 V with dense P2). Importantly, when using a porous P1 as the top layer with an n-type N2200 bottom layer, dynamic oxidative-reductive electrochromic switching is also realized. These results offer a proof of concept for development of new types of multilayer electrochromic devices where precise control of the semiconductor film morphology and polymer electronic structure is essential.

Prediction of the mechanisms of action of Qutan Huoxue decoction in non-alcoholic steatohepatitis (NASH): a network pharmacology study and experimental validation.

CONTEXT: Qutan Huoxue decoction (QTHX) is used to treat non-alcoholic steatohepatitis (NASH) with good efficacy in the clinic. However, the mechanism is not clear yet. OBJECTIVE: This study investigates the mechanism of QTHX in the treatment of NASH. MATERIALS AND METHODS: Potential pathways of QTHX were predicted by network pharmacology. Fourty Sprague Dawley (SD) rats (half normal diet, half high-fat diet) were fed six to eight weeks, primary hepatocytes and Kupffer cells were extracted and co-cultured by the 0.4-micron trans well culture system. Then, the normal co-cultured cells were treated by normal serum, the NASH co-cultured cells were treated with various concentrations of QTHX-containing serum (0, 5, 7.5 or 10 µg/mL) for 24 h. The expression of targets were measured with Activity Fluorometric Assay, Western blot and PCR assay. RESULTS: Network pharmacology indicated that liver-protective effect of QTHX was associated with its anti-inflammation response, oxidative stress, and lipid receptor signalling. 10 µg/mL QTHX significantly reduced the inflammation response and lipid levels in primary hepatocytes (ALT: 46.43 ± 2.76 U/L, AST: 13.96 ± 1.08 U/L, TG: 0.25 ± 0.01 mmol/L, TC: 0.14 ± 0.05 mmol/L), comparing with 0 µg/mL NASH group (ALT: 148 ± 9.22 U/L, AST: 53.02 ± 2.30 U/L, TG: 0.74 ± 0.07 mmol/L, TC: 0.91 ± 0.07 mmol/L) (p < 0.01). Meanwhile, QTHX increased expression of SOCS1 and decreased expression of TLR4, Myd88, NF-κB. CONCLUSIONS: The study suggested that QTHX treats NASH in rats by activating the SCOS1/NF-κB/TLR4 pathway, suggesting QTHX could be further developed as a potential liver-protecting agent.

Enhancing the osmotic energy conversion of a nanoporous membrane: influence of pore density, pH, and temperature.

Salinity gradient power, which converts Gibbs free energy of mixing to electric energy through an ion-selective pore, has great potential. Towards practical use, developing membrane-scaled nanoporous materials is desirable and necessary. Unfortunately, the presence of a significant ion concentration polarization (ICP) lowers appreciably the power harvested, especially at a high pore density. To alleviate this problem, we suggest applying an extra pressure difference ΔP across a membrane containing multiple nanopores, taking account of the associated power consumption. The results gathered reveal that the application of a negative pressure difference can improve the power harvested due to the enhanced selectivity. In addition, if the pore density of a membrane is high, raising its pore length is necessary to make the energy harvested economic. For example, if the pore length is 2000 nm and the pore density is 2.5 × 109 pores per cm2, an increment in the power density of 213 mW m-2 can be obtained by applying ΔP = -1 bar at pH 11 and 323 K, where a net positive power density can be retrieved. The performance of the system considered under various conditions is examined in detail, along with associated mechanisms.

Vertical organic electrochemical transistors for complementary circuits.

Organic electrochemical transistors (OECTs) and OECT-based circuitry offer great potential in bioelectronics, wearable electronics and artificial neuromorphic electronics because of their exceptionally low driving voltages (<1 V), low power consumption (<1 µW), high transconductances (>10 mS) and biocompatibility1-5. However, the successful realization of critical complementary logic OECTs is currently limited by temporal and/or operational instability, slow redox processes and/or switching, incompatibility with high-density monolithic integration and inferior n-type OECT performance6-8. Here we demonstrate p- and n-type vertical OECTs with balanced and ultra-high performance by blending redox-active semiconducting polymers with a redox-inactive photocurable and/or photopatternable polymer to form an ion-permeable semiconducting channel, implemented in a simple, scalable vertical architecture that has a dense, impermeable top contact. Footprint current densities exceeding 1 kA cm-2 at less than ±0.7 V, transconductances of 0.2-0.4 S, short transient times of less than 1 ms and ultra-stable switching (>50,000 cycles) are achieved in, to our knowledge, the first vertically stacked complementary vertical OECT logic circuits. This architecture opens many possibilities for fundamental studies of organic semiconductor redox chemistry and physics in nanoscopically confined spaces, without macroscopic electrolyte contact, as well as wearable and implantable device applications.

Identification of a novel ANK1 mutation in a Chinese family with hereditary spherocytosis: A case report.

The present study describes the clinical profile and ankyrin 1 (ANK1) mutation status of a Chinese family with hereditary spherocytosis (HS). A young male patient (proband) was diagnosed with HS after presenting with anaemia and jaundice. The Coombs test was negative and spherocytes were found in peripheral blood smears. Magnetic resonance imaging showed splenomegaly and splenic iron depositions. The red blood cell osmotic fragility test was positive. The eosin-5'-maleimide binding test showed reduced mean channel fluorescence. Whole-exome sequencing revealed a novel ANK1 mutation (c.4707G>A), resulting in a nonsense mutation (p.Trp1569*). The patient's father, paternal aunt and paternal grandmother exhibited comparable clinical symptoms and Sanger sequencing confirmed the same mutation in these family members. To the best of our knowledge, an HS pedigree with this novel ANK1 nonsense mutation has not been previously reported. At the same time, the unique clinical presentation of this pedigree helps our understanding of the heterogeneity of clinical manifestations of HS.

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

A cell model for high-throughput screening GLP-1 receptor agonists / 中国药理学通报

Aim To establish a high-throughput screening cell model for GLP-1 receptor agonists. Methods A pEGFP-GLP-1R-3 C recombinant plasmid was constructed and transfected into HEK293T cells. The cells were screened with G418 and flow cytometry. The established stable cell line was named HEK293TGLP-lR-3C-eGFP cell line. The expression level of GLP-1 R-3C-eGFP protein was confirmed by Western blotting and laser confocal microscopy. Then cyclic adenosine monophosphate (cAMP) response element reporter gene was transfected into the HEK293T-GLP-lR-3C-eGFP cells. The luminescence values were detected by One-Step Luciferase Reporter Gene Assay Kit after stimulation with different concentrations of GLP-1 peptide. The luminescence values reflected the cellular cAMP level, which was verified using the cAMP kit (E L I S A). Results HEK293T-GLP-lR-3C-eGFP cell line was successfully constructed. The relative light unit change trend after stimulation with different concentrations of GLP-1 was similar to that of the cellular cAMP level change trend. The value of Z' in this experiment was 0.52. Conclusions A recombinant HEK293T cell line is established, which can be used for high-throughput screening of GLP-1 receptor agonists.

Nicotinamide Mononucleotide Adenylyl Transferase 2 Inhibition Aggravates Neurological Damage after Traumatic Brain Injury in a Rat Model

Objective@#: Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. @*Methods@#: The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. @*Results@#: NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). @*Conclusion@#: NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

Prevalence and Management Recommendations for Disease-Related Malnutrition in Chronic Kidney Disease Patients with and without Diabetes.

Objective: To investigate the nutritional risk, malnutrition, severe malnutrition, and malnutrition prevalence of different stages in chronic kidney disease (CKD) patients with and without diabetes mellitus using the Global Leadership Initiative on Malnutrition (GLIM), and to analyze the causes of malnutrition and to improve the clinical outcomes of patients for early intervention. Methods: A total of 683 patients with CKD who were hospitalized in our hospital from January 2020 to January 2021 were enrolled and divided into subgroups 1 to 5 according to whether they were complicated with diabetes and glomerular filtration rate. Using the second step of the malnutrition (GLIM) diagnostic tool and 2 previously commonly used malnutrition assessment methods (body mass index <18.5 kg/m2 with poor general condition, 3 points for nutritional deficiency in nutritional risk screening), combined with clinical research on the main causes of malnutrition, the intervention measures were discussed. Results: The prevalence of malnutrition was 16.7% (114/683) in the patients included in the survey using the diagnostic criteria of malnutrition (GLIM) (excluding whole body muscle mass index). The prevalence of malnutrition in CKD patients with and without diabetes was 23.7% and 12.6%, respectively. The overall prevalence rate of severe malnutrition was 14.2%, and the prevalence rates of those with and without diabetes were 19.0% and 11.4%, respectively; the results of the two methods of malnutrition assessment showed that the prevalence of malnutrition in CKD patients with diabetes was higher than that in the uncombined group. There was no severe malnutrition in patients with CKD stages 1 and 2. From CKD stage 3 onwards, the severe malnutrition in the diabetic group was significantly higher than that in the uncombined group. Conclusion: With the progression of CKD, the incidence of malnutrition also gradually increased, indicating that malnutrition is related to primary diseases and concomitant diseases. Attention should be paid to the malnutrition of CKD patients with diabetes, and clinical medical staff need to pay early attention to various diseases that lead to the progression of CKD, such as diabetes, primary nephropathy, and other factors, to prevent complications and delay the progression of CKD.